YALE
MEDICAL LIBRARY

HISTORICAL
LIBRARY

TYPHUS FEVER

WITH PARTICULAR REFERENCE

TO THE SERBIAN EPIDEMIC

BY

RICHARD P. STRONG, M.D., S.D.

DIRECTOR OF THE AMERICAN RED CROSS AND INTERNATIONAL SANITARY COMMISSIONS TO SEBBIA
PROFESSOR OF TROPICAL MEDICINE, HARVARD UNIVERSITY MEDICAL SCHOOL

GEORGE C. SHATTUCK, A.M., M.D. A. W. SELLARDS, A.M., M.I).

MEMBER OF THE AMERICAN RED CROSS SANITARY

COMMISSION TO SERBIA

GENERAL MEDICAL SECRETARY, LEAGUE OF

RED CROSS SOCIETIES

MEMBER OF THE AMERICAN RED CROSS SANITARY

COMMISSION TO SERBIA

ASSISTANT PROFESSOR OF TROPICAL MEDICINE

HARVARD UNIVERSITY MEDICAL SCHOOL

HANS ZINSSER, M.D.

BACTERIOLOGIST OF THE AMERICAN RED CROSS

SANITARY COMMISSION TO SERBIA

PROFESSOR OF BACTERIOLOGY, COLUMBIA UNIVERSITY

J. GARDNER HOPKINS, M.D.

BACTERIOLOGIST OF THE AMERICAN RED CROSS
SANITARY COMMISSION TO SERBIA

PUBLISHED BY THE AMERICAN RED CROSS

AT THE

HARVARD UNIVERSITY' PRESS
CAMBRIDGE, MASS.
1920

COPYRIGHT, 1921
HARVARD UNIVERSITY PRESS

if

I

TABLE OF CONTENTS

PART I

TYPHUS FEVER WITH PARTICULAR REFERENCE
TO THE SERBIAN EPIDEMIC

BY

RICHARD P. STRONG

PAGE

Typhus Fever with Particular Reference to the Serbian Epi-
demic 3

Conditions in Serbia Relating to Epidemic 4

Origin of Epidemic 18

Organization 20

Preventive Measures 23

Summary of Previous Epidemics 38

Method of Transmission 42

Aetiology 49

The Significance of Rickettsia in Relation to Disease ... 51

Weil-Felix Reaction 86

Bacteriological Studies in Serbia 86

Course of Serbian Epidemic S7

Acknowledgments 90

End of Epidemic 93

The Polish Epidemic of Typhus, 1916 93

Russia as an Endemic Center of Typhus 94

The Present Polish Epidemic 94

Action by the League of Red Cross Societies 98

Response to Appeal of League of Red Cross Societies . . 103

Further Need of Personnel and Supplies 104

Importance of Further Administrative Measures in Com-
bating the Epidemic L05

iii

iv TABLE OF CONTEXTS

PART II

CLINICAL OBSERVATIONS OX TYPHUS FEVER
IX SERBLA IX 1915

BY

GEORGE C. SHATTUCK

PAGE

Prefatory Note . . . Ill

Literature on Typhus 112

Usual Course of the Disease 114

Material and Plan of Work 115

Observations

I. Fever 116

II. The Skin 118

III. Circulatory Signs and Symptoms 124

IV. Pathology of the Circulatory System 131

V. Blood 136

VI. Respiratory Signs and Symptoms 138

VII. Pathology of the Respiratory System 141

VIII. Digestive System: Signs and Symptoms 142

IX. Pathology of the Digestive System 145

X. The Nervous System: Signs and Symptoms 146

XL Pathology of the Nervous System 149

XII. Genito-L'rinary System 152

XIII. Bones and Muscles 153

XIV. Organs of Speclal Sense 153

XV. Complications and Sequelae 154

XVI. Convalescence 160

XVII. Diagnosis 160

XVIII. Treatment in General 165

XIX. Symptomatic Treatment 172

Appendix

Case Groups (a) Typhus Fever: Recovery 177

(6) Typhus Fever: Fatal — With Autopsy . 208

(c) Typhus Fever: Fatal — Xo Autopsy . . 232

(d) Problems in Dl^gnosis 235

TABLE 01 I 0NTENT8 v

PART III

LABORATORY EXAMINATIONS IX
TYPHUS FEVEB

BY

ANDREW WATSON SELLAKDS

PACE

Introduction 243

Examination of the Blood in Typhus Fever 244

Red Blood-Cells 244

White Blood-Cells 245

Examination of the Urine . 249

Differential Diagnosis 240

Bacteriological Cultures in Typhus Fever

Animal Experimentation

Question of the Mode of Transmission of Typhus Fever ...
Experimental Transmission of Typhus to Monkeys by the
Body Louse 2"

PART IV

REPORT OF BACTERIOLOGIST OF THE

AMERICAN RED CROSS SANITARY

COMMISSION TO SERBIA

BY

HAXS ZINSSER

Establishment of Laboratory 261

Bacteriological Examinations 263

Vaccination 267

vi TABLE OF CONTENTS

PART V

SUPPLEMENTARY BACTERIOLOGICAL REPORT OF

THE AMERICAN RED CROSS SANITARY

COMMISSION TO SERBIA

BY

J. GARDNER HOPKINS

PAGE

Blood Culture Studies 269

Agglutination Studies 271

Autopsies 272

Guinea Pig Inoculations 272

Later Cases 272

Results 272

LIST OF ILLUSTRATIONS

plate rAcrxo rxai

I. American Red Cross Hospital at Ghevgheli 8

II. Fig. 1. Black flags indicating deaths from typhi b within the

houses.
Fig. 2. Typhus victims awaiting burial (Photo by Miss Tetraulti _'o

III. Fig. 1. Camp of unit of American Red Cross Sanitary Commis-

sion.
Fig. 2. Professor Zinsser and Dr. Maitland at the Paget
typhus hospital

IV. Fig. 1. Type of motor truck most successfully employed.

Fig. 2. Disinfection of carriages 24

V. Fig. 1. Evacuation of badly infected district prior to its de-

struction by burning.
Fig. 2. The usual method of transportation in Serbia .26

VI. Figs. 1 and 2. Refugees for disinfestation 26

VII. Fig. 1. Women and children about to be bathed and disin-

fected.
Fig. 2. Austrian prisoners about to be deloused 28

VIII. Figs. 1 and 2. Refugee women and children, and men after

BATHING AND DISINFESTATION '->

IX. Fig. 1. Refugee camp.

Fig. 2. Austrian prisoners after being bathed and disinfested 28

X. Detachment of Serbian army after disinfestation and vacci-

nation 30

XI. Figs. 1 and 2. Disinfecting unit in charge of Dr. F. Criyer 30

XII. Fig. 1. Steam bathing and disinfesting unit in charge of Dr.

T. W. Jackson.
Fig. 2. Men leaving tent before bathing 32

XIII. Fig. 1. Leaving bath.

Fig. 2. Returning to dressing tent . 32

XIV. Fig. 1. Construction of delousing plant with Austrian prison

labor.
Fig. 2. Bathing and disinfesting unit in charge of Dr. George

C. Shattuck 32

XV. Bathing and disinfesting unit in charge of Dr. George C.

Shattuck 32

vii

viii LIST OF ILLUSTRATIONS

PLATE FACING PAGE

XVI. Figs. 1 and 2. Preparation and disinfection of hospital wards;

UNIT IN CHARGE OF Dr. FRANCIS B. GrINNELL 34

XVII. Fig. 1. Typhus ward after cleaning and disinfecting.

Fig. 2. Antimalarial section at work in Macedonia .... 34

XVIII. Vaccination against cholera, typhoid, and paratyphoid fevers

by Professor Castellani's method 38

XIX. Troops being vaccinated after disinfestation by train unit in

charge of Major Edward Stuart 38

XX. Fig. 1. Filled cesspool.

Fig. 2. A typical Serbian town after eradication of typhus . 38

XXI. Figs. 1 and 2. Rickettsia bodies in the excrement of normal

lice 80

XXII. Figs. 1 and 2. Temperature charts of two cases of experi-

mentally PRODUCED TRENCH FEVER 84

XXIII. Chart showing decrease in fever cases, typhus, relapsing,

and typhoid among the civilian population, may to
August, 1915 90

XXIV. Sir Thomas Lipton on board the "Erin" 92

XXV. Dr. Edward Ryan convalescing from typhus fever and Miss

Gladwin, chief nurse, A. R. C 92

XXVI. Photographic illustrations of cases at Lady Paget Hospital.
Fig. 1. Double parotitis.

Fig. 2. Three cases of slight gangrene following typhus

fever.
Fig. 3. Gangrene after typhus 156

TYPHUS FEVER

WITH PARTICULAR REFERENCE

TO THE SERBIAN EPIDEMIC

PART I

TYPHUS FEVER WITH PARTICULAR REFEREN< I
TO THE SERBIAN EPIDEMIC

By RICHARD P. 8TRON< i

The epidemic of typhus which occurred in Serbia in 1915 waa
one of the most severe which the world has known in modern
times. It not only interrupted and suspended for approxi-
mately six months all important military activities of the
Serbian army, but it also delayed the military advance of the
central powers against that country during this period. The
epidemic was moreover partieularhr characterized not only by
its magnitude, but by its high virulence and high mortality.
During the height of the epidemic the number of new fever
cases entering the military hospitals alone reached as high as
2500 per day, and the number of reported cases among the
civilian population was approximately three times this number.
How many more unreported cases actually occurred, one will
never know. The mortality during the epidemic varied at dif-
ferent periods in different localities between 30 and 60 per cent .
and in complicated cases sometimes reached 70 per cent. Over
150,000 deaths occurred within six months before the epidemic
could be suppressed. Coincident with the epidemic of typhus
there occurred an epidemic of relapsing fever, and there was
present much typhoid fever. Under the conditions existing at
the time in Serbia, often little discrimination in the diagnosis oi
the nature of the fever could be made, and most eases of fever
occurring in the army were sent or found their way to the mili-
tary hospitals which were practically all used for typhus eases
during one period of the epidemic. These individuals, if they
actually did not have typhus on entering a hospital, were, in the
early stages of the epidemic at least, very liable to contract the
disease. The figures of fever cases which I have given therefore

4 TYPHUS FEVER

include the cases of relapsing fever and of mixed infection with
typhus and this disease, as well as a number of cases of typhoid.
It has not been practicable for the writer, particularly on ac-
count of almost continuous foreign service during and in con-
nection with the war, to publish before an extended account of
the activities of the American Red Cross in connection with the
suppression of the typhus epidemic in Serbia. Even today
much statistical material collected in Serbia in connection with
the epidemic is not at hand for inclusion in the report. How-
ever, on account of the very wide prevalence at the present
time of typhus fever in epidemic form in Eastern and Central
Europe, and of many problems to be met in relation to the erad-
ication of these epidemics, it has been considered advisable to
summarize the Serbian experience and to publish without
further delay the report in its present form.

Conditions in Serbia Relating to the Epidemic

It will be recalled that before Serbia had time to recuperate
from the Turkish and Bulgarian wars of 1912 and 1913, she was
plunged into the third and greatest world war in 1914, which
obviously taxed to the utmost all her resources. The previous
wars she had undergone, accompanied by outbreaks of disease,
notably of cholera in 1913, had already considerably reduced
her available medical personnel and her hospital and sanitary
supplies. Serbia thus war-worn and weakened; with her re-
sources already greatly overburdened, was in no position to
combat such an epidemic as that with which she was confronted
in 1915, and when this outbreak of disease was well started it
spread almost unrestrictedly throughout the land. There were
only approximately 350 Serbian doctors in the country prior to
the outbreak, and these bravely took up the fight against ty-
phus in 1915, but their number grew less day by day, and the
steady increase of the disease and the uninterrupted strain to
which they were submitted by their military duties, as well as
by the superimposed epidemic, finally brought them to ac-
knowledge the futility of continuing the attack upon such a foe
unaided. Indeed, the majority of the small number of Serbian

TITE SERBIAN EPIDEMIC

doctors sooner or later became afflicted with the disease, 1 2H
them succumbing to it, a mortality of 36 per cent. I recall, very

shortly after reaching Serbia, visit i no one of the firs! hospitals
I saw where I found six of. the seven Serbian doctors sick with
typhus. Of the thirteen physicians in the hospital at Pirot.
twelve contracted the disease and six died of it. Indeed it was
not an unusual thing to find one or more doctors in the differ-
ent hospitals sick with the disease. In an institution originally
reserved for surgical cases with 400 beds, there were approxi-
mately 1600 patients, 1100 of which were suffering from typhus.
This hospital had formerly a staff of 42, including doctors
and their assistants and nurses, and only three of this number
remained who were free from the disease. Those physicians
who remained well were busily occupied with treating the sick
or the wounded from the battlefields, and general methods for
prevention throughout the country were impracticable or were
not undertaken. There were obviously not enough hospitals in
which the sick could be. properly cared for or even properly
sheltered. Under such conditions, with no efficient sanitary
personnel or sanitary regulations, wounded soldiers or those
affected with minor diseases or relapsing fever wandered into
the hospitals whenever they were so inclined and entered the
wards filled with typhus cases, frequently occupying the same
beds with them. Indeed, it was exceptional in most of the
hospitals to find only one patient in a bed, usually there were
two or three patients in the same bed and the available floor
space was also covered with patients without beds; sometimes
lying upon straw, on blankets, or closely huddled side by side
on the wooden flooring, often even under the beds. The condi-
tions in many of these hospitals were about as bad as they well
could be. There were no lavatory or bathing or toilet facilities
for the patients, no clean linen or clothing for them, and no
systematic disinfection of such linen or the beds. There were
usually no nurses, and often only* a few Austrian prisoners
as attendants. Worst of all, during the height of the epidemic
many of the patients in the hospitals received no care or atten-
tion whatever, for the reason that there was no one at hand to

6 TYPHUS FEVER

render it. As the severe type of the disease prevailed with de-
lirium lasting several days, it was sometimes impossible for
patients, particularly those in the wards upon the second floor,
to visit the latrines outside the hospital. Under such conditions
the mortality was naturally great, and reached in some in-
stances as high as 70 per cent. In certain hospitals where pa-
tients had removed their clothing upon entrance, I have seen
many piles of such clothing lying in the entrance room with
thousands of living lice and ova upon the garments not yet dis-
infested. Indeed many hospitals were without apparatus for
sterilizing or disinfesting, or possessed only unsatisfactory ap-
pliances for this, and patients came, and left if they recovered,
without their clothes being washed or disinfested. In a few
hospitals the conditions were so bad that the dead lay unburied
for days at a time. The conditions in the prison camps were
often worse; the buildings used as prisons were almost invari-
ably greatly overcrowded and insufficiently ventilated. The
prisoners were frequently confined in stables also with very
poor ventilation. In these there were no wooden floors and
they were compelled to lie upon the ground or upon straw
sacks or loose straw. The latrines were usually filled to over-
flowing and in a most unsanitary condition. Inmates of these
prison camps I always found very lousy on first inspection.
These camps were very dangerous to inspect, and during the
war many cases of typhus were undoubtedly contracted in con-
nection with work in the various prison camps.1 In Serbia they
proved to be veritable death traps. It was necessary to insti-
tute rigid sanitary reforms in almost every one of these prisons
before the disease could be eradicated. Over one-half of the

1 Low, The Ann. Report, Local Government Board, 1914-15 (xliv) gives a list of six-
teen prison camps in Germany in which typhus broke out in 1915, in ten of which British
soldiers were confined. "In the camp at Langensalza, in April, 1915, nearly the whole
of the 1000 prisoners contracted typhus (Leonetti). It is said that on an average thirty-
five men died daily. They were ill-attended, without medicines, and their clothing was
insufficiently disinfected. In the camp at Niederzweren typhus also made serious rav-
ages. It was only when the epidemic attacked the civil population and the garrison that
precautions were finally taken. At Erfurt there were 600 cases among 20,000 prisoners.
In the camp at Gustrow the hygienic conditions were equally deplorable. The 12,000
prisoners, suffering from cold and hunger, were crowded together on mouldy straw, with
a single blanket apiece, which was worn, and often torn."

THE SERBIAN EPIDEMIC 7

70,000 Austrian prisoners in Serbia died of typhus during the
epidemic. The Serbians supplied their prisoner*
food as it was possible for them to furnish, but the -anitary
eonditions of the people of Serbia in general precluded the plac-
ing of their prisoners under proper sanitary conditio: -

In the early part of the epidemic, there were no hospitals for
the women and children, so that when they were affected with
the disease they were compelled "to remain at home or wherever
they were taken sick, and hence usually were not attended by
physician?. Nevertheless, the mortality among them was fre-
quently lower because they at least received some care and at-
tention from members of their family and were probably
usually fed more or less regularly.

In order that the reader may better realize the conditions in
Serbia, a few extracts from reports of those who witnessed these
scenes will be quoted. Sir Thomas Lipton who did so much for
the Serbian people, and whose own health was greatly impaired
for a number of months owing to hardship and exposure under-
gone in Serbia during the epidemic, recounting the conditions
there in March. 1915 says:

"T met on the country roads many victims too weak to
crawl to a hospital. Bullock-carts were gathering them up.
Often a woman and her children were leading the bullocks,
while in the cart the husband and father was raving with fever.
Scarcely enough people remain unstricken to dig graves for the
dead, whose bodies lie exposed in the cemeteries. The situation
is entirely beyond the control of the present force, which im-
peratively needs all the help it can get — tents, hospitals,
doctors, nurses, modern appliances, and clothing to replace the
garments full of typhus-bearing vermin."

His picture of the hospital at Ghevgheli. where Dr. James F.
Donnelly of the American Red Cross died, is appalling. S
Thomas calls Dr. Donnelly one of the greatest heroes of the
war. In his description of tins hospital he says:

"The place is a village in a barren, uncultivated country, the
hospital an old tobacco factory, formerly belonging to Abdul
Haniid. In it were crowded 1400 persons, without blankets

8 ■ TYPHUS FEVER

mattresses, or even straw; men lying in the clothes in which
they had lived in the trenches for months, clothes swarming
with vermin, victims of different diseases — typhus, typhoid,
dysentery, and smallpox — were herded together. In such a
state Dr. Donnelly found the hospital, where he had a force of
six American doctors, twelve American nurses, and three Ser-
bian doctors. When I visited the hospital three of the American
doctors, the three Serbian doctors, and nine of the nurses were
themselves ill. The patients were waited on by Austrian pris-
oners. The fumes of illness were unbearable. The patients
objected to the windows being opened, and Dr. Donnelly was
forced to break the panes. One of the first things he did on his
arrival was to test the water which he found infected. He then
improvised boilers of oil drums in which to boil water for use,
and he built ovens in which to bake the clothes of the patients,
since the hospital was not provided with proper sterilizing ap-
paratus. The street cleaning and hospital waiting was done by
Austrians whose numbers were rapidly thinning from typhus
and other diseases."

Captain Bennett of the British Red Cross in describing one of
the prison camps in Serbia writes :

"It is not a hospital, remember, but simply an area where
750 Austrians have been collected; nevertheless the disease has
fallen like a blight upon the camp. At an earlier date one doc-
tor was in charge of this camp, but he is now stricken down by
typhus, and various forms of infection of the malady are raging
unchecked. Typhus, dysentery, smallpox, and diphtheria
have swept over the place with devastating effects. Last week
only twenty men out of 750 could stand on their feet. There
they lie in utter wretchedness. Here and there one finds a mat-
tress and here and there a little straw, but the bulk of the sick
men are stretched out on the muddy ground. Their clothes are
foul and alive with vermin which spread the deadly typhus.
The silence of the camp is broken only by sighs and groans. A
recent visitor noticed a number of recumbent forms covered
with greatcoats and found on removing these that five out of
the number had already been dead several days. There was

American Red Cross Hospital at Gheygheli

PLATE I

THK SERBIAN EPIDEMIC

nobody to remove the corpses. Here and there some poor
wretch crawled about on his hands and knee* to fetch a cup of
water for his prostrate comrade. This was all the attendance
which was visible, and the shocking condition of the men and of
the ground on which they lie can be imagined. ( Ian any one be
surprised to learn that some sixty men die in this camp every
day? Every man in this hideous environment and all hie com-
rades who will enter it subsequently are practically appointed
to die, unless help comes speedily. Uskub is a veritable valley
of the shadow of death. If the tired nurses leave the crowded
hospitals for a little exercise and fresh air they are met by a
long procession of bullock wagons carrying rude coffins to the
cemetery. Sometimes three coffins with unfastened lids rest on
the same cart and the bodies of the dead are exposed as the
wheels jolt over the rough pavements."

With reference to one of the hospitals he writes:

" It is practically impossible to go near it; so overpowering is
the stench in the street outside that nobody who is not com-
pelled to approach the building can bear to be in its vicinity.
Details of the interior cannot well be printed."

Dr. Lilian Mary Chesney x points out that at the time when
she reached Serbia the medical organization there was more or
less paralyzed by the magnitude of the task, and cases of ty-
phus were not separated from others. A separation was ef-
fected in about a week, the typhus patients alone remaining in
her hospital. "The hospital itself was soon much improved in
condition. The great difficulty was the sanitary arrangements,
cesspools sometimes within the building and sealed up when full
being in use. The whole building was pervaded by the smell
of overflowing cesspools. The cesspools also overflowed outside
into the laundry, which was not a very desirable arrangement,
but it did not seem to disturb the mind of the director at all.
Coffins were mere open shells and used repeatedly, the bodies
being tilted out into the pits on reaching the cemetery."

Dr. Ethan Butler, who was Director of American Red Cross
Serbian Unit No. 3, in writing of the evidence leading up to the

1 Chesney, L. M.: Practitioner, 1916, xevi, 542.

10 TYPHUS FEVER

illness and death from typhus of Dr. Ernest P. Magruder on
April 8, 1915, gives an interesting account of the conditions he
encountered. Dr. Magruder was one of the five American
physicians to lay down their lives in Serbia during the epi-
demic, the others being Drs. Albert S. Cooke, John M. Kara,
James Francis Donnelly, and Leon Weiss. Dr. Butler, describ-
ing his hospital, says:

"Only by stretch of imagination could it be called a hospital.
As a matter of fact there was only one hospital, worthy of the
name, in all Serbia, the Military Hospital at Belgrade. Into
this factory, capable of holding no more than 750 patients on a
rational apportionment of floor space, had been huddled 1300
wretched beings, in filth indescribable. The majority of these
were suffering from badly infected compound fractures, the
result of shrapnel. By actual count there were 192 beds, many
of which required propping up to keep them on their legs. Of
mattresses, blankets, sheets, there were too few. A little corner
of the basement, about 25 feet square, filled chiefly by stair-
ways, was serving as laundry, presided over by six very dirty
peasant women. Needless to say, it was inadequate to meet the
demands made upon it. In another part of the basement was a
huge pile of exceedingly filthy clothes from the wards above,
and next this were stacked the supplies of food to be served
later to patients and staff, after passage through the squalid
little shed that was called a kitchen. Water came from shallow
surface wells. It was turbid and smelled and tasted badly.
Subsequent examination showed evidence of sewage pollution
in several of these wells. Excreta, sputum, and pus-soaked
dressing were scattered everywhere within and without the
building. Vermin, especially the body louse, were omnipresent.
The stench of the whole thing was overwhelming. Typhus was
present in sporadic cases even when we arrived and caused
some anxiety, but it was fully a month before the great epi-
demic that overwhelmed Serbia broke out. Our units were
hard hit. Of the twelve nurses, nine had contracted the dis-
ease prior to the end of February: all recovered. Of the six sur-
geons, four had become infected, and of these one, Dr. James F.

THE SERBIAN EPIDEMIC 1 1

Donnelly, had died. Dr. Magrudcr and myself had i
typhus. Dr. Magruder was unremitting In hie share of the
care of the staff individuals, nor did he spare any effort
gardless of the amount of the exposure Incurred thereby."

Later, Dr. Magruder, worn out by overwork, finally con-
tracted the disease and died on April 8. He felt that he was
unable to relinquish his duties and did not go to bed until he
had been ill for five days. As Dr. Butler has -aid of him, " II<
passed out honorably fulfilling the trust imposed upon him by
the American Red Cross, honorably upholding in the foreign
war zone the ideal of one of the noblest institutions of his nat We
land. A Christian of the true type that feared not to face death
that others might profit by his labors."

Dr. M. Jeanneret-Minkine of the French Mission describes
pathetically the conditions as he observed them in another part
of Serbia. Writing of his hospital in Pirot he says :

"At first, I had Serbian wounded who had become ill, but
shortly afterwards, a convoy of 250 sick prisoners, many of
them suffering from typhus, arrived and was sent to my
hospital.

"I wish to draw attention to the following fact which does
great credit to the Serbians: the sick prisoners were provided
with beds, whereas the Serbian soldiers suffering from the
same disease were accommodated in other hospitals, in which
they slept on straw mattresses placed on the bare floor.

"As I already had several cases of typhus exanthematicus in
my wards and was anxious to protect them from vermin. I gave
the following careful instructions to this effect:

"1. Owing to the absence of a reception room, the patients
will be completely undressed in the entrance hall and rapidly
conveyed on stretchers, naked, covered with a blanket, to the
rooms in which they will receive clean underclothing.

"2. The discarded clothes will immediately be put on a
cart and taken out of the town; they will subsequently be
spread out on a field and guarded by soldiers, pending their
disinfection.

12 TYPHUS FEVER

"3. The same" day, a steam sterilizer will be built in the
yard (the pharmacy could not supply me with sufficient sulphur
to proceed by sulphurization) .

"The uniforms of all the male nurses were immediately de-
loused partly in the small autoclave left from the old operating
room and partly by boiling in the kitchen boilers. The walls of
the rooms were washed with milk of lime.

"The convoy arrived during the night. The weather was ap-
palling, cold and snowy. Notwithstanding that the patients
were half frozen, I maintained my instructions, and saw that
they were enforced with regard to the first arrivals. Then,
being obliged to superintend the removal of the last wounded
to the neighboring hospital, I was absent for an hour. During
that time, a member of the Administration came along, and,
disapproving of my instructions, had the patients with all their
clothes on carried to the rooms in which they were undressed.

"The uniforms covered with vermin were only then col-
lected together in the corridors and sprinkled with diluted lysin.

"Result : My wards were immediately infested with vermin.
The uniforms in the corridors were literally alive, which gave
me the opportunity of studying their biology.

"While I was asking the Administration for an explanation,
the Superintendent had the uniforms, still covered with vermin,
locked up in the attic. ' We always do so,' said the Chief Ad-
ministrator, ' but only wait a few days, and everything will be
changed.' But all he did was to construct elegant portable
W.C.'s. He believed that typhus infection, similarly to ty-
phoid, was carried by fecal matter. This belief cost him his life.

"As regards the steam sterilizer of which I had drawn a plan,
and for the construction of which I required bricks, everybody
agreed with me about it, but I was nevertheless asked to wait a
few days. This was about the end of January.

"During these 'few days,' the epidemic spread with the
rapidity and force of a waterspout.

"In my hospital, most of the Serbians and prisoners admit-
ted for bronchitis or enteritis contracted typhus through infec-
tion from vermin. Within a fortnight, all the male nurses

THE SERBIAN EPIDEMIC 13

became ill and from day to day the virulence of the dia
increased by the rapid transmission from man to Ion
louse to man. The mortality increased at an appalling rate.
From 15 per cent in the first case, it rose to r>0 per rent. In
other hospitals of the town it was even worse, the vermin being
still more abundant.

"At the end of January, the surgeon of the hospital de-
veloped typhus, whilst in the next room his Austrian colleague
was becoming convalescent. He however recovered. The same
day, a Czech doctor was taken ill and died. Within the next
few days, the Superintendent of the hospital, a young physician
who worked under my supervision in an improvised hospital, a
Polish surgeon whose room I had just moved into, the Chief
Administrator of Sanitation, and later, a Roumanian doctor
who had taken his wife and children with him to Pirot, be-
came infected. All died one after the other. I myself con-
tracted typhus in March.

"In short, out of 13 physicians working in the town when I
arrived, 2 were immunized by a previous attack of typhus. 2
were taken ill at the outbreak of the epidemic and recovered.
8 contracted typhus when the epidemic was at its height . and 6
died within a month. Only one escaped unscathed.

"The disease caused similar ravages among the soldiers.
Every morning, cars drawn by small thin oxen conveyed piles of
coffins from the mortuary to the cemetery, preceded by priests
clad in sacerdotal vestments who appeared utterly exhausted
by the ceaseless repetition of the ceremony. The procession
was closed by a territorial guard, detailed day after day to this
melancholy task.

"I sometimes saw dead bodies piled like pieces of wood in the
mortuary. They were buried almost level with the ground
owing to the lack of time. Every day, the cemeteries were ex-
tended. The long lines of newly dug earth gave one the impres-
sion of a field ready for sowing.

"As the number of victims in my hospital continued to in-
crease, I several times attempted a further disinfection, in
which I was only partially successful.

14 TYPHUS FEVER

"I was unable to obtain my steam sterilizer, the persons who
had promised it having died, and although I was my own mas-
ter as regards the treatment of the patients, I had no power to
requisition equipment without authority from the Administra-
tion.

"When visiting the wards, I each day saw one or two para-
sites fall onto my overall, and on inspecting my underclothing,
which I did twice every day, would constantly find some. Even
the linen brought back from the laundry was not free from
vermin. Both my orderlies became infected and I was obliged
to allow one of them to lie down near the stove in my bed-
room. There was no room for him in the wards and he pre-
ferred, not without reason, dying in the streets rather than
entering the improvised hospital in the officers' casino.

" As, apart from my already very heavy work, I was obliged
to supervise other hospitals in which the regular doctors were
sick, dead or inexperienced, I was faced with the alternative of
attending to the patients only quite superficially, by distribut-
ing antithermics and digalen as had become customary else-
where, or of seeing only a certain number of cases daily. I
decided upon the latter course and then proceeded to select
some intelligent prisoners and taught them how to judge a
pulse and how to assist their comrades in the disinfection of
their mouth and nose, and to make wet packs (maillots).
These assistants were each put in charge of a certain number of
rooms and given instructions to give massive subcutaneous in-
jections of ethero-camphorated oil to all patients whose pulse
commenced to fail. In this way, I was able to give special at-
tention to the serious cases, those passing through the critical
period between the tenth and thirteenth day, and depend on
my assistants for the others.

"It must be admitted that if the Serbians showed humanity
in treating the sick Austrian prisoners on the same footing as
their own soldiers, the prisoners working as male nurses gave
me great satisfaction by their zeal, courage, and devotion to
the Serbians and to their compatriots. Further, when several
of these attendants died of typhus, there was no difficulty about

THE SERBIAN EPIDEMIC 15

replacing them, although nobody wa.< forced to undertake the

work and those offering their services were warned of the dan-
ger. However, in a month, my assistants were all convalf\s<
from typhus exanthematicus and were thus immunized.

"At the end of February, the epidemic still continued; yet
not a single hospital possessed a sterilizer. A new Administra-
tor was appointed who appeared full of good resolutions, bul
who lost his nerve from the very first. He was moreover no
longer young and, feigning sickness, did not appear until the
epidemic had of itself commenced to subside.

"In the barracks the epidemic claimed many victims among
the recruits sleeping on the bare floor in the long dormitories,
with straw mattresses as pillows. Their doctors made every
effort to combat the disease, the whole regiment, squad after
squad, being sent to the station of the military hospital reserved
for them where they were given shower baths and their clothes
disinfected by steam. The vermin however persisting, I con-
cealed tiny bags of paper filled with parasites and ova in the
uniforms. When they had been steamed for half an hour at
80° C, I found that the big ones were all dead, but several of the
smaller ones revived after being on the skin of a convalescent
patient for an hour, on which I had placed them wrapped in a
piece of linen covered with sparadrap. In some of the ova, the
movements of the air bubbles inside showed that the embryo
was still alive. It was therefore necessary to heat the sterilizer
to 100° C. and to leave the uniforms in it, less tightly packed,
for half an hour after this temperature had been obtained.
Moreover, in the larger wards, the recruits who had just been
deloused were reinfected by the men wTho had not yet been
disinfected.

"The civilian population did not suffer much from the epi-
demic, with the exception of the refugees and those in com-
munication with the hospital. Even the peasant women who,
although they should have been forbidden to do so, visited their
sick husbands on market days, rarely carried infection to their
villages as they were clean and fought the vermin. In the
town, at the sight of workmen busy painting names on new

16 TYPHUS FEVER

coffins, the women sitting outside their doors did not stop
weaving and spinning the many colored tapestries which are
the glory of their town. And when a group of Czech prisoners
organized a concert at which, after the Russian anthem, the
Serbian anthem, and the Marseillaise, music by Wagner was
played, the hall was crowded.

"I have already mentioned the very important part played
by fear in the prognosis of typhus exanthematicus, so will not
refer to it again. I wish however to say how much I was im-
pressed by the ease with which one became accustomed to the
idea of death, even of death without glory, from infectious dis-
ease. We watched our group of physicians and hospital em-
ployees rapidly diminish; the merry party round the dining
room table was reduced to three, but nevertheless remained
optimistic. Without any effort we had become used to the dan-
ger threatening us and faced it, smile on lip and joke ever
ready, like soldiers at the front. It is a curious psychological
phenomenon that the fact of seeing so many people die, causes
one to regard death as a very common event, even when it is a
question of one's own death. Life is very busy and there is an
adversary to be fought; the situation may be likened to an
exciting game of checkers which absorbs you and makes you
forget all the rest. Also one has faith in one's good star. The
reason for that man's death was no doubt because he was
afraid; the one over there was no longer young; that other had
over-disinfected himself with alcohol, another was too thin or
too fat, etc. One even went so far as to believe that typhus
would not be dangerous for one's self and was almost glad to
contract it in order to find out what it was like !

"And meanwhile, the epidemic continued its ravages. By
the end of February, the number of physicians who had died
from typhus in the Serbian reserve hospitals exceeded 100,
representing almost a third.

"I was obliged to go to Nish and found the hospitals there
better equipped than those of Pirot; they were however simi-
larly crowded. I was asked out to dinner by one of my friends
and found one of my fellow-students delirious with typhus in a

THE SERBIAN EPIDEMIC 17

corner of the room in which we were eating. In the neighbor-
ing hospital, another colleague who had come from Switzerland
was dying, without my knowing of his illness. In every town
the epidemic was raging. In one, as I was passing the cem< I

I saw more than 200 coffins standing out on the -now. waiting
to be put in the earth. The heads of the Sanitary Department
may have been anxious, but, in Serbian medical circles, a feel-
ing of fatalism and powerlessness prevailed. The Chief of the
Belgrade Pasteur Institute, to whom I expressed my amaze-
ment at seeing only anod}me measures employed, himself told
me that he was counting upon the spontaneous extinction of
the epidemic.

"At Uskub, I at last saw a hospital free from typhus. It be-
longed to an English Mission with a well-trained personnel,
beds, a sufficient quantity of linen, and which above all ac-
cepted only a limited number of wounded per room and per
doctor.

"With this exception, from Ghevgheli in the extreme south to
Valjevo in the north, typhus had spread to all the hospitals of
which I heard or which I visited. Everywhere, I saw the same
leaden-hued faces with an absent or stupid look in the eyes, the
some long rows of straw mattresses on which the unfortunate
soldiers were huddled together, semiclothed in their uniforms.
or again those beds which many doctors did not dare to ap-
proach.

" Fortunately , the first line troops did not suffer as much as
the others, the febrile cases being immediately evacuated and.
an excellent measure, the soldiers and even the officers being
forbidden to leave the zone of operation for fear of infection in
the towns.

"In March, during the full period of incubation of typhus. 1
left the country. An international hygiene commission was
shortly after appointed. The allied countries then despatched
a considerable number of courageous physicians to Serbia. In
May and June the cases of petechial exanthematicus were less
frequent than in February, and in August there were only
sporadic cases. The epidemic therefore appears to be over."

18 TYPHUS FEVER

These quotations, together with the descriptions I have at-
tempted to give, it is hoped will convey to the reader some idea
of the situation.

Origin of the Epidemic

Such, then, were the conditions which Serbia was facing
when the medical authorities, worn out and overwhelmed by
the increasing magnitude of the epidemic, became convinced
that outside assistance should be asked for. Accordingly the
government of Serbia appealed for foreign assistance in com-
bating the disease which was fast rendering her army inert as a
fighting machine and bringing about general demoralization of
the country. The valiant part which Serbia had played in the
history of the war is too well known to make it necessary to
emphasize the fact that Serbia was justified in both asking for
aid from her Allies in this connection, and in expecting that
such aid should be rendered her.

It will be recalled that in July, 1914 Austria-Hungary de-
clared war against Serbia and immediately thereafter launched
a severe attack which came as a surprise to the Serbian army
and compelled it to fall back. Belgrade, the capital, was bom-
barded and the government retired to Nish which became the
new capital throughout the period of the epidemic. The Aus-
trians, however, did not immediately follow up this first at-
tack and in their subsequent attempts to cross the Danube and
the Sava in the vicinity of Belgrade, they were always re-
pulsed. A more severe and concentrated attack, however, was
launched later by the Austrians along the Bosnian border, be-
tween Schabatz, Valjevo, and Ujitze, the Austrians forcing
their way across the Sava, and Drina rivers at several points
with the object of separating the Serbian armies at Valjevo.
This Austrian invasion was pursued with great bitterness and
was characterized by many cruelties to the civilian Serbian pop-
ulation. After five days' fighting in the valley of the Yadar the
Austrians were, however, repulsed and driven back across the
Drina, 20,000 Austrian prisoners remaining in the hands of
the Serbian army. In September the Austrians again attacked
along the Bosnian border. They were unable at first to make

Till: SERBIAN EPIDEMIC l'.t

any material advance, but gradually the Serbian an.-
compelled to shorten its line and fall back. In November the
Austrians attacked and advanced in greal force, this time
capturing Valjevo. Belgrade had also to be given up, the
Austrians occupying on December 2 a line extending from
that city to a point about 40 miles east of Qjitze. The situation
of the Serbian army was then precarious, it being exposed both
on the north and west flanks. However, with great fortitude
the Serbians took the offensive again and a few days Later they
drove the Austrians back through Valjevo and across the
Drina and Sava rivers, once more occupying Belgrade thirteen
days after its second capture by the Austrians.

Cases of typhus fever had undoubtedly occurred in the Ser-
bian army in October and November, 1914, the infection hav-
ing apparently been introduced from Albania, but no epidemic
resulted. Typhus, however, was present in the Austro-Hun-
garian army when it invaded Serbia. After the Austrian- re-
treated in December, when the Serbians had reoccupied the
invaded territory, a large number of Austrians, both wounded
and sick, many with typhus and relapsing fever, were left be-
hind, and these were found living under most unsanitary condi-
tions. It was necessary to confine these and the other prisoners.
As there was very little available shelter they were crowded
together in buildings where proper sanitary conditions were
impossible, and the number of typhus cases rapidly increased
among them. Many individuals who came into contact with
them were also attacked. This was particularly the case at
Valjevo which had been the Austrian military headquarters.
It was in this city, situated in the northwestern portion of
Serbia, that the disease first began to appear in serious form
among the Austrian prisoners, and from them it quickly spread
to the Serbians who had reoccupied the territory. With 00.0(H)
prisoners to care for, many already ill with typhus, the uewly
arrived troops, the refugees and wounded *in this district, the
available shelter was far from sufficient. Immediate steps were
therefore taken to evacuate many of the sick and wounded.
both by the railway which leads from Valjevo as well as by the

20 TYPHUS FEVER

carriage roads. The Austrian prisoners were also separated
into groups, and distributed throughout the country. The
seriousness of the situation from a sanitary point of view was
not realized; the patients infected with typhus were not isolated
but were allowed to go to their homes or were sent to various
parts of the country, introducing and spreading the infection to
other troops, to households, or to the inmates of hospitals. No
quarantine was placed upon the districts in which the typhus
cases were particularly occurring, and hence in a very short
time the greater proportion of the country was afflicted with a
terrible epidemic. The epidemic increased through January,
rose more rapidly in February and March, and reached its
height in April when the number of cases in the army and civil-
ian population was in the neighborhood of 9000 per day.
Those figures are only approximate because when I reached
Serbia there were no available statistics of the number of cases
or deaths in the various towns throughout Serbia, and only an
approximate number of the sick in the military hospitals could
be furnished.

Organization

In America the response to Serbia's appeal for aid in com-
bating the epidemic was almost immediate, and as the United
States had not yet entered the war the American Red Cross
responded to this appeal, and, recognizing the seriousness of
the situation, decided to send a sanitary commission, thor-
oughly equipped with materials and supplies, for the purpose of
eradicating the disease, in addition to the hospital units which
it had already sent and which were performing such excellent
work in connection with caring for and treating the sick. The
Rockefeller Foundation was interested in this sanitary com-
mission from the time of its organization, and generously sup-
ported it with funds in connection with the American Red
Cross. Great Britain, France, and Russia also recognized the
extreme gravity of the epidemic and the terrible ravages
caused by the disease and sent relief expeditions, though
largely from a military standpoint, to help in the situation.

Fig. 1. The black flags indicate deaths
from typhus within the houses

Fig. 2. Typhus victims awaiting burial

PLATE II

■^ar ,jn5BaR?56»cr5rr'C

Fig. 1. Camp of unit of American Red Cross Sanitary Coioossiofl

Fig. 2. Professor Zinsser and Dr. Maitland at the
Paget typhus hospital

PLATE III

THE SERBIAN EPIDEMIi

Owing to the ravages caused by the spread of the disease, al-
most complete demoralization bad resulted in many par-
Serbia. So many officials had succumbed to the di-
number of the remaining ones, apparently in the depti -
despair and thoroughly discouraged at the appalling condil
and the responsibilities which they had been call n to

face, appeared to be reluctant or unable to even attempt T<> deal
further with the situation. A number of them forsook their
offices and remained most of the time gloomily in thfir
dences. Almost even- Serbian family was in mourning
some relative or friend, and the black flags outside the h<
the sign of death within, were very common throughout the
towns.

One of the most immediate and important problems which
confronted me after my arrival in Serbia was that of central
organization and control, so that absolute authority over all
sanitary matters throughout Serbia could be secured. Owing
to the loss through sickness and death of many of S
most efficient physicians and sanitarians, such central control
was not being exercised, and no general campaign of attacking
the epidemic throughout the country was being pursued,
though individual relief and hospital units were already
work in connection with the disease. Under the conditions
which existed, and which I have attempted briefly to outline,
it could perhaps hardly have been otherwise. "When I first ar-
rived in Serbia, the services of several foreign relief units
which had arrived were not being employed at all and had not
even been assigned stations, and in some instances there
peared to be a diffidence on the part of some of the Serbian
sanitary officers in making assignments of the duties of the
foreign units and of supervising their work. Such voluntary
relief units as were at work, and the majority were performing
truly heroic service in treating the sick, were pursuing their
duties almost independently of one another, and two units
from the same country were found to be working almost side
by side with a different plan of action. Such central organiza-
tion and control of sanitary measures throughout Serbia was.

22 TYPHUS FEVER

however, secured through the establishment, with the consent
and aid of the Serbian government, of an International Sani-
tary Commission whose resolutions were immediately enforced
when necessary through the Ministers of the Interior and of
War. In addition, the Medical Director of this Commission
was invested with the necessary authority in sanitary matters
and in sanitary reform. This organization was effected par-
ticularly through the assistance of M. Pachitch, Minister of
Foreign Affairs, M. L. Jovanovitch, Minister of the Interior,
Sir Charles des Graz, British Minister, and M. Bopp, French
Minister to Serbia. Assistant Secretary of Foreign Affairs,
Slavko Grouitch, now Serbian Minister to the United States,
and Sir Ralph Paget, former British Minister to Serbia, who
had been placed in charge of the medical units in Serbia from
Great Britain, were also of very great assistance in bringing
about this organization. At my preliminary conferences with
some of the Serbian officials, it was feared that this organiza-
tion might lead to some friction among the Allies, but no ap-
preciable difficulties of this nature were encountered. The
commissions finally consisted of Sir Ralph Paget, Commis-
sioner of British Relief Units in Serbia; Colonel Karanovitch,
Chief of the Military Sanitary Department, Serbia; Dr. Ni-
kolitch, Commissioner of Health, Serbia; Colonel Sondermeyer,
Chief Inspector of Military Hospitals (representative from the
Serbian Parliament); Colonel Jaubert, in charge of the French
Relief Units in Serbia; and Colonel Solfatero, in charge of the
Russian Relief. The Prince Regent Alexander was asked to act
as Honorary President, Sir Ralph Paget as Vice-President,
Lieutenant Petronovitch as Secretary, and the writer served as
Medical Director. The headquarters of this Commission were
situated at the war capital of the government in Nish. The
country having been divided into sanitary districts, sanitary
personnel, or hospital units, sanitary stations and hospitals
were assigned or distributed to these.

Fig. 1. Type of motor truck most successfully employed

Fig. 2. Disinfection of carriages
PLATE IV

THE SERBIAN EPIDEMIC

Preventive Measures

The general plan of the campaign again.-t typhus included:
general disinfestation of people in badly infected districts;

general house-to-house inspection in such districts with re-
moval of patients to hospitals for typhus cases; disinfestation
of other inmates of such houses; disinfection or disinfestation
of houses from which patients were taken or in which deaths
from typhus had occurred; the establishment of quarantine
and bathing and disinfesting stations at important points
throughout the country; the limitation of railway travel by re-
ducing the number of passenger trains; and the establishment
of a system of limited travel permits and of inspection of travel-
ers, only cars with wooden seats with no upholstery being per-
mitted to be run; provision for the cleaning and disinfecting of
such cars after each journey; provision for the cleaning and dis-
infestation of public vehicles, particularly of cabs at the railway
stations; the sanitary inspection of restaurants and cafes, and
the establishment of regular hours of closing during the day for
cleaning and disinfection, and the methods to be employed for
such disinfection; regulations for hospitals in connection with
the disinfestation of the wards, beddings, and linen, and of the
inmates and their clothing; the establishment of free dis-
pensaries in various cities, not only for the treatment of the
sick but for the early detection of individuals suffering with
infectious disease; a campaign of education with printing and
distribution of circulars in the Serbian language regarding the
nature of the disease, the manner of its spread, and the pre-
cautions to be taken to avoid infection.

After the general plan of the campaign was prepared, it was
necessary to have accurate information as to the sanitary con-
ditions and the needs of the different districts in various parts
of the country, and it was found to be absolutely impracticable
to obtain such information unless an actual visit had rirst been
made to the district concerned. Hence a system of sanitary
inspection was inaugurated. Much work of this nature was also

24 TYPHUS FEVER

carried on personally by the writer and it involved frequent
journeys made in as quick a time as possible.

The usual method employed in these primary inspections
was comparatively simple. Upon arriving at a town a con-
ference was called of the prefect, the chief of police, the military
commander, and the senior military and civil medical officers
for the locality. After this conference, inspections would be
made with these gentlemen and a plan made for the carrying
out of such sanitary measures as seemed necessary. The req-
uisite sanitary personnel and supplies not at hand were then
sent to the district. Almost invariably at a later date reinspec-
tion of the district was carried out in order to ascertain whether
the sanitary measures in question had been or were being
actually carried out in a satisfactory manner.

For the purpose of making these inspections, the Serbian
government placed at my disposal a railway car, approxi-
mately half of which was fitted up with four sleeping berths,
with shower bath and toilet facilities, while the other half
served as an office and dining room. Although these quarters
were not as palatial as this brief description of them might
imply, they constituted as regards disease one of the safest
places in which to sleep in Serbia. Attached to this car was a
second flat car upon which two Ford automobile trucks were
carried. It was necessary to carry these automobiles because
the railways in Serbia are very few in number (in fact there are
only three main lines) and the great majority of the smaller
towns are situated away from the track, often at considerable
distances from the stations. When it was necessary to spend
the night in the open the second Ford truck was employed to
carry tents and supplies.

None of the hotels or inns were safe places in which to sleep
before being disinfested or unless one took special precautions
in connection with a sleeping uniform, and one enjoyed the
luxury of a tent in Serbia whenever there was an opportunity to
sleep in one. The Ford automobiles were found to be most use-
ful, particularly because, on account of the very muddy and
very bad roads, heavy cars could not be employed. It was

Fig. 1. Evacuation of badly infected district pkior to its destruction

by burning

Fig. 2. The usual method of transportation in Serbia

PLATE V

/

THE SERBIAN EPIDEMIC

usually a simple matter, with the assistance of one or two sol-
diers, to dig out the car when the wheel- sank into the mud

above the hubs (a not infrequent occurrence) and to then con-
tinue upon the journey.

In making the inspections just referred to every effort was
made to awaken interest among the people in combating the
disease and particularly to arouse to action the officials of the
district as well as the people in connection with the prevention
of the spread of the epidemic. The Serbian official, though al-
most invariably good-natured, is often apt to procrastinate in
connection with work which requires particular effort or in-
convenience, and considerable driving power, initiative, and
assumption of authority was often necessary in order to accom-
plish what was deemed necessary-. Obviously it sometimes
sorely taxed the patience of a Serbian military commander to
be informed, for example, that a certain sanitary measure
which required the performance of considerable labor should be
immediately carried out, or that other more healthy prison
quarters must be found for several thousand Austrian prison-
ers and certain sanitary measures insisted upon in the new
prison. While the authority vested in the writer by the Serbian
government was ample enough to secure in the end the carry-
ing out of all sanitary measures considered necessary in con-
nection with the epidemic, nevertheless I have often thought
that the natural cordiality and politeness of Serbian officials to
a foreigner often accounted for the good-natured maimer in
which they usually acquiesced in carrying out a piece of work in
connection with the epidemic, after they had been thoroughly
convinced that there was no other course to pursue.

Occasionally certain sanitary measures of importance were
of such a nature (for example, the entire evacuation of certain
badly infected districts and the destruction of buildings In-
burning, or the making of cholera vaccination general and com-
pulsory) as to render the enactment of special ordinances de-
sirable. When such special enactments were desired, they wore
immediately presented and secured at a meeting of the Inter-
national Sanitary Commission. The immediate construction of

26 TYPHUS FEVER

disinf esting stations and other sanitary measures often required
special and immediate expenditure of funds, it being inadvisa-
ble to wait for special appropriations from the Serbian Parlia-
ment. Funds for carrying on the campaign had already been
placed at the disposal of the writer by the American Red Cross
and the Rockefeller Foundation , and these were immediately
available for emergency work. The writer had also been pro-
vided with different funds from private sources which will be
referred to later in this Report.

As scientific experiment and evidence have demonstrated
that typhus fever is commonly transmitted from man to man
by the louse Pediculus humanus, and as this disease is com-
monly transmitted only in this manner, the bathing and disin-
festing of large numbers of people and of their clothing in a
short space of time was another urgent problem in connection
with the Serbian epidemic, and under the circumstances it was
imperative to use all available suitable existing apparatus and
to hastily improvise all conceivable appliances for disinfesta-
tion.

It was very necessary to lay special emphasis upon impro-
vised methods derived from whatever materials there were at
hand, as very little perfected apparatus was available or could
be secured.

In this connection it should be particularly emphasized that
one of the reasons why the epidemic was dealt with so success-
fully was because the people themselves were instructed and
were finally convinced of the fact that the disease was avoid-
able and that the epidemic could be arrested largely through
their own efforts if the proper assistance was rendered them. It
was not that the great majority enjoyed taking a bath or being
deloused, or having their clothing deloused. In fact, many had
not had a bath for over a year; in some instances, their faces
betrayed surprise, in others fear, when the water from the
shower bath touched their bodies. Many of them desired none
of these things, but they submitted to these inconveniences, in
fact often welcomed them, and did their part in seeing that
they were carried out, solely in order that they might not con-

THE SERBIAN EPIDEMIC j7

tract the disease and that the epidemic should be arrested and
that they should be freed from the dangers and inconveniences
which it entailed.

When I was first asked to go to Serbia to take charge of work
in connection with the eradication of typhus, I was si rongly ad-
vised on two occasions by prominent members of the medical
profession against undertaking the work. It was argued that in
order to exterminate typhus from Serbia it was necessary to up-
lift the whole race of Serbian people and to change their entire
habits and methods of living and that this would take years to
accomplish. At a recent important conference of international
sanitarians I heard another physician express a somewhat
similar opinion, namely, that before the typhus epidemic in
Poland could be put down, it would be necessary to elevate the
entire moral tone of the people and their mode of living. I am
not in agreement with this idea. I however do believe that
such conditions must probably be brought about in a country
where typhus has long been endemic if one is to rid it entirely
of all its endemic foci of this disease, but experience in Serbia
has demonstrated that an epidemic of typhus may be arrested
long before an appreciable advance, however desirable it may
be,' has been made in uplifting the people and changing their
entire habits and mode of living. The presence of typhus fever
in times of famine, squalor, etc., is obviously particularly due
to the fact that among people who are more or less starved,
widespread neglect of personal cleanliness occurs and an in-
creased prevalence of lousiness results. The feeding of such
individuals and the improvement of their nourishment, how-
ever, does not necessarily change permanently their entire
habits and mode of life. The epidemic of typhus in Serbia was
not accompanied by general starvation or famine and it was
entirely eradicated after six months intensive work, but I be-
lieve that the habits of the people will show very little per-
manent change as a result of the measures undertaken. The
majority of the people, I think, will not delouse and bathe
themselves very much more frequently than they did formerly
unless typhus should again visit them in epidemic form, and

28 TYPHUS FEVER

they will then undertake these inconvenient and perhaps to
many of them disagreeable measures again, not because they
are uplifted and their habits of life permanently changed, but
because they have been enlightened as to how to avoid the
infection and prevent another epidemic.

In the emergency which confronted us in Serbia, it often be-
came imperative, as I have intimated, to improvise on the spot
the requisite apparatus for disinfesting and bathing, and make-
shift methods of various types were then devised. The ma-
jority of these did not attain what might be regarded as high
standards of efficiency as disinfestors, but they usually served
their purpose in destroying lice and their ova. It is true there
were not in Serbia any of the excellent Thresh steam disin-
festors on 5-ton Foden steam lorries nor other similar types of
perfected disinfestors. Indeed there were very few disinfestors
in the country which could be considered of the most modern
type. It however was impossible to obtain better types in time
for them to be of any value, and therefore their employment
was out of the question. All portable steam disinfestors which
were present in the country were sought out by means of the
sanitary inspections I have referred to above. They were re-
paired if necessary and all put into regular use. But while the
use of the highly perfected steam machines such as the 5-ton
Thresh is obviously very desirable in an epidemic, experience
in the Serbian outbreak demonstrated that they were not ab-
solutely essential for overcoming the outbreak. One may in-
deed, when it is necessary, successfully combat typhus with
such essentials as improvised baths, clean clothing, fire for pro-
ducing heat, roughly constructed disinfestors of boards, bricks,
and earth, combined with sulphur and petroleum.

In such makeshift work the Serbian people often showed
themselves not inefficient. It was frequently only necessary to
sufficiently insist that there must be a bathing and disinfesting
plant in a district and to give an idea of what was to be ac-
complished in order for the Serbians to carry out the project in
some way, though it was often performed in what today would
be considered a very crude manner.

Figs. 1 and 2. Refugees for disixfestatiox

PLATE VI

FlG. 1. WoMEN^AND^CHILDREN^ABOUT TO BE BATHED AM) DISINFECTED

Fig. 2. Austrian prisoners about to be delottsed

PLATE VII

Figs. 1 and 2. Refugee women and children, and men after bathing
and disinfestation

PLATE VIII

Fig. l. Refugee camp

Fig. 2. Austrian prisoners after being bathed and disixfested

PLATE IX

THE SERBIAN EPIDEMIC 29

In view of the immense amount of time and work that has
been given to the subject of the construction
since the Serbian epidemic, and the number of impi
that have been devised, a detailed description today of many
of the makeshift types then employed is hardly justified. Xut-
tall l has recently collected from the literature description!
many of the important modern British and some of the Ger-
man types, and therefore these need not be described her
few of those employed in Serbia, however, may be mentioned
in the present article in order to demonstrate what can be ac-
complished by such methods.

The most crude and primitive type of disinfestor employed
by the Serbian people was made by digging holes upon sloping
ground for ovens and lining them with bricks or stones. In
these ovens fires were lighted and the opening closed by a
wooden cover, or by a metal one if metal was available. After
a short time the fire was scraped out and the clothing to be dis-
infested placed in the oven on a grating and the opening again
closed with the cover. The Serbians became very expert in
judging the degree of heat requisite to kill the lice and their
ova and yet not sufficient to injure the clothing by burning, by
placing a piece of white paper in the oven and removing the
clothes when the paper showed the first tinge of turning yellow
from the heat. Doubtless some of my readers will smile at this
crude method of disinfestation. but a very important principle
in connection with the suppression of the epidemic was in-
volved by such a practice. It demonstrated that individuals
who would really undertake to carry out disinfestation in this
patient maimer above described, and under such obvious diffi-
culties, were interested in protecting themselves from the dis-
ease and thus in putting down the epidemic. Large brick or
concrete ovens with double walls of a single brick in thickness
between which hot air circulated were constructed and -
extensively in many of the smaller villages. In these the in-
fected clothing was loosely placed or hung upon frames. These

■ Xuttall: Parasitology. 191S. x. 4oo.

30 TYPHUS FEVER

disinfestors, while they were obviously not entirely satisfactory,
nevertheless usually accomplished in a crude way the desired
purpose.

Another type of disinfestor that was introduced into Serbia
by Colonel Hunter and Colonel Stammers, and employed par-
ticularly by them in the work of their unit at Kraguevatz and
Mladenovac, was termed "the Serbian barrel." The top and
bottom of a barrel was knocked out and a grated wooden bot-
tom and a flat wooden lid provided. A short trench was dug in
the ground which would accommodate a shallow circular metal
tank or boiler with sufficient space for a fire beneath. The
metal boiler was placed on two iron bars resting upon the sides
of the trench, and it was constructed of the same diameter as
the bottom of the barrel which rested upon it. To complete the
fireplace in which wood or coal was used, a chimney was some-
times placed at the further end of the trench. After the fire was
lighted the clothes were placed in the barrel and the cover held
down by a few stones during the process of disinfesting. As
Nuttall has remarked, this arrangement might serve as a make-
shift but it has drawbacks which need not be emphasized.
However, as I have pointed out, it was necessary in Serbia to
employ all possible makeshift methods. While the barrel
method of disinfestation was nevertheless moderately satisfac-
tory for the individual, it was found to be more desirable to
construct, whenever possible, stationary and permanent de-
lousing stations where a larger number of people could be dealt
with. Disinfestation of clothing by hot flatirons was employed
very little, if at all, in Serbia.

For the disinfestation of very large numbers of people and
their clothing in a short space of time, the establishment of sani-
tary trains was found to be a particularly efficacious method.
The disinfection of railroad freight cars and of clothing and
blankets in them by steam from the engine in connection
with the suppression of epidemic diseases had been em-
ployed in Manchuria in 1910 and later in Germany, and freight
cars arranged as steam disinfestors were known to be in use in
Germany early in the year 1915. The efficacy of the sanitary

Figs. 1 and 2. Disinfecting unit in charge of Dr. F. Gruyer

PLATE XI

THE SERBIAN EPIDEMK 31

disinfesting train units we employed in Serbia was, how<
due particularly to the chief engineer of the Serbian rail
service who displayed considerable ingenuity in directing the
conversion of the cars for this purpose. Afi employed by us in
Serbia these sanitary train units consisted of three care
which was occupied by a large engine boiler for supplying th»-
steam; a second car, a large refrigerator one, was made air
tight, felt being placed at the edges of the side door, and a con-
necting steam pipe was so arranged that steam from the boiler
could be turned into it under low pressure, the nidi nan
tern of pipes in the roof of these cars, finely perforated, being
also thus connected up with the boiler engine, the steam pass-
ing from these fine perforations downward and through tin-
car. The clothing was hung loosely in the car on wire bus] tended
from hooks. Both lice and ova on the clothing wen- killed in a
very few minutes in this manner, as was shown by repeated
tests carried out by Dr. Thomas Jackson, Chief Sanitarian <>i
the American Red Cross Commission. In a third large car
shower baths were constructed with a reservoir for water
above. These sanitary trains were run upon railroad sidings
and large tents were erected near them. The people marched
to the tents, several hundred at a time. Usually their hair
was clipped, and then, after undressing, their clothing was
placed in the steam sterilizing car. They next passed to the
car in which the shower baths were placed, and after a thor-
ough scrubbing with soap and water here, they were sprayed
with kerosene as an additional precaution for killing the
vermin and then received either sterilized clothing or new
clothing.

While these units could bathe and disinfest the clothing of a
very large number of people in a short space of time, there are
so many towns and villages away from the railway in Serbia
that other means had to be devised in caring for the people in
these localities. In those towns and villages away from the
railway, as well as in the large cities, permanent bathing and
disinfesting plants were constructed and regular arrangements
made for bathing the people by districts, different hours being

32 TYPHUS FEVER

arranged for the men, women, and children. Buildings such as
factories, warehouses and breweries, and wherever facilities for
obtaining steam were available, were particularly employed in
forming delousing centres. Where no buildings existed which
were suitable for conversion into such plants, these were
constructed of rough boards or of bricks, Austrian prisoners
being employed for such construction. An attempt was made
to arrange for a disinfesting plant of some nature in every
town. All the available Turkish baths were used in this con-
nection.

