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CONTRIBUTORS TO YOLUME III 


ANDERS, JAMES M . M D 
BALDWIN, EDWARD R . M D 
BIRKETT, H S . M D 
BOGGS, THOMAS R , M D 
BROWN, LAWRASON, M D 
BROWN, THOMAS R , M D 
BRUCE, DAVID, CB,FRS.DSc,MB 
CHRISTIAN, HENRY A , M D 
CHURCHMAN, JOHN W , M D 
COLE, RUFUS I , M D 
DUNBAR, W P , M D 
DYER, ISADORE, M D 
HARE, HOBART AMORY, M D 
HERZOG, MAXIMILIAN, M D 
JAMES, WALTER B , M D 
LORD, FREDERICK T , M D 
MacCALLUM, W G , M D 
McPHEDRAN, A , M B 
OSLER, WILLIAM, M D 
PACKARD, FRANCIS R , M D 
RAVEN EL, MAZYCK, M D 


I 

, C M (Edin ) 



MODERN MEDICINE 


ITS THEOEY AND PEACTICE 


IN OEI&INAL CONTRIBUTIONS BY AMERICAN AND 
EOREION AUTHORS 


EDITED BY 

WILLIAM OSLEE, M.D. 

REGIDS PROFESSon OF MEDICINE IN OXFORD DMI ERSITT, ENGLAND, HONORARA PROFESSOR OF MEDICINE IN 
THE JOHNS HOPKINS HM\ ERSITI BALTIMORE FORMERLY PROFESSOR OP CDINICAL MI DICINE IN 

THE MNr\ ERSrry of pfnnsain ania Philadelphia, and of thi instithtfs of medicine 

IN MCGILL CNIVFRSITI, MONTREAL, CANADA 


ASSISTED BY 

THOMAS MCCEAE, M.D. 

ASSOCIATE PnorrSSOR of MFDICINF A^D CLIMCX-L TIirnArCUTICS IN THE JOH\S nOPIvINS UXIVFRSm 

B ALTIMORE 


VOLUME III 

INFECTIOUS DISEASES (CONTINUED)— DISEASES OF THE 

RESPIRATORY TRACT 

ILLUSTRATE D 



PHILADELPHIA AND NEW YORK 
LEA BROTHERS & CO 
1907 



Entered according to Act of Congress, in the year 1907, b> 
LEA BROTHERS & CO 

in the Office of the Librarian of Congress All nghts reserved 




CONTEIBUTOES TO VOL. III. 


JAMES M ANDERS, M D , 

Professor of the Theorj'- and Practice of Medicine and of Clinical Medicine in 
the Medico-Chirurgical College, Consulting Physician to the Jewish Hospital 
Association of Philadelphia, Consulting Physician to the Widener Home for 
Crippled Children, Philadelphia 

EDWARD R BALDWHN, M D , 

Saranac Laboratory for the Study of Tuberculosis, Saranac Lake, New York 

H S BIRKETT, MD, 

Professor of Laryngolog}'- and Otology in the McGill University, Medical 
Facult}'^ , Laryngologist and Otologist to the Royal V ictoria Hospital, Montreal, 
Canada 

THOMAS R BOGGS, JI D , 

Associate in Medicine in the Johns Hopkins University, Assistant Resident 
Physician in the Johns Hopkins Hospital, Baltimore, Md 

LAWRASON BROWN, M D , 

Adirondack Cottage Sanitarium, Saranac Lake, New York 

THOMAS R BROWN, M D , 

Associate in Medicine in the Johns Hopkins Medical School, Baltimore, Md 

DAVID BRUCE, C B , F R S , D Sc , M B , C M (Edin ), 

Colonel, British Army 

henry a CHRISTIAN, M D , 

Assistant Professor of the Theory and Practice of Physic m Harvard University, 
Physician-in-Chief to the Carney Hospital, Boston, Mass 

JOHN W CHURCHMAN, M D , • ‘ 

Assistant Resident Surgeon in the Johns Hopkins Hospital, Baltimore, Md 

RUFUS I COLE, M D , 

Associate in Medicine in the Johns Hopkins Medical School and Hospital, 
Baltimore, Md 

W P DUNBAR, M D , 

Director of the Hygienic Institute, Hamburg, Germany 

ISADORE DYER, M D , 

Professor of Diseases of the Skin, Associate Dean of the Medical Department of 
the Tulane University, New Orleans, La 

Hobart amory hare, m d , 

Professor of Therapeutics and Materia Medica in the Jefferson Medical College, 
Physician to the Jefferson Hospital, Philadelphia 


(V) 



VI 


CONTRIBUTORS TO VOLUME III 


IMAXBIILLIN HERZOG, JI D , 

Pathologist to the Michael Reese Hospital, Chicago, 111 , Professor of General 
and Comparatue Pathology in the Chicigo Yeterinar}' College, late Pathol- 
ogist in tiie Bureau of Science, Manila, P I 

WALTER B JAMES, M D , 

Professor of Practice of Medicine in the College of Physicians and Surgeons 
(Columbia University), New York Citj 

FREDERICK T LORD, M D , 

Assistant in Clinical Medicine in the Medical School of Harvard University, 
Pltysician to Out-Patients in the Massachusetts General Hospital, Boston, 
Mass 

W G MicCALLUM, MD, 

Associate Professor of Pathologj in the Johns Hopkins Medical School, 
Baltimore, Md 

A McPHEDRAN, M B , 

Professor of Medicine and Clinical Medicine in the University of Toronto, 
Toronto Canada 

WILLIAM OSLER, M D , 

Regius Pioiessor of Medicine m Ovford Unnersit}’^, Ovford, England 

FRANCIS R PACKARD, M D , 

Professor of Diseases ol the Nose and Throat in the Philadelphia Polyclinic, 
Assistant to the Out-Patient Department of the Pennsylvania Hospital, 
Laiyngologist to the Children’s Hospital Philadelphia 

MAZYCK P RAVENEL, M D , 

Professor of Bacteriology in the Unnersity of Wisconsin, Madison, Wis 



CONTENTS OF VOLUME III 


f 


PART I 

THE INFECTIOUS DISEASES— Continued 


CH4PrER I 

MALTA FEVER 17 

Bi Col David Bruce, C B , F R S , D Sc 

CHAPTER II 

BERIBERI (KAKKE) 29 

Bi MjVximilian Hek7og, M D 

CHAPTER III 

ANTHRAX, RABIES, GLANDERS 42 

By Mazi ck P Ravenel, M D 

CHAPTER IV 

TETANUS 76 

Bl James M Anders, M D 

CHAPTER V 

GONOCOCCUS INFECTIONS 88 

Btl Rurus I Cole, M D 

CHAPTER VI 

LEPROSY 121 

B\ IsADORB Dler, Ph B , M D 

CHAPTER VII 

TUBERCULOSIS HISTORY AND ETIOLOGY 137 

By Edward R Baldwin, Jil D 

(vu) 



VIll 


CONTENTS OF VOLUME III 


CHAPTER VIII 

THE PATHOLOGY OF TUBERCULOSIS 200 

Bi W G MacCallum, M D 

CHAPTER IX 

THE SYjMPTOMS OF TUBERCULOSIS 248 

By Lawraso^t Brown, M U 

CHAPTER X 

THE DIAGNOSIS AND PROGNOSIS OP TUBERCULOSIS 327 

Bi Laa\ rasok Brown, M D 

CHAPTER XI 

THE PROPHYLAXIS AND TREATMENT OF TUBERCULOSIS 361 

B\ Lawrason Brown, M D 

CHAPTER XII 

SYPHILIS 430 

Bi William Osler, M D , and John W Churchman, M D 

CHAPTER XIII 

INFECTIOUS DISEASES OF DOUBTFUL NATURE 522 

Bi Thomas R Boggs, M D 


PART II 

DISEASES OF THE RESPIRATORY TRACT 

CHAPTER XIV 

THE MECHANICS OF RESPIRATION AND OF THE RESPIRATORY 

TRACT ^ 549 

Bi Thomas R Brom n, M D 

CHAPTER XV 

DISEASES OP THE NASOPHARYNX, PHARYNX, AND TONSILS 586 

Bi Francis R Packard, M D 



CONTENTS OF VOLUME III 
CHAPTER XVI 

hay fever 605 

By W P Dunbar, M D 

CHAPTER XVII 

DISEASES OF THE LARYNX 622 

Ba H S Birkett, M D 

CHAPTER XVIII 

DISEASES OF THE BRONCHI 636 

Ba a McPhedran, M B 

CHAPTER XIX 

DISEASES OF THE LUNGS 723 

Ba Hobart Ajiora Hare, M D 

CHAPTER XX 

DISEASES OF THE PLEURA 780 

]3a Frederick T Lord, M D 

CHAPTER XXI 

PNEUIMOTHORAX 868 

Ba W alter B James, M D 

CHAPTER XXII 

DISEASES OF THE MEDIASTINUM 890 

Ba Henra a Christian, A M , M D 




PART 1. 


THE INFECTIOUS DISEASES-CONTINTJED. 


CHAPTER I. 


MALTA FEVER 

COL DAVID BRUCE, C B , F R S , D Sc 
Synon3n31 — ^iNfeditei ranean fevei 

Definition — ^A disease of long duiation, characterized ehmcally by 
continued fever, profuse perspiration, constipation, fiequent i elapses, 
rheumatic or neuralgic pains, swelling of joints, or orchitis , bacteiiologically, 
by the presence in the blood and oigans of the Mtci ococcus mehtensis (Bruce) , 
and, anatomically, by congestion of the spleen and other organs 
History — ^Tlus fevei has been elucidated chiefly by army medical 
officers, and its history may be briefly summed up as follows The first 
paper of any importance w as written in 1861 by Maiston ' In it he described 
the fever from the clinical side veiy completely and clearly, and it wull lepay 
anyone interested in the disease to read his account The next is by Veale,^ 
in 1879, in wffiich he describes the fever in patients invalided to England from 
Gibraltar, Malta and Cypius The next event of any importance w'as the 
discovery on July 9, 1887, of the specific oiganism of the disease, the 
Miciococcus mehtensis^ Ten years aftcrwaid, in 1897, Wiight and Semple 
applied the method of serum diagnosis lO this fever, and this, especially m 
Malta, has helped greatly to distinguish this disease fiom other continued 
fevers In this yeai, also, the late Surgeon-Captain hi Louis Hughes^ 
published his lengthy monograph on Mcdtienanean, Malta oi XJndulant 
Fevei, which contains everything knowm on the subject up to that date and 
also a full bibhogiaphy Nothing moie w^as done m the investigation of this 
fever until 1904, wdien a commission w'as formed, under the direction of the 
Loyal Society of I^ondon, to continue the investigation This commission 

^Army Medical Report, 1863, vol in, p 486 
Medical Report, 1881, vol xxi, p 260 

iSote on the Discoverj’- of a Microorganism in Malta Fever,” by Surgeon- 
tlJ?, Bruce, Practitioner, vol xxxix, 1887, and “The Miciococcus of 

luaita Fever,” Practitioner, vol xl, 1888, and “On the Etiology of Malta Fever,” 
Army Medical Report, 1892, vol xxxii, p 365 

i^ditcrranean, Malta or XJndulant Fever, MacMillan & Co , 1897 
VOL 3—2 


17 



18 


INFECTIOUS DISEASES 


has been at work up to the piesent jeai (1907), and has furnished seven vol- 
umes of repoits ^ 

Geographical Distnbution — ^This fevei has been leported fioin Spam 
— Gibialtar, Islands of the Mcdttenanean — Baleaiic Islands, Corsica, Sar- 
dinia, Sicily, Malta, Gozo, Cyprus, Crete, Italy, Gieece — Athens, T^l)- 
Ley — Constantinople, Smyrna, Palestine — Jerusalem, Ajnca — ^Tunis, 
Algiers, Alexandria, Suakm, Massowah, Zanzibai, Kimberley, Orange 
River Colony, Arabia — ^Aden, India, China — Hong Kong, Pacific — 
Philippine Islands, Fiji Islands, Noith Ainenca — Mississippi Valley, 
West Indies — Cuba, Poito Rico, South Anicnca — ^Venezuela, Brazil, Mon- 
tevideo 

It IS probable that many of these lepoited cases weie not leally Malta 
fevei The diagnosis was often made by the seium reaction to Mioococtw^ 
melitensis, a method which i\ hen used alone is apt to cause eri oi That the 
disease is a widespread one theie can be no question, but it does not appear 
to occui m large numbers in any place except INIalta, which is the home of 
this fevei It may also be said to be tiopical and subtropical in its distribu- 
tion, no cases, according to Hughes, having been lepoited noitli of 45° N 
latitude, 01 south of 40° S latitude 

Distnbution in Malta — Malta fevei nas thought at one time to be chiefly 
confined to the laige ton ns of Malta, but non it is known to occur in every 
part of the island, and the disease is very prevalent m seveial of the inland 
towns and villages The average incidence of the fevei among the 200,000 
Maltese is said to be about 30 per 10,000, whilst among the soldiers quartered 
in the island the incidence is about 370 per 10,000 In some yeais the 
incidence is double this, as, foi example, in 1905 there were 643 cases of 
Malta fever among the soldiers alone (750 per 10,000) of whom 382 weic 
invalided to England 

Etiology — The Micrococcus Mehtensis — This coccus, oi cocco- 
bacillus, is about 0 33u in diametei, and usually occuis singly oi in pans, 
but when grown in broth appeals in shoit chains A bacillaiy form also 
occurs m cultures which have been grown at oidmary tempeiatuies (18° C 
to 20° C ) It IS non-motile It stains readily w ith all the basic timline dyes, 
but loses its color rapidly wdien treated with alcohol oi other decoloiizmg 
agent, and becomes unstained by Gram's method 

Aitificial Cultivation — Growth is extiemely slow', and it is impoitant that 
media w'hich aie faintly acid should be used If markedly alkaline no giow’th 
w'hatever takes place It show's a very slow and scanty grow'th at a tempei a- 
ture of 18° C , grow'ing best at about 37° C oi 38° C At temperatures 
betA\een 40° C , and 42° C growth is suspended Above 42° C aitificial 
groAvths die It is aerobic, but also grow's in a feeble way anaeiobically 
The chief cultuial characteristics are as follow's 

In 1 per cent glucose peptone, theie is grow'th, but neither acid nor gas 
IS produced The same want of reaction occurs w'lth lactose, saccharose, 
and staich peptone 

In litmus milk theie is no clotting, and the leaction becomes distinctly 
alkaline m a few weeks 

'' Reports of the Commission Appointed hy the Admiralty, the War Office, and the 
Ciml Government of Malta, for the Investigation of Mediterranean Fever, Under the 
Supervision of an Advisory Committee of The Royal Society, Parts I, II, III, IV, V, 
VI and VII, London Harrison & Sons, 1905-06-07 



MALTA FEVER 


in 

On potato it grows well, the growth is moist, transpaient, and the foima- 
tion ot chains is well marked 

Growtli tn Bioth — ^After two or thiee days the bioth becomes turbid 
K allowed to stand for some time theie is a deposit of floccuh, but the fluid 
remains turbid, and there is no pellicle formation Indol leaction is negative 
No odor IS produced 

Gro%otli 011 Gelatine — Does not liquefy 

Giowth on Agai-agai — Cultuies made directly fiom the organs after 
death on this medium, if faintly alkaline, show no growth for about four days, 
if kept at 37° C , and seven days if kept at 25° C On sloped agar the colonies 
when they do appear are small and transparent, and resemble diops of dew 
Plate Cultivation — On ordinal y agar at 37° C , after three days, under the 
imcioscope the colonies on the surface are lound, with an even border They 
are blight and transparent, vith a slight brown tinge about the centre, and 
are finely granular As they grow older they become bioivner in color 
The addition of 1 per cent nutrose enhances and quickens the growth of 
the micrococcus To separate it fiom a mixture of others, it is best to use a 
medium to which glucose, nutiose, and litmus are added The fact that it 
does not ferment glucose, and renders milk and other media alkaline, is an 
important featuie, vliile the addition of nutrose adds somewhat to its rate of 
grovth On such a glucose-nutrose-litmus agar, the colonies appear blue, 
whereas many of the streptococci found in urine, faeces, etc , ferment glucose 
and give the medium an acid reaction 
In regard to the diagnosis of this species of bacteiia, Horrocks says that a 
microorganism which agglutinates Avith a specific animal serum m a high 
dilution, does not ferment glucose, lenders milk alkaline without coagulation, 
and does not retain stain by Giam’s method, may justly be regarded as the 
Mici ococeu'i ineliten sis 

Life of the Micrococcus Mehtensis Outside the Body — Vitality — It is 
faiily resistant when outside the body The most important facts are that 
it will resist desiccation m dust or on dry fabiics for sixty to eighty days 
It will live in tap- or sea-u atei for about a month Even in urine which 
has become maikedly alkaline it has been found alive after six days Expo- 
suie to the sun kills it in a few hours 

Habitat Outride the Pluman Body —-No one has, up to the piesent, found 
this paiasite in external nature Tlie vriter wiote in 1887 that, on account 
of the high tempeiature required for its growth, the length ot time wdiich 
elapses before the colonies appeal, and the absence of anv w'ell-marked 
morphological or cultural cliai act eristics, the seaich for it outside the body 
wall be very difficult, if not hopeless Many effoits have been made to find 
it m the air of wards, in dust from infected rooms, m the w'atei of the harbors, 
01 in the soil Examinations of these materials have been made by plate 
cultuies and by inoculation into susceptible animals, but without result 
How Does The Micrococcus Leave the Body‘s — All examinations of 
expired air, sw^eat, saliva, and sci apings of skin of patients have failed to 
show that the oigamsm leaves the body bv any of these routes The urine, 
on the other hand, fiequently contains them, sometimes m enormous num- 
bers, but, as a lule, they aie not nuineious, ranging fiom 3 or 4 to 300 or 400 
pel cubic centiinetei Kennedy, a meinbci of the Mediterranean Feiei 
Commission, lepoits that he made some thiee thousand observations on 
the urine and found the Miciococcui meliiensis m 10 per cent This, taken 



20 


IXFECTIOUS DISEASES 


in connection wntli the long-continued vitality and virulence of the oiganism 
in a drv condition, may be a factoi in the spiead of the disease, though it 
must be confessed that up to the present there is no direct proof of infection 
by naturally infected dust This excretion in the urine may go on for a long 
tune (two years) after the patient is convalescent, so that these microbes 
must be scattered bioadcast ovei the nhole of Malta It has not yet been 
ascertained how many cases of Malta fevei lemain unidentified, but theie 
can be little doubt thatmany do, and these add to the geneial contamination 
of the surface of the soil Shan' examined 525 dockyaid laborers and found 
that 79, or 15 pei cent , gaye a distinct agglutination with the Miciococciis 
meliiensi^ Of these 79, a maiked reaction was present in 22, who w'eie 
accordingly selected for a detailed examination In 3 of them the organism 
was reco\eied from both blood and uime, in 1 fiom the blood onlj^ and in 
6 from the mine only All these men weie up and about and m full wmik 
during the period of obseiyation Two weie kept under observation and 
continued to pass large numbers of micrococci in the urine fiom June, 1905, 
until the end of 1906, and are piobably still excietmg them (1907) 

Although the micrococci have onlv been directly observed in the faices of 
man on one occasion, they probably also pass out of the body by w^ay of the 
alimentaiy canal Eyre found miciococci thioughout the Aihole length of 
the intestine in artificially inoculated labbits Horrocks and Kennedy ha\e 
also found them in the gall bladdei of man 

A third w ay of leaving the body is by the milk, and this is by far the most 
important fiom the point of view of infection Naturally, it is difficult to 
obtain evidence of this mode of excietion in patients, on account of the 
absence of lactation in patients who have Alalta fevei Dm mg the summer 
of 1906, howevei, 3 women were examined and the micrococcus recovered 
fiom the milk of 2 of them 

Although these thiee modes of leaving the body aVe probably the most 
important, yet a fourth remains foi discussion The blood of Malta feyei 
patients contains micrococci, not in huge numbers as a rule it is true, but 
still in appreciable amount Now', a mosquito takes m about four milh- 
giams of blood at each feeding, and, therefore, it is quite possible for the 
mosquito to ingest this micrococcus with the blood Hoi rocks and Kennedy 
did m fact isolate M mehfensi^ on four occasions from the blood contained 
in the stomach of mosquitoes caught in fever w'ards 

How Does the Micrococcus Enter the Body ’ — ^The success of preventive 
measures probably hangs on finding the correct answer to this question 
Does the \irus enter by way of the alimentary canal, by the lungs, through 
mucous membranes, oi through the skin ’ In other words, is it conyeyed 
fiom the sick to the healthy by means of food, w'ater, milk, by the inhalation 
of dust, or IS it injected through the skin by suctorial insects ? 

In trying to frame preventive rules against an infectious disease it is 
evident that the important thing to strive for is the nairow'ing down of the 
paths of infection In yellow fever, as long as it w'as believed that it could be 
spread by contact, infected clothes, food, w ater, etc , nothing could be done 
The moment the mode of infection was nariow'ed down to a particular 
species of mosquito the problem of prevention w as simple In the same w'ay 
with Malta fe\er if it can be spread by contact, contamination of food or 


‘ Reports of the Mediterranean Fever Commission, vol iv, p 8 



MALTA FEVER 


21 


■\\ ater, by the inhalation of dust, sen ei air, etc , it will be impossible to do 
more than recommend the ordinary established rules of hygiene But, on 
the other hand, if the mode of spiead can be narrowed doi^n to such a 
vehicle as milk or a mosquito, something rapid and dramatic in the v ay of 
prevention might be attempted 

By Contact — ^Many expeiiments have been made on this point, as 
natuially, questions of segiegation of the sick, evacuation and disinfection of 
infected bairacks and rooms depend on this mode of infection In 1904 
two monkeys belonging to the hlediteiranean Fever Commission took the 
fever naturally They were both living close to affected monkeys, and it v as 
supposed, and probably rightly so, that they had taken the disease from their 
neighbois This was lepeated as an experiment on several occasions v ith, as 
a rule, positive results Experiments made m which the contact was limited, 
that IS to say, m vhich infection by urine was excluded, never succeeded 
It was theiefoie concluded that the monkeys probably took the disease by 
having their food contaminated vith the urine of their neighbois, or it 
might possibly be by eating ectoparasites containing blood, and that, 
therefore, contact resolved itself into a feeding expeiiment 
As the chance of man having his food contaminated m this way is very 
remote, it is probable that very few cases of Malta fevei arise m this mannei 
At the same time, this mode of infection cannot be absolutely excluded, 
and the high incidence, according to Johnstone, among those who nurse 
Malta fever patients may possibly be due to insufficient care in the handling 
of the mine of the patients But the fact that no case of Malta fevei has ever 
been known to occur m England, at Netley or Haslai Hospitals, vhere 
thousands of patients with this fever have been treated, is proof that, in 
practice, contact as a factoi in the causation may be almost put out of court 
By Contammated Dn&t — As the organism can retain vitality for a long 
time m a dry condition, it was thought probable that the infection might be 
conveyed from the sick to the healthy by means of dust Dust contammated 
vith urine from Malta fever cases might be blovn into the atmospheie and 
so be inhaled oi swallowed In ordei to put this to the test various experi- 
ments Mere made At first, aitificially contaminated dust was used The 
dust was steiilized, then made wet vith an emulsion of the organisms fiom 
agar cultuies, and finally diied Hoi locks relates 2 experiments, m 1 of 
which this dust v as blov n about the cage, and m the other blown directly 
into the nose and throat Both i\ere successful Shaw also describes 2 
experiments of blov mg contaminated dust about an air-tight box containing 
the monkeys, but both v ere unsuccessful In 2 experiments by him in which 
the dust Avas blown into the nostiils, 1 remained negative, and 1 gave a 
jiositive result Of 4 expeiiments in vhicli he frequently dropped dust into 
the conjunctival sac, 2 Aveie negative and 2 positive 

Fiom these expeiiments it may be concluded that aihficmUy contammated 
dust may comey hlalta fever to healthy animals This is not proof, how- 
ever, that this ever occurs naturally Aitificially contammated dust contains 
nnriads of the specific miciococci Dust in nature can contain but few, 
seeing how sparse they are in the urine as a rule The dust blow mg about 
under natural conditions must lapidly dilute the micrococci to an extra- 
ordmarv extent, so that we can only pictuie a micrococcus here and there in 
a gieat quantitA'^ of dust The natural conditions can be moie closely imitated 
if the dust IS contaminated with Malta fever urine and not from a cultuie 



22 


INFECTIOUS DISEASES 


By Dust Artificially Contaminated loith the Urine of Malta Fever Patients 
— urine containing micrococci ^\as used to contaminate the dust After 
drymg, the infective dust vas blm\n into the nostrils and added to the food 
of monkeys Four expeiiments aie reported by Horrocks, lasting from 
twelve days to tv o months, but in no case did infection occur It is difficult 
to understand why this experiment did not succeed The dust was infected 
by a urine containing exceptionally large numbers of the micrococci, and 
immediately dried It vas evidently added in fairly large quantities to 
the food, as three out of four animals suffered from severe vomiting and 
diarrhoea Shaw also reports that he experimented on four monkeys m the 
same vay, but did not succeed in conveying the infection m a single case 
These experiments aie much more severe than anything we can imagine 
occurring in nature, and tend to throw doubt on dust being an impoitant 
factor in the spread of Malta fever 

By Dust Collected pom Suspicions Places — ^This is, of course, the crucial 
experiment as far as infection by dust is concerned Judging from the non- 
success of the last series of experiments with urme-contaminated dust, it 
was little likely that this experiment would succeed It was, howevei, 
necessary to make the attempt Dust was collected from fever wards, from 
places where cases had occurred, fiom around urinals, etc , and blown about 
the cages and food of monkeys, or iniected subcutaneously Up to the 
present all these experiments have failed 

When one considers the numbers of ambulatory and convalescent patients 
w'ho must frequently be excreting this organism m the urine, one is led to 
think that this must constitute a means of spreading the disease At the 
same time there is no absolute proof that this is so, the micrococcus has 
never been recoveied fiom uime-contaminated places, or from the dust of 
such places, nor has the disease been set up in any animal by artificial 
inoculation with material fiom such places Theoretically, there seems to 
be danger from the scattering broadcast of such a viiulent and lesistant 
microbe, but it is possible that not a single case of infection occurs in tins 
way As sound practice, howevei, any sanitaiy measuies w'hich could be 
devised to prevent the fouling of the soil by infected mine w ould be advisable 

By Way of the Alimentaiy Canal — ^It has been repeatedly demonstrated 
by experiment that a small quantity of a culture applied to a scratch, oi 
injected under the skin, will give use to Malta fever in man and inonkejs 
Also that dust oi fluids containing the micrococci, if applied to the unbroken 
conjunctiva, nasal passages, phaijnx, interior of the larynx and trachea of 
monkeys, wall set up this fever 

This question of the micrococcus gaming entrance by W'ay of the alimen- 
tary canal is important It is most essential that it should be knowm without 
any shadow of doubt w hethei or not a man can take this fever by sw'allow mg 
the micrococci m his food or drink It would also be w^ell to know' if this 
mode of infection takes place readily and whether many micrococci are neces- 
sai y or some particular state of the digestive organs A careful study of the 
evidence must convince anyone that Malta fever can be conveyed to healthy 
animals by way of the alimentary canal Many animal experiments were 
made by the commission to settle this point, w ith the result that it is abun- 
dantly proved that animals can be readily infected by contaminated food or 
ilrink For example, a single drink of milk containing comparatively few 
micrococci almost certainly gave nse to the fever 



MALTA FEVER 


23 


By Mosquitoes oi Othei Bihng Insects — ^All the various species of mos- 
quitoes found in Malta, other biting flies, as Stomovys, fleas, etc , vere first 
fed on aftected animals and then at vaiious intervals of time on healthy 
monkeys The results of numerous experiments go to show that although 
such a method of infection is not absolutely disproved, it can only be of very 
lare occurrence 

As the result of all these experiments it stands out fairly clearly that the 
Mioococcus mehtensis is conveyed fiom the sick to the healthy by way of the 
ahmentaiy canal and tlierefoie by some infected food oi drink There is no 
leason to believe that contact, inhalation of infective dust, or biting insects, 
play any piominent role Then, again, fiom a study of the epidemiology oi 
the fever, no suspicion could be attached to the v ater supply or any particular 
foodstuff 

Infection by Means of Goats’ Milk — As part of an investigation of this 
sort, it IS necessaiy to examine the various domestic animals to find out if any 
of them, through which man might be infected, are susceptible to the disease 
The monkey was the only experimental animal known to take the disease 
naturally, but various othei s, such as the guinea-pig and rabbit, could be 
infected by various expedients 

Attention was diiected to the goats, which are so numerous and so mueh a 
feature of every-day life in Malta, and which supply most of the milk used 
m the island Healthy goats a\ ere m]ected subcutaneously with cultures of 
Miaococcus mehtensis, and, although they shoved no signs of fever or ill- 
health, an examination of their blood showed that the micrococci were 
living and gi owing This remarkable and unlooked-foi observation led to 
the examination of various herds of appaiently healthv goats perambulating 
the stieets, and supplying the inhabitants with milk, and the mipoitant 
discovery was made that about 50 per cent were affected by the disease, and 
that 10 pei cent were actually excietmg the micrococcus in their milk 
hlonkeys fed on milk from an affected goat, even for one day, almost invari- 
ably took the disease At this time, cuiiously enough, an important experi- 
ment on the dunking of goats’ milk by man occurred accidentally This is 
the case of the S S “Joshua Nicholson” In 1905 this steamer shipped 
sixty-five goats at hlalta for expoit to the United States of America Iflie 
milk vas drunk by the captain and many of the ciew, with the result that an 
epidemic of Malta fever bioke out on boaid the vessel, almost everyone who 
drank the milk being infected Even after the goats leached America and 
were placed in qiiaiantine, a woman who diank some of their milk had the 
fever 

Here, at last, a mode of infection was discovered which explained many 
of the cuiious ieatiiies m the epidemiology of hlalta fever The irregular 
seasonal pievalence and the number of cases during then inter months, v hen 
there are no mosquitoes and little dust It is true theie are more cases m 
summer, but this may be explained by the conditions being moie favoiable 
foi the multiplication of the micrococcus, by moie milk or cream being used 
for fiuit, in ice-cream, etc , and by the lowering of health during the hot 
months It v ould exjilam the large number of cases arising among patients 
in hospitals v hei e milk is used largely It v ould also explain the habihtv to 
attack of the officei being three times as great as the private soldier, since the 
former consumes much more milk than the latter It would also explain the 
isolated epidemics w Inch sometimes occiii in institutions, or in messes, such 



24 


INFECTIOUS DISEASES 


as that related by Johnstone, where a sergeants' mess ■\\as seveiely infected 
while the men living in the vicinity escaped 

Eesult of Preventive Measures Directed against the Use of Goat’s 
Milk — ^Preventive measures, as the lesult of the discovery of infection among 
the goats, were first begun m Malta in June, 1906 The lesult was very 
strilang In July, August and September, 1905, there had been 258 cases 
among the soldiers, vdiereas in the same months in 1906 the number fell to 
26 It must also be mentioned that 1906 began badly, there being an average 
incidence of 31 per 1,000 for the first si\ months of 1906 against 27 6 
pel 1,000 for the years 1899 to 1905 

Another striking example of the benefit of this simple preventive measuie 
16 given in the case of the Naval Hospital, Malta This is a fine modern 
building, situated in extensive grounds In spite of these advantages it had 
been in bad repute, on account of the number of cases of IMalta fever which 
occurred among the inmates Almost every patient who remained for a few 
weeks in the hospital took the disease The goats supplying the hospital 
with milk were examined and several found to be passing the micrococcus m 
their milk The use of goats' milk was forbidden, and from that date not a 
single case of Malta fever has appealed in the hospital 

A still more sti iking proof is aflorded in Gibi altar, where some years ago 
this fever was prevalent Gradually it grew less and less and finally has quite 
disappeared Horiocks, who investigated this point, found that IMalta fever 
had disappeared fiom Gibraltar pan passu with the disappearance of 
Maltese goats 

Taking all these facts into consideration, there seems reasonable ground foi 
the belief that nine-tenths of the cases of Malta fever v Inch occur m JMalta 
are due to infection by goats' milk, and foi the hope that Malta fever will be 
driven out and 74,880 days of severe illness blotted out of the yeaily medical 
reports of the army and navy This, if bi ought about, vill be a brilliant 
achievement in the annals of preventive medicine, and will once more 
demonstrate the value of expeiimental methods in the elucidation of the 
etiology of disease It is too eaiiy to be quite dogmatic, but the prospect 
appeals hopeful, and tlie result of next year's campaign against this fever 
will be awaited iMth some anxiety and much interest 

Age and Sex — ^There are no statistics available at the present time to 
enable us to state whethei age or sex has any bearing on the incidence 
In foimer papers by the writer, the opinion w^as hazarded that any age is 
liable and that sex has no influence 

Length of Residence — ^According to Johnstone,^ the heaviest incidence is 
among soldiers duiing their first year's seivice in Malta, and the severity of 
incidence continues to decrease with length of lesidence 

Mode of Prevalence —This is curious and must depend on some paiticu- 
lar cause The officeis and their wives and families, living m large, 
w^ell-ventilated, w^ell-cared-for houses, suffer more frequently than the non- 
commissioned officers and men, living in crowMed barrack rooms The 
disease occurs over all the island Water supply, sanitary arrangements, 
01 their absence, do not seem to affect the incidence Now' that the discovei y 
of the infection among the goats has been bi ought to light, this peculiarity 
in the mode of prevalence is ex-plained 


' Reports oj the Mediterranean Fever Commission, vol ii, p 33 



^ULTA FEVER 


25 


Months and Seasons — ^Tables and cuives have been constiucted by 
Johnstone/ and otheis, shoving the relation of hlalta fever to temperature 
and rainfall Fiom these it is seen that there is a close coirespondence 
betveen the tempeiature cuive and the Malta fevei cuive As Johnstone 
points out, the rise of the latter curve follov s that of the formei at an interval 
of about one month, vhich would be appioMinatclj’^ sufficient to allow for 
incubation and notification if the incidence of the fever v ere diiectly depend- 
ent on the temperatuie of the an The lamfall cuive is, broadly speaking, 
tlie opposite of the temperature cuive, but the relation of the fever to the 
rainfall does not seem to be as manifest as its connection with the tempera- 
tine It must be noted, hovevei, that, although the number of cases which 
occurs duiing the v et winter months is much smaller than that v Inch occurs 
in the summer months, yet the fever by no means dies out, but continues all 
the year round, theie being, roughly, a third as many cases notified during 
Februaiyas in August It is difficult to believe tliat this fever is mainly carried 
by means of dust, as has been advanced, if one-third as many cases occur 
in the depth of winter, in the lamy season, as occin during the rainless 
months of July and August 

Incubation Period — It is impossible to state evactl} what the period of 
ineubatioii is Johnstone, who has gone into this subject as fully as possible, 
provisionally states that the available data tend to suggest that the incubation 
period IS about fourteen days One case is reported by Bassett-Smith with 
an incubation period of two months, but it stands alone, and there is some 
evidence that cases have cccurred in as shoit a time as si\ days after arrival 
in Malta The subcutaneous inoculation of monkeys gives an incubation 
period of about five days, whereas if the disease is given by ingestion the 
inoculation peiiod appeals to be lengthened to about fifteen days 

Immunity from Second Attack — ^Although tliere is some diversity of 
opinion the waiter’s experience suggests that one attack of this fevei does 
piactieally confer immunity Lately, several monkeys W'hich had recovered 
from the disease were reinoculated wath a virulent ciJture and show'ed no 
reaction 

Special Pathology. — The anatomical changes are those due to high 
temperature and the circulation of toxins in the blood, and need not be 
described m detail There is absolutely no specific inflammation of Payer’s 
patches, oi other glands of the intestine The spleen is alw^ays enlarged, 
averaging 20 ounces in w’^eight The mesenteric glands are only moderately 
enlarged, show mg a marked contrast to typhoid fever The lungs are alw ays 
congested at the bases, but there is less liability to pneumonic consolidation 
til an m tj^phoid fevei 

Ssmiptoms — ^Theie IS no great necessity to enter into the sjonptomatology 
at great length, as the symptoms are those commonly met with in other 
fevers, such as tj'phoid fever Theie are, however, a few points wdnch 
should be noted For example, constipation is a marked symptom in Malta 
fever, m 65 cases, 48 are noted as being constipated throu^iout, whereas 
only 17 had diaiihoea at any time during the illness The temperature curve 
must also be noted On looking over a series of charts, the striking features 
are the extreme irregularity and the great tendency to relapses The follow - 
mg ehart may be taken as tjjfncal of a fairlj severe attack of hlalta fever, 
and from it can be judged the length and serious nature of the disease 

^Report of the Mediterranean Fever Commission, vol ii, p 35 



26 


INFECTIOUS DISEASES 


3?ia 1 



Duration of the Fever — The average stay 
of soldiers in hospital is ninety days, but this 
does not represent the true average, as many 
of these men are invalided to England Bas- 
sett-Smith gives the average duration m 50 
cases at one hundred and twenty days The 
length of this fever varies m different individ- 
uals between wide limits, while some return 
to duty within twenty or thirty days, on the 
other hand the writer has seen a case v Inch 
lasted for more than three years 

Another important symptom is the pain 
and swelling of the joints This complica- 
tion occurs m neaily half the cases, and is 
very characteristic of the disease Neuritis 
and orchitis come under the same category, 
and are fairly frequent The orchitis is 
painful while it lasts, but usually passes away 
in a few days without leaving any bad 
effects 

Sequelse —There is little to be noted 
under this heading Although considerable 
pain and inconvenience are caused by the 
swelling of, and effusion into, the joints, the 
aithiitis usually clears completely and does 
no peimanent damage Neuritis is frequent 
in various nerves, and naturally tends to 
cause, in a few cases, prolonged amesthesia, 
paresis, or even paralysis, of various regions 
and groups of muscles In time these return 
to normal, and one can, as a rule, safely 
assure the patient of a return to complete 
health sooner or later 

Mortality — The disease is not a very 
fatal one, 3 per cent being the case mortality 
in the army during a period of seven years 
Diagnosis — ^This is most important clin- 
ically in the distinction fiom typhoid fever, 
from which it differs chiefly m the longer 
duration, in the absence of rose spots, in 
constipation being the rule, in the frequent 
occuircnce of painful arthritic or neuralgic 
symptoms, and, finally, in the much smaller 
rate of mortality The surest method of 
diagnosis is the finding of the Micrococcus 
mehtensis in the blood, inirainiam, or grow- 
ing it from the spleen postmortem 

Shav examined the blood of Malta fever 
patients on 51 occasions and found the mi- 
crococcus 30 times His method was to draw 
off a few cubic centimeters of blood from a 






MALTA FEVER 


27 


vein of the aim and distnbute it ovei several broth tubes Zainiiiit also 
was successful 27 times m 50 observations He introduced a method v Inch 
does away with the need of entering a vein The finger or lobe of the ear 
IS thoioughly cleaned and the dry skin is punctmed vitli a needle A 
sterile cotton-wool pad is used to lemove the fust diop of blood and an 
assistant squeezes thepait foi the next diop A number of sterilized capil- 
lary tubes, one centimeter long, aie ready in a test-tube As soon as the 
drop of blood appears, one of these capillaiq^ tubes, held by steiihzed foi- 
ceps, IS brought in contact vith it, and vlien full, immediately diopped 
into a broth tube Six tubes are usually filled 
If it IS impossible to make a diagnosis m this way there remains the 
agglutination test The i\ riter must say that he has not as much confidence 
in this method of diagnosis as many piofess to have As one factor in the 
diagnosis it is valuable enough, but to tiiist to it alone is dangerous It 
is a method vliicli requiies some experience to get good results The 
peisonal factor comes in stiongly, what is positive sedimentation to one 
obsener is negative to another Every examination of blood by this method 
should be safeguarded by control experiments It must be borne m mind, 
lor example, that the Miciococctis mchten tts wull give a positive agglutination 
reaction with almost all specimens of serum in dilutions of 1 in 2 and that 
blood taken from cases othei than IMaha fe\ei wall sometimes show'^ signs of 
agglutination at 1 m 10, though tins is the exception A complete sedi- 
mentation IS never obtained at 1 in 20 unless the blood is fiom a patient wuth 
jMalta fevei The agglutinins may peisist in the blood for long periods 
It IS repoited that about 50 per cent of patients will sliow' the agglutination 
phenomenon two years after the illness in dilutions of 1 in 10, and one 
instance is lepoited as giving a positive reaction in a dilution of 1 m 20, seven 
yeais after lecovciy This souice of error must therefore be kept in mind 
One quality about the seium from patients with Malta fe\ei is that if it 
does agglutinate the micrococci it does this in no unceitam way The 
average dilution giving a complete reaction is given as 1 in 500, and cases 
have been repoited up to 1 m 6,000 In regaid to the time wdiich elajises 
from the commencement of the fevei to the appearance of the agglutinins 
m the blood, this is usually put dowm as occuiring on the fifth day As to the 
low'est dilution w'hicli may be accepted as proof of Malta fevei, some w'oikeis 
put it at 1 in 10, if the clumping is well marked and takes place at once oi 
within half an hour In the writer’s o 2 miion 1 m 20 is a safer dilution 
Prognosis — ^Tlus is very favorable as legaids life and ultimate recovery 
The mortality seems to be soniewheie between 2 and 3 per cent If the 
patient tides over the first two or three weeks, he usually recovers Death 
occurs, as a rule, m the first w'eek oi twm of the disease, and is jireceded 
by continued high temjieiatuie with a tendencv to hyperpyrexia, delirium, 
diy tongue and diarrhoea It is tiue that a patient sometimes dies at a later 
stage, the lesult of gradually increasing debility, but this is rare 
Treatment — ^The essential points 111 piojihylaxis aie evident from the 
discussion of the etiology Infection being frequent by the ahmentaiy tract, 
c\eiy care should be taken to exclude all articles of food fiom the diet 
which may contain the causal oiganism 

In the tieatment of this fevei, theie is no specific drug and the major ity of 
patients aie best treated bv leaimig out medicines altogether Quinine is 
useless and sahcihc acid and its deinatncs equally so The SMiqitoms must 



28 


INFECTIOUS DISEASES 


be tieated on ordinary principles as they arise Tlie tendency to hyper- 
pyrexia in severe attacks is one of the most important and dangerous of the 
symptoms and one of the most difficult to treat It is doubtful if any real 
good IS got from medicinal antipyretics, but careful v atchmg and timely 
recourse to the cold bath may sometimes save life Hydrotherapy is pioba- 
bly the most useful measuie, sponges or baths being given Sleeplessness, 
headache, arthritis and oichitis must be treated on ordinaiy piinciples 



CHAPTER 11. 


BERIBERI (KAKKE) 

By MAXIMILIAN HERZOG, M D 

Definition — ^Benben — polyneuritis endemica (Baelz), neuritis multiplex 
endemica (Sclieube) — may be defined as an acute, subacute oi chionic in- 
fectious disease, chaiacteiized clinically by disturbances of the circulation, of 
motion and of sensation, and associated anatomically \\ itli hypertrophy and 
degeneration of the heart and degeneration of the peripheral nerves and of 
the voluntary muscles Attention may be called primaiily to the fact that 
clinically the disease vanes considerably and that its etiology is still very 
incompletely understood Hence, it is leally almost impossible to give a 
concise, satisfactoiy definition of the disease, although the affection is un- 
doubtedly an entity, and can be diagnosed as a rule without much difficulty 
In Japan, vliich is the country where the disease is, or at least formerly was, 
most prevalent, and w'here it has been studied most extensively, both clini- 
cally and pathologically, the malady is knowm as Kakke ^ 

History — Geographical Distnbution and Racial Predisposition — ^The 
fiist mention of beiiberi is probably made m a w'oik by a Chinese physician 
w'luch appeared in the second century A D , and a good desciiption is to 
be found m a Chinese text-book on pathology, of the sixth century A D 
The first Japanese reports wdiich mention the disease weie written m the 
seventh and eighth centuries A D The disease is generally prevalent m 
tropical and subtropical countries, wdiere the humidity is, as a rule, con- 
siderable It IS found m Asia — m Japan, including Formosa, m China, the 
IMalay Aichipelago and Peninsula, the Dutch possessions and m eastern 
India, it IS also quite prevalent thioughout the Philippine Islands It 
occurs on the eastern coast of South America, paiticularly in Brazil, and a 
number of repoits have come from Africa of its presence there during the last 
tw'o decades Some isolated epidemics lia^e also occurred in England and 
Ireland, and sporadic imported cases have been encounteied in Continental 
Europe, the United' States and Canada 

Certain races aie particular^ susceptible to the disease, and wherever 
they tiavel are liable to disseminate it This has been observed especially 
m the Japanese, the Chinese, and the Malays The gieat prevalence of the 
disease m Japan has been emphasized by all wTiters on the sub]ect Baelz 
and IC Miura,^ m their recent article on beribeii, state that probably 
50,000 cases of beiiberi occui each ^ear in Japan These figures, how- 

^The disease is known by a vaiiety of names m different countries where it 
IS prevalent For further information on the nomenclature and on the real or sup- 
Jiosed etymology, the reader is referred to Sclieube, Die Bcribcn-Kran} heil, Jena, 
1S94, and Sclieube, Die KranUieiicn der uamien Lander, Jena, 1903 An almost 
complete list of the very extensne literature of the subject will also be found there 
• Baeb and K Mmra, “Beriberi oder Kakke," J/case’s Handbuch der Tropen- 
brankheden, Leipzig, 1905, ii, p 140 


29 



30 


INFECTIOUS DISEASES 


evei, are inucli too low foi the period of the late Russo-Japanese wai, 
because during 1904, from Februaiy to Decembei, moie than 50,000 Japan- 
ese soldiers sick with beribeii were brought back fiom the field to the home 
country, wRile m the Japanese army at home for the same peiiod of time 
seveial thousand cases moie developed These figuies, it is to be imdei- 
stood, do not include any cases which occuried outside of the army among 
the geneial population 

Etiology— In spite ot the fact that the pathological anatomy is well 
known, the etiology is far fiom being definitely and satisfactorily undeistood 
Wright,^ m giving a summary of the theories legarding the etiology of the 
disease, mentions the follow’ing (1) Gelbke’s theoiy that beriberi is due 
to dry fish infected with a tiichina, (2) M Mima’s theoiy that it is due to 
the ingestion of certain kinds of raw' fish, principally combridre, (3) Grimm ’s 
theoiy that it is due to the ingestion of infected fish, (4) Takaki’s theory 
that it IS due to a pathogenic diet m which nitiogen is deficient, (5) Ross' 
theory that it is due to aisenic poisoning, (6) the theoiy that it is due to the 
ingestion of mouldy iice, (7) Bi addon’s theoi y that it is due to the ingestion 
ot a specific organism which develops on gi owing rice, (8) Manson’s theoiy 
that it IS due to a place geim (eaith, floor or house) wdiich distils a toxin, 
volatile or otherwnse, that, being inhaled oi ingested, pioduces the disease, 
and (9) Glogner’s theoiy that it is due to a plasmodium Other theoiies as 
to the etiology aie that it is an an.emia of a pernicious type, that it is a 
modified and secondarily changed form of scoibutus, that it is clue to carbon 
monoxide poisoning, that it is caused by Anlixjhstomum (hiodenalc or by 
T? ichocephahi’} dispai 

Without going into details we mav say that not a single one of these 
hypotheses is tenable Some of them even lack the verv semblance of any 
support Many cases of beriberi occur m w'ell-nourished stiong individuals, 
and the blood examination in acute oi lecent cases show's neithei peinicious 
amemia nor any amemia at all The autlioi has examined the blood in a 
numbei of acute and chionic cases and has found no characteristic blood 
changes, although the cases of longei standing may show' a vaiying degree 
of secondary amemia 

While diet, and paiticulaily a moie exclusne iice diet, may act as a pre- 
disposing factoi, it cannot be a determining and final factor, because the 
disease occurs also in countries oi under conditions where little oi no iice is 
consumed The same is tine w ith reference to fish Exjieiiments made on a 
laige scale on several hundred prisoneis foi a peiiod of eleven months caused 
Wright to conclude that, even though the diet be qualitatively and quan- 
titatively coriect, beiibeii may neveitheless be contiacted He thinUs that 
these experiments positively eliminate diet as a factoi in the causation 

A number ot investigatois have laid claim to the discovery of a specific mi- 
cioorganism for the disease, as DeLaceida,Tayloi, Rost, Ogata (bacilli), Van 
Eecke (a coccus), Pekelharmg and Winklei (a bacillus and coccus), Wright, 
Dangeifield (cocci), Glockner (an amoeba) and Faiaido (a hremato/oon) 

Durham^ made some extensive expeiiments in ordei to asceitain if it was 
possible to infect monkevs, guinea-pigs and labbits with beiiberi His 
expeiiments included the feeding of clued fish and iice, biting by bedbugs, 
injection of seium fiom beiibeii patients, the feeding ot the gastio- 

'An Inquiry, etc , into Beriben, Singapore, Kelly and Walsh, May, 1902 

"Journal of Hygiene, 1904, n, No 1, p 112 



BEKIBERI {KAKKE) 


31 


intestinal contents of patients to monkeys, the admmistiation of dust fioin 
infected localities to monkeys, and throat to tliroat infection m these 
animals All his experiments were absolutely negative 

The most recent claim to the discoveiy of a specific geim for benbeii is 
made by Okata and Kokubo, two Japanese aimy surgeons, uho have had 
an excellent opportunity to study the most extensive beriberi material among 
the Japanese soldiers tiansieired fiom Manchuria to Japan during the recent 
liusso- Japan esc vai These investigators have isolated a coccus, uliich 
generally assumes the form of a diplococcus and uhich may also at times 
present itself as a staphylococcus They confidently maintain that this 
coccus IS the causative factoi m beribeii The authoi, vorking m the 
Hiroshima Kalcke Hospital undei the direction of Suigeon-Major Ixokiibo, 
has had an opportunity to isolate these identical oi gam sms from cases of 
beriberi in Hiioshima A study of the cultuies so obtained, as uell as of 
those isolated by Kokubo and Okata, has, howevei, by no means convinced 
linn of the specificity of these oiganisms The author' has besides failed to 
obtain the same coccus from tj'pical cases of beriberi in the Philippine 
Islands, and inoculation expeiiments on monkeys vith the Koluho-Olaia 
kahke coccus have been absolutel}' negatne In about fifty cases of beiibeii 
occurring m JManila, cultuial examinations by vithdraval of the blood from 
the cephalic vein, incubating it vith bouillon both aeiobically and anaeio- 
bically, have likewise failed to demonstiate any specific benbeii microbe 
Koch, who had previously examined the blood of benbeii patients by this 
method, liken ise had negative lesults In spite of the failuies to isolate in 
beriberi a specific oiganism as the cause of the disease, the evidence is 
decidedly in favor of the view expressed by Scheube, Baelz, K Miura, and 
otheis, that beriberi is an infectious malady It has been fi equently observed 
that the importation of a single case oi of a fen cases of this disease into a 
teiiitoiy heretofore free fiom it has been followed by an extensive gcneial 
outbieak, though the enviionmeiital conditions, the food supply, the nutri- 
tion of the population, etc , had not undergone any changes 

Largei outbieaks of benbeii aie geneially obseivcd nheie theie is a 
Cl on ding togethei of many individuals into a limited space, as in piisons, 
baiiacks, asylums, schools, vessels, etc Hence, benbeii fi equently has the 
chaiactei of an institutional disease The climatic conditions most favorable 
to the development of tlie disease are moistuie and heat It is most pi evalent, 
as stated above, in tiopical and subtiopical countries Hon evei, there is one 
marked exception to this lule, in that it occuis quite fiequently m Yezo or 
Hokkaido, the noitheinmost island of Japan, in nlnch the climate is some- 
what smnlai to that of the northein pait of the United States, Canada oi 
noithern Europe In Japan beriberi is most common in the months of Julj 
and August and laige epidemics ha\e been noticed particulaily during oi 
shoitly befoie these months, when the rainfall has been unusually licain 
In the Philippine Islands it likewise occuis most frcquentlv during the hottei 
months of the jeai and dining the height of the rami season In countries 
nheie benbeii occuis, it is usually found in the lowlands neai the sea or in 
alhnial teiritoiies along gieat rneis It is, as a rule, not found in the highei 
altitudes, although occasionally it does gam a foothold m mountainous 
legions The disease is much more common in the male than in the female 

^Thc PJuh-ppnie Journal of Science, \ol i No 2 1906 "Studies in Beriberi,” 
Ihid , No 7, 1906 



32 


INFECTIOUS DISEASES 


sex However, attention should be called to the fact that pregnant omen 
seem to be particularlj' liable to acquiie it 

It most commonly occurs between the ages of fifteen and tliii ty years It is 
generally very lare m infancy and early childhood, except in the case ol 
infants fed by motheis sick with beribeii There is ceitainl} no doubt that 
some races, such as the Japanese, the Chinese, and the hlalay, are particu- 
larly prone to contract the disease Ameiicans and Euiopeans aie generally 
not veiy susceptible even when living among the natives wheie the disease 
IS prevalent However, then iminimity is by no means absolute The 
author has seen a few cases of beriberi among Ameiicans in the Philippine 
Islands, some of which terminated fatally While beiiberi frequently 
attacks strong, well-nounshed young men, it is, on the othei hand, also 
commonly met itli as a complication in some chronic w asting diseases 
Among these may be mentioned particularly tubeiculosis and amoebic 
chsenteiy In many fatal cases of beriberi occunmg m Bihbid prison, the 
great penitentiary of the Philippine Islands, a complicating tuberculosis or 
dysentery has been found at autopsy 

Special Pathology — In bodies of patients dead of beribeii marked 
postmortem rigor geneially promptly develops However, m cases which 
succumb slowly to the atrophic t^qie or in wdncli complicating w asting dis- 
eases, such as tubeiculosis, amoebic dysentery, etc, aie present, the post- 
mortem rigidity may be quite insignificant, this, how'evei, is the exception 
and not the rule When death has occuired very rapidly, as in tli acute 
pernicious vaiiety, the authoi has obseived the postmortem iigor develop 
very early and become as strong as that met w ith in fulminating cases ot 
Asiatic cholera oi bubonic plague The skin is pale, wnth yanotic patches 
heie and theie Occasionally cutaneous hemonhages may be obseived 
On section, the superficial veins discharge a large amount of dark fluid 
blood, and m the majority of cases, excepting only those of the atrophic 
form of long standing, the subcutaneous tissue is cedematous The sub- 
cutaneous oedema is usually best marked in the anterior thoracic region and 
ovei the antenor surfaces of th lower extremities Hvdiopericardium, 
ascites and hydrothorax are very frequently encountered, hydropericardium 
being the most common The average among 256 ollected cases show" 66 
per cent of hydiopericaidium The author has likewis found hydroperi- 
cardium in the majority of his autopsies Subepic, rdial and subpleural 
petechne are also not infrequently encountered Of the internal organs, the 
heart shows charact eristic changes most constantly Tli myocardium, as a 
w"hole, IS hjqiertrophied, this is usually most maiked m the right ventricle, 
but the left may likewise be enlarged The organ then is increased in all 
Its diameters and in its weight Tlie average iveight m 93 cases reported 
by Yamagiwa was 368 grams, wdiile that of the normal Japanese heart is 
from 250 to 300 grams The right ventricle wxas hypertrophied in 73 ol 
these 93 cases, the average diametei being 6 1 mm , compared wutli a nor- 
mal diameter of 2 to 3 mm The right ventricle in particular is generally not 
only hyjiertrophied but also maikedly dilated, so that a relative insufficiency 
of the tricuspid valve is present All of the chambeis generally contain a 
large amount of daik fluid blood The coronaiy veins are much dilated 
The myocardium may be normal, but quite frequently it is found to be 
more or less cloudy and mottled m consequence of diftuse fatty degenera- 
tion The lungs are, as a rule, cedematous, congested and contain little an , 



BERIBERI (KAKKE) 


33 


ho^^cver, occasionally they aie emphysematous, and sometimes collapsed 
and diy Occasionally some catanhal bronchitis is seen, and, when the 
pncuinogastiic has been profoundly affected, aspiiation pneumonia has 
been observed 

The spleen shons no changes characteristic of the disease In the tropics 
considerable enlargement has frequently been obseived but this must be 
looked upon as a meie coincidence, because m tropical postmoitem material, 
no matter v hat the immediate cause of death has been, enlargement of the 
spleen is very frequently found Howevei, this organ fiequently shows 
cyanotic induration of a model ate degiee The kidneys m acute cases are 
markedly congested, and model ate cloudy swelling and fatty degeneration 
are occasionally observed The hvei is geneiall> somewhat swollen and 
congested Where chionic passive congestion has existed for some time, 
there is the chaiacteiistic appearance of the nutmeg liver In manv cases, 
paiticiilaily of the subacute variety, which have not existed for a ^ery long 
period, we find gieat Inqiermmia of the gastiic and duodenal mucosa and 
occasionally ecchymoses In some cases blood clots are present in the 
stomach, possibly due to persistent vomiting piior to death This condition 
of the gastric and duodenal mucosa has so impiessed several observeis that 
they maintain the stomach and duodenum to be the poital of entiance of the 
specific Auius of beiiberi The writei, like otheis, has observed this hyper- 
amiia m the majority of autopsies, but is inclined to look upon it as a purely 
mechanical “Stauungshyperamie,” due to general venous congestion, wdiich 
often finds so marked an expression in the h\er The small intestine, 
excepting the duodenum, and the large intestine show' no particular changes 

The peripheial nerves, particulaily those of the low'er extremities, are 
almost w'lthout exception piofoundly affected but the changes aie rarely 
noticeable to the naked eye The lesions found on microscopic examination 
clearly indicate that the most characteristic anatomical moibid process is 
the degeneration of the peiiphcral nerves This observation was first made 
hv Bael/, Scheube, Miuia and Yamagiwa, and has been confirmed by many 
other observers The microscopic changes aie a degeneration of the mvehn 
sheath and of the axis cylinder The foimei breaks up into roundish or 
nrcgiilai fiagments, wdiicli are aiianged more or less like a row' of beads 
Later the myelin sheath may also show' a honeyc ombed or foamy condition, 
or it may disappcai entiicly over longei distances of the nerve fiLei Wdien 
such IS the case, the axis cylinder likewise gives evidence of degeneration 
It IS iiregiilailv tw'isted and letracfed and finally also entirely disappears so 
that nothing is left but an empty collajised ncuiilemma The nuclei of the 
latter aic increased, but there is now'here any sign of an active inflammatory 
process, although theic may be a modeiate number of leukocj'tes, cMdently 
jihagocytes, w'hicli enelose material from the degenerating myelin substance 
The muscles supplied by such nerves hkew'ise show' degenerative processes 
These manifest themselves first by a loss of striation Y here the process is 
more advanced, the sarcoplasm is changed into ii regular hyaline masses, 
the fiber, as a whole, is shrunken, and between these masses clefts and 


spaces aie seen, which, dining life, weie filled with an oedematous exudate 
ainagiw a,‘ from a large autopsi material, enumerates the follow ing as 
the most impoitant pathological changes (1) Dilatation and h^qlertrophy 


‘laimgiwa “ Beitrage /!ur Kenntmss der Kakke,” Fir drc/i , 1899, chi, p 451 
loL 3—3 



34 


INFECTIOUS DISEASES 


of the right ventricle, and dilatation of the left, fatty metamoiphosis of the 
myocardium, (2) degeneration of the peiipheral nerves, (3) atrophy and 
degeneration of the skeletal muscles, (4) paienchymatous degeneiation of 
the kidneys, (5) hydiops In other vords, all the pathological changes are 
regressive in nature, nith the single exception of the hypeitiophv of the 
myocardium 

Varieties and S3nnptoms — ^From a clinical standpoint, beriberi may 
Fia 2 divided into thiee chief foims, namel}, 

acute pernicious, vet or oedematous, and 
dry oi atrophic beiibeii This classification 
is, hovevei, somevhat aibitiaiy Besides 
the three ell-defined foinis, a ludimentaiy 
vaiiety occuis quite fiequently, in which the 
symptoms are so mild that medical aid is 
generally not sought In these cases there is 
generally noticed a ceitain malaise, veak- 
ness of the lov er extremities, and inci eased 
heart beat on slight exertion These symp- 
toms may speedily disappeai spontaneously, 
or increase in intensity and lead to one of 
the seveier forms of the disease 

In the acute pernicious foim, the onset is 
generally quite rapid The patient becomes 
ill, apparently vithout piemonitoiy symp- 
toms A feeling of oppression develops in 
the chest, dyspnaa, loiced respiration, evi- 
dences of great venous congestion, frequently 
vomiting and the signs of lapid heait fail- 
ure appeal and death supeivenes Both the 
oedematous and the atrophic t-^qies geneially 
develop m the same mannei Picccding the 
actual outbreak, there is a period of malaise, 
during which dull pain in the stomach, lack 
of appetite, and heaviness in the lowei ex- 
tiemities and occasionally in the upper ones 
are complained of One of the earliest symp- 
toms usually ref ei led to by the patient is 
palpitation of the heart on slight exertion, 
next, pain in the legs is frequently noticed, 
particularly in the calves, vhich soon be- 
come tendei on pressure Latei the gait 
becomes unsteady, the patient valks as it 
it vere difficult, as indeed it is, to lift the 
Wet beriben, showing oedema of the fggt from the ground The gait of a person 
legs and feet (Author) bciiberi lias not been impioperly 

compaied to that of a man walking in soft and very sticky claj, or to that 
of a man, heavily diessed, vlio has been in the water and whose clothing 
IS heavy fiom the fluid absorbed At this stage, in the case of the iLct form, 
an oedema of the lower extiemities is geneially noticeable It is partic- 
ularly veil maiked over the anterior tibial region, ovei the dorsum of the 
feet and around the ankles Here the skin pits on pressuie In the dnj 





BERIBERI {KAKKE) 


35 


form, a slight oedema may be present at an early period, but tlus is not well 
marked and is transitory The loner extremities in this variety, instead of 
being swollen, progressively become more and more emaciated and the 
muscles become atrophic, often indurated and contracted Together nith 
the disturbances of locomotion, disturbances of sensation develop simulta- 
neously p 1 

Hypiesthesia of the loner extremities is the most common form ot dis- 

tuibance of sensation This generally begins on the anterior or external 
surface of the legs and frequently extends to the dorsum of the feet and toes 
It IS found m the territory supplied by the peroneal and saphenous nerves 
Accompanying hypmsthesia, there is a subjective parsesthesia If the skin is 
touched with a soft camel’s hair biush, the patient feels as if paper inter- 
vened betn een the skin and the brush The intensity and the extent of such 
distuibances of sensation vary not only in different individuals but also at 
different times in the same individual These disturbances have a tendency 
to spiead upward from the feet and legs In the severer cases the upper 
extremities are similarly affected The face is rarely involved, but occa- 
sionally distuibances of sensation aie found around the mouth True 
anaesthesia is rare, as is also hi^persesthesia The disturbances of motility 
generally begin as a sensation of weakness in the legs, vhich is first noticed 
m the calves and later on in the thighs Aftei these have lasted for some 
time, atrophy is generally evident or it may appear even before distinct 
paralysis becomes obvious Usually the anterior shaip edge of the tibia 
becomes moie prominent, the calf becomes thin and flabby and the thigh 


Fw 3 




r' 

Dry benben ■nith great atrophy of the muscles of the legs and eqmno\arus position 

of the feet (AutUor ) 

gradually becomes emaciated When moie oi less contraction is associated 
Mitli the atiophy, the foot assumes an equmovarus position In severe 
attacks, similar changes occur in the uppei cxtiemities Paralysis of the 
lower extremities is much more common than paralysis of the upper ones, 
but in the severest cases both feet and hands, including the toes and fingers, 
may be paralyzed The hands and fingeis in such cases may occasionally 
be more affected than the feet In the gra\est t-^qies neither the hands nor 
the fingeis can be flexed toward the dorsum, and there is complete wrist- 
drop 

I he electrical excitability shows various degrees of change, from a simple 
diminution to a complete reaction of degeneration According to Iv Miura, 
one can foretell from the position of the foot and toes the result of the 
electrical tests If the foot can be moved easih on the ankle-joint, one finds 
onh a diminution of electiical excitabihtj If the toes, but not the foot, car 


36 


INFECTIOUS DISEASES 


be flexed dorsally, we encountei only a partial degeneration reaction If, 
however, neither the foot noi the toes can be moved voluntarily, we then 
have a complete degeneration reaction Paralysis of the diaphiagm and of 
the intercostal muscles occurs only in the seveiest cases In addition to the 
nerves of the extremities, other nerves are also moie oi less frequently 
involved Paresis of the muscles of the larynx is by no means raie, in fact, 
it IS a very common occurrence to find hoarseness and moie or less complete 
aphonia Paresis of the facial neives and of the nervus abducens has occa- 
sionally been observed, as also have been disturbances of the optic nerves, 
manifested by central scotoma, and in laie cases by amblyopia Among 
the late symptoms, which at this time become frequently quite prominent, 
are contractions of the muscles, paiticularly of the gastrocnemius 

If an eaily examination be made, both in the hj’pertrophic foim and in the 
atrophic dry one, the following symptomatology may be found, the pulse is 
generally rapid, somewhat ii regular, lather veak and easily compressible 
On slight exertion, sometimes even so slight as sitting up in bed, the rate 
increases 20 or 30 beats a minute The apex of the heart, sometimes quite 
early and frequently later after the disease has existed for sevei.il days, is 
found displaced upwaidly and outwardly and the area of visible impulse 
is enlarged The area of heart dulness is increased to the right Where 
there is hypertrophy of the left ventricle, the aica of dulness is also inci eased 
to the left At the apex some change in the first sound may be found, but 
the most common sign is generally a marked accentuation of tlie second 
pulmonic sound Sometimes a definite systolic bruit may be heard at the 
apex Fiequently there is a reduplication of the second sound both at the 
apex and in the pulmonic aiea In a considerable numbei as vas fiist 
prqminently pointed out by M Miura, a musical sound is lieard over the 
crural arteries, which may be audible even at a distance of several feet from 
the patient 

In the early stages, sometimes up to the sixth or seventh day, the patellar 
reflex is increased Then a diminution of the knee-jerks appears, and 
finally they are entiiely absent Even in eases which terminate favorably the 
absence of the knee-jerk may last a long time and may be piesent aftei the 
disturbances of locomotion have disappeared AVhen the knee-jerk begins 
to reappear, it generally again becomes temporarily accentuated, and then 
finally leturns to the normal It has already been mentioned that the 
muscles of the calves of the leg are frequently painful and very tender to 
pressuie The skin, particulaily of the lower extremities, shows disturbances 
of sensation Theie is general hypaesthesia or pariesthesia, and less fre- 
quently complete amesthesia 

In mild eases the urine is somewhat deci eased in amount, and in severe 
ones considerably so The diminution is sometimes veiy gieat, and the daily 
amount may fall belov 100 cc The specific gravity in such cases is increased, 
but not proportionatelv to the great diminution in amount Albumin is 
generally not found When, hov ever, it is piesent, only traces occur How- 
ever sometimes, though raiely, a complicating nephritis develops in the later 
stages, and then albumin is constantly present Indican is very frequently 
found in the acute and oedematous vaiieties 

According to most authors, the temperatuie in uncomplicated cases is 
either normal or very slightly elevated When a maiked use of temperature 
IS met V ith, it is usually owing to some complication In all cases seen by the 



BERIBERI {KAKKE) 


37 


\\ nter m which there was a marked use m temperature during life, at autopsy 
some complicating lesion -was found 

In cases either of the oedematous or the atiophic form ^\hlch progicss 
unfavorably, the dyspnoea and the difficult lespirations increase and the 
resulting grave circulatory distuibances find their expression m a super- 
ficial venous congestion, with visible throbbing veins I\hile consciousness 
IS preserved, the dyspnoea and the suffering inciease, and the face of the 
patient presents a picture f giave anxiety, such as may be seen in angina 
pectoris Death frequently occuis quickly m consequence of heart failure 
Stanley' has drawn attenti n to the frequency of sudden hemt fathne in 
diphtheria and in beribeii His analysis of 340 cases of the latter disease 
shows 72 fatal instances, of which 31 died of rapid heart failure The pulse 
tension vas loweied in 254 cases, and dilatation of the heart existed in 98 
The second sound vas reduplicated m 245, and the first in 35 There vere 
cardiac murmurs in 84 When the disease ends m recovery, the disturbances 
of cii dilation decrease in intensity In the vet foim there occurs a piofuse 
secietion of mine and the oedema gradually disappears In both types v Inch 
piogress favoiably, the disturbances f sensation and the paralysis disappeai 
gradually and the patient legains the use of his limbs 

Beriberi occuiring in infante fed by mothers sick vith the disease has been 
desciibed by Hiiota In these the disease generally piesents the symptoms 
of the acute peimcious type, namely, restlessness, vomiting, dyspnoea, 
aphonia, rapid pulse, extension of the heart dulness toward the right, oedema, 
a musical sound over the ciural arteiy, and absence of fever When the 
child IS taken avay from the sick mother early, the symptoms generally 
disappear within two weeks 

Complications and Sequelae — ^The most common diseases associated 
with beiiberi aie tuberculosis and dysenterj’- When these co-exist the prog- 
nosis IS usually verygrai e While most cases of beriberi ^nd in rapid recovery, 
some h.iA'e a protracted course and general v eakness with or v ithout amemia, 
difficulty in the use of the lower extiemities, contraction and induration of the 
muscles of the calf, and also disturbances of motihtv in the uppei extremities 
with diminution and distuibance m the quality of the sensation, palpitation 
of the lieait and lapid pulse may remain for a long time As a rule, these 
s> mptoms all disappear undei propei treatment and diet It has been noticed 
in Euiopeans oi Americans \vho have suftered fiom severe attacks of beri- 
bcii and vho have letuined during convalescence to their natne country, 
that the disease assumes generally a protracted course from which recovery 
IS very slow 

Diagnosis — In many cases among the uneducated and ignorant Asiatics, 
the diagnosis must be made exclusively from the objective sj'inptoms, as an 
intelligible histoiy is unobtainable The most important points are the 
condition of the pulse v hile the patient is at rest and before he has been 
disturbed, and after he has been subjected to some physical exertion If 
the patient is not too ill, he should be made to leave his bed and v alk up 
and dovn the loom a few times While doing so the gait should be 
noted in older to asceitam vhether it presents the characteristic appear- 
ance already mentioned The pulse is then again to be counted In 
beriberi it is usually accelerated and the rapidity increases very mark- 


* British Medical Journal, December 26, 1903 



38 


INFECTIOUS DISEASES 


edly on slight exertion The percussion and auscultation of the heart are 
also of value Paiticular importance attaches to the enlargement of the 
right ventricle, to the accentuation of the second pulmonic sound and to 
a reduplication of the second sound The frequency of hydropeiicaidium, 
hydrothorax and ascites are valuable points, as also the increase of the 
patellar reflex in the early stages and the loss of it in the moie advanced 
ones The frequency of pain in the muscles of the calf, and of oedema 
in the leg and foot, have already been noted The great deciease or 
even the suppression of the urine in the early stages of the oedematous 
form IS also an impoitant factor The disturbances of sensation and 
of locomotion and the paralyses and contractions have already been 
emphasized 

Among the diseases which might be confounded with beriberi are the 
folloning Myehhs in wliicli aie present increased reflexes, ankle clonus, 
paralysis of the extremities without muscular atrophy, paialysis of the 
bladder and lectum, complete anaesthesia without pam in the muscles of 
the calf, no reaction ol degeneration and no symptoms on the part of the 
heart and ladneys In Lanchy’s paialysis theie is fever at the onset, 
and pain in the head, with much perspiration at the back and extremi- 
ties A study of the sensation and circulation reveals nothing ab- 
noimal Tabes should not be confounded \vith beriberi or vice versa In 
anaesthetic lepi osy a thickening of the peripheral nerves and a true anesthesia 
is found and not hvpassthesia, v Inch is generally encountered in beriberi 
In addition, in leprosy, spots or nodules or diffuse thickening of the skin are 
usually encounteied A careful search will reveal the presence of the lepra 
bacillus Certain cases of pcnpheial neuntis, depending upon chronic 
alcohol or arsenic intoxication, maj at times be exceedingly difficult to 
differentiate fiom beriberi In Europeans and Americans living in tropical 
countries where beriberi is prevalent, and presenting symptoms suggesting 
the possibility of an attack of this disease, alcoholic neuntis should first be 
excluded definitely before a diagnosis of beiiberi is made In Japan, and in 
the Philippine Islands, vliere beiiberi is so prevalent and so wellknovn, 
patients fiequently consult the physician vith the simple statement that they 
are suffering with this disease But, of course, such a statement cannot be 
accepted without verifying its coirectness by a proper examination 

Prognosis — ^The prognosis vanes greatly in different epidemics and in 
different localities It is perhaps most fatal (an observation commonly made 
as to infeetious diseases) when it first invades a new teiritory in which it has 
never been prevalent before A very interesting account of what appears to 
have been the first outbreak of beriberi in the Philippine Islands has been 
published by Koemger ^ This author reports tliat when the disease first 
broke out in Manila, in October, 1882, its victims succumbed without 
exception and that the mortality during the first few months was not less 
than 60 per cent 'kmong Chinese m Sumatra and Java, epidemics v ith an 
equally high mortality have been observed Stanley gives a mortality of 
20 per cent among the Chinese prisoners at Shanghai Among the Chinese 
patients of the Hong Kong government hospitals during the last ten years, 
the mortality has been 50 per cent ^ The death-rate in cases developmg in 

^Dmt Arch f Uin , 1884, xxxv, p 419 ..,0 

^Personal communication from Dr M V Koch, Physician m charge of the Govern- 
ment Civil Hospital for Infectious Diseases 



BERIBERI {KAKKE) 


39 


Bihbid prison at Manila is llke^^ isc quite high ' These instances, how ever, 
represent somew'hat exceptional and particulaily unfavoiable conditions 
Undei favorable conditions, the mortality is usually low In Dutch India 
among the troops, the death-iateis given as between 2 and Gper cent Among 
the English East Indian troops the figures are somewhat liighei Scheube 
gives an aveiage moitahty of 3 5 per cent for Jajian During the first year 
(1904) of the late Russo- lapanese w'ai there were sent back fiom the front 
to the Mihtaiy Resei ve Hospitals of Hiroshima, Tokyo, etc , 50,340 Japanese 
soldieis sick wnth beribeii Of these, 1,024, or less than 2 per cent , died 
During the same peiiod of time there developed among the troops in Japan 
3,337 cases, of wdiich only 44 died So, on the whole, taking a very large 
material as a basis, the prognosis is quite favorable 

No definite prognosis can be made in an individual case, because a fatal ter- 
mination from heart failiiie may occur at almost any stage during the course 
Unfavorable simiptoms are maiked dilatation of the heart, gieat weakness 
and iiiegularity of the pulse and other grave disturbances of cii dilation, 
cncumscribed oedema on the trunk, signs ot cedema in the lungs, and particu- 
laily peisistant vomiting The last symptom is almost invariably the pre- 
cursor of a rapid fatal termination in consequence of heart failure The 
moitahty in the acute permcous form is always high, that in the subacute or 
cliromc, oedematous type is low'ei but higher than in the dry atrophic variety 
A favorable sign is the appeaiance of a copious renal secretion aftei partial or 
complete suppression ot uiine Acute pernicious cases when fatal ahvays 
terminate by heait failure oi aspl^^ia, in chionic cases death results from 
paralysis ot the respnatoiy muscles, occasionally from aspiration pneu- 
monia or by general debility The latter event is particularly liable to take 
place when tuberculosis oi amoebic dysentery is piesent The average 
duiation of acute peinicious beriberi is A’^ery short, wdiile that of cases of 
moderate intensity and of moderately chronic character is perhaps between 
tliiee and six wrecks Besides these there are a large number of protracted 
cases, W'hicli extend over a period of months and sometimes may last more 
than a yeai These veiy chronic cases are characterized by muscular 
ati opines and ]oint fixations But generally even these patients, if properly 
(leatcd, and if placed under proper hygienic conditions, proper nutrition, 
etc , finally become completely well 

It has been, hoAvevei, frequently noticed in Japan, the Alalay Peninsula 
and the Philippine Islands, that if a patient has had one attack, although he 
recovci s completely, wdien exposed to the same conditions a\ Inch hi ought on 
the first attack, he suffers a second or even a third one In this respect ben- 
ben ma'\ be likened to diphtheria and some other infectious diseases, an attack 
of which in certain indmduals leaxes a predisposition to subsequent ones 

Prophylaxis —This is still in a decidedly unsatisfactory state The 
obsenance of the ordinary rules of hygiene and sanitation has frequently 
shown a fa\oiable influence m lestiictmg the disease However, in other 
instances, beriberi wall become preialent in certain localities and under 
certain conditions, in spite of all hA'giemc and sanitart measures The late 
luisso-Japanese war furnishes a confirmatorv example of this statement 
uhe lugiemc measures adopted in the Japanese armv proved sufficient to 
hiiiit to a minimum such diseases as tiqilioid, tiphus, discnterj, scorbutus, 

'Bihbid prison in ^Manila contains from 3 500 to 4 500 prisoners and the Ingicnie 
conditions, under the circumstances, foimcrlj uere necessarily not the Aerj best 



40 


INFECTIOUS DISEASES 


etc , but they "weie of no avail against beriberi Tlieie is one factor which 
beyond all doubt favors the occiirience and spreading of beriberi m those 
countries and among those races where it is at all prevalent, that is, the 
crowding togethei of laige numbers of persons into limited spaces, as prisons, 
bariacks, schools, factories, mines and ships If beribeii appears undei such 
enviionments, these places should, if possible, be abandoned as dwellings, 
at least, the number of inmates should be deci eased, and a thoiough dis- 
infection, ailing and drying should be undei taken The statements as to the 
effects of a change from a rice diet to some othei, as a prophylactic against 
beriberi, are up to the present time so hopelessly contradictory that reliable 
conclusions cannot be drawn from them Women sick vith beiiberi should 
not nurse children 

Treatment — ^There is no specific tieatment The patient should be 
confinea to bed Even if he is suffering from v hat appears to be only a mild 
attack, neveitheless rest, in the beginning, should be insisted upon, since it is 
impoitant to reduce the heait’s action as much as possible m order to guaid 
against future and often unexpected giave caidiac complications It has 
generally been found veiy advantageous to admimstei the saline laxatives in 
large doses during the first stages of benbeii A favorite Japanese pre- 
scription IS the following 

E Magnesii sulphatis 
Acidi munatici diluti 
Tmctune amaraj 
Aq q s ad 

30 cc d ounce) three tunes a day 

This is to be given for from five to seven days, follow'ed by an intermission 
of a few days, after which the tieatment is repeated Other drugs recom- 
mended are cream of tartar, infusion of senna, Carlsbad salts, oleum iicini 
and aloes and jalap in the form of pills Where there is marked oedema, 
Baelz and K Mima recommend potassium acetate (90 gr , 6 gm ), 
potassium nitrate (30 gr , 2 gm ), oi diuretin (45 to 60 gr , 3 to 4 gm , per 
day) Scheube has strongly recommended the use of digitalis, but most 
observers consider it of very doubtful value, and it has been repeatedly 
stated that in many cases it has a decidedly injurious effect in that it 
tends to produce anorexia, nausea and vomiting In severe acute cases 
with great w'eakness of the heait, Baelz fiequently observed good effects 
from large doses of cocaine given internally in amounts of fiom 1 to 
3 grains (0 05 to 0 20 gm ) per day In acute or subacute cases, w’lth signs 
of dilatation of the light heart, w4iile the pulse is still good, encouraging 
results have been obtained by bleeding, to the amount of several hundred 
cubic centimeteis However, when the pulse has become weak, this is 
dangerous, on account of the possibility of sudden heart failure With 
dilatation, venous congestion and a weakened pulse, the withdraw^al of blood 
by cups or leeches, applied over the precoidial legion, is often follow'ed by 
improvement The author has seen a considerable number of Japanese 
soldiers sick wuth beriberi wdio w'ere greatly helped by this How^evei, the 
improvement is frequently only tempoiary and a repetition of the piocedure 
may or may not bring about good lesults, or the unfavorable symptoms may 
increase in severity in spite of a temporary amehoiation 

The d%et should be light and nutritious and include considerable milk 
Both m Japan and in Java beribeii patients frequently receive as a part of 


30 to 50 grams 
1 5 to 2 0 cc 
4 0 cc 
200 0 cc 



BERIBERI (KAKKE) 


41 


their daily nourishment the Adzucki bean (PJiascohts radmiw}), which, it is 
believed, has both a favorable jiroph} lactic and a curatne tendenc} In the 
Philippines similar virtues are claimed for the iMoiigo or iMungo bean 
(Phaseolus Mxingo L ) Rice should, in private practice at least, be w ith- 
drawn fiom the diet This measure is necessaiy, not so much on account of 
its leal value, as on account of the fact that theie is still a widespiead popular 
belief, in many regions wdieie beribeii pievails, that a Lakke patient should 
not cat rice Hence, a physician who fails to remove iice fiom the daily 
dietary is liable at once to lose the confidence of his patient A person sick 
w itli a seveie t>qie of beribei i, accompanied by grave circulatoiy disturbances, 
should not undei oidinary conditions be moved to a distance Even duiing 
the early stages of lecoveiy, a long railroad journey may bring on a relapse 
with severe and dangerous heart symptoms But cases mild from the onset, 
and serious ones after recovery, may with advantage be removed from a 
beiiberi-infected neighborhood to a high and diy locality fiee fiom this 
disease If theie is a niaiked liyperiesthesia (wdiich, liowevci, is lare in 
beiiberi), bioniide of potassium oi morphia internally oi chloroform exter- 
nal! v are lecommended Vomiting and dyspnoea are frequently greatly 
ameliorated by the hypodermic administration of small doses of moiphia 

It IS veiy impoitant that the musculai ati opines and conti actions should 
receive early and pioper treatment However, it is not advisable to begin 
this as long as theie is maiked oedema of the affected extremities When the 
oedema has subsided, massage and passive movement are to be practiced 
systematically several times a day As soon as the patient is able to do so, 
and when theie is no longer any immediate dangei of cardiac failure, model - 
ate active exercise should be cautiously begun Should such exercise lead 
to a very maiked increase in the pulse rate, it should be postponed The 
atrophic muscles are to leceive electiical treatment When they still leact 
to the faradic current, the lattei is to be used Where theie is complete 
degeneiation leaction, the galvanic curient should be employed, with the 
cathode situated peripheially over the neive and the anode centrally applied 
In the use of the faradic current, Scheube recommends large sponge or 
rollci electrodes, to be employed in a massaging manner When there is 
parabsis of the phienic nerve, M Miura advises faradization, one sponge 
elcctiode being placed ovei the epigastric region and the othei above and 
inside of the steinoclavicular aiticulation, or the two electrodes may both 
be placed on the sides of the neck 

For Europeans and Americans wdio have suffeied from an attack of 
bciibeii, a change of climate and return to a more bracing atraospheie should 
be recommended 



CHAPTER III. 


ANTHRAX RABIES GLANDERS 
By MAZYCK P RAVENEL, M D 

ANTHRAX 

S3mon3miS — ^English, splenic fever, wool-sorters’ disease, malignant 
pustule, anthracsemia, French, charbon, sang-de-rate, mal-de-rate, 
fievre cliarbonneuse, charbon bact6ridien, anthrax, German, Milzbrand* 
Definition — ^Anthrax is a specific and highly contagious disease common 
to man and most domestic ammals, due to the Bacillus antluacis It occurs 
in two principal foims an external, due to diiect inoculation thiough a cut 
or abrasion, and an internal, caused by ingestion or inhalation of the spores 
or bacilli 

Historical — Anthrax has been known in man and animals for many 
centuries, and, although a number of inflammatory diseases have been 
described under the name, the descriptions of certain plagues given by 
ancient authois aie sufficiently exact to enable us to lecogmze vhat we now 
know as anthrax The sixth plague of Egypt is believed to have been anthrax 
by some authors It was not until the lattei pait of the sixteenth century 
that contagion from animals to man was suspected, and only duiing the 
latter half of the eighteenth century that order began to come out of chaos, 
chiefly thiough the efforts of Chabeit (1780), who fiist differentiated the 
disease from the inflammatoiy and gangienous affections with which it was 
universally confounded and gave a classification which is employed almost 
in its entirety at the piesent day He recognized three forms (1) Char- 
bonous fever, — internal anthrax, without external lesion, (2) essential 
charbon, maiked by a piimary external lesion, — ^malignant pustule, (3) 
symptomatic anthrax, in which there is pnmaiy fever, vnth secondary 
appeaiance of tumors The third foim is non known to be a separate 
disease (black-quarter, rausclibrand), confined almost exclusively to cattle 
and not communicable to man The contagiousness of anthrax Avas first 
experimentally proven in 1823, by Barth61emy, ivho infected animals Avitli 
the blood both by inoculation and ingestion 

The discovery of the bacillus by Rayei and Davaine^ was made in 1850, 
who observed in the blood of animals with anthrax “little filiform bodies, 
in length about twiee the diametei of a red corpuscle, and Avithout move- 
ment ” They did not recognize the significance of their discovery In 1855, 
Pollender announced that in 1849 he had observed the bodies seen by Rayer 
and Davaine He recognized their vegetable nature, but did not attribute 
any importance to them Brauell, in 1857, observed the rods in the 
cadaver, and also just before death He attributed to them a diagnostic and 


^ Comptes Rendus Soc Biol , 1850 


42 



ANTHRAX 


43 


prognostic value but did not suspect then causative relation to the disease 
In 1860, Delafond cultivated the bacilli by putting anthiax blood m glass 
flasks He foiesaw the formation of spores but uas unable to demonstrate 
them, nor uas he suie whether or not the rods were the effect oi the cause of 
the disease Pasteui’s work on butyric acid fermentation, in 1859, gave neu 
light to Davaine, and he once more took up the study of anthrax, in the belief 
that the rods he had discovered iveie the cause of the disease He shoued 
that they were constant in the blood of anthiax, and that, vhen filtered, sueh 
blood could be inoculated ivithout haim into other animals 
The bacillus vas cultivated on artificial media m 1876 by Koch, uho 
discoveied the spoies and pioved its etiological lelation to the disease In 
1877, Pasteui confirmed the vork already done and gieatly extended our 
knowledge of the biology and pathogenesis of the organism 
Anthrax m. Aiumals — Since anthrax m man is alw ays derived from ani- 
mals cithei directly or indiiectly, its distribution is a mattei of impoitance 
Known from the eaihest times, it lemains to-day one of the most widespread 
and destiiictive ol animal plagues It is found in practically ever> pait of the 
world, but IS especially pievalent in parts of Fiance, Geimany, Austria, 
Italy, Turkey, Russia, China, South Africa, and South America Considei- 
able losses occui in the United States fiom time to time, in widely sepaiated 
parts of the countiy In countiies wdiere it is endemic it is especially active 
during certain years 

The hcibivoious animals aie paiticularly affected In Russia, large 
nurabeis of horses perish from the disease, and their hair, which is largely 
used m nianufactuies, is responsible for the infection of man in distant 
poitions of the world The most dangeious hair comes from China, Russia 
and Sibeiia In Asia Minoi, anthrax is pievalent among the Angora goats, 
which supply much of the mohair of commerce, the souice of many of the 
cases of wool-soiteis’ disease 

Anthrax does not spiead fioin animal to animal by contact or association, 
infection taking place as a rule, through the intestine, from the ingestion of 
foiage containing the spores The retusc fioin tanneiies and the washings 
from infected wools haie been proven to play an imjiortant pait in the spread 
of anthiax, thiough the infection of pastuies A striking instance of infection 
from tanneries ocemred m Pennsylvania, where, almost simultaneously, 
anthrax appealed among the opeiatues of thiee tanneries quite widely 
separated, and in the cattle pastuied on the sti earns which icceived then 
diamage The souice of infection proicd to be a caigo of hides fiom China 
which had been clnided among the three plants Russell has repoitcd a 
similai case in Wisconsin, the tanneiv using hides from South Ameiica and 
China In Delaware, the inoiocco woiks using goat skins from South 
\nieiica aic a frequent soiiiee of infection for natue cattle Houston has 
found anthiax bacilli in the mud of the inei Yco at YcomI m England 
TIic dust from factories working up infected materials mai also spread the 
disc ise, as in the case repoitcd b\ Silbcrschinidt at Zurich, where 8 out of 22 
hoi-scs were infected by grazing in a lot exposed to the dust from a horsc-liair 
facton 

\ held once infected is difficult to nd of anthrax Pasteur showed that 
the spores from soil infected by the blood and eorjiscs of animals which had 
died of anthrix were brought to the surface by earthworms Fields are also 
infected b\ the use of y\aste products from tanneries and factories as fertilizer. 



44 


INFECTIOUS DISEASES 


In lessening tlie ravages of anthrax, Pasteur’s method of vaceination has 
played an important pait, and should be piactised in hoises, sheep, cattle, 
etc , V henever exposed Unfortunately the immunity produced is not lasting, 
but usually one vaccination a year is found sufficient Infected premises 
must be cleansed and disinfected, and cattle fiom infected herds should not 
be carried into new districts Most impoitant is the destruction of the 
carcasses of dead animals Whenevei possible they should be burned 
F ailing this, they must be deeply bui led and covered with quick-hme Under 
no circumstances should the skin be removed nor the body opened, as this 
admits oxygen and allows the formation of spoies In the absence of spores 
the anthrax bacillus is rapidly destioyed during putief action 

Etiology — ^The study of anthrax has a special inteiest, inasmuch as it 
was the first disease in ■which the etiological relation between a bacillus and 
a disease w'as ever shown Much of our general know ledge of the nature of 
bacteiia has been gained from the study of the anthrax bacillus, and it has 
also gone far to establish the geim theorj^ of disease 

Anthrax m man is ahvays derived fiom some domestic animal, or fiom 
some commercial animal product, especially the hide, hair, or w’^ool The 
bacillus does not penetiate the unbroken skin, but enteis some abrasion, 
scratch, or cut 

In the United States it occurs almost exclusively among veteiinarians, 
brush makers, leather wmikers, and tanners Farmers are sometimes in- 
oculated wdiile slvinmng animals wdiich have died of anthrax, and butcheis 
fiom handling the meat of diseased cattle Among others wdio are especially 
exposed to contagion aie knackeis, plastereis, felt makeis, and mattress 
makeis Intel nal anthrax is almost unknowm in this country It is quite 
common in certain portions of England, notably the Biadford district, where 
Avool and hair fiom many parts of the world are manufactured, and wdiich 
receives almost the total impoitation of w'hat are knowm as dangerous W'ools 
Much of our knowledge of this t-ype of the disease has come from the very 
excellent studies made in this district, wdieie it has received the name ”^Yool- 
sorters’ disease ” 

It was first observed aftei the introduction of alpaca and mohair, in 1837 
Outbieaks occurred from time to time, ivliich w'ere studied by eminent 
physicians, but the etiology w^as not definitely demonstrated until 1880, wdien 
Mr Spear and Piofessoi Gieenfield made an exhaustn’^e investigation at the 
instance of the Local Government Board, although in 1879, Bell had suc- 
cessfully inoculated animals with the blood of an alpaca soiter shortly 
before death, and lecovered anthrax bacilli from their blood, being the 
fiist to lecogmze the disease as anthrax 

Infection takes place usually in the sorting, combing, and spinning of the 
wmol, and is due to the inhalation of the spores of anthrax wdiich are given 
off in the dust arising from the wmol of diseased animals during these opera 
tions Other things being equal, the danger from w ool and hair is inA’^ersely 
propoi tinned to their moistuie or greasiness, aa'IucIi prevent the spore- 
containing dust fiom fljung off Cutaneous inoculation takes place fiom 
greasy w^ools, but never the internal form Wools from hot climates are 
often diy and dangeious The hair of goats, cow^s, horses, alpacas, etc , does 
not contain an} greasy matter, and is especially dangerous Even where 
goats and sheep are heided together and thus exposed in the same degree to 
antlirax, the wool ivill be comparatively safe to Avork AAuth, AA^hile the hair 



ANTHRAX 


45 


from goats equally contaminated will be dangerous The comparative 
danger fiom various materials is illustrated by the statistics gathcicd in 
England for the si\ ycais, 1S99 to 1904 inclusue, dining vliich time 261 
cases of all foims of anthrax vcre reported ^Mth 67 deaths, as folloiis 


AVorkers m vorsted and vool S8 

Workers in horse-hair and bristles 70 

AVorkers in hides and skins SG 

AVorkers m other industries 17 


AA^oikcis in hides and skins acquire almost exclusively external anthrax 
In London, of 92 cases observed among those working in the hide and 
skin trades, only 2 weie intestinal, while of S7 cases in the Bradford worsted 
distiicts, 30 weie external and 57 internal in foim 
The veiy fatal disease obseivcd m rag pickets in the paper mills in lower 
Austria {Iladc] nlranUieif) has been shown by Fiisch and Eppinger to be 
Intel nal anthiax 

Gastro-intcstinal anthrax may result from eating the flesh oi dunking the 
milk of animals with the disease Foitunately, the disease is so rapid in its 
course that danger from these souices is not very gieat The writei has 
know n an animal in the last stages of anthrax to be slaughtered and dressed 
for market by a thiifty farmer wdio saw his cow’ about to die, and wished to 
avoid loss Examination of the blood of this animal pi oi ed it to be sivarming 
with anthrax bacilli 


Billings states that in the Bavaiian Alps it is common for the farmers to 
conceal the piesence of anthiax in their cattle and to dress the diseased 
animals for food, preserving the flesh in pickle As spores do not form 
during life, noi aftei death unless the supplv of oxygen is abundant, such 
flesh will contain legetatne bacilli foi the most part, if not entirclv, and 
these are leadily dcstioyed in cooking 
External anthiax can unquestionably be conveyed by flics and othei 
insects, though this is piobably a larc method of infection 

Sex — ^Thc victims ot anthiax are almost always men, since women are not 
often employed m the callings ivhicli expose one to infection 
Bacteriology — ^The bacillus of anthrax is one of the laigcst of the patho- 
genic bactciia The individual lods arc 1 2/i thick and 6 to S/i long The 
ends aic charactciistic, being square-cut oi cien depressed, so that m chains 
the elements arc separated bv a Icns-shajicd space It forms leri long 
filaments m suitable culture media It stains readily with the usual basic 


aniline dies, and is not decoloii/cd bi Gram’s method Colonics on agai 
and gel itme are lerv chaiactcristic They are made up of wan masses like 
locks of hair, radiating fiom the centre The edges of growths on slanted 
agar present the same appeal anccs In bouillon, a delicate flocculent grow th 
takes place, resembling bits of Japanese paper, oi shieds of cotton suspended 
m liquid Later, the giowih tends to settle to the bottom In gelatine stab- 
cultures the growth is equalli characteristic Radiating from the central 
punctuie aie iiiniiineiablc leii delicate spikclcts pushing out into the 
gel itme, sometimes being sjnrals 

_^kcbicillus growi best at 35° C and ceases to grow below ]2°C oraboie 
^ owc^ much of its pathogenic power to its projicrti of forming 
sporc-s^ Ihis takes ]ilacc best at 12° C and the Jircscnce of oxigen IS iieces- 
sari riicsc spores are remarkable for their power of resistance to external 



44 


INFECTIOUS DISEASES 


In lessening the ravages of anthrax, Pasteur’s method of vaccination has 
played an impoitant part, and should be piactised in horses, sheep, cattle, 
etc , V henever exposed Unfoitunately the immunit} produced is not lasting, 
but usually one vaccination a year is found sufficient Infected premises 
must be cleansed and disinfected, and cattle from infected herds should not 
be earned into new districts Most impoitant is the destiuction of the 
carcasses of dead animals Whenever possible they should be burned 
Failing this, they must be deeply buried and covered with quick-hme Under 
no circumstances should the skin he removed nor the body opened, as this 
admits oxygen and allows the formation of spoies In the absence of spoies 
the anthrax bacillus is rapidly destroyed during putiefaction 

Etiology. — ^The study of anthrax has a special interest, inasmuch as it 
was the hrst disease m which the etiological relation betv een a bacillus and 
a disease was ever shown Much of oui general knowledge of the nature of 
bacteiia has been gained fiom the study of the anthrax bacillus, and it has 
also gone fai to establish the germ theory of disease 

Anthrax in man is always derived from some domestic animal, or fiom 
some commercial animal product, especially the hide, hair, or wool The 
bacillus does not penetiate the unbroken skin, but enteis some abrasion, 
sciatch, or cut 

In the United States it occurs almost exclusively among veteimarians, 
brush makers, leather woi leers, and tanneis Farmers are sometimes in- 
oculated while slcmmng animals which have died of anthrax, and biitcheis 
fiom handling the meat of diseased cattle Among others wdio are especially 
exposed to contagion aie knackers, plasterers, telt makers, and mattress 
makeis Internal anthrax is almost unknoivn in this country It is quite 
common in certain portions of England, notably the Bradford district, ivhere 
w^ool and hair from many parts of the W'orld are manufactured, and wdiich 
receives almost the total importation of what are knoivn as dangerous wools 
Much of our knoivledge of this tjqie of the disease has come from the very 
excellent studies made m this district, wdieie it has received the name “wool- 
sorteis’ disease ” 

It was first obseived after the introduction of alpaca and mohair, in 1837 
Outbieaks occuiied fiom time to time, wdiich were studied by eminent 
physicians, but the etiology w^as not definitely demonstrated until 1880, w hen 
Mr Spear and Professor Greenfield made an exhaustive investigation at the 
instance of the Local Government Board, although in 1879, Bell had suc- 
cessfully inoculated animals wuth the blood of an alpaca sorter shortly 
before death, and lecoveied anthrax bacilli from their blood, being the 
first to lecogmze the disease as anthrax 

Infection takes place usually in the soiting, combing, and spinning of the 
wool, and is due to the inhalation of the spores of anthrax wdiich are given 
off in the dust arising from the wool of diseased animals during these opera 
tions Other things being equal, the danger from w ool and haii is inversely 
piopoitioned to their moistuie oi greasiness, which prevent the spore- 
containmg dust from fl^ung off Cutaneous inoculation takes place from 
greasy wmols, but never the internal form Wools from hot climates are 
often dry and dangerous The hair of goats, cows, horses, alpacas, etc , does 
not contain anj greasy matter, and is espeeially dangerous Even where 
goats and sheep are herded together and thus exposed in the same degree to 
antlirax, the avooI will be comparatively safe to w^ork with, ivhile the hair 



ANTHRAX 


45 


from goats equally contaminated will be dangerous The comparative 
danger from various materials is illustrated by the statistics gathered in 
England for the si\ years, 1899 to 1904 inclusive, during which time 261 
cases of all forms of anthrax were reported with 67 deaths, as follow's 


Workers in vorsted and vool 88 

Workers in horse-hair and bristles 70 

Workers in hides and skins 86 

Workeis in other industries 17 


Workers in hides and skins acquire almost exclusively external anthrax 
In London, of 92 cases observed among those w'orking in the hide and 
skin trades, only 2 w'ere intestinal, wdiile ot 87 cases in the Bradford W'orsted 
districts, 30 W'eie external and 57 internal in form 
The veiy fatal disease obseivcd in rag pickeis in the paper mills m lower 
Austria {HadeniLianUieit) has been shown by Frisch and Eppinger to be 
internal anthiax 

Gastro-mtestinal anthrax may result from eating the flesh oi drinking the 
milk of animals with the disease Fortunately, the disease is so rapid in its 
course that danger fiom these souices is not very great The winter has 
knowm an animal in the last stages of anthrax to be slaughteied and dressed 
for market by a thiifty farmer who saw' his cow about to die, and washed to 
avoid loss Examination of the blood of this animal pioved it to be sw'arming 
W'lth anthrax bacilli 

Billings states that in the Bavaiian Alps it is common for the farmers to 
conceal the presence of anthrax in their cattle and to dress the diseased 
animals for food, preserving the flesh m pickle As spores do not form 
during life, noi aftei death unless the supply of oxygen is abundant, such 
flesh Mill contain vegetative bacilli for the most part, if not entirely, and 
these are readily destioyed in cooking 
External anthrax can unquestionably be conveyed by flies and other 
insects, though this is piobably a raie method of infection 

Sex — ^The victims of anthiax are almost alw ays men, since W'omen are not 
often employed m the callings wdiich expose one to infection 
Bacteriology — The bacillus of anthiax is one of the largest of the patho- 
genic bacteiia The individual rods aie 1 2/i thick and 6 to 8/i long The 
ends are chaiacteristic, being square-cut or even depressed, so that in chains 
the elements aie separated by a lens-shaped space It forms very long 
filaments m suitable culture media It stains leadily wath the usual basic 
aniline dyes, and is not decoloiized by Gram’s method Colonics on agar 
and gelatine are veiy chaiacteristic They aie made up of wavy masses like 
locks of hail, radiating from the centie The edges of growths on slanted 
agar present the same appearances In bouillon, a delicate flocculent grow'th 
takes place, resembling bits of Japanese paper, or shreds of cotton suspended 
m liquid Latei , the grow th tends to settle to the bottom In gelatine stab- 
cultures the growth is equally characteristic Radiating fiom the central 
puncture are innumerable very delicate spikelets pushing out into the 
gelatine, sometimes being spirals 

The bacillus glows best at 35° C and ceases to grow below' 12° C or aboie 
45° C It owes much of its pathogenic power to its property of forming 
spores This takes place best at 32° C and the presence of oxygen is neces- 
sari These spores are remarkable for thtir power of resistance to cxteinal 



46 


INFECTIOUS DISEASES 


agencies such as heat, drying, chemicals, etc , which destroy the vegetative 
bacillus readily When dry the spores letain their vitality and virulence 
indefinitely, and it is through their agency that the disease is tiansported 
from distant parts of the world on hides and wool Szdkely found the spores 
in dned cultures alive and fully viiulent after eighteen and a half years 
Moist heat of 70° C kills the bacilli m one minute, but the spores must be 
subjected to live steam or boiling foi moie than five minutes and to dry heat 
of 140° C for at least three hours to insure their destiuction Cold has no 
effect on them The writer has kept them immeised m liquid an at a tem- 
perature of 212° F below zero foi three hours without any perceptible effect 
They resist a 5 per cent solution of carbolic acid alnays for two or moie 
days, and sometimes for as long as foity days Corrosive sublimate (1 to 
1000) usually kills them m two houis, but Esmarch has found them to resist 
a 1 to 100 solution for three days, though virulence was lost m tventy houis 
The resistance of spores appears to vary somewhat m different cultures, but is 
always very gi eat Unlike the vegetative organism, they are unharmed by the 
action of the gastric juice, and m cattle, where inoculation generally occurs 
thiough the digestive tiact, aie practically always the agents of infection 
The ordinary piocesses of tanning leather do not affect them injuriously 
The writer has kept them immersed for two hundred and forty-four days in 
the stiongest tanning fluids — twice the usual time requiied in the piocess — 
vithout any perceptible change in their vitality or viiulence 
Spoies are not found in cultures kept at temperatures below 18° C noi 
above 42° C Grown above 42° C the bacillus loses the power of forming 
spores entirely, becomes gradually attenuated, and acqiiiies vaccinal pro- 
perties When brought to this condition tlie attenuated bacillus can be 
cultivated at ordmaiy tempeiatures, without regaining virulence or the 
spore-foiming powei The vaccines of Pasteur aie piepaied in this mannei, 
the degiees of attenuation depending on the numbei of da'ys the culture is 
kept at 42° to 43° C The first, oi weakest, vaccine is grovn foi about 
twenty-four days, at the end of which time it has lost the povei to kill laiger 
animals, and even guinea-pigs, but vill still kill white mice, the second 
vaccine is grown for about twelve days, and should kill guinea-pigs but not 
rabbits In practice, an interval of twelve to fifteen days is allowed to 
elapse between the two inoculations, which aie made subcutaneously 
Pathogenesis — Piactically all the domestic animals are susceptible 
Fowls are refractory under normal conditions, but can be made susceptible 
by lowering their temperatuie Dogs and cats aie sometimes accidentallj 
infected The herbivoia are most susceptible, the carnivora less so, although 
instances of the disease have been knoivn m lions, tigers, bears, jaguars, 
etc Man occupies an intermediate position in the scale of susceptibility 
The action of the anthrax bacillus has been the subject of much discussion, 
and IS not yet thoroughly understood Attempts to isolate the toxin, by 
Sydney Martin, Marmier, Hanlnn and Wesbrook, Conradi and others, have 
given very contradietory results, and none of them have succeeded m isola- 
ting from cultuies substances ivliich produce the effects on animals of the 
Imng bacillus Conradi doubts the pi oduction of a toxin There can be little 
doubt, however, that m the living body the bacillus elaborates bodies wdiich 
either directly or indiiectly aie toxic to the tissues In no other w'ay can the 
extensive inflammation and oedema be explained It is perfectly possible 
that in the body, substances are formed wdiicli are not elaborated in cultures 



ANTHRAX 


47 


Morbid Anatomy — Whatevei the ongmal port of entry, the postmortem 
appearances have the same general character, varying accoidmg to the 
duration and the localization of the lesions The body becomes quickly 
discolored — in two to four hours, — and decomposition sets m early The 
cellular tissues, especially about the neck and chest become the seat of a 
putrid emphysema, sometimes with very great distension From the mouth, 
nose and other orifices, luns a dark, chocolate-colored fluid The blood is 
fluid and almost black m coloi 

