CERTAIN FORMS OF INFECTION IN TYPHOID FEVER. 
BY 
SIMON FLEXNER, M. D. 
[Reprinted from The Johns Hopkins Hospital Reports, Yol. Y.] CERTAIN FORMS OF INFECTION IN TYPHOID FEVER. 
BY 
SIMON FLEXNER, M. D. JOHN MURPHY & CO., PRINTERS, 
BALTIMORE. V.—CERTAIN FORMS OF INFECTION IN TYPHOID 
FEVER. 
SIMON FLEXNER, M. D. 
(From the Pathological Laboratory of the Johns Hopkins University and Hospital.) 
A. Typhoid septicaemia associated with focal abscesses in the kidneys due to the 
typhoid bacillus. 
J5. General Infection with the typhoid bacillus; perforative peritonitis caused 
by the streptococcus pyogenes. 
G. Typhoid Fever associated with miliary abscesses in the kidneys due to the 
typhoid bacillus. Non-transference of typhoid bacilli from mother to 
foetus. 
D. Typhoid Fever with perforation of the intestine; acute peritonitis with bac- 
terial poly-infection. 
E. Typhoid Fever with perforation of the intestine (3rd week of the disease) ; 
acute streptococcus peritonitis and streptococcus septicaemia; absence of 
typhoid bacilli from cultures. 
F. Typhoid Fever; death from haemorrhage (6th week of the disease). Dis- 
appearance of typhoid bacilli. Infection with bacillus coli communis. 
The distribution of the typhoid bacilli in the body in typhoid 
fever must be considered as still presenting interesting features. That 
the bacilli may be present in the blood of these patients seems, 
in view of certain observations (Karlinski, Vincent), very probable, 
although the work of the earlier investigators (Riitimeyer, Almquist, 
Pasquale, Guarnieri, Neuhaus), who claimed to have cultivated the 
organism from the general blood and that of the rose-spots during 
life, has, through later studies (Janowski, Stagnetto, Grawitz, Frankel 
and Simmonds, Sittman), been discredited. It is, however, significant 
that the observations in which typhoid bacilli were believed to have 
been cultivated from the blood during life, and again at autopsy, as 
in the case of Karlinski, date from a time when the means of distin- 
guishing between these organisms and certain other bacterial varieties, 
much resembling them, were not so complete as now. 
It is a well-known fact that all cases of typhoid fever do not com- 
plete their course as a simple infection, by which is meant that the 344 
Simon Flexner, 
morbid process, from its inception to its close, is due entirely to the 
action of the typhoid bacillus. The possibility of the interaction of 
other micro-organisms, secondary invaders, is now not to be doubted, 
although the effects of these subsidiary organisms may be compara- 
tively slight, and entirely limited to the intestinal tract. It must 
always be a matter of importance—the question as to just what part 
of the intestinal lesions are caused by the typhoid bacillus acting 
alone, and how much of these are attributable to other micro-organ- 
isms, chief among which are the pathogenic staphylo- and streptococci. 
There are instances, however, in which the secondary micro-organisms 
come to play a more active part, as are seen in cases of metastatic 
abscess formation and inflammation due to the pyogenic bacteria 
(spleen, mesenteric glands, heart valves), the portal of entry into the 
system doubtless being the ulcerated intestinal tract; and in cases of 
perforative peritonitis the importance and significance of these organ- 
isms are hardly to be overestimated. 
Among the fatal cases of typhoid fever which have come to autopsy 
in the Hospital, those here given have been chosen on account of their 
possession of features which lend interest to them in connection first 
with the distribution of the typhoid bacilli in the body and the un- 
usual localized lesions directly attributable to them, and second the 
nature, distribution and effects of the secondarily invading bacteria. 
Case I.—Typhoid Septiccemia associated with focal abscesses in the 
kidneys, due to the Typhoid bacillus* 
In individuals who have died of typhoid fever, provided death has 
occurred not too late in the course of the disease, it is usually possible 
to cultivate the typhoid bacillus from various organs, among which 
the mesenteric glands, spleen, liver and kidneys (not to refer to the 
intestines) may be mentioned. The experience of this laboratory 
indicates that the bile is particularly rich in the typhoid organisms, 
and the autopsy records of the Hospital contain many instances in 
which they have been isolated from this fluid in pure culture. Now 
that Quincke and Stahlen have directed attention to it, the bone- 
marrow will doubtless be found to be a common habitat of the 
*This case, including plates and bibliography, appeared in the Journal of Pathology 
and Bacteriology, April, 1895. Certain Forms of Infection in Typhoid Fever. 
345 
organisms in the disease; and in several recent autopsies I have found 
them in considerable numbers in this situation. In cases of abortion 
they have been found in a conclusive number of cases to have passed 
through the placental barrier (Widal and Chantemesse, Hildebrand, 
Eberth, Ernst, Janizewski, Frascani), and to be present in the organs 
and even in the blood of the foetus. 
The bacillus of typhoid fever is, therefore, distributed in such a 
way as to indicate that it has, at some time during the disease, been 
present in the blood current. Yet it must be remembered that it is 
not, unless most exceptionally, found in the blood outside of organs, 
even at autopsies. The rarity of this condition is sufficient apology 
for recording cases in which a general typhoid infection of the body 
existed at autopsy. 
This case presents, in addition, another feature which is perhaps 
of interest. The recent contributions to the study of the relation of 
the typhoid bacillus to local foci of suppuration have tended to show 
that in a variety of inflammatory processes this organism alone is 
concerned. This view, first advanced by A. Fraenkel, has, as is well 
known, been vigorously contested by Baumgarten and E. Fraenkel. 
The latter have contended that other bacteria, particularly the pyo- 
genic cocci, were present, along with the typhoid bacillus, and were 
overlooked or had died out at the time of the examination. Now in 
the kidneys in this case a number of abscesses existed in which no 
other micro-organisms than the typhoid bacilli were demonstrable. 
Any assumption that other bacteria had been present is not to be 
reconciled with the short duration of the illness; and the numbers 
and relation of the typhoid bacilli to the foci of suppuration leave 
no doubt of their action. 
The clinical course of the case was unusual. lam enabled, through 
the kindness of Dr. Osier, to whose ward the patient had been admitted, 
to give an abstract of the clinical history. 
Clinical Summary.—lllness of two weeks' duration before admis- 
sion; moderate fever; enlarged spleen; rigidity of muscles of neck and 
of right arm; mental dulness and delirium; cutaneous hypercesthesia 
and increase of the reflexes; small amount of albumin, with red blood 
corpuscles in the urine; no diazo-reaction; for 3 days before death 
normal temperature; parotitis. 346 
Simon Flexner. 
Susan 8., set. 18, colored; admitted to the medical wards 23rd 
April, 1894, complaining of headache, pains in the abdomen, and 
general weakness. 
The patient is an only child; her father is living, her mother is 
dead, but from what disease could not be learned. There is a history 
of tuberculosis in the father’s family. 
She does not remember ever having had any of the diseases of 
childhood; was always strong and well; menstruated first at 17 and 
has been regular. Five weeks ago she began to have sick headaches, 
but without vomiting. She kept at work, though feeling wretched* 
until 2 weeks ago, when she began to have pains in different parts* 
of the body, and weakness. She was restless and feverish without 
appetite, slept very badly, and had diarrhoea. The patient was so 
dull and stupid that it was only with difficulty that a history could 
be obtained. 
On admission at sp. m. her temperature was 103.7°; the pulse 
120, soft and regular. She vomited a dark greenish material. That 
night she was restless, but the temperature did not rise above 103.5° 
She was sponged, and whisky was administered. The urine obtained 
and examined on the evening of admission was slightly brownish in 
color, acid; specific gravity, 1010; it contained a small amount of 
albumin, and microscopically showed leucocytes and red blood cells 
No casts were seen; the diazo-reaction was not present. 
24th April.—The patient is a small, thin, poorly nourished girl 
and looks as if she had been ill some time. She lies on her back 
with the eyes half closed, and the face has a dull, typhoidal expres- 
sion. The temperature was 102.6° at 8 o’clock; the pulse was 116 
regular. The abdomen is not distended, but is held rather tense* 
The spleen is palpable, fully 4 cm. below the costal margin. During 
the examination the patient complains much of tenderness everywhere 
The examination of the lungs and heart showed nothing abnormal 
The first sound at the apex was a little prolonged and dull. The 
patient had one stool since admission, which was small, firm, and 
somewhat clay-colored. 
25th April.—The patient had a better night; the temperature for 
the greater part of the last 24 hours has been below 102°. The urine 
is dark amber-colored, acid in reaction; specific gravity, 1010; no 
diazo-reaction; a small amount of albumin; contains leucocytes and Certain Forms of Infection in Typhoid Fever. 
347 
a small number of red blood corpuscles. The patient had one move- 
ment to-day, in which there was a small fsecal concretion, concen- 
trically laminated. She had through the day a good deal of vomiting, 
and she took her nourishment—milk and albumen water—very badly. 
26th April.—Patient has vomited less; temperature has not reached 
102°; no movement from the bowels; pulse is feeble, and ranges from 
112 to 120. Only 400 cc. of urine was collected; she passed some 
involuntarily. Towards the afternoon of the 26th it was noticed that 
the head was much retracted, and held very stiffly, and the right arm 
was in a condition of extension, somewhat rigid, and any attempt to 
flex it caused pain. 
27th April.—The temperature to-day was lower, and at 6 a. m. 
reached 98.9°, and the highest throughout the day was 100.6° at 6 
p. m. She vomited repeatedly, talked incoherently, and moaned a 
great deal. She had one small stool at 10 p. m. She seemed very 
sensitive to the slightest touch. The retraction of the head and the 
rigidity of the arm persisted. 
It did not seem possible to decide as to the nature of the case. 