Both the plan of the station and the mode of procedure
varied with the facilities available in the locality, and as to
whether there were laundry facilities at hand or an existing
bathing establishment, or whether shower baths had to be
erected. In the hospitals tub baths as well as shower baths
were particularly employed, the tubs and much of the piping
necessary for the shower baths having been brought from
America. These bathing and disinfesting plants were usually
arranged so that the infected individuals entered at one side
and emerged from the other after disinfestation. There was a
room for undressing and another for dry disinfestation, or a
shelter under which a steam autoclave was placed and where
the clothing was treated; a room for bathing, a room where the
individuals were sprayed with petroleum or sponged with car-
bolic solution, and another where their clean clothing was re-
ceived and where dressing was accomplished. Sometimes tents
were used for the requisite shelter.

Whenever steam was available or a spare boiler could be
found, which could be put into use, it was employed for disin-
festing clothing. Where steam was not obtainable brick ovens
were usually constructed and the clothing disinfested in these.
Indeed existing brick kilns were sometimes used for this pur-
pose where available.

For the reason that so many perfected delousing stations
have since been described, those constructed in Serbia are also
not considered in greater detail.

Fig. 1. Steam bathing and disinfesting unit ix charge of Dr. T. \Y. Jackson-

Fig. 2. Men leaving tent before bathing

PLATE XII

Fig. 1. Leaving hath

Fig. 2. Returning to dressing tent

PLATE XIII

Fig. 1. Construction of delousing plant with Austrian prison labor

Fig. 2. Bathing and disinfesting unit in charge of Dr. George C. Sh \

PLATE XIV

X

THE SERBIAN EPIDEMIC

As all tho hospitals were infected, il was n< ■
ically to disinfest these The patients were firsl removed from

the wards and were placed upon a scrubbing hoard where they
were scrubbed with soap and water and afterwards bathed

with dilute carbolic solution. They then received elean cloth-
ing and were placed in a ward which had previously
cleaned and disinfested. The wards after being sealed were
primarily disinfested by sulphur fumigation in order to de-
stroy the vermin. Then the beds were taken down and
scrubbing with soap and water were treated with carbolic acid
solution.

The mattresses and blankets, when there were any. were
steamed, and the sheets and other bed clothing boiled. The
floors and walls were often scrubbed or sprayed with carbolic
acid or bichlorid of mercury solution. In addition the interior
of many of the wards was whitewashed.

Every precaution was taken to protect the men working in
infected places from contracting infection by insisting upon the
use of a proper uniform. The Austrian prisoners were largely
employed in all this work, and as many of them had already
suffered from an attack of typhus and were therefore immune,
they were often of particular value.

A uniform which was found to be suitable for nurses and sani-
tary and medical officers consisted of a one-piece garment, the
stockings and trousers combined, to be worn preferably under
the outer clothing. A satisfactory uniform should include in
addition high boots or shoes, the shoes so constructed as to pre-
vent the entrance of pediculi where they are laced. A wide strip
of adhesive plaster should be lightly placed around the leg over
the top of the shoe or boot to close the opening. Rubber gloves
should be worn when handling infested individuals or clothing.
and there should be another strip of adhesive plaster around
the 'top of each rubber glove to prevent the ingress of the lice.
It is advisable, for women at least, to wear a closely fitting
headdress. The uniform in general should obviously serve to
close as completely as possible all openings of the garments and
thus prevent access of lice to the skin. Those who come into

34 TYPHUS FEVER

very close contact with the patient, and particularly those who
examine the throats of patients, until we know more about the
methods of transmission of the disease, should wear a simple
mask of gauze over the mouth and nostrils, the ends being tied
behind the neck. During the recent epidemic of typhus fever in
Serbia such a uniform as above described was frequently em-
ployed, and some of the physicians employed the simple mask
described. When traveling it is always desirable to have with
one a folding rubber bathtub and a small supply of powdered
naphthalene.

In the anti-typhus campaign in Serbia, heat, whenever it
could be employed, was considered by far the most satisfactory
means for the destruction of lice and their ova. Although cer-
tain experiments seem to show that the virus of typhus fever is
destroyed by a temperature of 55° C. for fifteen minutes, and
that both lice and their ova are killed by dry heat at 55° C.
within fifteen minutes, and also by water heated to 55° C.
within fifteen minutes, in our work in the Serbian epidemic,
when dry heat was used and thermometers were available to
register it, a temperature of about 60° C. for fifteen minutes was
regarded as a safer standard to assume for routine practice in
connection with the delousing of clothing and blankets. When
steam was available for disinfestation it was the custom to sub-
mit articles to a temperature of 100° C. for not less than fifteen
minutes, usually for half an hour, in order to allow the steam to
thoroughly penetrate all parts of the clothing. Fur coats and
shoes are obviously likely to be ruined by steam disinfection.
However, hot air at 60° C. for half an hour does not injure
either furs or shoes if they are dry before being heated to such
a temperature. Furs may also be disinfested by carbon di-
sulphid, but this is not recommended for general use and was
not employed in Serbia. Shoes may also be disinfested with
petroleum.

A great many chemical substances have been recommended
for destroying lice and their ova. Those particularly employed
in our anti-typhus campaign were petroleum, phinotos oil (a
lysol-cresol preparation), sulphur, and to a less extent crude

i mm 2. Pbkparatton and deses

rXIT EN CHARGE OF Dk. FRANCES B. GsENNBUi

PLATE XVI

Fig. 1. Typhus ward after cleaning and disinfecting

Fig. 2. Antimalarial section at work in Macedonia

PLATE XVII

THE SERBIAN EPIDEMIC

naphthalene and benzene. Spraying with petroleum from a
fine spray was rather generally employed after bathing. No

injurious effects were observed, and it did Q01 -<< m to cause
much dermatitis in the Serbian people. Petroleum often ap-
pears to kill lice within a minute, and does kill them almost
invariably within two or three minutes. The ova sometimes
survive for a longer period. Some laboratory experiments since
performed, by Nuttall l seem to show that nits are sometimes
not killed with petroleum in twenty minutes. In this connec-
tion the chemical composition of the petroleum must be con-
sidered. The petroleum largely used in Serbia for disinfesl at ion
was brought from the United States. Obviously a disinfestant
may be shown by occasional laboratory experiments not to
destroy all of the ova or lice under the conditions of the experi-
ment, and yet it may be a disinfestant of considerable practical
value. Moreover, the very extensive practical use to which
petroleum was put in Serbia in connection with delousing
enormous numbers of people has shown it to be a very satis-
factory disinfestant in connection with an epidemic of typhus.
Experimental work on the subject during the war does not
appear to have demonstrated a more valuable and more prac-
tical disinfestant for the purpose for which it was employed in
Serbia.2 Phinotos oil was particularly employed in the hos-
pitals in a strength of about 2.5 per cent for spraying or washing
the bodies of patients after bathing them. Both ova and lice are
usually destroyed by this strength of the solution within ten
minutes. This preparation in stronger solution, 5 per cent, was
also employed occasionally for disinfesting linen and for disin-
fecting the walls and floors of the houses in which many cases i >f
typhus had occurred, or in the hospital wards where patients
were present. Crude carbolic acid was sometimes employed in
disinfesting beds. Wards in hospitals and houses regarded as
badly infected were first disinfested by sulphur fumigation.

1 Nuttall: loc. cit.

2 Castellani and Jackson, from Jour. Trop. Med., 1915, win, 253. Kerosene has
also been employed with excellent results for disinfestation by the American Public
Health Service, Hicks, Am. Jour. Pub. Health, 1917, vii, 62$; also Cuxoming, Jour. Am.
Med. Assn., 1917.

36 TYPHUS FEVER

Among the American Sanitary Commission were a number of
men l who had a very wide experience in the use of sulphur with
General Gorgas in his campaign against yellow fever in Pan-
ama. All the necessary appliances including the sulphur itself,
alcohol, pots for burning, paper and paste for sealing, buckets
for mixing the paste, brushes, etc., were brought in enormous
quantities from the United States. The item of sulphur alone
amounted to 100 tons.

Sulphur fumigation in the disinf estation of potentially infec-
tive houses and wards during an epidemic, on the whole, is
probably the safest and most satisfactory disinfestant for gen-
eral employment at our disposal. If employed thoroughly and
in the proper manner the adult lice are destroyed, and although
in a number of experiments in which sulphur dioxid has been
employed, all the ova have not been destroyed, nevertheless
the chance that in disinfesting a room during an epidemic the
few surviving ova are infected and will later develop and still
transmit the infection, would appear to be rather remote.
Moreover, there is no definite proof that hereditary transmis-
sion of the typhus virus occurs in the louse, and the most
reliable recent evidence is opposed to this idea.

If the room is large and is not tightly sealed and rendered
approximately air-tight, the amount of sulphur dioxid gas
generated must of course be increased and the period of ex-
posure prolonged. In Serbia, for general disinfestation by sul-
phur fumigation, not less than five to eight pounds of sulphur
were employed per 1000 cubic feet, the room or ward being
carefully sealed up for a period of not less than twelve to
twenty-four hours, the time varying according to the nature of
the space to be disinfested. Sulphur has been used satisfac-
torily for disinfestation during the war, particularly in the
French and Italian armies, and in the German army.

Crude naphthalene was employed in finely powdered form
for individual prophylaxis. It was found convenient to carry
the naphthalene about with one in a bottle, and it was often
dusted over the underclothing, particularly after inspection of

1 Drs. Jackson, Caldwell, Graver, Colonel Gale and others.

THE SERBIAN EPIDEMIC .7

prison camps and other groups of Lousy men: al i the

sheets and pillows in hotels a1 night. Naphthalene, from a
practical standpoint, must also be regarded of considerable

value as a disinfestant for lice, though it is well known thai it i-
not an absolutely reliable one, and that it is dangr-roua to de-
pend too much upon it. Bichlorid of mercury in 1:500 or
1:1000 solution was occasionally employed in cleaning hos-
pitals. It is known that it is not very reliable for disinfi
tion in connection with lice, as lice sometimes survive for more
than an hour upon surfaces upon wThich a solution of 1 : 2000
or even 1: 1000 of bichlorid of mercury has been previously
sprayed.

A great deal of work in connection with other infectious dis-
eases was also carried out in Serbia. As cholera had occurred 1 in
places along the border between Serbia and Austria it was
deemed advisable to perform vaccination against this clis<
and so vaccination trains and parties were also established
which went about the country with the doctors and assistants,
who inoculated thousands of people daily. Vaccination againsl
cholera and typhoid fever was made compulsory in Serbia. At
first my own method of vaccination against cholera was em-
ployed, as it has the advantage of only requiring a single
inoculation. Later on typhoid and paratyphoid fever became
prevalent and a combined vaccine against all three of these
diseases was manufactured in our laboratories in Serbia by the
method of Professor Aldo Castellani and sent throughout the
country for use.

Dr. Castellani was placed in entire charge of the preparation
of the vaccines. No cases of cholera occurred in Serbia during
1915. The water supply of many of the towns was also greatly
improved, and artesian wells were bored in a number of in-
stances where the water of the vicinity had been condemned as
unsafe after it had been examined systematically in our labora-
tories, apparatus for boring these wells having been brought
from the United States. In fact, a systematic bacteriological
examination of local water supplies was one of the tasks which
was undertaken by our laboratories.

38 TYPHUS FEVER

An important problem in the reduction of the amount of
typhoid fever and the prevention of cholera was the disposal of
human excreta, and a large number of sanitary and fly-proof
latrines were constructed throughout the country, particularly
about barracks, hospitals, etc. In many cases the cesspools be-
came filled to overflowing, and there was not a sufficient num-
ber of hydraulic pumps in Serbia to empty a quarter of them.
Our Red Cross immediately supplied, upon my request, a large
number of these pumps. The construction of filter beds for
purification of sewage was also undertaken in a number of
places, and the sanitary condition of some of the cemeteries,
where there were numerous shallow pits in which twenty to
thirty bodies at a time had been buried and insufficiently
covered with earth, was improved.

A campaign for the destruction of the breeding places of flies,
in connection particularly with the spread of typhoid and
cholera, and of mosquitoes, in relation to the spread of malaria
in southern Serbia, was also undertaken.

In regard to the course of the epidemic of typhus in Serbia
and the influence of the anti-typhus campaign upon it, it is
interesting to refer briefly to the history of the disease in
previous epidemics.

Summary of Previous Epidemics

Hirsch x states that the history of typhus is written in those
dark pages of the world's history which tell of the grievous
visitations of mankind by war, famine, and misery of every
kind. In every age as far back as the historical inquirer can
follow the disease at all, typhus is met with in association with
the saddest misfortunes of thepopulace. From the writings of
Corradi we know that typhus fever was epidemic in Italy in
1505, and shortly afterwards spread from there all over Europe.
The disease was described more accurately by Fracastori in
1533, and from this date onward its history can be more readily
traced. It had evidently also prevailed extensively at an earlier
time and with great severity among the Castilian troops

1 Hirsch: Handbook of Geographical and Historical Pathology, 1883, i, 545.

X

Fig. 1. Filled cesspool

Fig. 2. A typical Serbian town after eradication" of typhus

PLATE XX

THE SERBIAN EPIDEMH

shortly after the siege of Granada. Later L557 it became
known in Spain under the name of el tabardillo the much
dreaded red cloak); and in this country there were repeated
epidemics. In a third epidemic in Italy in the second half of the

sixteenth century, it is said to have destroyed more than one
million people in Tuscany. In 1566 it became epidemic in tin-
army of Maximilian II of Hungary and extended its ravag
again over Europe, continuing for more than twenty-one years.
In the seventeenth century typhus was again one of the dis-
eases which caused the highest mortality. So great were the
miseries engendered by it and by the other events in connection
with the Thirty Years War, that Haeser, writing of this period
with reference to districts formerly well populated, says that
one could wander for miles without seeing a living soul, only
dead bodies decomposing and partially devoured by wolves,
dogs, and vultures, for want of a decent burial. Towards the
close of this century Morton implies that practically every hos-
pital in England was rilled with typhus victims. The eight-
eenth century saw no abatement of typhus epidemics, and
there is scarcely a year during this century that one may not
find references to epidemics of it.

Hirsch, however, distinguishes four periods during which the
disease was excessively prevalent; the first period was a con-
tinuance of the outbreaks which had occurred in Germany and
in Austria-Hungary as a result of the wars waged in those
countries. The epidemics died out about the year 1720. Dur-
ing the second period, 1734-44, the disease ravaged Central
and Eastern Europe. It was first noticed among the Polish
troops engaged in the war of the Polish succession. It spread
throughout Russia, Prussia, Silesia, and the central German
states and the Netherlands. The English and French troops
engaged in these wars were also affected. The third period
lasted from 1757-75. It owed its origin to the Seven Years War,
starting in 1757 between England and France. The epidemic
began in Prussia, extended all over Germany, and then spread
to France and Spain. In 1764 and 1767 extensive epidemics
occurred over most of Italy, it is said as a result of a total failure

40 TYPHUS FEVER

of crops in each case. The fourth and most extensive period
began in 1789 in France during the Revolution, and from there
spread over the whole of Europe. The disease persisted in
epidemic form throughout the duration of the Napoleonic wars,
and did not begin to subside until the conclusion of peace in
1815, after the Battle of Waterloo. This was said to be the
severest epidemic of typhus fever ever recorded on the con-
tinent. The disease was always most severe in those places
where the various battles and sieges occurred, but it spread to
many places far removed from the sites of war. The general
poverty and distress, the results of war, evidently aided greatly
in the spread of the disease in these localities.

After this severe epidemic over the whole of Europe no gen-
eral epidemic occurred until the years 1846 and 1847, when
typhus fever became widespread again over the entire con-
tinent; however, from 1816 to 1873 in Italy there were fifty-one
epidemics, and in France, there were sixteen.

In England there were definite references to epidemics from
1643. According to Creighton, in 1694 the fever deaths in Lon-
don were 5036. In 1741, during a general epidemic of typhus,
there were 7500. Another severe epidemic began in England in
1831, and continued its ravages there for more than ten years,
being at its worst, however, between 1837-42. Another serious
epidemic occurred between 1862-69, and particularly in London
between 1863-65. In England and Wales during the period
1869-83 there were 23,702 deaths from typhus. During 1884-98
there were 2249, while during 1899-1913 there were only 390.

Ireland had long been infected by typhus, and, particularly
from 1708, this country was ravaged by one epidemic after
another. At the beginning of the eighteenth century the popu-
lation of Ireland was estimated at about seven million, and
during 1846-47 the number of sick at one million, about one-
seventh of the population. In Dublin alone there were 60,000
cases of the disease. Since 1815, apart from smaller epidemics,
the disease has spread widely six times, the epidemic of 1846-
48 above referred to being one of the severest, and the last of
these six severe epidemics being from 1862-64.

THE SERBIAN EPIDEMU 11

In Mexico the disease heeame e])idemic in L530, shortly after
the conquest. Another outbreak occurred in 1 570, being -aid u,
have been imported from Spain. In 1734-36, L89,OQ0 people
are reported to have died from typhus fever in Mexico. There
have been numerous epidemics during the nineteenth century,
one of the most serious in 1861.

In the United States and Canada typhus also prevailed in
certain centers in the early years of the nineteenth century,
and there were severe epidemics following the Irish immigra-
tions in 1846 and 1847. In South America typhus was probably
imported from Spain to Peru at a very early period where it was
well known under the Spanish name of tabardillo in 1821, 1825,
and 1846. It also prevailed in Chili at the same period. The
Napoleonic, Crimean, Russo-Turkish, and recent Balkan wars
have all been accompanied by typhus. Early in the recent
great war, typhus appeared in Germany among the Russian
prisoners of war in Austria, and it also became epidemic among
the Turkish troops in the Erzeroum district.

It has not been my intention to attempt a complete sum-
mary of the history of typhus fever in this Report, but merely
to cite many of the important epidemics in order that it may be
seen that in earlier years the disease apparently raged aim. >>t
unrestrictedly. The epidemics often continued for a number of
years at a time and were not limited to or by any particular
season.

Hirsch writes that out of 147 epidemics which occurred in the
temperate and cold latitudes of the eastern and western hemi-
spheres, and of which we have accurate data as to the time of
their outbreak and their course, 30 reached their acme in
spring, 28 in winter and spring, 21 in spring and summer. 19 in
summer and autumn, 18 in autumn, 17 in summer, and 14 in
autumn and winter. He concludes that even if there can be no
doubt that the maximum of typhus cases falls distinctly in the
colder months (winter and spring) yet it is proved that typhus
is quite independent of season and weather in its development
and epidemic diffusion; that neither the upper nor lower ex-
tremities of temperature or moisture can further or hinder the

42 TYPHUS FEVER

disease in its breaking out and progress, nor any other condi-
tion of weather exert a perceptible influence in these respects.
It is in this sense that almost all the authorities express them-
selves.

Osier has remarked that the gradual disappearance of the
disease in Great Britain and on the continent has been one of
the great triumphs of sanitation and this also proved to be the
case in connection with the epidemic in Serbia. It will be re-
called that this epidemic of typhus fever was the first extensive
and serious one to occur since the demonstration of the method
of the transmission of this disease by lice in 1909-10. It should
be emphasized that the efforts of all of the physicians, sani-
tarians, nurses, and particularly of the people generally in Ser-
bia being directed against the spread of the disease by pediculi,
the suppression of the epidemic by intensive work was accom-
plished within a period of six months.

Method of Transmission

In connection with the Serbian epidemic, it is also important
to refer to the method of transmission of the disease.

As long ago as 1876, Murchison suggested, in addition to
other measures in connection with the prevention of typhus,
that in order to prevent an individual from acquiring such
infection, it was necessary to protect him from lice. In 1903, at
the International Sanitary Congress held in Paris,1 Dr. Cor-
tezo made a statement based upon his experiences in an epi-
demic at Madrid that typhus fever is transmitted by lice and
fleas, but no data of specific experiments were supplied demon-
strating these facts. It has been for a long time a well-recog-
nized fact that epidemics of typhus fever and of relapsing fever
occur side by side and under similar conditions, and the close
association of these two diseases has indeed been noted since
1739. This fact and the work carried out upon relapsing fever
by Sergent and Foley 2 and Mackie 3 and Smith 4 suggested

1 Official abstracts of Proceedings of the Conference, p. 343.

2 Sergent and Foley: Bull. Soc. de path, exot., 1908, i, 174.

3 Mackie: Brit. Med. Jour., 1907, ii, 1706.

4 Smith: Medical Thesis (London), 1909, John Bale Sons and Danielson, Ltd.

THK SKRBIAN KPIDKMIC 13

that lice were also probably the transmit tf-r> of typhu
However, in 1909, Nicolle ' working in Algiers showed In-
actual experiments that the chimpanzee could be infected with

the typhus virus by the injection of a small amount of blood
from a human active case of the disease. He then showed that
lower monkeys could be similarly infected by the inoculation of
the chimpanzee's blood, and that then the infection could be
transmitted from monkey to monkey by means of the bitea of
infected body lice (Pediculus humanus var. corporis) . This \v< uk
was shortly afterwards confirmed in the United States by
Ricketts and Wilder2 and by Anderson and Goldberger,' who
also showed that the lower monkeys might be infected directly
with human typhus blood or by the bites of lice that had fed
upon human cases of the disease. Later it was shown by dif-
ferent investigators, Wilder,4 Goldberger,5 Prowazek,6 Sergent.7
and Nicolle,8 that the disease may be transmitted to monkeys
by inoculating them with the contents of crushed lice or with
faeces of infected lice, the lice or their faeces becoming capable
of conveying infection from two to eleven days after feeding
upon typhus infected blood, and the blood in typhus fever
cases being found infective from the third to the tenth day i >f
the attack. A few experiments which have been undertaken
with bedbugs and fleas seem to show that these insects do not
transmit typhus fever. From other experimental work per-
formed, first by Anderson and Goldberger 9 and more recently
by Toepfer10 Nicolle11 and others, and from observations made

1 Nicolle: Compt. rend. Acad. d. sc, Paris, 1909, cxlix, 157; Ann. de I'lnst. Pasteur,
1910, xxiv, 243.

2 Ricketts and Wilder: Jour. Am. Med. Assn., 1910, liv, 403; Wilder: Jour. Infect.
Dis., 1911, ix, 9.

3 Anderson and Goldberger: Pub. Health Rep., Wash., 1910, xxv, 177: also Pull. Byg.
Lab., -U. S. P. H. S., Wash., 1912, Bull. No. 86, p. 13.

4 Wilder: loc. cit., 1911.

6 Goldberger: Pub. Health Rep., Wash., 1912, xxvii, 297: and Bull. Hyg. Lab.'l". S.
P. H. S., 1912, No. 86, p. 37.

6 Prowazek: Berl. klin. Wchnschr, 1913, 1, 2037.

7 Sergent, Foley, and Vialatte: Compt. rend. Acad. d. sc, Paris, 1914, clviii, 964.

8 Nicolle, Blanc, and Conseil: ibid., clix, 661.

9 Anderson and Goldberger: loc. cit., 1912.

10 Toepfer: Deutsch. med. Wchnschr., 1916, xlii, 1251.

11 Nicolle: Bull, de l'Inst. Pasteur, 1920, xviii, 49.

44 TYPHUS FEVER

by Foster in the Philippines * it seems not unlikely that Pedi-
culus capitis, the head louse, may also sometimes transmit the
disease. Further experimental work on this question, however,
would appear desirable. Nuttall 2 apparently inclines to the
belief that Goldberger's experiments are not entirely convinc-
ing but Nicolle3 states that P. capitis may convey the disease.
It has also been suggested that infection may occur in man
by the ova of infected lice being rubbed or scratched into
abrasions of the skin, but it has not yet been definitely demon-
strated if hereditary transmission of the typhus virus occurs in
lice, the evidence on this question being contradictory.

There have been no scientific and properly controlled actual
experiments performed upon human beings which demonstrate
that typhus is transmitted by lice, though Moczutowski in
1900 and Yersin and Vassal 4 and Ostero 5 demonstrated by
human experiment that the disease could be transmitted by
direct injection of typhus blood. However, in a few instances
in which accidental infection or experiments in man were car-
ried out in connection with transmission by lice, the evidence
has been in favor of the view that the transmission of typhus is
through this agency. These human experiments, however, had
not been adequately controlled as is evidenced from the follow-
ing summary of them.6

Sergent, Foley, and Vialatte,7 trying to prove the transmis-
sion of recurrent fever by the louse, made lice who had fed on a
patient of recurrent fever bite a man. Another man was inocu-
lated with similar lice, and still another with eggs from such lice.
All of them developed typhus. Sergent, Foley, and Vialatte
explained this by assuming that the patient was suffering from
typhus at the same time or was already infected with typhus.
This seems not unlikely, as it is well known that both of these

1 Foster: Arch. Int. Med., 1915, xvi, 363.

2 Nuttall: Parasitology, 1917, x, 52.

3 Nicolle: loc. cit.

4 Yersin and Vassal: cited by Thoinot, Paris Med., 1915, Nos. 49-50, p. 473.

6 Ostero: cited by Vincent and Muratet, " Exanthematic Typhus," Univ. of London
Press, 1917, p. 207.

G Banus: Intern. Jour. Pub. Health, Geneva, 1920, i, 69.

7 Sergent, Foley, and Vialatte: Compt. rend. Acad. d. sc, 1914, clviii, 964.

THE SERBIAN EpiDEMK 16

diseases occur together in epidemic form, and Kirkovic and

Alexieff1 have reported thirty-three cases in which both dis-
eases were present at the same time, and they state that in
most of these cases the recurrent fever appeared first . Another
instance of transmission to man is reported by Ussher,9 who

states that a male nurse allowed himself to be bitten by an in-
fected louse and developed typhus in five days. Nicolle, Blanc,
and Conseil,3 tell of the case of the warder in the penitentiary
at Tunis who caused infected lice to bite one of two workers
coming from the outside and with no contact with any typhus
patients. The bitten man developed typhus while the other
did not. They describe, too, another case, that of a laborat i >ry
assistant who was bitten accidentally by an infected louse and
developed the disease. This experimental evidence on human
beings alone of transmission of typhus by lice is obviously not
strong enough to be entirely convincing and does not exclude
the hypothesis of other means of transmission.

A great many physicians of different nationalities have died
from typhus during the war and a great many more have con-
tracted the disease. In many instances these physicians were
thoroughly cognizant of the method of transference of the dis-
ease by lice and of the precautions to be taken in avoiding such
infection. In a number of instances where particular care was
taken to avoid contamination with lice, nevertheless, infection
with typhus followed. For this reason it has been particularly
urged that infection sometimes must occur in man by another
manner than through the agency of pediculi, and it has been
suggested that the droplet method of infection after coughing
might sometimes occur in this disease. It is recognized that in
the early stages of typhus there are likely to be mflammatory
conditions of the mouth, nose, and throat. A number of in-
stances have been recently recorded in medical literature and
evidence given which is sometimes in favor and sometimes op-
posed to the idea of the possibility of droplet infection in ty-

1 Kirkovic and Alexieff: Arch. f. Schiffs- u. Tropen-Hyg., xxii, 2S9.

2 Ussher: Med. Rec, 1914, lxxxvi, 509.

3 Nicolle, Blanc, and Conseil: Compt. rend. Acad. d. sc, 1914, clix, 661; Ann. de
l'Inst. Pasteur, 1910, xxiv, 261.

46 TYPHUS FEVER

phus fever. As yet there has been no experimental proof that
the sputum or saliva in typhus fever contains the virus, but on
the other hand there have been no careful experiments per-
formed upon man in which the saliva or sputum have been em-
ployed for infection. Also, even if typhus may sometimes be
transmitted to man by droplet infection, the experimental
proof of this fact might be very difficult. In this connection we
have only to recall the negative experiments performed upon
man by Rosenau and his associates x in connection with the
transmission of influenza by the sputum and by droplet infec-
tion. It must be borne in mind that the virus of typhus fever
has repeatedly been shown to be present in the blood; that
Moczutowski inoculated himself in this manner and suffered an
attack of typhus fever after an incubation period of 18 days.
Yersin and Vassal also inoculated two men with typhus blood
who developed typhus after 14 and 21 days respectively.
While the experimental transmission of typhus infection to
monkeys and other animals is certainly sometimes very un-
satisfactory,2 and the proof that the infection has been actually
transmitted not always definite and convincing without the
most minute study, nevertheless, practically all such transmis-
sion experiments in animals are also in favor of the view that
the virus of typhus is present in the circulating blood and that
the blood is usually infected during the active period of the
fever. As the virus is present in the blood it would not be sur-
prising if some of the secretions also contained it. The experi-
ments recently performed on man in demonstrating the method
of transmission of trench fever are interesting in this connec-
tion.3 A series of inoculations in man with urine or urinary
sediments and with saliva or sputum from typhus cases might
give further information on this question. While it seems evi-
dent that the only common and important method of trans-
mission of typhus is through the louse, and that epidemics of

1 Rosenau: Jour. Am. Med. Assn., 1919, lxxiii, 311.

2 See in this connection, Friedberger, Ztschr. f. Immunitatsforsch. u. exper. Therap.,
1920, lxxix, 125, who states it is not possible to infect guinea pigs with typhus blood.

3 Trench Fever, Report of Commission Medical Research Committee, American Red
Cross, Oxford University Press, 1918, p. 37.

THK SERBIAN EPIDEMIC 17

the disease are due to this method of transmission alone, Q<
thcless, several careful observers have the impression thai
exceptionally and rarely typhus may be transmitted to those

who come into close intimacy and contact with patient- by
some other means. In cases of typhus in which there are
abrasions of the mucous membranes of the mouth, nose, and
throat, the possibility of infection through coughing should be
borne in mind. A number of observers are in favor of this idea .
Thus Kraus believes that there is some other means of trans-
mission than by the body louse, and states that this was the
belief of all the Galician doctors who based their views on the
observation that if the rooms containing typhus patient- were
kept well ventilated, no infection occurred among the person-
nel. Allan 1 is of the same opinion that, if a person not pro-
tected by a previous attack remains some time in a close, stuffy
room near the patient, he runs the risk of contracting the dis-
ease although no lice may be present. Walter 2 suggests the
danger of overlooking such a possibility and describes an epi-
demic which he could not entirely explain on the assumption of
transmission by the louse. Friedberger,3 in his account of the
epidemic in Pomerania, expresses doubts as to whether the
louse is the real carrier, because he found cases that he could
not ascribe to louse bites, among which were those of four
doctors who developed typhus without even having felt a louse
bite, and that of a lady who only once for a short time had
entered a room occupied by patients in order to give them some
apples.

The idea of droplet infection is also supported by Rondke,4
who bases it on the evidence of the case of one nurse who de-
veloped typhus when no new patients had been admitted for
ten days, while all the sick people were free from lice. She had
taken very carefully all the precautions advised, but did not
wear a mask. A similar case is reported by Sellards B and Shat-

1 Allan: Brit. Med. Jour., 1915, ii, 841.

2 Walter: Berl. klin. Wchnschr., 1915, lii, S51.

3 Friedberger: Ztschr. f. Hyg. u. Infectionskrankh., 1918, lxxxvii. 475.

4 Rondke: Med. Klin., 1915, p. 1152.

5 Sellards: Part III in this Report.

48 TYPHUS FEVER

tuck l in Serbia of a nurse who protected herself very carefully,
wearing a louse-proof suit. She had to sponge and swab the
throat of a very severe case with serious lung and mouth com-
plications. The patient was free from lice but coughing fre-
quently. The nurse developed typhus after two weeks. Of the
same opinion are Flueggi, Gaertner, Bujwid, Kisskalt, Uhlen-
huth, and Stroklosinski,2 Larrieu and Delarde and d'Halluin.
Delarde and d'Halluin 3 believe that in some cases of typhus
during the epidemic they studied in Germany, droplets of
saliva expelled in coughing were infectious, and when inocu-
lated to the mucosa produced the disease. They also report
the case of a physician who was found to be free from lice and
yet contracted typhus. One should not dismiss such evidence
with the mere statement that the small larval stages of lice may
well escape notice. It does not seem entirely improbable that
some of the doctors and nurses, who came repeatedly into very
close contact with typhus cases and who have lost their lives
from this disease during the war, contracted the infection per-
haps because they regarded the only possible means of trans-
mission to be by body lice, and only took precautions against
this means of infection. That typhus may be sometimes trans-
mitted by some other means than by the louse is a view held by
a considerable number of physicians who have had during the
war an unusual experience during epidemics, though little cre-
dence is given to this idea by some investigators who have no
such experience and who have formed their judgment that the
louse is the sole transmitter from the louse transmission ex-
periments recorded in the literature.

Granting that the spread of the disease in epidemics is due to
louse transmission, and that our methods in combating success-
fully this disease in epidemics need only be directed against
such a means of transmission, nevertheless, it must be borne in

1 Shattuck, G. C. : Harvard Graduate Magazine.

2 Flueggi, Gaertner, Bujwid, Kisskalt, Uhlenhuth, and Stroklosinski : Med. Klin.,

1915, p. 586.

2 Larrieu and Delarde and d'Halluin: Bull, et mem. Soc. med. d. hop. de Paris,

1916, xxxii, 320.

THE SERBIAN EJ'IDKMK' \U

mind that this does not exclude exceptional instances of infec-
tion by other means.
Typhus fever claims more victims in the medical profession

than any other epidemic disease. The mortality among phy-
sicians in epidemics is generally high. Osier state- in a period of
25 years in Ireland, among 1230 physicians attached to institu-
tions, 550 died of typhus. Minkine reports that out of 13 phy-
sicians working at the typhus hospitals, 12 contracted the
disease, and 6 of them died. Butler in connection with his
typhus hospital unit states that of 6 physicians, 4 contracted it
and 2 died. The mortality among the Serbian physicians, 126
out of 350, or 36 per cent, has already been referred to. More-
over, some of these physicians were immune from previous
attacks contracted before this epidemic. Friedberger,1 in re-
porting an epidemic at Schutzen in 1915, states that 24 of the
doctors were attacked and 14 died, a mortality of 58 per cent ;
that of 332 nurses, 71 fell ill of whom 15 died, a mortality of
21 per cent; at the same time the disease among the Russian
prisoners showed only a mortality of 7.8 per cent. Why is in-
fection with typhus so common and the mortality so high
among physicians? Is there an opportunitj1, of direct infection
by some means in which the virulence of the infection (as in
pneumonic plague) is uniformly greater than when it is trans-
mitted through the intermediate host, in the case of typhus,
the louse; and in bubonic plague, the flea?

Aetiology

Bacteriological investigations in regard to the aetiology of
typhus were carried out during the Serbian epidemic in con-
nection with several of the larger hospitals.

In spite of the very large amount of experimental work that
has been performed in relation to the causative organism of
typhus, there is no general unanimity of opinion upon the na-
ture of the virus. A number of different investigators working
in different epidemics in various parts of the world have de-
scribed species of cultivable bacteria as the cause; others

1 Friedberger: Ztschr. f. Hyg. u. Infectionskrankh.. 1918, lxxxvii. 475.

50 TYPHUS FEVER

believe the disease owes its origin to a species of protozoa, and
still others think that it is due to a filterable virus.

Rocha-Lima l and a number of other investigators regard the
so-called Rickettsia prowazeki as the cause. Different bacilli,
each regarded as specific, have been reported, particularly by
Horiuche 2 in 1909, Ricketts and Wilder in 1910,3 Plotz, 1914,4
Rabinowitsch,5 Arnheim,6 Rudisjicinsky,7 Petruschky, 19 15,8
and Zeiss, 1917.9 Specific cocci have been regarded as the cause,
particularly by Wilson, 19 10,10 Proescher, 19 15,11 Penfold, 19 16,12
and Danielopolu, 19 17,13 while pleomorphic organisms (diplo-
coccoid and bacillary forms) have been described by Prejet-
chensky,14 Fuerth, Mueller, Hort, and Ingram,15 and Topley16
and Gaston.17 In addition to these claims Futaki (1915) 18 has
described a spirochaete, Goldstein19 a motile diplobacillus, and
Milman 20 a non-motile diplobacillus as the cause of typhus.
Wolbach and Todd21 believe that the cause of Mexican typhus
fever is due to a new parasite which they call Dermacentroxe-
nus typhi: Weil and Felix,22 Felix,23 and Friedberger24 have be-

1 Rocha-Lima: Arch. f. Schiffs- u. Tropen-Hyg., 1916, xx, 17; Berl. klin. Wchnschr.,
1916, liii, 567.

2 Horiuche: cited by Ledingham, Lancet, 1920, i, 380.

3 Ricketts and Wilder: Jour. Am. Med. Assn., 1910, liv, 1373.

4 Plotz: ibid., 1914, lxii, 1556.

5 Rabinowitsch: Berl. klin. Wchnschr., 1914, li, 1458.

6 Arnheim: Deutsch. med. Wchnschr., 1915, xli, 1060.

7 Rudisjicinsky: New York Med. Jour., 1915, cii, 1175.

8 Petruschky: Centralbl. f. Bacterid., 1914-1915, Orig., Abt. 1, lxxv, 497.

9 Zeiss: Deutsch. med. Wchnschr., 1917, xliii, 1227.

10 Wilson: cited by Ledingham, Lancet, 1920, i, 380.

11 Proescher: Berl. klin. Wchnschr., 1915, lii, 805.

12 Penfold: Tr. Soc. Trop. Med. and Hyg., 1916, ix, 105.

13 Danielopolu: Presse med., 1917, xxix, 403.

14 Prejetchensky: Typhus Fever, cited by Cox, Commonwealth of Australia Quaran-
tine Service, 1917, Publication No. 13, p. 30.

15 Fuerth, Mueller, Hort, and Ingram: cited by Cox, Commonwealth of Australia
Quarantine Service, Publication No. 13, p. 31.

18 Topley: Jour. Roy. Army Med. Corps, 1915.

17 Gaston: Revue de m6d., 1915, xxxiv, 559.

18 Futaki: Brit. Med. Jour., 1917, pp. 265 and 491.

19 Goldstein: ibid., p. 167.

20 Milman: Jour. Am. Med. Assn., 1915, lxv, 2203.

21 Wolbach and Todd: Ann. d. lTnst. Pasteur, 1920,[No. 3, p. 159.

22 Weil and Felix: Wien. klin. Wchnschr., 1916, xxix, 33; ibid., 1917, xxx, 393.

23 Felix: Ztschr. f. Immunitatsforsch. u. exper. Therap., 1917, xxvi, 602.

24 Friedberger: Deutsch. med. Wchnschr., 1917, xliii, 1314.

THE SERBIAN EPIDEMIC 51

lieved that Bacillus proteus X 19 possesses specific propel
in connection with the disease, and Werner and Leoneanu
and Hilgermann and Arnoldi ~ have even made human inocula-
tions for protection against typhus with this organism. ( >n the
other hand, Nicolle, Hort3 and others believe that typhus is due
to a filterable virus. On account of the attention thai has been
recently called to the Rickettsia in relation to the disease and
the opportunities for the investigation of the aetiology of typhus
which will undoubtedly occur in connection with the epidemics
of this disease in Central and Eastern Europe, it seems advis-
able to present here a detailed account of the investigations
which have been already made in relation»to the Rickettsia.

The Significance of Rickettsia in Relation to
Disease

In 1916 Rocha-Lima called attention to the presence of very
minute bodies which were found in lice which had fed upon pa-
tients suffering from typhus fever. These bodies were present
not only in the contents of the alimentary canal, but especially
in the epithelial cells of the alimentary tract of these insects.
He regarded them as very minute microorganisms. They were
elliptical, oval, often found in pairs and bipolar in appearance.
The smallest forms measured from about .3 to .4 m and the
larger ones, sometimes biscuit-shaped, from .4 to .9 m. They
were best demonstrated by staining in Giemsa's solution.
These organisms were not at first found in lice which had not
fed upon cases of typhus fever. The lice were said to become
parasitized only after ingesting infected blood. Rocha-Lima
pointed out that while these bodies slightly resembled bacteria
in their morphology, they were in other respects more like the
Chlamydozoa-Strongyloplasmata. He therefore proposed for
them the name of Rickettsia prowazeki (n.g. n.sp.) evidently
choosing this name in memory of Ricketts and Prowazek, both
of whom succumbed to typhus fever which they contracted

1 Werner and Leoneanu: Munchen. med. Wchnschr., 1018. lxv. 587.

2 Hilgermann and Arnoldi: Deutsch. med. Wchnschr., 1917, xliii, 1582.
» Hort: Brit. Med. Jour., 1917, p. 265.

52 TYPHUS FEVER

while pursuing their independent investigations upon this dis-
ease. Subsequently, organisms having a similar appearance
were found by other observers and also by Rocha-Lima in lice
which had fed upon healthy individuals or on those suffering
with various other diseases. For this second form Rocha-Lima
proposed the name of Rickettsia pediculi. He believes that
Rickettsia pediculi differs from Rickettsia prowazeki in that the
former is found normally only in the lumen of the alimentary
canal of the louse, and does not multiply in the cells of the in-
sects' alimentary tract, or only does so exceptionally.

It is of importance in considering the study of the Rickettsia
to recall that the terms Chlamydozoa (Prowazek) x Strongylo-
plasmata (Lipschuetz)2 were proposed to include a group of very
minute pathogenic organisms or viruses which exhibited cer-
tain common properties, while exercising specific peculiarities
in each case. These viruses are believed during at least one
stage of their development (that of the "elementary cor-
puscles") to pass through bacterial filters without losing their
virulence. Within the cells of the host the elementary cor-
puscles are believed to grow into larger " initial bodies." The
chief characteristics of the chlamydozoa 3 were said to be
firstly, their minute size, smaller than any bacteria hitherto
known, enabling them to pass the ordinary bacterial filters
during one stage of their development; secondly, that they
develop within cells, in the cytoplasm or nucleus, and produce
characteristic reaction products and enclosures of the cell;
thirdly, that they pass through a series of developmental stages
and are specially characterized by their mode of division,
which is not a simple process of splitting as in bacteria, but is
effected with formation of a dumb-bell shaped figure as in the
division of a centriole. Two dots are seen connected by a fine
line like a centrodesmus, which becomes drawn out until it
snaps across the middle, and its two halves are then retracted
into the body. In appearance the chlamydozoa seem to consist
primarily of merely a grain of chromatin without cytoplasm

1 Arch. f. Protistenkunde, 1907, x, 336.

2 Handbuch der Pathogenen Protozoen, Leipzig, 1911, Prowazek and others.

3 Minchen: Introduction to the Study of the Protozoa, London, 1917, p. 472.

THE SERBIAN EPIDEMIC

and without a membrane of any kind. Hence they ap
represent the simplest form of living body. The chlamyd
have not yet been successfully cultivated, bul infections can be

produced with pure colloid-filtrates free from bacteria, bu1
containing the minute bodies themselves. They are char-
acteristically parasites of epiblastic cells and tissues. The
viruses of trachoma, vaccinia, scarlet fever, hydrophobia, mol-
luscum contagiosum, and more recently of typhus fever, have
been referred to the chlamydozoa.

Previous to Rocha-Lima's observations, several investig
tors had published articles describing microorganisms observed
in lice which had fed upon typhus fever patients, and Rickette
described a somewhat similar organism in connection with
Rocky Mountain fever. It, therefore, is advisable to consider
these investigations in chronological order in connection with
the discussion of this subject.

In 1909 Ricketts l reported upon the occurrence of diplo-
coccoid bodies and short bacillary forms in the blood of guinea
pigs and monkeys which had been experimentally infected with
blood from cases of Rocky Mountain spotted fever. These
organisms were also seen, but not so frequently, in the blood of
man. They were also encountered in the female tick {Dcnna-
centor occidentalis) and in the eggs of these ticks which had fed
upon infected guinea pigs. Ricketts describes his method of
examination and the organism itself, as seen in the eggs, as fol-
lows: "A number of eggs from the first day's laying were
crushed on cover glasses, fixed in absolute alcohol and stained
with Giemsa's solution. Each egg was found to be laden with
astonishing numbers of an organism which appears typical as a
bipolar staining bacillus of minute size, approximately that of
the influenza bacillus. Although definite measurements have
not yet been made, it is very common to find two organisms
end to end with their poles stained deeply. In some instances
thousands of these organisms were found, many staining
faintly." Morphologically, the organism appeared to him to be

1 Ricketts: Jour. Am. Med. Assn., 1909, lii, 379, and Med. Roc. N. Y.. 1009. lxxvi.
842.

54 TYPHUS FEVER

a bacillus, and he points out that its resemblance to the bacillus
of haemorrhagic septicaemia is striking, though he was not able
to cultivate it. He suggests that the organism in question be
called the bacillus of Rocky Mountain fever.

Ricketts and Wilder * in 1910 described the organism of
typhus fever, which disease they studied in Mexico. In prep-
arations of the blood of patients taken from the seventh to the
twelfth day of the disease, stained with Giemsa's solution, they
invariably found a short bacillus which had roughly the mor-
phology of those organisms belonging to the haemorrhagic
septicaemia group. Usually, this bacillus appeared to stain
solidly, but on minute examination an unstained or faintly
stained bar was seen to extend across the middle. The exact
measurements were not made, but when compared with the
size of the erythrocyte, their length was estimated at hardly
more than two micromillimeters and their diameter at about
one-third of this figure. They also described involution forms
of the organism. No active motility was observed in fresh
preparations. These bipolar organisms were found in the de-
jecta and in various organs of lice which had been infected by
feeding on typhus patients. While they were also found oc-
casionally in the faeces and intestinal contents of normal lice,
they were present almost constantly and often in large numbers
in lice from infected individuals.

Gavin and Girard 2 found in the blood of patients in Mexico
bacilliform bodies 2 p in length by 1.2 ^ in width, which when
treated with Giemsa's solution exhibited at the extremities
two small, deeply-stained masses united by a slightly stained
portion. They regarded the significance of these bodies as
obscure, and did not consider their aetiological significance
demonstrated.

In 1913 Prowazek,3 in the examination of the blood of 51
cases of typhus observed in Belgrade, found that the poly-
morphonuclear leucocytes showed striking changes. The nu-

1 Ricketts and Wilder: Jour. Am. Med.- Assn!, 1910, liv, 1373.

2 Gavin and Girard: Publ. del Inst. bact. nacional, Mexico, 20 mai et 20 juin 1910;
Bull, de PInst. Pasteur, 1910, viii, 841.

3 Hegler and Prowazek: Berl. klin. Wchnschr., 1913, 1, 2035.

THE SERBIAN EPIDEMIC

clous showed signs of fragmentation and the whole leuca
became filled with particles of chromatin. These cells stained
intensely red with Giemsa's solution and were found to contain
numerous rod-shaped and round bodies; diplococcue forms and
frequently irregular granules were also observed. At the begin-
ning of the infection many of the leucocytes were free from
these. bodies, but later more of them contained them. Pro-
wazek, in discussing the nature of these bodies, inclined to the
belief that they were related to the strongyloplasmata describe* 1
by Lipschuetz, which belonged to the chlamydozoa. These
bodies tended to disappear during the convalescence of the
patient. In addition, he observed in the blood of a number of
cases the curious double bodies similar to those first described
by Ricketts and Wilder, but he remarks that the significance sof
these forms is still very obscure. In the examination of seeti< »ns
of organs of typhus cases, trachoma-like bodies were observed
in the endothelial cells of the heart, lung, liver, and kidney.
Infected lice were carefully examined, and in one case small
coccoid bodies and also diplococcus forms were observed.

Sergent, Foley, and Vialatte 1 in 1914 working in Algeria
found in lice living only on the sick — never in those living on
healthy people or on people suffering from recurrent fever —
an organism of which the following description is given: the
microbe has the appearance of a coccobacillus. The staining of
the poles though never very intense is more pronounced than
that of the central portion, which is occasionally quite trans-
parent. The length varies from 1-3 ju and the thickness be-
tween .5 and .8 fi. Some of the small forms are shaped like
seeds with a diameter of .7 /x. These organisms are frequently
seen in pairs. When the germs are abundant they become
elongated, forming chains with hardly distinguishable links.
They were found in greater number in the bloody fluid of the
digestive tract of the lice than in smears of their organs after
crushing. The organisms were few during the first days of ill-
ness and could be observed only in a small proportion of the
lice examined; but their number increased gradually and more

1 Sergent, Foley, and Vialatte: Compt. rend. Soe. de Biol., 1914, lxxvii, 101.

-56 TYPHUS FEVER

lice became infected. A number of such lice were fed on
healthy individuals and the proportion of microbes seen be-
came much larger. From the twentieth to the twenty-fifth day
most of the lice showed signs of infection. The above-mentioned
authors did not succeed in cultivating this microorganism
on artificial media. They thought the microbe observed by
them might be identical with that described by Ricketts and
Wilder in the louse. They terminate their remarks with the
conservative statement that if the coccobacillus described
above does not constitute the virus of exanthematic typhus, it
may, however, be supposed that, as is the case in a number
of the pasteurella, it is a "temoin" microbe which accompanies
the true invisible infectious agent.

Nicolle, Blanc, and Conseil 1 in 1914 found in Tunis the
coccobacillus described by Sergent and his collaborators in five
per cent of the lice collected in districts which had been free
from typhus for two years. In consequence they considered
that this germ could not be the agent which produces typhus.
They found that lice fed on typhus cases did not become infec-
tive before the eighth day, but are constantly infectious on the
ninth and tenth days. Two attempts to filter the virus of
typhus obtained by grinding up 140 and 155 infected lice both
gave uncertain results and therefore they believed that the
filterability of the causative agent of this disease cannot be
regarded as certain. They could not detect any organism in
the blood and organs of guinea pigs infected with typhus.

Proescher in 1915 2 examined blood smears from nine typhus
cases after staining with one per cent solution of methylene-
azur-carbonate. Endothelial cells from the blood-vessels were
found containing very small diplococci and diplobacilli, meas-
uring from .2 to .3 m- They were found either singly in short
chains or in groups. Very few were seen in the plasma and in
the polynuclear leucocytes. These bodies were not found in
normal blood or in blood from cases of measles, mumps, scarlet
fever, cholera, and relapsing fever. The author suggests that

1 Nicolle, Blanc, and Conseil: Compt. rend. Acad. d. sc, 1914, clix, 661, and Arch,
de l'lnst. Pasteur de Tunis, 1914, ix, 84.

2 Proescher: Berl. klin. Wchnschr., 1915, Hi, 805.

THE SERBIAN EPIDEMIC 57

these minute bodies may he the cause of typhus, hut he
points out as they have not yet been cultivated this fad has
not been demonstrated. He believes the nature of the bodies
described by Prowazek is still uncertain and states they are
smaller than the diplococci and diplobacilli he has found.
Whether they are quite different structures or cocci under-
going phagocytosis degeneration products, or granules, is -till
doubtful.

Dorendorf 1 in the examination of the blood of typhus fever
cases in Serbia discovered in all cases examined during the
febrile stage of the disease the organisms previously described
by Prowazek. These bodies were found in the plasma, in the
polymorphonuclear and mononuclear leucocytes, either singly
or in pairs. Nuclear variations were a marked feature in the
blood picture of the severe cases, and these changes were also
seen in the mild cases at the height of the fever.

Stempell 2 in 1916, in dissecting lice collected from sick
people, found among the enigmatic parasites brownish bodies
in the intestinal epithelium of the louse which he named
Strickeria jungensi n.g. n.sp. He considered these organisms as
the cause of typhus. Coccoid forms encountered were attrib-
uted to the same parasite.

Lipschuetz 3 observed in the polymorphonuclear leucocytes
in blood from typhus cases bodies like those that Prowazek had
described. Of 23 cases examined, 18 were positive and 5 nega-
tive. These bodies were not found in control preparations from
typhoid fever and variola cases, or in normal blood prepara-
tions. He believes that while their nature is obscure they may
be of service in the diagnosis of the disease.

Csernel 4 describes the bodies found in typhus blood which
seem to be the causal agent of the disease. He gives illustra-
tions of these bodies. They show two distinct phases. One a
bipolar bacillus which he regards as the virulent form, and a
long bacillus which he believes to be a saprophytic one. In
three cases he detected flagella, and was unable to explain their
presence.

1 Dorendorf: Deutsch. med. Wchnschr., 1916, xlii, 345. : Stempell: ibid.. 439.
3 Lipschuetz: Wien. klin. Wchnschr., 1916, xxix, 549. 4 Csernel: ibid., 1643.

58 TYPHUS FEVER

Zollenkopf l in describing a new disease resembling inter-
mittent fever (probably Volhynia fever) found changes in the
red cells, consisting of blue dots and rods, as many as eight or
twelve in a corpuscule. These were not found in preparations
taken after the fever, and the author thinks they may be only
basophilic granules in the erythrocytes.

Rocha-Lima and Prowazek 2 found during investigations
carried out at the Prison Camp, Kottbus, that 95 per cent of
the lice taken from sick people were infected by a parasitic
microorganism. The organisms were found not only in the con-
tents of the alimentary canal, but especially in the epithelial
cells of the alimentary tract. They were not found in lice
living on healthy subjects, but on the other hand non-infected
lice placed on sick patients became infected with them. Refer-
ence has already been made in the beginning of this article to
the fact that Rocha-Lima believed that while these bodies were
somewhat bacterial-like in appearance, they resembled more
closely the chlamydozoa, and he therefore proposed the name
of Rickettsia prowazeki for them — n.g. n.sp. He believed that
this organism could penetrate the cells of the alimentary canal
of the louse and multiply actively there. He observed that this
parasite has been found in man only in the leucocytes.

Rocha-Lima 3 in another publication points out that in
December, 1914, in streak preparations made from lice which
had fed on typhus cases, he found large numbers of bacillus-
like bodies which stained red with Giemsa's solution. These
organisms did not stain well with the usual bacteriological
stains. When Prowazek arrived, he recognized that these
bodies were the same as those already seen by him in 1913 in
a preparation from an infected louse. By the examination of
a number of sections of lice from typhus cases, and of normal
lice, it was found that the bacillus-like bodies were present in
large numbers in the cells of the alimentary canal and in the
salivary glands of infected lice, but were not present in normal

1 Zollenkopf: Deutsch. med. Wchnschr., 1916, xlii, 1034.

2 Rocha-Lima and Prowazek: Berl. klin. Wchnschr., 1916, liii, 567.

3 Rocha-Lima: Arch. f. Schiffs- u. Tropen-Hyg., 1916, xx, 17.

THE SERBIAN EPIDEMIC

lice. Of 18 lice taken from a sick patient, 17 were infected by
this microorganism. The organism described by him appeared
as a coccobacillus which could be easily stained by Gien
solution. In the beginning, the parasite- were slightly elliptical
in shape. Later, during the course of the division they became
elongated. The two poles were deeply stained, and joined by a
faintly tinted envelope. The organisms did qo1 -tain well with
the usual reagents, and did not retain Gram's stain. In order 1 1 1
measure the microorganisms, he submitted them to a magnifi-
cation of 3000 diameters. The smallest forms measured from
.3 to .4 m, while the biscuit-shaped forms measured from .3 to
.9 m. Only a similar picture regarding the occurrence of these
bodies in infected lice had he observed up to the present time in
normal lice, and not an identical one.

The Rickettsia made their appearance in the cells of the in-
testine of lice on the fourth or fifth day after they had been
placed on the patient, but they did not achieve their complete
development before the eighth or ninth day. They developed
rapidly at 32° but not below 23°.

Rocha-Lima's experiments with respect to the filterability of
the typhus virus did not give positive results, the Rickettsia
appearing to remain in the Berkefeld V filter employed. At-
tempts to cultivate the organism of typhus on various agar
media with the addition of ascitic fluid, blood or extracts of the
organs of rabbits or of lice were also unsuccessful. He refers t o
the fact that of all the bacteria described as the cause of typhus.
the organism of Plotz might seem to be the most plausible.
However, he remarks that the almost entirely negative results
with animal experiments in an infection which is so easily trans-
mitted to animals as typhus confirms our scepticism regarding
it. He also refers to Petruschky's1 work, and points out that the
organism he has described has only been demonstrated in the
sputum, in which the virus has not been proven to be present.
He believes that the bacillus described by Arnheim - evidently
belongs to the pseudodiphtheria group of organisms. He con-

1 Petrusch%: Centralbl. f. Backteriol., Orig., Abt. 1, 1914-15. lxxv. 497.

2 Arnheim: Deutsch. med. Wchnsckr., 1915, xli, 1060.

60 TYPHUS FEVER

siders the bodies that he has described are really the aetiologic
agents, because he has transmitted the disease to guinea pigs
by the injection of lice containing these parasites, and the dis-
ease produced was identical to that produced in animals in-
oculated with the blood of typhus patients.

In a third article Rocha-Lima 1 alludes to the fact that
Ricketts and Wilder found polar staining organisms occasion-
ally in the faeces and intestinal contents of normal lice, whereas
they found them almost continuously and often in large num-
bers in similar material from infected lice. In proposing the
names of Rickettsia prowazeki for this organism as the cause of
typhus, he points out that the Gram-positive diplobacillus of
Rabinowitsch, the paratyphus-like bacillus of Horiuche, the
aerobic, bipolar bacillus of Prejetchensky, as well as the Bacil-
lus violentus parvus of Klodnitsky were even more strongly
agglutinated with typhus fever serum than the strict anaerobic
Organism of Plotz. He showed that a louse which was fed upon
a typhus patient on the fourth day of the disease showed the
presence of Rickettsia infection four days afterwards. This
louse was proved infective by animal experiment as well as by
microscopical examination, the animal inoculated with it
having contracted typhus infection.

In still another publication Rocha-Lima 2 admits that it has
not been conclusively proved that typhus fever is caused by
Rickettsia prowazeki. He, however, alludes to the fact that
organisms which are not dissimilar to the Rickettsia and which
may be identical have been described in connection with typhus
fever by Ricketts and Wilder, by Gavin and Girard and
McCampbell in the blood serum, by Prowazek in the leuco-
cytes, and by Rocha-Lima in the blood and organs and in sec-
tions. He thinks, however, that the final proof is still wanting
that these bodies are identical and are the cause of typhus, and
the dimensions given by Rocha-Lima for these organisms are
considerably below those given by Ricketts and by Sergent and
his collaborators. He believes that the bodies described by
Hanser in skin sections from cases of typhus fever are entirely

1 Rocha-Lima: Miincheri. med. Wchnschr., 1916, lxiii, 1381. 2 Ibid., 1917, lxiv, 33.

THE SERBIAN EPIDEMIC 61

different from the Rickettsia, and that the organism described

by Toepfer in typhus fever cases is not unlike the bacillus
scribed by Rabinowitsch in 1909.

Munk and Rocha-Lima ' further describe the difficulties in
distinguishing Rickettsia from other bodies such as elements of
tissue, granulations or coagula, and point out that they can
only be identified as microorganisms when in large numbers
and when distinctly stained. They believe that ft is really im-
possible even for the experienced eye to identify Rickettsia
prowazeki by its morphology alone, as has been demonst rated by
finding similar microorganisms in lice not infectious. They em-
phasize that the difference between Rickettsia prowazeki and the
Rickettsia pediculi is that the former develops in the epithelial
cells of the stomach and small intestine of the lice, while the
latter lies in the lumen of the digestive tube. They point out
that the Rickettsia found in lice taken from cases of Volhynia
fever and from other patients, or even from healthy people,
increase normally in the lumen of the alimentary canal and
penetrate only exceptionally into the cells. They remark that
Nicolle, Blanc, and Conseil found the^same organism in a cer-
tain percentage of normal lice, and that Toepfer and Jung-
mann found the Rickettsia in lice from Volhynia fever cases,
and that these Rickettsia also were intracellular. Rocha-Lima
and Munk believe that the intracellular Rickettsia are excep-
tional, except in connection with typhus, and are different from
those observed in the lice fed on Volhynia fever cases.

In relation to the microscopical study of the blood in Vol-
hynia fever, they remark that Jungmann, His, Toepfer. and
Korbsch thought this disease was due to a diplobacillus. while
Toepfer, Korbsch, and Riemer thought the cause was a spiro-
chaete. Rocha-Lima and Munk found diplobacillus-like forms
in the blood of Volhynia fever cases, but they also found the
same forms in the blood taken from patients with other diseases
or even from healthy people. For this reason, Toepfer and the
authors came to the conclusion that the bodies described by
the investigators named above, and by Jungmann and Ku-

1 Munk and Rocha-Lima: Mttnehen mod. Wchnschr., 1917. xliv, 1422.

62 TYPHUS FEVER

czynski, were probably not the cause of Volhynia fever, and
that this link in the chain of proof concerning the Rickettsia as
the cause of typhus also is still lacking, particularly since
morphologically the bodies found in normal blood cannot be
differentiated from those found in typhus blood. Rocha-Lima
and Munk were able to transmit Volhynia fever to guinea pigs
by the injection of the blood, but not to mice as Jungmann and
Kuczynski had done. From this, it would appear that they
were not working with trench fever since this disease has not
been communicated to guinea pigs. They were able to produce
the disease in two guinea pigs inoculated with the urine from
Volhynia fever cases, but a bacteriological examination of this
urine did not reveal the cause of the disease. The question of
the filterability of the virus of Volhynia fever they still consider
doubtful.