In rapid cases there may be only congestion of the lungs, ecchymotic spots 
on the pleurte and pericaidium, with a small amount of effusion, the livei 
and kidneys showing cloudy sv ellmg and enlargement Sometimes hemor- 
rhages are found in the lungs, heart, kidneys, and other organs In the 
majority of cases the lesions are moie marked They consist principally in 
serous or gelatinous effusions, sometimes blood-stained, into the tissues about 
the trachea, pharynx, loot of the lungs, anterioi mediastinum and kidneys 
These effusions aie fiequently seen also in the omentum and mesenteiy, in 
the subperitoneal tissues, and sometimes along the retropeiitoneal glands 
Laige serous effusions into the pleuiie and pericardium aie common Less 
frequently the peritoneal cavity contains fluid Theie is great enlargement of 
the bionchial glands, with ecchymoses and hemorrhages m and about them 
Hemorrhages, varying fiom minute points up to large exti avasations, occur 
in the lungs, mucous membrane of the trachea and bronchi, pericardium, 
heart muscle, undei the capsule of the ladneys, and sometimes m the cortex 
of the brain, and the pia mater The heart muscle is dark, soft and flabby 
The spleen is sometimes, but not constantly, enlaiged, congested and soft 
When much enlaiged the pulp is almost black and diffluent 

In pulmonaiy anthrax, Greenfield has made the most complete micro- 
scopic studies He describes the characteiistic lesion as occurring in the 
lowei trachea and larger bronchi The bacilli are found m large numbeis in 
the mucous and submucous tissues, chiefly in the lymphatic vessels, and in 
the IjTuphatic plexuses around the aiteiies Inflammation takes place, AMth 
exudation beneath the epithelium, and later hemorrhage into the substance 
of the membrane 

In intestinal anthrax the local lesions are found chiefly in the stomach and 
small intestine They appeal as hemorrhagic areas, someAAhat elevated, 
dark-red m color, and sui rounded by an cedematous,^ injected zone The 
centie of the lesion is sometimes ulceiated or gangienous Microscopically, 
the capillaiies are found to be dilated, and there is an albuminous exudate 
rich m leukoertes, oi hemorihagic exti avasations Bacilli are plentiful on 
the suiface of the ulcerations and in the deeper structures 

Malignant Pustule — Studies of the skin lesion aa ere first made by Dav- 
aine, and since by Wagnei, Koch, Strauss, Cornil and others In the 
pustule are seen the various stages of an acute exudative inflammation, aa Inch 
may be sero-fibnnous, hemorrhagic or necrotic 

DaA'ame, aaIio studied excised lesions tA\o and three days old, found the 
anthrax bacilli at the centre of the pustule, situated in the rete mucosum, 
in closely packed groups, separated by normal epithelium, the initial pro- 
liferation apparently taking place in the deep lasers of the epidermis 
According to Strauss, the black eschai is strictly deimic, consisting of the 
papillarA la'^er and upper portion of the derma It is coA^ered by a crust 
composed of coagulated amorphous exudate, and is separated from the 



48 


INFECTIOUS DISEASES 


under]3ung and living poitions of the skin by a thick layer of embryonal 
cells, which form, as it were, a line of demai cation, in which the bacilli aie 
found m very large numbers The deeper skin and subcutaneous cellular 
tissues are distended by a sero-albuminous exudate, very rich in leukocytes 
The mfiltiation is diffuse and not especially marked about the bloodvessels 
The bacilli are found in the Ij'mph spaces, not in the bloodvessels In the 
neighborhood of the pustule, the papillary lajer, the deima, and the sub- 
cutaneous tissues are the seat of an acute inflammatoiy oedema, with infiltra- 
tion of the tissues by leukocjdes and bacilli In chaibonous oedema, the 
bacilli are found exclusively in the subcutaneous cellular tissues — ^not in the 
skin, as in the malignant pustule 

Distribution of Bacilli — ^In the lower animals the bacilli are found in the 
blood m enormous numbers In man they are very much less numerous 
They are always found m and neai the point of inoculation, and in the 
lymphatic vessels to the neaiest gland They are geneially found in the 
serum of the vesicles about the eschar, and sometimes m the oedematous 
tissues several inches away In the late stages they may be found m the 
blood fiom the ear or fingers They are geneially present in the effusions 
into the seious cavities When the kidneys are involved, the bacillus may 
pass into the urine 

Sections of the various tissues and organs yield very vaiiable results m 
different cases Some bacilli can usually be found, and sometimes large 
numbers 

Symptoms — 1 External Anthrax — (a) Mahgnant Ptisiulc — ^This is 
the most common form m man, and is the result of direct inoculation It 
occurs almost always on those portions of the body which are habitually 
uncovered, such as the face, neck, and arms The lesion is usually single, 
though two and even three points of inoculation have been observed The 
period of incubation is from one to three days 

At the point of inoculation a small red papule with a central punctum 
appears, sometimes preceded and always accompanied by itching and 
burning By the second day a flattened vesicle has formed, vhich may be 
sui rounded by some redness and swelling The vesicle soon ruptures and is 
replaced by a yellowish erosion, which rapidly becomes biowm and, by the 
fourth day, a black, depiessed eschai has foimed, surrounded by a very 
characteristic bolder of small vesicles The circle of vesicles is slightly 
elevated, and may be complete oi irregular Moie oi less numerous vesicles 
may appear on the neigliboiing slcm The eschar growls laiger as ■well as 
deeper, and may attain a diameter of tivo to three centimeters The sub- 
lacent and surrounding tissues are the seat of a hard oedematous sivelling, 
■which IS often very extensive, mvolnng an entire limb, the face, or a large 
part of the trunk When the lesion is about the face, the deformity is veiy 
great The neighboring lymphatics are sometimes involved, becoming ten- 
der and enlarged 

The freedom from pain in and about the lesions is lemarkable Even 
■when very extensive, the patient complains only of a sense of iveight and 
fulness, wuth some tenderness on pressure Pus is never formed until the 
eschar begins to separate — from the ninth to the fifteenth day 

The general s^vmiptoms are very vanable, and bear no relation to the 
extent of the local lesion In severe cases the symptoms indicating general 
infection come on T\uthm hventy-four to thirty-six hours, in other cases not 



ANTHRAX 


49 


for some days or even a week The early symptoms aie lassitude, malaise, 
headache, chilly sensations oi slight rigois, loss of appetite, perhaps vomiting, 
restlessness, and disturbed sleep Fevei may be absent and is usually not 
marked 

The temperatuie IS not an index of the gravity, it may be high in favorable 
and low in fatal cases It frequently falls before death The pulse may not 
be affected at first It is usually more fiequent, but soft With the increase 
of giavity m the symptoms, it becomes weak, small, rapid and intermittent 
Among the later symptoms may be persistent vomiting, foetid diarrhaa, 
a sense of oppiession, with rapid bieathmg and a tendency to cyanosis, 
delirium, coma or convulsions, accoidmg to the internal localization of the 
infection Consciousness is usually lotamed until the end Death is some- 
times sudden ivith no premonitory symptoms 

(b) Malignant Anthiax (Edema — ^This form nas first described by 
Bourgeois, and lesembles the gelatinous oedema seen m many susceptible 
animals after inoculation It is seen chiefly about the eyelids, though it 
may occur about the lips, neck and tiunk Theie is no characteristic eschar 
The swelling may be very great and consists of a diffuse, painless, semi- 
tianspaient oedema, soft at fiist but growing haider as it increases Vesicles 
may foim on the surface, which aie followed by eschars, similar to the ordi- 
nary malignant pustule The course of the disease is more rapid and more 
fatal than in the ordinaiy form 

2 Internal Anthrax — (a) Intestinal Anih ax, Mycosis Intestinahs — 
This mode of infection is rare in man, but the usual one m cattle The onset 
is sudden There may be piodromal symptoms such as malaise, weakness, 
headache, chilliness, sweats, etc Gastio-intestinal symptoms come on 
lapidly Theie is complete anoiexia and thiist, soon followed by nausea, 
persistent vomiting, diarrhoea — which may be bloody, — and marked ab- 
dominal pain The symptoms have been mistaken for strangulation of the 
intestine The abdomen becomes distended, the respiration lapid, dyspnoea 
is often considerable, due partly to areas of congestion in the lungs, or to 
pleural effusions, the pulse becomes rapid and small, the skin cold and 
clammy, the face cyanotic 

The tempeiatuie is seldom high, and usually only slightly above normal, 
often falling and becoming subnormal before death The patient is pro- 
foundly adynamic and dies m collapse, letaining consciousness to the last, 
or else, delirium, convulsions, and coma may precede the end 
Death may take place m thirty-six to forty-eight hours, the sjmiptoms 
resembling those of acute gastio-mtestinal poisoning The usual duration 
IS five or six days 

(6) Puhnonaiy Anthi ax, Wool-soitcis’ Disease, AntJn accemia — In this 
the symptoms may be vague and slight until just befoie death, and even then 
the patient may not feel particulailv ill The patient may feel so little 
disturbance that no appiehension is felt, until suddenly he goes into collapse, 
becomes cold, pulseless, and dies vitliin a fev houis The initial symiptoms 
are malaise, slight chilliness oi shivering, a sense of extreme v eakness and 
fatigue, and uneasiness about the chest and stomach Vomiting occurs in 
about one-half of all cases, and may be peisistent Diairhoea is less frequent 
The lungs aie alw ays invoh ed There is a sense of constriction or oppres- 
sion m the chest, with lapid and difficult breathing Cough is generally 
present but seldom veiy annoying The sputum is seldom abundant and 

^ OL 



50 


INFECTIOUS DISEASES 


may contain blood or be lUsty Anthrax bacilli aie sometimes found in it 
The percussion sounds aie often cleai, impaiiment "when piesent is usually 
on the right side jNIoist lales may be heard The light lung is moie fre- 
quently and moie extensively involved, as a lule, than the lett 

The tempeiatuie is seldom veiy high The pulse may not be much 
altered until late m the disease As a lule, hovevei, it is lapid and veak 
out of proportion to the appaient seventy of the condition Towaid the 
end, it becomes small, iiiegular and lapid 

The urine is scanty, dark, and of high specific gravity — 1,040 in some 
cases It often contains albumin but seldom in laige quantity 

The duration vanes greatly Death takes place, in the majority of cases, 
on the second, thud, and fouith days Bell has reported fulminating cases 
with death in seventeen houis 

Diagnosis — In all foims of anthiax, the oceupation of the patient should 
excite suspicion Malignant pustule is almost ahvajs on some pait of the 
body habitually uncoveied It is distinguished fiom furuncle and car- 
buncle by the absence of pain and suppuration The absence of pain ivill 
serve also to diftei entiatc it from phlegmonous erysipelas and cellulitis When 
the lesion is fully developed the central, black eschar vith the "bravny 
oedema,” and sui rounding lesicles aie so chamcteristic that mistakes can 
hardly be made 

Intestinal anthrax is so much like other forms of acute gastro-mtestmal 
poisoning that diagnosis may be impossible Tlieie may be oedema about 
the root of the neck, ivliicli, v itli the occupation, may fuinish a clue Anthrax 
bacilli have been found in the seium before death 

Pulmonary anthiax is impossible to diagnose in the eaily stages Bell 
says that the slightest illness in persons exposed to infection should be looked 
upon with suspicion until the possibility of anthrax is excluded In cases 
which are not veiy lapid, and complicated vith pleuiisy and pneumonia, 
great piostration vith a weak, lapid pulse, not accounted for by the local 
lesions, should attiact attention Diagnosis is difficult 

Prognosis — This is bad in all foims Cases m vhich the onset is marked 
by decided symptoms and a tempeiature above 102 5°F are more favoi able 
than those in vliich the s^nptoms are vague The active sjmptoms indicate 
reaction on the part of the patient The danger fiom malignant pustule 
vanes with its site Lesions on the neck aie the most dangerous, on account 
of oedema of the lai-^mx, and involvement of vital organs Lesions on the 
eyelids are also especially fatal Limitation of the lesions by marked 
inflammatory reaction about them is a favorable indication Fever is more 
favorable than a low oi subnormal tempeiatuie Bell eonsideis the pulse 
the best guide, when full and moderately lapid, the prognosis is hopeful 
The outlook is bad when the pulse is small, veak and lapid 

Treatment — ^INIahgnant pustule begins as a local infection, and for some 
days the bacilli aie localized in and near the local lesion Destruction of the 
pustule IS theiefoie indicated, and it is of gieat impoitancc that it should be 
practised at the earliest possible moment When done befoie the bacilli 
have invaded the Bunpli channels and bloodvessels, a favorable issue may 
usually be confidently looked for The actual cautery and excision vath the 
knife are the two proceduies most to be recommended In either case 
extirpation must be thorough After excision vath the knife, vhich must 
include the tissues foi at least a half inch beyond the eschar, the wound 



ANTHRAX 


51 


should be well s'ftabbed ■v\ith carbolic acid Injections of carbolic acid 
should be made into the tissues at five or six points around the v ound and 
repeated at intervals of four hours if the symptoms are urgent Bell advises 
for this purpose 15 minims of a 5 per cent solution of carbolic acid m equal 
parts of uater and ether Over the whole should be applied an antiseptic 
dressing and an ice-bag 

In Europe, the actual cautery and chemical caustics are preferred Among 
the latter, caustic potash is highly recommended Graef has collected a 
series of 384 cases treated wuth caustic potash by himself and others wuth 
only 20 deaths Muskett regards powdered ipecacuanha as having a specific 
action, using it as a dressing and also giving it internally He treated 50 
cases without a death m this manner At Guy’s Hospital, London, it is much 
used, although excision is first practised The general treatment is support- 
ing and stimulant 

There is little to be ofi’ered in the W'ay of treatment m pulmonary and 
intestinal anthrax Indications must be met as they arise, and the patient’s 
strength kept up as far as possible by natntious foods and stimulants 

Serum Treatment — ^hlaichoux' in France, and Sclavo m Italy, inde- 
pendently demonstrated in 1895 the possibility of producing a specific serum 
w'liich IS both prophylactic and curative, the former using rabbits and sheep, 
W'hile Sclavo now uses the ass Statistics of 164 cases treated wnth the serum 
give a mortality of 6 09 per cent Legge^ has recently (1905) collected the 
statistics of 65 cases in which Sclavo’s seium was used, with 2 deaths 
The average duration of treatment, estimated from 44 cases m which the 
data w'ere precise, w^as eight days Marked improvement w'as usually 
observed by the thud day, as evidenced by arrest of development in the 
pustule, diminution of the oedema, and amelioration of the general symp- 
toms The initial dose should be large, as much as 40 cc , injected under the 
skin A number of favorable reports of Sclavo’s serum have been published 
m England 

Preventive Measures — It is difficult to cany out efficient preventive 
measures In some countries w here anthrax is very prevalent, such as China, 
theie IS no w'ay of getting reports of the existence or extent of anthrax, and 
no method of preventing the shipment of hides and haii from diseased 
animals packed wuth healthy mateiial 

No efficient way has yet been discoxmed of disinfecting hides without 
destroying their commeicial value Porteis handling such material should 
be required to have the arms and neck coveied In England, wool-soiters’ 
disease has been lessened by regulations requiring that dangerous wools 
and hairs shall be steeped and washed m hot suds and sorted while damp 
111 other cases the sorting is done ox^er wire screens proxoded xxitli suction 
apparatus The dust collected is burned All skin, clippings, and bags 
which hax'e contained dangerous materials, are disinfected before being sold 
Opeiatixns with soies or cuts are not allowed to work, and the proper 
apphanees foi disinfecting and treating such xxounds are kept on hand m 
the XX orkroom 


MnaaZ dc V InsMutc Pasteur, 1895 
•British Medical Journal, 1905, 1 



52 


INFECTIOUS DISEASES 


RABIES 

S3mon3miS — ^English, hydrophobia, madness, French, la rage, I’hydro- 
phobie, German, Hundswuth, Tolhvuth, Wuthkrankheit, Wasserscheu, 
Italian, idrofobia, rabbia, l}ssa 

Definition — ^Rabies is an acute, specific, rapidly fatal malady, com- 
municated to man from some lower animal It is always an inoculation 
disease, that is, communicated directly through a wound usually made by 
the teeth, the infective matter being the saliva, which contains the virus, the 
exact nature of which is unknown 

Historical — ^Rabies m the dog appears to have been unknown to Hippo- 
crates, but was distinctly described by Aristotle, 326 B C , who recognized 
its transmissibihty among animals, but denied its existence in man He 
said, “Dogs are subject to rabies, it makes them furious, all the animals they 
bite while m this state become rabid, except man ” 

The earliest description in man is found m the first century of the Christian 
era, the term “hydrophobia” being used This word is now properly 
restricted to the disease as seen in man Celsus gave a good description of 
rabies in man, and advised suction and the actual cautery for infected bites 
As early as 1591, transmission from volves to man is recorded Van Sweiten 
(1771) recognized the paralytic t'^'pe m man, which was confirmed and more 
fully described in 1822, by Berndt, of Gieifswald The virulence of the 
saliva of dogs was first clearly demonstrated by Gruner and the Corate de 
Salm, in 1813 This was confirmed by Berndt, who held that the saliva of all 
animals affected with rabies contained the virus By many it was believed that 
the herbivorawere an exception to this, an opinion quite current until the work 
of Rey, m 1842, proved the correctness of Berndt’s views Our piesent 
ideas are largely due to the labors of Pasteur and his students, begun m 1881 

Distribution — Rabies occms in almost every part of the world, Australia 
being the only country knovi. to be exempt, owing to the rigidly enforced 
quarantine It is very rarely seen in Holland, Denmark, Norway, Sweden, 
and Switzerland In France, Belgium, Hungary, and Russia, the disease 
IS ividespread In the latter country it is common among ivolves It is 
quite common m Italy and Spain, although the official figures are small 
In Germany, the disease is seen mainly on the fiontiers and is rare in the 
interior It is quite common in China and Japan England is practically 
free at the present time Rabies is common through the greater part of the 
United States, severe epidemics having been observed in several cities quite 
recently The census for 1890 gave 143 deaths, distributed m 30 states, and 
for 1900, 123 deaths These figures do not represent the full number of 
deaths from hydrophobia Salmon collected statistics from the health offi- 
cers of 73 cities wdnch shoived 230 deaths betiveen 1890 and 1900 

Animals Affected — ^All mammalia are susceptible and birds also con- 
tract rabies wdien bitten or otherwise inoculated Dogs are most frequently 
affected, and to them we ow^e the perpetuation of the disease It is not infre- 
quent among wolves, foxes, hyenas, jackals, skunks, etc Cats are rarely 
affected Among the domestic animals cattle are most often affected, swine 
least so It IS uncommon in horses The money losses from rabies are very 
heav^^ In England it has appeared among the deer in parks and m 1889, 
out of 650 deer belonging to the Marquis of Bristol, 500 died in four 
months from rabies 



RABIES 


53 


Etiology — ^Hydropliobia being abiajs the result of accidental infection 
from some lower animals, its incidence will follow closely that of rabies m the 
domestic annuals, especially the dog, wdiich is by fai the most frequent 
source not only tor man but toi all other animals Statistics of 16,172 persons 
bitten by supposedly rabid animals, collected at the Pasteui Institute, Pans, 
incriminate dogs in 15,021 cases, cats in 959, wolves in 14, foxes in 2, jackals 
m 9, horses m 32, asses and mules in 40, cattle 67, sheep 3, pigs m 12, and 
man m 13 

The danger following the bite of a labid animal depends on the species, 
and the location and extent of the w ounds The bite of w olves is more apt 
to be followed by rabies than that of any other animal, owing paitly to the 
greater activity of the virus, and partly to the savage mode of attack, the 
wounds being very extensive, lacerated, and often located about the head 
and face Next in point of danger come bites from cats, then dogs, and 
lastly other animals The report of the Pasteur Institute at Kharkoft for the 
fen years, 1892 to 1901, slioivs that, of 8,430 persons bitten by rabid dogs, 
77, or 0 91 per cent died, whereas of 193 bitten by rabid W'olves, 32, or 
16 58 per cent succumbed to rabies 

There seems to be no authentic instance of the transmission of rabies 
through the bite of man, but in view' of experimental evidence proving the 
virulence of human saliva for animals, such injuries must be regarded as 
dangerous, and be treated accordingly 

Bites on exjiosed parts of the body are more dangerous than those made 
through clothing, since the latter retains the virus, and the comparatively 
clean tooth enters the body For the same reason long-haired dogs w'hen 
bitten escape infection more often than short-haired ones 

Sheep are quite resistant to infection by bites, except after shearing It 
has been shown by Pasteur, and Horsley, that labbits which are shaven and 
exposed to the bite of a mad dog contract rabies more certainly and fre- 
quently than those bitten through the fur, even when the teeth penetrate 
deeply through the skin 

Bites m parts of the body having a rich nerve supply, as the face and hands, 
are partieularly dangerous In the former case especially, the virus is rap- 
idly conveyed to the medulla The same is true of bites in or about the 
large nerve trunks of the extremities 

The comparative danger is w ell show'n m the statistics of 18,645 treated 
at the Pasteui Institute m Pans, as reported by Pottevm 


Location 
of Bite 

Head 

Hands 

Limbs 


Number 

Treated 

1,608 

10,254 

6,783 


Deaths 

21 

40 

20 


Per Cent 
1 36 
0 47 
0 29 


Interesting figures on the same point aie gnen from the Pasteur Institute 
at Kharkoft for the jeais 1892 to 1901 


I ocation 
of Bite 

Number 

Treated 

Deaths 

Upper extremities 

5 301 

34 

Lower extremities 

2,601 

2 

Head and faee 

946 

73 

Bodj 

542 

0 


Per Cent 
0 64 
0 08 
7 72 
0 



54 


INFECTIOUS DISEASES 


Rabies may be tiansmitted by the deposit of saliva containing the virus 
on abraded surfaces, as by licking It may also be contracted through 
wounds received m making autopsies on animals oi persons who have 
succumbed to the disease In all cases a solution of continuity is necessary 
for the absorption of the virus, it cannot pass through the healthy skin It 
IS doubtful if the virus can be absorbed thiough the digestive tiact 

Not every person bitten by a rabid dog becomes infected Leblanc, as the 
result of careful investigation, gives 16 6 per cent as the proportion, an 
estimate which is generally accepted as conservative and collect Some 
series of cases show much highei figures Bouley leports 152 deaths among 
266 persons bitten, but of these, 120 were bitten on the face and hands, the 
greater danger from which has been noted The mortality following bites 
of rabid wolves is variously estimated at from 60 to 80 per cent 

Sex — ^hlen are not only moie liable to be bitten by rabid animals, owing 
to their various callings, but when bitten are more apt to contract hydro- 
phobia This IS doubtless due to the greater protection afforded by the 
skirts, and not to any inherent immunity m women 

Age — ^Two-fifths of all cases occur m childien under fifteen years of age, 
according to Bollinger Children of both sexes are particularly liable to 
bites, owing to their habit of collecting together for play m the stieets, then 
inability to recognize danger, and their lack of defence For obvious leasons 
they are often bitten about the face On the other hand, they appear to 
enjoy considerable relative immunity Brouardel says that of eveiy 100 
persons below twenty yeais of age bitten, 31 die, while above this age, 62 of 
every 100 die 

Influence of Season — ^The statistics of the Pasteur Institute, Pans, from 
1886 to 1893, show that the largest number of patients apply for treatment m 
March, April and May, the smallest m September, October and November 
The statistics of the Pasteur Institute at Lille for seven years, 1895 to 1902, 
show the following results 


January 

141 

February 

111 

March 

144 

April 

149 

May 

133 

June 

173 


July 

169 

August 

159 

September 

111 

October 

196 

November 

148 

December 

173 


A table compiled by D E Salmon, including 14,066 cases of canine labies, 
gives the following results by months January 943, February 1,045, March 
960, April 1,323, May 1,419, June 1,467, July 1,435, August 1,294, Septem- 
ber 1,145, October 965, November 933, December 1,137 It is seen that 
more cases occur from April to September, inclusive, than during the rest of 
the year, due, no doubt, to the fact that dogs are more apt to run abroad 
during the waim season than during the winter months 

Virus — Distnbution — ^The wrus is alw’^ays contained m the saliva, and 
appears to be excreted chiefly by the parotid gland, though not entirely so 
The salivary glands themselves are nrulent, though not so constantl> as the 
mixed saliva The saliva of the dog has been showm by Nocaid and Roux 
to be ahvays nrulent twenty-four to forty-eight hours before the animal 
shows any symptoms of illness The lachrymal glands, the pancreas and 
suprarenal capsules may contain the virus It is also excreted m the milk at 



RABIES 


55 


times The blood and l^nnph are ncvei virulent, and Ilelman has show n that 
It lb absent irom the lymph glands in leUition to the point of inoculation 
The muscles and oigans are innocuous 

Every part ot the central neivous system constantly contains the virus, but 
it is especially conceiitiated m the medulla The laige neive trunks aie 
usually vnulent, as is also the ceiebrospmal fluid Pasteui showed that the 
“entire neivous system, fiom centie to peiipher>, is capable of cultivating 
the vn us ” llou\ found that the peiipheial ncives, even on the side opposite 
moeulation, weie often virulent 

Nature — ^The exact nature of the viius is unknown The behavioi of the 
disease makes us certain that it is caused by a specific mitioorganism, 
wdiich, after inti eduction into the body, undeigoes a period of incubation, 
during which it multiplies and pioduccs a toxin ha\ang a special action on 
the central nervous system, as is the case in tetanus, to which it bears a 
striking analogy Nocaid in 1880, and Paul Btit in 1882, showed that, on 
filtration through plaster, the virus was held on the filter, the filtrate being 
devoid of pathogenic power Fuither studies by di Vestea, Beitaielli and 
Volpmo, Celh and Blasi, Remhnger and others, have shown that the virus 
will frequently pass a coarser filter, such as the Beikefeld V, and will some- 
times penetrate a Chamber land F, under pressure Several observers have 
found that the filtrate frequently produces cachetic and paraljlic phenomena 
not unlike rabies m dogs and labbits, but after death the medulla of the 
animal is ineapable of injunng other animals, showing that the condition is 
a toxic one In this respect also the analogv to tetanus is close, and from this 
fact the disease has been considered a toxoneiirosis It is friilher known 
that seiial passages through susceptible animals increase the powder of the 
virus, wdiile it is attenuated by drving, heat, light, etc , as many bactena are 

Innunieiable attempts hare been made to discorer the causative agent, 
and, fiom time to tune, obseners hare announced the finding of cocci, 
bacilli, yeasts, and protozoa which they believed to be the pathogenic 
oiganism None of thos^ discover les have stood the test of rigid investi- 
gation At the present day, the opinion is growing that labies is due to a 
micioorganism of the ultra-microscopic class, but considering our lack of 
definite knowledge, all opinions must be accepted with reservation 

Resistance — The r irus is destroved bv heat, drrang, and light In dry 
air, protected fiom the light and from putiefaction, the spinal cords of 
labbits lose then viiulente giadually in fourteen to fifteen davs, a fact made 
use of by Pasteur in preparing his vaccines When in thin k^ers, the virus 
is entnely destrored by dnnig in four to fire dars Direct sunlight destrors 
it nr about fortr horns In rratci the vans retains its porrer for trrenty to 
forty dars, or longei Ncutial ghcerine preserres it unchanged for a long 
time Roux found that aftci foui weeks m glrceime at 30° C the rams was 
unchanged ru pathogenic porrer 

Galticr has found the rirus actirc in the central nervous srstem of rabbits 
buried foi twentr -three dars, of sheep buried thirtr-one davs, and of dogs 
buried fortr-forir dars It is not injured br cold, resisting the prolonged 
application of a temperature 10° C to 20° C below zero It is destroyed by 
a tempera true of 50° C in one hour, or 60° C in a half hour 

Tnrestigators diflei greatlr as to the eflccts of rarioiis antiseptics The 
best ajipear to be corrosire sublimate, 1 to 1,000, citric acid in G per cent 
solution, and saturated rraterj solution of iodine The virulence of fixed 



56 


INFECTIOUS DISEASES 


virus IS destroyed in eight minutes by 1 part of a 5 pei cent solution of 
formalin to 3 parts of viius hlixed m equal parts it is destioyed in five 
minutes Bile rapidly destroys the activity of the viius When an emulsion 
of the bulb from a labid animal is mixed vith an equal volume of bile from 
either a healthy or rabid rabbit, and alloii ed to stand a few minutes, it may 
then be inoculated vithout danger of causing labies 

Penetration — Fiom the point of moculation the viius makes it vay to the 
central nervous system along the neive trunks, pioduung no symptoms 
until the central system has been the seat of the viius lor some time If the 
spinal cord of an animal is cut, and a viiulent inoculation then made in the 
hind extremity, it will be found, after a suitable period of incubation, that 
the spinal cord below the point of section is virulent, hile above, it contains 
no virus When the inoculation is made into the biam or uppei extremity, 
the descent of the virus can in like manner be pi evented by section of the 
cord Roux has shown that in labies developing sloiily aftei inoculation of 
the limb on one side, the virus may also be found m the peripheral nerves of 
the opposite side, if, however, the peiiod of incubation is short, only the 
nerves on the wounded side contain the virus Clinically it has been obseived 
that the paralytic and convulsive phenomena aie more maiked on the side of 
the inoculation It is said by di Vestea and Zagari that paraplegia is apt to 
follow bites of the loner extremities, while the lurious tjqie of labies is pro- 
duced by bites of the head and upper extremities Experimentally m small 
animals the circulation and lymph channels appear to play some part m the 
absorption of the virus 

Incubation — ^The average period in man is about forty days, but it 
varies between wide limits The great majority of cases occui betn een the 
twentieth and ninetieth day Cases have been leported as developing 
several years after infection but aie gcneially disci edited Gowers says, “It 
IS, however, certain that the disease may occur after an interval of a year or 
eighteen months, and it is difficult, therefoie, to deny the possibility of a 
longer interval ” The shortest period of incubation is about tii elve days 
The development of rabies is not common aftei three months, and is quite 
rare after six months 

Pathology — ^There are no characteiistic gross pathological changes In 
man, congestion of the lungs and emphysema aie common, due to the con- 
vulsive seizures The muscles of the chest and pleuise are sometimes 
ruptured m the same way Congestion of the fauces, oesophagus, stomach 
and larynx is commonly found Of the internal oigans, the kidneys and 
spleen most often show congestion The brain and spinal cord frequently 
show marked congestion The blood generally remains fluid after death and 
IS dark in color 

Pathological Histology — ^In 1872, Nepveu described the findings in a 
case of human rabies observed by Pollailon and himself They noted that 
the whole cerebrospinal axis vas strongly congested and that the Gasseiian 
ganglion was hypercemic and infiltrated vith round or oval cells, some 
hyaline in appearance, and which they considered "probably epithelioid cells 
from the capsule of the ganglion cells ” In the same year, Clifford Allbutt 
described changes observed m the cerebrum, medulla, pons, and spinal cord, 
which pointed “to the action of an animal poison acting primarily on the 
cerebrospinal nervous system ” hlany authois have described lesions of the 
nervous system which have been thought more or less characteristic 



RABIES 


57 


Gov, crs found distinct morbid changes in 7 out of 9 cases He describes 
“ dilatation of the small vessels, accumulation of leukocyte-like corpuscles 
aiound them and in the tissues, clots in small vessels evidently formed 
duiing life, and minute liemoirhages ” These changes were found m tlie 
cortex of the hemispheres, medulla oblongata, and the spinal cord, but neie 
most intense in the medulla, especially about the nuclei of the pneunio- 
gastric, hypoglossal, and spinal accessory nerves He obseived marked 
packing of leukocytes about the vessels, xiliich many times were so numeious 
as to entirely fill the peiivascular lymphatic sheath, and even extend into the 
adjacent tissue ^ About the nuclei nere found dense collections of coipuscles 
which he considered identical nith pus cells, and hence called them “miliary 
abscesses ” He did not considei the lesions pathognomonic in their char- 
acter, although their intensity and distribution Mere peculiar to rabies and 
constituted a distinguishing anatomical charactei 

Babes has desciibed nhat he consideis the essential lesion of rabies, — an 
accumulation of embiyomc cells in the neighboihood of the central canal, 
and especially about the laige modified cells of the motoi centres of the bulb 
and cold In the bulb he describes the pericellulai accumulations of embiy- 
onal cells found by Kolessnikoff, foi M'hicli he proposes the name “rabic 
tubeicle ” The cells of the bulbar nuclei undeigo degeneration and show 
the various stages of chromatolysis Theie is loss of the prolongations and 
progressive modification Mitli even total disappearance of the nuclei, a 
dilation of the pericellulai space, and an invasion not only of this space, but 
also of the neive cells by embryonal cells, at the same tune, there appear 
small coipuscles nlncli are hyaline, bronnish, and m paits metachiomatic 
Many of the neive cells become surrounded by a large 7one of embryonal 
cells, degenciation of the cell folloM’s, and Mhen complete the embryonal cells 
occupi the cell area entiiely, foiming the “rabic tubercle Babes has foi 
many years made routine examinations of the bulb of all cases for the purpose 
of diagnosis Reporting on the bulbs of 487 dogs, all of mIiicIi m ere controlled 
by inoculation of labbits, he finds the lesion so constant that he regards it as 
diagnostic of the disease 

In 1900, Van Gehuchten and Nelis discovered nhat they behe^ed to be 
the diagnostic lesion of the disease While recognizing and confiiming many 
of the lesions described by other nnteis, they consider them secondaiy and 
of little nnpoitance They believe that the virus aets bv pieference on the 
pciiplieial ceiebiospinal and sjinpathetic ganglia The most constant and 
niatkcd lesions aie found in the intervertebral and the pneiimogastnc 
ganglia They consist of the atrophy, the miasion, and the destruction of the 
none cells bv nen -formed cells, due to the proliferation of the cells of the 
endothelial capsule The nev -formed cells increase m numbei, invade the 
protoplasm of the neiwe cell, and finally occupv the entire capsule, the nerve 
cell propel havang complctelv disappeaied, while m its place is seen a mass 
of round cells The neive cells winch are not destroved niav show various 
dcgcneiativc changes of the protoplasm and nuclei, such as vacuolation, 
ecccntiicitv of the nuclei, chromatoRsis, etc In advanced cases practically 
all the nerve cells ma^ be destroved, and the section has much the appearance 
of an alveolar sarcoma These changes have been found in a great vanetv 
of animals They aie best observed m dogs and cows, but are quite charac- 
teristic 111 all aninials studied 



58 


INFECTIOUS DISEASES 


In 1903, Negn announced tlie discovery of cei tain bodies in the nerve cells 
of rabid animals They are found especially in the hoin of Ammon They 
are from 1 to 23 in diamater, oval, lound or triangular in shape, accord- 
ing to then size and position m the cell They die stiongly eosinophilic 
The Negri bodies are descnbed as consisting of a fundamental substance, 
which IS homogeneous, non-granular and hyaline in appearance, resembling 
coagulated albumin Within them aie clear, shining aieas, which at hrst 
sight appear to be vacuoles, but undei higher poweis show one oi moie 
points of deeper color They aie quite resistant to external agencies, remain- 
ing unchanged for a long time by putrefaction, desiccation (183 days), etc 
Material may be preserved in glycerine for eighty days without alteiing the 
Negn bodies They aie destroyed by 33 per cent solution of caustic potash 
They are well brought out by dilute solutions of acetic acid or by 10 pei 
cent osmic acid, or by immeision in 33 pei cent alcohol for forty-eight 
hours, or by staining after the method of Mann or Romanowsky They 
are especially numeious and laige in cases of rabies of long incubation 
period (Negn) They are best developed in the horn of Ammon, less in the 
cells of Purkinje, and less still in the spinal ganglia and vagus 
The nature of the bodies is unknown Negn believes them to be piotozoa, 
and considers them the causative agents of the disease Valenti reports that 
the virus of labies is neutralized in the test-tube as well as the living body by 
quinine, while no other alkaloid was found which had this power This is 
held as strong evidence of the protozoan natuie of the bodies 

Babes has made an exhaustive study of the matter and confirms the prac- 
tically constant piesence of Negn bodies m the brain in rabies, although he 
does not consider them the actual parasite, but rather evidence of the resist- 
ance on the pait of the cell, by which it is able to englobe and encapsulate the 
invading oiganism He believes the fine round granules coloring a blue or 
black with the Cajal-Giemsa stain to be the paiasite in its active state 
These granules aie found exclusively in the protoplasm of the degeneiated 
nerve cells in the most severely involved areas of the nervous system, whereas 
the Negn bodies occui m cells but little altered and having no close con- 
nection with the symptoms He believes the Negn bodies to be encapsulated 
parasites undergoing involution or degeneration 

Postmortem Diagnosis — ^Theie are no gioss lesions, either m man or in 
animals, which enable one to state positively that death has been due to 
labies In dogs, peihaps the most constant feature is the absence of food 
from the stomach and the piesence of foreign matter, such as straw, wood, 
hair, etc Axe found this condition in 90 per cent of cases Emaciation is 
usually marked and putrefaction takes place rapidly 

Until recently we have been obliged to resort to inoculation of animals for 
a positive diagnosis Rabbits are usually selected, and the inoculation made 
under the dura, since infection is more rapid and ceitain than when the 
inoculation is made elsewhere Symptoms appeal from the sixteenth to the 
twenty-first day, as a rule, but may be delayed for sixty days The t}q»e of 
rabies following inoculation is usually the paraljlic, though rarely the furious 
type IS seen The virus of rabies is concentrated m the medulla, and espe- 
cially in the floor of the fourth ventricle For inoculation the tissue is by 
preference taken from this aiea 

Microscopic Diagnosis — On account of the time required, the inoculation 
of annuals is of no service in deteimining the necessity of antirabic inocu- 



RABIES 


59 


lations The treatment is usually completed before an opinion can be gn en 
Fortunately it is now possible to make a rapid diagnosis by microscopic 
methods, owing to the discoveiies ot Van Gchuchten and NChs, and Negri, 
already describ^ed For diagnosis by the method of Van Gehuchten and 
NChs, the plexiform ganglion of the pneumogastric ner\c is selected, as it is 
easily dissected out, and presents the cliaiacteiistic changes in the ganglion 
cells In dogs, the ganglion is readily found by cutting don n on the pneunio- 
gastne nerve in the neck, and following it up Near the skull it divides into 
two branches, on one of which, the smaller, is found a small, oial, reddish 
ganglion, the ceivical The largei branch enteis the plevifoim ganglion, 
which IS easily recognized by its iusifoim shape, and white or grayish coloi 
It is seldom moie than a half inch fiom the foramen, and it is generally 
necessaiy to cut the nerve as it eineiges from the skull The ganglion may be 
prepared foi section by any of the* rapid methods 

The best stain for geneial use is hemalum (Giublei) made up with a 0 5 
pel cent solution of carbolic acid, and counterstained W'lth eosin This 
method has been in use at the laboratory of the State Live Stock Sanitary 
Board of Pennsylvania for hve years, and has been found most satisfactory. 
A large number of cases have been controlled by inoculation, and no erroi 
has yet been found Vdiile the lesions cannot be consideied specific, since 
similar changes have been noted occasionally in other toxic conditions, and 
m the ganglia of aged dogs, yet by then extent and constant occurrence m 
labies they have an unquestionable significance, and, taken in connection 
with even a meagie lustoi}', have an absolute diagnostic value 

Certain piecautions must be observed The animal must be allow^ed to 
die of the disease The lesions may be slight oi entirely w’anting in animals 
killed prematuiely, and in such eases then absence does not preclude the 
existence of rabies If absent after death from the disease, we can positively 
deny the existence of rabies 

A diagnosis can be made wuthin tiventy-fom hours by rapid fixation and 
mounting, and is easily made w'lthin fort 3 ''-eight houis 

The diagnosis by the method of Negri has advantages over the abox'e in 
that the Negii bodies are usuall)’’ found eailj’’ in the disease, aie not aflected 
by putrefactive changes incident to delay in obtaining the material, and the 
technique is more simple In practice a small portion of the biam should be 
taken from the cortex of the ceiebellum, and also from Ammon’s horn, 
as the bodies maj’’ be numerous in one area and not in the other The pieces 
of tissue may be fixed in Zenkei’s fluid, embedded in parafin, and stained 
with cosin and methylene blue The bodies show red against the blue back- 
ground of the cell The stains of Mann and Romanow skv arc especially 
recommended 

The process of hardening and cutting ma-^ be dispensed with and the 
examination for Negri bodies made directlj m the fresh tissues by the smear 
method, w Inch has been found a eiy satisfactory It has the great adr antage 
of giving piactically an immediate diagnosis It is described by Gorham 
as follows The top and occipital portions of the skull are remoAed, and, 
without taking out the brain, pieces 3 to 4 mm m diametei are taken from 
the cerebral coitex m the region of the crucial sulcus, the cortex of the cere- 
bellum, and the hippocamjuis maior Tlicso are placed on a well-cleaned 
slide and crushed undei a coAcr-glass until the matter spreads to the edge of 
the cover, aaIiicIi is then drawn sIoaaIa and cAenh the length of the slide. 



60 


INFECTIOUS DISEASES 


leaving a uniform film of brain matter The slide is then immeised in vood 
alcohol for one to three minutes and dried in the air The stain is made by 
adding 2 drops of a saturated alcoholic solution of lose aniline violet, and 16 
diops of a one-half satuiated aqueous solution of meth^dene blue, to 18 cc of 
distilled watei Flood the slide iMth this stain and heat gently until steam 
rises, wash in v atei and dry The Negri bodies appear as pink, crimson or 
magenta inclusions in the blue nerve cells The coloi taken depends on the 
condition of the material and the proper mixtui e of the stains In early cases 
the bodies are found only in the large cells, v hile in advanced cases they are 
found m all kinds of nerve cells 

Volpmo’s osmic acid method is rapid and simple A portion of the horn of 
Ammon is lemoved and cut into segments 3 to 4 mm thick, vliich are put 
into test-tubes containing 4 to 5 cc of a 1 per cent solution of osmic acid 
After five to six hours oi longer, they are removed and v ashed m water foi a 
half hour, then put into absolute alcohol for three to four hours They may 
then be cut by hand and mounted in glyceime It is not necessary to harden 
the tissue, since a faiily thin section can be readily pressed out on the slide 
The preparation is biowmsh in color, the cells are light coffee-color, the 
nuclei paler, and the nucleoli strongly colored The Negii bodies are seen 
in the cells, and resemble nucleoli There may be one or seveial to a cell 

The discovery of Negii has been abundantly confirmed, and while the 
etiological significance, as well as the nature of the bodies is still m doubt, 
they have been shown to be very valuable for the purpose of making a rapid 
histological diagnosis Beitarelli states that m more than 1,000 examinations 
the Negn bodies were never found m animals free from rabies, and, on the 
other hand, v ere present in all infected animals, with thiee exceptions Poor, 
at the Health Department Laboratory, New York, has examined mateiial 
from 17 cases of rabies from natuial infection, 16 cases of the inoculation 
disease, and 22 controls The Negii bodies weie found in all cases of natural 
infection, and in all of the inoculation cases except 1 dog which was killed 
on the first appearance of nervous sjanptoms Among the controls 1 case 
of experimental tetanus showed a few minute eosinophile bodies in the 
Purkinje cells of the cerebellum, winch, howevei, could be differentiated 
fiom the Negn bodies He confirms fully the diagnostic value of the method 

Symptoms — ^As a lule, theie are no sjmiptoms dming the peiiod of 
incubation The wound generally heals as any other similar injury without 
local thickening or glandular in\olvement In some cases mental depiession 
is marked, but it is usually due to anxiety and apprehension rather than to 
the disease Instances have, however, been reported by most lehable 
observers, in which mental symptoms Avere noted in children too young to be 
apprehensive of danger, and m peisons Avho AA'ere not aAAare that they had 
been bitten by a rabid dog 

Thiee stages are usually recognized, but they are not ahvays well defined 
The sjmiptoms marking the later stages are frequently prominent from the 
first 

1 Premonitory Stage — ^Tlns is often marked by iiritation, tingling or a 
feeling of numbness at the seat of the bite, or else there may be quite severe 
pain, lancinating in character, and radiating up the limb These sensations 
may exist for as much as a Aveek before othei sjmiptoms appear, although 
usually this stage lasts only tAAenty-four to forty-eight hours The patient 
complains of general malaise, depiession and melancholy, with extreme 



RABIES 


61 


anxiety and a sense of impending danger The sleep is distuibcd, often 
tlierc IS great restlessness and iiritability Tlic sensibilities are often \ery 
aeute, there may be hj pencsthcsia of the skin, photophobia, etc 
About this time symptoms referable to the throat appeal, sueh as slight 
difhculty in sw allowing liquids, or a slight ehoking sensation The xoiec 
bceoines husk>, often there is prccoidial distress, nitli a sense of oppression, 
the patient frequently taking deep inspirations Slight fevei, nith inerease 
of pulse late is comraonl} piesent, oceasional iigois oecur 

During the eaily stages of the disease many patients show s^unptoms xeiy 
much like those chaiacteristic of rabies in the dog an unnatuial suspicion, 
iriitabihty of tempei, surliness, desiie to be alone, alternating nitli peiiods of 
mental excitement and loquacity Delusions anti maniacal delirium appear 
as late symptoms 

2 Stage of Excitement — ^The symptoms all increase lapidlj in seventy 
The face takes on an expicssion of tciror xMth maiked pallor, the muscles 
aie draiMi and lestlcss, the eyes hax'c a “hunted look ” There is intense 
thirst, but ei ery attempt to sn allow w ater bi mgs on a spasm of the muscles 
of deglutition and respiration, — the typical h>diophobic spasm The 
extreme thirst impels the patient to make strong efioits to dunk The water 
IS taken mto the mouth, but as soon as it touehos the fauces, it is expelled 
with considerable foice, and violent spasmodic contractions of the muscles 
of deglutition and respiiation come on These attacks are accompanied bj' a 
sense of cxtieme d^spnoja, “eicn wdien the glottis is wndely opened or 
tiachcotomj has been performed” They mciease both in intensity and 
frequenc}, and there deielops a cutaneous hyperaesthesia, m consequence of 
which the slightest draught of air, oi contact with anUhing cold, is sufficient 
to detciinme an attack The sufteiing of the patient, both physical and 
mental, is intense during the spasms, and the dread of them produces a 
mental condition which increases the ease with which they aie excited The 
hypersensitnencss is so inaikcd m some cases that the sight oi sound of 
water, or e^cn the xcrbal suggestion of it, a strong light, oi the reflection 
from a polished surface or looking-glass, is sufficient to bring on a spasm 
To this dread of watei, acqiiiied by experience of its effect, is due the name 
“ In clropliobia ” In man these spasms constitute at once the most distressing 
featuie of the disease, as well as the most diagnostic symptom 
With the adiance of the disease, the comulsive attacks, which were at 
first confined to the muscles of deglutition and lespnation, mxohc other 
groups of muscles and become general Thev may be tetanoid w ith marl ed 
opisthotonos and suspension of rcspnation, or else be “coordinated and 
closely resemble Instcioid convulsions ” Not only is the frequenct and m- 
ti’iisit^ of the seizin es iiici cased, but the length of the paroxysms often becomes 
greater and death fioin asph>XM may occur Thej mat still be caused by 
ant of the excitants mentioned, but moie often conic on without appieciable 
cause The skin and jiatelku leflexcs aic iisuallt increased in this stage 
IMvuh distress is ficquentlt caused bt auditort and olfaetort lit per.cstliesia 
Slight odors precipitate attacks of siiee/mg and eten contulsions 

1 he mucous sui faces are cotcred with thick tenacious mucus, the salica 
is ahunclaut incl tiscicl, wliile iiiabihtt to sw afiott if is often present TIictc 
are constant attempts to expel it, which arc onlt partiallt successful, so th it 
it bangs from the patient’s mouth Vomiting is frequent, the ejected fluid 
being greemsh-brown and sometimes containing blood 



62 


INFECTIOUS DISEASES 


The horror of the convulsive attacks is so great that delusions oi even 
maniacal dehnum often appear The delirium is most marked during the 
paroxysms, the patient may thiow himself from the bed, and even inflict 
severe ivounds on himself without appaient pain He may attempt to bite 
his attendants or spit at them During the convulsions noises are made in 
the throat which have often been described as lesemblmg the bark of a dog 
The delirium is not constant During the inteivals the patient can be 
brought to consciousness and even leason by his attendants He often shows 
anxiety foi the safety of those about him, begging to be restrained from 
injuimg them 

The duration of this stage is from one and a half to thiee days 
3 Paralytic Stage — ^The convulsive attacks, with the attendant mental 
symptoms, usually abate a short tune befoie death, a paialytic condition 
taking their place, and the patient sinks lapidly, dying fiom exhaustion 
Coma may piecede death 

Temperatwc — ^Babes lays stress on an elevation of temperature during 
the period of incubation This has often been observed in animals, but its 
constant occurrence m man remains to be proven In the early stages, 
elevation of temperature is lacking or moderate, and throughout the disease 
may not exceed 100° or 101° F Usually the temperature rises as the symp- 
toms increase, ^ caching 103°, 104°, 105° F , or even more, just before death, 
and may continue to rise aftei death for a short time 
The urine frequently contains albumin, sometimes sugar and blood 
The pulse is quick thioughout During the last stages it becomes more 
quick, small in volume, and irregular Increased sexual desire is not 
infrequent in the early stages and may increase as the disease advances 
Persistent piiapism with emissions may add much to the difflculty of 
urination 

Paralytic Rabies — Sometimes the convulsive attacks, the excitement and 
delirium, and the hydiophobic spasms aie entirely lacking, and we have 
typical paralytic rabies, so often seen m dogs and in animals inoculated 
experimentally This tjqie is especially apt to follow extensive bites wheie 
the amount of viius is large Accoiding to di Vestea and Zagari, it is apt to 
follow bites about the lower extremities, while the fui lous tjqie is usually the 
result of bites about the head and hands The first symptoms are usually in 
the bitten limb, but sometimes violent pains extend from the lover tiunk 
down the limbs, vhich feel heavy and difficult to move Paraplegia soon 
comes on, and may be the fiist symptom The couise of the disease is an 
acute ascending paralysis, involving the sphincteis and the muscles of the 
trunk, and ending m death by paralysis of the muscles of respiiation, or by 
cardiac syncope Diagnosis may be impossible except by inoculation of 
animals, and microscopic examination after death 

Duration — Death usually occurs between the second and fifth days, 
larely the patient may suivive eight or nine days Bouley found that of 90 
cases, 74 died during the first four days — most of them on the second and 
third days In 16 cases life was prolonged beyond the fouith day 

In the paralytic type death often does not take plaee until the seventh day 
Rabies of the Dog — ^The disease is seen in two types, a furious, and 
tranquil or paralytic type 

Fmicnis Type — In the fuiious type the first symptoms consist solely in 
changes in disposition, manifested by distiess or uneasiness, and restlessness 



BABIES 


G 3 


The animal is ahiajs easily excited At this stage, he docs not iisualh show 
a disjiosition to bite, he is still docile and obeys orders, though not so 
quickly as m health, he soon seeks solitude and sho^\s a disposition to hide 
in dark comers, or burrow in the straw of Ins kennel, peiiods of calnincss 
alternating with marked excitement arc observed, he still shows affection 
for his master and may lespond to caresses even more affectionateh than is 
* his wont He may, however, be irritated by sti angers, or, being surprised 
by touch or blow , ma-\ inflict a bite The appetite is still good and may be 
exccssiv e Soon the restlessness becomes more marked , the dog is constantly 
in motion, he is apt to tear carpets, rugs, etc , w Inch may be in the loom w ith 
liim, he shows signs of deliiium, looking off into space apparently seeing 
some imaginary object, at times he will attack an imaginai> enem-y He 
will still respond to Ins master’s voice, bnt Ins attention cannot be held for 
anj' length of time At this early stage, the v'oice becomes modified, and 
this ma-y be regarded as one of the most t'ypical symptoms Instead of the 
deal and sharp bark winch is natural, the latter part of the note becomes 
prolonged and of a higher pitch, going off into a plaintive civ, v\hich has 
been likened to that of a dog fatigued in the chase, and in succeeding shoit 
barks v\hich may follow, the jaws do not close completely as in ordinary 
barking 

While tins sj'inptom is a striking one and quite constant, it may be lacking 
at times and certain dogs lemain quiet m spite of all attempts to excite 
barking The appetite diminishes about this time, food is taken with more 
or less difficulty, and soon it is refused, swallowing having become painful 
and difficult The animal may appear to have a bone stuck m its throat, a 
symptom which often tempts the ownei to make the dangerous examination 
for some obstruction Thei e is no fear of w ater, and the animal di inks w ater 
.ind othei liquids quite gieedily, until paralysis of the constrictor muscles 
of the phaivTix makes swallovsing impossible 

The excitement becomes marked and the animal is now furious If a 
stick or other object is presented to him, he seizes it w ith pow er, and attacks 
the bars of las cage If at liberty, heattacl^s evcij^thing in his way, swallow- 
ing all sorts of articles, such as wood, paper, straw, and stones, the piesence 
of w Inch in the stomach after death is one of the most striking postmortem 
featuics of the disease At this time he begins to wander, running with his 
tail hung, the mouth open, and the eyes with a wild look, he attacks every 
object or animal which comes m his path As a rule he runs straight ahead 
and docs not turn out of his way to attack animals The dog may tiavel 
tremendous distances, but is apt to return to his home, exhausted and 
covered with dust and blood, or else he may continue his couise until he 
falls exhausted, as manv as fiftv' miles being covered Very soon paraljsis 
sets 111, comuiencing in the hmd legs, and finally becomes general The dog 
IS no longer able to stand, vieakness becomes more marked and stupor 
sets in. from viliich the animal mav' be aroused, but which becomes deeper 
and deeper and ends in death The course of the disease is always rapid, 
cov Cling from six to ten davs, and averaging from four to fiv^e days The 
synnptoms aie so characteristic that once seen can scarcely be mistaken for 
any other disease The furious type just described is the most common 

1 aralijiic Type ^The paralytic tvjie, ordinarilv spoken of as “dumb 
rallies ( onstitiitcs from 15 to 20 per cent of all cases In certain countries, 
as 111 lurkcv, it is the prevailing type, which ex'plains the relative rantv of 



64 


INFECTIOUS DISEASES 


rabies in man in tins countiy where dogs abound The commeneement of 
the disease is the same as m the furious type, but the accesses of fuiy are 
lacking Foi seveial days the dog appears lestless, seelang seclusion and 
dark places The paialysis may commence m various paits of the body, but, 
as a rule, affects fiist the muscles of the ]aw, which soon diops, the dog being 
unable to close its mouth, and the tongue hanging out, the vhole expiession 
of the animal is pitiful m the extreme, an abundance of saliva luns fiom the ’ 
mouth, the taking of water is impossible, the mouth becomes diy, covered 
with dust, and brownish in coloi The animal is quiet, he does not respond 
to pi evocation, noi does he seem to uish to bite The piogiess of the disease 
IS more rapid than in the fuiious t}'pe The paralysis extends, and death 
occurs on the second oi third day 

Othei cases are observed m v Inch the t}q3e of the disease is more oi less 
intermediate between the two ]ust desciibed There aie some m which a 
very short period of fuiy is followed by a lapid paialysis, while in otheis 
the paralysis is more slow in its piogiess and the animal shows a slight 
disposition to attack when iiritated In the “dumb” type of the disease it 
IS common to suspect an obstruction in the throat, and in the attempt to 
locate it the saliva may infect uounds of the hand The animal never 
wanders and, being unable to bite, the danger of tiansmission is slight 

Diagnosis — Hydiophobia may be confounded with tetanus, hysteria, 
acute mama, and lyssophobia 

From tetanus it is distinguished by the longer peiiod of incubation, the 
absence of tiismus and the “iisus sardonicus,” and the complete absence of 
spasm duiing the inteivals The mental condition is different, the anxiety 
and the lestless iiiitabihty so chaiactenstic of hydiophobia aie lacking m 
tetanus The most chaiactenstic symptom of hydiophobia, vhich is lack- 
ing in tetanus, as well as the other diseases, is the lespiratoiy spasm excited 
by attempts to swallow water Hysteria sometimes simulates hydrophobia 
quite closely, especially in cases ivlieie the patient has been bitten by a dog 
and has been anxious about it In these instances there may be geneial 
convulsions with constant barking and biting A caieful review of the histoiy 
and s 3 miptoms, and especially the absence of the respiratory spasm, will 
usually make the diagnosis clear 

The differentiation from mama may be difficult at hist, and must depend 
largely on the history The rapid course of the disease will soon clear up the 
diagnosis As Gowers says, “No patient evei passed from mental health to 
a state of imminent danger in two or three days m consequence of simple 
insanity ” 

Lyssophobia is the name given to a senes of s>Tnptoms which are some- 
times seen m neivous peisons who have an exaggerated fear of hydro- 
phobia Auto-suggestion determines spasms in the throat on swallowing, 
and a dread of watei may follow m consequence The s^miptoms usually 
occur soon aftei the bite, soonei m fact than the shortest period of incubation 
in the true disease There is lacking also the tiue respiratory spasm, and 
the patient can usually be quieted by simple tieatment It has not been 
proven that death evei takes place from lyssophobia 

Prognosis — Instances of lecovery have been reported, but at best are 
so raie that a fatal outcome must always be looked for In dogs a few 
well authenticated instances of recovery following inoculation have been 
reported 



RABIES 


65 


T1i6 prognosis as regards bites by rabid animals, depends, as bas been 
stated, on the animal inflicting the bites, the size, number, character, and 
location of the wounds It depends also on the length of time which elapses 
between the injury and cauterization, and on the thoroughness with winch 
it IS done When done properly and thoroughly the protection is very great — 
in moderate wounds practically absolute The statistics of Proust shov 
that, m a series of 117 cases, which weie not cauterized, there were 96 deaths, 
while among 249 cases, in which cauterization W'as practised, only 89 deaths 
occurred When the wounds are multiple and lacerated, and especially 
when about the face and head, thorough cauterization is difficult or impossible 

The outlook is most favorably influenced by the Pasteur tieatment At 
the parent Institute up to January, 1904, 27,719 cases of all descriptions 
have been treated, wnth 117 deaths, a mortality of 0 42 per cent These 
figures exclude a small number of persons m wdiom the disease appeared 
during or w'lthin fifteen days after treatment 

As m other methods of vaccination, immunity is produced only after a 
certain lapse of time, and in cases of short incubation, oi of late commence- 
ment of the tieatment, the disease may manifest itself before the vaccinal 
effect has been procured For this reason certain cases of death are justly 
excluded from the statistics of the Pasteur treatment Their admission 
wmuld, however, raise the percentage very little The lecent w ork of Krauss 
and Kreissl throws much light on the production of immunity m man by the 
Pasteur treatment, and emphasizes the importance of beginning treatment 
promptly These authors find that the serum of healthy men, as a rule, 
does not contain any protective property against the virus of rabies, nor is 
any found immediately after the completion of vaccination, but twenty-two 
days later marked antirabic power is present, and is retained for a long time 
Cases m w^hich the treatment is unsuccessful are probably due to the absence 
of this property It is important that the treatment be begun wntliin one 
week of the bite Statistics collected by Hogyes, including 54,620 persons 
treated at 24 institutes, show' that the total mortality w'as only 0 77 per cent 
These figures prove, moreover, the harmlessness of the treatment 

In Hungary, w'here rabies is very prevalent, from 1890 to 1895 there 
w'ere 5,899 persons bitten, of wdiom 4,914 received the Pasteur treatment, 
w'lth a mortality of 1 20 per cent , wdiile among those not treated 14 94 per 
cent died of rabies 

Treatment — ^IVhen the disease has declared itself, the treatment is 
purely palliative, and directed to relieving as far as possible the suffering of 
the patient Our efforts must be diiected to preserving the strength, and 
lessening the frequency of the paroxysms Every source of annoyance, 
physical and mental, should be removed The room must be darkened, 
w arm, and quiet Only the necessary attendants should have access to the 
patient Especially must draughts of air and sharp noises be avoided The 
diet should be as concentrated as possible, and liquid Osier advises the use 
of cocaine to the fauces to facilitate the taking of liquids If the dysphagia 
is marked, recourse must be had to rectal enemata Thirst must be relieved 
by the same measures 

The list of drugs wdiich have been lecommended is a long one None 
have any specific value Hjqiodermic injections of morphia and inhalations 
of chloroform wall generally give more relief than any other drugs They 
should be used from the beginning, and no time w'asted by giving the milder 

A oxi 



66 


INFECTIOUS DISEASES 


antispasmodics Calabar bean and curara have been recommended Three 
cases of cure are credited to curara, one of which Gowers considers “un- 
doubtedly genuine ” As it acts by paralyzing the motor nerves, artificial 
respiration may become necessary 

Forcible restraint during the paroxysms is often required Tracheotomy 
has been advised, but is useless, since the dyspnoea is due to spasm of the 
respiratory muscles, and the glottis is not closed 

Preventive Treatment — ^The bite of any suspicious animal should receive 
prompt attention The invariable rule must be Cauterize as soon as 
possible and in the meantime do everything to get the virus out of the wound 
and prevent its absorption Open the wound freely so that every part of it 
can be exposed Encourage bleeding by cupping or suction with the lips, 
the mouth being well v ashed after each application Bathe abundantly, 
preferably with tepid water If the wound is on a limb, a ligature may be 
applied above the site As soon as possible the wound must be thoroughly 
cauterized For this purpose fuming nitric acid is the best agent It must 
be applied to every poition of the wound with a fearless hand, deep punctuies 
having previously been laid open with the knife In the absence of nitric 
acid, lunar caustic, the actual cautery, or strong antiseptics should be used 
The importance of early and thorough cauterization cannot be overstated 
There is strong experimental evidence that laying open the wound and the 
free use of nitric acid will save a certain pioportion of cases even after a 
lapse of twenty-four hours It should nevei be neglected, since it retards the 
development of the disease, and thus renders the Pasteur treatment more 
certain of effect 

Pasteur Method of Immunization — Pasteur observed that by residence 
in the nervous system of certain species of animals the power of the virus 
was exalted, while, on the contrary, bj residence in other species it became 
attenuated By inoculation of labbits in series, one from the other, we obtain 
a virus of greatly increased virulence, so that after about one hundred 
passages they will die with great legularity on the sixth or seventh day 
Beyond this point no increase of virulence can be obtained, therefore, 
Pasteur gave it the name “fixed virus ” On the other hand, when monkeys 
are inoculated in series, the period of incubation becomes giadually length- 
ened, until after a time the virus becomes so attenuated that it no longer 
causes death This viius may be restored gradually to its original power by 
serial passages through rabbits or guinea-pigs Thus Pasteur had at his 
command rabic virus of every degree of power, and in his eaily experiments 
he began his immunization with the greatly attenuated Viius obtained from 
monkeys, passing gradually up from the weakest to the strongest produced 
in this animal, then passing on to the exalted virus in the spinal cords of 
rabbits m the same way, until the fixed viius was reached At the end of the 
senes he found his animals immune, not only against the fixed virus but also 
against the bites of rabid dogs The method w s not absolutely certain, 
and was, moreover, impracticable for obvious reasons 

With the assistance of Chamberland and Roux the method m universal 
use to-day was worked out, depending on the fact that the rabic virus con- 
tained m the spinal cords and brains of rabbits becomes attenuated fairly 
evenly and regularly by drying when piotected from putrefaction, so that 
it IS harmless at the end of fourteen or fifteen days The method is carried 
out as follows Rabbits are inoculated subdurally with the fixed virus daily 



RABIES 


67 


At death, the spinal cord is removed with strict aseptic precautions, cut into 
three pieces, and suspended in large bottles containing a layer of caustic 
potash These bottles have an opening near the bottom as veil as at the 
top, both of which are plugged with cotton, so as to allow free passage of 
air * They are kept in a dark room at a constant temperature of 23° C 
Thus, a full series of cords from fourteen days up to one day old is at hand, 
giving various attenuations of the viius from the veakest to the strongest 
The usual dose is a portion of coid 2 to 3 mm in length, vliich is prepared 
for injection by trituration and suspension in noimal salt solution or bouillon 

After many experiments on dogs, during which it was proven that absolute 
protection could be given against the most powerful virus and also that the 
treatment was effective for animals even when instituted several days after 
infection, it was determined to try it on man The fiist patient ever treated 
was Joseph Meister, an Alsatian boy of nine years, who was severely bitten 
on the arms and legs, July 4th, 1885 The woist wounds had been cauter- 
ized with carbolic acid after an interval of some twelve hours Twelve 
injections were given in ten days, beginning with well-attenuated cords, and 
ending with a fresh cord which was fully virulent Rabbits were inoculated 
daily with the same emulsions as the boy Those inoculated during the first 
five days all escaped, while the remainder all died of rabies The boy 
showed no signs of injury and five years after the treatment was in good 
health 

As practised to-day at the Pasteur Institute in Pans, the treatment is 
modified according to the urgency of the case We have thus a “simple” 
treatment, lasting fifteen days, employed where the bites are slight, the 
ordinary treatment, extending over eighteen days, for cases of bites about the 
hand, limbs, etc , and an “intensive” treatment, which requires twenty-one 
days, applied when the bites are about the face and head and a short incu- 
bation period IS leasonably to be expected 

Calmette's Modification — ^The method of pieparmg the vaccines as 
given above requires a large number of animals and much attention, and is 
too expensive unless the numbei of patients treated is very large, which is 
seldom the case Calmette has introduced a modification which has been 
generally adopted in smaller institutes and found to be very successful 
The requisite numbei of rabbits are inoculated v ith fixed virus every tenth 
day The cords are removed at death, suspended over caustic potash, and 
placed m the drying chamber, as m the old method After forty-eight hours, 
a portion of a cord is cut off and placed in sterile glycerine contained in 
glass-stoppered bottles The operation is repeated each succeeding day 
until the fourteenth It has been shonn that cords so preserved retain their 
\nrulence unchanged for twenty-five to thirty days In this manner the full 
senes of vaccines is always on hand Inoculations are begun vith cord 
desiccated for fourteen days, and preserved twenty to twenty-five days in 
glycerine Duimg the last foui days cords are used -which have been in 
glycerine for five to ten days The dose is a section of cord 3 to 5 mm in 
length, made into an emulsion as described Experiments by Cabot show 
that the virulence is preserved unchanged for a longer time when the glycer- 
ine IS diluted He ad-suses that it be not stronger than one part to four of 
w ater 

Dilution Method of Hogyes — ^Pasteui believed that desiccation did not 
change the quality of the -virus but brought about attenuation by diminishing 



68 


INFECTIOUS DISEASES 


the quantity Acting on tins idea, Hogyes, after many experiments, perfected 
a method of immunization by dilutions He begins by injections of the cord 
of a rabbit killed with fixed virus, rubbed into a fine emulsion, and diluted 
with normal salt solution 1 to 10,000 Each day the degree of dilution is 
lessened, until at the end of the treatment it is only 1 to 100 His results, 
while good, are not as favorable as those obtained at the great majority of 
institutions where Pasteur’s method is practised It appears also from te^ts 
on animals that there is some danger of producing rabies, a iisk which is 
absent from the method with dried coids 

The Pasteur treatment should always be begun as soon after the bite as 
possible It IS useless after the symptoms have declared themselves The 
probabilities of failure are least in those who present themselves for treat- 
ment during the first week, since only those m whom the peiiod of incubation 
will be less than twenty days will fail to receive immunity The usual in- 
cubation exceeds this time considerably It has been abundantly shown 
experimentally, as well as by comparative mortality tables, that the period 
of incubation is lengthened in persons who succumb after partial or complete 
treatment 

Duration of Immumty — NIe have no statistics on this point for man 
It has been studied m dogs, m whom the protection has been found to have 
disappeared in 21 per cent at the end of one year, m 33 pei cent after two 
years, while in others it has persisted for five years Persons bitten a second 
time by a rabid dog should again receive treatment, unless a very short time 
has elapsed 

Serumtherapy — ^Babes and Lepp m 1889 reported experiments which 
showed that the blood of animals immunized against rabies acquired the 
power of more or less completely protecting other animals against the disease 
In 1891 Babes and Cerchez reported furthei work, showing that the 
blood of a strongly immunized dog would in some cases entirely protect 
other dogs from experimental inoculation, vhile m those not protected it 
would greatly retard the development of symptoms In rabbits it had no 
effect They further showed that the virus was destroyed in vitro by the 
immune blood after six hours contact Babes applied this method of treat- 
ment to 26 persons who were terribly bitten on the head by a rabid wolf 
Twelve received the immune blood of men or dogs m doses of 10 grams, 
with 1 death 

Tizzoni and Sclmarz, and Tizzoni and Centanm, have prepaied a serum 
which they believe to be both prophylactic and curative They employ 
sheep as the producing animal, and begin their injections with emulsions of 
virulent nervous matter treated with gastric juice m order to attenuate it 
After some tw^enty days the serum of the sheep has acquired such powder that 
wdien injected tw'entj^-four hours before inoculation wuth street virus it wull 
protect rabbits in the proportion of 1 part of serum to 25,000 of body 
w^eight In order to piotect against fixed virus, how'ever, the dose must be 
increased to 10 cc for each kilo of body w^eight In vitro, the serum destroys 
the virus in the proportion of 1 to 800 up to 1 to 1,600 In large doses it 
will protect rabbits against injections of street xurus into the sciatic nerve, 
even after seven days The vaccinal principle can be obtained from the 
serum m the foi-m of powder by precipitation with alcohol and drying 
Tizzoni and Centanm believe that treatment by their seium, or its active 
pnnciple, is especially indicated in cases where it is necessary to produce 



GLANDERS 


69 


immunity rapidly, as in persons with severe bites about the face and head, 
or m those who have delayed treatment 

Mane, as the result of numerous experiments, finds that it requires a long 
period of vaccination against rabies to produce an active serum in mammals 
The serum of non-vaccmated animals cannot neutralize fixed virus, but the 
serum of some birds possesses this power naturally 

At the present time it may be said that while the experimental results in 
the pioduction of an antirabic serum are very encouraging, its use has not 
gained headway practically, the method of Pasteur still being almost univer- 
sally employed 

Prevention — ^Rabies is a preventable disease Since more than 90 per 
cent of all cases are due to bites fiom dogs, and since it is kept alive in the 
canine race, our measures must be directed to the control of these animals 
It IS bettei and more humane to have them undei supervision than to sub- 
ject them to the extreme measuies sometimes enacted during the terror which 
reigns in a community in which an outbreak of rabies occurs The wholesale 
destruction of dogs sometimes seen is cruel and wholly unnecessary Among 
the measures proposed for the contiol of dogs may be mentioned high tax, 
muzzling, and the leasli, with the destruction of homeless and wandering 
animals The results of muzzling justify its recommendation, and there is 
little doubt that its strict enfoicement will eradicate labies from any com- 
munity in a short time Great Biitain furnishes a striking example of its 
efficacy In 1887 there were 217 cases of rabies m Great Britain, in 1888, 
160, and in 1889, 312 The increase caused alarm, and muzzling was 
enforced, as a lesult of which, in 1890, 129 cases were seen, 1891, 79 cases, 
m 1892, 38 cases There was much opposition to muzzling and the ordinance 
was relaxed In 1893 the number oi cases rose to 93, m 1894 to 248, and 
m 1895 to 672 Owing to the general alarm muzzling was again enforced, 
resulting at once in a marked decrease of cases, to 438 m 1896, 151 in 1897, 
17 m 1898, 9 in 1899, and none in 1900 


GLANDERS 

Synonyms — Greek, mahs, Latin, malleus, equinia, English, farcy, 
French, morve, farcin, German, Rotzkrankheit, Wurmkrankheit 
Definition — Glanders is a specific contagious disease of solipedes caused 
by the Bacilhis mallei, and transmissible to man by accidental inoculation 
The disease assumes two forms, an internal, to which the name glanders is 
applied, and an external, which is known as farcy 

History — ^As a disease of horses, glanders has been known for many 
centuries, the first systematic description of it being due to Vegetius Renatus, 
who recognized its contagious nature Solleysel, 1664^82, taught both 
direct and indirect contagion, and established the relation between glanders 
and farcy It nas not until 1749 that the question of spontaneous origin was 
raised by the elder Lafosse, who held that glanders was an inflammatory, 
non-contagious disease Although this view was combatted strongly by 
1 j Chabert, and the French governmental edicts of 1753 and 
1/84 held firmly to the doctrine of contagion, little by little the idea of 
Latosse gained ground Unfortunately the great veterinary school at Alfort 
and as most of the army veterinarians were educated there, the 



70 


INFECTIOUS DISEASES 


regulations against tlie disease were not enforced, and it became widespread 
The school at Lyon always held to the doctrine of contagion, as did many 
well-known veteimaiians m Germany, England and Italy Waldmger of 
Vienna, in 1810, gave warning of the danger to man m dissecting the bodies 
of animals dead of glanders, stating that giave accidents and even death 
could result from mtection through w'ounds During the following year, 
Lorm, a French mihtaiy surgeon, recognized glanders m man for the first 
time In 1821, Schilling gave the first accuiate description of acute gan- 
grenous glanders m man, ascribing it to some poison from animals He used 
the teim “erysipelas” how'ever In discussing this case, Naumann, director 
of the Berlin veterinary school, and Holbach, stated that, wdule malignant 
mfiammation and even gangrene sometimes followed injuries during the 
dissection of glandered horses, no instance of haim fiom living animals had 
been observed Holbach expressed his wullingness to inoculate himself wuth 
the mateiial, so suie was he of its inoffensive character 

Instances of transmission to man multiplied, and, m 1822 and 1823, cases 
were reported m the Edinhwgh Medical and Smgical Journal, which w'ere 
proved by the inoculation of an ass In 1829, Andiew Brown gave a most 
accurate description of a case, with autopsy A year later followed Elhot- 
sons’^ notable paper, with leports of cases and autopsies In 1837, the 
classic monograph of Rayer^ appealed, wdiich remains at the present day 
one of the most remarkable and best desciiptions of the disease m man The 
bacillus was discovered and cultivated byLoeffler and Schutz m 1882 Weich- 
selbaum first isolated it from glanders m man m 1885 

Glanders in the Horse. — ^The disease assumes two types, glanders 
proper and farcy, though they may co-exist In glanders the septum of 
the nose and neighboring tissues aie chiefly affected Nodules, wdiich are 
firm and translucent gray in appearance, form in the mucous membrane, 
accompanied by inflammation and a catarrhal discharge The nodules 
soften and break down, leaving irregular ulcers The glands m the neck, 
mediastinum, etc , are usually involved Nodules are ahvays found m the 
lungs, with areas of congestion, and quite often m other organs In farcy 
the disease affects chiefly the superficial lymph vessels and glands, w'hich 
become irregularly thickened and hard, forming the so-called “farcy pipes” 
and “farcy buds ” Softening and suppuration usually take place and 
ulceration follow's Secondary deposits often occur m the nasal mucous 
membrane and in the internal organs Farcy is apt to run a moie chronic 
course than glanders The bacilli are found in the nasal dischaige and 
in the suppurating lymph glands, and contagion is usually due to these dis- 
charges 

Etiology — Glanders m man is almost always contracted from the horse, 
and IS therefore practically confined to men wdiose occupation brings them 
into constant contact with hoises, such as hostlers, drivers, farmers, veterin- 
arians, knackers, etc Wright has lepoited the case of a bologna sausage 
maker employed in a factory wdiere worn-out hoises w^eie slaughtered It 
has been contracted by drinking from the same bucket, or using a cloth with 
which the nose of a glandered horse had been cleansed The disease is 
practically confined to men In 120 cases, Bollinger found only 6 w'omen 

Medico-Chinirgical Tran’sachons, vol xvi, 1830, vol xviii, 1833 
•Mem de VAcad Roydle de Mtd , Pans, 1837 



GLANDERS 


71 


All affected tissues contain the bacillus, and are virulent, the discharge 
from the nostrils is perhaps the most frequent medium of contagion The 
saliva is sometimes viiulent fiom admixture with the nasal discharge The 
blood rarely contains the bacillus and when present it is in small numbers 
They pass into the mine not infrequently Infection takes place most com- 
monly through some abrasion Mere deposit of matter containing the 
bacillus on the healthy skin is probably harmless Guinea-pigs can often be 
infected through the skin by rubbing with a pomade containing virulent 
bacilli, but It is probable that the bacilli enter through minute and unseen 
abrasions The bacillus probably penetrates the nasal mucous membrane 
quite readily Small animals are easily infected by the simple deposit of 
virulent material in the nose The conjunctiva is more resistant Infection 
through the digestive tract takes place readily, the resulting lesions appearing 
first in the lungs, as a rule Infection through the deeper respiratory tract 
appears to be rare Glanders has proved very fatal to bacteriologists, a 
number of whom have lost their lives through accidental infection while 
studying the bacillus 

Bacteriology — The bacillus n as discovered by Loeffler and Schutz in 
1882 It IS quite irregular in form and size, being 2 to 5/1 long, and 0 5 to 
1 fi thick It stains readily, but not deeply, with the ordinary aniline dyes, 
and gives them up just as readily, hence it is difficult to stain in sections of 
tissue It does not stain by Gram’s method It stains unevenly, presenting 
a beaded appearance It is aerobic, non-motile, and does not form spores 

Growth takes place at 25° C to 42° C , but best at body temperature It 
glows readily on most of the ordinary culture media when once isolated 
For isolation, blood sei um and glycennated potato are the best media On 
agar and glycenne-agai it forms a grayish-white moist growth, which is 
viscid and tenacious Bouillon is clouded uniformly, and a heavy slimy 
deposit IS formed after several days Later, a mycoderm may form on the 
surface The growth on potato is specially characteiistic By the third day 
a yellowish honey-hke growth is seen, which spreads and becomes darker, 
so that by the eighth day it is reddish-brown or chocolate-colored The 
potato often shows a greenish-yellow staining about the edge The organism 
IS quite delicate Cultures kept in the incubator usually die in two neeks 
Kept at room tempeiatuie they live six to eight weeks The bacillus soon 
loses its virulence in cultures, and must be passed through a susceptible 
animal in older to keep it up 

It IS usually killed by drying in fourteen days Exposure to light has a 
marked influence on it The nasal discharge spread on filter paper is 
destroyed m eight days in the light, but survives tv elve days in the dark It 
resists putrefaction tvo to three weeks The bacillus is destroyed by a 
temperature of 55° C in ten minutes, and by 61° C in one minute A 5 per 
cent solution of carbolic acid kills it in two to three minutes Corrosive 
sublimate 1 to 5,000 destroys it in three minutes 

The presence of the bacillus in pus or the nasal discharge is generally 
determined by the intraperitoneal inoculation of male guinea-pigs If it is 
present, in tvo to three da'^s there is observed a marked swelling and redness 
of the testicles Pure cultures are readily obtained from the testicles a few 
dajs later 

Mallcin IS an extract of the glanders bacillus containing the specific toxin, 
prepared by growing the organism for four to six w eeks in 5 per cent glycer- 



72 


INFECTIOUS DISEASES 


me bouillon It is then sterilized, evaporated to one-tentli of the oiigmal 
volume, and filteied through porcelain to remove the bacilli Before use it is 
diluted in a 1 per cent solution of carbolic acid When injected into glan- 
dered animals it provokes a definite fcbiile and local reaction 

Morbid Anatomy — Glanders is usually classed among the infectious 
granulomata Lesions may be found m almost every portion of the body 
Superficially w e find the various pustules, abscesses, and ulcers, with more oi 
less extensive areas of eiysipelatous and phlegmonous inflammation, all of 
which are apt to be about the face and limbs These have the general 
appearance of the suppuiative lesions common to different forms of pyiemia, 
and are especially characteristic of human glanders The mucous membrane 
of the nose is covered with a viscous muco-pus, under which are found 
ecchymoses, pustules, and ulcers The lattei, especially m chronic cases, 
may expose the cartilages and bones, which are necrotic 1 he septum, vomer, 
and even the palate bones are at times necrosed Cicatrices, winch are 
frequent and extensive m the horse, are larely found m man Similar changes 
are found in the frontal sinus, the pharynx, larynx, and trachea The joints 
frequently contain serous, sero-sangumolent, or puiulent fluid Osteo- 
myelitis and peiiostitis may be present, or there is more or less extensive 
necrosis of denuded bone All of the internal organs may contain nodules 
They are rarely absent from the lungs, though not apt to present the nodular 
character geneially seen in the hoise, in which animal the nodules h.^ve a 
strong connective tissue capsule, outside of which is a zone of cirrhotic lung 
tissue, in which the alveolar walls are very much thickened They are 
scattered throughout tlie lung, but are most numerous under the pleura 
They vary much in size Wright regards the lesion as essentially a focal 
pneumonia, with suppuiation and necrosis Around the nodules are formed 
areas of oedema, hemorrhage and interaheolar fibrinous exudate In chronic 
cases a capsule may be formed, as in the horse, and the central area becomes 
caseous, and, m the horse, even calcareous The serous cavities often con- 
tain serum and blood 

The spleen is large, soft and filled with blood 

The liver shows fatty degeneration, and is the seat of metastatic abscesses 

Symptoms — ^These vary with the fonn of the disease, which may be 
glanders or farcy, both of which may be acute or chronic Acute glanders 
does not pass into the chronic type, but frequently the chronic form ends m 
an acute outbreak 

Acute Glanders — ^The first symptoms may be chills, marked weakness, 
headache, anorexia, epistaxis, accompanied by more or less intense pains 
about the joints, which are more severe at night As a rule, however, local 
symptoms appear before the general phenomena The face, hands, and 
feet may become swollen and hard The lymphatics become inflamed, 
forming hard cords, tender on pressure, and the corresponding glands grow 
large and painful Phlebitis is sometimes observed In fine, the early 
symptoms are those of pvsemia After tvo or three days an erysipelatous 
condition appears about the face, and sometimes m the limbs or about the 
joints The nose, lips, cheeks, forehead, and even the scalp, are swollen and 
discolored Soon afterward a pustular eruption appears over these areas, 
somewhat resembling smallpox The pustules are, however, pointed or flat, 
and not umbihcated They are usually discreet, but may become confluent, 
forming purulent plaques Bullie containing sero-sangumolent fluid are often 



GLANDERS 


73 


me£ with, which rupture, leaving foul ulcers, or else, by drying, crusts 
Gangrene of the skin often occurs on the seat of these lesions, or follows the 
extravasation of blood into the cellular tissues Under the gangrenous skin 
large collections of pus form, and, if life is prolonged sufficiently, the separ- 
ation of the sphacelus may lay bare the tendons and even the bone 
In many cases, following the pains in the joints, hard tumors appear in the 
muscles on both sides of the body, which suppurate and discharge, often 
pointing beneath the bullous patches With the cutaneous eruption the 
characteristic nasal symptoms appear, preceded by a sense of discomfort 
and obstruction in the nose and nasopharynx Soon there appears an 
abundant muco-purulent, viscous dischaige, often streaked with blood, which 
causes excoriations of the hp Examination of the nose shows the mucous 
membrane to be red, excoiiated, and often ulcerated Pustules and ulcers 
may be found on the tonsils, pharynx, and larjmx The cervical and sub- 
maxillary glands enlarge, and sometimes suppurate 
As in the horse, a metastatic lobular pneumonia supervenes and hastens 
the end Cough becomes harassing and dyspnoea marked Impairment 
of resonance and rales are found, especially over the base of the lungs The 
expectoiation is muco-purulent 

The temperature is not much elevated at first, later it may reach 104° or 
105° F The morning remission is marked The pulse is rapid and weak 
Theie is often a foetid diarrhoea The urine contains albumin and sometimes 
blood 

Tlie mind is sometimes clouded early in the disease, and a typhoid con- 
dition, with stupoi, deafness, delirium or coma, may come on rapidly 
Death may occur with coma or convulsions 
Chrome Glanders — ^This form is met with usually as a sequence of chronic 
farcy, the nasal and respiratory symptoms coming on after a variable time, 
two to six months, though sometimes the type is chronic from the outset 
Diagnosis is very difficult in these cases The eaily symptoms are much the 
same as in the acute type, malaise, fatigue, pains in the muscles and joints 
Tlie mucous membrane of the nose and throat soon becomes involved The 
nose becomes more or less occluded, and sometimes there is severe pain 
about the root of the nose, passing up toward the frontal sinuses A muco- 
purulent discharge appeals, often streaked with blood and containing crusts 
and small blood clots Occasionally the discharge is abundant, again so 
slight that the nasal involvement may pass unobseived Examination of the 
nose leveals ulcerations, sometimes exposing the bone, or even perforating 
the septum Ulceiation of the mouth, palate and larynx may also be found 
The \oice is altered and deglutition difficult Cough is very annojung 
Often there is pain along the traehea and behind the sternum, with tender- 
ness on pressure Involvement of the lungs is manifested by dyspnoea, 
frequent cough, vith thick, grayish, blood-streaked sputum, profuse sveats, 
emaciation and exhaustion 

The other general sj mptoms are identical with those of chronic farcy — 
pains m the muscles and joints, neck and loins, diarrhoea, nausea, irregular 
chills and feiei, sveats and progressne emaciation 
The course of the disease is slow, and remissions occur Life may be 
prolonged for as much as six years, but cure seldom or never takes place 
Acute Farcy — ^Acute farcy differs from acute glanders chiefly^ in the 
absence of imohement of the nasal mucous membrane The general 



74 


INFECTIOUS DISEASES 


symptoms are much the same, chills, headache, nausea and vomiting, with 
pains in the muscles and joints The local symptoms are those of a poisoned 
wound The point of inoculation becomes an unhealthy looking ulcer, the 
lymphatic vessels and glands become inflamed, tender and enlarged The 
limbs become cedematous and erysipelatous About the sixth or seventh 
day multiple abscesses begin to form in various parts of the body without 
relation to the point of infection These may appear as inflammatory 
tumors, hard, tender, red or purplish m color, opening like furuncles, or as 
indolent, soft swellings with no reaction of the skin and surrounding tissues 
They contain usually a sero-sanguinolent fluid, rarely pus, and result m the 
formation of ulcers Besides these, large collections of pus form in the cellu- 
lar tissues The general condition of the patient is aggiavated at the same 
time, there is maiked fever and profound adynamia About the third or 
fourth week a pustular eruption appeals, which may be widely distributed 
over the face, limbs, and body The eruption is often accompanied by gan- 
grene From this point, the symptoms are identical with those of acute glan- 
ders, though life is more prolonged Dehiium and coma supervene about 
the fifth or sixth w'eek, sometimes in the third or fourth, and end m death 

Chrome Farcy — Chronic farcy is more common than chronic glanders 
The mode of onset is variable Ordinarily it follow's direct inoculation, with 
local manifestations of a poisoned w'ound, inflammation of the lymphatic 
vessels and glands appears in three or four days, accompanied wuth fever, 
nausea, and vomiting In other cases the onset is veiy acute, wuth headache, 
nausea, high fever and delirium, these symptoms subsiding after three to four 
days Again the onset is very insidious and slow There are vague pains in 
the limbs and joints, -with difficulty of motion There is loss of strength and 
vigor ivithout apparent cause After four to six w eeks, multiple abscesses 
form in the muscles or subcutaneous tissues, especially in the legs and about 
the joints They are usually not painful and there is no marked reaction in 
the skin and surrounding tissues The skin over them becomes purplish 
after a time Their size is variable, some containing as much as 500 cc of 
fluid, which may be blood, or blood and pus mixed Laudable pus is rare 
These collections may persist for six to eight months, opening externally 
finally, or sometimes being absorbed Less frequently phlegmonous 
abscesses are met with, wdiich form and open rapidly, discharging pus The 
rupture of the abscesses leaves fistul?e w’hich sometimes persist for a long 
time discharging an oily or gummy fluid, at othei times healing rapidly 
Successive crops of abscesses may follow each other for a long time, the 
patient becoming more or less emaciated and feeble 

The symptoms often abate and even disappear, so much so that cure may 
seem complete, but after a variable time, usually thiity to sixty days, relapse 
occurs and the disease resumes its course Pains in the joints and various 
parts of the body come on, digestive disturbances appear, marked by nausea 
and sometimes vomiting The abscesses foi the most part now leave 
fistulie or ulcers Emaciation progresses rapidly, the skin becomes dry, 
hectic fever wnth chills and night sw^eats comes on There is a persistent 
and foetid diarrhoea A dry cough is often present The patient falls into a 
delirium wdiich may end the scene More often acute glanders supervenes, 
and rapidly terminates life 

Diagnosis — ^This is difficult, except in acute cases where the history of 
inoculation is clear The symptoms following inoculation resemble closely 



GLANDERS 


75 


; 


those of any poisoned ound, the chief difference being that in glanders the 
period of incubation is usually thiee or foui days, ^^hlle in other forms, 
especially those due to streptococcus infection, the incubation rarely exceeds 
tiventy-four hours As soon as pus is foiined, a bacteriological examination 
should be made Glanders is best determined after the method of Strauss, 
by the intrapentoneal inoculation of male guinea-pigs 

In all cases the occupation of the patient should receive careful attention, 
though it IS often very difficult to trace any exposure to a glandered animal 
The eruptive stage may resemble smallpox The glanders pustules appear 
in successive crops and ulcerate rapidly They are not umbihcated and not 
so uniform as variolous pustules The chronic type may offer special 
difficulties Certain types of syphilis closely resemble chronic glanders 
Even the destructive changes about the nose are simulated The differ- 
entiation may rest on the eftect of specific treatment In tuberculosis the 
lungs are generally the chief seat of the disease The nose and skin are not 
usually affected 

Serum Diagnosis — ^hl’Fadyean has shown that the seium of glandered 
horses agglutinates the Bacillus mallei m dilutions as high as 1 to 1,600 The 
reaction is well marked in dilutions up to 1 to 1,000 Normal horse serum 
agglutinates slowly in dilutions up to 1 to 300 The cultures are giown in 
bouillon, and should not be more than two or three days old His results 
have been confirmed by many observers 
Prognosis — ^The outlook is bad m every form of glanders Acute and 
chronic glanders and acute farcy are practically always fatal Chrome farcy 
sometimes ends in recovery The remissions which occur may mislead one 
Hallopeau and Jeanselme have reported one case in which the remission 
persisted three years, new abscesses then appearing and the case resuming 
its course 

Treatment — If seen early enough, the seat of inoculation should be laid 
open and thoroughly cauterized, preferably with the actual cautery To be 
of value this should be done not longer than one hour after inoculation 
The treatment of the declared disease is local and general Abscesses 
should be opened as they appear, evacuated and swabbed with a solution of 
chloride of zinc 1 to 10, or other strong antiseptic, then dressed with iodo- 
form Ulcers should receive the same treatment Curettage has been ad- 
^^sed before the application of the zinc The nose may be washed out vith 
permanganate of potash or boric acid solution, followed by insufflations of 
lodofoim or aristol 

The geneial treatment is tonic and supportive There is no specific or 
any drug that appears to have any special value The best results seem to 
have been obtained from the use of sulphur and iodine m various forms 
Bendall recommends benzoate of soda at frequent intervals Nocard, 
M’Fadyean, and others, have conclusive^ demonstrated the curative effect 
of inallein in horses Babes and Bonome hav^e used it in chronic glanders in 
man in doses of t's to uh of a cubic centimeter, v\ ith apparently good results 
Great care must be taken with the discharges, soiled linen, etc , of patients, 
v\hich should be destroyed as far as possible Attendants should be varned 
of the danger from nasal discharge and the pus from the eruption, ulcers, 
and abscesses 



CHAPTERIV 


TETANUS 

Bi JAMES M ANDERS, M D , LL D 

Synonyms — ^Tnsmus, lockjaw, opisthotonos, German, Wundstar- 
krampf 

Defimtion — ^Tetanus is an acute infectious disease caused by the toxic 
products of the tetanus bacillus It is characterized clinically by painful 
muscular spasms, affecting first and principally the masseter muscles and 
those of the neck (trismus), and secondly, those of the trunk, especially the 
extensors of the spine and limbs (opisthotonos) The disease is endemic and 
rarely epidemic m large centres of population Occasionally there are small 
epidemics, the origin of which can be definitely traced, as a rule These have 
received various names according to the special circumstances under v Inch 
they develop, giving rise to so-called vaccination tetanus (from the use of 
tetanized vaccine), diphtheria tetanus (due to the use of contaminated 
antitoxin), and tetanus neonatorum, occurring in new-born children, e q , 
vhere cases have developed m the service of the same midwife Moreovei, 
hospital epidemics have been known to follow the use of infected vaccine 
virus and cat-gut sutures 

The so-called idiopathic or “rheumatic” tetanus does not exist, as was 
formerly supposed, but, according to positive recent evidence, the disease is 
invariably traumatic in origin This dictum receives striking confirmation 
from the results of a review of 1,201 cases by Anders and Morgan ^ The 
incidence of the affection, as compared with the population, is gradually 
decreasing 

A distinction into acute and chronic forms has been made The latter 
variety is commonly termed idiopathic or medical tetanus, it presents the 
same symptoms, however, as the acute or traumatic form, although less 
seveie, and runs a longer course 

Historical — In the writings of Hippocrates may be found brief and 
fairly accurate descriptions of tetanus He recognized clearly that the 
disease is usually a sequel of wounds and fully appreciated its gravity 
Among other ancient authors who described the affection were Galen, 
Celsus and Aretseus, but they distinguished the disease by the names of 
tetanus, opisthotonos, emprosthotonos and pleurosthotonos — appellations 
“expressive rather of the different inflexions of the body, than of any material 
variety with respect to the disease itself” (Cocke) Tetanus was not un- 
commonly confused with other diseases manifesting tonic muscular 
spasms, such as eclampsia, cerebrospinal meningitis, hysteria or hystero- 
epilepsy, and the like 

Galen maintained that the spinal marrow is the seat of morbid changes in 
tetanus — a view adopted by Fernehus, Hoffman, Wilhs, and other authors 

> Journal of the American Medical Association, July 29, 1905 

70 



TETANUS 


77 


More recently, Sir Charles Bell and Magendie advanced the theory, based on 
experimental observations, that the tractus motorius is principally involved 
As a natural sequel of this theory the belief gained currency, through the 
writings of Travers, Curling and others, that the disease is essentially of an 
inflammatory natuie, although the term “irritation” was adopted to account 
for the neivous phenomena or so-called reflex convulsions 

To Aretieus we are indebted for a graphic description of the symptoma- 
tology and he also laments the ph 3 'sician’s powerlessness to influence the 
fatal course The writings of Maitre and Fragault furnish proof of its 
frequent occurrence after operations In the military camps of the ancient 
wars it prevailed extensively, while m those of more modem times the 
disease showed a diminished prevalence According to many of the earlier 
contributions, the disease would appear to be confined principally to tiopical 
latitudes, but later opinion is, with justification, in more or less opposition to 
this view 

In more recent times are to be noted especially the writings of Larrey, 
Dupuytren, Laurent, Ternel, Verneuil, Curling, Eomberg, Fiiedrich, and 
Billroth The infectious nature of the disease vas fiist recognized by Ver- 
neuil but it remained for Rose to advance our knowledge of tetanus to a 
notable extent and to prepare the way for the discovery of its bacteriological 
cause Later, that philosophical observer, Nicolaier, demonstrated that 
pieces of infected earth the size of a pea would, when injected subcutaneously 
into the tail of a mouse, produce tetanus, while uninfected soil thus intro- 
duced into the animal failed to produce the disease 

Etiology — Bactenology — In 1885, Nicolaier discovered the Bacillus 
ictam It IS a long, slender rod, one end of which is often occupied by a 
spore, this distends the cell into a pm or “drumstick” shape The bacillus 
IS 2 to 4 in length and 0 3 to 0 5/i in thickness, but longer and thicker rods 
may be found m the cultures It grows at ordinary temperatures, more 
rapidly still at the temperature of the bod)', and in milk, gelatine, and agar- 
agar, it IS motile, IS easily stained by Abbott’s method, and is purely anaero- 
bic By means of Ehrlich’s method, the fully developed spores may be 
stained Kitasato was the first to make pure cultures, this is difficult since 
the presence of the smallest amount of oxygen interferes with their growth 
The bacilli can be isolated from the v ound in u Inch they develop, but the 
tetanus bacilli do not enter the circulating blood and hence are not found 
in the various oigans of the body Neither do they grow upon superficial 
vounds as a rule, owing to their anaerobic nature 

If pure cultures are injected into animals, tiqncal lockjaw ensues, but it 
uould appeal to be essential to loner the resistance of the infected locality 
in order to obtain the i irulent effect of the organism The bacillus produces 
a toxin, n Inch, w hen inoculated, causes the lethal s)'mptoms of the disease 
without the presence of the specific organism Bneger has obtained two 
poisons from sterilized pure cultures, terming the one “tetanin” and the 
other “tetano-toxin,” both being ^'lrulent poisons It is to these alkaloidal 
substances that the tonic spasms are due, so that tetanus is classed as an 
intoxication 

Mode of Action of the Toxins — ^According to Tiberti,^ whose long series 
of ex-periinents corroborate the work of Me^er and Ransom, the toxin passes 

^CcntraJbhtt fur Baht u Parasit On<7 , 1905, Band vxv\ ni, p 625 



78 


INFECTIOUS DISEASES 


to the nerve centres not by v ay of the lymphatics of the nerve, but through 
the plasma of the nerve fibers It is necessary, however, that the axis 
cylinders preserve their normal integrity m ordei that the nerve fibers may 
take up the tetanus toxin and conduct it in the direction of the nerve centres 
of the spinal cord and thence “through the centripetal neuion to the muscles 
of the same region” (Babes) Direct inoculation of the spinal cord is fob 
lowed by a brief incubation period and produces “tetanus dolorosus ” The 
so-called local tetanus is hi ought about by subcutaneous injections of the 
toxins or inoculation of special nerves Tiberti found that, following intra- 
venous injections, all the muscles of the body are affected simultaneously, 
because the toxin is absorbed synchronously by all nerve endings 

Bacillus Tetam Outside the Body — ^In the outer world the Bacillus ietani 
IS found in many localities, most commonly m manure, garden soil, street- 
sweepings, and putrefying liquids It is to be recollected that tetanus spores 
brought to a new locality may preserve their virulence for years, they may 
be contained m dust and earned into wounds and also into the respiratory 
and alimentary tracts, wheie they may set up their specific lesions in the 
presence of a diseased mucous membrane Babes, in 2 cases of tetanus 
occurring in the human subject, found that inoculations vith the fseces 
gave rise to the disease MacFarland, from an analytical study of 95 cases 
of tetanus complicating vaccination wounds, concludes that the tetanus 
organism may be present in the vaccine virus in small numbers, being 
derived from manure and hay 

Predisposing Causes — (1) Traumatism — ^^Vhile it is undisputable that 
tetanus may be caused by any soit of wound or breach of the surface, in the 
investigations by Anders and Morgan, it was found that the preponderating 
proportion of cases occuired from seveie contusions with penetration of 
foreign bodies These researches also corroborate the generally accepted 
view that the most common sites of infection are the extiemities, notably the 
hands and feet Thus, in 863 cases in which the infection atria were noted, 
the arms and hands were the gateway for the poison in 294 and the legs and 
feet in 347 cases, the hands alone in 226 and the feet alone m 280 It was 
found to be frequent after gunshot wounds of the extiemities and “Fourth of 
July hand injuries ” Next to the extremities, comes cephalic tetanus with 
53 cases Finally, the figures indicate susceptibility of all parts of the body 
to the poison 

2 Geographical Location — ^The disease is most common m tropical 
regions, although widely diffused throughout all civilized countries The 
sections of the United States in which tetanus is most frequent are “northern 
New York, along the Hudson Valley, Brooklyn and the surrounding districts 
of Long Island, southern Pennsylvania, Viigima, Georgia (at least about 
Savannah), southern Louisiana, Indiana, Illinois and southern California ” 

3 Seasons — ^The incidence is decidedly influenced by the diffeient 
seasons In the collective investigations cited above, the seasonal occurrence 
in 687 cases showed the following numerical ordei July, 129 cases, Octo- 
ber, 75, September, 68, June, 61, August, 59, May, 57, November, 47, 
April, 42, March, 41, December, 37, February, 36, and January, 35 The 
Fourth of July celebrations explain the great increase in July cases, but, 
independently of this fact, the statement holds true that tetanus is more 
prevalent in the hotter as compared ■nuth the colder months of the year 



TETANVS 


79 


4 — ^it js generally believed that tetanus is most common betv een. 
ten and thirty years of age, if v e except tetanus neonatorum The peculiar 
susceptibility of the new-born is due to wounds of the umbilical cord u Inch 
serve as infection atria The age in 583 of our cases shou ed betw een ten 
and fifteen years, 130, and betv een five and ten years, 99 From the fifth 
to the fifteenth years, 229 cases occurred (39 3 per cent ) Betu een the ages 
of fifteen and twenty-five years there were 145 cases (24 9 per cent ), while 
between twenty-five and thirty-five years, there were 86 cases (14 8 per 
cent ) Beyond fifty years there w^ere only 14 cases 

5 Sex — In 981 cases of the above senes, there w^ere 778 males and 203 
females Tlie greater incidence m the male is readily explained by the more 
frequent occurrence of wmunds 

6 So-called idiopathic tetanus is believed to follow’^ exposure to cold or 
sleeping on the damp earth, but according to the most modern view^ there is 
in all cases a wmund or injury of the skin oi mucous surfaces, how'ever 
tiinal, wdiich serves as a portal of entry It has been contended that this 
explanation is scarcely admissible in accounting for the sudden appearance 
of the disease, as happens raiely a few' hours after exposure to the cold, damp 
ground The only tenable position, how ever, is to regard colds and catarrhal 
affections as favoring causes, and w'eakened conditions as increasing sus- 
ceptibility 

Special Pathology — ^There are few definite lesions and no constant 
changes in the biain or spinal cord A careful postmortem examination often 
reveals small w'ounds, abrasions, or evidences of injuries or penetrating 
foreign bodies, most commonly m the hands and feet Splinters are some- 
times discovered under the nails Various appearances are presented by the 
w'ound or injured part, it may show' the presence of pus, collateral hyperm- 
mia and moie or less hemorrhagic extravasation The nerves leading from 
the w'ound are often the seat of inflammation and the same is true of the 
umbilicus in cases of tetanus neonatorum 

In acute cases the density of the cerebral tissue is increased and the gray 
substance is distinctly hyperiemic In the chronic form the brain and 
meninges are somewhat oedematous, and minute hemorrhages have been 
observed Congestion of the nerve centres of the medulla and cord often 
resulting m inflammation and softening, especially in the territory of the 
anterior horns, is commonly noted Perivascular exudations and granular 
changes m the nerve cells are among the histological changes 

Immunity — Behring and Kitasato have produced artificial immunity m 
animals by the inoculation of cultures of the tetanus bacillus after the addi- 
tion of iodine trichloride to dimmish their strength 

Ssmiptoms — ^The duration of the period of incubation in human tetanus 
depends on the course, whether acute or chrome In the acute form it ranges 
from a few days to two weeks, the usual period being from seven to nine 
dajs, while m the chronic, all the way from tw'o weeks to months after the 
injurj There are exceptional instances in which the incubation period is 
less than twenty-four liours In experimentally produced tetanus in animals 
(c <7 , in mice) the s’\’mptoms appear m from one to several days after inocu- 
lation with the specific bacillus and somewhat earlier still when the toxins 
are injected 

Symptoms of Acute Tetanus — ^In a mmoritj of the cases, mild pro- 
dromes, such as headache, pain m the back languor and slight ngiditj of 



80 


INFECTIOUS DISEASES 


the extremities^ are present for a short period, after ^^hlch the character- 
istic manifestations develop either acutely or gradually In many cases the 
patient quickly finds that he cannot open the mouth without great difficulty, 
and there is soon bilateral tonic spasm of the massetei muscles (tn'smits) 
More commonly, perhaps, the patient first complains of stiffness and tension 
in the muscles of the neck, this is followed, after a day at most, by spasm of 
the massetei s, vhich renders the facial muscles immobile and locks the jaws 
{lockjaw) The rigidity of the muscles of the back of the neck is shov n by 
the retraction of, and partially successful attempts at raising, the head 
Rose points out that participation of the cervical muscles is evidenced by 
the fact that the patient can hardly touch the chest with his cbm In fully 
developed trismus the masseters are of stony hardness with palpable borders, 
and the physiognomy is often highly characteristic, it is immobile, the 
forehead commonly wrinkled, the eyes paitly closed and drawn in, the 
corners of the mouth retracted, and the lips more or less protruded, pro- 
ducing a distinctive smile — 'luiis sardomcus 

At this time the teeth are, as a rule, firmly clenched and a little later the 
muscles of the body become rigid, first the trunk (orthoionos), and then all 
the muscles of the entire back become affected, bowing the spine, the con- 
vexity presenting anteriorly {opisthotonos) After a couple of days the 
rigidity of the anterior abdominal muscles (especially of the recti) is observed, 
and their contractions may throw the body forward — empwsihotonos 
Finally, nearly all of the voluntary muscles manifest tonic, preceded by 
clonic, contractions, although those of the arms usually escape Curiously 
enough, m contrast ivith the upper extremities the legs show marked iigidity 
in extension The patient assumes the lateial decubitus by preferance, as a 
rule, and maintains almost absolute quiet, he is readily disturbed 
Voluntary urination often becomes impossible ownng to suppression oi 
impediment caused by the muscular contractions, and the same is occasion- 
ally true of defecation While the position of the body is one of continuous 
rigidity, from time to time exacerbating, convulsive seizures accompanied 
wuth most agonizing suffering, thoracic oppression, dyspnoea and more or 
less cyanosis (due to interference ivith the respiratory function), occur 
The diaphragm may be similarly involved, causing sharp, lancinating pains 
at the base of the chest In one patient, “convulsive dysphagia” (as in 
hydrophobia) was noted These spasms are reflex in origin, although, 
according to Rose, m the advanced stage they cannot be produced volun- 
tarily, and yet recur at frequent or infrequent intervals wuth great sudden- 
ness and severity They can, hoivever, usually be induced by slight external 
irritation, e g , hy touching All of the reflexes are decidedly exaggerated, 
but the sensorium remains unclouded 

Profuse sw'eatmg is commonly observed Brown has reported a moderate 
leukocytosis (14,000 per cmm ) Leukocytosis as a symptom of tetanus has 
not received elaborate mention by w riters, it is probably due to the suppura- 
tion in the vicinity of the wounds that serve as infection atria The urine 
rarely shoivs tiaces of albumin and it has been demonstrated that the uiea 
IS not increased According to Senator, neither creatin nor creatmm show 
an increase m the urine Although at first sight a surprising fact, it is 
generally believed that tissue metabolism is practically unchanged in tetanus, 
the higb and prolonged muscular tension notwithstanding Fever ot a 
moderate degree is generally present, although an afebrile course may be 