Though it looked more like typhoid fever on her admission, the 
retraction of the head and rigidity of the neck muscles, the general 
sensitiveness and the rigid extension of the right arm suggested, 
very naturally, cerebro-spinal meningitis. The blood was carefully 
examined for malarial organisms, and cover-slips were stained for 
tubercle bacilli; the leucocytes numbered 6,000 to the cubic milli- 
metre. The urine was yellow, acid, distinctly cloudy, with heat and 
nitric acid; no diazo-reaction. Microscopically there were many epi- 
thelial cells, chiefly from the bladder, some leucocytes, and a smaller 
number of blood cells. The sediment was collected and stained for 
tubercle bacilli with negative result. 
28th April.—On account of the vomiting she has been fed, for the 
past 24 hours, by rectal injections. At the morning visit she was 
lying with the head thrown back, and resisted slightly any attempt 
to bend the neck. She replies to questions in a confused and hesi- 
tating manner. There is no photophobia; the pupils are equal and 
react to light. After being aroused, she lies with her eyes open, but 
with rather a staring expression. She moves the left arm readily, 
but the right is extended and motionless by her side. It is not so 
rigid to-day, though she winces and cries out when any attempts are 348 
Simon Flexner. 
made to flex it. The deep reflexes in the left arm are active; in the 
right they cannot be tested. The knee jerks are a little exaggerated, 
and there is well-marked ankle clonus on both sides. The abdomen 
is not swollen; not especially tender. As satisfactory an examina- 
tion as possible was made of the uterus, but nothing abnormal could 
be detected. The temperature fell to 98.2° this morning, and the 
highest registered through the day was 100.1°. The patient had 
one well-formed stool. 
29th April.—The rigidity of the muscles of the neck is still marked, 
and the stiffness in the right arm persists. Mentally she seems some- 
what clearer, says she has no headache, and puts out her tongue when 
asked. From 10 o’clock last night the temperature has been a little 
below 99°. She has been passing urine involuntarily. 
30th April.—The temperature continues normal; was 98.2° at 8 
p. m. and 98.4° at 8 this morning. The pulse is feebler, just 100, 
and not irregular. There is no strabismus. She moves the left 
arm about freely; the right arm shows slight clonic movements, 
and at intervals becomes quite rigid. The ankle clonus could not 
be obtained to-day. The abdomen is flat, and not more sensitive 
than in other parts. 
May Ist.—Until 8 a. ra. the temperature was about 99°. This 
morning it was noticed for the first time that there was a soft swelling 
in the left parotid region, which is not painful. The vomiting has 
been very obstinate. She retains the nutritive enemata. To-day the 
right arm is easily flexed, and can be moved in all directions. The 
heart sounds are, and have been, perfectly clear. There are few rales 
at the bases of the lungs, but there has been no diffuse bronchitis. 
The temperature rose a little through the day, and reached 100.2°; 
the pulse became more rapid and feeble, and she died at 5.30. 
Autopsy 17 hours after death. 
Anatomical Diagnosis.—Typhoid fever (ileo-typhus and colo- 
typhus); haemorrhagic enteritis; acute splenic tumor; multiple abscesses 
in the kidneys; parenchymatous degeneration of the liver and, kidneys; 
purulent infiltration of the parotid gland; oedema of lungs and glottis. 
Body of a small, sparely-built negro girl. Subcutaneous fat in 
small amount. Muscles bright red in color. 
Peritoneal cavity.—No excess of fluid. The intestines are distended. Certain Forms of Infection in Typhoid Fever. 
349 
Pleural cavities.—Both dry. The lungs are free from adhesions. 
Both are voluminous. 
Pericardial cavity.—No excess of fluid, and both layers of the peri- 
cardium are smooth. 
Heart.—Right auricle and ventricle contain dark and partly de- 
colorized clots. In the left ventricle a small, partially decolorized 
clot. All the valves are normal. 
Lungs (Right).—The upper and middle lobes are oedematous; the 
lower lobe is congested. The bronchi are filled with frothy serum. 
Vessels at base free. (Left).—Lower lobe congested; the upper lobe 
oedematous. Bronchi contain frothy serum; vessels at base free. 
, Liver.—Weight, 1700 grms. It is soft, swollen, and the sharp 
edges are rounded. On section it is fatty in appearance, the lobular 
markings being obscure. The bile is thin, light-colored, and contains 
a granular sediment. 
Spleen.—Weight, 420 grms. The capsule is thin and distended. 
On section the substance is soft and pulpy; the follicles are visible 
and apparently not enlarged. 
Mesenteric glands.—Swollen and congested. 
Adrenal glands.—Apparently normal. 
Kidneys.—They together weigh 320 grms. (Left).—Large and 
pale. The capsule strips off easily, and beneath it, imbedded in the 
cortex, a number of small white nodules, larger than miliary tubercles, 
can be seen. Others are visible in the cut sections of the kidney. 
(Right).—ln general the same as the left. In this kidney there are 
several larger white areas, the largest of which is triangular in shape; 
the base of the triangle, measuring 4 mm., is situated at the surface. 
The capsule corresponding with this area contains small haemorrhages. 
Parotid gland.—On the left side it is swollen and infiltrated with 
pus. 
Larynx.—The posterior epiglottic tissues and the aryteno-epiglot- 
tidean folds are infiltrated with serum, and present a gelatinous 
appearance. 
Intestines.—The small intestine is bile-stained throughout. The 
mucous membrane is cloudy, and sticky mucus covers its surface. 
The patches of Peyer in the upper parts of the small intestine present 
the shaven-beard appearance. The first ulceration occurs in the ileum 
200 cc. above the valve. It is round, about the size of a 1 -cent piece, 350 
Simon Flexner. 
and is superficial and clean. 160 cm. above the valve there is a large 
ulcer, involving the entire circumference of the gut; it is 10 cm. 
in width, is irregularly convoluted superficially, and the surface is 
necrotic and sloughy-looking. This ulceration apparently does not 
reach beneath the submucosa, but the whole thickness of the intestine 
is involved in the infiltration. On the serous surface small white 
points (lymphomata) can be seen. Between this ulceration and the 
ileo-caeca! valve there are several smaller losses of substance. The 
lower end of the ileum is, together with the valve, inclosed in one 
larger ulceration of the same general appearance as the larger ulcer 
already described. Some of the solitary follicles of the caecum are 
ulcerated, others are swollen, the centres of these often being necrotic. 
The ascending, transverse, and in part the descending colon, show 
the same conditions as the caecum. 
Beginning at the larger ulcer, 160 cm. above the valve, and con- 
tinuing downwards to the latter, the mucous membrane is infiltrated 
with blood, the surfaces of the valvulse conniventes being more affected 
than other places, except immediately about the ulcers. The swollen 
and ulcerated follicles in the large intestine are surrounded by a zone 
of haemorrhage. 
Fresh frozen sections of the heart muscle show it to be free from 
fat; sections of the liver and kidneys show parenchymatous and fatty 
degeneration of the epithelial elements of these organs. 
Bacteriological examination.—Cover-slip preparations made at the 
time of the autopsy from bile, spleen, and nodule in the kidneys, 
showed many bacilli having the form and staining properties of the 
typhoid bacillus. This organism was found alone in these cover- 
slips. From the pus of the parotid gland the cover-slip preparations 
showed many streptococci. 
Cultures.—Agar-agar plates were made at the autopsy from the 
heart’s blood (right auricle), lungs, kidneys, mesenteric glands, spleen, 
bile, liver, bone-marrow (femur), and parotid gland. These plates, 
kept at 37° C. for 48 hours, gave the following results:— 
Bile.—Crowded with colonies, apparently all of the same kind. 
Proven to be a pure growth of the typhoid bacillus. 
Spleen, mesenteric glands, and bone-marrow, all contained many 
colonies of the typhoid bacillus. Certain Forms of Infection in Typhoid Fever. 
351 
Kidney.—Two cultures were made from this organ. The first was 
taken from one of the white nodules, the second from the intervening 
kidney substance. From the nodule many colonies developed, and 
they consisted entirely of the typhoid bacillus. The other plate con- 
tained fewer colonies, from which two kinds of organisms were 
separated, one agreeing with the typhoid bacillus, the other with the 
Bacillus coli communis. 
Lungs.—From the congested portion of the right lower lobe three 
organisms were isolated—(l) Streptococcus pyogenes; (2) Typhoid 
bacillus; (3) Bacillus coli communis. 
The streptococcus colonies predominated. 
Heart’s blood.—On this plate 20 to 30 colonies, all having the 
same features and proving to be the typhoid bacillus, developed. 
Parotid gland.—The agar-agar plate was crowded with minute 
colonies of the Streptococcus pyogenes. Sections of the gland hard- 
ened in alcohol showed a pure streptococcus invasion along the ducts 
into the gland acini, associated with an interstitial and parenchy- 
matous infiltration of leucocytes, with polymorphous nuclei. 
In studying the bacilli isolated from this case, special attention 
was paid to distinguishing between the typhoid and the colon bacil- 
lus when they occurred together (lungs and kidneys), and to proving 
that the organisms found in the heart’s blood, kidney nodules, as 
well as in the other organs mentioned, were really typhoid bacilli.* 
* The recent writers on the means of distinguishing the typhoid and colon bacilli 
regard the fermentation (Smith, Chantemesse and Widal, Fuller, Dunbar, Welch, 
Valentini, Germano and Murea, Silvestrini), milk (Dunbar, Maloz, Yalentini, 
Welch, Blachstein, Silvestrini), and indol (P4re, Ferrati), tests as sufficing to estab- 
lish this distinction, and my own experience accords with that of these authors. 