Munk and Rocha-Lima performed further experiments in
cultivation of the Rickettsia, but these were not successful.

In 70 experiments on patients of whom Munk had made the
diagnosis of Volhynia fever, 51 gave a positive result with re-
gard to the infection of one louse at least with Rickettsia pedi-
culi, 11 remained negative, and 6 were doubtful. Among the
negative instances were some typical cases which, although
repeated, gave the same results. In 33 control tests of pa-
tients whom Munk considered did not have this fever, 26 re-
mained negative, and 6 infected in the same way as the lice
from the Volhynia fever cases, while 1 test remained doubt-
ful. These control tests were made on people in the hospital for
other diseases, such as malaria, scarlet fever, measles, diph-
theria, trichinosis, typhoid fever, tuberculosis, rheumatism,
stomach and bladder diseases, and inguinal hernia. The 6
cases upon which the lice were fed, which later were positive for (
Rickettsia were — 3 with malaria, 1 with bladder disease, 1
with bronchitis, and 1 with inguinal hernia. One who had
never suffered from any disease gave rise to particularly
strongly infected lice. Among infected lice taken from 14
people, examined at Hamburg, the lice from 2 of these peo-
ple were found severely infected by a microorganism which

THE SERBIAN EPIDEMH

could not be differentiated from HicLetlsia [icdiculi cither in
smears or in sections. One case was undiagnosed. The second

was that of a workman who had never been ill. who did not
leave Hamburg, and had never been in connect ion with soldiers
at the front. These results confirm those formerly published.
In all these cases the intracellular characteristic development
of Rickettsia prowazeki was absent. The author stales t hat one
might think Rickettsia pediculi the cause of Volhynia fever, but
the fallacy of such an idea is shown by the fact that these or-
ganisms have been found in a number of control tests in lice
from healthy people in a country free from Volhynia fever.
The author admits that it is not impossible that the Rickettsia
pediculi may be the cause of Volhynia fever, but it is im] >< »sil »le
to differentiate this form for the present from that found in lice
fed on healthy human beings. Rocha-Lima, however, does not
believe that Rickettsia pediculi is the cause of Volhynia fever.
He states, moreover, that it is only a supposition that this dis-
ease is carried by lice. Both Korbsch and himself attempted
the propagation of this disease with lice, but their experiments
were not successful, although the lice were strongly infected.

Noeller l believes in the pathogenic properties of Rickettsia
prowazeki, though he gives no important evidence of the proof
of this idea. He demonstrated in a series of experiments that
lice from pigs transferred from infected guinea pigs to pig blood
lived long enough for the Rickettsia to develop in them, and
that the pig blood was not detrimental to the development of
the Rickettsia. He did not think that the infection of the lice
was hereditary with this organism.

Toepfer and Schuessler 2 carried out investigations upon
about 2000 lice taken from patients. In 400 lice which had fed
on 35 patients, bacteria-like organisms were found in the in-
fected lice. These organisms, whose form and appearance they
say are characteristic, were constantly present in the intestinal
canal of the lice removed from typhus fever patients. They
were also often present in the cells of the alimentary tract.

1 Noeller: Berl. klin. Wchnschr., 1910, liii, 778.

2 Toepfer and Schuessler: Deutsch. med. Wchnschr., 1916, xlii, llo7.

64 TYPHUS FEVER

Control lice fed on other individuals than those suffering with
typhus fever remained free from these organisms. From mi-
croscopical examination, the organisms seemed to be in pure
culture in the infected lice. This organism was found only in
lice which had been fed for some days on the blood of patients
during the febrile period. Lice fed during the postfebrile period
did not apparently become infective. The eggs and offspring of
the infected lice were not found capable of producing infection.
The parasites continued to develop in the intestine of the lice
and apparently remained infective indefinitely. They were
not able to cultivate the organism. The injection of the con-
tents of the alimentary tract of an infected louse into a healthy
guinea pig produced a febrile condition similar to that pro-
duced by the injection of the blood of a typhus fever patient.

In connection with Volhynia fever Toepfer 1 called attention
to the presence of characteristic bodies in the blood in Volhynia
fever. In three cases of this disease he observed spirochaetes.
In one instance, in a fresh specimen, the organism was motile.
In lice taken from typhus fever patients he found bodies
similar to those described by Rocha-Lima. He is unwilling to
commit himself whether a connection exists between these
bodies and the spirochaetes.

In another paper relating to Volhynia fever, Toepfer 2 ex-
presses the opinion that the organisms described by His and
Werner as the cause of this fever were accidental artefacts. He
found in the blood small parasitic-like bodies, but did not con-
sider that these were diagnostic. He, however, convinced him-
self that the virus was circulating in the blood in this disease
as he performed experiments by injecting five cubic centimeters
of blood intraperitoneally into guinea pigs and obtained similar
temperature curves to those which were injected with blood
from typhus patients. He found that lice taken from typical
cases of Volhynia fever contained in their alimentary tract
bodies similar to the typhus fever organism. These bodies were
found both free and inside the cells of the louse, and appeared

1 Toepfer: Berl. klin. Wchnschr., 1916, liii, 323.

2 Ibid. : Munchen med. Wchnschr., 1916, Ixiii, 1495.

THE SERBIAN EPIDEMIC"

as small short rods. Polar staining rods and diplobacilli U
were present. He believes these organisms to be bacilli and not

protozoa, and considers that they are the cause of the di.-ea-e.

Toepfer1 in a more recent work examined smears and
tions of 500 lice. He believes he has confirmed his former ob-
servations regarding the presence of an organism in inf<
lice. He criticizes the name of Rickettsia prowazeki as giving a
wrong impression of the nature of these organisms.

He found the same parasite in lice (Pediculus capitis) taken
from the heads of patients, and he was also able to artificially
infect normal lice of this species by placing them upon the sick.
Smears made from lice which had previously fed on the blood of
patients infected with typhus fever were found to contain
nearly pure cultures of the organisms.

In another paper on the aetiology of typhus, Toepfer 3 de-
scribes the organism found in tissues of typhus patient- and in
infected lice as intracellular diplobacilli.

Hanser4 reports that he has confirmed Toepfer's discovery
of bacteria-like forms in the intestinal cells of lice fed on typhus
fever patients.

Toepfer 5 in another article upon war nephritis describes
similar organisms to those which he had observed in lice fed
upon cases of typhus fever or of Volhynia fever. He regards
this form of nephritis as a specific disease, probably transmit-
ted by lice. He also considers it plausible that the virus circu-
lates in the blood. Guinea pigs inoculated with blood from the
nephritic cases grew lean and had bloody urine, but no rise in
temperature. In the lice from the nephritic cases, especially
those which had fed during the early stages of the disease,
definite bacteria were found almost without exception. He also
infected lice by feeding them on the nephritic cases, and in
order to control these results he put lice of the same breed upon
healthy people and these remained uninfected. These or-

1 Toepfer: Deutsch. med. Wchnschr., 191(3, xlii, 1251.

2 Rocha-Lima (ibid., 1353) in a subsequent paper controverts the statement of
Toepfer regarding the nature of Rickettsia prowaaeki found in the intestinal cells of
infected lice.

3 Toepfer: ibid., 1383. 4 Hanser: ibid.. 1254.
5 Toepfer: Med. Klin., 1917, xiii, 67S.

66 TYPHUS FEVER

ganisms appeared to be identical with those he had found in
lice from typhus and Volhynia fever cases. Anaerobic cultures
of these bacteria were successful if the contents of the intes-
tine of the lice were placed in dextrose agar, but the colonies
were so small that they were of no value for specific reactions.
Toepf er thought that the germs of the nephritic cases could be
differentiated from those seen in typhus fever by the fact that
the latter developed more markedly in the intestine of the lice.
He believed that the three different organisms appear in the
epithelial cells of the louse. He states that the similarity in
appearance between the three forms of bacteria found in lice
which he described as the cause of spotted fever, of Volhynia
fever, and of nephritis cannot be regarded as an argument
against their specificity, because in stained preparations the
bacillus of typhoid fever cannot be differentiated from the
colon bacillus and several other bacteria. Having found similar
organisms in spotted fever, in Volhynia fever, and in nephritis,
the author believes that the three diseases, which are clinically
so different, belong to the same group. The author thinks that
not only from an aetiological standpoint is this true, but that
between nephritis and spotted fever there are histological re-
semblances which he observed in the study of sections of the
skin of the oedematous, tissue in nephritis cases, a general dis-
turbance of the capillaries being present in both diseases,
though in spotted fever the capillaries are much more affected.
In the nephritic cases, the kidneys. are obviously particularly
affected! The author believes that the oedema and nephritis
are only partial results of the infection, that the. infection ex-
tends from the capillaries over the whole body, and that the
oedema and nephritis may be entirely lacking in some instances.

In conclusion, he states that he believes that war nephritis is
an infectious disease in which several organs are attacked, and
that it is caused by an inflammatory and proliferative disturb-
ance of the capillary endothelial cells, and as a result of this a
disturbance of the circulation follows.

Otto and Dietrich 1 attempted to confirm the work of Rocha-

1 Otto and Dietrich: Deutsch. med. Wchnschr., 1917, xliii, 577.

THE SERBIAN EPIDEMU

Lima in relation to the Rickettsia to typhus fever. Lic<

closed in small cardboard boxes were covered \\ii h a fine 1
of gauze and then placed on the under surface of I he arm or in-
side the thigh of typhus fever patients at various stages of the
disease and for various periods. The lice placed on the patients
during the febrile period became infected from the fourth day.
70 to 80 per cent being infected if they were allowed to i
during the period of seven to eight days. Of these lice placed
on the patient towards the end of the disease, only a few be-
came infected. The infection was never found to be heredi-
tary. In addition to the usual bipolar staining organisms i'< >und,
they also observed short, rodlike, and long, filamentous forms.
The threadlike forms were noted in the case of a louse taken
from a patient on the fourth day, and were absent in lice which
had fed for nine days. They suggest that these forms may 1 e
transition stages in the life history of the parasite. They suc-
ceeded in infecting lice with Rickettsia by feeding them on
a case of typhus fever without the exanthem. Attempts to
transmit the infection to guinea pigs by the injection of the
gut contents of infected lice were only successful in a small
percentage of the experiments. The authors endeavored
to prove by agglutination tests with the serum of typhus
cases and an emulsion of the gut contents of the infected
lice, that the Rickettsia prowazeki is the causative agent of
typhus.

Wolbach 1 in the study of Rocky Mountain spotted fever
points out that the essential lesions of spotted fever are found in
the vascular system and that bacillary bodies are present in
large numbers in the endothelial cells of guinea pigs infected
with the virus of Rocky Mountain spotted fever through the
bites of infected ticks. These bacillary bodies had some of the
characteristics of those previously described by Ricketts. The
endothelial cells accumulate in the vessel walls and around
vessels and in the lymphatics. The organisms are diplobaeilli
in character and show polar staining. The staining, however,
is not that commonly seen with most bacteria, and indicates

1 Wolbach: Jour. Med. Research, 1916, xxxiv, 121.

68 TYPHUS FEVER

that the organisms have some of the characters of spirochaetes.
All attempts at cultivating them have so far failed. In another
paper Wolbach 1 reports the presence and distribution of this
organism in experimentally infected ticks (Dermacentor venus-
tus, Banks). In the infected ticks, parasites were found similar
to those previously observed in the tissues of monkeys and
guinea pigs, but never in non-infected ticks. The parasites
were present most abundantly in the striped muscle, also in the
malpighian tubes, salivary glands, and ducts and brain ganglia.
They were numerous in the muscle fibers of the uterus and
vagina, and have been seen in the spermatozoa.

In a third paper Wolbach 2 gives the characteristics of these
bodies as follows: "In guinea pigs and monkeys, in sections, a
minute rod in pairs, often lanceolate and surrounded by a clear
zone or halo and staining with difficulty, occurring in large
mononuclear cells (endothelial cells) and smooth muscle cells.
Larger and smaller forms were mentioned, the former lance-
olate, the latter occurring in smooth muscle cells. In smear
preparations from guinea pigs there were noted lanceolate
paired forms, rods with irregular staining, and rods with chro-
matoid granules.

"In ticks, in sections (1) a lanceolate paired form, (2) a
smaller, more slender rod-shaped form, and (3) a minute, oval-
coccoid form; in size, just within the limits of resolution with
the best optical equipment."

He also describes in this last paper the presence of these
bodies in the lesions of the blood-vessels in fatal human cases of
Rocky Mountain spotted fever, and thinks they are forms of a
new organism.

Lopez 3 in a study of the blood in typhus fever found the
intraleucocytal bodies discovered by Doehle 4 in cases of
scarlatina and also recognized by Preisich and others in dif-
ferent diseases. Lopez found these bodies in 77 out of 90 cases

1 Wolbach: Jour. Med. Research, 1916, xxxv, 147.

2 Ibid., 1918, xxxvii, 499.

3 Lopez: Bol. de la Direction de Estudios Biol., 1917, ii, 92 (reviewed in Trop. Dis.
Bull., 1918, xii, 108).

4 Doehle: Miinchen. med. Wehnschr., 1912, July 23, No. 30.

THE SERBIAN EPIDEMIC

of tyj)hus fever examined by him. From one to three b
were found in one leucocyte, and the percentage of leucoc

always polynuclear containing them varied from 3 to s,» per
cent. They were best stained by Giemsa'e method. Be re-
marks that the blood must be taken from well-marked
the disease and at the height of the fever from the sixth to the
tenth day to contain these bodies. He thinks that they may be
chlamydozoa, but does not express a decided opinion regarding
their nature.

Schmidt ] found in three patients only out of many <
five-day fever examined, almond or sickle-shaped organisms in
the blood which showed one or two round chromatin bodies in
the interior, situated either peripherally or centrally. They
were best demonstrated by Giemsa's stain. The size varied,
but is comparable with that of blood platelets.

Jungmann and Kuczynski 2 found in the blood of typhus
patients during the first days of the rash an organism which
they believe to be identical with Rickettsia prowazeki which
they had also found in cases of trench fever. As they had never
found this organism in other diseases, they conclude there
must be a relation between typhus and trench fever.

Werner and Benzler 3 in examining lice which had fed upon
cases of febris quintana found in the stomach of some of them
organisms resembling spirochaetes. In one, the stomach con-
tents of the louse showed bodies which could not be distin-
guished from those described by Rocha-Lima in typhus and
by Toepfer in febris quintana, and which had previously been
cultured by him anaerobically.

Brumpt4 studied 72 body lice (Pedieidus corporis) taken
from prisoners of war who had been living in France for some
time, and whose state of health was quite satisfactory. No
case of typhus fever had ever been reported among them.
Twenty-seven lice from the head {Pedieidus capitis) taken
from a healthy child at Rennes were also studied. Of the 7'2

1 Schmidt: Deutsch. med. Wchnsehr., 1917, xliii, 682.

2 Jungmann and Kuczynski: Ztsehr. f. klin. Med., 1017, lwv, J"d.

3 Werner and Benzler: Munchen med. Wchnschr., 1917, lxiv, 695.

4 Brumpt: Bull. Soc. de path, exot,, 191S, ii, 249.

70 TYPHUS FEVER

body lice from 7 healthy prisoners of war, 53 were found in-
fected by the microorganism described by Rocha-Lima under
the name of Rickettsia prowazeki, and considered by him to be
the causative agent of typhus fever. Of the 53 lice with para-
sites, 18 were considerably infected. Their alimentary canal
and a number of the cells contained what may be described as
a pure culture of the microorganism in question. In the 35
remaining instances, the infection was slight. H erpetomonas
pediculi was not observed. Brumpt's investigations are so im-
portant that it is advisable to consider them in greater detail.
A group of 16 lice taken from healthy prisoners of war were all
found to be infected with Rickettsia. Infection was marked in
1 case, moderate in 13, and mild in 2. Twenty-four lice taken
at the same time from these same men were fed upon the author
himself once a day for three days and kept in the incubator at
a temperature of 20° C. After the third day the surviving lice
were dissected, and the following results were obtained : severe
infection was found in 5 cases, moderate infection in 5, slight
infection in 3, and no infection in 7. Lice from another healthy
prisoner were fed upon the author. Thirteen of these surviv-
ing lice were dissected, when 1 was found to be strongly in-
fected, 5 moderately infected. In 2 the infection was slight,
and 5 showed no signs of infection. Eighteen lice taken from
another healthy person were fed on the author. In 4 of these,
intense infection was found, in 1 moderate, 2 slight, and in 5,
no infection was present. Lice were taken from another healthy
subject arid fed on the author. Of the 6 lice which survived, 5
showed severe infection, and 1 no infection. Lice taken from
another healthy prisoner of war were fed on the author for four
days. The 9 surviving lice were dissected with the result that
in 2 instances a severe infection was present, in 2 a moderate
one, and in 5 no infection was found. The microorganism in
question was found practically as a pure culture in the dejecta
of the louse. No sign of infection was found in the alimentary
canal of 27 head lice taken from a healthy child. The germs
found in 73 per cent of the lice taken from healthy individuals
were either elliptical in shape, occasionally spherical, but

THE SERBIAN EPIDEMK 71

generally coccobacillary in form. There is always b pn domin-
ating shape; in the Rickettsia encountered in one louse. '1
arc cither practically round or slightly elongated. The or-
ganisms stained like spirochaetes in the blood. They aho
intensely tinted poles, joined by a faintly stained central por-
tion. The average dimensions of the organism varied between
.4 and .6 /x for the round forms, 1.2 to 1.4 y. in length, .5 m in
width for the average forms, 1.65 \x to 2 \x long by X> m wide for
the largest forms. The last were seldom met with. The author
never observed the parasites in chains. He concludes thai his
observations lead him to identify the organisms found in lice
taken from healthy people with those previously described by
Rocha-Lima under the name of Rickettsia prowasn hi. Seventy
of these lice were fed upon himself and 53 were found infected
with the above described organism; but he remained healthy.
The author points out that although this organism in question
which has not been cultivated maybe encountered in the blood
or in the organs of some of the patients, it need not for t his rea-
son be considered the pathogenic agent of typhus fever as it
may have been inoculated by the louse and have no path-
ogenic action. The author points out that the lice infected by
the coccobacilli retain the infection during their entire life.
The lice carrying the typhus virus are active from the eighth to
the tenth day.

Arkwright, Bacot, and Duncan * reported that in their in-
vestigations they used a clean stock of lice bred in captivity
and kept under observation for over three years. They fed
these normal lice on trench fever patients both during and after
febrile periods. Either the feeding on the infected person was
for one day only, followed by feeding on a healthy man. or
after the first infecting meal the lice were fed regularly on the
same or another infected man, and between the feedings the
lice were kept in an incubator at a temperature of about 27°C.J
or in an inside pocket. They were later examined micro-
scopically either by films made from the excreta, or from the
gut contents, or in microscopic serial sections. The films were

1 Arkwright, Bacot, and Duncan: Brit. Med. Jour., 191 S, ii. 307.

72 TYPHUS FEVER

treated with acid alcohol to fix and to remove haemoglobin
debris, and were then stained with Giemsa's solution. The
following conclusions were reached by them, confirming and
extending the work of previous workers :

1. If a box of lice is fed on a trench fever patient, and the
excreta collected after a period of about ten days, large num-
bers of Rickettsia bodies can almost invariably be found in
films. Smears of the guts of lice from such a box contain large
numbers of these bodies after about the same interval of time.
Of 253 specimens from boxes of lice which had been fed on
trench fever patients at least five days previously, 150 showed
Rickettsia bodies, 83 gave a negative result, and 20 a doubtful
result.

2. The excreta from sixteen boxes of lice which were ex-
amined daily after an infecting meal showed Rickettsia bodies
for the first time twice on the fifth day, three times on the
seventh, three times on the eighth, four times on the ninth,
three times on the tenth, and once on the twelfth day from the
first infecting meal. When first seen only small numbers were
noted in the films, but three or four days later enormous num-
bers appeared. These experiments show that after an infecting
feed there is a period during which these bodies are not recog-
nizable on account of their small numbers, or of some difference
in form. When a box has once become infected with Rickettsia
the excreta collected from it continue to show the bodies for
two or three weeks, or till the lice which partook of the infect-
ing feed are dead.

3. All lice from an infected box do not show Rickettsia.;
only a small proportion do so in the first week; the proportion
increases until after two and a hah to three weeks the great
majority show these forms. Experiments at Hampstead have
also made it probable that after the same time a considerable
proportion of lice are infective.

4. Trench fever patients can infect lice with Rickettsia
bodies during the fever, between the attacks, or even several
weeks after an attack during a non-febrile period.

5. Normal lice, fed on persons who have not been exposed to

THE SERBIAN EPIDEMIC 7 ;

trench fever infection, have remained free from Rickettsia. ( »f

245 specimens from 22 boxes fed on seven healthy ;

one specimen of excreta was found to contain forms which

closely resembled Rickettsia microscopically. It is not sur-
prising, considering the difficulty in recognizing such small

bodies by their morphology, that occasional error- should oc-
cur. Four other specimens from two boxes showed these
bodies, but they were being fed on a man who had been working
with infected excreta in the laboratory for five weeks, and had
also been feeding infected lice on himself for the same period.
He developed trench fever three days after that upon which
the first one of the four positive specimens was found. It is
most probable, therefore, that he had been infected for some
days before the bodies were observed in the lice.

They further pointed out that Rickettsia bodies are very
small and approach the limits of filterability of a Berkefeld
filter. In their experiments the Rickettsia bodies did not make
their appearance in lice till about the fifth to the twelfth day
after an infecting meal. In 53 experimental inoculations of
volunteers, the lice or excreta of lice used as the virus were also
examined microscopically. In every case the lice had pre-
viously been fed on a trench fever patient. Twenty-seven ^\
the specimens showed Rickettsia bodies and caused trench
fever; 10 specimens did not show Rickettsia bodies and did not
cause trench fever; 1 specimen showed Rickettsia bodies but
did not cause trench fever; 2 specimens did not show Rickettsia
bodies but caused trench fever; 4 specimens gave doubtful
results microscopically, or the inoculation was followed by
fever of a doubtful nature; 9 specimens showed Rickettsia
bodies but did not cause trench fever. The authors thought
this was because the virus had been heated or treated with
disinfectant, or because the volunteer inoculated had recently
passed through an attack of trench fever and was probably
immune. They believe the agreement between the demon-
strable presence of the virus and the Rickettsia bodies is very
close, and that a very close correlation has been shown to exist
between the presence of Rickettsia bodies in lice or the excreta

74 TYPHUS FEVER

of lice and the virulence of these materials when inoculated into
man.

Most of the observers so far mentioned in this article, who
have regarded the Rickettsia as representing microorganisms,
apparently have believed that they were either chlamydozoal
or protozoal in character or at any rate were of a non-bacterial
nature. Other investigators, however, have believed the bodies
described as Rickettsia are really bacteria, and more recently
it has been suggested that the bacillary forms are identical
either with the bacillus described by Plotz as the cause of
typhus fever or with the Bacillus proteus X 19, believed by
others to be the cause of this disease.

Rabinowitsch * in 1914 refers to the fact that in 1908 he dis-
covered the causative agent of typhus naming the organism
Diplobacillus exanthematicus. In fresh cultures the organism
practically always appeared as a diplobacillus. Degeneration
forms only developed in old cultures. In fresh cultures, the
organism was always Gram-positive, while in old ones it be-
came Gram-negative. Cultures were best obtained the author
says by using a medium consisting of equal parts of ascitic broth
mixed with 4 per cent glycerin. One hundred c.c. of this mix-
ture were to be inoculated with from 3 to 5 c.c. of the blood of
a typhus patient obtained shortly before the crisis. After the
crisis the organism seemed to disappear from the blood. He
points out that guinea pigs can be infected both by the injec-
tion of cultures and by the blood of typhus patients, the incuba-
tion period varying from 5 to 37 days. He examined the
blood of 58 typhus patients. In the films stained deeply with
Giemsa's solution he found peculiar, very deeply staining
leucocytes which had a very basophilic protoplasm. They
often constituted from 3 to 8 per cent of the white cells. He
thought that these might furnish a means of diagnosing the
infection.

Mueller 2 made bacteriological examinations of various cases
of typhus occurring amongst the Bosnians in the Marine Hos-

1 Rabinowitsch: Berl. klin. Wchnschr., 1914, li, Part 2, 1458.

2 Mueller: Munchen. med. Wchnschr., 1913, Ix, Part 1, 1364.

Till. SERBIAN EPIDEMK 75

pital of San Bartolomeo, Trieste. In Gieinsa-stained pr(
rations, diplococci, cocci, and ovoid rod-shaped bodies were
found present in the Mood of nil t he cases of typhus examined,
and also in four patients thai no Longer showed any fev< r.
cultural examination of the blood of eleven patiente gave five
positive results, in each case a diplobacilhis developing in tin-
broth. Attempts to cultivate the organisms on ascitic
succeeded only three times. The isolated cultures seemed to be
identical with those obtained by Fuerth from case- of typhus in
Tsingtau. The organisms were non-motile rods which readily
round off into coccoid forms in the various culture media. The
pathogenicity of the culture organism toward- Miim«l« was
only very slight. When mice were inoculated with enormous
doses, they succumbed within 24 hours, and the diplobacilli
were found in every part of the body. A rabbit show* da -ingle
parasite after an incubation period of seven days. On the other
hand, three monkeys inoculated with the cultures remained
normal. According to the author there can be no doubt that
this diplobacillus isolated at San Bartolomeo is identical with
the organism described by Rabinowitsch and others.

Olitsky, Denzer, and Husk 1 state it is their opinion that the
Bacillus typhi exanthematici described by Plotz corresponds
to the organism described by Rocha-Lima as Rivkvttsi<i pr<>-
wazeki. They point out that while Rocha-Lima found the
Rickettsia to be Gram-negative, and that the bacillus described
by Plotz was Gram-positive, that the organism described by
Plotz may be sometimes Gram-negative 2 in the first subcul-
tures made from lice or in smears made direct ly from typhus
infected lice, as has been shown by Baehr and Plotz/ and
Baehr and Plotz have reported the occurrence of the Plotz or-
ganism in infected lice and have grown it under anaerobic-
conditions. They have also produced typhus fever by the in-
jection of infected lice. For these reasons they think the
Rickettsia and the Plotz bacillus are identical. They think the

1 Olitsky, Denzer, and Husk: Jour. Am. Med. Assn., 1917, lxviii. 1165.

2 Baehr and Plotz: Jour. Infect. Dis., 1917, xx, 201.

3 Olitsky, Denzer, and Husk: ibid., 1910, xix, 811.

76 TYPHUS FEVER

reason that the bodies described under the name of Rickettsia
have not been cultivated by other observers is owing to the
fact that improper methods have been used. Popoff * believes
that the Rickettsia prowazeki described by Rocha-Lima is the
same organism as the bacillus described by Plotz as the cause
of typhus fever.

Kuczynski 2 carried out his experiments with a view to
determining the role played by Bacillus proteus X 19 in typhus
fever. Seventy-two body lice were artificially infected with a
pure culture of this organism. After examining the lice which
survived for 72 hours, he came to the conclusion that Bacil-
lus X 19 and Rickettsia are not identical, and that it is possible
that infection with Rickettsia prevents the development of
X 19 under natural conditions. He found that X 19 developed
in the louse and believes that the rod and threadlike forms de-
scribed by other authors as developmental stages of Rickettsia
are probably stages in the development of X 19. He fed these
experimental lice upon himself and as he remained healthy he
came to the conclusion that X 19 is not pathogenic. In another
paper 3 he made histological investigations upon material from
typhus fever cases.

In the petechiae of typhus he was not able to find anything
which appeared definitely to be the causative organism. In the
investigation of sections of the liver in the endothelial cells of
the capillaries and in free phagocytic cells, two different micro-
organisms were found. First, large bacilli-like bacteria which
appeared similar in appearance to the proteus bacillus; and
second, bodies in sections stained by Giemsa's solution, re-
sembling the Rickettsia as described by Rocha-Lima in the
intestinal cells of lice. The author believes he could differen-
tiate these bodies from other histologic elements by their
intracellular position, their spherical grouping, and their inten-
sive stain. ...

1 Popoff: Med. Klin., 1917, No. 14, p. 397.

2 Kuczynski: Arch. f. Protistenkunde, 1918, xxxviii, 376.

3 Ibid. : Centralbl. f. allg. Path. u. path. Anat., 1918, xxix, 279.

THK SKUBIAX I.I'JM.MK

. -

The following table summarizes the reports of different in-
vestigators with reference to Rickettsia bodies in connection

with disease.

Year Investigator'

1909 Ricketts

1910 Ricketts and Wilder

1910 Gavin and Girard

1912 Doehle
Preisich

1913 Prowazek

1913 Mueller

1914 Sergent, Foley, and
Vialatte

1914 Nicolle, Blanc, and
Conseil

1914 Rabinowitsch

1915 Proescher

1916 Dorendorf

Rifkettoia bodies or orKariinrrm NMaMbm them fou*.

Bacilli in blood of guinea pigs and monkeys infi
with blood from Rocky Mountain
cases. Also seen in blood of man, and in female
tick (Dermacentor ocridentalis) and in eggs of these
ticks fed upon infected guinea pigs.

Studies in Mexico. Bacilli in blood of typhus pa-
tients. Also in dejecta and various organs of Bee
fed on typhus patients. Occasionally found in
faeces and intestinal contents of uormal lice.

Blood of patients in Mexico. Significance of bodies
obscure.

Discovered intraleucocytal bodies in scarlatina cases.

Recognized same bodies in other diseases.

Blood of 51 typhus cases in Belgrade. In examina-
tion of sections of organs of typhus eases, tra-
choma-like bodies observed in endothelial cells of
heart, lung, liver, kidney. One infected louse con-
tained coccoid bodies and diplococcus form-.

Blood of typhus fever cases. Inoculated mice and
rabbit.

Lice living only on the sick, never in lice living on
health}' people, or recurrent fever patients, in
Algeria. Found especially in bloody fluid of diges-
tive tract of the lice. A number of such lice fed on
healthy individuals and proportion of microbes
seen became much larger. Could not cultivate
microorganism on artificial media.

Tunis, in 5 per cent of lice collected in districts free
from typhus for two years. Lice fed on typhus
cases are constantly infectious on ninth and tenth
day, not before the eighth. Organisms not detected
in blood and organs of guinea pigs infected with
typhus.

In 1908 discovered DiplobactihiS cxanthemalici. - -
the causative agent of typhus. Organism found in
blood of typhus patients.

Blood smears from nine typhus cases showed bodies
in endothelial cells from blood-vessels. Very few
seen in plasma and in polynuclear leucocytes.
These bodies not found in normal blood or in
blood from cases of measles, mumps, scarlet fever,
cholera, relapsing fever.

Blood of typhus fever cases in Serbia examined, and
organisms described by Prowazek discovered in all
cases examined during febrile stage — found in
plasma and in polymorphonuclear and mononu-
clear leucocytes.

78

TYPHUS FEVER

Year Investigator

1916 Stempell
1916 Lipschuetz

1916 Csernel
1916 Zollenkopf

1916 Rocha-Lima and
Prowazek

1916 Rocha-Lima

1916 Wolbach

1916 Wolbach

1916 Noeller

Rickettsia bodies or organisms resembling them found in

Among the enigmatic parasites in the intestinal
epithelium in dissected lice collected from sick
people.

Polymorphonuclear leucocytes in blood from typhus
cases; twenty-three examined, eighteen were posi-
tive. These bodies not found in control prepara-
tions from typhoid fever and variola cases, or in
normal blood preparations.

Typhus blood.

In describing a new disease resembling intermittent
fever (probably Volhynia fever) found changes in
red cells. Not found in preparations taken after
the fever.

Investigations at Prison Camp, Kottbus, 95 per cent
of lice taken from sick people were infected by
parasitic microorganism. Organisms found in
contents of alimentary canal, and' especially in
epithelial cells of alimentary tract. Not found in
lice living on healthy subjects. Non-infected lice
placed on sick patients became infected. This
parasite found in man only in the leucocytes.

In 1914 (December) in streak preparations made
from lice feci on typhus cases, found large numbers
of bodies. Recognized by Prowazek as the same
as seen by him in 1913 in preparation from in-
fected louse. In examination of sections of lice
from typhus cases, and of normal lice, bodies found
in large numbers in cells of alimentary canal and
in salivary glands of infected lice; not in normal
lice. Seventeen out of eighteen lice from a sick
patient were infected. Rickettsia appeared in
cells of intestine of lice on fourth or fifth day.
Louse fed on typhus patient showed Rickettsia
four days afterwards.

Bacillary bodies are present in large numbers in en-
dothelial cells of guinea pigs infected with the
virus of Rocky Mountain spotted fever through
the bites of infected ticks.

Organism found in experimentally infected ticks,
similar to those previously seen in tissues of mon-
keys and guinea pigs, but never in non-infected
ticks. Parasites most abundant in striped muscle,
malpighian tubes, salivary glands, and ducts and
brain ganglia. Numerous in muscle fibers of
uterus and vagina, and seen in the spermatozoa.
Also in lesions of blood-vessels in fatal human
cases of Rocky Mountain spotted fever.

Lice from pigs transferred from infected guinea pigs
to pig blood.

TIN'] SERBIAN \A'\\)\M\<

:■•

Year Investigator

L916 Toepfer

1916 Toepfer

1916 Hanser

1917 Munk and Rocha-
Lima

1917 Toepfer and Schues-
sler

1917 Toepfer

1917_[Otto and Dietrich

Rickettsia bodies or organism* ret

Blood of Volhynia fever. Abo in lio
fever patients.

Lice from t} pica! Volhynia fever contained bodi
alimentan trad similar to ' • pi
Bodies both free and inside the cells.

Examined smears and section* i 500 lice. I
firmed his former observations regarding organism
in infected lice.

Same parasite found in lice from heads of pata
and in artificially infected normal lice of this
cies by placing them upon the sick. Smears from
lice fed on typhus blood contained organism.

Described intracellular < 1 i plobacflli in tissuet
typhus patients.

Confirms Toepfer's discovery of form- in LatestinaJ
cells of lice fed on typhus pati<

Found diplobacillus in Mood of Volhynia fever c
but also found same in Mood from patients with
other diseases or even from healthy one.-.

Munk made 70 experiments on patient- diagnosed
as Volhynia fever cases, -51 positive for R.
pcdiculi, 11 negative, 6 doubtful. Among Q< g -
fives were some typical cases.

Among 33 control tests, l'i; were negative and •'> in-
fected same as lice from Volhynia fever c
These 6 cases upon which the lice were fed which
proved positive for Rickettsia were 3 malaria. 1
bladder disease, 1 bronchitis. 1 inguinal hernia.
One normal gave rise to strongly infected lice.

Rocha-Lima and Korbsch attempted propagation of
Volhynia fever with lice, but not successful
although lice were strongly infected.

In 400 lice which had fed on 35 patients, bacteria-
like organisms were found in the infected lice.
Organisms found constantly in intestinal canal of
lice removed from typhus patients and often in
cells of alimentary tract. Control lice fed on other
individuals than those suffering with typhus fever
remained free. Organism found only in lice fed on
blood of typhus patients during febrile {not post-
febrile) period.

In article on war nephritis describes similar or-
ganisms to those seen in lice fed on cases oi typhus
or Volhynia fever. Found similar organisms in 3
diseases, i.e., spotted fever, Volhynia fever, and
nephritis.

In lice placed on patients. Infection not hereditary.
They infected lice with Rickettsia by feeding them
on a case of typhus fever without the exanthem.

80 TYPHUS FEVER

Year Investigator Rickettsia bodies or organisms resembling them found in

1917 Lopez Blood of typhus fever, found same intraleucocytal

bodies, in 77 out of 90 cases. Blood must be taken
from well-marked cases and at the height of the
fever, to contain these bodies.

1917 Schmidt Organisms found in 3 cases only, out of many cases of

five-day fever examined.

1917 Jungmann and Blood of typhus patients during first days of the

Kuczynski rash, and also in trench fever. Had never found

organism in other diseases.

1917 Werner and Benzler In the stomach of lice fed upon cases of febris

quintana.

1918 Brumpt 53 out of 72 body lice taken from healthy prisoners of

war, pure culture found in the alimentary canal
and in some cells.
16 lice, from healthy prisoners of war were all in-
fected, etc.

1918 Arkwright, Bacot, Lice fed on trench fever patients. Normal lice fed on
and Duncan persons not exposed to trench fever infection re-

mained free from Rickettsia.

1918 Kuczynski In the petechiae of typhus cases, in sections of liver

in the endothelial cells of the capillaries, and in free
phagocytic cells.

Our studies regarding the occurrence of Rickettsia bodies in
lice which have fed upon healthy persons have confirmed those
of a number of observers already referred to. Lice collected
from healthy men in different parts of France, where neither
typhus fever nor trench fever were present, were often found to
contain Rickettsia in their dejecta: from 20 to 40 per cent of
such lice examined, collected in different groups, revealing these
bodies. In some of these normal lice, microscopical examina-
tion of the excreta or material from the alimentary tract
showed them to be severely infected with Rickettsia bodies.
Others were only moderately or very slightly infected, while in
the remaining no definite Rickettsia were observed. Obviously
from a microscopical examination, it is sometimes extremely
difficult to say whether these bodies are not present in small
numbers in the lice. Plate XXI, Figures 1 and 2, demonstrate
the Rickettsia bodies in the excrement of normal lice.1 There

1 These photomicrographs were kindly made at the Pasteur Institute by Dr. P.
Jeantet, who is in charge of the photomicrographic work of this Institute. I wish to ex-
press my thanks to both Dr. Roux, the Director of the Pasteur Institute, and to Dr.
Jeantet, for this courtesy.

■ w

w *

i

w

M

■

p§

* J<

ms *"

^ J

J

Ik . * *

^^k

Figs. 1 and 2. Rickettsia bodies ix the excrement
of normal lice

(Reprinted with permission of Paul B. Hoeber, Publisher of
Osier Anniversary Volume)

PLATE XXI

THE SERBIAN EPIDEMIC 81

was not opportunity to search for them in the intestinal epi-
thelium. The lice are referred to as normal bcr-ause they pro-
duced no disease either in their original host from which they
were collected, or when they were placed upon or fed upon

other healthy individuals.

A critical examination of the literature regarding the relation
of Rickettsia to disease reveals the fact that these bodies
been found in lice which have fed upon cases of typhus fever,
Volhynia fever, trench fever, war nephritis, malaria, bron-
chitis, inflammation of the bladder, and inguinal hernia, as
well as in a large number of lice collected in different parts of
the world which have fed only on healthy people in whom they
produced no disease. Rocha-Lima maintains that in lice,
Rickettsia prowazeki, which is regarded by him as the prob-
able cause of typhus fever, differs from Rickettsia pedicuH
(which is found in lice not infected with the virus of typhus in
that the latter does not occur normally in the epithelium of the
alimentary canal of the louse. However, Toepfer, Brumpt, and
others have reported the presence of Rickettsia in the intesti-
nal epithelial cells of lice fed upon healthy individuals or in
those fed upon Volhynia fever cases, or cases of war ne-
phritis. Rickettsia have also been found in ticks that have fed
upon cases of Rocky Mountain spotted fever. They have in
addition been observed in the blood of man in a number of dis-
eases, for example, in typhus fever, in Rocky Mountain spotted
fever, in Volhynia fever, and trench fever. Rocha-Lima also
believes that he has seen in the blood of healthy persons similar
bodies to those observed in the blood of Volhynia fever by
other investigators, and described by them under the name oi
Rickettsia.

Further, when we come to consider the aetiologies! signifi-
cance of Rickettsia in human disease, it is apparent from the
evidence already presented in this article that not one o\ the
three classical postulates regarded necessary for the proof of
the aetiological factor of an infectious disease has yet been
demonstrated for the Rickettsia. (1) They have not been
found in every case of the disease they have been said to be the

82 TYPHUS FEVER

cause of; moreover they have been found in connection with
other diseases than the one it is maintained they give rise to.

(2) They have not been isolated and grown in pure culture.1

(3) The disease which they are said to be the cause of has not
been produced by the inoculation of such culture.

It seems very probable that the Rickettsia bodies are micro-
organisms, but as they have been found in lice from patients
with so many different diseases, as well as in lice from healthy
individuals, obviously no specificity for them could be justly
claimed without further investigation. It is true that Rocha-
Lima, Toepfer, and Olitsky, Denzer and Husk report the pro-
duction of typhus infection in animals by the inoculation of the
contents of the alimentary tract of infected lice. In this con-
nection Rocha-Lima claimed that the disease developed in the
inoculated animal because the Rickettsia were present in the
lice used for the injections, while on the other hand, Olitsky,
Denzer, and Husk claim the disease developed because the
Plotz bacillus was present in the lice used in the inoculation of
the animals. Obviously we can draw no definite conclusions
from these experiments save that the infecting agent visible or
invisible was present in the lice. Nothing can be said from them
regarding the definite nature of the infecting agent. Sergent,
Foley, Vialatte, and Brumpt all pointed out that the Rickett-
sia might merely accompany the infectious agent.

Observations and experiments recently made in connection
with trench fever may be of interest in the study of Rickettsia.
In relation to the aetiology of trench fever, as has been the case
in the history of most infectious diseases, a number of widely
differing microorganisms have previously been described as its
cause, but none of these claims have been substantiated, and
although very extensive studies have been made by a large
number of observers, it is still a question whether the organism
causing trench fever has yet been definitely seen in man either
with the microscope or the ultramicroscope. Our experiments

1 Kuczynski (Med. Klin., 1920, xvi, pp. 706, 733, 759) has since reported to have cul-
tivated R. proiuazeki in blood plasma modified to resemble human tissue lymph in cel-
loidin capsules in the abdominal cavity of guinea pigs. He has also claimed to have pro-
duced typhus infection in guinea pigs with such cultures.

THE SERBIAN EPIDEMIC

carried on in relation to the aetiology of trench fever have since
shown that the causative organism of this disease is under

tain circumstances filterable and that it hen- some resem-
blance in its behavior to the filterable virus of hog cholera.1

Our work regarding the filterable qualities of the virus of trench
fever has recently been confirmed by Major General Sir John

Rose Bradford, Captain E. F. Bashford, and Captain J. A.
Wilson.2 The organism causing trench fever being bo minute

is obviously separated only with great difficulty from the sur-
rounding structures in the media in which it occur- naturally.
Thus, while we have demonstrated that the virus of trench
fever is present in the plasma of the blood of trench f<
cases, in the febrile stages of the disease it is frequently very
difficult to separate it from the blood corpuscles themselves
by repeated washings of these with saline solution.3 Also in the
alimentary canal of the louse fed upon trench fever case- and
in infected louse excrement, the virus on account of its minute
size must be closely intermingled with other cellular struc-
tures present.

We have also seen that in different examinations of lice fed
only upon healthy individuals, the Rickettsia have been dem-
onstrated in from 20 to 74 per cent of them. Knowing these
facts let us suppose that lice already containing such sapro-
phytic Rickettsia in variable number had been fed upon trench
fever cases and had become infected with the virus of trench
fever, and such lice (containing the Rickettsia which may in the
meantime have multiplied or increased in number) were then
placed upon healthy human beings whom they subsequently
infected with trench fever, obviously then erroneous con-
clusions might be drawn that the Rickettsia were themselves
the aetiological factor of trench fever. It is evident that great
difficulty would be experienced in a separation of the virus o\
trench fever from such bodies under the circumstances de-
scribed above. Probably only by successful filtration e\-

1 Trench Fever: Report of Commission of American Red Cross Research Committee,
Oxford University Press, 191S.

2 Bradford, Bashford, and Wilson: Brit, Med. Jour., 1019, i. 127.

3 Loc. cit. : Trench Fever Report, p. 27.

84 TYPHUS FEVER

periments, such as we have performed with lice excrement
in connection with trench fever, could the separation be
accomplished.

It of course may be argued that Rickettsia have a filter-
able stage as have other so-called chlamydozoa, and this idea
receives some support from the fact that the virus of trench
fever is under some circumstances filterable with difficulty, and
attempts to infect human beings with the filtrates of infected
material are often unsuccessful. Thus in ten filtration exper-
iments performed with infected blood and urine from trench
fever cases, and infected louse excrement, only three with urine
gave undoubted positive results. The temperature charts of
two cases of trench fever experimentally produced by the in-
jection of the filtered trench fever virus are illustrated in
Plate XXII.

Bradford, Bashford, and Wilson 1 have since reported upon
the cultivation of the trench fever virus from filtrates which
have previously passed through porcelain filters and have also
shown by human experiments that such filtrates contain the
infectious agent.

It is conceivable that the Rickettsia, whether they possess a
filterable stage or not, may be parasites of lice and not path-
ogenic for man, and Brumpt has suggested that the finding of
them in human blood may simply be an indication that the
individual has been previously infested with lice. On the other
hand, there is the possibility that the bodies sometimes de-
scribed as Rickettsia may constitute products of degenerated
cells, for example, basophilic granules, which are more numer-
ous in the blood in certain febrile diseases, in which case they
would also increase in number in the lice fed upon such cases,
and might then merely accompany the very minute or invisible
aetiological factor of the disease. Finally, there may be at
least three distinct species of Rickettsia, — R. prowazeki, R.
Volhynia, and the third form either intra or extracellular,
found in lice, and non-pathogenic for man.2

1 Bradford, Bashford, and Wilson: loc. cit.

2 Rocha-Lima: Deutsch. med. Wchnschr., 1919, p. 732.

|

'<■ .'

saw
r^::^::::::::::::::::::::;:::,

Figs. 1 and 2. Temperature charts of two cases of experimentally
produced trench fever

(Reprinted with permission of Paul B. Hocber, Publisher of Osier Anniversary V.

PLATE XXII

THE SERBIAN EPIDEMIC

In connection with the significance of Rickettsia

aetiological factor in typhus, trench fever, and other di.~e.-i-.--
it may be of interest to recall that in 1903 an organism de-
scribed by Parker, Beyer, and Pothier ae Myxococcidium
stegomyiae was found in infected stegomyia mosquitoes, and
was for a time supposed by these investigators to be the
parasite causing yellow fever. Later this organism was found
to be a species of yeast, and to occur not only in mosquitoes in-
fected with the virus of yellow fever, but also in those not in-
fected with such virus, and the virus of yellow fever was shown
to be filterable and supposedly ultramicroscopic.1

From a review of the evidence presented in this paper re-
garding Rickettsia, it appeared obvious that until more definite
results were obtained from further experimental work that we
were not justified in finally concluding that the Rickettsia have
a definite specific aetiological significance in relation to typhus
fever, even though there was much evidence in favor of this
idea. Hence it seemed advisable for the Medical Department
of the League of Red Cross Societies to appoint a special Com-
mission to study anew the question of the aetiology of this
disease. This Commission, consisting of Dr. S. B. Wolbach of
Harvard University, chairman, and a staff of seven members
including Dr. John L. Todd, associate professor of parasitology
at McGill University, Dr. A. Bacot, entomologist of the Lister
Institute, London, and Dr. Frank W. Palfre};, instructor in
medicine at Harvard University, have now nearly completed
their investigations upon the aetiology of this disease and their
full report upon this subject will shortly be published.- Their
very painstaking and careful studies seem to show that typhus
fever' is caused by the Rickettsia proicazcki of Rocha-Lima.

However, while there has been much difference of opinion
regarding the specific organism of typhus fever, as we are
familiar with the method of transmission of the disease, the

1 Noguchi's recent experiments, however, point to the fact thai the organism of yel-
low fever is a spirochaete. This according to other experiments is filterable at least at
one stage of its life history. (Jour. Am. Med. Assn., 1019, lxxii, 187

2 Wolbach, Todd, and Palfrey: Intern. Jour. Pub. Health. Geneva, 1920, ii. 211.

3 Nicolle: Bull, de l'Inst. Pasteur, 1920, xviii, 1.

86 TYPHUS FEVER

exact nature of the aetiological factor in connection with the
control of epidemics is of importance particularly in connection
with the hope that when the organism causing the disease has
been definitely isolated and cultivated, a satisfactory form of
protective inoculation or a satisfactory method of serum-
therapy will be developed.

Weil-Felix Reaction

The Weil-Felix reaction (agglutination or clumping of Bacil-
lus proteus X 19 obtained from the urine of cases of typhus by
the serum of typhus fever cases in dilutions of 1-100 to 1-2000
or higher) was not described by Weil and Felix until 1916,
although Wilson 1 had isolated in 1910 from the faeces of one
case and from the urine of two cases a variant form of B. coli
communis which was agglutinated by the serum of seventeen
cases of typhus and not by normal serum. Very extensive ex-
periments performed since 1916 have demonstrated that the
Weil-Felix reaction occurs in from 90-100 per cent of typhus
cases, and sometimes in dilutions of the serum as high as
1-30,000, about 50 per cent of the cases giving the reaction by
the fifth day and practically all by the tenth day of the disease.
Even though it is the consensus of opinion that the reaction is
not specific, and that Bacillus proteus X 19 cannot be identified
as the cause of the disease, its value as a method of diagnosis
of typhus is generally acknowledged. However, the value of
the reaction as a means of diagnosis in typhus fever had not
been emphasized in 1915, and the reaction was not employed
in Serbia in our laboratories for the diagnosis of the disease.
During the severe period of the epidemic, the admissions into
the hospitals were so high as to have precluded the use of any
such method, the diagnosis from the clinical manifestations of
the disease being the only method at all practical under the
circumstances already described.

Bacteriological Studies in Serbia

The bacteriological studies that were carried on in Serbia
during the epidemic did not confirm the fact that any one of

1 Wilson: Jour. Hyg., Lond., 1910, x, 155.

THE SERBIAN EPIDEMIC

the bacteria previously described as specific was in fad the

aetiological factor in the disease. The invest igatione cani
by Zinsser, Sellards, and Hopkins, of the American Red (
Sanitary Commission, did not confirm the fad thai the fi
lus typhi exanthematici described by Plotz was t|,« aetiologica]
factor, and no other organism was isolated which was regarded
asspecific. These investigations arc referred I toil) greater detail
later in this Report.1

Reference has also been made to the work of Topley who
also failed during the Serbian epidemic to isolate the Bacil-
lus typhi exanthematici of Plotz, though it was Bought for.
Topley, however, reported the finding of a diplococcufl which
he regarded as specific, but this isolation was not confirmed by
other investigators.

Penfold, 1916,2 was also not able to isolate the Bacillus typhi
exanthematici though he too isolated a coccus from four cases
of the disease. Muriel Robertson3 was unable to immunize
monkeys against typhus infection with this coccus. On the
other hand, Plotz's colleagues, Olitsky, Denzer, and Husk/
and Baehr,5 Paneth,6 and Popoff,7 have all reported the isola-
tion of this organism from cases of typhus. With so many
contradictory reports, and particularly when one compares the
results of Plotz and his colleagues with those obtained by
Rocha-Lima, Toepfer, Schuessler, Noeller, Wolbach, Todd, and
others in relation to Rickettsia, it seems obvious at least that
further experimental work will be necessary before unanimity
of opinion is secured.

Course of Serbian Epidemic

As has been stated, the epidemic increased steadily through
January, February, March, and April, reaching its height for
all of Serbia in April. By this time almost one in five of the

1 Wolbach, Todd, and Palfrey also failed to isolate this organism in their recent work
in Poland.

2 Penfold: loc. cit. 3 Robertson: Jour. Path, and Bacterid., 1917, x\i. 173.
4 Olitsky, Denzer, and Husk: Jour. Am. Med. Assn., 1916, lxvi, 1692.

6 Baehr: Jour. Infect. Dis., 1917, xx, 201.

6 Paneth: Med. Klin., 1916, p. 647, and Arch. f. Hyg., 1916, lxxxvi. 63.

7 Popoff: Deutsch. Med. Wchnschr., 1916, xlii, 471.

88 TYPHUS FEVER

Serbian people had contracted the disease.1 Toward the end of
April, however, the effort throughout the country to overcome
the spread of the disease had generally become determined and
united. The greatest credit is due to the Serbian medical
officers and other officials and to the Serbian people themselves,
for the heroic and determined manner in which in the midst of
their sufferings this anti-typhus campaign once organized was
pursued by them, practically all attention and effort in Serbia
being centered upon the extermination of the disease.

At this period there were engaged in combating the epidemic
in addition to the Serbian sanitarians, doctors, and other
officials, detachments of physicians, sanitarians, and nurses
from France, Great Britain, Russia, Belgium, Holland, and the
United States.

The foreign personnel consisted particularly of Colonel
Jaubert with 100 French physicians and sanitarians; Sir Ralph
Paget with a number of hospital units from Great Britain under
the individual direction of Lady Paget (with Dr. Maitland
as chief physician), Dr. Elsie Inglis, Dr. Alice Hutchinson of
the Scottish Women Hospitals, Mrs. Stobart, Dr. Barrie, Dr.
Berry, and Captain Bennet, also a military sanitary mission
under Colonel Hunter with whom were Major Stammers and
Captain Topley with twenty-one lieutenants; a contingent of
Russian, Belgian, and a few Dutch physicians employed in
connection with the Serbian army; the American Red Cross
hospital units under the general direction of Dr. Edward Ryan
at Belgrade; the American Red Cross hospital units of Dr.
Ernest Magruder and Dr. James Donnelly (both of whom gave
up their lives during the epidemic), of Dr. Ethan Flagg Butler

1 It has been suggested that the reduction of passenger travel from two trains to one
on one of the railways extending from the north through Kraguevatz on March 16 had a
decided effect upon the admission of typhus cases to the hospitals in this district. This
is undoubtedly true since fewer patients were brought or came by train to these hospitals
during this period. On resumption of travel, however, more cases were again sent to these
hospitals and their records began to show an increased admission of typhus cases. During
the period of partially interrupted train service many of the typhus cases were evacuated
by ambulances to other hospitals in central and southern Serbia. It should be noted that
by March 16 typhus was widely disseminated throughout Serbia and hence measures
taken locally obviously could not and did not materially affect the course of the disease
throughout the country, and particularly its course in the civil population.

THE SERBIAN EPIDEMIC

and Dr. Kirby-Smithj as well as a number of American phy-
sicians assigned to the Serbian army in addition to the Banil

commission of the American Red Cross, numbering in all ap-
proximately 100 physicians. Of the American Sanitary (
mission, Dr. Thomas W. .Jackson was chief sanitary inspector;
Dr. Hans Zinsser, bacteriologist; Dr. Aldo Castellani, con-
sultant in tropical medicine and bacteriology; Dr. George ( '.
Shattuck, clinician; Dr. A. Watson Sellards, chief of clinical
laboratory; Dr. B. W. Caldwell, hospital administrator; l>r.
F. B. Grinnell, sanitary inspector; Mr. Edward Stuart, sani-
tary engineer; Dr. Hopkins, assistant bacteriologist; and Mr.
Arthur's. Ward, secretary.

I wish particularly to emphasize that it was the combined
efforts of the Serbian medical and sanitary officers and other
officials and of the Serbian people themselves, together with
those of the personnel of the foreign detachment- referred
to, which soon began to show definite effects upon the
course of -the epidemic and from the beginning of May until
August, when the epidemic was at an end, the decline of t<
cases, not in any one locality alone but throughout the coun-
try, was- continual. The accompanying chart which shows the
curve of fever cases, typhus, relapsing, and typhoid, in the
civilian population throughout the country for this period,
strikingly illustrates this fact. Undoubtedly the approach o\
warm weather aided not only the officials concerned, but the
people themselves in the success of the campaign, but no one
who was concerned with this campaign can doubt the efficacy
of sanitary measures in connection with the prevention of the
spread of typhus fever. If no such anti-typhus campaign had
been carried out, it is extremely probable that the disease would
have diminished during the summer months only to reappear
with greater intensity during the following winter, which is
what has happened in Poland.1

1 Typhus appeared in Poland in epidemic form particularly in 191t>. Satisfactory
preventive, measures were not carried out, and the hope was expressed that the disease
would disappear during the summer. However, the arrival of summer seemed to have
little or no effect in stopping the epidemic, though the cumber of cases was somewhat
decreased during the summer months. Each summer the same hope has been expn ss
the epidemic continues to rage, now in its fourth year.

90 TYPHUS FEVER

The work of these various foreign units in Serbia referred to
above has been reported upon in various publications made by
their respective directors and hence will not further be alluded
to here.

Acknowledgments

It is perhaps proper, however, in this report of the American
Red Cross to say something regarding the American Sanitary
Commission, and to quote from a preliminary report l made to
the American Red Cross in 1915 upon this subject and not
widely circulated. " The American Red Cross and Rockefeller
Foundation have supported the American Red Cross Sanitary
Commission in every way and have supplied it with all the nec-
essary equipment and personnel. Every request which I made
was granted. I cannot speak too highly of the personnel of
the Commission, and I do not believe that a finer and more
competent group of sanitarians and physicians were ever got-
ten together. Much of the success of the work in Serbia was
due to their efforts.

"In this brief statement it is impossible to do justice to all,
but the names of Dr. Thomas W. Jackson, chief sanitary in-
spector, whom I left in charge after my departure; Dr. Hans
Zinsser, bacteriologist; Dr. Francis B. Grinnell, sanitary in-
spector; Dr. George C. Shattuck, clinician; Dr. A. Watson
Sellards, who had charge of the clinical laboratory work; Dr.
B. W. Caldwell, hospital administrator, and Dr. Aldo Castel-
lani, consultant in tropical medicine and bacteriology, are
deserving of the highest mention. All of these gentlemen with
the exception of Dr. Castellani, who joined shortly afterwards,
went to Serbia as members of the first commission. The name
of Mr. Edward Stuart, the sanitary engineer of the Commission,
also calls for special mention. His advice and work in connec-
tion with the many important sanitary problems in Serbia have
been invaluable.

" Among the second group of men attached to the Commis-
sion, Colonel Gale, Doctors Mendelssohn and Gruver, Mr.
Brink and others, and among the still later arrivals Dr. Harry

1 American Red Cross Magazine, 1915, x, 346.

Chart showing decrease in fever cases, typhus, relapsing, and typhoid
among the civilian population, may to august, 1915

PLATE XXIII

THE SERBIAN EPIDEMIC 91

Forbes and Dr. J. G. Hopkins, all held responsible positions in

the Serbian work."

Mr. Arthur S. Ward acted as secretary during the most
ing periods of the epidemic, and Mr. Charles Pi. Cross, who
afterwards died while performing other war service in France,
was disbursing officer of the Commission, while .Mr. I). B.
Tripcevich and Mr. Ranko Jovanovich acted as interpreters
and translators, particularly in connection with official records.

At the time of the organization in 1915 of the ( lommission,
" Major General Gorgas, Surgeon General of the United States
Army, most generously gave me his advice in relation to the
equipment and personnel of this Commission, and I am glad I < -
have this opportunity of expressing again my gratitude for t In-
most valuable assistance. Later he generously offered to give
up his position as head of the Medical Corps of the United
States Army, if necessary, and come to Serbia if the epidemic
could not be controlled. Fortunately for the army this sacri-
fice on his part did not become necessary.

" Surgeon General Rupert Blue, United States Public Health
Service, and Colonel Fisher, Medical Corps, United State-
Army, have also made valuable recommendations, and Miss
Boardman was untiring in her efforts of organization.

"Yale University, particularly through the offices of Pro-
fessor Beebe, Madame Slavko Grouitch and others, and Har-
vard University, particularly through Dr. F. C. Shattuck and
others, sent special funds for the work and Mrs. William H.
Forbes, of Boston; Mrs. McMullen, of New Rochelle. and Mr.
W. H. Converse have also generously given me financial assist-
ance for relief work in Serbia.

"Through the International Sanitary Commission at Nish,
the most complete and cordial cooperation was secured between
the French, British, Russian, and American and other phy-
sicians and sanitarians working in Serbia, I cannot speak too
highly of the work of many of my foreign colleagues. Among
the British relief workers in Serbia the work of Lady Paget
and of her husband, Sir Ralph, and of Sir Thomas Lipton, must
be specifically mentioned. Lady Paget 's hospital, which she

92 TYPHUS FEVER

directed herself until she became a victim of typhus, and of
which she again assumed the directorship as soon as she was
convalescent, is equipped with over five hundred beds and has
done most admirable work. It is only equalled in efficiency
by one other hospital in Serbia. Sir Ralph Paget has worked
untiringly and faithfully in the discharge of his duties, as has
his wife. Sir Thomas Lipton,1 apart from the financial support
he has given and secured for Serbia, has encouraged and sup-
ported the medical and sanitary work in Serbia in many ways
and has rendered innumerable kindnesses and supplied count-
less comforts for Red Cross workers in Serbia."