TETANUS 


81 


pursued Sudden and extreme exacerbations of fever to 110° or 112° F 
occur and are pre-agonal as a rule Hyperpyrexia, however, is not invariably 
fatal, it was present in 2 among the 1,201 cases analyzed by Anders and 
Morgan, both of which ended in recovery These untoward elevations of 
temperature are probably due to paialysis of the heat-regulating centres 
A postmoitem rise of temperatuie may also be observed The pulse is 
accelerated, but in the majoiity of instances only to a moderate extent 
On the other hand, the pulse rate may be much quickened and at times a 
rapid increase to 148 to 180 is noted Such a phenomenal use is attended 
with anhythmia and a marked falling away in force and volume of the 
pulse, it is ominous 

Although commonly fatal and ahiajs exceedingly grave, recovery is 
possible even in aggravated cases, a favoiable couise is indicated by a 
gradual diminution m the intensity and the gi eater infrequency of the 
spasms, -while muscular rigidit-^ also slowly disappears The danger from 
exhaustion often followed by collapse of the cii dilation must be borne in 
mind The writer saw' one patient m wdiom apparently favorable lelaxation 
of the tonic musculai rigidity w as quickly follow ed by a fatal degree of heart 
failure The principal causes of death aie given by Cheyne and Burghard, 
as follows (1) severe larjmgeal spasm, terminating in fatal aspliyw-ia, (2) 
spasm of the diaphragm or other respiiatoiy muscles, (3) ariest of the heart’s 
action, this may be due either to spasm or paralysis, (4) profound exhaus- 
tion and inanition, and (5) severe hjpei pyrexia 

The visceial compheahons are few, but pneumonia and acute nephritis 
are occasionally obseived Inability to expectorate the bionchial secretion, 
as pointed out by Strumpel, may lead to the dcvelojnncnt of bronchitis or 
even of inhalation bronchopneumonia Various accidents and rare clinical 
phenomena have been leported The extreme violence of the tonic spasm 
may result m rupture of the muscles 

Of the senes of 1,201 cases review'ed by Anders and hloigan, certain 
interesting features and complications were levealed In 1 the trismus w'as 
so great that the teeth w ei e crushed dowm to then i oots In 3 cases, in wdiich 
no antitoxin w'as used, extensive desquamation of the skin, similar to that of 
scarlet fever, occurred It is w'ell understood that cases treated wuth anti- 
toxin manifest erythema and uiticaiia with oi without desquamation In 
3 cases the first symptom w'as seveie pain in the legion of the diaphiagm 
Fracture of the spinous processes of the vertebrae resulted from severe 
convulsions in 1 case J W Ward reported to us a case in a man wdio 
had been bitten by a dog, the diagnosis of hydrophobia w'as maintained in 
this instance for several days In 1 patient the j^ulse, followung an opera- 
tion, remained above 100 wuthout discoveiable cause until tetanus super- 
vened Another patient showed signs of iiiitabihty with unreasonable 
outbursts of anger, accompanied by ^erky spasmodic movements, with a 
tendency to throw the head back, and nystagmus 

Chronic Tetanus — The symptoms of trismus, or the first stage of the 
disease, develop less abruptly than m the acute foim and are less pionounced 
There are other cases in which the condition remains incompletely developed, 
the patient being able to separate the jaw's sufficiently to allow of nourish- 
ment being given In such cases the symptoms may suddenly become 
aggravated, soon to be follow'ed, how'ever, by a remission In favorable 
cases the intervals of partial freedom from the painful tonic muscular spasms 



82 


INFECTIOUS DISEASES 


grow longer and thus finally the stage of convalescence is reached However, 
in certain cases the sequence is characterized by a gradual progressive 
intensification of the trismus and othei symptoms, at last ending fatally The 
cases that never become matured manifest slight if any constitutional dis- 
turbance, and not uncommonly terminate in recovery Under these cir- 
cumstances, the course of the affection may be greatly protracted However 
mild a given case may be, the fact mentioned above, that it may suddenly 
manifest the severest symptoms, should be recollected more especially in 
connection vnth the question of the piophylactic treatment Relapses are 
not uncommon unless the antitetanic serum is used 

Head Tetanus — ^This is a special variety first discovered by E Rose, and 
due to injuries, often trivial, confined to the distribution of the cranial nerves 
or more commonly of the facial nerve This variety is uncommon, only 5 
per cent being due to face and head injuries The most distinctive features 
are rigidity of the masseter muscles, and spasm of the pharynx and oesopha- 
gus, paralysis of the face on the side of the injury being usually associated 
There are cases m Avhich the spasmodic contractions of the oesophagus 
suggest a clmioal analogy between the disease in question and hydrophobia 
All other symptoms of ordinary tetanus are manifested in a more or less 
typical fashion, although the abdominal muscles are rarely involved The 
great majority terminate fatally Willard’s statistics indicate that 25 per 
cent of the chronic cases end in recoveiy, but m the acute form less than 
10 per cent survn'e 

Tetanus Neonatorum — ^Tetanus m the new-born should be biiefly de- 
scribed The cases are divisible into two classes, e g , early and late, the 
former developing several days, and the latter eight or ten days, aftei birth 
The most pronounced feature is tiismus, Avhich prevents both crying and the 
administration of food Within a day or tA\ o opisthotonos supervenes and 
death soon follows In the cases that develop late the violent muscular 
spasms occur at more frequent intervals, they rarely terminate favorably 
The condition is often overlooked 

A collection of 1307 cases^ from the United States showed the greatest 
prevalence in Louisiana, the District of Columbia, Maryland, Michigan, 
Illinois and Pennsylvania In this connection it is of interest to note that 
the census report from Louisiana for 1870 and 1880 shoivs a total of 806 
cases, of which 642 were instances of tetanus neonatorum Happily the 
mortality figures show a marked decrease for the period between 1890 and 
1900, as compared Avith the three previous decades 

Sequelse — ^The most common sequel is more or less muscular rigidity or 
stiffness, Avhich may outlast tetanus for a period of months Thus, m one 
patient of the series cited above, recovery ensued m eight Aveeks, but decided 
stiffness remained for eighteen months In another, marked mental dis- 
turbance A\ as noted for two months after recovery from tonic spasms, with 
perfect restoration at last In another instance, acute nephritis followed the 
cessation of muscular contractions, and, later, suppuration of both parotid and 
the submaxillary glands occurred Paralysis is a rare sequel, Kitasato has 
produced paralysis m man by the injeetion of small quantities of tetanus 
to\m into the femoral vein Relapses are common , this is especially true of 
the trismus 

* Anders and Morgan Journal of the American Medical Association, December 
22, 1906 



TETANUS 


^3 


Diagnosis —The usual history and characteristic mode of invasion, 
especially the early appearance of trismus, followed by rigidity of the cervical 
and dorsal muscles, justify an assured diagnosis There are, however, 
certain affections which bear a clinical lesemblance to tetanus Chief among 
these are cerebrospinal meningitis, hydrophobia, hysteiia or hystero-epilepsy, 
tetany, and strychnine poisoning In the subjoined table the distinguishing 
features of tetanus and strychnine poisoning are contiasted 


Tetanus 

Reception of a wound, generally fol- 
lowed by a variable period of incu- 
bation 

Begins with lockjaw, then tonic spasm 
of muscles of neck, later spreads 
downward, the arras and hands es- 
caping 

Reflex spasms not present at the outset 

Rigidity IS persistent, except in the 
chronic form, m which partial relaxa- 
tion may occur 

The course is prolonged into days or 
weeks 

Cultures made from the discharges of 
the wound show the Bacillus tetani 


STniCHNiNE Poisoning 

Ingestion of strychnine, follow'ed im- 
mediately by the symptoms 

Begins with gastric disturbance or a 
tetanic contraction of the extremities 
Hyiieroisthesia of the retina occurs 
and objects look green 

Violent convulsions present from the 
commencement 

Intervals of complete relaxation 


Course is brief, terminating speedily in 
death or recovery 

Chemical examination of the gastric 
contents shows strychnine 


Tetany is distinguished by protracted spasms limited to the extremities 
(the hands m paiticular), and the laiyngeal muscles, with complete inter- 
missions, also by an increased electiical and mechanical excitability of the 
motor nerves and a characteiistic posture Moieovei, it occuis chiefly in 
young subjects and there is no history of a wmund 

In hystena or hystei o-cpilcpsy opisthotonos may be piesent but tiismus is 
rarely observed, and, when fixation of the jaws occurs, the conti actions of the 
muscles of mastication are manifested at iiiegulai inteivals Hystena also 
presents associated characteristic nervous phenomena and theie is an absence 
of the history of a primary wound 

Hychophohia — ^This can be distinguished by a history of the bite of an 
animal, by the violence of the reflex spasms of the respiratory apparatus, 
the great intensity of the psychical distuibance, and the absence of tiismus 
and opisthotonos Cases of tetanus have been reported, although rarely, 
caused by the bite of an animal, e g , the dog If in such instances laryngo- 
spasm and dysphagia arise, the resemblance to hydrophobia is close and 
somewhat puzzling, but the shorter period of incubation and the trismus and 
opisthotonos of tetanus would serve to eliminate hydiophobia 

Cerehospinal meningitis show-s rigidity of the ceivical muscles and theie 
may be opisthotonos, but true trismus does not occur Again, the history 
and the associated clinical phenomena, such as vomiting, hypereesthesia, 
herpes, and disturbances of the sensorium, suggest meningitis 
Certain cases of mild trismus will be found on careful investigation to be 
due to pharyngitis, tonsillitis, inflammation of the sphenomaxillary fossa or, 



84 


INFECTIOUS DISEASES 


finally, arthntis of the temperoma\illary articulation In all of these con- 
ditions, neither rigidity of the neck nor opisthotonos aie present On the 
other hand, they aie at once shown to be non-tetanic, by the detection of then 
special cause In doubtful cases, the main element, after excluding the 
commoner sources of tetanus infection, is a careful local inspection of the 
oral cavity, pharynx and the masseters both externally and internally In 
tetanus, moreover, on passing the finger into the mouth of the patient, the 
acute edge of the iigid masseters is felt between the ]aw and the zygomatic 
arch Finally, the discharge from associated injuries should be examined 
bacteriologically for the Bacillus tetani m doubtful cases 

Prognosis — In the majority of cases death ensues and the mortality is 
highest in those instances that arise after seveie traumatism The late- 
appearing cases, following an injury, give the most favorable prognosis 
Anders and Morgan analyzed the incubation period of 858 cases with 
especial reference to the mortality rate It was found that 194 (22 3 per 
cent ) showed an incubation of five days or less, with a mortality of 58 8 
per cent , 394 developed in from five to ten days v ith a mortality of 63 per 
cent , 148 gave an incubation of from ten to fifteen days with a death-rate 
of 42 per cent , and 98 cases developed m from fifteen to twenty-five days 
with a mortality of 40 per cent Regarding the duiation in 870 cases, it 
was observed that the highest death-rate occuiied on the seventh days, or in 
86 cases, the second day showed 71 deaths, the third, fouith and fifth days 
were rather constant, with about 50 deaths From the tenth day gradually, 
and the fifteenth rapidly, the mortality progiessively deci eased Again, of 
cases lasting five days or less, there vere 338 with a mortality of 275, or 
81 4 per cent , in those giving a duiation from five to ten days, or 231 cases, 
144 deaths occurred, or 63 per cent , and those lasting fiom ten to fifteen 
days, 91 cases with 27 deaths, or 30 per cent Acute tetanus or that which 
developed within ten days gave a total of 568 cases and a moitahty of 74 per 
cent On the othei hand, 211 cases lasted OA'er fifteen days, vith only 18 
deaths, or 8 5 per cent mortality 

Wilson, ‘ in an analysis of 52 cases following vaccinia, found the incubation 
to be longer on the average and the mortality also somewhat higher than in 
the ordinary variety With A C Morgan, the WTitei has collected 635 cases 
of w'hicli 615 died, 4 recovered, w4iile in the remaining 16 the issue was not 
stated 

The early direct treatment of injuries has been effective m reducing the 
death-rate of this disease, its pievention by the use of antitetamc serum is 
also quite possible Unfortunately, we haA'e no drugs that exeicise an un- 
questioned influence ovei the disease Complications and accidents of a 
serious character aie rare 

Treatment — (1) Prophylaxis — Certain measures of prevention are of 
first importance The immediate ladical cleaning of wounds, in wdiich there 
IS ground for suspecting that tetanus may develop, e g , those soiled wuth 
earth from gardens, punctured and lacerated wmunds, is of the highest import 
This embraces thorough disinfection and then cautenzation The cautei- 
izing agents must be brought into contact with every part of the wound, 
hence, punctured wmunds must first be laid open Under eertam circum- 

* Proc’edings of the Philadelphia County Medical Society, vol xxm, No 1, pp 
119-165 



TETANUS 


85 


st&ncGS^ excision of tlie wounds oi even mnputntion is to be ndvised Tlie 
.smallest foieign bodies (splinters) must be removed promptly Friediicli 
recommends, in all wounds suggesting the possibility oi tetanus, total 
excision of the focus and foreign body, supplemented by preventive injec- 
tions of antitoxin In the new-boin the wound at the navel must receive the 
utmost caie and attention to insme successful prophylaxis According to 
Beunier, the infective agent may be conveyed by unclean hands oi bandages 
as well as the raising oi dust m the puerperal bed-chamber 

Many of the correspondents during the course of the collective investiga- 
tions cited above, testified to the great efficiency of the dried serum used as a 
dusting povder after thorough excision and incision of the infected vounds 
Prophylactic injections of antitetanic serum are undoubtedly effective and 
should be employed in all cases which call for v ound purification Not less 
than 600 antitoxic units should be administered for this purpose Schreck 
reports his experience as follows “In 1903 there were 66 cases of Fourth 
of July injuries treated, with 16 deaths from tetanus resulting, in 1904, 37 
accident cases were given prophylactic injections of serum, with the result 
that no cases of tetanus developed ” 

Among other local measures maj' be mentioned caibolic acid, which, 
according to Baccelh, should be employed by subcutaneous injection 
Other writers recommend that the suspected wound be sponged out with 
the undiluted acid Again, the ice treatment of tetanus, which consists in 
immersing the part affected in ice n ith salt, or putting the patient in a very 
cold room, e g , & cold storage chamber, has been advised, this has been 
much employed in connection vith the local use of the dried serum, with 
encouraging results, but is in the wntei’s opinion less effeetual than the 
combined aseptic and antitoxin treatment 

2 Treatment of the Attack — (a) The geneial vianagemont of the 
individual case is of considerable significance The patient should occupy a 
quiet room from which the light has been in great part excluded All 
possible sources of external irritation must be strictly avoided and a trained 
nurse should always be in charge 

{b) The diet should consist of nourishing liquids The feeding should be 
systematic, the state of the patient being well considered In those in whom 
the amount of food that can be administered by the mouth is insufficient, 
rectal feeding must be resorted to and nourishment may be introduced by 
means of a small soft stomach tube or catheter passed through the nares 
Care is to be exeicised to minimize the disturbance of the patient during the 
administration of food by these methods 

(c) Stimulant'! — Although the painful tonic spasms of the muscles depend 
on a hyperexcitabihty of the motor tracts, cardiac stimulants should not be 
Withheld when heait enfeeblement supervenes Alcoholic stimulants are to 
be employed and the commencing dose should be one-half ounce of either 
whisky or brandy, to be increased if the effect be favorable in direct pro- 
portion to the urgency of the indications Other stimulants may be ad- 
ministered m combination vith alcohol Of these, strychnine, camphor, 
and digitalis hjqrodermically are the most serviceable 

3 Medicinal Treatment — Medicinal treatment has the double object 
of allaying the excitability and eliminating the toxins The first indication 
IS met by the employment of such drugs as opium, chloral hydrate, the 
bromides, calabar bean, chloroform by ihhalation, cocaine, curare and the 



8G INFECTIOUS DISEASES 

like In the writer’s experience the spasms are best controlled by chloroform 
inhalations, keeping the patient somenhat under the influence of either 
morphine or chloral duiing the intervals In view of the persistency of the 
musculai spasm, slallful care in the administration of the chloroform is' 
absolutely necessary 

Opium or morphine is to be given with due caution m view of the fact that 
it exercises an inhibitory effect upon the respiratory centies, death in tetanus 
being usually by paralysis of respiration Despite this theoretical objection, 
many authors legard this as the most serviceable lemedy Unfortunately, 
massive doses aie requiied in many cases either to induce sleep or afford 
relief from painful muscular iigidity and convulsions The best mode of 
administration is by hypodermic injection As a hypnotic more may be 
claimed for the combined use of chloial hydrate and morphine than for the 
latter alone The chloral may be given by enema, when there is inability 
to swallow, in doses of 4 gm (gi 60) eveiy eighth hour, while the morphine 
may be used at the same time subcutaneously, the doses being large (gr ss, 
gm 0 03) The heroic administration of chloial is not unattended with 
danger and cardiac stimulants should be given during its employment 

Accoidmg to the investigations of Morgan and the writer, the chloral- 
bromide treatment has been more generally employed, and the results 
obtained have been, on the whole, somewhat more encouraging than those 
from other methods Calabar bean may be combined advantageously with 
opium or chloral, oi employed separately It has yielded satisfactory results 
but only m isolated cases Cocaine has been injected under the spinal mem- 
branes, but has given only tempoiary relief from the convulsions Babes 
speaks in favor of Bacilh’s method, which consists of the subcutaneous 
injection of 5 to 10 cc (5 i to ij) of a one-half per cent solution of carbolic 
acid along the spinal column, beginning at the neck, every two hours Ac- 
cording to this observer, however, Bacilh's treatment has been largely 
abandoned m Italy Rarely, nitrate of amyl, physostigma, belladonna, 
cannabis indica, and curare have been found useful 

4 Antitetanic Serum — ^The piesent view concerning the value of anti- 
tetanic serum is that, unless given before the appearance of the tiismus, or 
before fixation of the toxins m the nerve cells takes place, it is of little, if 
any, utility It should, therefore, be well understood that the responsibility 
of preventing the full development of this disease lests with the physician 
by the timely use of pi ophylactic injections of the antitetanic serum m cases 
where infection is probable 

MacFarland reviews a group of tetanus cases that occurred m the Phila- 
delphia Hospital following vaccination After 5 fatal cases had occurred, 
every suspicious vaccination vound was thoroughly excised and treated 
antiseptically Notwithstanding these precautionary measures, “11 addi- 
tional cases developed trismus and muscular rigidity, although after the 
administration of enormous doses of antitoxin they all recovered ” Stmtzing 
found that out of a total of 96 cases treated with Behiing’s serum, only 35 
deaths ensued Behring insists upon administering the serum within twenty- 
six houis after the onset of the attack Again, massive doses as recommended 
by Copley (30 cc , to be repeated at least every six hours until improvement 
IS noted) should be administered When the antitetanic serum exerts a 
favorable influence, the spasms recur at longer intervals and with diminished 
intensity, improvement being gradual Reports of cases in which Tizzoni’s 



TETANUS 


87 


dried antitoxin was employed internally were at first decidedly encouraging 
The dose of the serum is 2 25 gm at the first dose, and 0 6 gm at sub- 
sequent doses Roux and Borrel have found that interceiebral injections of 
antitoxin offer no decided advantages The use of antitetanic serum has 
been followed by various results but appears to be without special thera- 
peutic value in fully developed cases, it manifests its efficacy chiefly in cases 
of moderate giavity, but must be administered early. 



CHAPTER V. 


GONOCOCCUS INFECTIONS 
B\ RUFUS I COLE, M D 

Introduction — ^The role which the gonococcus plays in human infec- 
tions IS now known to be an important one The consideration of the local 
infections caused by gonococci m the genital tract does not belong heie, but 
apart fiom these infections, gonococci not infrequently induce lesions in 
other paits of the body, either pnmaiily, by extension, or by metastases 
The following pages deal mainly with these exti a-gemtal lesions, the great 
variety and gravity of vliicli are astonishing By the laity, gonoirhoea has 
been largely considered as a mild and, aside from the social aspects, unimpor- 
tant disease But the physician, who legards its far-reaching consequences, 
which are hardly secondary to those of syphilis, does not considei it so lightly 
Considering the difficulty of cure of the lesions induced and the insidiousness 
with which the gonococcus acts, it is an adversary to be well reckoned with 
Historical — Gonococcus infection is one of the oldest knon n diseases 
and IS mentioned (probably) in the Bible Up to the present century, how- 
ever, it was confused with syphilis, being considei ed one of the manifesta- 
tions of the latter disease In the early part of the piesent centuiy there 
were still two schools, the identists, vho believed in the identity of all forms 
of veneieal infection, and the unicists, who thought gonorrhoea and syphilis 
were distinct diseases The former were supported by the veil-known 
experiment of John Huntei, said to have been peifoimed on himself, m 
which he inoculated gonorrhoeal pus and syphilis resulted Unfoitunately 
for himself and the tiutli, he inoculated a mixed virus But the umcists, 
under the leadership of Ricord, v ho recognized but one form of syphilitic 
infection, finally tiiumphed It was not, howevei, until the discovery of 
the etiological agent of gonoiihoea that the identists were finally silenced 
While ceitain of the extra-genital manifestations of gonorrhoea, such as 
arthritis, vere long ago thought to have an obscure association vith that 
disease, it has only been m the past few jeais that the fiequency and multi- 
form nature of the extra-genital gonorrhoeal infections have been made 
evident by the isolation of the infectious agent from these foci 

Gonococcus ■ — ^Tlus organism vas first desciibed by Neisser (1879), who 
saw it in the purulent secietion from cases of urethritis and conjunctivitis 
neonatorum Its specificity remained somewhat in doubt, however, until 
its grov th m pure culture by Bumm in 1885 

The gonococcus, as it usually appears in pus, occurs in pans, each indi- 
vidual having a form usually described as like a biscuit or coffee bean, the 
flat sides of the individuals being approximated Such a pair usually 
measures in the long axis 0 8 to 1 6/t and m cross diameter 0 6 to 0 8 As 
seen typically in gonoiihceal exudate, many of the pairs are found within 
leukocytes In contradistinction to streptococci and staphylococci, these 

88 



GONOCOCCUS INFECTIONS 


89 


oro'amsms decolorize w/ien stained by the Giam method Lastly, they do 
not, under ordinary conditions, glow on the usual culture media, but require 
a medium containing uncoagulated albumin The above points are the 
mam diffeiential ones It must be insisted upon that moiphology alone is 
not sufficient to distmguish this oiganism Stieptococci, especially vhen 
obtained fiom animal exudates, may occur in biscuit-shaped pairs Most 
closely related, howevei, to gonococci aic Mioococcus meningitidis and 
Miciococciis catav halls In moiphology and staining properties both of 
these resemble the gonococcus, but dilYoi fiom the latter in grouing on the 
ordinary ulture media "While these oiganisms arc not likely to cause errors 
in the study of urethial exudates, in the more unusual extra-genital lesions 
this possibility must alv ays be home in mind On the other hand, gonococci 
in cultures do not always shou the typical form mentioned above, but may 
appeal m somewhat oval pairs, oi as rounded individuals 

These organisms grow best on a culture medium composed of hydrocele 
fluid, ne part, and nutrient agai-agar^ two parts, or even bettei on a medium 
omposed of human blood, ne part, and agar-agar three parts Up to the 
present time no animals except man have been shown to be truly susceptible 
to infection with the gonococcus 

The production of a toxin has been demonstrated by de Christmas, 
Wasserman and others There is still a diftei ence of opinion as to the exact 
nature of this toxin, whethei it is an endotoxin and so only set fiec by the 
disintegration of the bacteria, or n hether it is a toxin produced m media by 
the metabolism of the rgamsms The part which this toxin plays m the 
production of infection is still undetermined 


PRIMARY LESIONS CAUSED BY THE GONOCOCCUS 

The usual seat of infection by the gonococcus is one of the mucous mem- 
branes Most frequently this is m the genital tract, the urethra in the male, 
the urethia or more rarely the vaginal or uterine mucosa in the female "Why 
there should be this special susceptibility of these tiacts is entirely unknown 
The infection of these membranes may be acute oi it may have a very chronic 
course, uiethritis lasting foi months or even years with occasional exacer- 
bations occurring not infrequently Often the infection does not remain 
localized, but by direct extension the infection passes into the structures 
immediately surrounding the original scat Prostatitis and epididymitis 
occur with great frequency in the male The work of Wertheim and others 
has shown the great frequency with which inflammation of the tubes, ovaries 
and pelvic peritoneum occurs in women It is these lesions especially which 
render this organism such a cause of misery m the human race While all 
of these lesions are especially treated by the gemto-urinary and gynecological 
specialist and are considered in boofc devoted to diseases of the genito- 
urinary tract, it must be remembeied that these infections may be produc- 
tive of the most obscure general manifestations Young men are not infre- 
quently treated for typhoid fever who are suffering from prostatitis, and 
women with pelvic peritonitis aie tieated for malaria and other infections 

It should be boine m mind that a most unusual train of symptoms m''y be 
associated vith a chronic piostatitis Aside fr m the neurasthenic features 
and indefinite pains, which so often are but a manifestation of this condition. 



90 


INFECTIOUS DISEASES 


the patients may complain of abdominal pain, even of such seventy as to 
suggest a renal calculus Or the pain may be in the legs, like that of sciatica, 
or in the lumbar region, or the main symptom may be a severe pruritus am 
According to some writers, m one-halt to three-fourths of all cases of gonor- 
rhoea the prostate is involved, especially in the chrome cases, and by keeping 
this possibility in mind in cases presenting the above symptoms, the physician 
may by proper treatment relieve patients of these most distressing complaints 

The obscure symptoms associated with salpingitis and pelvic peritonitis 
in the female are better knov n 

Primary gonococcus infections occur not only in the genital tract, however, 
but they may occur elsewhere, and a knowledge of these latter infections is 
of the greatest importance The other localities in ivhicli primary infections 
by the gonococcus have been demonstrated are the eye, the rectum, the 
mouth, the nose, and possibly in external v ounds of the skin As compared 
V ith the genital tract, hov ever, all of these localities must be quite resistant 
to infection with this organism 

Gonorrlioeal Conjunctivitis — The association of purulent conjunc- 
tivitis with venereal disease was long recognized, but the absolute proof that 
it might be due to the same etiological agent as urethritis, was given only by 
the discovery by Neisser of gonococci in the purulent secretion from such 
inflamed eyes, and their cultivation by Bumm and Wertheim, and finally the 
experimental production of ophthalmia ivith pure cultures These experi- 
mental inoculations were primarily undertaken for therapeutic purposes in 
cases of panus and of trachoma, as it had been noticed that a complicating 
conjunctivitis often had a decided beneficial effect in these conditions The 
demonstration that the conjunctmtis of the new-born is due to this organism 
through infection from the mother during birth is of very great importance 
Next to urethritis, conjunctivitis is the most frequent primary gonococcal 
lesion, and formerly its results v ere only slightly, if at all, inferior in impor- 
tance to the genito-unnary lesions The introduction by Cred6 of the pro- 
phylactic use of silver nitrate in the eyes of the new-born, and so preventing 
this terrible disease, forms one of the most important and brilliant accom- 
plishments of scientific medicine Before this time, in the obstetrical institute 
in Leipzig, 10 8 per cent of all new-born children suffered from conjuncti- 
vitis Since then the frequency has diminished to 0 1 or 0 2 per cent The 
great importance of this disease is shov n by the fact that it is estimated that 
10 per cent of the cases of blindness m Europe are due directly to it 

Conjunctivitis in the Adult — ^The healthy conjunctiva of the adult must 
possess a relative degree of immunity to infection with this organism, since, 
notwithstanding the very "widespread distribution of urethritis and the fre- 
quent opportunities for the infectious material to be carried to the eye, cases 
of conjunctmtis in the adult are relatively rare It must be borne in mind, 
ho'v\"ever, that the opportunities for prolonged and severe infection of the eyes 
during childbirth are much greater than are at all likely to occur in adult life, 
and that also the natural protective mechanism of the eye in the adult is 
much more highly developed than in infancy 

The condition usually starts "viuth great suddenness and intensity Follo'vi"- 
ing the early signs of conjunctivitis, great swelling of the lids develops, the 
conjunetiva becomes roughened, and the secretion becomes purulent and 
frequently forms a grayish membrane upon the eyeball Usually but one eye 
13 affected at first, and the first care of the phjsician should be directed to 



GONOCOCCUS INFECTIONS 


91 


protecting the other one This should be covered by a shield, the inner edge 
of which should be sealed with collodion, and eveiy effort should be made to 
prevent the infective secretions gaming entrance to the healthy eye 

Ti eatment — Cold compresses should be applied to the affected eye and 
very frequent irrigations with mild antiseptic solutions, such as boracic acid 
or potassium permanganate (1 to 5,000) After the great swelling has dis- 
appeared and the membrane is no longer present, 2 per cent silver nitrate 
may be applied several times a day It is of the greatest importance that 
physicians should not treat lightly any case of conjunctival infection wheie 
there can be any possibility of its being gonococcal in origin The great 
danger is the involvement of the cornea and the formation of ulcers, lead- 
ing to scar formation with resulting total blindness 

Conjunctivitis Neonatorum — ^The onset is usually within three days after 
birth The sjunptoms do not differ essentially from those occurring m the 
adult, except that m general the course is milder The bulbar conjunctiva 
IS usually not so seriously involved, and involvement of the cornea, while 
still frequent m improperly treated cases, is apparently less common than m 
adults 

Treatment — The treatment is essentially that to be employed in adults 
It IS important to institute prophylactic measures m all new'-born infants, 
both m private practice and m hospitals, whethei the occurrence of gonor- 
rhcea is suspected or not The child should be bathed, without allowing the 
bath w^ater to touch the eyes, and then into each eye a drop of 2 per cent 
silver nitrate should be instilled The objection to this application m all 
cases IS that occasionally the silver causes a slight irritation lasting for 
several days This has undoubtedly tended to prevent the universal applica- 
tion of this method, but, m the present light, physicians cannot neglect it 
without making themselves responsible m case infection supervenes A 
commission appointed by the American Medical Association to investigate 
this subject, m the hope of inducing universal application of prophylactic 
measures, has decided to recommend the use of 1 per cent silver nitrate 
solution, as being less irritating, and so overcoming any objections to its use, 
since experience has showm that a 1 per cent solution is apparently as effica- 
cious as stronger solutions For further details m the prophylaxis and 
treatment of this condition the reader should consult the wmrks on 
opthalmology 

Gonorrhcsal Proctitis — ^Tlus condition is undoubtedly more common 
than IS generally supposed According to Baer,^ infection of the rectum 
occurs m 30 per cent of all cases of gonorrhoea m women, while Huber^ 
places the number at 25 per cent In 50 cases of vulvo-vagmitis infantum, 
Buschke found the rectum involved in 4, while Flugel demonstrated its 
involvement in 11 of 56 cases 

The mode of infection is usually, first, from the vaginal secretion, which is 
permitted to flow over the perineum into the rectum , second, from the use 
of soiled nozzles, rectal tubes or specula, third, by the rupture of an abscess 
into the rectum , or lastly, a result of abnormal coitus The first mentioned 
mode is undoubtedly the most common one and explains the greater fre- 
quency of this form of infection in wmmen 

* Deutsche med Wchnschr , 1896, vol xxii, p 116 

^Arch f Dermal u Syph , 1897, vol xl, p 237 



92 


INFECTIOUS DISEASES 


There are two groups of cases of gonorrhoeal pioctitis, first, the acute, 
with severe pain m the region of the anus and with tenesmus, frequently 
associated with the foiination of ulcers in the rectum, and second, a gioup 
of cases in which the symptoms are veiy mild, and to which the attention 
of the physician is frequently not drawn unless the condition be suspected 
and looked foi Cases of cither the first or second group may run a pro- 
longed course and lead to the formation of stiictuie Konig has stated that 
gonorrhoea causes rectal stricture with greater frequency than syphilis 

Treatment — ^In the acute stages the condition should be tieated by irri- 
gations of silver nitrate (1 to 4,000) or potassium permanganate (1 to 5,000) 
The sphincter should be dilated, and if ulcers are present these should be 
touched with the silver nitrate stick Jadassohn^ speaks of observing 
perirectal abscesses secondaiy to proctitis In 2 cases in men such gono- 
coccal abscesses weie observed wheie the lectal mucous membrane appeared 
perfectly healthy 

Gonorrhoeal Stomatitis — ^IVhile gonorrhoeal infection of the rectum is 
usually lecogmzed by its direct association with infection of the genitalia, 
the nature of such an infection of the mouth may be difficult to determine 
The first definite proof that such a lesion may occur was given by the culti- 
vation of gonococci from the diseased mucous membrane by Jesionek ^ It 
IS not sufficient foi the demonstiation of gonococci from this situation, that 
only morphology and staining reactions be considered, owing to the fre- 
quent occurrence m the mouth of Mtoococcus caimihahs and other organ- 
isms closely resembling gonococci The mode of infection may be by the 
transference of infectious material on the fingers from the urethra or con- 
junctiva, or the mouth may be primarily infected by impiopei practices In 
infants, in whom this form of infection is most common, the infection may 
occur from the mother during birth 

Symptoms — The lesions usually consist of round, slightly elevated, gray- 
white spots scattered over the tongue and cheeks They vary in size fiom 
that of a pinhead to that of a pea, or these smaller spots may be confluent 
over larger areas There is no ulceration The tongue is swollen, red and 
dry Often the mucous membrane about the teeth is also swollen The 
breath is foul In some cases infection of the sublingual glands has occiiried 

Diagnosis — ^The diagnosis depends upon the histoiv, the lapid course, 
the absence of ulceration, but above all on the cultivation of the organism 
directly fiom the lesions 

Treatment — ^The treatment consists in antiseptic washes, careful cleans- 
ing of the mucous m cmbianes of the gums and about the teeth, and m severe 
cases the application of silver nitrate 

Cases of infection of the nasal mucous membrane have been reported, 
but tlie clinical course has been atypical, and the bacteriological proof that 
such lesions are truly gonococcal is still lacking 

Local Wound Infections — ^Following arthrotomy for gonococcus aith- 
ntis, infection of the incised wounds with goi ococci may occur, as in 2 < ases 
reported by Young,^ and in at least one other seen by the writer Bagmsky 
and others have also reported such infection of the umbilical cord in infants 
Juilhot has reported a case of gonococcal infection of the wound following 

Deutsche Klinil, Berl , 1905, vol x, pp 601-660 

Deutsches Arch f Ihn Med , 1898, vol Ixi, p 91 

Johns Hophins Hospital Reports, Baltimore, 1900, vol ix, p 677 



GONOCOCCUS INFECTIONS 


93 


a radical operation for hernia, and F MeyeF observed in a patient with 
vaginal gonorrhoea and multiple joint involvement, the gonorihoeal infection 
of a wound on the right middle finger A panaiitium developed and 
gonococci were found in the pus Jadassohn states, that gonococci have been 
found in vesicles on the upper hp in association with stomatitis 


GENERAL INFECTION CAUSED BY THE GONOCOCCUS 

It IS now genei ally recognized that the local lesions at the portals of entry 
and in the adjacent structures are not the only ills attributable to the gono- 
coccus Evidence is rapidly accumulating to show that fiom these local 
lesions gonococci not very mfrequentlj'^ invade the blood This is shown by 
the cases in which gonococci have been cultivated from the ciiculating blood 
as V ell as by the strong probable evidence shown in the cultivation of gono- 
cocci m foci far distant from the primary seat of infection, the probability 
being that the gonococci have been transported through the blood current, 
though of course this is not absolutelj’’ necessaiily so 

Why in certain cases gonococci invade the blood and cause a septicaemia, 
or are carried to distant parts, setting up secondary infections, is not known 
It V as formerly thought that infection of the postenpr urethra was always 
the preliminary event in a general infection But it is now known that a 
general infection may be secondaiy to a conjunctivitis or other local primary 
infection It lias been considered by others that rheumatic and tuberculous 
affections, diabetes and alcoholism predispose to this occuirence Otheis 
have considered that too active local treatment may give rise to a general 
infection It was formeily thought that a too early stopping of the urethral 
discharge might be responsible for the occurrence of complications Finger 
considers that in certain cases the bloodvessels of the pi estate gland he 
directly under the epithelium, and that these cases are more likely to have 
general infections than in cases wheie the bloodvessels are deeper Pieg- 
nancy has been considered a favoring factor Certain vriters have con- 
sidered that special laces of gonococci are moie likely to cause general 
infections, and in suppoit of this quote cases m which husband and wife, or 
man and mistress, have infected one another, and both have developed 
metastatic lesions None of these views, however, have much foundation 
on actual fact and the real conditions are still unknown 
Gonococcus Septicsemia — ^The first probable demonstration of the 
invasion of the blood by gonococci was made by Wertheim, vho, in sections 
made from an infected bladder, demonstrated the gonococci invading the 
small venules The absolute proof, however, rested with the cultivation of 
these organisms from the circulating blood by Thayer and Blumer^ in 1895 
Since this time gonococci have been cultivated from the circulating blood 
m 5 other cases occurring in the Johns Hopkins Hospital, making 6 m all 
A review of the literature has enabled the writei to collect 29 cases in w hicli 
there has been definite proof of gonococcus septiciemia by the isolation of 
the gonococcus from the blood during life It is haidly possible to draw any 
sweeping conclusions from this small number of cases In general they 
probably represent the more severe general infections, although some ran a 

^ Deutsche med Wchnschr , 1903, xxix, Ver Beil 226 
Bulletin of the Johns Hopkins Hospital, 1896, vol vii, p 57 



94 


INFECTIOUS DISEASES 


comparatively mild course Besides these well-authenticated instances, 
many others have been observed m which either from postmortem bacte- 
nological examinations, or from the general features, the evidence is strong 
that a gonorrhoeal septicaamia existed This is especially tiue of the endo- 
carditis and puerperal cases Also, m most of the cases of local infection 
at points far distant from the portals of entry, we must suppose that the 
organisms have been carried through the ciiculation In most of these, 
however, the number of organisms carried through the blood has been too 
few for us to speak of the condition as a septicaemia, or even as a bacte- 
naemia 

A study of the 29 septicaemia cases so far reported shows that they may be 
divided into four groups 1 The cases in which endocarditis has been 
present It is somewhat surprising to find that only 11 of the 29 cases belong 
to this group In most of them the clinical features have been those of malig- 
nant endocarditis, with fever, sweating, chills, and frequently the association 
of septic infarcts In 1 of them, however, there vas only a mitral insuffi- 
ciency of moderate grade, and this patient recovered All but one of the 
remaining patients died 

2 The cases in which local suppurative lesions m the internal organs or in 
the subcutaneous tissue have occurred and the general features have been 
those of pyaemia In this group belong 6 of the cases Among the local 
lesions were subcutaneous abscesses, abscess of the prostate, suppurating 
inguinal buboes, suppurative seminal vesiculitis, epididymitis, parotitis, 
peritonitis, pleurisy and pneumonia Of these, 3 died and 3 recovered, 2 of 
the latter after surgical intervention In one occurring in the Johns Hopkins 
Hospital, the blood cultures v ere made 5 days after operation foi peritonitis 
Probably in this case the general infection occurred only secondarily as a 
terminal event 

3 Cases with no metastatic local infections, or only very mild and rela- 
tively insignificant ones There were 10 of these, all of them recovered 
Possibly, strictly speaking, most of these cases should be included m the for- 
mer group, as the majority showed arthritis, some of them polyarthritis, but 
in most the ]oint involvement was mild, in some only joint pains were pres- 
ent The only instance of strict gonococcus septicaemia, without any local 
foci whatever, occurred m the Johns Hopkins Hospital and is of gieat inter- 
est In this patient, three months after an acute attack of gonoirhoea, there 
vas a continuous fever lasting seven weeks, with headache, general malaise, 
an enlarged spleen and general features resembling typhoid fever TheWidal 
reaction was negative and cultures made from the blood showed the presence 
of gonococci The patient made a perfect recoverv and the absence of endo- 
carditis IS evidenced by the fact that there were no signs of any cardiac lesion 
five months after his discharge This case shows that gonococci maj'^ cause 
a septicfemia of moderate grade, the general features of which are not unlike 
those of typhoid fever It is possiWe that such cases occur with greater 
frequency than is now suspected, and this case may throw light on certain 
cases of continued fever which are now regarded as obscure 

4 Cases of gonorrhoeal puerperal septicaemia Two such cases have been 
reported, 1 of them from the Johns Hopkins Hospital This latter instance 
was associated with malignant endocarditis The other followed an infec- 
tion of a perineal tear, with the development of a pelvic pentonitis, and later 
a general infection Both of these patients died The exact role which gono- 



GONOCOCCUS INFECTIONS 


95 


COCCI play m puerperal fever is still unsettled Some authors state that as 
many as 25 per cent of all cases of puerperal fever are due to gonococci 
This includes, howevei, the cases in vliich the infection is only a local one 
The cases of general infection are probably much more numerous than the 
fact that there have been only 2 definite eases reported would indicate 

Taking the entire 29 cases, it is found that 12 died, 16 recovered, and 
the result in 1 vas not stated The piognosis, therefore, is not neces- 
sarily hopeless when gonococci are cultivated from the blood The prog- 
nosis IS worse when endocarditis is present 

Method of Making Blood Cultures — In making cultures from the blood 
when gonococcus septicBemia is suspected, Harris has shown that it is not 
necessary that the blood be greatly diluted, as is the case with certain other 
infections, such as typhoid The growth also occurs better on solid than m 
fluid media An essential point is that the media contain a large amount of 
albuminous mateiial, and this may be furnished by the blood itself In 
making cultures it is advisable that at least f 0 cc of blood be obtained, under 
proper precautions, from one of the larger veins, m a sterile syringe, and this 
be added to melted agar m the proportion of 1 to 2 or 3, and that the mixture 
be then immediately poured into Petri dishes and allov ed to solidify Or the 
blood ma}^ simply be poured in a thin layer over the surface of slanted agar 
tubes or agar plates and allov ed to clot After from twenty-four to forty- 
eight hours the small colonies may be easily lecogmzed Owing to the sus- 
ceptibility of the gonococcus to moderate heating, it is important that the 
temperature of the melted agar to v Inch the blood is added be not above 
40° C 

Treatment — ^The treatment of gonococcus septiciemia does not differ 
from that of septicsmia due to other pyogenic agents If local suppurative 
foci of infection be present, these should be treated surgically if they are 
accessible At present there is no specific treatment for this form of infection 
Possibly treatment by vaccines, controlled by the opsonic index, may be 
applicable in this form of infection, as it has been in other forms of septi- 
c.Bmia The writer knov s of no case in which this method has been tried 


SECONDARY (METASTATIC) LESIONS CAUSED BY THE 

GONOCOCCUS 

Besides the cases showing secondary lesions in distant parts of the body 
111 vhich the metastatic nature of the infection is rendered probable by the 
demonstration of gonococci in the circulating blood, there aie other cases in 
vhich such definite proof is wanting, but yet m which the gonoiihoeal nature 
of the local focus is shown by the cultivation of gonococci from it, or is 
rendered probable by the clinical association of the secondary focus Avith the 
primary lesion There are several views as to the origin of these foci first, 
that the infection is through the blood, second, that it is through tlie lympha- 
tics, and lastly, that the lesions are due to toxins There is practically no 
evidence at present that infection to distant parts of the body occurs through 
the lymph We have heady stated that the role played by the toxins is 
largely hvpothetical The frequency with which gonococci are cultivated 
from extra-genital lesions seems to be directly proportional to the care mth 
which they are looked for Until the evidence with regard to toxins is more 



96 


INFECTIOUS DISEASES 


convincing, it seems probable that these extia-genital lesions are due to the 
localization of bacteria in loci iritnoiis i esisientiw, vliere they are able to set 
up lesions, even though the bact''ria are in very small numbeis The possi- 
bility, however, that toxins alone may cause local lesions cannot be denied 

A word should be said here in regard to the treatment of all metastatic 
foci While cairying out appropnate local treatment, the piimaiy focus 
should not be overlooked This is most often an acute urethiitis or conjunc- 
tivitis, but not infrequently it is a chronic prostatitis or vesiculitis in the 
male, or salpingitis in the female Obscure foci are too often entirely over- 
looked, with corresponding delay in resolution of the secondary lesions It 
has been claimed by some that treatment of such primary foci may stir up 
the infection, cause increased re-moculation, and so do more harm than 
good There is little eyidence foi this, and the wnter has never seen any 
harm come from proper treatment of the primary focus Of course violent 
measures should be avoided as far as possible 

GONOCOCCAL LESIONS OP THE HEART AND VESSELS. 

1 Endocarditis — ^The association of endocarditis with uiethiitis, and 
especially with gonorrhoeal arthritis, iias recognized as early as 1847 by 
Ricord, and later by Trousseau, Brandes and others The proof, however, 
that the same etiological agent vas concerned in the production of the endo- 
carditis as m that of the urethritis was only furnished by the isolation of 
gonococci m pure culture from the circulating blood dm mg life, and their 
demonstration m smears from the thr mbus on the heart valve after death, 
by Thayer and Blumer' in 1895 Thayer and Lazeai^ obseived a similar 
case in 1896, with cultivation of the gonococci fiom the circulating blood and 
also in pure culture from the vegetations on the heart valve after death In 
the following year Lenhartz obtained the organism in pure culture fiom the 
heart valve, and demonstrated its specific natuie by inoculation into the 
human uiethra 

During the past ten years the number of cases in w Inch the absolute bac- 
teriological proof of the specific nature of the endocarditis has been furnished 
has grown laige In the Johns Hopkins Hospital alone 6 cases of endocar- 
ditis have occurred in wdiich the gonococcal nature has been demonstrated 
by the cultivation of this organism from the blood during life, from the 
heait lesions at autopsy or by both methods 

Much doubt w'as at first expiessed as to the possibility of the gonococcus 
alone setting up an endocarditis, and this w'as thought to be due to the ordin- 
ary pyogenic cocci w^hich had invaded the body through the local venereal 
lesion This view rested largely on the cultivation of streptococci by Weich- 
selbaum and otheis from the endocarditic lesions in cases considered 
gonoirhoeal Further study has shown that there are piobably tw'o groups 
of cases 

1 Those in which the lesion is a tiue gonococcal one To this the name 
“endocarditis gonorihoica” has been giA'en 

2 Cases in wdiich there has been a mixed or secondary infection To the 
cases of this group the teim “endocarditis post gonoirhoeam” or “endocar- 
ditis post gonorrhoica ” has been applied 

^Arch de med exper et d’anat palliol , 1895, vol vn, p 701 
^Medical Record, New York, 1897, vol In, p 497 



GONOCOCCUS INFECTIONS 


97 


Pathology — ^Little is known of the exact pathological changes present 
in the cases of simple endocarditis winch usually recovei and in which, 
therefore, no pathological study is possible In the more severe cases in 
which the ewdence as to the specific nature is more convincing, and m 
winch there have now been frequent opportunities for postmortem study, 
the conditions aie bettei loiown These have sliown the usual appearance 
of ulceiative endocarditis with polypoid thrombus formations In many 
cases the extent of the latter has been enoimous, with great fungoid masses 
extending from the surface of the valve, and by some this has been regarded 
as somewhat characteristic of this form of endocarditis It may occur, 
however, in other forms, and is not infrequently seen in malignant strepto- 
coccus endocarditis 

As to the valves involved, it is of inteiest that in a considerable number 
of the cases in nhich the pure gonococcal nature was probable, the right 
heart was involved In 15 cases collected by Thayer the following valves 
Avere affected ' 


f aortic 7 

Left heart •{ mitral 2 

[ both 2 


Right Bide 


/ tricuspid 
\ pulmonary 


1 

2 


11 ==73 3 per cent 

Both sides, all four valves 1=6 6 per cent 


3 =20 per cent 


Kulbs* has lately reported an additional instance and has collected all of 
the cases in the liteiatuie He has included all in Avhich there is evidence 
that the endocarditis was gonococcal, even though this is not aln ays abso- 
lutely convincing Of the 49 cases, 36 were in men and 12 in women 
Involvement of the right side of the heait occuried in 10 cases, 20 per cent 
Of the valves involved 


Aortic m 
Mitral m 
Pulmonic in 
Tricuspid m 


28 4ortic and mitral m 3 

8 Mitral and tricuspid in 1 

6 Aortic, tricuspid and mitral in 1 

1 All valves m 1 


The abovfe statistics show the apparently greater fi equency of involvement 
of the light heart in g nococcal than in simple endocarditis, even greater 
than that of other foinis of ul ratn'e endocarditis, in ivhich it is ivell known 
that in general there is a greater tenden y to right-sided involvement than in 
simple endocarditis 

Olimcal Features — As in other forms f local gonococcal infection, males 
are more frequently affected th n f males, and young adults are most liable 
to the disease, though cases have be n r ported in children and in the aged 
There are two groups of cases showing clinical features corresponding to 
the anatomical lesions (1) In one group the symptoms aie those seen in 
othei forms of simple endocarditis It is difficult to be certain that these are 
truly goiiocoecal in nature, though the report by Prochaska of a case of 
simple mitral insufficiency vitli recovery, in which the organisms weie 
obtained from the circulating blood during life, renders it quite piobable 
that the cases reported as simple gonococv.al endocarditis have been really 
such It is quite possible that certain of the cases f chronic endocarditis 


^Wien Uin TFc/inscftr , 1905, vol xx, p 11, 


voi. 3—7 



98 


INFECTIOUS DISEASES 


m which no definite history of an acute infection can be obtained, oiiginated 
from a mild urethritis Further study along this line is desirable (2) The 
symptoms in the cases of malignant endocarditis which have been carefully 
studied are essentially the same as those occuriing m cases due to other pyo- 
genic organisms The fever is usually intermittent or leimttent, chills and 
sweating occur frequently There is usually a modeiate leukocytosis and 
a rapidly progressive aniemia, at times as marked as that associated v ith 
general streptococcus infections Arthritis is frequently associated with the 
endocarditis, though this is not invariable, and m many cases septic embolic 
infarcts may develop, or there may be involvement of the serous membranes, 
pericarditis, pleurisy or peritonitis These two groups, hov ever, are prob- 
ably not sharply limited, and probably cases occui of all degiees of severity 
from the mildest to the most severe 

Diagnosis — ^The diagnosis is made in the same way as in other forms of 
endocarditis Its gonococcal nature may be rendered pi obable by the asso- 
ciated lesion at the portal of entry but the definite proof can only be obtained 
by the cultivation of the organism fiom the blood during life, which may 
frequently be accomplished without veiy great difficulty 

Treatment — ^This does not differ from that of other forms of endocar- 
ditis The considerable frequency with which this condition occurs should 
cause one to consider as suspicious all patients with urethritis having a con- 
tinuous or irregular fever In these the heart should be carefully and 
frequently examined, and, if there is any suspicion of cardiac involvement, 
the patient should be put to bed, an ice-bag placed over the heart, and the 
diet restricted As in other forms of endocarditis, rest of the heart is 
probably the greatest factor in preventing advance of the process As to 
the time which patients should be kept in bed after the acute stages are 
past, in the majority one may say as long as possible 

Pericarditis — This occurs much less frequently than endocarditis, but 
may be present with endocarditis, as in the case of Thayer and Lazear, or 
in association with myocarditis, as in the case of Councilman The wnter 
knows of no cases of pericarditis without other cardiac involvement The 
amount of exudate may be very slight, or, as in Councilman’s case, very 
large, the pericardium containing at autopsy 800 cc of a hemorrhagic 
exudate 

Myocarditis — Changes in the myocardium of gi eater or less extent have 
been mentioned m association with most of the cases of endocarditis Some 
have shown necrosis and embolic abscesses Councilman has reported a 
case with severe hemoirhagic necrosis m the muscle wall m which gonococci 
could be demonstrated on cover-glasses Another case of suppurative myo- 
carditis has been reported by Iwanoff 

Phlebitis — French writers especially have dravn attention to the occui - 
rence of phlebitis m association with gonorrhoea Heller‘ has been able to 
collect 25 such cases from the literature, besides 1 of his ov n The patho- 
genesis of the condition is not certain Theie have been no obsen^ations as 
yet to show whether the condition is due to the direct action of gonococci 
upon the wall of the vein, that is, A^hether it mav be considered a specific 
gonococcus lesion, or only an associated phenomenon Considering the 
great prevalence of gonorrhoea, one must be careful m attributing all lesions 

^Berl Uin Wchnschr , 1904, vol xli, p 609 



GONOCOCCUS INFECTIONS 


99 


winch occur during the course of a urethritis to the gonococcus The occur- 
rence of phlebitis without any apparent cause and unassociated with gonor- 
rhoeal aftections, to winch Briggs^ has drawn attention, must be kept in 
mind 

The ivritei has seen a case of spinal paraplegia associated with an acute 
gonoirhoea and complicated by incontinence of urine and cystitis During 
the illness bilateral thrombosis of the femoral and piobably the external 
iliac veins developed The fuithei course showed the spinal lesion to be of 
syphilitic rather than of gonococcal origin, and the venous thr mbosis was 
probably due to an inflammation extending outward from the bladder, it 
may have been a specific gonococcus infection, but more hkf^ly was due to 
secondaiy invasion Howevei, the diiect association with urethritis and the 
frequent association with othei well-known complications of gonorrhoea, 
such as arthiitis, m many of the leported cases make it extremely probable 
that the gonococcus alone may induce a tiue phlebitis In 15 of the 26 cases 
collected by Hellei arthritis also occurred 

The veins of the lowei extremities aie most likely to be involved, especially 
the internal saphenous The clinical features do not differ from those of 
othei forms of infectious phlebitis Fever may or may not be present 
CEdema follows the venous obstruction In 16 out of 26 cases complete 
lecovery lesulted In 1 of the cases gangrene resulted and amputation was 
necessary 

Treatment — ^The tieatment is the same as of othei foims of phlebitis, 
wiappmg the extremity in cotton, immobilization and elevation 

GONOCOCCAL ARTHRITIS 

This is probably the most fiequent and also the most important compli- 
cation of gonorihoea 

Historical — ^The relation between aithiitis and urethral inflammation 
was recognized by many of the older wiiteis The confusion which existed 
m the differentiation of syphilis and gonorihcea, how'ever, renders it difficult 
to determine wdiether they were desciibmg the arthritis of syphilis or true 
gonorrhoeal arthiitis BrandeV article m 1854 is the first cleai discussion 
of the subject Pollowung this the condition w as fully studied and its clinical 
features and association w ith gonorrhoea made clear The proof, how^ever, 
that the arthritis might be metastatic in origin and due diiectly to the 
presence of the gonococci rests upon the demonstration of these oiganisms 
m the joints In 1883 Petione described what w^ere piobably gonococci in 
microscopical pieparations from the joints, but it w^as not until 1893 that 
HoclP succeeded m obtaining pure cultures and thus added the final proof 

Etiology — At piesent twm views aie held as to the direct cause of the 
aithritis first, that it is due to the action of soluble toxins elaborated at the 
seat of local infection, and second, that it is due to the localization in the 
joints of gonococci which have gained access to the geneial circulation, oi 
have passed from the local lesions to the joints thiough the Ijonphatic 
channels The mam evidence m favor of the foimei view is that adduced 

^ Johns Hophns Hospital Bulletin, Baltimore, 1905, vol xvi, p 228 
^ Arch gen de med Pans, 1854 vol n, p 257 
^Wien klin Wchnschr , 1893, vol vi, p 736 



100 


lAFLCTIOUS DISEASES 


by Wasseimcinn, who aftei injecting the toxin into his own body noticed pain 
in his limbs and joints, which lasted a couple of days That, however, a 
true inflammatory reaction occurred in the joints is not stated While 
possibly the action of toxins may explain some of the cases, the evidence in 
favor of this view is not veiy convincing 

On the other hand, the view that the lesion is due to the localization of 
gonococci in the joints is now well established by the cultivation of these 
organisms from the joints m a large numbei of the cases It must be 
admitted, however, that from many of the infected joints no gonococci can 
be grown, even though the cultures are made with the greatest care It is 
piobable, however, that often the organisms are located in the tissues, even 
where the examination shows the exudate to be steiile In a patient lately 
under observation, no bacteria, even with the gieatest care, could be demon- 
strated in the fluid obtained by aspiration, yet smeais made fiom a villus 
obtained from the joint, which was opened immediately aftei the aspiration, 
showed great numbers of gonococci In 16 cases at the Johns Hopkins 
Hospital gonococci have been cultivated from the inflamed joints, while in 
2 others gonococci weie demonstrated on cover-slips, but could not be 
cultivated In at least 13 other cases, howevei, no bacteria could be demon- 
strated on cover-slips oi in cultures As cultures were made, howevei, only 
from the more seveie cases, it is probable that the above figuies indicate a 
larger proportion of positive cases than can ordinarily be obtained by our 
present methods Other obseivers have demonstrated their presence in a 
large proportion of the cases In Komg’s clinic, gonococci have been 
cultivated in one-thiid of the cases Rindfleisch obtained positive results 
m 18 out of 30 joints examined Weiss collected 121 cases fiom the hteiature 
m which a bacteiiological examination of the joints Avas made Of these, 
92 Avere positn^e, but in only 21 Aveie the organisms obtained in culture, 
in the remainder the evidence Avas obtained by microscopic examination 
alone Baur obtained positive results m 19 out of 27 cases, by making 
cultures in Wassermann’s nutrose-serum medium He emphasized the 
importance of making the culture early in the disease, as m all of the positive 
cases the cultures were made befoie the sixth day, and in 8 of the positive 
cases second cultures made aftei the sixth day AA'eie negative Moynihan 
Avas able to obtain positive results m 8 out of 27 cases 

Certain wi iters have laid great stress on the role Avhich secondary and 
mixed infections play m the etiology In the Johns Plopkins Hospital no 
other oiganisms have been cultivated from the joints and it is probable that 
other bacteria play little or no part in this affection 
That the organisms may persist in the joints after disappeaiantc of the 
symptoms is shoAAm by a patient, lately under the obserA'ation of the niitci, 
Avho had been under treatment AVith vaccines foi gonorrhoeal arthritis of the 
light elboAA'^, and Avas discharged on NoA'embei 12th, the sAA'elling liaAing 
disappeared and the pain entirely gone He Avent back to work, but con- 
tinued to visit the hospital eA'eiy lew days foi the pin pose of liaAung his 
opsonic index taken On December 12th, he returned Avith lobar pneumonia 
He enteied the hospital and died iiorn pneumonia on December 18th Taa o 
days befoie death some sAvellmg of the right elboAv Avas noticed At autopsy 
an acute and subacute inflammation of the elboAv Avas found, from Avhich 
gonococci were obtained m pure culture. 



GONOCOCCUS INI' NOTIONS 


101 


By what channels the gonococci leach the joints iioni the local lesions is in 
most cases not demonstrable of pi oof In a few cases of arthritis the organ™ 
isms have been cultivated from the circulating blood, but these have been the 
more severe cases usually associated with other features of septicremia It 
is altogether piobable, however, that the path is through the blood curient 
The exact conditions under nhich the organisms leave the local lesion and 
are cairied to distant paits are not known There is much difference of 
opinion as to why the joints are seats of predilection for the secondary 
localization of these bacteiia The frequency vith which slight injuries 
occur in the joints, so rendering them /on imnoris resistenhw, may be one 
factor, but it cannot be the only one It must be remembered that in othei 
forms of general infection, joint lesions occur not infiequently 

Pathology —The suigical method of treating these inflamed joints has 
afforded opportunities foi anatomical study of the more seveie cases Konig 
has made the following classification of the forms of gonorihoeal joint 
involvement 

I Hydrops gonorihoicus 

II Aithritis sero-hbnnosa et catarrhalis 

III Arthiitis purulenta (empyema of joints) 

IV Arthiitis phlegmonosa (essentiallv the pen- oi para-articular form) 

These forms, hon evei , pass gradually one into the other and there is no 

sharply dividing hue The moderately severe cases which are most fre- 
quently seen at operation are not simple hydiops and yet have not reached 
the stage of empyema 

In joints of moderate severity which are frequently opened, there is quite 
marked oedema and infiltiation of the peri-aiticulai tissues On opening 
the joint a laige amount of tuibid fluid escapes, nhicli not infrequently 
contains large masses of fibrin The synovial membrane is much injected 
and the vilh are markedly swollen and led Usually no erosion of the car- 
tilage or bony change is piesent 

In the moie severe foims the exudate is veiy purulent and marked erosion 
of the cartilage and even of the bone may occur In the later stages, wheie 
there is maiked limitation of movement, there is usually an extreme grade of 
thickening of the capsule and peri-aiticular tissues, but occasionally there is 
true bony ankylosis with maiked thickening of the bones The occurrence 
of osteophytes is lare but they are undoubtedly present in some cases 

The a-rays examination in the acute stages usually shows only the peri- 
articular swelling but no changes in the bones or caitilages In the more 
severe cases the caitilaginous and bony eiosions may be seen and later the 
thickening and ankylosis Kienbock has pointed out that marked atiophy 
of the spongy portion of the bones occurs, as shown by the lessened intensity 
of the bone shadows This, however, does not indicate any inflammatory 
process in the bones themselves and is not peculiar to gonorrhoeal arthritis 
but occurs in all foims of joint infections 

Frequency — Vaiious writers estimate that from 2 to 5 per cent of all 
patients wuth gonorihcea suffer from this compheation It must be borne in 
mind, hoM ever, that many patients leave the genito-urinary clinic at the 
onset of arthritis and are treated in medical wards, that many infections are 
verv mild and the patient or physician does not associate the joint trouble 
n ith the urethritis, and finally that many cases are wrongly diagnosed by the 
phjsician, so that probably the frequency is greater than that given above 



102 


IXI'ECTIOUS DISEASES 


In 1905, 37 cases of aithiitis diagnosed as gononlioeal neie admitted to tlie 
waids of the Johns Hopkins Hospital Uiuing the same year 31 cases of 
acute rheumatic fever vere admitted Therefore, during the year, gono- 
coccal arthritis was more frequent than acute articular rheumatism, and 
almost as common as tuberculous arthritis, of vhich there were 44 cases 
Konig considers this the most frequent form of joint involvement, and states 
that “vhen a man has a purulent or sero-purulent joint inflammation, the 
urethra should alv avs be examined, and in 90 out of 100 cases a tripper v ill 
be found ” 

Arthiitis may follow any form of local infection with gonococci As 
urethritis is by far the most frequent local gonococcal infection, arthritis is 
most frequently associated wath this, but cases of arthritis complicating 
opthalmia neonatorum in infants or vaginitis in young girls are not at all rare 
Arthritis followang the inoculation of “tripper pus” into the eyes of trachoma 
patients for the cure of this condition, have been described 

Age — As urethritis is most common dining early adult life, gonorrhoeal 
arthritis occurs most commonly during this peiiod No age, however, is 
exempt It occurs in infants, secondary to opthalmia neonatorum 

Sex — ^This complication occius more fiequently among men than wmmen 
Of 223 cases collected by Weiss, 117 were men, 76 w'omen and 30 children 
Of Noithrup’s 252 cases, 230 were men and only 22 women Of 50 cases in 
the Johns Hopkins Hospital, but 7 were females Possibly the greater 
frequency of genital gonorihoea among men than wmmen largely explains the 
difference, but it is probable that many cases in women are unrecognized 
This IS especially true of post-pueiperal arthritis, many cases of which are 
gonococcal in origin Begonin collected 42 cases of puerperal “rheuma- 
tism,” and fiom their study concluded that they were gonoirhoeal in nature, 
and the wwiter has lately seen a patient in whom the gonococcal nature of an 
arthritis following childbuth seemed very piobable, if not absolutely definite 
Race — Fourteen of the 50 Johns Hopkins Hospital cases w'ere in the 
negro The latio of all colored to white patients in this hospital is 1 to 
7 The greater prevalence of gonorrhoeal arthritis in the colored is prob- 
ably explained by the greater pievalence of veneieal disease among them 
Clinical Course — ^Theie are three forms of gonorrhoeal arthritis, that 
seen by the gemto-urinaiy specialist, that seen by the physician, and that 
seen by the surgeon Every genito-uiinary surgeon is familiai with patients 
who, during an attack of acute urethritis, complain of a little tendeiness oi , 
pain in one or more joints Little or nothing is to be discovered on exami- 
nation of the joints, there is very little fevei and in a few’^ days the pains 
disappear In a second group, or rather a second stage during wJnch the 
physician is usually consulted, the joint pains are moie severe, the joints are 
led, hot and sw ollen,theie is fever, and the patient is often forced to go to bed 
These are the cases which are so often mistakenly called acute articular 
rheumatism There is a third stage, in which the brunt of the attack falls 
on one or twm joints, or the earlier stages may be so slight and transient that 
the patient does not mention them in giving the history, and the w^hole 
picture IS that of an acute suppurative arthiitis These are the patients 
who consult the surgeon, and it is for this reason that the picture of this 
malady is painted in such dark colors by many surgeons 

Onset — ^The view' is sometimes expressed that arthritis is more likely to 
occur during the course of a chronic gleet than during an acute urethritis 



GONOCOCCUS INFECTIONS 


103 


This view does not receive suppoit fiom oui statistics, as in all but 9 of oui 
43 male cases, the aithiitis iolloiied the onset of acute urethritis in from one 
day to four months In 23 of the cases, the arthiitis occuired during a first 
attack of urethritis The onset of the arthritis may follow the urethritis very 
quickly In 1 patient the urethial dischaige was noticed three days following 
exposure to venereal infection, and on the following day he had pains in the 
knees and ankles A case has been described by Resnikow in which a 
sixteen year old girl developed urethritis and arthritis four days after niar- 
iiage to a man suffeiing fiom gonorrhoea 

On the other hand, the arthritis may occur during a second, or even later 
attack of uiethiitis Eleven of our patients gave a history of from one to 
lour previous attacks of luethritis, and in 6 of these arthritis had occurred 
Avitli the previous attacks of gonorihoea The viei\ has been expressed that 
if aithritis occur during an acute urethritis, subsequent attacks are most 
likely to be accompanied by arthritis There are not enough available 
statistics to enable us to decide this point 

In many other patients, on the other hand, no liistor}' of local infection can 
be obtained This is especially true in women In men there is usually a 
history of a past attack of uiethritis, sometimes an unrecognized chronic 
gleet is present Nine of oui cases were not associated with acute urethritis, 
but in all but 4 there v as a Instoi y of attacks one to ten years previously, and 
in all but 1 there were evidences of a chronic urethritis in the shape of 
"tiipper-faden” in the urine or the presence of a urethral discharge con- 
taining gonococci 

The first symptom complained of is usually pain m the smaller joints of 
the hands and feet, though occasionally one of the larger joints, as the knee, 
may be involved from the beginning The pain is frequently fiist noticed 
w hen the patient arises in the morning Occasionally a history of exposure 
to cold and w et previous to the onset is obtained This occurred in 7 out of 
our 50 cases In this series a histoiy of trauma was rare Slight general 
malaise may occur for a few' days before the onset, but the pain may occur 
w ith very great suddenness and w ithout w arning In one instance the patient 
was perfectly comfortable, eating his dinner, when he w'as seized wuth a very 
severe pain in his hip, which so increased in intensity wnthin a very few' 
minutes that he was in agony and required morphia to relieve the veiy acute 
suffering A chill may occasionally occur at onset and pi of use sw'eating is 
not very uncommon 

General Features — Joint Involvement — Contraiy to the usual state- 
ment, in almost all cases more than one joint is involved In all but 3 of our 
50 cases theie w'as polyarthritis On the other hand, the records in the 
surgical service of the Johns Hopkins Hospital show' a considerable pro- 
poition of cases w'lth monarticular involvement Among 252 cases collected 
by Northrup, 56 w'ere monarticular, of 348 cases collected by Julhen, 143 
w ere monarticular The probable reason for this discrepancy is that many 
are seen only m the later stages, W'hen the disease is frequently localized in 
one or tw'o of the larger joints, and the early history is not carefully con- 
sideied In many cases the early involvement of the small joints is slight, 
with few' or no objective features In other cases, how'ever, a number of the 
joints show' considerable swelling, redness and tenderness The poly- 
articular involvement may last only for a few' days, or a number of the joints 
may lemain sw'ollen during the entire course Contrary to what occurs in 



104 


INFECTIOUS DISEASES 


acute articulai rheumatism, it is seldom that after recoveiy occurs in a joint 
it again becomes inflamed All the joints are not necessarily involved at 
once, how evei One joint may recover and others be involved in succession 
As to the lelative fiequency of involvement of the various joints, statistics 
differ, probably owing to the fact that frequently the mildei infections aie 
overlooked The following table shows the relative frequency of involve- 
ment of the various joints In column I are the statistics of 862 cases col- 
lected by Finger, Northrop, Weiss and Marklieim These figures probably 
include only the joints v ith fairly marked involvement In column II, are 
the statistics of 50 cases from the Johns Hopkins Hospital These include 
the joints showing marked involvement, as well as those in which the 
objective featuies v ere very slight or even entiiely absent, the determination 
of joint inflammation resting entiiely upon the patient’s history Lastly, for 
comparison in column III, the joint involvement in 310 cases of acute 
rheumatic fever, as given by McCrae fiom the Johns Hopkins Hospital, 
are quoted * 



I 

II 

III 


S62 eases 

50 cases 

310 cases 

Joints Involved 

(Finger, 

(Johns Hop- 

Acute 



Nortnrup, 

kins Hospi- 

rheumatic 


Weiss, 

tal ) 

fever 



Markheim ) 

(McCrae ) 

Knee 

346 

75 


170 

Ankle 

184 

49 


114 

Wrist 

Carpo-metacarpal 

?'} Ill 

1 29 

} 

83 

Shoulder 

76 

20 


95 

Elbow 

76 

16 


68 

Hip 

59 

34 


66 

Small joints of foot 

61] 

] 

51 1 


Metatarsal 

7 ] 73 

\ 35 


■ 55 

Toes 

5 J 

J 

4 J 


Toes and heels 

21 




Small joints of hands 

21 ] 

] 

53] 

1 

Finger joints 

35 ] 75 

13 

1 

1 

[ 61 

Phalanges 

Heel 

19 J 

J 

7 

8 J 

I 

Sterno-clavicular 

11 

7 


4 

Tempero-mavillary 

26 

2 


0 

Sterno-costal 

1 

1 


0 

Vertebral 

5 

5 


3 

Sacro-ihac 

5 

0 



Chondro- costal 

2 




Pereneo-tibial 

1 




Crico-arytenoid 

2 




Scapulo-claviculai 
Symphysis pubis 


1 


1 


1074 

294 


720 


* These figures only include the joints acutely involved while the patient was in 
the hospital If those involved before admission were added the number would be 
larger 







GONOCOCCUS INFECTIONS 


105 


A study ot these figuies shoMs that the lelative frequency of involvement 
of the various joints is about the same m gonorrhoeal arthritis that it is in 
acute rheumatic fever, except in the case of the tempero-maxillary joint, v Inch 
IS not infiequently involved in gononhceal arthiitis and vith extreme rarity, 
if at all, m acute articulai iheumatism The most striking fact brought out 
by these hgures, however, is that from the totals of columns I and III, one 
might conclude that the average number of joints involved in a case of 
acute articular rheumatism is almost 2^, vhile in gonorrhoeal arthritis, the 
average number is only about Ij If we consider the figures in column II, 
V Inch shov the total number of joints involved, mild as n ell as severe, it is 
seen that the average number of joints involved in cases of gonorrhoeal 
artlnitis in the medical service of the Johns Hopkins Hospital is about 6, or 
over tv ice as many as in acute rheumatic fevei While larger statistics may 
show that this difference is not so marked, they nevertheless shov what many 
have recognized for a long time, namely, that gonorrhoeal arthritis in most 
cases IS a polyarthritis, just as is acute rheumatic fever 

The affected joints aie usually held quite firmly fixed The pain and 
tenderness may be severe and constant but are usually markedly increased 
by motion The pain may be partly due to the stretching of the capsule by 
the effusion, as in many cases aspiration markedly diminishes the pain It 
may be severe, hov^ever, where the effusion is very slight The effusion is 
usually most marked in the larger joints, especially the knee, in which case 
there is riding of the patella But, no matter hov' large the effusion, one 
practically never sees the marked lelaxation of the ligaments, vnth resulting 
dislocation and deformity, that sometimes occurs in the severe suppurative 
joints The sv^elling is not alv ays confined to the joint, but in the elbo\v may 
extend upwaid to the shoulder and downward almost to the wrist Often 
on palpation points of especial tenderness are found These are more often 
, over the inseition of the tendons than directly over the bony prominences, 
as IS seen in tuberculous arthritis Frequently crepitus is obtained on 
passive motion, though this is not constant Often the crepitus is due to 
involvement of the tendon sheaths 

Fluid aspirated from the affected joints may be quite cleai or it may be 
distinctly purulent Cytological examination of the ffuid shov's a pre- 
ponderance of polymorphonucleai leukocytes The fluid frequently has a 
slightly greenish tinge, a feature first pointed out by Komg This is not 
characteristic of this form of aithritis, however, it may be present in acute 
rheumatic fever The vritei has seen brownish, probably blood-stained 
fluid aspirated from a joint vhich had not previously been aspirated 
Generally the more severe the joint involvement, the more purulent is the 
exudate, though this is not an absolute rule 

Fever — ^Theie is usually an irregular fever of moderate grade In 50 
cases the highest temperature was 103 5° F , but usually the temperature did 
not rise over 102°, in some not over 100° F It is important to note that the 
fever may entiielv disappear, vhile the local condition in the joint remains 
unchanged 

Blood Changes — ^Theie is usually some anaemia, but not so marked as in 
acute rheumatic fever In 19 cases the average number of red blood cor- 
puseles was 4,685,000, and the lowest count 3,872,000 The average 
hajinoglobin estimation in 23 cases was 78 per cent , the lowest 50 per cent 
A moderate grade of leukocytosis is the rule In 38 cases the average count 



lOG 


IXFECTIOVS DISEASES 


■\^as 11,500, the highest 20,200, and the lo^\est 5,000 In 23 of the cases the 
count ■was over 10,000 Thcie is no apparent relationship between the 
degree of leukocytosis and the severity of the lesions 

Diagnosis — In certain cases this is difficult The conditions ivith ivhich 
it is likely to be confounded are acute rheumatic fever, other forms of septic 
joints, tuberculosis, gout, and the acute stages of arthritis deformans The 
wniter has lately had undei observation a patient in ivliom, folloivmg an 
acute urethritis, an arthiitis appeared with a clinical course very like that 
of gonorihoeal arthritis When the patient came under observation, only the 
light ivrist w^as involved The presence of tophi in the ears, how'ever, led to 
some confusion, though neither the clinical course nor appearance of the 
joint suggested a gouty aithritis Finally an r-iay examination showed a 
bony destruction and fusion much moie like that seen in tuberculous joints 
than in gonococcal joints The low opsonic index of the blood foi gonococcus 
(0 5) suggested that the original diagnosis was the coriect one, especially as 
no leaction occuried aftei the admimstiation of tuberculin In such cases, 
wheie aspiration cannot be perfoimed and where the organisms cannot be 
cultivated directly fiom the joint, the correct diagnosis may be impossible 
and finally only be made with piobabihty by the further clinical course 

The presence of urethritis, especially with the demonstration of gonococci 
in the dischaige, is of gieat importance, although the possibility that the 
urethritis may be associated w'lth some other form of arthritis must ahvaj's 
be kept in mind Entire failure to obtain relief of the pain by the use of 
salicylates is of considerable assistance in differentiating from acute rheu- 
matic fevei 

In the early stages the course does not aid materially Certain of the 
smaller joints are not infiequently involved The persistent involvement of 
one joint, how'ever, especially if there be much eftusion, is in favor of the 
condition being gonoirhoeal Involvement of the tempero-maxillary joint ^ 
occurs more frequently in gonoiihoeal arthritis Sweating is often not so 
pronounced in gonorrhoeal arthritis as in acute rheumatic fever, wdiile 
cardiac involvement is moie fiequent in the latter Examination of the blood 
gives little assistance In doubtful cases, especially in the later stages, the 
a-ray examination is often of aid, especially in the differentiation from 
tuberculosis In gonococcus infections of the joints the outline of the bones 
usually remains distinct, even though the cartilages are eroded, w'hile in 
tuberculosis, the outline is often entnely gone and the bones appear as if 
fused In gonococcus and other acute infections the atrophy of the bone is 
quite uniform, but in tubeiculosis it is focal and ii regular, and on the plate 
the bone appears mottled and “pitted ” 

The demonstration of gonococci in the fluid aspirated fiom the affected 
joint foims the only absolutely positive means of arrmng at a diagnosis 
In making cultures the fluid should be obtained by aspnation, the most 
rigid care in technique being employed Cultures should be made by adding 
3 cc of h-ydrocele fluid to 10 cc of melted agar and to this 1 cc of the joint 
fluid IS added and, after mixing, a plate is poured Eight to ten such plates 
should be made and examined aftei tw'enty-four hours for the presence of 
minute colonies \ 

Meakins has laielv studied the opsonic index to gonococcus in cases of 
gonorrhoeal infections, especially arthritis, as w^ell as in other foims of 
arthntis In 26 cases of gonorrhoeal infection, the index at the first examin- 



GONOCOCCUS INFECTIONS 


107 


ation (before giving vaccines) as, in all but 1, below 0 75, 1 being as low 
as 0 2 In the one exception, the index was 0 S3, and in this case the diagnosis 
was doubtful In 14 cases with non-gonoirhoeal infection, the index ranged 
from 0 05 to 1 If this is constant, it is quite evident that it will be of con- 
siderable value in the diagnosis of the gonorrhoeal metastatic infection It is 
evident, howevei, that it will be of moie negative than positive value, inas- 
much as in many cases in which the exact nature of the lesion is doubtful, 
an acute urethritis is present, and this of itself would probably account for 
the low index On the other hand, a normal or high index offers some 
evidence against the gonococcal nature of a joint affection The variation 
in the index must be of sufficient extent that the possibility of technical 
error may be excluded The absolute accuiacy and value of this method 
of diagnosis is still uncertain 

Treatment — In the mild attacks the main treatment should be directed 
to the genital lesion Whethei m these cases re-infection from the genital 
lesion IS constantly occuirmg is not known, but there is little doubt that the 
patients recovei moie quickly when theie is active and successful treatment 
of the primary lesion The joints should also be protected from injury, and 
this IS best accomplished by putting the patient to bed Wiapping the 
infected joints in cotton, or the application of compresses soaked in a lead 
and opium solution often relieves the pain In the acute stages the joints 
should be kept peifectly at rest, and this can best be done by fixation on 
splints It IS very doubtful whether diugs do any good Many physicians 
employ potassium iodide, gr 15 to 20, every four hours, vith vhat are 
thought to be beneficial results In a doubtful case it is Avell to try salicylates 
but if it be gonoirhoeal arthritis, little result can be expected 

Rogers^ has advised the use of an “antigonococcus” serum, which has 
been prepared by Torrey by the injection of cultures of the gonococcus into 
rabbits The nature of the action of this serum has not yet been definitely 
determined and its value is uncertain 

Lately, the writer, m association with Meakins, has treated 15 patients 
with gonorrhoeal arthritis by the injection of a gonococcus vaccine, con- 
trolling the dosage and time of administration by the determination of the 
opsonic index of the blood serum according to the method of Wright 
The vaccine consists of an emulsion of gonococci in 0 85 per cent salt 
solution The numbei of bacteria per cubic centimeter is estimated by a 
special method, and the vaccine is then heated to 65° C for one hour, to kill 
the organisms The usual dose in starting is two hundred million bacteria, 
and this is repeated, or a larger dose is given, as the index, after the first rise, 
IS falling The attempt is made to keep the index as high as possible A 
detailed report of these cases will be found in the Johns Hopkins Hospital 
Bulletin, 1907 The results so far have been encouraging, and sufficient to 
justify a more extensive application of the method The mam value has 
been in the more acute cases, though there has also been decided improve- 
ment in some of the more chronic ones With this treatment, each patient 
must be carefully studied and followed, otherwise it is possible that the 
vaccines may do more haim than good 

Counterirritation, either by the application of the Paquelin cautery or by 
baking, seems frequently to have a beneficial influence In using the oven, 

^Journal of the American Medical Association, 1906, vol xlvi, p 261 



108 


INFECTIOUS DISEASES 


the joint should be \\iapped in flannel, and the temjieiatuie laised to 250° 
to 300° I'i' for tA\enty minutes, then the oven is allowed to cool before 
lemovmg the extremity Of late yeais the method of pioducmg passive 
hypeifemia, intioduced by Bier, has been largely employed as a therapeutic 
measure A\ith appaiently good lesults In applying this to the knee, a 
flannel bandage is first placed on the foot and lover leg Then, a shoit 
distance above the knee, tvo or thiee turns of a thin, light rubber bandage 
are applied This must not be tight enough to cause arterial obstruction 
The toes should lemain vaim and the skin over the knee should become 
flushed and hot If it is pale and cold, the tourniquet is too tight If it 
causes pain it is too tight, and should be at once leadjusted It is advised to 
leave it on the first time not ovei three or foui hours, but this time may be 
inci eased fiom day to day, so that aftei a few days the bandage remains on 
for tw elve out of the tw enty-foui hours, or even longer 

Whenevei the joint becomes distended wnth fluid this should be aspirated 
at onee This is a veiy easy proceduic if the knee be aftected, but moie 
difficult m the case of the othei joints Veiy gieat care in technique should 
be employed in perfoiming this operation The removal of the fluid fre- 
quently gives gieat relief fiom pain, but often the fluid quickly le-accumu- 
lates Repeated aspiiation may be performed under these circumstances 
The application of a tight flannel bandage immediately aftei may aid in 
preventing re-accumulation The winter has had very little experience with 
the injection of lodoforimzed oil, dilute carbolic acid oi solution of bichloride 
of meicury through a trocar Guyot,* however, claims good results in 13 
cases by w'ashmg out the joints, through a trocai, wnth bichloride of mercury 
solution 1 to 4,000 When such a procedure, how^ever, is indicated, w'e feel 
that undei circumstances where the surgical technique is good, it is better 
to perfoim arthrotomy and thoioughly irrigate the joint w ith one of the above 
solutions 

As soon as the most acute stages are ovei, passive motion should be begun 
and persisted in, despite the pain pioduced In many joints shownng firm 
fixation, this could have been pievented by the eaily application of passive 
motion and massage Too much stress cannot be laid on this part of the 
treatment It often requires considerable persistence on the part of the 
physician and much courage on the patient’s part, but is fiequently the only 
way to obtain a good functional result Baking, massage, the Bier method 
and passive motion should all be employed during the latei stages There is 
no condition for w^hich so much can be done by active treatment and none 
in which such deplorable results follow neglect 

Surgical Treatment — ^The above described methods suffice in a consider- 
able numbei of cases, but unfortunately, not in all, and in spite of the greatest 
caie, some of the more severely affected joints wall go on to erosion of the 
cartilage and bone w itli ankylosis, unless other measures are employed It 
IS to prevent this unfortunate result that recourse must frequently be had to 
surgical measures Opening the joint and careful irrigation wath antiseptic 
solutions will, in the majority of these cases, prevent the progress of the 
infection, and bring about rapid and complete recoveiy The gieat difficulty 
IS to make an early decision as to the joints w'hich it is necessary to open 
The demonstration of gonococci in the joint fluid has been considered by 


‘ These de Pans, 1906 



GONOCOCCUS INFECTIONS 


109 


some to be a positive indication for arthrotomy Certainly where gonococci 
are found, it is much safer to call in a surgeon, but on account of the frequent 
difficulty in demonstrating the presence of gonococci in the joints, even when 
they are present in considerable numbers, we cannot rely on this criterion 
alone On the other hand, we cannot state positively that every joint from 
which gonococci aie cultivated will go on to suppuration and ankylosis 
The writer has had one patient under observation m whom gonococci were 
cultivated from the joint fluid, the patient refused operation and the joint 
recovered completely A\ith perfect motion 

Even though gonococci are not demonstrated, however, we feel that if on 
aspiration a very turbid cloudy fluid is obtained, and if the local and general 
symptoms are quite severe, the treatment should be surgical Also, although 
the fluid obtained on aspiration be quite clear, if it repeatedly re-accumulates 
and the symptoms and signs lemain marked, it is much safer to have the 
joint opened It is impossible to give any absolute indications Much must 
be left to the discretion of the physician in the individual case It is fre- 
quently a difficult question, but it is bettei to eir in occasionally opening a 
joint unnecessarily, than to allow one joint to become fixed and ankylosed 
In coming to a conclusion, one is necessaiily influenced bj' whether conditions 
permit perfect suigical technique or not Of course this is absolutely 
essential, but with good surgeons and suitable sunoundings, secondary 
infections should nevei occui , only a small incision, not over an inch long, 
need be made into the capsule The joint should then be thoioughly 
irrigated with a solution of bichloiide of mercuiy, 1 to 10,000, followed by 
normal salt solution 

Where ankylosis has alieady occiiried, the treatment is most difficult If 
the stiffness is due only to peiiarticular thickening, the adhesions may occa- 
sionally be broken up under a general anaesthetic, and by subsequent passive 
motion and massage a movable joint obtained It may be necessary to 
repeat the movements undei a geneial anaesthetic on one oi more occasions 
There is so much pain associated with this method, and it requires such a 
degree of Spartan fortitude on the part of the patient to keep up the motion 
in such a joint, that sometimes the result is haidly woitli the effort, and it is 
extremely rare that a patient can be induced to persist sufficiently to obtain 
a satisfactory result The method should ahiaj^s be tiied, lion ever If 
bony ankylosis has occuned, the treatment must be entirely suigical 

Results — ^With the methods outlined above, and especiallv vith early 
operation in the moie severe cases, the results are very satisfactory The 
great danger is that permanent ankylosis may result, or that the condition 
may become chronic and a condition like arthiitis def rmans result 

Relation to Arthritis Deformans — Permanent ehanges m the joints not 
infrequently follow the more severe cases of gonoirhoeal arthritis These 
changes may be associated vith more or less persistent pain, and there 
may be mild exacerbations extending over consideiable periods of time, e\en 
years These features have led some vriteis to suggest a veiy close re- 
lationship between gonorrhoeal aithritis and arthritis deformans, some 
even going so far as to suggest that gonococci may be the cause of certain 
cases of the latter disease Stev art found a previous history of gonorrhoea 
m 30 per cent of his cases of arthntis deformans This, however, does not 
agree with the statistics of 110 cases reported by McCrae, in w'hicli this 
li.story w’as found only m 14 cases, or about 13 pei cent Goldthwait makes 



110 


INFECTIOUS DISEASES 


a distinction on both pathological and clinical giounds between the cases of 
chronic arthritis following the acute infections, such as gonorihoea, and tiue 
arthritis deformans New bone formation may occur in the foimei, but the 
thickening is similar to that ^^hlch follows aseptic peiiostitis and occuis 
wherever the periosteum is present, and is not a thickening of bone at the 
edge of the caitilage, as is seen in true aithiitis deformans 

Of special interest m this connection is the lelation of gonoirhoeal aith- 
ritis to so-called spondylitis defoimans In 1879 Biadfoid‘ desciibed a case 
of ankylosis of the veitebiie following repeated attacks of gonorrhoeal 
arthritis Konig has desciibed a similar case, and HeihgenthaP mentions 
cases leported by Bier, hlarie, Raymond, Rendu and Renauld The wiitei 
has seen seveial cases of spinal iigidity in v Inch the onset v as m ith aithiitis 
associated with gonorrhoea Whethei anatomical and pathological diftei- 
ences in these cases will be found on fuither study lemains to be seen At 
piesent the whole question as to the lelation of chionic gonorrhoeal joint 
changes to arthritis detoimans must be left open, until fuithei work is 
done on the etiology and pathology of the lattei disease 
Painful Heel, Gonorrhoeal Heel, Painful Foot, Talalgia — The 

exact relation of this affection to gonorihoea has only lately been demon- 
strated It w^as at first consideied as an intercmrent affection in gonorihoea, 
or a manifestation of a numbei of conditions, as gout, rheumatism, trauma, 
etc Whethei the same manifestations may occm in all these conditions or 
not IS still uncertain, but it is now quite definite that the gieat majoiity ot 
cases are gonorrhoeal in oiigin In 9 cases Vincent was able to show' its 
direct association with gonoiihoea in 7, and of 10 cases repoited by Duithe®, 
8 weie undoubtedly gonoiihoeal in oiigin It occurs most frequently m men, 
especially in those actively engaged on then feet The symptoms usually 
appear shoitly following an attack ol uiethritis, oi associated with it Fie- 
quentlywith this aithritis occurs in one oi moie joints It occuried alone 
in only 2 of Fomniei’s 11 cases, and only once in Duithe’s 8 cases In the 
early stages the patient complains of pain in the feet on w'alkmg In the 
acute stages, the pain may not be localized, and the entire foot is soie and 
painful, w'lth tender points ovei the tendons and small joints When the 
patient consults a phvsician, the tenderness is usually localized to the plantai 
surface of the heel The patient has a peculiar gait, in which most of the 
W'eight of the body is boine bv the toes Usualh the pain is not present when 
the patient is at lest The affection is almost alw ays bilateial There maj' be 
marked inciease in the deep leg leflexes, even ankle clonus, and, as in a 
patient seen by the wiitei, the condition may at fiist suggest an organic 
lesion of the cord The most tioublesome featuie is the chionicity It often 
lasts for months, even foi many yeais 

The natuic of the undeilying condition has been much discussed In 
several cases m wffneh operation A\as perfoimed, Fiench obseiA'eis liaA'e 
found a bursitis But tl is lesion has been found in very few of the cases and 
CA'en then has not been A'erA sti iking oi definite Otheis have found a 
fibious tlnckening ovei the plantai surface of the calcaneum 

The impoitant changes Aveie firot desciibed by Jacquet in one of his cases 
On the plantai suiface of the heel, especially at the seat of oiigin of the 

^Boston Medical and Surgical lournal 1879, c'ol ci, p 098 

’’Centralbl f d Grenzqeb der Med u Clnr , 1900, vol iii, p 58 

^ These de Paris, 1903 



GONOCOCCUS INFECTIONS 


111 


flexor bi'evis digitorum muscle, was an exostosis He thought this lepie- 
sented a late stage of the disease, wdiich in the early stages consisted of 
changes in the osteofibrous structures over the plantai surface of the cal- 
caneum, wnth subsequent bone foimation, either a new' deposit in the fibrous 
tissue, or a new outgrowdh of bone It w'as thought that this bony out- 
giow'th rarely occurred, as it w'as only found in 1 case, and in 8 cases de- 
scribed by Durthe radiographs revealed its piesence in only 1 case Baei,^ 
how'ever, has lately described 6 cases, in all of which this exostosis w'as sliown 
to be piesent by radioscopic examination It is theiefoie probably not a 
rare form or stage of this affection, but occuis wnth considerable frequency' 
Five of these cases w'eie operated upon and 4 w'eie examined bacteriologi- 
cally In 3 of the cases gonococci w'ere demonstrated, once in puie culture, 
and twnce m stained sections, thus furnishing the absolute pi oof of the 
relationship of gonococci to this condition He thinks, how'evei, that other 
infectious processes may cause a similai condition 

Removal of the exostoses by incision on the lateral aspect of the foot has 
completely relieved these 5 patients, so that surgical interference is indi- 
cated in all patients showniig exostoses 

Gonococcal Bone Lesions — ^The acute bone lesions, as periostitis, 
osteitis and osteomyelitis have not been very caiefully studied Lately Watts 
has recorded a case of acute periostitis, wnth cultures of the gonococcus 
from the lesion Osteomyelitis is of veiy rare occurrence Undoubtedly all 
of these lesions may occur, but apparently the bony sti uctures are not fre- 
quently attacked by this oiganism These acute lesions have a more impor- 
tant suigical than medical inteiest and need not fuither be discussed here 
In the discussion of the gonoiihoeal heel, we have shown that true exostoses 
may be due to the gonococcus Undoubtedly erosion of the ends of the bones 
in arthiitis may afteiw'ard lead to new' bone formation Aside from the 
gonorrhoeal heel, however, true exostoses are undoubtedly lare 

Gonococcal Tenosynovitis — ^This is frequently associated wnth artlm- 
tis, but may occur independently The infection usually occurs in the 
tendon sheaths about the ankle orw'rist joints Gonococci have been obtained 
from the exudate by Jundell, Bloodgood, Flexnei and others It is best 
treated by fixation and the application of the Paquehn cautery over the 
infected areas 

Gonococcal Chondritis and Perichondritis —Tins is an exceedingly 
rare manifestation of gonococcal infection In a case in an infant reported 
by Kimball,^ an abscess of the larynx betw'een the mucous membrane and 
the thyroid caitilages w'as found at autopsy Cultures made from the pus 
show'ed a pure grow'th of Diplococciis gonoi ? Iwica A case has lately occui red 
m the Johns Hopkins Hospital, in w'hich duiing an attack of gonorrhoeal 
arthritis, tenderness and sw'elhng developed ovei the thj'roid cai tilagc This 
Jiatient made a perfect recovery Finger has reported a case in w hich a pure 
culture of gonococci w'as obtained from an aiea of perichondritis about the 
cartilage of a rib 

Gonococcal Myositis — Muscular Atrophy and Non-suppurative Myo- 
sitis ^Associated W'lth aithiitis in almost all cases, more oi less extensive 
atrophy of the adjacent muscles occuis This, as is w ell know n, is not pecu- 

^ Surgery, Gynecology/ and Ob-itetrics 1906 vol ii, p 168 

^Medycal Record, vol Kiv, p 761, 1903 



112 


INFECTIOUS DISEASES 


liar to gonorrhoeal aithritis, but occurs in association with all sorts of joint 
lesions Whether this is an “atiophy of disuse” as it was foiinerly consideied, 
or due to so-called “iefle\ trophic distmbances,” or whether it results fiom 
direct extension of the inflammation from the joint to the surrounding mus- 
cles, probably vanes in different cases Kienbock and others have ascribed 
this atrophy in certain cases, wheie it is very extensive and associated with 
much pain, to neuritis, which they consider not infrequently associated with 
arthritis In the cases like those of Dercum and Kienbock, where the atrophy 
IS out of all proportion to the joint involvement, and where it progresses in 
spite of improvement in the joint condition, the atiophy is almost certainly 
due to a polyneuritis Probably in some of the cases a true non-suppurative 
myositis occurs in association v ith the joint lesion The differentiation of 
nerve and muscle involvement, however, especially when there is a great 
deal of peri-aiticular infiltration and oedema, offers very great difficulty, and 
it IS questionable whether it can be done 

The occurrence of a non-siippuiative gonorrhoeal mjositis unassociated 
vvnth joint lesions has so far not been demonstrated 

Suppurative Myositis — Acute inflammation of the muscles v\ith pus 
formation may occur either as an extension fiom an infected joint or as a 
local manifestation of a general infection The former probably occurs with 
considerable frequency, the latter with v'eiy great rarity (see Decoussei, 
Thhse de Pa) is, 1905) Harris and HaskelP hav'e reported a case of purulent 
myositis in wdnch neither the history nor careful search at operation gave any 
indication of joint involvement In this case the abscesses were m the 
gastrocnemius and soleus muscles and in the muscles ovei the sacrum The 
treatment in these cases is surgical, free opening and drainage 

Gonococcal Adenitis — Cases of adenitis with the isolation of gonococci 
from the infected gland have been repoited by Pithevm and Raymond, Petit 
and otheis The course is not characteristic and the treatment does not 
differ from that employed in other forms of suppurative metastatic infec- 
tion of the glands 

COMPLICATIONS INVOLVING THE NERVOUS SYSTEM 

Symptoms of involvement of the nervous system occui not infrequently 
in association wuth gonorrhoeal infections The etiological relationship is 
not clear, howevei According to some writers, the lesions m the nervous 
system aie due to the action of toxins, this view"^ being based mainly on the 
experimental work of Moltschanoff ^ This observer produced an ascending 
parah^sis m animals by the injection of killed cultures of gonococci, and he 
was able to demonstiate definite microscopic lesions m the spinal cord and 
peripheral nerves IMany of the yepoited cases have undoubtedly been 
examples of purely accidental association of jiervmus lesions and gonorihcea 
The writer has seen an instanc of spastic paiaplegia associated with gonor- 
ihoea, and at fiist it was thought that the lesion of the cord might be gonoi- 
ihceal in origin On caieful inquiiy, howevei, a histoiv of syphilis was 
obtained, and the nervous sjaiiptoms entirely disappeared under anti- 
syphihtic treatment A sufficient numbei of cases, how ever, have now been 

* Johns Hopkins Hospital Bulletin, 1904, vol x\ p 39o 
^ Mvnehen vied TTc/mscftr , 1899, vol xhi, p 1013 



GONOCOCCUS INFECTIONS 


113 


lepoitecl to render it quite piobable either that the gonoiihoeal infection 
favois the development of ceitain nervous lesions winch are not strictly 
gonoirhceal in oiigin, or that the gonococcus itself, oi its toxins, may induce 
specific nerve lesions So far, however, no specific clinical or pathological 
features have been noted 

The mam lesions which have been described are the following 

Neuritis and Neuralgia — Dunng an attack of gonorrhoea there may 
occur either a neuralgia associated with paroxysmal attacks of pain in the 
course of the nerve trunks, oi a neuritis, wnth moie continuous pain, and 
tenderness over the nerves, with consecutive muscular atropliy and electrical 
reactions oi degeneration These foims of nerve involvement occur especially 
m association with inflammation of the adjacent joints In many cases it is 
difficult to differentiate the symptoms of neuritis from those associated wnth 
the arthritis, especially where there is much muscular atrophy secondary to 
the joint involvement 

The nerves which are most frequently involved, aside from those associated 
with inflamed joints, are those in proximity to the genitals, especially the 
sacral trunks In some of these cases, however, disease of the sacro-ihac 
joint may be present Of Eulenberg’s^ 9 cases of neuritis, in 6 there was 
involvement of the sciatic nerve, in 2 of the tibialis, and in 1 of the radiahs 
and medianus All the cases of sciatica show^ed bilateral involvement 

Sciatica — Lesser has drawm special attention to the gonorrhoeal sciatica, 
and thinks that many of the cases of sciatica wuthout obvious cause, especially 
m w omen, have this origin He points out as distinguishing features the very 
sudden onset during or shortly after an attack of acute urethritis, the infre- 
quency of recurrence except W'lth a fresh attack of urethritis, and the presence 
of fevei Bernhardt^ has reported a case of paralysis in the distribution of 
the musculo-cutaneous nerve, in wdiich there w'as appaiently no joint involve- 
ment whatever Cases of optic neuiitis and neuritis of the othei cerebral 
nerves m association wuth gonorrhoea have been reported, but the natuie of 
the association has not been made clear 
Generalized Polyneuritis and Meningomyelitis.— Cases of general 
neuritis unassociated wnth arthritis occur with very great rarity Kienbock® 
was able to collect but 4 such cases He regards these cases as toxic in 
origin The association of lesions of the spinal cord with gonorrhoea has 
long been recognized In 1803, Everard Hume reported a case of gonoi- 
ihoea with sjmiptoms attributable to involvement of the spinal cord 

There have been several views held at various times as to the nature of 
the cord lesions occurring during gonorrhoea 

1 The early view that the symptoms are due to reflex impressions on 
the cord from the local lesion, the so-called ” urinary paraplegia ” There 
have been various modifications of this theory, but for none is there any 
evidence 

2 That a myelitis is present, originating by extension upw^ard of a neuritis 
invohnng the neiyes supplying the genito-urmary organs 

3 That a true meningomyelitis is present, due either to the gonorrhoeal 
toxins or to a localization of gonococci m the cord Levden especiallv^ has 
drawn attention to the occurrence of gonorrhoeal myelitis In 1894, Barrie 

^Deutsche mod Wchnschr , 1900 vol i p 686 
’’Bcrl klin Wchnschr 1905, vol xlu, p 1097 
' ^Saml Urn Vortr , Leipz , 1901, No 815 


VOI 3 — S 



114 


INFECTIOUS DISEASES 


collected 25 of these cases, in only a very few, liowevei, was the clinical 
diagnosis confirmed by postmortem evamination In the only case with pos- 
itive bacteriological findings, staphylococci were cultivated The whole 
question requires further elucidation, and the matter can only be settled by 
the further study of cases with modern methods 

Neuroses — Of more importance probably than the organic gonorrhoeal 
nervous lesions, is the functional psychic disturbance ivliich so often accom- 
panies and follov s the gonococcus infection, especially when this is pro- 
longed and associated with metastatic foci While properly not strictly part 
of the gonorrhoeal infection, it belongs to the so-called “paragonorrhoeal 
complications” (Jadassohn), namely, these processes in which neither the 
gonococcus nor its toxin may be regarded as the direct cause of the phenom- 
ena The syinptoms may be of any grade, from slight mental depression 
and psychoneurosis to hysteria, psychasthema or marked melancholia 
These symptoms die not infrequently seen m patients with arthritis and 
form d distressing feature of this condition They are especially marked 
in chronic prostatitis In some cases, a\ ith the relief of the piostatic irritation, 
the mental featuies entirely disappear It must be remembeied, however, 
that the local treatment has a maiked suggestive influence, and it may be 
difficult to determine whethei it has been the psychic or organic treatment 
which produced the desired result In many cases with prolonged pain, as 
in arthritis, the patients are conscious of a constant feeling of self-reproach, 
and unless they are skillfully treated and encouraged, the neurosis may be- 
come of more serious import than the gonorrhoeal infection itself 

PULMONARY COMPLICATIONS 

Pneumonia. — ^Either lobar or lobular pneumonia may occur during an 
attack of gonorrhoea, and pneumonia has been present in certain cases of 
gonorrhoeal septicremia The pneumonia occurring undei these conditions, 
however, shovs no special features, and the absolute proof is still v anting 
that gonococci play a direct role in the production of this lesion The finding 
of gonococci in the sputum of these cases must be accepted with caution, 
unless care has been taken to exclude Miciococcus cataii halts In a case 
reported by Bressel,^ of a young man Avith acute and severe gonococcal ure- 
thritis, who had lobai pneumonia, Giani negative diplococci veie not only 
demonstrated m the sputum — only on microscopic examination, hoivever — 
but t-^qiical gonococci vere cultivated from the ciiculating blood While 
this cannot be considered absolute proof that the pulmonary lesion itself 
Avas due to gonococci, yet it renders such jirobable This patient recovered 

Pulmonary infarction has occuried m cases of gonorrhoeal endocarditis 
(case of Thayer and Lazear) 

Pleurisy — A considerable number of cases of pleuiisy said to be due to 
gonococci have been reported In most of these the proof is lacking The 
demonstration of the etiological agent m the pleural eftusion m so many 
cases of pleurisy, especially the tubeiculous form, is attended Avith so much 
difficulty that negatiA’’e cultural results are very little evidence that a pleurisy 
IS gonococcal in origin Also in pleurisy due to the pneumococcus, the 
organisms in the fluid often show degenerative forms and stain poorly and 

' Mnnchen msd Wchnschr , 1903, vol 1, p 562 



GONOCOCCUS INFECTIONS 


115 


resemble gonococci, so that little reliance can be placed on the microscopic 
study alone of the pleural exudate Theie seem to be only 3 cases in hich 
the proof seems fairly good, by the demonstiation of gonococci in both cul- 
tuies and cover-slips, that the pleurisy was due to this organism These are 
the cases of Chiaiso and Isnardi, Mazza, and Cardile These were all in 
females, 2 of them m young girls In 2 aithritis as also present In 1 case 
the pleurisy AA^as bilateral, all were with effusion In all the course Avas 
prolonged All recoveied From the few cases it is impossible to give any 
accurate clinical picture of the condition 

RENAL COMPLICATIONS 

Albuminuria — ^Albuminuria frequently occurs during the course of 
gonorrhoea As LeAvek has shown from a study of 155 cases, the albuminuria 
IS usually associated Avith the presence of blood and pus, and has no signif- 
icance as to the presence of a renal lesion In the feAA cases where the 
amount is too large to be accounted for m this Avay, it may be due to a febrile 
albummuiia, the fevei being due to the other complications usually piesent 
in such cases, or the albuminuria may be associated Avith irritation of the 
kidneys by administeied drugs, such as sandal-AAOod oil or copaiba In 
none of LcAvek’s 155 cases Avas a kidney lesion present There is no evidence 
that the gonococcus or its toxin plays any role m the production of an acute 
or chionic non-suppurative nephritis 
On the othei hand, it is undoubtedly true that suppurative kidney lesions 
may be due to the gonococcus, either as a result of ascending infection from 
a cystitis, or as a focus of infection in pyaemia The proof of this rests 
largely on the aa ork of Young In a patient AA'ith all the features of a bilateral 
pyonephrosis, gonococci in puie culture aa eie obtained fiom the mine This 
seemed to be a case of ascending infection In a case of Beig’s, of fatal 
gonoirhoeal endocarditis, a mild grade of pyelonephritis AAas present, 
appaiently due to the gonococcus The repoited cases of pyelitis, pyelo- 
nephiitis and pyonephrosis coming on dining acute gonorrhoea aie not 
uncommon The actual demonstiation that these are true cases of gonor- 
ihceal infection of the kidney, hoAA'ever, has usually not been foithcommg 
Ceitdin of these cases, as Young’s, haA'e had a veiy chionic course, but the 
clinical features haAe not yet been A\ell enough studied to differentiate con- 
ditions due to gonococci from those due to the ordinaiy pus organisms 

Cystitis — ^That gonococci alone may induce an acute cystitis has been 
shoAAm by the AAOik of Young, ^ aaIio from such a case obtained a puie cul- 
ture of gonococci in the urine by suprapubic aspiration of the bladdei 
That gonococci, hoAveA^er, may be present in the bladder AAithout inducing 
a cAstitis has also been shoAin by Young A second factor therefore must 
occur in the etiology Aoung has also reported a case of chionic cystitis, in 
AA Inch this organism AA^as shown to be the sole bacterium present 