Recently a new medium has been introduced by Wurtz for separating these two 
forms. It consists of lactose-gelatine colored with an alkaline litmus tincture. The 
colony growth in this medium can, through the change in the reaction produced in 
it, be used for this purpose. The colon bacillus colonies are said to become pink, 
whereas the typhoid remain blue. In several tests recently made with this medium, 
agar being used in place of gelatine, I found that the typhoid bacilli produced suffi- 
cient acid when acting upon lactose to turn the medium slightly pink; but the acid- 
reaction is less strongly marked than that caused by the colon bacillus. I have, 
moreover, had the opportunity of observing a variety of the typhoid organism 
which, when planted in litmus milk, gives at first a typical reaction; that is, after 
24 to 48 hours at 37° C., it causes a faint pink color to appear. This color persists 
for some days (5 or 6 in the thermostat), when it changes back to blue, the blue 
gradually increasing in intensity until after 10 days or 2 weeks, the alkaline-reac- 352 
Simon Flexner. 
The weight of opinion among bacteriologists at this time, is that 
the colon group of organisms can be sharply differentiated from the 
typhoid bacillus. However, it no longer suffices for distinguishing 
them to observe the colony growth upon agar and gelatine plates, or 
the growth upon potato; neither does the possession of motility and 
stainable flagella serve to distinguish the typhoid from the colon 
bacillus. On the other hand, the power of acid and indol-produc- 
tion, the property of setting up fermentative changes in sugar with 
the liberation of gas, and the coagulating influence upon milk, pos- 
sessed by the colon group of organisms, separate it from the typhoid 
organism, which produces alkali, does not yield indol in cultures, is 
not capable of fermenting sugar, and has no coagulating effect upon 
milk. 
The bacilli separated from this case were tested by these means, 
by observations of their growth upon different solid culture media, 
as well as by microscopical study; and it was found that in the 
heart’s blood, spleen, bile, liver, mesenteric glands, bone-marrow, 
and abscesses of the kidneys, the typhoid bacillus was present in 
pure cultures.* 
The number of observations at the present time referring to the 
typhoid bacillus as the cause of post-typhoid inflammations is so large 
as to admit of little doubt of an etiological connection between the 
tion is very prominent. This fact agrees with Wurtz’s observations on the alkaline 
(ammonia) producing power of the typhoid bacillus, as opposed to the acid produc- 
tion of the colon bacillus. Pfeiffer has, moreover, just pointed out that animals 
rendered immune from the typhoid bacilli, contain an anti-toxine in their blood 
which is bactericidal to them, and not to the colon group of organisms, and other 
forms which seem to be even more closely related to the typhoid bacillus. 
*The typhoid bacillus has been found in local inflammations as follows:—In con- 
nection with bone giving rise to osteomyelitis and periostitis, by Ebermaier, Orlow, 
Yalentini, Achalme, Chantemesse, Colzi, Melchoir, Dupraz, Buschke, Sultan; in 
abscesses of skin and muscle and periarticular abscesses, by Melchoir, Raymond, 
Rosin and Hirschel, and Swiezynski; in acute endocarditis, by Carbone, Vincent, 
Girode; in circumscribed peritonitis, by A. Frankel, Lehman; in cerebro-spinal 
meningitis, by Kamen, Honl, Hintze, Stiihler, Mensi and Carbone, Vincent; in 
abscesses in the spleen and mesenteric glands, by Roux and Vinay, Lehman, 
Flexner; in purulent cholecystitis, Gilbert and Girode Chiari; in sero-fibrinous 
pleurisy and empyema, by Ferret, Loriga and Pensuti, Valentini, Spirig, Weintraud; 
in purulent strumitis, by Colzi, Honl, Jeansalme; in suppurative epididymitis, by 
Gilbert and Girode; in suppurative orchitis, by Tavel; and in a suppurating lipoma 
of the knee, by Sittman. Certain Forms of Infection in Typhoid Fever. 
353 
organism and the pathological process. The length of time during 
which this organism can remain in the body is not a little surpris- 
ing. Among the first of the observations bearing on this point, is 
that of Welch, who found in a rabbit which had been inoculated with 
typhoid bacilli 4 months previously, and had recovered, and which 
later succumbed to another experiment, that the typhoid bacilli 
which had disappeared from all other situations were still present in 
considerable numbers in the bile of the animal. The longest period 
yet recorded in which the typhoid bacillus had been found in the 
body after recovery from a typhoid fever, is that reported by D. 
Buschke, in which, in a rib-abscess, they were present seven years 
after. The list of cases in which this organism has been found in 
local foci of suppuration is now very large, and includes most situa- 
tions in the body. In the study of some of these it is not improbable 
that the strict bacteriological requirements, concerning, in the first 
place, the identity of the bacillus, and in the second the absence of 
other organisms, may not have been carried out. But a few care- 
fully studied cases, in which the typhoid bacillus is proven to have 
been present alone, renders the doubtful ones more probable. In 
the study of the abscesses in the kidneys * in this case, this fact was 
kept in mind. Therefore, examinations were made—(l) of cover- 
slip preparations from the abscesses, (2) of cultures in agar-agar, etc., 
(3) sections from the kidney hardened in alcohol were stained in 
various ways, as will appear, for organisms, with the result that the 
typhoid bacillus was found alone in the lesions. 
The abscesses can be separated into two groups, depending upon 
their sizes. The smaller ones are limited to the cortex of the kidney. 
*The typhoid bacillus has been found in the kidney by the culture method in 
many instances, in which no lesions have been detected, and in association with 
lymphomata by several authors, viz., Konjajeff, Spirig, Karlinski. Faulhaber was 
able to grow from an anaemic infarction of the kidney, in a case of typhoid fever 
associated with fresh vegetations on the mitral valve, a large number of typhoid 
colonies. The lymphomata are described as usually microscopic in size, but they 
may reach a size sufficiently large to be seen with the unaided eye. They are com- 
posed of accumulations of round cells with single nuclei. The bacilli are present, 
so far as they can be seen, in small masses and groups, lying amid the cellular infil- 
trations. Konjajeff saw them in both capillaries and tubules, while Spirig could 
not clearly ascertain their situation. Neither discovered them in the glomeruli. 
Yon Wunschheim has just published a report of 2 cases, in which abscesses in the 
kidneys were produced by the typhoid bacillus. 354 
Simon Flexner. 
Their shape, as found upon microscopical examination, is linear rather 
than round, the central zone richly infiltrated with pus cells, being 
surrounded by a wide but less thick, round-cell infiltration. Speci- 
mens stained for 2 hours in Loeffler’s methylene blue, differentiated 
in 1-1000 acetic acid, dehydrated in absolute alcohol, and cleared in 
oil of cloves, show, under a low power,—objective No. 3, ocular No. 
3,—large masses of bacteria; in a single section as many as six of 
these collections of bacteria may be visible. These masses of bacilli 
are entirely and promptly decolorized by Gram’s method of staining, 
and no other organism could be found, after painstaking search, in 
specimens stained in this manner. The same result was obtained 
with Weigert’s fibrin stain. 
Towards the centre of such an area the cellular infiltration is so 
great as to obscure the structure of the tissues; and when the latter 
can be made out the staining is feeble, and in it many nuclear frag- 
ments are to be seen. The infiltrating cells vary in form, some of 
them possessing single and others compound (polymorphous) nuclei. 
At the edge of the infiltration it can be readily seen that many of the 
cells are intertubular. These partake as a rule, although not exclu- 
sively, of the character of small round cells. Some of the tubules are 
dilated and filled with polyform leucocytes. The masses of bacteria 
are often so surrounded by cells that their location is not always to 
be made out with certainty. But they appear at times to be intra- 
tubular; besides the large masses described, smaller foci of bacterial 
accumulation are to be seen among the cells. 
The larger abscesses involve the medullary as well as the cortical 
part of the organ. From the surface the infiltration extends in 
somewhat irregular parallel lines for a considerable depth into the 
pyramids. In such an area the nuclei of the cells are to a large 
extent of the polyforra (polynuclear) variety. However, between 
the tubules, at a little distance from the thickest infiltration, there 
are many small cells with spherical nuclei present. In the central 
foci of leucocytic infiltration the kidney tubules are dilated and filled 
with pus cells. Tubules of the convoluted type are often distended 
to more than twice their normal size, and the straight tubules of the 
medullary rays are equally affected. Following the tubules down- 
ward into the pyramid, the intratubular exudate is very common, 
while the intertubular is more scanty. Certain Forms of Infection in Typhoid Fever. 
355 
The bacteria are in large masses and in smaller aggregations, and 
may now be seen to be distinctly inside of the tubules and surrounded 
by pus cells. Indeed, some cells appear to have taken up the bacteria. 
The forms of the bacteria are readily made out in the smaller accumu- 
lations. They consist of short, plump rods, with rounded ends, which 
in the alkaline methylene-blue fluid show an irregularity of staining. 
The larger masses can be easily seen with a No. 3 objective (ocular 
No. 3), whereas the smaller groups require the aid of the one-twelfth 
in. oil immersion to bring them to light. A few small groups of 
bacteria were observed between the tubules, probably intravascular. 
An interesting feature was observed in several glomeruli in infil- 
trated areas. Masses or thrombi of bacteria were seen in the afferent 
vessels, and similar bacilli were present in the glomerular capillaries, 
and had passed through these, as they were found again in numbers 
in the capillary space. The epithelium lining the capsule of Bowman 
was in such cases entirely degenerated. 
The epithelium of the cortical tubules, particularly of the convo- 
luted portions, is swollen, granular, and often degenerated. Those 
tubules, which are adjacent to, or within, the areas of cellular infil- 
tration, show at times an absence of stainable nuclei in the lining 
cells. The form of epithelial degeneration, which is seen most fre- 
quently, is, however, of the hyaline variety, and the hyaline material, 
which is highly refractive, can be seen to run together to form actual 
tube casts. Those tubules, in which many pus cells occur, have no 
demonstrable epithelium, or are lined by low, compressed cells, often 
still possessing stainable nuclei. 
So far as these foci are concerned, the process is not distinguishable 
from acute suppuration, although the tissues show no particular ten- 
dency to soften and break down. 