"The best equipped and managed hospital in Serbia is the
American Hospital in Belgrade, of which Dr. Ryan is the direc-
tor and Miss Gladwin the chief nurse. Here patients receive
the same efficient care and comfort which they do in many of
our best hospitals in the United States. Dr. Ryan, during the
height of the epidemic, worn out with overwork, was stricken
with typhus. He kept at work, however, until he became
delirious, when he was taken charge of and treated by Dr.
Kirby-Smith. As soon as his fever subsided, he resumed
charge of his hospital. I could not do justice to the great work
Dr. Ryan 2 has done in Serbia in a few words, and Miss Glad-
win's work also merits the highest praise.

"Colonel Hunter and Major Stammers of the British Sani-
tary Unit also were of much assistance in the suppression of
the epidemic, the former being in charge of the sanitary work
of the army about Kraguevatz and the latter in charge of one of
the sanitary vaccinating trains and other sanitary work for a
part of the time. These gentlemen unfortunately were recalled
to render aid to the British wounded in the Dardanelles. The
French physicians, under the able leadership of Colonel Jau-
bert, and the Russian staff, under Colonel Solfatero, also rend-
ered most important assistance.

1 Sir Thomas Lipton on voyages with the Erin brought numerous physicians and
nurses, and sixty tons of medicines and hospital comforts.

2 Dr. Ryan and his assistant surgeons were in Belgrade during all of its bombard-
ments and surrenders.

Sir Thomas Lipton on board the "Erin"

PLATE XXIV

Dr. Edward Ryan convalescing from typhus fevbb ind
Miss Gladwin, chief nurse, A.R.C.

PLATE XXV

tiik skkhian i;iMi)i;.\nc

" Assistance that was particularly welcome was given by Un-
American Relief Clearing House in Paris, especially through

Messrs. Scott, Hargis, and Carter."

I wish to particularly express my appreciation to Mise
Catherine M. Casassa, Secretary of the School of Tropical
Medicine at Harvard University Medical School, for much
valuable assistance in connection with the preparation of thie
entire Report, and for having read the proof of the same.

End of Epidemic

Writing in 1915 I expressed the opinion that the sanitary
demonstrations and instruction in the prevention of typhus
fever which had been given to the Serbian people, and the con-
struction and use of the various permanent disinfesting plants
which had been established through the country, would pre-
vent the occurrence of another epidemic of such severity as to
destroy in the neighborhood of 150,000 people.1

This opinion seems to have been justified and there has been
no epidemic of this disease in Serbia of any magnitude since
this time. However, typhus fever is and has been endemic in
the Balkans for many years and a few cases of it still occur and
others are introduced into Serbia from time to time.2

The Polish Epidemic of Typhus, 1916 . . .

On account of the assistance which the American Red Cross
and other national Red Cross societies under the coordination
of the League of Red Cross Societies are extending to Poland
in connection with the typhus epidemic now raging in that
country, it also seems advisable to review in this report the
existing conditions in Poland, and the steps already taken in
connection with this epidemic.

1 The official record of the Secretary of War at Serbia gives the number of deaths
from all cases for the army in 1915 as 171,725.

2 Typhus fever was reported prevalent in Macedonia in 1919, the disease being trace-
able to refugees returning from Bulgaria, especially from Varna, and other Black Sea
ports. A number of cases were reported present at Drama, but without spread of the
disease. At Kavala about 300 cases were officially reported: the outbreak was success-
fully dealt with locally by Dr. Samuel J. Walker of the American Red Cross.

94 TYPHUS FEVER

Russia as an Endemic Center of Typhus

Poland was formerly recognized as an endemic area of typhus
and Russia itself has been regarded as one of the great endemic
centers of typhus in Europe. Epidemics in Poland have oc-
curred in the nineteenth century particularly in 1830-31, when
the disease was introduced by troops, and in 1842-46 when
there was a general epidemic throughout Poland. In Galicia
where the disease is also regarded as endemic, we know that
typhus was general in 1846-47; but complete statistics from
these countries have not been available. However, for the ten
years preceding 1916, in the whole of Russian Poland, with a
population of about thirteen million, the average number of re-
ported typhus fever cases was less than 2000 annually.1 In all
Congress Poland, before the war it has been estimated by the
Polish Ministry of Health that there were in the neighborhood
of 6000 cases annually. Low, 19 16,2 gives as the number of
deaths from typhus fever for Galicia from 1895-1904 (ten
years) 5592; and for 1905-12 (8 years only), 2181; while for
Poland from 1905-11 (7 years), 1126.

The Present Polish Epidemic

Towards the latter part of 1916 typhus became epidemic in
Poland, the chief area at first affected being the governmental
district of Warsaw. This district at the time was occupied by
German troops, and was then being administered as German
territory. From the returns published by the Central Imperial
Health Department in Berlin, it appeared that 26,099 cases
were reported in about twelve months in the government dis-
trict of Warsaw which had a population of only two and one-half
million, 853,000 of which resided in the city of Warsaw. In
Congress Poland and Galicia combined, the cases reported for
1916 were 34,538. The measures taken against the epidemic in
1916 and in 1917 failed to check its spread, but the hope was
expressed that the epidemic would disappear in the summer
months. The summer of 1917 however seemed to have little

1 Lancet, London, 1918, i, 150.

2 Low: Eleventh Annual'Report, Local Government Board, 1914-15.

THE SERBIAN EPIDEMI<

effect in reducing the aumber of cases of the disease, and for the
year 1917 the cases for the same territory cumbered 13,840.
The epidemic was again not suspended the oexl year by the
summer months, and in 1918 the number of cases more than
doubled those in 1917, amounting to 97,082. Since December,
1918, Poland as an independent state has had control over this
territory and the Polish government has carried on measures
against the epidemic. During the first year of the existence of
the Polish Public Health Service the number of cases of typhus
reported to the Ministry of Public Health was as follow- .

Caeee Deaths Per rent

Congress Poland 161,042 1 2,632 7.8

Galicia 70,158 7,250 10.3

Poznania 100 9

Total 231,306 19,891 8.6

During the months of January and February of 1920 the
number of cases notified was as follows:

Congress Poland ] 2,0'.i.s

Galicia • 34. 476

During the spring and summer of 1919 the disease showed a
considerable decrease in certain portions of Congress Poland,
but the number of cases again rose in November, and this
number has remained practically stationary. Nevertheless it
about equals the number of cases that were present during
January and February a year ago (1919). In Galicia, however,
the disease has not even remained stationary. There was a dis-
tinct rise in December, 1919, which has continued through
January and February of 1920. These figures speak for them-
selves. They show that the epidemic is now well into its fourth
year and they demonstrate that the measures which have been
employed by the Polish government to combat the epidemic
have not yet been as successful and as effective as was hoped.
Colonel H. L. Gilchrist of the United States Army Medical
Corps, attached to the Polish Ministry of Health, and fighting
typhus fever in Poland, in a report written in March. 1920.
says "the typhus epidemic which for the fourth year in suc-
cession has been raging in Poland, has increased in intensity

96 TYPHUS FEVER

each year, due probably to the large influx of refugees and
prisoners of war from Russia, and to the thousands of cases
being imported from the interior of Ukrania and other eastern
territories. The situation at present is getting beyond control."
In describing the conditions in parts of Galicia, he writes :
" In Galicia whole towns are crippled. Schools are closed and
business practically suspended from the effects of the disease.
In the northeast of Poland, American inspectors report the
disease raging as affecting nearly every home, with a high
mortality. Starvation and lack of clothing and medicines are
also in evidence. There are few doctors and no nurses. As a
result of the ravages of the past war, and the fact that Poland
has been occupied by several armies which, when retreating,
either destroyed or took with them all the materials of any
value, the eastern country has been left with only absolutely
meager essentials. Homes which for the most part are only
rudely constructed affairs, and without furniture of any kind,
offer shelter for thousands of these sufferers. They have no
beds and lie on straw or hay-strewn floors. The same materials
answer the purpose of protecting them against the Polish win-
ters. Many of these small huts consist of but a single room,
and here father, mother, and several children reside. The pres-
ent article of diet in the majority of cases consists of potatoes,
beets or other vegetables, and these in only starvation quanti-
ties. They seldom see bread. Meat is furnished only occa-
sionally. At present nearly every house has from one to five
cases of typhus fever, all lying on the usual beds of straw or
hay. Houses have been visited by me in which the entire
families were stricken, some delirious, and without medical
attention of any kind. Some cases were found in which the only
nourishment consisted of raw potatoes or raw beets. The
friendly natives are doing what they can to relieve this suffer-
ing, but due to the shortage of the essentials of life their aid is of
little avail. Doctors and nurses are unknown to these people,
the peasants acting as combined doctors, nurses, and under-
takers. If the dead have no near relatives to claim their effects,
the bodies are stripped before burial and their clothing taken

THK SKRBIAN EPIDEMIC 97

away in ignorance by the peasants to distant parte to be sold,

thus implanting the disease in new area-

The circumstances which have been given by the Polish Min-
ister of Health as responsible for the spread of theepidemie an-:

1. The war devastation of Congress Poland and ( ralicia and
its consequences.

2. The administrative chaos which followed the sudden
withdrawal of the authorities occupying the Polish territories,
and the disorderly demobilization as well as the reemigration
and the return movement of war prisoners from the East.

3. Great scarcity of sanitary materials and of professional
personnel.

4. The absence of every kind of sanitary sendee in the east-
ern territories at the time of their occupation by the Polish
troops.

5. The breaking up of the various Russian and Ukranian
armies of Deniken, Petlura, Bredow, and the admission of these
returning troops which the Polish government felt compelled
to receive into their lines.

6. The impossibility of maintaining a rigid sanitary cordon
on the eastern confines of the Polish civilian and military ad-
ministration, owing to the lack of essential supplies and scar-
city of personnel.

The Polish Minister of Health believes that the cause of the
epidemic in Poland must be sought outside Polish borders and
namely in the existence of a permanent focus of infection in
Russia where according to Russian official sources 1,600.000
cases were notified during 1919. The Polish Minister reports
that a campaign against the epidemic is being carried on par-
ticularly along the following lines: first, the establishment of a
series of quarantine stations along the eastern borders of the
country; through this line of stations it is stated that there
passed between November 1, 1918, and January 1. 1920.
652,604 prisoners of war returning westward from Russia, and
627,088 reemigrants flocking back to Poland from the East.
Secondly, through the establishment of epidemic hospitals with
a^total of 13,077 beds and with a subsequent increase of some

98 TYPHUS FEVER

7000 beds between September, 1919, and April 1, 1920. This
number of beds does not, however, include those in the military
hospitals at the front. Thirdly, by the establishment of mobile
field sanitary columns 294 of which it is said they were operat-
ing in 1919, each employing a disinfecting apparatus. These
columns carried out in the late summer and autumn of 1919 a
mass cleaning-up campaign in the epidemic territory, and in all
the counties of Poland. The Polish Minister states that "the
number of people dealt with amounted to 311,374; 72,731
habitations were disinfected, and in addition to these, 19,400
people were bathed by four bathing motorized columns of
Colonel Gilchrist's American Unit, while the units of the Brit-
ish Society of Friends have dealt with 15,860 people and 2800
habitations." In addition to these measures the report states
railway stations on all Polish lines are being cleaned once
weekly and the railway cars are being disinfected at three
points. The erection of public bathing and delousing places is
also being encouraged.

Action by the League of Red Cross Societies

Owing to the grave representations presented to the League
of Red Cross Societies regarding the wide prevalence of typhus
fever in Poland and the danger of its spread westward across
Europe, it was decided that the League should interest itself in
the control of this disease as an emergency relief measure. The
importance of this step was particularly emphasized by the
urgent request made to the League by the Polish Minister of
Health for assistance in preventing the spread of the disease
westward, and in the suppression of the epidemic in Poland
itself.

At a conference held in Paris in June, 1919, at which the
Minister of Public Health of Poland, then Dr. Janiszewski, Dr.
Ludwik Rajchman, Mr. W. Frank Persons, Director of De-
partment of Organization, League of Red Cross Societies, and
the writer, were present, the Minister, in a written statement,
requested that the League of Red Cross Societies should assist
the Polish government in its campaign against typhus, and

THE SERBIAN EPIDEMK

presented two proposals in this connection: first, thai the
League of Rod (toss Societies should take over the mai
mont of two lines of sanitary cordon (permanenl and mobile
on the eastern frontier of Poland, organizing those stations
which were not yet working; secondly, that the Ministry of
Public Health should conduct a campaign on the territory of
the late Congress Poland and Galicia, the .Mini-try applying to
the Supreme Economic Council for the acquisil ion of n<
supplies; and that the League of Red Cross Societies should
help the Ministry in obtaining the services of suitable salaried
personnel. In the second proposal, the Minister stated,
"that I am most anxious to see a very close cooperation be-
tween the League and our own public health service, and this is
the reason why I am bringing forward now a new proposition
which we did not discuss at our meeting this afternoon, but
which appears to me to secure that end better than the first
scheme. It would consist in the following: (1) the Ministry to
obtain supplies from the Economic Council as under the first
alternative; (2) the Ministry would organize a Central Com-
mittee for fighting typhus in Poland. This Committee would
appoint one delegate who conjointly with one delegate of the
League of Red Cross Societies would conduct the whole action
of combating typhus in Poland in accordance with the scheme
of organization propounded in the annexed memorandum."

In connection with assisting the Polish Minister to obtain
personnel, Colonel H. L. Gilchrist of the United States Army
Medical Service, who had had wide experience in disinfesting
troops, having been in command of such work in the American
Expeditionary Forces in France subsequent to the Armistice,
was invited to meet the Polish Minister of Health at one oi
these conferences with the idea of enlisting his services and
those of his sanitary detachment in connection with the anti-
typhus campaign in Poland. In a previous conference held
with Mr. Herbert Hoover, American representative of the
Supreme Economic Gouncil, and representatives of the League
of Red Cross Societies, it had been agreed that the Supreme
Economic Council would interest itself in securing for Poland

100 , TYPHUS FEVER

necessary sanitary and medical supplies from the surplus stores
of the United States Army, and that the League of Red Cross
Societies would interest itself in attempting to obtain the med-
ical and sanitary personnel desired by the Polish Minister. As
the matter, however, seemed to be an urgent one, Mr. Hoover,
at the same time that he arranged for the sale to the Polish
government of these supplies, also presented to the President
of the United States, at the time of his departure from France,
the question of the detail of Colonel Gilchrist and his sanitary
detachment for work in Poland, and this officer and his de-
tachment were subsequently ordered by the Secretary of War
of the United States for assignment to the Polish Minister of
Health for duty. Unfortunately, it apparently was not recog-
nized that the Polish Minister of Health did not have jurisdic-
tion over much of the territory of Poland in which typhus was
at its worst, such territory being under military authority;
hence the services of this sanitary detachment were only avail-
able in Congress Poland where the Polish Minister of Health
had jurisdiction.

The sanitary and hospital supplies purchased by Poland on
credit at this time for the epidemic campaign from the Ameri-
can Liquidation Board alone were valued at a greatly reduced
price at four million dollars. These supplies required thirty-
two trains each of over fifty cars to transmit the material into
Poland. Included in this equipment were the following impor-
tant items : all the steam sterilizers which were not used by the
American Forces in France; 27 mobile steam laundries; 500
mules with harnesses, hundreds of carts, drags, etc.; 10,000
beds; 40,000 sheets, blankets, and pillow slips; 40,000 towels;
100 tons of sOap; 17 motorized bath plants; 300 portable bath-
ing plants; 4000 Serbian barrels; 50 tons of washing soda; 1
million suits of cotton underclothing; 160 5-ton Packard
trucks; 324 Ford ambulances; 160 Ford touring cars; 3 mobile
machine shops, together with hundreds of other items too
numerous to mention.

In order that the League of Red Cross Societies might be in a
position to act most intelligently in connection with the re-

THE SERBIAN EPIDEMIC 101

quests of the Polish Minister, the writer, ae General Medical
Director of the League, after consulting with the ( ftairman and

other officers of the International Office of Public Health, and

the officials of the British Ministry of Health, recommended
that an Interallied Commission consisting of Assistant Surgeon
General Hugh S. Cumming (now Surgeon General of the
United States Public Health Service) ; Dr. ( leorge S. Buchanan,
Senior Medical Officer, British Ministry of Health; Dr. Aldo
Castellani, Lieutenant Colonel Italian Medical Service, and
Dr. F. Visbecq, Medecin principal de premiere classe, French
Army, Service de Sante, be appointed to proceed to Poland for
the purpose of making a careful investigation of the medical
and sanitary conditions in that country. This Commission,
upon its return from Poland, rendered a comprehensive report
to the League, summarizing the knowledge of medical and
sanitary conditions in that country, and making recommenda-
tions of the measures which should be undertaken and the
personnel and medical and sanitary supplies which should be
furnished for the campaign against typhus fever and other in-
fectious diseases epidemic there. It also pointed out that for
the protection of Eastern Europe and of other regions, it is
essential that the Polish government should receive help in the
fight against typhus and other epidemic diseases, not only in
Poland proper, but along the eastern frontiers through which
infectious diseases are being constantly introduced by refugees
and prisoners, and are liable to spread immediately into the in-
terior of the country. On account of the magnitude of the task,
the Director General of the League pointed out that the case
seemed to be one which called for active assistance from gov-
ernments as well as from voluntary organizations, and that
it should be frankly stated and generally understood that the
resources of the Red Cross were insufficient to provide all the
assistance required by Eastern Europe in this great emergency.
The Report of this Medical Commission was, therefore, pre-
sented not only to the national Red Cross societies, but also to
the Secretary of the League of Nations and the Supreme Eco-
nomic Council, with the request that all possible assistance be

102 TYPHUS FEVER

given. A copy of this Report was also sent to the International
Offices of Public Health at Paris. The Committee of this Office,
after pointing out that it understands "that the League of Red
Cross Societies considers the necessary action to be beyond
what could be undertaken by the Red Cross organizations, and
that the League has therefore presented the Report of its Com-
mission to the various governments which are able to help by
supplying material and personnel, and that it has insisted upon
the necessity of the said governments helping in as great a
measure as possible and as quickly as possible in the campaign
against typhus in Poland which the Polish government is un-
dertaking," states that the Committee of the International
Office fully associates itself with the above suggestions, being
convinced that the fight against typhus in Poland is of the ut-
most importance for the protection of other countries against
the propagation of this terrible disease.

The League then took further action in connection with the
Report of its Medical Commission and designated Mr. Wil-
liam C. Boyden as commissioner to Poland, and Colonel Henry
A. Shaw as medical representative, who with a medical staff
were sent to Poland to render such assistance as was pos-
sible for the League of Red Cross Societies to give the Polish
government, and particularly to assist this government in
carrying on an extensive campaign against typhus as had been
requested by the Polish Minister of Health. The plan of
campaign proposed included both field and sanitary work, com-
prising general disinfestation of people in badly infected dis-
tricts, with removal of patients to infectious disease hospitals;
disinfestation of other inmates and disinfection of the houses
from which patients are taken; the establishment of quaran-
tine and disinfe'sting stations, particularly in relation to the
movement of refugees and the disinfection of railway trains
and other vehicles of transportation; as well as the establishing,
equipping, and running of hospitals for infectious diseases; the
securing of personnel for the sanitary and hospital work, and
provision for an educational campaign which would include the
preparation of pamphlets and circulars upon infectious dis-

THE SERBIAN EPIDEMU L03

eases, printed in the language of the country, and practical
demonstrations to be supplemented by cinematographic exhibi-
tions on the public health measures concerned.

The League also arranged with Dr. S. Burl Wolbacb of
Harvard University and a staff of seven members, which in-
cluded Dr. John L. Todd, associate professor of parasitology
McGill University, Dr. A. Bacot, entomologist of the Lister
Institute, London, and Dr. Frank W. Palfrey, instructor in
medicine at Harvard University, to make thorough investiga-
tions regarding the aetiology of typhus fever, particularly with
the hope that new knowledge might eventually be obtained
regarding its prevention by vaccination and its treatment by
serum-therapy, and the report of this Commission has already
been referred to.

Response to the Appeal of the League of Red Cross Societies

Following the appeal of the League for assistance in Poland
from the national Red Cross societies, a generous response was
obtained from the American, Australian, Belgian, British,
Italian, Japanese, Portuguese, Roumanian, Serbian, and
Spanish Red Cross societies. Also in the summer of 1919 the
British government at the instance of the Supreme Economic
Council contributed jointly with the British Red Cross, on a
pound to pound basis, £60,000 for military and civilian relief
work under the League of Red Cross Societies in Eastern
Europe. Twenty thousand pounds of this amount were made
available for Poland. The British Red Cross Society had al-
ready expended one hundred thousand pounds on hospital re-
quirements, according to the Report on Economic Conditions
in Central Europe, transmitted with Sir William GoodVs
despatch of January 1, 1920, and a further one hundred thou-
sand pounds out of British credits was provided, which was to
be used for the purchase of drugs and medical accessories.

The American Red Cross has been pursuing its activities in
Poland under the direction of its commissioner, Lieutenant
Colonel A. J. Cheslejr, since early in 1919. Its personnel at
the present time in Poland, according to the statements of

104 TYPHUS FEVER

Lieutenant Colonel Kendall Emerson, Deputy Commissioner
to Europe of the American Red Cross, numbers 187. Since
October 1, 1919, 378 carloads of supplies have been shipped to
Poland. These include such articles as medical and hospital
supplies, food, clothing, and motors for transportation. The
relief work of the American Red Cross has included the general
distribution of clothing to refugees, as well as medical care
and advice; maintaining and operating delousing plants, and
clinics and dispensaries; the equipping of hospitals and the
establishment and operation of hospitals.

In addition the American Red Cross has heartly cooperated
with the plans and activities of the League of Red Cross Socie-
ties relating to Poland and Eastern Europe, having donated
1500,000 to the League to cover cost of investigations and sur-
veys. It has also set aside $400,000 of its own funds for ex-
penditure in Poland in accordance with the League's program.

Further Need of Personnel and Supplies

In a recent report made to the General Council of the League
of Red Cross Societies by the writer, it was emphasized that fur-
ther assistance is urgently needed, since typhus fever in certain
districts of Poland is still on the increase, and the manner in
which the national Red Cross societies can still be of particular
assistance was reiterated as follows : in relation to personnel, it
is suggested that physicians be furnished who should prefer-
ably have a special knowledge of infectious diseases and their
treatment. These physicians would be stationed in the dif-
ferent hospitals for infectious diseases already established in
Poland; other physicians should be bacteriologists with partic-
ular knowledge of public health laboratory work, while others
should have special knowledge of field sanitation and should be
preferably medical men trained as health officers or at least
graduates of schools for health officers; sanitary engineers with
special knowledge of water supplies and the sterilization of
drinking water will also be required; nurses trained partic-
ularly for work in infectious diseases hospitals, and others
trained for visiting and public health nursing are also greatly

THE SERBIAN EPIDEMIC 105

needed. The writer has been informed by the Polish Mini

of Health that foreign units rather than individual personnel of
the nature described above are pari icularly desired.1 ( Complete
equipment for hospitals for infectious diseases is also urgently

required.

The Interallied Medical Commission of the League senl to
Poland also reported that the following supplies are indispen-
sable for carrying on the campaign: soap, outer garments for
refugees and convalescents), linen, blankets, outer garment -
(particularly for patients), hospital equipment and mobile
hospitals, drugs, various types of vehicles, delousing plants,
both stationary and mobile; and particularly tools and material
for construction of wooden buildings.

Importance of Further Administrative Measures in
Combating the Epidemic

In a recent report made in March, 1920, Colonel Gilchrist
writes: " After seven months of active work in Poland as
the Commanding Officer of the American Typhus Fever Ex-
pedition ... I am convinced that before typhus fever can
be eliminated from Poland the entire matter will have to be
placed under the control of a commission preferably inter-
national . . . which will have to have absolute control over all
matters pertaining to the elimination of typhus fever in the
country."

It has been pointed out that the Polish Minister of Health
has not had jurisdiction over much of the territory in which
typhus has particularly prevailed, such territory being under
military administration, and that therefore there had not been
as great cooperation and efficienc}1" in prosecuting the cam-
paign as was desirable. Recently, however, the Polish govern-
ment has appointed Colonel Godlewski as Chief Epidemic
Commissary, whose power it is said will extend over the whole
of Poland including the country both under civil and military
administration. Provided therefore that the Polish govern-

1 The League of Red Cross Societies is at the present time about to issue a further
appeal in connection with the relief of Poland.

106 TYPHUS FEVER

ment will seriously impel and support the campaign there
would seem to be every reason to feel that under the efficient
direction of Colonel Godlewski, who has been placed in entire
charge of this work, assisted by Colonel Shaw in charge of the
inspection service, Colonel Gilchrist in charge of bathing and
delousing work, and Colonel Chesley in charge of distribution
of American supplies, we may look forward with confidence to
the administration of the campaign. The present plan of cam-
paign includes a comprehensive scheme for cleaning up central
Poland inasmuch as all reports indicate that the disease has ob-
tained a firm foothold throughout the entire territory of Poland
and is no doubt spreading more or less extensively from these
foci. It is the intention, however, that there should be no re-
laxation but an additional prosecution of the work of excluding
the disease along the eastern and southern frontiers.

Poland, however, has so many serious problems confronting
her that neither many of the governmental officials nor the
people at large have as yet become thoroughly and sufficiently
aroused to the importance and necessity of ridding the country
of the disease. The epidemic has not been sufficiently prevalent
or the mortality sufficiently high as to convince the people of
the necessity for an intensive efficient anti-typhus campaign
and of the inevitable inconveniences which must accompany
it. Indeed the general attitude of many of the people in Po-
land is hostile to anti-typhus work, perhaps because often
during the German occupation the people were compelled to
submit to the necessary delousing measures which were ap-
plied by the Germans with military severity. As has been em-
phasized in this article in discussing the Serbian epidemic, one
of the most important features in the suppression of this epi-
demic was the cooperation of the people in all efforts to eradi-
cate the disease. In Serbia, however, the disease was general,
and the very great majority of the families in the entire country
has suffered from it. In Serbia also the mortality was in the
neighborhood of 50 per cent, whereas in the Polish epidemic it
has scarcely been above 9 per cent. As Colonel Shaw writes, it
is manifestly impossible to compel a whole population to sub-

THE SERBIAN EPIDEMIC 107

mit against their will to delousing measures. The first problem

is to change their mental attitude so that they will be willi:
cooperate and spread the doctrine of the campaign. For this
reason it has been recommended that there should be institute <i
as an important part of the new campaign a comprehensive
plan of education regarding the prevention of typhus designed
to reach practically the entire population. Particular effort
will be made to arouse and stimulate the activities of the people
generally through religious organizations, schools, the press,
through cinema exhibitions, relief organizations, magistrate.
and other officials of towns and villages, and prominent busi-
ness men. In this connection a play has been written by Major
Richard Taylor of the staff of the League of Red Cross Socie-
ties, which is now being performed in Poland. This play, which
is in the form of a drama, depicts the terror of this widespread
disease, particularly among the poorer classes of the populate m
in Poland, and at the same time it shows how it may be fought
successfully by proper measures. One of the most interesting
scenes depicts the arrival of a relief commission for health work
in a village which is ravaged by typhus.

Dr. Buchanan of the Ministry of Health of Great Britain,
and a member of the Interallied Medical Commission of the
League of Red Cross Societies to Poland, since his return from
Poland has not relaxed his efforts in Great Britain in connec-
tion with the medical relief of that country. Very recently at
the British Ministry of Health an International Health Con-
ference was held at the instigation of the Council of the League
of Nations, at the sessions of which relating to Poland Dr.
Buchanan presided. Representatives of the Polish govern-
ment and of the League of Red Cross Societies furnished this
Conference with information concerning Poland's needs in com-
bating the typhus scourge; and the Conference agreed that
action by the League of Nations was necessary. The measures
necessary to combat this epidemic on a large scale were set
forth, namely, the establishment of sanitary cordons, hospitals.
delousing stations, the provision of food and fuel: and expert
direction of the work; and it was recommended that, whenever

108 TYPHUS FEVER

possible, surplus war materials be secured for use in Poland.
The task of furnishing medical and sanitary personnel, nurses,
and hospital units and certain supplies was to be carried on
under the auspices of the League of Red Cross Societies. Reso-
lutions relating to these activities were passed before the Con-
ference adjourned. The League of Nations in connection with
one of these resolutions has already appointed a Typhus Com-
mission with Lieutenant Colonel Vaughan-Morgan as Chief
Commissioner, and Dr. Norman White as Medical Commis-
sioner. The League of Red Cross Societies will also be repre-
sented upon this Commission.

In view of this additional governmental assistance, we may
then have greater hope that the epidemic will be soon brought
under control.

Nevertheless, writing at this time, the writer feels it necessary
to emphasize the fact that the anti-typhus campaign in Poland
is even not yet being prosecuted by the Polish government in
an energetic and satisfactory manner. While the greatest sym-
pathy is due the Polish people and many of its officials for the
terrible plight in which Poland has been placed by the war
and on account of the several very grave war problems which
she still has to face, all concerned in connection with this epi-
demic must nevertheless realize the fact that at no time during
the past four years has the anti-typhus campaign been pur-
sued with that activity and energy which is desirable and
necessary to overcome the epidemic. Today the Polish govern-
ment almost overwhelmed with military problems is less able
than ever successfully to cope with the situation and foreign
assistance seems imperative if this is to be accomplished. The
government of Poland therefore not being in a position to deal
successfully with the epidemic, an opportunity is obviously af-
forded to the League of Nations, in addition to the League of
Red Cross Societies, to extend aid in this connection in that
country. It should however be realized that the mere furnish-
ing of supplies is not sufficient. If an additional large amount of
sanitary equipment and vast hospital stores are sent to Poland
without sufficient and efficient personnel to make proper use of

THE SERBIAN EPIDEMIC 109

thorn, the effort in the; lighl of past experience is liable I

but little.1 It therefore would seem to be exceedingly desirable

that the League of Nations should extend ite efforts not only to

obtaining such material but should also particularly endei
to arrange that a vigorous and really efficienl anti-typhue cam-
paign be waged and supported in every way praci cable by the
Polish government.

Typhus, however, is no longer a Polish question. It has be-
come a world-wide question, demanding energetic measures.
Besides the possibility of'its spread to Western Europe and
even by occasional cases across the Atlantic, and in addit ion to
the industrial and social unrest which accompanies it. there is
the fact that the economic rehabilitation of Eastern Europe
cannot proceed satisfactorily until this disease is stamped out.
Not only is it sapping the resources of Poland, it is causing
other nations to set up barriers against her; it is fostering isola-
tion in its most deadly form. For example, every person arriv-
ing in France from tj^phus-infected areas in Eastern Europe is
liable to be subject to medical inspection and quarantine. In
Great Britain regulations have been recently issued by the
Ministry of Health extending and strengthening the powers of
port and riparian sanitary authorities against the introduction
of this disease. At Cherbourg and Rotterdam quarantine and
disinfestation of all second and third class passengers coming
from countries east of Switzerland and proceeding to the
United States is already required. Nations are tightening, in-
stead of relaxing, the cordon of their frontiers.

It is costing the world more to tolerate typhus than to elimi-
nate it. It is a disease which spreads very rapidly and which is
very deadly; but it is one which can be checked with sufficient
men and material. The cost of " cleaning up " Poland would be
less than the loss typhus now occasions.

If the world does not fight typhus in Poland, it may soon
have to be fought not in those countries alone where it is
liable to become epidemic but in others in which isolated cases
of the disease will from time to time slip through quarantine
and set up new centers of infection.

1 See pages 99 and 100 of this Report.

PART II

CLINICAL OBSERVATIONS ON TYPHUS I KYI I;
IN SERBIA IN 191.3 •

By GEORGE C SHATTUCK

Prefatory Note

As clinical member of the American Red Cross Sanitary ( !om-
mission it became my duty to study the clinical manifest at ions
and treatment of typhus fever.

Near Skoplje or Uskub, occupying the buildings formerly
used by the Military Academy, was situated the institution
known as the Lady Paget Hospital, superintended by Lady
Paget, with a staff of doctors of the British Red Cross in charge
of Dr. Maitland. Before our arrival, early in May, this hospital
had already become one of the principal fever hospitals of Ser-
bia. It was proposed that Dr. Zinsser, our bacteriologist, Dr.
Sellards, our clinical laboratory member, and I should pursue
our investigations at the Lady Paget Hospital and we gladly
availed ourselves of the opportunity.

The hospital consisted of two large three-story buildings de-
voted partly to wards and partly to quarters for the staff, and
three pavilions, in each of which there were two large wards.
One of these pavilions was put in my charge. Its wards ac-
commodated ninety patients without overcrowding.

There were in May about four hundred patients in the hos-
pital. New patients entered daily in variable numbers, gen-
erally a few at a time, but on one occasion eighty new patients
arrived, and about forty of these were sent to my wards.

In the spring most of the patients in the hospital were suf-
fering from typhus or its sequelae, but there were many eases
of relapsing fever, a certain proportion of tuberculosis, and a
small number of cases of other diseases. As the season ad-
vanced the proportion of typhus declined. Relapsing fever

1 Prepared in 1916 as part of report of work done as a member of the American Red
Cross Sanitary Commission to Serbia. Revised for publication April, 1920.

Ill

112 CLINICAL OBSERVATIONS

increased for a short time and then rapidly diminished, so that
by the middle of July there were very few fresh cases of either
disease in the hospital. Malaria was increasing rapidly, and
dysentery of a mild form was becoming common. About this
time I left the Paget Hospital at the request of Dr. Strong to
take up other work.

Just before we began work Lady Paget and Dr. Maitland
sailed for England, leaving Dr. E. Bellingham Smith in charge
of the hospital. Through the courtesy of Dr. Smith, and of Dr.
A. H. Holmes, another member of the staff, I was allowed to
examine patients and to take notes in their wards.

The autopsies were performed by Dr. Zinsser, until he re-
turned home in July, after which I performed a number of them.

The urinalyses were performed jointly by Dr. Sellards and
me. Dr. Sellards made all the Sahli haemoglobin determina-
tions, the red and white counts, most of the blood film exam-
inations, and the Widal tests.

Dr. Dalyell, the British bacteriologist, kindly examined a
number of blood films for the spirillum of relapsing fever, and
was helpful in many ways.

To all of those mentioned and to the members of the British
Staff in particular, it is a pleasure to express thanks.

Literature on Typhus

The distinguished men of-medicine who have made impor-
tant contributions to the knowledge of typhus, since it was
clearly differentiated from typhoid by Gerhard, are too numer-
ous to mention here.

The clinical descriptions of Gerhard,1 William Jenner,2
Murchison,3 Curschmann,4 Thoinot,5 and Moore 6 are pre-

1 Gerhard: Am. Jour. Med. Sc, 1837, xix, 289; xx, 289.

2 Jenner: Med. Times and Gaz., Lond., 1849, xx, 401, 418, 456; xxi, 15, 113, 135, 233,
453.

3 Murchison: Medico-Chir. Trans., Lond., 1850, xxxiii, 23. Continued Fevers of
Great Britain, 3d ed., ed. by Cayley, Lond., 1884.

4 Curschmann: Nothnagel's Encyc. of Pract. Med., Eng. trans., ed. by Osier, Phil,
and Lond., 1901.

6 Thoinot: Ann. d'Hyg., Par. 1915, 4th Series, xxiii, 6.

6 Moore: Allbutt and Rolleston, System of Medicine, Lond., 1906, ii.

TYPHUS IN SERBIA 1 13

eminently good. Again, in the Gulstonian Lecture, on the

acute specific discuses, in which charuclcri-tic-. r< ~<!,,hl.i!
and differences are compared, Jenner's mastery of the subject
is revealed. Stokes2 recognized differences between typical
typhoid and exanthcmatic typhus but, finding the "typhoid

state" common to both, he believed to the last thai they were

varieties of the same disease. Nevertheless, his observations
on circulatory conditions in these fevers are of .ureal value.

The "Clinical Reports on Continued Fevers" comprising
a careful analysis of 164 cases, by Austin Flint, contain im-
portant observations on circulatory conditions and causes oi
death, and also an able summing up of the evidence then avail-
able for and against the view that typhus and typhoid fever are
different diseases. He favored the conclusion that they were
different but remained skeptical.

The pathology of typhus was first well described by Ger-
hard,4 was discussed in detail by Murchison,5 and summarized
by Moore6 and Thoinot.7 AschofP and Prowazek 9 more
recently studied it anew.

Important points for treatment were brought out by Ger-
hard,10 Stokes,11 Murchison,12 and Castelloi (quoted by Dot}
Curschmann,14 Moore,15 and Doty13 admirably discussed this
aspect of the subject.

An extensive bibliography can be found in Murchison's
book16 and a list of the recent literature on typhus with ab-

1 Jenner: Gulstonian Lectures, Lond., March, 1853.

2 Stokes: Diseases of the Heart and Aorta, Lond., 1S54; Lectures on Fever. Deliv. at
Meath Hosp., Dublin, ed. in Phil., 1876.

3 Flint: Clinical Reports on Continued Fever, Phil., 1855.

4 Gerhard: loc. cit.

6 Murchison: loc. cit,

6 Moore: loc. cit.

7 Thoinot: loc. cit.

8 Aschoff : Med. Klin., 1915, ii, 798; Abst. Trop. Dis. Bull., 1916, vii. 1 Is.

9 Prowazek: Original, Beitr. z. Klin. d. Infections-krankheiten u. z. Inununitatsfor-
schung, iv, No. 1; Med. Rec, N. Y., 1915, lxxxviii. 21. Editorial.

10 Gerhard: loc. cit, u Stokes: loc. cit.

12 Murchison: loc. cit.

13 Doty: Therapeusis of Internal Diseases, Forehheimer, X. Y.. 1913. ii.

14 Curschmann: loc. cit. 15 Moore: loc. cit.
16 Murchison: loc. cit.

114 CLINICAL OBSERVATIONS

stracts of many of the articles was published in the Tropical
Diseases Bulletin 1 of March 15, 1916.

Many valuable articles have appeared recently about typhus
epidemics in 1914 and 1915 and several are of unusual interest
from the clinical standpoint. In this connection the follow-
ing names require mention: Maitland,2 Gastou,3 Jurgens,4
Michaud,5 Milhit,6 Siebert,7 and Weiner.8 Foster 9 described
an epidemic in the Philippine Islands, Michie10 published an
account of his observations in Mexico, and Brill11 has compared
the endemic typhus of New York with the more virulent form
seen in epidemics.

Usual Course of the Disease

An epitome of the typical course of typhus may be useful for
comparison with the observations discussed later in this article.

The course of the disease has been divided into periods as
follows: (1) incubation; (2) invasion; (3) nervous excitement; (4)
nervous depression; (5) defervescence; (6) convalescence.

The duration of the incubation period or latent stage is given
by different observers as from five to twenty-one days. Ac-
cording to Minkine it averages eight days; according to Netter,
eleven; and according to Moore,12 usually about twelve days.
During this period there are no recognized symptoms.

The stage of invasion lasts from three to five days during
which the temperature rises rapidly with slight morning remis-
sions. The onset of symptoms is abrupt. A sense of extreme

1 Bibliog. of recent work, typhus. Trop. Dis. Bull., 1916, vii, 137.

2 Maitland: Brit. Med. Jour., 1915, p. 283.

3 Gastou: Rev. de med., 1915, xxxiv, 559.

4 Jurgens: Zeitsch. f. arzt. Fortbild., 1915, xii, 201; Berl. klin. •Wchnschr.,
1915, Hi, 654.

6 Michaud: Rev. m6d. de la Suisse romande, 1914, xxxiv, 554.

6 Milhit: Progres meU, 3d Series, No. 32, 1915, p. 382.

7 Siebert: Berl. Klin., 1916, xxvi, 1.

8 Weiner: Wien. klin. Wchnschr., 1915, xxviii, 407.

9 Foster: Arch. Int. Med., 1915, xvi, 363.

10 Michie: Med. Rec, N. Y., 1915, lxxxvii, 214.

11 Brill: ibid., lxxxviii, 914.

12 Moore: loc. cit.

TYPHI'S IN Si;i:hl \ ] 15

weakness often obliges the patient to remain in bed on the

third day.

The stage of nervous excitement is characterized in
cases by signs of acute toxaemia and by the development of the

eruption which generally comes on the fourth or fifth day.
This period lasts two or three days and is followed by the -
of nervous depression which is characterized by the "typhoid
state." This condition does not develop, however, in mild 01
abortive cases.

Defervescence is generally rapid, but is very variable in
duration and is accompanied, in favorable cases, by marked
diminution in the symptoms of toxaemia. Failure to show such
improvement when the temperature is falling in the usual wax-
is universally regarded as a most unfavorable sign. It is at
this stage or later that most of the deaths occur.

The duration of the fever was found by Murchison x to aver-
age between thirteen and fourteen days, in cases that recover.
In his fatal cases it averaged fourteen to fifteen days.

Material and Plan of Work

Several hundred cases were observed and of these over 100
were studied in detail. Autopsies were performed in twenty
cases. In three of these cases lesions of other diseases were
found and the evidence of typhus is not absolutely certain.
Many of the cases which came to autopsy were not under my
care during life, and regarding these cases I have little or no
clinical data.

Work was planned along the following lines: firstly, to ob-
serve the signs and symptoms with especial reference to diag-
nosis; secondly, to classify the varieties of the disease on the
basis of prominent symptoms; and thirdly, to determine the
cause of death as indicated by symptoms, autopsy findings, or
both, with the object of improving treatment.

Case reports have been appended to illustrate the observa-
tions made. These cases have been grouped under the follow-
ing heads:

1 Murchison: loc. cit.

116 CLINICAL OBSERVATIONS

(a) Typhus with recovery — 13 cases.

(6) Typhus followed by death — with autopsy — 20 cases.

(c) Typhus followed by death — no autopsy — 2 cases.

(d) Diagnostic problems — 7 cases.

An index and list of numbers has been provided. It precedes
the case reports. All case numbers mentioned in the text refer
to the illustrative cases.

Observations
I. Fever

Of the onset there is little to say. In two mild cases which
developed in the hospital the fever rose with moderate morn-
ing remissions, reached its maximum in four or five days, main-
tained a high level for a few days, and dropped by rapid lysis
with marked morning remissions to normal again. In these
cases the patient's strength returned quickly and convalescence
was short.

Ordinary cases differed from these in greater severity of
symptoms, more prolonged high fever, greater prostration, and
slower return of strength.

Statements of the patients about duration of illness were not
considered of much value because the patient was often too ill
to given an intelligent answer, because it was difficult to as-
certain whether he counted from the first symptoms or from
the time when he took to his bed, and because the stage of the
rash often indicated a probable duration which did not corre-
spond with the patient's story.

The temperatures were all taken by rectum by the nurses
and are, therefore, reliable.

Analysis of the charts shows that few patients were ill in the
ward for more than four or five days before the temperature
began to fall, showing that few were seen in the early stages.

The mean temperature before it began to fall varied in dif-
ferent cases from 102° to 105°; the greatest number having
fever of 103.5° to 104°.

The daily fluctuations of the temperature during the period
of high fever amounted, generally, to about one degree, and

TYPHUS IN SERBIA 1 17

seldom to more than two degrees. They were characterized by
morning remissions and evening exacerbations, and this

quence was rarely disturbed.

The defervescence was nearly always by lysis with marked
morning remissions. The duration of the lysis in different
cases varied considerably.

Out of twenty charts in which the defervescence proei c<\<><\
without interruption only two show the temperature dropping
to normal within twelve hours. In four the lysis was rapid, la-t-
ing in two cases for two days, and in two other cases for three
days. It lasted four days in five cases, five days in four cases, six
days in three cases, seven days in one case, and eight days in
one case. The proportion of cases with fever terminating by
crisis in twelve hours was considerably smaller than these
figures indicate. In fact, it was so unusual as to excite con-
siderable interest.

It has usually been stated by the older authors that typhus
fever terminates ordinarily by crisis, but many have since
denied that this is the case. The dispute results largely from
using the term crisis in different senses. To some of the older
writers it signified a rapid improvement in the patient's con-
dition, "a change so definite that one might name the day el-
even the hour when it began "; to others it signified a rapid fall
of temperature as compared with the gradual descent in ty-
phoid; and to this generation, more familiar with lobar pneu-
monia than with typhus, the word crisis has come to signify
a precipitate drop of temperature from the original high level
to normal or lower within less than twenty-four hours.

Two charts reproduced by Murchison l show gradual de-
scent of the fever, and two others rapid descent, the shortest
period of defervescence, however, being three days. That is to
say, the fever in all these cases ended by lysis.

He says of the temperature: " After attaining its maximum
there may be little change for several days, but some time be-
tween the seventh and tenth day, except in severe eases, there is
usually a slight remission, and then the temperature gradually

1 Murchison: loc. cit.

118 CLINICAL OBSERVATIONS

falls until about the fourteenth day, when it rapidly subsides
to about the normal standard. In a single night it may fall
from four to six degrees, but when there is pulmonary conges-
tion, the fall is slower. Occasionally an elevation of two or more
degrees precedes the final fall, and then a brief fall of moderate
amount may intervene between the final rise and the rapid
descent. This sudden fall of temperature about the fourteenth
day is peculiar to typhus and may be useful in diagnosis. Be-
fore attaining its maximum the daily variations of tempera-
ture are slight, but during the second week they may amount to
two degrees, the maximum being usually, but not always, in the
evening."

Curschmann,1 figures a series of charts which illustrate the
points made by Murchison.2 They show also great variations
in the length of defervescence.

As compared with typhoid, typhus shows a marked tend-
ency to rapid defervescence, but with lobar pneumonia as the
standard, the reverse is true.

Murchison 2 says that a remission is to be expected about the
seventh day; and Curschmann 3 observed remissions in some
cases a few days* before the beginning of the final defervescence.

None of my charts show this remission distinctly, but in
some of them a secondary rise of temperature gives the appear-
ance of an intercurrent relapse such as occurs in typhoid.
Relapse is believed to occur in typhus fever extremely rarely,
if at all. The secondary rises in my cases might be accounted
for by complications.

Sweating, more or less profuse, was not infrequently asso-
ciated with fall of temperature.

II. The Skin

The Eruption, according to Murchison,4 generally appears
on the fourth or fifth day.

In the few early cases that I saw, a scanty, pink, maculo-
papular rash was first discovered about the clavicles and on the

1 Curschmann: loc. cit. 3 Curschmann : loc. cit.

2 Murchison: loc. cit. 4 Murchison: loc. cit.

TYPHUS IN SERBIA 1 19

shoulders. On the succeeding day it was always widespread,

and could be found more or less abundantly on the trunk,
arms, legs, the backs of the hands and feet, and often on the,
palms and soles. It seemed to have do preference for flexor or
extensor surfaces, it did not spread progressively, dot did it
appear at intervals in crops, but it often became more abund-
ant on the third day than it had been on the second.

Careful examination of the mouth and pharynx failed to
show a definite eruption, but in a few cases several spoi
doubtful significance were seen.

On the forehead near the edge of the hair, and on the scalp in
several cases lesions were found which might either have be-
longed to the eruption or have been due to other causes. I siw
not a single patient with a definite rash on the face, nor do I
believe that any such occurred in the Lady Paget Hospital
while I was there. Dr. Sellards, however, told me that he saw a
pronounced eruption on the face in a fair-skinned patient in
Belgrade, and that in this case the character of the lesions was
the same on the face as on the body.

In the earliest stage the rash was rose pink, not dirty pink as
described by some authors. Subsequently its color changed to
red, then to purple in some cases and to rusty red in others.
Before disappearing the remnants turned to a faded, dirty
brown color. Most of the spots faded without leaving any pig-
ment behind, whereas others, the darker ones, and especially
those on the wrists, ankles, and backs of the hands, showed
purple or brown haemorrhagic pigment, which persisted for a
considerable number of days.

The remnants of the rash are rather characteristic but diffi-
cult to recognize with certainty when first seen at this stage.
and particularly so when, as is often the case, the patient's
body is sprinkled with minute ecchymoses resulting from flea
bites. These ecchymoses differ as described below from typical
typhus spots. Nevertheless, on the ground of this possible
error, I have excluded from the list of undoubted typhus cases
a considerable number that first came under observation at a
late stage.

120 CLINICAL OBSERVATIONS

The change in color of the rash seems to be due to two
causes: firstly, to increasing hyperaemia often followed by
lividity, and secondly, to the deposit of brownish pigment.
The amount of pigment was greater in the larger, elevated
spots than in the smaller ones or in the macules. It seemed to
be proportional to the degree of local congestion.

In the pink stage the color of the spots completely disap-
peared on pressure, in the red stage most of it disappeared
leaving a faint rusty tinge, but in the cases in which the erup-
tion became livid, pressure had little influence on the color of
the lesions.

The spots did not all change color at the same time or in the
same way. When the eruption was abundant, large pale pink,
smaller rose pink, rusty red, and purple spots might be mixed
together, and the predominance of one or another variety
determined the general color.

" Subcuticular mottling" or "marbling" of the skin has
been found by many observers associated with the spots and
has been considered by them to be a part of the typhus erup-
tion. It is clearly shown in the colored illustrations of Murchi-
son,1 Jenner,2 and Curschmann.3

In a few of my cases vague, pale pink blotches were ob-
served among the brighter spots at an early stage of the erup-
tion, but they did not give a definite marble-like effect. In
other instances the rash was so profuse that mottling could not
have been readily distinguished if present. In the majority of
the cases " subcuticular mottling" was looked for in vain, but
in the case of Series No. 61, when the eruption was in an early
stage and spots not very numerous, much pink mottling and
blotches of irregular outline were observed, and in the case of
Autopsy No. 25, a peculiar mottling was noted on the front of
the chest during life.

Not infrequently, in the period of nervous depression, the
limbs showed large, bluish, marble-like markings. They were
associated with duskiness of the skin and resembled ordinary
cutis mormorata. Probably they had nothing to do with the

1 Murchison: loc. cit. 2 Jenner: loc. cit. 3 Curschmann: loc. cit.

TYPHUS IN SERBIA 121

eruption but should be regarded as local circulatory phe-
nomena.

The typhus eruption is notoriously variable in appearance.
The pictures of Jenner,1 Murchison,2 and Curschmann show

many differences in detail.
The eruption in our cases was so carefully examined thai

typical marbling could scarcely have been overlooked had it
been visible when they arrived, but the dark skins of many of
our patients may have rendered it invisible. Moreover, it
seems probable that mottling or marbling is most distinct in the
early stages of the eruption and may even disappear altogether
after a few days. If this be so, failure to find it in more of our
cases can be explained on the ground that most of them were
not seen by us until the later stages indicated by the purple
phase of the rash.

The spots of the eruption were macular or papular and were
very slightly elevated. Generally, there were both macules and
papules, the latter having irregular, ill-defined margins. Some-
times they were confluent, often they were very close together.
When discrete they were roughly circular in shape. They varies 1
in size from about one to three or four mm. in diameter. The
variation was always considerable in the individual case, but in
some patients the larger, and in others the smaller, lesions pre-
dominated. In profuse eruptions the larger type generally
prevailed.

Dr. Smith showed me a patient in the early eruptive stage
whose skin was almost as dark as that of the average negro.
There was a profuse crop of small papular lesions clearly visible
on account of their elevation but scarcely perceptible by their
color. Papules were easily detected in many cases by palpation
when the elevation was almost imperceptible to the eye.

Murchison 2 and Jenner * say that the rash is elevated only at
first. This rule was not invariably true in my cases. On the
contrary the larger and darker papules often remained ele-
vated until the later stage when they had become haemor-
rhagic.

1 Jenner: loc. cit. 2 Murchison: loc. cit. ,; Curschmann: Loc. cit.

122 CLINICAL OBSERVATIONS

There seems to be a certain amount of confusion as to what is
meant by the terms "petechial" and " mulberry rash."

Murchison x quotes Wilson2 as follows: "When the san-
guineous spots (of purpura) are minute they are termed pe-
techiae," and it would seem, therefore, that this word should be
used to signify small haemorrhagic spots like those of purpura.
Keating's dictionary,3 on the other hand, says under the head
of petechiae: "It. petechio, ' flea bite.' Small reddish spots on
the skin like flea bites." Apparently the term has been used
variously by different authors, but it is as good as any we have
to describe the small haemorrhagic spots so common in typhus.

In typical cases the typhus eruption shows differences from
purpura which should be emphasized. The spots of purpura
are haemorrhagic from the beginning and sharply defined,
whereas those of typhus are neither.

The fresh flea bite is distinguishable from the pink maculo-
papule of the early eruption by the haemorrhagic point in its
center. The old flea bite differs from the petechial typhus
macule in being of a brighter red color, more circular in shape,
and in having a more sharply defined outline. Flea bites are
more uniform in size, and are distributed chiefly on the body
but typhus spots in the last stage generally show best on the
wrists, ankles, and on the backs of hands or feet. Flea bites,
however, may be so numerous on the body and limbs as
strongly to suggest a typhus eruption and the fact that, in
some cases, the typhus rash consists chiefly of small spots,
leaves an opening for error. I saw two cases sent to the hos-
pital with the diagnosis of typhus in which enormous numbers
of flea bites were scattered all over the body and limbs. One of
the patients probably did not have typhus, and in the other
case, the diagnosis remained in doubt owing to the difficulty of
distinguishing the eruption among the bites.

The term "mulberry rash" was first used by Jenner 4 who
says that " the spots " . . . " have a dusky , pinkish-red color,

1 Murchison: loc. cit.

2 Wilson: Dis. of the Skin, 3d ed., 1851, p. 337.

3 Keating: Diet, of Med., Phil., 1892.

4 Jenner: loc. cit.

TYPHUS IX SERBIA 123

somewhat like the stains of mulberry juice." The term 1 1
fore serves to describe cases of profuse eruption in the later

stages.

Hyperaemia. Coincident with the appearance of the rash,
and perhaps earlier, there was a hyperaemic flush which wag
most pronounced over the malar prominences and on the ears.

Later, the ears became bluish red, and the color in the malar
region dull red. This coloring was peculiar and rather char-
acteristic. It was considerably darker than the ordinary flush
of fever, less sharply circumscribed, and less transitory. It
often persisted well into the convalescent period.

Sometimes the hyperaemia extended mask-like across tin-
nose and cheeks and up to the eyes, and a separate patch was
seen over the end of the chin. In other cases, and particularly
in t^ie early stages of the rash, the entire face and neck were
hyperaemic, and the redness often extended in a V-shape on to
the upper part of the sternum. It showed a pronounced tend-
ency to be limited to the parts which had been exposed to the
sun, but in a few instances it was found also on the front of the
chest and shoulders. In one case it covered the greater parr < >f
the trunk.

In the later stages of fever, the flush which had been due to
active hyperaemia was replaced by congestion with cyanosis,
or by a leaden hue, in those about to die. In other cases the
malar flush persisted but the ears became cyanotic and the
rest of the face assumed a muddy tint with underlying pallor.

Pigmentation. Repeatedly the face was observed to be
decidedly browner in convalescence than it had been at the
time of admission to the hospital. This was noted not only in
those skins which had been darkened by exposure, but also in
several patients having light complexions. It seems probable
that the intense hyperaemia and prolonged congestion left
behind some pigmentation analogous to that following expo-
sure to the sun. The writer has found in the literature no
mention of such an increase of pigmentation.

The Taches Bleudtres were looked for but not found. Failure
to find them may have been due to the rather dark skins of most

124 CLINICAL OBSERVATIONS

of our patients. Not only were their skins originally dark in
most cases, but a multitude of bites and scratchings had added
to the pigmentation.

When there was more or less acne intermingled with an
eruption and a multitude of bites the picture was confusing.

Purpuric Spots were found singly in a few cases beneath the
finger nails or on the pads of the fingers during convalescence.
One of the latter developed into a small pustule.

Sudamina were frequently observed about the neck and
shoulders.

Yellowness of the palms of the hands was noted in two cases
late in the disease.

Herpes was observed repeatedly, most often on the ears,
several times about the nose or lips, and occasionally on other
parts of the face.

III. Circulatory Signs and Symptoms

Heart Rate and Pulse Rate. The pulse rate corresponded with
that of the heart except when the pulse was extremely weak.
In the case of Autopsy No. 23 on the last day of life such a dis-
crepancy occurred.

In the first half of the febrile period the pulse rate was low,
as a rule, in proportion to the temperature. It ranged most
often between the upper eighties and one hundred or slightly
higher with temperatures of 103° to 104°. Sometimes the pulse
rate remained low throughout the illness (Series No. 48). In
other cases, particularly in the sicker patients, the rate in-
creased gradually to 120 (Series No. 59) or higher. Most of the
patients whose pulse rate went above 130 died. Rates between
140 and 148 were counted, however, in a few patients who
recovered (Series Nos. 9 and 93). The pulse often followed the
temperature closely (Series Nos. 9, 61, and 93). In fatal cases
with a terminal rise of temperature the pulse usually followed
the temperature (Autopsy Nos. 18 and 25). Two patients dy-
ing with moderate fever had pulse rates that were relatively high
(Autopsy Nos. 23 and 24) on the last days.

An old man who died suddenly and unexpectedly with a

TYPHUS i\ SERBIA 126

temperature of 102.5° had a pulse rate of only 108. The au-
topsy showed a dilated heart with brownish, boA myocardium.

The myocardial change was believed to be due in lai
to chronic degeneration (Autopsy No. 20

With the decline of the fever, except in fatal cases, the pulse
became slower. Frequently, after several days or a week of
normal or subnormal temperature, there was a bradycardia
with rates between 44 and 64, which lasted for three or four
days. (Series Nos. 10 and 57.)

The bradycardia in Series No. 57 cannot be attributed to
digitalis because the patient received none. In Series No. 10
digitalis was used, but was omitted two days before the pulse
rate reached its lowest point. The digitalis may have caused it
in this case. It almost certainly did so in the case of Series No.
83, in which heart-block seems to have developed.

Jenner x observed that the bradycardia following fever was
brought about by lengthening of the diastolic pause and with-
out change in the first sound, but that bradycardia due to
cerebral conditions was characterized by a lengthened 6rst
sound and normal diastolic pause.

The disproportionate slowness of the pulse in relation to
temperature, so common in typhoid fever, was not marked in
my typhus cases. It was seen most often in the earlier stages i >f
the illness. It seldom persisted until the beginning of defer-
vescence.

Rhythm. With the exception of the supposed case of digitalis
block mentioned under bradycardia, pronounced changes in the
cardiac rhythm were not observed.

In most of the cases, however, in which the pulse became
very weak it was found to be markedly irregular in force and
slightly so in rhythm. A corresponding slight irregularity was
noted in the heart's action.

Murchison 2 shows a series of sphygmographic tracings oi
the pulse after Sanderson. Murchison's Figure 6 corresponds
to the bounding type of pulse. His Figure 7. which he calls
"the irregular pulse of irritative fever,"' corresponds to that

1 Jenner: loc. cit. 2 Murchison: loc oit.

126 CLINICAL OBSERVATIONS

above described as being irregular in force and rhythm, and
Figure 8, which he called the " irregular undulatory pulse of
advanced typhus," depicts the small, weak or "thready" type
of pulse. Measurement of this last tracing shows no variation
in rate but slight differences in size of the waves. These varia-
tions seem to indicate fluctuations in pressure.

In his chapter on acute febrile affections of the heart (on p.
280, Figs. 169 and 170), Mackenzie * gives illustrative tracings
of a type of irregularity which he attributed to failure of con-
tractility. He says that he found this kind of arrhythmia in all
his fatal cases of pneumonia. Murchison's 2 Figure 7 probably
illustrates the same condition.

Mackenzie's x Figure 176, p. 286, shows a rapid pulse which
is irregular in force but little, if at all, in rhythm. This type of
pulse, he says, is "usually associated with greatly relaxed ar-
teries, and a sphygmogram shows little or no sign of a dicrotic
wave, indicating great lowering of the pressure during diastole
of the heart." " Figures 172-176 show the characteristic fea-
tures of the pulse in acute fatal pneumonia in a young, pre-
viously strong and healthy child."

Apparently, Mackenzie believed that the tracings on pp.
280 and 286 of his book represent varieties of arrhythmia due to
the same cause, namely, to failure of contractility.

Hay 3 also figures an irregularity of force, without change in
rhythm (Fig. 119, p. 158 of his book), which he says is found in
"pneumonia, pericarditis, septic and other conditions, and in-
dicates a grave prognosis."

The existence of irregularity in force of beats was strikingly
demonstrated in the case of Series No. 10 on April 28 when, on
taking the blood-pressure by auscultation under the cuff, some
beats registered 90, others 70, and still others were not heard at
all. (See also Series No. 9.)

Premature systoles were heard occasionally in Series No. 92.

Heart Sounds. The commonest abnormality was faintness,
shortening, or blurring of the first sound. This was observed in

1 Mackenzie: Diseases of the Heart, 3d ed., Lond., 1913. 2 Murchison: loc. cit.
3 Hay: Graphic Methods in Heart Disease, Lond., 1909.

TYPHI s IX SKKBIA 127

practically every case, and was generally the earliest cl
develop and the last to disappear.

Inmost cases the second sound in the aortic ar< di-

minished, but, at the same time, that at the apex mighl be
accentuated. With the diminution in the second sound in tin-
aortic area that in the pulmonic area became relatively louder.
Sometimes it was definitely accentuated.