GONORRHCEAL PERITONITIS 

That a local circumscribed peritonitis may be caused by the gonococcus 
alone AAas definitely established bA Wertheiin in 1891, so oveithioAAing the 

'Young Johns HopJ ms Hospital Reports, vol ix, p 677 



116 


INFECTIOUS DISEASES 


view previously held that the peiitoneum possesses an immunity to infection 
vith this organism This local peritonitis is usually associated with salpin- 
gitis, and has mainly a gynecological interest 

Pelvic peritonitis occurs also m the male and Battez^ has collected 30 cases 
It IS almost always secondary to gonoiihoeal cystitis, prostatitis, or especially 
epididymitis and vesiculitis Theie is usually intense pain in the inguino- 
scrotal region radiating to the iliac fossa It has a shoit duration, intense 
local and general symptoms, and a xelatively favorable prognosis Rectal 
examination is of the greatest value for diagnosis 

The occurrence of a pure gonorrhoeal general peritonitis, ■while long 
suspected, i^as only, definitely established by the demonstration, by Young, 
of gonococci in pure culture in a case of general peritonitis occurring in the 
Johns Hopkins Hospital in 1898 ^ Up to the present, 9 cases of general 
gonococcus peritonitis have occurred in the vards of the Johns Hopkins 
Hospital These have been collected and the subject discussed by Hunner 
and Harris,® who v.eie able to collect 18 cases m which theie was absolute 
bacteriological proof as to the nature of the condition, and 21 cases in 
addition in which there was good clinical evidence That within a period of 
four years, 9 cases should have been treated in one hospital, shows that the 
condition is not an extremely rare one and that many cases must be un- 
recognized 

The condition occurs principallj’^ in young girls, oi in women duiing or 
just after menstiuation, or during the puerperium Five of the 39 cases 
collected by Hunner and Hams were in children under 7 years In all 
cases so far reported, the infection has apparently reached the peritoneum 
by ascending through tlie Fallopian tubes The onset of tlie symptoms is 
usually quite acute and the features are those of the other forms of geneial 
peritonitis While these symptoms maij be of great severity, they frequently 
are milder than are seen in the other foims of peritonitis, except in the tuber- 
culous form The collapse is usually not so extreme, and frequently after 
three or four days of marked symptoms of general peritonitis the condition 
improves There are no definite clinical features, hoi\ever, by which this 
form of peritonitis may be diftei entiated fiom the more severe forms caused 
by the pyogenic cocci Symptoms of general peritonitis coming on suddenly 
in a young child oi in a Avomen during the puerperium or just after menstru- 
ation, especially if the presence of an infection vith gonococci at the same 
tune can be demonstrated by the isolation of these organisms from a urethral, 
vaginal or cervical discharge, make the diagnosis A'eiy piobable Tins is still 
more probable if, on pelvic examination, the piesence of salpingitis is found 
HoAiever, recognizing the difficulty of differentiating certain cases of acute 
salpingitis from those of acute appendicitis, it is questionable whether one is 
able to make a positive diagnosis in eveiy case 

Prognosis and Treatment — Of the 3*9 cases collected by Hunner and 
Harns, 27 recovered, 12 died, and of the 27 recovering, 8 received only 
palhatne and medical treatment On account of the relative mildness of 
this form of peritonitis, and the good lesults obtained by the expectant plan 
of treatment, the question has arisen as to the value of surgical procedures 
in these cases It seems best that, at least until the clinical features are 

' ThCse dc lA/on, 1901 

"Cushing Johns Hophins Hospital BxiUehn 1899, vol x, p 75 

^ Johns Hopkins Hospital Bulletin, 1902, vol xin, p 121 



GOJ^OCOCCUS INFECTIONS 


117 


better known and the means of diagnosis more certain, treatment should be 
surgical, or at any rate the surgeon should be permitted to take the responsi- 
bility of delaying operation 


METASTATIC OCULAR COMPLICATIONS 

Aside from the primary ocular gonococcus infections, to which reference 
has already been made, certain other eye lesions may occur, which are 
manifestly metastatic in origin, and lepresent either the effect of the gono- 
coccus toxin upon the eye, oi aie true local manifestations^ of a general 
gonococcal infection 

Metastatic Conjunctivitis —There has been much discussion as to 
whether such a condition really occurs, but from a study of the reported cases 
it seems probable that a conjunctivitis sometimes occurs during gonorrhoea, 
in which a diiect transplantation of the virus from without can be excluded 
In 1866, Fournier drew attention to this form of metastatic conjunctivitis 
analogous to the metastatic joint lesions Since then a considerable number 
of cases have been reported These have been collected by Carroll, i\ho has 
also reported a case of his own with a bacteriological report This form of 
conjunctivitis must occur with relative infrequency, however, since in the 
eye clinic of Fuchs, in which 20,000 cases are treated yearly, but 2 examples 
have been observed It seems to have certain special featuies The symp- 
toms are much milder than those occurring in the ordinary form of con- 
junctivitis, and the course is much shoiter, there being a tendency to spon- 
taneous recovery in six to fourteen days Both eyes are affected, and the 
condition is usually accompanied by other metastatic lesions, frequently 
arthritis and iritis Recurrences are common Gonococci have m most 
cases not been demonstrated either in the secretions or in the conjunctiva 
itself On the other hand, they have been found by Lipsly and van Mull 
The theory that this foim of metastatic lesion may be due to the action of 
circulating toxins seems to be supported by the experiments of Morax and 
Elmassian, who produced an inflammation of the conjunctiva by the 
instillation of the Altered culture medium of the gonococcus into the eyes of 
rabbits It was necessary that this instillation be extremely prolonged — ^from 
two to seven hours Nei ertheless the conclusions in regard to the patho- 
genesis of other forms of metastatic lesions [apply here as well The treat- 
ment consists in mild antiseptic washes and absolute rest for the eyes 

Metastatic Intis — ^This condition is of especial interest, as it usually 
Occurs m association with arthritis, and the clinical features are almost 
exactly identical v ith those of rheumatic iritis This complication occurred 
5 times 111 the 252 cases of arthritis collected by Northrup, and 3 times in 
hlaikheim’s 52 cases Among 40 cases of severe arthritis occurring in St 
Bartholomew’s Hospital, Yeld found 5 complicated by iritis Of 159 cases 
of primary iritis, S u ere gonorrheeal in origin Intis occurred ti\ ice among 
the writer’s 50 cases of arthritis De Lapersonne gives its frequency, as 
compared ivith all other eye diseases, as about 1 in 14,000 cases 

It may occur either as the so-called spongy iritis, or any of the various 
mrms of plastic iritis, and even the hemorrhagic form has been described 
Only one eye may be affected, or both may be attacked, simultaneously or 
in succession A tendency to recurrence during subsequent attacks of 



118 


INFECTIOUS DISEASES 


gonorihoea has been observed Practitioneis should look on any eye symp- 
tom occurring during the course of gonorrhoea vith suspicion, otlieivise this 
condition may be oveilooked, and when discovered the damage be iirc- 
parable 

Mydiiatics should be used as soon as possible to prevent adhesions leading 
to closure ot the pupil Usuallj the course is mild, and wdien pioperly 
treated, complete recoveiy is the lule The treatment is exactly the same as 
that employed in rheumatic and othei foiras of iritis 

Dacryo-ademtlS — Cases of so-called metastatic gonococcal inflamma- 
tion of the lachiymal gland have been reported and aie collected by Cause ‘ 
Bacteriological pioof of the gonococcal nature of this foini of infection has 
not yet been adduced In none of the 6 cases collected by Caus6 did sujr- 
puration occui 

Othei lorms of metastatic eye lesions, eithei piimaiy, or by extension from 
one of the above-mentioned forms of metastatic foci, have been recorded, 
such as tenonitis, keratitis, iridocyclitis, iridochoroiditis, retinitis, neuro- 
retinitis, and optic neuritis The exact relationship of these lesions to the 
gonococcal infection is not yet clear 

GONORRHOEAL SKIN ERUPTIONS 

The occasional occurrence of skin eruptions during the course of^gonoi- 
rlioea, especially where associated wntlr extra-genital complications, has long 
been noted The relationship of these to the gonorihoeal infection has not 
been deal and even now' definite proof of an etiological relationship is 
wanting The relatively frequent occurrence of these lesions in severe 
cases, and the occasional recuirence of the skin lesion with recurrence of 
gonorrhoea in the same patient, make it altogether probable that specific 
gonorrhoeal skin eruptions do occur Care must be taken, however, to 
exclude the cases in which the eruption is associated with certain medication, 
or, in the more severe ‘ cases, with secondaiy infection Certain of the 
hemorrhagic skin eruptions may be due to an associated pyogenic septicfemia, 
in wdnch such lesions aie not rare 

Buschke,^ w ho has made a complete study of these lesions, divides them 
into four gioups 

1 Simple Erythema — ^Tlns is the most frequent form, but in many 
cases IS often but a sequel of certain foims of treatment It may occui, 
how'ever, in conjunction with gonococcus septiciemia In the winter’s case 
of septicfenna mentioned previously, small erythematous patches resembling 
rose-spots occurred 

2 Urticaria and Erythema Nodosum — Certain of the cases have 
showm exactly the lesions of erythema nodosum, with raised tender nodes 
and deep infiltration of the subcutaneous tissue In most of them theie have 
been joint pains, m some a typical gonorrhoeal arthritis In Buschke’s first 
cases endocarditis occurred also, in the second case pericarditis 

3 Hemorrhagic and Bullous Eruptions — Such lesions have usually 
appeared in cases with the manifestations of a severe septiciemia, and they 
are probably (as is quite certainly the case in other infections such as stiep- 

* ZtscJir f Angenh , Berl , 1904, vol xi, p 399 
^ Arch f Dermal u Syph , Wien, 1899, vol xlvni, p 181 



GONOCOCCUS INFECTIONS 


119 


tococcus) embolic m origin Paulsen^ has reported a case of gonorrhoeal 
arthritis in a young child, in -which a papulovesicular and bullous eruption 
occur! ed over the inner sidfe of the legs and over the face Smears made from 
the vesicles, and also from the pus from the joint, showed the presence of 
gonococci Cultures, however, were not made and the proof as to the 
metastatic nature of the skin lesions cannot be consideied absolute 

4 Hyperkeratosis — ^Tlns is by far the most interesting group, as the 
lesions are apparently specific Tnese lesions and the clinical features have 
been more extensively desciibed by Baermann ^ This lesion is undoubtedly 
rare, though possibly cases are overlooked The skin eruption usually 
follows a severe general infection, usually associated with joint lesions 
Owing to this, emaciation and anannia occur Then suddenly, on the plantar 
surface of the feet, palmar surface of the hands, or about the nails, an 
eruption appears This may remain localized or become widely distributed 
ovei the body The eruption consists of scaly efflorescences on an entirely 
re-actionless base After these fall off, no scar remains On the hands and 
feet the eruption may be diffuse and confluent Often the extremity most 
involved is the one in which the joint lesions are most marked With recovery 
from the joint lesions and other gonorrhoeal manifestations, the skin lesion 
heals of itself Gonococci have not been found in these local lesions, and 
the association with the gonoiihoeal infection is not cleai The French 
■writers consider the condition a trophoneurosis, due to toxic changes in the 
' nerve endings 

Baermann does not think the crust formation is a true keratosis, but 
thinlcs the term dcimahtts 'papilla) is pai aleraiotica is better The condition 
must be diagnosed from luetic eruption and from psoriasis Roth also does 
not consider the condition a true keratosis, but considers that it belongs 
among the “angiopathic” skin eruptions 


GONOCOCCUS INFECTIONS IN CHILDREN 

On account of the veiy great frequency of this condition, as showm by 
Holt,® Baei^ and otheis, this subject is of very great impoitance, not only to 
the pediatrician and genito-uiinary surgeon, but to the general practitioner 
as ivdl While of greatest importance in connection w itli the care of children 
in hospitals, in ivhich the epidemic occurrence of this infection renders it a 
most difficult and impoitant problem, it probably occurs in private practice 
■with much greater frequency than recognized or has hitherto been imagined 
The first recorded epidemic of gononhoeal vaginitis in children occurring 
m a hospital is probably that of Atkinson,® rvho reported 6 eases occurring 
m a charitable institution in Baltimoie Baer has collected the statistics 
from 19 epidemics -with 660 cases The studies of Holt and Reed from 
institutions for babies in Nerv York, show that this condition is almost con- 
stantly present in practically all of these institutions, and that epidemics of 
greater or less extent are almost constantlj’^ recurring Dunng eleven years, 

^Mnnchcn mcd Wchnschr , 1900, vol xhm p 1209 
®Arc/! f Dermal v Syph , Wien, 1904, vol Ixix, p 363 
A cm 1 orli McdicaJ Journal 1905 vol Kwi, pp 521-589 
* Tomnal of InfecUous Diseases 1904 vol i, p 313 
^America)) Journal of the Medical Sciences, 1878, vol Ixxv, p 444 



120 


INFECTIOUS DISEASES 


in the Babies’ Hospital, New York, 273 cases occuiied, of i\hich 172 weie 
undoubtedly acquired in the hospital The disease is almost entirely con- 
fined to females, as during this time there was only 1 case of gonococcus 
uiethiitis in a male child 

The usual mode of spread in these young children is through the medium 
of napkins, by the use of baths, or by the use of infected thermometers, 
syringes, and possibly tongue depressors The disease is undoubtedly 
carried from child to child by nurses iiho care for the infected as well as the 
uninfected children The infection may be spiead from childien uith 
conjunctivitis, as well as those vith vulvo- vaginitis or urethritis The vulvo- 
vaginal tract of young children must be extremely susceptible to this form 
of infection, just «is the conjunctiva of young children has an increased 
susceptibility as compared with that of adults The condition is very chronic 
and resistant to treatment 

The recurrence of this infection in hospitals can only be prevented by the 
exclusion of infected children, and this can only be done by the systematic 
microscopic examination of the vaginal secretion of all patients applying for 
admission, and by the rigid isolation of all children m whom infection 
develops, oi is only discovered after the child is admitted Some of the 
cases are very mild and without bacteriological examination are easily over- 
looked 

The importance of this infection is dependent not only on the local infec- 
tion induced, but on the complications which are liable to occur Endo- 
metritis, salpingitis, oophoritis and peritonitis, frequently leading to sterility, 
are not very infrequent occurrences Metastatie foci also occur with con- 
siderable frequency Among them, arthritis is most common, and Holt 
states that in eleven years in the Babies’ Hospital in New York City, 26 
cases of gonococcus arthritis occurred, all proven by bacteriological exam- 
ination Nineteen pf these cases were male babies, and as m only 1 was there 
other manifestation of gonococcus infection, the mode of joint infection is 
of great interest on account of its obscurity Holt expresses a conviction 
that m these cases the primary infection is through the mouth, though at 
present there is no bacteiiological evidence to substantiate this view'^ In 
only 5 cases was but one joint involved, three or more joints being involved 
m 16 cases, the largest number in any case being eight joints On account 
of the difficulty of detecting mild grades of involvement m young children, 
however, it is probable that multiple joint involvement occurred wnth 
greater frequency than the above statistics would indicate The serious 
nature of the condition is showm by the fact that 14 children died In many 
of these cases, how'ever, there w^as an associated condition of general maras- 
mus Many of the cases closely resemble acute rheumatic fever, but this 
disease is very rare m children under one year In arthritis m very young 
children, especially if there occur suppuration, the possibility of its gono- 
coccal nature should be kept in mind In cases of gonorrhoeal ophthalmia 
metastatic foci, especially arthritis, are not at all rare 



CHAPTER VI 


LEPROSY 

Bi ISADORE DYER, Ph B , M D 

Synon3Tns — Lepia, Elephantiasis Griecoruin, Hebrasorum, Leontia- 
sis, Satyriasis, Ophiasis, Tzaraath (Hebrew), Kushta (Indian), Juzam 
Dolfil (Aiab), Fa-Fung, Ta-ma-Fung (Chinese), Boasi (South American) , 
Lebbra (Italian), Radesyge, Spekalshed (Norwegian), Aussatz (Geiman) 
Definition — ^Leprosy is an endemic disease, contagious m type, due to the 
direct presence of the Bacillus lepiae, which in its development produces 
structural changes m the skin and mucous membranes, nerves, bone and 
other tissues, usually resulting in more or less alteration m the configuration 
of the tissues involved, at times causing actual defoimity and mutilation 
Historical — ^The early histoiy of leprosy is obscuie, even confusing The 
Bible refeiences* to the disease are sufficient to establish its existence, but the 
descriptions are maccuiate and the leprosy of ecclesiastical hteratuie seems 
to have been geneiic for a numbei of skin affections Both the Talmud and 
the Koran tate cognizance of the disease and apocryphal viitmgs discuss it 
Knowledge of early lepiosy appears to have restricted the disease to Egypt 
and the Orient and m India the disease Mas recognized as eaily as 1500 B C 
In 600 B C the Peisians instituted measures against leprosy (Leloir) ^ 
As early as 636 A D lazarettos M'eie established m Italy In the tenth 
centuiy the islands of Great Britain M^ere afflicted In the eleventh and 
tvelfth centuries the disease spread all over Europe, directly attributed to 
the returning crusaders iMeasuies M'ere adopted for its control, chiefly 
consisting m the establishment of leprosaiiums Of these it is stated there 
M ere 19,000 in Europe, and 2,000 m France alone The colonies of European 
countiies suffered next, until to-day there are fev' lands free of the disease and 
it IS estimated that there are nearly 3,000,000 lepers m the Mmrld Of these, 
the largest number is m China (estimated at 2,000,000) , the next is in India 
(estimated at 200,000), mIiiIc the other parts of the M'orld afflicted are the 
folloMung Japan (20,000 knoM'n lepers),® Northern, Eastern and Southern 
Africa, Madagascai, Arabia, Peisia, Russia, Norvay, Sveden, Italy, 
Greece, Spam, (Germany, Fiance and Austiia, excepting Hungary, are 
practically' free of the disease) , the islands of the Pacific and Indian Oceans 
Leprosy is also endemic m Central and South America The United States 
of Columbia, Ecuador, Venezuela, Brazil, Chili and Peru have each recorded 
statistics concerning the disease In Mexico and m almost all of the islands 
of the West Indies leprosy is found and m most of these provision is made 
for it 

In North America a number of the United States are involved, notably 
Louisiana, California, Nev' York and Minnesota In Louisiana the disease 

t 

’Exorfus IV, 6, Lcuiticiis XIII, 24, 25, 43, 52, A^wmbcrs I, XIII, Deuteronomy "S-TL 
'Leloir Traitc de la Lepre, Pans, 1SS5 
’ Transactions of the Berlin Lepra Conference, 1897 


121 



122 


INFECTIOUS DISEASES 


IS endemic, occurring almost wholly among the native boin or peisons long 
resident m the state, while other centres show simply an increasing number 
of cases m recent years Since 1905 about 400 cases have been recorded 
in the United States ^ New Brunswick in Canada, at Tracadie, and 
British Columbia, at Darcy Island, have a few cases 

The numerical importance oi the disease has carried considerable force 
with various governments to the end that legislative action, aimed at segrega- 
tion, control and treatment, has become general In some countries the 
provisions are fulfilled under piivate charity but for the most part govern- 
ment provision of funds has accompanied the execution of enactments 
These results have followed the Beihn Lepra Conference of 1897 and m all 
countries an intelligent effort is now being made to accomplish a better know - 
ledge of leprosy and its eradication, through sanitation and treatment 

Etiology — Contagion. — The consensus of opinion has accepted the 
Bacillus lepras as the cause of leprous lesions and their effects and the evi- 
dence points to the introduction of the organisms of the disease through the 
nasopharynx This theory is strengthened by the absence of an initial lesion 
of leprosy at any particular point of inoculation, the absence of specific 
inoculation or the history of such, and the frequent occurrence of the disease 
under conditions which favor the inhalation of the disease-bearing secretions 
from the original case Fiequent cases in the same family, the spreading of 
the disease in districts and in cities, countries, and states, suggest the more 
likely spread through the respiratory tract 

Among those wdio have strongly urged this theory are Goldschmidt, 
Morrow, Sticker, Jeanselme, and others (Babes, Gluck, von Peterson) more 
recently Emilio Martinez, of Havana, personally stated to the WTiter that m 
almost every patient w ith leprosy he had been able to examine, he had found 
an early excoriated lesion in the nasal mucous membrane showing the bacilli 
of the disease 

Heredity — ^Heredity is still held a factor by a few observers but the vast 
majority have dismissed it as a consideration The results of the British 
Leprosy Commission m India in 1893 show'ed less than 3 per cent of cases 
developing among children of lepers removed at birth and these showing the 
disease after the third year, the absence of any record of a leper born as 
such in any of the many centres of the disease still places the burden of proof 
on the few who claim this as a factor 

Race — Race undoubtedly bears a close relation to the spread and to the 
element of susceptibility to the disease Records m almost every country 
show the native born the most frequent victim wdnle the foreigner is slow to 
acquire the disease This is paiticularly exemplified m China, Japan, India, 
the Hawaiian Islands, the Philippines, Colombia, the Polynesian Islands, 
Madagascar, Mexico and Louisiana There is no doubt, how^ever, that the 
likelihood of exposure to contagion is more apt to occur m the family and 
community life among these, and this must, therefore, be taken into consider- 
ation 

Diet — Quite a number of leprologists have urged diet as an element in 
the spread of leprosy and the prominence of some of these protagonists 
demands a consideration of the theory Jonathan Hutchinson has supported 
the fish origin of leprosy for many yeais His observations and deductions 

1 “Leprosy in North America” (Dyer), Transactions International Dermato- 
logical Congress, Berlin, 1904 The author’s notes record 219 cases in Louisiana 



LEPROSY 


123 


have been almost entirely derived from British India and as yet the theoi} is 
unproven Ashmead, Blanc and others have expressed a belief that fish may 
be the occasion of lejirosy Hutchinson propounds the idea that leprosy 
occurs chiefly in India among fish-eating peoples vho are not particularly 
careful about the fieshness ol the food, otheis argue the possibility of fish 
acting as the intei mediate host for the leprosy bacillus As yet no one has 
discovered the bacillus of leprosy in fish or in any othei food supply and the 
disease occurs alike in those v ho eat fish and those who have no fish to eat 
Almost as a unit the students of lepiosy in India, the Hawaiian Islands and 
111 other lepei centres deny the evidence of any such origin The obseiveis 
in India point rathei ceitamly to v idespread occurience of the disease among 
those castes who by lehgious obligations are forbidden fish 

Diet in its lelation to the individual lepei is another matter and particulai 
emphasis is laid upon its importance as it may aftect the resistance or othei- 
wise to the disease 

The habit of oial feeding of infants m the Hawaiian Islands and the 
family promiscuity in eating “poi” vith the fingers is held as possibly 
accountable foi the spread of the disease by contagion 

Climate — ^^¥arm climates evidently favor the development of leprosy but 
it occuis in any climate as is exemplified by the long pievalence m Noivay, 
Sweden, Iceland and Japan Seaboard countries seem to have suffered 
most fiom the disease but this is easily accounted for as these are natmally 
most exposed through their leady intei course vith infected countries 
thiough oidinary va)s of commerce Leprosy spicads, hovever, in eveiy 
countiy where it is introduced Wheie community life, hygienic environ- 
ment and standaid of metabolism are high, the disease does not spread 
lapidly 

Vaccination — ^Vaccination has been discussed as a piobable method of 
the spread of leprosy but no pioof has followed the tentative theory and m 
these days of bovine virus such a likelihood is precluded 

Insects — ^Recently the proposition has been made that fleas might be the 
medium of spreading leprosy jMosquitoes, bedbugs, and other accidental 
paiasites attacking the human body hax^e been consideied in the same way 
Nuttall levievs the various opinions on this point, and considerable voik 
vas carried on by the Biitish Lepiosy Commission without lesult Within 
the past SIX months, E S Goodhue, of Holuloa, Hawaiian Islands, has 
announced the finding of the Bacillus leprw in mosquitoes and in bedbugs 
Other Diseases — Fitch of San Riancisco and some adherents argued the 
possibility of lepiosy as a “fourth stage” of sjqihihs, but so many cases of 
syphilis conti acted by persons already lepers have been reported that the 
theory has fallen, even if other evidence had not sufficed The identity and 
coi relation of leprosy and tuberculosis is a more recent idea which has been 
rathei ventuied than tried 

While the contagiousness is capable of only indirect proof the ^ ast amount 
of evidence points to this as the sole method of spread of the disease, and as 
more exact opportunity is now aftorded to study earlj cases, it is likely that 
an initial lesion may be found, particulai h as that has already been sug- 
gested as probabb present m the nasopharynx 

Pathology ery e^^dence of leprosy in the human economy is essen- 
tially due to the lepra bacillus, no matter what organ may be affected This 
has been firmly established since the original discovery of the bacillus by 



124 


INFECTIOUS DISEASES 


Hansen m 1868 The Bacillus lejua: is described as a small lod bacillus, 
iiom one-half to three-quarters of the diameter of a red blood corpuscle in 
length ( 5 ^ of an inch) and in breadth about one-fifth the length Ac- 
cording to Cornil, the largest are found in the parenchymatous organs, 
while in* the skin lesions they are less developed owing to compression The 
bacillus is straight 01 slightly curved, with pointed or rounded extremities 
It occuis in short chains or beads, resembling the tubercle bacillus, and may 
have its extremities club-shaped (Byron) The lepra bacilli are more abun- 
dant than the tubercle bacilli and are more frequently found m clumps and 
masses in the tissues and are more readily stained with the usual methods 
In instances of doubtful determination, inoculation experiments establish 
the diagnosis of tuberculosis and exclude leprosy Arning’s inoculation 
experiment with a Hawaiian leper (Keanu), in 1884, has been disci edited 
owing to the strong probability of contagion from near relatives who were 
lepers 

In animals, Damsch, Campana and Vossius succeeded in reproducing the 
disease in loco, but not generally Melchior and Ottmann succeeded in 
distributing the disease to the visceral organs, etc , following the mtioduction 
of a freshly extirpated leprous tubercle into the anterior chamber of a rabbit’s 
eye Experiments ivith the human subject have been rare and without 
authoritative verification (Daniellson and Boeck) The bacillus may be found 
in almost any tissue, but is selective of particular oigans, tissues and regions 
The bacillus occurs in the nasopharyngeal and other secretions, the saliva, 
the fseces, vaginal and urethral secretions, and in the semen, milk and sweat 
Sticker claims that the presence of the bacilli m such large numbers in the 
nasal secretion commends the early examination of this as a means to diag- 
nosis The fluid from artificial blisters as well as serum drawn from deep 
tissues have been examined for the bacilli with positive results 

The smears from these secretions and fluids are dried and fixed m the 
ordinal y way and stained with carbol-fuchsin, as for tubercle bacilli, decolor- 
ized with a weak solution of acid (3 to 5 per cent ), completed with alcohol 
and counter-stained with methylene blue The cigar-bundle shaped masses 
take up aniline stains (Gram method) at the room temperature and retain them 
tenaciously Unna lecommends staining in a twenty-four hour old Ehrlich’s 
solution newly filtered for twelve to tventy-four hours at the room tem- 
perature or one to two hours in the incubator, wash for ten minutes in water, 
and place in 20 per cent nitric acid until greenish-black Wash in absolute 
alcohol until pale blue and in watei until colorless, dry and mount 

Attempts^ at culture of the bacillus have met with varying results Byron 
made a pure culture in agar-agar Bordom-Uffraduzzi, Babes, Czaplewski, 
Spronk and Kediowski claim to have succeeded The organism grows 
slowly and the cultures resemble those of the tubercle bacillus The organ- 
isms, however, differ from those found in the body in not being acid-fast and 
it is questionable if they are identical The media used were mixtures of 
blood serum, peptone and glycerine The glycenne seems to be essential 

The bacilli are vndely disseminated throughout the body, having been 
found in practically every organ and including the penpheral nerves, spinal 
cord, brain, and in the skin (even in scrapings of the skin), interstitial con- 

* Babes “Die Lepra,” Nothnagel's Pathologic und Therapie, XXIV Bd , 1901, 
Nt em (A very complete bibliography on leprosy is given ) 



LEPROSY 


125 


nective tissue and in the muscles In general the number ol bacilli has no 
relation to the severity of the accompanying tissue changes 

Scheube* gives a comprehensive summary ot tissues where the bacilli have 
been observed 

The skin and mucous membranes, earliest m the anaesthetic patches 

In the peripheral nerves and lymph glands, especially in the sheaths and 
in the lymph gland secretions 

The internal organs involved are the lungs, liver (especially the liver 
cells), the intestines, kidneys and lumen of the uiinary tubules, the testicle, 
its tubules and ducts, and the ovaiy 

In the tonsils, the eye, in the sweat glands, hair follicles and sebaceous 
glands betiveen the epidermal cells, and in the arrectores pilorum the bacilli 
are found 

The connective tissue of the cutaneous nerves, m the Pacinian corpuscles, 
the salivary glands, pancreas, adrenals, spleen, larynx contain the organisms 
They are also found m the substance of the brain and coid and m the Pur- 
kinje cells of the cerebellum, in the choioid, retina and ciliary body, mthe 
muscles and tendons, and in the periosteum, bone and medulla In the acute 
stages of leprosy, the bacilli are found as contents of the blood cells and in 
fluid lesions of the disease The bacilli aie very numerous in the infiltrative 
tissues, and in nodules and tubercles, but in the erjdhematous patches and 
nerves they are scanty 








* L 

- Av 

C ‘A' 

, 11 . '' 


Outside the human body the Fw 4. 

bacilli have been found in the hab- 

itations of lepers and m the ground ® -> 
ovei lepers graves Various tish 
have been examined for the bacilli 
but with negative results 

The leprous nodules belong to 2^~ S ''' i 

the group of granulation tumors '-x, 

and are similai to those of syphilis 
and tuberculosis Microscopically 

they consist of a small amount of ^ 

fibrillar connective tissue with nu- >1"' 

inerous cells of vaiious forms, 

mostly small, round epithelial cells, G n y'vV 

spindleformed, and the lepiosy cells . V^)'' ' 'i 

iliese aie mostly large, round or ^ f 

oval cells, with many nuclei and J \ ^ 'n'^' , 

vacuoles They contain the lep- Z- — > 

rosy bacilli These cells are diag- , 'O' 

nostic of the disease and are found 

most numerously m the tubercles , 

and nodules of leprosv Neisser ob- 
served the gradation m the devel- bacJl, m groups . zoogl.a masses-giant 
opment of the lepra cell in size and c- chamsofbacm (Lete) 

contained nuclei and bacilli, also the degenerative lesion show mg numerous 
extra-cell bacilli Virchow , Neisser, Gerlatz, and others argue the consistent 
type of the lepra cell as the container of the bacilli, the exception being 


1 *'5- , 


-X.' \ ■£. ' 


B bacilli m groups , zooglia masses — giant 

cells C chains of bacilli (Leloir ) 


^Dte Kranlhciten der Warmen Lander, Iller aufl , Jena, 1903, pp 320-392 fWith 
a very complete bibliography ) irr v,yhuu 




126 


INFECTIOUS DISEASES 


against the rule, Unna is the chief piotagonist of the “extra” cell theory, 
claiming that the lepra cell is only a mass of agglutinated bacilli, which 
are habitually aggiegated m the lymph spaces 

In the trophic, or neive type, the changes are found m the peripheral nerve 
trunks and their eutaneous blanches, the central changes occurimg second- 
ary to geneial changes oi infection The leprous deposits aie especially 
found m nodules along the ulnai, median, radial, musculo-cutaneous, mtei- 
costal, humeral and peroneal nerves Thickening of the nerve is common 
The trophic changes follow the invasion of the nerve itself by the bacilli 
Symptoms — ^The uncertainty of fixing any particular period of incuba- 
tion and the lack of observation of the eaily stages of the disease compel a 
study of the piehminary symptoms only upon the subjective histoiy and 
after tangible manifestations aie in evidence Even in leprosy centies, 
suspicion of the disease aiises only when local conditions appeal and pie- 
monitory signs of the disease have been ignoied That these do exist many 
obseivers agiee and the arrangement of these is based upon a supposed 
period of incubation, as this cannot be exactly known The histoiy of 
exposuie is usually absent and, even wdien ascei tamable, the length of time 
IS too vaiiable to admit of any accurate statement This period vanes from 
a few^ w'eeks to many years Some instances are related in which twenty 
yeais had elapsed since knowm exposure to the disease had occuried Con- 
tinuous exposure over long peiiods has been noted, howevei, in the instance 
of several members of the same family or community being aftected and heic 
the prodromal symptoms have been studied 

The one most constant symptom is the occurience of fevei, mteimittent 
and iiiegular m period and m tj'pe Malaise, anorexia, dyspepsia, epistaxis, 
dryness of the nasal and lespiratoiy passages, vertigo, headaches, neuialgias, 
pains in the aims and legs, and exaggeiated functions of the fat and sw^eat 
glands aie among the notable symptoms The sweating is particularh 
striking, as it is periodical and evidently associated w ith nci vous distuibances 
There is in all instances a sense of anxiety, of anticipated calamity 

There may be marked hyperiesthesia of the skin, shown m aieas of pi untie 
exaggeiation with localized neuralgias The intestinal tiact may be dis- 
turbed by frequent diaiihoea and as a lesult it is quite usual foi the patient 
to lose in weight 

So far as the specific manifestations aie concerned, the usual diagiamma- 
tic method of resolving leprosy into fixed types is faulty and often misleading 
While these ceitainly come undei observation, the unusual cases are the rule 
The evidences of lepiosy are directly due to the invasion of the Bacillus 
lepicc and according as any particular oigan oi tissue is involved the symp- 
toms are manifest While any organ oi tissue may be attacked, the vast 
majority of patients show the skin and the nerves as the selected sites 
Dependent directly upon the degiee of this invasion and upon the in- 
dividual resistance, are the evidences m the skin and m the nerves them- 
selves In the history of every patient some logical course is follow'ed m the 
expression of the disease but all do not follow^ exactly the same development 
If the skin shows the first evidence, this may appeal either m explosive 
lesions, as bullie, m simple erjdhematous patches, oi in exactly localized 
areas of bacilli colonized m masses and foimmg tubercles 

When the nerves are attacked, along the couise of the neive involved there 
IS eithei thickening of the sheath or of the neive itself, oi nodes of vaiying 



LEPROSY 


127 


size are formed At the terminal ends of the branches of these nerves, skin 
lesions m the form of bull®, pigmentation, thickening oi atrophy of the 
epidermis may appear oi there may be actual neuritic changes in the muscles, 
tendons and bones 

Skin leprosy piesents its several lesions eithei separately or together at the 
same time and while the macule often occurs as a preliminary eiuption it may 
be the sole evidence of the disease So with the tubeicles of leprosy These 
may appear at once or may develop upon the areas previously outlined by 
the er^hematous or macular eruptions All of these lesions may occur 

Fig 5 



together and again they separately or together are often found concomitant 
with the neive lesions and changes, which they may also precede or follow 
The first evidences of skin or neive leprosy are the bull®, found upon the 
extremities, especially on the hands and feet With skin leprosy these are 
usually small m size, numerous and superficial They occur bilaterally and 
symmetrically, usually on the dorsum of the hands and feet and especially 
over the fingers They break quickly and dry, leaving a superficial erosion 
vhich heals spontaneously, and the site of the lesion is maiked by a uhite 
seal, usually uith a pigmented and iiregular border 



128 


INFECTIOUS DISEASES 


With neive leprosy these lesions aie more often single, laige, and oceur 
ovei the joints of the phalanges, as a rule they peisist, even ulceiating 
deeply at the point of oiigin Even if healing should occui, there is a 
tendeney foi a new lesion to foim at the site of the scai and ulceiation 
develops, causing necrosis of the area affected As any joint of any finger oi 
of all hngeis may be involved the process may be progiessively destiuctive, 
resulting m actual loss of one or moie of the phalanges, either distal oi 
intermediate The piocess may stait at the end of the digit, involve the 
nails, and result in the ultimate destiuction of the whole digit, leaving the 
hand or the foot minus fingers oi toes lespectively 

The erythematous eruptions are evanescent or peimanent In the first 
instance they occur as the evidence of a geneial infection and come as an 
exanthem They select paiticulai regions, notably the cheeks, shoulders, 
buttocks, thighs and legs, sometimes the aims, foreaims and hands The 
eruption is bilateral, symmetrical and marked by an iricgulaiity in the size 
of the aieas involved, which aie sometimes no larger than the thumb nail, 

while again the aiea maymvolve 
the whole of the legion affected, 
as over the buttocks The 
patches aie deep red in color, do 
not fade entiiely on pressure 
and have a suggestion of tur- 
gcscence in a certain amount of 
ele\ation and lounding of the 
lesions In a few daj s or weeks 
these disappeai and may not 
lecui Oftenest, howevei, the 
aieas o\erthc buttocks, thighs, 
kgs and shouldeis lemain de- 
fined as they fiist appeal, grow- 
ing duskj red in color, often 
mottled and thickening vith 
asre The pel iplieiy grows moie 
elevated and thickened, also m- 
ci easing m depth of color to a 
biowmsh-ied, vhile the centre 
fades to a buff oi even to a duty 
V lute The patches grov some- 
vliat elliptical in shape and 
remain m this general foi m and 
vith this consistency throughout, or the holders break up into distinct 
masses of tubeicles, each lepiescntmg a colonized accumulation of the 
bacilli "When the face is iinolvcd theie is often confluence of the eiythe- 
matous areas making a mask over the whole of the face, and involving 
the neck and ears Here the thickening destroys the noimal expression and 
produces a fixed, satyr-hke appearance giving rise to the term “sahpians,” 
sometimes applied to the disease The nose, ears, lips and eyelids become 
pendulous, occasioning a maiked interference with the ciiculation and a 
consequent sv elhng Ectiopion follon s and a bleary stare lesults With the 
geneial thickening, the face rolls m folds and forms m parallel masses 
cohered vith a shining telangiectatic, smooth or tuberous, sometimes fis- 



Satyriasis Tubercular leprosy (Cooper ) 




LEPROSY 


129 




sured, skin, the lips grow swollen and everted and “ Iconhasis” has devel- 

*^^Nerve leprosy seldom extends bej ond the developments of the disease at 
the extremities Heie and there along the ulnai and sciatic nerves and their 
branches, on the surface of the skin an eiythematous eruption may appeal, 
usually only tempoiary and expressing some fresh leproma of the nerve 
Of course the processes in neive leprosy may go on at the same time that 
skin leprosy develops and it is usual to see the one oi other superimposed 
as the condition progresses One lare instance of a correlation oi nerve and 
skin leprosyis the atrophic type Here, 7 

consequent upon the erythematous ^ ^ 

eiuption and the pigmented areas, a ' 1 

general atrophy of the skin occuis, ' 

the musculai and kei atm elements m * 

laige degree disappearing and leaving ‘ r 
a true skin atiophy, with loss of the , 

appendages, including the uhole of 
the hair, the nails, and loss of func- ^ 

tion m the glands Emaciation fol- 7 i 

lows rapidly and death is swift it 

Tubercle leprosy is essentially skin 'r>’x *' -4 

leprosy The location ot these lesions ‘ "1 S 

IS not constant but they have sites of ^ 

predilection The face presents these > ^ ‘ 

on the foiehead, nose, alie nasi, lips, "'j,, ' 
chin, cheeks and ears The aich of / ‘‘J "w" 

the ej'ebiows IS a frequent site The '< ■v > ' ^ 

hands and feet, legs, thighs, buttocks, ^ 1 

shoulders and foiearms are the next ^ 

m order of frequency ' 

The lepiosytubeicle maybe single, ^ 

clusteied, disseminate 01 diffuse Leontiasis Terminal Stage of Tubercular 

The single tubeicle is usually large, Leprosy (Cooper ) 

moie or less flat and found on the face, cheeks, hand or foreaim, usually 
few occur The color is blight biowmsh-red with the centre of the flattened 
lesion lighter than the bordei The clustered tubeicle is usually rounded, 
closely aggregated and selective of the alte nasi, ears, chin, hands and lower 
third of the leg, the buttocks may also be involved These lesions occur 
vith a classical bilateral symmetry and aie characterized by the almost olive 
and red color of the skin involved 


- ~ji "‘f w'si' 






Leontiasis 


Terminal Stage of Tubercular 
Leprosy (Cooper ) 


The diswimnate leprosy tubercle 15 small, about the size of a pea, hard 
and round, uniform m size, occurring generally over the body, bilaterally 
and sjTnmetrically, the lesions aie separated by areas of clear skin and 
distinguished from all other tubercles by the waxy v lute appearance, as if 
white wax showed through a dirty brown transparent covering Almost 
always this type of skin leprosy argues the occuirence of like lesions in the 
thoracic and abdominal viscera, as these cases rapidly become acute and 
result fatally in short ordei 

In each of the varieties of skin and nerve leprosy, and especially in the 
foimer, there aie peiiods of quiescence and exacerbation A stiiking featuie 
in the periods of exaceibation is the “lepra fever” mentioned by a number of 



130 


INFECTIOUS DISEASES 


observeis C B Coopei, Chairman of the Committee on Leprosy of the 
Hawaiian Government, has best desciibed this phase of lepiosy, although the 
condition seems more severe in his locality than elsewheie He calls the 
condition “swollen head fever” as this iias the teim given it at the Havanan 
settlement at Molokai He descnbes this as “an acute, epidemic, painful, 
inflammatory lepious fevei, in which the head and face become gieatly 
swollen, and in v hich the lymphatic and glandular system becomes charac- 
teristically involved, especially the cervical and sometimes the axillaiy and 

inguinal glands as well ” He was 
^ able to And the leprosy bacilli in 


— ^ the blood duiing the stage of fever 

Concomitant with this condition is 
a typical lepra exanthem, differing 
fiom any of the eruptions above 
fiiW'j ’’ described Cooper lays no stress 

r, Tf* ^ vritei’s obser- 

1 ” ' s vations at the Louisiana Leper 

f Home, these weie fiequent enough 

T' ^ j to be considered impoitant The 

\ ' ! eruption consists in the occurience, 

{t, i ’ />. -■v almost univeisally over the body, 

< bright red papules, lentil shaped 

’ ^ and uniform in size, usually hyper- 

I ^ ^ festhetic and at times painful, even 

* \ seveiely so With lessening of the 

'' geneial symptom, the eruption dis- 

, ' " appears, usually leaving, however, 

, an inciease in number in the pre- 

I - J vious lesions 

Single lesions Tubercular Leprosy (Cooper) Altered Sensation So mucll 

stiess is laid upon this that special 
attention should be given to it All skin lesions in leprosy excepting the 
evanescent eiythema and the exanthem of papules in lepious fever are 
anaesthetic to pain, sometimes to touch, heat and cold 

Hyperiesthesia is marked in the prodromal period and sensation is exag- 
gerated in the exanthematous lesions With nerve lepiosy, h^qiersesthesia is 
maiked for weeks and months befoie the evidence of an affected nerve is 


complete This is shown in pain along the extiemity and m the hands and 
feet Often distinct points ot pain are recognized As soon as the nerve is 
thickened and the nodes aie formed, amesthesia becomes complete along 
the areas of cutaneous distiibution of the nerve involved Usually the 
amesthesia begins at the distal end of the nerve and tiavels toivard the source 
The little fingei is usually the first point of amesthesia noticed, and more 
often on the left side 


Effete Leprosy — ^The lepiosy in Biittany and that m the Orient, as veil 
as many cases found in old leprosy centies, piesents types vdiich seem to 
show no acute symptoms at all, but vhicli evidence tiophic changes of slow 
development and unattended v ith inflammatoiy processes Zambaco-Pacha 
and von Duhiing have described these and most of them are of pure tropho- 
neurotic tjqie They present the claw-hand, loss of phalanges, facial para- 
lysis, etc , usually considered as sequel® of nerve leprosy 




LEPROSY 


131 


Sequel®.— As the direct result of leprous changes in the body, destructive 
processes in the inteinal organs, ultimately producing death, may result 
Hillis tabulates the causes of death as marasmus (38 per cent ), septicaemia 


Fig 9 



01 mtercurrent disease, as nephritis, (22 5 per cent ), pulmonary diseases, 
including tuberculosis, (17 per cent ), diarihoea (10 pel cent ), anaemia (5 per 
cent ), lemittent fever (5 pei cent ), and peritonitis (2 5 per cent ) 

The natuial necrosis, attending the final degeneiation ot tubercles, results 
in the loss of the nasal bones, often of the nose itsell , in the ulceration on the 
lace and m involved aieas tlieie is scariing, with contracting cicatrices, pro- 
ducing facial and other deformity Most trophic nerve types develop one or 
more ulcers at the extremities, with consequent destiuction of tissue Accord- 
ing to the limit of the piocess there may be simple contraction of muscles, 
atroplp of bones and subsequent deformity, oi the whole of the member 
involved may slough off 

Diagnosis — ^The customary observ^er of leprosy needs little aid to a diag- 
nosis, as the facies, the coloi, and the classic lesions are well known to him 
So much lesponsibility, honever, rests m determining leprosy that due care 
should be exeicised by those to n horn it is a casual disease 

The diagnosis is absolute v, hen destructive lesions exist m Vvhicb the lepra 
bacillus may be demonstrated in section, in the fluid contents, or in culture 
Clinically there should be little difficulty if the cardinal features of the disease 
are kept in mind The essential points may be summarized as follows 



132 


INFECTIOUS DISEASES 


1 The habitat, community or domicile, suggesting exposure 

2 A history of exposure or contact with persons aftected 

3 Eruptions or bullae on the extremities 

4 Areas of discoloration w^ith anaesthesia 

5 Trophic disturbances (a) Perfoiating ulceis, (b) muscle atrophy, 
especially of the hands, determining the “clawMiand”, (c) clubbed fingers, 
(d) deformity of the hands and feet from loss of phalanges, (e) persistent 
ulceis at the articulations of the phalanges of the fingers and toes, (/) facial 
paralysis 

6 Discolored and blunted nails 

7 Symmetrical eruption of macular aieas wuth bilateral distiibution 
(a) blarked by dusky red oi “ cafe-au-lait ” discoloration, (b) AMth elliptical 
shape, the peiipheral ring being elevated and deeply pigmented, Avhile the 


Fm 10 



Trophic leprosy (Leloir ) 


centre remains hghtei oi a duty w'hite in coloi, (c) marked anaesthesia 
thioughout these macular aieas, (d) a predilection for particular regions, 
notably the buttocks, legs and foreaims 

8 Tubercles aa ith typical modes of appeal rag and of distribution 

9 Loss of expression m the face, satyriasis, leontiasis, ectropion of eye- 
lids and of lips , furtive look m the eyes 

10 The early involvement of the nasopharynx and the larynx, resulting in 
a charactenstic involvement of the vocal cords, determining a peculiar 
metallic resonance m the speech wdiich is distinctive The note is nasal 
and raucous 



LEPROSY 


133 


Particular diseases mistaken for lepiosy are few and the differentiation 

^^%rijthema miilhforme presents lesions which are evanescent, fade on 
pressure without pigmentation and are not amesthetic 

Syphilis IS differentiated by the coloi of the lesions, the symmetrical dis- 
tribution of the leprous tubercles, their amesthesia and course of develop- 

™SarcoOTa (multiple) by the pain, the size and couise of development, the 

color and consistency .1 j j? 

Lupus vulgaris by the color, distribution, consistency and method ot 
development of the lesions The examination of the section or culture is 
sometimes necessary 

Morphaa by the absence of amesthesia, and the coloi 

Raynaud's disease by the progressive ulcerative process, limited to the 
extremity involved, and by the absence of the nerve trunk involvement The 
leprous perforating ulcer is nauseating, the ulcerating lesions of Raynaud’s 
disease are simply offensive m odoi 

Fia 11 



Cla^\ hand (Griffe) of nerve leprosy (Leloir ) 

Syringomyelia — So many obseivers have related cases of leprosy possess- 
ing all the features of this disease and it so often occurs that cases diagnosed 
as syringomyelia are subsequently proven leprous that it is impossible to 
differentiate these except through finding the lepra bacillus, or postmortem 
evidence of changes in the cord without leprous inimlvement 
Prognosis — ^Leprosy is like all other bacillary and infectious diseases , 
it IS self-hnnted Its evidences may last for years, or only for iveeks or 
months Often the disease w ill have periods of abeyance and exacerbation 
Most often the course is run to a fatal issue or the victim may present scars 
or mutilation as the final expression of the spent morbid process The 



134 


INFECTIOUS DISEASES 


average duiation is about eight yeais The mixed and tubercular are the 
moie rapidly concluded, in liom foui to twelve yeais, unless shoitened by 
some mtercurient disease The spontaneous involution of lesions may be fol- 
lowed by no recurrences, but this is usually only a process m the final result, 
though the longevity of the individual may be inci eased by this remission 
Treatment — ^Until recent yeais the sole treatment was directed to sani- 
tary control, in some countries admmisteied undei barbaiic restrictions and 
methods To-day most countries afflicted with the disease are provided with 
hospitals and asylums, the majoiity of these being under hygienic regu- 
lations so far as habit and food are concerned Only a few leper institutions 
maintain systematic medical supervision of the disease itself, but the incli- 
nation IS to expand the measuies of amelioiation foi the inmates In some 
asylums where leprosy has been studied and tieated, a direct result has been 
obtained m a reasonable time In some instances lepiosy has been reported 
cured This is true of the work of Rost m India, Goldschmidt m Trinidad, 
Tonkin m Jamaica, Caiiasquila in Colombia, and of the vork m Louisiana 
Besides this, individual cases are occasionally reported as cuied The most 
striking thing m the repoited cures is the variety of remedial measuies 
employed From the radical samtaiy and individual measuies employed m 
the time of Moses down to the latest seium devised by Rost, the number of 
leprosy remedies has grovn vastly We cannot as yet proclaim a specific 
but we may draw deductions as to the theiapeutic indications 

In all cases under treatment the piogiess m amelioiation is slow On the 
other hand, the disease may be absolutely self-limited without treatment, the 
evidences disappearing without a relapse oi lecuirence The result of tieat- 
ment depends directly upon the individual patient and upon the lesistance 
he possesses or mav acquire against the morbid piocess 
The treatments which have availed most have been supportive and 
hygienic Drastic or reducing methods aimed at specific action have been 
temporarily lemedial, but the disease le-avakens usually m the depleted 
subject Serum treatment has been attempted, but hitherto has been 
successful almost solely m the hands of the one introducing it Rost’s serum 
IS too new to have a final judgment 

The treatment of leprosy may be arranged m several divisions according 
to the method employed, vtz alterative, supportive, empirical, serum, 
sanitary, and suigical 

The alterative treatment has been based upon the idea that such medi- 
cation would reduce hyperplastic conditions and aid then absorption 
Remedies so employed have been bichloride of mercury (Crockei), salicylate 
of soda and salol (Haw^aiian Islands), euiophen (Goldschmidt), chlorate of 
potash (Chisolm, Carreau) and the iodine salts The results have been 
variable, though Crocker has reported 2 cases and Hutchinson 1 case evi- 
dently cured by hjqiodermic injections of the bichloride of mercury, Gold- 
schmidt used europhen hjqiodermically successfully and Gruenfeld of Odessa 
confirmed this result , all of these cases have been isolated instances, how'- 
ever, arguing the first conclusion that the resistance is the essential factor 
Supportive or tonic treatment includes such remedies as hoangnan, 
strychnine, arsenic (Hutchinson and G H Fox), mercurial salts, general 
tonics, each of these having a paiticulai champion for the time being 

Empirical treatment has had a continuous history, even to the present 
wRen every now and then some new' discovery is brought out That much 



LEPROSY 


135 


P'ood has been accumulated by experimental use of remedies is true, but 
no exact deductions have been drawn m the study of those measures 

India has supplied most of the drugs employed Chaulmoogia oil seems to 
have survived almost all the othei herbaceous remedies and is now exten- 
sively employed universally While this may stand as an empirical remedy it 
must also be considered as supportive, as the oil is in large part assimilated 
The dosage depends upon the patient, but to be effective this should be 
increased to 100 to 150 drops at the dose, or 300 to 450 drops a day Begin- 
ning with 3 to 5 diops of the oil in capsule, coffee, hot milk, or cordial, the dose 
may be increased gradually to tolerance The oil may be given m pill form, 
eombined with tonics, as iron, aisenic and strychnine or nux vomica The 
consensus of opinion places chaulmoogra oil fiist among all remedies hitherto 
suggested More cuies have lesulted from its use than from any other one 
remedy, and within a few w'eeks after its use amelioration is noted, even m 
advanced cases 

South America has contributed tw o remedies, assacon {Hui a hraziliensis 
Martin) and tua-tua, both used in the green state by macerating the leaves 
or berries and giving the lesulting liquid The reports on these are meagre 
and questionable The red mangrove, or mangle, has been used in Key 
West and Havana First suggested by a Key West druggist, tins remedy w'as 
extensively exploited by M Duque of Havana The powdered bark and 
root, used in tmctuie or pill, and also employed in the bath, w'ere experi- 
mented w'lth Only one patient was leheved of symptoms by this treatment 
and doubt was tliiowm on this because of previous treatment with chaul- 
moogra oil 

Ichthyol and the mixed toxins of erysipelas, tuberculosis and vaccinia, are 
among other empirical remedies wuthout marked lesult Unna reported 
improvement under ichthyol but he abandoned this for chaulmoogra oil 

The Fiji Islands practice a scorching process wdnch has its merits the 
patient is placed upon a pyre of green leaves of a tree supposed to be 
specific against leprosy In the sIoav process of cooking wdnch the skin 
receives, the disease is supposed to disappear, and if the victim survives, he 
is expected to recovei 

The West Indies and some parts of South America carry the superstition 
that the bite of a venomous reptile wull cure leprosy and occasionally a native 
victimizes himself to this end Influenced by the report of the condition 
resulting from the accidental biting of a lepei by a viper in the West Indies 
the writer used the antn^enomous seium of Calmette in a senes of patients, 
wuth almost unifoim good lesults Three of the patients lecovered In- 
jections were made at frequent intervals, sometimes daily, and the dosage 
varied from 5 to 20 cc The buttocks and the shoulders ivere the usual sites 
of injection, though frequent injections were made m the lesions themselves, 
wutli the inteiesting result that these were directly influenced to favorable 
resolution The cost of the tieatment precluded extensive expeiimentation, 
so normal horse serum was employed in the same manner m a new series of 
cases but wuthout lesult 

The seia of Carrasquilla and of Laverde, deiived from the leprosy bacillus 
and tissues, may be mentioned Both w'ere successful to a greater or less 

egree at the hands of the originators, but failed elsewdiere Quite recently 
a new seruin has been introduced by Rost of the Indian Medical Service 
1 Ins, w Inch he calls “leprohn,” is derived from a toxin of the Bacillus Icprm 



136 


INFECTIOUS DISEASES 


Cultures of the lepra bacilli in special media ere allowed to grow for six 
weeks at a tempeiature of 37° C , then sterilized and passed thiough a Pas- 
teur filter, when glyceime w as added The dose of leprohn is 10 cc , equiv- 
alent to 50 cc of puxe culture of the bacillus The injection should be made 
into the muscles of the buttocks oi of the arm Tivo or three days is the 
usual interval, but both the dosage and the interval are regulated by the 
reaction and the dosage is increased if a reaction of 100° F does not occur 
By increasing the dose in this ivay a proportionate improvement has been 
observed Lepiohn is contia-mdicated where pulmonary or kidney compli- 
cations are present In conjunction -with the treatment, salt is freely adminis- 
tered and equal paits of salt and vaseline are lubbed into the angesthetic areas 
In every patient under treatment, marked impiovement was noted and of 
120 cases treated, 14 w^ere discharged as cured, and a number of others are 
rapidly recovering sensation wuth loss of lepious evidences Unfortunately 
no confirmatory experimentation has been possible, owung to the limited 
supply of serum, but the published results aie most encoui aging 

Treatment resolves itself into the essential fact that the disease is one 
in which a method of reconstruction is necessary, based upon hygiene, diet, 
and medication Experimental tieatment should be secondary to w’ell-knowm 
practice and only wdiere evidence of improvement under recognized treat- 
ment IS absent Tieatment above all must be constant and the patience of 
both physician and the patient must be great 

The regular practice ivitli the winter is to insist upon daily hot alkaline 
baths, a liberal diet without indigestible food, and a legulai dosage wuth 
strychnine in ^ to gi doses (1 to 2 milligrams) Arsenic, iron, the 
phosphates, olive oil, etc , are given selectively The majority of patients are 
treated wuth chaulnioogia oil, but now and then some other tieatment is 
indicated Under this general regime, 12 cases of leprosy have been cured 
since 1894, (10 of these have aheady been reported') 

Surgical treatment is directed at the condition present and consists m 
amputations, neive stretching and electiotherapy The use of r-raj treat- 
ment may be mentioned Gilchrist succeeded m i educing the tubercles 
after a number of exposures Similar repoits have emanated from the 
Philippines but as yet ladiotherapy must be entei tamed only as an aid 
So fai as concerns the United States m the geneial sanitary caie of leprosy. 
Congress has enacted several bills, diiected at the investigation of the dis- 
ease, and m February, 1905, a bill ivas entertained looking to a national 
leprosarium As yet nothing has come of this Meantime, Louisiana regu- 
larly caies for her lepers m a model home under hygienic and systematic 
medical administration The rest of the United States takes little inteiest m 
the subject, excepting San Francisco, where a large Chinese contingent com- 
pels a system of segiegation Massachusetts has established a temporary 
asylum for five lepeis on an island m Boston Harbor 

Earnest effoit throughout the woild promises lelief from the disease in one 
or another way — either by obliterating it by segregation or of finding a 
panacea 

^Medical News, New York, July 29, 1905 



CHAPTEE VII 


TUBERCULOSIS HISTORY AND ETIOLOGY 
By EDWARD R BALDWIN, MD 

HISTORYA 

In Antiquity — Pulmonary tuberculosis, consumption, or phthisis has 
existed from ver}^ lemote times It transcends all other maladies m the total 
number of its victims and the cost to society in civilized countries Tuber- 
culosis was a disease familiar to the most ancient civilizations, ]udging 
from the cuneiform inscriptions on tablets found m Babylonian remains, 
which represent the earliest known human recoids Whether or not it 
existed in the most primitive state of man is a question without present hope 
of solution Consumption may have been known to the Egyptian phy- 
sicians who weie entrusted with the embalming of the dead, and refer- 
ences in the Bible (Leviticus, 26 16, and Deuteronomy, 28 22), written about 
B c 1500, indicate that it was this disease which Moses pronounced as a 
curse to be visited for disobedience Commentators consider the original 
meaning of the passages to have included various wasting disorders It is 
also evident that the laws lecorded m the Talmud (Mischna, B c 500) 
indicated the recognition of tuberculosis in cattle, and forbade the use of 
diseased animals m which ulcers existed 

Hippocrates (b c 460-376) was the first to give an intelligent description 
of phthisis, although empyema and “phyma,” abscess of the lung, were 
included m his classification Otherwise his poitrayal of the symptoms of 
consumption was unsurpassed for many centuries, and his works became 
classic The etiology of phthisis, according to Hippocrates and other early 
writeis, Avas principally the nutation of the lungs caused by the “flux” or 
mucus of the body floAving from the head into the air passages and causing 
ulceration by its retention m the bronchi The Hippocratic school believed 
m the cm ability of phthisis in all stages and the benefits of a change of 
residence Contagion was mentioned by Isocrates Aristotle, also a con- 
temporary of Hippocrates, notes that it was a general belief among the 
Greeks of his day that phthisis was contagious Celsus (b c 30) wrote of 
the disease m three forms atrophy, cachexia, and ulceration Aretaeus 
(a d 50) gave a a ery cleai description of the disease and differentiated it 
from empyema He beheAed in the efficacy of sea Aoyages and country 
air Pliny also lauded pine forests for their healing poAvers 

' The venter is indebted for much of the lustory and chronologj^ in this chapter 
to the Asoiks of Waldenburg, Die Tv.berkulo’ie, 1869, also that of Predolil, Die 
G^chichic der Tiiberkidose, 1888, and Johne, Die Gesclnclite der Tuberhidose des 
Rindcs, etc , 1883 


( 137 ) 



138 


INFECTIOUS DISEASES 


Galen (a d 131—201) considered the disease an ulceration which should 
be treated by measures designed to dry the secretion He therefore sent 
patients to the high land of Phrygia In other details the conceptions of the 
disease held by Galen were like those of Hippocrates , nor w as any further 
light shed upon the nature of consumption for 1400 years, when anatomi- 
cal study began 

From Sylvius to Laennec —The celebrated Sylvius (1695) was the first 
to indicate the connection between tubeiculous nodules and phthisis He 
regarded these nodules as enlaiged lymph glands in the lung, analogous to 
scrofula, and on the scrofulous constitution depended the inheritance of 
phthisis True phthisis always meant lung ulceration, and depended on 
two chief causes, which may be expressed as constitutional and local, the 
first affecting the nutrition of the lung, the second causing the ulcerations 
He gave a careful description of the symptoms, and believed m contagion 
Wilhs (1622-1675) would not accept the teaching that phthisis arose from 
the secretions of the head, and disputed the connection between ulcus pul- 
monum and phthisis Bonnet (1620-1689), who made more than 150 sec- 
tions, published observations, among which were cases of obvious miliary 
tuberculosis, but made no careful distinction between lung aftections 
Manget (1700), who levised Bonnet’s work and added his own investigations, 
first likened miliary tubercles to millet seed, and described them in organs 
other than the lungs He also mentions the caseation and softening of the 
lung tubercles, the latter of which he considered to be of scrofulous natuie 

Morton (1689), whose celebrated book was widely known among English 
physicians, brought the tubercle prominently to attention as the true cause 
of phthisis, tubercles ^ere either benign or malignant and due to obstructed 
glands in the lung fiom excess of lime in the lymph or hypersecretion causing 
stagnation and hardening He described fifteen kinds of consumption, of 
which the scrofulous was the most important, he also believed m heredity 
and contagion Morgagni (1682-1771) was uncertain that tubercles and 
glands were identical, and thought that phthisis could originate from other 
things, he regarded it as extremely infectious, and refrained from doing 
autopsies on consumptives 

The noted Sydenham (1624-1689), Boerhaave (1668-1738), and his pupils 
Auenbrugger and Van Swieten, wrote of phthisis vithout adding anything 
of importance to the previous conceptions of its nature, but largely repiesented 
the views of Hippocrates, Galen, Sylvius, and Morton Mention should be 
made of Cullen (1800), the celebiated Scotch teachei, under whom Benjamin 
Rush, of Philadelphia, studied Cullen wrote a celebrated treatise on phthisis, 
but did not emphasize the tubercle or its contagiousness, scrofulous glands 
in the lungs were the antecedent of phthisis to him The teachings of 
Benjamin Rush exerted a powerful influence on American medicine of 
Revolutionary times He wrote Thoughts upon the Causes and Cure of 
Pulmonary Consumption (1783), in which it was regarded as a disease of 
debility and tubercles the result of hj^ersecretion from the bronchial vessels 
He believed in contagion at first, but doubted it in later life His treatment 
was ^^gorously antiphlogistic bleeding, purging, etc , in the acute or febrile 
stages, and supporting measures in the debilitated stages ^ 


* H B Jacobs has presented an excellent account of Benjamin Rush and other 
American vTTiters on tuberculosis in Johns Hoplsns Hospital Bulletin, 1902, vol xiii 



TUBERCULOSIS HISTORY ANH ETIOLOGY 


139 


A definite advance came in the latter part of the eighteenth and beginning 
of the nineteenth centuries, when Stark (1785) accurately described miliary 
tubercles and prepared the way for the coirect understanding of their 
nature and relation to phthisis Reid (1785), who edited Stark’s work, 
considered the glandular or scrofulous nature of tubercles questionable 

Ivortum (1790), Baume (1795), and Hufeland (1796) held substantially 
the same opinions as Cullen An important contemporary work by Baillie 
(1793) cairied the knowledge of tubercles beyond that of Stark He recog- 
nized the transition stage of tubercles from small to large by coalescence and 
then to soitening He was the first to recognize the tubercles m other organs 
than the lung, but called them sciofulous Portal (1780) coincided with 
Baillie generally and disbelieved m infection, but introduced confusion by 
naming all caseous material “tubeiculous ” Vetter (1803) also confirmed 
Baillie’s results by independent studies 

Most noteworthy is the work of Bayle (1803), who is justly named by 
Waldenburg as the founder of the correct teaching about tuberculosis He 
studied miliary tubercles m all stages and laid stress on their varying degrees 
of opacity, earlier gray tubercles were “granulations” of quite different 
character True tuberculosis wms a constitutional affection w^hicli can cause 
the development of nodules in all the organs and not originate in inflamma- 
tion, although often complicated wnth it, it depended upon the “tuberculous 
diathesis,” and was of scrofulous nature There were si\ kinds and the three 
classic stages of progress described 

From Laennecto Villemin — ^Laennec (1819), wdiose work soon folloived 
Bayle’s, consummated and simplified the knowdedge thus far gamed He 
lecognized the unity of all phthisis as tuberculosis and scrofula as tuber- 
culosis of lymph glands, his ideas in general as to causation and infection 
were distinctly modern, and his descriptions of the tubercle and its trans- 
foimation towmrd ulceration aie unexcelled Most valuable of all Avas his 
gift of the art of auscultation No genius like that of Laennec so far antici- 
pated his OAvn day 

The teachings of Bayle and Laennec w^ere not accepted wuthout opposition 
Broussais (1816), aaRo attributed most chronic diseases to inflammation, 
viCAA'ed phthisis as a chionic pneumonia Bichat (1823) inclined to the same 
theory Gendnn (1828) held that serous membrane “granulations” w'ere 
diffeient from actual tubercles Magendie (1821) and Andral (1829) 
introduced the theory of tubercle as a secretion product and regarded 
caseation as inspissated pus, an inherited predisposition as well as active 
inflammation w^as needed to induce tubercles Louis (1825) established 
Laennec’s teaching, but returned to the idea that the small, gray granulations 
aa ere not tuberculous until caseated He Avas the first to make a scale of the 
incidence of phthisis in the different life periods 

During this period America was represented but meagerly m original 
investigation until 1834, aa hen Samuel Morton, of Philadelphia, published 
the first pathological studies on consumption He w as a student of Laennec, 
and his conclusions as to the nature of tubercles Avere fairly accurate, they 
were ascribed to altered secretion and not to inflammation Morton’s 
work on Pulmonanj Conswwpi'ion found much faAor m America, and 
included excellent therapeutic adAuce as to open-air life and exercise 

Inociilation Experiments — During the period of pathological study at the 
end of the eighteenth century the subject of the infectiousness of phthisis 



140 


INFECTIOUS DISEASES 


excited some attempts at experimental inoculation The belief in contagion 
was universal, but m varying degree English, American, and German 
physicians accepted the piobabihty of infection undei special conditions, 
but the strongest opinions were held by the Latin races, among whom the 
disease was said to be more viiulent The influence of Valsalva and 
Morgagni was certainly most potent m causing fear in Italy 

The first recorded inoculations were by Kortum (1789), which, like those 
of some of his successors (Lepelletier, 1830, Goodlad and Deygalheres, 1829), 
were fortunately unsuccessful, since they were partly upon human beings, 
including themselves The stiife over the question of the danger of inocula- 
tion of sciofula with vaccination led to these first attempts Klencke (1843) 
first announced successful mtiavenous inoculation of a rabbit Meanwhile, 
other experiments with quicksilver (Gaspaid, 1812, Cruveilhiei, 1826, 
Lombard), with glanders (Schilling, 1822), and others, whereby tubercle- 
hke nodules were produced, led opinions astray as to a specific chaiacter m 
tubercle , so that Klencke’s obsei vation was apparently without effect Gieat 
attention was bestowed upon the microscopic and chemical investigations 
during the fiist half of the nineteenth century, owing to the improved instru- 
ments and methods, and hypotheses multiplied about tuberculosis, based 
on the result of these studies Some of them may profitably be enumer- 
ated heie Tuberculosis was regarded as a fibrous exudate due to a special 
dyscrasia by Rokitansky (1842), who was the first to record the micioscopic 
appeal ance of the tubercles Vogel (1845) also considered tubeicles as 
fluid exudates Engel (1844) believed the cause to be the same as tj'phoid, 
only the dyscrasia caused a difterent exudate Escherich (1845) empha- 
sized the influence of soil Eichmann (1845), changes m the sympathetic 
nerve Eurnivall (1842) attributed it to deficient innervation Dupuy 
(1817) and Baron (1822) to hydatids In England tuberculosis was 
ascribed to scrofula, which in turn was due to an unknown cachexia, 
Alison (1824), Glover (1847), Simon (1850), Carswell (1843), and James 
Clark (1836) 

The theory of Addison (1843) that tubercles originated from leukocytes 
caught m capillaries and transformed into abnoimal epithelial cells was 
interesting The studies of Lebert (1849) evolved a claim for a peculiar 
cell associated with tubercle which he called the “tubeicle corpuscle ” 
This was refuted by Henle (1847) and Reinhardt (1850), who found them m 
ordinary pus Virchow (1847-50) classed scrofula and tuberculosis entirely 
apart, restricting the latter term to the miliary foim and considering it a 
form of lymphoma due to an unknown diathesis, caseation was a non- 
specific process Hence the idea of unity in tuberculous diseases received 
a serious rebuff m spite of the important diseoveiy by Buhl (1857) that 
miliary tubercles were most often associated with preexisting caseous 
foci, from which he thought the specific poison originated The micro- 
scopic studies had brought out valuable data, but withal much confusion of 
ideas 

The chemical analyses of tuberculous tissue, especially of cheesy material, 
had brought no better result, and the epoch-making expeiiments of Villemm 
could not have been better timed 

Period from Vlllemin to Koch — ^Ihllemm presented his important com- 
munication m December, 1865, “On the Cause and Nature of Tuberculosis 
and the Inoculation of the Same from Man to Rabbit ” His eonclusions 



TUBERCULOSIS HISTORY AND ETIOLOGY 


141 


were positive “(1) Tuberculosis is a specific affection (2) It has its origin 
m an inoculable agent (3) The inoculation from man to rabbits is very 
successful (4) Tuberculosis pertains, therefore, to the virulent diseases, 
and should be classed with variola, scailatina, syphilis, or, better still, vith 
glanders ” He covered a wide field in his inoculations, employing fiag- 
ments of lung tubercle, sputum, blood, sciofulous gland, and peilsucht 
or bovine tubeicle, with positive results in neaily all cases He failed to 
infect sheep, goats, and birds, and thought them probably immune, later 
e\periments on dogs and cats showed only relative immunity m the car- 
nivora His contiol experiments with cholera deiections, pus fiom glanders, 
cancel masses, worm nodules, and pneumonic lung veie all negative 
Therefore, while there was nothing specific in the structure of the tubercle 
or in caseation, true tuberculosis was always inoculable, this was the only 
test for Villemin Sciofula vas not invariably tuberculous, because not 
always infective Villemin’s conclusions excited widespread discussion and 
contiol experimentation, for such far-reaching statements commanded 
attention 

A new era of science was founded about the same time by Pasteur, and 
had not he become engaged m othei investigations it is permissible to think 
that his genius might have crowned the woik of Villemin by anticipating 
Koch’s discovery by several yeais It was not vithout great turmoil and 
strife of opinions that the truth finally emeiged, foi the contradictory results 
of inoculations Mere difficult to interpret Every conceivable method of 
inoculation in contiol experiments M'as used Besides tuberculous piod- 
ucts there m ere those of cancer, syphilis, typhoid, pneumonia, and suppura- 
tions, inoigamc substances, such as cinnabar, glass, silica, coal-dust, organic 
mateiial, filter paper, hair, coik poM'der, lycopodium seeds, croton oil, 
moulds, etc Comcidently exhaustne histological studies M^ere earned out 
and their results discussed with fervor The majoiity of experimenters 
corroborated Villemm’s results in part, but much weight M'as bi ought against 
his conclusions about the specificity of tubercles by those Mdio obtained 
tubercle-like nodules fiom indiffeient substances The old idea of inflam- 
mation dominated many, vdio legaided tuberculosis as simply a leaction to 
many kinds of iiritation Lebeit, Andren^ Clark, Cohnhcim and B Frankel, 
Aufrecht, Wilson F ox, and Waldenburg M^ere pi oinment among the opponents 
of specificity The inhalation experiments of Schuller (1877), Tappeiner 
(1878), the eye inoculations of Langhans (1868), Cohnheim and Salmonsen 
(1877), Baumgarten (1880), and the feeding and other expeiiments of Klebs, 
Chaveau (1873), Bollinger (1873), together Mith the accuiate histological 
studies, gradually restoied the belief in a specific iirus common to human 
and bovine species 

The contest over the specificity of the giant cell, the importance of wdiich 
M'as emphasized by Langhans (1868), Avas settled in the negative Tubercles 
M'eie studied m all the tissues hitherto unassociated with the conception 
of tuberculosis, as fungous pints, caucus bones, and lupus, by Koster 
(1873) and Friedlander (1873) Tlie deielopment and spread of miliary 
tubercles M^ere traced to venous infection by IVeigert (1879-82) The 
patliMay of infection M^as already inferred by the many feeding and 
inhalation experiments, so that Mith the lapidty developing im estigation of 
bacteria caused by Pasteur’s discoveries search m as being made for a specific 
living organism E Klebs (1877) was the first to observe actual trans- 



142 


INFECTIOUS DISEASES 


ference of the virus by artificial cultuie on egg albumen through several 
generations before inoculation, but he did not succeed in lecognizing the 
bacillus, instead he found a motile organism, the Mo7ias tnhci cidosnm, which 
he piesumed to be the contagium vivum Schuller (1879), Reinstadler 
(1879), and Touissant (1881) also succeeded m cultivating the still unknown 
virus Aufrecht (1881) and Baumgaiten (1882), independent of ICoch, 
described bacilli in the centre of the tubercles, whicli, ov ing to lack of cultuie 
and staining methods, w ere not positively identified as the infective agents 
Thus the actual achievement was due to Robert ICoch, who was a liealth 
officer in an obscuie Geiman town 

Koch’s demonstiation of the causative i elation of the tubercle bacillus 
to tuberculosis vas so complete that but little of impoitance has been 
added since The fiist attempts at staining the organism were by means 
of methylene blue made faintly alkaline by caustic potash and with vesuvm 
as a contrast stain With these stains ICoch Avas able to demonstrate the 
bacillus in all kinds of tuberculous tissues of man and animals, except Avhen 
the tubeicles vere calcareous or otheiwise healed Moieover, by cultuies 
on blood seium through seveial generations and le-inociilation the pi oof 
Avas made complete, and the long dispute about the nature of scrofulous 
gland and skin diseases as AA^ell as A^aiious pneumonias Avas finally settled 
It IS true that skeptics and experimenteis Avith faulty methods continued to 
arise and cast doubt upon the truth, but they giadually disappeaied Never- 
theless the logical application of tlie knoAvledge, so conclusiA'^e and simple 
as to the infectiousness of sputum, has lequired many Aeais to become 
general Much aid aams giA^en in this direction by the investigations of 
Comet (1888) on the presence of bacilli in dust 

The subsequent announcement of tuberculin as a piobable cure (1890), 
the moie lecent discussion as to the lelationship betAveen human and boAune 
tuberculosis excited by ICoch (1901), the vaccination studies, and the still 
more radical aucaa^s mtioduced by v Behring (1902) as to the source, time, 
and patliAvay of infection, constitute periods in the recent history of tubei- 
culosis to AAlnch may be added tlie lapid extension of pieventiA'c measures 
and the sanatorium moA^ement 


ETIOLOGY 

Statistics — General Statistics — The prevalence of tubeiculosis is uni- 
versal, no othei disease is so Avidespiead or pioduces so much poverty and 
long-continued distress Mortality tables do not conA’^ey a tithe of the 
number actually infected as rcA'ealed by pathological examinations, yet 
even such figures as are obtainable from death and census returns sIioav an 
appalling annual sacrifice Fi om one-seventh to one-tenth of all deaths and 
an enormous proportion of invalidism are due to it ICayserhng stated at the 
recent Pans Tuberculosis Congress (1905) that one-third of all deaths and 
one-half the sickness among adults m Germany can be chaiged to tuber- 
culosis A NeAvsholme states that 11 3 pei cent of all deaths in England 
and Wales are still due to it The last United States Census (1900) gives a total 
of 111,059 deaths from consumption, including general tuberculosis, the 
rate being 109 9 per 1000 deaths, or about one-ninth of the deaths from all 
knoAvn causes Other forms of tuberculosis and deaths from mtercurient 



TUBERCULOSIS HISTORY AND ETIOLOGY 


143 


diseases in the course of consumption do not appear in the last-mentioned 
statistics, so that the true figures are appreciably greater ^ 

The following are the totals for the yeai 1900 m tA\o countries 

Population Cases 

76.000. 000 111,059 

56.000. 000 118,706 

Total 132,000,000 229,765 

The lack of uniform systems of registrations of deaths makes a comparison 
of various countries and states imperfect at best The impoitant factors 
influencing the mortality tables are density of population, occupation, social 
condition, race, color, and se\ Quoting from the United States Census, 
1900, Part I “The death late from consumption was about the same in the 
cities m the registration States (204 8 per 100,000 population) as in the 
cities m the non-registration States (204 9), in both of -nhich it was much 
higher than in the rural districts of the registration States (134 1) The death 
rate of the colored race from consumption (490 6) was nearly thiee times 
that of the whites (173 5), and that of the foreign whites (231 1) '\\as much 
higher than that of the native whites (155 4) For the last-mentioned class 
the death rate for those having one or both parents foreign (184 8) was also 
much higher than those of native parents (126 5) The death rate of males 
fiom this disease (white 188 3, colored 527 3, including Indians and Chinese) 
was considerably higher than those of females (white 158 8, colored 455 1) ” 
As to the last statement the leverse is true in the country as a whole, the 
female rate being higher in the rural disti icts 
Occupation and social condition appear to have the most intimate relation 
to the ratio of mortality Stonecutteis, cigarmakeis, and plasteieis head 
the list with about half the deaths in these occupations, faimers and persons 
undei the best social conditions have less than one-eighth due to tuberculosis 
The greatest moitality from tuberculosis is between the fifteenth and forty- 
fourth year of life, when it causes one-third of all the deaths occurring during 
that period The months of greatest mortality are March, April, and May, 
when other respiiatory diseases are at their height 
The economic loss from tuberculosis is enormous even with a low valua- 
tion placed upon an indnidual life Taking an average of 8500 as the 
earning power during the most productive years, the cost to the United States 
for the year 1900 was approximately §45,000,000, there being 89,305 deaths 
between the ages of fifteen and sixty, or more than foui-fifths of the entire 
number In the German Empiie there were 85,280 deaths in the same year 
Estimating the loss of earnings according to Cornet at 600 marks per annum, 
the sum was 51,168,000 marks When it is recalled that the average time 
of paitial or complete disability of a consumptive is at least two years, and 
the enormous cost of nursing and support has not been included, the above 
sums may be trebled with fairness Biggs estimates the cost to New York 
City alone as $23,000,000 It is safe to say that tuberculosis costs the United 
States $150,000,000 to $200,000,000 yearly 

’ In the United States 88 5 per cent of the tuberculosis mortality (1900-1904) in 
the registration area y as classified as ‘tuberculosis of the lungs ” A Newsholme 
goes 69 per cent for England and Wales (1903), Comet 813 per cent for the 
German Empire (1896 to 1900) 


United States 
German Empire 



144 


INFECTIOUS DISEASES 


Geographical Distribution — ^Tuberculosis is prevalent at all latitudes and 
altitudes and in all climates It is most frequent m tempeiate zones and 
lowlands and is rare m the elevated plateaux and Aictic regions The influ- 
ence of occupation and density of population explain to a large extent the 
differences m its incidence rather than geographical location alone There 
seems, nevertheless, to be a distinctly protective influence m the climates of 
and regions, and especially in elevated, invigorating climates, as Colorado, 
Mexico, and the Alps The tiopical countries furnish no statistics as to the 
frequency of tuberculosis, but it is said to be less common than in temperate 
regions, although more rapid m its course In Natal, South Africa, the 
disease is infrequent according to J F Allen ‘ Prmzmg^ has made a com- 
parative study of the death rate to emphasize the relatively gi eater importance 
of other factors than geographical situation For example, the average 
tuberculosis mortality for the year 1891 to 1900 m Switzerland was 26 1 
to 10,000, while m England it was 20 1, but m Ireland 27 8 Likewise in 
Germany the rate was 24, but m Austria 34 5 and in Hungary 3G 4 
Kace — The question of varying susceptibility in different laces has been 
much discussed and is closely connected with that of inherited oi acquired 
immunity It is certain that the aboriginal and uncivilized peoples easily 
acquire it m a rapidly fatal form, even when their conditions of living are 
favorable Notable among such races are the American Indians, Negroes, 
and Hawaiian Islanders The so-called half-breeds and mulattoes are 
especially liable to the disease, and it has usually followed the advent of the 
white races among uncivilized natives Benjamin Rush stated that the 
disease was unknown in America among the Indians m their natural wild 
state, but the early New England physicians mention its prevalence among 
the natives in their day The lecent emigration to Alaska has been follov ed 
by the decimation of the Indians from various diseases, especially measles 
and tuberculosis in acute foims It is reasonable to suppose that the gi eater 
virulence is in part due to greater susceptibility of tissue, though undeniably 
the chief factors are filthy habits, poverty, and predisposing diseases The 
mortality from consumption m recently immigrated races m the United 
States IS generally much higher than those of longer residence Among 
those whose mothers were of foreign birth the rate was highest in the lush 
(339 6), French (187 7), Scotch (172 5), Germans (167), while the rate was 
lover (71 8) in the Russians, Poles (107 7), and in the Hungarians and Bohe- 
mians than m the natives of the United States (112 8) That this different 
mortality is due to vaiying susceptibility is very doubtful On the other 
hand, the Hebrews are thought to have relative immunity to tuberculosis 
Decrease of Tuberculosis — 'One of the most encouraging and mstructn e 
facts IS the remarkable deciease in the death rate in civilized countries 
during the last fifteen j^ears It is at once a confirmation of the value of 
the hygienic measures and one of the obvious benefits of improved condi- 
tions of life for the laboring classes m large cities From being the greatest 
scourge during the nineteenth century, when Good thought it no exaggeration 
to estimate that one-fourth of the population of Europe died of consumption, 
it IS becoming so greatly lessened that in twenty years, from 1885 to 1903, the 
1 ate for Prussia fell nearly one-half, or 3 1 to 1 9 per 1000 living (Kayserhng ) 

^ Transactions of the British Congress for Tuberculosis, 1901, vol iii 

’ Zeitsch f Hygiene u Infek , 1904, vol xlw 



TUBERCULOSIS HISTORY AND ETIOLOGY 


145 


The same is true of England, Avhere a decrease of 50 per cent has taken place 
in forty years In the United States there was a decrease of 54 9 per 100,000 
living between 1890 and 1900, the rate being 254 4 and 109 5, respectively 
This^ decrease is principally in the large cities. New York being the most 
conspicuous by a lessening of 40 per cent in 16 years (4 06 to 2 68 per 1000, 
1887 to 1902) “During the last ten years there has been a decrease of 40 
per cent in the death rate from pulmonary tuberculosis and tuberculous 
meningitis m children under fifteen years It is precisely in the youngest 
element of the population that one would first look for definite results from 
the enforcement of measures for the restiiction of the diseases” (Biggs) 
Massachusetts has exhibited a marvellous decrease of over 50 per cent (7 77 
to 3 1) in the fifty-one years between 1851 and 1902 The decrease has 
steadily continued in all the Eastern and Middle States and to a consid- 
erable extent in the rest of the country In five of the New England 
cities the death rates decreased from 30 7 to 21 4, and m seven of the Middle 
States cities fiom 31 4 to 23 4 per 1000 population The latest mortality 
leports (1906) fiom the United States registration cities bung the average 
per 100,000 from 1900 to 1904 to 190 3, as compared with 204 8 in 1900 and 
265 6 m 1890 

In some foreign countries the decrease is less marked during'twenty 
years, but yet distinctly evident, as in London (3 12 to 2 34), Berlin (3 6 to 
^ 2 39), and Vienna (7 2 to 4 76) No decrease has occurred m Pans to 1900, 
wheie the rate was very high (5 46) A Newsholme,^ who has made exhaustive 
studies, finds that the factors accompanying the decrease are very com- 
plex, and that much of the decrease had occurred before the discovery of 
the tubercle bacillus and the increased hospital and sanatorium care, the 
latter, however, he considers the most important factoi “Segregation in 
general institutions is the only factor which has varied constantly with the 
phthisis death rate in the countries that have been examined It must 
theiefore be regaided as having exerted a more powerful influence on the 
prevention of phthisis than any of the other factoi s of which none has varied 
constantly v ith the phthisis death rate ” 

To summarize the facts (a) The death rate from tuberculosis has decreased, 
in the places where special attention has been given to the hygienic control 
of the disease, from one-seventh of all deaths in 1890 to one-tenth in 1900 
(6) The general mortality from all diseases registered has declined from 
19 6 to 16 7 per 1000 m the United States between 1890 and 1904, princi- 
pally because of the lessened rates from tuberculosis and children’s diseases 
It IS significant that the development of sanitation has been rapid during 
this decade 

Zoological Distnbution — Animals in Naim al State — ^Tuberculosis is 
practically unknown in animals or birds in the wild state or among those 
M ho hai e never been confined or brought m contact with domesticated 
species Cattle who roam m ild upon the plains are very rarely found to be 
affected In abattoirs the number for all the cattle inspected, coming chiefly 
from the plains, as but 0 134 per cent in 28,000,000 ^ It is quite other- 
wise vith animals in menageries and zoological gardens, here the disease is 


' Joimial of Hygiene, 1906, vol m, p 374 
United States Bureau of Animal Industry Reports, Postmortem Inspection, 1900 
to 1905 


’'OL III — 10 



146 


INFECTIOUS DISEASES 


frequent among a great variety of lierbivoia, but less often among carnivora, 
in whom it is also more clironic in charaeter Monkeys and apes are the 
chief sufferers, labbits and guinea-pigs larely acquire it spontaneously 
Instances are known of the disease in the giraffe, antelope, zebra, lion, tiger, 
jaguar, panther, fox, jackal, tapir, etc Wild birds m aviaries are likewise 
subject to a\ian tuberculosis, but, excepting paiiots, rarely acquire the mam- 
malian type Occasionally, carnivoious buds like the hawk, eagle, owl, 
and stork have been found tuberculous, as well as watei fowl — ducks, geese, 
swans, and cranes (Nocard, Woods Hutchinson, Weber and Taute, 
Rabinowitsch) Spontaneous tubereulosis in reptiles, fishes, and other 
cold-blooded animals has been long legarded as a possibility, though rare 
Inoeulation experiments with mammalian tubercle bacilli also seemed to 
confirm this opinion, but more careful lecent investigations (Webei and 
Taute 1903) have revealed that the disease in these animals is probably a 
form of pseudotubeiculosis produced by a sapiophytic bacillus 

Domestic Animals — All domesticated animals and birds are known to be 
liable to tuberculosis, but the frequency is greatest m dany cattle The 
proportion is estimated as from 10 to 15 pei cent in America, but is much 
greater m the British Isles and Em ope, whereas high as 30 per cent has been 
discovered by inspection and the tubercuhn test It is said to be unknown 
on the islands of Jeisey and Guernsey, also in Japan, where a certain insus- 
ceptibility appeals to exist among the native stock (Kitasato) The greater 
ineidence of tubeiculosis among highly bred cattle is significant of the 
effect of more careful housing and hence greatei opportunity foi contagion 
The increasing use of the tubercuhn test has levealed an enormous prevalence 
of latent tuberculosis m apparently healthy cows Next in frequency to 
dairy cattle, hogs are most subject to this disease and suftei ehiefly from 
the bovine type of tubercle, from which fact it is evident that they obtain 
the infection from cattle, both by association and m food, especially milk 
The practice of feeding offal obtained from abattoirs is a frequent source of 
infection The United States Reports of Inspection show 0 23 per cent in 
119,000,000 hogs slaughtered during 1900 to 1905, but it is more fiequent 
in Europe ’ The disease m hogs is often acute, but also presents a chronic 
lymphatic type, hence the name “scrofula,” from scwfa, a sow 

Sheep are seldom affected, there being but 0 003 per cent in 37,000,000 
inspections, many of which were probably instances of pseudotuberculosis 
Horses aie larely attacked, only one instance in 9544 inspections being 
reported Nocaid mentions having seen eleven cases of abdominal tuber- 
culosis in hoises, which were evidently deiived fiom intestinal infection of 
bovine origin Goats and asses are likewise relatively immune to spon- 
taneous mfeetion, but European veterinarians have reported several cases 
among goats Camels are occasionally tuberculous Dogs and cats, like 
other carnivora, are quite insusceptible, yet several hundred cases have 
been recorded, and the disease is acquired by contact vith consumptives, 
m most instances from swallowing or inhaling sputum Kittens are quite 
easily infected from milk containing tubeicle bacilli (Nocard) Among 
rodents, rats and mice are highly lesistant to experimental tuberculosis and 

' The United States Report for the year 1905 shows a large increase in hogs, which 
reached about 3 per cent in the largest abattoirs, and is to be made the subject of 
special inquiry 



TUBERCULOSIS HISTORY AND ETIOLOGY 


147 


are not spontaneously diseased On the other hand, rabbits, guinea-pigs, 
and gophers are readily inoculated, yet seldom acquire it even in confinement 

Avian or tov 1 tuberculosis is most frequent among chickens, in whom it 
may become epidemic when once introduced into a flock It''seems to be 
common in Europe, but relatively infrequent m America Pigeons, turkeys, 
ducks, geese, and pheasants have it to some extent, by reason of their habit 
of feeding with chickens whose infected excreta contaminates the food 
Cases among canaries and other small pets are recoided, but moie often 
parrots have obtained the disease from human sputum by accidental inocula- 
tion 

Bacillus Tuberculosis — ^Morphology — The tubercle bacillus is a minute, 
colorless rod, and according to the classical desciiption of Koch has a slightly 
bent shape, with generally uniform contour and slightly rounded ends 
It IS very variable m length and somewhat so in thickness The foims 
usually found in sputum vary m length fiom 0 0015 to 0 004 millimeter 
(1 5 to 4 /i), from one-fourth to one-half the diametei of a red blood cell 
and in diameter about one-fifth the length of the rods 

Staining Pioperties — The most striking peculiarity which distinguishes 
it from most other bacteria is the powei to hold aniline dj^es in spite of long 
exposure to acids and alcohol The exceptions which may cause confusion 
are few the smegma and the piobably identical so-called syphilis bacillus, 
the leprosy and the various pseudotuberculosis bacilli The acid-alcohol 
resistance is due to the pecuhai waxy nature of the bacillus, which substance 
by extraction wuth alcohol and ethei may be entirely removed, and with it 
the specific staining reaction Ordinary basic aniline dyes stain this organ- 
ism wuth difficulty 

Pleomorplnsm and Classification — The many modifications m form and 
size wdiich can be pioduced by varying the growth conditions have led 
bacteriologists to class the tubercle bacillus as a parasitic fungus capable of 
a higher older of development than ordinary bacteria The observations 
of Roux, Metchnikoff, Maftucci, Klein, Fischel, Coppen-Jones, Craig, 
Abbot and Gildersleeve, Wolbach and Ernst, and others have conclusively 
showm that under favoiing conditions for saprophytic giow’th, bizarre forms 
W’lth lateral branches and long filaments with club-shaped ends or swellings 
and vacuoles may appear, of a sti iking similarit} to actinomyces This 
plcomorphism of tubercle bacilli is rarely found in the tiue parasitic condition 
of growth, 1 c , in the tissues of animals, but may be found in sputum, w here 
they are probably evidences of growth on the inner surfaces of lung cavities 
Coppen-Jones, Lubarsch, Friedrichs, and Schulze have also observed the 
club foims and fiingus-like radiate airangement in tubercles of rabbits 
inoculated wuth human, ai lan, and pseudotubercle bacilli These branched 
forms and other morphological ^arlatIons are most often found m cultures 
of fow 1 tuberculosis, but also in those of human and bovine types O^^olb^if-b 
and Ernst) 

The more easily a particular strain of bacilli may be artificially cultnated, 
and the longer it has thus grown as a saprophyte, the more frequently 
it assumes the irregular foims In consideration of these similarities to 
other fungi, bacteriologists are inclined to place the tubercle bacillus in 
a class inteimediate between the bacteria and streptothrices, hence the 
name proposed b-\ Coppen-Jones, “tuberculom-^ ces,” and by Marpmann, 

im cobactcrium tuberculosis ” 



148 


INFECTIOUS DISEASES 


Spore Formation and Involution Forms — Koch described highly refi acting 
bodies in the tubercle bacillus, most of which took no stain, but some were 
intensely stained and unusually resistant to acids He considered both to 
be evidences of spore foimation, but the unstained segments familiarly known 
in many sputum bacilli have since been recognized as vacuoles or breaks 
m the protoplasm The globular, deeply staining bodies aie, however, 
more nearly allied to spores, though not possessing the heat-resisting powers 
of other known spores They often occupy one end or the middle of a bacillus, 
and the deeply stained balls with a faintly stained rod attached, which is 
usually of lesser diameter, are veiy characteristic foi old or inactive cultures 
They are also seen in considerable numbers in sputum from chionic cases 
All the bacilli may show them, and the conclusion is justified that they are 
resting foims even if not strictly signs of sporulation They resist drying 
longer and are found in dust specimens (Coppen-Jones) It is possible 
also to produce forms resembling them by ovei heating a slide specimen 
Degeneration forms of tubercle bacilli are often seen together with the 
nodulated bacilli The vacuolation is due to shrinkage and loss of proto- 
plasm, which then loses moie or less of the acid resistance in decolorized 
preparations of old or dead bacilli Young living cultures may occasionally 
present vacuolation when cultivated on brain media (Wolbach and Ernst) 
In the mam, however, young forms do not have many vacuoles in ordinary 
cultures, nor m sputum from acutely progressive disease They may readily 
be produced m an artificial way by extraction with solvents 

Vaneties — At the present time it may be stated that theie are four fairly 
distinct types of strictly infectious tubercle bacilli the human, bovine, avian, 
and reptilian or piscine Besides these there are certain saprophytic bacilli 
which are probably distinctly related to the preceding and properly classed 
as pseudotuberculosis bacilli All four paiasitic forms of tubercle bacilli 
have certain characteristics in common, but are sufficiently variable in otheis 
to be distinguished from each other Many observations in the past tended 
to show that these varieties were mainly accounted foi by difteiences in the host 
which harbored them, being capable of comparatively lapid transformation 
one into another and originating from a common source oi stock This, 
in fact, was the original belief of Koch at the time of his first inoculation 
experiments, but the studies on the morphology and virulenee of mammalian 
bacilli by Theobald Smith (1898) and those of Lartigau, Ravenel, Schutz, 
and others raised doubts as to their identity and to disputes as to the inter- 
inoculabihty of the human and bovine types The constaney of these dif- 
ferences led Koch to a negative position as to the danger of ‘'perlsucht” 
or bovine tubercle bacilli foi man, and to a diligent study of the whole 
question since the diseussion at the British Congress for Tubeiculosis (1901) 
Out of much strife the truth seems to be emerging in favor of an intermediate 
position between the standpoint of those who hold the belief in strictly 
distinct varieties and those who favor an absolute unity foi all While the 
German Imperial Commission^ appointed to study the question has reported 
in favor of radical distinctions as held by Theobald Smith, the United States 
Bureau of Animal Industiy" finds that the types of tuberele bacilli are very 

' Kossel, Weber, Heuss, Taute, and Beck Tiibei ciilo^e Arheiten am dan Kaiser- 
hche Gesundheitsamtc, vol i, 3 

^ De Schwemitz, Dorset, Schroeder, and Cotton United States Bureau of Animal 
Industry, Bulletin No 52, I-III 



TUBERCULOSIS HISfORY AND ETIOLOGY 


149 


inconstant The conclusion of v Belli mg that varying types and transition 
forms depend solely upon the animal host, and that the viiulence of a given 
strain of bacilli fuinishes no criterion as to its original source, is practically 
concurred m by the British Royal Commisson on Tubeiculosis,i whose report 
of extensive experiments with bovine and human cultures speaks for the essen- 
tial unity of these two forms Nevertheless, while the mam point of contention, 
namely, that the bovine type of bacilli is capable of infecting human beings, is 
now considered settled affirmatively, there is yet sufficient reason for a broad 
distinction betw'een the human and bovine types, and still more betw^een 
them and the avian and reptilian bacilli It is theiefore important to note 
the points of difference possessed by the most characteristic individuals 
in each class 

Human Type — ^This form, already described above, has a greater length 
(2 to 2 5 fj) than the bovine, and is thinner and more regular m outline and 
staining, but is less easily to be distinguished microscopically from the avian 
type It giow's more readily on all media, produces increased acidity in 
culture broth (Smith), and is less virulent for small and large herbivora 
than the bovine It rarely infects carnivora, and yet moie rarely fowls, 
birds, and reptiles 

Bovine Type — ^The average length is from 1 to 1 5 In comparison 
Avith the longer human and avian types the outline is more irregular and 
often oval and plump with blunt ends , the staining is less uniform, but vacuola- 
tion IS not so evident The growdh is slower in cultures, though ultimately 
not different in appearance from the human and produces an alkaline re- 
action in culture broth (Smith) It is infectious for all mammals so far tested 
by inoculation experiments, and is more virulent for them than the human 
type It has been found m the mesenteric and cervical nodes of human 
beings, and in the sputum at least once Its infectiousness for foivls has 
been open to doubt (Weber and Bofinger), although v Behring reports an 
instance of spontaneous infection m chickens from which he isolated bacilli 
vnulent foi cattle 

Avian Type — The bacillus of chicken tuberculosis is similar to the human 
tj^e m general appearances, but show's pleomorphism more frequently The 
rods are often more slender and longer than the other vaiieties, and much 
less adherent to each other m grow'th , therefore, they do not form the com- 
pact masses seen m stained smears of the human and bovine types Grow th 
IS rapid on all media and is distinguished by a moist, creamy consistence 
seldom seen m the others, it thrives at a higher temperature (43° C ) and 
produces an alkaline reaction in broth cultures (Bang) It is highly infectious 
tor barn-yard fowds, but less so foi pigeons and carnivorous birds Very 
few animals are susceptible and guinea-pigs are nearly immune Rabbits 
inaj easily be infected Mice, rats, and pigs have been successfully 
inoculated and liaie been found spontaneously diseased (Rabmowntsch), 
but the larger animals are quite refractory, it w'as, how'ever, found m a 
monkey by Rabmow itsch Cases have also been reported w here the aA lan 
bacillus has been found in human sputum (Kruse, Pansini, Rabmowutsch) 
and m intestinal tuberculosis m cattle and horses (Johne and Frothingham, 
Nocard), but they lack complete proof of their origin from axuan sources 

Report of the Royal Comvnssion, etc , 1907, Part II, \ppendix. 