It should be mentioned that in a few places there are considerable 
masses of bacteria inside of tubules, showing less reaction around 
them, on the part of the tissues, than that described. Such appear- 
ances are uncommon in the cortex, but in the pyramids, in the collect- 
ing tubules, masses of bacilli are embedded in pus cells, with little or 
no surrounding intertubular infiltration. 
There can be no doubt that the bacilli gained entrance into the 
tubules through the glomerular capillaries. This is shown not only 
by the appearances already described, but also by the almost complete 356 
Simon Flexner. 
absence of the bacilli in the intertubular tissue. It would appear 
that most of the pus cells seen in the pyramidal tubules also come 
from places higher up in the kidney. 
The size of the masses of bacteria in some of the pyramidal tubules 
suggests that an increase must have taken place after these parts were 
reached. In a few instances a tubule, usually in the papillary portion 
of the pyramid, has been completely filled by a growth of the bacilli, 
and around these there may be no reaction whatever, so that a post- 
mortem increase is not to be excluded.* 
In considering the features presented by this case in the light of 
the literature bearing on the typhoid bacillus, it would seem as if it 
were necessary to regard this organism as being concerned in a variety 
of pathological conditions. Just as a larger and fuller acquaintance 
with the properties of the diplococcus pneumoniae has shown it to be 
at one time able to cause as definite a pathological process as acute 
lobar pneumonia, at another abscess formation, and at still another a 
general infection of the body, so the typhoid bacillus seems capable of 
jwoducing on the one hand the typical lesions and classical features 
* A few cases of especial interest have been reported in which the typhoid bacillus 
has been widely distributed in the body in association with definite lesions, or in 
which this organism has been isolated from the organs at autopsy with very slight 
or even entire absence of lesions in the intestine indicative of typhoid fever. It is 
at this time becoming to be very circumspect in the interpretation placed upon these 
cases, unless the most rigid requirements as to the identity of the organism are 
carried out. Hence in the cases reported by Banti and Karlinski of a typical typhoid 
fever, where no definite lesions of typhoid fever existed, and yet the organisms were 
obtained from the blood during life, and the organs after death, it may be questioned 
whether they are to be accepted as conclusive. But the same is not true of the case 
reported by Du Cazal in which, upon the closest inspection, no lesion could be found 
in the intestine. Yet typhoid bacilli which behaved in a typical manner upon 
various culture media, and did not ferment lactose nor redden Wurtz’s agar, were 
isolated from the much enlarged spleen. The symptoms during life were those of 
typhoid fever, and at the autopsy the mesenteric glands, spleen and kidneys were 
swollen and congested. The case of Vincent contained a number of superficial ulcers 
in the ileum, and a deeper one just at the valve. The spleen was swollen, and in it 
was an abscess the size of a walnut, containing thick, viscous, white pus; the mitral 
valve contained several fresh vegetations; there was a haemorrhagic infiltrated 
placque, the size of a 5-cent piece, at the summit of the left ascending parietal con- 
volution, and from all these typhoid bacilli in numbers were obtained in pure culture 
They were also grown from other organs and the heart’s blood. The bacilli were 
decolorized by Gram’s method, and grew like typical typhoid bacilli in bouillon 
Vincent’s (carbolic acid) bouillon, and upon agar-agar. Certain Forms of Infection in Typhoid Fever, 
357 
of typhoid fever, and on the other of localized foci of inflammation 
and suppuration, and finally a genuine typhoid septicaemia. 
It would be interesting if not profitable to inquire into the peculiar 
conditions which permit at one time the invasion of the blood by this 
organism, whereas, as a rule, it does not find in it a suitable medium 
for development. The fact is too well known to need repetition, that 
normal human blood serum quickly kills many typhoid bacilli. It 
is not improbable, therefore, that in such instances the germicidal 
power of the blood has been either annihilated or diminished, and it 
may be well to ask whether, as in the experiments of Vincent and 
Chantemesse and Widal with the streptococcus and its soluble pro- 
ducts, or of Sanarelli with the products of the bacillus coli communis 
and the bacillus proteus, the general infection might not be explained 
by the development of a concomitant infection, in this case a strepto- 
coccus parotitis, Vincent has shown, moreover, that in human beings 
a streptococcus invasion of the body makes the prognosis very grave, 
even when it occurs towards the close of the disease, and after the 
typhoid bacilli have almost disappeared from the system. Among 
his cases is one that was complicated by an otitis media of strepto- 
coccus origin, in which on the fifteenth day there was augmentation 
of the fever, and an inverse type of temperature. Seven days later 
death occurred. The autopsy showed a general streptococcus and 
typhoid infection, the former organisms predominating in the heart’s 
blood. But as opposed to such a supposition as the above, are the 
many instances of suppuration due to the pyogenic cocci, in the course 
of typhoid fever, in which there is an absence of evidence pointing to 
an invasion of the blood by the typhoid organisms. However, it 
may be well to study more particularly the relation of the typhoid 
bacillus to the blood in human beings in this class of cases. 
Case ll. General infection with the typhoid bacillus; perforative 
peritonitis caused by the streptococcus pyogenes. 
Barbara W., aged 21, admitted to the medical wards (Dr. Osier) 
September sth, 1893, complaining of pain in the neck, chest and ab- 
domen, and great weakness. 
Two of her brothers are ill with typhoid fever in ward F, and 
several other members of the family have had the disease this summer, 
and she has recently been nursing a brother who died of the disease. 358 
Simon Flexner. 
With the exception of pneumonia at thirteen, she has been very- 
healthy. 
Present illness began about two weeks ago, with headache and loss 
of appetite; bowels were constipated, and she had at times slight 
pain in the abdomen. She had also cough and pains in the chest. 
She has been keeping up in order to help her mother do the nursing 
at home. 
On admission the temperature was 102.5°, and rose in the even- 
ing to 104.°. She had retention of urine and was catheterized. 
Patient was a healthy looking, wTell nourished girl; face a little 
flushed; tongue swollen and furred. The abdomen was everywhere 
soft; there were no rose-spots; the spleen was not palpable. The 
examination of the lungs and heart was negative. The temperature 
range was not high, and during the first three days in the hospital 
she had only six baths. At first the bowels were constipated • then 
on the eighth she had four stools. 
On the 9th and 10th the temperature was higher and more per- 
sistent. The pulse was regular, of good volume, and not dicrotic. 
The abdomen was not distended; spleen was not palpable, and there 
were no rose-spots to be seen. She had two or three soft movements 
a day. 
On the 11th and 12th the temperature kept between 103° and 
104°. The abdomen was soft, not distended, not painful. The 
tongue was furred, not dry. 
On the 13th she was not so well; pulse was more rapid, reached 
130; temperature was nearly 105°. She complained of pain in the 
abdomen, but there was no special swelling. She had three move- 
ments on the 13th. 
On the 14th the temperature was almost constantly above 104°, 
and at 2a. m. reached 105.2°. The abdomen was slightly distended. 
The diarrhoea had increased very much ; the respirations were 
short and costal. The hands and feet were cold and clammy. The 
gravity of the general condition contrasted with the comparatively 
slight local features. The abdomen was not much distended, and 
only on deep pressure painful. There was foetal heart rhythm. 
Throughout the night of the 14th she became much worse; move- 
ments were frequent, and the collapsed condition was marked. She 
was given subcutaneous injections of salt solution. The pulse was Certain Forms of Infection in Typhoid Fever. 
359 
very rapid, and almost uncountable. The patient took her nourish- 
ment well. The abdomen became more distended, tympanitic, and 
tender. There was 3 cm. of liver dulness in the right nipple line. 
The patient became much worse throughout the day and died at 2 
p. m. in the afternoon of the tenth day after her admission to hospital, 
and about the 21st day of the disease. 
Autopsy seventeen hours after death. 
Anatomical Diagnosis.—Typhoid fever ; perforation of the ap- 
pendix vermiformis, with peritonitis due to the streptococcus pyogenes ; 
general infection with the typhoid bacillus. 
Body of a well nourished girl, 162 cm. long; rigor mortis present 
in the extremities. Abdomen much distended, the tympany extend- 
ing upwards over the liver. 
The peritoneal cavity on incision permits an escape of gas and con- 
tains a considerable amount of yellowish brown fluid. 
The intestines are matted together by fresh fibrino-purulent exu- 
date, most abundant in the right iliac region. Coils of the small 
intestine have a dry glazed appearance, and are much distended by 
gas; the serosa is intensely injected. On separating the ileum from 
the caecum, to which it was attached by fresh adhesions, the enlarged 
and swollen appendix was brought to view. This runs over the 
right brim of the pelvis. In the appendix, almost at its extremity, 
there is a perforation leading into its lumen. There is no attempt at 
localization of the abscess. The diaphragm on the right side is at the 
third space; on the left side, at the fourth rib. 
Intestines.—Throughout the entire ileum and the lower part of 
the jejunum the solitary glands and the Peyer’s patches are uni- 
formly enlarged. As the ileo-caecal valve is approached the patches 
of Peyer become much more prominent, and many of these are capped 
with small yellow sloughs. Beginning about 40 cm. above the valve 
there are actual ulcerations, none of them, however, being clean. The 
mucous membrane of the caecum and the ascending colon is much 
swollen and congested, the solitary follicles being enlarged, the apices 
of some capped with sloughs. The vermiform appendix is 9 cm. in 
length; its mucosa is swollen, and varies from 4to 5 mm. in thick- 
ness. There are large areas of necrosis of the mucous membrane 360 
Simon Flexner. 
present, and 2 cm. from its tip a perforation occurs, whose diameter 
is 5 mm. 
The mesenteric glands are greatly swollen and congested. 
The spleen weighs 280 grammes; the capsule is free from adhe- 
sions ; on section it presents a purplish-brown color, and it is of very 
friable consistence. 
The liver weighs 1350 grammes; the capsule is smooth; on sec- 
tion the organ is of uniformly yellowish-brown color and friable. 
The gall bladder contains a very little turbid yellowish-brown bile. 
The kidneys are essentially alike. They are somewhat swollen; 
the surface is smooth ; on section it is moist; the cortex is opaque. 