Normally loud, or even accentuated heart sound- sometimes
accompanied a small weak pulse, suggesting that the circula-
tory deficiency was to be attributed to loss of tone of the vascu-
lar system rather than to weakness of the heart. (Autopsy No.
24, June 16.)

It has long been believed that vascular dilatation may cause
circulatory weakness in typhoid fever. William Stokes ! in
1854 devoted a chapter to the heart in "typhus fever." In the
summary (par. 33) he says: "In certain cases of the worst
maculated typhus an excited state of the heart may exist
throughout the disease, although the pulse be feeble and the
extremities cold." This points to vascular dilatation.

His observations on the heart in fever are careful and in-
teresting, but lose some of their value from the fact that, al-
though recognizing symptomatic differences between typhoid,
typhus, and relapsing fevers, he believed them to be varieties of
the same disease, and did not always make it clear of which he
was speaking.

Stokes seems not to have appreciated the interrelation of
cardiac action and vascular tone.

Ortner 2 made an important contribution to this subject in a
study of typhoid fever in 1904. He states that "stronger"
cardiac action may compensate for diminished vascular tone,
and thus maintain the normal blood-pressure.

The case of Series No. 9 illustrates accentuated heart sounds
and small weak pulse followed on the next day by heart sounds
of poor quality and a weaker pulse. Prompt improvement after
an infusion of salt solution in this case points to the conclusion

1 Stokes: loc. cit.

2 Ortner: Verhandl. d. Cong. f. inn. Med., 1904, xxi, 255.

128 CLINICAL OBSERVATIONS

that the vessels were mainly at fault, but a subsequent infusion
brought out presumptive signs of cardiac weakness also.

In the case of Series No. 10 the heart sounds were never
good while the patient was under observation, the pulse was
always irregular in force, and heart dulness to the right be-
came increased. When drugs failed to act salt solution was
tried, but without much benefit. The second infusion was dis-
continued after a small quantity had been given because the
heart failed to respond satisfactorily. In this case, whether or
not there was vascular relaxation, the heart itself presumably
was weak. These facts point to myocardial as well as to vascu-
lar disturbances and perhaps to diminution of contractility as
suggested above.

Murmurs, systolic in time, were heard in many cases. Gen-
erally they were loudest in the pulmonic area and were not
transmitted to the axilla. They were believed to be of func-
tional origin.

Dilatation of the heart, evidenced by increase of dulness, was
observed in the case of Series No. 10 only. At autopsy dilata-
tion of the whole heart was found occasionally, but dilatation of
the right ventricle alone was more common. In other cases
there was no dilatation, and sometimes the heart was firmly
contracted.

The Pulse was often of the bounding type particularly in the
earlier part of the illness. Later it became small and softer.
In the severer cases it was small and weak or " thready" when
rapid. Occasionally, when it had been holding up well under
digitalis, it would suddenly go to pieces, and the patient would
seem to be in an alarming condition. After an injection of
strychnin, of camphor, or of ether, however, it often improved
promptly. This occurred once before anything had been ad-
ministered, so that it is doubtful what would have happened in
the other instances had nothing been done. Whether the phe-
nomenon was of cardiac or vascular origin is uncertain. In the
case of Autopsy No. 24 this condition recurred repeatedly.

There were other cases in which the pulse became weaker
gradually, and several of these responded well to intravenous

TYPHUS IN SERBIA 129

saline infusions. Sometimes the infusion had to be repe
in from 12 to 24 hours. It was used mosl often when alarming
weakness of the pulse persisted for some hours in spite of other
stimulants. When there were signs of deficient ingestion of
fluid, or after persistent diarrhoea, infusions were also used.

Pulses of poor quality often improved after the morning care
and feeding, remained pretty satisfactory through the day. and
weakened again in the evening. The nurses frequently re-
ported cases in which death seemed imminent during the night
although the condition during the day had been relatively
good. They used hot drinks, strychnin, and camphor freely. I
was often surprised in the morning to find patients still alive
whose condition the evening before had been anything but
encouraging.

In the case of Series No. 21, in which pulmonary symptoms
were prominent, the pulse was notably good until and even
after the death agony began. There was no autopsy.

Dicrotism, so common in typhoid fever, was looked for in all
my cases, but was never found fully developed. Curschmann 1
says that it is rare in typhus.

Blood-pressure readings both systolic and diastolic were
taken in most cases with the stethoscope below the cuff of the
sphygmomanometer. The systolic pressure showed a tendency
to fall gradually during the course of the disease. It was more
or less reduced in practically everj^ instance. It varied be-
tween the extreme limits of 75 and 125, but lay most often
between 95 and 110 mm. of mercury. In convalescence it
worked up again gradually.

The diastolic pressure level was generally between 60 and 75.
The limits of difference were 30 and 85. Sometimes there was a
marked reduction in diastolic pressure associated with a bound-
ing pulse. (Series Nos. 1 and 49.) In the case of Series No. 49
the diastolic pressure soon rose again, but in Series Nos. 1 and
59 it remained low while the high fever lasted. More often the
diastolic pressure was approximately proportional to the
systolic pressure, i.e., equal to about three-quarters of it.

1 Curschmann: loc. cit.

130 CLINICAL OBSERVATIONS

The case of Autopsy No. 24 showed a falling systolic and a
rising diastolic pressure.

The pulse pressure in general showed a gradual fall until the
beginning of convalescence. With the bounding type of pulse
it was large. In the case of Series No. 59 it dropped from 80 to
50 with a drop in systolic pressure from 125 to 95. During this
time the patient's condition was becoming progressively worse,
but his pulse remained relatively good in volume. The reverse
order took place in the case of Series No. 49. In this case, with
a falling temperature and general improvement, the diastolic
pressure rose from 50 to 70, and the systolic only from 105 to
110, so that again the pulse pressure was reduced. More com-
monly, in convalescence, the pulse pressure was increased by a
gradual and marked rise in systolic and little change in the
diastolic pressure. (Series No. 1.)

Several times in the later stages of the illness the Corrigan
type of pulse was noted. In a case in which this was observed
the blood-pressure was recorded at that time as 90 S-40 D.
No diastolic murmur was heard. In the case referred to under
Autopsy No. 5 with a similar pulse a diastolic murmur was
heard, but at autopsy no lesion of the valve was found to ex-
plain it.

Such murmurs have been explained on the basis of failure of
the aortic ring to contract, and a resulting relative insufficiency
of the aortic value.

Ortner * reported such a condition in a case of typhoid fever.

Summary

Clinical evidence, therefore, points to the existence of myo-
cardial as well as vascular disturbances in typhus.

A similar conclusion was reached by Ortner 1 in regard to
typhoid fever.

Myocardial weakness appears to be decidedly more fre-
quent, however, in typhus than in typhoid fever.

1 Ortner: loc. cit.

TYPHUS IN SKIMilA 131

IV. Pathology of the Circulatory SysU m

The heart in our scries of twenty autopsy cases presented a
variety of conditions ranging from softness to firmness of the

muscle, and from a state of general font taction to one of general
dilatation of the chambers. The intermediate condition un-
represented by hearts in which the left ventricle was con-
tracted and the right ventricle dilated or relaxed. Firmn<
the muscle and contraction of the cavities generally went to-
gether, but in some of the contracted hearts the muscle was
soft. It was soft, also, in all the dilated hearts, and in some of
these it was pale in color.

Engorgement of the great vessels with blood was noted
specifically in two cases in which the heart was soft, and in two
in which it was contracted. Probably there was engorgement
also in other cases in which it was not specifically noted. This
engorgement seems not to have borne a definite relation either
to softness or to dilatation of the heart.

Marked passive congestion of the lungs was found in eleven
cases, but dilatation of the whole heart or of the right ventricle
alone was observed in only six cases. In other words, passive
congestion of the lungs bore no obvious relation to dilatation
of the heart.

Of the cases with dilated hearts one died in the period of ner-
vous depression, one during defervescence or later, and one in
the postfebrile period.

Of the three cases with dilated right ventricles one died
at the end of the period of nervous excitement, one in the
postfebrile period, and one at an intermediate stage of the
disease.

The two patients that showed merely relaxation of the right
ventricle without dilatation died in the postfebrile period.

The cases permit of no deductions as to the frequency of
cardiac dilatation in the stage of nervous excitement because
there was only one death at that stage but, of the six cases
above mentioned in which more or less dilatation was found.
half of them died in the postfebrile period.

132 CLINICAL OBSERVATIONS

The relation of cardiac dilatation to symptoms may be
worthy of investigation. In the case of Autopsy No. 5 there
was slight dilatation and flabbiness of the muscle, but the pulse
was relatively good until the day of the patient's death. The
symptoms were those of cerebral toxaemia and exhaustion. In
the case of Autopsy No. 12 the presenting symptom was coma
associated with a soft and irregular pulse; and in the case re-
ferred to under Autopsy No. 22 weakness of the pulse was the
only striking symptom for several days before death. There
were no important complications in any of these cases. In the
first of them the pulse gave no warning, by feebleness or irregu-
larity, of weakness of the heart muscle. In the other two cases
there was weakness and irregularity of the pulse.

The cases of Autopsy Nos. 6, 9, and 13 showed dilatation of
the right ventricle. In that of No. 6 an old mitral stenosis was
found. The violent delirium of No. 9 gave every reason to ex-
pect cardiac dilatation to develop even though the pulse was
full and strong at first. In the case of No. 13 cardiac dilatation
might have been inferred from the fact that the patient died in
an attack of dyspnoea and distress.

The number of cases is too small to admit of safe deductions
as to the relation of dilatation to symptoms. The same may be
said of it as a possible factor in causing death.

The only other case in which either clinical or pathological
evidence points to cardiac death is that of Autopsy No. 20.
In this case there was weakness of the pulse and myocardial
changes were found which seemed to be chronic, but the heart
was not dilated. This patient died very suddenly.

If it be assumed that dilatation of the whole heart, or of the
right ventricle, only found at autopsy, is evidence that cardiac
weakness was an important cause of death in these cases and
add to them the one last mentioned, it may be inferred that
cardiac weakness was largely responsible for death in seven of
the twenty cases autopsied.

But, if we subtract from these cases the one in which an old
mitral stenosis of extreme degree was found, and the last case
in which the myocardial changes seemed to be chronic, there

TYPHUS IN SERBIA

remain five fuses in which acute myocardial weakn<
have led to cardiac dilatation and death.

Three of these five, however, died in the postfebrile period in
a state of emaciation and exhaustion from which they were
unable to rally. Would it not be reasonable in thes*
to suppose that death was due chiefly to general exhaustion
rather than to the nature or degree of the changes in the h<
muscle ?

This view receives some support from the histological find-
ings of Dr. Mallory. His studies of the pathological material,
however, are not completed at the present writing, but sections
have been examined from nine hearts selected to include some
that were soft and dilated and others that were firmly con-
tracted. Dr. Mallory says that slight fatty degeneration and
small foci of cellular infiltration exist in all of these hearts to
about the same degree, but that these changes are much less
extensive than are usual in cases of diphtheria.

The evidence at hand seems to show that acute myocardial dam-
age is seldom the most important factor in death from typhus.

Nevertheless, circulatory phenomena such as cyanosis,
lividity, coldness of the extremities, and a pulse which is small.
soft, and unequal or irregular are so common in typhus cases
and develop so often a number of da}rs before death, and low
blood-pressure, small pulse pressure, and modification in the
heart sounds are so constant in the severe cases of typhus that it
seems impossible to escape the conviction that circulatory abnormal-
ities are of great importance and that they arc a frequent imme-
diate or contributory cause of death.

The two italicized conclusions are reconcilable if the circula-
tory abnormalities be attributed less to myocardial lesions
than to loss of vascular tone associated with dilatation o\ the
vessels. Lesions in the walls of the blood-vessels, or the direct
effect of toxins upon them, or the indirect influence of exhaus-
tion, or perhaps a combination of influences acting on the
vasomotor mechanism might bring about the dilatation.

Following this hypothesis deaths occurring before tJie period of
defervescence may be attributed to toxaemia with resulting disturb-

134 CLINICAL OBSERVATIONS

ances of the vascular circulation; and later deaths could be ex-
plained as due primarily to general exhaustion and secondarily to
vascular lesions or functional circulatory derangements.

My clinical observations accord well with this hypothesis,
and, therefore, exhaustion was assigned as the principal cause
of death in six of the seven cases in which death occurred in the
postfebrile period. In the seventh case death was due to severe
secondary infection.

In the cases that died earlier the toxaemia affected different
systems in varying degrees. The case of Series No. 87, in which
there was no autopsy, showed cerebral, pulmonary, and circu-
latory disturbances in a high degree. This case seems to be an
instance of severe general toxaemia with incidental circulatory
derangement. For two days before death weakness and rapid-
ity of the pulse was the most alarming sign. In the case of
Autopsy No. 24, on the other hand, exhaustion was followed
late in the disease by circulatory weakness, and in that of
Autopsy No. 9 cerebral toxaemia causing violent delirium was
followed early by physical exhaustion, the pulse having been
good during the period of delirious activity.

The first part of the aorta, in a large proportion of cases,
showed a few small, soft, yellowish spots. Whether or not they
developed in the course of the typhus or were there before it
began is doubtful.

Murchison 1 says: — "In a large number of cases, the mus-
cular tissue of the heart is flabby, soft, and easily torn.". . .
"The softening is independent of the duration of the disease,
the age of the patient, the external temperature, or the interval
since death. In many cases it is confined to the left side of the
heart."

Curschmann,2 on the other hand, says: — "There is almost
always unilateral dilatation of the heart. In cases where death
occurs relatively early, the muscle is flabby, friable, dull, and of a
yellowish red color, with occasional reddish streaks and linear
and punctate markings. We unquestionably have to deal with
the form of infectious myocarditis that has recently been

1 Murchison: loc. cit. 2 Curschmann: loc. cit.

TYPHI H IN SKKIilA L35

studied by the aid of modern microscopic technic in typhoid

fever, scarlet fever, diphtheria, etc."

The histological changes, according to Moore,1 are cloudy
swelling and granular, fatty degeneration in the heart in'.
Hyaline degeneration and necrosis of the inner coaU of tfu small
vessels in the skin were observed by Prowazek.

The fact that in ten out of twenty of our autopsy cases the
heart was found contracted and that the muscle of the left
ventricle was soft in only two of these cases is of interest in rela-
tion to Murchison's 2 experience. In one of our cases the right
ventricle was dilated and in two it was relaxed. Autopsy No.
9, the only case in which death occurred relatively early,
showed softness of the muscle and dilatation of the right
ventricle such as Curschmann's 3 statement would lead one to
expect.

The theory which regards circulatory disturbances of vas-
cular origin as an important cause of death receives some sup-
port from the findings of Prowazek.4

Summary

Lesions have been found in both heart and vessels in typhus.
Clinical signs point to weakness of the heart in some cases, and
to vascular dilatation in others. Most often the symptoms
point to a combination of cardiac weakness and vascular dilata-
tion.

The observations of Stokes 5 and of Jenner 6 in typhus and
other fevers, the clinical work of Curschmann ' and of Ortner B
in typhoid, Wiesel's 9 histological studies of the heart and blood-
vessels in typhoid, and the experiments of Stejskal10 and of
Romberg's11 pupils with toxic substances, and the study of the
pathology of the heart in diphtheria by Councilman. Mallory.

1 Moore: loc. cit. 6 Stokes: loc. cit.

2 Murchison: loc. cit. 6 Jenner: loc. cit.

3 Curschmann: loc. cit. 7 Curschmann: loc. cit.

4 Prowazek: loc. cit. 8 Ortner: loc. cit.
9 Wiesel: Prag. Ztschr. f. Heilk., 1905, xxvi. 107.

10 Stejskal: Ztschr. f. klin. Med., 1902, xliv, 367; 1903, li. 129.

11 Romberg: Deut. Arch. f. klin. Med., 1S99, lxiv. 632

136 CLINICAL OBSERVATIONS

and Pearce * are of special interest in connection with the
problem. •

Tests of the functional capacity of the vasomotor mechanism
and of the heart muscle have recently been performed by Por-
ter and Newburgh 2 in experimental pneumonia, and Means 3
has studied the respiratory mechanism in pneumonia. The
work of these riien is extremely significant, throwing further
light, as it does, on the nature of these circulatory changes.

V. Blood

Counts of the red and white cells, differential counts, ex-
amination of blood smears, and Widal tests were performed
by Dr. Sellards, and have been discussed by him in another
paper.

Dr. Sellards also made haemoglobin determinations of blood
from the ear with Sahli's instrument. In some instances the
percentages found were far above normal.

My own estimations were made with the Tallquist scale
which is not adapted for abnormally high concentrations. In
some cases it was evident that the blood was darker in color
than the 100 per cent shade of the scale, and, accordingly,
the observation was recorded as 110 per cent or 100 per
cent plus.

Determinations by both the Tallquist and Sahli methods
have been recorded on the charts of the illustrative cases.

There were marked differences in the results of the two
methods. In an extreme instance of this sort the Sahli reading
was 135 per cent and the Tallquist reading 85 per cent on the
same day. More often, high color of the blood was recognized
by means of the Tallquist scale and recorded as 110 per cent or
100 per cent plus, but the Sahli estimations were doubtless

1 Councilman, Mallory, and Pearce: "Diphth. pathology of incl. heart." Jour. Bos-
ton Soc. Med. Sc, 1900, v, 139.

2 Porter and Newburgh: Am. Jour. Physiol., 1908, xxiii, 131; Boston Med. and Surg.
Jour., 1908, clviii, 73; Am. Jour. Physiol., 1914, xxxv, 1; Am. Jour. Med. Sc, 1915, cxlix,
204; Jour. Exper. Med., 1915, xxii, 123; Am. Jour. Physiol., 1915, xxxvi, 418.

3 Means, Newburgh, and Porter: Boston Med. and Surg. Jour., 1915, clxxiii, 742;
ibid., 1916, clxxiv, 464.

TYPHUS IN SERBIA 137

more accurate. Discrepancies may be explained in pari by tin-
fact that estimates by the two method- were never made
simultaneously and local circulatory changes may have oc-
curred in the interval.

High haemoglobin percentages with more or less increase of
the red count were obtained in the cases of Series Xos. '.) and 10.
These were among a group of patients that had spent n
days on the train before reaching the hospital. All of them
were not only markedly emaciated, but they also presented a
dried up appearance as if they had not received sufficient fluid.
Their high red counts might, therefore, be accounted for on the
basis of dehydration of the blood as a whole. The estimate of
haemoglobin of 135 per cent above mentioned may have been
due to similar causes.

Another possible explanation for high red counts combined
with high haemoglobin is irregular distribution with local ac-
cumulation of red cells. The frequent occurrence of marked
local hyperaemia, often associated with slight cyanosis of the
ears, favors this hypothesis as the more probable in some cases,
if not in all.

Authority for such an hypothesis is provided by Cabot,1
Wood,2 and Sahli.3

Increase of the color indices is not so easily explainable. The
indices were 1.13 in No. 9, and 1.10 in No. 10, the cases cited
above. In Series No. 47 with a normal red count the index was
approximately 1.15. In Series Nos. 1 and 57, although the red
counts were slightly low, the indices were still higher. They were
respectively 1.75, and approximately 1.30.

In the days when bleeding was practised as a routine in fever
it was observed that the blood of typhus patients was ab-
normally dark in color and slow to clot. Dark color and
fluidity of the blood at autops3T has been commented upon
repeatedly, and was observed also by us. The question suggests
itself as to whether methaemoglobin is formed in typhus. The

1 Cabot: Clin. Exam, of the Blood, X. Y., 1901, p. 75.

2 Wood- Chem. and Mic. Diag., N. Y., 1909, p. 127.

3 Sahli: Diag. Methods, Trans., Phil.. 1905. p. 628.

138 CLINICAL OBSERVATIONS

studies of Peabody l with the pneumococcus suggests that this
may be the case. If so, a high color index could be attributed
to the presence of methaemoglobin.

Repeated haemoglobin estimations by the Tallquist scale in-
dicated that a slight anaemia develops in the later stages of
typhus. Pallor during convalescence lent support to this view,
and Curschmann 2 states that diminution of red count and of
haemoglobin is found at the height of the fever and during
convalescence.

VI. Respiratory Signs and Symptoms

Epistaxis was observed several times at the height of the
disease (Series No. 21). Slight bleeding during convalescence
was evidently caused, in one instance, by picking the nose
which was ulcerated from herpes. Murchison 3 says that
epistaxis is rare in typhus. Certainly, it is not so commonly an
early symptom as in typhoid.

Pharynx and Tonsils. Reddening of the pharynx, the pillars
of the fauces, and the tonsils, with slight swelling of the latter,
seems to be common in the earlier stages of typhus. Pro-
nounced catarrh of the pharynx associated with accumulation
of tenacious sticky mucus which clogs the patient's throat and
which is difficult for him to expel is a later condition. Toward
the end of the period of high fever dried mucus is often seen
adhering to the pharynx and giving it a glazed appearance.

The Larynx was seriously affected in only one of my pa-
tients. He was very ill when I first saw him and could scarcely
make a sound. Later, he developed peculiar sepulchral tones.
The voice was husky throughout convalescence but the sub-
sequent recovery was complete.

In several other cases slight hoarseness was observed. None
had obstructing oedema. Oedema of the larynx is one of the
recognized dangers in typhus fever.

Lungs. Signs varied from those of slight passive congestion

1 Peabody: Jour. Exp. Med., 1913, xvii, 587; 1913, xviii, 1 and 7.

2 Curschmann: loc. cit.

3 Murchison : loc. cit.

TYPHUS IN SERBIA

of the bases to evidence of rapidly developing, genera

oedema. Bronchitis was slight or severe. Lobular and 1
pneumonia were observed. Pain in the chest, probably pleu-
ritic, was not uncommon, but no perfectly characteristic fric-
tion rub was heard, and pleural effusion was neither diajnmx-d
nor found at autopsy.

Bfonchitis. Autopsy generally showed the bronchial muc
slightly swollen, injected, and bathed in glairy, sticky, blood-
stained mucus. In other cases the bronchial secretion was
mucopurulent.

Bronchitic rales were found in almost every case sooner or
later. They increased as the fever advanced. They were scat-
tered bilaterally throughout the chest. The rales, as a rule,
were of the coarse, moist type; but piping rales were heard fre-
quently. When the bronchitis was pronounced, sonorous
rhonchi and fine moist rales were often present. The rhonchi
could be heard all over the chest, but especially in the upper
part; and the fine rales were generally limited to the bases,
indicating that passive congestion was superimposed upon the
bronchitis.

Passive Congestion was not found clinically except in the
severer cases, and in these it was obscured by the bronchitis.
Good nursing, I think, kept it at a minimum. In fatal <
which came to autopsy, however, passive congestion was found
nearly always, and sometimes it was extreme.

Pneumonia, as a complication, was diagnosed at first on the
basis of rapid, shallow, and labored breathing associated with
inspiratory extension of the nostrils, use of the accessory
muscles of respiration, and rather indefinite signs of consolida-
tion consisting of slight dulness and distant bronchial breath-
ing. The autopsy findings in some of these cases, however,
were not typical of pneumonia, so that this diagnosis was later
made with more reserve. This subject is again discussed under
" Complications. ' '

Atelectasis of small portions of the lung was found in several
autopsies and may have explained some of the signs attributed
to pneumonia.

140 CLINICAL OBSERVATIONS

Respiration. Movement of the nostrils and rapid but easy
breathing was sometimes observed when there was no passive
congestion and little if any bronchitis. In such cases the rapid
breathing has been attributed by most authors to the action of
toxins. Dissociation between the rates of pulse and respiration
in typhus has been observed by many. Methaemoglobinaemia,
if present, may have been a factor, and the question of acidosis
requires consideration.

In other cases in which the breathing was rapid and labored,
extensive bronchitis, or congestion, or both seemed to be the
essential factors in its production. Series Nos. 21 and 87 died,
apparently, by gradual drowning: which seems also to happen
in some cases of pneumonia. There was no autopsy in either
of these cases so that pneumonia cannot be excluded. Exten-
sive pulmonary oedema existed undoubtedly in both cases.
These patients were obliged to struggle for breath for several
days before death, without rest or sleep.

The Sputum in cases of this sort was extremely viscid and
could be expelled by the patient only with the greatest diffi-
culty. It was often blood streaked. In other cases with mani-
fest bronchitis it was mucopurulent or purulent.

Pulmonary symptoms were far more prominent in my typhus
patients than they commonly are in typhoid or in any other dis-
ease with which I am familiar, except pneumonia. Pneumonia
as a complication is discussed below.

Cough was a constant symptom. In many cases it was dis-
tressing not only by its frequency but also because of the effort
required to expel the sticky secretion. Sometimes the patient
almost choked in the process.

The Sputum, as a rule, was mucoid, tenacious, sometimes
frothy, and often tinged or streaked with blood. At first it was
glairy, later whitish, yellowish, or mucopurulent. Occasionally
it was purulent, but this was due, probably, to a well-marked
complicating bronchitis. Microscopical examinations were
made in three cases in which pulmonary complications existed.

For several days one of these patients lay propped up in bed,
the accessory muscles brought actively into play, and the

TYPHUS IN SERBIA 1 II

breathing rapid and laborious. The sputum wm abundant,

mucopurulent, and contained influenza-like bacilli and M
coccus catarrhalis in large numbers, as well as a few pneuim »c
and some large bacilli. Bronchopneumonia almost certainly
existed in this case.

The sputum in the case of Series No. 93 consisted of very
viscid, thick, whitish mucus, and contained few Leucocytes.
There were many pneumococci and various other bacteria,
among them a few influenza-like bacilli and spirochaetae. At
times the sputum was foul-smelling and purulent but never
copious, and a secondary rise of temperature occurred when the
pulmonary symptoms became most marked. Gangrene and
bronchiectasis were considered, but inasmuch as the cough and
expectoration cleared up later it was probably a case of bron-
chitis and bronchopneumonia with retained secretion.

A third patient (Series No. 59) undoubtedly had pulmonary
gangrene. A large quantity of frothy, tenacious sputum which
later became extremely offensive was brought up in fits of
laborious, spasmodic coughing during convalescence. Signs of
trouble were found at the right base and there was pain in this
region. The sputum contained great numbers of influenza-like
bacilli, a few pneumococci, and bacteria of other kinds. Re-
covery was slow.

Tubercle bacilli were looked for in these cases but none were
found.

VII. Pathology of the Respiratory System

The more severe lesions found at autopsy are described lie-
low under " Complications and Sequelae."

Bronchitis with swelling and redness of the mucous mem-
brane has been described by others and is probably present in
most severe cases of typhus.

Passive congestion was found in most of our fatal cases, but
not invariably. There was none in the case of Autopsy No. 21.

Series No. 21, in which there was no autopsy, certainly died
from asphyxia preceded by gradually increasing bronchitis,
and pulmonary oedema. Perhaps there was pneumonia as well.
Just before death the pulse was remarkably full and strong.

142 CLINICAL OBSERVATIONS

This was due probably to the rise of blood-pressure which
usually accompanies asphyxia.

Wiener found lobar, lobular, or "hypostatic" pneumonia in
one-third of his 39 autopsies. He mentions finding petechial
haemorrhages in the larynx and large bronchi. To these he
attributed the bloody sputum of some cases.

Bronchitis and pulmonary congestion in typhus seem seldom
to result in death unless there is marked circulatory disorder,
severe general toxaemia, extreme exhaustion, or pneumonia as
well. Series No. 21 was unique among our cases in this respect.

There seem to be several varieties of pulmonary congestion.
Sometimes it is chiefly of the hypostatic or passive type. In
other cases it is localized in circumscribed areas and is intensely
haemorrhagic in character suggesting that lobar pneumonia
was developing. In still other cases in which congestion was not
localized, the secretion was so viscid as to point to inflammation
rather than passive congestion as its cause. In these cases it
seemed to result from an intense bronchitis. These three types
of process were often so intermingled as to render interpreta-
tion of the findings difficult (see "Pulmonary Complications'').

The findings of Means, Newburgh, and Porter 1 in experi-
mental pneumonia may have counterparts in typhus. If so,
disturbances of the respiratory mechanism may play an im-
portant part in producing serious symptoms or death in typhus,
and perhaps, some of the circulatory disturbances are second-
ary to disorders of respiration.

Peabody's 2 discovery of methaemoglobin in the blood of
severe cases of pneumonia suggests that it may be formed also
in typhus, and that it may explain the existence of cyanosis or
dusky discoloration of the face in some cases in which the con-
dition of the lungs and general circulation do not seem to
warrant the change in color.

VIII. Digestive System: Signs and Symptoms

The Tongue was always coated, white at first, becoming later
brown, dry, and often cracked. This is the "parrot tongue" of

1 Means, Newburgh, and Porter: loc. cit. 2 Peabody: loc. cit.

TYi'ins ix si;i;i',i.\ 1 13

typhus. During convalescence it turned red along tl
first.

Brown Sordes accumulated with great rapidity on the teeth)
so much so that in very sick patients it was practically impos-
sible for the nurses to keep the mouth clean for an hour.

Anorexia was marked, as a rule, while the fever remained
high, but appetite often began to return early in defervescence,
and was generally good before the end of the febrile period.
Many patients at this stage would sit up in bed and beg for
more black bread when they were already receiving the usual
amount and much other nourishment.

Vomiting of greenish bile occurred in a few cases. It was
persistent only in one case (Series No. 57). No special cause
was found for the symptom.

Haematemesis was observed once. It did not recur, nor was it
followed by other gastric symptoms.

Abdomen. Pain was seldom complained of, but slight gen-
eralized sensitiveness to firm pressure was common. Gerhard ■
says that abdominal sensitiveness in typhus is usually a mani-
festation of a general hyperalgesia of the muscles or skin. This
was true in some of my cases, but, as a rule, I think the sensi-
tiveness was local.

The abdomen, generally, was flat or concave and quite unlike
the doughy, slightly distended abdomen of typhoid.

Meteorism was unusual. It occurred in a few of the sicker
patients who recovered and in a number of fatal cases (Series
No. 87, death but no autopsy).

Pain and swelling in the lower abdomen resulting from over-
distention of the bladder was seen in several cases (Series No. 9
and Autopsy No. 24).

Gurgling in the right iliac fossa was noted in two cas -
Murchison2 says that it is quite exceptional in typhus, and
that when it does occur it is not limited to the right iliac fossa.
and that it is associated with diarrhoea. One of my eases does
not bear out this statement, for this patient had no diarrhoea.
However, the gurgling may have been due to the transit ory

1 Gerhard: loc. cit. 2 Murehison : loc. cit.

144 CLINICAL OBSERVATIONS

effect of a cathartic. In Series No. 57 the gurgling was most
marked in the right iliac fossa, but was not limited to that re-
gion. Here, again, there was no diarrhoea.

The Stools that I saw were dark colored, fluid, and rather uni-
form in appearance. A nurse told me that they were always
liquid, but this may have been due to free use of cathartics, for
Murchison x says that when the bowels move spontaneously
without medicine the stools are usually of normal consistency
and color.

Diarrhoea was pronounced in a few cases and slight in others.
It began most often with the first indications of defervescence
and lasted, as a rule, only two or three days. Series No. 59 had
exceptional looseness of the bowels. The day before the crisis
when his condition was desperate, they moved seven times.
The diarrhoea continued for a considerable number of days and
required opium to control it. A patient of Dr. Smith's that I
did not think could live another day developed a severe
diarrhoea coincident with the beginning of convalescence.
Several fatal cases also had diarrhoea (Autopsy No. 24), and
it was troublesome in Series No. 93.

The Spleen was felt in a small proportion of cases only. In a
larger proportion there was increase of dulness in the splenic
region. Adding together these two groups of cases and assum-
ing that the increase of dulness was due to splenic enlargement,
there was evidence of enlargement at the first examination in
about half the cases. When not palpable at first the spleen was
not felt later. Curschmann 2 says that the " enlargement rarely
exceeds a moderate degree, and the consistence of the organ is,
on the average, less than in other infectious diseases." He be-
lieves that the spleen can be felt, however, in most cases if
examined early enough; that the enlargement comes with the
first symptoms and that it generally disappears before the
beginning of defervescence. Failure to feel the spleen may be
accounted for in some cases probably by extreme softness of the
organ, and in other cases because it may no longer be enlarged
when the patient is first seen at a late stage of the disease.

1 Murchison: loc. cit. 2 Curschmann: loc. cit.

TYPHI'S IX SERBIA 1 15

The Liver edge was felt in a few cjisc.- There ws& never much
enlargement.

In 1861 Barrallier1 (quoted by Murchison*) found slight en-
largement of the liver in 30.6 per cent of 365 cas< ».

Jaundice is not mentioned by Murchison - but Michie
found "slight haematogenous jaundice" in cases of Mexican
typhus, and Michaud 4 saw five cases of jaundice associ
with enlargement of the liver among fifty-eight case- oi
European typhus. He found urobilinuria in twenty-one cases
of the same series. Wiener 5 says that he saw jaundice fre-
quently in Hungary. Repeated tests for bile in high-colored
urines from our cases were negative, nor was jaundice observed
in any of them.

Intestinal Parasites. An ascaris was vomited up by several
patients.

IX. Pathology of the Digestive System

Intestines. With the exception of a few minute ecchymoses
found occasionally on the serous surfaces, and marked disten-
tion of the stomach, colon, or intestines in a few instances,
nothing abnormal was observed.

Autopsy No. 26, however, in which endocarditis was found
and the diagnosis of typhus uncertain, showed many minute
red dots on the mucosa at the lower end of the ileum.

Wiener 5 says that haemorrhages in the submucosa of the
colon can often be seen from without, that they are dark red.
generally sharply circumscribed and paler at the edges. They
varied much in size, and the extravasation sometimes extended
all over the colon. Ecchymoses in or on the intestines have
been described also by others.

Gastou 6 found the mucosa of the intestines and especially
that of the colon congested, the folds prominent, and the walls
thickened.

The Liver often showed nutmeg markings. Sometimes it was

1 Barrallier: Du typhus epideroique a Toulon, Paris, 1861.

2 Murchison: loc. cit. •' Wiener: loc. cit.

3 Michie: loc. cit. 6 Gastou: loc. cit.

4 Michaud: loc. cit.

146 CLINICAL OBSERVATIONS

dark colored and engorged with blood. In other cases it
seemed to show more or less fatty degeneration. Its size was
normal or slightly increased.

The Spleen was generally enlarged, sometimes much enlarged
and very soft. In a few cases it was firm and of normal size.

X. The Nervous System: Signs and Symptoms

Mental States. The facial expression varied between individ-
uals and at different stages of the disease. It most often ex-
pressed stolid patience, indifference, or lethargy until toward
the end of defervescence, when the patients began to ask for
more food or to be allowed to go home. Those that were not
very toxic were less somnolent than is the rule in typhoid. As
the disease advanced the features became sharp and drawn.

In a group of about forty patients who entered my wards at
about the same time, after having spent many hours, if not days,
in transit, probably with little care, scanty food, and insuffi-
cient water, the expressions were strikingly alike. The face was
pinched, the malar flush pronounced, the brows knitted im-
movably as if by pain long endured, and the eyes were watchful
but showed no sign of emotion. The patients made no sound,
nor moved at all in bed. They submitted passively to being
examined, and although fully conscious, gave no sign of interest
in what was being done.

Particularly in the days immediately preceding defervescence
the mentality was clouded, and there was usually quiet de-
lirium at night if not in the daytime. Many cases of this sort
had carphology, subsultus, and intention tremor of the hands,
and in some cases of severe toxaemia, twitching of the jaw and
facial muscles was observed. Twitching of the arm muscles was
brought on at times by passive motion of a limb or by taking
the blood-pressure.

A Russian medical student (Series No. 87) who showed all of
these symptoms retained enough understanding to grab for his
chart when it was being examined before him. Later he be-
came completely delirious, and died after a few days. Con-
trasting with this case was that of a Serbian officer (Series No.

TYPHIS IN SKRBIA 1 17

21) who apparently appreciated hie condition to the end ff
nervous system showed little outward sign of Intoxication.

Series No. 9 was somnolent on admission and later fell into
a stupor but was never completely comatose. Thifi <
complicated by nephritis, but the patient recovered. A
case of Dr. Holmes' (Autopsy No. 12) was in deep coma foi
about two days before death. The kidneys showed *
abnormalities.

Stupor verging on coma was the rule in the sicker patients
even in the absence of renal lesions, and few patient- in which
it was pronounced got well.

The typhoid state with fatal issue was well illustrated in the
case of Autopsy No. 24.

Series No. 61 was troublesome by trying to leave the ward.
He was not violent or excited except during one night when he
had to be tied in bed.

Dr. Smith had a case of wild delirium analogous in all re-
spects to delirium tremens. This patient slept only when ex-
hausted. His pulse was very full and bounding at first, but he
died apparently from pulmonary oedema or beginning pneu-
monia with cardiac dilatation.

A patient of mine (Autopsy No. 25) was somnolent but easily
aroused. For days he refused food and medicine and drank
scarcely any liquid. This condition persisted even when the
temperature was down to normal.

Hyperemotionalism during the febrile period was illustrated
by a man of middle age who was extremely thin and feeble
when admitted. He begged tearfully to be sent home, and ap-
parently expected to die, but he recovered. During conva-
lescence normal control and cheerfulness returned quickly as a
rule.

Early in defervescence nervous symptoms began to diminish
and the appetite to return in favorable cases. When a change
for the better was not coincident with a fall of temperature, the
outlook was very unfavorable. Recovery of cheerfulness and
mental activity was often astonishingly rapid, but in a few
cases intellectual lethargy was persistent.

148 CLINICAL OBSERVATIONS

Marked intellectual debility and lack of control was seen in
the case of a nurse returning home some weeks after typhus.
Another nurse had hysterical tremor, emotionalism, and
speech disturbance which persisted for weeks. In this case a
perinephritic abscess was discovered and when it had been
drained the symptoms passed off. Her attack of typhus had
been mild. Hysteria was seen also in a man, a big Serbian, who
was convalescent and doing well and who happened to have old
suppurating glands of the neck. He developed tremor, lame-
ness, and became very apprehensive after seeing a patient
operated on for parotitis. He was relieved temporarily by the
simplest suggestive methods but under like circumstances the
symptoms recurred (Series No. 48) .

Frontal headache was almost invariably complained of in the
earlier stages of the fever. It lasted several days and did not
return. Sometimes, also, there was pain in the eyes or at the
nape of the neck.

Stiffness of the Neck and Kernig's Sign were found in a large
number of cases. In a series of thirty-one cases the neck was
stiff in all but three. The stiffness was slight in twenty-one
cases and moderate or marked in seven cases.

Kernig's Sign in the same series was absent in three cases,
present on one side only in one case, slight in twenty-three
cases, and moderately developed in four cases. In one case
the neck was moderately stiff but there was no Kernig's
sign, in another there was a slight Kernig's sign but the neck
was not stiff, and in two cases neither sign was found. The
stiffness was due to muscular spasm, but could not be ac-
counted for by sensitiveness of the muscles because this was
much less common than spasm, and was often entirely absent in
the presence of spasm. The spasm was seldom so pronounced as
is usual in meningitis. It was attributed to meningeal irritation.
Stiffness of neck or legs was observed also in a few cases of
disease which may have been mild typhus but which were not
so considered. It was slight in these cases and in none of them
was it considerable enough to be designated as "moderate" by
comparison with that found in the typhus cases.

TYPHUS IN SERBIA 1 l!>

One patient (Autopsy No. 23) dad pronounced twitching and

tonic spasm of the arms as well as a very stiff neck. The au-
topsy showed marked oedema of the brain and small haemor-
rhages along the vessels in the motor areas of the cortex.

Reflexes. The knee-jerks and abdominal reflexes were not ably
sluggish in some of the sicker patients. The abdominal re-
flex was not always obtained. The knee-jerks were present
except in Series No. 93, in which the right knee-jerk was
sluggish and the left was not obtained, in Autopsy No. 23, in
which case there had been pronounced meningeal symptoms,
and in two cases in which other signs justified the diagnosis of
tabes.

Neuritis was not diagnosed in any case although it may have
been the cause of the pain in the shoulder of Series No. 93 or < A
the weakness of the hands in Series No. 9.

There were no "tender toes." Special efforts were made to
avoid pressure of the bedclothes on the toes because this, prob-
ably, is the cause of " tender toes" in typhoid.

Hyperaesthesia. One very sick patient was so extremely
sensitive that he apparently suffered great pain when touched
anywhere. Several other patients at the height of the disease
showed a similar hypersensitiveness but of lesser degree. I do
not remember having seen this condition so strikingly exem-
plified in any other disease, although it occurs sometimes in
cases of prolonged sepsis and especially after the free use of
morphine. According to Gerhard l and other writers hyper-
sensitiveness is common in severe cases of typhus.

This symptom was present in slight degree in a fatal case of
pneumonia seen recently.

XL Pathology of the Nervous System

Marked cerebral oedema was found in two cases, the only
ones in which the brain was examined (vide Autopsy Nos. 12
and 23). Both cases have already been mentioned. The first
patient had slight renal changes and died in deep coma. The
second had tonic spasms of the arms, and, in addition to the

1 Gerhard: loc. cit.

150 CLINICAL OBSERVATIONS

excess of fluid in the meninges, there were whitish streaks and
minute haemorrhages along the vessels in the motor area.

Excess of fluid and more or less oedema of the brain have
been observed often not only in typhus but also in other in-
fectious diseases, but no definite relation between oedema and
cerebral symptoms has been proven. It is said by older writers
to be as common in cases without pronounced cerebral symp-
toms as in those that have them. The presence of the fluid is
sometimes accounted for by the assumption that it replaces
atrophy. Until very recently the fluid has not been observed
to be under tension. Danielopolu 1 presents interesting obser-
vations on these points.

Cortical haemorrhages, also, have been found in cases that
had convulsions but there is doubt whether they were the
cause or the result of the convulsions.

Convulsions in typhus may be attributed to cerebral con-
gestion, to haemorrhage or to uraemia (e. g., Autopsy No. 16);
but Murchison 2 says that they can sometimes be ended by
catheterizing an overdistended bladder.

Inflammatory foci were found in the brain by Prowazek.3

Embolism, doubtless, produces hemiplegia in some cases,
and thrombus formation in the left side of the heart might
account for it.

Among our autopsy cases four at least were comatose for
hours or days before death, suggesting cerebral lesions or
toxaemia as the primary cause of death. In some cases the
coma developed gradually and was not complete until a few
hours before death. In other cases it lasted for days. This was
so in the cases of Autopsy Nos. 12 and 21. The immediate or
secondary cause of death in these two cases seems not to have
been the same. The former had a weak and irregular pulse and
has already been mentioned in the discussion of the pathology
of the circulatory system as a case of cardiac dilatation. The
latter showed nothing abnormal about the heart except some
fibrous thickening of the mitral valve and there was no pul-

1 Danielopolu: Le Typhus exanth6matique, Bucarest, 1919.

2 Murchison: loc. cit. 3 Prowazek: loc. cit.

TYPHI'S IN SKKBIA 151

monary oedema and little, if any, evidence of passive coi
tion in the viscera. Moreover, the pulse was good until shortly

before death. Lesions of the circulatory system and marked
derangement of the circulation, therefore, can be excluded a!
the primary cause of death in this case. Pulmonary Lesions can
similarly be excluded. Apparently the patient died from
cerebral causes with terminal circulatory disturbanc

In two other cases there was marked and increasing pul-
monary congestion for several days, probably due to a com-
bination of bronchitis and oedema. Coma developed toward
the end. These patients probably died of asphyxia as did the
case of Series No. 21 (see "Pathology of Respiratory System "
The pulse in these cases remained good until shortly before
death, but the lungs of both showed extensive lesions.

Jurgens l attributes death in defervescence or in the afebrile
period of typhus to cerebral poisoning rather than to primary
cardiac weakness. The writer recognizes that cerebral symp-
toms may persist in these late stages, but thinks exhaustion
more often important as a cause of death at this period (see
"Pathology of the Circulatory System").

Gastou 2 says that the epidemic in Serbia was characterized
by the frequency and severity of derangement of the nervous
system. He found excess of fluid, sometimes clear, sometimes
cloudy in the meninges and ventricles; thickening of the
arachnoid, cortical ecchymoses, enlargement of the spinal
ganglia, and softening of the cord.

The number of our patients having stiffness of the neck and
Kernig's sign, or both, is striking. None of the authors quoted
mention these signs as being common in typhus. Certainly,
however, they are much less frequent in typhoid fever than
they were among our typhus patients.

Derangement of the nervous system with coma seemed
sometimes to be the primary cause of death, but more often
severe general toxaemia with marked secondary circulatory
disturbances and extensive pulmonary lesions was followed by
coma or deep stupor as its terminal phase.

1 Jurgens : loc. cit. 2 Gastou: loc. cit.

152 CLINICAL OBSERVATIONS

XII. Genito-Urinary System

Bladder. The sicker patients were always incontinent for
a few days before the beginning of defervescence or earlier.
As a rule, the bladder emptied itself satisfactorily, but one of
my patients required the catheter twice, and another had to be
catheterized regularly for several days (Series No. 9 and case of
Autopsy No. 24). A third patient, in Dr. Smith's wards, had
retention for several days. This patient and the preceding one
died.

Murchison x says that retention of urine may cause convul-
sions and that catheterization may stop them.

Urine. Albumen was often found in small quantity, and
there were usually a few casts. Tests for acetone and diacetic
acid were made in a few cases. They were negative. Acetone
bodies, however, have been found occasionally in the urine
from cases of typhus. (Curschmann.2)

An enormously heavy whitish precipitate was noted in the
urine which had been standing in a few cases during conva-
lescence. This precipitate was believed to be composed of
urates (Series No. 1). Various authors mention this as a fea-
ture of convalescence.

The diazo-reaction was performed in a considerable number
of cases. It was nearly always positive until the beginning of
defervescence when it became atypical or negative.

H (hemoglobinuria was suspected in several cases owing to the
smoky color of the urine and the absence of blood in the sedi-
ment. I have failed to find any author who clearly states that
it occurs in typhus. Moore 3 speaks of "a dark color in the
urine caused by typhus dissolution of the blood," and Aschoff 4
says that "haemoglobin secretion was found in the kidneys,
with haemosiderin pigmentation."

Urobilinuria was found by Michaud 5 in twenty-one out of
fifty-eight cases of typhus. I have seen no other mention of it.

Cases of nephritis are described below under " Complications
and Sequelae."

1 Cited by Gastou: loc. cit. 3 Moore: loc. cit. 5 Michaud: loc. cit.

2 Curschmann: loc. cit. 4 Aschoff: loc. cit.

TYPHUS IN SERBIA 153

XIII. Bones and Muscles

Pain in the muscles, in the hones or in the joint* occui
various stages of typhus. With the onsel of fever, pain in the
back and limbs is common, and is said to be Dearly aa s<
in smallpox. Many of my patients in the early stag< - of the

eruption complained of pain in the legs. It was often .
ciated with sensitiveness of the muscles of the calf, and some-
times of the hamstrings as well.

During convalescence, again, nearly all patients complained
of pain in the legs and feet. No objective cause for it was
found.

Muscular twitching and spasm has been discussed under the
head of the nervous system.

Atrophy of individual muscles, most often affecting the
deltoid, has been frequently recorded but was not observed 1 >y
the writer.

In the case of Series No. 9 there was atrophy of the small
muscles of the hands.

XIV. Organs of Special Sense

Eyes. More or less injection of the conjunctivae was found in
practically every case. It seemed to correspond to the flushing
of the face and, probably, it often appeared before the eruption.
It persisted until the end of the fever, but was most marked at
first. Sometimes it covered the conjunctiva, but in other cases
it was limited to the part exposed between the lids or to one
side of the conjunctiva. Occasionally it was present in only one
eye.

Photophobia, if it existed, was slight.

Many authors speak of the "ferret eyes" of typhus, and it is
assumed that the comparison has reference to color rather than
to any peculiarity of expression, although watchfulness is
mentioned by several writers and one of them says that con-
traction of the pupils is the characteristic of "ferret eyes."

The pupils, as a rule, were not remarkable, but in some cases
in the stage of nervous excitement slight contraction was ob-

154 CLINICAL OBSERVATIONS

served, and in a number of patients whose condition was
critical pupillary contraction was moderate or even extreme.

Wide dilatation of the pupil followed a few days later but
contraction was seen in the case of Autopsy No. 17. Dilatation
has been observed as a precursor of death by others, but the
writer has no note of its occurrence under these circumstances
in typhus.

Pupillary contraction seems to be a rough index of toxaemia.

Corneal ulceration developed in a few cases in spite of care,
and all of the patients in whom it appeared eventually died
(Autopsy No. 25).

Ears. Bilateral deafness without purulent otitis media is so
common in typhoid that it was a surprise to the writer not to
find it so in typhus. When deafness was observed it was gen-
erally unilateral, and nearly always followed by a purulent dis-
charge from the affected ear. In a few cases there was pain for
a few days but no discharge. Deafness is stated by several
authors to be very common in typhus.

Herpes on the ears was mentioned above under the head of
"Skin."

XV. Complications and Sequelae

Urticaria was seen in five or six cases during the febrile
period, and was probably caused by unsuitable diet. The food
available was far from ideal for febrile patients, and could be
supplemented only in part from the special stores of the Lady
Paget Hospital.

Erysipelas, starting near the nostril or from a discharging
ear, was observed in several cases. In the cases that I saw it
was accompanied by little constitutional disturbance and soon
cleared up.

Suppurative Lesions. During the convalescent stage ab-
scesses were not uncommon and sometimes they were large.
One patient had empyema of the knee-joint, followed by an
abscess near the thyroid gland. Perinephritic abscess was a
late sequel in one case.

Small boils were common. They sometimes appeared suc-
cessively, but never in crops.

TYPHIS IX SKHMIA L56

No case of ulceration in the throat or of noma was encoun-
tered among our patients, although Dr. R. P. Strong informed

me that at Monastir he had seen cases of this sort.

There were very few bedsores which is remarkable consider-
ing the number of patients who were incontinent for longer or

shorter periods. Much credit is due the nurses for this.

Parotitis was a frequent complication of the periods of defer-
vescence and convalescence. I saw many cases in other wards

but had few in my own. In one of these cases (Series No. 60)
unilateral parotitis appeared when the rash was still visible od
the body. It developed gradually. The swelling was very hard
and but slightly sensitive, improved under poulticing, flared up
several times as if about to suppurate, and finally began slowly
to disappear. Some swelling still remained when the patient
was discharged from the hospital. No incision was required in
this case.

In a second case, when the temperature was dropping rapidly
toward normal, parotitis first appeared on the right, and on the
following day on the left. (Plate XXVI, Figure 1.) Incision
on both sides and under the chin was of no avail. The tissues
were oedematous and little pus was encountered. The swelling
increased rapidly, extended to the glands under the jaw and met
underneath the chin. Pain was great, the patient was scarcely
able even to swallow liquids. On the sixth day, starting from
100°, the temperature rose steadily to 106.5° on the following-
afternoon. The patient then died. (Autopsy No. 19.)

All the cases that I saw were characterized by hardness of the
swelling and by extreme slowness of recovery. Incision was re-
sorted to in most instances but the amount of pus evacuated
was always small.

Suppurative Otitis Media and Mastoiditis were observed not
infrequently. One patient in the hospital on my arrival had
otitis media and signs of meningitis. He died a few days later.
Lumbar puncture showed an opalescent fluid with white floc-
culi in it. The diplococcus of cerebrospinal meningitis was
looked for but not found, neither were any other bacteria seen.
The case had been diagnosed as typhus, and probably correctly,

156 CLINICAL OBSERVATIONS

although proof of it is lacking. Meningitis is said to be a rare
sequel of typhus. Danielopolu's 1 observations on the cerebro-
spinal fluid are of special interest.

Another patient had otitis and pain in the region of the
mastoid followed by purulent discharge from the ear. The
other ear subsequently became painful but did not discharge.
A third patient had pain and mastoid tenderness of the same
character which cleared up without discharge from the ear,
and a fourth had a marked secondary rise of temperature asso-
ciated with pain on attempting to swallow. No abnormality
could be seen in the throat, but, after a profuse yellowish
discharge had been expelled from the mouth, the patient re-
covered. A fifth case of typhus, transferred to me in conva-
lescence, had an abscess in the neck originating in the mastoid.

Paresis of the Hands was observed in the case of Series No. 9
during convalescence. Very little motion of the fingers was
possible, the grasp became very weak, but improvement was
rapid, and when discharged after a protracted convalescence,
the patient could use his hands fairly well. The nature of the
condition is uncertain.

Cardiac Complications, apparently, were not numerous al-
though a weak and rapid pulse often heralded the approach of
death several days in advance. The rate and character of the
pulse, the variations in blood-pressure and the pathology have
already been described.

Acute endocarditis is regarded as one of the very rare com-
plications of typhus. We had two cases of endocarditis but
owing to the lack of data regarding the early part of the illness
when a typical typhus rash may have been present, the diag-
nosis of typhus remains in doubt.

Autopsy No. 2 showed many large, recent vegetations on the
valves. In the case of Autopsy No. 26 the lesions were of the
small verrucous type and there were few of them.

Thrombus formation in the auricles is generally regarded as
not uncommon in typhus so that pulmonary infarction or
hemiplegia might result. In two of the cases autopsied by Dr.

1 Danielopolu: loc. cit.

Fig. 2. Three cases of slight gangrene following typhus fever

Fig. 1. Double parotitis
Case of Autopsy Number 19

Fig. 3. Gangrene after typhus

This case is the one shown on

the right in Pig. J

Photographic illustrations of cases at Lady Paget Hospital

(From photographs presented by Dr. Sellards)

PLATE XXVI

TYPHUS IX SERBIA 157

Zinsser mural thrombi were found in the apex of the left
ventricle. These thrombi were believed to have origin
before death, but of this Dr. Zinsser was riot quite certain

(Autopsy No. 4.)

Phlebitis of a mild type is believed to have existed in the <
of Series No. 47. In the case of Autopsy No. 8 a typical ] pul-
monary infarct was found.

Vascular Complications. Gangrene of the feet seems to 1.
been very common during the cold months in the early part i if
the epidemic. Dr. Strong said that he saw many cases of gan-
grene in some of the hospitals and that in some cases the nose or
ears were affected.

Maitland 1 made some interesting observations on it. He
noted that before gangrene appeared the feet and hands be-
came blue and cold and the pulse " thread}'," i. e., small and
weak, that red patches of hyperaemia then appeared on the
feet, and that gangrene developed in the areas which had be-
come thus congested. Reasoning from the fact that a part
once frostbitten remains for some time afterwards sensitive to
exposure he inferred that frostbite or exposure incidental to
warfare may have played a predisposing part by injuring the
vessels.

That this form of gangrene is not embolic is evidenced by its
frequent symmetry. Moore 2 believed that gangrene results
from arterial thrombosis, but it seems probable that Maitland
is right in supposing that exposure may be a factor in its pro-
duction. Another factor which was probably operative during
the early months and particularly in some localities is lack of
nursing. The feet of the patients may have been allowed to
remain cold for long periods during the illness when the circula-
tion was sluggish, or the circulation may have been handi-
capped by leaving the boots on. In the presence of some of
these predisposing factors local infection may have aided in
the formation of a thrombus, or its development may. per-
haps, have been determined by changes in the walls oi smaller
arteries such as Prowazek 3 found in those of the skin.

1 Maitland: loc. cit. 2 Moore: loc. cit. 3 Prowazek: loo. cit.

158 CLINICAL OBSERVATIONS

Gangrene heals very slowly. It seems to develop most often
in the later stages of typhus or during convalescence. Conse-
quently there were many old cases of it in the wards when we
began work. Others were brought in after the rash had disap-
peared. Typical instances, slight in degree, are shown in Plate
XXVI, Figures 2 and 3.

Whether or not all the cases of gangrene which we saw were
in reality due to typhus it is impossible to say with certainty.
During the summer, few cases of gangrene developed in the
hospital and none in my wards. The comparative scarcity of
gangrene at this period was due apparently to. two causes:
firstly, warm weather; and secondly, good nursing.

Series No, 33a was brought in with severe gangrene, and
several other patients admitted at the same time had cold, dis-
colored feet which looked as if about to become gangrenous,
but the circulation was restored by the application of heat
locally. Special care was taken with all typhus patients to keep
the feet warm and to avoid pressure upon them even by the
blankets.

Pulmonary Complications. Bronchitis and passive conges-
tion were so common as to be considered features of ordinary
typhus rather than complications. Both were found in most
of the cases that came to autopsy.

Pneumonia. The dyspnoea during life often suggested pneu-
monia, and in cases of this sort faint bronchial breathing could
sometimes be found in the back, but at autopsy definite con-
solidation was seldom discovered.

There was extensive lobar consolidation in only one instance
(Autopsy No. 7).

In Autopsy No. 25 bronchopneumonia was caused by inhala-
tion of food.

Two probable cases of bronchopneumonia with recovery
were mentioned above under the head of "Sputum." (Series
No. 93.)

Capricious localization of intense haemorrhagic oedema in
several cases suggested the possibility that pneumonia was de-
veloping. The condition in question was found in the case of

TYPHIS IX SERBIA

Autopsy No. 18. It was localized at the top of the right lo
lobe. In this case the ordinary signs of passr boi gestion

absent. In Autopsy No. 9 a similar condition exi the

base of the left lung, and in Autopsy No. 20 it was combined
with passive congestion of the ordinary type.
Pleuritis. Extensive pleuritic adhesions, some old, some

more recent, and others obviously fresh were found in many
cases. No typical friction rub was heard, but pleuritis prob-
ably accounted for some of the pain in the chest which was
complained of not infrequently.

A fresh haemorrhage was found on the pleural surface of the
lung at the right apex in the case of Autopsy No. 4, and in that
of Autopsy No. 8 there was a recent infarct.

Pulmonary gangrene. Typical pulmonary gangrene de-
veloped during convalescence in the case of Series No. 59 men-
tioned above under "Respiratory Signs and Symptoms."

Pulmonary gangrene may be caused by embolism from sep-
tic areas (Murchison x) or by inhalation of septic material
from perichondritis of the larnyx (Curschmann2).

Renal Complications. The urinary sediment during the
febrile period, in the case of Series No. 1, indicated nephritis
by the presence of many hyaline, granular, and fatty casts and
compound granule cells. There was little albumen, however,
and the condition of the urine improved rapidly during conva-
lescence. A renal irritation of less degree, which scarcely re-
quires to be classified as a nephritis, was found in another i
The urine showed in this case a specific gravity of 1024. a trace
of albumen, many granular casts, and a few red blood-cells.

In the case of Series No. 9 the urine was like that in Series
No. 1, but the patient subsequently developed oedema of the
face and legs, and the nephritis seemed to be passing into a
chronic form when the patient was discharged.

In the case of Autopsy No. 16 there was a chronic nephritis
which undoubtedly antedated the typhus, and there were also
acute kidney changes attributable to the typhus. This patient
died in a convulsion, probably of uraemic origin.

1 Murchison: loc. cit. ': Curschmann: loo. cit.

160 CLINICAL OBSERVATIONS

In a number of other cases slight fatty degeneration of the
kidney was found at autopsy. Curschmann * says that most
authors regard acute nephritis as a comparatively frequent
complication of typhus. Among our cases well marked evi-
dence of nephritis was rare, but signs of more or less renal
irritation, such as is common in severe febrile diseases, were
frequently present.

XVI. Convalescence

Even after the most severe symptoms, convalescence was
rapid considering the emaciation and weakness of the patients.
The gain of strength from day to day, the improvement in ap-
pearance, the increased ability to assimilate food, and the in-
crease of mental activity was rapid as compared with typhoid.

Frequently patients whose temperatures had not yet
reached normal would sit up in bed and ask either for solid
food, or to be sent home on furlough. Some patients were fit
for discharge after a week of normal temperature. Those who
had been very ill were kept longer in the hospital because dis-
charge often meant walking to their homes which were, per-
haps, many miles away.

Pain, more or less severe, in the legs and feet was a very
common symptom of convalescence.

Slight recurrences of temperature often terminated promptly
after a cathartic had been taken.

In a few cases rapidity or irregularity of the pulse persisted
for a considerable time.

XVI I . Diagnosis

The differential diagnosis of typhus may be discussed by
taking up the various stages of the disease separately.

Stage of Invasion. Before the appearance of the eruption in-
fluenza may easily be mistaken for typhus or vice versa on
account of the conjunctival injection, the redness of the
pharyngeal mucous membrane and of the tonsils, and the slight
signs of coryza associated with symptoms of general infection.

1 Curschmann : loc. cit.

TYPHI'S FN SI-iPliJA 161

Siebert,1 who studied typhus recently in a camp bad

prisoners, says that there were at fir.-l mild illnesses like in-
fluenza, which were followed later by cases of iindoul
phus with more severe symptoms. He had the impression that
among the early influenza-like cases there were some
abortive typhus. Similar cases of mild typhus were obeei
toward the end of the typhus epidemic.