150 


INFECTIOUS DISEASES 


Reptilian and Piscine Type — It has been customaiy to include among 
tubercle bacilli certain varieties winch grow leadily at low tempeiatures 
(20° to 25° C ), and are found in fishes and cold-blooded animals, such asfiogs, 
snakes, lizards, and turtles These are now relegated to a class by themselves 
and are only infectious to reptiles and fishes undei unknown conditions, 
but not to mammals and birds so far as known The studies of "W eber and 
Taute have apparently shown that they belong to the class of pseudotubercle 
bacilli which can grow in nature as saprophytes and cannot be aseribed to 
an alteration of mammalian or avian types under natuial conditions ^ 

Pseudotiibercle Bacilli — During recent years an increasing number 
(between 30 and 40) of acid-proof bacilli have been encountered which 
strongly resemble true tubercle bacilli in morphology and staining properties, 
but more often show actinomyces-like foims The most important are the 
milk and hay bacilli of Moeller and the butter bacilli of Rabmowitsch, 
Petri, and others They are generally rather thicker and less acid-proof 
than true tubercle bacilli, and all grow more lapidly and at low temperatures 
Cultures of the various milk, pseudobovine, and grass bacilli, of which many 
varieties have been described, are similar in so many features that it is very 
likely that they are closely related if not identical in origin Some form 
yellowish-red pigment in mature cultures, but otherwise much resemble 
tubercle bacillus growths 

The smegma group forms another series of acid-proof bacilli which are 
of more importance in causing confusion in the diagnosis of tuberculosis 
They are found about the external orifices of both man and the lo^^ er animals, 
and there is evidence to show that the presence of sebaceous fat at these 
situations has mueh to do with their resistance to decolorization 

The reptilian bacillus cultures are more like the avian in their soft, creamy 
consistence, and practically indistinguishable from mammalian and avian 
types m stained specimens None of this class can claim parasitic importance 
for mammals, yet inoculation may produce localized tubercles which soon 
disappear without caseation in guinea-pigs and labbits, thereby indicating 
that they are like the result of any foreign body iiritation ^ 

No evidence has been forthcoming that any spontaneous disease results 
from these organisms except in fishes and reptiles (Dubard, Friedmann, and 
Kuster) ® They have been a source of error in some of the earlier researches 
in connection with milk and butter, nor can they be negleeted in connection 
with the diagnosis of human tuberculosis, especially of the gemto-urmary 
and intestinal tracts They have been found in cases of lung abscess and 

‘ The fish bacillus of Bataillon, Terre, and Dubard, the blind-worm bacillus of 
Moeller obtained from a worm inoculated with sputum, and the turtle bacillus of 
Friedmann are forms supposed to ha\e been produced by the alteration of mam- 
malian types Sorgo and Suess (Cf Baht , \ ol hii) also found this true m their 
inoculation experiments with cultures of human bacilli on snakes and worms, m which 
they produced tubercles and apparent infection 

^ An exception appears in the Bacillus tuherculoides II (Beck), which has the 
morphologs’- and staining peculiarities of the pseudotubercle bacdli, but the actual 
position of which is not yet certainly w ith that class, since it is infectious for guinea- 
pigs, rabbits, and white rats, and "was isolated from the tonsil of a consumptne 
w'oman It may be an intermediate variety between the pseudobacillus and true 
human bacillus, but m rapidity of growth resembles the former 
^ One case of enteritis m a cow is reported by Borgeaud as due to them Cf 
Balt , ^ol xxxix. Ref 



Tl'BERCULOSIS HISTORY AND ETIOLOGY 


151 


(rantrrene, as ^^ell as m cerumen fiom the ear and in the nasal secietion 
Attempts to associate various acid-pioof bacilli m the same class nith the 
true parasitic forms of tubercle bacilli, on the ground that guinea-pigs 
inoculated nith them react to tuberculin similaily (Zupnich), oi that extracts 
made from cultures known as “paratuberculin” resemble tuberculin 
(Irimescu), and that they can immunize against tuberculosis to a certain 
degree (Klemperer, Moeller, Friedmann), are open to the objection that 
many non-specific bacterial substances can produce like results Neier- 
tlieless, tliese experiments and those of Koch, nho shoved that specific 
tuberculosis-agglutinating serum caused agglutination of grass bacilli and 
precipitation of their culture fluid, suggest group reactions comparable to 
those of the tj^rhoid and colon bacilli, and, therefore, relationship 

Differentiation — Differenhahon by Stammg — All forms of tubercle bacilli 
stain deeply with acid-fuchsin-phenol or aniline-water, but retain the stain 
with ^arymg tenacity undei treatment with acids and alcohol In general, 
the pseudobacilh decolorize more easily than the true parasites According 
to Abbott and Gildersleeve they can generally be decolorized by 30 per cent 
nitric acid The smegma bacillus usually loses the dye upon repeated 
treatment with alcohol, but m doubtful cases such tests are unreliable, and 
inoculation should be done 

By Culture — ^The diffeiences in reaction produced m broth cultures are 
noted elsev here Theobald Smith and Bang consider that the human can 
be differentiated from the bovine and avian types m this way 

By Btochcvi'ical Bcachons — Bonome claims that specific differences in 
precipitating power can be determined by means of the serum and plasma 
extracted from tubercles, which seive to distinguish bovine from human 
infection 

Biology — The tubeicle bacillus is a facultative parasite, requiring con- 
ditions fonts gi owth outside of animals v Inch do not exist in nature so far 
as known 1 The requirements aie (a) temperatuie betveen 29° C and 
42° C (optimum 37 5° to 39° C ), (b) moisture, (c) a moderate amount of 
oxygen, (c/) protection from light, and (e) suitable pabulum containing 
easily assimilable nitrogen and phosphorus Its multiplication is lelatiiely 
slov, being far outstripped by most bacteria, and this fact alone vould 
render its existence difficult except in pure culture, since the associated 
organisms vould soon exhaust the soil The tubercle bacillus is non- 
motile and grovs more rapidly and more luxuriantly the less is its virulence, 
comcidently it becomes less sensitive to change of culture media These 
ohseriations coupled vith its veil-known loss of virulence after prolonged 
cultivation haie suggested the possibility that at a remote period m the past 
it may have possessed a saprophyflic existenee in nature, a property long 
since departed from it m its struggle to adapt itself to animals vdio had 
1 ecen ed it v itli their food 

dlie jiroperty of pleomorphism has led some bacteriologists to regard it 
as an abortive form of a fungus, unable to complete its cycle of development 
as a parasite The discoiery m recent lears of a series of sapiophytic, 
acid-resistmg bacilli vhich resemble the tubercle bacilli and under certain 

Ihe possibility of a limited reproduction in the moist sputum deposited in a 
and dark room mai not be denied Some unconfirmed expenments by 
Arthur Itansome would point to its samtarj importance 



152 


INFECTIOUS DISEASES 


conditions can produce tubercles in animals (in the sense of nodular cell 
collections) strengthens the idea that they all belong to a common gi oup the 
individuals of which have been modihed by difteient environment and 
selectivity They are also alleged to have interacting, immunizing, and 
agglutinating powers and allied chemical products Notwithstanding these 
properties, the constancy of the four diftei ent parasitic types and their readi- 
ness to return to parasitic conditions, whereupon their virulence is quickly 
restored, prevent such generalizations about the tubercle bacillus at present 
Transformations mto Other Types and Variations m Virulence — Conclusive 
proof IS thus far wanting of an actual or permanent transformation of one 
type into another by passage through animals or by culture Much interest 
was excited in this subject by Koch’s announcement of the non-identity of 
human and bovine tuberculosis in 1901, and it was still a subject of difference 
of opinion at the Pans Congress of 1905 On the whole, the evidence is 
against such a change, although an increase of virulence of the supposedly 
human type for goats and cattle is apparently shown by the inoculations of 
V Behring, Pearson and Ravenel, and especially by Dammann and Musse- 
meier and Karhnski Against these are the negative lesults of Theobald 
Smith, Kossel, Weber, and Heuss Others represent the opinion that 
transition forms exist between the two types (v Behring, Dorset, Fibiger 
and Jensen, Eber, Rabinowitsch, L and M ) Piactical difficulties stand 
in the way of an easy solution of the question, and also the determinations 
of inherent differences of viiulence grade of the human type for man by 
inoculation into rabbits and guinea-pigs That these diffciences exist is 
apparent in the varying clinical couise of tuberculosis m certain families 
wheie the source of infection may be assumed to be the same for each mem- 
ber Some are mild and chronic, others acute and rapidly progressive, 
nor can assumed differences in susceptibility always account for this 

From the extensive work of C Frankel on the question of diffeiences in 
virulence, there would seem to be considerable variation between cultures 
from human sources m this respect Furthermore, the capacity of some 
tubercle bacilli for homogeneous giowth in liquid media is accompanied by 
a marked loss of virulence and points to a reversion to saprophytic exist- 
ence, since many pseudotubercle bacilli possess or assume this pioperty 
Variations m the chemical composition of tubercle bacilli and the products 
of their growth m cultures are also associated with difference m vnulence 
Cultivation — Difficulties beset the cultivation of the mammalian bacillus 
from the tissues of the diseased animal, and it grows reluctantly at first on 
most media The first evidence of growth to the eye is a group of minute 
dull or glistening points after five to ten days, rarely less than eight days 
The increase is slow, but in three weeks the surface is covered either by a 
thin, dull pellicle or small, mealy grains, isolated or crowding together, which 
form slow ly heaping-up masses or wrinkles During active growth mamma- 
lian bacilli preserve a dull, ground-glass, grayish-white appearance which, 
when multiplication is suspended, slowly become moist and soft if water 
or glycerin is still present In drying and m the presence of oxygen old 
cultures of the human tjqie become reddish brown and even reddish coloied 
on certain media, especially potato, the bovine type does not show this 
property The multiplication of tubercle bacilli is presumably by end 
fission, which results in peculiar S-shaped curls or tapering, curved tufts 
in beginning growths, these are composed of masses of parallel rods and are 



TUBERCULOSIS HISTORY AND ETIOLOGY 


153 


caused by the longitudinal c^o^\ ding of the 3 oung bacilli In stained prep- 
arations of undistui bed colonies the curls are Avell shoun and the individual 
bacilli are seen cohered b}"^ an amoiphous, cement-like substance In old 
dr3 cultures which retain the stain poor^', e\eept at the brilliantly stained 
nodes or “spores,” the appearance of the parallel bacilli has been aptly 
compared to a school of intant fish swimming m one direction 

Freshly isolated cultures from animal tissues on serum or egg tubes are 
usually shorter, more homogeneously stained, and uniform 111 size than 
further transfers on other media Under some conditions of lapid grovth 
the youngest bacilli, being pool in protoplasmic wax, may retain the stain 
but faintly under acids “primthf bamllcs” (Marmorek) The tubercle 
bacillus will not grow directly from the animal tissue m a liquid medium, but 
the thin pellicles which spread over the condensation water of serum cultures, 
01 scales caiefully lifted from the solid surface, aie transferred easil}^ floated 
upon broth, and glow luxuiiously as a vrmkled crust over its suiface 
The broth underneath remains clear, which fact provides a rough test foi 
the absence of contamination Should the flakes become agitated and the 
crust wet, the growth ceases and the soaked bacilli sink to the bottom 
On mg to its need for oxygen the tubercle bacilli grow readily on the surface 
of broth, but b}' special manipulation some cultures ma}" be trained to grov 
homogeneousl}'' through the liquid (Arlomg and Couimont) Frequent 
shaking IS necessary to accomplish this and the avian type is best suited for 
the puipose The power of motility is claimed foi such bacilli, but it cannot 
be legaidcd as an3'thing but “Browmian” or “molecular” motion 

Imnting Pine Culhnes — Koch succeeded first in isolating pure cultures 
by the use of coagulated blood scrum, and it lemams to-day one of the best 
sources of fiesh cultures Dorset’s egg medium is probably the simplest 
and easiest method for isolating pure cultures fiom tissues It is made by 
breaking fiesh, cleansed eggs into a sterile flask and thoroughly mixing the 
yolk and ivliite, after which the mass is strained through sterile cheese-cloth 
and distributed into sterile tubes No neutralization is lequired and the 
tubes may be coagulated at once at a temperature of 78 ° C inclined m a 
blood-seiiim OAen, or, better, heated three successive da3"s at 70 ° C Before 
use, a little sterile normal salt solution or wmter is best added to the bottom 
of each tube to pieserve moisture 

After scorching the suiface of a fresh tuberculous spleen, lung, or other 
oigan w ith a hot scalpel 01 spatula, bits of the subjacent cheesy or otherw'ise 
tuberculous tissue are torn out and squeezed between the broad blades of 
forceps or sterile glass slides from wdiich they are quicklj’^ transferred bj^ a 
platinum loop or spatula to the surface of the egg and gently rubbed about 
on the middle of the slant Tearing the surface of the medium is to be 
molded, and to be faiorable the surface should be fragile and elastic 

F 10m Spiiium — This may be done ^e^y successfully by means of Hesse’s 
agdr> if a fresh sputum rich m bacilli is at hand The contaminating bacteria 


' The formula is 

Hej den’s NahrstofF 

KaCl 

Gh cenn 

Apar 

Sol Na Coj (cn st ) 28 G per cent 
Water 

Other albumose foods, such as somatose 


5 gm 
5 “ 

30 “ 

10 " 

5 cc 
1000 cc 

or nutrose, are said to be equallj good 



154 


INFECTIOUS DISEASES 


m sputum do not thrive on this agar, so the tuberele bacillus has a chance 
to grow The method is as folloivs A bit of morning sputum is selected 
and examined for bacilli If abundant the bit is tiansferred from one dish 
of sterile normal salt solution to another, through five to ten changes, 
shaking it m each dish After diaining the surplus moisture fiom the 
particle of sputum, on the side of the last dish, it is gently dragged m a 
ciicular direction over the surface of a Petri dish containing Hesse’s agar, 
thereby leaving a delicate trail of sputum Incubation foi four dajs in a 
moist chambei is sufficient in many cases to shov minute curls or tufts, 
which may be seen under a low powei, and can be identified as uncontami- 
nated bacilli and tiansferred by a platinum wire to serum, egg, or agar in 
pure culture This procedure avoids a long delay in obtaining them by 
animal inoculation 

By Inoculation — For this guinea-pigs are best and should receive the 
sputum under the skin of the abdomen The animal should be killed m 
three or four weeks — not permitted to die, since terminal infections aie 
likely to defeat attempts to cultivate the tubercle bacillus by contaminating 
the tubes 

Cnltwe Media — A great variety of cultuie media are available foi the 
tubercle bacillus As stated, blood serum is most useful m isolating fiesh, 
virulent cultures, it is best prepared in Loeffler’s mixture, but not coagulated 
as hard as foi diphtheiia cultuies Dog, sheep, and beef serum aie to be 
preferred in the order named, as already noted, eggs are the best substitute 
Sputum agar has been employed successfully Potato slices to which 2 5 per 
cent glycerin-watei has been added and calves’ brain serum (Ficker) are 
also useful for isolating cultures from animal tissue For further growth 
3 to 5 pel cent glycerin agar is useful All kinds of broths and vegetables 
besides synthetic media are very successfully used Cultures for diagnostic 
tuberculin are now usually made on beef broth with 2 5 per cent gly- 
cerin 

Synthetic Media — Various peptone-free media and inorganic salt solu- 
tions, introduced by Kuhne, de Schweinitz, and Proskauer and Beck, have 
been valuable in the chemical investigations of the bacillus It was found 
that a thiifty grovth took place even upon ammonium carbonate, potassium 
phosphate, magnesium sulphate, glycerin, and water The notable pecu- 
liarity about culture media for the tubeicle bacillus is the high degree of 
acidity due to acid salts vliicli is favoiable for their giowth 

Dination of Life — Tubercle bacilli in cultures retain vitality at least six 
months if preserved fiom drying They may die m three weeks when not 
so protected, or at least cannot easily be revived by tiansplantation Avian 
cultures retain life much longer, accoiding to Maffiicei, who recovered 
cultures and pioduced infection after tw o years A more important question 
IS the vitality of the human bacillus in the (clinically healed) diseased foci 
where the bacilli are encysted and dormant The observations on this 
subject are unsatisfactory Cornet infers that their life is short in the tissues 
because of the difficulty in growing cultures from old tubercles On the 
other hand is the fact of apparent latency for years, during which time all 
evidence of giovth has ceased, yet lecurrence of the disease may ultimately 
occur m the immediate vicinity of the former focus, this is especially manifest 
in lupus The early inoculation experiments by Baumgarten vith “latent” 
tubercles and those of Kurlow and Lubarsch with healed tubercles indicated 



TUBEliCLLOSIS HISTORY AND ETIOLOGY 155 

tlie persistence of a irulence in old caseous tubercles not > et calcified or onb 
jiartly calcaieous 

Schioeder and Cotton’s results from inoeulations of virulent human 
bacilli into cahes, which pioduced localized subeut.ineous abseesses, aie 
significant of considerable latency Guinea-pigs vere readily infeeted 
from the pus after periods of fi\e months to one and a half -^ears Positive 
lesults from inoculations have been obtained from bmphoid tissue vhere 
no signs ot tubeicles veie disco\ered (Loomis, Weichselbaum and Bartel, 
Boscnbergei) Hov long these bacilli v ere actually latent or had suspended 
grovth IS, of course, uncertain, but expeiiments by Weichselbaum and 
Bartel, Peiez, and Manfredi and Frisco on labbits tend to show that their 
vitality IS limited to but fev months, when the inoeulations remain latent with- 
out fuither grov th The geneial result of inoeulation experiments indicates 
tliice to SIX months as the period during which the bacillus may live in the 
tissues wilhovi m-t/liiphjvig, although clinical observations are difficult to 
haimonize with this statement Weakening of virulence has been noted by 
hlanfiedi and Frisco in their experiments, but Haibitz vas unable to detect 
any differences in this respect in lymph glands fiom children of diffeient 
ages 

Presence of Tubercle Bacilh Outside the Body — The human sputum being 
the chief souice of the tubercle bacillus, it is natuiall}^ present in the dust 
of infected rooms, besides being attached to the furnishings, walls, and 
floois of such rooms It is raiely found m the open except in the dust of 
Cl ow'ded streets, and the enoi mous dilution of the an and ivater renders it very 
infrequent m natuie The customary disposition of urine and freces render 
these souices of small account The presence of bovine bacilli is practically 
limited to the stables of cattle and hogs wnth open oi ulcerated tuberculosis, 
and these are uncommon The exhaled breath is free from bacilli, but 
thc^ may escape m all other excietions and be secreted m milk Altogethei, 
the opportunities foi tubercle bacilli outside the body are directly dependent 
upon the degree of cleanliness used m the disposition of the sputum, urine, 
and faices, and their presence m milk from tuberculous coivs Cornet 
made it clear in his investigations that the presence of bacilli w as only to be 
.issumed m places fiequented by careless consumptives 

Powers of Resistance — Heai — ^The low est fatal temperatui e for the tubercle 
bacillus IS 55° C (131° F ) moist heat, acting for a period of six hours (Cornet) 
Di ) heat is borne to 100° C for an hour w ithout killing the bacillus, according 
to Schill and Fischei m expeiiments with dried sputum Moist sputum 
mai be sterilized in fne minutes by boiling m water, but thiek masses require 
a longei time The thermal death point for tubercle bacilli m milk is of 
great praetieal impoitancc, and mani experiments haAe been made which 
detci mined that fiom 60° C (140° F ) to 75° C (167° F ) was suffieient if 
continued foi one houi hlore recenth, Theobald Smith, Hesse, Bang, and 
othcis ha^c shown that the usual method of pasteurizing milk at about 
60° C to 65° C in an open ^esscl or bottle is insufficient to kill them, since 
thc^ come to the top m the seum and thus remain cooler than the under- 
hing liquid Theiefore, if pasteurization is desiied the milk should be 
sOrred or placed in a closed cesscl and heated at least twent'\ minutes to 
05° C (140° F ) Bang conehided tint 85° C , the Danish legal requirement, 
was a sufficient temperature to sterilize the dair^ refuse fed to cabas and 
hogs 



156 


INFECTIOUS DISEASES 


Cold — ^Tlie tubercle bacillus is not destroyed by any degree of cold The 
experiments of Galtiei , by which alternate fi ee/ing and thawing of tuberculous 
tissue ^^as tried foi several eeks, show ed no decrease in virulence, those of 
Cadeac and Malet preserved vitality foui months Comet found frozen 
dry sputum virulent after six w'eeks, Twichell wuth frozen moist sputum 
found the same after neaily four months Swithinbank found liquid air 
ineffective on cultures, but alternations of thawing and freezing w eie destruc- 
tive to virulence 

Diying — Dry bacilli from cultures may lose virulence in three wrecks, but 
the more important question as to their vitality in natuially dried sputum 
involves such varying conditions that the presei\ation of infective pow'er 
depends upon the size and thickness of the sputum mass, its quality, its 
place of deposit wuth reference to the character of the surface, and, most 
important of all, its exposure to light, heat, and air When sputum of tena- 
cious character is dried in large masses the bacilli are shut out from the air 
in the hard, glue-hke crusts, and in a dark, cool place, such as a basement 
room or the corridor of many city dw'elhngs, the maximum period of vitality 
may be assumed to be from six to eight months, this is the estimated limit 
given by Cornet as the lesult of his own and numerous other researches 
A valuable series of studies by Flugge and his associates in recent yeais 
have revised to some extent the conclusions of Cornet as to the virulence 
of dry sputum in dust which is capable of floating m the air The ingenious 
experiments of Kirstem wuth sprayed and dried sputum brought into the 
form of dust, indicate but a shoit lifetime for bacilli thus exposed to air 
and in diffused daylight The following w^ere his conclusions Dust from 
library books was found infectious aftei eight but not after fourteen days, 
pow'dered sputum alone, after four but not after seven days, lint fiom 
sputum-smeared clothing, aftei five but not after ten days, sputum mixed 
wuth street dust, after three but not after eight days 

Watei — Experiments by Chantemesse and Widal showed that the bacillus 
tuberculosis could live in sterilized watei fiom the Seme from fifty to 
se\enty days Galtier pieserved them four months in w^ater The influence 
of light and decomposition hasten their death under natural conditions in 
w^ater 

Ptdi ef action — Putrefaction of sputum and tuberculous animal tissues 
usually destioys the tubercle bacillus wuthin a few' days (Baumgarten and 
Falk, deToma, Schill and Fischer) It is dependent, however, on the nature 
of the process and how' rapidly it takes place wdiether the products of de- 
composition are haimful to the bacillus or not Galtiei w^as able to infect 
animals after two months with putrid spleen and lung This question is of 
interest in i elation to the persistence of virulence in the diseased cadavers 
and excreta of man and animals because of the possible danger of transmis- 
sion by means of infected earth, insects, etc Cadeac and Mallet found 
buried tuberculous lungs virulent after five months, but Klein not after 
seven w eeks Gartner concluded that tubercle bacilli could survive months 
m fieces Lortet and Despeignes showed that earth-worms could harbor 
bacilli wdien in contact with sputum, but decomposition ordinarily must 
obviate danger from such sources 

Syrnhions loith Other Bacteria — In the experiments by Prudden on mixed 
infection with Streptococcus pyogenes the tubercle bacillus w^as not prevented 
from growung on broth by their presence Bonhoff found that they were 



TUBERCULOSIS HISTORY AND ETIOLOGY 


157 


restrained w hen tlius grow n together, but the explanation may be simply 
that the reaction 'ivas altered or the nutrient material lessened 

GasUic Jincc — The tubercle bacillus can be destiojed by the noinial 
gastric juice in a test-tube experiment, but this lesult is due to the h>dio- 
chloric acid and not to the pepsin Under actual conditions m the In mg 
stomach there is little likelihood that all the bacilli are killed because of the 
varying acid strength and their mixture ivith food The experiments of 
Falk, Straus and Wurtz, Cadeac and Bournay, Zagari, and Ferranini agiee 
in the conclusions that bacilli introduced into the stomach ivith food, sojourn 
too short a time to be killed 

Light and Other Radiations — The effect of light is distinctly injurious to 
the tubercle bacillus Koch’s first observations indicated that cultures 
ivcre sterilized in a few minutes’ exposure to strong sunlight ivlien m thin 
layers Diffused daylight required from fi^e to seven days Heie, again, 
the natural conditions under wdiicli tuberculous material may be exposed to 
light play a very important part in determining the degree of its disinfectant 
pow'er The experimental observations give very wide ranges as to the 
tunc required to kill tubercle bacilli in sputum exposed to the sun under 
larymg conditions Foi example, Migneco, m Italy, found sputum \nulent 
after ten to fifteen hours’ sunning, but not aftei tw enty to tw enty-four hours 
during the hottest houis Mitchell and Crouch, in Den\er, Col , found that 
sputum deposited in sand remained virulent from ten to thirty hours 
Dclepme and Ransom used a variety of tests wnth dried sputum and in the 
foim of dust, wdiich show'ed a loss of vitality after one to eighteen hours’ 
exposuie Jousset and also Tw'ichell exposed sputum from one to seven 
hours and found it occasionally innocuous These results taken together 
show' that a speedy death of sputum bacilli occurs wdien it is exposed m a 
dry and dusty condition to sunlight or even diffused daylight Experiments 
b> Bang, m the Finsen Light Institute, w'lth unconcentrated electric (arc) 
light acting on cultures, usually killed the bacilli m from three to nine 
minutes’ exposure, nevertheless, the piobabihtv of some direct bactericidal 
influence upon lupus bacilli in the tissues is ^ely slight, since Khngmuller 
and Halberstaedcr excised bits of tissue, after a period of sei enty minutes’ 
treatment, whieh were infectious for guinea-pigs The Rontgen rays have 
been found to be bactericidal to some extent for the cultures of the tubercle 
bacillus by Rieder, who excluded light and heat rays in his expeiiments 
De Renzi, how'CAer, did not discover any effect on sputum Radium 
has probably a harmful effect on tubercle bacilli as on other bacteria (Pfeiffer 
and Friedberger), but no studies are recorded on the former 

Anhiepiic’f, etc — The tubercle bacillus is more resistant to chemical dis- 
infectants than most pathogenic bacteria, except anthiax and a few other 
spore-bearing forms It is, how'cver, restrained from growth m cultures 
Aery readily CAen by Aolatile agents, such as hydrofluoric acid (Villemin 
and Trudeau), formaldehyde creosote, oil of eucabptus, peppermint, etc 
Ihe commonly used disinfectants, phenol, mercuric chloride, and formalin 
require a long time to disinfect moist sputum bA reason of its abilitA' to resist 
penetration on account of the coagulation produced on the outer surface 
aaIiicIi protects the inner portion Fne per cent phenol is sIoaa m action, 
requiring tAAentA-foui hours in Schill and Fischer’s tests upon sputum, 
while CAcn 2 per cent mercuric chloride was not effectiAe Since the prac- 
tical usefulness of disinfectants must depend upon the penetratiAc poAAer, 



158 


INFECTIOUS DISEASES 


those Inch have a solvent action aie to be preferred In this class is tysol, 
vhich IS effective m 1 per cent solution Other combinations of soap and 
the kresols are very valuable Tv o per cent lysol is the most useful agent 
to disinfect sputum m cuspidois, but its odor is piominent, caustic alkalies 
and strongly alkaline soaps suffice in suitable receptacles to rendei sputum 
harmless Calcium hypochlorite is an excellent disinfectant for sputum 
and fiEces The use of foimaldehyde gas has practically displaced sulphur 
for the fumigation of rooms, and the results are satisfactoiy m disinfecting 
the suiface of objects exposed foi a sufficient time to the moist vapor in a 
well-sealed room, this is, unfortunately, not always accomplished, and 
bedding, rugs, and othei objects likely to have folds, if contaminated with 
smears of sputum, escape disinfection Masses of sputum large enough 
to be visible cannot be rendered harmless by ordinary fumigation The 
numerous iodine preparations used in surgical tuberculosis and employed 
internally have only a weak germicidal effect diiectly upon the tubercle 
bacillus, but slowly liberate iodine in the tissues and possibly exeit a 
restraint upon the growth m this way 
Chemical Composition of the Tubercle Bacillus — The facility with 
which large quantities of tubercle bacilli can be grown on fluid cultuie 
media made chemical analyses far moie feasible than with most bacteria, 
and the use of proteid-fiee solutions of chemically pure salts for media 
has still further aided m exact deteimination of the pioduets of giowth 
De Schwemitz and Levene have made a special studj'^ of the lattei Ham- 
merschlag was the first to publish an analysis of tubercle bacilli, he having 
found a peculiar acid-resisting proteid substance m broth and agar cultures 
The most important analyses have been made by de Schwemitz and Dorset, 
Proskauei, Ruppel, and Levene 

Elementary Analyses — The composition of tubercle bacilli varies consider- 
ably with the medium upon which they glow, as shown by the following fiom 
Levene 



Broth 

Jlannite (synthetic) 


per cent 

per cent 

Alcohol and ether extracts == Fat 

31 56 

22 18 

C 

55 58 

47 41 

H 

8 46 

7 05 

N 

9 39 

7 91 

S 

1 39 

0 25 

P 

0 59 

2 67 

Ash 

5 92 

10 00 


Moie than one-half of the ash consisted of phosphorous pentoxide, with 
sodium, calcium, and magnesium oxides m about equal quantities for 
the remainder De Schwemitz made determinations of the phosphorus 
contained m the ash from virulent and Aveak-vu ulent human cultures, 
Avhich indicated a less phosphorous content foi the vii ulent and also for the 
bovine bacilli, coi responding with their lesser fat-content 
Nucleoproteids or Nuclem — Mucin-hke substances ivere originally ex- 
tracted from the bacilli by Weyl and Hoffman and identified by ICuhne 
and de SeliAA'eimtz as nueleoproteids Latei, Ruppel and Levene inde- 
pendently examined the reactions and analyzed the decomposition products 
of this important ingredient, which proAed to contain the essential poison 
This IS a peculiar nucleic acid present in the body of the bacillus and its 



TUBERCULOSIS HISTORY AND ETIOLOGY 


159 


soluble secretions Water dissolves one-lialf of the pulverized body- 
subtance and the solution is precipitated by acetic acid, but contains no 
ordinary coagulable proteid The cement-hke substance which agglutinates 
the bacilli in masses is composed of this nucleoproteid Digestion of the 
bacilli with pepsin oi tijqisin removes but little substance, and saline extiacts 
also contain very little simple pioteid Levene discoveied three foims of 
nucleoproteid in bacilli grown on synthetic media and extracted by S pei 
cent ammonium chloiide, they diftered in solubility, heat coagulation 
point, and phosphorous content The so-called toxins formed in the bioth 
cultuies are identical wnth these and appear to be dissolved out of the bacilli 
rather than secreted from them 

Nucleic Acid or Tuberculmic Acid — ^The decomposition "of the nucleo- 
proteid above described sets free a special nucleic acid containing from 9 to 
11 per cent of phosphorus It can be precipitated by alcohol and forms 
the most toxic substance yet isolated fiom the tubeicle bacillus By fur- 
ther decomposition tuberculmic acid is split into thymin and a neutral 
substance called "tuberculosin” (Ruppel), besides several bases Lecene 
and Kitajima also found tl^nnin in the nucleic acid The effects of tubei- 
culin are ascribed by v Behring to the th> min fi action in the nucleic acid In 
the precipitated nucleoproteid is found “tuberculosamin” (Ruppel), a pro- 
tamin wdnch is a base in combination wnth the nucleic acid The most 
striking peculiarity of this toxic nuclein is its cxtiaordinaiy resistance to 
heat and chemical decomposition It has also unquestionably important 
disease-producing capacity and constitutes in all probability tlie essential 
endotoxin of tubeicle bacilli 

Fats and Wax — Second only in impoitancc to tbe nuclein are the fats of 
the tubercle bacillus De Schw'einitz and Doisct, Aronson, Kieshng, Bul- 
lock and McLeod, and Ritchie ha^e made exhaustive anabses of these with 
the result that a great variety of extracts have been isolated Estimates of 
the proportion of fat in the bacilli vaiy from 10 to 40 per cent , far in excess 
of all other bacteria, and the quantity depends on tlie age, rapidity of giow'th, 
virulence, and composition of cultuic medium Bovine and viiulent human 
bacilli w'ere found by de Schw'einitz and Doisct to have less wax than weak- 
virulent cultures The fatty acids isolated have been partly identified as 
palmitic, lauric, butyric, oleic, etc Cholesterin, lecithin, and other alcohols 
have been found The alcohol and acid lesistance is asciibed to an, as yet 
unidentified, alcohol by Bullock and McLeod Von Behiing holds that the 
tiue vaccinating substance of the intact tubeicle bacillus is a combination 
between a lecithin and a nuclein 

Other Components — Cellulose has been detected by some chemists and 
carbohydrates of the sugar class by others Bendix found a pentose and 
Levene discovered glycogen m combination wnth the nucleic acid 

Secretions dunng Growth — There is no evidence that tubercle bacilli 
secrete or excrete anything in cultures during active growth except a trace 
of volatile fatty acid and a slight amount of soluble nucleopioteid having 
the same reactions and properties as that obtained by maceration or extraction 
of the bacilli It is probably set free from degenerated or dead bacilli 
The fatty acid is the source of the ahnond-like odor developed in cultures 
Alkaloids and toxalbumins have been described by various investigators m 
fte past, but improved chemical methods have failed to demonstrate them 
They corresponded in their reactions to the heat-coagulable nucleoproteids 



160 


INFECTIOUS DISEASES 


found by Levene in the culture filtrates Differences between the acidity 
of human and bovine broth-culture filtrates have been noted by Theobald 
Smith, which he regards as a means of identification The human broth 
cultures have an increased acidity, while the bovine become moie alkaline 
The significance of this has not been determined definitely, although the 
higher percentage of free fatty acids found by de Schiveinitz and Dorset m 
human bacilli is suggestive, since the piesence of glycerin was found to bear 
some relation to the production of the acid reaction Bang has confiimed 
Smith’s observations and also found that the avian bacilli behave like the 
bovine m producing an increased alkaline reaction 

Tuberculm — This term was applied at first by Koch to the filtered and 
concentrated broth m winch full-grown cultures had been boiled It con- 
tained, theiefore, a glycerin-broth extract of the bacilli, together with such 
soluble products of the bacilli as were foimed during their growth and not 
precipitated or destroyed by heat This original tuberculin, or. “T O ” 
(also called “old tuberculin,” “A T ”), was the first of several modifications 
experimented with by Koch 

Analyses were made of crude tuberculin by Proskauer and Brieger, and 
especially by Kuhne, who found an albuminate and a peculiar “acio- 
albumose,” not present in the bioth constituents, but piesent in cultures on 
proteid-free media Further analyses by Ruppel identified the active 
substances m tubeicuhn with the nuclein and tubeiculinic acid previously 
described It is precipitated by 66 per cent alcohol and the re-solution of 
this precipitate was called “purified tuberculin ” Tuberculm m this foim 
when subjected to tryptic digestion wholly loses its activity, thus indicating 
its essential combination with proteid It is, however, very resistant to 
physical and chemical agencies, heat, light, etc , and loses but little activity 
in concentiated form by age 

Modifications — ^The various modifications of tubeicuhn merit description 
with reference to their nature and mode of pieparation, although the use of 
some has been abandoned Hunter’s and Trudeau’s modifications were 
attempts to precipitate the active substances with ammonium sulphate and 
by dialysis to purify the residue from salts 

Tuberculocidin and Antiphthisin (Klebs) represented the precipitate 
obtained m a similar way after the lemoval of the so-called alkaloids by 
potassium-bismuth-iodide 

Oxytubercuhn (Hiischfeldei) was the original tuberculm treated by 
boiling m hydrogen peroxide (HjO,) 

Tuberculoplasmin (Hahn) was the fluid expressed from fresh bacilli by 
hydraulic pressure 

Tuberculol (Landmann) contained extracts of tubercle bacilli prepared 
at different temperatures separately, then combined and evaporated at a 
low temperature 

Water extract (Maraghano) consists of the concentrated extract of 
tubercle bacilli digested for six days on a water-bath at 90° to 95° C and 
filtered 

Water extract (v Ruck) differs from the last mentioned m that the 
washed bacilli aie first extracted with alcohol and ether, pulverized, and then 
extracted until water at 50° C 

Tuberculin (Denys) (“B F”) is the unaltered filtiate from broth cul- 
tures 



tuberculosis history and etiology 161 

“Perlsucht” tuberculin (Spengler) is made from bovine bacilli, after 
the manner of the original tuberculin 

Tuberculin (Beraneck) is prepared by evaporating in vacuo the full- 
grown culture filtrate to one-tenth the original volume, the broth containing 
no peptones in its composition The concentrated filtiate is then pre- 
cipitated with 60 per cent alcohol and the lesidue collected The bacilli 
are extracted with 1 per cent orthophosphoric acid at 70° C , and the two 
products mixed in equal quantities 

Various tuberculins were also prepared by Koch, Weyl, Vesely, Arloing 
and Gurnard, v Belli ing, Thamm, and others, representing alkaline or 
other extracts of tubeicle bacilli, and which weie used chiefly in animal 
experiments 

Paratubercuhn is the name given to extracts of pseudotubercle bacilli 
prepared like the original tuberculin 

Tuberculosis Vaccines — Tuberculin K (“T R ”) (Koch) was introduced 
in 1897 as an improied form of tuberculin toi immumving as well as theia- 
peutic use In contiast to the various extiacts it is an emulsion of the 
residue from living, virulent bacilli after pulverization and extraction with 
water 

“Bacillen emulsion” ("B E ”), Koch’s latest product, consists of an 
emulsion of the entire substance of the pulverized living bacilli in 20 per 
cent glycerin, only the coarser particles being excluded Glycerin is 
depended upon to sterilize any bacilli not lemoved by centrifugahzation 

"Bovovaccine” (v Behring) is the first immunizing virus introduced 
by V Behring for cattle, and consists of unsterihzed dried bacilli from a 
human culture passed through guinea-pigs It is used intravenously and 
keeps but one month 

“Tauraman” (Koch and Schutz) is the analogous vaccine for cattle 
introduced by Koch, but is preserved m a more virulent condition It is used 
intravenousl}’^ 

“Tuberculase” or “T C ” emulsion = ‘‘Tubercle Cytm” (v Behring), 
IS the latest immunizing agent whose natuie and method of prepaiation, so 
far as has been made known, consists of an emulsion of the baeillus residue 
after extraction successively with alcohol, watei, 10 percent sodium chloride, 
and other extractives as yet undesenbed The bacilli, which aie further 
treated with chloral hydrate and are still intact, are said to be unable to 
grow, yet are easily absoibed by the tissues without producing tubeicles 
They nevertheless create tuberculin susceptibility for a time Its use is 
restricted to animals 

“Tulase” (v Behring) IS described as related to tuberculase, but is a 
clear, yellowish, honey-hke liquid foi therapeutic use on animals and human 
subjects, and contains all the constituents of tubeicle bacilli, including the 
latter in a condition for easy absorption 

“Tulaselactin” is the latest name applied by v Behring to his tulase 
prepared m the form of a milky emulsion, and which is said to possess but 
slight tuberculin-reacting powei when fresh, but owing to instability acquires 
it after a short time It then becomes weak m immunizing power 

It may be said of the various tubeicuhns that, viewed fiom a chemical 
standpoint, they all contain the peculiar nuclein substance or its derivatives 
m greater or less quantity and degree of solubility In some the endotoxin 
has been altered or decomposed by heat or extractives, but all are capable 

VOL HI — 11 



162 


INFECTIOUS DISEASES 


of producing the characteristic reaction in tuberculous subjects ‘ The 
vaccines form either preparations of living bacilli or their substance as 
nearly unchanged as possible 

Chemical Pathology — Action of Dead Bacilli — It as early demonstrated 
that dead bacilli could produce tubercles essentially identical with those 
caused by living bacilli Caseation is, hoiievei, absent unless large amounts 
are injected, which generally leads to abscess foimation m subcutaneous 
injections Besides the local effects, Maffucci and his pupils showed that 
nephi itis, atrophy, and disturbance of nutrition such as are seen m the cachexia 
of advanced tuberculosis can be produced by sterilized bacilli Recent 
investigations by Cantacuzene on the changes m fatal poisoning by dead 
bacilli freed fiom wax, show that an acute neciosis of the cardiac muscle, 
renal epithelium, and polynuclear leukocytes takes place and that eosmophiles 
appear in abundance m the blood Von Behring also regards the leukocytes 
and lymphatic tissue as having a special affinity for the specific toxin, and 
describes cell metamorphoses recognizable by staining, due to the bacillus 
residue or “tuberculase ” 

Koch, m the experiments upon tuberculous guinea-pigs which led to the 
discovery of tuberculin, found that dead bacilli injections modified the course 
of the disease so as to cause healing of the inoculation ulcer, many others 
confirmed and extended these observations 

Effect of the Nuclein — As already mentioned, nearly all the extracts 
obtained from tubercle bacilli contain the poisonous nuclein or its decom- 
position products The effect of model ate doses on healthy animals of the 
water or glycerin extracts is not immediately harmful Repeated large 
doses produce fever and wasting without noticeable microscopic changes 
Large doses cause death in healthy guinea-pigs m twelve to foity-eight 
hours from slov collapse, the only microscopic lesions being local extravasa- 
tions at the site of injection In tubeiculous animals very small doses cause 
high temperature and local reactions at the seat of disease, accompanied by 
a polynuclear leukocytosis Veiy model ate doses cause death m a few 
hours, with hj^othermia, leukopenia, and extensive extravasations of blood 
about the tubercles Von Behring and Ruppel prepared pure tuberculmic 
acid whose toxicity was very great for tuberculous guinea-pigs, but further 
decomposition of this toxin weakened its effect De Giaxa also produced 
coagulation necrosis with the nucleic acid piepared from tubercle bacilli 
In its most insoluble form the nuclein or endotoxin which lemains after 
thorough extraction of the bacillus is the most piolonged m its poisonous 
effects, and probably gives rise to the so-called “tuberculin hj'persuscepti- 
bihty,”^ because of its very slow absorption and the specific adaptation 
required of the cells to absorb and disintegiate it 

Effect of the Wax — ^IVhen isolated m a pure form, the alcohol, ethei, 
chloioform, or benzole extract has the effect upon the tissues of an insoluble 
irritant Auclair has produced caseation by means of the ether, chloroform 
and xylol extracts, and ascribes to the fatty secretions of the bacilli the case- 

« 

‘ It IS claimed by C Spengler and Bandelier that bovine tuberculin (Perlsucht 
T 0 ) IS less actn e on human subjects than the human, while Kanda found the 
opposite for cattle Quantitatn e differences are not readily excluded m such 
tests 

^ Von Behnng now believes this results from an affinity between the so-called cjdin 
cell-substance and a similar substance (“T C ”) in the tubercle bacillus 



TUBERCULOSIS HISTORY AND ETIOLOGY 


163 


ating property of the tubercle bacillus It is undoubtedly tiue that the fatty 
acids in tubercle bacilli play some part in the coagulation necrosis of tubercle, 
but it IS very doubtful that they aie the chief agents 

Volatile distilled products of tubeicle bacilli have not been isolated in 
quantities sufBcient to establish their piobable importance m the disease 
The local effects of tubercle bacilli may faiily be attiibuted to the highly 
resistant wav, combined m ith the necrotismg action of the nucleic acid and 
fatty acids It is uncertain whether these caseating substances are chiefly 
set free during the multiplication of the bacilli oi aftei tlieir death and 
disintegration The soluble products of the bacilli \\ Inch ha^ e thus pei ished 
are unquestionably the cause of the constitutional symptoms in tubeiculosis, 
such as the fever and amemia Moreover, the tovrcmia closel} resembles 
that produced experimentally by the nuclein or dead bacilli abo^ e described 
Maraghano claims to haie found a toxin in the blood and mine of cachectic 
consumptives which pioduced tubeiculm effects, while others ha^e demon- 
strated albumoses m the urine (Lenoir) and sputum (Simon) \\ Inch lesembled 
tuberculin 

The question of a selectne action of the toxin foi certain tissues has 
received attention by v Behring m recent ears, and his researches led him 
to the opinion that the leukocytes and endotlieha of the alveolai capillaries 
and serous membrane are the especially sensitne cells On the basis of 
this theory he explains the local reaction to tuberculin * 

Effect of Tvbei culm — ^The phenomena of tuberculin poisoning have already 
been described as those of the endotoxin or nuclein of the tubercle bacillus 
The chief interest centres about the local reaction in tuberculous foci and m 
the acquisition of tolerance or immunit'^ to this poison by all the tissues 
In moderate doses no perceptible effect is produced upon the tissues oi blood 
in health Large, repeated injections into the ^ ems hai e caused endarteritis, 
degeneration of Inei and kidney epithehimi, follo^^ed by atiophy of these 
viscera All forms of tuberculin act similarly m causing local reactions 
about tubercles, but vary greatly in the time and intensity of the reaction, 
owing to their greater or less solubility The oi iginal tuberculin acts more 
violently than some of the modifications, doubtless because it contains more 
of the simple derivatives split off by heat from the maceiatcd bacilli - 


' “Aggressive" Activity — The parasitic power of the tubercle bacillus is ascribed 
bj" Bail to a special "aggressm,” a secretion or bod\ substance b^ w Inch the leu- 
kocytes are repelled or injured, thus permitting the bacilli to grow According to 
this tlieorj', the ability of a arioiis bacteria — tuberculosis, antlirax t} phoid, etc — to 
grow in animals is due to this aggressn e property Expenmental e\ idence of such a 
substance so far has been unsatisfactory in the case of tubeiculosis, for products of 
the baciUi obtained from the animal or extracts in the test tube from dead or In ing 
cultures, whether of high or low imilence, accelerate death in health's guinea-pigs 
without preientmg phagocs tosis, as found bj"- Baldwin and Price Von Behnng 
states that w ater extracts of higlilj a indent bacilli are more toxic than those of w eak 
j. irulence and that the nrulent bacilli are less readih phagocjded It is not clear, 
howeier, that a toxin or “aggressm” of different nature accounts for these differ- 
ences The hj pothesis of Theobald Smith, w ho suggests that the bacillus becomes 
surrounded bj' a protecting en\ elope as it becomes more parasitic, has more plausi- 
bihty than that of an “aggressm ” 

’ K furthermore contains the constituents of the broth-culture medium, peptone 
and beef extractives, unused bj the bacilli in growdh These hai e some enhancing 
influence upon the reaction m large doses, but for the purposes of diagnosis, for 
wnich it is prmcipalljf used, tlus is inappreciable 



164 


INFECTIOUS DISEASES 


Local Reaction — ^The marked local selective action upon the tubercles 
winch characterizes tuberculin requires detailed description, for it illustrates 
the mechanism by which the tissues combat the disease 

Following the administration of tuberculin, within four to twelve hours, 
dilatation of the small arterioles and capillaries sui rounding the tubercles 
takes place, and a serous and cellular exudate follows sufhcient to cause 
Msible s^^elhng in the case of lupus, the /one of lymphoid and epithelioid 
cells already about the foci becomes augmented by additional cells, chiefly 
polynuclear leukocytes, and m violent leactions extravasations of red cells 
may appear These phenomena reach then height in fiom six to twenty- 
four hours and quickly subside, unless very laige or quickly lepeated doses 
are given After foity-cight hours lupus foci have become smaller and less 
conspicuous than before, and iihen favorably treated the lymphoid cells 
are either gradually absorbed or tiansformed into Sbrous tissue as in the 
natural cicatrization of tubercles undergoing healing The local reaction 
varies in intensity according to the situation, extent, and age of the tubercles, 
as V ell as in the sensitiveness of the cells composing the tubercles in respond- 
ing to the toxin 

Neither the local noi general reaction is absolutely specific, vaiious nucleo- 
proteids, yeast nuclein, bactei lal proteids in genei al, and digestive products, 
such as albumoses, are capable of producing similar eftects Cinnamic 
acid, canthandin, pilocarpine, and other alkaloids also act to some degree, 
although less as local iiritants than general leukocyte stimulants There are 
analogies in other diseases vith focal points of infection, such as anthrax, 
sjqihiiis, and streptococcal infections, wheie local and general reactions 
may result from a specific stimulus Moreover, tuberculous sub3ects> are 
•well known to be markedly sensitive to fever from transient mental or 
physical excitement as Niell as digestive disturbances It is unnecessary to 
suppose that theie is an actual local reaction in all such cases, although it can 
be observed at times in lupus and laryngeal ulcerations A slight increase 
in the lymph flow from the heightened blood pressure can cause more 
absorption from the foci These facts have tended to discredit the value 
of tuberculin as a delicate diagnostic agent, but in practice need not cause 
confusion in cases of recent tuberculosis 

Theories of the Reaction — The explanation of the reactive phenomena 
has been puzzling, and several contradictory theories have been proposed 
which need not be revieived The most satisfactory theory, -which accords 
wnth the modern immunity studies, is in essence that first proposed by 
Ebei, Babes and Pi oca, and modified by Theobald Smith, wdiich assumes an 
enzinne actnity in the cells immediately surrounding the bacilli and their 
products Under ordinary conditions a slocv disintegration and digestion 
of the bacilli take place, but ith the added stimulus of tuberculin injections 
the process is accelerated in the foci, if enough irritation has occurred, soluble 
or parti V digested products of the bacilli are freed rrhich are sufiicient to 
cause local and general reactions It is also possible that in severe local 
reactions precipitation or coagulation of the toxin occurs in the small arteries 
or capillaries nearest the tubercles, as v Behring held in his explanation of 
the reaction It is not to be assumed that this alone or invar lably is the cause 
of the congestion, but the antibodies arc presumably set free to a greater 
extent by the cells most under the influence of the toxin Whether the 
function of these cells be tir ofold — i e , precipitating and fermentative or 



TUBmCULOSIS HISTORY AND ETIOLOGY 


165 


not, both phenomena appeal to play some pait m the reaction Recently 

Belli ino' reasons that the tliynim substance in tubeiculin has an especial 
affinity foi the “ T C ” oi cvtin of the tiibeicle bacillus which has preMOusly 
combined nith the body cells and is the cause of then sensitiveness It is, 
hence, capable of lemoMiig it fiom its combination and thus ci eating the 
reaction It is not clcai that an en/yme function is excluded by such an 
explanation 

Repetition of the injections in iiici easing doses gradually cieates a toler- 
ance which IS explained m tno ways (o) By the neiitiali/ation of the tuber- 
culin by antibodies bcfoie it i caches the tubeulc (probably precipitins), 
and {h) the exhaustion of toxin accessible to the reacting cells The toler- 
ance IS consequent!} not a lasting one, as the reaction ponci may return 
after cessation of the injections so long as cells remain nliicli retain sensi- 
tiveness ^ 

The Mechanism of Resistance and Immunity — The animal tissues 
present a certain degree of normal resistance against the in\asion of the 
tubercle bacillus and poisoning bj its toxins It is obvious that the normal 
resistance inaj become giadiially increased bi many exposures nliicli liaAC 
been successfully o\eicome nithoiit the de\clo])nient of actual disease, this 
general biologichl Ian finds no exception in the case of tuberculosis, although 
m case the infection has once taken root in an mdiMdiial, even if reco\ery 
takes place, a subsequent mcieascd susccptibiht} appeals to follow in many 
instances, as m scrofula 

The protecting mechanism is feeble in infancy, but if cailj infection is 
a\oided or successfully pi evented without a foothold gamed by the bacilli, 
the adult human individual in noimal health seems to be jnactitally immune 
to natural infection From the picseiit aspect of the pioblem of infection, 
W’^e must conclude that the mucous membranes and hmjihatic tissues are 
chiefly concerned in the piimaiy resistance to tubcicle bacilli rathei than 
the pulmonary aheoli, as formerly supposed Tliese facts aie of the utmost 
importance, and are deduced from man^ obscuations m the past wdiich 
harmoni7e with experimental evidence m icccnt yc.iis on animals, and liaie 
been further strengthened by the studies on latent tubeiculosis of Ilarbitz, 
Rosenberger, Furth, and others 

According to the piescnt view, m pnmaiy infection the bacilli are able 
to reach the lymph nodes connected w'ltli then path of cntiance without 
necessarily leaving any trace at the latter, and cieatc no apparent resjionse 
to their presence for some time If, liow'cvei, they suivive the noimal lytic 
action of the cells, they may be earned faithei oi excite the local icactne 
process, wdnch leads to tubercle formation The struggle for mastery is 
essentially a local one, although, as in miliaiy tuberculosis, many foci may 
begin simultaneously Lymphocytes are prominent in the formation of the 
tubercle, and the w'andeiing leukocytes participate togethei with connective- 
tissue cells in localizing the bacilli If the organism is successful m effect- 
ually localizing the invaders, a more oi less rapid piocess of disintegiation oi 
bacteriolysis ensues which destroys the bacillus and disposes of its pioducts, 
possibly leaving behind changed cells in the tissues as a consequence of 

Wasserman and Bruck found both antitubcrculm and tuberculin m the tubercles 
ana gave an explanation of the reaction on the theory of local antibodv action , 
Weil conclusive in showing the presence of tuberculin, as shown by 



166 


INFECTIOUS DISEASES 


their absorption of some specihc ingredient of the bacillus which stamps 
tuberculin susceptibility of longer or shorter duration on the individual On 
the other hand, many cells may die in consequence of the direct and prolonged 
exposure to the toxin and caseation of greater or less degree is the common 
result, which reall> protects the enclosed bacilli from further lytic action by 
the living cells The tubercle forms, theiefore, the object of study as the 
unit or type of the mechanism of resistance, for the tissues in general expeii- 
ence but slight effect from the presence of a few tubercle bacilli well localized, 
and there results a lack of effective resistance from absence of a general 
stimulus at favorable moments in most cases of chronic tuberculosis The 
ultimate result consequently often depends on the efficiency of the cell 
nutrition throughout the body to bear repeated severe exposures without 
harm 

Heightened Susceptibihty to Reinfection and Tubercuhn. — ^This character- 
istic is one of the results of a previous infection and may arise from partially 
healed or latent tubercles as well as lecent active disease Koch first noted 
that a second infection produced marked reaction at the point of inoculation 
M ithout spread of the infection from this point, and it led to his discovery of 
tuberculin Von Baumgarten also studied the phenomena of primary and 
secondary infection Straus and Gamaleia observed that great sensitiveness 
had been acquired by animals injected with dead bacilli to a repetition of 
the injections 

The analogous lesults with tubercuhn are well known, severe and even 
fatal reactions being possible in tuberculous subjects from doses which are 
practically meit foi healthy peisons The subject has been thoroughly 
studied by v Behring, Theobald Smith, Trudeau, And others, and the con- 
clusion is unquestionable that the phenomenon is one of specific resistance 
There are analogous hjqiersensitive reactions resulting from the injection 
of various foreign serums and other proteids, the so-called “serum disease,” 
vhose symptoms and period of development are closely comparable and 
leave no doubt of a close relationship Yon Behring finds in natural infection 
of calves that three months is the usual peiiod required for tuberculin 
susceptibility to develop to a noticeable degree It requires from eight to 
fourteen days after experimental inoculation m guinea-pigs Prom this 
time fevei and local reactions follow the injection of tuberculin or allied 
proteids This period is the same which is required for the formation of 
all kinds of antibodies, and we may infer that the development of reaction 
susceptibility signifies a lytic power or an affinity acquired by the cells of 
the tubercle acting both on its own accumulated toxin and the injected 
tuberculin, which liberates a poisonous substance or combination affecting 
the V hole oi ganism ^ This susceptibility has an important bearing both 
on the development of new foci in the presence of existing disease and the 
acquirement of immunity of which it is probably a phase 

So long as this susceptibility persists, there is reason to expect that new 
infections v ith tubercle bacilli v ill be localized at the point of entrance into 
the tissues, and that they are either disposed of there without actual infection 


* The delicacy vith which the reaction occurs m response to minute doses of 
tubercuhn in the incipient stages of tuberculosis is often increased by repetition 
of the same dose mthin short intervals Ihis fact forms the basis of a method of 
tuberculin diagnosis advocated by Loewenstem and Rappoport 


TUBBIiCULOSIS HISTORY AND ETIOLOGY 


167 


or produce foci with ulceiation, as m the laijn\ and intestine during the 
latei stages of pulmonary tuheiculosis oi during periods of lo'\^ eicd resistance 

The reaction po^er implies a ceitain change m the organism in refeience 
to tlie tubeicle bacillus tovin Minch causes an immediate lesponse by the 
tissues, this IS obviously intended to fix and dcstioy the bacillus, and is the 
result of specific antagonistic poMcis dc\ eloped oi latent in the body from 
an existing or previous infection The leason Mhy this condition does not 
mean efficient jmmunity m all cases is explained by Theobald Smith as due 
to the greater \uhierabihty of the lungs where a second infection is pi one to 
occur and be focused, instead of being cairied into the lymph nodes and 
destroyed as in a piimaiy infection An cxteinal exposed focus in a more 
vulnerable tissue is thus to be regarded as moic dangeiousfoi theindiMdual 
whose specific immunity is incomplete than foi one in whom only noimal 
reacting power exists Such may not, howc\er, hold good loi an exposuie 
to bacilli outside the body where the numbci of bacilli is infinitely less than 
from ulcerating tubeicles in the diseased peison Von Behring, fiom his 
extensive im estigations in cattle tuberculosis, rcgaids this sensitiveness in 
tlie light of an actual acquiied predisposition, and behc\cs that it can persist 
for some time in cattle alter an inoculation of human bacilli, e\en whcie no 
tubercles can be found He is inclined, neceithelcss, to doubt that this 
predisposition favors a lenewcd infection fioin without, lather does it oppose 
this, but promotes its furthei spread in the indnidual with ahradtj laient 
disease In tlie present state ot our knowledge this reaction susceptibility 
cannot be considered a nccessarilj unfaiorable factor in an adult individual 
W'ho has a chnicalh healed pulmonary tubeiculosis Its duiation aftei this 
stage in man is unknowm, but it remains at least for ten ycais * It was not 
transmissible to the calves born of immunised cow s in the hlaiburg experi- 
ments, 3 'et Cornet admits the possibility of an inherited toxin susceptibility, • 
although assigning small impoitance to it as a picdisposition - 

Immunity — No disease has show n so little e^ idence of apparent immunity 
conferred by one attack as tuberculosis, the contrary is the universal clinical 
experience on superficial obseivation Ne^cltheless, there aie certain 
characteristics of the clinical course of the disease, and in some cases of 
recover}’-, wdnch on closer examination point to an acquired lesistance which 
amounts to practical immunity Even the more chronic couise of the disease, 
seen, as a rule, m peisons classed foimeily as “heicditarily disposed” and 
sciofulous, but now’ regarded as instances of eaity infection, maj' be regarded 
as a sign of specific resistance 

Likewise, the slow’ progress and often benign couise of tuberculosis in 
subjects beyond middle age are readily attributable to an acquired resist- 
ance due to previous infections 3 Both Turban and Solly found a greater 
percentage of chronic, prolonged, arrested cases among those patients w'lth 
family tubereulosis wdio do not die in the onset of the disease than those 
without such a history Unfortunately, such comparatively mild infeetions 

* Personal obseri ations of the author 

Bosenau also offers the suggestion, that tuberculin susceptibility may be trans- 
mitted to offspring, as he has shown to be possible with serum anaphylaxis, and 
thus form a predisposition to tuberculosis 

The exacerbations during the course of the disease often ha^e a w'ell-defined 
limit, ranging from ten to fifteen days, which is significant when taken in connec- 
tion with the period of antibody formation m the blood after bacterial inoculations 



16S 


INFECTIOUS DISEiSES 


as are seen in persons iMth weak constitutions of phthisical build are not 
reallj often reco\ered from in the sense of lestoration to robust health, the 
disease no longer progresses, but secondary amemia, weak digestive func- 
tion, and poor assimilation frequently accompany an actual disappearance of 
the former symptoms Theie is m consequence but slight reason to speak 
of an adrantageous immunity conferred by pieviously healed tuberculosis 
in such persons too often it plainly pioduces the opposite eflect, or is only a 
transient heightening of resistance H M King has made the interesting 
observation that the course of the disease in 103 fatal cases w'as a j^ear 
longer m subjects of phthisical parentage than in those without it Such 
facts speak quite as much for acquired resistance from repeated early infec- 
tions as for inheiited immunity Ne\ ertheless, the acquisition of relative 
immunity by certain families and races which have long been subjected to 
the conditions of life far orable to tuberculosis and exposed to the infection, 
has considerable support m connection wuth the Jewish and English races, 
who have intermarried less wutli other races than those of Central Europe 
ReibmajT holds this theory and predicts a diminution and decreasing viru- 
lence of tuberculosis comparable to that of syphilis 

Experiments in Tuberculosis Immumty — The first encouraging results 
from experimental researches on tuberculosis immunity and specific treat- 
ment began with Koch in Germany, Hericourt and Richet in France, and 
Trudeau in America in 1 889-90 A host of others have follow^ed with notable 
contributions, among whom de Schw'emitz, hlacFadyean, Maraghano, 
Pearson and Gilliland, Koch, and Neufeld should leceive special mention 
Von Behring and his associates have unquestionably made the most extensive 
investigations, and practical results are already apparent in his “bovo- 
vaccine” method of immunizing cattle wnth human bacilli, and the coincident 
, application of the same principle by the American veterinarian, Pearson 

The very persistent studies and animal experiments m this field have at 
least demonstrated that a high degree of artifical protection is possible against 
tuberculosis Complete immunity under extreme conditions of experi- 
mental inoculation has proA ed disappointing as compared AVith some other 
diseases Nevertheless, it is reasonable to state that the problem has been 
practically solved so far as the bovine race is concerned, although the dura- 
tion of the protection is yet unceitam and may require years to determine 
It is not too much to hope that harmless immunization of A^ery young calves 
may be accomplished to such a degree that natural infection Avill be pow'eiless 
against them when supplemented later by the natural resistance of adult 
life, eA en if the specific resistance then fails It is eA'en possible that a safe 
immunization may be applied to human infants, as v Behring, Vailed, and 
others hope from their recent experimental Avork It is premature to 
conjectuie how long such protection A\ould last, but if sufficient to prevent 
infection during childhood it w'ould be conceivably of great value The 
prospects for a passn e or transferred immunity by means of serum, milk, 
or otherAAise are less promising 

The production of immunity by means of serum or by extracts of the bacil- 
lus has thus far failed, and preparations of the living bacillus have provided 
the best protectne vaccine for animal experiments Some increase of 
resistance can be obtained by the injection of the various tuberculins and 
dead bacilli, and it is to be hoped that still better results may be possible 
along this line AAithout the necessity for the use of living organisms An 



TUBERCULOSIS HISTORY AND ETIOLOGY 


169 


ideal vaccine should theoretically contain all the immuni/ang piopeities of 
thelivmo' bacteiiain a loim both incapable of infection and easily absoibed 
by the tissues, these qualities are claimed to be possessed bj v Behring’s 
“tuberculase” and “tulase ” 

The Mechanism of Specific Immumty — Specific immunity against tuber- 
culosis, in the meaning at piesent undeistood of immunity to bacterial 
diseases m geneial, lequiies an ability on the pait of the tissues to disintegrate 
the bacillus and destroy oi neutralize its toxin, in short, a combined bacterio- 
lytic and antitoxic immunity Whethei this foim of expression correctly 
states the problem as applied to tuberculosis or not, there aie facts that point 
to a bacteiiolytic function which may be evolved by vaiious methods of 
immunization The question as to the pioduction of a literal antitoxic 
property is yet a matter of conjecture, for when bacteriolytic power is devel- 
oped to a high degree, there may still be a lack of complete toleiance of 
the toxin It is, hence, possible that the disease may be aiiested foi a time, 
only to result m a chionic poisoning because of tlie bacilli disposed of in 
greater numbers, and v hose toxin the tissues ha\c inadequate pover to 
neutralize at the time most needed There follow s in consequence perma- 
nent injury to the eells 

Many clinical facts attest the truth of the above statement and explain 
the succession of arrests and relapses in the course of the disease Possibly 
because of the unequal rise and fall of the tw o necessary functions complete 
immumty is made more difficult 

Owing to the restricted action of the toxin, the cells not composing the 
tubercle fail to get the propei stimulus to resist its action w hen the constitu- 
tional condition is in a favoiable state for this It is also fanly established 
that such immunity as is acquired by an animal to this disease rests m its 
cells and is not dlsco^elable in the behavior of its serum This fact foims 
the chief rationale foi specific therapy in tuberculosis by tuberculins, foi it is 
desirable to impiess the wdiole organism with the specific stimulus in suffi- 
cient quantities and at proper intervals to maintain a high resistance The 
exact mechanism of the acquisition of inci cased tolerance by the cells is 
undoubtedly a very subtle thing and closely connected with the tuberculin 
susceptibility phenomena Elaborate and abstruse hjpotheses are ofteied 
by V Belli mg Briefly stated, they assume a physicochemical process of 
union betw'een a lecithin-pioteid substance contained m the tubercle bacillus 
and certain constituents of cytoplasm wdiich have an affinity for it A 
transformation follow's that eventually adapts the cell for future attacks 
of the toxin The duration of specific immunity is as yet unknowm 

It is assumed by v Belli ing that the lymphatic tissues and leukocytes are 
especially concerned in maintaining immunity How'evei this may be, 
the excessive inflammatory reaction seen in experimental inoculation of 
immunized animals is accompanied by a large collection of mononucleai 
and polynuclear leukocytes about the bacilli and all the phenomena of a 
prolonged tuberculin reaction Since complete absorption of the focus and 
disappearance of the bacilli may follow wnthout caseation resulting, it is 
natural to suppose that the process is an immunity reaction, even though it 
be only an exaggeration of the normal one w-hicli results in caseous tubercles 
in the unvaccinated animals In calves immunized by v Behring, tuber- 
culin-reaction susceptibility must w'ane before he regards them as sufficiently 
protected, but this wmuld mean a perfect tolerance on the part of the cells. 



170 


INFECTIOUS DISEASES 


with an unfa^ orable condition for the growth of the bacilli whose mechanism 
IS not as yet explained 

Antibodies — Agglutinins or precipitins are leadily produced against 
tubercle bacilli and their products by repeated injections ot these substances, 
and appear to some extent in the course of the disease, as found by Arloing 
and Courmont A high agglutination power nevertheless may exist without 
immunity, as in the course of typhoid fever A close relationship obtains 
between the precipitins and agglutinins of tubercle bacilli as they aie interact- 
ing upon the solutions and emulsions of the bacillus substance 

O'psomns which aid in the phagocytosis of tubercle bacilli have been 
distinguished as specific antibodies quite distinct from the agglutinins by 
Wright and Bullock, and have some similarity to the serum complement 
This function prepares the bacilli for ingestion by the leukocytes and can be 
increased by tuberculin injections It may therefore have some beaiing 
on the production of immunity, but its relative importance is yet undeter- 
mined Neither can the opsonic index alone nor the agglutination test at 
present be regarded as a measure of immunity nor of absolute diagnostic 
value for tuberculosis, because normal agglutinins and opsonins which act 
on tubercle bacilli to a greater or less degree are piesent m healthy persons 

Antitoxins oi Antiiuberculins have been demonstrated by Maraghano 
and others in the serum of animals injected with ex ti acts of bacilli Their 
true nature is in doubt, and although they have been shown to neutralize 
fatal doses of tuberculosis toxin, it is not clearly established that they are 
analogous in action to those of diphtheria and tetanus, whose toxins are of 
a different nature It is difficult to disassociate the possible action of a lysin 
and precipitin, both of which are probably present m these seiums as m 
those from animals injected with other bacterial proteids and bacteria 
(typhoid, choleia, etc ) The presence of a bacteiiolysin has indeed been 
claimed for Maraghano’s serum 

Bactoiolysin — It has been difficult to experimentally demonstrate a 
bacteriolytic powei in serums acting on tubercle bacilli in vitro, probably 
owing to the inherently great resistance of this organism to disintegration 
and the long time required for such action Moreover, the participation 
of living cells may be an essential condition not susceptible of imitation in 
the test tube The existence of such a function is nevertheless undoubted, 
as progressive stages of disintegration in the bacilli which are introduced 
into immunized animals are manifest by staining 

The therapeutic exi^eriments with antituberculosis serums have usually 
been disappointing or unconvincing as to a specific value Some have 
proved harmful, like those of Maffucci, Bibes, and v Behring Further- 
moie, too little attention has been given to the physiological effect of repeated 
injections of heterologous serums apart from any specific antibodies that they 
may contain ^ Whether the specific precipitins, opsonins, or antitoxins 
found m the serum are essential to a high resistance is at present only con- 
jectural, they at least accompany the development of specific resistance oi 
active immunity in animals, but attempts to transfer the immunity to others 
by means of the serum have not succeeded Therefore, the outlook foi a 
successful serum therapy in tuberculosis cannot be regarded as hopeful at 
present 

' Normal serums alone under these conditions ha\e been shown to excite anti- 
bodies against the serum per se, whose effects must be reckoned with 



TUBERCULOSIS HISTORY AHD ETIOLOGY 


171 


To summarize tlie present knowledge of specifie reaction products against 
tubeiculosis, Me can say that specific agglutinins and opsonins are readily 
recognizable in the seium and that piobably lysins and to\in-assimilating 
or digesting functions exist ivliich act m conjunction with the body cells to 
pioduce lelative immunity 

Conditions Influencing Infection — It is hardly possible to enumei ate all 
the factors involved in bunging about infection in tubeiculosis, since they 
must be regarded as extiemely complex in many instances and fai vider 
ranges obtain betveen susceptibility and piactical immunity than in the 
other infectious diseases It cannot be said, as in choleia or diphtheiia, 
that, given an equal exposure, a large percentage of individuals i\ ill develop 
the disease in a iirulent form Moieovei, theie is a stiong piobabihty 
that the sloivness of lepioduction mIiicIi is chaiacteiistic of the tubercle 
bacillus furnishes a better oppoitumtj foi the animal host to create an ade- 
quate defence, vhereas there is no time for this in the inoic acute diseases 
In any consideration of these laiying conditions leading to infection both 
parasite and host are subjects of possibly equal nnpoit.ince in determining 
the balance of poiver 

Number and Virulence of Tubercle Bacilli — On the paitof the tubeicle 
bacillus the dose and virulence must be conceived to be of pi line importance 
It has been slioivn in animal expeiiments that a model ate infection may be 
completely overcome ivhile a gi eater one is fatal It is thus intelligible that 
repeated and frequent exposures seem oidinaiily necessaiy to pioduce the 
disease m human adults If a single cxposuie m'cic sufficient, the fact Mould 
be difficult to pioie anyM.iy, because of the sloM development of the disease, 
yet Its occurrence cannot be considered impossible, especially in childien 
The actual number of bacilli m room-dust capable of floating in the air is 
small compared Muth those in the heavier particles ol moist oi diy sputum 
on the floor or contaminated clothing M’hich cannot remain suspended 
Hence, the number of bacilli SMalloMed must be much greater than those 
inhaled, hoM^ever they are taken m, and a single exposure might be sufficient 
to infect a child m this Mmy 

The virulence is also knoMm to be^allable Some strains of tubeicle 
bacilli are able to infect in the minutest dose m hen implanted in susceptible 
animals, while others seem very feeble Chnicallj’' this fact may be only 
surmised by the different forms of the disease, Mdiether chionic oi acute, 
and by instances of apparently dnect contagion, ndiere the disease develops 
in rapid succession in a numbei of um elated individuals On the other 
hand, the most virulent strains of bacilli aie M'eakened bj' diying and expo- 
sure to light and an, Mdnch conditions usually exist to some extent in indiiect 
infection and Mdnch piobably neutralize oi delaj’^ the manifestation of diftei- 
ences m virulence What the vnulence of a given stiain may be is difficult 
to determine from the course of the disease m human subjects, Mdiere so many 
other factors enter into the pioblem 

Natural Resistance of the Human Organism — In analyzing the nature 
and mechanism of man’s natural resistance to tubeiculosis, one must include 
his environment relative to climate and altitude, his residence, whether 
urban or country, together Muth his occupation and cellular defences An 
invigorating climate inviting to an open-air life is an obvious advantage, 
Mdnle elevation above sea level promotes inci eased function and strength 
of the heart and lungs The greater purity of the an and less stienuous 



172 


INFECTIOUS DISEASES 


life of the country d^^ellel naturally contribute to the maintenance of normal 
vigor 

In the first rank for the natural piotection of the mdi\idual is the epithelial 
covering of all surfaces exposed to external influences The exteinal skin 
IS not easily penetrated by tubercle bacilli unless a lesion exists, and it ofteis 
an effective barrier m adult life, though less in childhood The nasal and 
pharyngeal mucosa with intact ciliated epithelium is a strong defence, as 
IS also that of the trachea and bronchi, the normal adult gastio-mtestmal 
tract likewise appears but slightly permeable If the infection gams en- 
trance, there are other mechanisms set m operation which tend to fix the 
bacilli at the portal of entry or to check its progress m the neighboring lymph 
nodes These are comprehended under the head of immunity reactions, 
elsewhere considered An intimate knowledge of their nature defies our 
present powders of research, but some insight has been obtained 

The determination of the opsonic index appears to be one measure of 
resistance w Inch w'e possess to-day, although its limitations are not yet fully 
knowm When the complex nutritive processes aie bettei knowm, othei 
reactions of equal value may be discovered At present the sum of our 
know’ledge of good physiological resistance is expressed indefinitely as good 
cell nutrition Hence, good eaters with sound digestions are w'ell armed 
against this disease The gouty diathesis is undoubtedly an evidence of 
relatively gi eater resistance to tuberculosis according to clinical experience, 
wdiile certain diseases mechanically oppose it hlitral heart disease with 
resulting pulmonaiy venous stasis acts as a protection possibly for that reason, 
yet the matter is rather too complicated for positive proof Emphysema is 
also supposed to aftoid some degiee of immunity against tubeiculosis An 
open-air occupation oi one requiring active musculai exercise is another 
important aid to resistance Musicians w'ho play wund instruments are 
infrequently tuberculous, according to Rogers ^ Ceitain occupations have 
been claimed to be especially piotective against tuberculosis because of the 
gases inhaled by the workmen Such are the sulphuious acid fumes pro- 
duced in the so-called sulphite process in the manufacture of wmod-pulp, 
also those of ordinaiy coal-gas and ammonia The proof of such a protection 
IS not convincing enough for serious attention Agricultural pursuits and a 
seafaring life are naturally best adapted to maintain a strong constitution 
if other conditions are favoiable Lastly, a naturally vigorous mental and 
moral equipment is second only to the physical 

Reduction of Resistance — Disposition — A w^ell-founded belief in a 
“tendency” to tuberculosis has existed m all ages of medieal history It 
received a check at the time of the discovery of the bacillus, and is still 
belittled by the contagionists (Cornet) A broader view" has again taken root 
which modern biological research supports, and w'hich claims the accept- 
ance of a middle ground, giving due prominence to both the parasite and 
host m disease pi eduction 

The Nafnic of Di"}posihon — A satisfactory definition of the actual nature 
of wdiat W’e term disposition or predisposition is as yet w’anting In the last 
anab sis it has to do W’lth the cell activities of the animal body It may in- 
clude a positive element m that the soil is abnormally favorable by reason of 
a certain chemical composition or functional excess of the tissue metabolism, 


^Medical Record, October 6, 1906u 



TUBERCULOSIS HISTORY AND ETIOLOGY 


173 


or, on the other hand, a negative one which consists in the absence of 
some chemical ingredient or weakness of the noimal defensive mechanisms 
On the surface, the chemical theory of predisposition has support in the 
well-knov n susceptibility of diabetics, because sugai is known to be a favor- 
able component of cultuie media foi the tubercle bacillus The grade of 
alkalescence of the blood and especially of the bronchial mucus has also 
been suggested as a factor (Hesse), since an alkaline sputum is a more 
favorable culture medium There are other theories, such as variations 
m the composition and stuictuie of the elastic fibers (Hesse, Tendeloo), 
in the amount of silicates in the connective tissue (Kobert, Schulz), the 
“demineiahzation theory” of tlie French autiiors (Robin and Bmet), ^^hlch 
assumes a deficiency m the tissues of mineral salts, especially of calcium 
and the phosphates, due to inci eased respiratoiy change oi excess of oxi- 
dation and the converse of the gouty or arthiitic diathesis, which is accom- 
panied by an excess of these salts All these theoiies have found support 
m the analyses and experiments of their authors, but are too narrow and 
lack completeness for a subject of such complexity ‘ The studies in luema- 
tology and antibodies of the seium have led to the probability that a sub- 
normal resistance is associated w'lth a deficiency in certain forms of leukocytes 
(Arneth) and of normal alexins and agglutinins in the blood fluids More 
lecently the ^aluable work of Wright and his associates indicates that a 
low ered opsonic index oi deficient phagocytic pow'ei is a sign of predisposition 
wdiich promises much importance 

A subnormal resistance to tuberculosis may be (1) From causes arising 
wnthin the body — (a) natuial and (6) acquired Under natural causes 
w'e shall consider (1) Race, (2) Heredity, (3) Individual constitution, 
(4) Age, (5) Sex 

Natural Predisposition — Race — The question of racial diffeiences in 
susceptibility has aheady been noted It is yet undecided what factor or 
factors are most important in the apparently gi cater Milneiabihty of the 
Negro and aboriginal Indian races An attractne theory is that they at 
present lack the gradual immunity acquired by more resistant races through 
centuries of civilization and exposure to the infection, the more resistant 
individuals having sunuved among the lattei From this jioint of i lew racial 
susceptibility is simply a passive quality lathci than a peculiarly difteient soil 

Heredity — One of the most complex problems in medicine is that of an 
inherited disposition to tuberculosis Theories have changed as new' facts 
have developed, but the belief in such family inheritance is w'cll-nigh universal 
Elaborate statistical studies and genealogical tables have been made by 
Riffel, Leudet, and others to show the predominant influence of heredity, even 
to the one-sided view that the infection is of secondary importance, on the 
other hand, Cornet, v Behring, and Boeg ascribe little if any importance 
to heredity Practically the only question to be decided is w'hether an 
inheiited w'eak constitution has a specific tendency to implantation of the 
bacillus Little value can be placed upon genealogical data to settle this 
question, for the impossibility of excluding congenital or infantile infection 
IS apparent Testimony for and against specific inheiitance fiom family 
records is of equal importance For example, Riffel gives the history of 

‘A good review of the subject is found in the very complete work of Sclilueter, Die 
Anlage der Tuherculose, 1905 



174 


INFECTIOUS DISE iSES 


se\eral generations of tuberculous families wheic the infection could fairly 
be excluded in some descendants who became tuberculous However, 
Cornet criticises this study for gross inaccuracies On the other hand, 
Boeg studied the mortality from tuberculosis among the Faroe Islanders, who 
are closely intermarried and ha^ e had no opportunities for outside infection, 
but he found no support for the inheritance theory J E Squire gives more 
valuable cMdencc against the importance of specific susceptibility by com- 
paring the children of consumptive parents v ith those of non-consumptives 
ot the same class and condition m life He found only 10 pei cent more 
of the former had become tuberculous m a study of 1000 families, an excess 
easily accounted for by the gieater opportunities for infection rather than 
actual heredity 

A truly specific inherited susceptibility must imply transmitted properties 
thiough the germinal cells, and strictly construed should not include influ- 
ences acting during intra-utenne life, which aieieally congenital Adami 
believes that tv o possibilities may result from parental tubeiculosis according 
as the disease is progressive or unresisted the germinal cells become weakened 
by the specific poison and the offspimg especially susceptible to tuberculous 
infection, or if well resisted the child may acquire an inereased resistance 
to the same disease Some experimental support to this idea has been 
attempted, but the matter is difficult to control ‘ Moreover, the argument 
of Ilueppe, who is an exponent of the importance of disease predisposition, 
may be adduced, that “immunity and immunization directly prove biologic- 
ally that predisposition must be a positive pioperty of the protoplasm, for 
otherv’ise there could be no immunization 

In a matter of such subtlety, future studies may make the truth clearer, 
but certain clinical obseivations tend to confirm a belief m an inherited 
specific susceptibility of a certain kind One of the most interesting and 
suggestive is that of Turban on the inheritance of a locus mtnoiis 1 esistentice, 
V hereby the disease was found to begin m the corresponding lung of the 
parents and the children m 19 families out of 22 (86 4 per cent ) Among 
the writer’s cases 78 per cent of 28 families wheie parental tuberculosis 
existed had children with the corresponding lung first involved In one 
family the father and four children had the same lung fiist affected Ogilvie 
found similar instances A striking example also of the apparent trans- 
mission of susceptibility IS found on the Isle of Man, vhere tubeiculosis 
IS nearly tv ice as frequent as m England and Wales Davies, who made 
a study of the conditions there, concluded that consanguineous marriages 
for many centuries were chiefly responsible for the excessive amount of 
tuberculosis 

The youngest child m large families was found by Brehmer to be more 


' Camere claimed that the joung of animals injected with toxins of tubercle 
bacilli ■i\ere more easilj infected than those of control animals Sicolla and Palmieri 
found the progenj of tuberculous guinea-pigs abnormal^’’ susceptible to tuberculin 
Analogous hj persensitn eness to certain poisons appears to be transmissible from 
parent to offspring 

^ The transmission of tuberculin susceptibihtj to the cahes from immunized 
cov s did not occur m a Behring’s expenments, nor is it reasonable to expect the influ- 
ence of tuberculosis toxins to be manifest m the offspring unless the disease is active 
in the mother dunng pregnancj , it is entireb^ problematical how paternal tuberculosis 
can hai e any influence 



TUBERCULOSIS HISTORY AND ETIOLOGl’ 


175 


susceptible than the older children, but Shively in a critical study of 1176 
cases in families of foui to thiiteen children came to the opposite conclusion 
The inheritance of nutritional faults and structural defects in the chest, 
size of heart and arteiies, the so-called “paratuberculoses” (Hutinel, Mosny, 
LandouzjO, etc , which aie elsewhere mentioned as important disposing 
factors, cannot strictly be classed as specific qualities established by the 
parental disease m all cases, since they may proceed quite certainly from 
non-tuberculous individuals Nevertheless, for piactical purposes, these 
observations cannot be ignoied because the matter is complicated and not 
necessarily connected with tuberculosis in the parent 

Defects of development or diseases in the parents often stamp sufficient 
weakness upon the offspring to constitute a lessened resistance to tuberculosis 
quite as important as that entailed by tubeiculous paients upon theirs 
Prominent among these parental diseases is syphilis, alcoholism and vaiious 
psychoses aie also regarded by many as of great impoitance Statistics 
which will bear criticism have not been taken as to the lelative incidence of 
tuberculosis among the children of such parentage, but as less than a third 
of tuberculous individuals give a history of tubeiculous parentage, it may 
be assumed that other diseases and abnoimahties in the parents have no 
small part in whatevei hereditaiy weakness maj^ be attiibuted to the 
remainder It is, therefore, only in the broadest meaning that the inheritance 
of predisposition to tuberculosis can be consideied of especial importance, 
% e , any defects or injurious influences acting upon die parent may possibly 
be a source of predisposition for the child 
Constitution or Habitus Phthisiciis — Constitutional weakness oi mal- 
development (whether truly inherited or congenital) has always claimed 
importance as a disposition to tuberculosis Hippocrates described the 
habitus phthisicus as the blonde, dehcate-skinned individual vith winged 
scapulae and long, flat chest Besides the delicate, ovoid-featured tjqie of 
persons with long, thin bones, knovn as the tuberculous by the oldei wiiteis, 
the scrofulous was also recognized, with broad face, thick lips and nose, 
coarser skin, and heavier figure These two tjqies have been fairly distin- 
guished m composite portraits made in recent j ears by Galton and Mahomed 
of 442 tuberculosis patients, thus confirming the accuiacy of the early 
observations In olden times no account seems to have been taken of the 
numerous exceptions among consumptives who veie without stiuctural 
defects, nor could a distinction be made during the “prebacillus era” 
betMeen the inborn and acquiied changes resulting fiom the disease itself 
In consequence of greater enlightenment these constitutional factors have 
lost some of their import, although many of the so-called stigmata of tuber- 
culosis undoubtedly favor the disease Rokitansky was one of the first to 
give a detailed description of the habitus phthisicus, and laid stress on the 
poor muscular development and shape of the chest — a nariow anteroposteiioi 
diameter, but of greater length than noimal, and with small abdomen The 
lung volume, however, was considered piopoitionately gieatei By the 
careful clinical studies of Brehmer and the pathological ones of Beneke 
still further anomalies became recognized According to Brehmer, volumi- 
nous lungs were associated with an abnormally small heart, which therefore 
failed to adequately nourish them, thus predisposing to the disease His 
^stem of sanatorium treatment, especially the gradual hill-chmbmg, was 
based on this theory, and was supported by 500 anamneses and thousands 



176 


INFECTIOUS DISEASES 


of obsenations Beneke found in many comparative measurements, 
besides large lungs and small hearts, relatively nariow arteiies and short 
intestines 

Bony deformities of the nose and javs -whieh cause mouth-breathing are 
nov properly included among the constitutional defects The life msuiance 
companies of today doubtless wisely letam the old conceptions of piedis- 
position m their inquiries about the shape and expansion of the chest and 
the relation of height to v eight, although the tall individual with immobile, 
flat chest, depressed sternum, and sloping shoulders can no longer be con- 
sidered necessarily a bad risk The recent measurements of Biovn and 
Pope of the patients at the Adiiondack Cottage Sanitarium tend to deny any 
special type for the tuberculous chest, although theie was some tendency 
for the thoraces to be slightly rounder, flatter, and of greater length than 
normal The favorable types of the disease, however, are selected foi this 
institution Among 647 patients of a poorer elass m the clinic at Cracow, 
Poland, only 38 per cent exlnbited a phthisical form of chest, 41 6 pei cent 
with and 36 per cent without tuberculous heredity (Kwiatkowski) Turban, 
whose patients belong to well-to-do classes, found 36 3 per cent with an 
habiius phtlmmis It is evident that many anomalies when combined m 
the same person may form a constitutional disposition, but singly have little 
importance, since they may be compensated for without impairment of the 
general vigor 

Local Predisposition — A local disposition natural to certain tissues or 
organs, especially the lung apices, has much mteiest and possible importance 
Most of the theories urged as the cause of primary apical disease can be 
expressed by the term local malnutiition The mechanical theory of the 
older authors, which attributed the local weakness to a lessened aeration and 
greater opportunity for the retention of dust due to the pooler expulsive 
power of the apices, has become less tenable since the knowledge that by 
luematogenous infection as well the apices are primarily involved m man 
Nevertheless, the observations of Birch-Hirschfeld that a small posterior 
apical bronchus is an especially fa\orable situation for primarj’^ bronchial 
tuberculosis includes not only a mechanical theory but also that of local 
malnutiition This author has shown that these bronchi are deflected at a 
sharp angle from the larger tubes, and because of the slower air currents 
the opportunities for gatheiing foreign mattei are much gieatei than m the 
lower lobes, where the respiratory movements aie stionger The stagnation 
of secretions and poorer aeiation are also a souice of lowered lesistance to 
the tissues, v hether the infection be aerogenous or hiematogonous An 
abnormally great predilection for this situation m some individuals, according 
to Birch-Hirschfeld, is caused by congenital or acquired iriegularities, 
vith narrowing of the posterior apical bronchi The possible relation of 
Turban’s inherited lociis mmons icsistcntm to this fact is noteworthy 

Freund first called attention fifty years ago to a nariow mg of the apices 
associated with a premature ossification of the first iib caitilage wdiicli 
restricts the development and causes greatei immobility of the apex Hart,^ 
111 an exhaustive monograph, has recently emphasized anew' the importance 
of Freund’s theor}' in local predisposition and the inheritance of this anomaly 
He considers that it gives rise to a shortening of the first rib and a “stenosis” 

’ Die Mcchamsche Disposition d Lungenspitzcn, etc , Stuttgart, 1906 



TUBERCULOSIS HISTORY AND ETIOLOGY 


177 


of the apex, and is dependent upon deficient development of the first-rib 
cartilage or the rib itself on one or both sides Rothschild, ^ furthermore, 
found the same predisposition connected with insufficient movement at the 
sternal joint between the corpus and manubrium at Louis’ angle, which is 
favorable to the paralytic type of thorax Schmorl discovered a fmrow on 
the lung surface extending diagonally downwaid from the posterior aspect 
of the apices, where the pleura was thickened and near which the primary 
tubercles are formed Cornet thinks the greater frequency of right apical 
diseases is due to the larger right bronchus receiving more dust 

Taken separately these larious anatomical theories do not carry much 
weight When, hoveier, they aie combined vitli the physiological condi- 
tions of the blood and lymph circulation m the apices as compared \vith 
other regions of the lungs, an explanation of the early involvement of the 
apices becomes dealer In the first place the atmospheiic pressuie varia- 
tions during respiration are much greater m the basal paits of the thorax, 
as shown by Meltzer and also by Hofbauer, whereas there are almost no 
variations at the apices The consequent lesser aei ation and rapidity of the 
blood and lymph flow m the apices favors the lodgement of the tubercle 
bacilli, while the same reasons render the tissues more vulnerable The 
work of Tendeloo^ led him to a similar view It has also been suggested 
that the upright posture in man favois venous stasis in the lung bases, 
which in turn forms a hindrance to infection, according to the studies of 
Bier 

Little can be said in explanation of the appaiently greater susceptibility 
of the lungs, kidneys, and joints as compared with the Iner, spleen, and 
muscular tissues Aufrecht has long maintained that the piesence of ter- 
minal arteries m the lungs had much to do with the infection and tliat the 
infarcts caused by bacilli m the bloodvessels formed the primal y foci lake 
conditions may account for localizations in the kidnej^s and joints Hence, 
mechanical and physiological reasons favoring the lodgement of the bacilli 
sufficiently account for these differences in some cases ivithout invoking a 
humoral theory or that of a special chemical affinity between certain cell 
forms and the tubercle bacillus Future research may associate these latter 
factors more satisfactorily with lowered resistance than can be done at 
present 

Age — The resistance to tuberculosis varies with age and is least in child- 
hood, when the tissues readily permit the infection to enter at various places 
and be more easily distributed It is also well known that the lymphatic, 
meningeal, bone, and joint forms of the disease predominate in early life, 
but after the tenth year the pulmonary form increases in fiequency 

Whether this difference is due to a greater susceptibility of these tissues 
in childhood or to a difference in the avenues and opportunities for infection 
IS a complex problem As mentioned elsewhere, \ Behring holds that the 
pulmonary form m adults is chiefly a sequel to gastro-intcstinal or other 
mucous membrane infection m infancy due to the incomplete development 
and ready peimeabihty of the mucosa, which offers no bairicr to absorption 
However this may be, there is a tendency m adults for the disease to develop 
at the site where the infection is presumed to enter in the lungs or mucous 

I (Anjrulus Ludovici) in Anat physiol u path Himicht, 1900 

Ursachen dcr Lungenhrankheiten, 1901 
voii III — 12 



178 


INFECTIOUS DISEASES 


surfaces, liereas in childhood it usually spreads farther before the tissues 
respond by tubercle formation Evidence is accumulating that a primary 
infection is far more fiequent m childhood than hitherto suspected, and it is 
fallacious to consider the fiequency of tuberculosis at different life periods 
as an mde\ of susceptibility at those ages This depends, as Cornet says, 
upon external causes and varying exposure to infection 

It has been observed that puberty and the menopause m females aie epochs 
during which the disease may de\elop rapidly An appaient inheritance 
of susceptibility at certain ages is observed m some tuberculous families, 
whereupon the disease begins in the children as thej^ successively reach the 
fatal age — usually between e ighteen and twenty-five These instances are 
probably associated with infection at an early age, though the facts are used 
in support of the theory of actual baeillai}' inheritance 

Sex — Little diffeience exists between the sexes in their liability to tuber- 
culosis except that during menstruation, pregnancy, and lactation women are 
temporarily rendered less resistant It is even debatable Whether pregnancy 
as such faiors susceptibility, but there is no doubt that the strain of labor 
and the puerperal period give an impetus to the disease if latent and in- 
creases the danger of infection In 46 (5 25 per cent ) of the adult females 
among the author’s private patients, pregnancy, labor, or lactation was the 
predisposing cause assigned The female skin being more delicate than 
that of the male, there is also greater opportunity for local infection Lupus 
IS nearly twice as frequent in women as in men, according to Cornet’s 
statistics 

Acquired Predisposition — Constitutional Diseases — Scioftdons — ^This 
much disputed term deseives retention, m the opinion of the writer, only 
when applied to chronic non-tuberculous enlargements of the lymph nodes, 
and to the constitutional weaknesses of the skin and lymphatic apparatus 
■well described by Virchow, wdio regarded the condition as due to a mal- 
development of the glands and lymphatics Repeated microbic infections 
other than the tubercle bacillus, such as the streptococcus, staphylococcus, 
and influenza, can undoubtedly cause a persistent hyperplasia of the lymph 
glands which give a predisposition for tuberculosis Whether such in- 
stances can be distinguished clinically from actual tubeiculous lymphadenitis 
IS indeed doubtful Opinions are not w'anting that the entity known as 
scrofula alwmys indicates tubeiculosis Cornet differentiates three forms 
of sciofulosis (1) Tubeiculous, x c , produced by the tubercle bacillus, 
(2) the non-tuberculous or pyogenic, chieflj' caused by the streptococci and 
staphylococci, (3) a mixed form m wdnch the fiist twm are associated He 
also recognizes a congenital predisposition to sciofulosis, an abnormal 
permeability of the skin, mucous membranes, and lymph passages wdnch is 
inherited as w ell as acquired Von Behring of late has explained the scrofu- 
lous diathesis as due only to the effects of actual tuberculous infection, wdnch 
alters the Ijonph and blood\essels and lea^es a tuberculin susceptibility 
stamped upon the tissues The arrested infantile tuberculous infection 
thus prepares the w a'v for a secondary infection and forms a specific predis- 
position This aspect of scrofulosis makes the decision no less difficult 
because the presence or absence of tubercle bacilli, ? c , of an actual latent 
tuberculosis, is not the criterion, but rather the piesence or absence of tuber- 
culin susceptibility At present the question may still be considered open, 
while for practical purposes the term scrofulosis can be used to mean an 



TUBERCULOSIS HISTORY AND ETIOLOGJ’ 


179 


important predisposition to pulmonary tuberculosis, which is associated 
with it in 25 per cent of all cases 

Diabetes — The presence of an excess of sugai in the blood favors bacterial 
growth and doubtless diabetics are especially prone to tubeiculosis for this 
reason alone, whether or not other factors are of greater moment It is esti- 
mated that one-fouith to one-half of all diabetics, especially young persons, 
succumb to tuberculosis in a progressive form 

Syphilis — This disease may act as a disposing factoi in reducing the 
general vitality, and both diseases are piesent m many peisons of the depraved 
class Turban found a previous history of lues in 6 4 per cent of 408 cases, 
Sokolowski m 3 per cent of 8074 cases, the author, 1 3 per cent of 1690 
private cases An idea once promulgated that s^’phihs confers a relative 
protection against tuberculosis is entirelj^ without foundation 

Nervous Diseases — Psychoses — An irritable neivous system is so fre- 
quently associated with pulmonary tubeiculosis that neui asthenia, hysteria, 
or nervous instability in general have long been considered predisposing 
factors Papillon even considers neui asthenia as a symptom of suspected 
latent tuberculosis The relation of these chaiacteiistics to tuberculosis as 
effects rather than causes is therefore equally probable It cannot be denied, 
however, that those persons who possess by inheritance oi otherwise a delicate 
nervous organization frequently fall victims to the disease T J h'lays goes 
so far as to ascribe a nervous origin to all cases of tubei culosis and dependent 
upon degeneration in the pneumogastric nerve Here again cause and effect 
are difficult to separate and too great emphasis is given to a single factor 
In the true psychoses there is an undoubted predisposition, especially vith 
imbecile melancholics Snell found that 41 2 pei cent of the latter died of 
phthisis and 27 1 per cent of maniacs Epileptic families are also prone to 
tuberculosis 

It should not be thought that the fiequent incidence of tuberculosis is the 
direct result of nervous disordeis, but rathei that the defective functions and 
nutrition of such persons render infection easier Increased opportunity for 
infection, especially in public institutions, has also played an important 
part in the past 

Chlorosis and Ansmia — Chlorosis and aniemia secondary to other diseases 
are to be considered predisposing factors m a limited number of cases 
Latent tuberculosis, however, can be excluded in but few of these cases, 
according to some results obtained by the tuberculin test in late years 

Previous Disease of the Lungs and Thorax — The impoitance of acute 
respiratory diseases in developing a latent tuberculosis and favoiing a new 
infection is apparently great Turban found 34 5 per cent of his cases 
preceded by a tendency to inflammations and catarrh of the air passages 
The relation of lobar pneumonia to tuberculosis is in dispute, some authors 
holding that the latter is relatively raie as a sequel to pneumonia and that 
caseous pneumonia begins as such, vhilc others maintain that it is developed 
from a latent focus by the pneumonic process Jacob and Pannwitz 
found 195 in 3295 cases with a history of precedent pneumonia and therefore 
regard it as predisposing It was found in 110 of the author’s 1690 patients 
in whom a predisposing cause was assumed 

Influenza is a frequent and important agent in bringing to light latent 
tuberculoses, and during the last decade has become prominent in the 
histones of tuberculous patients Allowing amply for mistakes in diagnosis 



180 


INFECTIOUS DISEASES 


where the presence of tuberculosis is overlooked, influenza must be classed 
as an important exciting cause if not a true predisposition Jacob and 
Pannw'itz found it to have occurred shortly before the tuberculous outbreak 
m 479 (14 5 per cent) of their cases, w'hile 389 (11 S per cent) gave a 
history of antecedent colds Among the authoi’s cases 262 (15 5 per cent ) 
ga%e a histoiy of influenza and 376 (22 2 per cent ) of colds 

Measles, scarlatina, variola, diphthena, tonsillitis, and whooping-cough 
are in the same category ivith the respiratory diseases because the loweied 
resistance produced by these maladies is accompanied by inflammation of 
mucous membranes and lymph glands wdiere tubercle bacilli may have 
already lodged In order to distinguish betiveen the instances of latent 
infection w^hich are spread by these diseases and those fresh infections for 
which the soil is made favorable, the time elapsing before the tuberculous 
outbreak takes place forms some guide It may be assumed that the longer 
the interval the greater the probability there is of a new infection having 
occurred Whatever may be the sequence of e^ents, the acute infectious 
diseases are of the greatest importance in the development of tuberculosis, 
especially of the lymphatic foim in children Measles and whooping-cough 
claim the first rank m this connection In the author’s series of 1690 cases, 
all over 15 years of age, the above diseases preceded the tuberculosis in 61 
(3 6 per cent ) cases 

Bronchitis simplex and chiomca in adults have no favoring influence 
tow'ard tuberculous infection in themselves that can be proved, wdiile 
emphysema is possibly even protective against pulmonary tubeiculosis 
The frequency of bronchitis and asthmatic affections piior to recognized 
lung tuberculosis cannot be regarded as causative, rather aie they symp- 
tomatic of existing tuberculosis A recent study of 700 cases of asthma by 
Soca indicated that a large proportion (500) wxre appaiently associated with 
pulmonary tuberculosis Asthma w^as given as a precedent disease m 11, 
bronchitis m 52 of the author’s senes Catanhal diseases of the upper an 
passages of a chronic charactei cannot be cons’dered as diiectly aiding 
infection except in children, considering their frequency in otherwise healthy 
persons On the other hand, nasal obstructions and adenoid hypertrophy 
resulting from catarrhal affections are potent aids to infection by causing 
“mouth-breathers ” E F Ingals found nasal diseases in only 28 per cent 
of 830 cases of tuberculosis, whereas 75 per cent of the geneial population 
suffer from them In 29 of the authoi’s cases it w'as assigned as a 
factor 

Pleuritis of the primary form is in such a large proportion of instances a 
symptom of tuberculosis that it needs no furthei mention here Secondaiy 
pleurisies due to trauma, pneumonia, and othei respiratory diseases may 
act predisposingly 

Raclniii being an expression of defective nutrition favors infection, 
presumably both for that reason and because of the thoracic deformities 
which form a hahitui phthisicus and impaiied chest movements It was 
found in 10 8 pei cent of Turban’s cases Well-marked deformity w'as 
found in but 41 (3 per cent ) of the author’s cases 

Typhoid fcvci and gastro-inte'itinal discaic are undoubted!) occasionally 
followed b) tuberculosis Opinions diflei as to the frequency of tuberculosis 
follow ing t'V'phoid fe\er, as the diseases are frequently confused, the diagnosis 
of tj phoid often being made at the onset of tuberculosis. No certain rela- 



TUBERCULOSIS HISTORY AND ETIOLOGY 


181 


tionship has been established between the diseases A histoiy of typhoid 
fever \\as given by 74 (4 2 per cent ) of the writer’s patients 

Malana is a frequent history obtained from tuberculous patients who 
reside in malarial regions Such was given by 49 (2 09 per cent) of the 
writer’s series Its actual position as an etiological factor is doubtless much 
exaggerated by the confusion of the S3'mptoms with those of tuberculosis 
Gemio-unnai 1 / disease, vephitis, and caicinoma are predisposing to some 
extent, as is also cJnomc heait disease with aortic stenosis Congenital or 
acquired stenosis of the pulmonary artery is especially predisposing, w'hereas 
mitral stenosis confers an apparent protection against the disease 

Injuries — Tiauma is important in creating favorable conditions for 
infection or spreading that which may be present The ruptured blood- 
vessels and extiavasated blood arrest the bacilli, wdiicli may enter the circula- 
tion and hence form the nidus for infection after contusions Joint, pleural, 
and meningeal tuberculosis is vei}'^ naturally associated wnth injuries m the 
popular belief, and quite justly Blows on the chest are considered equally 
important in connection rvith pulmonary tuberculosis Five of the author’s 
patients gave a historj" of blow s on the chest and tw o of falls Concussions 
and nervous shocks, such as are produced bj' falls and railroad accidents, 
should have place m the etiology of tuberculosis The relationship of 
injuries in modern American athletic contests to subsequent tuberculosis 
may not be unimportant and demands study Surgical operations upon 
tuberculous glands and joints are occasionally follow^ed by dissemination of 
the infection In 18 of the author’s patients, surgical operations (13 being 
for appendicitis) appeared to play a piedisposing part 
Environment — Caines Acting on the Body fiom Without — Of equal 
importance to constitutional or acquired weakness are the surioundings and 
mode of life of the individual Every relation in life is a factor m some degree 
for or against the development of tubeiculosis 

Clim^e — The predisposing influence of lowq damp climates was greatly 
overestimated m formei times, because of ignorance of the essential infec- 
tion At the present day the opinion lias reached the opposite extreme, 
that no importance is directly attributable to this element in man’s surround- 
ings so tar as tuberculosis is concerned The truth, doubtless, lies m a mean 
between these extremes The debilitating heat of the tropics, with its 
high humidity and the depressing effect of the fogs and w'et wnnds of the . 
Atlantic coast, must only be contrasted with the invigorating highlands of 
the interior and the and deserts and sunny table lands of the far West to 
admit that climate is a potent factor m physiological resistance to tuberculosis 
On the other hand, that it can be a specific predisposition is' no longer 
claimed, for m the statistics adduced to show this, too many uncontrolled 
factors entered which are of much gieatei importance The same may 
be said of the separate elements of climate, such as altitude, humidity, soil, 
wand, etc The classic observations of the late Henry I Bowditch, of Massa- 
chusetts, and of Buchanan, of England, that phthisis prevailed more m dis- 
tricts having w^et soil, have lost some of their force with further enlightenment, 
but it must be acknowledged that the conditions in such places are more 
favorable for preserving the vitality of the infection, as well as for the develop- 
ment of other diseases wdiich are predisposing, than well-drained regions 
wnth dry or sandy sod Gordon, of England, has also apparently demon- 
strated, by comparison of countries otherwise similar in race, occupation, 



182 


IXFECTIOUS DISEASES 


etc, that A\et -ninds increase the moitality of tuberculosis It is furthei 
believed to be more acute in hot climates ‘ On the other hand, no exemp- 
tion from tlie disease is found m any climate when the other conditions for 
infection and development of the disease aie present 

Density of Population — The prevalence of tuberculosis is universally 
greater in cities than m rural communities, and no moie constant factor is 
brought out by statistics This fact is, hovevei, bound up with so many 
conditions that it has little meaning taken by itself The occupations and 
manner of life, together with the ciowdcd dwellings of urban peoples, directly 
favoi infection as contiasted with lesidents of the country, yet by absence 
of sanitation, country hovels may paiallel the dangers m city tenements 
Occupation — Certain dust}’^ occupations especially predispose to tuber- 
culosis &tonecutteis, quarrymen, metal and glass grinders and pohsheis 
are the most important Organic dust is of much less importance, yet acts 
deletenously to some extent upon millers, woollen and cotton weaveis, cigar- 
makers, etc Noxious gases also depress the health and irritate the air 
passages of smelters, chemists, and foundrymen Extremes of heat and 
cold act similarly iqion bakeis, stokers, and plumbers Aschei' has made 
a statistical and experimental study w'hich indicates that smoke is also a 
directly predisposing factor, but the tuberculosis mortality statistics of the 
mill ton ns m America, such as Pittsburg, do not confirm this view The 
sedcntai y employments, such as book-keeping, clerking, and other mental as 
distinguished from physical occupations, act more indirectly, by reason of 
long hours of confinement m a sitting or stooping posture, added to nervous 
strain Out of 1947 piivate patients recorded with some occupation, the 
writer found 316 clerks and book-keepers, 147 students, and 97 teachers 
The subject is so complicated with all the other things that make for ill- 
health that the prevalence of tuberculosis m any given occupation is not 
a certain index of the harmfulness of the calling itself For example, persons 
of weak physique are moie likely to select indoor sedentaiy employments 
which are not necessarily predisposing to vigorous persons The excellent 
study by Lilian BrandP sumraaiizes the characteristics which make a calling 
appear to favor tuberculosis as follow's 

“1 A low rate of w ages, entailing discomfort and privations in the home 
“2 Unsanitary conditions of place of employment 
“3 Exposure to dust arising from marble, stone, plaster, wmod, metals, 
or textiles 

“4 Excessive physical exertion or a continued constrained position 
“5 Close confinement wutliin doors 
“6 Exposure to excessive heat 
“7 Temptations to intemperance 
“8 Long or irregular hours ” 

Bad habits contribute a most powerful predisposition Alcoholic excess 
IS a frequent history among the tuberculous wdio are othenMse free from 
predisposition Tobacco and drug habits are less clearly predispositions, but 

‘ An interesting tlieon promulgated bj’- Surg -Maj Woodruff, U S A , is that 
blonde races who originate in higher latitudes become more susceptible to diseases, 
including tuberculosis, when transplanted to regions wuth strong sunlight, by reason 
of insufficient skin pigment —The Effect of Tropical Light on White Men 
* Der Einflitss del Eaiiches aiif die Atmvngsorgane, 1905 
’ Handbook on the Prevention of Tuberculosis, 1903 



'rUBlSRCULOSIS BlSfOliY ABD ETIOLOGY 


183 


lessen nutiition and the defensive powers Mastuibation, sexual excesses, 
and perveisions fa^ol infection by weakening the nervous energy and 
vascular tone A consideiable propoition of tuberculous males of good 
physique give a history of gonoirhoea and alcoholism Irregular and insuf- 
ficient sleep, extreme exertion, mental or physical, also cooperate vith 
depraved habits to bring about the disease in many otherwise resistant 
individuals Among the writer’s cases 94 (5 5 per cent ) gave a history of 
dissipation alone, and 174 (10 3 per cent ) of overstrain, frequently com- 
bined with the former 

Povprhj — No single element m predisposition appears so important in 
the development of tuberculosis as this Statistics of pauperism and con- 
sumption coincide in their variations, the causes that lead to poveity are 
potent in inducing this disease, and the consequences of poveity are yet more 
so, because crowding, squalor, poor and insufficient food, filth, and ignorance 
accompany the downward trend in humanit}' Consumption is the social 
disease pat excellence at the teiminal stage of poveity Korosi established 
for Budapest that among 10,000 living inhabitants, 40 well-to-do persons, 
62 7 model ately well-to-do, 77 7 poor, and 97 paupers died of consumption 
On the other hand, poverty as a lesult of famiN tubeiculosis has not been 
sufiiciently studied to make sure that such figures are not exaggeiated 

Danger of Infection — Bwelhngs vliich are crowded and pooily lighted 
and ventilated are the source of easy infection and foim the chief danger to 
the poor in great cities The “lung blocks” so giaphically displa 3 '^ed by the 
New York Health Depaitment and by the Phipps Institute in Philadelphia 
appear to shov clearly how tuberculosis piedominates m the most crowded 
sections of those cities Besides the close contact of individuals, the air of 
the rooms is greatly vitiated, and the excessive heat and moistuie debilitates 
the inmates The classic ex-periments of Trudeau on the fatal effect of 
cramped and poorly ventilated quarteis on tuberculous rabbits, as compared 
^Mth the recovery of those permitted to live m the open, directly illustrate 
the baneful effects of crowding 

Family — Tuberculosis is so largely a family disease, with from 40 to 
60 per cent of all patients disclosing a history of others in the household, 
that the importance of family infection can hardly be exaggeiated The 
opportunities are innumerable in the homes of the poor and larely wanting 
among the wealthier classes Apart fiom the usual delay in recognition 
of the disease where it progresses steadity to an advanced stage, there 
are many undetected pulmonary cases which become chronic or recover 
and masquerade under the names of la grippe, catarrh, bronchitis, asthma, 
typhoid fevei, and malaria These must be reckoned vith m a study of 
family infection, and doubtless nould swell the numbers materially The 
danger to children is of first importance because of the ease with which 
infection occurs at this period of life, while adults are usually brought into 
a condition of susceptibility by illness, depiessmg care, and solicitude for 
the consumptive relative, besides the vicissitudes of life in general which 
fall heavily upon consumptive families 

Mai ) lage ^The influence of marriage or of married life m relation to 
tuberculosis has been studied carefullj'’, and the danger of infection of 
husband or wife appears relatively far less than for the children It is 
obviously greater for the wife when the husband is the invalid, because the 
nursing is often a grievous burden m addition to other family cares, and 



1S4 


INFECTIOUS DISEASES 


especially during childbeai ing and lactation The husband, on the contrary, 
IS usually an ay at n ork and a nurse or some othei relative performs the duty 
The percentage of cases due to infection between the paitners m marriage 
IS given as high as 23 per cent by Cornet, but othus atliibute only 3 to 6 
pci cent to mutual infection Cornet’s figures are from very poor people, 
the others from better-situated families Mortality statistics have aheady 
been mentioned nhich indicated a generally higher death rate for widows 
and widoweis from tuberculosis than for the single at those ages Weinberg 
hnds that the surviving partners of the tuberculous have twice the mortality 
from tubeiculosis that is found in the general population at the same ages 
Many other factors, however, play a part in such results, and the disease is 
actually less prevalent among the mairied than the single, “partly due to 
the fact that marriage in itself is more or less a process of natural selection, 
and partly to the greatei regulaiity and soberness of life induced by marriage” 
(iMayo Smith) 

Facial y or Shop — Formerly these places were nearly ahvays imsamtaiy, 
poorly lighted, scantily heated, and without ventilation, all of which con- 
tributed to the danger of infection In the large cities these conditions still 
prevail to a great extent, and the consumptive w'orkman can unquestionably 
communicate the disease to his fellows it tliey are m close quarters and he 
IS careless wuth his sputum Cornet cites seveial instances of successive 
tuberculosis m factory employees Clerks, salespeople, and employees m 
public offices wdiere many persons congregate are not only exposed to then 
tuberculous fellow'-employees, but to the indeterminable numbei of visitors 
wdio may bring the infection directly by coughing, spitting, or indirectly 
from their hands, handkerchiefs, clothing, etc We may not believe, as 
Cornet states, that a consumptive wmrkman is a greater danger to his fellow- 
w'orkmen than to his family, for if he is so careless in his habits at w'ork, 
he IS likely to be so at home, wdiere the far more susceptible children are 
exposed On the other hand, it may w'ell be true m the exposure of the child 
laborer, that disgrace of civilization the sum of W’hose disease and misery 
wall never be fully known 

Instiiution^, Sanatoivums, and Health Rcsoits — A great deal of divergent 
eiidence exists for and against the danger of hospital infection for the 
employees, physicians, nurses, and attendants Cornet i elates that among 
the Catholic hospital nursing ordeis 62 88 per cent died of tuberculosis m 
the cloisters during tw^enty-five years, according to a government inquiry, 
w Inch included 74,306 persons The conditions m Ameiica are apparently 
much better for nurses, although it is asserted that 10 per cent of the 
medical internes of Bellevue Hospital have developed tuberculosis, and it is 
doubtless tiue of many other general hospitals where both nurses and 
phjsicians are in intimate contact wuth patients and under nervous strain 
from responsibility 