The glomeruli are visible and red. 
The heart weighs 185 grammes; is free from valvular lesions; its 
muscle is soft, pale, and relaxed. 
The lungs are bound by old adhesions to the costal wall. On 
section they are quite uniformly congested. 
The other organs apparently are normal. 
Cultures in this case were made from the peritoneal cavity, the 
heart’s blood, the bile, and all organs upon agar-agar. From all 
the sources, including the heart’s blood, a growth was obtained which 
was proven to be the typhoid bacillus. In the peritoneal cavity, 
cultures of which were made from the purulent exudate, the only 
organism found was the streptococcus pyogenes. 
Case 111.—Typhoid fever associated with miliary abscesses in the kid- 
neys due to the typhoid bacillus. Non-transference of typhoid bacilli 
from mother to foetus. 
Clinical history.—Anne M., set. 23, white, admitted to the medical 
wards (Dr. Osier) 14th of January, 1892, complaining of fever and 
general malaise. 
The patient stated that her father, mother, brothers and sisters were 
all drowned. Previous to the drowning she had lost neither brother 
nor sister; they had always been healthy. 
She has always been healthy, this being her first illness. Catamenia 
began at 15; married at 18. She had one child, now 2 years old, 
which is healthy. 
Her present illness began five days ago with “ quickening move- 
ments.” Her catamenia have been absent five months. For the last Certain Forms of Infection in Typhoid Fever. 
361 
five days she has complained of fever; appetite poor; bowels consti- 
pated. She suffered at times from pain in the back. 
At the time of admission she was very feverish, skin hot and dry, 
pulse 120. The spleen was just palpable, and several rose-spots were 
present over the abdomen. The uterus reached nearly to the umbilicus. 
The temperature was 105° F. on entrance, and on January 15th it 
fluctuated between 101.6° and 104.3° F. The patient has been 
sponged every three hours since her admission, and to-day (January 
15th) she looks distinctly brighter. 
January 15th.—Patient is well nourished, lips and mucous mem- 
branes of good color, tongue dry and brown. Sordes on the lips. 
Pulse, 24 to the quarter, of distinctly better quality than on entrance, 
though the tension is rather low. There is a marked dulness of both 
cornese, and the upper incisors show the Hutchinsonian nicking dis- 
tinctly. Thorax.—Respiration and resonance clear in front; in the 
back an occasional moist, hoarse rale is heard. Heart.—Apex in 4th 
space, outside nipple. Dulness does not pass 3rd interspace. At the 
apex the Ist sound is followed by a soft, blowing murmur which is 
heard a short distance into axilla, over the whole cardiac area, and 
loudest in the pulmonic region. Heart’s action regular. The 2nd 
pulmonic rather sharp. The mammae are enlarged, areolae of nipples 
dark in color, follicles prominent. Hepatic flatness at 6th rib in 
mammary line reaches to costal margin; border of liver not palpable. 
Splenic dulness markedly increased, beginning at 7th rib and reach- 
ing nearly to costal margin. The border, which could be just felt 
yesterday, not palpable to-day, owing to abdominal resistance. Abdo- 
men evenly distended over the lower portion. There is pigmentation 
about the umbilicus and linea alba. A smooth, rounded, fluctuating 
mass can be felt extending from the pelvis within one inch of the 
umbilicus. This tumor is regarded as the pregnant uterus. There 
are typical rose-spots over the abdomen and chest. On the left ulna, 
near the elbow-joint, there is a slight prominence. The right tibia is 
fairly smooth; the left shows a slight prominence at about the junc- 
tion of the lower and middle third. Urine.—Amber, hazy, reaction 
amphoteric; sp. gr. 1010; no albumen; distinct diazo-reaction; no 
sugar. Microscopical examination.—Triple and amorphous phos- 
phates, leucocytes and epithelial cells. 362 
Simon Flexner. 
January 19th.—Urine dark brownish-red in color; flocculent de- 
posit; sp. gr. 1018; distinct diazo-reaction; distinct trace of albumen • 
epithelial cells and leucocytes in sediment; no casts seen. 
January 21st.—From the 15th to the 19th the temperature of the 
patient remained very high, touching every day points above 104° F. 
Yesterday the highest point reached was 102° F.; this morning it is 
101.7° F. Mental condition clear; tendency to constipation rather 
than to diarrhoea. The pulse is regular, 26 to the quarter and of 
fairly good quality. 
January 22nd.—Urine—no albumen, no casts, distinct diazo-reac- 
tion. 
January 27th.—Diazo-reaction still present. Color of the urine 
reddish-brown ; neither albumen nor casts present. 
January 30th.—Temperature from 21st to 24th remained about 
the same—touching 104° F. every day; from 24th to 27th the tem- 
perature was somewhat lower and the patient seemed rather easier 
Yesterday at 10 a. m. temperature reached 105° F. Pulse more rapid 
and the patient complains of pain in the right breast where a slio-ht 
caking can be felt in the middle of the gland. This morning the 
temperature fluctuated between 100° and 100.4° F. a fall of 4 6° F 
having occurred between 2 p. m. yesterday and 2 a. m. this morning! 
The rose-spots are fading, tongue still dry and coated, and emaciatioli 
is beginning to become evident. The pulse is 28 to i and of dis- 
tinctly better quality than for the last two days. 
February 4th.—ln the last five days the temperature has varied 
between 98° and 104.6° F. The quality of the pulse seems no 
worse; this morning it is 29 to the quarter. The urine was ex- 
amined several times since the last report, the diazo-reaction havino- 
gradually grown fainter at each examination, to be missed on the 
4th inst. 
February 9th.— Since the 4th the temperature has ranged between 
99.8° and 104.6° F. The pulse has been more rapid°and rather 
smaller in volume. Wednesday a fresh crop of rose-spots appeared 
on the abdomen. 
February 11 and 12.—The diazo-reaction began to appear again 
in the urine. 
February 13th.—For the last four days the temperature has 
touched a point above 104° F. daily; pulse 120-140, perfectly reo-u- Certain Forms of Infection in Typhoid Fever. 
363 
lar, though the volume is low. The rose-spots, which lately appeared, 
are now almost gone. The foetal movements are lively. 
February 15th, 16th and 18th.—The condition of the patient 
remains about the same. The temperature continues to rise to 104° 
and over. On the 16th a fresh crop of rose-spots appeared. Pulse 
on the 15th ranged from 132 to 150. 
February 19th. A number of small boils, quite superficial, 
appeared on the arm, axilla and back. The patient has been wander- 
ing slightly in her mind. 
February 22ud.—The foetal heart was for the first time audible. 
February 23rd.—Since 10 p. m., the 21st, the temperature has not 
touched a point beyond 100.8° F.; the pulse has been slower, and 
the general appearance of the patient is better. Last night she was 
quite restless. Urine dark in color, turbid, acid, sp. gr. 1012, con- 
siderable albumen, hyaline casts covered with leucocytes, some red 
blood corpuscles and many leucocytes. 
February 25th.—Yesterday morning the patient became considera- 
bly hoarser, she could not speak above a whisper, and at noon there 
was considerable interference with respiration. A considerable degree 
of oedema was made out about the glottis. Dr. Halsted saw the 
patient at 8 p. m., and tracheotomy was performed with temporary 
relief; during the night the patient failed and died at 5.05 this 
morning. 
Autopsy 5 hours post-mortem. 
Anatomical Diagnosis.—Typhoid fever of late date with nearly 
healed and healing ulcers; ulceration of mucous membrane of the gall 
bladder; multiple miliary abscesses of kidney due to the typhoid bacil- 
lus; furunculosis of arm and suppuration of axillary gland due to 
the staphylococcus cereusflavus ; oedema glottidis ; tracheotomy ; bronchitis 
and broncho-pneumonia. Pregnancy of 6th month; cerebral haemor- 
rhage and general oedema of foetus. 
Body of a medium sized, slightly built, somewhat emaciated woman. 
Surface pale. A tracheotomy wound extends from the thyroid carti- 
lage to within 4 cm. of the sternal notch. On the right arm, near 
the shoulder several small swellings occur, two or three of which 
present small external openings which lead into small abscess cavities, 
containing creamy pus. The corresponding axillary glands are en- 364 
Simon Flexner. 
larged and on incision contain pus. Lymphatic glands of the body 
generally, not swollen. 
Peritoneal Cavity.—Both layers of the serosa are smooth, glisten- 
ing and moist. The peritoneum covering the small intestine shows 
a few reddish patches, corresponding to which the serosa is thickened. 
The mesenteric glands are swollen, dark-red in color and softened 
Small Intestines.—Show many ulcers. These extend from the 
caecum to within 2 metres of the pylorus. Commencing at the upper 
portion of the gut, the ulcers are in general small and superficial 
with unclean bases and irregular margins. The large ulcers are cir- 
cular in outline and their edges are low and covered over with gran- 
ulation tissue. At of some of these there are smaller areas 
in which either a new ulceration has taken place, or a part of the old 
ulcer is left uncovered. Not infrequently a number of ulcers occur 
close together, these presenting about the same characters. They 
have clean centres which extend to the muscular coat, the edges beino> 
covered over by irregular granulations, or even at times being over- 
laid by the undermined mucosa (overhanging ulcers). At the ileo- 
csecal valve the area of ulceration is very large, the circular muscle is 
exposed in the base of the ulcers, many of which have overhanging 
edges. Those in the higher parts are for the most part nearly 
healed or rapidly healing, in a few instances, entirely healed, while 
lower down the healing is far less advanced and fresh ulceration is 
occasionally met with. 
Spleen.—Large, weight 250 grams. The capsule is slightly 
roughened by small connective tissue outgrowths. Consistence of the 
organ moderately firm. On section the cut surface is intensely 
hypersemic; the Malpighian bodies are visible but not enlarged. 
Liver.—Enlarged; weight, 2300 grams. The surface is smooth. 