The experience of Jurgens 2 among Russian prisoners
like that of Siebert.1 He says that just before the typhus epi-
demic they had influenza to deal with, but that when the ty-
phus appeared there was no more influenza.

During the same epidemic in Hungary, Wiener1 observed
mild cases of typhus like those described by Siebert.1 He says
that the febrile period may last from three to six days and that
the disease is like influenza except that often there are chills at
the beginning or during the course of the fever. In other cases
he observed headache, malaise, nasal catarrh and cough, and
sometimes angina from ten to fourteen days before the out-
break of "the real disease."

Apparently, influenza may prepare the way for typhus or
may go with it in the same epidemic as relapsing fever so often
does.

These observations are of special interest to the writer be-
cause at the end of the epidemic in Serbia we saw many cases of
transient fever which were thought at first to be influenza, but
later, the question of pappataci or "three-day fever" was
raised. Dr. Castellani, who was familiar with this disease, said
there were many cases of pappataci fever in the town close by
at that time.

The cases in question at the Lady Paget Hospital showed in-
jection of the conjunctivae, flushing of the face, and catarrh
of the respiratory passages. Some of them also had transient
eruptions. When first seen the patients said they had been ill
two days. They complained of malaise, headache, and pain in
the back and limbs. On the third day, as a rule, the tempera-
ture fell abruptly to normal.

1 Siebert : loc. cit. 2 Juxeens: loc. cit. 3 Weiner: loo. cit

162 CLINICAL OBSERVATIONS

It would seem that to distinguish between abortive cases of
typhus, pappataci fever, and influenza may be extremely diffi-
cult because there is no doubt that typhus infection may ap-
pear in a very mild form, and that such cases are likely to
appear at the beginning or end of an epidemic. It is possible,
therefore, that some of our patients with supposed pappataci
fever may really have had abortive typhus. The appearance of
a rash in several of these cases strengthens that hypothesis.

The fact that " influenza-like" bacilli were found in the
sputum of two cases of undoubted typhus, and that in one of
these cases they were very numerous (see "Respiratory Signs
and Symptoms," above), points to the probable coexistence
of influenza infection among our patients at the time when
the doubtful cases were developing.

The bacilli in question were described as "influenza-like,"
not because they differed from the bacillus of influenza in size,
shape, or staining reaction, but because their identity was not
confirmed by cultivation. The observations of Wiener,1 Sie-
bert,2 and Jurgens,3 made during the same epidemic of typhus
in another locality, increase the probability that influenza and
not pappataci fever may have been the real cause of some of
the mild cases in question. If so, mild typhus, influenza, and
pappataci fever apparently prevailed at the same time. Series
Nos. 88 and 100 are included to illustrate difficulties of diag-
nosis.

Inasmuch as some epidemics of "influenza or grippe" have
proven to be really due to pneumococcus bronchitis still
another possible source of error in diagnosis suggests itself.
Series No. 100, just mentioned, was a case of pneumococcus
bronchitis.

Another important fact is that influenza cannot be entirely
excluded because of the presence of an eruption. Not many
years ago in Paris an extensive epidemic prevailed which was
finally diagnosed as influenza although many of the patients
had an eruption which resembled that of typhus (Wagener 4).

1 Weiner:loc. cit. 3 Jurgens: loc. cit.

2Siebert: loc. cit. 4 Wagener: Med. Klin., xv, No. 25.

TYPHI'S [N SERBIA 163

Relapsing fever may be confused, in the beginning, with the
stage of invasion of typhus. In typical eases, the onset of re-
lapsing fever is more abrupt than in typhus, the temperature
rises much more rapidly, goes higher, and the constitutional
symptoms are slight in comparison with the- fever. Conjunc-
tival injection, if present, is slight, but the face may Ik- flushed
and its appearance may be strikingly like that of typhus. En-
largement of the spleen is easily demonstrable in relapsing fever.

Relapsing fever, in a number of cases, developed during
convalescence from typhus. It may have preceded it in others.

Tertian malaria and aestivo-autumnal malaria caused no
great difficulty in differential diagnosis. These cases became
numerous as the summer advanced.

The onset of smallpox is said to resemble that of typhus.

Stages of Nervous Excitement and of Nervous Depression . The
presence of a well-marked eruption having the usual distribu-
tion and character of typhus was considered sufficient for a
positive diagnosis, but when atypical rashes were seen, as in
Series Nos. 88 and 100, it was believed that a diagnosis of ty-
phus could not be made with anything like certainty. When,
also, the subsequent course of the disease was atypical the di-
agnosis remained in doubt. Criteria based on the degree of
severity of symptoms or on the course of the fever can have
little value for recognition or exclusion of abortive typhus. No
sign or symptom of typhus was nearly so characteristic as the
eruption. When the eruption was well developed the disease
ran a course which varied little.

If there are cases of typhus in which no rash is present at any
time, it would seem extremely difficult to diagnose such cases
with certainty, even during an epidemic of typhus, because of
the various other diseases that may be prevalent at the same
time.

Murchison 1 says that if there are cases of typhus without
even a transient eruption they must be very rare.

The diagnosis of "typhus without eruption"' has been made
not infrequently by some persons on the ground that the prog-

1 Murchison: loc. cit.

164 CLINICAL OBSERVATIONS

ress of the cases resembled typhus in other respects and that
the patients were known to have been exposed to this infec-
tion. Having seen no such case I am skeptical of the diagnosis
of "typhus without eruption."

If there were cases of typhoid among my patients I failed to
recognize them although this disease was always borne in mind.
There should be no difficulty in distinguishing typhoid from
typhus when the eruption is well marked and typical, but, after
a transient or scanty eruption has disappeared, doubt may
arise.

Typhus with eruption on the face, as in the case seen by Dr.
Sellards, might bring measles into question. The subsequent
course of the fever and the characteristic changes in the rash,
however, would soon settle the diagnosis.

The Widal reaction has lost much of its value for diagnosis
since antityphoid inoculation has become such a common
practice. Moreover, McClure x says that a positive. Widal
reaction in low dilutions is common in typhus. Clumping oc-
curred in a few of our typhus cases at a dilution of 1 in 25.
Agglutination tests for paratyphoid A and B were always per-
formed with the Widal test. They were uniformly negative.

The bites of fleas and of other vermin, when numerous, may
resemble an eruption, or may confuse the picture when an erup-
tion also exists. Similarly, scabies may mask a rash or even
lead to an erroneous diagnosis of typhus fever. (Series No. 33.)

The case of Series No. 88 presents a particularly complex
combination of skin lesions. Drug eruptions, a profuse crop of
rose spots in typhoid, haemorrhagic eruptions in the acute ex-
anthemata and skin lesions in secondary syphilis, plague or
influenza may require to be differentiated from typhus. The
spots of purpura, cerebrospinal meningitis or acute endo-
carditis are not likely to cause difficulty.

The association of scurvy with typhus, which has been ob-
served in some epidemics, and the possibility of combined
infection of typhus with typhoid, dysentery, diphtheria, re-
lapsing fever, or the exanthemata should be borne in mind.

1 McClure: Handbook of Fevers, N. Y., 1914, p. 321.

TYPHUS IX SERBIA 165

Stage of Defervescence. Diagnosis a1 bhif stage depends on the
exclusion of typhoid fever, relapsing U-vcr, tuberculosis,
laria, and Malta fever, of which we had two probabl<
and on the presence of reasonably characteristic remains of the
eruption. The recognition of this was discussed in the section
on "Skin."

At this stage, also, acute endocarditis may come into ques-
tion because heart murmurs are generally present in the later
stages of typhus. The cases of Autopsy Nos." 2, 11, and 26 illus-
trate the difficulties of late diagnosis.

When, during a typhus epidemic, a patient is brought in with
gangrene of the leg (Series No. 33a), or with parotitis following
a fever of many days duration, it is probable that the lesions
are sequelae of typhus; but, whereas they develop sometimes
also in other infectious diseases a diagnosis can scarcely be
made with certainty in cases of this sort after the rash has
disappeared.

XVIII. Treatment in General

As a basis for rational treatment the causes of morbidity and
of mortality require to be understood.

It is certain that filth, famine, overcrowding, and lack of
ventilation favor the spread of typhus. They favor it not only
by increasing opportunity for transmission of infection but
also by weakening in advance the resistance of the person in-
fected. Notwithstanding some apparently Contradictory evi-
dence, it seems certain that bad conditions of living tend to
lower the resistance of the individual and to increase morbidity
as well as mortality in an epidemic of typhus.

The first fundamental principle of treatment rests on these
facts. It demands maintenance of the patient's remaining
strength by every possible means (1) by removal from unsanitary
surroundings (2) by good nursing, and (3) by a well-regulated
diet. These points are elaborated below.

Fresh air and cleanliness are certainly beneficial. It is prob-
able, therefore, that suitable tents would make better wards
than ill-ventilated rooms. Maxwell * says that the Italians in

1 Maxwell: Brit. Med. Jour., 1915, No. 1, p. 528.

166 CLINICAL OBSERVATIONS

Tripoli preferred to use tents or huts for the sake of ventilation
and ease of destroying vermin.

Good nursing saves the patient needless suffering, and helps
very much to maintain strength.

It is probable that parotitis, ulcerative lesions of the mouth
and throat, otitis media, and external infectious processes in-
cluding bedsores can be prevented in most cases by a skillful
nurse if she has sufficient time to do her work thoroughly; and
that hypostatic congestion, pulmonary complications, and gan-
grene of the extremities will be far less common among her
patients than among those lacking such care.

The kind and quantity of nourishment should b'e suited to
the digestive capacity of the individual and must vary with the
stage of the illness and the nature of the symptoms. The effort
should always be made to administer the greatest quantity of
nourishment that the patient can digest. Liquid nourishment
only can be taken by the sicker patients, but when soft solids
can be taken they should be administered. Good judgment is
needed to get the best results. Therefore the physician should
personally supervise the dietary.

The methods advocated above are important not only to
combat pre-existing weakness in cases admitted late in the dis-
ease, but also to counterbalance the exhaustion and loss of
flesh incidental to typhus in its severer forms. Prostration is
more often extreme in typhus than in any other similar dis-
ease. A most striking fact is the occurrence of many deaths
after the period of defervescence even when severe complications
have not developed. It is probable that extreme exhaustion,
with attendant depression of vital functions and consequent
inability to recuperate, is the essential factor in the fatal result
in most of these cases (Autopsy Nos. 13 and 14). That exhaus-
tion is also an important factor in many deaths which occur
during defervescence, and in some that occur still earlier, seems
extremely probable (Autopsy Nos. 9 and 24).

Maintenance of strength, therefore, seems to be important at
all stages of typhus as a means of saving life. That this prin-
ciple is of special importance for the treatment of middle-aged

TYPHI'S IN SKKBIA 167

or elderly patients is suggested by statistic- of mortaHt
known that, after the period of childhood, percentage mor-
tality increases steadily with advance in years, and thai |t
becomes extremely high in elderly persons. Murchison's '
Diagram II based on more than 18,000 cases demonstrates the
truth of this statement.

It is not possible to determine the stage of the dift
which death occurred in all of our cases which were autopsied
but more than a third of the fatalities (seven at leasi occurred
after defervescence from the primary fever. In at least fi\
these cases the dominant factor seemed to be exhaustion.
Death in the sixth case was from parotitis and sepsis, and in
the seventh case from exhaustion and pneumonia. In three
of the earlier deaths exhaustion seemed to play an important
part (Autopsy Nos. 6, 9, and 24).

Inasmuch as a large proportion of patients die after having
passed the acute period of typhus it is clear that efforts to con-
serve strength should not be relaxed until after the patient has
made decided improvement.

Nasal feeding was used in several patients who were unable
or unwilling to swallow enough food. It served well in several
cases that might not have recovered otherwise. Unfortunately,
one delirious patient, who struggled against the feedings and in
whose case they were tried as a last resort, developed inhala-
tion pneumonia.

The place of alcohol in the treatment of typhus is an impor-
tant question.

When a patient is rapidly losing strength because he cannot
assimilate food, I believe that alcohol should be administered.
not in small doses, but freely. Alcohol has been abused in the
past, and many now deny that it has any value, but they are
probably mistaken.

In suitable cases alcohol acts apparently as a food which is
readily absorbed, and capable to a considerable degree of re-
placing other nourishment. If this is true, it is important that
the indications for administering alcohol should be clearly
understood.

1 Murckison: loc. eit.

168 CLINICAL OBSERVATIONS

Gerhard1 on the subject of typhus says: — "In the later
stages of fever, wine, porter, and in a few cases even brandy
were given with much benefit. It is difficult to conceive the
extreme prostration in which our patients were left after a
severe attack of fever. The skin is usually cool and the pulse
weak and fluttering, but there is still muttering delirium and
great feebleness. Under these circumstances, wine, combined
with quinine, and a nutritious diet produced an effect which
was almost magical." "The amount of wine given in twenty-
four hours varied from 4 to 16 ounces. It was generally from 6
to 8 ounces. Practitioners have remarked that a moderate
dose of wine is capable of producing all the good effects which
can result from it. In our observations a similar result was ob-
tained, and we rarely exceeded eight ounces daily except as a
temporary prescription to obviate extreme prostration. The
quantity given with that object was not limited but was increased
until the strength of the patient improved." "Where the fever
was higher and the prostration less, wine became less useful.
We therefore restricted its employment to the periods of prostration,
when it was indispensably necessary." (The italics are mine.)

Stokes 2 taught that where there was f aintness of the heart
sounds at the apex and 'weakening of the cardiac impulse with a
pulse which was rapid and of poor quality, alcohol was re-
quired; but he took into consideration also the state of nutri-
tion of the patient. Two cases, described by him in Chapter
XXVIII of his book, show that he used alcohol very freely in
the presence of extreme prostration and emaciation. He ad-
vises against its free use when there is "active irritation of the
brain," but says that alcohol may be tried even then'if cir-
cumstances demand.

Murchison 3 complained of the indiscriminate use of alcohol
common in his day and doubted the wisdom of administering
more than twelve ounces of brandy in twenty-four hours under
any circumstances, but he valued alcohol too. He says that
most patients over forty are benefited by alcohol from the com-
mencement of the second week or earlier, that persons of in-

. ' Gerhard: loc. cit. 2 Stokes: loc. cit. 3 Murchison: loc. cit.

TYPHUS IN SERBIA

temperate habits require alcohol earlier and in greater quantity

than others, that the chief indication for tfu " • of alcohol <
rived from observation of the pulse and heart a. stated hy <'.
and that the more the typhoid state is developed the men will al-
cohol be needed. Slowing of the pulse under alcohol and dim-
inution of delirium were regarded as evidence of beneficial
effect and vice versa. Other indications for alcohol were cold-
ness of extremities and a dry, brown tongue. Profuse perspira-
tion without contemporaneous improvement indicated a need
for more alcohol, and a hot, dry skin or scantiness of the urine
were considered as contra-indications for alcohol.

The question of whether alcohol was a food or a stimulant
troubled Murchison l and he concluded to call it a stimulant.

Indications for the use of alcohol in typhoid fever were given
by F. C. Shattuck 2 as follows: — "If the heart shows distinct
signs of undue weakness, if hypostasis is threatened or marked.
if the power to take, retain, or appropriate nourishment is
unduly lowered, I believe it to be a grave error in judgment to
withhold alcohol." If alcohol is useful in typhoid it is needed
more often for the same indications in severe typhus.

Dr. F. C. Shattuck has taught that "in acute infections,
especially toward their later stages, the toleration of alcohol may be
greatly increased over that of health, and that it may then rend* r
inestimable service, notably when the power of taking or assimilat-
ing food is greatly impaired. No measured limit can be set
down for its use. No more should be given than is burnt up,
combustion being determined by the presence or absence of the
smell of alcohol on the breath, in combination with the symp-
toms of the patient, and the influence upon the latter appar-
ently exerted by the alcohol."

To discuss experimental evidence as to the effect of alcohol
on nutrition, circulation, respiration, etc., would be out of place
in this paper but a few facts may be stated. It is well known
that a certain quantity of alcohol is quickly absorbed, and
readily oxidized in the healthy body, that it can supply some of

1 Murchison: loc. cit.

2 Shattuck, F. C: Therapeusis of Internal Diseases, Forchheimer. X. Y.. 1913, ii

170 CLINICAL OBSERVATIONS

the energy ordinarily derived from carbohydrate or fat, and
that, in so doing, it prevents the destruction of body tissue
which ensues when the quantity of fat or carbohydrate ingested
is insufficient for requirements. Less is known of its action in
disease of various kinds.

It is reasonable to suppose, however, that the beneficial
effects of alcohol in ill-nourished patients are due in large
measure to energy supplied by the alcohol, and that, when the
patient is exhausted and emaciated, alcohol by acting as a food
may increase vital energy and thus indirectly improve circula-
tion and respiration. It is the experience of Dr. F. C. Shat-
tuck, as stated above, that conditions may occur in disease
which greatly increase the power to assimilate alcohol.

Patients under my care received alcohol in considerable
quantities and apparently with benefit. It may, at least, be
said that no typhus patient died in my wards after the period of
high fever except from severe Complications.

The earlier the stage of typhus, the less prominent seems to
be exhaustion as a cause of death. It may, however, be an
important factor in exceptional cases as it seems to have been in
the case of Autopsy No. 9.

The principal cause of early death when it occurs in typhus
is toxaemia. There may be lesions in the heart and other or-
gans, but severe functional disturbances without corresponding
known lesions seem to be the direct result of toxins circulating
in the blood. Some of the older writers have denied that cere-
bral congestion and oedema are the cause of cerebral symp-
toms, claiming that these occur to the same degree in cases in
which cerebral symptoms were not marked, and that the
excess of fluid merely replaces atrophy of brain tissue. Quite
different views have been expressed by Danielopolu * in his
recent book on typhus. More light is needed on this question.

The second fundamental principle in the treatment of typhus
is based on the belief that toxaemia is an important cause of
death and that, therefore, it should be combated in every pos-
sible way.

1 Danielopolu: loc. cit.

TYPHUS IX SERBIA 171

Toxaemia in typhus can be attacked by attempting to dilute
the toxin in circulation, by promoting its elimination, <>i
cording to Danielopolu,1 by neutralizing or destroying the
toxin in the blood by means of intravenous injection!

chlorinated salt solution. This last met hod was unknown when
this paper was originally written.

Circulating toxin can be diluted by the administration «>f
abundant water by mouth. When sufficient water cannot he
ingested it can be given in the form of enemata, or as salt
solution by hypodermatoclysis or intravenously. These meth-
ods were used freely.

They caused marked increase in the excretory activity of the
kidneys and seemed also to improve the circulation. Tim-.
they may have benefited the patient by diluting toxin and by
favoring its elimination through the kidneys both directly and
indirectly.

The question of how much liquid should be ingested by the
patient daily in acute fevers has not been settled. McCrae -
advocates three liters per diem as a minimum in typhoid, prefers
five or six liters, and has administered much larger quantities. 1 1
may be asked whether this internal hydrotherapy, when carried
to extremes, may not cause disturbances which more than
counterbalance its benefits. For example, may it interfere
with digestion? May it put undue strain on the heart in c
in which the heart is weak? May it, in typhoid, increase the
frequency or severity of intestinal haemorrhage?

In typhus the possible danger of overtaxing the heart by
rapidly administering very large quantities of fluid should be
borne in mind because the heart muscle seems more often to be
weak in typhus than in typhoid fever. On the other hand,
damage to the heart and blood-vessels might be minimized by
ingestion of large amounts of liquid if begun early in the disease.

The bowels should receive special attention in typhus, a dis-
ease in which constipation is the rule, in order to prevent
absorption of toxins from them. Slight recurrences of fever
in convalescence frequently yield promptly to free catharsis.

i Danielopolu: loc. cit. 2 McCrae: Modern Medicine, ed. by Osier. Phil.. 1907.

172 CLINICAL OBSERVATIONS

When, in typhus, the face becomes cyanotic, the breathing
rapid, and signs of general toxaemia are well marked it seems
probable that moderate purgation with a saline cathartic, such
as magnesium sulphate, may have a beneficial effect. There is
a striking resemblance between some of these cases and certain
instances of influenza with bronchopneumonia which were
treated in France in the autumn of 1918. Purgation seemed in
these cases of bronchopneumonia to be definitely beneficial.
Whether the improvement resulted from elimination of toxic
material or otherwise is uncertain. It may have benefited the
heart by reducing the volume of the circulating fluid.

XIX. Symptomatic Treatment

Among symptoms of a serious nature in our cases of typhus
were those of circulatory insufficiency. This condition seemed
to be the contributing cause of death in most of the fatal cases.
Less often it was regarded as the principal cause of death.

Digitalis was administered in all cases in which the pulse be-
came weak and irregular or the pulse rate rose above 120 per
minute. The dose by mouth varied from 0.2 to 0.4 gram daily.
In several instances bradycardia was thought to have been
caused by the digitalis (Series No. 83) . It seems impossible to
tell whether or not the patients would have done as well with-
out the digitalis.

A number of patients had occasional sudden attacks of cir-
culatory weakness from which they rallied promptly after
administration of whisky by mouth, a drink of hot tea or soup,
or a subcutaneous injection of strychnin, camphor in oil, or
ether. During these attacks the patients seemed to be in an
alarming state of collapse. The pulse was extremely weak or
even imperceptible. The recovery was prompt and striking.
One patient recovered, however, before anything had been ad-
ministered, so that doubt is cast on the value of the treatment
used for the others. The patient referred to in Autopsy No. 24
had many such collapses before he died.

I am not prepared either to attach much value to these
methods of cardiac stimulation or to deny them all value, but

TYPHUS IX SERBIA

incline to the belief that they may, in Borne cases, produce
transient reflex rise of blood-pressure which may have a tem-
porary beneficial effect. For example, we know thai pain causes
a temporary rise of blood-pressure. A subcutaneous injection,
therefore, may act through pain even if the substance injected
is medicinally inert. Locally irritating substances like camphor
or ether probably act mainly in this way.

As a heart stimulant strychnin has no demonstrated value
It was not used by me for this purpose. The work of Richard
C. Cabot and the more recent studies of Newburgh ' throw
light on this subject.

When a patient had had one attack of circulatory collapse it
was found that another might be expected to follow. The na-
ture of circulatory insufficiency in typhus has already been
discussed under "Pathology of the Circulatory System " where
reasons were given for believing that the disturbance originated
sometimes in the vascular system and sometimes in the heart.
More often, apparently, the two kinds of disorder were com-
bined.

Salt solution was administered intravenously in a number of
cases of different types. In the cases in which the circulatory
disturbance seemed to be mainly due to vascular relaxation the
response was gratifying.

In the case of Series No. 9 the circulation improved re-
peatedly after the infusions, and life seems to have been pro-
longed by them for several days until a favorable turn of the
illness was followed by recovery.

Salt solution by intravenous infusion was used also in the
cases of Series Nos. 10, 59, and 93, and in the cases described
under Autopsy Nos. 24 and 25. In the case of Series No. 10 the
infusion gave little benefit. During the second injection tem-
porary improvement of the pulse was followed by signs of
heart weakness which made it necessary to stop the procedure.
A slight rigor followed soon after the injection. Infusions were
used in the case of Series No. 59, not to improve the pulse.
which was fairly good, but to replace fluid lost by diarrhoea

1 Newburgh: Am. Jour. Med. Sc, 1915, xlix, 696; Arch. Int. Mod.. 1915, xv. 158

174 CLINICAL OBSERVATIONS

and to prevent expected circulatory collapse. The first injec-
tion did good. The second was soon followed by transient
weakness and irregularity of the pulse. This time the solution
may have done more harm than good. In the case of Series No.
93 two infusions were given. Both were followed by rigors.
Nevertheless, even in this case, the effect on the whole may
have been beneficial. After the rigors were over the patient's
condition was more satisfactory than it had been before the
infusion was administered.

In the case of Autopsy No. 24 the first infusion caused a
marked temporary improvement in the circulation but tran-
sient violent delirium followed, and, later, another circulatory
collapse occurred. A second infusion given several hours after-
wards called forth little circulatory response. This case seemed
to be one of the sort which is hopeless from the beginning.

Autopsy No. 25 is a somewhat similar case. Salt solution
improved the pulse in this case but delirium increased and a
rigor took place. After the second infusion, morphine was in-
jected, no rigor occurred, and the pulse remained satisfactory for
twenty-four hours after administration of the salt solution.

The cause of the rigors which so often followed infusions of
salt solution in my cases is not clear. Apparently, they were not
due to errors of technique because they were not prevented by
the most careful preparation of the solution, by using freshly
distilled water, or by carefully maintaining a warm tempera-
ture of the solution while it was being administrated.

It is of special interest that Gastelloi (quoted by Doty x)
administered normal salt solution several times daily in the
dose of 250 to 300 c.c. totalling from 600 to 1800 c.c. per day
in 136 cases; and that he had only 9 deaths under this regime
as against 13 deaths in 113 patients under "purely symp-
tomatic treatment."

Sponge baths served to reduce temperature, but no very cer-
tain benefit resulted.

When there was marked pulmonary congestion and bron-
chitis no form of treatment seemed to relieve the patient. It is

1 Doty: loc. cit.

TYPHUS IN SERBIA 175

difficult to see what, beyond general measures, can I"- done far
such cases; The frequently existing acute inflammation of the

bronchial mucosa would seem to contra-indicate the lift
"stimulating" expectorants. Atropine mighl be expected to
make the condition worse by increasing the viscidity of the
secretion and thus preventing its expulsion. The associ
bronchitis, when severe, contra-indicates morphine because it
prevents expectoration.

The urine should be watched for signs of nephritis and ap-
propriate modifications of diet should be instituted when there
is evidence of nephritis.

The stools should be inspected, especially when there is
diarrhoea, to see if the food is being well digested. Curds of
undigested milk are a frequent cause of diarrhoea in typhoid
fever.

The prevention of complications was spoken of above under
"Treatment in General" and nursing. Special attention should
be paid to the mouth and throat. The legs and feet should be
kept warm, and pressure on the feet, even from the bedclotli<<.
should be avoided lest it contribute to the production of
gangrene.

At first sight the treatment for gangrene of the toes might
seem to be amputation, but Dr. Smith informed me that, even
when amputation was performed rather high, the gangrene
sometimes recurred. When the gangrene was not extensive he
preferred to keep his patients in bed and to wait for recovery by
spontaneous separation of the dead tissue. The process was
slow but loss of substance was surprisingly small and the re-
sults were excellent. When pieces of bone had been exposed
they sloughed off and the skin grew over the stumps.

It seems possible that pituitrin might be useful in cases of
circulatory collapse in typhus. Having none it was not tried.

CASES OF TYPHUS FEVER WITH RECOVERY

INDEX OF ILLUSTRATIVE CASES

(a) Typhus Fever, Recovery
Series Number 1 177

9.
10.
36.
48.
49.
57.
59.
60.
61.
83.
92.
93.

181
185
188
188
190
192
195
198
199
200
202
204

(b) Typhus Fever, Fatal. Autopsy
Autopsy Number 4 208

5.

6.

7.

8.

9.
10.
12.
13.

208
209
209
210
211
211
212
213

Autopsy Number 11

16

L' I 1

17

2 1 .-,

18

216

19

_• 1 «v

20

21

22

22

23

22

24

22

25

(c) Typhus Fever, Fatal. No Autopsy

Series Number 87

21

(d) Problems i.\ Diagn

Autopsy Number 2

11 _ •

■ 26

Series ■ 33 -

33a 237

" " 88 238

100 240

Series Number 1. Diagnosis:
severe; with mild acute nephritis.

Typhus fever, moderately

Clinical Notes

Austrian prisoner, age 30, working as a mason, admitted to the hospital
on April 23.

April 24- Present Illness: For three days fever, constipation, and loss of
appetite. No vomiting. Pain in the eyes began early and persists. Deaf-
ness in the right ear began yesterday. There is no coryaa or sore throat.
Bowels moved four times last night after calomel. There is pain in the left
knee and calf, but none in the back.

177

178 CASES OF TYPHUS FEVER WITH RECOVERY

Physical Examination: The patient is well developed and nourished.
There is a bright flush over the malar region and a slight suffusion of the
eyes. The tongue is moist and shows a moderately heavy white coat. The
throat is negative. There is no glandular enlargement.

Heart: Dulness not increased, action rapid, rate 92. The pulmonic
second-sound is louder than the aortic second-sound. The first-sound at the
apex is indistinct. A soft systolic murmur is heard in the pulmonic area.
The pulse is large and bounding, the vessel walls soft, and the blood-pres-
sure, 115/S.-50/D.

Lungs: Negative.

Abdomen: Full and soft, not sensitive to pressure.

Liver and Spleen: Not palpable, but the splenic dulness is increased.

Reflexes: The right abdominal is present, but that on the left is in-
definite. The knee-jerks are present.

Calf Muscles are sensitive to pressure.

The Eruption consists of pink macules varying in size, irregular in shape,
disappearing on pressure, profusely and uniformly distributed over the
trunk, legs, and arms. A few are seen on the backs and soles of the feet.
The hands and the face are free from spots. There are some bright pink
spots on the scalp.

April 25. The eruption seems more profuse on the body and some spots
no longer disappear on pressure. The general color of the rash is purplish.
Spots have appeared on the backs of the hands.

The mind is clear, and the expression phlegmatic. In the afternoon the
patient vomited some greenish fluid and had pain in the abdomen. The
bowels moved three times today. The coat on the tongue has become yel-
lowish. There is no cough. The abdomen is soft and not sensitive. Haemo-
globin (Tallquist), 95 per cent. White count, 24,000. Urine: normal in
color, acid, sp. gr. 1016, albumen a trace, no sugar, diazo-reaction present.
Sediment: coarse granular casts.

April 26. The eruption is clearly visible on the palms of hands. Many
spots on the body are still pink and disappear on pressure. A few others
have begun to turn brown. The mind is clear and the expression brighter.

April 27. Mentally duller today: complains of weakness, heaviness in
the head and pain over the eyes. Slight Kernig's sign present. Attempt to
flex neck does not cause pain but the neck is slightly stiff. The pupils are of
normal size.

The Calf Muscles are slightly sensitive to firm pressure.

The Sputum is viscid and frothy with yellowish streaks.

Urine: A 24-hour mixed specimen is light, but slightly smoky in color,
acid, sp. gr. 1015, albumen a slight trace, no sugar, diazo-reaction positive.
Tests for acetone or diacetic acid were negative. The sediment shows many
granular casts. The quantity of urine has increased.

(ASKS OF TYPHUS FEVER Willi l:i 17'.»

April, 28. Bipod: White count, 12,000; haemoglobin 9ahli . L20pei
(Tallquist), 100 percenl ; red fount. 1,000,000; color index, 1 .75; differ
count: — polymorphonuclears, 92 per cent, large mononuclears, 1 pea
other types, 4 per cent. The red cells appear normal. The platelel

scarce.

Heart: The sounds are rather feeble. The first-sound i- abort.

blood-pressure is 65/S.-50/D.

The tongue is dry, and the face bronzed and dusky. There i- modi
loss of flesh. The eruption is purple and brown. The patient Le drowsy but
his mind is clear.

Urine: Normal in color, acid, sp. gr. 1010, albumen a Blight trace. The
diazo-reaction is positive. The sediment shows many hyaline, granular, and
fatty casts, and compound-granule and other cells.

May 2. There has been a gradual fall in pulse rate and temperature for
the pastfour days with slow improvement in the general condition of the
patient.

Heart: The sounds are of good quality, the pulse rather small and -
the rate 95. The nails and lips are slightly cyanotic, and the face and ears
are dusky in color. Blood-pressure, 80/S.-60/D.

The patient complains only of frontal headache. He looks comfortable
and placid as always. The color of the face is distinctly darker than at the
time of admission. It seems to be more pigmented. White count . lti.i ioo.

May 3. The diazo-reaction is negative.

May 4- Heart: The first-sound is blurred and faint, and the second-
sounds are of good quality. Blood-pressure, 90/S.-50/D.

The injection of the conjunctivae is practically gone.

May 6. Haemoglobin (Tallquist), 85-90 per cent. Blood-pressure,
100/S.-60/D.

The eruption is fading but brown mottling remains distinctly visible.

Urine: Normal in color, sp. gr. 1018, no albumen, the diazo-reaction is
negative. The sediment shows a very large quantity of amorphous material
which is readily dissolved either by heat or by acid. This sediment was be-
lieved to be composed of urates.

White count, 10,700.

May 8. Digitalis was ordered after the patient had been in the ward a
few days. It was omitted today because the pulse rate fell to 18.

Urine: Normal in color, sp. gr. 1019, no albumen, many hyaline casts.

May 9. Heart action regular and slow. The pulmonic second-sound is
accentuated and louder than the aortic second-sound . The second-sound at
the apex is accentuated. The first-sound is almost replaced by a soft
systolic murmur which is heard also in the pulmonic area but is not trans-
mitted to the axilla. Blood-pressure, 105/S.-70 D. Haemoglobin (Tall-
quist), 85 per cent. White count, 7200.

180 CASES OF TYPHUS FEVER WITH RECOVERY

May 11. The eruption is brownish, with a faint purplish tinge. It is still
clearly visible on the body and arms.

Heart: The pulmonic second-sound is accentuated, and louder than the
aortic second-sound. The second-sound at the apex is accentuated. The

CLINICAL CHART

NAME, .Scrips. *1 __

MEDICAL RECORD BOOK, \OL .

WARD BED NO. DATE_AfT.ll _.*. ..f\ n»„.l%lS.

PAGE DISEASE Jyokll-S.. feuex- _

D. 7:, .J
Month

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39

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8

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11

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3

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Series Number 1. Typhus fever moderately se-
vere; with mild, acute nephritis. Admitted to
hospital April 23, 1915. Haemoglobin estimations,
red counts, white counts, and blood-pressure are
recorded on the chart

first-sound is obscured by a systolic murmur which is not transmitted to the
axilla. Blood-pressure, 120/S.-65/D.

Urine: Normal in color, neutral, sp. gr. 1012, no albumen, rare hyaline
casts.

May 18. The first-sound is still blurred. Blood-pressure, 125/S.-65/D.
Haemoglobin (Tallquist), 65 per cent. The eruption is pale pinkish brown in
color.

CASES OF TYPHUS FEVEB WITH RECOVERY 181

May 16. The Widal test and agglutination teste for paratyphoid A and

B were negative in dilutions of 1 to 25 and 1 to 50.

The patient was discharged from the hospital in excellent condition.

Series Number 9. Diagnosis: Typhus fever, severe, with
nephritis apparently becoming chronic.

Clinical Notes

Serbian, age 30, admitted to hospital on April 26.

April 27. Present Illness: The patient says that he has been ill for
three days. The color of the rash suggests that he has boon ill at least a
week but he may have worked until three days ago.

Physical Examination: The patient is moderately emaciated, the face
browned by the sun, the malar region flushed, the eyes hollow, the nose
sharp and the facies typical of typhus. The skin is dry, and the conjunc-
tivae are moderately injected. The tongue has a slight brown coat. The
nostrils move with respiration and the breathing is rapid and rather deep.
Muscular twitching of the hands is frequent.

The eruption is scanty on trunk and legs and more marked on the
and hips. It is macular and punctiform in character and purple in color.
The face, the backs of the hands and those of the feet show no spots.

April 28. Heart: The action is rapid and regular. All heart sounds are
accentuated. No murmurs are heard. The pulse is small and weak.

Lungs: Many fine rales are heard in the back, especially at the bae
There is no dulness and the breath sounds are normal.

The abdomen is concave and soft.

The abdominal reflexes are lively and the knee-jerks are very sluggish.
The neck is moderately stiff and Kernig's sign is present to a slight degree.
The muscles of the left calf are sensitive to pressure.

There is muttering delirium at times and the patient is not fully con-
scious. The facial expression is that of pain. Gestures indicate pain in the
forehead and in the legs. The breathing is very rapid.

The Urine is of normal color, acid, sp. gr. 1015, and shows a trace of al-
bumen. The test for sugar is negative. The sediment shows ninny granular
and fatty casts.

April 29. The body is emaciated and the skin is dry.

Heart: The sounds this morning are of poor quality, and the pulse is
very weak. The systolic blood-pressure is 70 nun.

The patient is conscious but mentality clouded and his movements are
tremulous. He has a frequent, dry cough.

This morning about 720 cc. of salt solution were given intravenously.
The pulse rate dropped from 140 to 120 while the first 500 cc. were going
in and the pulse improved much in quality at the same time. The injection

182 CASES OF TYPHUS FEVER WITH RECOVERY

was terminated later because the pulse rate rose again to 130, and its qual-
ity deteriorated. The heart sounds, however, remained excellent. At 5 p.m.
the heart sounds were clear, the action regular, and the fate 134. The blood-
pressure was 75/S.-60/D., and the pulse small and weak. At 6 p.m. salt
solution was again administered. The pulse improved much at first during
the injection, but after about '48C cc had been given the patient coughed
repeatedly, the heart sounds which had been abnormally loud became
less so, and the pulse deteriorated again. The patient did not look quite
so well and seemed rather prostrated. Therefore the injection was dis-
continued.

The blood examination made one hour after the first infusion of salt
solution showed a haemoglobin (Sahli) of 125 per cent, a red count of
5,500,000, a white count of 4000, and a color index of 1.13.

April 30. This morning the patient is weaker and semicomatose. He
slept better, however.

The pulse is of very poor quality but the heart sounds are fairly good.
In the afternoon the pulse was much stronger for a time, but weakened
again later. Salt solution was administered at 6 p.m. and again at midnight
in small amounts with good effect.

May 1 . The pulse is of fair quality this morning and the heart sounds are
good.

The temperature has dropped abruptly to normal and the pulse rate has
fallen to 92. Muscular twitching persists.

May 8. This morning the patient is, semicomatose and can only be
roused with difficulty . The pulse is very weak and irregular in force. After
about 720 c.c. of salt solution had been given intravenously at 11 a.m. the
heart sounds became loud. The blood-pressure was then 95/S.-70/D.

May 4- The patient looks rather dried up this morning, but feels well
enough to smile.

The heart sounds are loud and the pulse is of fair quality, the rate
being 70.

The temperature has remained normal for 24 hours. The respiration rate
has varied from 20 to 24 during the past three days.

May 5. Patient passed only about 15 cc. of urine today. The bowels
moved once today and three times freely yesterday. The abdomen is
markedly distended and is tympanitic. It shows slight general tenderness.
There is no dulness in the region of the bladder.

The nurse says that the patient frequently takes from 240 to 300 cc. of
liquid at a time. She reports also that at times the pulse is slow and of
poor quality. Since the administration of a little bra ndy one hour ago it has
been excellent. The heart sounds are now of good quality and the rate
moderate. Digitalis, was then prescribed.
..The patient seems mentally dull and physically weak.

CA8E& OF TYPHUS FEVEB WITH RECOVEB 183

Shortly after the time mentioned in the la-i note an eneo
with little effect on the bowels bul boob the patient raided about 720

urine and the abdominal distention Dearly disappeared.

May 6. The patient is better this morning. Forthepasl threi
has been asking for bread.

The pulse is of good quality and the blood-pressure is 9 I I >

There is no distention. Patient is taking 240 cc. of water ever}
hours and eating well. His face is less emaciated. Haemoglobin Tallq
90 per cent.

The urine is acid, the sp. gr. 1025, and the diazo-reactioD lb i j
The sediment shows many hyaline and granular casts, some of them with
fat and cells adherent.

In the afternoon the left side of the face on which the patienl had
lying was distinctly oedematous.

May 7. The face and eyelids are slightly swollen and there ifi -light
oedema of left leg. The patient is very drowsy. Muscular twitching
cough have stopped. Limitation of the ingestion of liquid was prescribed.

Digitalis was discontinued on account of bradycardia.

May 9. The right side of the face is still slightly swollen. The pat ii
weak and drowsy. The bladder is distended nearly to the umbilicus. The
patient was, therefore, catheterized. Haemoglobin (Tallquist), 90 per cent.
Blood-pressure, 100/S.-80/D.

May 11. The patient now urinates normally. He is gaining strength.
There is no oedema. The ingestion of liquids has been limited to 100(> c-c.
in 24 hours.

The aortic second-sound is accentuated, and is louder than the pulmonic
second-sound. The first-sound is faint and blurred. Blood-pressure. 105 >.-
65/D.

May IJf. The patient is passing more urine and his condition is improv-
ing steadily.

The heart action is slow and regular, the pulmonic second-sound is ac-
centuated and louder than the aortic second-sound. The second-sound at
the apex is accentuated, and the first-sound is nearly replaced by a systolic
murmur which is heard equally well in the pulmonic and mitral areas, and is
not transmitted to the axilla . Blood-pressure, 105 S.-70 D. Haemoglobin
(Tallquist), 75 per cent.

May 26. The Widal test and the paratyphoid A and B agglutination
tests are negative in dilutions of 1-25 and 1-50.

May SO. The urine is normal in color, the sp. gr. 1008. and there is no
albumen.

The general condition of the patient is good.

The fingers were almost completely paralyzed for a time but their
strength is returning.

184 CASES OF TYPHUS FEVER WITH RECOVERY

June 2. The second-sounds of the heart are now of good quality. The
pulmonic second-sound is louder than the aortic second-sound. The first-
sound is blurred by a systolic murmur which is heard all over the precordia.
It is loudest in the mitral area and is not transmitted to the axilla. It dis-
appears when the patient sits up. The cardiac dulness is slightly increased

CLINICAL CHART

MEDICAL RECORD -BOOK, VOL

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Series Number 9. Typhus fevere severe. Ne-
phritis apparently becoming chronic. Admitted
to hospital April 26. Haemoglobin estimations,
red counts, white counts, and blood-pressure are
recorded on the chart

to the left and the apex impulse, when the patient lies on the left side, is felt
in the mid-axillary line. Its force is greater than normal. Blood-pressure,
115/S.-75/D.

The lungs are negative. The skin and mucous membranes are abnor-
mally pale. Haemoglobin (TaUquist), 75 per cent.

The patient is much stronger. He was discharged today, advice having
been given about diet with regard to signs of nephritis.

CASES OF TYPHIS FEVER WITH RECOVEB

Series Number 10. Diagnosis: Typhus fever moderal

severe with marked irregularity of the pulse.

Clinical Notes
Serbian, age 37, admitted to hospital on April 26.

April 27. The patient is said to have been sick for three days, but :
probably he has been so for a week.

Physical Examination: The patient lies on the Bide. Be if apatl
but mentally clear when aroused. He then becomes nervous and excitable.
There is a malar flush, the eyes are sunken, the conjunctivae are injected,
there is moderate emaciation, and the skin is dry. The pupils are large,
equal, and react to light. The tongue shows a white coat. The throat :
There is no glandular enlargement.

The eruption consists of scattered pink or purple macules on the el
abdomen, and back. The face, the arms and the legs show no eruption.
The pink spots disappear on pressure, and the purple ones fade, but do not
disappear.

Heart: The dulness is normal and the action regular but slightly rapid.
The aortic second-sound is muffled and the pulmonic second-sound is faint.
The sounds at the apex are of poor quality and the pulse is soft.

The Lungs are negative.

The Abdomen is concave, soft, and not tender. The liver and spleen are
not palpable.

Reflexes: The abdominal reflexes are absent, but the knee-jerks are
present. The neck is moderately stiff and there is a slight Kernig's sign.

The calf muscles are not sensitive to pressure. On the left hip is a purple
spot about 6 cm. in diameter, due probably to pressure.

Treatment: Ordinary care and cathartics were prescribed.

April 28. The face which is much browned by the sun has a tinge of
cyanosis. The patient is fully conscious but drowsy.

The palms of the hands are bright yellow in color and t he soles of the feet
are slightly yellow.

The systolic blood-pressure is 80 by palpation. By auscultation it
varied from 90 to 70 but there were heart beats which gave no sound in the
artery which shows a marked irregularity of force. The haemoglobin
(Tallquist) was considerably above 100 per cent.

Urine: Color high, acid, sp. gr. 1016, albumen a very slight trace, diazo-
reaction strongly positive.

April 29. Temperature falling. General condition about the same, pulse
weak.

Haemoglobin (Sahli), 130 per cent, red count, 5,900,000. color index.
1.10, white count, 16,600, platelets scarce; differential count: polymor-

186 CASES OF TYPHUS FEVER WITH RECOVERY

phonuclears, 72 per cent, lymphocytes, 8 per cent, large mononuclears,
17 per cent, transitional cells, 2 per cent, unclassified, 1 per cent.

April 30. Lungs clear. Sputum frothy, white, very viscid. Pulse of poor
quality in the morning, better in the afternoon. Salt solution was admin-
istered by rectum.

May 1. The heart sounds are of poor quality. The aortic second-sound
is very indistinct but the second-sound at the apex is fairly loud.

May 2. The patient is better this morning.

The pulse has been irregular in force and rhythm ever since admission
and the heart sounds have been of poor quality most of the time. This
evening at 6 p.m. the pulse rate at the wrist had risen from 110 to 120. The
heart rate at the same time was 132. The face was markedly flushed and
there was slight cyanosis of ears, face, and finger nails.

Heart dulness to the right was slightly increased.

The patient has been getting salt solution by rectum every six hours and
had 720 cc. yesterday afternoon intravenously. It was administered be-
cause the skin was very dry and the body emaciated as if in need of liquid.
Last night 240 cc. of salt solution were given intravenously, but the in-
fusion was then stopped because the heart sounds had become faint, and
because the pulse rate had not diminished. The pulse had improved, how-
ever, in quality. Shortly after the infusion the patient had a slight rigor.
Nothing of this sort followed the first infusion.

Blood: White count, 14,200, haemoglobin (Sahli), 100 per cent, red count,
5,900,000.

May 8. This morning the patient is decidedly better.

The aortic second-sound is faint, but the pulmonic second-sound is good.
The first and second-sounds at the apex are excellent. Blood-pressure,
85/S.-55/D.

May 4- The patient is much brighter.

The heart sounds are of good quality. Blood-pressure, 90/S.-60/D.

There is considerable cough with scanty, viscid expectoration. The
conjunctivae are still injected. The tongue is clean. White count, 9700.

May 5. Urine: Color normal, sp. gr. 1017, albumen a very slight trace.

May 6. A few days ago the patient complained of pain in the tip of the
right middle finger. A small, red, purpuric spot was seen under the skin.
Following this there was swelling of the finger tip. Yesterday a little pus
was evacuated by incision.

The general condition of the patient is improving steadily. The entire
face and ears have been flushed and are so still. The conjunctivae are no
longer injected.

Herpes appeared on the ear several days ago.

Blood-pressure, 85/S.-60/D. Haemoglobin (Tallquist), 80 per cent.
White count, 6300.

CASKS OK TYPHIS MAM; with KIXOVEH 187

May7. Haemoglobin (Sahli), 100 per cent. RedcouE 100.

May 8. Urine: Color high, acid, sp. gr. 1023, albumen a slighl
May9. The heart action is regular, and slow. The aortic t ugd

is louder than the pulmonic Becond-eound. The first-Bound i.~ blurred by a
faint systolic murmur. Blood-pressure, 95 B. 60 D White cou]

NAME. Stiies * 10

MEDICAL RECOBO BOOK. VOL

CLINICAL CHART

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Series Number 10. Typhus fever, moderately

severe with marked irregularity oi the pulse. Ad-
mitted to hospital April 26. Haemoglobin, red
counts, white counts, and blood-pressure are re-
corded on the chart

Digitalis was omitted yesterday morning, and the brandy which the
patient had been having for several days was omit tod a few days earlier.

May 11. Haemoglobin (Tallquist), 100 per cent.

The heart sounds are of good quality. The pulmonic second-sound is
louder than the aortic second-sound. A systolic murmur is heard over the
precordia, loudest in the mitral area, and not transmitted to the axilla.
Blood-pressure, 105/S.-50/D.

188 CASES OF TYPHUS FEVER WITH RECOVERY

May IS. The face is desquamating.

The pulse is of good volume and tension. The pulmonic second-sound is
louder than the aortic second-sound and both are accentuated. The first-
sound is blurred by a systolic murmur. The second-sound at the apex is ac-
centuated. Blood-pressure, 100/S.-55/D.

Today the patient was out of bed for the first time.

May 19. The patient's condition is improving rapidly.

The heart action is slow and the sounds are of good quality except the
first-sound which is faint. The pulse is small. Blood-pressure, 100/S .-
60/D. Haemoglobin (Tallquist), 80 per cent.

May SO. The urine is normal in color, sp. gr. 1018, no albumen. The
patient was discharged today in excellent condition.

Series Number 36. Diagnosis:
Mild typhus. Bradycardia, no drugs

used.

Clinical Notes

Serbian, age 26, admitted on April 26.

April 26. Said to have been ill ten days.

April 28. Urine: Normal in color, acid,
sp. gr. 1017, no sugar, albumen a slight
trace. The sediment shows a rare hyaline
cast.

Eruption Present: A complete examina-
tion was not made because the condition
of the patient was satisfactory and other
work pressing.

May 8. The tongue is clean. The con-
junctivae are injected on the right side of
each eye but not on the left side. The skin
shows a few spots of doubtful nature. The
patient is gaining rapidly in strength and
his state of nutrition is good but he looks
anaemic. Haemoglobin (Tallquist), 80 per
cent. Blood-pressure, 120/S.-55/D.

May 1 1 . The patient was discharged as
cured.

Series Number 48. Diagnosis:
Typhus fever; with chronic cervical
adenitis and hysteria during conva-
lescence.

CLINICAL CHART

!..3j6_ ..-DATE April vrt.nyi.iai5

MEOICAL RECORD

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Series Number 36. Typhus fever,
mild. Admitted to hospital April
26. Bradycardia. No drugs were
prescribed

CASES OF TYPHI'S V\]\\M WITH 1:1.' OVBBY

Clinical Not

Serbian, age 30, admitted May 12, by transfer from the Fourth Hospital
to which he went for cervical adenitis eighteen d

May 12. Physical Examination: On the ri^ht side of the neck is
siderable swelling due to enlarged glands embedded in swollen, indurated
tissue. In this region there is a discharging sinus which is not draining
freely. There is an enlarged gland beneath the jaw. This swelling i«
moderately sensitive.

The tongue shows a white coat, the teeth are good, and the pillars of the
fauces and the soft palate are slightly red. There is a single dark red papule
on the inside of the right cheek. The patient is tremulous and breathes
rapidly. There is an occasional hard cough. The sputum is scanty and
sists of frothy, viscid, blood-streaked mucus. The entire face and eai
hyperaemic, the malar region not more so than the rest .

The eruption is rose-red in color and chiefly macular in character. There
are a few papules. They are not petechial. The spots are numerous on the
chest, abdomen, and back; fewer on the arms, legs, and feet; and absent on
the hands and face.

The heart action is regular. The pulmonic second-sound is slightly
centuated and louder than the aortic second-sound. The first-sound is of
good quality. The pulse is of good volume and fairly good tension. The
systolic blood-pressure is about 100. Pressure from the inflated cuff of the
instrument caused the arm to twitch so that an accurate reading was im-
possible.

The lungs show a few scattered, fine and coarse, moist rales.

The abdomen shows no tenderness or reflex spasm but there is voluntary
rigidity. The spleen is not palpable but splenic dulness is slightly increased.

The knee-jerks are present. The calf muscles are slightly sensitive to
pressure. Kernig's test shows slight spasm of leg muscles ami causes pain.
The neck is stiff and there is pain when passive flexion is attempted.
Haemoglobin (Tallquist), 90 per cent.

May IS. The heart sounds are of good quality and the pulmonic second-
sound is louder than the aortic second-sound. The blood-pressure is 95 S
80/D.

May 15. The heart sounds are all loud, but are obscured by coarse rales.
Blood-pressure, 115/S.-60/D. There is considerable cough but the secre-
tion is less viscid. The temperature, pulse, and respiration are falling and
the patient looks better. Haemoglobin (Tallquist), 70 per cent.

May 16. White count, 16,000.
• May 19. The temperature was normal last night. The swelling on the
neck and the local tenderness have diminished much under poulticing.

190 CASES OF TYPHUS FEVER WITH RECOVERY

The heart sounds are loud and of good quality. A faint, systolic murmur
is heard in the mitral and pulmonic areas. Blood-pressure, 105/S.-65/D.
Haemoglobin (Tallquist), 90 per cent.

May 21. White count, 3000.

June 2. The patient's condition has improved rapidly since the tempera-
ture touched normal. The nutrition has been well maintained.

Yesterday the patient walked outdoors and fell down but sustained no
apparent injury. Today his happy smile is gone and he shakes all over
when approached. The knee-jerks are much exaggerated. He walks with a
limp, but can walk without it. The patient had a similar nervous disturb-
ance a week ago following an operation done in the ward on a man with
parotitis. The disturbance is clearly hysterical. When eating his meals the
patient appears perfectly well. After reassurance and sitting outside on the
steps for a little while, he regained his normal condition.

The glands in the neck remain hard, but there is much less swelling, and
the sinus is smaller. There is no discharge now.

Blood-pressure, 115/S.-75/D. Haemoglobin (Tallquist), 90 per cent.

The patient was discharged in good condition early in June.

The adenitis was better but not cured.

Series Number 49. Diagnosis: Typhus fever; typical case of
moderate severity.

Clinical Notes

May 18. Serbian soldier, admitted to hospital today, says he has been
ill in barracks four days and complains of pain in forehead, eyes, and legs.

Physical Examination: Well developed and nourished. The breathing is
rapid and accompanied by grunting and movement of the nostrils, but the
patient breathes deeply and without effort. There is a hard dry cough. An-
swers to questions are intelligent and prompt. The pupils are equal and of
moderate size, the conjunctivae are deeply injected, and the tongue shows a
heavy, white coat. The teeth are good, the pharynx and pillars of the
fauces are bright red, and the tonsils are enlarged.

Glands: The epitrochlear glands are barely palpable; those in the
axillary and inguinal regions are not enlarged, and the posterior auricular
glands are not palpable.

The whole face and the upper part of the neck are flushed. The suffusion
is brightest on the ears and in the malar region.

Eruption: There is on the face one papule and several minute purple
spots which might be old flea bites. There are many macules on the chest,
the back and the arms, and a few on the neck, hands, legs, and upper
abdomen, but none on the lower part of the abdomen. The rash consists

CASES OK TYPHIS I i;\ Ki: Wlllf 1:1/ ()\ !

191

chiefly of macules but there arc also some papul. - resembling flu- i
of typhoid, and a few punctate purple spots, undoubtedly flea l-r
Heart: The action is regular and rather rapid, the aortic
sound is accentuated and louder than the pulmonic 9eoond-60tmd. The

NAME., Series "43

CLINICAL CHART

waro etc. ..-, :,.-- f\a.y 13, 13J3.

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case of moderate severity. Haemoglobin, white
count, and blood-pressure are recorded on the
chart

first-sound is loud but blurred. The second-sound at the apex is accen-
tuated. Cardiac dulness is normal. Blood-pressure. 105 S.-oO D.

Lungs: A few coarse rales are heard.

Abdomen is soft and shows slight, general sensitiveness. The spleen
is not palpable but splenic dulness is increased. The knee-jerks are present .
The calf muscles and hamstring muscles are sensitive to pressure. Kernig's
test causes pain. The neck is very slightly stiff. Haemoglobin (TaHquist),
85 per cent.

192 CASES OF TYPHUS FEVER WITH RECOVERY

May 15. The eruption is beginning to turn purple but most of the spots
are still pink.

The heart sounds are all of good quality, the aortic second-sound equals
the pulmonic second-sound and the pulse is of the bounding type. Blood-
pressure, 105/S.-60/D. Haemoglobin (Tallquist), 70 per cent.

May 16. White count, 12,800.

May 19. There has been a rapid fall of temperature associated with
steady improvement in the condition of the patient. The nutrition is well
maintained. The eruption is turning brown. The leg muscles are no longer
sensitive.

The second-sounds are accentuated, especially the pulmonic second-
sound. The first-sound is of fair quality, the pulse is full and soft, and the
blood-pressure is 110/S.-70/D. Haemoglobin (Tallquist), 95 per cent.

May 21. The patient is doing well. Blood-pressure, 110/S.-70/D.
Haemoglobin (Tallquist), 75 per cent.

May 26. The convalescence is rapid. Blood-pressure, 110/S.-60/D.
Haemoglobin (Tallquist), 90 per cent. The Widal test in dilution of 1-25 is
positive but in that of 1-50 it is negative. Agglutination tests for para-
typhoid A and B are negative at 1-25 and 1-50.

The patient was discharged well about June 1 .

Series Number 57. Diagnosis: Typhus fever; persistent
vomiting in convalescence, and bradycardia. Four-hourly tem-
perature chart, showing crisis.

Clinical Notes

May 17. A Serbian, age 20, admitted yesterday afternoon; and said to
have been sick twelve or thirteen days.

Physical Examination: The patient lies on his side sleeping comfortably.
The breathing is rather rapid and deep but the nostrils do not move. When
aroused the patient grunts occasionally when breathing.

The face is brown and slightly flushed especially in the malar region. The
ears are particularly red.

The pupils are equal and of normal size, the conjunctivae moderately in-
jected, the tongue shows a white coat, and the throat is slightly red.

The Eruption is macular. The spots are irregular in shape and of various
sizes. Their color is purplish or bluish pink. There are a few spots on the
neck, legs, and back, and many on the shoulders, upper chest, flanks, and
abdomen. The face, mucous membranes, hands and feet show no spots.

The Heart Action is regular and not rapid. The aortic second-sound is
accentuated, and the pulmonic second-sound much accentuated and louder

CASES OF TYPHI 8 FEVEB WITH l.l.< OVERT

than the aortic second-sound. The first-eound ifl blurred by B Byatolfc mur-
mur which is heard also in the pulmonic area bul i ool transmitted to the
axilla. The second-sound at the apex is slightly accentuated. There is a

CLINICAL CHART

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chart showing crisis

marked pulsation in the neck. An excessive pulsation is soon in the second
and fourth interspaces over the heart.

The heart impulse is increased in force and is best felt in the fourth
interspace in the mid-clavicular line. When the patient lies on the left side
an excessive impulse is felt in the fourth interspace in the mid-axillary Une.
No murmurs are heard. Blood-pressure, 110 S.-85. D.

The Lungs are negative.

The Abdomen is flat, soft, and not sensitive. Pressure causes gurgling.
especially in the right iliac fossa. The liver and spleen are not palpable
and the splenic dulness is not increased.

194 CASES OF TYPHUS FEVER WITH RECOVERY

The neck is slightly stiff and there is a slight Kernig's sign but the test
does not cause pain. The leg muscles are not sensitive. The knee-jerks are
present. \ %

Haemoglobin (Sahli), 110 per cent, red count, 4,600,000, white count,
7800, color index, approximately 1.30.

Treatment: Routine without drugs.

CLINICAL CHART

name_ Stri&s. ...«.S..7_

_DATE .fin y. ..*■ . Jun£j.aiS

MEDICAL RECORD BOOK, VOI PAGE DISEASE ...!}< p.h.LLS_.f:e-Ve.r...

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Series Number 57. Typhus fever; persistent
vomiting in convalescence, bradycardia, crisis

May 19. All the second-sounds are accentuated and especially the
pulmonic second-sound. The pulse is full, and the blood-pressure, 105/S -
65/D.

The eruption is fading and turning brown. Haemoglobin (Tallquist), 95
per cent.

May 22. The patient is very thin. He has vomited frequently. (No
drugs have been used.)

GASES OF TYPHUS FEVER will! RECOVERY 195

The second-sounds are accentuated, especially the pulmonic seco re-
sound. The first-sound is of fair quality. The second-Bound at the sp
accentuated and the pulse is of fair quality. Blood pressun 5 I).

Haemoglobin (Tallquist), 90 per cent.

May 23. The patient still vomits everything. Examination of tl,.
domen is negative. Calomel was prescribed yesterday in -mall, repi
doses and feeding was attempted in very small quantities every hour but
the patient vomited even water. Nutritive enemata and sail solution by
rectum were prescribed.

May 26. The patient has not retained the salt solution well ami has
tinued to vomit until yesterday afternoon when he was able to keep down a
little water. This morning he has taken 240 c.c. of liquid nourishment and
looks better.

The heart sounds are of good quality, the pulmonic second-sound is ac-
centuated and louder than the aortic second-sound. The second-sound at
the apex is accentuated and the first-sound is of good quality. Blood-pres-
sure, 105/S.-65/D.

June 2. Improvement is marked and rapid.

June 11. There is now no stiffness of neck or legs. The patient i- very
thin, but is fairly strong. Blood-pressure, 120/S.-65/D. He will be dis-
charged tomorrow.

Series Number 59. Diagnosis: Typhus fever; diarrhoea,
crisis, pulmonary gangrene in convalescence.

Clinical Notes

May 19. Serbian, age 22. He says that his left eye became inflamed
about twenty days ago and that he has had fever for seven days. There has
been no pain except in the eye.

Physical Examination: The patient is well developed and fairly well
nourished. He is fully conscious and mentally clear. The face is brownish,
the cheeks moderately flushed, and the forehead slightly so. The ears and
nose are' red.