On the other hand, the record of special hospitals and sanatoriums for 
tuberculosis is quite the reverse, as m the case of the Brompton Hospital in 
London (Theodore Williams) Moreover, no case of tuberculosis has been 
know n to develop among the employees of the Adirondack Cottage Sanitarium 
since its foundation, twenty-tw'o years ago These included w^aitresses, 
chambermaids, and laundresses, many of wdiom were badly nourished on 
entering the ser\ ice The same absence of infection among nurses and 
attendants w'as claimed by Dettw'eiler, of the Falkenstem Sanatorium 



TUBERCULOSIS HISTORY AND ETIOLOGT 


185 


From these contradictory e'qreriences it is evident that there are marked 
differences m the hygienic conditions and control of the patients, whose 
habits largely depend upon their intelligence and station m life, oi else 
entirely false inferences have been derived fiom incomplete data Further- 
more, the close confinement and devotional duties of the Roman Cathohe 
sisters m Germany is to be contiasted with the greater fieedom of the Amer- 
ican hospital nurses, who are also selected in the main for good physique 
In the consumptive wards of general hospitals the presence of bacilli has 
been repeatedly demonstrated in the dust, and Straus found them m the 
nasal secretions of one-third of the physicians, nurses, and other attendants 
at the Charit6 Hopital m Pans There can be no doubt, therefore, of the 
possibilities of infection m these institutions foi susceptible individuals 
It has been thought that the presence of tubeiculous patients in general 
hospital wards endangered the other patients, and instances are cited in 
recent literature in which convalescing typhoid and pneumonia patients 
subsequently developed tuberculosis While these have only the value of 
circumstantial evidence, the separation of consumptives fiom such patients 
IS logically demanded 

Of late much fear has been excited about the danger of infection to the 
residents m health resoH-i No foundation for such feai has been demon- 
strated in any American lesort, and the most unbiased investigations have 
even proved tlie contrary, for relatively fewer cases of tuberculosis develop 
than among othei communities not resorted to by the tuberculous Several 
factors tend to obviate danger, such as the geneially open-air life of the 
invalids, v ho are as a rule intelligent, and have comparatively little indoor 
contact with the residents Furthermore, the disease is usually properly 
recognized and some piecautions instituted, whereas these are often delayed 
at home or concealment is purposely practised 

Pi isons and asylums have furnished a harvest of tuberculosis m the past 
Villemin noted that the mortality from this disease Avas three times as great 
m the French prisons as among the free population Quite similai records 
have held good for other countries The deaths fiom tuberculosis in the 
Eastern Pennsylvania State Penitentiary from 1878 to 1902 Avere 60 8 per cent 
of the total mortality (Hinsdale) In the Ncav York State prisons 75 pei 
cent of the deaths were reported as due to tuberculosis m 1890 (Ransom) 
Cornet shows that there is greater danger in the penitentiaries than m the 
prisons Avliere solitary confinement is enforced It is far from clear, hoAvever, 
that contagion is especially frequent, since so many prisoners are already 
infected on admission, the confinement and depression of prison life develop- 
ing the disease among a class especially prone to previous infection by their 
manner of life Great improvement has been made m the construction and 
hygienic management of such institutions during the past ten years, and a 
corresponding decrease in tuberculosis has occurred in the more enlightened 
countries The same is true for reformatories and institutions for the insane 
and imbecile 

Schools — ^The question of school infection has received attention of late 
m increasing degree Many teachers have the disease m an open form, and 
Avliile their contact with the pupils is relatively less than that of the parents 
it constitutes a real danger Because pulmonary tuberculosis is infrequent 
in childhood, the infection fiom fellow-pupils cannot be a frequent risk 
Suppuration of lymphatic glands or bone tuberculosis may transmit the mfec- 



186 


INFECTIOUS DISEASES 


tion, but this also is a comparatively slight danger on account of the few 
bacilli m these discharges Tuberculosis is, nevertheless, present in a large 
number of public-school children, as revealed by the modem inspection in 
\ogue m some cities In a lecent investigation at Cleveland, Ohio, 7 5 
per cent of 504 children of tuberculous families or exposed more or less 
intimately to a tuberculous individual ere found to have some form of the 
disease, 12 6 per cent were suspected (Lowman) ^ Altogether, 20 per cent 
of these children were considered in need of surveillance 

Giancher has discovered similar conditions in Pans Among 4226 school- 
children 15 per cent were deemed to be certainly tuberculous or strongly 
suspicious The minimum estimates are appalling enough, but speak 
stronger for family infection than for the exposuie m school 

Infection — Histoncal — The reference to the belief m contagion by 
Aristotle and Galen has been mentioned, and every century has had writers 
vho recoided their opinions that consumption was infectious as veil as trans- 
mitted from parents The leaders m medical thought, Morgagni and Val- 
salva, excited the public fear to such an extent during the eighteenth century 
that drastic laws were enforced m Italy piovidmg for isolation of consump- 
tives, notification by physicians, and destruction of the clothing and effects 
of consumptives (Naples, 1788) 

Similar dread of contagion pi evaded in all the Latin countries, and it 
vas customary to bum the clothing and bedding of consumptives in France, 
Spam, and Portugal In fact, it was dealt with like a pest, as shown by the 
sad experience of Chopin, who was travelling m Spam m 1839, this is graphic- 
ally described by George Sand m a letter written while travelling with him 
The extreme unreasoning fear of contagion which was prevalent and still is 
a part of the folk-lore in southern Europe has reappeared m the bacterial 
era, fortified and exaggerated by half-truths m the minds of intelligent people 

During the early part of the nineteenth century the belief in contagion 
was lessened by the influence of Bayle and Laennec, who emphasized tuber- 
culous diatheses, predisposition, and heredity, although admitting contagion 
m some instances Then followed the development of microscopic study 
and a confusion of ideas as to etiology The pathologists focused attention 
upon the morbid changes in the tissues and the inheritance of this disease 
became a firmly fixed belief among all classes of physicians Virchow’s 
teaching still further sepaiated the idea of infection from tuberculosis be- 
cause it uprooted the belief in the unity or speeificity of tuberculous caseation 
and the identity of scrofulosis and tuberculosis He believed m an inherited 
and acquired predisposition, which required no mysterious contagion to 
excite the disease These ideas were dominant when Villemm’s discoveries 
led to joint investigations by physicians to determine if possible evidences 
of infection In America out of 500 physicians questioned by Holden in 
1878, 250 replied, of whom 126 believed m contagion, but of the 10,000 
members of the British Medical Association, Cornet states that only 1028 
replied, and of those, 262 believed m the possibility of contagion — not a great 
shoving of hands Nevertheless, such inquiries were continued in other 
countries with more success, although the belief m heredity was predominant 
When, therefore, Koch’s discovery vas announced, much attention was 

* Transactions of the National Association for the Study and Pievention of Tuber- 
culosis, 1907, vol 111 



TUBERCULOSIS HISTORY AND ETIOLOGY 


187 


triven to the possibility of the direct transmission of the bacillus from parent 
to offspring Baumgaiten has to the present time persistently maintained 
this to be the chief source of tuberculosis in spite of accumulated evidence 
for the importance of external infection 

The notable studies of Comet next indicated the piobable mode of infec- 
tion to be from the dust of infected looms and surroundings of consumptives, 
this foimed the basis for the modern prophylactic measuies foi the disposal of 
sputum and disinfection of apartments When the inhalation of sputum- 
dust had about achieved univeisal recognition in explaining infection, 
Flugge and his associates mtioduced strong expei mental evidence of moist 
“droplet” infection, by which theory the predominant dangei was attributed 
to the presence of a hard-coughing consumptive Lastly, v Behring has 
mtioduced the more revolutionary idea that in most cases the infection is 
derived from milk and begins in infancj”^ through the intestinal channel, and 
IS often from bovine sources Amid all the confusion and readjustment of 
ideas in progress, it is small wondei that a general dread of any contact 
with tuberculous persons has steadily inci eased, in spite of definite knowledge 
of the sources of danger and the measures to combat it 

The Sources of Infection — These are sufficiently well established to permit 
positive assertions to be made concerning them at present, ijiough contro- 
versies are still being waged over the relative dangers of human and bovine 
tuberculosis 

The human sputum is the gieatest factor in the dissemination of bacilli, 
whether by direct transmission in the moist condition or indirectly through 
the medium of dust m contaminated rooms, or of food, clotlung, and other 
objects Many millions of bacilli are contained in the consumptive’s sputum 
and a large proportion of them are capable of growth when first dischargedj 
judging from the culture experiments of Hesse with sputum directly upon 
agar and contrary to the former findings of Kitasato On the other hand, 
the discharges from surgical tuberculosis contain veiy few virulent bacilli 
and are not conceivable as a frequent source of infection under ordinary 
conditions Urine and feces doubtless play some role indirectly through 
soiled garments and bedding, as well as the hands of the unclean, but in 
these cases the danger should be restricted chiefly to advanced invalids 

The milk and flesh of tuberculous cattle have long been regarded as sources 
of danger, but convincing proof of this has been difficult to obtain That 
this IS now entirely satisfactory may be confidently asserted The sensa- 
tional denial by Koch in 1901 of any serious importance from bovine infection 
for human beings led to an industrious study of the subject throughout 
the world and to the creation of tAvo governmental commissions for this 
purpose, those of Germany and Great Britain Both have rendered reports 
which confirm the earlier findings of Theobald Smith and Ravenel in the 
United States, who detected bacilli of boAune type in the mesenteric nodes of 
infants The United States Bureau of Animal Industry has also conducted 
valuable experiments, all tending to shoAV that bovine infection is not unim- 
portant for man Perhaps the most convincing proof thus far adduced is 
from the experiments of Fibiger and Jensen, aaJio isolated cultures Aurulent 
for calves from tAAm young children known to haAm receiA^ed milk from coaa^s 
Avith tuberculous uddeis, and in whose families no human tuberculosis 
existed The value of the statistical studies on the frequency of bovine 
tuberculosis m man as gauged by the number of primary intestinal infections 



ISS 


INFECTIOUS DISEASES 


has been doubtful m the absence of such culture and inoculation tests as the 
afoic-inentioned The number of cases with stiongly piesumptive evidence 
of bovine oiigin is noi\here so great as to compaie in importance with the 
human source, but if it should latei be demonstiated, as suggested by 

V Behring, that the bovine type of bacilli may undeigo a ti ansformation of 
Mrulence by long residence m the human body, so that they aie indistin- 
guishable from the human types, the statement vould lequire modification 
That the milk and flesh of tuberculous animals are proved souices of human 
tuberculosis must be admitted, but obviously they are of varying impoitance 
according to the prevalence of the disease m domestic animals In America 
boi me tuberculosis must be a relatively small factor m the causation of the 
human disease, because it is relatively infrequent, while m Japan it is entirely 
wanting, according to Kitasato, because not only is no milk used by the mass 
of people, but the few cattle in that country are free from tuberculosis 
The same conditions concerning the use of milk are alleged to exist m 
Greenland (Djier), the Gold Coast (Fisch), China, the Philippines, Turkey, 
Sicily, and Sardinia, yet in all these countries tuberculosis is prevalent m 
all forms and to the same extent as m Europe and America 

On the other hand, it is thought to be of great moment in the British Isles 
and European countries by Raw, Woodhead, v Behring, and others ^ Tuber- 
culosis in swine, sheep, goats, and the smaller domestic animals is a piactically 
negligible danger, owing to the comparatively slight use of uncooked flesh 
and infrequency of the disease among them, as well as m the paits of the 
animal used for food 

Hereditary Transmission — The ancient belief m the diiect inheritance 
of the disease dies hard in spite of the weight of evidence against it as a 
frequent source The direct transmission of tuberculosis involves the 
transfei of the bacillus in one of several ways (1) Fiomthe father through 
the seminal fluid or by means of the spermatozoa, (2) from the mother through 
the ovum or placental blood 

Evidence for the pateinal transmission rests on the positive findings of 
tubercle bacilli in the human semen and on certain experiments m which 
the testes of animals were inoculated (Gaertner, Cornet), or where bacilli 
vere injected into the vagina before copulation (Friedmann) Sinee genito- 
urinary and miliary tuberculoses are infrequent and bacilli have not been 
found m the semen of ordinary pulmonary tuberculous patients the chance 
for paternal transmission is very small Moreover, the experiments by 
Gaertner, Cornet, and others were unsuccessful on guinea-pigs and labbits, 

V hile the successful results of Friedmann, who found bacilli m the young 
(eight-day) rabbit embryos, were obtained under entirely abnoimal conditions, 
noi IS there much doubt but that these embryos would have failed to mature 
In fact, the experiments of Seige controvert those of Friedmann, as under 
similar conditions he obtained healthy progeny The conception of an 
actual infection of the spermatozoa with the bacillus is quite out of the 
question from any facts m our possession If baeilli succeed in penetrating 
the ovum from the semen it is altogether probable that they must first infec't 
the mother In Gaertner’s and Cornet’s experiments genital infection of 

‘ Yet Speck, after a collectne ln^ cstigation, states that only 27 per cent of 8010 
adult consumptnes in Europe Mere fed on com s’ milk during the first three months 
of infancj 



TUBERCULOSIS HISTORY AND ETIOLOGY 


189 


the females occurred without producing disease in the offspring All in 
all, there is no evidence, clinical or experimental, of a paternal transmission 
m the sense of inheiitance The infection of the ovum is equally doubtful 
before impregnation, although Baumgarten claims success in one rabbit’s 
ovum artificially fecundated The well-known experiments of Maffucci, 
Avho inoculated 19 hens’ eggs and hatched 9 delicate chicks Avhich died soon, 
some having evidence of tuberculosis, are not exactly applicable to mammals 
It IS more than likely that human ova in which tubercle bacilli might lodge 
AA ould be unfruitful Clmicall}', ovarian and tubal tuberculosis is uncommon 
and a complication AA'hich usually interferes Avith impiegnation 

Placenial ti ansimssion is practically the only foim of inheritance Avhich 
merits attention, and this is, strictly stated, congenital infection from the 
mother Exhaustive search has been made for cases of tuberculosis to 
support the inheritance theory and a list of tAventy has been collected by 
Schluetei Avhich aie considered to haA'e been undoubtedly derived fiom 
intia-uterme infection Schmorl and Kockel reported the first cases of 
placental tuberculosis associated Avitb disease in the child m 1894, and many 
pathologists haA'e added cases aa'IiicIi aie moie or less doubtful Confusion 
Avith congenital syphilis Avas fiequent and easy, so that the only definite 
proof has been by inoculation of portions of placental or foetal tissues or 
the demonstration of the tubercle bacillus by staining, thus the actual 
number of observed cases is really very small m man, although it has been 
found more frequently in late years It is also comparatively moie frequent 
in cattle (Schlueter collected 70 cases) Waithm and CoAvie have made a 
special study of placental tuberculosis Not mfiequently the bacilli have 
been demonstrated by inoculation with the fcetal tissues Avhen no signs of 
tuberculosis Avere evident m them, this has been used by Baumgarten as an 
argument in favor of his Avell-knoAvn theory of latency and insusceptibility 
of the infant tissues to the formation of the tubercle, oaa mg to their great 
activity of growth Experimentally, the question of inheritance from the 
mother has been studied extensively Gaertner’s positive results are fre- 
quently quoted m support of the inheiitance theory, but he inoculated 
female white mice Avith large amounts of tubercle bacilli Avhich they aie now 
knoAvn to harbor in the blood more than other animals (Roemer) On the 
other hand, Sanchez-Toledo, Cornet, and Hauser obtained only negative 
results m numerous inoculated guinea-pigs and rabbits aa'Iiosc young Avere 
m turn used to inoculate other animals Even intravenously inoculated 
rabbits raiely transmitted the bacilli 
The methods by Avhich mtra-uterine infection can occur are by the direct 
passage of bacilli from the blood of the mother to the child through a lupture 
m the vessel Avails of the vilh or by means of an actual placental focus from 
aaIucIi bacilli may escape into the foetal circulation Cornet discusses this 
mechanism Avith especial fulness, but considers the transfer of bacilli only 
exceptional, being possible solely m cases of far-advanced or miliary tuber- 
culosis m the mother, AA'hich lesults in abortion or a short-liA'ed infant, should 
it reach full term He argues very propel ly that if bacilli can traA'erse 
Ae placental wall, the toxins must also pass through and injure the foetus 
The claim of Baumgarten for inheritance of the parasite and a dormant 
stage in its hfe-history is well combated by the relatively feAv cases where 
the conditions are piesent for tiansmission of the bacilli and the acute course 
of infantile tuberculosis in general Among 1005 surgical tuberculous 



190 


INFECTIOUS DISEASES 


patients between the ages of ten and fifteen, Lannelongue found only 3 
whom he could denominate congenital Sinee the opportunity for external 
infection begins at birth m ]ust these supposedly heieditary cases, we are 
not justified in regarding them as such, nor can we consider the inheritance 
of the bacilli an important factor in the conveyance of tubeiculosis from 
parent to child Atavistic inheritance of the bacilli from the grandparents 
IS v holly inconceivable 

External Modes of Transmission — The opportunity for receiving tubercle 
bacilli into the body from outside begins with birth and the means of trans- 
mission are numerous in infected surroundings Cases aie on record where 
consumptive midwives are supposed to have infected infants by blowing 
into the mouth to start respiration at birth (Cornet) Inoculation experi- 
ments with the milk of consumptive mothers have been generally negative, 
as would be expected, since actual disease of the mammary gland is rare 
Yet breast-fed infants can readily get the bacillus from sputum-soiled fingers 
of the mother which are frequently in contact with the nipples or put into 
the infant’s mouth The same is true of the bottle-fed nursling apart from 
the danger of bovine sources of infection Perhaps next in importance are 
the fingers and toys of the creeping infant, frequently soiled, as they certainly 
must be in the dwellings of the consumptive poor, from infected dirt of the 
floor as well as from the clothing, and especially the handkerchiefs of the 
consumptive mother or nurse Bacilli have been found to be frequent on 
the hands (Dieudonn^) and under the nails (Preisich and Schutz) of children 
in consumptive families The use of handkerchiefs to receive the expecto- 
rated sputum or to wipe the mouth is quite universal among otherwise cleanly 
persons, and unquestionably constitutes a potent means of transmission, 
both m the moist condition and after drying Contamination of the pocket, 
dress, or pillow is frequent by the customary method of handling handker- 
chiefs, but particularly affects the hands of the patients (Baldwin) 

Bacilli are decidedly more virulent m the moist condition, and it is conceiv- 
able that the hands may convey them frequently from the parent to child 
indirectly by food, confectionery, drinking cups, dooiknobs, pencils, etc 
The frequent use m common of spoons, forks, glasses, towels, etc , is also to 
be recalled The contamination of food is also possible by means of the feet 
and excrement of house flies which have previously alighted on sputum 
(Spillman and Haushalter, Moeller, Lord), also by cocl^oaches (Kuster) 
and lice (Weber) 

Sputum may be brought into houses on shoes and trailing garments, 
and by pets, especially dogs, which habitually he upon the sidewalks and 
doorsteps, also, they may convey infection to children by their habits of 
indiscriminate licking It is an open question whether the inhalation of 
sputum dust from floors and clothing and the moist spray from the cough 
constitutes the most serious danger in childhood The deep inspirations of 
the crying infant give the opportunity, it is true, but the dose of infection 
in this form is likely to be less than in the other modes 

We knoM through the numerous examinations of dust that it is a means 
of transmission, but the bacilli have but limited vitality when dry, and as 
nev conceptions of infection have come to view the role of dust diminishes 
in seriousness The demonstration by Flugge that moist particles of sputum 
vere coughed out so impalpable as to float in the air some minutes and 
could be inhaled brought out a factor formerly recognized by Cornet in 



TUBERCULOSIS HISTORY AND ETIOLOGI 


191 


his experiments, but not sufficiently valued In view of the remarkably 
ingenious experiments which support each side of the contioversy between 
these experimenters we must assume that both -modes of infection are of 
some importance The danger of so-called droplet infection results chiefly 
from expulsive coughing, but may occur in hawking, loud talking, laughing, 
singing, and sneezing Ordinary breathing carries no infection, as many 
experimenters have shovn 

How little danger there is foi adults even when directly exposed to the 
cough, spiay, and dust is shou n by the investigation of Saugman Among 
174 previously healthy sanatorium physicians whose average service was 
three years and who were followed three and a half yeais further, but 2 
developed tuberculosis, also among 64 laryngologists fiom eight clinics 
none were affected during or after their service Considering the close 
contact with patients and frequent demonstration of bacilli on the head 
mirrors and even in the nasal mucus of physicians (Stiaus. Moeller), the 
record is noteworthy and evidence against the frequency of adult infection 
as well The act of kissing on the lips is not only unsanitary, but may be 
a danger to children, though for adults this is probably overestimated in the 
popular mind 

Some other means of transmission are suggestively possible, but of exag- 
gerated importance in the lay mind as far as evidence goes Such are 
the blankets of sleeping cars, telephone transmitters , money, particularly 
paper currency, and library books (Mitulescu) It may be admitted that 
m some instances young children are endangered m these ways, but it is 
altogether doubtful that adults undergo danger vTOrthy of mention 

Paths of Infection — It has been customary to consider three distinct 
modes of primary infection in tuberculosis apart from inheritance, in accord- 
ance with former theories of the reception of the bacillus into the body These 
were by (1) inoculation, (2) inhalation, and (3) ingestion Since changed 
conceptions have been introduced and the probability that combined inhala- 
tion and ingestion make the mode of infection fiom the exterioi less simple 
than the above division implies, it seems more useful to make the dis- 
tinction only between the three kinds of surfaces exposed to invasion from 
without, namely, (1) the cutaneous, (2) the mucous membranes, and (3) 
the pulmonary alveolar By this division all sources of infection are 
recognized and included without undue emphasis being placed on any one 
mode That it has not been a simple matter to establish the exact path of 
entrance of the tubercle bacillus into the human body is evidenced by the 
mass of experimental work devoted to the problem through many years, 
out of which disputes and confusion have arisen and still leign 

Cutaneous Inoculation — Infection through the external skin is of slight 
importance in the production of generalized tuberculosis The conditions 
are not favorable for an easy proliferation of tubercle bacilli in the skin itself, 
possibly because of deficient nutriment and the insusceptibility of the skin 
epithelium The mere rubbing of tubercle bacilli into the skin is insufficient 
to infect adults, but abraded surfaces, especially in children, are occasionally 
the starting points of fatal infection Inoculation tuberculosis is for the 
most part localized at the site of the wound or at most spreads only to the 
nearest lymph nodes It is seen frequently on the hands of pathologists 
and bacteriologists who have to do with tuberculous material and ex- 
perimentation, and it IS surprising that more serious results do not follow. 



192 


INFECTIOUS DISERSES 


Laennec himself, m 1799, received an moeulation on the hand and died of 
pulmonary tubereulosis twenty years later It is doubtful from the evidence 
aiailable that there was any eausal connection between the two events, 
although Villemin cited this as an illustration of the moculabihty of tuber- 
culosis, and V Behring has recently declared himself in favor of this theory 
of Laennec’s case, m conformity to his belief in the slow development of the 
disease Nevertheless, man is certainl}’’ quite resistant to cutaneous or 
subcutaneous infection, considering by contrast the ease with which suscep- 
tible laboratory animals develop piogiessive tubeiculosis from slight inocula- 
tions into the skin Many instances of cutaneous inoculation aie recorded 
in the hteiature, some of which may be enumeiated here The cuts from 
broken cuspidors and chamber vessels, from eai -lings, from splinters m an 
infected floor into bare feet, from the opeiation of tattooing, m perfoimmg 
circumcision, from scratches in seabies and eczema with infeeted finger- 
nails, also of the nose and by the use of handkerehiefs previously used by 
consumptives Bruns has colleeted five cases produced by hypodermic 
injections, three of whom were morphine habitues (Cornet) 

Infection of the nasal fosste and corners of the mouth and eyes not rarely 
leads to lupus of the face, many of these lupous subjects also have tuberculosis 
elsewhere which is the source of the infection Autocutaneous infection is 
rarely produced, considering how frequently the hands and nails are soiled 
with sputum One case seen by the writer was that of a consumptive seam- 
stress who had infected her forefinger with her needle, which she was wont 
to put into her mouth Subsequently, her wrist-joint became involved, 
presumably from the infected finger 

Vaccination was foimerly regarded as a possible source of danger from 
the inoculation of tubercle bacilli with the human lymph, but the modern use 
of calf lymph with the precautions taken m its prepaiation leaves no basis 
for fear Calves employed for pioducing vaccine are selected free from 
tuberculosis by the tuberculin test Moi cover, the experiments of Carini 
indicate the improbability of the lymph containing tubercle bacilli even when 
prepared from tuberculous animals ^ The comparatively mild effects of acci- 
dental or intentional subcutaneous inoculations (Baumgarten, Klemperer, 
Kleme) with bovine bacilli have been used as proof of the lelative harmless- 
ness of bovine bacilli for man with questionable propriety, m view of the fatal 
results of such infection through the intestinal channel, and the instances of 
even progressive disease ascribed to skin infection (Ravenel) The ultimate 
outcome of the bold self-inoculations in the arm with virulent bovine bacilli, 
in the case of both C Spengler and Klemperer, should be a source of anxiety, 
although a real contribution to science 

Mucous Membrane hifechoii —SNheJi the number of mucous surfaces 
exposed to agencies from without the body is considered, it may at once be 
suspected that the tubercle bacillus finds entrance most frequently through 
the many wounds and abrasions of the orifices of the body, or by absorption 
from the upper respiratory and gastro-intestinal tract, whether inhaled or 
ingested with food 

Primary moculaiion iubcrcuhsis is nevertheless not often recognized, if 
indeed it occurs frequently, as believed by some, from abrasions m the mouth 

' The possibilit\ of skin inoculation from the bites of insects, such as house flies and 
bed-bugs, -nhich may ha\e ingested sputum may be admitted, especially in the case 
of children V hen asleep, although actual proof is v anting of this means of infection 



TUBERCULOSIS HISTORY AND ETIOLOGY 


193 


and tongue, such as are produced by carious teeth or after then extraction, 
and following operations upon the nose, nasophaiynx, larynx, and tonsils 
Still rarer are instances of genital, rectal, and conjunctival infection from 
injuries It would be surprising how infrequently infection apparently 
results from lacerations in the mucosa, which lea\e an open door for 
tubercle bacilli with conditions favorable lor absorption, were it not evident 
that the virus is not universally present and not ah>^ays in a virulent cc > 
dition 

In youngest infancy and childhood, howevei, abiasions of the gums m 
dentition and the coincident transport of bacilli from duty fingers both of 
the child and mother into the mouth may lead to infection, as emphasized 
by Volland and Westenhoefter The same is true of the habit of picking 
the nose How often infection actually occurs m these vays has never 
been ascertained, since it is veil recognized that the portal of entrj’^ may not 
show signs ol disease, especially m infancy Fuithermore, the assumption 
formerly made as an axiom by Cornet and others, that the nearest lymph 
nodes to the pathway of infection vould alvays first become diseased is 
now seriously questioned The experiments of Weleminsky, Harbitz, 
V Behring, Bartel, and others, in which living tubercle bacilli were demon- 
otrated by inoculation ot lymph nodes into guinea-pigs when no signs of 
disease were present m the nodes, indicate the possibility of an unsuspected 
path of entrance, especially m childien in whom no trace may be seen at the 
Site of infection On the other hand the objection made that sooner or later 
the regional nodes would show the disease if infection really occurred, is 
a strong one, and on this basis statistics of lymphatic tubeiculosis about the 
face and jaw do not favor great frequency for traumatic infections m those 
regions 

When not strictly construed, inoculation tubeiculosis applies to infection 
through the mucosa whenever a deficiency'^ of epithelium is pi oduced, whether 
by injury or disease It is nevertheless quite as accurate to consider this 
as infection by absoiption The leadmess with which the glandular and 
especially the adenoid tissues of the nose and throat become the seat of 
transient infections has long furnished an argument in favor of this path- 
way also for tuberculosis (Aufrecht, Fieudenthal)' Moieover, m the situa- 
tion of the postnasal and faucial tonsils w'lth their crypts and fissured sur- 
faces, then frequent hypertrophy' and loss of epithelium, theie is abundant 
opportunity for the lodgement of inhaled or sv allowed bacilli When pul- 
monary tuberculosis is present, secondaiy disease of the faucial tonsils is 
very common, yet primary tuberculosis of these structures is comparatively 
rare 

Jonathan Wright, Broca, and many otheis have made microscopic exami- 
nations of "adenoids,” with generally negative results Cornet’s summary 
of 1745 cases gave 4 1 per cent of positive results Primary tuberculosis 
of the faucidl tonsils is less rare, but closei observation of late and inocula- 
tions of all these tissues have revealed latent bacilli present more frequently 
than hitherto suspected (Dieulafoy', Lartigau and Nicoll, Harbitz) 

^ The statistics of primaiy tuberculous cervical adenitis or pronounced 

scrofula have hitherto been taken as a fan index of the frequency of 
infection through the uppei air passages and mouth, and more particularly 
through the medium of the tonsils, but the proportion is far below that of 
supposedly primary disease of the bronchial nodes Submaxillary and 
VOL in —13 



194 


INFECTIOUS DISEASES 


ctrvical nodes are so frequently enlarged m chddren from pyogemc infections 
that the decision as to the frequency of primaiy tuberculous infection of 
tins lymph system is by no means easy ^ 

Tins fact demands more attention because of the more important studies 
m recent years (MacFadyean and McConkey, Spengler, Walsham, and 
others, but especially by Harbitz), which by more careful microscopic exam- 
ination combined with inoculation tests have disclosed the fact tjiat lymph 
nodes presenting nothing but simple hypertrophy or even noimal appear- 
ances may contain virulent tubercle bacilli without other evidence of tuber- 
culosis It IS disquieting to note that Harbitz found them most frequently 
(13 out of 18 cases) only m the cervical group of nodes and m the youngest 
infants, mostly less than a year old These aie significant facts beaiing 
upon the absorption of bacilli from the mouth and nasopharynx Whether 
lodgement or retention of tubercle bacilli m these nodes foi a time necessarily 
implies infection oi not is a question yet more difficult to decide Moreover, 
it IS unexplained as yet n by pigmentation of the cervical nodes does not occur, 
as m the bronchial system, from the absorption of dust, if bacteiia are so 
readily taken m by the emigiation of leukocytes outward and inward on the 
surface of the tonsils Nearly all the dust that is inhaled is eaught m the 
nose, or, during mouth-breathing, in the mouth or pharynx The coarser 
particles of dust are soonest deposited and normally cast off by the mucous 
flow and movement of cilia m the nose or frequently swallowed from the 
pharynx Relatively little reaches the larynx, trachea, and bronchi by 
direct inhalation or is aspiiated secondarily fiom the nasopharynx and 
mouth 

Localization of tubercle bacilli in the mucosa of the lower lespiratory 
tract IS lare as a piimary disease so far as pathological studies have revealed, 
although It is by no means certain that bacilli do not frequently pass througli 
into the ad]acent lymph nodes and produce the first recognizable changes 
m the lung hilus and bronchial nodes, leaving no trace on the mucous sur- 
face Slight eiosions of the laryngeal epithelium aie so common that the 
chances for piimary infection on such sites should be liequent, yet careful 
study has revealed only isolated cases The paucity of such observations 
both m the trachea and Ijronchi has been a favorite argument against the 
pulmonaiy inhalation theoiy of tuberculous infection, but a most valuable 
study by Abrikosoff brought to light 8 cases in 453 adults dying of other 
diseases, m which beginning tuberculosis was demonstrated m the walls 
of small bronchi and involving only the mucous membrane and excluding 
all sources of the infection except inhalation ^ 

The gastro-mtestinal tract has been brought to the front m recent 
years as the most important pathway of entrance for the tubercle bacillus 
While a few pathologists long ago held to the idea of ingestion infection 
from their successful feeding experiments, the weight of evidence seemed 

’ Volland estimated that 94 per cent of children between the ages of seven and 
twelve 5 ears had enlarged cervical nodes Neumann summarized 4883 children 
betw een one and nine j^ears, of wdiom only 6 38 per cent had presumably tuber- 
culous enlargement of the nodes, while Laser considered 32 4 to 58 9 per cent of 
cerv ical enlargements tuberculous in 1216 school-cliildren 

* The difficulties in such examinations aie well indicated by Schmorl, who found 
onlv 42 cases in 4000 where a decision could be made as to the starting point of 
infection in the lung, in only 10 of these was the disease confined to the bronchial 
vail. 



TUBERCULOSIS HISTORY AND ETIOLOGY 


195 


to be m favor of lung infection Nevertheless, v Behiing aioused the 
question anew in 1902 by announcing his conviction that food infection 
accounted for all the results of previous ev-periments, questioning the 
validity of Cornet’s and Flugge’s interpretations, and presenting his 
own observations that lung tuberculosis was primarily of intestinal origin 
and from infected milk This revolutionary idea has found slov accept- 
ance, but has led to many new experiments with partly confirmatory results 
and to a pionounced modification of the theory of primary infection by 
way of the pulmonary alveoli, since careful pathological studies have been 
made of the earliest signs of infection in the lymphatic system (Harbitz, 
Weichselbaum, Malloiy and Wiight, and others) It is only necessary to 
mention here that v Behring and Roemei have demonstrated the easy pei- 
meabihty of the stomach and intestinal mucosa of the neAvly born animal 
for bacteria and unchanged proteid This they legard as the time of great- 
est danger from tuberculous infection in the family, and the condition is 
ascribed to incomplete development of the gastro-intestinal epithelium and 
digestive ferments Later in life the passage of bacilli is favored by eiosions 
due to catarrh or other abnormal conditions and diseases The baeilh 
may pass directly into the blood thiough the thoracic duct or be arrested 
m the mesenteric nodes in primary infection without a tiace of their site of 
entrance, but they tend to localize in the mucosa and Peyer’s follicles if a 
previous infection has created a susceptibility Baumgarten maintains that 
a focus IS always produced sooner oi later at the point of entrance, although 
it may be microscopic Many recent experiments have shown tliat the bacilli 
can pass into or between the intact epithelium and can be traced step by step 
to the mesenteric nodes or thoracic duct, chiefly from the lower part of the 
ileum or ciecum , the stomach is rarely penetrated except in newly born animals 

The demonstration of primary mesenteric node infection in young infants, 
and adults as well, without othei signs of the disease (Harbitz), leaves no 
doubt of the possibility of intestinal infection under some conditions The 
only questions at present mooted aie (a) Their frequency compared to the 
respiratory route, (6) the lelative numbei of bacilli needed, i e , the dose, 
since Flugge claims to have shown that vastly moie are lequired m feeding 
experiments than by inhalation, (c) finally, the important matter of its 
relation to pulmonary tuberculosis is yet unsettled 

Infection of the genito-unnary tract and conjunctiva is, so far as known, 
01 at least proved, of traumatic origin when from the exterior and too rare to 
deserve special consideration 

Pttlmonai ?/ Ylvcolai Infection — In spite of the somewhat modified con- 
ceptions of the pathways of infection, the belief in the leception and absorp- 
tion of tubercle bacilli thiough the delicate epithelial walls of the pulmonary 
alveoli persists 

The most important fact in favoi of this theory is the piesence of pigment 
m the cells themselves or in the inteistitial spaces, especially under the pleural 
surface The convincing experiments of Arnold remain to-day the chief 
foundation foi the inhalation theory, m spite of attempts to show that pig- 
ment can be deposited m the lungs after feeding cxpeiiments (Vansteen- 
berghe and Grysez) ^ When carefully contiolkd, such ex-peiiments have 
produced quite opposite results (Bennecke, Aschoff) Hence, the deposit of 
coal-dust and stone-dust in the lungs of miners, etc , cannot be interpreted at 

* Annates de Institut Pasteur, 1905, \ol xix 



196 


INFECTIOUS DISEASES 


present in any way but by inhalation diiectly into the alveoli oi small bronchi 
It must follow logically that the bacilli in the form of fine dust must also 
lodge there and be earned into the subpleural and inteistitial spaces, as is 
true of anthracosis The problem seems simpler at fiist sight than it really 
IS, because the A'ery earliest changes in the inhalation infection experi- 
ments are not usually m the alveoli, but in the lymph nodes, probably from 
mucous membrane absoiption, since obviously less inhaled dust oi spray 
penetrates as far as tlie alveoli hloreover, the gieat frequency of bronchial 
lymph -node tuberculosis before any discoverable changes in the lungs, 
especially in children, and the greater permeability of the lymph spaces at 
that age have thrown doubt on toimer theoiies of the mechanism of primary 
infection It is especially since v Behring has called attention to the fact 
that subcutaneous inoculations anywhere into the lymphatic system, 
such, for example, as under the tongue, can lead to typical pulmonary tuber- 
culosis identical in appearance to that produced by inhalation that a new 
aspect of the problem demanded attention This mode of lung infection 
IS accomplished by way of the bronchial glands in most cases which 
receive the lymph from a large area and pass it into the blood very directly, 
thus carrying the infection to the small capillaiies in the alveoli, where 
they lodge These observations have received ample confirmation and 
indeed were not novel, but hitherto had escaped emphasis This renewal 
of attention has brought out many ingenious experiments, conspicuous 
among which are those of the United States Bureau of Animal Industry by 
Schroeder and Cotton, Calmette and Gu6iin, Weichselbaum and his pupils, 
Bartel, Newman and Spieler, while the defenders of the inhalation theory 
(Cornet and Flugge) have repeated their experiments with precautions to 
exclude paths of infection other than the lung It is impossible to give space 
to the many points in the controversy, but enough may be mentioned to show 
that primary alveolar infection is possible m various ways, including inhala- 
tion Hodenpyl, m 1899, decided that the subpleural pigmented nodules so 
frequently found were often tuberculous when no other focus was discoverable, 
and Ribbert has recently accepted the same view, but thinks the deposit of 
pigment generally precedes and aids the retention of tubercle bacilli by 
clogging the lymph spaces and minute subpleural lymph nodes The 
frequency of tuberculosis among stonecutters strongly supports this view 
In contrast to this are the observations of Wamwright and Nichols, who 
examined the lungs of coal-mmers and conclude that the connective-tissue 
grow th stimulated by coal-dust acts as a protection against implantation by 
tubercle bacilli, thus accounting for their relatne immunity 

Moreoier, Schroeder and Cotton have ingeniously produced pulmonary 
tuberculosis m cahes by inoculations into the tail as veil as by feeding 
experiments It is therefore maintained that the lung capillaries act pre- 
eminently as a filter for the blood and lymph circulation, and indirect infec- 
tion frequently occurs by way of the intestine, mesenteric nodes, or thoracic 
duct, thence to the blood stream and lungs ^ 

A modified opinion is therefore necessary at present in reference to the 
frequency of directly inhaled primary infection of the alveoli, in that it is 
less frequent than formerb supposed 

‘ It IS e\en argued bj tVeleminsky that a reverse h^ph flow from the bronchial 
nodes to the lung peripherj^ accounts for manj cases supposed to be primarj ah eolar 
inhalation tuberculosis 



TUBERCULOSIS HISTORY AND ETIOLOGY 197 

Relative Frequency of Modes of Infection —As there is a general agreement 
that infection through the external skm is not of much moment except m 
infants, the statement that it forms but a fraction of the whole number is 
justified Much disagreement exists about the othei avenues, howevei, 
more especially as to the lung and intestine The weight of opinion w as in 
the past in favor of the lung because the statistical compaiisons of cases of 
supposedly primaiy lung and bronchial node disease were far m excess of 
those in the intestine and mesenteric nodes The estimates vaiy greatly, 
however, langing m the case of primary intestinal invasion from 2 to 30 
pel cent Such differences were largely due to the failure to make a careful 
study of the veiy incipient stages or latent forms m the lymph nodes on the 
part of the older observers and the absence of microscopic and inoculation 
tests When the later work of Councilman, Mallory, and Pearce, Harbitz 
and Rosenbergei is examined it is seen that the bacilli are much more fre- 
quent in the mesenteric nodes than was supposed How often they go on to 
the production of actual disease may still be an open question At present 
the figures suggest that one-fouith of all cases of tuberculosis, m children 
at least, leceive the infection by way of the gastro-mtestmal route, either 
simultaneously wntli or independent^ of otlier ivays of entrance A consider- 
able proportion of primary infections through the upper air passages have 
also been overlooked m the past because no special attention was paid to 
the cervical nodes, and no estimate can at present be made of their frequency 
Therefore, due allowance must be made for these m reckoning the numbei 
of primary bronchial node cases, so that altogether the knowledge now 
available tends to lessen the importance of primary inhalation infection 
thiough the bronchi and alveoli, yet by no means places it second to othei 
channels There is some reason to think that below the age of fifteen years 
infection by other channels is moie fiequent and perhaps preponderant by 
W'ay of the digestive tract, and localizes m the lymph nodes at first, yet the 
possibility of simultaneous inhalation and ingestion infection prevents a 
certain conclusion In adults the first focus of disease is more often at the 
portal of entrance, wdiich supports the inhalation theory for the origin of 
pulmonary phthisis in the majority of cases, whether it be primaiy or 
so-called “supermfection ” Furthermore, the greatest proportion of latent 
or healed tubercles found in the lung apices coincides wuth the increased 
age of such individuals and is best explained by inhalation infection ^ 

Latent Infection — This expression is intended to apply only to the 
presence of the disease-producing agent in the body wnthout actual tubercle 
ioimation, a true "pretuberculous” stage of the disease 

Baumgarten has long stoutly maintained that bacilli could be inherited 
and rest for long periods m the body, restrained by the active tissue grow^th 
of the infant There is little reason to think this to be true, as already ex- 
plained Tubeicle bacilli have been found m the lymph nodes without 
apparent effect on them except to produce a slight hyperplasia, at least, 

’ Von Behring maintains tliat secondarj tuberculous infections tend to localize at 
the point of entrance because of a susceptibility acquired from the first infection, 
thus accounting foi ulceration in the lung and intestine found in adult life He 
beheres that the condition of susceptibility' corresponds to that knowm as “scrofu- 
losis when well established This theory needs extended observations to confirm 
this explanation of the phenomenon, but has an experimental basis and clinical 
support in the greater frequency' of superficial ulcerations m adults as compared 
with children, and the large number of persons who show susceptibility to tuberculin 



19S 


INFECTIOUS DISEASES 


specific clianges may be absent for some time (Loomis, Manfredi and Fusco, 
Harbitz, etc ) Bartel and Neuman, by means of feeding experiments m rab- 
bits, found that living bacilli could be present one hundred and four days in 
the nodes without specific changes, and finally disappear without leaving traces 
Cornet thinks, howerei, that no prolonged latency is possible and ascribes 
these results to mild infections with weak bacilli v Inch do not gam a hold in 
the body, while v Behring regards mild infections m childhood as predis- 
posing or immunizing to later infection according to their severity From 
what IS known of the biology of the bacillus the probabilities are that virulent 
bacilli go on to growth aird tubercle formation within a few weeks, and that 
less virulent strains may remain alive several months and eventually die 
out rvith or rvithout traces of their presence being left In the absence of 
evidence to the contrary it must be assumed that m the instances of prolonged 
latency of the disease itself, which are so frequent, the bacilli must slorvly 
multiply at times, or assume a dormant stage unknown m artificial culture 
Reinfection — Crmiulative Infection —In an individual previously infected 
with tuberculosis rve knorv that tuberculin susceptibility may exist for a 
long time after clinical healing has occurred 

It IS, therefore, of interest to know whether such persons are capable of 
further infection from a source outside the body The matter is very diffi- 
cult to investigate and the pi oof quite circumstantial wdren relapses m healed 
pulmonary tuberculoses are referred to a fresh infection Exjreiimentally 
reinfections are not easily produced nr animals, yet successive infections 
are usually assumed to have occurred m persons rvho have had a history of 
healed lymphatic tuberculosis m childhood (Cornet) 

If future experiment and observation shall demonstrate that a primary 
infection is sufficient to account for the source of all subsequent developments 
of the disease, ■which position v Behring norv Irolds, it rvould be more in 
keeping rvith the results of experimental immunity studies On the other 
hand, cumiilatne infection in tuberculous families seems impossible to 
deny in young children under repeated exposure 
Frequency of Infection m General — As to the frequency of tuberculous 
infection m general, Naegeh’s remarkable findings of 99 per cent m 500 
autopsies, and those of Burkhardt, wdio found 91 per cent in 1262 sections, 
are doubtless too high for the general population, since the material w'as 
taken from hospitals m manufacturing cities (Zurich and Dresden) Fur- 
ther objection is made that many of the cicatiices, adhesions, and challq 
foci assumed to be remains of tubercles rvere m reality not such or may have 
been caused b'^ dead and weak virulent bacilli Inoculations of calcareous 
nodules do not prove positive mfectivity as a rule (Kurlow% Weber), even 
when the microscope reveals bacilli present L Tlabinowitsch w’’as success- 
ful m 5 cases, but considered the virulence W'eaker than normal The 
percentages estimated by most pathologists, who usually regarded only 
gloss appearances m determining tuberculous foci, vary betw'een 30 aird 
60 per cent of all sections Probably the recent estimate of Harbitz from 
50 to 70 per cent for all ages represents an approximation of the truth in 
a matter the decision of which is of unusual difficulty 

An effort has been made to reach conclusions as to the frequency of tuber- 
culosis by the tuberculin and agglutination tests While the figures obtained 
br Beck (tuberculin) and Romberg (agglutination) correspond m a geneial 
waj to postmortem findings, too many disturbing factors impair their value 



TUBERCULOSIS HISTORY AND ETIOLOGY 


199 


Summary of Present Views on Infection — It is highly desirable to arrne 
if possible at some definite conclusions fiom the mass of facts now at oui 
disposal and compare them in relative impoitance In the first place 
the doctime of inheiited or acquued susceptibility still holds sway except 
that a specific susceptibility is m doubt and at most not common, next, that 
all infants are susceptible, and that susceptibility lessens with increasing 
age, lastly, that adults are comparatively insusceptible when vithout general 
or local lowered lesistance and repeated or prolonged exposure As to the 
sources of infection, the consensus of opinions and ascertained facts point 
to the sputum as of ovei whelming importance, and that in certain cases, and 
especially m restricted areas having a large percentage of tuberculous cattle, 
cows’ milk IS an important factor, the flesh of tuberculous animals being of 
minor importance, lastly, that the mother’s milk, the urine, teces, or other 
excretions of tuberculous individuals are not frequent sources of the infection 
In the means of tiansmission there is a growing belief m the greater impor- 
tance of infected food — especially milk — for infants and childen rather than 
foi adults, that the food may be infected directly by coughing oi by dirt and 
dust from the floor and hands, that fingers and many other objects that find 
their w^ay to a child’s mouth are dangers To adults both dust and moist 
droplets are the direct carrieis of infection more often than infected food 
It IS doubtful whether inhaled dust is as dangeious as formerly supposed, 
but equally doubtful that the coughed spray plays a greater part than dust 
when the menace to adults is being considered Infection is not often 
received thiough the skin, but most frequently through the mucous mem- 
brane of the mouth, air passages, and intestine Alveolar lung infection is 
doubtless primaiy in some cases, but is being relegated to second place by 
some, m comparison ivith the upper air passages and digestive tract Pul- 
monary tuberculosis is often secondary to the latent lymphatic form con- 
tracted eaily m life The infection may be dormant a few iveeks before 
exciting the formation of tubercles, may then die out and leave no trace, or 
pi ogress to the stage of actual tubercles, and finally after a prolonged incu- 
bation stage in the lymphatic apparatus become distributed to various organs 
It is uncertain that a second infection fioni outside the body is of frequent 
occurrence after clinical healing of pulmonary tuberculosis m adults, 50 per 
cent of the general population acquire an actual implantation of tubercle 
bacilli at some time during life 

Secondary Auto-mfection by Tubercle Bacilh (External) —When 
tuberculous foci ulceiate oi burst through the epithelial layers the opportu- 
nities for further spread of the disease are enormously increased m spite of the 
possible relative immunity acquired by the lymphatic system As already 
mentioned this relatne immunity may indeed favor the arrest of the bacilli in 
the skin and mucosa from the hypersusceptibihty acquired, and thus lead to 
the great frequency of secondary ulcerations on the surface Considering 
how numerous the bacilli are in the sputum it is not strange that the exten- 
sion of the disease m the lungs should be attributed largely to secondaiy 
infection both of the alveoli and small bronchi from an older focus ulcerating 
into the lumen of the air passages In the same wmy the foci in the larynx, 
tonsils, and intestine are the frequent sequelse of ulcerative phthisis, thus 
making tlie decision about the primary patlway of infection practically 
impossible in ad^ anced tuberculosis 



CHAPTEE VIII 


THE PATHOLOGY OF TUBERCULOSIS 
W G MacCALLUM, M D 

The Effects of the Tubercle Bacillus on the Tissues —The action of 
the tubercle bacillus on the tissues is in its essentials similar to that of most 
other infectious agents which give rise to inflammatory piocesses, and it 
seems that rathei too sharp a line of distinction between these anatomical 
effects and those of othei inflammatoiy irritants has usually been diawn 
Nevertheless, the changes aie sufficiently characteiistic to be lecogmzable 
with a fair degiee of ceitamty which is rendered complete by the demon- 
stration of the bacilli m the tissues The anatomical changes aie not 
uniform, but may present rather widely different appearances according to 
the mode of invasion and virulence of the bacilli All such altered tissues 
have, howevei, in common the tendency to undergo a type of neciosis with 
the formation of a caseous material 

Perhaps the most characteristic of the results of the invasion of the tubercle 
bacillus is the formation m the tissues of minute grayish and tianslucent 
nodules of film consistence, the miliary tubercles, so called from then 
resemblance m size to a millet seed So characteristic, indeed, were these 
thought to be that the disease and the bacillus naturallv leceived thiir names 
from this circumstance Such nodules vaiy a great deal in size, and it now 
appears that those which are truly miliaiy, that is, resemble a millet seed in 
size, are by no means the smallest oi ultimate tubeicles, which may be so 
small as to be just within the limit of vision of a practised eye This varia- 
tion IS in some degree dependent upon the tissue involved, the most minute 
tubercles being frequently seen m the liver, while those m the spleen and 
kidneys aie usually laiger They may occur embedded deeply m the sub- 
stance of solid organs, scattered upon the surface of such organs, m the 
lining of cavities, or m the walls of vessels, or they may form part of a sort 
of gianulation tissue iihich lesults from the activity of the bacilli The 
tendency to their formation is very strong, so that m the tuberculous lesions 
uhich are apparently not of this nodulai character, especially after they 
have leached the latei stage m their development, abortive attempts at the 
formation of such ciicumscribed nodules are always recognizable, new 
tubeicles being formed as the old ones are destroyed and merge into the 
caseous mateiial 

In their fiesh condition the tubercles are visible, or often more readily 
palpable, as rounded oi ovoid oi flattened granules firmer than the surround- 
ing tissue, and pearly giay or at times almost entirely translucent They 
may be scattered singly, but more fiequently they are grouped together or 
coalescent m such abundance as to encroach very greatly on the surrounding 
tissue The translucence of the small tubercles persists for no great length 
( 200 ) 



THE PATHOLOGY OF TUBERCULOSIS 


201 


of time, for within a short peiiod, usually two or three days only, after then 
formation a central spot of opacity, usually of grayish or yellowish-white 
color, appears which giadually increases in size, and when adjacent tubercles 
coalesce becomes confluent with that in the next nodule This opacity 
indicates the beginning of the ultimate neciosis or caseation which so gener- 
ally befalls the tubercles Fiesh miliaiy tubercles are, however, frequently 
found at autopsy, since their formation in most cases is a more or less contin- 
uous process, new crops of nodules appearing as the result of dissemination 
of the bacilli from the older foci In certain instances — and these are the 
cases of acute genet ahzed m/iliaiy tubet culosis — thousands of such tubercles 
appear simultaneously not only throughout the lungs, but thickly scattered 
throughout all the organs and tissues of the body, studding the surfaces, and 
roughening the cut surface of every organ by their prominence These 
thousands of tubercles usually result from the wholesale introduction of 
the hacilh into the blood stream from an older focus which invades a vein or 
the thoiaeic duct, and the patients die before the individual tubercles have 
had time to undergo much alteration 

Finally, such minute tubercles may under certain conditions remain more 
or less translucent, and without undergoing any caseation become converted 
into firm fibroid nodules m vliich the characteristic structure of the fresh 
tubercle is lost and only a hyaline mass of dense fibrous tissue remains 
This may be regaided as a piocess of healing 

Microscopically, the miliary tubeicle m its fully formed state is composed of 
a roughly concentric mass of cells of elongated foim, with long, oval, vesicular 
nuclei These cells, which aie quite closely arranged often in easily recogniz- 
able concentric layers, are usually designated from their form epithelioid 
cells At the margin or outer limit of the nodule they are continuous with 
the cells of the surrounding tissue, but even under the microscope the outline 
of the tubercle is fairly distinct Among these cells, especially in the outer 
portion of the nodule, numbers of smallei cells are usually seen which are 
round and have relatively large, deeply staining round nuclei, cells which 
resemble very closely the lymphoid cells of the blood and are by most recent 
writers identified with those cells These cells are supported by a netv ork 
of reticulum of resistant fibrils which can be demonstrated by suitable 
methods Similarly a netwmrk of fibrin filaments can usually be rendered 
visible throughout the nodule by the aid of the Weigert stain Many tuber- 
cles show' no further striking elements in their structures, but in the majority 
the well-knowm giant cells described by Langhans and Schuppel also occur 
These are huge masses of protoplasm similar in general appearance to the 
epithelioid cells and often drawn out into long processes wdiicli ramify among 
the surrounding cells They are provided with a large number of nuclei, 
often ten to twenty or more, which are usually arranged at the poles of the 
protoplasmic mass and often at its penpheiy in a ring so as to leave a central 
area devoid of nuclei and faintly granular 

Tuberele bacilli may usually be demonstrated by the staining method of 
Koch-Ziel-Nielsen and its modifications, lying among the epithelioid cells 
or in the protoplasm of these eells or of the giant cells No vascular supply 
whatever can be seen m such nodules Mdiatever vessels or capillaries 
existed at the point where the tubercle is formed become obliterated and 
disappear, and no new' ones are formed among the new'-formed cells A 
colored mjeetion of the vessels of an organ studded wuth tubercles, therefore. 



202 


INFECTIOUS DISEASES 


leaves the tubercles as vhite nodules ^^hlch stand out prominently on the 
deeply colored backgiound ot the rest of the tissue This circumstance 
probably aids in bringing about the subsequent neciosis of the mass, 
although by itself it Avould not suffice to cause the death of such a minute 
nodule which might absorb sufficient nutiiment fiom the sui rounding fluids 
to maintain the life of the cells Much more impoitant in this lespect is the 
action of the poison produced in the tissue by the bacilli, which first causes 
degenerative changes and finally the complete destruction of the cells The 
nuclei of the epithelioid cells shrink and become twisted and distorted, and 
often so change their position as to he with their long axis radially placed 
For a time such nuclei take a very deep stain, but later they lose all power 
of taking up the stain There appears among them, sometimes involving 
first the giant cell, but usually rather the adjacent portions of the tubercle, 
an area of complete disintegration of the tissue, the cells being converted 
into formless hyaline debris and caseous material 

Much discussion of the ultimate stiuctuie of the tubercle and of the origin 
of its elements has appeared recently in the literature Fundamental 
work on this subject came from Baumgarten, but as to the earliest stages the 
more recent paper of Wechsbeig seems ot especial interest He points out 
that in experimentally produced tubercles the initial change produced by the 
bacillus consists in an injury to the cells immediately about them as they 
lodge m the tissue Following the destruction of tissue cells comes an 
mwandering of phagocytic leukocytes, which, however, are soon masked 
by the extiaordinary prohfeiation of the fixed tissue elements of the connec- 
tive-tissue nature, a proliferation analogous, it seems, to a healing process, 
but in this instance quite disproportionately intense when compared with 
the injury done to the tissues Apparently there is a continuous injury or 
iriitation which maintains the proliferation, and Baumgarten, indeed, holds 
that the primaiy effect of the tubercle bacillus is to cause the growth of tissue 
by the formative stimulus which it exerts 

As to the exact origin of the epithelioid cells opinions differ somewhat, 
some authors holding that they are derived from the endothelial cells of 
the vessels, while others regard them as arising from the neighboimg con- 
nective-tissue cells or from epithelium, certain French authors even main- 
taining that they originate from wandering macrophages It is now quite 
generally held that the lymphoid cells are phagocytic cells which have 
wandered into that position fiom the crevices of the tissue or from the 
blood stream, but there are those who still regard them as cells newly formed 
711 iiiu The giant cells seldom if ever show evidences of mitotic division in 
their nuclei, and doubt, therefoie, still exists as to whether they are the 
product of the coalescence of sec eral cells or of the continued division of the 
nucleus of a cell without the coincident division of the protoplasm Baum- 
garten maintains that their presence is quite distinctive of tubercles as 
contrasted with miliary gummata, but the weight of evidence does not 
seem to favor this view , and it is probably impossible to distinguish betu een 
those two lesions merelj’^ upon their microscopic anatomical details 

As stated abo\ e, the tubercle nodules by no means alv ays maintain their 
isolated character, but commonly become confluent or congloTncratcd, so that 
instead of forming rounded bodies the distribution is usually such that little 
groups or miilbcrrc-hke masses of tubercles arise In these masses the 
concentric arrangement of the cells is often somewhat disturbed and irregular, 



THE PATHOLOGY OF TUBERCULOSIS 


203 


especially m the interioi Such confluent masses of tubercles may reach a 
considerable size, although usually not without undergoing the characteristic 
necrotic process, so that it is not uncommon to see in the spleen or elsewhere 
partly caseous tuberculous masses reaching a diametei of 1 cm or moie 
Indeed, the so-called sohtaiy tubercles are of a fai gi eater size, sometimes 
even i caching a diameter of 4 oi 5 cm These are circumscribed masses 
of dense caseous matter suriounded by a capsule of distorted tubercles 
and tuberculous granulation tissue, which are appaiently foimed by the 
continued production and confluence of tubercles with degeneiation and 
caseation of those more centrally placed They appear most frequently 
111 the brain, although usually associated with tuberculous lesions elsewhere 
in the body, and may constitute a tumor which by its bulk gives rise to disas- 
trous consequences 

The common fate of the tubeicle is caseation or necrosis of the more 
eentral portion If sufficient time has elapsed perhaps the only exception 
to this IS the conversion of certain small tubercles into a hyaline fibroid tissue, 
the fibroid tubercles mentioned above The fact that a thin layer of living 
tuberculous tissue always lemains about such caseous masses is probably 
due to the continuous extension and new foimation of that tissue, nevertheless, 
it, too, IS constantly encroached upon, leaving only lagged, distorted remnants 
of confluent tubercles 

The consistence of the caseous material varies m different cases, being 
sometimes very soft or semifluid, at other times firmer or of the consistence 
of cream cheese, while as time advanees it may become dry and friable, or, 
when there is a deposit of lime salts, mortar-like Fin ther inspissation and 
the continued deposit of calcium leads with great frequency to the complete 
conveision of the caseous material into a stone-hke substance, which is then 
practically an innocuous foreign body as far as the host is concerned These 
changes, which tend toward the solidification of the caseous substance, 
indicate a diminution m the activity of the tubercle bacilli , the destructive 
process ceases to advance and the mass gradually becomes encapsulated 
by a growth of granulation tissue, just as in the case of any other foreign body 
This encloses it completely and walls it off from the surrounding tissue, 
so that any remaining tubercle bacilli are imprisoned Such encapsulated 
easeous nodules, sometimes as large as a cherry, are not uncommonly found m 
the lungs The capsule is film, hard, and deeply pigmented with coal and 
blood pigment, and the whole stiucture contracts until the nodule, even if 
it be not calcified, acquires a great degree of firmness Anatomical evidence 
that a reinfection of the surrounding tissue may arise from such a nodule 
after it has become firmly encapsulated is very unsatisfactory, and m the cases 
of a renewed flaring up m an apparently healed focus, the new infection is 
probably not from any such healed lesion as just described, but rathei from 
a still active though latent focus oi from a new infection from outside 

The lodgement of tubercle bacilli in the tissues is not, however, alvays 
folloived by the formation of definite tubercles alone Frequently, espe- 
cially on free surfaces, the formation of an abundant granulation tissue is 
associated with such tubercles This tissue is highly vascular, and may be 
distinguished from oidinary granulation tissue not only by the presence 
of tubercles recognizable by their form and structure, but also bj the abun- 
dance of epithelioid cells, identical with those which compose the tubercles, 
and which aie scattered irregularly thioughout Giant cells quite similar 



204 


INFECTIOUS DISEASES 


to those seen in the tubercles may also be found In such tissue there are 
even more definite evidences of the exudation of phagocytic cells from the 
bloodvessels than m the miliary tubercles themselves Not only are there 
great numbers of lymphoid cells, but all those varieties of phagocytic cells 
which Maximow derl^es from the outwandered lymphoid cells are to be 
found in abundance Particularly striking are the large iriegular or rounded 
cells vith laige nucleus and very abundant piotoplasm which are often 
most actnely phagocytic, being found laden Avith fragments of cells and 
nuclear debris of all sorts Tj^pical plasma cells occur also in great profu- 
sion, and indeed it was m such tissue that Unna fiist lecognized and des- 
ciibed these cells Polymorphonuclear leukocytes are not lacking and 
appear often m the most bizarre and distorted forms The more superficial 
parts of the granulation tissue are usually somewhat oedematous and fibiin 
filaments can be demonstrated throughout Such tissue, despite its rathei 
rich vascular supplv, contains tubercle bacilli and consequently undergoes 
the same necrotizing process as described for the miliary tubercle Areas 
or foci of yellowish opacity appear beloAV the surface of the pale grayish- 
pink, translucent granulations, and soon become confluent In the same 
way the more superficial parts become opaque and yellow, and soon the whole 
becomes covered with a ragged grayish-yellow, pasty material, which is 
readily dislodged from the surface, and when the granulations form the 
lining of a sinus, constitutes, in pait at least, the discharge When formed 
upon a surface such as that of the pericardium and pleuia the gianulation 
tissue IS usually covered with a thick, shaggy, yellow layer of fibrin, and is 
associated with an abundant exudate of fluid, which may be quite clear or 
turbid, with floating shreds of fibrin, or at times deeply blood-stained 

While the fresh granulation tissue in an active piocess shows the char- 
acters just described, there are tuberculous processes so slow in their develop- 
ment that there is time for the contraction and induration of the new tissue, 
and much of it escapes neciosis The result is a scar-hke tissue which 
may become extremely haid and firm and which may finally reach a consider- 
able bulk When this appears over the surface of the lungs or heart in the 
form of adhesions, binding the opposing surfaces together, it may by its 
rigidity and continued contraction cause great disturbances m the function 
of those organs In the substance of organs such as the lung it may produce 
the densest and most widespread induration The presence of such tissue 
in quantity is of course an indication of the very slov' progression of the dis- 
ease Microscopically it is found to consist of an extremely compact fibrous 
tissue, in which no indication of its tuberculous nature may be found over 
large areas Foci of plasma cells and lymphoid cells v ith scattered granules 
of blood pigment may occur In other places, however, patches of caseation 
and groups of epithelioid cells oi occasional giant cells may give indication 
as to its nature 

Other t^qies of tuberculosis occur m which the lesion is for a time at least 
exclusively exudative in nature, i e , an acute inflammation These are the 
instances m v Inch the introduction of quantities of virulent bacilli into the 
tissues of a person of feeble resistance results in a destructive lesion which 
ad\ances vith extraoidinaiy rapidity Acute tuberculous inflammations 
are seen m their purest form m the lungs, but occur also m other places, 
such as the serous caMties and the meninges The invasion of the bacilli, 
for example, into the lungs seems to produce an injury so intense that it is 



THE PATHOLOGY OF TUBERCULOSIS 


205 


responded to by a sudden pouring out of the elements of the blood almost 
e\actly as in the case of the ordinary lobar oi lobular pneumonia The 
alveolar epithelial cells are desquamated and fall into the air cells, together 
with the abundant leukocytes and red corpuscles, which with the fibrin 
network and exuded fluid soon form a solid exudate very much like that m 
the simpler types of pneumonia Characteristic of this sort of acute inflam- 
mation IS its inevitable fate, which is necrosis oi caseation involving not 
only the exudate but the included tissue If the patient lives even a short 
tune after the completion of this process, fuither proof of its tuberculous 
nature is given by the development of oidmary tubercles and tuberculous 
granulation tissue about the caseous area, and if life be further continued the 
picture may come to resemble closely or precisely that produced m the other 
ways described 

The intimate relation which exists between these forms of tuberculous 
lesion may be readily seen Since the demonstration of the tubercle bacillus 
by Koch there can be no further question as to the unity of the process, 
although Orth still seeks to maintain a duality on anatomical grounds It is 
plain that although bacteria which are secondary invaders may occasionally 
appear, the tubercle bacillus is the essential cause of all the changes Fur- 
ther, even on anatomical grounds there is no very sharp line which we can 
draw between them The acute inflammatory form involves the most 
rapid reaction on the part of the vessels and v andering cells and it is only 
in the later stages that proliferative processes occur, although finally they 
also occui In the miliary tubercles, as Wechsberg has shown, we have 
also a primary injuiy, a response on the part of the leukocytes, which, how- 
ever, IS soon masked by the excessive reaction among the fixed cells The 
fact, however, that if sufficient time elapses there are almost invariably 
traces of the formation of tubercles and the analogous tuberculous granula- 
tion tissue m the margins of the areas of acute mflammation shows clearly 
enough that these are varieties of the same process The differences m the 
anatomical result seem to be due to a number of circumstances, among which 
perhaps the specific power of resistance of the individual is most important 
In certain persons the bacilli meet with unfavorable conditions for growth, 
so that probably m the majority of those into whose tissues they pass they 
are almost at once destroyed by the phagocytic cells or at most produce only 
a small local lesion which is soon completely encapsulated and healed 
In others, however, they spread like fire m flax, destroying the tissues with 
frightful rapidity Further, the virulence of the particular organisms 
introduced and their number are of great importance m determining the type 
of lesion, for while small numbers of bacilli inhaled into the respiratory 
tract may be fairly well restrained m their grov th for a time, they may multiply 
slowlj'^ m the tissue, gradually gaming power to overcome the destructive 
influence of the protective agents of the body Such a focus of “acclimated” 
tubercle bacilli may appear, for example, as a caseous area in a bronchial 
IjTiiph gland then if the adjacent bronchial vail be eroded through by the 
advancing necrosis, great quantities of highly virulent bacilli are suddenly 
discharged into the bronchus and further into the lung, usually causing the 
so-called phtlmis florida or galloping consuvipUon In this case, although 
the changes m the bronchial lymph gland are found to consist of conglom- 
erated and caseous tubercles, those in the lung have the type of an acute 
exudative inflammation 



206 


INFECTIOUS DISEASES 


Again, the exact mode of the introduction of the bacilli and the anatomical 
character of the tissue m n hich they find lodgement are important Thus, 
if such a caseous gland erodes the wall of a vein and discharges its infected 
contents into the blood stream, the common result is the simultaneous 
appearance of miliary tubercles thickly sown throughout all the organs of 
the body, and while these are perfectly typical in such organs as the liver 
and spleen they often partake more largely of the nature of minute broncho- 
pneumonic patches in the lungs 

There is in common among these varieties of anatomical lesions the ten- 
dency to coagulative necrosis or caseation, with the consequent destruction 
not only of the exudate or newly formed tissue cells, but also of the tissue 
within which this process takes place The injury pioduced by the tubercle 
bacillus to the tissues, while so slight at fiist as to have been long overlooked 
m the general inteiest aroused by the proliferative reaction, is continuous and 
finally leads to the destruction of all of the new-formed tissue as well as the 
included structures The spread of the tubeiculous process and the con- 
sequent destruction of tissue are limited in greater or less degree by the 
erection of a resistant barrier of scar tissue by the surrounding structures, 
which may in time accomplish the complete healing or cicatrization of the 
lesion In fact, one may discover, m nearly ever> autopsy upon the body 
of persons m advanced life, the pigmented scars of such healed tuberculous 
lesions These are, it is ti ue, usually quite small, and show that the lesion 
was never an advanced one, but m some instances quite extensive tuber- 
culous infections are found to have been overcome, and even a relatively 
large cavern in the lung may be cleaned out and be conveited into a smooth- 
walled cavity nhich is finally relined by epithelium Indeed, the frequency 
of such healed lesions in the bodies of those v ho have reached adult life is 
astounding, as may be gathered from Naegeh’s statistics, in which, m the 
examination of 500 cases at autopsy, recognizable tuberculous lesions -were 
found in 98 per cent The significance of this m showing the ability of the 
human body to resist the inroads of the bacilli is very important 

In addition to the actual destruction of tissue, ceitain general results of 
the existence of tuberculosis in the body become apparent Great emacia- 
tion of the whole body usually accompanies the disease, although in excep- 
tional cases extreme obesity persists In the later stages the emaciation 
IS associated wnth a pecuhai cachexia -which is very characteristic With 
this, amemia of a secondary t-^qie may become extreme In the inteinal 
organs the effect of the toxins is often to cause epithelial degenerations, so 
that It IS not uncommon to find profound fatty metamorphosis of the liver 
and kidneys, doubtless partly due also to the amemia Indeed, one some- 
times finds in a tuberculous case m wdiich the emaciation has proceeded to 
the greatest extreme, the liver weighing far moie than normal and loaded 
with fat 

Modes of Entry and Distribution of the Bacilli —The conditions of 
existence of the tubercle bacilli outside the body are sufficiently w ell know n 
to explain fairly well the mode of its entrance into the bodj^, although of 
late much spiiited discussion has arisen as to the relative fiequency of these 
difleient modes of entry 

Of these the inhalation of the bacilli into the lungs oi at least into then 
laige an passages has long been regarded as the most important Until 
recent b , too, it w as generally thought that the most fa-\ orable conditions 



THE PATHOLOGY OF TUBERCULOSIS 


207 


for this are those in which the bacillus is perfectly dry, and mingled ith 
the dust of dried sputum, etc , is blown about in the air and thus directly 
breathed m The work of Flugge and Ins pupils, how ever, seems to shoiv 
that an equal if not greater danger exists in the lespiration of air immediately 
about consumptives, ivho have been shmvn to send off m breathing and talk- 
ing, but especially m coughing, sneezing, laughing, etc , a fine spray of 
minute droplets, many of which are laden wnth tubercle bacilli Such a 
cloud of spray may extend for a distance of at least four feet from the patient’s 
face and be breathed m by anyone within that radius This idea has been 
repeatedly confirmed by the microscopic study of slides exposed before the 
face of such a patient and by experiments with susceptible animals similarly 
exposed 

The bacilli may enter the nose and mouth, and aie in large part like other 
dust received by the cilia of the upper respiiatoiy tract and wafted back 
harmless Others, hoivever, gam lodgement, and it is as to the point of then 
primary lodgement that so much dispute has arisen 

Two probabilities aie prominent either the bacilli wdiich escape the 
action of the cilia may reach the smaller bronchi or the tissues of the lung, 
01 they may pass into the walls of the air passages In the latter case they 
aie usually transported to the neighboring mass of lymphoid tissue In 
both instances they may immediately produce a local lesion or pass into the 
tissues precisely as coal-dust oi any other fine, innocuous particles, and be 
carried by the lymphatic channels to the Ijunpli glands ivhich dram that 
area, ivlieie they then lodge and produce the characteristic lesion These 
initial lesions will be described in dealing with tuberculosis of the respiratory 
tract, and it may merely be said here that in the invasion of the upper air 
passages it is chiefly the superficial lymphoid tissue which is so abundant 
in the pharynx (tonsils, Luschka’s tonsil, numerous scattered lymphoid 
nodules, etc ) ■which is thought to become the channel of entry of the bacilli 
or in other more fortunate cases the means of their destruction 

Great differences of opinion have pievailed as to the importance of those 
ljunphoid structures of the pharynx and the cervical lymph glands in the 
production of tubeiculosis of the lungs While Giober claims that infection 
of tlie cervical chain may conduct the bacilli directly to the dome of the 
pleura and thence to the lungs, and others state that infection of the bronchial 
glands may be brought about in a similiar w'aj , Beitzke m a recent paper 
shows by careful injection that particles can be transferred from the cervical 
glands to the lungs only by way of the mam Ijmphatic trunk, the right 
heait, and the pulmonary artery 

Renewed attention has recently been directed to infection by ingestion 
of food containing tubercle bacilli, by the writings of v Behring, who 
holds that perhaps a majority of the cases of tuberculosis m young people 
aie the result of the introduction of tubercle bacilli through the intestinal 
i^all from infected milk This infection takes place at a very early age, 
the bacilli remaining latent or dormant until much later, wdien, on the 
advent of a condition of low^ered lesistance, they begin to grow and destroy 
the tissues Klebs had pieviously enunciated the possibility that pulmonary 
tubereulosis might result from an intestinal infection wnthout necessarily 
being associated wnth any extensive tuberculosis of the intestine, and the 
requent occurrence of widespread tubeiculosis of the mesenteric glands in 
children seems to add w eight to the theory It is difficult, how ever, to con- 



208 


INFECTIOUS DISEASES 


vmce one’s self that this plays a prominent part in the inception of tuberculosis 
in more advanced life, and it seems more plausible to regard the intestinal 
ulcers so frequently found in those cases as entirely secondary and due to 
the swallowing of tubercle bacilli in the sputum fiom the diseased lungs 
Nevertheless, the enormous danger to childien in the ingestion of milk 
containing the bacilli must not be underestimated The recent work of 
Ravenel and others m feeding tubercle bacilli in butter to animals, with the 
demonstration of bacilli in the mesenterj', although no actual lesions of the 
intestinal mucosa are produced, is important 

We are less well informed as to infections through the skin or by way of 
wounds There are various tuberculous affections of the skin, such as 
lupus, which are probably due to direct infection Actual tubeiculous 
ulcers may also occur The infection of m ounds with the tubercle bacilli 
IS not a very common cause of generalized tuberculosis The so-called 
necrogemc tubercles are not usually productive of geneial tuberculosis, 
although in certain instances the}' have been followed by the disease Nor 
IS it usual to find any extensive distribution of tubercles from infected 
wounds, although in at least one instance recentl}' seen a definite tuberculosis 
of the epitrochlear gland occurred consequent upon a tuberculous infection 
of the finger of a student who had performed an autopsy on a tuberculous 
patient 

Tuberculous infection of the genital tract by means of coitus with a peison 
suffering in a similar way may occur, but cannot be regarded as common, 
and most of the cases of genital tuberculosis, both in males and females, 
are with more justice consideied to be due to a spread of the process 
from other and perhaps concealed foci Baumgarten, howevei, described 
the infection of the epididymis along the vas deferens and, further, the experi- 
mental production of tuberculosis ot the lungs by the introduction of tubercle 
bacilli into the urinary bladder 

After the admission of the active bacilli into the body there aie certain 
conditions which govern their localization and growth Of these the mechan- 
ical means of distribution are very important, but certain tissues offer 
more favorable soil for the growth of the organisms than others Thus, 
for reasons with which we are not acquainted, the apical poitions of the 
lungs are particularly prone to such lesions So also are the adrenal glands 
and the epididymis, while tuberculosis of the lower pait of the lungs ordi- 
narily appears only later and secondarily, and tuberculosis of the testicle 
almost regularly only as a result of tuberculosis of the epididymis Even 
more important and interesting are the points of least resistance which may 
be constituted temporarily by some injury of the tissue or disturbance of 
its nutrition Good examples of this are described by surgeons in the 
de\elopment of tuberculosis of bones or joints after their injury by fall or 
strain 

The mechanical distribution of the bacilli is effected in several ways, 
depending largely upon their mode of entry Of these one of the most 
common is that m which the bacilli are carried along the lymphatic channel 
un^il they lodge in the a essels of the sinuses of the lymph glands which form 
stations m those channels In their course along these channels many of 
them adhere to the endothelial ^lalls and there produce tuberculous lesions 
M Inch may be readily visible as grayish or yelloi\ ish nodules, and where, as 
in the case of the mesenteric Ijmphatics, an opaque lymph is oidmarily 



THE PATHOLOGY OF 7UBEECUL0SIS 209 

carried, these become veiy conspicuous by then distention with chjious 
fluid which can only with difficulty pass the obstiuctmg tubeicles 

Thus we find the penbionchial lymph glands regularly involved in a 
tuberculous, caseating process when there is tuberculosis of the lung, the 
mediastinal and retroperitoneal glands in cases of tuberculous peritonitis, 
mesenteric glands in intestinal tuberculosis, and so on Nor is it always 
easy to explain the distribution on the supposed direction of the lymph 
stream, for there are sometimes found to be glands diseased winch do not 
seem to be in the line of flow toward the centre, and this has given use to 
the idea of a retrograde transport, i e , the passage, wlietliei by obstiuction 
or reversal of the stream or by growth and extension of the bacilli, tovard 
glands which are situated in a position xvhicli ordinarily drams vnio the 
affected area and not out of it The distribution in the lymphatic system 
IS thus seen to correspond closely with that of any foreign particles which 
get into the tissues or with the cells of an invading carcinoma In certain 
cases even the thoracic duct becomes the seat of mural tuberculous lesions 
which may cause partial obstruction, but which allow of so extensive sifting 
of tubercle bacilli into the blood stream as to give rise to a generalized acute 
miliary tuberculosis 

This IS one common mode of wholesale introduction of bacilli into the 
blood stream, but another method exists, namely, the rupture of a caseous 
gland directly into a vein The wall of the vein becomes iniolved in the 
tuberculous process from without, and as caseation advances it slowly eats 
through the wall until finally a friable plug of yellow material loaded ivitli 
bacilli projects into the blood stream, or the semifluid caseous material 
is actually washed out of the gland into the vein This, again, is almost 
always followed by a widespread miliaiy tuberculosis 

Similarly, the gieat serous cavities may become infected by the rupture 
into them of adjacent caseous lymph glands or by direct extension from a 
tuberculous lesion immediately underlying the wall of such a cavity, as, for 
example, a tuberculous ulcer of the intestine Direct extension of the lesion is 
perhaps better exemplified in the so-called ascending gemto-uiinary tubercu- 
losis m which, one after another, epididymis, vas deferens, seminal vesicles, 
prostate, bladder, ureters, and pelvis of the ludney are affected, although 
whether the extension occurs m this order or not has been the subject of 
recent discussion 

In a very similar way tubercle bacilli may be transported from one part of 
the intestinal tract to another, giving rise to ulcerative lesions as they go, 
and from one part of the lung to anothei along the bronchi by the aid of the 
resniratoiy currents of air and giaxuty 

Acute Miliary Tuberculosis — It is not easy to drav a shaip line betv een 
generalized and acute imliaiy tuberculosis and the occurrence of scattered 
tubercles of larious ages in the oigans in association vitli tuberculous disease 
of longer standing The tjqie, howeier, of acute miliaiy tuberculosis as 
generally recogni/ed is that condition m which with high fever and a stupor- 
ous intoxication lesembhng that of t^^phoid fever theie is found at autopsy 
a general distribution of minute tubeicles, all of piactically the same age and 
size throughout almost all of the tissues In such a case i\e may presume 
that the bacilli i cached the tissues at about the same time and therefore 
tint the> must haie been com eyed by the blood stream The same is 
true of those tubercles v Inch arc scattered m numbers in the organ, but 
lOL HI — 14 



210 


INFECTIOUS DISEASES 


which vary greatly in age and size, except that in that case the bacilli appar- 
ently gam access to the blood stream a few at a time, and possibly not at 
all m the sudden wholesale v ay which may be demonstrated m the tj^pical 
generalized mihary tuberculosis In those typical cases it has become 
more and moie evident since AVeigeit’s publications on the subject, that if 
sufficient search be made an intravascular tubeicle directly distributing 
bacilli into the blood stream or an ulcerative tuberculous lesion of the thoracic 
duct may be found The percentage of positive lesults m the search for 
vascular tubercles m cases of mihary tuberculosis is very high (70 8 per cent 
m Weigert’s cases, 82 8 per cent m Sigg’s, and over 90 per cent m Schmorl’s 
cases) 

The tissues eontam a verj'’ great number of nodules, not billions, however, 
but thousands, as Cornet points out, and still if one lemembei the small 
size of the bacilli, it will be seen that enough baeilh to produce so many 
nodules may be easily furnished by a small quantity of caseous material 
rich m organisms Thiberculous lesions of the vessels which involve the 
direct exposure of caseous bacillus-holdmg material to the blood stieam 
are found most commonly m the pulmonary veins, although they also have 
been found repeatedly m the vena cava superior and less often m the azygos, 
adrenal, jugular, and cerebral veins Careful examination of these lesions 
shows that they fall into two groups which, as pointed out by Benda m 
his recent admirable review (Lubarsch and Ostertag’s Eigehmsse), are the 
result of different processes In the one instance a tuberculous process 
approaehmg the vessel from without eiodes its outer wall, and may m time per- 
forate it, either eausmg thrombosis or by its more sudden advance entering the 
vessel before it has time to be obliterated and dischaigmg the easeous material 
with bacilli into the passing blood stream This is the so-called periangeitis 
caseosa 

On the other hand, the tubereulous lesion may be limited to the intima 
of the vessel and evidently produced by the deposition of floating tubeicle 
bacilli from the blood stream upon it Such lesions may occur m the endo- 
cardium or in the intima of the aorta or even of the smaller aiteiies, but are 
more eommon in the veins In a recent case in which such a caseous mass 
was found in a pulmonary venule, the lumen of the \enule was completely 
filled so that no blood passed, and it would have had no significance in the 
further distribution of bacilli had it not grown to project free into the larger 
vein into w Inch the bianch emptied From this fiee end there was sufficient 
distribution of bacteria to produce tubercles m all the organs The fiee 
surfaces of this projection were perfectly smooth and rounded, but, as Benda 
points out, it IS quite possible that enough material had been broken off from 
this projection to produce tubercles everj'where, and that then the deposit 
of fibrin and the constant passage of the blood stream smoothed over the 
end of the caseous mass In a study of these cases Whipple has been 
able to ascertain the existence of tubercles formed in the walls of large 
bloodvessels evidently by the entranee of the bacdli into the vasa vasorum 
He has further observed that m the ease of intimal tubercles the caseous 
material is rarely found to be directly exposed to the eirculating blood, but 
is rapidly eovered with a thrombus over wdueh the endothelium may 
grow wnth great rapidity, thus temporarily prev'enting the further dis- 
charge of bacilli This lenders it probable that these vascular tubercles 
ma'^ after all deliver their tubercle bacilli to the blood, in instalments, as it 



THE PATHOLOGY OF TUBERCULOSIS 


211 


were, and thus produce se\eral crops of tubercles often differing but little 

Fmally, tuberculosis of the thoracic cUict may be the result of the invasion 
from neighboring tissues, but apparently more often follows the distribu- 
tion of bacilli upon its mtima or the extension of caseous thrombi of its 
branches into it It may affect only one area, or almost the whole length 
of the duct may be involved with occlusion here and there and ulceration 
of the masses which line it Stasis of lymph and the development of col- 
lateral circulation are generally evident Such a duct v ill of course pour 
quantities of bacilli into the subclavian veins and thus into the light heart 
and pulmonary circulation It seems important also that cases occur in 
which no lesion of the thoracie duct is to be made out, but in which, 
nevertheless, abundant tubercle bacilli are demonstrable in the contents 
of the duct, probably swept into it from caseous abdominal lymph 
glands Several such cases have recently come to the writer’s notice, and it 
seems quite possible that m this way alone theie might arise a wide distribu- 
tion of tubercles 

It IS important to remember that tubercle bacilli are extremely small, 
and can readily pass where a red corpuscle can pass There is, therefore, 
no reason why they should not pass through the lungs from a systemic vein 
and be deposited in some other organ Still, it has been shown that they 
are very quickly removed fiom the blood and do not circulate long nor 
increase in number in the moving blood Thus it is that the lungs, forming 
as they do the first sieve for the blood, usually show the tubercles m a more 
advanced stage than elsewherei vhile in the case of invasion of the portal 
vein the liver may be the first organ to develop tubercles 

In reaching the tissues the bacilli may immediately produce lesions at the 
point of deposition or be transported as innocuous foieign particles for a 
small distance into the tissues and there set up destiuctive changes Thus 
m the acute miliary tuberculosis of the lungs it is not uncommon to find, on 
closer examination of the nodules, that instead of centring as nodules about 
the capillary vessels they are really minute areas of tuberculous pneumonia 

But little need be said furthei in regard to the pathological anatomy 
of the condition Usually, there are older caseous foci of tuberculosis to 
vliicli the development of the vascular lesion may be tiaced and the acute 
miliary tuberculosis is then in a way the terminal event of a chronic tuber- 
culosis Why symptoms of such profound intoxication should arise in these 
cases IS not quite clear, for there are many other conditions which do not 
show any such intense symptoms, in which theie is quite as much or far 
more tuberculous tissue and as many or more tubercle bacilli growing in 
the tissue 

According to the duration of life of the host after the distiibution of the 
bacilli the tubercles, wdiich are scattered ever^'where, may %aryfiom minute 
translucent grains to larger nodules with a central point of beginning 
caseation There may be a difference in the size of the nodules in the lungs 
and m the other organs, but lery often this does not appear No oigan 
seems exempt Serous surfaces, bone-niairow , retina, myocardium, thjroid, 
etc , may show' miliary tubercles Little mention is made of them, how'e\ er, 
m the muscle and skin 

Tuberculosis of the Respiratory System —Nose —The mucosa of the 
nose IS probably more often the seat of tuberculous lesions than is generalb 



212 


INFECTIOUS DISEASES 


supposed It may be infected fiom soiled handkerchiefs oi fingers, from the 
passage of tuberculous sputum ivhen the lungs aie affected, or pel haps by the 
direct inhalation of tubercle bacilli Experimentally it has been sho^^ n that 
tuberculosis of the nasal mucosa of guinea-pigs may be produced ithout any 
wound of the mucosa by spraying tubercle bacilli into the nostril Furthei', 
it has been shown that in noimal individuals tubeicle bacilli may sometimes 
be demonstrated m the nasal secietion The lesions, according to Herzog 
and others, may be ulceiative upon an mfiltiated base, they may form 
circumsciibed tumois, oi they may consist m a combination of these types 
They affect most often the vault of the nasal caMty vheie it passes over into 
the pharynx, the septum, and the mferioi tmbmate The accessory sinuses, 
however, may be involved and caries of the sphenoid and othei adjacent 
bony structuies has been reported In eeitain cases, as is true also of the 
mouth, pharynx, and even of the laiynx, the lesions of lupus, with their 
shallow ulceiations and subsequent scairing, may extend fiom the skin into 
the nasal cavity 

Larynx — ^The tuberculous alterations of the laiynx are m piinciple similar 
to those of the nasal cavity They are common m association with pulmo- 
nary tuberculosis, but occur also as a primai y affection There seems little 
doubt that when the larynx shows tuberculous ulcerations co-existmg with 
a tuberculous cavity m the lung, the laryngeal tuberculosis is secondary 
and due to infection of the larynx by the passage of the sputum Theie aie 
those, however, who hold that it is of luematogenous oi igm and m certain 
cases in which miliary tubercles are found m the mucosa alone this may be 
correct The evidence m favor of the direct infection by sputum is ovei- 
whelmmgly strong, and even when the lesions m the laiynx are more exten- 
sive than those m the lung it remains possible to explain the fact on the ground 
that the pulmonary lesions have ceased to advance so rapidly as those m 
the laiynx 

Tubeicles appear in the mucosa as minute gray nodules, usually under the 
epithelium Evidently the bacilli may be absorbed between the epithelial 
cells as foreign bodies and produce a lesion only after reaching the underly- 
ing tissues The coalescence, extension, and subsequent caseation of such 
tubercles results m the foimation of ulceis These may be small, lounded, 
shallow losses of substance, sometimes edged with a yellow, opaque line, and 
showing a reddened base, oi they maybe laige, lagged, iiicgular, and deep 
ulcerations The first or aphthous eiosions may occupy a large part of the 
lining mucosa and are especially often found to extend in great numbeis 
along the course of the trachea The more extensive ulceiations affect most 
commonly the true and false ^ocal cords, the arjdenoid caitilages and the 
epiglottis, but may of couise involve any part oi all of the laiynx, oi even 
extend to the adjacent jiharynx and tiachea Like similar ulcers elsewheie, 
thej aie irregulai m outline, sometimes very piecipitous v ith ragged margins 
and reddened base, often shoving njiay oi '^ellov, opaque nodules and a 
lining of shreddy material or a consideiable caseous and purulent secretion 
They may extend deep into the tissues, and cause gieat destine tion of the 
\ocal cords, the edges of vhich aie so excavated as to be incapable of per- 
forming their function The laiyngeal vails m gencial aic often deeply 
eroded and the destriictne effects may be especially disastrous in the case of 
the epiglottis, v hich ma'v be completely destioyed so that sv allov ing becomes 
very difficult The tuberculous perichondi itis, vdiich is part of this process, 



THE PATIIOLOGl OF TUBERCULOSIS 


213 


by clestro>ing the peiichondiium, causes neciosis of the caitilages, winch 
finally become denuded and often deeply eroded Sometimes m the course 
of such a destructive ulceiative pioeess a secondaiy infection may occur, 
pioducmg a phlegmonous oi gangrenous laryngitis, often with a rapidly 
fatal result 

Lupus-like piohfeiatne forms of tubeiculosis occui in the larynx and 
may be diiect extensions from similai lesions m the pharynx They produce 
flattened elevations and shallow ulcerations and subsequent!} extensive 
scars Recently, Pan/er and otheis have pointed out that papillary excres- 
cences foimerly regarded as papillomatous m nature may in many cases be 
tuberculous These are often pedunculated or sessile, cauhflower-hke 
striictuies which are bluish m coloi and ragged or uneien superficially, and 
.ire largely composed of tubercles and tuberculous granulation tissue 
Cases of he.almg of tubeiculous ulceration of the larynx are extremely rare, 
partial healing may of course fiequently occur and cicatrization may m some 
instances be extensive enough to produce stenosis of the larynx 
Trachea — In the trachea the shallo\A, aphthous ulcers foim the common 
type of the tuberculous lesion, and may be found closely set throughout the 
vhole mucosa or scattered singly here and there Fiequently such tubercu- 
lous lesions of the larynx and trachea aie associated with caseous foci m the 
immediately adjacent lymph glands A\hich may become adherent Indeed, 
as in a case lecently seen at autopsy, sinuses may form, connecting the 
lymph glands with the perforated ulcers in the trachea, and the extension of 
tlie process may lead to the complete isolation of the trachea which comes 
to he in a soitof sheath lined with tuberculous granulation tissue and oozing, 
caseous fluid matter The question might well arise m such a case as to 
whethei the focus in the lymph glands outside the trachea was not the primary 
one, the ulceration of the tracheal mucosa being due to their ruptuie into its 
lumen 

Bronchi — Tubeiculous lesions of the bionchi are practically mvaiiably asso- 
ciated with tubeiculosis of the lungs and may be described with that condition 
Tuberculosis of the Lungs — llie pathological anatomy of tuberculous 
diseases of the lungs presents a remarkably varied picture, the changes 
differing gieatly m charactei according to the intensity of the affection and 
the consequent duration of the disease These variations depend upon the 
number and virulence of the bacilli and their mode of introduction, and, on 
the other hand, upon the resistance of the individual 
Under oidinaiy ciicumstances the disease begins m the apical portion 
of the lung, not quite at the apex, but usually at a point about 2 cm below 
the extreme apex, and there the primary lesion usually takes the form of a 
small, caseous focus involving the termination of the small bronchus which 
extends to that point Indeed, Birch-Hirschfeld insists that the mode of 
foimation of the initial lesions consists essentially m the primary localiza- 
tion of the inhaled bacilli m the terminal portion of the bionchus just as it 
passes o\er into the atrium and m the formation there of a caseous and 
ulceratne bronchiolitis vliich soon extends to iniolve the adjacent air cells 
and the neighboring bronchial vail This simple explanation is not agreed 
on m all, Ribbeit thinking the apical lesion to be most frequently the result 
1 ^ 'j secondary introduction of the bacilli into the lung after they have 
1 re.ad^ passed through it and been transported to the bionchial Ijunph 
glands as any innocuous particles of dust, being again set free into the 



214 


INFECTIOUS DISEASES 


lung by the lupture of the caseous gland into a bionchus or bloodvessel 
Klebs, Baumgarten, and others think that many distal portals of entry may 
serve for the introduction of the bacilli and Baumgarten has by experiment 
produced such lesions by the introduction of the organisms into the urinary 
bladder of rabbits The exact leason foi the localization of the process m 
that particular part of the lung is not cleai, for other portions are readily 
seen to be quite susceptible to such infection It is generally explained, 
howevei, as the lesult of the relatively imperfect mobility of the apex, its 
insufficient aeration and less abundant blood supply winch renders it a soil 
more favorable for the giowth of the bacilli The course of the bronchus 
leading thither has also been brought forward as a factor favoring the entrance 
of the bacilli into that portion, but it seems that this can hardly be of great 
importance 

Whatever the determining cause be, the frequency of primary develop- 
ment of tuberculosis m the apical portions of the lungs is very great, and at 
autopsy m almost all cases, no matter how advanced, one can generally 
find traces of the oldest lesions at that point Objection has recently been 
made to this by Hansemann, who thinlvs that one can frequently show by 
the extent of the lesions, especially m cases of tuberculous bronchopneu- 
monia, that the older lesions are distributed lather throughout the lower 
lobes 

The apical lesion may undergo cicatrization or extend to other parts of 
the lung Probably cicatrization results m a very great number of individuals 
m whom tuberculosis has never been recognized and thus permanently cuts 
short the progress of the disease Such are the cases m which tight adhesions 
are found between the pleural layers over the apex of the lung and beneath 
them a rather thin, flattened scar which entends only a short way into the 
substance of the lung In other cases there are no adhesions, but merely 
a scale-like puckered thickening of the pleura at that point, with much gray 
and black pigmentation, both m the scar and m the immediately adjacent 
lung substance There seems room for doubt as to the exact nature of such 
scars, although they are generally regarded Avithout question as tuberculous 
They are extremely superficial and involve the destiuction of very little of 
the lung substance and not that portion (subapical) which is usually seen to 
be affected m the primary tuberculous lesions Further, they frequently 
show microscopically no evidence of caseation nor anything resembling a 
tuberculous tissue, nor can bacilli be demonstrated mthem They consist 
merely of dense fibious tissue in which remnants of partly obliterated alveoli 
vnth thickened epithelium and terminal bronchioles may persist and in 
which gianules of coal-dust and blood pigment are usually abundant The 
evidence of their tubeiculous nature m such cases is therefore largely pre- 
sumptn e Much more definitely tuberculous m nature are those scars which 
extend m piTamidal form much deeper into the tissue, and pucker and 
distort the apex of the lung Such masses of hard, dry tissue are also deeply 
pigmented and sometimes contain calcified areas The microscope fre- 
quently reveals definite remains of tuberculous tissue and encapsulated 
caseous tubercles m these Whether such scars offer any menace to the 
indmdual depends of course on the completeness of the encapsulation of the 
bacilli, but m general they are probably to be regarded as finished 

"i^flien the conditions are more favorable for the growth of the bacilli the 
apical lesions may ex-te^d vitli varjang degrees of rapidity to the other parts 



THE PATHOLOGY OF TUBERCULOSIS 


215 


of the lung Usually tlie extension is at first quite local and leads merely 
to the enlaigement of the focus with the involvement of the suriounding 
pulmonary tissue This may proceed by the rapid appeaiance of a group 
of small conglomerated tubercles which occupy the air cells, to the exclusion 
of the air, and soon associate with tliemselves so much cellular exudate and 
tuberculous granulation tissue as to render that area quite solid The casea- 
tion soon extends from the cential bionchus to involve all the cential part 
of this solid tissue, including m the necrosis the walls of the air cells, blood- 
vessels, and all that was formerly the lung tissue With the advance of the 
necrosis the bloodvessels become completely obliterated so that when the 
caseous mateiial is finally liquefied and discharged into the central bronchus, 
whose walls were the first to be destro}ed, no hemorrhage takes place In 
such early lesions the dischaige of the caseous matter into the bronchus 
IS practically always possible on account of the inevitable wide connection 
of the bronchus with the cavity or vomica thus foimed, and one can at autopsy 
almost invariably pass a probe fiom any tuberculous cavity directly into a 
bronchus The caxity thus formed may be very small and no larger than 
a marble, but the emptying of its contents into a bronchus is usually the first 
step in the wide involvement of the lung in the tuberculous process The 
presence of the material, loaded as it is with tubercle bacilli, m the larger 
bronchi provokes violent respiratory movements and cough, and these aided 
by gravity soon effect the distribution of the bacilli back into the previously 
uninfected bronclii 

When the aspiiated substance reaches the finest bronchioles and the 
associated an -containing tissue, tuberculous lesions quickly result, and these 
again vaiy somewhat m character according to the virulence and number of 
the bacilli and the consequent rapidity and extent of the change Apparently 
they are ordinarily of pneumonic or exudative character m the earliest 
stages, but when they come to view at autopsy they have usually had time 
to undergo a partial caseation, together with the marginal development of 
iiiegulai conglomerated tubercles which add to the firmness of each patch 
and rendei them indistinguishable from partly caseous conglomerated 
tubeicles, except by the fact that the microscope reveals the framework of 
the air cells undisturbed m its lelations, wliicli is outlined throughout the 
caseous area b'^ the elastic tissue vhich persists for a long time This 
seems chaiacteristic of a pneumonic area, for the primary development of 
conglomerated tubercles in the air-containing tissue leads to the great dis- 
placement of the V alls of the an cells and their great distortion before they 
haie time to undergo caseation Nevertheless, it is by no means uncommon 
in such cases to find abundant inihaiy and conglomerate tubercles scattered 
throughout the lung as the result of the aspiration of infected material 
If the anatomical study of the lung can be carried out soon enough after the 
aspiration of the bacilli it is easv to distinguish microscopically betveen the 
minute areas of pneumonia and anj' definite fresh tubercles vhich may occur 
Still, as described, the exudatne processes, the proliferative process, and 
the process of necrosis are so quickly combined that m principle a fairly 
uniform result ensues The gioss appearance of such a lung ma'^, hovever, 
^arv greatb It is most common on section to find the lung moist, but not 
particularly h'\'perremic and studded throughout with firm patches of xarious 
SI7CS vliich are usually ranged around the bronchi like clusters of grapes 
about the stem These consolidated patches, vhen ^ery small, may be 



216 


INFECTIOUS DISEASES 


jDeaily gray and semitranslucent, and most easily recognized by the pal- 
patmg fingei, but when large they present a flat surface elevated a little 
above the cut surface of the lung and roughened and opaque oi dull in appear- 
ance In color, they alter AVith age fiom a giayish red, thiough giay to a pale 
yellowish white With the fuithei lapse ot time they undergo softening and 
liquefaction and a gieemsh hue may become apparent in the caseous material 
About them the lung substance is usually moist and reddened oi grayish in 
color It is moi e ti anslucent than noi mal and exudes on pressure a tenacious, 
glutinous fluid In other instances the patches are much firmer and pro]ect 
mulberiy-like above the cut surface, giving it a very nodulai appearance 
Such IS the ordinary appeaiance of the tuberculous lobulai pneumonia 
or bronchopneumonia which lesults fiom aspiration of the contents of the 
primary apical cavity, and this maj'^ be regarded as by far the commonest 
type of pulmonary tuberculosis Associated lesions of the pleura, lymphatic 
system, etc , always occur, but tliese may be described separately 

No fundamental distinction can be made between this tjqie of pulmonary 
disease and that which was so clearly described bj' Frankel and Tro]e under 
the name of acute pneumonic phthisis In tliat condition tlie sudden intio- 
duction of large numbers of virulent tubeicle bacilli into the bionchi results 
m the rapid appeaiance of a widespread consolidation of a whole lobe or 
even of the whole lung, so that the condition is often regarded as ordinary 
acute lobar pneumonia In no essential point, except in degree of involve- 
ment and rapidity of development, does this alteration differ from that just 
described m the acute lobular bionchopneumoma The appearance of the 
lung IS, however, veiy character istic, especially m the more advanced stages 
At first the consolidated area has practically the appearance of that seen in 
acute lobar pneumonia The whole lobe is evenly consolidated, its pleural 
surface being dulled by an opaque deposit of fibrin The cut surface is 
roughened by minute fibrinous plugs, and the whole opaque, dull-loolung 
area has a giayish oi grayish-ied color The adjacent lung not actually in- 
voh ed 111 the definite consolidation has the gelatinous semitranslucent appeal - 
ance described also for the lobulai pneumonia, and if one stroke it with a knife 
it IS sometimes possible to draw up into strings the gelatinous fluid which 
exudes from it It is lare, however, that the lung in this condition shows 
only these appearances, ordinarily some part or all of the consolidated area 
has undergone the inevitable caseation or coagulative necrosis so chaiaCter- 
istic of tuberculous lesions Usually, this is irregularly distributed so that the 
cut surface has a marbled appearance, but sometimes, as in a recent case at 
the Johns Hopkins Hospital, the whole lung is quite uniformly converted 
into a homogeneous, yellowish-white material which cuts smoothly like cream 
cheese and shovs no living tissue ivith the exception of the largest vessels 
and bronchi In this case the small cavity in the apical portion of the lung 
showed clearly the mode of distribution of the infectious agent If an 
attempt be made to inject such tuberculous lungs, it is found that the injec- 
tion mass stops short at the margins of the necrotic areas, although the 
capillaries are still quite patent in the gelatinous areas and m the fresher 
portions of the pneumonic consolidation It results from this that m such a 
case as that described, m which the whole substance of the lung had under- 
gone caseation, the colored mass Mould enter only the larger vessels 
Microscopicallv, the development of these lesions is about as follov'S 
Under certain circumstances the bacilli may spread along the lymphatics 



THE PATHOLOGY OF TUBERCULOSIS 


217 


or for a short distance through the tissue and set up the foiination of miliary 
and conglomerated tubercles of the usual type As will be described, such 
tubercles may develop throughout the lung when the bacilli entei by the 
blood stream 

As to the earliest stages in the formation of the more usual or pneumonic 
lesions we aie able to judge as m ordinaiy pneumonia, chiefly from the 
appearances of the changes in the neighborhood of the moie advanced 
lesions There we find bloodvessels distended witli blood and the air cells 
filled no longer with air, but with a fluid the viscidity of which is indi- 
cated by the deep eosin stain which it takes in the section Many large 
cells with round, vesicular nuclei and abundant protoplasm, often studded 
with fat globules, he m this fluid, and are for the most part to be regarded 
as the desquamated alveolar epithelium from the walls of the air cells 

Mononuclear leukocytes of various sizes, a feiv red corpuscles, and in- 
cieasingly abundant polymoiphonuclear leukocytes are soon associated 
■with these A dense nehvork of fibrin is not long m forming, and finally, 
except for the gieat abundance of desquamated epithelial cells, the appear- 
ance IS not unlike that of ordinary pneumonia 

Scarcelj", hoivever, is the exudate completely formed ivhen the change 
occurs ■ndiich is paiticulaily chaiacteristic and which wull serve at once to 
distinguish tuberculous pneumonia from the ordinary foims Tins is the 
process of coagulative necrosis which changes the cellular exudate into the 
led staining, formless material, in wdiich at first abundant deeply staining 
fiagments of nuclei are visible They are seen as fine dust-like particles 
in clouds about the maigiii of the caseous area, wdiere they aie con- 
spicuous by their deep blue stain Elsewhere the whole area is conveited 
into a faiily homogeneous refiactile granular pink or red staining sub- 
stance In tune the caseous material becomes more and more homo- 
geneous although at first shadowy outlines of the cells of the exudate 
aie distinguishable The w'alls of the air cells xvhich are also involved m 
the necrosis fade aw^ay gradually and are finally lost in the softening debris 
As long, how^ever, as the caseous material letains its firm consistency these 
walls can be distinguished usually as famt lines of pale blue By the aid 
of Weigert’s special stain foi elastic tissue they may be plainly brought to 
view' as a netw’oik of deeply staining fibrils, for it is chiefly owing to the 
gieat abundance and great powers of lesistance of the elastic tissue that they 
leinain visibh so long Even after the caseous area becomes liquefied and 
is expectorated through the bionchi, shreds of elastic tissue persist and may 
be recognized in the sputum The presence of the elastic tissue, m the nor- 
mal aichitectuial arrangement witliout distoition, tliroughout the caseous 
area, gnes proof, as mentioned, of the pneumonic origin of the lesion 
lather than its dependence upon the formation and subsequent caseation of 
tubeicles Certain other structures persist wutliin tlie caseous areas and may 
remain recognizable for a long time Particularly resistant are the larger 
bloodiesscls the walls of which become extraordinarily thickened on the 
stimulus of the advancing destiuctne process The tliickenmg is especialh 
seen m the inner la'iers, which become so increased m bulk as to obliterate 
the lumen of the 'v essel — the so-called obliteratn e endarteritis Coal pigment 
m the walls of these ^essels is an aid m their recognition The bronchi 
which aie included are also often distinguishable b-y the presence of coal 
pigment m their walls, but thej show fai less power of resistance than the 



218 


INFECTIOUS DISEASES 


bloodvessels Indeed, their walls are quite commonly involved m the 
caseous piocess throughout considerable lengths In some instances the 
bronchi are rendered conspicuous by the great thickening and subsequent 
caseation of their walls, even when they are not completely surrounded by 
caseous material, so that they run as thick-walled tubes of opaque, yellow 
material through the gelatinous or partly consolidated lung 

Even vhen the caseation is apparently quite homogeneous over an area 
of the lung, it is often seen on microscopic examination that there are in the 
fiimer caseous substance rounded and irregular cavities which contain a 
loose network of coarse fibrin filaments, often with scarcely any cellular 
remains These are often at the terminations of the small bronchioles, vhere 
they pass over into the vestibule and atria, m many cases they are surrounded 
by the remains of the walls of normally disposed air cells and have not been 
produced by the breaking of one air cell into another The most plausible 
explanation of their presence seems to be that the solid caseous material 
once formed may be m small part discharged through the bronchus or it 
may contract m such a way as to leave cavities such as are seen in a Swiss 
cheese The coagulation of new fluid which permeates into their cavities 
results in the coarse, loose networks of fibrin described 

Up to this point, then, we have larger or smaller areas of pneumonic 
consolidation m which the greater portion is completely necrotic, although 
still showing indistinctly the architecture of the tissue, while the marginal 
portion, although still living, is densely infiltrated with the cells of the exudate 
fluid and fibrin Such aieas are surrounded by wide halos of the gelatinous 
infiltration in which the air cells are filled with fluid and desquamated 
epithelial cells This is the so-called caseom and gelatinous pneumonia 
The fuither outcome of this condition vanes considerably Actual reso- 
lution IS probably unusual if not entirely impossible when the consolida- 
tion IS completed In the areas of collateral oedema or gelatinous pneu- 
monia which surround the patches of consolidation it seems probable that 
the exudate may disappear m case the actually caseated area becomes limited 
and encapsulated This must be chiefly a mechanical process, for any 
such general autolysis and dissolution of the exudate as occurs in lobar 
pneumonia of the ordinaiy type seems to take place only in the slightest 
degree, if at all, in tuberculosis Further, the obliteration of the bloodvessels 
which IS practically never observed m the ordinary pneumonia, takes place 
very early in the tuberculous process, and that area is then completely cut 
off from any hope of favorable influence from without 
IVlien the caseation is complete it is usually found, m those cases in which 
the patient has lived at least a short time after the death of the tissue, that 
organization of the exudate which has not become necrotic occurs This 
accordingly affects the contents of the alveoli around the margins of the 
caseous area and is a process m every way analogous to that seen in ordinary 
pneumonia, m the margins of the necrotizing areas in glanders of the lung, 
in actinomycosis, etc Ordinarily the organization as it appears a little 
distance from the caseous area is non-specific m character and not to he 
distinguished from that seen in any bronchopneumonia Within this, 
hovever, and immediately adjacent to the caseous area, abortive irregular 
tubercles and dense tuberculous granulation tissue develop m which giant 
cells are frequent and epithelioid cells form the predominant element These 
processes together form a fairly dense fibrous wall about the caseous mass. 