On section it is pale, homogeneous and cloudy in appearance. Beneath 
the capsule of the right lobe there are several small ecchemoses 
Gall bladder.—Distended with bile. The raucous membrane con 
tains several small superficial ulcers and erosions. The ulcers have 
sharp edges, and they extend apparently no deeper than the mnn,mo 
, T , A IiiULUUS 
membrane. In some the mucosa appears to be advancing over the 
edge of the ulcers. No concretions present. 
Kidneys.—They are both of the same size and general appearance 
Together they weigh 400 grams. The capsule strips off readily; the Certain Forms of Infection in Typhoid Fever. 
365 
general surface is pale. Imbedded in the kidney substance, just 
beneath the capsule, numerous greyish foci which can be seen to be 
composed of light-colored points closely crowded together occur. In 
addition to these larger single ones are scattered through the cortex. 
On section the larger collections present somewhat the appearance 
of infarctions extending into the pyramids. The centres of these 
are of a greyish color, the periphery being surrounded by a zone of 
hypersemia. The cortex of the kidneys is pale, the markings obscure, 
the regions of the convoluted tubules appearing more opaque than 
other parts. 
Larynx.—The tissues of the epiglottis are infiltrated with serum 
and present a gelatinous appearance. 
Heart.—Weight, 276 grams. All the valves normal. The myo- 
cardium pale and easily torn. 
Lungs.—ln the posterior portion of the lower lobe of the right 
lung several broncho-pneumonic areas are present, surrounded by 
oedema. In the left lung there are fewer such foci. 
Uterus.—Enlarged. It extends 7 cm. above the symphisis pubis 
and contains a foetus and foetal structures. The foetus apparently is of 
the 6th month. It measures 32 cm. in length. No malformation in 
it was observed. The subcutaneous tissues contain much fluid, and 
they are pale in color. The serous cavities are filled with clear fluid. 
The brain substance of the foetus is softened, and into the left cerebral 
hemisphere a haemorrhage has taken place which has much lacerated 
its substance and extended into the lateral ventricle on that side. 
The other organs present no noticeable abnormal appearance. They 
are, however, very soft and oedematous. 
Frozen sections.—Sections from the liver, kidney and heart muscle 
of the mother showed them to be quite fatty. In addition, in the liver, 
there were many typical “ lymphomatous ” nodules. The fat in the 
kidney was situated in the epithelium of the convoluted tubules, but 
was not present in very large quantity. The secreting cells generally 
presented a swollen and coarsely granular appearance. The heart on 
the other hand was very fatty, the fat being distributed diffusely 
throughout the myocardium. 
Bacteriological examination.—This examination consisted in the 
study of cover-slips and the preparation of Esmarck roll-cultures 
from all the organs. In addition, in the case of the kidneys, the Simon Flexner. 
lesions there were studied in sections of the alcohol-hardened tissues 
as will appear. Furthermore a set of Esmarck roll-cultures (in agar- 
agar) was made from all the organs and the meconium of the foetus with 
the uniform result of finding them completely sterile. Only the results 
of the bacteriological study will be given here, it being understood 
that the same methods for the differentiation were used as in the 
previous case. 
Heart’s blood and spleen, no growth. 
Mesenteric and csecal lymph glands, liver, bile and kidney, pure 
cultures of the bacillus of typhoid fever. 
Lung (broncho-pneumonic area), pure culture of a streptococcus 
growing in conglomerate masses without clouding the bouillon. 
Pus in axillary gland, pure culture of the staphylococcus cereus 
flavus. 
In the case of the kidney two roll tubes (agar-agar) were made, 
one from the kidney substance and the other from the greyish-white 
nodules. In both cases the same organism were obtained, which were 
shown to be the bacillus typhoideus. 
Histological Examination of the Kidneys.—The small foci de- 
scribed are found to be caused by a purulent infiltration of the tissues. 
The pus cells are present in the interstitial tissue and within the 
tubules. They are absent from the capsular spaces of glomeruli, 
even when the surrounding tissue is intensely infiltrated with them 
and they extend into the pyramidal part of the organ. The tubules 
in the infiltrated areas show necrosis of their epithelia which at times 
form consolidated masses within their lumina, the adjacent tubules 
presenting a hyaline degeneration of their lining cells. The affected 
cells are filled with hyaline droplets of various sizes which stain with 
Weigert’s fibrin stain. Fibrin filaments are by this method shown 
to exist in some of the tubules and to be intimately associated with 
the necrotic cells. The suppuration seems to differ from ordinary 
suppuration by the less extent of necrosis and the greater amount of 
hyaline degenerative changes, the tissues, at the same time, not tend- 
ing to soften and break down. Typhoid bacilli * in considerable 
* In addition to the method given for the demonstration of typhoid bacilli in tis- 
sues the following has been employed with excellent results. With it groups of 
typhoid bacilli, as small as 3 or 4 may be clearly shown among the pus cells, and 
the fact of their occurrence within pus cells was in this case established. Stain for Certain Forms of Infection in Typhoid Fever. 
367 
numbers are found among the pus cells in the tubules. Other micro- 
organisms could not be demonstrated. 
Case IV.—Typhoid fever with perforation of the intestine; acute peri- 
tonitis with bacterial polywfection. 
Clinical History.—Matthias G., set. 26, white; admitted to the 
medical wards (Dr. Osier) August 28, 1891, complaining of headache 
accompanied by chilly sensations and fever. His present illness be- 
gan eight days ago. 
The patient (German) has been in this country for 9 months; his 
occupation is that of a carpenter. His father died at 53 probably of 
pneumonia; mother living. He has two brothers and three sisters 
living—none dead. He does not know of having had any sickness 
as a child. 
On admission it is noted that he was of large build, that his face 
was flushed, the tongue thinly furred, the skin dry and hot. Thorax 
well-formed; clear on percussion and auscultation. Heart sounds 
clear. Abdomen shows a diffuse erythematous eruption which extends 
upwards to the lower portion of the chest. A few bright red papules 
also present which fade on pressure. General tenderness is present 
over the abdomen, growing more acute in the left iliac fossa. Spleen 
not palpable. Temperature ranges from 99 to 102.5° F., pulse 88, 
respiration 24. Blood examination negative. 
August 30th.—The spleen is palpable to-day ; the urine is of a 
dark amber color, fairly clear, of acid reaction, does not contain albu- 
men or sugar, and does not give the diazo-reaction. The sediment 
contains granular casts. 
September 2nd.—The temperature has not ranged above 103° F.; 
the pulse has varied from 90 to 108; respiration 20-24. Fluid clear, 
abdomen not distended. A few rose-spots over abdomen. Heart and 
lungs clear. 
September sth.—The spleen is palpable below the ribs; the range 
of temperature between 99 and 103° F., pulse from 99 to 102. 
10 minutes in Stirling’s Gentian-violet (Gentian-violet sgrms., Alcohol 10 cc., Ani- 
line Oil 2 cc., water 88 cc.; filter), place in 1:1000 acetic acid solution for some 
minutes, dehydrate quickly in 96 per cent, alcohol, transfer to the slide, blot, add 
011 of cloves to clear and differentiate. Change the oil several times until the de- 
sired differentiation is obtained. 368 
Simon Flexner. 
September 9th.—Yesterday at 4 p. in. the temperature rose to 
104.6° F.; the falls are marked after the bath. Patient was deliri- 
ous and restless last night. The pulse, in the last twenty-four hours, 
has been much more rapid; this morning the temperature is 98.2° F., 
the pulse 118, the respiration 32. At present the patient lies on his 
back with knees drawn up, his eyes are bright, and pupils dilated. 
He is delirious and restless. The abdomen is uniformly distended, 
rather tense and tympanitic. The skin is dry and harsh. Urine 
turbid, alkaline, pale-yellow in color, gives a faint diazo-reaction, 
contains many hyaline and granular casts, urates and phosphate 
crystals. 
September 10th.—During the afternoon, yesterday, the pulse 
became much more rapid (142) and dicrotic. The patient lies in a 
state of muttering delirium. The urine contains albumen and many 
casts and red blood corpuscles. The sp. gr. is 1022. The tempera- 
ture has ranged between 104.2° F. at 8 last night to 95° F. at 6 this 
morning. The abdomen is considerably distended, very tense and 
tympanitic ; on pressure the patient flinches. 
Death at 6.20 a. m. September 11th. 
Autopsy five hours post-mortem. 
Anatomical Diagnosis.—Typhoid fever, with clean and deep ulcer- 
ation; perforation ; fibrino-purulent peritonitis. Acute splenic tumor ; 
swelling and softening of mesenteric glands; ulceration of epiglottis; 
lung emphysema and congestion (hypostatic). Polyinfection with bacteria. 
Body 164 cm. long, strongly built and well nourished. At differ- 
ent points on the body congested areas are apparent and a few darker 
and smaller injected points. The abdomen is distended, the blood 
vessels of the neck turgid and contain with fluid blood. Muscles well 
developed and deep red in color. 
Peritoneal cavity.—On incision there is a free escape of gas. The 
upper portion of the small intestine is greatly distended. The blood 
vessels of the serosa over the whole peritoneum are injected; the 
serosa itself is cloudy, and coagula of fibrin, loosely adherent, are 
scattered over it. In the dependent parts of the cavity about 200 cc. 
of turbid, yellow fluid are contained. A perforation 2 mm. in diameter 
is found, located in a loop of intestine, situated in the left iliac fossa. Certain Forms of Infection in Typhoid Fever. 
369 
Intestines.—The large intestine is firmly contracted; its mucous 
membrane is pale, and it contains tolerably firm, yellow faecal masses. 
The vermiform appendix is somewhat dilated, and in the swollen 
mucous membrane several superficial small ulcerations are apparent. 