The right pupil is very large, but it reacts to light. The left eye is in-
flamed and sticky. The tongue shows a whitish coat, the throat is red,
and the tonsils are slightly enlarged.

The glands in the axillae are enlarged but the posterial auricular glands
are not palpable.

Eruption: The face and mucous membranes are free from spots. There
are a few spots of doubtful nature on the neck. On the arms, the chest,
and the backs of the hands there are a few typical, pink spots which
disappear on pressure. On the abdomen there are a few macules and

196 CASES OF TYPHUS FEVER WITH RECOVERY

papules. Macules are seen faintly outlined on the legs and feet. The back
shows many reddish papules of doubtful nature.

The Heart Action is regular and rapid. The pulmonic second-sound is
accentuated, and louder than the aortic second-sound. The second-sound
at the apex is accentuated. The first-sound is blurred by a systolic murmur
which is loudest in the pulmonic area and is not transmitted to the axilla.
The pulse is of the bounding type. There is excessive pulsation in the neck.
The arteries are soft. Blood-pressure, 125/S.-45/D.

The Lungs are negative.

The A bdomen is soft , full , and not sensitive . The spleen is palpable about
4 cm. below the costal margin and the splenic dulness is much increased.

The Neck is decidedly stiff but an attempt at flexion does not cause pain.
The neck muscles are not sensitive. There is a definite Kernig's sign with-
out sensitiveness of calf or thigh muscles. The knee-jerks are present.
Haemoglobin (Tallquist), 95 per cent.

Routine treatment and brandy in small quantities were prescribed.

May 21. White count, 3900.

May 22. The patient is losing weight rapidly although taking nourish-
ment well. His color is not good, the pulse is of poor quality. Blood-pres-
sure, 105/S.-50/D. Haemoglobin (Tallquist), 75 per cent.

Digitalis and extra diet were prescribed.

May 23. The patient is taking nourishment well but continues to lose
weight and strength. His condition is critical. The eruption has become
profuse all over the body and limbs, and is turning purple.

Nutrient enema of syrup, 60 cc. in 480 cc. of water were administered
every six hours.

May 26. Urine: Color high, neutral, sp. gr. 1012, no albumen, diazo-
reaction strongly positive.

May 28. The patient began to have diarrhoea yesterday and it became
profuse to day. The stools are of the pea soup variety, and not offensive.
There is incontinence of the bowels.

The mouth has been very foul. The nurse says it has required cleaning
hourly.

The patient is mildly delirious, picks at the bedclothes, and is extremely
weak.

The pulse has remained full and of good quality. Blood-pressure at 6 p.m.
95/S.-45/D. The aortic second-sound is faint and the pulmonic second-
sound of fair quality. The first-sound is faint and second-soUnd at the
apex is accentuated.

May 29. The patient's condition was so bad yesterday evening that he
was not expected to live through the night. He was extremely weak and
seemed too tired to breathe, but the pulse continued pretty good. Salt
solution, 480 cc, was given intravenously in the evening with benefit.

CASKS ()!•• TYPHIS I l.\ l.l: WITH |<);< OVEIH

197

This morning after the crisis, the patient - condition i- -till bad. Although

the pulse whs satisfactory, Ball solution w.i- given .'tu'/iin intr.v.enou

make up fur fluid lost by diarrhoea. Fifteen minute- after tin- infusion Ihe
pulse became very weak and irregular, a ml thepatienl aeemedaboul U

NAME, Stfies " 59

MEDICAL KC.COm BOOK, VOL

CUNICAL CHART

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Series Number 59. Typhus fever; severe diar-
rhoea, crisis, pulmonary gangrene in convales-
cence

The pulse afterwards improved slowly, and in the evening it was decidedly
better.

June 2. Opium was used for a few days to check the diarrhoea, luit the
stools then became foul. The opium was consequently discontinued, the
quantity of food was reduced, and castor oil administered. Today the
patient seems out of danger. He has a small black pat eh over the sacrum
which appeared about the time of the crisis but which, probably, will not
slough.

198 CASES OF TYPHUS FEVER WITH RECOVERY

June 11. Since June fourth there has been gradually increasing irregular
fever with slight constitutional symptoms.

About the time of the crisis and for several days the patient was ex-
tremely sensitive all over. Any motion or attempt at motion caused great
pain.

Examination today with the patient lying on the left side shows a few
rales at the left base behind and slight sensitiveness in the right flank with-
out spasm. The patient's appearance suggests tuberculosis. He has been
raising much sputum which is frothy and tenacious.

June 12. Urine: High colored, sp. gr. 1013, no albumen or bile.

June 2If. The sputum became foul about a week ago and a small area of
dulness with a few rales was found at the right base in the axilla. The rales at
the left base meanwhile disappeared.

Moderate elevation of temperature persists. The sputum continues to be
raised in considerable quantity and is foul at times. More often it is frothy
and inoffensive. Microscopic examination shows no tubercle bacilli. There
are great numbers of Gram-negative influenza-like bacilli, besides bacteria
of many kinds, and a few pneumococci and spirochaetae.

• The patient remained in the hospital on account of these pulmonary
symptoms and had periods of improvement followed by exacerbations. He
was last seen about the end of August still in the hospital.

Series Number 60. Diagnosis: Typhus fever. Mild paro-
titis in convalescence.

Clinical Notes

May 19. Physical Examination: The patient is too dull and confused to
reply to questions rationally. The face is much tanned and the cheeks are
slightly flushed. The pupils are equal and of normal size. The tongue
shows a brownish coat. The throat is negative and the mucous membranes
are free from spots.

The Eruption is scanty on the neck and hands and indefinite on the legs.
The chest, flanks, abdomen, back, and arms are profusely covered with
small purplish-brown spots. There are a few minute purple spots on the
forearms and elsewhere. Evidently they are flea bites.

Heart: The pulmonic second-sound is accentuated and occasionally
reduplicated. It is louder than the aortic second-sound. The second-sound
at the apex is accentuated. The first-sound is faint, and blurred by a soft,
systolic murmur which is best heard in the pulmonic area . Blood-pressure,
90/S.-50/D.

The Lungs are negative.

CASES OF TYPHUS IIAI.K WITH KKGOVERl

The Abdomen is flat, soft, and not tender. The liver and spleen an
palpable and the splenic dulness is ool increased.

The neck is very slightly stiff, but the Deck musclet are oof lensil
Kernig's sign is present, slight in degree. The teal cawea no pain. The
muscles are not sensitive to pressure.

Treatment consisted of routine measures without drugs.

May 22. The right cheek began to swell yesterday in the region of 'In-
parotid gland. The temperature rose a little. Cold compresses were applied
locally.

June 2. The tenderness and swelling of the parotid have never ;
great. The swelling diminished markedly two days ago after poulticing.
Now there is no tenderness and no pain. The swelling which remai]
slight, and very hard. There is slight, irregular fever, but the patient looks
and feels well.

June 10. Discharged well except for slight, hard swelling of the parotid
gland.

Series Number 61. Diagnosis: Typhus fever; severe case,
eruption peculiar, delirium violent.

Clinical Notes

May 20. Patient was admitted yesterday.

Physical Examination: The patient is drowsy but rational. The entire
face is flushed, especially the cheeks and ears. The pupils are small, equal,
and react to light. The conjunctivae are red. The tongue shows a brownish
coat, the throat is slightly red, and the mucous membranes are free bom
spots.

Eruption: The lower part of the neck, the chest, and the arms -how
many rose-pink macules which disappear entirely on pressure and which
are not elevated. There are a few macules on the abdomen, legs, and feet.
The flanks show a few papules which are redder in color than the macules
and which do not disappear entirety on pressure. The face and hands are
free from spots.

Extensive pink mottling is seen on the back and there are blot chefl of
irregular outline and considerable size scattered over the trunk. They re-
semble pityriasis rosea.

Heart: Dulness is normal in extent. The sounds are of good quality
except the aortic second-sound which is rather faint. The pulse is of good
volume and tension.

The Lungs are negative.

The Abdomen is very soft and tympanitic. It shows considerable general
tenderness without spasm. The spleen is palpable on deep breathing and
the splenic dulness is increased.

200 CASES OF TYPHUS FEVER WITH RECOVERY

The neck muscles are very sensitive to pressure and the neck is stiff.
The hamstring and calf muscles are very sensitive, and the thigh muscle in
front is less so, and the biceps is still less sensitive. Kernig's sign is positive
but slight in degree. The test causes pain. Routine treatment prescribed.

May 21. White count, 8C00.

May 26. The patient has been delirious since admission. At first he
would get up and try to leave the ward. The night before last the delirium
became so violent that the patient had to be tied in bed. This morning he
was quiet but mentally confused.

The face has become several shades darker in color. The conjunctivae
are still deeply injected. The patient lies on his back and dozes with eyes
half open.

Heart: The pulmonic second-sound is accentuated and louder than
the aortic second -sound. The first-sound is of good quality. The pulse is of
good volume. Blood-pressure, 95/S.-65/D. Haemoglobin (Tallquist), 75
per cent.

May 27. The pupils remain contracted.

June 12. This patient has been very ill and has gained strength slowly.
He has been drowsy and lethargic but now looks decidedly better. For
several days his bed was put out of doors but for the past three days he has
been able to walk out. Today he returned complaining of headache. The
weather has been very hot.

Three days ago white spots, like thrush, appeared in the throat. They
are clearing up now.

Examination of the heart shows the first-sound short but louder than
the second-sound and the pulmonic second-sound louder than the aortic
second-sound which is faint. Blood-pressure, 125/S.-60/D.

The skin and mucous membranes are pale. Haemoglobin (Tallquist), 90
per cent.

An iron tonic and small doses of digitalis were prescribed.

June 18. The patient is rather pale and lethargic. His condition is
otherwise satisfactory. He will be discharged tomorrow.

Series Number 83. Diagnosis: Typhus fever. Bradycardia;
heartblock (?). Digitalis used.

Clinical Notes

May 25. The patient says he was ill for a week before admission.
Physical Examination: The patient is mentally clear and alert. The
tongue shows a brownish coat.

CASKS OF TYPHI'S FEVER WITH RE( 0\ I

20]

The Heart Action is regular, the Bounds al bhi d quality

but at the a |)cx they are faint. The pulmonic second-sound is accent i
and louder than the aort ic second-sound. The pulse i- small and rapid.

CLINICAL CHART

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Series Number 83. Typhus fever. Bradycardia,
heart-block (?). Digitalis used

The Lungs are negative.

The Abdomen is negative. The spleen is not palpable but splenic tin':
is increased.

The neck is not stiff and Kernig's sign is absent. The knee-jerks are
sluggish. Digitalis was prescribed.

May 26. (Morning.) The soft palate and the pharynx are red. On the
palate is a single minute red spot. The entire face is flushed and especially
the cheeks and ears. The conjunctivae are much injected. The pupils are
small.

There are a few spots on the neck. The chest, the back, the abdomen.
and the backs of the feet and hands are profusely sprinkled with spots.

202 CASES OF TYPHUS FEVER WITH RECOVERY

The neck is not stiff or sensitive. There is a slight bilateral Kernig's sign
more definite on the right. Performance of the test causes pain in the ham-
string muscles. They are slightly sensitive to pressure.

The patient is rational but rather dull.

The pulse has been of poor quality since admission. Blood-pressure,
75/S.-55/D. .

The condition of the patient is otherwise excellent. Haemoglobin (Tall-
quist), 90 per cent. The urine is high colored.

Increased ingestion of water was prescribed and a small dose of strych-
nin every four hours.

May 26. (Afternoon.) Every third or fourth heart beat is skipped. The
sounds are loud. The pulse is now of good volume and tension. Digitalis
omitted. The doses taken since admission have not been large.

May 27. The cardiac irregularity is less pronounced but the pulse rate
continues to fall.

June 12. Haemoglobin (Tallquist), 90 per cent.

The heart action is rapid again and regular. The pulmonic second-sound
is louder than the aortic second-sound. The first-sound is louder than the
second-sound at the apex. In the aortic region a short, scratchy systolic
murmur resembling a pericardial friction rub is heard. Blood-pressure,
115/S.-75/D. Digitalis was prescribed again.

June 13. Because the pulse rate fell markedly and irregularity recurred
the digitalis was omitted this morning. In the afternoon the pulse was
again more rapid and there was no arrhythmia. The patient had been
walking about the ward a little. Blood-pressure, 120/S.-80/D.

June 20. Discharged in good condition.

Series Number 92. Diagnosis: Typhus fever in an old man;
mild; premature systoles.

Clinical Notes

June 11. Nationality Turkish, age 60.

Present Illness: Admitted yesterday having been "sick eight days." The
patient was incontinent last night and is so today. He was stuporous
yesterday but is brighter today. He is taking nourishment fairly well in
small quantities. There is no cough or expectoration.

Physical Examination: The patient is very drowsy, but when aroused
replies intelligently. He lies most of the time with the eyes half closed and
the mouth open, grunts occasionally but breathes easily and does not
cough. The skin is rough and dry. The body is well developed but ema-
ciated and dried up.

The face is very brown but markedly flushed. The hyperaemia extends
over the forehead and neck and down on to the upper part of the sternum.

CASKS OF TYPHUS FI.YI.l: WITH RECOV1

The conjunctivae are moderately injected. Th<- pupil- ar.- equal, of n.
ate size, and react to li^ht . The tongue show- a heavy browni
dry and fissured. The throat is red and sticky inucuf adherefl to it.
Eruption: The chest, arms, abdomen, and back -how mai
midway between the pink and purple Btagee. The spots an macular

*33

CUNICAL

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Series Number 92. Typhus fever in an old man;
mild; premature systoles

they nearly disappear on pressure. The legs, backs of the forearms, hands

and feet and face are free from spots.

The heart's action is regular. The aortic second-sound is slightly ac-
centuated and the pulmonic second-sound is faint . The second-sound at the
apex is accentuated and the first-sound has a valvular quality. Blood-pres-
sure, 85/S.-65/D.

The Lungs are negative.

The Abdomen is soft and is not sensitive. Peristalsis is visible. The liver
and spleen are not palpable and splenic dulness is not increased.

204 CASES OF TYPHUS FEVER WITH RECOVERY

The neck cannot be bent forward at all, but rotation is free. There is no
sensitiveness of the neck muscles. The Kernig's sign is present and this
test causes pain. The knee-jerks are present, but very sluggish. The ab-
dominal and plantar reflexes are present and lively. Haemoglobin (Tall-
quist), 85 per cent.

Prescribed brandy, 15.0 cc. and digitalis, 0.6 gm. every four hours.

June 15. The heart sounds are of fair quality. Single or double prema-
ture systoles are heard occasionally. The pulse is of good volume and fair
tension. Blood-pressure, 90/S.-55/D.

The eruption is fading. Only a few pale, brown spots remain.

The patient sleeps a great deal. He has always taken nourishment well
and seems to be improving. He has given no cause for alarm. Constipation
is very obstinate.

June 18. The aortic second-sound is faint, the pulmonic second-sound is
of fair quality, and the first-sound is short. The second -sound at the apex is
good. Blood-pressure, 90/S.-55/D.

June 25. Discharged in good condition.

Series Number 93. Diagnosis: Typhus fever; broncho-
pneumonia; dry pleurisy.

Clinical Notes

Present Illness: Serbian, age 40, admitted to the wards of a colleague
June 5 and transferred to the writer on June 8. The patient is said to have
been ill eight days before admission and to have had an eruption which
first appeared nine days ago.

June 11. Physical Examination: The patient is drowsy, but easily
aroused and is then apprehensive because every movement which involves
the shoulder causes pain. He appears to be rational. The respiration is
rapid and shallow and the nostrils move.

The face is very brown and there is a slight malar flush. The pupils are
equal, of medium size, and react to light. The tongue shows a heavy brown-
ish coat. The throat is reddish and there is sticky mucus adherent. The
skin is dry and rough.

The eruption is profuse, purple, blotchy, and is beginning to turn brown.
It is abundant on the chest, abdomen, and back, and less so on the arms and
thighs. The forearms, lower legs, feet, and hands are free from it or nearly
so.

The heart action is very rapid but regular; The aortic second-sound is
louder than the pulmonic second-sound. The second -sound at the apex is
accentuated. The first-sound is short and has a valvular quality. The
pulse is small and of low tension. Blood-pressure, 80/S.-60/D.

CASKS OF TYPHUS FEVEB WITH RECOVERY

The Liukj:; ;ue negative.

The Abdomen is soft and seems to be acuterj sensitive all over, r
anywhere on the abdomen causes the patient's face '" Bhow pain.

The spleeD is not palpable and the splenic dulness If not increased.

The neck is very stiff and the neck muscles are sensitive. The bead ro-
tates freely but cannot be bent forward. The Kernig'fl sign i- well marked.
The muscles of the thighs and calves appear to be very aensitivi
sure.

For three days the patient has been receiving 0.0 gin. of digitalis and
15.0 cc of brandy every four hours. The night before last salt solution by
rectum every six hours was prescribed. At first it was all retained, but now
some of it is being lost. The bowels became incontinent yesterday.

The patient coughs much but expels the secretion with greal difficulty
because he is very weak and the sputum is extremely viscid. It frequently
causes a rattle in the throat.

The nourishment was well taken until last night.

The pulse is more rapid and becomes bad whenever the patient i- dis-
turbed. The blood-pressure at 11.30 a.m. was 75/S.-65 D. The aortic
second-sound was of fair quality. The pulmonic second-sound and the
first-sound were faint. At 5 p.m. the blood-pressure was so S. 55 D., and
the heart sounds as before. The pulse was very weak. The area of heart
dulness was less than normal. (Front of chest hyperresonant.)

The Lungs were practically clear and the breathing easy but rapid. At
5.30, about 480 cc of salt solution were administered intravenously.
During the injection the pulse improved in quality, and the heart sounds
became stronger; the blood-pressure after the injection was 83 S.-60 D.
Half an hour before the injection the pulse rate was 140. Immediately after
the injection it was varied between 132 and 136. About 15 or 20 minutes
after the infusion the patient had a prolonged and severe rigor during which
his color became dusky and the pulse scarcely perceptible. The rigor lasted
about 15 minutes and the patient's condition afterward was much the same
as before the infusion. Haemoglobin (Tallquist), 100 per cent.

June 18. The temperature is falling and the condition has improved.

June 15. Yesterday afternoon the patient's condition again became
critical. He was given tea last night. He rallied again this morning and
now seems decidedly better. The eruption is fading. Blood-pressure at
noon, 90/S.-75/D.

For the past three days he has been taking nourishment poorly.

June 17. There has been severe diarrhoea for several days. Opium and
an astringent mixture were given to check it .

Last night the circulatory condition was unsatisfactory. Salt solution.
about 360 cc, were given intravenously. There was no rigor. The pulse
is of fair quality this morning.

206

CASES OF TYPHUS FEVER WITH RECOVERY

There is a good deal of cough and a considerable quantity of thick,
whitish expectoration. Nourishment is taken better this morning.

Urine: Normal color, sp. gr. 1016, no albumen, no bile.

The pulse in the afternoon became poor in quality. The rate was 104.
Salt solution was prepared in the most careful way, the temperature care-

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Series Number 93. Typhus fever, severe; bron-
chopneumonia, dry pleurisy

fully regulated, and about 480 cc. were given intravenously. The patient
had a severe rigor after it. He was then given a small dose of morphin
subcutaneously and slept well.

June 18. Blood-pressure this morning 100/S.-75/D.

June 24. Since the 19th there has been a gradual fall of temperature and
slow but steady improvement in the patient's condition.

About June 20 a friction-rub was heard at the right base. Yesterday the
lungs were negative except for a few rales at the bases.

CASES OF TYPHI'S VKYl'Ai WITH RECOVER -'"7

The patient occasionally expectorate! thick lumps of whiti-h rn .
with great difficulty on account of weakness. Be succeed! only with help
and encouragement from the nurse.

The sputum looks as if it came from the nasopharynx, but tin- qui
sure that it is raised from the chest. Microscopical examination of the
sputum shows no tubercle bacilli, but many pneumococci and variolic <>?hf-r
bacteria are present. There are a few spirochaetae and influenza-like bacilli
and a very few pus cells. The sputum has had a foul odor occasionally.

July. When last seen the patient was convalescent and had no oough.
But for the remarkably assiduous care of the nurse the pulmonary oompHcar
tions would almost certainly have proved fatal.

The diagnosis of bronchopneumonia in this case was based on severe
pulmonary symptoms combined with a secondary rise of temperature

TYPHUS FEVER, FATAL CASES. AUTOPSY
Autopsy Number 4. Patient of Dr. .

Diagnosis: Typhus fever, pulmonary oedema, bronchitis.
Died, probably, during the stage of nervous depression.
Apparent Cause of Death: Acute myocardial weakness,
chronic nephritis, and (?) early pneumonia.

Clinical Notes
Rapid breathing, etc., before death suggested pneumonia.

Autopsy Findings ■

Postmortem performed 24 hours after death. Body emaciated and
livid.

Heart: Not dilated, muscle pale, rather flabby. Mitral orifice slightly
large. Valves natural. An ante-mortem (?) thrombus was found in the left
ventricle.

Lungs: Many pleural adhesions, bilaterally distributed, some old, others
more recent. On the pleural surface at the right apex a fresh haemorrhage
was found. The right upper lobe was oedematous and congested. The left
lung was deeply congested throughout. Even the apex was oedematous.

In the bronchioles of the left lower lobe purulent exudate was found.

Liver: Pale and slightly fatty.

Spleen: Large, dark red, confluent.

Kidneys: Slightly diminished in size, capsules firmly adherent. Surface
of section pale, cortex and medulla not markedly abnormal but slightly
congested.

Specimens: Left kidney, right ventricle, lower lobe of left lung, spleen,
and liver.

Autopsy Number 5. (A I.) Patient of Dr. Smith.
Diagnosis: Typhus fever.
Died during the postfebrile stage.

Apparent Cause of Death: Gradual exhaustion and cardiac
weakness.

Clinical Notes

The day before he died the patient was semicomatose, delirious, and
prostrated. The pulse was of the Corrigan type and a diastolic murmur was

208

TYPHUS FEVEB FATAL CASES IUTOH

heard near the fourth left costal cartilage. About 360cc. of salt solutio]
given under the pectoral muscle in the afternoon. The next morning

patient's condition was worse, bul the fora and volume of the ,

good. Half an hour later he died. The patient h.id passed throng
febrile period of typhus before dentil.

Autopsy Finding*

Body of young man, extremely emaciated.

Heart: Slightly dilated ; muscle flabby. Slight old thickening of mitral

valve. Aortic valves normal.

Passive Congestion of all organs.

Stomach: Extremely distended with air.

Specimens: Heart muscle, liver, spleen, kidney.

This case called to mind one in which Dr. Smith saw tetany for Beveral
days, followed by recovery. Was the tetany due to gastric dilatation?

Autopsy Number 6. (A II.) Patient of Dr. Smith.
Diagnosis: Typhus fever.

Died during the stage of nervous depression or later.
Apparent Cause of Death: Gradual exhaustion. Old mitral
stenosis found.

Clinical Notes

Age 45. Died late in disease.

Autopsy Findings
The body is emaciated.

Heart: Left ventricle considerably hypertrophied and firmly contracted.
Right ventricle dilated, muscle firm. Mitral orifice stenosed, cresentic in

shape, admits one finger with difficulty. Other valves natural.

Lungs: Many dense fibrous adhesions of the pleura. A nodule at the left
apex, probably tuberculous; old scars at right apex.

Spleen: Large and soft, surface of section pale.

Liver: Large, deeply congested, slight fatty degeneration.

Kidneys: Appear normal.

Specimens: Left ventricle, spleen, liver, kidney.

Autopsy Number 7. Patient of Dr. Holmes.

Diagnosis: Typhus fever, lobar pneumonia.
Death during the stage of nervous depression or later.
Apparent Cause of Death: Lobar pneumonia as a complica-
tion.

210 TYPHUS FEVER — FATAL CASES — AUTOPSY

Clinical Notes

On admission, April 26, patient was said to have been sick eight days,
but the presence of a scanty, old rash made it probable that he had been ill
longer than the time stated.

The temperature dropped to 101° on the second day after admission and
continued at about that level, with the pulse at from 90 to 100, and the
respiration at from 24 to 26 until the patient died on May 5.

Autopsy Findings

Postmortem performed four hours after death.

Body covered with small petechial spots.

Heart: Muscle firm and dark in color. No dilatation. Valves not re-
markable.

The Aorta showed slight atheroma of the first part of the arch.

Lungs: All except the apex of the upper lobe of the left lung was con-
solidated as was also the right lower lobe. The process was evidently recent.

Liver: Deeply congested.

Spleen: Large, soft, dark red.

Kidneys: Marked passive congestion.

Specimens: Left ventricle, kidney, heart. (No. A.)

Autopsy Number 8. Patient of Dr. .

Diagnosis: Typhus fever.
Died during the postfebrile stage.

Apparent Cause of Death: Gradual exhaustion with circula-
tory weakness, probably vascular in origin.

Clinical Notes

Toward the end of defervescence the patient developed signs of circula-
tory weakness which increased in spite of medication until he died a week
later. Salt solution was not administered.

Autopsy Findings

Postmortem performed sixteen hours after death.

Extreme emaciation, muscles very dry.

Heart: Right ventricle not dilated. Left ventricle firmly contracted.
Valves appear normal.

Lungs: Pale, anterior borders emphysematous, posterior margins con-
gested. There is a recent infarct, deep red in color, 2.5 to 4 cm. in diameter
at the anterior margin of the right lower lobe.

Liver: Large, passively congested.

TYPHUS FEVER— FATAL CASES AUTOPSY 211

Spleen: Small, dark, firm.

Kidneys: Congested, not otherwise remarkable.

Specimens: Lung infarct, liver, kidney, bear! . No. I

Autopsy Number 9. (C.) Patient of Dr. Smith.

Diagnosis: Typhus fever.

Died during late stage of nervous excitement or early in that
of nervous depression.

Apparent Cause of Death: Acute exhaustion probably with
terminal circulatory weakness. Slight old mitral sten<

Clinical Notes

Age 53. The patient was violently delirious, especially at night, for
several days before death. The delirium prevented sleep and continued
every night until the patient became exhausted. Then he would !».- quieter
for a time. When active he presented the appearance of delirium tremens,
sat up in bed grinding his teeth, looked about wildly, and rolled bifl
Apparently, he had terrifying delusions. Mucus collected rapidly in the
throat and required frequent attention. The pulse at first was rapid and of
the bounding type. The breathing was very rapid.

The afternoon before death, faint, distant, bronchial breathing was
heard at the left base behind. No dulness was found. The breathing was
rapid and labored, and the general picture was that of pneumonia in an
alcoholic individual.

Autopsy Findings

Body not emaciated. Traces of rash persist.

Heart Muscle: Soft and dark in color. Left ventricle in systolic contrac-
tion. Right ventricle slightly dilated. Mitral orifice admits two fingers
with difficulty. Valves slightly shrunken and thickened. No evidence of
recent damage. Other valves natural. Great vessels engorged with blood.

Lungs: Bloody exudate in left lower lobe representing perhaps the first
stage of pneumonic consolidation. Both lungs emphysematous in front.
Right lung not otherwise remarkable.

Liver and Kidneys: Markedly congested.

Spleen: Large, dark, confluent.

Specimens: Liver, spleen, kidney, heart. (No. C.)

Autopsy Number 10. (C.) Patient of Dr. Holmes.

Diagnosis: Typhus fever.

Died during the postfebrile period.

Apparent Cause of Death: Gradual exhaustion.

212 TYPHUS FEVER — FATAL CASES — AUTOPSY

Clinical Notes
Age 30. Ill about five weeks.

Autopsy Findings

Postmortem performed twelve hours after death.

Considerable emaciation. No visible eruption. Subcutaneous fat small
in amount.

Heart Muscle: Pale. Otherwise normal in appearance.

Aorta: Shows a trace of atheroma.

Lungs: Bilateral pleural adhesions, apparently rather recent. Hypo-
static congestion at bases, greater on the left than on the right.

Liver: Few old adhesions to surrounding structures. Organ enlarged but
not cirrhotic.

Spleen: Large, soft, rather pale.

Kidneys: Of normal size, capsules adherent in places, moderately con-
gested. Otherwise not remarkable.

Specimens: Liver, spleen, kidney.

Autopsy Numbek 12. (S. No. 45.) Patient of Dr. Holmes.

Diagnosis: Typhus fever.

Death during the stage of nervous depression.

Apparent Cause of Death: Acute myocardial weakness.

Clinical Notes

Serbian soldier, admitted May 7.

May 8. White count, 12,000.

May 9. (Examination by writer.) On cheeks, nose, and chin are large
blotches of haemorrhage beneath the epidermis. They are sharply defined
and dark red in color. Traumatic excoriations on back. The patient is said
to have had a fight in barracks.

The trunk, back, arms, and legs show an abundant, macular, purplish
eruption. The patient lies on the back, comatose, snoring, and can be
aroused with difficulty. He breathes through the mouth rapidly and
deeply.

Heart Sounds of poor quality, action rapid, no murmurs.

The pulse is soft and of fair volume, but irregular in force. Blood-pres-
sure, 90/S.-65/D.

Lungs: Clear in front and at sides, back not examined.

Blood: Haemoglobin (Tallquist), 100 per cent + + ; by Sahli, 115
percent. Red count, 5,000,000.

May 11. Coma increased and patient died.

TYPHUS FEVER- FATAL CASES AUTO! 213

Avio/i .■;// Findii
May 12. Body well nourished.

Heart: Both ventricles much dilated, flabby, and full of blood. \

not remarkable.

Lungs: Showed a few old adhesions.

Intestines: Showed a few old adhesions. The colon wBt enormoudy
tended with gas.

Kidneys: There seemed to be a slight excess of connective tissue and -
fatty infiltration.

Passive Congestion of all organs.

Brain: Very oedematous. No gross lesion found.

Specimens: Whole heart and pieces of organs.

Autopsy Number 13. (S. No. 50.) Patient of Dr. Smith.
Diagnosis: Typhus fever.
Died during the postfebrile stage.

Apparent Cause of Death: Gradual exhaustion, myocardial
weakness.

Clinical Notes

The patient had a profuse eruption at the time of admission. Defer-
vescence by lysis followed, the temperature remained normal for scvm
days and during this time the patient was apparently improving slowly.
Then fever recurred without apparent cause and four days later the
patient died with "dyspnoea and distress " which came on during the night .

Corneal ulceration appeared at about the end of the febrile period.

Autopsy Findings

Body of man past middle age, extremely emaciated. Muscles much
wasted and very dry, but plenty of blood in veins.

Heart Muscle: Flabby. Right ventricle moderately dilated. Valves
natural.

Lungs: Bilateral pleural adhesions, some old, others more recent . Slight
congestion of bases.

Liver: Engorged with blood. Slight fatty degeneration.

Spleen: Small, dark, firm.

Kidneys: Apparently there is some fatty infiltration without evidence
of interstitial change.

Specimens: Pieces of organs.

214 TYPHUS FEVER — FATAL CASES — AUTOPSY

Autopsy Number 14. (S. No. 51.) Patient of Dr. Smith.
Diagnosis: Typhus fever.
Died during the postfebrile stage.

Apparent Cause of Death: Gradual exhaustion, myocardial
weakness.

Clinical Notes

111 for a long time. Temperature reached normal nine days after admis-
sion and remained there except for slight recurrences until the death of
the patient nineteen days later.

Autopsy Findings

Body of man past middle age, extremely emaciated. Muscles extremely
wasted. Abdominal wall lies against spinal column.

Heart Muscle: Pale, flabby, no dilatation, valves natural.

Lungs: Many pleural adhesions which appear to be of recent formation.
One small pleural fibroma, perhaps tuberculous. No fluid in pleural cavi-
ties, no congestion, and no consolidation.

Larynx: Shows slight chronic swelling of mucosa. Vocal cords normal.

Thyroid Gland: Not remarkable.

Liver: Slight passive congestion.

Spleen: Of normal size, soft.

Kidneys: Capsule strips easily. There is slight interstitial fibrosis and
moderate passive congestion.

Specmens: Thyroid, liver, spleen, kidney, lung.

Autopsy Number 16. (S. No. 58.) Patient of Dr. — — .

Diagnosis: Typhus fever, acute and chronic, nephritis, en-
larged thymus.

Died during the last stage of the febrile period or imme-
diately after it.

Apparent Cause of Death: Uraemia as a complication.

Clinical Notes

Admitted May 16, age 30. Eruption typical. The temperature
dropped by rapid lysis. The urine was scanty. The patient died in a con-
vulsion.

May 17. Haemoglobin (Sahli), 115 per cent. Red count, 5,000,000.
White count, 15,000.

Autopsy Findings

May 19. Postmortem performed three hours after death. Body slightly
emaciated, eruption visible.

TYPHUS FEVEB FATAL CASES AUTOP 215

Heart Muscle: Firmly contracted, w:dl of lefl ve&trit
little hypertrophied. A few small patches of atheroma in the sinuses of

Valsalva. No other abnormalities seen.

Lungs: Pleural cavities nearly obliterated by adhi Some <>f those

on the right appear to he recent, the other.- are old. Posterior DO
lungs congested.

Thymus Gland: Larger than normal. Adhesions between Bternum and
mediastinal contents.

Abdominal Cavity: Shows many old adhesions of omentum to abdominal
wall and to intestines.

Liver: Thickly covered with old fibrous adhesions.

Spleen: Buried in a mass of old adhesions, much enlarged, and \

Kidneys: Both much enlarged. Surface of section gritty, pale, and
grayish in color. Appearance suggests acute process superimposed on a
chronic nephritis.

Specimens: Left ventricle, liver, spleen, kidney.

Autopsy Number 17. (S. No. 53.) Patient of Dr. Smith.

Diagnosis: Typhus fever.

Died during the stage of nervous depression.

Apparent Cause of Death: Coma, bronchitis, and pulmonary-
congestion.

Clinical Notes

Admitted May 14.

May 15. (Examination and notes by writer.) Patient lies on back,
eyes closed, knees drawn up and apart, breathing rapid and shallow, but
without effort; wakes frequently and looks about anxiously as If having bad
dreams. There is a slight rattle in the throat and the patient groans from
time to time. The face is dark brown and cyanotic as are also the lips and
ears. The conjunctivae are injected. The pupils are equal and unusually
large.

The Eruption is chiefly macular but some of the spots are elevated to the
touch. The color is brownish purple. The trunk and arms are so profusely
covered by the rash that no normal skin can be seen. There are many spots
on the legs, and a few on the backs of the hands and feet . There are a few-
circular, red spots of uniform size and smaller than the head oi a pin. They
are old flea bites.

The Heart Action is rapid, and the sounds are of fair quality, but partly
obscured by rales. The first-sound is short. The pulse is regular, of good
volume, and diminished tension.

Lungs: Chest of barrel type, hyperresonant in front. There are many
medium rales in front, and coarser rales behind, but no bronchial breathing
or dulness.

216 TYPHUS FEVER — FATAL CASES — AUTOPSY

Abdomen: Shows slight general sensitiveness. The bladder is distended
to the umbilicus. Urine and faeces are passed involuntarily.

The Knee-jerks are present. There is a slight Kernig's sign. The muscles
of the calves and thighs are not sensitive. The neck is very slightly stiff.

Haemoglobin, 100 per cent or more. The color does not correspond well
with that of the Tallquist scale.

Blood-pressure, about 95/S.-80/D-, but variable. Some systolic sounds
are heard at a pressure of 100 mm. showing variation in force of the pulse.
The variation seemed to be dependent on the phase of the respiration.

May 17. Blood-pressure, 100/S ,-85/D. Breathing easier, cyanosis less,
no rattle in throat, rales heard only at the backs. Mildly delirious but
brighter. Haemoglobin (Sahli), 130 per cent. Red count, 5,600,000.
White count, 4300.

May 21 . Since last note the patient has alternately improved and re-
lapsed. He has been constantly more or less delirious. Yesterday he be-
came comatose. The pulse today is smaller and weaker than it was. The
pupils are very small. The patient died at 10 p.m.

Autopsy Findings

Postmortem performed twelve hours after death.

Body strongly developed and well nourished, apparent age 40 years.
Extreme lividity.

Heart: Normal in size, in systolic contraction, neither ventricle dilated,
muscle firm. Otherwise natural. There is a very small patch of atheroma
on the aorta.

Lungs: Congestion slight in right lung, marked in the left. No consolida-
tion. The bronchi contain thick, blood-stained mucus. Mucous membrane
of bronchi red and swollen.

Liver: Moderately enlarged and congested.

Spleen: Adherent to the abdominal wall in the flank, twice the normal
size, soft.

Kidneys: Appear normal.

Urine from bladder contains much albumen, some pus, a few red blood-
cells and casts.

Specimens: Whole heart, liver, spleen, and kidney.

Autopsy Number 18. (S. No. 71.) Patient of writer.

Diagnosis: Typhus fever.

Died during the stage of nervous depression.

Apparent Cause of Death: Coma, beginning pneumonia (?).

TYPHUS FEVER— FATAL CASES AUT

217

Clinical Noh

May 19. Patient transferred today from another ward, feeble and
mildly delirious. There was a profuse purple eruption when \\<- was ad-
mitted to hospital on May 14.

Heart Sounds: Obscured by rales. Pulse good.

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CUNICAL CHART

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Autopsy Number IS. Typhus fever.
Coma, (?) beginning pneumonia

Lungs: At the right base there is dulness with diminished breath
sounds and rales. At the left base there are rales, and at the angle of the left
scapula distant bronchial breathing is heard.

May 20. The patient takes fluid badly but excretes it well. He coughs
occasionally, but lacks strength to spit. The respiration is very rapid, and
suggests pneumonia. The arms, and especially the hands, twitch constantly.
The patient sweats profusely and is comatose and incontinent.

May 21. Died this morning.

218 TYPHUS FEVER — FATAL CASES — AUTOPSY

Autopsy Findings

May 21 . Body of man of middle age, well nourished. The eruption has
faded.

Heart: Several milk patches on visceral pericardium. The heart is rather
small and contracted. The muscle appears normal and the valves natural.
There are a few small patches of atheroma on the aorta. The coronary
orifices are normal.

Lungs: No pleural adhesions. Near the apex of the right lower lobe there
is a patch of congestion about three inches in diameter. There is no con-
solidation. The bases are not congested, and the lungs, otherwise, appear
normal.

Abdomen: Colon much distended with gas. A mass of old fibrous ad-
hesions surrounds the spleen.

Spleen: Shows thick patches of fibrous tissue on its surface.

Liver: Definitely but slightly cirrhotic, and slightly enlarged.

Kidneys: Congested, not otherwise remarkable.

Specimens: Whole heart and pieces of organs.

Autopsy Number 19. (S. No. 81.) Patient of Dr. Smith
and of writer.

Diagnosis: Post-typhus parotitis and cellulitis with septi-
caemia.

Died during the stage of nervous depression.

Apparent Cause of Death: Parotitis and septicaemia.

Clinical Notes

Austrian soldier. Transferred from another ward in the later stages of
typhus fever. Previously, he had a definite rash which has now disap-
peared.

May 19. The patient is extremely thin. Both cheeks are much swollen,
hard, and moderately sensitive, causing much pain and making swallowing
very difficult.

May 21 . Increased fever. Fluctuation can be definitely felt on the right
cheek in front of the ear. An incision was made by Dr. Smith under
chloroform anaesthesia and several ounces of thick pus were evacuated.
White count, 9100.

May 22. The temperature remains high and the pulse rapid. There is
little discharge from the incision on the right and the swelling has increased.
Therefore another incision was made at the angle of the jaw on the same
side but very little pus was found. A third incision was then made on the
left side below the ear and 15 to 30 cc of thick pus were evacuated.

TYPHUS FEVER— FATAL < VSES AUTOPSY

May 23. Today the skill and conjunctivae showed slight jaundi
patient has been practically without aourishmenl for several days. A lit t Kf
was given through a nasal tube. [Jrine, sp. lt. lois, bik present.

May 24- The swelling under the chin which began s few has

increased in spite of the incisions over both parotids. The tempi

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Autopsy Number 19. Typhus fever.
Parotitis and septicaemia

very high and breathing is difficult. Under local anaesthesia Dr. Smith
made a deep incision under the chin but the amount of pus evacuated was
small. The tissue was firm and oedematous. The patient died at 7A5 PJf.

Autopsy Findings

Postmortem performed thirteen hours after death.
Body of man of about 35 years of age. Extremely emaciated.
Heart: Slight excess of clear yellowish fluid in the pericardial sack. The
organ is of normal size, and firmly contracted. The muscle is pale, and

220 TYPHUS FEVER — FATAL CASES — AUTOPSY

rather soft. On one curtain of the tricuspid valve and on the wall of the
heart above it are patches of oedema with a little extravasation of blood.
The valves appear otherwise normal.

Lungs: Appear normal. There is little if any oedema.

Abdomen: Intestines moderately distended with gas.

Liver: Rather small. The surface of section is shiny and stained with
bile. The markings are indistinct.

Spleen: Much enlarged and very soft.

Kidneys: The left kidney is about twice the normal size. The capsule
strips easily. The surface of section shows pale streaks in the cortical region
and the markings there are indistinct.

The right kidney is about one-half the normal size, and is moderately
congested, but otherwise normal in appearance.

Larynx: Mucous membrane slightly swollen and injected but not ©ede-
matous.

Specimens: Pieces of organs.

i
Autopsy Number $0. (S. No. 84.) Patient of writer.
Diagnosis: Typhus fever.
Died during the state of defervescence.
Apparent Cause of Death: Chronic myocardial degeneration.

Clinical Notes

May 26. The patient is an old man sent yesterday from another ward.
He is well developed, but poorly nourished. He is mentally clear.

The face is not flushed. The conjunctivae are slightly injected. The
pupils are equal and of normal size. The tongue shows a slight, white coat.
The throat is negative except for shreds of thick mucus adherent to it.

The Eruption is small, macular, and purplish-pink. Most of the spots
disappear completely on pressure. The spots are best seen on the inner sur-
faces of the arms and wrists and on the sides of the chest where they are
numerous. There are few or none in other parts.

The Heart Action is rapid and regular. The second -sounds are of good
quality. The first-sound is short and valvular, and the pulse small and
weak. The arteries are palpable. Blood-pressure, 75/S.-60/D.

The Abdomen is flat, and shows slight general sensitiveness. The spleen
is not palpable and splenic dulness is not increased.

The knee-jerks are present. There is no sensitiveness of the leg muscles,
and no Kernig's sign. The neck is not stiff. Haemoglobin, 85 per cent.

Date (?). The patient has vomited a little. He dislikes liquids, but eats
bread.

TYPHUS FEVER— FATAL CASES AUTOPSY

At midnight the patient was given something to drink ai 1 all

right. At 12.30 a.m. when the nurse returned to the wax6 to g
the patient made a sudden motion and died immediately.

Autopsy Findings

Postmortem performed ten hours after death. Body emacia
Heart: Normal in size and not dilated. Muscle brown and flabby.
Cardiac vessels not tortuous. Slight old thickening of the mitral \

Autopsy* 2.0
name, (Strits * 64-)-

CLINICAL CHART

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Autopsy Number 20. Typhus fever. Chronic
myocardial degenera t ion

the orifice of which admits two fingers. The other valves, the aorta . and the
coronary arteries are natural.

Lungs: Many pleural adhesions on left side. The back of the left lung and
especially the apex of the lower lobe is dark in color, and on section a haem-
orrhagic fluid exudates. The lung feels leathery. The apex of the left lung

222 TYPHUS FEVER — FATAL CASES — AUTOPSY

remains distended and feels like a cyst. On cutting it a clear fluid exudates.
On the right side there are fewer adhesions than on the left and the lung is
less congested than the left.

Abdomen: Intestines moderately distended but otherwise normal in
appearance.

Liver: Of normal size. Surface of section pale brown in color and
greasy. It is pitted here and there and shows yellowish spots. (Slight
fibrosis and fatty changes.)

Spleen: Firmly adherent to surrounding structures. Capsule nearly
covered with patches of old fibrous tissue. Organ much enlarged. Pulp
almost fluid.

Kidneys: The left is large, and its markings are vague and confused by
whitish streaks and spots. The right is smaller than the left, and is similarly
abnormal in appearance but to a less degree.

Specimens: Whole heart and pieces of organs.

Autopsy Nttmbek 21. Patient of Dr. Smith.
Diagnosis: Typhus fever.
Died during the stage of nervous depression.,
Apparent Cause of Death: Coma and diarrhoea with terminal
circulatory collapse.

Clinical Notes

On admission the patient had a typical and very profuse rash. He died
three days later. The nurse said that the patient was comatose from the
time of admission, that the throat was covered with dry, hard mucus, and
that there was cough, incontinence, and diarrhoea, and that the patient had
to be fed with a nasal tube. He was very cyanotic, but breathed easily.
The legs on the morning before death were icy cold. The pulse remained
good until 6 p.m. when it became very feeble. The patient died an hour later,
three days after admission.

Autopsy Findings

Body of man apparently about 30 years of age. Well developed, poorly
nourished. No rash visible. Many sudamina.

Heart: Not dilated, muscle firm and normal in appearance. There is
slight fibrous thickening of mitral valve which admits two fingers. The
other valves are normal in appearance. The coronary openings are normal.
There are a few small yellowish spots on the inner surface of the aorta.

Lungs: Normal in appearance. No congestion.

Abdomen: The intestines appeared normal externally.

Liver: On section the markings are indistinct. The color is rather pale
brown.

TYPHUS FEVER FATAL CAS]

Spleen: Adherent to surrounding structure and covered with fit •
adhesions. It is slightly enlarged and rather soft.

Kidneys: Normal in size; capsule -tups easily. I >u » ction marking -
distinct. Cortex shows yellowish mottling.

Specimens: Whole heart and pieces of organs.

Autopsy Number 22. Patient of Dr. Smith.

Diagnosis: Typhus fever.

Died during the stage of defervescence or later.

Apparent Cause of Death: Late circulatory weakni 38.

Clinical Notes

The eruption was fading at the time of admission. The nurse says that
at this time the patient was rather cyanotic and t he pulse scarcely palpable,
and that it improved later, but was never good . The patient gained a little

at first and took food well until the last day. The stools were loose and
there was slight diarrhoea. There was quiet, muttering delirium. The pa-
tient did not look as if dangerously sick. On the last day of life three saline
enemata were given and all were retained. The patient got very cold six
hours before death and died at 11 p.m.

Autopsy Findings

Body of man apparently about 35 years of age. Well developed and
nourished. Much post-mortem discoloration.

Heart: Relaxed; muscle very flabby. Several small milk patches on
epicardium. Edges of mitral valve show slight fibrous thickening. The
orifice easily admits two fingers. The other valves appear normal.

Lungs: Pleural cavities normal in appearance. Anterior surface of limes
natural. Marked acute congestion posterially and especially at bases. No
consolidation or atelectasis.

Abdomen: The intestines and stomach are distended with gas.

Liver: Normal in size and consistence, moderately congested.

Spleen: Few fibrous adhesions. The organ is several times the normal
size and very soft.

Kidneys: Markedly congested; otherwise natural in appearance.

Specimens: Whole heart, and pieces of organs.

Autopsy Number 23. (S. No. 95.)
Diagnosis: Typhus fever.
Died during the stage of nervous depression.
Apparent Cause of Death: Coma, with cerebrospinal inflam-
matory phenomena and excess of cerebrospinal fluid.

224 TYPHUS FEVER — FATAL CASES — AUTOPSY

Clinical Notes

June 12. Turkish prisoner, age 40. Admitted last night. Does not know
how many days ill. Condition good.

Physical Examination: The patient looks comfortable, breathes through
the mouth, respiration rapid and shallow, nostrils move with respiration.
He is semicomatose, but replies to questions when roused. There is oc-
casional dry cough.

The pupils are equal and very small. The conjunctivae are deeply in-
jected. The tongue is brown, fissured, and dry. The pharynx and soft
palate are red and glazed, with sticky mucus adherent.

The forehead and cheeks are flushed. There is a slight flush on the neck
and on the upper sternum. The ears are not flushed.

The Eruption is seen on the lower part of the neck. It is profuse over the
front and sides of the chest, on the upper abdomen and on the back, less
abundant on the lower abdomen and upper arms, scanty on the forearms,
legs, and hands, and slightly more marked on the feet. It consists of irregu-
lar, ill-defined macules, some large and some small. The color is purple with
a pinkish tinge.

Heart: Size apparently normal, action rapid, regular. The aortic second-
sound is of fair quality, the pulmonic second-sound is rather faint, and
the first-sound at the apex has a valvular quality. The pulse is full and
of the bounding type. The tension is low. The blood-pressure is 90 /S-
50/D.

Lungs: There is no dulness or bronchial breathing. Many coarse, dry
rales are heard and at the base of the right axilla some fine moist rales.

The Abdomen is soft, and there is slight general sensitiveness with volun-
tary spasm. The liver and spleen are not palpable but the splenic dulness is
much increased.

The muscles of the neck are not sensitive but the neck can be bent for-
ward only a little . Rotation is free . The muscles of the thighs and calves are
sensitive to firm pressure. Those of the arms are not so. The knee-jerk is
sluggish on the right and is not obtained on the left. Kernig's sign is well
marked. Haemoglobin (Tallquist), 100 per cent.

June 15. The patient's color is becoming dusky. He never sleeps. Digi-
talis has been administered subcutaneously because the patient takes
medicine badly. He took food well the first day, but since then has taken
little food or water.

He coughs a little but raises nothing. There are a few fine rales at the
right base and many coarse and medium rales in the same region and extend-
ing upward to the mid-scapula.

Heart Sounds are of fair quality. The blood-pressure at 11.30 a.m. was
100/S.-80/D.

TYPHUS I'i;\i;i(- FATAL < \SI> AUTOPSY

The eruption is fading. Some of the spoti are brown an are

purple.

June 16. In the evening fche pal ten. became reel leec and made peculiar

movements with the arms. There was tonic spasm of Qu n

MEDICAL BECORO BOOK. VOU

CLINICAL CHART

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Autopsy Number 23. Typhus fever.
Coma and cerebrospinal inflamma-
tory phenomena

and the fingers were clenched but not in the position of tetany. The knee-
jerks were absent.

June 17. The patient's color has become almost leaden but the pulse
continues relatively good. The respiration is more vapid.

The spasms of the arms have ceased, but stiffness oi the neck has in-
creased. Neither forward bending of the head nor rotation are now possible
without pain. The patient is becoming comatose. The lungs show a few
rales.

The patient died at noon.

226 TYPHUS FEVER — FATAL CASES — AUTOPSY

Autopsy Findings

The muscles are not dry. Much blood escaped from the great vessels
when the heart was removed. The subcutaneous fat is moderate in amount
and very tough and dry.

Heart: Firmly contracted; muscle firm and normal in appearance.

Lungs: On the surface of the left lung at the apex are a few fresh adhe-
sions and several small patches of blood-stained fibrin are adherent to the
lateral and posterial aspects of the lower and middle portion. The lung tis-
sue is leathery and pinkish on section. There is a small amount of oedema
not confined to the bases. The bronchial mucosa is moderately reddened
but not swollen. There is a little viscid exudation in the larger tubes. The
condition of the right lung is practically the same as that of the left.

Abdomen: The intestines are not distended and are normal in appearance
externally.

Liver: Yellowish, with nutmeg markings.

Spleen: Slightly enlarged, rather soft.

Kidneys: Appear normal.

Brain: On opening the skull a large quantity of fluid escaped. There was
some blood with it which may have come from the veins or sinuses as a
result of removing the skull .

The pia is markedly oedematous in the region of the motor area. The
oedema is haemorrhagic and particularly so along the course of the arteries.
There seemed to have been small haemorrhages in this region. These
changes were more marked on the left side than on the right.

Specimens: Whole heart, and pieces of organs.

Autopsy Number 24. (S. No. 94.)
Diagnosis: Typhus fever.
Died during the stage of nervous depression.
Apparent Cause of Death: Exhaustion and circulatory insuffi-
ciency of vascular origin.

Clinical Notes

June 12. The patient arrived yesterday at 10 p.m. having travelled some
distance on the train. He was too sick to be communicated with satisfac-
torily. At the time of admission the limbs were cold, the pulse of poor qual-
ity, and the heart sounds faint. Brandy was administered by mouth, coffee
by rectum, and heaters were applied.

The face is flushed and the conjunctivae are injected. The pupils are of
pin-point size. The tongue is dry with a brownish coat. The soft palate is
red and dry. The patient breathes through the mouth rapidly and super-
ficially.

TYPHUS FEVKR -FATAL CASES ABTOF 227

The Eruption is profuse on the chest and abdomen. Less so on tl
back, and legs. It is macular In form and purple in color.

The Heart Action is regular. The aortic second-sound i- slight!:

tuatcd and louder than the pulmonic second-sound. The I ad ■

sharp and louder than the second at the apex. Blood-pressure I"
80/D.

The Lungs are clear except for a few rales a1 t he righl base.

The Abdomen is soft. The bladder is overdistended. Catheterization
was required daily.)

June 15. At noon the patient became almost pulseless. Almost in
diately after a subcutaneous injection of ether the pulse returned. a
minutes later the patient swallowed a little brandy. Immediately
that the blood-pressure was 100/S.-90/D. Normal Ball solution

was then given intravenously. During the injection the hearl Bounds be-
came louder and the aortic second-sound became accentuated. Imme-
diately after the injection the first-sound was short but of fair quality, and
the others were good. The second-sounds were about equal, the pulse was
full, and the blood-pressure was 110/S.-90/D. At 4.45 p.m., about fifteen
minutes after the infusion, the patient had a slight rigor which Beemed to
affect his condition little. When a nurse returned a few minutes later, the
patient was again almost pulseless. After that he became very delirious
and tried to get out of bed. In a short time he became quiet again and I Im-
pulse and heart sounds were once more of good quality.

The patient has been having diarrhoea and has taken little food for
days. He is rapidly losing flesh and strength.

June 16. During the night the patient again became pulseless and 360
c.c. of salt solution were given intravenously but the circulation imp;
little. The injection therefore was discontinued. The patient then received
ether subcutaneously and the pulse improved.

This morning he became pulseless again. The respiration was very
rapid. The patient was conscious but very weak.

Bronchial breathing of moderate intensity and a few rales were heard at
the right base. The lungs were otherwise negative.

The pulse remained impalpable or nearly so throughout the day. In the
morning, in spite of the bad quality of the pulse, the heart sounds were loud
and clear. The patient died at 5 p.m.

Autopsy Findings

The postmortem was performed sixteen hours after death.

Body of man apparently about 45 years of age, much emaciated, muscles
not dry. Much blood escaped from the great vessels when the heart was
removed. Subcutaneous fat moderate in amount. Very tough and dry.

228

TYPHUS FEVER — FATAL CASES — AUTOPSY

Heart: Firmly contracted, muscle firm and normal in appearance, valves
natural, coronary openings normal.

Lungs: The right lung in front and the left lung at the lower part pos-
terially are bound to the chest wall by adhesions which appear neither
recent nor very old. The left lung shows a moderate degree of passive COn-

Autopsy* 2.4
name. (Senas'* 9+) . ._

MEDICAL RECORD BOOK, VOL. . .

CLINICAL CHART\

..... ..date June. .11, 1315.

disease Typhus f^ver. .

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Autopsy Number 24. Typhus fever.

Exhaustion and circulatory

insufficiency

gestion especially at the base. The right lung shows a large area of haem-
orrhagic oedema in the central portion with increased consistency but no
consolidation. The lower portion behind is atelectatic.

Abdomen: The cavity appears normal.

Liver: On section shows yellowish mottling.

Spleen: Slightly enlarged, rather soft.

Kidneys: Appear natural.

Specimens: Whole heart and pieces of organs.

TYPHUS FEVER- -FATAL CASES AUTO]

Autopsy Number 25. (S. No. 90.)

Diagnosis: Typhus fever.

Died during the postfebrile stage.

Apparent Cause of Death: Gradual exhaustion; inhalation

pneumonia.

Clinical Notes

The patient was admitted to anol he r \\ .n <l on Jum 3. H had no erup-
tion then. It was first noticed on June 7.

June 9. The patient refused to take medicine.

Digitalis, 0.00065 gm., was administered every four hours subcut
ously.

June 11 . The patient breathes rapidly hut easily and ha- occasional dry
cough. He is mentally apathetic and his replies to questions aeem in<-<>-
herent. The face is not definitely flushed hut the ears are red. The con-
junctivae are not injected. The pupils are equal and of medium sue. The
lids of the right eye remain practically closed hut there is do apparent
muscular paralysis. The tongue shows a heavy brownish coat. The skin r»f
the body is moderately pigmented, especially on the front of the chi -

Eruption: On the shoulders, the arms, the backs of the hands and
and the sides of chest there are many purple macules irregular in shape,
varying in size. The abdomen is profusely covered with maculopapules.
On the back and thighs there are a number of reddish-purple macules. The
lower legs are free from spots but they present numerous recent Bears and
crusted ulcers, apparently syphilitic.

The Heart Action is regular, the sounds faint, the cardiac dulness di-
minished, and the pulse of low tension. Blood-pressure, 95 S— 75 D.

The Lungs are hyperresonant at the right base. There are many rales
and the breath sounds are diminished. There arc a few rales at the left
base but no bronchial breathing.

The Abdomen is flat and shows slight general sensitiveness but no spasm.

The Spleen is not palpable but the splenic dulness is increased.

The knee-jerks are sluggish. The neck is slightly stiff and sensitive
behind. The left leg can be raised perpendicularly without pain, but an
attempt so to raise the right leg causes slight pain. The calves are not
sensitive, but the thigh muscles are so. Haemoglobin, 90 per cent.

June 12. The patient began to be delirious at night on June 7 and has
been so ever since. He has been very difficult to feed and has taken little
nourishment. His condition is becoming serious. He was fed with a nasal
tube last night. His mouth is very dirty and he refuses to have it cleaned.
Evacuations are involuntary.

June 15. There is slight improvement today. The rash is fading and has
become purple and brown; it is still clearly visible. Xasal feeding has been

230

TYPHUS FEVER — FATAL CASES — AUTOPSY

continued with considerable difficulty. The patient is now beginning to
drink a little liquid when given with bread. There is considerable muttering
delirium this afternoon.

At night the patient is very delirious. He has taken so little liquid that
360 cc. of salt solution were given intravenously at midnight. One hour

*„„ CLINICAL CHART

Autopsy *2.5
name.. (Series.* 90). ward bed.no _ ._ oate June. 3>191^5.

MEDICAL RECORD BOOK. VOL - . PAGE . DISEASE Ty p. h 14 S feVer. _.

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Autopsy Number 25. Typhus fever. Inhalation
pneumonia

and a half after the infusion he had a severe chill. The salt solution had
been freshly prepared with care.

June 17. The delirium is quieter today, and the patient weaker. A
small abscess on the buttock was opened yesterday, and today another
appeared on the thigh.

In the afternoon the patient was very weak and the pulse was of poor
quality. Salt solution, 450 cc, was given intravenously. Fifteen minutes
later the delirium increased and the patient had a chill. A small dose of

TYPHUS FEVER — FATAL CASES AUT01

morphine was given subcutaneously after which the pulse improved much
and the patient slept well. The pulse remained good in th<- evening. The
salt solution was used because the patient was taking practically nothing by

mouth and fought off attempts to feed him with the nasal tube.
Junel8. This morning the patient's condition is aboul the same. I

delirious, apathetic, and weak, but the pulse is of fair quality. He i
nourishment better.

Corneal ulceration began several days ago.

June 19. The patient is semicomatose and the pulse extremely bad.

June 20. For the last two days the patient's condition has been getting
worse. Symptoms suggested pulmonary lesions, but no definite signs have
been found. The lungs were not examined yesterday.

The abscess of the buttock became a slough and is increasing.

The stiffness of the neck continues slight this morning and the patient is
practically pulseless and comatose. He died about 9 a.m.

Autopsy Findings

Postmortem performed one hour after death. Body much emaciated.

Heart: There is a milk-patch on the anterior surface of the heart . The
left ventricle is firmly contracted. The right ventricle is flabby and perhaps
a little dilated. The heart muscle is apparently in good condition. The
aortic, mitral, and tricuspid valves show slight fibrous thickening. There
are a few minute yellowish spots on the aorta.

Lungs: The left pleural cavity contains about 30 cc. of pus. The
pleural surface of the lung is cloudy and show's several small patches of
fibrin. The right pleural cavity contains no pus but the surface of the Lung
is like that of the left except that the changes are less marked. In both
lungs are numerous small, hard nodules, some of which, on section, yield
pus. At the left base there is atelectasis. In the right lung a bright red,
narrow area of consolidation follows the posterior margin.

Abdomen: The intestines appear normal externally.

Liver: Shows slight nutmeg markings.

Spleen: Firm, and slightly enlarged.

Kidneys: Capsules adherent in places, cortex variable in width, markings
indistinct, color rather pale.

Specimens: Pieces of organs.

TYPHUS FEVER, FATAL CASES
NO AUTOPSY

Series Number 87. Patient of Dr. Holmes.
Diagnosis: Typhus fever.
Died during the stage of nervous depression.
Apparent Cause of Death: Severe toxaemia with general
symptoms.