Tlin PlTJIOLOG'i OF TUBERCULOSIS 


210 


a -vvall ^^hlch is, ho^\c\cl, ])ionc to furthei necrosis .iiul disintegr.ition The 
^^alls of the air cells .incl \e,ssels, which in this t>pc of pneumonia become 
especially intenscl> mfiltiatcd with the tcllul.ii cMidate, are included and 
built up into this capsule 

Sometimes such an encajisulation is cllcctne in limiting the further action 
of the tubeiclc bacilli upon the tissues, the caseous material is retained b} it 
and becomes denser and dr^cl, until hnailywith the deposition of caleium 
salts it inaj practicalh he converted into a stony or mortar-likc substance 
Usuall}, howeiei, a quite dincrcnt result ensues The caseous material 
becomes softened and finalh liquefied oi biokcn down into a musb>, thick 
fluid winch IS discliargcd into the open Iironclius and when mingled with 
the mucous secretion of the bronchus forms the gicen sputum which, accord- 
ing toFr.mkcl and Trojc, is so characteristic of the acute caseous pneumonia 

The discharge of this material Icaccs a caMt^ which, when all the caseated 
tissue IS liquefied and cxjicctor.itcd, corrcsjioiids in form and si/c with the 
focus of pneumonia In some cases, in which the caseation acKances with 
great rapidity and quickU nnohes large areas of the lung, the caMt> forma- 
tion ma'^ also be extreme^ rapid and extensneso as to practical^ completeh 
dest^o^ the lung within a \cr\ short time — theso-called^i/zt/nsif yloric/o The 
c all of such a ca\lt^ consists of a more or less dense membranc-like la^er 
cf tissue, the lining of which is composed of neciotic, shreddy material which 
remains after the dischaige of most of the caseous are.i Beneath this 
13 the tuberculous gramil.ition tissue which is essentialK the same, no 
mattci where formecl E^en outside of this in the eaihcr st.ig&s there is the 
lung tissue paith consolidated In cellular exudate, ]iaith b^ loose plugs of 
fibrous tissue which ho in the air cells There is a constant attempt at the 
production of a firmer wall b> the jiroliferation of fibrous tissue cells, but when 
the bacteria ale^cr} Mrulcnt and abundant and the resistance of the indi- 
cidual slight, as in the case of phlhi'tn florula, contmned extension of the 
caiity may occur Such a caMt^ usualh contains a considerable quantity 
of residual fluid and caseous material in which .i great ■c.iriety of bacteria 
and occasionalb e^en moulds and fungi m.n be demonstrated This 
abundant flora has been extensnely studied b\ Stephen Artault and others, i 
and there has arisen some quastion as to the part pla>ed by the tubercle 
bacillus in the production of the lesions The weight of eMdcnce is in facor 
of the idea that the whole process, as far as complete caseation, may be and 
IS produced by the tubercle bacilli alone The liquefaction of the caseous 
material may, how ever, result from a sccondai j infection, and it is apparently 
quite true that many of the symptoms — fc^cr, general eMdcnces of intoxica- 
tion, etc — which arise mthe late stages after tlie caMtj has become fuithci 
infected, through its wide communication with the bionchus, are largel} 
dependent upon the presence and growth there of other organisms 

The walls of the caiit^ are, as a rule, not smooth, but roughened bj the 
irregularities of the necrotic substance Further, there aie usually promi- 
nent ridges or sometimes cord-hke stiucturcs, stretching across, which on 
section are found to be bloodvessels whose walls arc greatly thickened and 
very firm They are on this account so resistant as to lemain after the tissue 
around about them has been destroyed and removed, and they are quite 
isolated Frequently they are entirely obliterated and on section are seen 


* Arch dc Parasitologic, 1898, tome i 



220 


INFECTIOUS DISEASES 


to be merely solid cords of fibrous tissue Sometimes they are eroded through 
and the ends hang free m the cavity This type of obhteiating endaiteiitis 
IS ob^'lously a protectn e process, pi eventing hemorrhage from even the larger 
vessels, A^hlch would otherwise be rapidly opened by the ulceiative process 
Occasionally, the advance of the destructive piocess is more rapid than the 
obliterative change in the ^essels and a seveie hemoirhage may lie the result 
The bronchi usually stop abi uptly as they enter the cavity, their walls having 
been destroyed They may be somcw hat dilated, but, as a rule, especiallv in 
the rapidly destructne cases, the changes which aie evident m those portions 
of the bronchi which remain consist chiefly in the ulceration of their walls, 
the shallow ulcers pass into the mucosa and submucosa and leave a rough, 
raw surface within the bronchi 

The cavity, which is mosl commonly in the upper lobe of the lung, although 
by no means always so, may involve practically the whole lobe, or by exten- 
sion nearly the whole lung Such large cavities are always associated with 
abundant tubereles and areas of tuberculous pneumonia m the remaindei 
of the lung Often the lung is reduced to a mere sae, of which the thickened 
pleura forms practically the only wall, all the lung substance having been 
destioyed Occasionally, if the pleural cavity has not been obliterated by 
adhesions, a perforation may take place through this thin wall, with the escape 
of fluid and an into the pleura In every instance of such extensive cavity 
foimation there is tuberculous pleurisy, but m such a case the admixture of air 
and abundant foieign bacteria and necrotic material sets up & 'pyopneamo- 
thomx 

Death is not necessarily the immediate result when such destructive 
processes occur m the lung Indeed, the tendency toward healing, which is 
recognized m the attempt at encapsulation of the lesions, is often given play 
by the continued life of the individual, so that extensive scar formation takes 
place and the consistency and appearance of the lung may be greatlv altered 

It has been mentioned that in the tuberculous pneumonia, ete , the sub- 
stance of the lung tissue, the walls of vessels and bronchi, and the septa 
betv een the air cells become much infiltrated with cellular exudate Perhaps 
m consequence of this intimate affection of the tissue the fibrous tissue is 
stirred up to proliferation and the Avails of the air cells become thickened 
Such general thickening of the tissues, AA'hich m course of time become 
Aery firm and scai-hke, is often spoken of as mduiatiA^e or interstitial pneu- 
monia, and although it is found in connection aa ith other infections is perhaps 
most commonly seen m tuberculosis 

In certain instances the Avails of the air cells become so thick and rigid 
that they are no longer capable of distention, and the lining epithelium 
AA liereA er it is preserA^ed returns to its embryonic high cubical form so that 
the air cells come to look almost like the acini of a gland Sometimes, 
indeed, they are aa idely separated by thick bands of fibrous tissue Such 
an indurated lung is firm and elastic and has a giayish-black color In the 
cases AA here the poAA er of resistance of the individual is sufficient to allow 
of such a scar formation, the caseous areas and cavities usually become 
AA ell AA ailed oft, although it is self-cAudent that in such indiAuduals the caAuties 
and caseous areas could hardly reach the maximum extent Actual healing 
ma> be accomplished or the tuberculous areas at least so far encapsulated 
as to be rendered practically harmless The same thing may, under excep- 
tional conditions, occur m the case of caAuties of considerable size, AAdnch then 



THE PATHOLOGY OF TUBERCULOSIS 


221 


become cleaned out, and all the necrotic material expectorated, Ica-sing a 
smooth, firm, fibious A\all, o^el Aihich epithelium glo^^s fiom the bionchus 
This, lion e^ er, must be regarded as unusual 

All possible combinations of destruction and induration oi protective 
changes ma} be obsened in the lungs of jihthisical individuals, the pie- 
dominance of one or other condition at autopsy indicating nith fan ceitainty 
the degree of rapidity n itli nliich the disease piogicssed as veil as the ponei 
of lesistance of the indnidual and the Miulcncc of the bacteiia It ina> be 
repeated, honexei, that the commonest jneture in an> gicat senes of cases 
IS that m nhich at the apex oi in the subajiical icgion there is a c.ivity in 
open communication ^Mth a bronchus and dcinaicatcd from the adjacent 
lung by a layer of tuberculous granulation tissue, ^\ bile in the low ci portions 
of the lung there are areas of ear'^ing sivc usually langcd in clusters aiouiid 
the bronchi, in which the lung substance is consolidated, and in part, .it 
least, c.aseous These may be pureh pneumonic in chaiactcr, in the ficshest 
cases, or m others thc-y m.n be indistinguishable from conglomerate tubciclcs, 
but m most instances they aic rccogni/ablc as caseous pneumonic aieas m 
the margins of which tubciclcs and tuberculous gianulalion tissue ha^e 
de\ eloped It is, howe\cr, to be cniphasi/ed that tubeiculosis of the lungs 
IS in most cases a chronic aflection of some duration, and that, therefore, the 
indurati\e changes arc generalh jiresent 
Although tubercles of ^arIous foims and si/cs occur regularh in connection 
w’lth the tuberculous processes which aflcct the lung, sometimes as the basis 
of a tuberculous granulation tissue about the jmeumonie aicas pioduccd by 
the bacilli, sometimes mdependenth, from the local distribution of the bacilli, 
the diffuse miliary tuberculosis of the lung is gcncrallc the icsult of the 
entrance of the bacilli into the blood sticain This is shown In the fact that 
such lesions are all of the same size and .igc, and aic ciisliibuted as is onh 
possible bj the agency of the blood stream Further, ow mg to the width of 
the capillaries of the lung, it is unusual to find a Epical diflusc milmiy 
tuberculosis of that organ which is not p.nt of a gcncrah/ed miliary tubei- 
culosis In its oiigin, therefore, mihan tuberculosis of the lung agiecs with 
most foims of generah/ed miliary tubeiculosis, althougb the intensity of 
the process m the lungs ma> difiei from that in othci oigans Tims, when 
the tuberculous lesion which iinadcs the bloochcsscl pouis its bacilli into a 
systemic lem oi into the thoi.icic duct the lungs aie the first to iccene and 
sift out the bacilli On the othci hand, when the mcachng lesion aflccts a 
branch of the pulmonary vein the systemic oigans first leeene the bacilli 
It must be remembered, howe^er, that the bacilli aic so minute that they 
pass fairly readily through any c.ipill.aiics, and there need, thcicfoic, be no 
very striking diftercnccs m the chaiactcr of the lesions m the lungs and 
systemic organs, no matter what the point of cntiv of the oiganism 'I’hus, 
in a recent case m wdiich a mortal -like, soft, caseous mass projected into a 
branch of the pulmonary vein the lungs and systemic oigans weic alike 
the seat of a fresh outbieak of mihaiy tubciclcs 
The freshest mihaiy tiibeicles m the lung may picsent the chaiacteiistic 
structuie Quite fiecpiently, hoAccvei, they show' a pneumonic icaction 
even in the early stages, the aheoh about the point ol localization of the 
bacilli in the capillaiies of the alvcolai Avail bung filled Avilh desquamated 
epithelial cells and cells of leukocyte type exuded fiom the vessels Indeed, 
it seems doubtful Avhether an absolute distinction could be draAvn betAveen 



222 


INFECTIOUS DISEASES 


the miliary tubercles of the lung, arising from the introduction of tubercle 
bacilli through the blood capillaries and those which could result from the 
accession of scattered tubercle bacilli to the air cells 

The miliary tubercles often remain discrete so that the lung is readily 
insufflated and the intervening air cells are still functional, but they may 
become confluent and caseous Ordinarily, however, the patient does not 
survive long enough for any extensive changes to occur, although cases are 
occasionally seen in which the tubercles scattered every^vhere through the 
lung have actually become healed and converted into a firm, hyaline, fibrous 
tissue 

Still other possibilities exist in the development of tuberculous lesions 
in tbe lung, for it is not infrequent to find, m the absence of the extensive 
areas of pneumonia or cavities, single, isolated, caseous nodules, which are 
spherical m form and tightly enclosed m a dense, deeply pigmented capsule, 
sometimes these are calcified and may have the consistence of friable pebbles 
embedded m the lung They seem to indicate a considerable degree of 
resistance on the part of the individual, in whom further extension of the 
process has been so promptly arrested Sometimes these nodules reach a 
large size, and they are doubtless often regarded as gummata of the lung 
In most instances, however, the history and the infectious nature of the 
lesion on inoculation into a guinea-pig Avill reveal the true character of the 
change 

Tuberculosis of the Pleura — In all cases of active tuberculosis of the lungs 
when the lesion approaches the surface there is involvement of the pleura 
In certain cases, however, there is no very conspicuous lesion m the lung, 
sometimes an adjacent caseous lymph gland or other tuberculous lesion by 
extension gives rise to the process Whether a tuberculous pleurisy may 
arise m the complete absence of tuberculous lesions m the adjacent tissues 
seems verv questionable 

Anatomically, the tubercle bacillus may produce directly or indirectly a 
great variety of lesions m the pleura and all transitions may be obseived 
between the dry, fibrinous form, in which vithout the presence of any fluid 
exudate the pleura has lost its gloss, and the most advanced tubereulous empy- 
ema Recent writers tend more and more to look upon pleurisy which begins 

V itliout apparent cause and without definite pulmonary lesions as tuberculous 
m origin These are the so-called idiopathic pleurisies, but caieful seaich 
will usually reveal some associated lesion generally of tuberculous character, 
or with the lapse of time widespread and definite tuberculosis may appear 
Peron has shown by bacteriological studies the predominant tuberculous 
nature of such pleurisies, and Aschoff, by inoculation of the exudate into 
guinea-pigs, was able to produce tuberculosis m the animal as often as by 
the inoculation of material from definite tuberculous pleurisy 

Peron distinguished two t^qies of tuberculous pleurisy, the pleuritis tuber- 
culosa serofibnnosa and empyema tuberculosa, although there are of course 
all mter\enmg forms The anatomical changes are fundamentally identical 

V ith those seen elsewhere Over an area of tuberculous inflammation of the 
lung there may appear a local or quickly generalized fibiinous exudate, thick 
enough at times only to destioy the gloss of pleural surface, or in other cases to 
be pulled off as a thin, coherent layer If the lesion in the lung be small and, 
as in the case of the apical foci, soon undergoes a healing process, the pleural 
exudate may also disappear or leave behind it an area of fibrous thick- 



TJJE PATHOLOGY OF TUBERCULOSIS 


223 


ening or adhesion ith the parietal layer In other cases the whole pleura 
may° be rapidly invoh ed Fluid sometimes to a bulk of two liters or 
more may appear, ^\ ith gieat compicssion of the lung An exudate of fibrin 
and leukocytes, fiequently ^ery hemorrhagic in chaiactei, may be associated 
with this, soon to be encroached upon and m part replaced by the tuberculous 
o-ranulation tissue, A\hich springs up and leads to the great thickening of 
the pleural layers In other cases the fluid is less abundant, and instead 
of being merely turbid is thick and creamy, ^Mth lagged shreds of fibiinand 
later caseous or necrotic material 

The tuberculous granulation tissue which lines the cavity becomes giad- 
ually thicker and denser, and except superficially loses its sti iking tuberculous 
character, so that it appears merely as a ^crv haul, fibrous tissue This 
usually goes hand in hand w ith the process of fibroid induration in the lung 
described abo^e, and when, as is usual, the two laycis of the pleura thus 
thickened become bound together, the icsult is that the indurated lung is 
extremely firmly united to the chest w all 

Occasionally when the pulmonary lesions are lapidly destructue, the 
pleuia may quickly come to form the only wall of a l.iige caMty in the lung, 
all the lung tissues haung been destroyed If the jileural layers aic tightly 
bound together, this may be a safe-enough condition, but sometimes they 
ha^e not so completely effaced the pleural caMty, and with the ad\ancc of 
the erosion of the tissue the caMty may be open into theplcuia by a hole in this 
thin w all Then the content of the ca\ ity, usually' by that time infected w ith 
various organisms, is poured into the pleuia and a Molcnt acute pleuritis is 
thereby' occasioned Since the ca^ ity is in communication w ith a bronchus, air 
enters into the pleura and the condition of pyopneumothorax aiises The an 
may pass in and out freely, but usually there is a sort of ^al^e action, so 
that while it passes easily into the pleura, it does not so easily escape As a 
rule, since this condition arises only aftei cxtensnedestiuction of the lung, 
it may be regarded as practically a terminal process 
Tuberculosis of the Lymphatic Tissues— The Tonsil — hluch has been 
w'ritten of late upon the relation of the tonsil to tuberculosis, especially w ith 
regard to its importance as a portal of entry', but e\cn yet aftei the study of 
hundreds of cases there is no great unanimity of opinion That the tonsils 
become infected by the tubercle bacillus is undoubtedly tine, commonly' m 
connection AMth pulmonary tuberculosis, but sometimes piimaiih As to 
the frequency of its involvement eve may’ quote the figuies of Piffl and 
Rethi Rethi found primary tuberculosis 0 times m 100 cases, while 
Piffl found 3 certain cases in liis senes of 100 cases Much depends upon 
the method of examination, for w bile by' inoculation Dieulafoy found numbei s 
of tuberculous tonsils, Cornil by' microscopic study ns Acell as inoculation 
(but excluding the infected surface of the tonsil) found only' 4 cases of tuber- 
culosis in 70 

Secondary to pulmonary tuberculosis it is not uncommon to find the 
tonsils set AMth conglomerated tubercles, and ulcerated or caseous Occa- 
sionally, lupus or superficial tuberculosis may extend from the mouth, Avhich 
as in the nose gives rise to tumor-hke nodules, and may later shiink aAvay 
and leaAe scars More important than these, from the theoretical point 
of vicAv, are the cases of latent or inconspicuous tuberculosis of the tonsil, 
in AA'hich merely an hypertrophy of the tonsil or even no change at all is 
present Such infections may take place fiom the air, sputum, or food, 



224 


INFECTIOUS DISEASES 


and may give use to tubeieulosis of the cervical and mediastinal glands, 
and thus to a generalized tubeieulosis Giobei, in studying the dissemina- 
tion of bacilli liom the tonsil, coneludes that it is quite possible that tubei- 
culosis of the apical vault of the pleura may be due to diiect tianspoitation 
of the bacilli from the tonsils, and suggests that the apical lesions of the lung 
may arise m the same way, that is, byway of a piimary tonsillar aftcction, 
with secondary tuberculosis of the cervical glands and tuberculous pleural 
adhesions '■ 

Tuberculosis of the L3nnph Glands. — When definite anatomical tubei- 
culosis of the glands is demonstrated there can be no dispute as to the natuie of 
the condition, but a series of cases appears to exist m which definite pi oof of the 
tuberculous nature of the swelling of the glands is not brought foiward, but 
m which there is still the general impression that the whole condition is of 
a tuberculous nature Such cases aie classed loughly under the name of 
sciophula or scwfula, a name formeily much moie used than at piesent, 
which has fallen somewhat into disrepute This condition, which occuis 
cluefij' m children and young persons, is characterized (Czeiny, Bios, Neu- 
mann, and others) by general pallor, hypeiplasia of the lymphoid tissue, 
especially about the throat, susceptibility to infections, and certain other 
special phenomena, such as circular canes of the teeth, phlyctenulai con- 
junctiMtis, and especially the seborrhoeic eczema of the cheeks and the 
infantile prurigo (a nodular eiuption Avhich itches intensely and tends to 
suppurate) 

There seems to be no clearly outlined anatomical basis foi this conception 
of the condition The changes described are thought to be due to some 
chemical poisoning, possibly by the toxins of the tubercle bacilli absoibed 
in some way (Solltmann suggests its absorption from the placental blood in 
mtra-uterme life) which makes the child pi one to infection and the develoji- 
ment of definite tuberculosis Possibly the determination of the opsonic 
index in such children might shed a cleaiei light upon the natuie of the 
change The term is apparently used m recent years to express a general 
condition and not to describe the actual lesions m the lymph glands, resulting 
m their caseation and adhesion with the surrounding tissue, for these are 
undoubtedly definitely tubei culous 

The clearly tuberculous lesions may well attract inoie attention In 
general the glands become infected by the absoiption of tubei cle bacilli 
from a tuberculous lesion in tissues drained by then after ent lyrnpli trunk, 
or by the transportation of tubercle bacilli as ineit dust-like bodies along 
this afferent track until they are entangled m tire lymph sinuses oi in the 
lymph nodules of the node Thus the bronchial glands at the hiliim of the 
lung may become tuberculous fiom the absorption of bacilli from tubci culous 
lesions m the lung, or they may be infected by bacilli which have been 
drawn into the lung with the inspired air and which instead of producing 
any lesion m the lung have been taken into the lymphatic channels which 
course through the lung and transported to the bi onchial glands, whcie they 
first show their injurious activities The lesions produced in the gland are, 
however, not alv ays the same, and it a\ as this difference m their appearance 
Avhich led to the difficulties of pathologists m interpreting them 

In some cases the glands become greatly swollen and firm, and on section 


' Khn Jahrb , 1905, Band xiv 



THE PATHOLOGY OF TUBERCULOSIS 


225 


show a surface mottled with yellow patches oi umfoimly yellou , opaque, 
and dry thioughout The cut suiface is peifectly smooth and the substance 
IS friable and crumbly Such w'ere the glands often spoken of as scrofulous 
They frequently soften into a fluid consistence and the sunoundmg tissues 
may be affected by this process, .i widespread inflammation of the capsule 
and adjacent tissue being set up Villemin, Cohnheim, and others show ed 
that they are infectious and on their inoculation tubeiculous lesions result 
m the animal thus treated Koch could find tubeicle bacilli in them and 
microscopic examination often revealed tubeicles aiound the margin of the 
caseous area, but still the idea of scrofula as something diflcient fiom tuber- 
culosis persists 

On the other hand, another condition occiiis in winch the glands become 
su ollen and fairly firm On section f hc> are graj ish and ratlier succulent, 
and are studded with gray, translucent nodules w Inch, how’e^ er, may later 
become conglomerate and undeigo caseation and softening, as in the pier lous 
case This has always been iccogni/cd as tuberculosis of the glands 

The two appearances are fundamentally identical In the fiist instance 
the introduction of the bacilli in numbcis causes a difivise injuiy and a diffuse 
exudation of phagocytic cells with proliferation of the epithelioid conncctne- 
tissue cells With the appearance of caseation the tissue at the maigin of 
the caseated area always sliows the abortive tubercles, which aie also to be 
found about the areas of caseation in the acute pneumonic phthisis 
In the second case the seattcied gioups of bacilli rcxict upon the adjacent 
tissue 111 the ordinary way to pioducc tubeicles Tiibeiciilosis of the lymph 
glands with caseation is j) irticiilarly common in the mck, and especially 
in negroes in this latitude The channels of infection hare alicacly been 
discussed and the poital of entry iiiav exist ainwlicie in theiippci icspnatoiy 
tract or m the mouth, the masses of hmphoid tissue situated tlicie piob- 
ahly acting as the direct fi iiismittcis ol the bacilli d'he glands become 
much enlarged and fiiin, so that great jiackcts of them m.iy st.incl out on 
each side of the neck below’ the angle of the jaw ith the extension of the 
caseation the capsules become iiifl lined, and the glands finally quite tightly 
bound together and to the neighboiiiig tissue, so that then opciative lemoval 
may offer great difficulties In many cases the caseation and liquefaction 
may end m rupture into the iiitcrmuscnlai tissues, and the dischaigcd 
raateiial then bin lows its way’ until often the skin is uplifted and finally 
broken thiough A fistulous opening icaching down to the old packet of 
glands is the result of this clischaige, and this becomes lined with thick, 
tuberculous granulation tissue, which shows little tendency to healing, w’hicli 
IS often long delayed and sometimes only temporal y When it docs occui it 
leaves a gieat, unsightly scai 

- In connection w'lth tnbeiciilosis of the glands of the neck, invohement of 
the axillary and mediastinal glands is not uncommon and lai ge packets of 
tuberculous glands may occasionally be found in the axilla w ithont definite 
involvement of the eeivical senes These aie possibly, m some cases at 
least, due to tubeiculous infections of the hand oi aim In the inguinal 
region gioiips of enlaiged and caseous glands mav occui scxondaiy as a inle 
to tuberculous lesions of the genitalia, although in seicial instances tubeicu- 
lous cutaneous alterations m the foot and ankle seem to be the origin 

The glands most commonly tuberculous are doubtless those situated at 
the hilum of the lung about the bronchi These receive the materials 
\OL in — 15 



226 


INFECTIOUS DISEASES 


absorbed by the lymphatics of the lung, and ith them often tubercle bacilli 
They, like the glands of the mesentery, may thus receive tubercle bacilli 
when the general health of the patient is good, and perhaps this may account 
for the fact that they especially frequently contain completely encapsulated 
or fibroid tubercles, or sometimes calcified nodules, which represent obsolete 
tuberculous lesions With the advance of the caseous process m these glands, 
bronchi or bloodvessels may be eioded and the bacilli emptied into them, 
i\ith results recorded above Similarly tuberculous pericarditis is often the 
result of the ruptuie of adjacent tuberculous glands Tuberculosis of the 
mesenteric and retroperitoneal and other abdominal lymph glands is largely 
a consequence of tuberculosis of the digestive tract or at least of the absoi ption 
of bacilli from the intestinal tract, foi it must be repeatedly emphasized tliat 
the bacilli are not always leady to destroj" the tissue, but may behave, in 
their passage through such tissue as the intestinal wall, as inert particles and 
leave no trace of their passage In children it is not uncommon to find the 
glands m the mesentery swollen into tumor-hke masses which on section aie 
found to contain a soft, cheesy materia) This is the so-called tabes mescnienca, 
in which there is usually an associated widespread tuberculosis if the child 
lives long enough, but in which the abdominal tuberculosis is undoubtedly 
the oldest lesion Occasionally in adults this form of tuberculosis may occur, 
with really enormous, firm mesenteric glands, and sometimes with packets 
of indurated glands along the aorta In horses and sometimes cattle the 
same condition occurs These glands, like the bronchial group, are prone to 
become calcified if the caseous mateiial is not quickly softened, and we 
have observed instances m which, AVith a complete disappearance of active 
tuberculosis, the mesentery was distorted by the presence of large, irregular, 
stone-like masses, which replaced the glands 

Tuberculosis of the lyrtipliahc channels themselves is rarely observed 
except m the thoracic duct and the intestinal and mesenteric lymphatic 
vessels, probably because sufficient attention is not directed to them In the 
walls of the intestine the lymphatic channels which dram the area involved 
in tuberculous ulceration of the mucosa are usually distended and rendered 
conspicuous by the development of tubercles in their lining in such a way as 
to obstruct the flow of chyle The tubercles aie usually visible, both there 
and m the adjacent peritoneum, but the lymphatics are especially prominent 
on account of the stasis of the white chyle pioduced by their presence 
obstructing the lumen In the thoracic duct the effect may be similai, as 
tuberculous nodules develop in its mtima and partially occlude its lumen 
They soon become caseous, and the disintegiation of these masses gives rise 
to an infection of the venous blood and the inevitable development of a 
miliary tuberculosis 

In many cases m which no definite tuberculous lesion of the wall of the 
thoracic duct is discernible, but in which caseous processes in the mesenteric 
gland or tuberculous ulcerations m the intestine occur, tubercle bacilli may 
be found m numbers m the contents of the thoracic duct, and are apparently 
being swept into the blood without affectinii the channel itscK 

Tuberculosis of the Circulatory System — Pencardium — Tuberculosis 
ot the pericardium, v hile less common than that of the pleura and peritoneum, 
isb} nomeansan unusual affection Itexliibitsagieatidiietyof foims, ailof 
V Inch, howe\ei, aie in principle much alike In cases o^^ generalized miliaiy 
tuberculosis the pericardium may become studded with miliary tubercles 



THE PATHOLOGY OF TUBERCULOSIS 


227 


Wliat IS moie geneially regarded as tuberculous peiicarditis, however, is not 
merely part of a geneiahzed process The tubeicle bacilli gam access to the 
pericardial cavity most frequently from the adjacent pleura and lung in cases 
of pleuial and pulmonaiy tubeiculosis, but in many othei instances they aie 
intioduced from adheient caseous lymph glands In some cases it ib difficult 
to trace the course of the infection and theie may even be no distinct focus of 
tubeiculosis elsewhere In the earliest stages the tubei culous peiicarditis 
maj closeh simulate a seiofibrmous percaiditis of non-tubei culous character, 
so that It IS difficult to be sure of its tuberculous nature u itli the naked cj e 
alone In a recent case of this kind the surface of the peiicaidium vas 
e^ery^^here coveied vith a corrugated fibrinous laver, uhile the peiicaidial 
canty was widely distended by a great quantity of peifectly cleai fluid 
Only the closest examination of the ^ertlcal section of the epicaidium, 
which revealed here and there minute tubei cles, made its natme deal In 
other instances hemorrhages niaj'' occui and the fluid exudate is blood- 
stained In others it is rendered thick and turbid by flakes of fibrin and 
cellulai exudate Tuberculous granulation tissue is soon associated iiith 
the fibrinous exudate and is thickly studded with tubei cles itli the 
advance of time the caseation of this tissue ensues and the caseous material 
is added to the rest of the exudate Ordinarily a sufficient accumulation of 
fluid to keep the peiicardial layers iicll apart is found only in the more 
rapidly developing cases, and therefore in thenioie chionic forms the apposed 
surfaces become adherent at least in places and later firmly bound togcthei 
by the thick growth of tuberculous granulation tissue, throughout vliich 
caseous foci may be obsened In seieral specimens recently obseived at 
autopsy the parietal pericardium was closely bound to the heart, and on section 
a mass of partly caseous tuberculous granulation tissue, fully 1 cm in thick- 
ness, intervened between the visceral and parietal layers In anothei case 
the easeous substance had become liquefied, so that it escaped on incising 
the thick covering of the lieait, leaiing iiregulai, buiioiiing canals, iihicli 
ran m the substance of the pericardial adhesions around about the heart 
In other cases the adhesions may become leiy film and scai-hke, iiith 
caseous patches rather spaisely scattered and sometimes calcified Whcthei 
a tuberculous infection of the pericardium may heal and give i ise to a clean, 
fibious, adhesive pericarditis is difficult to determine hleltzci has desciibed 
a form of tuberculous peiicarditis in which firm nodules wcie found similai to 
those in the perlsucht of cattle 

Myocardium • — Tuberculosis of the myocardium is fai less common than the 
analogous disease of the pericai dium It is, howevei , pi obablj more common 
than IS usually supposed, especially m the form of a diffuse miliary tubercu- 
losis, which forms part of a generalized miliaiy tubeiculosis The fiequency 
of this condition was first pointed out by Weigeit, and Poliak has since le- 
viewed the subject ‘ It has piobably no clinical significance Anothei foim 
consists m the appearance of large, solitary caseous masses in the niyocai- 
dium, vhich may sometimes project into the cavity of the heart A diffuse 
interstitial myocarditis with giant cells, but without caseous foci, is also 
described, but the bacilli must be demonstrated in such a case to pioie 
its tuberculous natuie 

Endocardium — ^Tuberculosis of the endocaidium occui s eithci as scattcied 
tubercles in the endocardial lining of the heart oi as actual tuberculous vegeta- 

' Ztschr f him Medtcm, 1892, Band xxi 



228 


INFECTIOUS DISEASES 


tions affecting the valves or extending on to the walls of the chambers The 
tubercles when miliary in foim are usually subendocaidial, according to 
Benda They appear as minute white spots usually in the conus arteriosus 
of the right ventricle, and on section show the oidinary typical stiucture of a 
miliary tubercle In a recent case no giant cells were found even in a 
senes of sections, and the endothelium vas faiily intact over the tubeicle 
Actual tuberculous vegetations upon the valves have been found to contain 
tubercles and tubercle bacilli, and aie explained as due to the implantation 
of the bacilli upon the valves, but these cases ai e rare Any of these processes 
may aid m the furthei dissemination of the tuberculosis 

Vessels — Mention was made of the tuberculous affections of the vessels in 
speaking of the origin of general miliary tuberculosis Benda has pointed out 
that at least two distinct types of tuberculous lesion of the vessels may occur 
one m which the adjacent caseous tuberculous focus encioaches upon the vessel 
from without and finally may erode even to the point of dischaigmg caseous 
material into the lumen of the vessel, and the othei m which the bacilli are 
deposited from the blood stream upon the mtima and there produce a tubercle 
which becomes covered with a thiombus and may latei undeigo caseation 
and softening Such intimal tubercles are found m the aoita (Blumer, 
Longcope, etc ) and smaller arteries, as well as m the veins and thoracic 
duct An example was recently seen iii a pulmonary vein into which the 
rounded caseous mass projected from a branch which it completely occluded 
This caseous mass was in pait overgrown by endothelium and fibi oblasts, 
but it was entirely within the internal elastic lamella, there being only a 
slight new-giowth of epithelioid cells and occasional giant cells outside that 
membrane 

To these tvo foims Chiaii adds a thud, pioduced by the transpoitation 
of bacilli into the vasa vasoium It is possible that the adventitial tubei- 
culous lesions of the bloodvessels in tubeiculous meningitis may aiise in this 
way, but there is also the possibility that the lymjihatic channels in the 
vessel walls form the channel of infection, while Hektoenand othei s regaid 
these vascular changes as due to bacilli which ai c biought by the blood stream 
of the lessels themselves The lesion m such a case usually affects the 
adventitia moie intensely than the intima, and leads to the foimation of an 
eccentric caseating nodule m the Aessel wall PeiivascuHi tubeiculous 
lesions developed m the lymphatics of the vessel vail aie by no means 
uncommon in the lung in cases of extensive pulmonaiy tuberculosis, as 
recently emphasized by Letulle 

Probably the most frequent tubeiculous affections of the vessels belong to 
the first group Extension of the caseating pioccss takes place just as 
elsewheie, there being always a proliferation of epithelioid cells in advance 
In the case of small vessels, and indeed of all A'essels when the process ad- 
vances slowly enough, an obliterative endarteiitis arises, vliich protects 
the vessel by obliterating its lumen oi by thickening the Avail in fiont of the 
necrotic aiea In other cases the AAall of the A'essel is Aveakened by the 
erosion, and the picssure of the blood bulges it out at that point into a sort 
of small, aneurismal sac Such are the altered vessels Avhich on bin sting 
at this dilatation gne use to extensne pulmonaiy hemoiihagc If the 
Aessel be approached by a caseous area of small extent and completely 
encapsulated, as, for example, a lymph gland Avith central caseation, a 
communication may be established through the Aessel AA'all with this caseous 



TII-E P miOLOGY OF TUBERCULOSIS 


229 


area and an edd>in" cunent of blood -wdl ^^ash the tascous material 
out into the blood stieam Fuithei, il the visstl .itlackcd be a \ein ot 
considciable si/ie and not obhtciated, the tubciculoiis tascous mateiial 
may extend into its lumen, and by tiiimbhng a^\aysetf^cegleat quantities 
of tubeiclc bacilli into the passing blood, wliith aa ill oidmaiily go to pioduce 
an acute miliai} tubeiculosis 

Interesting and impoitant is the relation of tiibucic foim.ition in general 
to the smairbloodvcsscls It has bet n pointed out that a stimulus A\hich 
sets up the production of a tubcitlc nodule docs not excite the new formation 
of bloodvessels, and that those a\ hicli are by any thantc included m a tubcicle 
soon become obhteiatcd and disappeai Nevertheless, the oidmaiy tuber- 
culous granulation tissue shows the picsente of abundant capillaiy loops, 
indeed, it differs m no respect except the piesence of the tubercles and the 
tendency to caseation fiom othei granulation tissue 
Tuberculosis of the Digestive Tract — Mouth — The mouth is not 
commonly the scat of tubeiculous adeetions, still thcie liaAc been leported 
cases in wdnch the lips, gums, edges of the tongue and jialate, as avcU as the 
fauces, Avere infiltrated and ulcerated Tubeiculous ulcerations m these situ- 
ations have the same chaiactei as clsewdiere, they aie iiregulai m outline, 
with somew’hat mduiatcd oi undcimmcd edges, and with unccen base, fie- 
quently showing small, caseous nodules Such ulceration is cen r.iiely 
primary, but is usually secondaiy to pulmonaiy tubeiculosis In connection 
w ith caries of the teeth, how'e\ or, direct infection ma'\ occ ur and c\ en extend 
to the adjacent alveolai process of the jaw' As m the case of the nose, 
pharynx, and tonsil, lupous granulations which have extended fioin lupous 
areas on the skin may occui m the mouth 

CEsophagus — Tuberculosis of the oesojihagus is also exticmely rare, 
possibly largely because of the veiy smooth lining, Achich gives no foothold to 
organisms, and partly because ot the lapid transit of infectious materials 
Infection may, hoAvever, occur fiom food containing bacilli oi by sw'allowmig 
tuberculous sputum, and the lesultisthe production of nodules which ulcei- 
ate sometimes quite deeply The oesophagus may be iin olved in a gcneiah/cd 
miliary tuberculosis, but the othci impoitant type of tubeiculous lesion is that 
in wdnch it is affected from cvithoiit and encioachcd upon by an advancing 
tuberculous process, cither m adjacent lymph glands oi pei icardiuin or picuia 
Even caseous areas in the lung may become adherent and cause ciosion of the 
wall of the oesophagus 

Stomach — The rarity of tubeiculous ulccis of the stomach is attested by 
Simmond’s figures, in cvliich among 2000 autopsies upon tubeiculous patients 
8 cases w^ere found Glaubitt’s percentage is higher, as among 2237 such 
autopsies he found 47 cases of tuberculous ulcers Various explanations for 
the relative immunity of the gastric mucosa haem been given The antiseptic 
action of the gastric juice is apparently legarded as the most important 
factor, for, although as showm by the common ulcers m the intestine a\ Inch 
result from the deglutition of sputum in tuberculosis of the lungs, the bacilli 
are not killed by the gastric juice, they are still prevented from settling and 
OTowmg in the mucosa An injury to the mucosa affords chance foi such 
localization, and any lesion wdiich by pyloric obstiuction or in any other W'ay 
cimses a diminution in the acidity of the gastric juice wull set up conditions 
which greatly favor tuberculous infection 

Several distinct forms of tuberculous affection of the stomach occur 



230 


INFECTIOUS DISEASES 


As p.iit of a generalized miliary tiibciculosis nodules appear in the gastiic 
^\all, doubtless with consideiable fiequency Willins has desciibed m detail 
tubeiculosis of the stomach m which the walls weie thickly studded -with 
small tubercles Solitary tubei cles oi encapsulated tuberculous loci may occui 
raiely in the stomach wall, and one such case has been reported recently by 
Van Wart The stomach may also be approached fiom without and eioded 
by a caseous tubei culous mass Finally, there are the ulceiations, sometimes 
single, often multiple, which doubtless arise from the direct deposition of 
bacilli from swallowed infectious material The ulcerations are usually i athci 
small, with nregular outline, elevated, somewhat undeimmed, induiated 
maigin and rough base, sometimes with tubercles Such an ulcer may in 
rare instances e\tend deeply and erode a vessel Tubei cle bacilli may be 
demonstrated m these ulcers, although the diagnosis ismoie certainly estab- 
lished by a histological examination, for it is not impossible that tubei cle 
bacilli from the swallowed sputum may adhere to the surface of an ulcer 

Intestines — Tuberculosis of the intestine is both absolutely and relatively 
of frequent occurrence, the lesions being rarest m the duodenum, and occui- 
rmg more abundantly as one passes towaid the ileocmcal valve, wheie they 
aie only less common than tubei culous lesions of the lungs In the colon 
some evidences of tuberculosis are usually found whenever the small intes- 
tine IS diseased, and sometimes there are ulcerations there when there are 
none m the ileum 

As to the mode of infection it may be stated that, with the exception of 
certain cases, especially in children m whom the tubercle bacilli reach the 
intestine with such food as milk, they are neai ly all secondary to tuberculous 
infection elsewheie m the body and especially m the lungs When there is 
a cavity m the lung it is obvious that the swallowing of bacillus-holding 
sputum will tend to the infection of the intestine 

It IS an interesting question as to whether the bacilli may really be trans- 
ported like inert particles of dust through the intestinal wall without leaving 
a noticeable trace behind them Such is apparently the case in the lung, 
m which the bronchial glands may show the first lesion, although the bacilli 
are apparently recen ed by the way of the lung V on Behiing, indeed, makes 
great use of this possibility in his explanation of tuberculous infection in 
general m sucklings In suckling infants he shows that certain proteids 
may pass the intestinal wall unchanged, and, indeed, that such bacteiiaas 
anthrax may reach the circulation and give rise to a general septicaemia, 
although they pass along the intestinal tract of adult animals without being 
thus absorbed Reasoning in the same way he believes that m nevborn 
infants tubercle bacilli may be received m the milk, and pass directly through 
the intestinal wall to some distant tissue, perhaps the mesenteric lymph 
glands, where, after lying latent for a long time, they finally give rise to a 
spreading tuberculosis Von Behring apparently ascribes many cases of tubei - 
culosis developing m young people to the beginning activity of tubei cle 
bacilli, which taken m the food at an early period passed the intestinal 
wall without causing a lesion and remained latent m the tissues 

Infrequent and ill-defined as these cases of primary tuberculosis of the 
intestine are, those which are due to the sw'allowmg of tuberculous sputum 
are common and familiar The bacilli adhere to the mucosa and w'ork 
their way into its substance Orth holds that the lesions begin alwxays m 
the lymph nodules, but it is difficult to be sure that the bacdli do not occasion- 



THE PiTHOLOG'i OF TUBERCULOSIS 


231 


ally produce their fiist effects clsu\heic in the mucosa The first change is 
in the appearance of lubeiclc nodules in the substance ol the iiiUcosa and 
\ ery frequently in the b inphoid nodules oi Pcyci’s patches These tubercles 
soon become confluent and uiideigo caseation and soitenmg, and finally 
setting free their soft contents into the lumen of the intestine, an ulcer is 
left, the base of which is covered with necrotic tissue Such ulcers may at 
first be small and round and appear as punched-out cavities in the centres of 
enlarged solitary nodules Latei, w ith the extension of the tuberculous pro- 
cess, they become largei and ragged in outline, bounded alnays by a rather 
prominent, elevated inaigin which is sometimes undermined The base is 
still covered vith grayish, opaque material, but ficquently shows minute 
translucent or opaque, yellon isli nodules Such nodules are also to be seen 
and felt in the maigin of the ulcei, and by then confluence and continued 
caseation they occasion the extension of the ulcers The intestinal wall may 
be eroded to varying depths, and sometimes a tuberculous granulation tissue 
studded vith tubeicles is formed m the submvicosa and constitutes the base 
of the ulcer, at least foi a time In other cases, hilc this gi anulation tissue 
is to be found at the margins and m the substance of the n all, the muscular 
bundles are laid bare in the floor of the ulcei Indeed, nith lapid advance 
of the process the musculature maj be eioded and the intestinal wall finally 
perforated so that the contents escape into the peiitoneum, more often vith 
the ad^ ance of thd tuberculous ulcei ation theic is such a thickening of the 
intestinal wall and such formation of adhesions that if the vail is finally 
perfoiated the contents aic kept fiom the geneial peritoneal caMty by the 
adhesions Communication may be set up betv cen adjacent loops of bov el 
in this vay, or intiaperitoneal fa?cal abscesses or ecen a false anus may arise 
Tuberculous granulation tissue prone to caseation foims throughout the 
vail about the ulcer and in the subserous tissue nodules of the characteiistic 
t^qie soon appear, often in great numbeis, so that the position of the ulcer is 
plain from the outside on account of the \asculai gi anulation tissue and 
opaque or translucent nodules vliich accumulate opposite the ulceration 
The ulcers may come to occupv the position of Peyei’s patches, but more 
commonly their long axis lies moie transi ersely, and in many cases the 
ulceration extends especially transiciscly so as to finally enciicle the intestine 
and produce the so-called “giidle ulceis” This distribution obviously 
depends upon the course of the lymphatics in the intestinal wall, which are 
quickly invaded by the bacilli, and v hicli in that vay aid in the propagation 
of the tuberculous lesion, step by step, around the intestine In the larger 
trunks of the lymphatic channels in the intestinal vails, tubercle bacilli 
settle and produce tubercle nodules vhich may occlude the channels at that 
point Stagnation of the chyle then makes that lymphatic veiy conspicuous, 
and it IS not uncommon to see the lymphatic channels running away to the 
mesentery , from the region of the ulcer , studded with gray or opaque nodules, 
between vhich the canal is greatly distended with opaque, yellowish-white 
chj le Often these may be traced to the mesenteric l^rniph glands, vdiicli are 
themselves m such a case usually caseous or at least thickly studded with 
tubercles 


It seems probable that such a condition could readily occasion the abun- 
dant distribution of tubercle bacilli into the thoracic duct, vdiich, even if no 
lesion of the thoracic duct arose, could go far torvard the production of a 
generalized miliary tuberculosis 



232 


INFECTIOUS DISEASES 


In the lower end of the ileum, where stagnation of the fa tal material is 
^a^Oled, the iilceis become vciy Luge and confluent, so that often iieaily the 
whole mucosa is destroyed l^vcn the intcivcnmg mucosa m such cases is 
not unaffected, being usually the scat of a cataiihal inflammation, which m 
the colon gives use to tlic diaiiheca so common in this condition In the 
appendix, tiibeiculous ulceis of tire same cliaiactci may occui and even go on 
to pciforation In the colon the ulceiations aie moic commonly iiregular 
and lounded, although m ceitain cases they assume the giidlc foim The heal- 
ing of such ulceis is usually mteiiujjted, if it begins at all, by the death of 
the patient, but sometimes the advance of the process ceases and scairing 
of the cleansed ulcei begins The flooi of the cavity contiacts so as to 
bring the oieihangmg epithelial maigms close togethci oi e\en to push them 
upwaid into the intestinal lumen Some new-giowth of epithelium fioin 
these edges may take place, but the dc\clo]nncnt of scai tissue is usually so 
great as to foim the most piomment featuic and to cause actual stenosis of 
the intestine iihen the ulcer is an extensne one of the girdle form 

The extension of tiibeiculous ulceiation thiough the iiall of the intestine 
commonly gives use to f.ecal abscesses in the ncighboi mg tissue, oi, if the 
conditions are favoialilc, to the extension of the bun owing to another canty 
or even to the outci suiface of the body Thus, tiibeiculous infection of the 
mucosa of the anal poition of the icctum may cause in time the foimation 
of a peiirectal abscess, i\hich on luptuiing at the anus pioduccs a fistula 
The gieat majoiity of anal fistuke have been shoiin to be of a tuberculous 
natuie, the infection aiising fiom bacilli mIiicIi haic been swallowed oi which 
come fioin secondaiy iilccis liiglin up, the localization of these is faioied 
by the excoiiations of the mucosa of the sjihmctci region, iihich aic so 
common The canal is usually lined with vciy abundant tiibeiculous 
granulation tissue Tuberculosis of the omci may also appeal m the foim 
of lupous gi an Illations which have extended fiom the adiacent skin suifaccs 
or even as one of the laiei papulai tubeicuhdes of the skin ^ 

Salivary Glands — Tubciculosis of the sahvaiy glands, foimcily thought 
to be exticinely laie, has been rcpoited icccntly m a laige numbei of cases 
The paiotid is most frequently aftcctcd, the siibmaxillai y less often, and up to 
the present thcie is no icpoit of a case of tuberculosis of the sublingual gland 
Infection may occui ( 1 ) by vay of the gcncial blood sticain, m 11111011 case 
the salivai}" glands become the scat of miliary tubciclcs, just as do the 
other organs, 01 may show a moie extensive cascatmg infiltiation, ( 2 ) 
infection may occur along the course of the duct from the mouth, especially 
when favored by the presence of caucus teeth, and ( 3 ) theie mav be 
extension of a caseous process from adjacent tuberculous lesions m lymph 
glands, bones, etc The change in the gland m most cases appeals either 
in diffuse form, with caseous infiltration and softening or subsequent scarring, 
or as a focal lesion, forming a caseous, encapsulated nodule 

Pancreas — ^The pancreas seems especially resistant to tuberculous infection, 
and references to tuberculous lesions other than miliary tubercles are hardly 
to be found Lefas describes tivo cases, but thinks that m those, too, the 
tuberculous process is really an affection of embedded lymph glands 
ParenchjTnatous degeneration and interstitial scleiosis of the pancreas are 
often observed m cases of v idespread tuberculosis 

Liver — In sharp contrast v ith the pancreas stands the liver, in which 
tuberculous lesions are extremely frequent, being estimated bySimmonds as 



THE PATHOLOGY OF TUBERCULOSIS 


233 


occur! uio- in 82 pu cent of the cases of tnbeiculosis winch he studied The 
lesions afe, hoii evci , seldom extensive, but consist ol the most part m exti emelj 
minute tubcicle nodules, scaieely visible to the naked eye, but which tend 
to become eonfliient, so as to foim small oi miliaiy, caseous nodules These 
nodules have the chaiacteis typical oi the ultimate tubercle, as described 
above, and appeal usualb m the peiipoital connective tissue, later invading 
the substance of the lobule They lesnlt fioin a tiansportation of bacilli 
by the blood stream, which can take place citliei through the hepatic arter}^ 
m which case they foim pait ot a gcneraii/ed distribution, oi they may be 
secondary to lesions of the intestine oi spleen, winch distribute then bacilli 
into branches of the poital ^cnl and thus into the liver Klcbs suggested 
that the bacilli mat be earned along the lymphatics into the hvei, but this 
seems impiobablc The tubeicles aie sniallei in the Incr than elsevheie, 
probably because of the unfa voi able action of this tissue of the liver upon the 
growth of the bacilli, although the attempts to deteiminc this effect experi- 
mentally hate so far failed In the coiiise of then growth they compress 
and destioy a considciable poition of the hvei tissue and suiiound them- 
selves with seal tissue It the jiiocess last a sufficient time a definite cirrhosis 
of the In 01 mat arise, mtihich the changes are quite analogous to those 
of the ordinary" enrhosis, the tubercle bacilli constituting the injurious 
agency which destroys many In ci cells, and vhile tliese aie leplaccd by scar 
tissue, stiis up the icmammg hvei cells to a compensatory hypertiophy 
Anatomically, tliepiescnce of the tubeicles may be the only point ot distinction 
between these two conditions 

Largei or sohtaiv tubeicles may laicly occiii m the Inei, often near the 
capsule, sonietnnes m relation with the pciiiioital connective tissue, eom- 
monei than these aie the so-callcd gdl-duct tubeicles, as to the origin of 
which there has been so much debate hlany of the miliaij tubercles 
mentioned abo\e may be bile-stained, but these gall-duct tubeicles arise 
near the bile duets and dnectly invade then wxills, so that there is soon an 
open communication between the caseous ccntic of the mass and the bile 
ducts, they assume the ajipcaiance of abscesses w itli gicen, seniifluid contents 
It IS probable that these tubeicles arise fiom bacilli bi ought in by the 
stream and peihaps tiansniittcd back again by the lymphatics in the wall 
of the bile ducis, and that they develop outside the bile duct, iniadmg its 
w’all from without Ncveithcless, attempts have been made to show' that 
they arise fiom the ascending infection ol the bile ducts b} bacilli from the 
intestine, and that they extend from the epithelial lining of the duct outw'ard 

Gall-bladder — Tuberculosis of the gall ducts and of the qall-hladdei have 
been described in association wuth gallstones, the whole lining of the gall- 
bladder having been caseous m one instance 

Tuberculosis of the Peritoneum — anons types of tuberculous periton- 
itis occur, conditioned appaiently by the virulence and number of the bacilli 
and by their mode of entry, for wdiile the less virulent seem to produce miliary 
tubercles and a great outpouimg of fluid, the moie virulent set up a lapidly 
destructive caseating process, w ith exudation of fibrin and many cells The 
portal of entry for the organisms may be the blood stream or the intestinal 
w'all in cases of tuberculosis of the intestine, or the Fallopian tubes in cases 
of genital tuberculosis or any caseous focus wdiich may extend to the perito- 
neum In all of these instances it is therefore secondary to some other lesion, 
but it seems to have been fairly shown that m some instances it may be the 



234 


INFECTIOUS DISEASES 


only tuberculous lesion found, and it must be supposed that the bacilli are 
brought to the peritoneum ■without causing any extensive lesion elscwheic 

Anatomically, we may find minute miliary tubercles upon the peiitoneal 
surfaces and hidden m the folds of the omentum iMthout any lemarkable 
accumulation of fiuid or exudation of fibiin The peiitoneum ovei them 
looks quite smooth In other cases theie is a thin exudate of fibiin about 
them and a quantity of cleai oi slightly turbid fluid is present m the cavity, 
sometimes a gieat quantity sufficient to float up the intestines, which are then 
quite separate and free In still other cases a rather vascular, giayish, trans- 
lucent, tuberculous granulation tissue, thickly studded with tubercles and 
giving rise to friable adhesions between the intestinal coils, appeals on the 
peritoneal surfaces These adhesions aie most marked when there is no 
accumulation of fluid m the peritoneum, and indeed they may become quite 
umveisal and bind the whole contents of the peritoneum into a dense mass 
which can hardly be disentangled without teaiing the intestines The 
omentum m such a case becomes tightly rolled and folded upon itself, so as 
to assume the form of a film, solid mass of tissue, which stretches acioss the 
abdomen vith the transverse colon It is mottled with yellow and giay 
patches, which correspond with the alternating tubercles and remnants of 
fat In course of time the tuberculous adhesions become the seat of exten- 
sive caseation and it is not uncommon to find secondarily formed spaces and 
canals burrowing between the coils of intestine in these adhesions Fre- 
quently, such a matted condition of the peritoneal organs is the result of 
discharge of tubercle bacilli from intestinal ulcers, and the perforation of 
such ulcers into the adhesions may give rise to frecal abscesses between the 
loops of intestines or to abnormal communications between adjacent loops 

Localized tubeiculosis of the peritoneum is not uncommon, the bacilli 
apparently affecting the parts of the peritoneum, into which they can sink 
and rest quietly, such, for example, as the pouches of the pclyis and hernial 
sacs, which are very often tuberculous On the other hand, the couise 
of partrcles rn the rntact peritoneal cavity is predominantly to'ward the 
diaphragm, and hence it is common to find tubercles deyeloping m gieat 
numbers on the under surface of the diaphiagm 

Healing may occur, especially after operative interference, vhen the tuber- 
cles become gradually smaller and converted into a dense fibrous mass, 
apparently with the death of the bacilli Whether the dryer types of peri- 
toneal tuberculosis with extensive adhesions and caseation can heal is doubt- 
ful It IS m the cases with well-marked ascites that the best results have been 
obtained from operation Evei y possible suggestion has been made in explana- 
tion of this fact, such as stimulus of the operation, exposure to air, production 
of venous stasis, relaxation of the tissue and improved circulation, exudation 
of antibacterial serum after the operation, etc What seems the most 
plausible explanation is put forward by A E Wright, who finds that the fluid 
in these cases is poor m opsonic power as compared v ith the blood plasma 
of that patient, ? e , it has little power to aid the phagocytes to engulf the 
tubercle bacilli On its removal, liorrever, new fluid, the blood plasma 
itself, enters the peritoneum, and by its high opsonic power greatly fayors 
phagocvtosis 

Healed types of peritonitis are sometimes obseryed, as in the instances in 
■v\hich the peritoneum over the Iner, spleen, etc , is greatly thickened, even to 
the extent of contracting and compressing the underlying organ This in 



THE P VniOLOGY OF TUBERCVLOSIS 


235 


association ^^lth similai changes in the pciicaiclium and pleura is usually 
leo-aided as tubeiculous, but pcihaps not upon \eiy conclusive evidence 
Healed caseous nodules hanging by long hollow stalks tiom the peritoneum 
were deseiibed by the wiitei ^ 

Genito-urinary Tuberculosis — Kidneys — Tuberculosis of the kidney 
may assume videly difteient foims accoiding to the mode of mtioduction of 
the bacilli and othei less v ell-defined f actoi s Only a few channels seem open 
to the bacilli m then entrance into the kidney, and of these the most obvious 
seem to be the blood sticam and the uieteial tiact and pehis It is true 
that Boirel claims invasion b'^ way of the hmphatic channels, but this seems 
haidly plausible It is, hov evei, quite possible for a neighboiing tuberculous 
lesion to extend to the kidnej" and pioduce a moie or less localized tubeiculosis 
of that oigan 

In association v ith tuberculosis of othei organs in Inch there has been 
some dissemination of the tubercle bacilli bj' the blood stream, it is not 
at all uncommon to find small tiibeicles scatteied throughout the coitex or 
in the pyramidal poition These may be lery small and tianslucent, but 
moie frequenth thej arc conglomeiated into masses whicb stictch m lines 
between the tubules and vertically to the sin face of the kidney, and are 
soon caseous and opaque m the ccntial part The> may sometimes reach 
a considerable size and undergo a central softening They may be foimed 
b^ the lodgement of tubeicle bacilli anpihcie in tbe tissue, lust as mother 
oigans, but Benda has described especially the foimation of tubercles about 
glomeruli m w Inch he finds tw isted rolls of bacilli so bulkv as to block the 
glomerular capillaiies About these, after a shoit time, an emigration of 
leukocytes occurs and later w ith destruction of the glomciulus the loimation 
of a surioundmg area of epithelioid and giant cells This t'^pe of icnal 
tuberculosis is of lelatneh slight importance, since it is usually associated 
with much more serious and destructive tuberculous lesions m other oigans 
In the kidneys of patients d>ing of chronic phthisis, how'evei, one may some- 
times find seals and dcpicssions which by some aie regarded as the remains 
of tubercles Interesting and important m this connection is the occurrence 
of a chronic nephritis, w'lth extensne degeneration of the epithelial cells 
and increased permeability of the kidney, which is appaientlj due to the 
action of a circulating toxin (Landouzy and Bernard) 

There is another f^qie of tuberculosis of the kidney which is usually 
associated wnth tuberculous lesions of the rcmaindei of the genito-urinary 
system, but not necessarily with any general or disseminated tuberculosis 
This IS a localized process not necessarily affecting both kidneys, as m the 
other form, but beginning usually in the pyramids, wdiere they he adjacent 
to the pelyis and thence eating out the substance of the kidney until m some 
cases little of its tissue is left 

Its mode of origin is somew^hat doubtful, although until lecent years it had 
been quite generally held to be an ascending infection fiom tubeiculous 
lesions of the remainder of the genito-urinary system, analogous to the 
pyelonephritis wdnch follow^s urethial obstruction and cystitis Recently, 
many writeis, especially surgeons, maintain that it, too, is the result of the 
dissemination of the bacilli by the blood stream Efforts to produce the 
condition experimentally have been almost entirely unsuccessful, although 


‘ Johns IJophins Hospital Bulletin, 1901 



236 


INFECTIOUS DISEASES 


Baiimgarten by ligating the meter with a tliread infected with the bacilli 
has produced a similai affection Injections of bacilli into the bladder or 
even into the ureter hav'e usually failed, but the exact degree of obstruction 
necessary to success in those cases seems not to have been pioduced Pels 
Leusden has recently attacked the problem from the other side and attempted 
the production of tulseiculosis of the kidney by the injection of bacilli directly 
into the renal artery of one side His results ai e as yet not convincing 
The age of the various lesions encountered m any case of gemto-urinary 
tuberculosis are important in determining then relation to one another, and 
still the analysis of any considerable numbei of cases will reveal the great 
difficulty m di awing any definite conclusions upon this point In many 
instances the process is so advanced m the kidneys, bladder, prostate, and 
epididymis that it is impossible to say which was first affected 

In the Johns Hopkins Hospital 36 cases have been studied at autopsy, in 
which one form or other of tuberculosis of the male gemto-uimary system 
occurred, of these 19 showed tubeiculous changes in the kidneys Of these 
19 cases theie were only 2 wdiich did not show coincident lesions of the 
genitalia, the prostate and epididymis being often the seat of lesions In 2 
cases there was tuberculosis of the kidney, in 1 case with tubciculosis of the 
ureter and bladder, in the other without eithei, and m both without changes 
in the genitalia In none of the other cases could it be definitely stated that 
the lesions m the kidney w ere more advanced than those m the prostate or 
epididymis In 13 of the 19 cases there w^as more or less extensive tuber- 
culosis of the bladdei, although the intensity of this lesion coi responded only 
m a geneial w ay w ith that of the piocess m the kidneys or in the genitalia 
Of the 36 cases, 29 show'ed tuberculous lesions m one oi both epididymes, 
and 22 had caseous areas m the prostate Of the 34 cases which showed 
tuberculosis in some part of the genital tract, in 19 the lesion seemed to be 
oldest in the epididymis, in 9 it was clearly most advanced in the prostate, 
while in 6 it had developed to about the same degree in both The testicle 
w as involved in 16 and the vesiculie seminales in 17 cases It seems entirely 
probable that the infection of the kidney, at least in men, may result fiom 
the tianspoitation of the bacilli from an older lesion affecting the genital 
tract and bladder, in spite of the objection that it is difficult to explain this 
transportation against the stream of uiinc in the ureter The mechanism is 
quite the same as m the cases of ascending pyelonephritis following infection 
of the bladdei, and the entry of the oiganisms into the ureteral orifice is 
sometimes facilitated by the destruction of the soft tissue which guards 
(valve like) that orifice Hasmatogenous tuberculosis of the kidney of this 
localized type is of course easily conceiv'able, but it would m most instances 
be necessary to admit that a luematogenous infection of the epididymis or 
prostate had also occurred some time before In v^omen the relation to 
genital tuberculosis is much less clear and there is less objection to the assump- 
tion of a haematogenous origin However, it is the growing tendency among 
surgeons to regard these lesions in the kidney in men also as hasmatogenous 
m origin, and it may w'ell be that the autopsy material alone does not furnish 
a fair v lew of all sides of the question 

The condition is less often seen at autopsy in w'omen than m men (6 cases 
in w omen to 19 m men in this series), but the surgeons see many more cases 
which are diagnosed as tuberculosis of the kidney in women It is most 
often unilateral, but m many cases it affects both kidneys and ureters 



THE PATHOLOGY OF TUBERCULOSIS 


237 


The lesion seems to begin m the papillary portion of the pyiamid, ^^he^e 
in one of this series quite isolated, eioding tuberculous lesions were to be 
found, m the complete absence of tubeiculosis *of the rest of the uiinary 
tract Such cases speak stiongly foi the tiansportation of the bacilli to the 
kidney by the blood stieam Usually, when one examines the kidneys the 
tuberculous piocess has aheady involved the pelvis and some part of the 
ureter and has ulcerated av ay portions of the pyramids and adiacent tissues, 
hollowing them out into ragged caiities widely open into the pelvis and lined 
witli a thick opaque layei of caseous material Tubercle nodules may be 
visible in the vails of these cavities, and the} may be also scatteied about m 
the cortex of the kidney Usually the pelvis is hyperiemic and covered 
with a partly caseous granulation tissue, oi it may show extensne shallov 
ulcers and a much thickened and indurated v all In these more advanced 
cases the pyramids may be completeh destioyed and the eavities extend 
fai into the cortex, so that onh i thin la}ei oi coitical tissue peisists In 
ad^ance of this process theie is always the ncv foimation of tuberculous 
granulation tissue, and vhen the kidney substance is completely destroyed 
this may still foim the vail of a ca\ity, vhieh is sometimes much laigei 
than the kidney itself Indeed, in a lecent ease the large, tumor-hke mass 
found in the position of the kidney plo^ed to be composed of a group of sacs 
matted togethei and containing a caseous material, but only lemotelv 
resembling the kidney in form, all the kidney substance having been destroyed 
Occasionally, the process may make e^en gieatei strides and giie rise to a 
perirenal tubeiculous abscess oi to a fistula extending outvaid to the skin 
When the patient’s power of resistance is great theie maybe a more efiective 
pioduction of scar tissue and the piocess of caseation may be less rapidly 
destnictne One specimen of this type showed an cnoimous enlargement 
of the kidney, to which the thickened capsule v as densely adheunt, the v hole 
organ was practically con^ cited into a translucent fibrous tissue, in which 
veie numerous pyramidal, lagged, caseous aicas The uietei was enoi- 
mously thickened, the lumen being piactically obhteiated, but choked with 
caseous material Anothei specimen shoved lounded, caseous areas in 
the substance of the kidney', well encapsulated and shaijily separated fiom 
the suiroundmg kidney substance In still another theie v as great contiac- 
tion of the kidney about a moitai-hkc, caseous mass which filled the pelvis 
and the eroded cavities in the kidney substance, the metei being obliterated 
The presence of othei healed and healing tubeiculous lesions makes it 
probable that this was a tubeiculous piocess and not meiely a softened 
renal calculus 

Pelvis and Ureter. — ^The lesions in the pelvis and uietei consist in the 
formation of tuberculous granulation tissue which undcigoes caseation and 
ulceiation, thus excavating the tissues of the wall The walls of both 
pelvis and ureter usually become much thickened, so that the uietci may 
readily be palpated as a thick, firm cord Of special significance is the 
damage pi oduced by the ulceration of the mucosa about the ureteral orifice 
m the bladder, which destroy's its valve action and lenders leguigitation 
from the bladder possible 

Bladder The bladder may show a vaiiety of lesions Miliary tubeicles 
may occur in the mucosa, usually about the trigonum oi at the beginning of 
the prostatic urethra In other cases slight erosion of the mucosa may' be 
marked by the presence of abundant sticky', mucous exudate o^ ei the w'hole 



238 


INFECTIOUS DISEASES 


surface Widespread ulceration may occur either in the form of minute, 
closely set erosions covered with caseous material, Avhich give the appeal ance 
of a diphtheritic exudate, or as shallow, irregulai, ragged ulcers which destroy 
wide areas of the mucosa These are sometimes deeper and erode the mus- 
cularis, even perforating the whole wall, when they usually give rise to fistulaj, 
extending to the skin oi elsewhere By maiked conti action and thickening 
the bladder may be reduced to a very small size Whether tubeiculous 
cystitis can arise primarily is doubtful It seems probable that it usually 
depends upon tuberculosis of the prostate and genitalia, although even if the 
lesion of the kidney be held to be the result of the tuberculosis of the bladder 
there is no reason why it in turn should not become more extensively infected 
from the kidney 

Urethra — Tuberculosis of the urethra is very uncommon and the mucosa 
seems to have a certain degree of immunity from the invasion of the bacilli, for 
there are surely quantities of tubercle bacilli poured over it at intervals in every 
case of genito-urnary tuberculosis In two such cases recently seen at autopsy 
there was extensive, almost continuous, ulceiation of the urethial mucosa, 
the ulcers extending quite to the meatus The flat ulcers were covered v ith 
a thick, caseous layer, and extended only into the underlying connective 
tissue Tuberculous ulcerations of the glans penis and prepuce were not 
present in these cases, but have been frequently reported, usually as a conse- 
quence of infection during the ritual of circumcision from the saliva of the 
person officiating The possibility of infection by coitus with a woman with 
genital tuberculosis has of course been suggested, but Franck in a critical 
review of the literature could find no ci edible instance of this 

Prostate, Seminal Vesicles, Vasa Deferentia, Epididymes, and Testicles — 
The prostate, seminal vesicles, vasa deferentia, epididymes, and testicles 
are frequently tuberculous The tubercle bacilli are brought to them either 
by the blood stream or by direct invasion from the urinaiy tract The 
weight of evidence seems to favor the hiematogenous origin of genital tubei- 
culosis m the male from an older focus elsewhere, the point of predilection 
being commonly the epididymis, although both Krzywicki and hlahnski 
make the statement that the prostate is m the great maprity of cases first 
affected, the infection of the seminal vesicles, vasa deferentia, and epididymes 
being secondary 

Tuberculosis of the testicle is less frequent, and usually is distinctly the 
result of extension from the epididymis When the lesions do occur there 
they appear as grayish nodules gradually undergoing caseation, oi they may 
take the form of a gradually advancing aiea of caseation continuous vith 
those in the epididymis The tubercles foim in the testicle m and among 
the tubules and show the characteristic structure In the epididymis the 
lesion begins ithin the tubules and leads to the destruction of their epithe- 
lium, the tubules becoming greatly thickened and distended with a caseous 
debris in which fragments of nuclei are seen Definite tubercles may develop 
m the neighborhood, and it is not long before in the greatly enlarged epididy- 
mis a coalescent, caseous mass represents all that is left of the structures 
This may extend until adhesions with the skin of the scrotum are produced, 
and It IS not uncommon to see sinuses leading from the skin into the cavity 
of the muth altered epididymis and testicle, which by that time has usually 
been incaded The tunica lagmahs may become infected and react as the 
peritoneal surface would under similar circumstances The vas deferens 



THE PATHOLOGY OF TUBERCULOSIS 


239 


becomes filled and choked with caseous material, which is largely due to the 
infection and ulceiation of its walls In the seminal vesicles the infection 
may finally bung about veiy great distention of the cavities with an opaque, 
caseous mateiial, disintegration of the Avail may take place, but is not usual 
Destruction of the tissue of the pi estate is, however, not infrequent, caseous 
aieas appearing thiough the substance of the gland, and by their liquefaction 
often leaving it riddled with cavities 

Female Gemtaha — Tuberculosis of the female genitalia has been de- 
scribed as a primary affection, but it is usually found as a sequence of tuber- 
culous lesions elsewhere 

The cxiernal gemtaha are sometimes affected, lupous-like nodules of a 
bluish coloi , prone to ulceration, being formed about the labia and introitus 
The vagina is relatively A’^ery lesistant, and lesions there are practically ahr ays 
in association with otheis of the uterus and tubes There may be isolated 
tubercle nodules scatteied in the mucosa, or, as m a case described by David- 
sohn, a tuberculous granulation tissue thickly flecked aa itli caseous areas 
may line the canal In tlie utcnis itself the mucosa of the body is by far 
more commonly affected than that of the cervi\ oi portio a aginahs The 
lesions maj'^ be m the form of discrete nodules in the mucosa, but more com- 
monly there is a AAidespread destiuction of the mucosa, AA'hich is conA^eited 
into a thick, caseous layer, Avhich extends deep into the muscle Sometimes 
in case any obstruction to the cervical canal is present a quantity of necrotic 
and fluid mateiial ma} accumulate m the cavity of the uterus, producing 
a sort of tuberculous pyometra Tumor-hke nodules of cauhfloAver-like 
form have been observed m the cerAux and about the extei nal os, sometimes 
giving rise to difficulty m diagnosis on account of then resemblance to cai- 
emomatous groA\ ths The Fallopian tubes, of all parts of the genital tract, 
are most commonly tuberculous The usual lesion consists in gieat thicken- 
ing and rigidity of the Avail, Avith destruction of the Avhole mucosa and the 
caseation of the lining laj er of tuberculous gi anulation tissue The complete 
occlusion of the tubes by this material accounts for the almost invariable 
sterility of Avomen with genital tuberculosis Both in the tubes and uterus 
proliferative changes in the epithelium in course of deA’^elopment of the 
tuberculous lesions haA'e been obserA^ed, and have greatly complicated the 
histological appearances 

The ovanes are less commonly tubeiculous When they aie affected 
the lesion consists of caseous aieas dcA^eloped m the stroma and usually 
not connected Avith the follicles Tuberculosis of cysts in the ovary has, 
hoAiever, been obseived 

ExtensiA'e adhesions about the tuberculous peh ic structures and a tuber- 
culous peritonitis are very common accompaniments of the condition 
HoAACA'er, tuberculosis of the bladdei and kidneys occurs in this connection 
hy no means so frequently as in genital tuberculosis in males This is easily 
understood on account of the less intimate anatomical association of the 
organs in the female 

As to the pathogenesis of the condition the question arises at once as to 
the mode of extension of the infectious agent There aie those who regard 
the direct infection of the vagina and uterine caAuty by the use of infected 
instruments, etc , and by coitus Avith a tuberculous man as a prominent 
factor, but Avhile such a possibility cannot be denied, the Aveight of evidence 
IS not in favor of this vieAv even in married Avomen, to say nothing of virgins 



240 


INFECTIOUS DISEASES 


and children, in whom the condition frequently occuis Numerous efforts 
to produce tuberculosis of the uterus and tubes by the expeiimental inocula- 
tion of tubercle bacilli into the vagina of animals have sometimes sueceeded, 
but Baumgarten, m a recent paper ivith Basso, claims that although tuber- 
culosis of any portion of the genital tiact may be produced by inoculation, 
an ascending genital tuberculosis does not occur Tuberculosis of one tube 
or cornu does not infect the other, and evtension is always in the direction of 
the stream of secretion Hegai speaks of an ascending and a descending 
genital tuberculosis, explaining the ascending form as due to the transmission 
of the bacilli by the lymphatics m the para-vagmal and para-uterme connective 
tissue The descending form, he thinks, may aiise from the entiance of 
the bacilli into the fimbriated end of the tubes from a peiitoneal tubeiculosis 
or even from intestinal ulcers from which the bacilli have leached the jieri- 
toneum Most authors, however, raise objections to the idea that tuberculosis 
of the tube may be secondary to tuberculous peritonitis, since the peritonitis 
IS usually less advanced than the tuberculosis of the tube, and very often is 
entirely lacking 

The bacilli may be cairied to these oigans by the blood stieam from an 
older focus elsewhere, and this idea is the most widely accepted Why the 
tubes should be most frequently the seat of the lesion and show moie exten- 
sive changes than the rest of the tiact is not clear, but it may peihaps be 
regal ded as a specially favorable tissue for the growth of the bacillus 
Tuberculosis of Various Glands. — Breast — ^The breast was foimcily 
thought to be immune fiom tubeiculosis, but is now known to be affected not 
infrequently Several possible paths foi the entrance of the bacilli into the tis- 
sue have been pointed out, of which the blood sti earn and efferent ducts are 
perhaps most important Cases have been reported in v Inch canes of the ribs 
or a tuberculous pleurisy have by extension given i ise to the infection, and 
otheis have believed that m cases m which the axillaiy glands were s^^ollen 
and caseous the infection may have travelled backwai d along the lymphatics 
from those glands It seems moie piobable, howevei,that the tuberculosis 
of the axillaiy glands may have been m those cases, as m so many otheis, 
secondaiy to the tuberculosis of the breast The disease has not been 
observed in children before puberty It occui s chiefly m women, but has been 
seen in men It may affect all ages, but is much favored m its development 
by pregnancy and lactation, and most frequently affects women m the pi ime 
of life 

The lesions are found m the form of discrete, caseous nodules, usually m 
the interstitial tissues, or as large, abscess-hke areas m which the semifluid 
content has resulted from the destruction of a great deal of tissue The 
tubercle formation and caseation are exactly as elsewhere The acini are 
encroached upon and gradually grovn through and obliterated Similarly 
the lumen of the ducts may become occluded Such rather small nodules 
may run a slow course and be healed, at any rate m part, and it is on that 
account that tuberculosis of the breast is so often ovei looked The larger 
tuberculous lesions cause the breaking down of acini and interacinar tissue, 
and ma-^ sometimes produce sinuses ’\\hich extend to and througli the 
skin Such changes have been frequently desciibed under the name of 
“cold abscess ” 

Spleen — Tuberculosis of the spleen, notwithstanding that there have been 
descriptions m the literature of a primary affection, may be regarded as 



THE PATHOLOGY OF TUBERCULOSIS 


241 


always secondary to tuberculous lesions of other organs and the mode of 
entry of the organisms is doubtless always by the blood stream In practi- 
cally all cases of disseminated tubeiculosis tubercles in the spleen are found 
These may be mihaiy, but it is %\ell lecogmzed that such lesions tend to 
reach a relatively great size in the spleen as compared with the liver and 
various other organs Such conglomerated tubercles rapidly undergo 
caseation and stand out prominently against the surrounding dark-red pulp 
as lounded, opaque, yellow masses In one specimen the caseous tubercles 
reached a diameter of 2 cm , and were quite sharply outlined by a gra>, 
fibrous capsule Most often they are small and extremely numerous, 
projecting from the splenic pulp as gray or opaque, yeJlow nodules Their 
histological character is the same as m other tissues As they are usually 
associated v ith an acute splenic tumor, they give rise to a considei able enlarge- 
ment of the spleen, and m the cases of so-called piimary splenic tuberculosis 
this enlargement has been especially conspicuous and has led to the idea that 
the spleen was the first tissue to be affected 

Thyroid Glands — ^The thyroid, long held to be almost immune from tubei- 
culosis, has been shown m lecent jeais to possess no such complete immu- 
nity, although it IS ti lie that tuberculous lesions of the thyroid are uncommon, 
primary tuberculosis of this gland being especially rare In autopsies on 
tuberculous individuals Chian has found in 100 casts 7, Fi ankel in 50 cases 5, 
' Simmonds in 100 cases 3, and Hegai in 1563 cases 57 cases of tuberculosis of 
the thjToid It appears usually in the foim of scatteied miliary tubercles m 
the couise of an acute general mihaiy tubeiculosis, but sometimes as a local- 
ized tuberculosis ivith caseous nodules These have i n general the character 
of such lesions as seen elsewhcie, and may, as in Peteison’s case, reach con- 
siderable size They are geneially pooi in tubercle bacilli Tomelhni has 
recently made a minute study of the pathogenesis of tubeiculous lesions in 
this gland experimentally pioduced by injection of bacilli into the caiotid 
in rabbits, and finds that they develop essentially as m othei tissues He 
concludes that the thyioid exhibits no special immunity in this infection 

Roger and Gamier and othei more leceiit wiiteis, including de Queivain 
and Ins student Saibach, ha^e emphasized the occuiieiice of a geneial 
sclerosis of the thyioid in cases of tubeiculosis m which theie aie no actual 
tuberculous lesions of the gland itself This injuiy to the epithelium and 
resulting scleiosis aie held to be the effect of the action of ddfusiblc toxins 
produced hy the tubeicle bacilli in the affected lungs oi elsewheie No 
symptoms have been noted m any of these cases, but Cainot and Dehon 
have lecently leported a case of tubeiculosis of the lungs wnth tetaii} and 
death m convulsions, m which they found caseous lesions of the paiath^ioid 
glands at autopsy 

Adrenal Glands — ^The adienal glands show" no such lelative fieedom from 
tuberculous lesions, but are frequently affected, scattered mihaiy tubeicles 
being perhaps less often described than largei, caseous areas, wdnch produce 
great destructive changes Isolated tuberculosis of the adienals has been 
described several times, probably as the result of some inconspicuous primaiy 
lesions, but it foims, as a rule, part of a moie generalized affection The 
caseous areas appear as opaque, yellow’ patches m the enhiged gland, involv- 
ing both cortex and medulla, and not infrequently including the associated 
s>'mpathetic nerve structures In some cases there is an attempt at encapsu- 
lation, and very large masses of necrotic material may extend beyond the 

VOL III — 16 



242 


INFECTIOUS DISEASES 


normal limits of the gland, sui rounded by fibrous tissue, then lelations being 
recognizable only by the peisistence of small poitions of the gland substance 
In other cases the tuberculous lesion may be shrunken to a small, scarred, 
calcified aiea, buried m adhesions with suiioundmg organs 
Interest in tubeiculosis of the adienals depends chiefly upon the symptom- 
complex of Addison’s disease so frequently associated with it It is quite 
true that any other change which destroys the adrenals gradually will bung 
about this disease, and, fuithei, that there are many cases of tuberculosis of 
the adrenals in which a great part of the gland is destroyed without any such 
symptoms , so that it is really not known which of the various constituents 
of the gland are responsible for the symptoms Apparently their appear- 
ance m characteristic form depends upon the gradual destruction of the 
gland, and de Vecchi has reproduced them by the injection of tubercle 
bacilli into the gland, which by their destructive influence gradually con- 
verted the glands into caseous material Extirpation of one gland is 
without effect, but extirpation of both leads to the death of the animal 
within a very few days, or even hours, ivith symptoms of an intense intoxi- 
cation Couzm has described an acute form of Addison’s disease which 
IS fatal within a few days, and which is without the well-known bronzing 
of the skin, but shows the intense toxic and nervous symptoms Evi- 
dently this IS dependent upon the more rapid destruction of the glands by 
the tuberculous process, which, as Couzm shows, prevents the normal neu- 
tralization of a poison which he thinks is produced by the activity of the 
muscles, and which then appears in the blood The theoiy of Wiesel that 
the appearance of these symptoms depends upon the destruction of the 
whole chromaffine system, which is constituted by cells in the sympathetic 
ganglia and in the medulla of the adrenal, while the cortex of the adrenal 
IS not concerned is tempting, and goes far to clear up the inconsistencies of 
various cases, but his observations have not yet been widely confirmed, and 
are disputed by Karakascheff 

Tuberculosis of the Central Nervous System —While cases of tuber- 
culous affection of the brain and meninges are of rather common occurrence, 
they form a relatively small proportion of all cases of tuberculosis Only on 
the supposition that some hidden tubeiculous lesions elsewhere haie been 
overlooked, or by the possibility of transmission of tubercle bacilli through 
the ethmoid plate of the nose, can such lesions be thought of as primary 
or unconnected with other tuberculous disease m the body In the great 
majority of cases the primary affection is found m tuberculosis of the lungs 

Brain — ^The most common form of tubeiculosis of the brain is that which 
affects chiefly the meningeal covering, the pia of the base of the brain being the 
portion which usually shows the most extensive alteration Nevertheless, the 
tubercles there are very often associated v ith others in various parts of the 
brain It is thought that the tubercle bacilli are brought there by the blood 
stream, and Hektoen traces the development of the tubercles fiom the inner 
vails of the bloodvessels, they soon affect, however, the Avhole tissue of the 
meninges, and there is usually to be found, on examination of such a brain, a 
thick, j ellov , opaque exudate over the basal portion covering the pons, the 
medulla, and the optic chiasm, and extending m the sulci along the course of 
the vessels toward the upper surface of the brain Close inspection v ill reveal 
small, gray nodules embedded m this exudate, and arranged along the course 
of the bloodvessels These are often especially clearly seen on pulling aside 



THE PATHOLOGY OF TUBERCULOSIS 


243 


the temporal lobe and examining the vessels m the Sylvian fissuie These 
lesions, which are accompanied by hypeimmia of the tissues, usually fade 
away to a great degree as one passes toward the suiface of the cerebral 
hemispheies, and over the spinal cord they aie also usually less intense 
Microscopically, one finds m those cases which have developed very rapidly 
a considerable percentage of polymorphonuclear leukocytes in the exudate, 
but usually it is composed chiefly of polj'blastic cells of vaiious foims, all 
members of the senes being found, from the numerous small cells to the very 
large, actively phagocytic cells with large, vesicular nucleus and abundant 
protoplasm The bloodvessels are especially affected, then walls being 
eccentrically thickened by masses of new'-formed tissue of tuberclc-like struc- 
ture, which have developed chiefly m the adventitial coat, less advanced new" 
formation of tissue is evident m the intimal coat, the media being passively 
encroached upon from both sides This mass of epithelioid cells, usually 
w'lthout definite giant cells, is very prone to caseation w"ith fi agmentation of the 
nuclei, and hence the opacity of many of the nodules seen along the vessels 
Partial or complete obliteration of the affected vessels is not uncommon 
Similar changes are frequently found in the ependyma of the ventnclcs, 
w'here definite minute tubeicles often appear wdiich are visible as tiny grams 
upon the choroid plexuses and are not to be confused, as Ophuls has pointed 
out, w itli the minute, dense nodules found in the same position in ependy- 
mitis granulans, which occurs w'lth various chionic diseases As seen in 
some cases, these minute tubercles have elearly the structure of tubercles, 
and tubercle bacilli have been demonstrated m them They aie often 
accompanied by an abundant exudate of fluid, with w'andeiing cells and 
fibrin, w"hich produces the internal hydrocephalus, thought by some winters 
to be so chaiactenstic of tuberculous meningitis The amount of fluid 
varies greatly, but m most cases is not great Tubeiculous meningitis is 
frequently associated with allied lesions of the brain itself, w"hen the condition 
may best be described as tuberculous memngo-encephahtis These changes 
in the brain consist m the piesence of caseous tubercles in the brain 
substance, usually just under the meninges and continuous w'lth the 
tubercles m the meninges, but they may be deeply embedded in the tissue 
of the brain In general, such tubercles are i datively large and appear 
as lounded, yellow areas of opacity suiiounded by a zone of red As a 
rule, there are but few of these, and careful sectioning of the biam must 
be made to discover all of them Sometimes, and then often W'lthout any 
associated meningitis, there may be but one or tw"o such caseous masses 
These solitary tubeicles may reach a great size, and m tw o cases seen lecently 
there were tumor-hke structures of the size of a hen’s egg occupying the 
greater portion of the cerebellum, leading to symptoms of ataxia Composed 
chiefly of caseous material, the margins of these masses exhibited beautiful 
tubercles with giant cells, partly obliterated tuberculous bloodvessels, and 
tubercle bacilli Such large tubercles are sometimes seen in the spinal 
cord, where thej" cause great disturbances by interrupting the nerve tracts 
The nerve roots are also sometimes involved, and in a recent case extensive 
paralysis of the low"er portion of the body W"as due to the invasion and 
destruction of nerve roots by tubercles developed within the dura 
Tuberculous lesions of the dmia are usually produced by extension from 
caseous areas m adjacent bones, and are, as a lule, localized in that 
neighborhood 



244 


INFECTIOUS DISEASES 


Tuberculosis of the Bones and Joints — ^In all instances except m those 
m which the skeletal structures are encroached upon by tuberculous processes 
arising in adjacent tissues the bacilli must be brought to them by the blood 
stream, and it is practically certain that such bacilli come fiom some piimary 
lesion i^hich may be so small as to be overlooked oi may be healed when 
the osseous lesions have developed 

Such osseous lesions arise very frequently in young childien, but are by 
no means uncommon in more advanced age They aftect most frequently 
the short bones in which cancellous tissue is abundant, such, for example, 
as the vertebrae, the carpal and tarsal bones, and the epiphyseal portions of 
the long bones, while the diaphysis of these latter and the bones of the skull 
are less commonly their point of origin 

Beginning m the cancellous bone as grayish-red, tianslucent infiltiation, 
the process soon extends with the formation of many tubercles and a tuber- 
culous granulation tissue among the mairow spaces This is usually 
associated with both rarefaction and ebui nation oi induiation of the bony 
material, the inflammatoiy process promoting in places the excessive new 
formation of the bone, while the neighboring bony tiabeculie are eioded 
and thinned out Caseation follows, often with the complete destruction 
of the affected area, sometimes with sequestration of the indurated part 
A cavity is formed filled with soft, yellow, caseous material, often containing 
fragments of necrotic bone Exceptionally such a focus may heal sponta- 
neously, but usually it advances either toward the diaphysis of the bone or 
more commonly towaid the articular suiface and the joint In early life 
the destruction of the epiphyseal cartilage by such disease may sciiously 
limit the growth of the bone, but probably moie impoitant is the limitation 
of growth and actual atrophy which results fiom the inactivity of the limb 

Extension of the tuberculous process into a joint is followed by different 
results, according to the rapidity of advance If the joint be invaded while 
m its normal geneial condition a dissemination of bacilli thioughout its 
cavity usually lesults, and the development of an exudate of seiofibrinous 
character, which may then be absoibed and followed by the growth of a 
tubeiculous granulation tissue ovei the synovial suiface This may in 
time become very thick and tianslucent, and is often accompanied by agreat 
accumulation of fluid, and by maiked oedema oi fibious induiation of the 
tissues about the joint (e cj , the so-called vhite svelhng of the knee), or 
without much or any exudation of fluid the tubeiculous gianulation tissue 
may rapidly undeigo caseation and eiosion The caitilage of the joint is 
entirely passn e and may be lifted up and dislodged oi ei a caseous focus in 
the bone, or may undergo a softening with loss of its elasticity, so that it in 
some cases becomes actually “smeary” m consistence and is soon destroyed 
by the apposed ends of the bones In such cases the exposed and partly 
caseous bony ends aie often crushed into one another and extensive de- 
formity IS produced Often befoie the caseous focus in the bone reaches 
the joint, the synoiial cavity has become obliterated in part or completely by 
inflammatory adhesions, so that there is no longer a question of a synovitis, but 
the tuberculous process continues to extend from one epiphysis to the next 

Other cases progress much inoie sloMl3’'and theie is time for extensive new 
formation of tissue m and about the joint, not only m the form of exostoses 
■which often limit the mobihtj’’, but also in thickenings and villous outgrowths 
from the sjnovial membrane itself Degenerative and mechanical com- 



the pathology of tuberculosis 


245 


pression of the fibrinoid synovial outgrowths produce in some cases the 
pedunculated or free corpora oryzoidea, oi rice bodies, which are smooth 
and of about the size and form of a melon seed Tubercle bacilli have been 
demonstiated in them In othei instances the so-called lipoma aiborescens 
results fiom the great overgiowth of the tissue of the joint, producing polypoid 
branched structures sometimes several centimeters m length These are 
composed largely of fat, but usually contain tubeicles Usually, the active 
destructive processes in the joints, leading to the loss of the synoMal mem- 
brane and the cartilage and the eiosion and crushing of the ends of the bones, 
are not confined to those tissues, but the adjacent structures become involved, 
and not only is there oedema and cellular infiltration and induration of those 
tissues, but sinuses and fistulie are foimed which burrow along the fasciae, 
often to a great distance, until thej' leach the skin A bluish, abscess-hke 
swelling shows itself foi a time, and finallj opens to give drainage through 
the tortuous channel to the caseous debris from the bone and joint 

Extensive collapse and displacement of the bones may occui m the 
rapidly progressing cases, so that, for example, while the head of the femur 
remains fixed m the acetabulum, the caseous neck breaks and the trochanteric 
end of the femur becomes dislocated to a point high upon the pelvis, u ith 
great shortening of the leg This destruction is perhaps most frequently 
seen m the lertebise, vheie caseous aicas deielop usually fiist under the 
anterior ligament, producing a preiertebral abscess, but quickly extend to 
soften and destioy the cancellous bone This allows of the collapse of the 
centrum, uith the angulai defoimity of the spine, uhen only one centrum 
is affected the spinous projection m the back is a sharp one, if a number 
of vertebra? arc destroyed there is produced a rounded kjphosis From 
such a vertebra uith its prevertebral abscess similar sinuses are often seen 
to Irurrow their v ay down through or beneath the psoas muscles until thev 
can appear at the skin in the gioin or on the inner side of the thigh — the 
so-called psoas abscesses 

Periosteal tuberculosis, as, for example, in the ribs and other boires which 
he near the skin, may gne use to quite large accumulations of exudate and 
caseous material, nliich have long been known as cold abscesses 
As to the pathogenesis of the bone and joint lesions of a tuberculous nature 
it may be said that in many cases it is impos^ble fiom the advanced stage 
of the disease to tell whether bone or joint rras first affected Konig main- 
tains that the synovial cavity is always fiist infected, but Guillemin and 
many others hold the opposite view and support it by statistics, v Inch show 
that in the majority of cases the adjacent focus m the bone gives rise by its 
extension to the infection of the joint 
Tuberculosis of the Muscles, Tendons, and Fasciae —The muscles, 
tendons, and fascirn are generally involved m tuberculous processes as the 
result of extension of the lesion from an adjacent caseous area in bones or 
elsewhere, but cases have been described m which isolated hsematogenous 
foci were found embedded in the muscle The lesion produces cavities m 
the muscle filled with a soft, caseous material, and lined with a tuberculous 
granulation tissue with giant cells of the usual character The muscle fibers 
in the immediate vicinity are in large part atrophic, but some are greatly 
enlarged V arious French authors, among whom Hemery may be mentioned, 
istinguish three forms the cold abscess of muscle, disseminated tuberculous 
myositis, and tuberculous muscular sclerosis 



246 


INFECTIOUS DISEASES 


Bursae — Isolated tuberculosis of bursae may also occur, but are usually a 
sequence of tuberculosis of adjacent bones and joints Scliuchardt describes 
three foims of tendon-sheath tuberculosis which closely resemble those seen m 
joints, namely, tuberculous fungus of the sheath, m which the lining is covered 
with a tubeiculous gianulation tissue, a nodular form in which a persistent, 
tumor-hke, gray, non-caseatmg mass is formed, and finally the i ice-body 
hygioma analogous to the similar change in the joints 

Tuberculosis of the Skm — Much confusion still seems to exist in the 
classification of tuberculous lesions of the skin, and theie aie several affections 
the tuberculous nature of which is still a matter of doubt Distinctly 
tuberculous are those forms known under the names lupus, scrofuloderma, 
tuberculosis ulcerosa, and tuberculosis veirucosa cutis, to Avhicli Kaposi 
has recently added another group with the designation tuberculosis miliaris 
cutis Besides these there are certain affeetions, such as lichen scrofulosorum 
and lupus erythematosus, which frequently occui in association -n ith tuber- 
culosis, but the strictly tuberculous nature of which is not yet decided 

Lupus, which by some authois (Unna) is divided into circumscribed and 
diffuse forms, is an affection of the skin pioduced by infection from with- 
out, and not necessarily associated with tuberculosis of theinteinal organs 
or underlying tissues The lesions occur either m the form of pale broi\ nish 
or bluish, non- vascularized nodules, sharply maiked off fiom the adjacent 
normal skin, oi as spreading hypermmic aieas elevated above the suirounding 
suiface, and showing their brown pigmentation only when the bloodvessels 
are emptied by pressure All possible transitions between these forms occui 
■« ith various modifications produced by the excessive growth of the epidermis, 
etc They appear usually upon the exposed surfaces of the body, as, for 
example, m the skm over the nose and cheeks The course of development 
IS usually slow, and the lesions are extiaordmarily peisistent, reappeaiing 
often after they had apparently undergone healing Ulceration is frequent, 
with extensive destruction of the tissue and subsequent scaiiing, which 
proceeds sometimes to such a degree as to cause the most unsightly deformities 
of the face 

Histologically, these nodules are composed of tubercles quite similai to 
those seen elsewhere, developed m the skm sometimes m the foim of compact, 
non-vasculaiized nodules, at other times as a soit of vasculai granulation 
tissue studded with tubercles Tubeicle bacilli can be demonstrated in 
this tissue, ■\\ Inch proceeds to caseation, and in that way to the formation of 
ulcers m the skin The localized nature of the disease may often be shovn 
by the possibility of bringing about healing 

The term scrofuloderma is applied to those tubereulous lesions of the skin 
which are directly pioduced by underlying tuberculous foci m bones, joints, 
lymph glands, and other tissues Such aie the changes described above as 
resulting from the extension, of sinuses from tuberculous foci in bone to the 
skin They appear at first as soft, fluctuant elevations of bluish-red color, 
Mhich finally break down and, liberating a quantity of caseous material, 
remain permanently open Such deep cavities arc lined with ah abundant 
tuberculous granulation tissue, the caseation and ulceration of which often 
extends \\ idely to the neighboring skin This, as is evident from the descrip- 
tion, IS a lesion of the skin of distinctly secondary nature The third form, 
tuberculosis ulcerosa, is less common, and appears m individuals suffering 
from severe visceral tuberculosis as ragged, superficial ulcers m the mouth 



THE PATHOLOGY OF TUBERCULOSIS 247 

and adjacent skin, about the external genitalia, etc , evidently due to an auto- 
inoculation of the skin 

Rather different in chaiacter fiom these is the verrucose foim of the dis- 
ease, ivliieh is due to direct infection of the hands, in most cases from contact 
with tuberculous mateiials The nodules aie often spoken of as ncciogemc 
tubercles, oi “Leichentuberkeln,” on tins account Appealing as nodules 
covered by a much thickened and keratinized epidermis, and formed m the 
depths of the skin of an infiltrated connective tissue with tubercles, these 
areas often tend to heal spontaneously Tliey are in many instances later 
associated vith widespread internal tuberculosis, but on the whole they 
present a mild form of the cutaneous tuberculous affection They cannot 
be very sharply separated m any classification from the cases of lupus 
The miliary form of tuberculosis of the skin which Kaposi has recently 
emphasized has been long known as a part of a generalized miliary tuber- 
culosis occurring m the form of multiple, scattered nodules of a tuberculous 
nature m the skin, and tending to caseation and ulceration 

As to the affections mentioned above, wdnch are frequently associated 
with tuberculosis of the internal organs, it may be said that wdnle it cannot 
in most cases be demonstrated that lichen scrofulosorum and lupus 
erythematosus aie anatomically tubeiciilous m nature, it is thought by 
many that tliey may be the exqiression of the effect of the toxins of the 
tubercle bacillus upon the skin (Hallopeau) 

Jacobi, Riehl, and others haie demonstiated tubercle-hke structures in 
cases of lichen scrofulosoium with giant cells, but these aie not typically 
tuberculous, and the bacilli have not been definitely demonstiated, inocula- 
tions were negative Interesting, although not conclusive, evidence in favor 
of their tuberculous relations is found m the fact that they react to tuberculin 
injections in much the same w^ay as the lupous nodules Practically the same 
doubts exist as to lupus erjdhematosus, and Jadassohn is forced in respect to 
it, as in the case of lichen scrofulosorum, to leave the question undecided 
after considering the evidence on both sides 



CHAPTER IX 


THE SYMPTOMS OF TUBERCULOSIS 

By LAWRASON BROWN, M D 

In a chronic disease, whose average duration is at least three or four years, 
symptoms command for long periods the attention of both patient and physi- 
cian Their importance m diagnosis has foi some time been recognized, but 
their relation to immediate piognosis, that is, whether the patient is im- 
proving or fading, has not been so clearly stated The value of recording 
symptoms accurately has not been sufficiently emphasized In some cases 
pulmonary tuberculosis is almost entiiely a disease of symptoms, in otheis, 
it IS tiiie, of physical signs, but these are fai m the minority 
The symptoms can be grouped in tAvo classes first, the geneial, and 
second, the localizing symptoms The geneial symptoms aie often not 
sharply defined and may be so slight as to escape the patient’s notice They 
are of less importance in localizing but of more importance in determining 
the presence of the disease The lelatiA’e importance of these symptoms is 
difficult to deteimine, but none is of gieatei value to the physician than 
fcA ei 

Fever — ^This is chaiactcuzcd by chionicity, ])ostmciidian occuiience 
(often folloAAing a subnoimal inoimng tempeiatuic), occuirencc in attacks, 
Avhich may supeiA^enc upon a noimal or slightly elevated tempcratuie and 
often by slight constitutional disturbance The inaMmum and minimum 
temperatures, although A'aiiable m height and duiation, usually occur at 
the same times each day in any mdnndual patient The piescnce of fcAer, 
AAdien not due to complications, indicates that the disease is actwe FcA^ei 
may pieccde all other symptom^ Fcav patients are apyietic throughout 
the entire couise, but m no othei chrome disease AAitli elcAation of bodily 
temperature aie tlie constitutional symptoms of fcA'cr so often lacking In 
fact the slight discomfoit caused by the fcAer may be said to be its most stiik- 
mg characteristic It is not unusual to find a patient up and about and fairlv 
comfoi table Avhose temperature is 102° cAmry afteinoon, and some patients 
even feel stimulated Avhen their temperature rises Most incipient cases arc, 
hoAvcA er, afebrile as soon as their life is Avell regulated 

It is of the greatest importance to knoAV the temperature of each patient 
He should be provided AAuth a good thermometer recently tested, and a little 
care m teaching him hoAV to take his temperature is invaluable If taken by 
mouth, in cold Aveather he should be m a warm room for ten to thirty minutes 
Avith his lips closed If taken by rectum, it is aa ise not to take the temperature 
soon after a stool, and care must be used to aA'oid feces m inserting the 
thermometer Menstruation and pelvic inflammation may affect the 
rectal more than the oral temperature Rise of temperature is usually 
perceptible earlier by rectal than by oial measurement Without doubt 
(24S) 



THE SI MPTOMS OF TUBERCULOSIS 


249 


tlie rectal temperature is more acciuate and less subject to minor variations 
It IS always important to determine roughly the vaiiation between the mouth 
and rectal tempeiatuies foi each patient, and when once determined it can 
be taken by mouth only, -which many piefei Some even in this case take 
both tempeiatuies moining and evening and only the oral during the day 
In patients with fevei the difteience is alwajs most marked foi the lower 
temperatuies and least for the highei 

The temperature should be taken every tA\ o hours, beginning on awaken- 
ing, until the medical adviser is fully acquainted with the range Then if 
the tempeiaturebenoimal it may be taken on vaking, at the time when the 
daily maximum occuis, and at S P m The morning temperature should 
always be taken befoie the toilet is begun INluch individualization is 
necessary when patients take then o\\n tempeiatures In neurotic patients 
much tact must be employed, fiequentlj the thcimometer must be dis- 
carded to oveicome “thermometer fe^ei,” and as little attention as is con- 
sistent with pioper treatment should be paid to the temperature This 
consists, in afebiile patients, of taking the tcmpeiature for two da-^s eveiy 
two to four weeks, and during the inteival if there is the slightest suspicion 
of fever If the patient cannot sleep oi 1 as headache he should take 
Ills temperature during the night, as in some cases the use occurs at night 
only, or a second use may occur at that time 

The “noimal” iempciaiuic laries shghtlj foi indniduals and tonsidciably 
with rest, exeicisc, and time of day The indnidual \aiiation, while slight 
for the rectal tcmpciatuic, is moic pronounced foi the oial During rest 
in bed the rectal tcmjiciaturc may be said to be noimal when it canes be- 
tween 97 3° and 98 5° on awakening, 98 6° and 99 1° m the forenoon, and 
991° and 99 5° in the aftcinoon In some cases, how'ever, it may reach 
nearly 100° The oral temperatuie raicly sinks below' 97° in the moining 
and seldom coes above 99 2° in the afternoon oi evening The temperature 
w'hen the patient is excicising, and cspcciall-^ just follow'ing exercise, is highei 
and less certain Exeicise affects the lectal temperatuie much more than 
the oral Simply getting out of bed in the moining may raise the rectal 
temperature some tenths of a degree, and aftei exeicise a lectal tempeiatuic 
of 101° has been frequently iccoidcd in appaiently noimal individuals A 
rectal temperat-uic of 100 4° iinincdiateh aftei exercise is not to be con- 
sidered abnormal The oral temperature rarelj show's much elevation after 
exercise and may be low ered foi some time on account of the cooling influ- 
ence of the more lapidly respiied air Tubciculous patients ecen with a 
normal temperature at lest show' after exeicise a much greater rise (by 
rectum) than normal persons (Penzoldt’s phenomenon) Fat amemic 
individuals may have elevation of temperature, especially aftei exercise 
In old age the normal temperature is low'ei than in adult life, w'hile in 
childhood the lange is much greater 

Cause of Fever — This is primarily the effect upon the heat centre of 
the tuberculous toxin or protein, absorbed from the tuberculous focus, 
rendered no doubt more irritable by previous absorption of the same irritant 
in doses too small to cause fever The fever produced by the injection of 
tuberculin proves that secondary organisms and their products are not 
necessarily its cause The fever late in the disease, the hectic or absorption 
fp'er, IS due m part at least to the absorption of bacterial proteins other 
than those produced by the tubercle bacillus and to the absorption of the 



250 


INFECTIOUS DISEASES 


necrotic matter from the softening tissue or pneumonic processes Some 
hold that the tubercle bacillus pioduces a second to\m which can lowei the 
temperature and that the labile temperature in the tuberculous is due to 
the action of these two toxins 

The temperature cuive with its daily rise or rises can be readily explained 
by the effect of bodily exercise upon absorption The absence of fever after 
the long rest at night is thus explained as veil as the afternoon use aftei the 
exertion of the morning No doubt this ex-plams also the use of tempeiature 
at night in some patients, with severe cough on Ijnng dovn Absoiption, 
therefore, plays an important part, and the higher fever m acute tuberculosis 
or m acute attacks is due to the gieatei absorption through the more patent 
lymph channels (Cornet) It has long been recognized that the disease in 
patients with fibroid phthisis or with chronic cavity formation may be 
afebrile, although advancing In other cases fever occurs only when the 
outlet of the cavity is plugged or when fresh areas vith patent lymph 
channels are involved Fever caused by overexertion may not occur lor 
several days 