The largest number of losses of substance is found in the ileum ; the 
most advanced ones are situated at the ileo-ceecal valve. The mucosa 
of the valve itself is ulcerated. The ulcers are surrounded by swollen 
edges which are undermined, and in their clean bases the circular 
muscular tunic is visible. A small quantity of necrotic material is 
found still adherent to a very few of the ulcers. Between the ulcers 
are swollen solitary and agminated follicles. Situated 22 cm. from 
the valve there is an ulcer 2 cm. in diameter, the clean base of which 
is formed by the circular muscular coat, whose edges are necrotic and 
in the centre of which there is a perforation 2 mm. in diameter. The 
first losses of substance are found in the upper part of the jejunum. 
The stomach contains dark-brown contents. Its mucous membrane 
is apparently normal. 
Mesenteric glands.—Enlarged, congested and softened. 
Spleen.—Bound to diaphragm by old adhesions, which cannot be 
broken down without lacerating the organ. It weighs 510 grams; 
the capsule is covered in part with fibrinous coagula; the consistence 
is moderately firm. On section it presents a dark brown color, and 
the Malpighian bodies are prominent. 
Liver.—Capsule covered with fibrinous masses; otherwise it is 
smooth. On section it is pale, the lobules fairly distinct; no increase 
in fibrous tissue. Weight 1870 grams. 
Kidneys.—Both of approximately the same size and general appear- 
ance. Together they weigh 510 grams. The surface is smooth; the 
capsules stripping otf readily, and the stellate veins are injected. On 
section the striae are visible; the glomeruli are easily seen; the cortex 
generally is pale and varies in thickness from 5 to 7 mm. 
Adrenal glands and pancreas apparently normal. 
Heart.—No valvular lesion; coronary arteries smooth ; myocar- 
dium pale and soft. Weight 240 grams. 
Lungs.—Free from adhesions; a small amount of fluid in each 
pleural cavity; the posterior borders of the lower lobes are intensely 
congested. The upper lobes are moderately emphysematous. The 
bronchi are intensely congested. 370 
Simon Flexner. 
This case derives especial interest from the bacteriological exami- 
nation. It illustrates to what extent a mixed infection with bacteria 
may occur in human beings. Of course the infection atrium was 
the intestine, the perforation found there opening the way for the 
escape into the peritoneal cavity of a considerable variety of micro- 
organisms which happened to be present in its lumen. Soon the 
several kinds, although perhaps not equally, made their way into 
other parts and organs, and this very difference between those bac- 
teria present in the peritoneum and those found elsewhere in the 
body is not without its instructive side. I cannot help holding up 
as an example the present case in comparison with the first two of 
our series in support of the fact that the conditions which enable the 
typhoid bacillus to flourish, if not to exist at all in the blood, must 
be very peculiar. As will be seen shortly in this case the typhoid 
bacillus found its way with other bacteria into the peritoneal cavity, 
and there seems to be no reason why it should not have been spread 
with the same facility through the body as its associates; and yet its 
distribution at autopsy was by no means so universal as some of the 
other forms. 
The close association of the typhoid bacillus and the colon bacillus 
in this case will be remarked. With respect to the means used to 
separate them I would again refer to the remarks on this subject in 
the first case. In the course of the study of this case it was necessary 
to make many plate, roll and other cultures, and to keep the organisms 
under observation for considerable periods of time; and yet after cer- 
tain colonies, existing side by side perhaps, in the original plates, had 
been isolated, and through their properties determined to be colon or 
typhoid, no transition of one to the other could be detected in the 
subsequent study of these forms. 
The method pursued in the isolation of the several bacterial species 
was the use of various media and plate and roll cultures. Many 
hundred colonies were examined microscopically and grown upon all 
sorts of culture media with the result of separating the following 
forms from the different situations mentioned. 
a. Bacilli, varying in length, short forms 2 to 3 times as long as 
broad; larger forms several times as long as broad. Colony growth 
upon agar-agar and gelatine resembles colonies of typhoid bacilli. 
They do not coagulate milk after several weeks; on potato the growth Certain Forms of Infection in Typhoid Fever. 
371 
is either invisible or slight, moist, showing little tendency to spread, 
and of yellowish-brown color. Drop cultures 24 hours old show 
active motility. No indol production. Does not ferment sugar. 
Bacillus typhoideus. 
h. Bacilli, a little coarser than the preceding, all or nearly all are of 
the short form. Colony growth on agar more opaque than last; on gel- 
atine it forms thin filmy surface colonies which show a blue translu- 
cence. Visible luxuriant growth upon potato of brownish-yellow 
color. Drop cultures 24 hours show no perceptible motility. Pro- 
duces indol; ferments sugar. Bacillus coli communis. 
c. Cocci, growing readily on all the culture-media, in the form of 
grape-like clusters. On potato an abundant yellow growth ; in gela- 
tine stick culture rapid liquefaction. Staphylococcus pyogenes aureus. 
d. Minute white colonies showing no tendency to spread, but a 
little larger when on the surface than in the depth of the culture 
media; cover-slips show them to be composed of chains o cocci. 
Streptococcus pyogenes. 
e. Bacilli, variable in length, motile, rapidly coagulate milk, 
quickly liquefy gelatine; colonies spreading (migrating). Proteus 
vulgaris. 
These organisms were distributed in the following manner : 
Peritoneal cavity.—Bacilli typhi abdominale, coli communis, pro- 
teus vulgaris. Staphylococcus aureus; streptococcus. 
Mesenteric glands.—Pure culture of the typhoid bacillus. 
Iliac lymph glands.—Typhoid and colon bacilli. 
Retro-peritoneal lymph glands.—Typhoid and colon bacilli. 
Spleen.—Pure culture of the typhoid bacillus. 
Liver.—Typhoid bacillus and streptococcus. 
Bile.—Pure culture of the typhoid bacillus. 
Kidneys.—Bacillus coli communis and streptococcus. 
Lungs.—Pure culture of the bacillus coli communis. 
Blood.—Taken from the azygos vein. Bacillus coli communis and 
streptococcus. 
Thoracic duct.—Bacillus coli communis and streptococcus. 
Ulcer of intestine.—Bacillus typhoideus; bacillus coli communis; 
bacillus proteus vulgaris, and streptococcus. The colon colonies pre- 
dominated. 372 
Simon Flexner. 
Case Y.—Typhoid fever ivith perforation [3rd week of disease); acute 
peritonitis; general streptococcus infection. Absence of typhoid 
bacilli from the cultures. 
This case is included as illustrating the importance of the secondary 
micro-organisms in typhoid fever, even after the disappearance from 
the body of the typhoid bacilli. Although the disease was yet at its 
height, the evidence of the cultures in this case is to the effect that the 
typhoid organisms themselves had either entirely disappeared or were 
so few in number that they were not transplanted with the tissue 
juices to the culture media. 
Henry R., set. 35, white, admitted to the medical wards (Dr. Osier) 
November Ist, 1892, complaining of chilly sensations and fever. 
The patient’s father is living and well; the mother died of pneu- 
monia (?). One brother and one sister living ; none dead. 
He had measles when a child, but since that time he claims to have 
been healthy up to the present illness. 
The present illness began about one week ago with pain in the back 
of the neck, stiffness of knees and a sense of fatigue. Four days ago 
he felt giddy and generally badly. No cough or expectoration. For 
the past five days he had been in bed constantly. Examination of the 
blood showed no malarial organisms. 
November 2nd.—Temperature 104°, pulse 120, respiration 32. 
Yesterday afternoon the skin was flushed, hot and dry, and over the 
trunk a well-marked, but faint roseola could be seen. Spleen palpa- 
ble; tongue dry and coated. This morning the pulse is 112, and 
slightly dicrotic. Thorax clear throughout. Heart.—Point of maxi- 
mal impulse not to be distinctly localized; cardiac flatness entirely 
obliterated by pulmonary resonance. Sounds are heard loudest in 
about normal position in sth space, and appear of normal relative 
intensity. Liver border not palpable; abdomen not distended. 
There is slight tenderness in the ileo-csecal region; some gurgling; 
no distinct rose-spots; urine brownish-yellow, clear, acid, specific 
gravity 1026, distinct trace of albumen, diazo-reaction present, epi- 
thelial cells, leucocytes and granular casts seen; no sugar. Blood.— 
Leucocytes 8,500. 
November Bth.—The temperature between the 4th and Bth ranged 
between 100.6° F. and 104.2° F. Last night, during the bath, the Certain Forms of Infection in Typhoid Fever. 
373 
patient had an involuntary movement and the pulse became very 
weak. Since midnight the temperature has not been below 103.6° 
F. This morning the patient is rational, but the pulse is rapid ; at 
the time of the visit, it was 144. Tension and volume not bad. The 
abdomen is not especially distended, but it is held very tense, and is 
generally tender. A number of typical rose-spots are present. Later 
note. For the past 18 hours the temperature has reached 104° F. 
The patient is less bright than he was, but there is no delirium. 
Pulse 130, tension low. The abdomen is much distended, especially 
in the epigastric region, which is very prominent. The patient sank 
during the evening and died at midnight. Note by Dr. Osier: 
“When I saw the man at 12 o’clock, noon, there were no marked 
symptoms of collapse. The pulse was rapid, but not small; face not 
pinched or anxious, and he answered questions readily. There was 
no pain in the lower abdomen. The tympany was higher than I have 
ever seen.” 
Autopsy 10 hours post mortem. 
Anatomical Diagnosis.—Typhoid fever (early and late ulcers) 
and swelling of follicles; perforation; fibrino-purulentperitonitis ; acute 
splenic tumor ; parenchymatous degeneration of viscera. General in- 
fection ivith streptococci. 
Body 160 cm. long; well-nourished; subcutaneous fat in moder- 
ate amount; muscles deep brownish-red in color. 
Peritoneal cavity.—On incising this cavity there is an escape of 
foul smelling gas. The surface of the intestines are much injected. 
In the cavity there are about 1000 cc. of turbid fluid. Covering the 
loops of the intestine occupying the right iliac region are flakes of fibrin. 