Clinical Notes

A Russian physician, admitted May 21. A slight eruption was first
observed on that day.

May 27. Physical Examination: The apparent age is about 23. The
patiejnt lies on the back propped up. He is conscious but the mind is
clouded. The eyes are closed, the respiration is rapid and shallow. The
cheeks and eyelids are brightly flushed and the ears are bright red. The
arms twitch occasionally, the hands move aimlessly and pick at the bed-
clothes.

The eruption is profuse on the chest, and dull red in color. The color
partly disappears on pressure. The spots are irregular in size and shape.
Most of them are macular but on very close inspection a few are seen to be
slightly elevated. The elevation is more easily appreciated by palpation.
The rash is clearly seen on the backs of the hands, and is abundant on the
arms, abdomen, and legs. On the abdomen are a few maculopapules which
are darker red and more elevated than the others. From these the color
does not disappear on pressure. The rash as a whole is beginning to assume
a purple tinge.

The Heart Action is rapid and regular. The first- sound is faint and the
second-sounds are accentuated. The pulse is large and of the bounding
type.

Lungs: No rales are heard in front. The backs were not examined.
There is an occasional cough like that of bronchitis.

June 1 . The patient's condition has been critical for several days. The
respiration is very rapid and the pulse is very rapid and of poor quality.
There is slight cyanosis. When the patient coughs there is rattling in the
throat but he is unable to raise anything.

Three days ago he grabbed his chart and carefully examined it. Yester-
day he was too sick to do this. He lies most of the time with eyes closed
and when approached looks nervously from side to side.

232

TYPHUS FEVER— FATAL CAS] Al TO!

The chin twitches most of the time and the other musclei of the

move continually. The hands move convulsively and in a futOe manner.

The eruption is purple; and is beginning to fade. The I
are free from rales. There is do dulness or bronchial breathing. Nourish-
ment is taken fairly well. There is considerable perspiration.

Abdominal distention is now very marked. The colon can be f«-lt
through the abdominal wall. The distention can be reduced temporarily
by enemata and the pulse rate then falls bul the distention returns in a
short time and then the pulse rate rises again. The temperature remains
high.

June 2. The patient died last night.

Series Number 21. Patient of Dr. Holmes.
Diagnosis: Typhus fever.
Died during the stage of nervous depression.
Apparent Cause of Death: Pulmonary oedema, sudden as-
phyxia.

Clinical Notes

May 1. Present Illness: A Serbian officer, said to have been ill six days
before admission. He complains of pain around the eyes and in the back of
the head, but not in the legs. There is cough and a little expectoration.

Physical Examination: The apparent age is about 35. The patient is
well developed and nourished. The face is much tanned, the ears are red.
and the hands are slightly so. The tongue shows a white coat. The con-
junctivae are not injected. The pupils are equal and of normal size.

The Eruption is profuse and consists of pink macules on chest, abdomen,
and arms. The hands, face and neck are free from spots.

The Heart Action is rapid and regular. The sounds are of good quality
and there are no murmurs. A few coarse rales are heard at the apices
behind.

The Abdomen is negative. The spleen is not palpable and splenic dulness
is not increased.

The Neck is slightly stiff. There is a slight Kernig's sign associated with
muscular spasm but no pain. The calves are not tender.

May 8. The diazo-reaction is mildly positive.

May 5. The severity of the illness is increasing. The patient is men-
tally dull and confused but recognizes people .

There was epistaxis today, moderate in amount.

The expectoration is considerable in quantity and very tenacious. The
breathing is rapid and shallow. Many rales, most of which are of the coarse.
dry variety, are scattered throughout the lungs.

234 TYPHUS FEVER — FATAL CASES— NO AUTOPSY

The rash is fading and turning brown.

Blood-pressure, 90/S.-55/D. Haemoglobin, 85 per cent.

May 7. There is an occasional spasm of hiccough. The patient is
cyanotic. The breathing is rapid and makes a whistling sound at the nose.
The nostrils move with respiration and there is a rattle in the throat. The
cheeks are flushed. The forehead, which was very white on admission, is
now slightly pigmented.

The heart sounds are obscured by coarse rales. Blood-pressure, 110/S-
55 /D. The patient takes food badly but water and lemonade freely.

May 9. This afternoon, in the absence of the physician in charge of the
ward, the patient was reported to me as being in a dangerous condition.
When seen within a few minutes he was found gasping and unconscious but
with a full, strong pulse which was not rapid. There was a loud rattle in the
throat. The patient was quickly turned on his side and the jaws held open.
He then began to draw deep breaths at long intervals but in two or three
minutes the pulse and respiration both stopped and the patient died.

PROBLEMS IN DIAGNOSIS

The three following cases, Autopsies Nos. 2, 11, and
illustrate either errors of diagnosis or interesting complications

of typhus fever.

Autopsy Number 2.

Patient of Dr. .

Clinical Diagnosis: Typhus fever.
Pathological Diagnosis: Malignant endocarditis.
Autopsy Number 11.

Patient of Dr. .

Clinical Diagnosis: Typhus fever.

Pathological Diagnosis: Typhoid fever with perforation of the
intestine.
Autopsy Number 26.
Patient of Dr. Smith.
Clinical Diagnosis: Typhus fever (?).
Pathological Diagnosis: Endocarditis, typhus fever (?).

Clinical Notes

The patient was admitted June 14. His age was 30 and he is said to have
been ill four days. No eruption was seen on admission or later. The patient
was conscious at first and became comatose later. The breathing was noisy
and difficult. There was muscular twitching. The general appearance of
this patient suggested typhus fever. On June 22 the neck was markedly
stiff and there was a slight Kernig's sign. The patient died at 3.40 p.m.

Autopsy Findings

Postmortem performed five hours after death. Body fairly well nour-
ished.

Heart: There is a large milk-patch on the anterior surfaee. The left
ventricle is firmly contracted, and there is no dilatation of any of the cham-
bers. The mitral valve shows a continuous row of small, pearly white, soft
vegetations along the edge. Beneath the endocardium a little above one of
the cusps is a small area of haemorrhage. There is no ulceration. The other
valves are natural. The intima of the aorta shows a few very small yel-
lowish patches. The coronary openings are free.

235

236 PROBLEMS IN DIAGNOSIS

Lungs: The left shows much oedema, especially at the base. The base of
the right is oedematous and atelectatic.

Abdomen: The intestines are normal in appearance. The lower part of
the ileum was opened and no ulceration or swelling was found but the
mucous membrane showed many minute red dots.

Liver: Much congested.

Spleen: Normal in size, rather firm.

Kidneys: Extremely congested.

Brain: Shows whitish streaks along some of the larger arteries on the
upper and lateral surfaces of the hemispheres. No pus on the meninges.
Cranial fluid perhaps a little in excess. Meninges not oedematous. Base of
brain natural. Lateral ventricles contain a pale and slightly turbid fluid.
Lumbar puncture after death showed that the fluid was not under tension.
Several cubic centimeters were removed with a syringe. The fluid was clear
and greenish yellow in color.

Series Number 33.

Diagnosis: Scabies, typhus fever (?) .

Clinical Notes

May 8. Serbian, apparent age about 20. The patient says he has had
typhus for a month which probably means that he has had scabies for a
month.

Physical Examination: The patient is well developed and nourished.
The skin and mucous membranes are pale. The conjunctivae are slightly
injected.

The skin of the body and face is somewhat pigmented and shows many
brown macules of various sizes. There are many excoriated papules upon
the front of the chest, abdomen, upper armSj axillae, groins, wrists, and
genitals. There are no such papules below the knees. The forearms, wrists,
and hands show many crusted papules of moderate size and there are
similar ones on the lower legs.

On the chest there are a few pink macules which might be interpreted as
a scanty eruption in a mild case of typhus.

The other lesions, clearly, are due to scabies.

Heart and Lungs: Negative.

Abdomen: Soft, not tender. Spleen not palpable; splenic dulness not
increased.

Knee-jerks present. No stiffness of neck or legs.

Haemoglobin (Tallquist), 100 per cent +. Blood-pressure, 105/S.-
65/D.

May 13. Throat slightly red. Heart, lungs, and abdomen negative.

PROBLEMS IN DIAGNOSIS

2 :

May 14. Skin improving under -treatment foi
remain.

June I. Patient discharged well.

Note: The temperature curve in this case point- to an acute infei
of some sort and the small amounl of local infection of the skin lesionc

CUNICAL CHART

NAME.- StriCS *33 WARD BID MO OATl f\oylr.

MEDICAL RECORO BOOK. VOL PACE OrsCASC SoobitS V-TyphuS f«»lr?

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Series Number 33. Scabies, (?) typhus t'ewr

not explain it. Although more irregular than the curve usually is in typhus
the chart suggests this disease and the pink macules above mentioned
strengthen such an hypothesis.

Series Number 33a.

Diagnosis: Gangrene of foot and leg, probably a sequel of
typhus fever.

238 PROBLEMS IN DIAGNOSIS

Clinical Notes

April 26. A Serbian. Brought in with a number of typhus patients that
arrived together on a train. Said that he had been ill eight days.

Spots were seen which may have been a fading typhus rash, but which
were not sufficiently definite for a positive diagnosis.

At the time of admission there was pronounced discoloration of the left
foot and of the leg halfway to the knee, a line of demarcation existed at the
"point of election."

May 5. The patient was transferred to a surgical hospital for amputa-
tion of the leg.

Note : This case illustrates the difficulty of satisfactory diagnosis after
the eruption has faded.

Series Number 88.

Diagnosis: Pappataci fever (?). Abortive typhus (??).

Clinical Notes

May 26. The patient has been sick two days. He complains of pain in
the temples, thighs, and back.

Physical Examination: The patient is rather drowsy, but mentally clear
and alert when aroused. The pupils are equal and of moderate size. The
conjunctivae are moderately injected. The tongue shows a thin, white
coat. The throat, the soft palate, the pillars of the fauces, and the pharynx
are red. There are no spots on the mucous membranes.

The Heart is negative, the pulse of good quality, and the blood-pressure,
90/S.-60/D. Haemoglobin, 80 per cent.

The Lungs and Abdomen are negative. The splenic dulness is not in-
creased and the spleen is not palpable.

The knee-jerks are present. There is no stiffness of the neck or legs. The
thigh muscles are slightly sensitive to firm pressure.

Skin: The face is covered with a red flush which extends two-thirds of
the way down the neck and, in front, covers a V-shaped area extending on to
the sternum. A slighter flush extends over the lower part of the neck to the
shoulders and over the clavicles to the second ribs where it gives place to
rose-colored macules. The ears are very red. On the sides of the chest, the
flanks, and the abdomen there are a few bright red, clearly defined spots the
size of a pinhead and a few purplish spots of about the same size which do
not disappear on pressure. (Old flea bites?)

On the inner aspects of the arms and of the flanks " taches bleuatres " are
numerous. In the center of some of these is a bright red, circumscribed spot
like those already described on the sides of the chest and flanks. These
spots are believed to have been caused by bites.

PROBLEMS IN DIAGNOSIS

On the hips and on the backs of the hand
maculopapules some of which are capped by a small . ■ ride. The nature of

these spots is uncertain. They resemble acne more than anything el
June 2. On the day after admission of the patienl the temperature

dropped to normal. On the same day ;i rash ron.-isting oi groupf of

CLINICAL CHART

name. Scried *66 Dm fluy X\lO\S.

MEDICAL BECOTO BOOK. VOL DSEASC TypKul f««*r.

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Series Number 8S. Pappataci
fever (?). Abortive typhus (??)

small, irregular papules was found on the flanks and sides in the morning.
In the afternoon it had nearly disappeared and in the evening there was no
sign of it. The patient's condition today is excellent.

June 11. With the exception of a rise of temperature to 99° on one day,
there has been no recurrence of fever. The patient is to be discharged
tomorrow.

Note: The probability in this case seems in favor of the diagnosis of
pappataci fever.

240

PROBLEMS IN DIAGNOSIS

Series Number 100.

Diagnosis: Pneumococcus bronchitis.

Clinical Notes

Typhus fever (??).

June 21 . Admitted to hospital today. Duration of illness ten days.
Physical Examination: The face is flushed and the conjunctivae are in-
jected. There is pink mottling of the skin on the chest and abdomen but

CLINICAL CHART '

name, ... 5 eri.ei *.1.Q.Q..- _ ward bed no date Jan e..HX , 1315.

MEDICAL RECORD BOOK. VOL .. ._*.PAGE DISEASE Typhis fr^Py. „..

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Series Number 100. Pneumococcus bronchitis.
Typhus fever (??)

there are no macules or papules. The tongue shows a brown coat. The
mind is clear and the general condition is good. The spleen is not palpable.

June 24- There is profuse purulent expectoration. The face is still a
little flushed and a band of injection extends across the conjunctivae.

The lungs were negative yesterday and today.

PROBLEMS l\ DIAGNOSIS 241

The patient is improving and doea not look seriou
scopical examination of the sputum shows pneumococci in greal nam

and few other bacteria. No tubercle bacilli were found.

Note: The most probable diagnosis seems to be bronchitis caua
pneumococcus. The "mottling" on the chesl ma] en due to the

application of a counterirritant of some sort.

There seems no reason for believing the case to be one of typhus I
although the patient was sent in as such.

PART III

LABORATORY EXAMINATIONS IX TYPHI -

FEVER

By ANDREW WATSON SELLARDS

Introduction

In order to complete the arrangements of the commission for

conducting sanitary work, a central laboratory was organised
by Dr. Hans Zinsser in Skoplje at the Lady Paget Hospital.
The scope of this laboratory included the preparation i >f vari< >us
vaccines, the sanitary examination of water supplies, and more
particularly, special investigations of typhus fever. The op-
portunity was afforded me to carry out clinical laboratory
examinations on typhus fever patients.

The general findings in typhus fever were observed with the
special object of differentiating this disease from other infec-
tions which were prevalent and in which an early clinical di-
agnosis could not be made. Of the acute infections which gave
rise to confusion, the two most troublesome ones were typhoid
and relapsing fever. Indeed the clinical similarity in the onset
of these three diseases gave rise to a local custom in the Balkan
States of designating them all by the one name "typhus." It
was often only by the context that one could determine
whether reference was made to typhus exanthematicus, typhus
recurrens, or typhus abdominalis. The rapid clinical differen-
tiation of typhus and relapsing fever would have been advan-
tageous since, in the management of the sanitary work, it had
seemed desirable to the authorities to reserve the Lady Paget
Hospital solely for typhus cases. Once the cases had been ad-
mitted, the prompt diagnosis was important to prevent, as far
as possible, the development of cross infections in the hospitals.

243

244 EXAMINATION OF THE BLOOD IN TYPHUS FEVER

Examination of the Blood in Typhus Fever

In the literature on the clinical microscopy of the blood in ty-
phus fever certain important statements occur which, for the
most part, have remained unconfirmed. Even as regards the
actual blood counts, and the morphology of the blood-cells,
the statements are somewhat conflicting. In searching for para-
sites, Ricketts and Wilder 1 in a preliminary note reported the
finding of bacteria in blood films stained by Giemsa's method;
with similar preparations Prowazek 2 noted the occurrence in
the white cells of inclusion bodies of the general character of the
chlamydozoa.

Red Blood-Cells

Prompt confirmation was obtained of the high count of red
blood-cells, figures of 5,500,000 and 6,000,000 being common,
the haemoglobin content being increased often in greater pro-
portion than could be accounted for by the increase in the
number of red cells. The percentage of haemoglobin was de-
termined with a Sahli apparatus standardizing the instrument
by comparing it with several normal healthy adults and con-
sidering this value as 100 per cent. The blood examined was
taken in all cases from the ear. This increase in cell count and
haemoglobin was most marked at the height of the infection.
With the progress of the disease, the count usually fell to nor-
mal or even to slightly subnormal values; a definite anaemia did
not develop in typical cases. Some of the conditions bearing on
this increased count were considered. Clinically, there was no
increase in the size of the spleen in contrast to the spleno-
megaly which sometimes accompanies polycythaemia. Many
of these patients showed the effects of depletion in their supply
of fluids. The explanation of this lay not in an excessive loss of
fluid due to any effect of the typhus infection, but to the in-
ability of the patients to obtain water during their long journey
to the hospital. In order to determine in how far the poly-

1 Ricketts and Wilder: Jour. Am. Med. Assn., 1910, liv, 1373.

2 Prowazek: Med. Rec, N. Y., 1915, lxxxviii, 21; Beitr. z. Klinik d. Infections, u. z.
Immunitatsforsch., iv, No. 1.

TYPHUS IX SERBIA _M"

cythaemia was due to deprivation of water, a Beri untfl

was made upon selected cases in whom the therapeutic if
tion of salt solution was required. These injections were n

intravenously, in quantities of one-half to three-fourth- i
liter. The first injection often showed surprisingly little effect
upon the blood-count; repeated injections usually reduced the
red count and the haemoglobin considerably. The values often
remained slightly higher than normal even after sufficient
fluid had been injected to restore the tissues approximately to
their normal condition. Signs of this restoration con.-:
chiefly in the return of the elasticity of the skin, the improve-
ment of the pulse, and the free secretion of urine. It seemed
justifiable to conclude that the deprivation of water was re-
sponsible in a large measure for the high red counts and high
haemoglobin, though one could not exclude the possibility that
other factors may play a minor role.

In fresh preparations and in stained smears the red cells were
essentially 1 normal. In a small proportion of the cases the red
cells showed coarse basophilic stippling and occasionally
polychromatophilia. This feature occurred indifferently both
in the cases with moderately low counts and also in some in-
stances in which the red cell count was as high as 6,000.000.

White Blood-Cells

In regard to the white blood-cells there is a prevalent opinion
that a leucocytosis of high grade often occurs late in the dis-
ease, characteristic large mononuclear cells appearing in the
blood. The total number of white cells was found to be rather
variable. Often the count was normal or a little high. In a few
instances a marked leucopoenia was present. These leuco-
poenias, however, were rather transient instead of persisting
over a period of days or weeks as in typhoid fever. Occasionally
a striking leucocytosis developed during the second week of the
disease. Thorough examination often revealed some focus of

1 The Giemsa stain was used exclusively, partly because this stain keeps very well in
warm climates and also because the work of Ricketts and Prowazek is based upon
smears stained with Giemsa's method.

246. EXAMINATION OF THE BLOOD IN TYPHUS FEVER

secondary infection. Two patients with high counts in whom
no complications could be found developed, after a few days, a
small patch of pneumonia. A few cases developed leuco-
cytosis, however, in which no suggestion of secondary infection
could be detected.

The differential counts showed considerable variation. Fre-
quently the mononuclear cells were increased at the expense of
the polymorphonuclears and often the large non-granular
mononuclear cells were unusually prominent. These cells were
often difficult to classify. Polymorphonuclear cells that ap-
peared to be rather young were seen not infrequently. An
occasional neutrophilic myelocyte was seen in the peripheral
blood. These were rare being by no means as frequent as in
some of the high grade bacterial leucocytoses.

A thorough examination of the blood in ten active cases of
the disease failed to reveal either the bacilli described by
Ricketts or the inclusion bodies of Prowazek. Most of these
patients were examined for the first time at about the fourth or
fifth day of the disease and subsequently throughout the re-
mainder of the course at intervals of two or three days.

The platelets were abundant in the blood smears and they
were normal in appearance. The bleeding time and the coagu-
lation time were within normal limits. The latter was deter-
mined by drawing the blood in a syringe from a vein and
noting the time required for coagulation in a test tube.

It is not infrequently stated that the blood of typhus cases is
very prone to give the reactions of agglutination and comple-
ment fixation with various antigens. Cameron 1 has empha-
sized the occurrence of positive Widal reactions with the sera
of typhus patients. In view of his observations, some macro-
scopic agglutination tests were carried out in the Lady Paget
Hospital using B. typhosus and the two paratyphoid strains, A
and B. Twenty typhus cases were examined three of which
were active and the others were convalescent. No positive re-
actions were obtained with either of the two strains of para-
typhoid. With the typhoid strain there were five cases which

1 Cameron: Brit. Med. Jour., 1915, i, 785.

TYPHUS IX SERBIA

TABLE I. — BLOOD COLNTS AND HAIMOGLOBIN DETER Ml
ON TYPHIS CASES I PON ADMISSK

Case no.

Day of disease

l;< '1 '<ll r-ounts

blood-oath

Millions per cmm.

NurnUr |^r ojmn.

.-a- !.

1

4

4,0

12,000

3

8

6,0

6,000

8

- 10?

5,6

5,000

9

8

5,5

1,600

I-'.'.

10

8

5,9

16,600

130

11

5

4,0

6,000

15

14*

4,0

7.200

100

16

18*

4,1

3,200

110

17

14*

5,6

6,000

120

18

5

4,7

1.500

19

5

4,4

8,800

105

20

16*

3,9

4,800

85

21

6

3,5

3,900

Illl

35

5

4,5

7.D00

Ill)

41

6

4,7

3,700

110

45

8?

5,0

4,000

115

46

2

5,1

10,600

115

47

7

4,9

4,800

115

53

?

5,6

4,300

130

55

4

6,2

5,800

147)

56

6

5,2

10,200

115

57

12

4,6

7.S00

110

58

10

5,0

15,000

115

* These are patients who reported themselves ill from some unknown cans.' and in
whom typhus fever developed as an intercurrent infection.

gave good agglutination at a dilution of 1 : 25, but not at 1: •">< I.
In the entire series there was but one case which gave agglu-
tination at 1: 50 and the clinical diagnosis of typhoid fever had
already been made in this patient. In the cases agglutinating
at 1:25 no record was available in regard to their previous
history of typhoid fever and of antityphoid vaccination: con-
sequently, even if an occasional positive Widal had been ob-
tained in the typhus cases it would not have been oi any
especial significance.

For completeness sake some of the data of the blood counts
are appended. The data in regard to the time of onset of the
disease are extremely unsatisfactory. Main- patients were too

248 EXAMINATION OF THE BLOOD IN TYPHUS FEVER

ill to give a reliable history; others did not consider themselves
ill unless a rash or high fever developed. The data for the " day
of the disease" as given in Table I are compiled in part from
the history of the patient and in some cases from the apparent
stage of the disease as judged by the clinical findings.

In ten additional cases occurring toward the close of the
epidemic and showing no complications, the white count dur-
ing the first week of the disease varied from 3800 to 13,000.

In Table II some typical differential counts are recorded.

TABLE

II. — DIFFERENTIAL COUNTS

ON TYPHUS CASES

Day of

Total

Polymor-
phonuc-

Large and

Large

Transi-

Unclassi-

Eosinophiles

disease

count

lear neut-
rophiles

phocytes

nuclears

cells

fied cells

Number seen

1

4

12,000

92%

3%

4%

0%

1%

None

3

8

6,000

77

13

10

0

0

One cell

8

10?

5,000

72

18

6

2

2

Two cells

9

8

4,600

82

8

6

0

4

None

10

8

16,600

72

17

8

2

1

One cell

11

5

6,000

72

20

6

1

1

None

17

?

6,000

72

20

4

2

2

18

5

1,500

47

31

15

3

3

None

19

5

8,800

73

17

2

5

3

None

20

?

4,800

76

18

2

2

2

Two cells

21

6

3,900

70

18

6

3

3

None

87

4

12,000

76

21

2

1

0

None

These percentages are based upon counts of 300 cells.

The eosinophiles were unexpectedly scarce, never being as high as one per cent.

An attempt was made to follow the blood-counts from the
onset of the disease throughout its course in a small group of
uncomplicated cases. The effort to secure such a series was not
very successful. In Table III, although the exact day of the on-
set is not accurately known, still the figures give a very fair
idea of the stage of the disease. These counts were made from
uncomplicated cases or at least the patients were free from
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scesses failed to produce a polymorphonuclear leucocytosis.

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I

• TYPHUS IN SERBIA

Examination of the I it

Examination of the urine showed an almosi constanl arid

early development of some inflammation of the kidney. Mod-
erate amounts of albumin were presenl and granular
fairly numerous. These signs were usually transient, clearing up
promptly with the drop in temperature. In one instance only,
a severe nephritis developed during the height of the dia
which did not entirely clear up during convalescence; in this
case a preexisting nephritis could not be excluded.

The diazo-reaction was found to be almost constantly pi
ent and usually very strong. However, it did not occur early
in the disease and it was not of definite value in the differentia-
tion of early or doubtful cases.

Differential Diagnosis

We do not at present possess routine methods which are ade-
quate for the recognition of atypical cases of typhus fever or for
the early diagnosis before the typical clinical picture has de-
veloped. Among the French physicians a high percentage of
cases are frequently diagnosed as typhus "sin exanthem";
while this type may occur more or less frequently, it is a di-
agnosis which is extremely difficult to establish. The more
common laboratory procedures give evidence in typhus which
is essentially negative in character. Of the few positive find-
ings, the occurrence of the diazo-reaction in the urine and the
tendency of the mononuclear cells of the blood to increase were
of only very minor assistance. The diagnosis of typhus by the
laboratory findings must be made by exclusion. This is fre-
quently unsatisfactory for its differentiation both from typhoid
and from relapsing fever.

The application to typhus fever of some of the more elabo-
rate experimental procedures gives results which are char-
acteristic. The inoculation of the virus of typhus fever into
monkeys and guinea pigs often gives rise to a characteristic
temperature curve; studies of complement fixation and agglu-
tination to B. typhi exanthematici have in the hands of Plotz.

250 CULTURES IN TYPHUS FEVER

Olitsky, and Baehr * given results of diagnostic value. The
transmission of the virus to lower animals is at present out
of consideration as a diagnostic method; the results are so
inconstant that the procedure is suitable only for the labora-
tory study of typhus. Jahlous 2 reports that there is a general
tendency of the serum of typhus cases to give non-specific com-
plement fixation with the Wassermann antigens. This possi-
bility in typhus fever should be taken into consideration in any
diagnostic methods involving complement fixation. Olitsky *
finds that an antigen of B. typhi exanthematici fixes comple-
ment readily with the sera of typhus cases but not with other
sera. Furthermore, antigens prepared from other bacilli fail to
fix complement with typhus sera. Olitsky's results though very
striking have not yet received any wide confirmation. The
final establishment of diagnostic aids by the use of comple-
ment fixation either with a specific or a non-specific antigen
requires an enormous amount of empirical work carried out
preferably in a number of different laboratories.

Bacteriological Cultures in Typhus Fever

In the search for the specific organism of typhus fever, the
blood is the most suitable material for examination. Injection
of blood from typhus patients into normal men reproduces the
disease, thereby demonstrating that the virus occurs in the
circulating blood. Numerous bacteriological cultures have
proven that the virus as it occurs in the blood is practically
pure.

Of the many organisms that have been described as the
specific aetiologic factor in typhus fever there is none on which
so much work has been done or for which so much favorable
evidence has been offered as in the case of the anaerobic bacil-
lus described by Plotz and his associates. The following at-
tempts at the confirmation of this organism were made in
Belgrade and its vicinity. The technique described by Plotz

1 Plotz, Olitsky, and Baehr: Jour. Infect. Dis., 1915, xvii, 1.

2 Jahlous: Jour. Med. Research, 1914, xxx, 131; Delta, Centralbl. f. Bakteriol.,
I, Abt., Orig. 1915, Bd. lxxvi, 50.

TYPHIS IX SERBIA 261

was followed carefully but in view of the proportionately

large number of negative results obtained by I)r. Zinsser in
Skoplje some additional cultures were made with certain n .
modifications of the Plotz technique. These consisted in an en-
richment of the medium and an increase in thed< i
biosis. Three samples of ascitic fluid were used. T!
free from bile and the specific gravity varied from l.ni
1.018, but in view of the possibility that they might qo1 be <n-
tirely suitable for the growth of the Plotz bacillus pie©
kidney tissue were added in some instances. Tin- procedure
had given successful results in Plotz 's experience but was re-
garded by him as an unnecessary refinement. Some of the
Plotz cultures to which kidney tissue had been added were
given a higher degree of anaerobiosis by placing the tube- in a
jar from which the oxygen had been absorbed by yellow
phosphorus.

In the selection of cases, only those patients were chosen
from whom cultures could be made some time during the first
half of the period of the exanthem, except in one instance when
a fulminating case was cultured who died eight hours later.
The cultures from this patient developed numerous colonies,
some cocci growing aerobically, and some bacilli growing an-
aerobically; the latter were longer and coarser than the or-
ganism described by Plotz. Cultures from twelve additional
cases remained sterile for one month with the exception of an
occasional mould or coarse coccus growing on the surface -
the media toward the end of this period. No anaerobic growth
occurred either in the cultures made by Plotz s technique or in
those tubes to which kidney tissue was added some oi which
were placed in an anaerobic jar. Five of these twelve c
were cultured either on the first or second day of the appear-
ance of the rash. Moreover, the work was done under very
favorable conditions. The laboratory at Belgrade was hoi
in a substantial building and wras well equipped with modern
French apparatus. In Serbian Macedonia it had been neces-
sary to work practically under field conditions with, a labora-
tory set up in what wras formerly a Turkish artillery shed, where

252 CULTURES IN TYPHUS FEVER

the exposure to dust storms added greatly to the difficulty of
the work.

It is hard to understand this failure to obtain the Plotz
bacillus under favorable conditions in view of the practically
constant recovery of the organism from acute cases by Plotz
and his associates. Although it is exceedingly treacherous to
work with unheated and unsterilized media, yet in a large
series of control blood cultures Plotz failed to obtain this or-
ganism in a single instance. It is evidently a highly parasitic
organism but I am not yet convinced that it occurs only in
typhus fever or that it is pathogenic for man. Although
Plotz has collected a large amount of evidence in favor of
this organism, there are still some serious objections to its
acceptance.

Anderson has pointed out that the cultures on injection into
animals give rise to a transient fever which does not especially
resemble the temperature curve of typhus fever; moreover
these animals on subsequent injection with typhus fever virus
may react with a typical rise in temperature. If a liberal dose
of the living organism fails to protect an animal against typhus
virus, some doubt is raised as to whether the usual small vac-
cinating dose would give efficient protection in man.

In addition to the failure to obtain the anaerobic bacillus
isolated by Plotz, I was likewise unable to confirm the work of
Topley.1 In kidney tissue ascitic fluid agar, Topley reports the
clouding of the media due to the growth of minute cocci or
bacilli. On this medium, cultures of a diplococcal organism
were obtained in each of eight cases.

As regards the bacteriological examination of the urine no
confirmation could be obtained of the small coccobacillus re-
ported by Hort and Ingram.2

Specific biologic reactions such as agglutination and com-
plement fixation were not attempted in view of the negative
results in these cultures and the inability to secure a strain of
Plotz 's organism at this time.

1 Topley: Jour. Roy. Army Med. Corps, 1915, xxv, 215.

2 Hort and Ingram: Brit. Med. Jour., 1914, ii, 15.

TYPHUS IN SERBIA

Animal Experimeni \'i i

The reported transmission of typhue to animals, < specially
to guinea pigs, has given rise to considerable confusion. The

recognition of the disease depends almost wholly on the I
perature reaction. The highest febrile reaction produced by
the typhus virus is usually not greater than the maximal nor-
mal temperature of the guinea pig. However, after a definite
incubation period, this maximal temperature is sustained
steadily over a period of several days without remissions such
as occur in normal animals. There may be considerable doubt
about the specific nature of the rather transitory rises in tem-
perature following the injection of the virus of measles and
scarlet fever into lower animals. However, in the case -of ty-
phus fever it would seem that guinea pigs are definitely suscep-
tible and permit the growth and multiplication of the virus f< >r
a time. However, not all individuals react. Indeed, there is
every gradation between a typical febrile curve and no reac-
tion. Since the normal temperature of the guinea pig varies
considerably, it is often impossible to interpret mild reactions.
Indeed, some of the important statements in the literature are
based upon the interpretation as positive of reactions which in
no way differ from normal fluctuations in temperature.

In the following work, the animals were inoculated from
cases of typhus during the first or second day after the appear-
ance of the rash. Guinea pigs were injected intraperitoneally
with 3 to 5 c.c. of blood from several typical cases but the reac-
tions which followed were not satisfactory. Moreover, after a
period of incubation subinoculation from the first guinea pig to
a second one was likewise unsuccessful. A reaction in guinea
pigs corresponding to those described by French and American
authors was obtained, however, by passing the virus first
through a monkey and then through a guinea pig. analogous
to the method for securing the infection of rats with relapsing
fever. The reaction in a monkey produced by an injection oi
blood from a human case is illustrated in the accompanying
chart, together with the chart of a control animal. Blood cul-

254 EXAMINATION OF THE BLOOD IN TYPHUS FEVER

tures taken from this monkey on the second day of the fever
were negative.

Such a slight rise of temperature over a short period of time
is, in a single instance, without significance. The evidence,

TEMPERATURE, CFAHRENHEITS SCALE)

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however, that the virus of typhus multiplies in the monkey
and guinea pigs and is responsible for this rise in temperature
lies in the fact that one can in a certain proportion of cases
duplicate these results; moreover the monkeys appear dis-
tinctly ill during the febrile period. In contrast to this febrile
reaction, an instance was observed of natural immunity in the
monkey, a feature that was emphasized by Anderson and Gold-
berger. The frequency of the occurrence of immune animals

TYPHUS IX SERBLA

and of indefinite reaction- renders the procedure emery

tedious and treacherous as a laboratory method. It i- -
sidered that one of themosl essential features for further i
ress in animal experimentation is the development i

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means for the recognition of typhus in animals. This is espe-
cially necessary in view of the great importance attached to the
experiments on the louse transmission of typhus in the lower
animals.

256 TRANSMISSION OF TYPHUS FEVER

Question of the Mode of Transmission of
Typhus Fever

Some of the cardinal features concerning the mode of trans-
mission of typhus fever are still undetermined. In the case of
malaria and yellow fever it is not only proven that these dis-
eases are commonly transmitted in man by mosquitoes but it is
clearly established that they are not propagated in any other
manner. This, of course, is an extremely fortunate circum-
stance in the management of these two diseases. In typhus
fever there is ground to believe that it may be transmitted
either by droplet infection or by the louse. The evidence re-
garding louse transmission is in a somewhat confused condi-
tion.

The transmission of typhus to monkeys by the human body
louse has been investigated by three groups of authors, namely,
Nicolle and his associates,1 Ricketts and Wilder,2 and Ander-
son and Goldberger.3 These authors have all arrived at the
same conclusion : namely, that typhus is transmissible to the
monkey by the body louse. However, it is very striking that
the data and the fundamental premises of the various authors
frequently vary widely and even conflict seriously. Thus the
results on which one group of authors base their conclusions
would frequently be unacceptable to the other two. Ricketts
and Wilder considered that all normal monkeys are susceptible
whereas Anderson and Goldberger frequently found natural
immunity in monkeys. Nicolle found that monkeys which
were bitten by lice without developing fever were subse-
quently susceptible to the injection of virulent blood, whereas
Ricketts obtained the opposite result. Nicolle as well as An-
derson and Goldberger determined infection in the monkey by
the febrile reaction whereas Ricketts in his experiments on

1 Nicolle, Comte, and Conseil: Ann. de PInst. Pasteur, 1910, xxiv, 261; Nicolle and
Conseil: ibid., 1911, xxv, 109; Nicolle, Blanc, and Conseil: Compt. rend. Acad. d. sc,
1914, clix, 663.

2 Ricketts and Wilder: Jour. Am. Med. Assn., 1910, liv, 1304; ibid., lv, 309; Wilder:
Jour. Inf. Dis., 1911, ix, 9.

3 Anderson and Goldberger: Bull. Hyg. Lab., U. S. P. H. S., 1912, No. 86.

TYPHUS l\ SERBIA

louse transmission did nol obtain a sufficiently definite

temperature to ])crmit of a positive diagnosis; reliaj
placed primarily on the appearance of malaise and <>v
immunity test. Nicolle in contrast to the other authors found
that monkeys infected by the bites of lice showed two distinct
febrile periods. The accompanying outline gh immary

of the results of these authors.

EXPERIMENTAL TRANSMISSION OF TYPHIS TO MONKEYS BY
THE BODY LOUSE

Feeding experiments

Injection of emulsions of lice

Positive 1 Negative Doubtful

Positive

itive Doubtful

By Nicolle and His Collaborators

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of experiments

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(a) These animals are regarded as positive by the authors on account of their n i
ture reactions but three of the four might more critically be considered doubtful or
negative.

(6) Two of these three negative animals were bitten by lice which had fed on typhus
patients only four days previously.

(c) These animals were injected with lice which had their infecting feeding two to
seven days previously.

(d) Anderson and Goldberger obtained positive results also with head lice.

(e) The temperature reaction in this animal was not very convincing.

(/) Typical temperature reactions were not obtained but typhus was diagnosed be-
cause these animals appeared ill.

Some evidence is also available in regard to the transmission by
the louse in man. Two of Nicolle's laboratory attendants in
Africa were accidentally bitten by lice that had fed on infected

258 TRANSMISSION OF TYPHUS FEVER

monkeys. These attendants did not develop typhus fever. In
another instance an attendant in a jail in Africa transferred
lice from a typhus patient to a healthy individual. This in-
dividual developed typhus after the usual incubation period.
While this patient was presumably not exposed to typhus in
any other way the conditions were not under control and no
definite conclusions are permissible.

While no direct experiments on man have been undertaken,
some data were obtained by Sergent, Foley, and Vialatte 1 in
the course of some work on relapsing fever. A normal man, who
was bitten by lice that had fed upon a case of relapsing fever,
developed as a consequence typhus fever. A second individual
injected with lice that had fed on this case of relapsing fever
and a third man injected with eggs of these lice also developed
typhus fever. Apparently none of these individuals developed
relapsing fever, although the lice contained large numbers of
spirochaetes. These authors conclude that the case of relaps-
ing fever must have been infected also with typhus fever and
that the latter was transmitted by the bites and by the injec-
tion of the lice.

Although there is considerable confusion in the data of the
experimental transmission of typhus to monkeys, still there is
good reason to accept the idea of louse transmission of the dis-
ease both experimentally in animals and in man under natural
conditions. Such circumstantial evidence as we were able to
obtain in Serbia was in full accord with the theory of louse
transmission. Certainly the vast majority of all patients had
been bitten repeatedly by lice. However, with the approach of
hot weather the incidence of typhus and of relapsing fever ap-
peared to diminish more rapidly than the disappearance of
lice.

It should be emphasized that the establishment of louse
transmission does not militate against the possibility of the
disease being transmitted by other methods also. Indeed the
possibility of droplet infection in typhus must be considered

1 Sergent, Foley, and Vialatte: Compt. rend. Acad. d. sc, 1914, clviii, 964.

TJ I'll! S IN SERBIA

seriously. A few cases of typhus developed in the Lad P
Hospital among the staff under circumstances which per-
mitted careful observation. Some of th<
directly traceable to louse infestation; other- could not readily
be explained on this basis. This was especially true in the i
of a nurse who protected herself carefully againsl insects in all
of her hospital work. Toward the end of the epidemic, the
ward under her charge had been free from activ f<»r

about ten days when a patient extremely ill with typhus was
admitted. It happened that this case had developed serious
mouth, throat, and lung complications, necessitating frequent
sponging and swabbing, the cleansing process often provoking
more or less coughing. It is significant that both this patient
and presumably the ward itself were free from lice, thai the
nurse also wore an effective louse-proof suit, that at no time
had she any reason to suspect louse contamination, but thai
she did not wear the gauze masks providing for protection
against droplet infection. No further typhus cases came under
the care of this nurse; about two weeks later in Belgrade, while
en route to England, in surroundings perfectly free from ty-
phus, she developed a typical attack of the disease. While
none of those instances occurring spontaneously under natural
conditions can afford any exact proof, nevertheless they are
sufficiently striking to merit consideration.

The members of the Commission working in the hospital
with typhus cases adopted precautions both against ins
and against droplet infection, although some authorities advise
against the employment of precautions for droplet infection.
The precautions taken against the louse were twofold in their
nature, consisting in the destruction, as far as possible, of the
lice and the wearing of the louse-proof uniforms. In the first
place, the entire hospital was theoretically free from lice, all
patients being carefully cleansed before admission. Practi-
cally, it was impossible to keep the wards absolutely and con-
stantly free from lice though the living quarters of the staff
were always free from such contamination. Accordingly the
louse-proof suits were worn only in the wards and were then

260 TRANSMISSION OF TYPHUS FEVER

left in a changing room and were never worn in the staff quar-
ters. This regime necessitated the use of a fresh uniform at
each visit to the wards. The uniforms for each day were col-
lected and exposed overnight to chloroform vapor and were
then ready for use the next morning. This procedure for de-
stroying lice was suggested by Dr. C. T. Brues of Harvard
University and it proved to be very simple and effective. In
addition to the use of these uniforms, antiseptic baths were
taken at the end of each day's work.

An ordinary surgeon's mask was used for protection against
droplet infection. Essentially no other precautions were
adopted.

Boston, Mass., December, 1915.

PART IV

REPORT OF BACTERIOLOGIST OF THE AMI l!I< \\
RED CROSS SANITARY COMMISSION

TO SERBIA

By HANS ZINSSER

The bacteriological supplies were shipped on March 19, and
the writer left with the main party of ten on the h
d'Abruzzi, on April 3. He arrived at Uskub (Skoplje! on the
evening of May 1, where a general survey of the contents of
the hospitals was made. After consultation with Dr. Strong it
was decided that the bacteriological work should begin at
Skoplje, since there seemed to be a greater concentration of
typhus material here than in other places. Accordingly, about
a week after arrival at Skoplje the writer, together with Doc-
tors Shattuck and Sellards, moved out to the Sixtli Reserve
or Lady Paget Hospital, situated on the heights along the Var-
dar, about two kilometers outside of the town. There were Baid
to be at that time a few more than 400 cases of typhus fever at
the hospital. There was a very small room which the British
unit were using as a laboratory, equipped only for the simplest
clinical tests, available at the time, but such as it was. the full
courtesies of everything at hand were extended by the British
physicians. The writer wishes to lay stress at this place upon
the generosity and uniform courtesy with which the officials of
the Serbian government and the British hospital received and
treated the American workers at Uskub throughout their stay.

Establishment of Laboratory

The first task, of course, was the establishment of a bac-
teriological laboratory in which suitably controlled work could
be done, the writer conceiving it as his mission not only to work

261

262 REPORT OF BACTERIOLOGIST

on typhus, but to attempt the establishment of a laboratory to
which the general bacteriological and sanitary work of the
Commission could be referred. Although the supplies shipped
from New York had not arrived, and did not arrive at Skoplje
until May 17, the interval was spent in becoming familiar with
typhus in its clinical aspects, the preparation of a' laboratory
space and autopsy room, and the performance of autopsies.
By the courtesy of the Serbian government, a portion of the
main artillery shed next to the Administration Building was
placed at the disposal of the Commission for the establishment
of a laboratory. A partition had been put up in this shed, but
otherwise it consisted of a bare cement floor, with windows
unsuitable for microscopic work, without running water, with-
out electricity, and without gas. The labor of several Austrian
prisoners and of a local carpenter were placed at the disposal of
the bacteriologist, and the space was divided into a smaller
autopsy room and a main laboratory room. Windows were
broken through the walls, another door was broken through,
cement sinks were put in, and a pipe was run from a well, in the
yard, to the laboratory. A tin tank of about four cubic feet
capacity was found and placed on the partition between the
autopsy room and the laboratory, and from this, pipes were run
to the sinks. When the supplies arrived it was found that the
box containing thermometers, syringes, and the more expensive
smaller apparatus — platinum wire, etc. — had been lost in
transit. The electrical apparatus taken along, as well as that
requiring gas, could not, of course, be used. Fortunately, a
petroleum lamp incubator had been taken, and Primus kero-
sene stoves were bought. The British laboratory worker, Dr.
Dalyell, permitted the transfer of all her available apparatus to
this laboratory, joining forces with the American laboratory.
Without this aid and cooperation the work of the Commission
would have been very seriously hampered, because of the fact
that so much of the apparatus brought was not suitable for the
conditions encountered. Finally the apparatus was put in
place and the laboratory was in suitable working condition by
about the twenty-fifth of May.

TYPHUS l\ SERBIA

During the period preceding this, the writer thought thai
although not all the criteria for properly controlled bacterio
could be fulfilled under the circumstances, it would be better to
begin work with what was available Fortunately , bj th<
sight of Doctors Shattuck and Sellards, some extra supplies had
been taken with the party of ten, some of which duplicated the
special bacteriological orders, and with these, together with
what was borrowed from the British, work was begun. An
Austrian prisoner, placed at the disposal of the bacteriologist,
was trained as a laboratory assistant, was taught to make
agar, broth, sterilize, etc. Autopsies were done on most of tin-
cases of typhus that died during this time, and smear studies
were made from the spleen and organs.

Bacteriological Examinations

Cultures also were made, from the spleen and heart's blood
and other organs, but one or two of these only wen- of any
great value, since most of the cases that died at this time
died very late in the disease, after the temperature had been
normal for anywhere from two to ten or twelve days, and
secondary invaders, such as streptococci and Gram-negative
bacilli, were often found in these cultures. Blood cultures were
made at this time on many of the living patients, although
few of the cases were in the early stage of the disease when
they came under observation at the hospital. The large
majority of the cases that came in were well along in the
disease, having often been brought in from considerable dis-
tances under conditions that did not permit speed oi trans-
portation. In none of these early cultures was it possible
to fulfill the criteria laid down by Plotz for the cultivation
of his organism. Ascitic fluid was hard to obtain, since at this
time almost all the patients in the hospitals were cither typhus
or relapsing fever, and small specimens of chest fluid only
could be obtained. These were often not sterile, and in no ease
during this early period did we obtain an ascitic fluid oi 1015
specific gravity or over, which could be used in the unheated
and unfiltered condition as required for the Plotz method.

264 REPORT OF BACTERIOLOGIST

During this period, blood culture "5," taken with one of the
specimens of chest fluid, which showed no growth in the con-
trols, showed in a high tube in glucose agar a colony about two
inches from the top, not gas-forming, with a white halo about
it due to acid formation, which on fishing showed a short bacil-
lus, slightly diphtheroid in form, morphologically correspond-
ing roughly to the organism of Dr. Plotz. Comparing smears
from an old culture of the Plotz bacillus with this organism,
great similarity was seen, except that our organism appeared to
be very slightly larger than the Plotz organism and a little more
irregular in form. We were not successful in carrying this cul-
ture to the second generation, probably because we were at that
time not in possession of suitable ascitic fluid. We wish to em-
phasize distinctly that we did not, at this time, consider our
blood culture a5" of great scientific value because the ascitic
fluid with which it had been taken had not been sufficiently
controlled before use.

When our own supplies arrived it was found that all the
ascitic fluid shipped from New York was either contaminated
or probably because of aging and shaking had settled out, so
that its specific gravity in no case exceeded 1012. However, by
this time (the end of May) cases of ascites appeared at the hos-
pital, and these were tapped. From two cases, ascitic fluids
"X" and aY" were obtained, fluids which we thought more
nearly approximated the conditions set down by Plotz. With
these fluids a number of blood cultures were taken, "X" hav-
ing been well tested for sterility. In some blood cultures both
fluids were used. From blood culture "5" to blood culture
"35" no repetition of the diphtheroid anaerobic organism was
obtained; a majority of these cultures were negative when the
control tubes were negative, in two of them streptococci were
obtained, and, in several others, large Gram-positive bacilli
were present, which were taken to be evidences of contamina-
tion. It may be said that all blood cultures which showed any
evidence of contamination were indiscriminately thrown out.
It should also be stated that during this period hardly any of
the cultures could be taken before what we would consider at

TYPHUS IN 8ERB1 \

leasl tlic eighth or ninth day of the di and most

were older than this. In blood culture* 35 one

of which (38) had developed in the hospital, early blood cul-
tures were obtained, most of the tubes being taken with ascitic

fluid "X." In one tube of each of these a number of hi
colonies containing small Gram-positive diphtheroid bacilli

were found, but these diphtheroid organisms showed g
similarity to contaminating diphtheroids found in control
tubes with one of the other ascitic fluids. These colonies, there-
fore, were not considered to have any significance. In blood
culture "41," another early case which had developed in the
hospital, the blood culture was taken on what we assumed to
be the third or fourth day of the disease. In this ca>«- ascitic
fluids "X" and "Y" were employed in different tubes. This
blood culture was taken on June 12. By the twentieth two of
the tubes taken with ascitic fluid "Y" were grossly contami-
nated. On one tube with "X" ascitic fluid which had shown
no contaminations in controls, a suspicious colony appeared,
which showed small Gram-positive bacilli, which were trans-
planted on ascitic agar slants in Buchner tubes and in ascitic
glucose agar stabs in Buchner tubes. Two of the transplants
grew. This culture, in the original appearance of the colonic-.
in the appearance of the transplants, their anaerobic growth
requirements, and their morphology and staining properties
corresponded to the Plotz organism.

We may briefly summarize the results of something i >ver u >rt y
blood cultures on cases of unquestionable typhus by stating
that only two of these showed organisms which corresponded to
the Plotz bacillus. Cultures from the older cases showed
casional streptococci and Gram-negative bacilli, as did many
of the cultures taken from recently dead bodies at autopsy, and
these we regarded as secondary invaders. Indeed, we obtained
the general impression that secondary bacterial invasion oi the
blood stream was not uncommon in typhus fever.

It did not seem to the writer that his own experience justified
drawing definite conclusions about the Plotz bacillus. His
opinion was against the aetiological significance oi this organ-

266 REPORT OF BACTERIOLOGIST

ism because of the rarity with which it had been found, and
because of the fact that the necessity of using unfiltered and
unsterilized ascitic fluid in these cultures made it impossible to
exclude absolutely that the organisms had originated in the
ascitic fluid rather than in the case. While the difficulty under
the circumstances of adhering accurately to the criteria set
down by Plotz for the cultivation of his organism did not per-
mit the writer to draw definitely negative conclusions concern-
ing this organism, yet he felt that his work as a whole was
more against it than in its favor.

The laboratory meanwhile had been, we consider, well or-
ganized, and it had been possible to extend its facilities to
Dr. Castellani. who. with his personal assistant, used it during
this period to make large quantities of cholera and typhoid
vaccines for the use of the Commission for the Serbian army.
Autopsies had been done on typhus cases and on other
cases which interested the various physicians at the hospital
whether or not typhus, and the laboratory was made as
generally useful to the hospital as a whole as was possible at
the time. During this time also it was used by Dr. Sellards
in the pursuit of his special studies until his departure for
Belgrade.

Guinea pig work was necessarily limited since three guinea
pigs only survived, of the fifty taken from Xew York, probably
owing to the rough weather and cold on the way over, which
took pretty nearly a month, with many changes of weather and
many transshipments en route. Five further guinea pigs were
obtained at the end of May by the great courtesy of Dr.
Kopanaris. sanitary chief of Greek Macedonia, in Salonika.
Inoculations into these, intraperitoneally, of blood directly
from the patient were made immediately after arrival at the
hospital, and one of these after twelve days showed what we
considered a typical rise in temperature. A transfer from
this pig to another resulted in a temperature suggestive of
typhus, though it did not exceed 104CC. at any time. Trans-
fers from this one were also made, but showed no temperature
reaction.

TYPHUS i\ SERBIA

When the Kopanaris pigs arrived, all of them were u
from patients at various times, and in a numl them the

peritoneal cavity was punctured by the Pfeiffer method, I

three, and six days after inoculation with the typhus bl
and cultures and smears made from the puncture fluid. In one
of these pigs small Gram-positive bacilli were Been on 'Ik- third
day after inoculation with typhus blood. Smears of tbic
were studied very carefully, both by the writer and by Dr. <
tellani, and both believed that they were in a general way
similar to the Plotz organism, but none of the other pigs
showed such organisms, and cultures from the pigs with the
materials used both aerobically anaerobieally were entirely
negative. Two of the pigs were injected rather a short tin if
before leaving in the hope that the virus might be kepi going
for Dr. Hopkins on his arrival.

Vaccination

At about this time the question arose whether or not the
Serbian troops should be vaccinated with the Plotz organism.
The question was put to the bacteriologist by the director,
Dr. Strong, and, as may be easily seen from the above report,
the writer was not yet in a position at this time to either con-
firm or deny the aetiological importance of the Plotz organism.
The isolated apparently positive findings in the blood cultures
described above were not deemed by him sufficient basis for
advising extensive vaccination which would subject the Ser-
bian government to much administrative trouble, to expense,
and difficulties of mobilization at a time of critical military-
necessities. Moreover, the epidemic was distinctly on the
wane at this time, the decline being progressively more rapid
as the weather turned warmer. The writer, therefore, dis-
tinctly advised the director that there was no information at
his disposal at this time to justify a general vaccination of
Serbian troops and population. This statement is made in
order to make clear that in omitting a vaccination order at
this time the director of the expedition asked the advice oi the
writer and obtained the above negative reply.

268 REPORT OF BACTERIOLOGIST

The writer started South on the twenty-ninth of June after
turning over his material to Dr. Sellards and leaving the lab-
oratory under the direction of Dr. Castellani. Dr. Sellards
took charge of the typhus materials and the culture of the
supposed Plotz organism isolated from the case above de-
scribed, which he turned over to Dr. Hopkins who came over
shortly after to continue the work.

PART V

SUPPLEMENTARY BACTERIOLOGY \l. REPOR1

OF THE AMERICAN RED CRO VNTTAR^

COMMISSION TO SERBIA

Bi J. GARDNER HOPKINS

The writer left New York on the steamship Thessalonica
June 19 and arrived at Skoplje on July 19. Typhus had been
for some time on the decrease, and by this time there were very
few acute cases available for study. On arrival at Skoplje.
however, it was found that a dozen cases from the civil jail at
Cavadara had recently been brought to the Sixth Reserve
(Lady Paget) Hospital, five of which were in the acute stag
the disease, and the writer proceeded at once to the hospital to
study these cases. He found there a well-equipped l»a<--
teriological laboratory, which had been organize* 1 by Dr. Zins-
ser and his coworkers, which was then being used by Or.
Castellani of the American Commission for the preparation of
typhoid, paratyphoid, and cholera vaccines for the Serbian
army. There were two Austrian prisoners, assigned to labora-
tory duty, whom Dr. Zinsser had trained in the work. The
use of the laboratory was put entirely at the disposal of the
bacteriologist, and he was also given full charge of the typhus
cases through the courtesy of Dr. Maitland, the chief physician
of the Lady Paget Hospital. Cultures were made from one
case with materials at hand in the laboratory, and as soon as
agar, pleural fluid, and blood serum could be prepared, cul-
tures were taken on other acute cases. Two days later an addi-
tional case in the acute stage of the disease was brought in
from Cavadara.

Blood Culture Studies

Cultures were made by the method described by Plotz. the
blood being taken from the arm vein with a sterilized syringe,
and mixed with 2 per cent glucose agar, to which ascitic fluid or

260

270 SUPPLEMENTARY REPORT OF BACTERIOLOGIST

human blood serum was added. The mixtures were made in
deep tubes, and some of the tubes from each of the first eight
cultures were placed in Buchner tubes before the agar had
solidified. Considerable emphasis has been laid by Plotz on the
specific gravity of the ascitic fluid used in the culture, arid some
difficulty was found in obtaining fluid which answered the re-
quirement, that is, in which the specific gravity was over 1015.
The only fluids available at the hospital were those obtained
from cases of pleurisy with effusion, in which the specific grav-
ity ranged from 1011 to 1018. In one culture a specimen of
ascitic fluid was employed which had been kindly furnished by
Dr. Plotz and had been found satisfactory in his work at Mount
Sinai Hospital. In other cultures blood serum obtained by
venesection in cases of nephritis was used, as it seemed that
this must have all the advantages of a specimen of ascitic fluid
with high protein content. Other specimens of ascitic fluid of
lower specific gravity which had been brought from New York
were also used.

The cases from which the cultures were made were all con-
sidered by the physicians who had studied the typhus epidemic
in Serbia to be typical cases of typhus. They had high, con-
tinuous fever, ranging from 102° to 105° and profuse rash ap-
pearing, in some cases, on the palms of the hands. The cultures
were all made during the febrile period, from the seventh to the
eighteenth day of the disease, as nearly as could be ascertained
from the history.

Twelve cultures in all were taken from the six cases available,
and were observed for at least three weeks' incubation. The
tubes before being discarded were emptied into sterile Petri
dishes and the cylinder of agar cut into thin slices in order to
detect any small colonies which might have escaped observa-
tion in the rather opaque medium. A number of tubes showed
surface contaminations, due probably to the fact that the wards
in the hospital were exceedingly drafty and it was impossible
to avoid occasional contaminations from dust. In only one in-
stance, however, was a deep growth obtained which in any way
resembled the organism described by Dr. Plotz.

TYPHUS IN SERBIA 271

This one positive culture, No. 10. wae obtained on the
fifteenth day of the disease from a patienl who died the follow-
ing night. The temperature at the time of the blood cull
was 102°. Two tubes from this culture showed each
large colony in the depth of the medium, which appeared after
ten days of incubation. The colonics were surrounded b
zone of precipitated albumen and showed morphologically
small Gram-positive bacilli, strongly resembling those in the
culture which had been furnished by Dr. Plotz. ( >n subculture
the organism proved to be an obligate anaerobe, until it had
been preserved on artificial media for nearly two montl
which very faint growth in aerobic cultures was obtained.
Like the Plotz organism it rapidly produces acid in ghj
serum media as shown by the precipitation of the protein. [1
grows somewhat more heavily than the cultures of Dr. Plotz
which the writer has seen, and produces dee]> yellow pigment,
at times with a pinkish tinge. Inoculation of the culture in the
third generation into a guinea pig was without result. Since
this organism showed no pathogenicity, did not give tin1
agglutination reaction described by Plotz and Olitsky. and
resembled organisms described by Torrey as occurring a- sa] >fi »-
phytes in pathological lymph-nodes, it could not be regarded
as significant.

Agglutination Studies

As the patient from whom the culture was obtained died
before recovery of the bacillus, it was impossible to test the
organism against his own serum. Macroscopic and micro-
scopic agglutination tests were, however, carried out with the
serum of convalescent typhus cases in the hospital which had
had a normal temperature for a period of ten days to several
weeks. Later, on going to Nish, a case was found which had
had a normal temperature for only five days, and serum ob-
tained through the courtesy of the Russian Red Cross phy-
sician in charge was also tested against the organism in
question. None of the typhus sera gave definite agglutination
in excess of that obtained in normal controls.

272 SUPPLEMENTARY REPORT OF BACTERIOLOGIST

Autopsies

Autopsies were performed on three cases of typhus that died
during the febrile period. Cultures made from the spleen were
negative except for post-mortem contaminations.

Guinea Pig Inoculations

Two guinea pigs were inoculated from acute cases in the
Lady Paget Hospital, and one from an emulsion of spleen of a
typhus case obtained at autopsy, but no typical reactions were
obtained.

Later Cases

As no further cases of typhus were available at the Sixth
Reserve Hospital, attempts were made to locate cases suitable
for study in other parts of the country. On a rumor that cases
were developing in Galicnik, on the Albanian frontier, a trip
was made to this place with a bacteriological outfit in the hope
of obtaining specimens, but the rumor turned out to be false.
Later two cases were located at Mladinowatz. These were
mild cases, and were seen in conjunction with Dr. Sellards,
Dr. Baehr, and Dr. Plotz. Dr. Baehr and Dr. Plotz made cul-
tures from these cases, and Dr. Sellards and the bacteriologist
inoculated a monkey and four guinea pigs, all of which failed to
react. Other guinea pigs injected from these animals at a time
when reaction might have been expected also failed to show
any characteristic rise of temperature. Two cases of probable
typhus were also visited at the Serbian military hospital at
Ralja. Blood cultures taken from these cases were negative.
Although they were considered typhus by the physician in
charge, they were certainly not outspoken cases.

Results

Of six outspoken cases of typhus studied in the acute stage,
all gave negative blood cultures except one. From this an
organism resembling the Plotz bacillus was obtained, but, as
it failed to agglutinate in serum of typhus patients and failed

TYPHUS IN SERBIA

to produce.' any typical reaction in a guinea i>i'~r. \i

carded. The results of these studies were oo1 conclusive on

account of the few cases available for study. H< the

failure to isolate an organism corresponding to thai d<
by Plotz,from the typical cases studied, has a certain valu

negative evidence. While these experiments are too limit.
be considered as disproving the reports of Plots and hie a (work-
ers as to the aetiology of typhus, they failed to confirm these
results, and the writer so reported to the chief of the commis-
sion, Dr. Strong.

As there seemed little likelihood of obtaining further suitable
material for study, the writer left Serbia on the fifteenth of
September.

In conclusion, acknowledgment should be made of the
hospitality and courtesy extended by Lady Paget 's British
unit in charge of the Sixth Reserve Hospital and the invariable
courtesy of the Serbian physicians and officials.

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CAMBRIDGE, MASS., V. S.A.

3 9002 01040 3138

Accession no.

Author Oj^ J^'

'ffrphM.s (f&wr y

Call no. flC/??^

YALE