Fever m Chronic Pulmonary Tuberculosis —Every known type of fever 
may occur, but the usual tempeiature curve is one which is normal or slightly 
subnormal in the morning and rises to 99 5° or 100° (by mouth) between 
noon and 9 pm The fastigium lasts usually for two or three hours, but may 
be so short that it is recorded only when the temperature is taken every two 
hours As a rule, the maximum is between 3 and 5 P ai , the minimum 
between 2 and 4 am Many patients have a slight rise for months before 
their attention is called to it by some other symptom As the disease advances 
the febrile attacks are sharpei and in some instances more protracted, but the 
acute exacerbations of fever are often of ten to fouiteen days' dmation, 
the time which is required in expeiimental tuberculosis for the formation of 
agglutinins 

In still more advanced stages, fever is present at some time every day, and 
may be continuous, inteimittent, or, as is moie usual, remittent Several 
minor oscillations may be present each day, or the temperature may fall 
to normal for a day or two a week The temperature seldom exceeds 104°, 
but IS frequently subnormal A fall of tempeiature is often observed aftei 
the formation of a cavity In many cases, however, the tempeiature goes 
from normal or slightly below to 100° or 101° with great regularity The 
division of tuberculous fever into fever of tuberculization, of ulceration, and 
of absorption cannot be maintained, as in geneial all three processes occur 
simultaneously 

It must not be expected that the temperature curve will alwavs follow the 
course just outlined, undisturbed by other causes Complications, tuber- 
culous and non-tuberculous, as well as an advance of the tuber culous process 
111 the lungs, may cause fe^er A sudden and sharp use of tempeiature 
vithout vaining rarelj' occurs in the ordinary progression of the disease 

The temperature of the tuberculous patient is very unstable, due in part 
at least to the effect of the tuberculous toxin upon the nervous system, 
especially upon the heat regulating centre Slight mental excitement or 
slight physical exercise causes more rapid heart action and inci eased stimula- 
tion of the heat centre, either from the increased toxin m the blood or from 
an increased amount of toxin in contact with the heat centre Hoveiei 
this may be, the tuberculous invalid is prone to rise of tempeiature from 



THE SYMPTOMS OF TUBERCULOSIS 


251 


trivial causes, as Avell as from bronchopneumoma, acute gastritis or enteritis, 
influenza, and almost any intercurrent disease The rise of temperature 
in 50 to 60 pel cent of patients from one to seven days before or during the 
menstrual peiiod and the "digestion fe\ei” said to occui in some patients, 
usualh aniemic, aftei the chief meal of the day, are due, no doubt, to this 
lability of the temperature 

Rise of temperature, if of any duration and not due to complications, 
indicates actnity m the pulmonaiy lesion The disease, hovever, can 
progress without discoverable use of temperature, although this takes place 
usually only when the individual has no longer sufficient poweis of resist- 
ance As a rule, the degree of activity can be told from the temperature 
chart Even slight rise of the minimum temperatme is to be regarded as 
suspicious of increased tuberculous imolvement, while the maximum 
temperature usually shows the intensity of the disease or the activity of the 
secondaiy oiganisms If the minimum temperatme is normal oi nearly so 
and the maximum 100 5° to 101 5°, and seldom above, a slow disintegra- 
tion with an absorption of the inflammatory products is moie likely than an 
advancement of the disease (Saugman) High intermitting fever indicates 
a severe and deep-seated lesion and often quick destruction of tissue Fever 
may occui and the patient show all signs of inci eased activity, but several 
dajs may elapse befoie any increase m the physical signs becomes evident 
In fact, some patients recovei from the febrile attack before the lesion causing 
it is discovered A rise to 106° oi 108°, if present at all, usually occuis 
shortly befoie death, but m the writer’s expeiience it is much more common 
for the temperature which has been high to fall below normal for a day oi 
two before death Hiemoptysis, repeated at inteivals for seveial days, is 
usually accompanied by a slight use in tempeiatuie When an extension of 
the tuberculous process oi an aspiration pneumonia follows hiemoptjsia 
the temperature usually becomes high and continuous In a few cases the 
temperature falls after hmmoptysis when the amount of blood lost is not large 
The temperature on the two sides of the body may vary and is highest usualh 
on the side affected The face and ear aie fiequently more flushed on the 
affected side 

Fever m Acute Pulmonary Tuberculosis — In these cases fever is usually 
a marked symptom and may closely simulate that of tjphoid fever oi pneu- 
monia In lare instances it suggests malaria, a diagnosis far from un- 
common in pulmonary tuberculosis The temperature cuive, however, 
seldom closely simulates a single tertian infection In a few cases the rise 
extends over a period of two days to become normal on the thud This 
maj' be repeated a number of times In most cases of acute tuberculosis 
the temperature is continuously high, wuth but slight morning remissions 

In acute miliary tuberculosis, either primary or secondary, the temperature 
IS usually high, continuous, with very' slight morning remissions, and may 
range betvv'een 102° and 105° for davs Marked remissions with a normal 
temperature of sev'eral day's’ duration may occur The “inverse” type of 
temperature is rarely observed either in this or other forms of pulmonary 
tuberculosis Its occurrence usually indicates that the temperature rises 
during the night and does not fall until G to 9 A Ji If a tw o-hour chart is 
kept throughout the night it is more frequently noticed, especially' in sub- 
acute or chronic cases It has been observed m only three or four patients 
at the Adiiondack Cottage Sanitarium, and then but for a short peiiod It 



252 


INFECTIOUS DISEASES 


IS said to be the only temperature curve due solely to pulmonary tubercu- 
losis 

In acute pneumonic tuberculosis the tempciatuie cuiAe is at times similai 
to that of typhoid fe\ei in the second \\eek, or pneumonia, but more often 
it resembles typhoid in the third or fourth week, with more oi less marked 
remissions The temperature usually ranges from 100° or 101° to 103° or 104° 

Frbroid tirberculosis may occur with slight or no elevation of temperature, 
or the temperature may be subnormal High intermittent fe\er, often 
rei} iiregular, suggests, in early stages of the disease, tuberculous enteritis, 
salpingitis, etc 

Some affirm that the presence of mixed infections can be told from the 
temperature and that the “streptococcic” curve is characteristic This 
curve, due no doubt in part to secondary organisms, shows marked vacilla- 
tions In the morning the tenrperature is often markedly subnormal, and 
Lebert records one case m which it reached 89° In the afternoon or even- 
ing the temperature rises rapidly to from 101° to 104° A variation of 4° or 
5° IS frequent, and as much as 14° has been observed Mixed infection 
cannot be diagnosed from the temperature curve, although Koch has 
stated that a temperature over 100 4° is due to secondary infection In 
patients with a favorable prognosis, e g ,m those at the Adirondack Cottage 
Sanitarium, the temperature rarely fell below 95° (91° lowest recorded) 
and rarel} exceeded 105° (106° higlrest recorded) In 123 of these patients 
whose temperature reached 102° or o\er, 43 per cent did not go abo\e 
102°, 26 per cent reached 103°, 29 per cent 104°, and 2 per cent 105° 
The greatest recorded rariation in twenty-four hours vas 10° Uncom- 
plicated tubciculosis of the serous membranes may produce a hectic 
ier er 

Weight — ^Loss and Gam — Wasting has long been recognized as the 
symptom most characteiistic of pulmonary tuberculosis, popularly termed 
for this reason “consumption” or “phthisis ” It is the result of the disease, 
stands usually in direct lelation to the stage and chronicity, and is not a 
conservatne process as some affirm (Pollock) This wasting affects all 
the organs of the body except the liver, vliich maj undergo a fatty change, 
and possrbly the bonts The fatty and rnusciilai tissues are most affected 
Loss of weight may be the most prominent and m a fev cases the only s'\mp- 
tom It may occur so gradually that it escapes attention for some time, 
or it may be veiy rapid in the early as well as m the later stages The scales, 
v itlr the thermometer, gi\ e usually the most reliable information concerning 
theprogiess of the patient, but those vith slowly advancing disease may lose 
little or no w eight This is no doubt due to individual resistance, but may 
depend upon the low virulence of the tubercle bacilli present A slight loss 
usually occurs during menstruation, but is quickly regained Loss of y eight 
IS m proper tion to the duration of the disease and young patients lose more 
rapidly than older 

The “normal” weight of patients vith pulmonary tuberculosis is about 
ten pounds less on an average than what they should weigh The bearing 
of this fact upon diagnosis is readily seen and should be given more regard 
m life insurance york than the occurrence of pulmonarj^ tuberculosis m 
some member of the family y ith y horn the patient has never come m contact 

The cause of loss of y eight is best explained as the effect of the toxin 
absorbed from the pulmonary lesion upon cell nutrition m general Ha}s 



THE SYMPTOMS OF TUBERCULOSIS 


253 


recognizes this as the pnmarj cause of the loss of weight, A\hich is due 
directly to the increased metabolism caused by the fever and also to a 
deficiency of the digestn e ferments Later, the adaption of the organism 
(more digestive fluids of an inferior quality) to the changed condition 
would, he holds, pi event loss and furthei gam In any case the digestn e 
organs are often early affected, producing defective assimilation, loss of 
appetite, lomiting, and consequent emaciation Loss of eight is not de- 
pendent upon fever, as it may occur in the absence of this s} mptom, but 
usually they go hand in hand, the \\ eight increasing as the fe^er decreases 
The loss ot eight occasioned by nervous excitement and exercise can be 
explained by the increased absorption of toxin Forced muscular exercise 
is nearly alvays follorred by loss of weight Intercurrent diseases and 
complications, c g , diabetes melhtus and influenza, may cause a rapid and 
considerable loss of weight Montenegro has observed, n hen a closed be- 
comes an open lesion, a replacement of loss of n eight by a slight gam 

Loss of iv eight m chronic disease may amount to one-thiid to tno-fifths 
of the previous weight If a patient lose one-fouith of his normal theoretical 
n eight his nutrition is apt to be considerably disturbed and a loss of one- 
third is a grave omen Patients with extensive oedema may be up and about 
and a considerable loss of i\ eight (ten or twelve pounds) may easily escape 
detection A larger percentage of weight can be lost by fat individuals 
Great emaciation is rarely present m acute disease The greatest loss 
recorded is 130 pounds m a man r\eighmg 271 pounds in health A loss 
of 5 or 6 pounds a week is not unusual for a short time 

Gam m Weight — This depends not upon ingestion, but upon assimilation 
One patient may eat little and gam and another eat an enormous quantity 
and lose Patients nho are so fond of meat that little else is eaten are less 
likely to gam than good general eaters Some foods seem to hare especial 
influence upon gam m weight, e q , eggs, milk, cream, and cod-liver oi olive 
oil Many patients who hare had high ferei gam m r\ eight when the 
ferer decreases, although a continuously elevated tempeiature may still be 
present Antipyretics aie of value when they decrease afteinoon fever 
and enable the patient to eat Patients with fevei need an amount of food 
greater than normal to maintain then u eight, and when kept out-of-doors 
they fiequently digest enormous amounts of food well 

Gain 111 weight, if much loss has occurred, is practically a necessity for 
improvement and may' occur at any stage Gam usually occurs as soon as 
the life of a patient is properly regulated Change of climate is not so 
essential m the case of the poor as good hygienic conditions For the 
v ell-to-do, u ho have looked upon these conditions as necessities and ahrays 
enjoyed them, change of climate, at least at first, is often necessary to 
stimulate nutrition and gam in u eight Many' patients m advanced stages 
gam 111 weight for three or four months after a ehange of climate, but then 
gradually lose 

Cold seems to have a marked influence upon weight-gaining in the healthy 
as well as m the tuberculous The u eight curve in pulmonary tuberculosis, 
if not influenced by change of climate or other factors, uses from August 
to Chiistmas (sometimes to November), remains moieor less stationary uitli 
minor fluctuations fiom Christmas to Easter (March), and srnks gradually 
rom Easter to August This coi responds closely' with the normal weight 
curre and is based upon a study of the weight charts of 1200 patients at the 



254 


INFECTIOUS DISEASES 


Adirondack Cottage Sanitarium Gabrilowitcli, at Halila, has found that 
patients gain moie in the very short days in wintei than in the longer, 
warmer, and sunniei summei days Bergei, however, has failed to note 
this Great dryness in itself is not conducive to gam m weight The effect 
of exercise upon gam in weight is at times striking Some patients at rest 
gam little, but put upon carefully regulated exercise begin to gam at once 

The average gam in weight undei treatment depends upon whether or 
not forced feeding is employed, the activity of the symptoms, and the amount 
of V eight that has been lost Patients with far-advanced disease and con- 
siderable loss of weight usually gain more on an average vhen the disease 
becomes quiescent than those with advanced but less than those with 
incipient disease A study of 164 patients at the Adirondaek Cottage Sani- 
tarium who had gained 20 pounds or moie (average 21 6 pounds) shovs that 
these patients do better as a rule, but a large gam of v eight does not assure 
cure Of these patients, the 22 who have died gained on an average 2SJ 
pounds, 2 pounds more than those who have remained •well The largest 
gam m weight that has come under the writer’s notice occurred m a man v ith 
a cavity, rathei extensive disease on one side, and a slight affection of the 
opposite apex Returning to his work against advice, his weight fell from 
145 to 115, and his lung condition became worse During a second sojouin 
of two years his weight increased to 215 pounds Men as a rule lose moie 
weight and gain less than women 

The average gam m weight of 901 patients at the Adirondaek Cottage Sani- 
tarium was 14 pounds In 2 patients, in early stages, without much loss of 
weight, gams occurred respectively of 15 pounds m fifteen days and 27 pounds 
in twenty-eight days A gain of 2 pounds a week is satisfactory Weight 
may be gained irregularly, t c , a gam may occur on the first and third days 
and a loss on the second The mental condition diiectly affects the weight 
The gam in -w eight m many cases occurs first on the chest and face 

The persistence of the gain in weight is often lemarkable In some cases 
(about one-third, Berger) the gam is continued when the patient returns to 
his home and lives properly W^eight gained during exercise is more perma- 
nent than weight gamed at rest Weight acquii ed tin ough a liberal use of milk 
and eggs, especially if without exercise, is often quickly lost The explana- 
tion of this rests less upon the hypothesis of Dobell, that “ the stability of the 
fats of the animal body m resisting too lapid oxidation is dependent upon 
the degree of sohdit-^ -which they possess at the temperatuie of the living 
animal at any given time,” than upon the fact that such obser\ations are 
usually made in advanced stages, when patients have lost much v eight and 
vould quickly lose any weight gamed, even if the ingestion of “mateiial 
capable of supplying the adipose tissue with solid fat” was the cause of the 
tempoiary gam 

Metabolic Changes — Proteid and Fat — The emaciation is due to a toxin 
absorbed from the seat of disease, which, while it acts upon the nervous 
system, causes also directly a loss of appetite and so prevents repair of the 
normal waste of the body Late m the disease, Aomitmg and diairhoea 
act in the same ay This xveakens the resistance and so favors extension 
of the disease The increased amount of toxin thus produced acts directly 
upon the cellular protoplasm, which m time loses its power of regeneration 
When the toxin is absorbed in sufficient quantities fever is produced, xxhich 
in turn affects the metabolism The body fat is little affeeted until later 



TJIE S\ MPTOMS OF TUBERCULOSIS 


255 


when dvs])noea, chills, and other pronounced symptoms occur Foi these 
reasons May holds that the severest toxic action and the most lively tissue 
destiuction are seen in caseous pulmonaiy tubeiculosis 
Inorganic Salts — Changes also occur in the excretion of other organic 
and inorganic substances Calcium phosphate as well as lecithin and nuclein 
are increased, and Mitulesku finds the phosphorous output parallel with 
the nitrogenous Magnesium and calcium salts are increased m the ter- 
minal stages, especially vhen fevei and loss of appetite are present (Ott) 
The “demineralization” of the French observers is not peculiar to tubercu- 
losis, but occurs first and irregularly in later stages Ferrier holds that 
phosphaturia and tuberculosis are closely related Decalcification, he be- 
lle^es, IS of much importance, and should be vigorously combated This 
work still lacks sufficient confiimation 
The excretion of ammonia and of indican, espeeially m intestinal complica- 
tions as well as when cavities become septic, is increased The different 
phenols and skatols are also increased m destructn e processes Urobilin is 
increased usually, but m very acute processes is decreased 
Respiratory Exchange — ^The gaseous exchange m the lungs, in spite of 
marked destructive processes, undergoes practically no alteration Rohm 
and Bmet have asserted that more oxygen is absorbed and more COj excreted 
than in health (increase of pulmonarj ventilation 80 per cent and over), 
and advance this as a means of diagnosis This work has failed to be con- 
firmed by many obseiveis 

Loss of Strength — This often occurs as the primary manifestation, but 
IS rarely recognized as such at the time Many patients begin early to tire 
easily, and work which once was a pleasure begins to drag This debility 
may be present to a very marked degree and out of all proportion to the 
extent of the discoverable lesion A point often mentioned by the patient is 
that while he seems to have as much muscular power as ever for a single act, 
he IS incapable of sustaining for any length of time muscular or, m some cases, 
mental work His enduiance is considerably lessened The muscular 
tonicity has been found to be greatly diminished m the incipient stage, even 
when the muscular power and nutrition aie good The loss of strength is 
most probably due to the effect of the disease upon the nervous system 
As the disease pi ogresses and, in fact, often within a few weeks after the 
patient has “given m,” he feels much better Loss of strength is of course 
diiectly propoitional to the general condition Nothing is moie deceptive 
than the robust appearance of many patients undergoing the modern 
treatment compared with their lack of strength The slow return of strength 
IS a most striking feature in many cases and one of no inconsiderable impor- 
tance m tieatment In fai -advanced cases the debility may become extreme, 
and yet, on the other hand, it is remarkable what many patients, seemingly 
totteiing on the bunk of the grave, can accomplish Steienson fully recog- 
nized this m Aes Tnplc% and m his own life 
Night-sweats — ^These, while rare in the eaily stages, occur more fie- 
quently m pulmonary tuberculosis than m any other disease In a few cases 
they precede all other symptoms and even physical signs This, however, is 
rare, as they are usually associated with fever and a subnormal morning 
teinpeiature As the disease piogresses, or during acute attacks, the night- 
sv eats become more frequent, and m the later stages drenching sweats are 
common, and may occur not only at night, but whenever the patient falls 



256 


INFECTIOUS DISEASES 


asleep (sleep-sweats) The sweating, so exhausting, so unpleasant, and 
so depressing that the patient dreads going to sleep, usually oceurs early in 
the morning and possibly not until during a nap follo'w ing the morning cough 

The sweats vary much in severity At times so slight as to be scarcely 
perceptible, they may be so profuse that the night robes have to be changed 
three or four times a night and possibly some of the bedding as well Sweats 
were absent in 10 per cent of Louis’ cases and in 41 per cent of 2344 cases at 
the Phipps Institute, Philadelphia Sudamina, more frequent m acute, rarely 
occur in chronic cases following sweats Acute inflammatory processes and 
diarrhoea may hold the sweats in abeyance for a time They are less frequent 
in children, and m patients with diabetes melhtus Hemidrosis may occur, 
but IS accidental The night-sweats are general v hen severe, but the slighter 
forms are often moie localized, and occur most frequently about the head 
and neck or extremities The sweat has been found in some cases to give a 
tuberculin reaction on iniection, but nevei contains tubercle bacilli No 
record of the amount of sweat has been published, but in some cases it 
exceeds twenty ounces 

Cause — ^The sweat glands are under the contiol of centres which can 
stimulate or inhibit the secretion Increased blood supply to the skin 
increases secretion of sweat, and consequently these glands are closely con- 
nected With the vasomotor centre Early in pulmonaiy tuberculosis, sweat- 
ing IS usually the result of poisoning of the sv eat, vasomotor, and heat 
centres by the tuberculous toxin, in the moie advanced stage the sweat 
may be the result of fever, which stimulates the sweat centres, the vaso- 
motor centies (causing dilatation), and the glands, and late in the disease 
the sweat centres or glands may be stimulated independently of the heat and 
vasomotor centres by the toxins of the secondaiy oiganisms as veil as by 
those of the tubercle bacillus 

The increased fiequency of sweating in acute piocesses is due piobably 
to the moie rapid absorption of toxins Some hold that oveistnnulation 
of the vasomotor (constiictoi) centie finally gnes ivay during sleep to a 
greater lelaxation than normal The inci eased blood supply then causes the 
sveat The piesence of the toxin, ho^\e^el, is not alvays sufficient to cause 
sv eating, and some pathological changes in the cii dilation and nutiition 
are geneially necessaiy The absoiption of neciotic mattei oi pus is, 
accoiding to some, the chief cause In most cases the sveat glands lespond 
to slighter stimuli than noimally The connection of sweating vith use 
and fall of tempeiatuie some think is diiect, A\hile otheis hold both due to 
the same cause Bradycaidia, weakness, and aniemia ha^e been suggested 
as causes, but m some cases aie lacking Lessened respiratoiy suiface, and 
therefoie lessened secretion of moisture and CO^, vith stimulation of the 
sweat centres, has also been advanced as an explanation, but this would 
only explain sweats in the late stages 

Chills — ^These may occur early in the disease, and vhen piesent daily 
often give rise to a diagnosis of malai la They occui usually before, seldom 
after, the rise of temperature Slight shivering, blueness of the nails, 
or gooseskm are early signs of fever Following a sveat, chills are not 
infrequent Complications are sometimes ushered m with chills 

Blood — ^The blood picture ■\aiies AMth the stage, the acuteness, and 
the complications In patients with incipient disease it is often normal, 
and dining treatment the erythrocytes and the peicentage of hiemoglobin 



THE SYMPTOMS OF TUBERCULOSIS 


257 


are frequently above normal Other patients are amemic from the outset 
The earliest and most constant change is the reduction of the color 
index, and chlorosis in many instances is masked tuberculosis A slight 
diminution of the erythrocytes is frequent in this group of cases, while 
the leukocytes may be either slightly increased, decreased, oi, as is more 
usual, normal When the disease reaches the advanced stage, the pallor 
of the face, which may be present earliei, becomes often very marked, 
and is at times m strong contrast with the red color of the lips and mucous 
membranes The blood heie is often normal m eveiy particular, and the 
erythroeyte count and hiemoglobin may be above normal The leukocytes 
are usually very slightly if at all inci eased The explanation of this lies m 
the concentration of the blood and a real leukopenia The large amount of 
fluid lost by the increased salivary and bronchial secretions, the night-sweats, 
and diarrhoea if present, and probably also the action of the tuberculous 
toxin producing an increased flow of lymph to the tissues, are all factors In 
far-advanced cases, when secondary infection has taken place, the blood 
presents usually the same conditions that occur m toxaemia 
Ei 7 throc 3 d;es — These may be as low as 1,000,000 to the c mm , but they 
rarely fall under 3,000,000 m uncomplicated cases Counts of 6,000,000 
in patients undergoing treatment are not uncommon Fever, unless it is 
septic, has no effect upon the erythrocytes In general a diminution of the 
red cells is the dominant characteristic Many degenerative changes have 
been described, but none seem to be characteristic Shoitly after haemoptysis 
the blood shows a slight reduction of er 3 throcjtes (counts of 1,000,000 or 
even 360,000, hovievei, hav^e been made), and a transitor}' leukocytosis, 
present only in some cases and proportional to the severity of the haemop- 
tysis Nucleated red cells are rarelj" found The hygiemc-dietetic treatment 
produces a marked increase in the amount of blood as v\ ell as an increase of 
the erythrocytes and percentage of haemoglobin m patients who are improving 
The erythrocytes in 155 patients at the Adirondack Cottage Sanitarium 
(elevation 1600 ft ) taken on admission to the institution (some patients, 
however, having been under treatment for several months) gave the following 
figures 


Erythrocytes 

Male Fem ^.le 

Incipient Advanced Incipient Advanced 

4,000,000-4,500,000 

2 

0 

1 

1 

4,500,000-5,000,000 

6 

3 

16 

4 

5,000,000-5,500,000 

13 

17 

6 

15 

5,500,000-6,000,000 

9 

9 

6 

8 

6,000,000-6,500,000 

4 

1 

3 

1 

6,500,000-7,000,000 

7 

5 

2 

2 

7,000,000-7,500,000 

1 

3 

3 

2 

7,500,000-8,000,000 

1 

3 

0 

1 

Total 

43 

41 

37 

34 

Av erage 

5,618,605 

5,831,171 

5,386,216 

5,529,941 


Hsemoglobm — Many patients under treatment or w ith advanced disease 
show a percentage considerably above normal With progression of the 
disease the percentage usuallj" falls and may leach a low figure The 
luemoglobm m this series v\ as estimated usualty by the Tallquist scale, but 
in a few cases the von Fleischl apparatus was used The results in 154 
cases are as follows 

VOL III — 17 



258 


INFECTIOUS DISEASES 


Maw 1 1 M \Li 


H'cmoglobin 

65-69 percent 

70-74 “ 

Incipient 

Ad^ aiiced 

IliLipicnt 

1 

1 

Ad\aiiced 

75-79 “ 

2 

2 

0 

2 

80-84 “ 

2 

3 

5 

1 

85-89 “ 

8 

4 

11 

5 

90-94 “ 

16 

18 

11 

IS 

95-99 “ 

9 

11 

4 

5 

100 “ 

6 

2 

4 

3 


— 

— 

— 

— 

Total 

43 

40 

37 

34 

A\ erage 

91 0% 

90 4% 

88 2% 

90 3% 


The spectroscopic examination of the oxyhiemoglobin shows similai 
results In a majority of all cases the coloi index is reduced 

Leukocytes — ^These aie at times somewhat reduced in numbei, and it is 
possible that the cause of the leukopenia may act in a similar way to 
reduce the leukocytosis usual in some of the complicating diseases Counts 
of 3000 to 5000 aie frequent m incipient stages In advanced stages 
10,000 to 12,000 aie not unusual, and in a few cases, late in the disease, 
the leukocytes may CAen be higher In acute miliaiy tubeiciilosis of the 
lungs, leukopenia is moie often present than leukocytosis The latter is at 
times piesent in caseous pneumonia In chiomc fibroid conditions leukocy- 
tosis IS usually absent unless a ca\ ity is piesent Tuberculous complications, 
unless accompanied by secondary infection, laiely pioduce much increase 
in the leukocytes Duimg softening a leukocytosis is usually present and it 
may occur with tuberculous hypeiplasia of the glands with slight destruc- 
tive pulmonarj’^ changes Leukocytosis is said to be a constant accom- 
paniment of cavity formation, and a piolonged absence of leukocytosis is held 
to exclude this condition Such, howevei, is not always the case, especially 
m chronic cavities (Ewing) Acute tuberculosis supervening upon a leu- 
kaemia may leduce markedly the numbei of leukocytes, but chronic pul- 
monaiy tuberculosis and ieukamna may coexist without reduction m the 
number of leukocytes 

The difteiential count shows consideiable v.iiiation The polymoipho- 
nucleai cells vary between 60 and 95 per cent , but are usually about 
SO to 84 pel cent Leukocytosis m pulmonarj tuberculosis is almost 
always due to increase of these cells Recent work upon the cellular 
elements of seious eftusions has drawn much attention to the laige num- 
ber of mononuclear cells It seems, however, to be more constant in 
pleuritic effusion than in the blood either of these or of other patients wath 
chronic pulmonary tubeiculosis Some have tried to show^ a piognostic 
value for this type of leukocytosis, believing a low' mononuclear count 
decidedly less favorable than a highei one In low' counts the laige and 
small lymphocytes are usually lelatively and possibly absolutely increased 
Myelocytes may be present, but mastzellen rarely occur Much interest 
w'as aroused by Teichmuller’s observation on the eosmophiles m the sputum 
in fa\orable cases How'evei this may be, as the disease advances some 
hold the number of the eosmophiles in the lilood decreases, and as it retro- 
giades the numbei increases, but Ullom and Ciaig question this The 
leukocytes counted in 155 cases at the Adirondack Cottage Sanitarium, 
before breakfast, w'hile fasting, gave the follow'ing results 



THE SYMPTOMS OF TUBERCULOSIS 


259 



Male 

Llmall 

Leukocytes 

Incipient 

Ad\ ancod 

Incipient 

Advanced 

4,000- 5,000 



2 


5,000- 6,000 

1 

1 

2 

2 

6,000- 7,000 

6 

4 

5 

3 

7,000- 8,000 

5 

8 

12 

3 

8,000- 9,000 

8 

4 

6 

7 

9,000-10,000 

6 

7 

1 

4 

10,000-11,000 

3 

8 

2 

5 

11,000-12,000 

t 

2 

1 

4 

12,000-13,000 

2 

2 

3 

3 

13,000-14,000 

3 

1 

3 


14,000-15,000 

2 

1 


1 

15,000-10,000 

1 

2 


1 

16,000-17,000 

1 

1 



17,000-18,000 




1 

18,000-19,000 

1 




Total 

43 

41 

37 

34 

Average 

9950 

9637 

8485 

9744 


The blood platelets are normal or increased Even in the most advanced 
stages their number is not reduced 

Arneth, from a study of the pob morphonucleai leukocytes, found that 
in health 5 per cent contained a single nucleus, 35 per cent two nuclei, 
42 per cent three, 17 per cent four, and 2 per cent five nuclei Othei 
observeis have found in health a considerably larger percentage of cells with 
one nucleus, and more cells with two nuclei In pulmonary tuberculosis 
the number of cells with fewer nuclei u as much increased lodophiha is of 
little value m pulmonaiy tubeiculosis 
The blood serum seems to possess a more or less specific agglutinating 
power for the tubercle bacilli Maraghano’s work shows that the seium of 
tuberculous patients with toxsemic sj mptoms has a toxic effect upon healthy 
and tuberculous animals, which resembles tuberculin poisoning 
The bacienology of the blood has been frequently investigated with very 
contradictoiy results That tubercle bacilli occur in the blood cannot be 
questioned and some recent work would seem to prove that more exact 
methods iiill yueld more positne results Up to this time. Iron ever, tubercle 
bacilli have raiely been found m the blood except in acute conditions, in the 
preagonal stage, and at ]rostmortem Inoscopy (Jousset) and the use of 
leeches (Gary) seem to aid mateiially in the search The positive results 
obtained for other organisms are inoie numerous, but many have been 
questioned Faulty technique ivould no doubt account for some, but there 
remain a number of cases m which other organisms haie been recoiered 
The results m hectic patients haie not upheld the theory of septicfemia, as 
m most cases the blood vas apparently sterile The tubercle bacilli are 
said to be more frequent m blood from the spleen, and some hai e unwisely 
suggested aspiration of the spleen for diagnostic purposes 
The dry tesidue of the blood is lessened and the specific gravity lowered 
Cellulose (glycogen) and calcium phosphate may occui Fibrin is mcieased 
at first and deci eased m tbe last stages With the course of the disease the 
non and potassium salts and phosphates deciease, the sodium salts m- 
ciease The reaction of the blood is moie veakly alkaline than noimally^ 
ClTCUlatlOIl — The Pulse — The frequency and tension are early^ and 
often peimanently changed The size of the pulse, its fulness and regularity. 



260 


INFECTIOUS DISEASES 


bear less definite relation to the pulmonary disease than the frequency and 
tension, and often until the late stages aie only slightly if at all abnormal 
The radial pulse is said to be influenced by tlie position of the arm on the 
affected side m hen contraction of the apex has occurred, and Foss has found 
a paradoxical pulse in 61 per cent of 120 patients, while Sorgo noted a weaker 
pulse on the affected side in 8 per cent of 397 patients 

Frequency — ^Until thermometry was introduced this i\as the most im- 
portant single phenomenon in the disease Unquestionably it is nearly as 
important as the temperature, and in many cases is far more accmatc foi 
prognosis The pulmonary patient bordeis constantly upon the verge of 
excitement, and the visit of the ph 3 'sician or a call at his office will often 
increase the pulse twenty beats a minute The best record is that taken at 
the patient’s home by a nurse to whom he is accustomed This instability 
of the pulse has some connection with the decrease of blood pressure and a 
paresis of the vessels Altitude increases the pulse rate somewhat, which 
may decrease in a short time or persist 

Increased frequency is often a stiikmg feature and is of gieat value in 
diagnosis, as it stands most often m direct relation to the activity and extent 
of the disease and strength of the patient The majority of all patients 
have at first a slightly increased rate (90 to 100), even when apyretic, and 
frequently when at rest m bed The pulse rate and temperature may be 
independent, but more usually there is aiather close connection between the 
two, which some have tiled to express by allowing ten beats for each degree 
of fever An increase above this rate, they think, is due to caidiac weakness 
Forced feeding may produce slight acceleration of the pulse foi a time In 
some cases the pulse shows increased rapidity for short periods, but this is 
rather unusual, as when it once becomes rapid it usuall}' remains so for 
some time Mental excitement, slight physical exercise, attacks of coughing, 
and a full meal have a strong tendency to increase the rate m early as well as 
in advanced cases In the latter, however, the pulse tends to be constantly 
rapid, and, varying somewhat with the temperatuie, increases slightly every 
afternoon The range is usually between 88 and 120 This tachj^cardia 
IS seldom noticed bj’' the patient Often as he improves and after the 
temperature has become noimal the pulse rate gradually decreases, but 
it may quickly fall to normal and lemain so Slight tachj^cardia may pei- 
sist in healed pulmonarj'' tuberculosis 

The cause of the increased frequency is still unsettled It has been 
attributed to pressuie upon the vagus by enlarged tracheobronchial lymph 
nodes, an explanation which certainl 3 >- does not suffice m many cases 
Brehmer thought the underdevelopment of the heait and the overde\elop- 
ment of the lungs were important factors Another view is that it is due to the 
increased work thrown upon the heart by a narrowing of the lumen of the 
pulmonarj' vessels, or to a narrowing of the air passages, which Mane found 
diminished the number of respirations and accelerated the heart A neuritis 
of the vagus, the fall in blood pressure, irritation of the sympathetic, increased 
irritability of the cardiac ganglia oi muscle fibers, mj ocarditis, anaemia, and 
dj'spepsia have all been suggested as factors The most probable cause, 
especially m incipient stages, is a weakening of the cardiac muscle and its 
nervous eontrol due to the tuberculous toxin, but this hardlj explains the 
persistent tachycardia in some healed patients Valvular disease of the 
heart m pulmonary tuberculosis exerts little influence upon the pulse rate 



THE SYMPTOMS OF TUBERCULOSIS 


261 


Blood Pressure — In many cases this is lowered from the very outset, 
and some have held that hypotension is piesent m the piedisposed A 
much greater variation exists between the blood pressure m a reclining and m 
an upright position than m health Potain believes that this hypotension 
can be used to differentiate a tiue chlorosis fioni the secondary amemia of 
tuberculosis The hypotension is held by many to be due to the tuberculin, 
which undoubtedly loweis tension (Teissier) As the disease advances and 
pionounced constitutional symptoms occur, the blood pressure becomes less 
and 90 mm of Hg (Riva-Rocci manometer, with 9 in cuff) is not uncommon 
When complicated by emphysema, nepliiitis, arteiiosclerosis, diabetes 
(Teissiei), oi caidiac hypei trojiliy the blood piessuie may be raised 

Heart- — ^The heart may sliov little change throughout the entire course 
R has long been held that it is reduced in size, and upon this Biehmer founded 
one pait of liis plan of tieatment, graded walks More recent observations 
have shown that hypertrophy is only a little less frequent than atrophy, 
which usually occurs only m cachectic patients In 70 necropsies at the 
Phipps Institute the heart was normal m size in 32, enlarged in 26, and de- 
creased m size m 12 Many complications produce an hypertrophy, so that 
it IS difficult to diaw any conclusions at autopsy m regard to the heart early 
111 the disease The orthodiagraph has, it seems, shov n a slight atrophy in 
incipient and hypertrophy or dilatation m far advanced stages 

Displacement of the heart usually occurs gradually, but m some patients 
transposition to the light side seems to take place within a few days The 
shrinking of the right lung frequently mereases the area of pulsation and 
may so displace the heart that the pulsation is limited entirely to the light 
side, extending in some cases beyond the midclavicular line Retraction 
of the left lung may cause caidiac symptoms varying fiom slight discomfort 
to pseudo-anginal attacks 

Murmurs are not uncommon eithei at the apex or base, but in the writer’s 
experience are moie frequent at the apex and usually sjstohc Some occur 
m patients in whom amemia can be excluded, where the displacement of 
the heart, if any, is slight, and Avhere we are led to explain the murmur as 
due to pressure upon the gieat vessels These patients show no eardiac 
hypertiophy In a few patients murmurs occur m the mterscapular region 
Consolidation may transmit these murmurs widely A cavity near the heart 
ma> alter the sounds, and murmuis synchronous with the systole are not 
infrequent in these cases hlurmurs are at times produced in cavities by 
the systolic distention of a laige vessel or of an aneurism 

Acute dilatation of the light ventricle occurs far less frequently m tuber- 
culosis than in other pulmonary diseases In many chronic cases, where 
the intrapulmonary I'essels are either obliterated oi reduced m size, accent- 
uation of the second pulmonic sound occurs and the shock is at times easily 
palpable Over the second left intercostal space the second sounds are at 
times reduplicated (best heard vhen the patient reclines) A weakened 
first sound is lather frequent in well-advanced stages, and is often more 
pronounced during acute attacks 

Dilatation of the right side of the heart in advanced stages is, howei^er, 
more fiequent than many obsen^eis have held Norris states that dilatation 
or Iq pertrophy of the right side occurred in 27 per cent of 2344 patients m 
adianced stages, and m 21 per cent of 143 autopsies Accentuation of the 
second pulmonic sound occurred in 35 per cent , accentuation of the second 



262 


I\FnCT10VS DISEASES 


aortic sound in 18 per cent , and icduplication of the second sound in 40 
pel cent of 2344 patients, hypci trojdiy oi dilatation of the left lieait in 2G 
per cent , tachycardia (pulse late o\cr 120 at fiist visit) in 17 pei cent , biad)- 
cardia (pulse late below 05 at first Msit) m 1 5 per cent , and displacement of 
the heait in f 7 per cent 

Palpitation — ^This in neurotic subjects is usually a venous phenomenon 
associated with hypotension The shghtei forms aie frequent and fev 
patients entirely escape them The severe forms occur occasionally after 
too Aigoious exercise, and are most likely to be met vith in advanced stages 
They are more frequent at pubeity and at the menopause, sometimes pie- 
cede hfemoptysis and accompany dyspepsia Some have noted pain in 
the neck along the vagus When a patient complains of palpitation the 
lungs should always be examined Caidiac distress may also be found in 
a few patients not suffering fiom palpitation 

Vessels — Pulsation in the cervical vessels is of frequent occurrence 
Temporal}' dilatation of the subclavian arteiy has been described by West, 
Avho thinks it not rare Dilatation of the venules upon the upper thorax 
and about and above the costal margin is quite common A murmur over 
the subclavian artery, first described by Stokes, is not unusual under the outer 
thud of the clavicle, and has been held to be of diagnostic importance It is 
more common on the left side and is rare m women It may appear or 
increase during inspiration or expiration, and is due either to amemia oi to 
compression of the vessel by a thickening of the pleura or bv a muscle The 
muimur is not constant, is usually soft and blowing, and the position of 
the arm or pressure by the stethoscope may increase or produce it OEdema 
of the lower extremities is lare except in the ^ery late stages, when it almost 
invariably indicates great caidiac weakness 

Cyanosis — Tins may persist foi years while the patient enjoy'S com- 
parative health In many it is moie pronounced in the morning In the 
late stages the lips and nails become blue and the face and extremities aic 
often cyanotic In eaily stages it seldom occurs except as the lesult of seveie 
pleurisy or cardiac complications 

Skin — ^The skin undergoes changes produced by' malnutrition In 
many patients m early stages, especially those undergoing treatment, the skin 
IS clear, ruddy, and noimal m every' particulai The chilliness and undue 
sensitiveness to cold aie less fiequent now than formerly In the majority 
some palloi of the skin is piesent and often the vessels aie well seen thiougli 
the “skim-milk” complexion (tubeiculous diathesis) In some the skin is 
dull and opaque and the complexion muddy (sciofulous diathesis) In 
late stages the skin is often dry' and harsh, and even furfuraceous (pityiiasii 
tabescentium) This occurs most frequently on the trunk and extremities, 
and the skin feels like cloth rubbed against the nap The sebaceous as well 
as the sweat-glands may be stimulated and the skin become oily A pun- 
gent odor from the sweat is often noticed 

Pigmentation occurs rather infrequently' and may' consist in a general 
bronzing of the skin, less marked than in Addison’s disease, or in a patcln , 
light yellow to pale brown, often shiny pigmentation, Avhich may occur on 
the face or trunk, the so-called chloasma phthisicorum A connection 
between intestinal disorders oi change in the spleen and lymph glands 
has been suggested as the cause of this, vhich is said to be more common 
when the peiitoneum is im olved Icterus is rare An eiy thema is occasion- 



THE SYMPTOMS OF TUBERCULOSIS 


263 


ally present, and, while usually accidental, may at times be due to a tuber- 
culous toxin It occuis m connection iMth acute conditions and adenitis, 
and in some appeals only when the fe^er is at a maximum It may closely 
lesemble the rash of seal let lc\ci,but usually spares the mucous membranes 
PetechicB rarely occin Puipuia is seldom met with except m acute miliary 
tuberculosis, but some think it is occasionally due to the tuberculous toxins 
CEdema of the skin larely occuis except in complications or late m the dis- 
ease The hectic flush m late stages or a reddening of one cheek and ear 
m moderately advanced patients is common Subcutaneous emphysema, 
with crackling on palpation, due to a rupture of the lung, is a raie complica- 
tion Local tubercle may develop on the hand Herpes labialis occuis 
periodically with slight gastric disturbances in some patients, and is not 
uncommon aftei a tuberculin reaction 

Hypci cBsthcsia of the skin is common and is often elicited on percussion 
It is larely noticed below the thud rib, is said to spiead or contract with the 
advancement oi retrogi ession of the disease, and to be more acute when the 
tempeiature is elevated In lesions of the uppei lobe it is most frequently 
present in the supraspinous fossa 

Hair. — ^The nutution of the haii suffers espeeially during fever It often 
becomes diy and lank} , and may split The hair may come out in consider- 
able quantities, but the alopecia is seldom patchy, partial, or complete Pre- 
matuie grayness occuis accidentally, but may be due to pooi nutrition The 
arcus senilis may also occui early In children and young persons the body 
IS sometimes covered v ith a growth of fine, downy hair (Kidd) 

Nails — ^Tlie down-curving of the nails may occui without, although 
usually with, clubbing of the fingers (Hippocratic digits), and is thought 
to be due to the loss of fat on the palmai surface and malnutrition of the 
matrix, as well as circulatory distuibances It is said to occur more fre- 
quently m women, and is most usual beteveen ten and thirty years of age 
The ridges and furrows which occasionally occur are also due to pooi 
nutiition 

Alimentary System — Symptoms referable to the alimentary tract aie 
present sooner oi latei m nearly exery patient, and xvhile not as frequent as 
symptoms referable to the respiratory system, rank second in impoitance to 
none 

Gums — The gums in advanced cases, owing to the pooi nutrition, are often 
spongy and soft, and pyorihoea is not infrequent A red line on the gums, 
first described by Fredencq m 1851, and pictured by Thompson, is not 
peculiar to pulmonary tuberculosis, but occurs in many wasting diseases and 
111 some healthy persons The cause of this bluish-red line is undoubtedly 
a mild gingn itis Bleeding of the gums is x ery common and m streak} 
luEinoptysis should alxvays be excluded Caries of the teeth is frequent, due 
possibly to the gingivitis, and is of great importance on account of the 
necessity of thorough mastication Thirst is rarely great unless diabetes 
inellitus or fever is present or unless the patient breathes through the mouth 

Tongue — The condition of the tongue x aries directly xx itli the condition 
of the patient In incipient cases xvitli good digestion it is clean, moist, 
and normal, as also m many adx'^anced cases When gastric complications 
occur or x\ hen the patient sleeps wnth an open mouth, the tongue is usually 
cox'ered xxitli a xxliite fur, xxhicli may become dark from food or medicine 
In advanced stages sordes or a deeply fissured tongue may be present 



264 


INFECTIOUS DISEASES 


Tonsils — The tonsils may be hvpeitiophied, but adenoid tissue is rarely 
present Chionic gianular pharyngitis is common Stomatitis is infie- 
quent in eaily cases, but aphthous ulcers occui at all stages Salivation or 
stoppage of Whai ton’s duct, ivith oedema of the mouth, tongue, and neck, 
is rare and probably accidental Thrush may oecui on the soft and hard 
palate, ton&ils, tip and loot of the tongue, and mucous mcmbianes of the 
cheeks Usually of slight importance, it may penetrate into the deeper 
vessels, cause thiombosis, and e^en pioduce ceiebral metastasis 

Digestion — The digestion may be good to the end and many patients 
recover -without the slightest digestive disturbance A majority, hoiveiei, 
sutler at some time from digestive disorders (70 to 90 per cent ), and omen 
more than men The type of the disease seems to exert less influence than 
its acuteness Patients v ho escape have usually been good eaters, and the 
appetite is the best guide to the digestion Alcoholics and those vho have 
abused their digestion pay usually heavy penalties Distress or anorexia 
may occur vhile apparently all the gastric functions are normal, but on 
the whole the gastrie tolerance is remarkable and the amount of food con- 
sumed by some patients, even while at rest, is tiuly astonishing In many 
patients with gastric disturbance no pathological changes m the stomach, 
except possibly slight hyperaemia, have been found Dyspepsia v hen present 
usually becomes less marked as the pulmonary disease advances, and when 
it is ai rested the dyspepsia generally subsides 

The gastric juice is normal m many early cases (50 per cent , Brieger), but 
as the disease advances it is fiequently abnormal, and m severe cases over 
80 per cent (Biieger) show some change Hyperacidity may be present in 
early stages, while latei subacidity is moie common The weakly aUcahne 
sputum must be swallowed m large quantities to pioduce any effect by 
neutiahzation upon the gastric acidity The secretion of HCl is inde- 
pendent of the fever, but with other constituents of the gastiic juice seems 
to be reduced m far-advanced stages The digesting powei of the gastric 
juice has been found to be reduced in some cases 

The motor functions of the stomach usually run paiallel with the condition 
of the muscles m geneial, and accordingly the motility may be deficient in 
advanced but also m some early eases With loss of motility, dilatation of 
the stomach occurs 

The rapidity of absorption is little changed at first, but with dilatation 
and loss of motility it is much diminished Gastioptosis in these cases is 
occasionally present 

The gastnc disoideis have been well studied by Marfan, who, under the 
“usual djspepsia of phthisis,” discusses the variable modes of onset and its 
frequent teimmation by gastritis The appetite usually fails and after meals 
some distiess is noticed, varying from slight distention to actual pain or 
cramps Eructations are not uncommon, but pyrosis is infrequent The 
gastnc mucosa is very irritable and m some cases eating is followed by cough 
and cough by vomiting without nausea This occurs more frequently after 
the evening meal, as the morning cough has m most cases completely cleared 
the air passages The vomitus m these cases usually consists of undigested 
food A pecuhant) of the vomiting thus produced is the fact that the patient 
is often able and willing to eat again at once In these cases the motilitv of 
the stomach and the digestu e power of the gastric juice may be lessened 
Such changes are probably purely functional and not connected with the 



THE SYMPTOMS OF TUBERCULOSIS 265 

fever Lasegne has remarked that a patient ^^ho eats and digests well 
■while having fevei is a “phthisikei ” 

This dyspepsia may fiist call the attention of the patient to his health or 
it may de^elop at any stage It is often preceded by hyperacidity and its 
accompanying symptoms, and is caused by irritation of the peptic glands, 
by the tuberculous toxins or of the mucosa by swallowed sputum, or possibly 
IS due to the anieima Disturbances of the nervous system may be the cause 
of slight digestn e disorders Hays holds that the eaily digestive disturbances 
are due to the alteied gastiic juice, and that the disappearance of the symp- 
toms which often takes place later is due to an adaptation of the organism, 
namely, an increased sccietion of gastric juice of lessened digestive po■^^er 
Fenwick thinks that chemical alterations in the blood, occurring at the 
onset, are diiectly lesponsible for both the digestive disturbances and the 
amemia 

The terminal gastiitis is characterized by a furred tongue m ith led papillfe, 
an absolute anorexia, and a peisistent diarrhoea Besides these the other 
symptoms of the initial dyspepsia may all be present and exaggerated, and 
dilatation and motor insufficiency are constantly present The abdomen 
IS often sensitive, most maikedlj about the umbilicus 

Anoicxia — ^When tissue hunger is greatest, wiote Dettweiler, the appetite 
IS often least Anoiexia, however, is rarely complete in the earlier stages 
unless piofound constitutional symptoms aie present Many patients 
complain of no appetite, but eat, and eat n ell, and these are less liable to 
digestive disturbances Again, many patients are hungry until they see the 
food 01 until a few mouthfuls are taken, then appetite may be replaced by 
nausea The appetite is frequently eapncious, good foi one meal and 
lacking for several, or good one day and lacking for several, but on the whole 
it diminishes as the disease progresses The tastes may undergo striking 
ehanges, and food once lehshed becomes lepugnant and strange or bizarre 
articles of diet are ciaved An antipathy to fats exists m some patients 
Desiie foi food is at times closely connected with the temperature, and at 
noon 01 evening, nhtnever the maximum temperature occurs, the appetite is 
poor or lacking This is not always the case, as many patients with high 
fevei eat well In a surprisingly large number the appetite remains good 
until shortly before death 

Pain — Slight gastralgia is frequent in early as well as m late stages Often 
it IS fleeting and needs no treatment In others the pain occurs legularty 
either immediately after eating or later, and is rarely the only symptom 
present Distention is a frequent cause Pam m the epigastrium, imme- 
diately aftei eating, may occui when the stomach is normal and ulceration 
IS present m the transverse colon 

Gastric fermentation, due in many cases to overfeeding, is probably the 
most frequent of all gastric disturbances The resulting distention may come 
on immediately after each meal, and varies from a feeling of fulness and 
discomfoi t to one of acute pain In some cases it seems to varj^ n ith the 
temperature, and, beginning during the afternoon, leaches its crisis in the 
early e\ening 

Navsca — ^Nausea is very common at all stages It may occur for some 
time before the plpsical signs are sufficiently pronounced for diagnosis 
In the teiminal stages it is often present and accompanied by vomiting 
•Manj times it is manifested onh in the morning, and may prove most 



266 


infectious diseases 


stubborn Again it comes on, when after one oi two mouthfuls tlie appetite 
vanishes and the patient tiies to foice down a little mole food It often 
occuis without vomiting, and may cause much distiess 

Vomiting — ^This may occui vitli oi without nausea Without nausea 
it is usually due to violent parexj^sms of cough, the emetic cough of hlorton, 
and IS more frequent in basal lesions This vomiting usually takes place just 
after meals oi when a change of postuie is made, generally on arising One 
patient with a laige cavity m the uppei lobe vomited eveiy morning and 
neA er expectorated at any time The vomiting m these cases is mechanical 
Vomiting after nausea or other gastiic sj'^mptoms is less frequent, but fai 
from uncommon, especially m the later stages In the first case the patient 
IS often able to eat again at once, m the second the thought of food is repug- 
nant Other causes of vomiting are nervousness, piessure upon the vagus 
by bronchial glands, hyperiesthesia of the posterior pharyngeal wall (sputum 
furnishing the necessary iiritation), and nasopharyngeal catarrh Vomiting 
may precede all other symptoms and peisist after the disease is arrested 
Litestmal — The intestinal secietions and the peristalsis may undergo 
changes of varying intensity Constipation, which is more frequent than 
diarrhoea except m the very last stages, is no doubt in part due to the milk 
diet, m part to lessened peristalsis, caused possibly by the weakened mus- 
culature Whatever the cause, constipation and at times obstipation is 
most troublesome and needs careful attention It may be piesent until 
death, notAMthstandmg severe intestinal ulceration 

Dial lima — This may occur for months befoie a diagnosis is made 
One patient avIio had coughed since Christmas, began m April to have 
infrequent (one or hvo a day) loose stools Avhich lasted until August, when 
aftei a hemoptysis tubercle bacilli were found m the sputum, which he 
ceased to swallow Treatment had been of no avail, but from this time on 
his stools were normal The swalloAved sputum can in many cases set up a 
catarrhal enteritis, aaIiicIi is more marked by its chromcity than by the 
frequency or profuseness of the stools This form is more frequent m women, 
but may be caused by sputum sAvalloAved during sleep The tubereulous 
toxins may cause diarrhoea by irritation of the sympathetic system and 
mereased peristalsis, by catarihal enteritis, or by superfieial erosions (catarrhal 
ulcers) This AAOuld no doubt explain the diarrhoea AAdneh m rare cases 
follows tuberculin 

Many tuberculous patients haA^e diarrhoea from apparently trifling causes 
In some, milk or raAV eggs Avill m the course of time pioduee a pronounced 
griping and diarrhoea A chilling of the abdomen and slight indiscretion 
m diet, especially indigestion due to overfeeding, are sufficient in otliers 
The cough and expectoration may dimmish when the diarihoea in- 
ci eases 

In any digestive disorder the stools should be examined for undigested 
food and for baeilh to exelude the SAAalloAAing of sputum 

Liver — A. fatty In^ei is said to be of frequent occurrenee, due to the aetion 
of the tuberculous toxins on the liA'er cells Possibly the laige amount of 
food 01 alcohol preAuously taken may liaA'e some effect 

Spleen — Enlargement is rare and occurs practically only m acute miliarj 
tuberculosis or m acute exacerbations Amyloid degeneration may occur 
The Gemto-urmary System —The gemto-unnary organs present fcAV 
SA'mptoms m uncomplicated pulmonarj’’ tuberculosis 



THE .S'l MPTOMS OF TUBERCULOSIS 


267 


The Unne ' — This is usually normal in evei> paiticular in eaily stages, 
but when fe\er is piesent it may be concentrated and deposit urates The 
amount is otten inci eased, especially at fiist, and the maiority of patients arise 
one or more times at night The hbeial milk diet no doubt often accounts 
for this, but a true polyuiia can occui Some oliguria may be piesent in far- 
advanced cases llobin has found the solid lesidue m 46 fatal cases to be 
about 30 gm , in 6 v ho failed 33, and in 21 who remained stationaiy oi 
improved 51 gm pei diem He consideied a patient who excieted less than 
30 gm per diem as in the beginning of the cachectic stage The urinai> 
salts vaiy with the temperature and the stage of the disease The chlorides 
may decrease m exaceibations or ^\hen profuse expectoration occuis, but are 
usually normal 

Phosphatuiia is held by some to be an early indication of pulmonary 
tuberculosis (Powell) Calcium phosphate predominates and increases as 
the emaciation pi ogresses Both calcium and magnesium inciease at first 
and latei decrease Cioftan considers a high calcium content important in 
eaily diagnosis Phenol has been found in the urine, especially ]ust before 
death Indicaii occurs more frequentlj', especially in children, than in 
health It is of little or no value m diagnosis The urea varies in 
amount, frequently normal at first and often decreasing late m the 
disease, it vanes with the diet, exercise, and temperature Acetone, 
sugar (without diabetes), peptone, and albumose have been found Albu- 
minuria IS rare m early and is usually met with only m far-advanced stages 
Teissier has described an intermittent form occui ring m young individuals 
with a family history of pulmonary tuberculosis The diazo reaction occurs 
inconstantly in some patients m advanced stages, who usually present 
marked symptoms, constitutional and local 

In 666 patients at the Phipps Institute, Philadelphia, foi the most part in 
a far -advanced stage, sugar was piesent in 13, albumin in 153 Casts uere 
noted in 37 and the diazo reaction in 60 among 495 cases Poisonous sub- 
stances, ptomams, have been found in the urine of patients with apparently 
normal kidneys, and it has been claimed, but notpioved, that tubercle bacilli 
m the urine may be the only means of diagnosing an earty pulmonary lesion 
Flick and Walsh have found tubercle bacilli in the urine of patients with 
pulmonary tuberculosis m 73 per cent of 60 cases (the differential diagnosis 
being based upon the use of alcohol and Gabbett’s solution), while Supino 
i\as unable to recoiei them after veiy painstaking reseaiches In 14 out 
of 17 far -advanced patients inoculation experiments shoved tubercle bacilli 
m the urine (Walsh) It is no proof that because injection of urine or its 
icsidue causes a “reaction” similai to that produced by tuberculin, tuber- 
culin IS m the urine, for other substances may cause this reaction 

Inflammation and displacement of the uteius, common in pulmonary 
tuberculosis, are probabh caused by an aggravation of preexisting tiouble, 
and in some cases to cough 

Menstruation — ^This may be scanty or cease early m the disease, especially 
when the patient is amemic Change of residence may also aflect some 
patients An onset at the time of puberty may delay menstruation for years 
As the disease advances the menses usually, if not preyiously disturbed, be- 
come irregulai and finally cease With improyement menstruation begins 


’ See Clemens in Ott’s Chenneal Patholoqi/ of Tvbctnilosts 



268 


INFECTIOUS DISEASES 


again InafeA\ the menstiual function continues to the end Menonhagia 
occurs in a few cases, butiaielypeisists It is a common tendency wnth w'omen 
to attiibute many exacerbations of the disease to the recurience of the men- 
strual periods, and in some cases the symptoms aie undoubtedly moie pro- 
nounced at tins time The piemenstrual fevei occurring foi about one 
w^eek befoie menstruation is w'^ell recognized, while many hiemoptyses occur 
and recur at this time The expectoration may be increased oi piesent 
only during this period 

Pregnancy — Pregnancy can occur in veiy adAanced stages and one 
patient, failing giadually for months, became unconscious foui days befoie 
term and died duiing delnery Dining pregnancy the disease is often held 
111 abeyance, to pioceed more lapidly alter paituiition 

The Nervous System — ^The neivous system is often eaily affected, and 
few patients entiiely escape some neivous distuibance This wmuld be 
expected in neurotic individuals, but wdnle usually moie pronounced it is by 
no means confined to them A tuberculous family taint is supposed to 
render the patient moie liable to neivous disordeis 

Psychical Changes — An appaient change in the disposition of the patient 
IS not infrequent It is in many cases only “ajipaient,” as m a large number 
the real character is laid baie By many all sham and pietension aie tliiow n 
aside, perhaps unwittingly, and selfish traits, previously fosteied by foolish 
parents, may become so pronounced that the patients try to exeit despotic 
swmy over all their associates and attendants They wall not brook the 
slightest mteifeience with then w'lshes, and, wdien opposed, eithei fall into a 
rage or burst into tears Fortunately, these examples aie rathei rare On 
the othei hand, some dispositions, naturall}’’ quiet and lefined, seem as the 
disease advances to become so unselfish, so etheieal that they suggest another 
sphere in more wmys than one Chronic invalidism raiely leaves the char- 
acter unchanged, and tieatment which constantly enfoices self-consideration 
IS not conducive to unselfishness And yet years of institutional life, months 
spent in health lesorts, and the constant solicitude of the family and friends 
affect singulaily little the charactei of many chionic tuberculous patients 

The restraining influences of early training, of edueation, of A'ocation, of 
the mannei of life, all seem to lapse m many patients, and sanatorium exqieri- 
ence teaches that many act as if they were still school-children, looking upon 
physicians as boys do upon tutors or preceptors and endeavoiing by man) 
little ruses to gam their owm ivay A foolish act undetected they think can 
do no harm The emotions, too, are less resti ained, and unexplainable mis- 
understandings and ditfeiences may arise Many cannot bear to heai of 
suffering, and in some, tiifling causes produce tears Emotional weakness 
IS common Jealousy, especially m lAomen, is at times marked to a high 
degree 

Indecision, vacillation, and changeableness are frequent chaiacteristics 
in some patients Fancied grievances turn them against old fiiends Their 
judgment of men and affairs, their plans and outlooks often change fiom dai 
to day, or maj be entirely reversed Forced mactnity produces lack of 
concentration in some Only the most exciting liteiature can arouse them 
In others again eieiy act is characterized by morbid haste and impulsn'eness 
and, to use a familiar expression, the patient becomes a “bunch of nen^es ” 

The mental faculties are generally w'ell preseri ed to the end and, in fact, 
ma) become more acute and out of all proportion to the bodily strength 



THE SYMPTOAIS OF TUBERCULOSIS 


269 


The patient may plan and attempt to put into execution many schemes 
consigned to failure at the outset He may endeavor to acquire a monopoly 
of the cottages m a health resort and sign many foolish contiacts What- 
ever he plans he must be about at once, little realizing the effect upon his 
jaded body “Death catches him like an open pitfall, and in mid-career, 
laying out vast projects, and planning monstrous foundations, flushed with 
hope, and his mouth full of boastful language ” In a fev , ideas of self- 
importance and of grandeur, great nervous irritability, suspicion and sus- 
ceptibility to suggestion are marked 

This, however, is not a true picture of the ordinary tuberculous patient 
The vast majority, though depressed at first, soon rebound and improve oi 
fail, they remain the same men and women they v ere before they became 
sick They may he optimistic, pessimistic, sanguine, choleric, or phlegmatic 
The s'pes phthisica is common and may be pronounced even to the end, but 
the vulgar opinion has been until recently so pessimistic that it is not possible 
foi the patient to escape its influence, and many arguments are necessaiy to 
convince him of the possibility of a “cure ” He quickly recognizes the seri- 
ous illness of a fellow-patient, and it seems impossible that he should not 
realize the gravity of his case Fortunatelj , these patients are little given to 
cl frank discussion of their piospects, but when they can be led to discuss 
dispassionately their disease they often frankly acknowledge their despair 
Familiarity luckily removes many stings, and he who faces death constantly 
often comes to face it fearlessly The reierse is the case in some sad in- 
stances, and the physician is called to no harder trial than to listen to a dying 
consumptive pleading for life, which he cannot sustain 

Neuroses — Neui asthenia is more common m pulmonary tuberculosis 
than in any other disease No doubt it has an organic basis m the toxic 
poisoning of the higher centres, but, hov ever that may be, few escape it 
At first It may be so pronounced that it masks the tuberculosis, which may 
be 01 ei looked for some time In other cases it develops only when the 
patient is well on the road to recovery', and forms a serious complication 
Phj'sicians and nurses, when attacked, are peculiarly prone to this neuras- 
thenia Pressure in the head, giddiness, feai, anxiety, vasomotor disturb- 
ances, and especially sleeplessness are common When pulmonary' tuber- 
culosis occuis m neurasthenia or hysteria the nervous symptoms arc usually 
increased 

Hysteria occurs much less frequently and most often just before or duiing 
the menstrual period It tends to disappear with the progress of the pul- 
monary disease, and is larely' seen in men Aphonia is not uncommon, but 
convulsions or spasms are rare In one patient a spasmodic contraction of 
the oesophagus permitted the swallowing of fluids only' 

Psychoses — Psychoses are very' much rarer in pulmonary' tuberculosis 
than pulmonary' tuberculosis m psy'choses Tii'o classes may' be recognized 
first, a group peculiar to the disease itself, second, a group including the 
usual types of insanity determined by a lowering of nutrition” (McCarthy') 
In the fiist class are patients with no hope of recovery', but happy' and con- 
tented and often with a decided grade of unreason They closely' simulate 
paresis In 1674 cases of pulmonary' tuberculosis, McCarthy' found 4 
patients, all v itli advanced disease, terminating fatally', but m whom a happy', 
contented state of mind existed, with expansive ideas and distinct delusions 
of grandeur Their sjieech was paretic, and tremor of the tongue and hand 



270 


INFECTIOUS DISEASES 


marked This type of McCarthy’s differs fiom the form described by 
Clouston, where depression advances to melancholia, and morbid suspicion, 
maiked loss of memory, a desire to be alone, irritability, and delusions of 
persecution occur 

The second group includes melancholia, mania, dementia priecox, hys- 
terical insanity, and delusional insanity Melancholia develops m a few 
cases shortly after the diagnosis has been impaited to the patient, or it may 
occur in moderately advanced cases In fai -advanced cases it seems to 
be lare Suicidal tendencies aie not uncommon in these Onset of the 
disease with mania is ^ery uncommon, and latei m the disease mania is 
also raie The age incidence of pulmonarj'^ tuberculosis is the same as 
that of dementia prmcox, and the association of the two diseases may be 
thus explained Vertigo, cephalalgia, buzzing m the ears due to cerebral 
aniemia maj" occur, as iiell as hypeiremia, simple meningitis, pachy- 
meningitis, and inflammation of the dura, m ith symptoms of hydrocephalus, 
especially in children, and ton aid the end somnolence and disturbance of 
consciousness, due, Ruehle holds, to ceiebial oedema 

Tiemors are common and usually occur on voluntaiy effort They may 
persist aftei recoieiy, and no doubt m some cases existed previously to the 
onset of the pulmonary tubeiculosis The leflexes are often exaggerated, 
but may be decreased oi absent, especially in marked asthenia The knee- 
jerk IS increased m one-half of the eaily cases The ulnar reflex, a distinct 
unnklmg of the exteinal bulge of the hypothenai eminence, elicited by 
scratching the skin on the anterioi suiface (ulnar side) of the foiearm with a 
pointed instrument, is held by McCarthy to be very suggestive of pulmonary 
tuberculosis, and may occur only on the affected side This author has also 
found Chvostek’s phenomenon, rapid conti actions of the fibrillie of the 
facial muscles, elicited by tapping over the distribution of the facial nerve, 
present m 16 out of 287 cases of pulmonary tuberculosis These phenomena 
depend upon the hypeiiiritabihty of the peripheral neuionic system Tabes 
dorsalis, multiple sclerosis, and general paialysis have been attributed to the 
tuberculous intoxication, but Avithout sufficient reason 

Neuritis — The peripheral nei ves are seldom affected, and sensoi are 
much more fiequent than motoi distuibances The frequency of neuritis 
IS difficult to determine, as many are found at autopsy to have neuritic changes 
of degeneiation, which duiing life cause no symptoms (latent neuritis), and 
occur chiefly uhen cachexia has developed, but whethei they aie due to the 
toxins of the tubeicle bacillus, of the secondary oiganisms, or of the softening 
lung is still unsettled 

The lesion can be limited to a single neive, a plexus, or involve all the 
peripheral nerves The leg is usually more affected than the arm, and the 
exteinal perineal nerve may be the first affected Atiophy of the affected 
muscles occurs, but usually a feu are spared m an extiemity, and so some 
motion IS pieseived Parmsthesia often piecedes this type Sensory 
neuritio ma> affect the skin, muscles, peiiosteum, and joints, oi an entiie 
extremity (acropaifesthesia) Neuralgia of the intercostal nerves, the tii- 
geminus, of the sciatic and othei nenes aie common Ai thialgia, melalgia, 
mialgia, and deimalgia all occui Tenderness on piessure oier the nerves 
IS not aluays present, but if continuous sensitneness to external piessuie, oi 
to actne or passne movement, especially to mo^ement uhich sti etches the 
nerves, exists, if spontaneous pain occurs, if the pain be continuous for a week 



THE SYMPTOMS OF TUBERCULOSIS 


271 


in spite of local theiapy, and if the deep refle\es be lost, a neuritis is usually 
present If, however, the pain he not constant, and if in the interval pies- 
siire or movement causes no pain, if it yields to i datively slight therapeutic 
measures it is due to an irritative cause and not to inflammatory neuiitis 
The mononeuritis frequently heals, but a polyneuritis is usually fatal, either 
quickly or, more commonly, after many months 
Pressure neuritis may occur in the vagus, due to enlarged bronchial glands, 
and is manifested by rapid pulse, cough, dj^spnoea, hoarseness, and larjmgeal 
spasm or paralysis Pressure on the sympathetic by retraction or thickening 
of the pleura may, by its cervical and brachial connections, cause a dilatation 
or contraction of the pupil or neuralgia in the arm Dilatation of the pupil 
may occur before the pulmonaij^ symptoms are manifested Pressure of 
glands upon the recurrent laryngeal nerve may cause hoarseness 
Pulmonary disease can cause, as Head has shown, referred pains, irri- 
tative phenomena, hyjiei algesia and neuialgia, in the skin of the neck and 
thoiax by the connections of the sympathetic and vagus Connection with 
the trigeminal nerve may cause pain in the forehead, eyes, and head The 
neuralgic pam may occur suddenly, dait from front to back, is little affected 
by ordinary^ breathing, but may be by' deep respiiation Pressure lessens 
the pain, which is most frequent in the initial stages, but may recur tem- 
porarily during a i elapse 

The vasomotor nerve supply is ^ely' unstable, and limited redness of the 
skin, especially' of one cheek on the affected side or of both cheeks, elevated 
temperature in limited areas, localized asphyxia, sweating and ecchy'mosis, 
and a syndrome closely simulating exophthalmic goitre, are all probably 
the result Myoidema is probably a functional neivous derangement of 
the muscles Hoarseness, especially' the premonitoiy type, depending upon 
a yveakness of the adductors, is due also to the same cause 
Sexual desne is held by many to be inci eased, but this is in all probability 
lather due to the fact that pulmonary tubei culosis usually attacks young 
adults m the prime of life, and that the treatment consists of o\ei feeding or 
at least of abundant feeding, enfoiced lest, and lack of occupation It is 
usually decreased 

Herpes zostei , due to changes in the posteiioi root ganglion, is not rare 
It IS most frequent in the ninth to the twelfth dorsal segments, but occurs on 
the face, and in one patient extended oa er the i ight leg as low as the knee 
The discomfort is often slight, but the pain may' be so severe that the patient 
has to be kept undei the influence of morphine for several day's There 
seems to be no connection between the site of the pulmonary' lesion and the 
affected side In some cases the hemorrhagic variety' occurs 
Headache is of fiequent occurrence (in about 10 pei cent , Cathala) and 
is often stubborn, hard to control, and seems to bear no relation to the extent 
01 stage of the tubereulosis It may be so severe that sleep is lost but this 
is rare 

Headache is frequently due to overuse of the ey'es with poor muscle balance 
or weakened musculatuie, but is said to occur from functional disturbances 
as veil as fiom organic lesions 

Sleep — Insomnia is not infrequent Change fiom an actne to a quiet 
life, indigestion, cough, sweats, and moie larely pleurisy may' all contribute, 
but neurasthenia and nervousness aie most fiequently the cause It often 
occurs periodically', and high altitudes in some cases greatly' increase it 



272 


INFECTIOUS DISEASES 


Cough — Frequency — Cough is the most frequent and, as a rule, the most 
constant of all symptoms m pulmonary tubeiculosis It usually fiist dra^^s 
attention to the lungs, but a slight cough may exist for months and attract 
little notice Its absence is more important m diagnosis than the absence 
of either night-sweats, emaciation, loss of strength, or dyspnoea A cough 
caused by deep breathing should always be looked upon with suspicion Au- 
frecht believes cough is not a symptom of the initial stage, but is lather to 
be looked upon as a complication, caused by laiyngeal catairh, Flick, that 
it IS due only to breaking down of tissue or to secondary infection In 
rare cases cough is absent throughout, and not very infrequently a patient is 
seen with a well-marked cavity whose cough has passed entirely unnoticed 
Othei things being equal, the cough varies in frequency with the amount 
and character of the expectoration, but no direct relation exists betv een the 
gravity of the disease and the severity of the cough It depends to a consider- 
able extent, however, upon the part affected and the neivous excitability of 
the patient Cough and expectoration may both increase dining the 
menstrual period, and j^uth as well as fever seem to increase the cough 
The mucosa of the respiratory tract is not equally sensitive throughout, and 
IS most irritable in the posterior mteiar^'tenoid space at the bifurcation of 
the trachea The irritability decreases downward, but an irritation once 
begun may rapidly mciease and spread to parts shoving pieviously slight 
susceptibility The pulmonary tissue has little or no sensitiveness It is 
probable that wdien the primary focus is situated near one of the main bronchi 
which becomes involved early the cough is moie seveie Involvement of 
the bronchi is often present m cases with seiere cough In some instances 
the patient can select a definite point on one side as the origin of irritation 
causing cough An acute pleurisy raiely causes and frequently checks 
cough, but a chionic pleuritic iiritation may produce a diy, hacking cough 
Varieties and Cause — Cough in the majority of cases is at fiist short, 
drj^, hacking, not haid, and rather frequent It may occur throughout 
the day or more fiequentlj" be limited to the early morning hours or night 
As the disease pi ogresses the cough becomes looser, pioductive, and in many 
cases more frequent, especially Avhen softening is taking place In patients 
with a catarrhal onset the cough is frequently loose from the onset The 
character varies with the amount of secietion and the part of the lespnatory 
tract affected Before the bronchi are affected the cough is usually dry, 
short, and hacking, after they are affected the cough is similai to that in 
simple bronchitis Cough may be divided into dry and moist or pioductive 
A dry cough may be due to irritation of the i espiratory tract or to a reflex 
The productive cough is caused by the nutation of the mucosa, usually 
by the slowly oi rapidly collecting secietions The morning cough is usually 
the result of the irritation of the sputum slowly gathered during the night 
Change of position and sudden contact of the secretions vith other parts 
of the mucosa no doubt play some part This is true in many cases with 
cavity, w^here either a change in position or an oveiflowing of the cavity 
causes continuous cough until the vomica is emptied 

The explanation of the cough fiequent with many patients on letinng 
is moie difficult Sudden contact of the secietions ai ith parts of the respira- 
tory mucosa hitherto for a time free, impact of air on parts of the larynx 
preAuously protected, congestion of the larynx due to the position of the head, 
hi periemia of the internal organs due to contraction of the peripheral A'essels 



THE SYMPTOMS OF TUBERCULOSIS 


273 


from the contact of the skin with the cold sheets, increased difficulty of 
expectoiation, hj^erfeinia and consequent increased irritability of the re- 
spiratory centre (which is lessened during sleep), have all been offered as 
exjilanations Many patients cannot sleep on the affected side, due possibly 
to the increased blood supply 

In a few patients cough continues to be noticed after meals, especially 
after breakfast, when it has ceased at all other times This is due chiefly 
to the hot fluids taken with the meal, but increased cough may occur from 
food by irritation of the upper respiratory tract, rendered more sensitive 
from inflammation or ulceration, either by direct contact v itli the food or by 
the mo\ ements of the oesophagus or pharynx, by direct pressure upon the 
trachea or bronchi by enlarged glands as masses of food pass by them, by 
the temperature of the food, by the pressure of the distended stomach upon 
the diaphiagm, or by the inhalation of steam from v arm drinks Increased 
frequency of respiration is a common cause of cough Laughing, singing, 
rapid talking, fast v alking, and deep breathing may all cause cough 

Paioxysmal cough may be due to the emptying of laige cavities, to ulcera- 
tion at the tracheal bifurcation, or to irritation by enlarged bronchial or 
mediastinal glands The respiratory efforts are not so close together, but 
fully as prolonged and as exliausting as in v hooping-cough 

The emetic cough is common in adr anced stages It is most frequent in 
the morning, but may occur after each meal and lead to lapid emaciation 
The stomach plays a passive part and the vomiting is largely mechanical 
The cough causing the vomiting may be dry 

Nervous cough is often continuous and irresistible, without any intervals 
betveen the paroxysms It usually inereases suddenly and often is absent 
at night, and can last for months with little effect upon the general health 
It IS diy and high-pitched, and is frequently replaced by other nervous 
s} mptoms 

The untoward results of cough are numerous and m some instances 
serious Involuntary passage of the urine is not uncommon in women, 
but involuntary discharge of the fieces is rare unless the sphincter is weakened 
Djspnoea and cyanosis aie frequent and emphysema may occur Pneu- 
mothorax and subcutaneous emphysema are both in part the lesult of cough 
Pain m the chest from excessive cough is common and the abdominal wall 
may become very tender The excessive exercise from coughing may com- 
pletely exhaust the patient and pioduce profuse sveats Haemoptysis due 
to increased blood pressure may be traced to cough as v ell as cerebral con- 
gestion and hemorrhage Hernia, displacement of the uterus, and eAen 
abortion may be caused by it Aspiration of a fluid sputum into healthy 
bronchi may take place during paroxysmal cough Tachycardia due to 
severe coughing is more frequent in eaily than m late stages 

Expectoration — Few symptoms are more troublesome than this It is 
closely associated v ith cough, and man-^ patients cough simply because the) 
must expectoiate In a few cases from the outset and m many only after 
much training will the patient allow the sputum to collect iiist below' or in 
the larynx, when by clearing the throat it can be raised Bronchorrhoea 
IS sometimes adistiessing symptom, and the patient may be forced to spit da) 
and night, losing much sleep and strength in consequence The rales in 
the trachea due to tenacious mucus may prose sery anno)ing, especially 
vhen the patient letires This often persists and in fact may be accentuated 

SOL III — IS 



274 


INFECTIOUS DISEASES 


as progiess is made toward recovery In a few cases slight expectoration 
may be the only symptom, and it is not rare to have attention called by 
hiemoptysis to a small quantity of sputum m the morning which, on examina- 
tion, IS found to contain tubercle loacilh As the disease becomes airested 
the sputum may be the only symptom i emaming, and it may peisist foi months 
or even years, and after the disappearance of tubeicle bacilli Destiuction 
of the cords (true and false) renders ex]5ectoiation much moie difficult 
If the amount of expectoration is out of proportion to the strength the 
condition is grave, and when x\ eakness is pi onounced it is impossible for 
the patient to raise the sputum The relation of the extent of ph-^sical 
signs to the amount of sputum is veiy unceitain, for patients with slight signs 
may have profuse expectoration, and vice veisa Patients vith moderately 
coarse “moist” rales ovei an entiie chest may be entiiely free from expectora- 
tion, due either to the fact that the rales are pleuritic m origin or to absoiption 
of the secretions in the lungs The latter can haidly take place vhen the 
sputum contains tubercle bacilli 

Respiration — This is usually quickened and i.uely falls below 20 or 
exceeds during rest 30 per minute, except with an acute exaceibation or 
m far-advanced stages It is astonishing to see the amount of pulmontiiy 
involvement present without dyspnoea except on overexertion, although 
marked dyspnoea may be present without physical signs 

The majority of all patients, however, are short of breath on excition, 
and a rate of 95 per minute has been recorded (Damasehino) In many 
early cases this symptom is noticed only on hill-chmbmg, lapid ^^alklng, 
or running Later m the disease, emotion or exertion may produce Molciit 
dyspnoea, but orthopnoea is very lare Patients with a nervous tempeia- 
ment usually have more rapid respiration, and with previous emphysema 
the dyspnoea is usually greater Lebert found dyspnoea pronounced in 20 
per cent of his cases, distinct m 50 per cent , and absent m 30 pei cent 
Oppression in the chest may be present without dyspnoea 

The causes of shortness of breath, apart from fevei and toxremia, maj 
be classified as follows 

1 Rapid extension of the disease (mechanical, orpiessureof tubcicles on 
the vagus) (a) Bronchopneumonia, (5) Miliaiy tubeiculosis 

2 Changes m the ciiculatoiy system (a) Anccmia, (b) Palpitation, 
(c) Cardiac weakness and oedema of the lungs 

3 Chronic fibrosis of the lungs or thickened pleura, followed by enlarged 
right heart with or without cyanosis 

4 Emphysematous pulmonary tuberculosis 

5 Complications (i) Respiratory tract — (a) Pneiimothoiax, (b) Pleuiisy 
(dry or with effusion), (c) Hminoptysis, (fZ) Hypericmia, (e) Bionchitis, 
(f) Aspiration of secretion, (g) Pressure of enlaiged glands on the vagus, 
bionchi, or trachea (ii) Abdomen — (a) Piegnancy, new-growths, (b) 
Meteorism, ascites 

The cause is most frequently mechanical, and is due to the imolvement 
of lung tissue and the lessening of the complemental an space An obliteia- 
tive pleuritis, or a tracheobronchial adenopatlp, may pioduce marked 
dyspnoea Serous effusion, accumulating very gradually, and, in a few cases, 
pneumothorax, cause no respiratory distress Aspiration of secretions into 
the air passages may cause pi onounced dyspnoea Dyspnoea seems to be 
due less to the extent than to the lapidity of the in vehement, less to the stage 



THE SYMPTOMS OF TUBERCULOSIS 


275 


than to the extent of the lesion, and is most pronounced in those cases ^\llere 
miliary tuberculosis of the lungs supervenes upon a chronic piocess Short- 
ness of breath is influenced mechanically by food, and v hen it occurs later 
during digestion is more probably due to slight abdominal distention than to 
the entrance of the chyle into the blood, as Andral suggested The lack of 
dyspnoea in many advanced eases is no doubt due to the fact that the lessened 
•\ohime of blood needs less respnatory surface for proper oxj^genation 

Dyspnoea may be toxic in origin With a rise m temperature the rate of 
respiration is usually increased and the depth diminished, but in many in- 
stances this IS due to an increase m the pulmonary imolvement Amemia 
may be the cause in a few patients 

In chronic forms, cardiac weakness, dilatation of the right heart following 
a fibrosis of the apices, or thickened pleura may cause pronounced dj spnoea 
Palpitation or cardiac weakness in debilitated patients is also a cause Pam 
in the chest in many instances causes rapid, shallow bieathing and attendant 
dyspnoea, as also the onset of pneumothorax 
The 1 elation of the respiration to the tempeiature and pulse is not constant 
The respiration rate usually increases m the afternoon or evening and may 
follow closely the temperature cuive, but is geneially independent of the 
actual temperature The pulse-iespiration latio is commonly 1 to 3 oi 4, 
but varies from 1 to 2, to 1 to 7 or 8 The extremes are often m persons 
of unusual stature (Fox) As the pulse usually follov s the temperature 
rather closely, ratios of 1 to 2 occur more often vith low temperature 
jMarked change m the ratio m either direction is unfa^ orable Cheyne- 
Stokes breathing is rarely met with except n hen meningitis has occurred 
Biot’s type of breathing occurs shortly before death 
Haemoptysis — While often applied to a spitting of blood from any source, 
luemoptysis is here used to denote a spitting of blood vhich has escaped 
into the an passages belov the larynx 
Its relation to pulmonary tuberculosis has long caused much discussion, 
and not until the discovery of the tubeicle bacillus was it finally settled that 
li.einoptysis did not cause pulmonary tubeiculosis Hippocrates, Galen, 
Aretacus, Boerhaa-ie, and Van Swieten thought pulmonaiy tubeiculosis 
followed h.-emoptysis, while Richard Morton m 1689 doubted it, and Portal, 
Bayle, Laennec, and Louis denied it Andral occupied middle ground, and 
G^a^cs, followed b> Hoffmann, Niemcyer, and Reginald Thompson, revned 
the first A'lew, wdnch was that the blood itself could pioduce caseous nodules, 
and Weber, Baumlei, Carswell, and Rokitansky upheld them Traube 
and Walslic, how'ever, early held to the vicav that pulmonary tubeiculosis 
always pieceded the hiemoptjsis, as signs of prcMOus failing health weic 
found 111 the maionty of the patients Traube also called attention to the 
f.ict that if blood caused pulmonaiy tuberculosis the signs should be most 
frequent at the base and not as they arc at the apex Webei and Reginald 
Thomjison ad^anced elaborate theories, explaining the possibility of tbe 
blood reaching the apex thiough aspiration On the discoA er^ of the tubercle 
bacillus, Williams found this oiganism m the blood, and later researches 
ha^e shown it to bepiesent m a proportion of all cases, settling the cause 
of the rapid extension of the disease that follows some lucmophses 
Frequency — This may be said to be about 60 per cent of all cases, but 
Aarics according to different authoiities from 24 per cent to 80 per cent 
In 2344 patients at the Phipps Institute it occurred m 48 per cent Age has 



276 


INFECTIOUS DISEASES 


a maiked effect upon the frequency It is rare before puberty, but a fatal 
case has been reported in an infant of ten months fHofinung) In old age 
hfemoptysis is also uncommon, but probably more fiequent than m infancy 
and childhood Se\ and age together seem to exeit some influence on its 
frequency In 905 males at the Adirondack Cottage Sanitarium, 49 pei cent 
had haemoptysis at some time Of those under twenty years of age, 43 per 
cent had it, of those from twenty to twenty-nine years (495), 54 pei cent , 
from thirty to thirty-nine years, 45 per cent , and over forty years, 38 pei 
cent Herard, Cornil, and Hanot state that haemoptjsis is as common 
after forty years as before Among 890 women, 40 pel cent sufteied from 
haemoptysis, as follows accoiding to age, undei twenty yeais, 47 per cent , 
tw'enty to twenty-nine years (502 cases), 39 pei cent , thirty to thirty-nine 
years, 38 per cent , over forty years, 48 per cent Of these 1795 cases, 45 pei 
cent had haemoptysis A comparison of the figuies shows that while in 
males more haemoptyses occur in the third decade, in females moie occur 
before tw^enty and after forty It also shows that more males than females 
have haemoptysis, and that m males this s 3 mptom occurs more frequently 
in the years of greatest activity 

It IS said to be more frequent in tall indniduals than in shoit This w^as 
no doubt suggested by the fact that many patients who have a “phthisical 
build” are above the aveiage height Of 174 males at the Adirondack 
Cottage Sanitarium under 5 ft 8 in and of 183 males ovei 5 ft 8 in , 50 per 
cent in each instance had hiemopt^^sis The same was practically tiue for 
the females, 34 pei cent of those (148) undei 5 ft 4 in and 39 per cent of 
those (168) over 5 ft 4 in had haemoptjsis Theie seems, therefore, to be 
no connection between height and hajmoptysis 

Haemoptysis is an accident wdiich may occur in any form of pulmonary 
tuberculosis, and is not a sufficient basis for classification In the moie 
acute varieties it is much less common, but occasionally ushers in an acute 
process engrafted upon a chronic form Fowler has reported a fatal case 
occurring in acute miliaiy tuberculosis, and A Frankel one in pneumonic 
phthisis It IS said to occui most frequently m the earlj' stages of the chionic 
pulmonary form, and severe hfemoptysis is said to be most fiequent m the 
first thiee months of illness (Pollock), but this may be questioned Patients 
with a famil)' history of tuberculosis seem very little more liable than 
those w ithout this taint It is unusual to find a patient w ho has had but one 
hfemopfysis, and some patients, usually those semi-arrested, have a maiked 
tendency to it Many of them do well, and Andral reported a case w’here 
hcBmoptysis occurred from the twentieth to the eightieth year At autopsy 
numerous calcified tubercles w’^eie found in the lungs 

The connection between hfemopt>sis and physical signs is notoiiouslv 
uncertain It may be severe in patients wnthout physical signs, and a fatal 
case has been reported in a child where the total aiea in%olvcd could be 
covered bj^ the tip of the finger (Fowder) On the other hand, patients may 
have extensive ulceration and large cavities in both lungs without hfemoptysis 
In sanatoriums and open health resorts it has fiequently been noticed that 
it IS usual for sei eral patients to have hamoptysis about the same time, in 
other wmrds, an epidemic of hfemojit^sis 

Site and Pathology — The distinction betw een bronchial and puhnonaiy 
hfemoptj'sis, so long insisted upon by some w liters, is of little value Small 
hfcmoptyses, bloody streaks in the sputum, can unquestionably come fioiil 



THE SI 3IPT03IS OF TUBERCULOSIS 


277 


tlie bronchi, but more blood than this comes almost invariably from the pul- 
monarj^ Acssels Pink and rusty sputum may be due in many cases to 
diapedesis from the bronchial or pulmonary capillaries, and, v hile usually 
not serious, may prove fatal (Fowler) Such sputum, however, is most 
common after hiemoptysis of larger amounts Some (Rindfleisch, Ruehle 
and See, Aufrecht) hold that the lumen of the pulmonary'^ vein (more rarely 
the arterj') in some early cases is narrow ed by a tubercle in its w alls, and that 
there is a consequent rise of blood piessuie, especiallj at this point, wheie 
the rupture occurs Fatal hremoptj^sis from ulceration of a vessel wall 
w ithout the formation of an aneurism is e' ceedingty rare, and some of the 
reported cases are probably due to the fact that the aneurism has been com- 
pletely detached from the vessel Trained observers rarely fail to find a 
ruptured aneuiism in fatal lunmoptjsis (in 70 out of 80 cases, Kidd) 

These aneurisms are nearly always found on a middle-sized branch of 
the pulmonarj' artery, rarely on the pulmonarj’- vein, and then early in the 
disease, and more rarely on the bi oncliial arterj The larger vessels, owung to 
more elastic tissue, lesist erosion, at least until thrombosed The aneurisms 
are globular, rarely fusiform, and occur generally upon the unsupported side 
of a lessel in the w'all of a small eavitv, which thej'^ may fill For this reason 
some look upon severe hiemoptjsis as a sign of caMty Their size, usually 
that of a large pea or small cherrj , seldom exceeds that of a small w^alnut, and, 
w hile frequently single, they may occur in numbers (22 m one case, Kidd) 
Aneurisms may be found in the w'alls of the bronchus They are most 
frequent m the middle area of the lung, near the periphery, ^ e , the low er 
part of the upper lobe (more common) or the upper part of the low er lobe, 
where the pulmonarj’’ movement in respiration is greatest (West) The 
rupture usually occurs at the distal boundarj' of the dilatation 

Amount of Blood — The amount of blood varies from the slightest trace 
to several liters (m one case 9 liters were lost in 50 days, in another, 3 
liters at one time) R is usually slight in amount, and in 2882 (69 pei cent ) 
of 4125 cases of luemoptysis at Brompton Hospital the amount was less 
than -1 ounce (15 cc ) The blood, usually frothy, may be coughed up by 
moutlifuls even' few minutes for days, or it may come up m a gush and pour 
out of the mouth and nose and large quantities enter the stomach In some 
cases the blood slowly collects in a cavity, finally overflow's, irritates the mu- 
cous membrane, and is then coughed up In raie instances w'lth large 
excavation, the patient may die from hemorrhage into the cavity, w'lth 
little or no luemoptysis Usually, hov oa er, a few' ounces of blood are expec- 
torated, frequently at night, and the patient may be aw'akened Hsemoptyses 
seldom occur singly, and generally tw o to four follow' each other in the course 
of fiAe or SIX days The sputum is almost invariably blood-stained for 
scA eral days aftenvard 

For clinical purposes it is sufficient to classify hmmoptysis as streaky, 
slight (more than streaks and less than 30 cc ), moderate (30 to 100 cc ), 
scA ere or copious (100 to 250 cc), and profuse (oA'er 250 cc ) These 
amounts refer to the quantity of blood lost in tw'enty-four hours In 50 
per cent of all cases the hiemoptvsis is streaky, in 15 per cent moderate, 
and in 10 per cent seA ere and profuse As 25 per cent of all patients have 
no haemopbsis, it IS an urgent sjmptom in about 10 per cent (West) It 
IS not possible to estimate the size of the bleeding A'essel from the amount 
of blood lost 



278 


INFECTIOUS DISEASES 


The blood vanes in color from bright red to >eiy dark, depending more 
upon the time it has remained m the lung than upon its origin In any case 
bright-red blood cannot be said positively to come tiom a vein, as the bron- 
chial arteiies contain such blood The blood is laiely clotted at fiist, although 
m some instances no fresh blood is evei raised As the haimoptysis ceases 
clots are more frequent, and m some cases casts of the bionchi which may 
cause dyspnoea are expectoiated The expectoiated blood usually clots 
quickly and is alkaline Ortal has found that the blood in some cases 
possesses the power to agglutinate tubercle bacilli The bacillary contents 
of the blood vary considerably, but, as Williams fiist showed, it often contains 
tubercle bacilli, andm a “primarj’-” haemoptysis should always be carefully 
examined Recent work by Flick, Ravenel, and Irwin has shown that pneu- 
mococci and streptococci are frequent in the blood 

The causes may be divided into intrinsic and extrinsic The former, 
the underlying factors m every case, have to do with the pathological changes 
in the vessel wall Haemoptysis other than capillary nevei occurs unless 
the vessel walls are weakened by disease In some cases the vessels seem 
to behereditaiily weak, and these patients may suffer fiom frequent haemop- 
tysis Extension of the disease piocess into the vessel wall usually occurs 
in the lung, but diseased glands may ulcerate into a vessel and expulsion of 
lung stones seems in some instances to be connected with haemoptysis 

The systemic blood pressure is much lowered in most cases of advanced 
pulmonary tuberculosis, but the pressure in the pulmonic system is m many 
advanced cases apparently raised and an accentuation of the second pulmonic 
sound IS frequent The frequency of the pulse is often in inverted relation 
to the arterial pressure In advanced stages the diminished volume of blood 
reduces the frequency of haemoptysis Naumann investigated 100 cases of 
pulmonary tuberculosis, 69 of which had high blood pressure (measured by 
Gaertner’s tonometer) Of these, 44 (or 63 pei cent ) had haemoptysis 
Dividing these cases into stages (Tuiban), 85 per cent of the first, 55 per 
cent of the second, and 42 per cent of the third stage had haemoptysis, 
showing that it is most fiequent in early cases with high blood pressuie 

In the majority some rapid increase of blood pressure is held necessary 
for its pioduction This is generally thought to be afforded by some ex- 
trinsic cause, such as violent exeition, paiticularly of the arms and thoiax, or 
violent respiratoiy and general exertion, sueh as is entailed m mountain 
climbing It IS a singular thing, however, how rarely haemoptysis follows 
immediately on any single act of overexertion, and a large percentage 
(nearly 80 per cent ) cannot be connected with overexei tion iNvo-thirds are 
said to occur during quietude, and the rest, with but rare exceptions, only 
during that degree of physical effoit or mental excitement usual m ordinary 
life (Povell) Cohn has shown that on exertion the pressure m the pul- 
monary artery is increased much more rapidly than in the aorta Hiemop- 
tysis can be divided into two classes m one it seems to be an accident m 
the couise of the disease, and m the other it is simply one of the symptoms of 
an acute exacerbation When it is accidental the same fact holds true, that 
a large majority seem to have as yet no definite cause and aie certainly 
not connected vith exertion 

Hiemoptjsis occurs frequently in the early morning hours, a time when 
the blood pressure in the pulmonaiy system is subject to marked varia- 
tions Some, howcA er, can be traced to prolonged overexertion, but occur 



THE SYMPTOMS OF TVBERCVLOSIS 27 ^) 

many hours latei (twenty-four to seventy-two) Emotion stands in a some- 
vhat similar relation 

An attempt has been made to connect haemoptysis with barometric changes 
— vmd, moisture, precipitation, sunshine, and cloudiness — and combinations 
and quiclv variations ot them, but this has so far failed High elevations 
are said to have no effect upon its occurrence, but patients who exercise 
immoderately on arrival aie more liable to it than m lower elevations Sup- 
pression of blood, either from hemorrhoids or from menstruation, has been 
held as a cause Howevei it may be, hsemoptysis frequently occurs m 
M'omen about the menstrual period, and some patients have slight hsemoptyses 
every month over long periods These often have little effect upon the 
general health, and cease usually when the disease is fully arrested Coitus 
may cause luemoptysis (Phque) Irritant gases may be a cause, and one 
case was observed where small luemoptyses oceurred twice after the adminis- 
tration of ether Exposure to the sun has been said to cause it Much 
stress has been laid upon the seasonal variation of haemoptysis, and many 
efforts have been made to connect the occurrence with v inter, summer, or 
spring and fall It is more frequent (Gabrilowitsch) during the spring 
and fall, and the sudden thermometric and baiometric changes have been 
adduced as the causative factor 

Recently, Flick, Ravenel, and Irwin have drawn attention to the frequency 
of the pneumococcus in the blood of hiemoptysis and in the sputum of many 
patients who suffer fiom it In pneumonia rusty sputum is common, but 
brisk hccmoptysis rare The seasonal incidence of pneumonia closely fol- 
loi\s that claimed by some for hmmoptysis, and this work is suggestive 
The examination of all sputum for the pneumococcus and the isolation of 
patients with luemoptysis and of those in whose sputum the pneumococcus 
IS abundant would follow natuially if this work be confirmed 

The immediate efect of luemoptysis depends upon the quantity of blood 
lost, the amount of fundamental disease, and the complications The effect 
on the ultimate termination is very variable, and no matter how severe or 
how slight hemoptysis has been, it is well to gn e a guarded prognosis A 
slight hemoptysis may be the precursor of a severe and fatal bleeding fiom 
the lungs, but as a rule the earlier the stage the less seiious the prognosis, 
which after twenty-four to forty-eight hours is more faxorable, as by this 
time a thrombus can foim In a few cases hemoptysis is followed by some 
improvement — fall of temperatuie and loss of feeling of oppression, often 
this IS only temporary Heart action which produces high blood pressure 
and consequent hemoptysis is also favorable to healing An initial hemop- 
tysis is often of advantage to a headstrong patient who, thoroughly frightened, 
is willing at once to take all precautions For this reason it is wise not to 
pass over an initial hemoptysis lightly It is difficult to see how hemop- 
tj sis can cause an “ elimination en masse of the tubercle bacilli, and thus 
finally effect a cure,” as some (Knopf) have affirmed 

In a much larger proportion, hemoptjsis seems to exeit no effect whatso- 
ever upon the immediate course and appears to be simply an accident 
Except a few days’ rest m bed it entails no discomfort upon the patient 

In some it has to be considered as simply one of the symptoms of a 
progressive lesion, with accompanying dyspnoea, rapid pulse, and elevated 
temperature In this case the most usual occurrence is an attack of tuber- 
culous bronchopneumonia of more or less severity Aspiration of the blood 



280 


INFECTIOUS DISEASES 


into a whole lobe 's raie and affects the lower lobes more frequently The 
lesulting pneumonia may be due to the secondary organisms, and run a 
more or less atypical course, or to the tubercle bacilli, when the result is 
much moie serious The fear and consequent behavior (gieat agitation 
and refusal to follow advice) of some patients seem to have a marked 
influence upon the frequency of this complication, although the amount of 
blood IS also of importance The entrance of pus and secondary organ- 
isms into the circulation can take place through the ruptuie 

It IS not unusual after hsemoptysis to have gieat dyspnoea, rapid pulse, 
high temperature, cyanosis, and death in a few weeks from acute miliaiy 
tubeiculosis of the lungs In fact, any bleeding follov ed by one of these 
four symptoms is to be looked upon as seiious, and an absence of these 
indicates that little immediate fear need be entertained Slight fever 
usually occurs for a day or tv o, due no doubt to the absorption of exuded 
blood Piofound prostration may follow the loss of a slight amount of 
blood when no physical signs aie to be detected A profuse hEemopt^sis 
may turn the tide against the patient 

Death may result from loss of blood, either immediately oi in a few days 
or weeks, and comprises about 2 per cent of all deaths in pulmonarj^ tuber- 
culosis According to Williams, fatal hiemoptysis is nearly tv ice as frequent 
xvhen softening begins and nearly five times as common where there is excava- 
tion It is much more frequent in males and vuth rare exceptions comes from 
a ruptured aneuiism When bleeding takes place fiom a vessel on the side 
of a large ca's ity it may be fatal and hmmoptysis slight or absent In other 
cases the blood pours out so rapidly that death from suffocation follows, 
the common cause in fatal hmmoptysis Cerebial amemia and syncope is a 
more common cause of death than exhaustion Death from shock oi acute 
ansemia is of rare occurience 

So much has been wiitten upon hiemoptysis as a favorable symptom that 
it has been deemed wise to abstract the conclusions of an analysis of 1810 
cases from the records of the Adirondack Cottage Sanitarium This shows 
that males vith haemoptysis did not do as Avell duiing sanatorium residence 
as those vdio had no hiemoptysis In the females no difference could be 
noticed A study of 1276 cases discharged from the institution two to 
tventy years previously slioivs that for males a slightly larger number of 
deaths have occuired among those vdio had hiemoptysis, Avhile for the 
females this is not so Von Ruck found unfavorable results in 70 per cent 
of all cases vath hiemoptysis Hemorrhage from the lung can take place 
into the pleura, and some (Sticker, Dieulafoy, etc ) hold that spontaneous 
hiematoma of the pleura is almost alv’^ays the result of a preexisting pul- 
monary tuberculosis 

Pam — Few^ patients Avhose disease runs a more or less chronic course 
escape thoiacic pain Herard and Aufiecht found it in two-thirds of their 
cases In 1513 patients at the Phipps Institute, Philadelphia, 71 per cent 
had some pain, including that referred to the extremities It ma^ be the 
first oi thioughout the most pronounced symptom and should always leceive 
careful attention 

The cause is verj’ uncertain, and is said to be due to pleurisy, neuralgia, 
neuritis, myositis, nervous erethism, pulmonary congestion, pressure from 
enlarged glands, localized fatigue of the muscles used in respiration or in 
couglung, extension of inflammation to the intercostal nen es, contraction of 



THE SI MPTOMS OF TUBERCULOSIS 


281 


old cavities, traction on pleural adhesions or on the heart, pneumothorax, 
tubeiculosis of the iib, as well as to the intrapulmonary disease (the referred 
pain of Head) 

Pam over the upper front is most frequently referred or due to acute 
pleurisy oi to traction on pleural adhesions Pam over the base of the lung 
IS usually pleuritic, while pain in the mterscapular area may be referred, due 
to pleurisy or to pressuie fiom enlarged glands Pleurisy is not always 
accompanied by pain, as the friction can at times be heard several feet from 
the patient and cause little oi no discomfort, but pulmonary tuberculosis is 
piactically ahvays accompanied by pleuiisy, and it is an exceedingly rare 
tiling to find no pleural adhesions at autopsy Pleuritic pain may be seveie 
01 slight, may occur only after a deep inspiration, expiiation, cough, snceye, 
or 3 'awn, oi may be continuous and every breath be attended wuth pain 
This pain a aiies from a vague discomfort, a sense of pressure or of tension, to 
a sharp, lancinating pain wdnch cuts the breath short and produces sw'^eats 
and gieat piostration It may occur m any part of the chest, but is most 
frequent in the mterscapular, subclai icular, and mfia-axillary regions The 
pain may be noticed upon the opposite side, m the epigastrium, the hypo- 
chondrium, the sacrum, the shoulder on the affected side, and even radiate 
down the aim (diaphiagmatic pleurisy) Singultus is not frequent Slight 
pleuritic pain is often accompanied by a short, hacking cough and fever A 
sudden cessation of pain suggests fluid 

The pseudopleural lub of Rosenbach, heard over the complementary 
space, existing betitreen the low^er bolder of the lung, the diaphragm, and the 
chest w^all in patients with w'lde intercostal spaces, is believed by many to 
be due to muscular conti actions, and Frankel holds that Koll’s sinus- 
pleuritic IS the same phenomenon Hodenpyl, how'e^ er, found nodules and 
patches in the pleura wdnch he believed w'ere the results of tuberculosis m 
iieaily 50 per cent of 91 adults who had no pulmonary tuberculosis 

Patients often complain of pain that cannot definitely be said to be due to 
pleiiris}, and m many cases is no doubt the referred pain of Head The 
site varies, but it usually occuis on the affected side The most common 
locations aie the mfiaclavicular area to the thud rib, the mterscapular and 
the mfra-axillary regions Pam also occuis, but less frequently, at the apex, 
in the suprascapular and subscapular areas, and may ladiate dowm the aim 
Cases have occuired wdiere angina pectoiis wms suspected from the localiza- 
tion of the pain The chaiacter of the pain is very vaiiable, being most 
frequently a slight feeling of discomfoi t, of localized fatigue, or soreness It 
may be constant m location and time and last for days, months, oi even 
years It is most fiequenth fleeting, difficult m some cases to localize, and 
in others so laiiable m its location that the pain is thought to be “rheumatic ” 
The pain in some instances escapes the patient’s notice until a physical 
examination is made and percussion begun In other instances deep pres- 
huie is necessarj'^ to elicit it, and again the skin may be so sensitne that the 
slightest touch causes se^ ere pain, the clothes cause great discomfort, and the 
jiatient lies on the opposite side In these cases of hypersesthesia the skin 
IS often A ery sensitn e to pressure betw een the fingers At times the pain is 
described as going “through and through” In many cases the pain is 
independent of the respiratory movement, in others it is increased on any 
unusual respiratory movement, and is frequently noticed only on coughing, 
yaw ning, or sneezing 



282 


infectious diseases 


Pam often precedes haemoptysis and may disappear on its occunence 
Intercostal neuritis with the classical points of tenderness is rare An 
intercostal myositis has been described by Coplm and by Aufrecht Louis 
attributed the pain m some instances to tubercles m the lungs, and Andral 
the pains which appeared with fever to the softening of tubeicles, but the only 
pains connected with the pulmonary parenchyma are the referied pains of 
Head Sokolowski, howevei, when stubborn pain, vith poor general condi- 
tion, chills and fever are present, believes a deep focus is extending towaid the 
periphery of the lung Severe pain from heipes zoster (before the eruption 
of the rash) or from pneumothorax (v hen many adhesions are present) may 
not be attributed to the proper cause foi some days Pam due to cough 
about the thorax, over the insertion of the diaphragm as well as m the 
abdominal and dorsal muscles, is not uncommon 
Voice — Changes of the voice aie of frequent occurrence The slight 
“prodromal” hoarseness, often only temporary and fleeting, but recurring, 
may be the first indication of the pulmonary disease The larynx may be 
perfectly normal, as 1 out of eveiy 12 patients with pulmonary tubeicu- 
losis suffering from hoarseness shows no laryngeal changes (Gerhardt) 
In advanced stages the voice often becomes weak, is easily fatigued, and 
on prolonged use may disappeai The quality is often changed and some 
thickness or hoarseness is common In other cases the voice is strong until 
death Excluding tuberculous laryngeal changes the cause of the hoarseness 
has been attributed to nervous conditions (one-third of cases, MacKenzie), 
neuritis of the laryngeal nerves, atrophy of this nerve (more commonly of 
the right, due to pressure upon it from pleural thickening, apical contraction, 
enlarged glands), laryngeal catarih, or straining of the cords through severe 
cough, and collection of irritating sputum upon the cords 


THE PHYSICAL SIGNS OP TUBERCULOSIS 

The chief importance of these relates to diagnosis Physical signs of 
little or no significance alone vhen coupled with certain symptoms aie of 
the greatest value, and every general piactitioner should be constantly on 
his guard against error, as carelessness and the use of faulty methods of 
examination are the chief reasons why the early physical signs are over- 
looked To a limited extent the physical signs v