A small perforation occurs in one of the loops of intestine in this sit- 
uation from which a yellowish semi-solid faecal mass protrudes into 
the peritoneal cavity. The diaphragm on the right side is at the 3d 
intercostal space ; on the left side at the 4th rib. 
Intestines.—Beginning with the ileum, the patches of Peyer are 
swollen. At a distance of 80 cm. above the valve an ulcer measuring 
5x2 mm. is situated which passes through all the coats of the intes- 
tine in its midportion, the perforation being 1-5 mm. in diameter. 
The edges of this ulcer are undermined and its base quite clean. 
From this point downwards the solitary follicles are all swollen, and 374 
Simon Flexner. 
in the centres of some of these small losses of substance have occurred. 
The ulcers are very few in number until the valve is reached; here 
they are quite numerous, larger and extend to the circular muscular 
coat. Some of these have undermined edges, and while in some the 
slough has been completely removed, to others dirty necrotic material 
still adheres. Neither the vermiform appendix nor the large intes- 
tine contains any ulcers. 
Mesenteric and retro-peritoneal glands swollen and congested. 
Spleen.—Enlarged ; it weighs 750 grams; its capsule is wrinkled, 
and on section it is soft, of a brownish-red color, the pulp is abundant, 
and the Malpighian bodies are easily visible. 
Liver.—Weighs 2400 grams. The surface is smooth, except over 
the right lobe, where there are several depressed spots which on sec- 
tion present a dark haemorrhagic appearance. On section it is opaque, 
of a yellowish color; the lobules are invisible. 
Kidneys.—Together they weigh 450 grams. Surface smooth and 
pale; stellate veins prominent. On section striae obscure, cortex pale, its 
average thickness being 8 mm.; the glomeruli are visible and red in color. 
Heart.—Weight 300 grams. All the valves normal; myocardium 
of a brownish-red color and firm consistence. 
Lungs.—Free from adhesions, except a few light ones over the 
right lobe. On section they are moderately congested and cedematous. 
Mucous membrane of bronchi congested. 
The pancreas, adrenal glands, stomach, testicles and bladder 
apparently are normal. 
Frozen sections.—Kidneys.—No increase of the connective tissue. 
The epithelium of the convoluted tubules is swollen and granular, 
and a few of these tubules are quite fatty. A very small amount of 
fine fat can be made out in the glomeruli. 
Liver.—The liver cells are swollen and granular; the Kuppfer’s 
cells are fatty. No connective tissue increase. Many so-called 
“lymphomata” are present. These latter very in size and appear- 
ance. The larger show, in addition to the necrotic cells, much detri- 
tus; the smaller show only hyaline liver cells. Surrounding these 
foci the liver cells are very fatty. 
Bacteriological examination.—Cover-slips from the peritoneum 
show many streptococcus chains which were usually short, and bacilli 
of apparently only one species. Cover-slips from the spleen negative. Certain Forms of Infection in Typhoid Fever. 
375 
Cultures.—Agar-agar Esmarck rolls were made from the fluids 
and viscera. 
Peritoneum.—Colonies of the streptococcus and the bacillus coli 
communis. 
Retro-peritoneal lymph glands.—Streptococcus colonies. 
Spleen.—Two streptococcus colonies only. 
Bile.—One colony of the streptococcus. 
Kidneys.—Streptococcus and bacillus coli communis. Former pre- 
dominate. 
Lungs.—Many colonies each of streptococcus and bacillus coli 
communis. 
Heart’s blood.—The roll is thickly studded with streptococcus 
colonies. No other kind of micro-organism present. 
There can, we think, be little doubt but that the perforation of the 
intestine, the peritonitis and subsequent death were in this case directly 
attributable to secondary infectious agents, especially with the strepto- 
coccus pyogenes. 
Case VI.—Typhoid fever; death from haemorrhage (sixth week of 
the disease). Disappearance of the typhoid bacilli. Infection 
with bacillus coli commune. 
Wallace H., colored, aged 23, admitted to the medical wards (Dr. 
Osier) July Ist, 1895, complaining of pain in the head, stomach and 
shoulders. 
The patient states that his father died of dropsy. His mother is 
living and well; the same is true of four brothers and four sisters, 
with the exception of one brother, who has rheumatism. Two broth- 
ers died in infancy. 
He states that as a child he had measles, mumps, whooping-cough, 
chicken-pox, but has not been ill since that time. 
His present illness dates two weeks prior to his entrance, and was 
ushered in with a violent headache over the frontal and occipital re- 
gions. Soon afterwards he complained of pain in his stomach, which 
has continued up to the present time. He has vomited several times. 
About one week ago he had profuse epistaxis. For ten or twelve 
days he has had diarrhoea. 
July Ist.—The patient is found to be a large, well-made, well- 
nourished man. Dorsal decubitus is present. The skin is dry and 376 
Simon Flexner. 
smooth; eyes dull; color of mucous membranes good. The tongue is 
coated. There is marked abdominal tenderness on pressure, particu- 
larly in the lower parts. The spleen is palpable. The thorax is clear. 
The heart’s impulse is seen at the fifth space in the nipple line. On 
auscultation the first sound is replaced by a rumbling, soft systolic 
murmur, which is transmitted to the axilla. The second sound is 
clear and loud. The second pulmonic is accentuated; the second 
aortic fairly loud and clear. 
July 2nd.—Pulse is 22 to the quarter, markedly dicrotic. On the 
back of the arms there are a number of slightly raised papules. 
Respiration is clear; the splenic flatness is practically obliterated by 
abdominal tympany. 
July 4th.—The splenic flatness is increased, beginning at the 
eighth rib and extending to the eleventh costal margin. The border 
is not palpable. Patient appears drowsy. 
July 11th.—Temperature is still elevated, but falls after baths. 
General condition appears somewhat better. 
July 17th.—The stool to-day was semi-fluid, of a bright yellow 
color, containing a small quantity of bloody mucus and a few milk 
curds. 
July 22nd.—Since the last note the condition of the patient has 
remained about the same. The temperature on the 18th and 19th 
ranged a little lower, the registered pulse having been for three days 
below 100. At about 7.40 a. m. on the 23rd the patient had a stool 
of bright, fresh blood, appearing to be about a quart in quantity. 
Fifteen minutes later he had another stool of about one pint of clots; 
fifteen minutes after this a third stool of a pinkish fluid character. 
The temperature at 8 a. m. was 98.2°. Almost immediately after the 
haemorrhage the patient became almost pulseless, and rapidly sank in 
spite of all stimulation, dying about 8.30. 
Autopsy five and a half hours post-mortem. 
Anatomical, Diagnosis.—Typhoid fever (ileo-typhus and colo- 
typhus); death from haemorrhage ; acute splenic tumor ; parenchymatous 
degeneration of the organs. 
Body of a well nourished man, 169 cm. long; rigor mortis in the 
extremities; the surface and mucous membranes very pale; muscle 
dark red in color. Certain Forms of Infection in Typhoid Fever. 
377 
Peritoneal cavity contains a small amount of clear fluid. The 
mesenteric and retro-peritoneal glands are swollen and slightly con- 
gested. 
Intestines.—Beginning 280 cm. above the valve there is a series of 
ulcers, the first being discrete and superficial, the lower ones larger, 
confluent, deeper, in many instances exposing the muscular coat of the 
intestine. Just above the valve there is a large mass of ulcerations 
involving nearly the whole of the intestine at this part. For the 
most part the ulcers are clean; a few of the superficial ones still con- 
tain the remains of the necrotic mucous membrane. The colon and 
rectum show superficial ulcerations similar to those found in the small 
intestine. These are quite numerous. The large intestine contains in 
its lumen a considerable amount of fluid blood. The eroded blood 
vessel was not found. 
The spleen weighs 350 grams ; the capsule is smooth ; consistence 
is soft; on section it is dark red in color, and almost diffluent. The 
Malpighian bodies are very indistinct. 
The liver weighs 2130 grams; the surface is smooth; on section 
the organ is homogeneous, of a yellowish color; the lobules being 
very indistinct. 
The kidneys are the same in size and general appearance, and 
together they weight 320 grams. The surface is pale; on section 
the cortex is pale, swollen, averaging 9 mm. in thickness; the striae 
are indistinct, and the glomeruli are pale. The other organs present 
no especially remarkable condition. 
Cultures were made from the heart’s blood, and the various organs 
upon agar-agar. The plates from the liver, kidneys, bile and blood 
remained sterile. Those from the lungs and spleen contained numer- 
ous greyish-white colonies which were composed of short, plump 
bacilli, giving all of the reactions distinctive of the bacillus coli com- 
munis. Numerous attempts to isolate the typhoid bacillus, involving 
the examination and study of a large number of colonies from these 
plates, were entirely unsuccessful. 
It is not an uncommon observation in cases of typhoid fever which 
have terminated fatally, late in the course of the disease, at a time 
when the ulcers in the intestine have become entirely, or for the most 
part cleai|/dnd healing has already begun, to find that the typhoid 378 
Simon Flexner. 
bacillus refuses to be cultivated from the tissues including the peri- 
toneal lymphatic glands. The bacteriology of these cases may lead 
to some confusion concerning the fixity of the typhoid species of 
organism if it should so happen that in place of the typhoid bacillus 
forms with the properties of the bacillus coli communis are met with, 
unless it be borne in mind that the colon group of organisms finds 
the lesions existing in the intestinal wall very favorable for their 
emigration. At least the cultivation from these cases of colon bacilli 
should never awaken the suspicion that the two species are trans- 
mutable. For we now know, thanks to the observations upon the 
bacillus coli communis by Dr. Welch, that lesions of far less severity 
than are present in these cases suffice for their escape from the intes- 
tinal canal and their dissemination throughout the body. The present 
case is cited as an example in which, after the entire disappearance of 
the typhoid bacilli from the body, so far as failure to demonstrate 
them in cultures can be taken to exclude their presence, the colon 
bacilli were found in the tissues at autopsy.