NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
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encapsuled bacilli were seen in leucocytes. In the capillaries of the brain some of
the endothelium cells were packed with this organism. Some of these post-mortem
appearances would appear to have been due to a secondary bacterial infection.
AUTOPSY 6.—Man aged about 45. Cause of death, large meningeal
hæmorrhage.
Spleen large, firm, dark red, and not pigmented.
Liver large, pale and mottled. The lobules shewed the changes described
in case 4.
Small intestine. —Normal.
Large intestine. —Numerous small ulcers extending to the muscular coats
were scattered over the whole length of the gut. There were several raised
plaques formed by papillomatous-like outgrowths. On microscopical examination
the projecting mass was seen to be granulation tissue, and the crypts of Lieber-
kuhn in the neighbourhood were infiltrated with new tissue and in process of
destruction.
Brain.—Under the dura mater of the left hemisphere there was a large clot
covering the greater part of the cortex and occupying the space at the base of the
brain. There was no fracture and no extravasation of blood outside the dura
mater nor in the tissues of the scalp. There was no blood in the ventricles. The
brain substance appeared normal.
The larger arteries were free from atheroma.
The heart, lungs, pancreas and kidneys appeared normal.
The skin. —There were no skin lesions.
The distribution of the parasite. —Bodies were present in large numbers in
the spleen, liver and bone-marrow. They were not detected in an inguinal
lymphatic gland nor in the skin. The distribution of the bodies in the other organs
has not yet been worked out.
AUTOPSY 7.—Girl aged about 16. In hospital for large sloughing ulcer of
the foot. Cause of death— noma of the vulva.
Spleen large, firm, dark, and not pigmented.
Liver large, pale and mottled. Lobular changes as in case 4, very marked.
Small intestine. —Normal.
Large intestine. —There were many depressed and pigmented areas
scattered over the whole of the mucous membrane of the large bowel. Except
that the ulcers had healed, the condition was very similar to that found in
autopsy 6.
Skin.—On the inner side of the left heel was an ulcer about the size of a
rupee. On the dorsum of the right foot was an ulcer the size of the palm of the
hand, exposing the deep tissues and bones. The vulva was in a sloughy and
very foul condition.
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Distribution of the parasite. —Bodies were very abundant in the liver and
spleen. The bone-marrow was not examined. In both ulcers single bodies were
seen lying in the organised granulation tissue in the bases and also in the healthy
tissues beyond. Large cells crowded with the bodies were seen here and there
in the small vessels in the neighbourhood of the ulcers.
GENERAL POST-MORTEM APPEARANCES.—It will be seen from the seven
autopsies now described that there are certain constant pathological appearances
associated with infection by the new parasite. We may summarise these as
follows.
The post-mortem appearances of the liver and spleen are in themselves
almost pathognomonic. The spleen has a peculiar smooth, firm and solid look,
and it retains its shape after removal from the body like an organ hardened in
situ. The substance is dark red, granular and homogeneous. The trabeculæ
shew up clearly against the dark pulp. The consistence is firm but friable and
the sensation given to the finger is quite different to that given by a tough fibroid
spleen. The liver retains its shape after removal. The liver substance is firm but
friable. The surface is mottled, suggesting the nutmeg liver of passive engorge-
ment, but the general colour is lighter instead of darker than normal. On section,
the mottled look is seen to be due to a white tissue which occupies the centre of
the lobules and gives rise to an arborescent appearance. Microscopical examina-
tion shews that the white tissue is a new deposit formed of macrophages and their
contained bodies, which have practically replaced the liver tissue of the centre of
the lobule.
The large intestine shews, almost constantly, extensive multiple ulcers which
are deep and sloughy and tend to perforate the muscular coats. The occurrence
of fungating granulation tissue which has a papillomatous appearance is seen in
association with the ulcers.
Purulent peritonitis and bronchopneumonia are frequent, arising, respectively,
from the perforation of intestinal ulcers and as a sequel to cancrum oris.
Septic conditions associated with the formation of infarcts in the organs are
sometimes superadded.
The small intestine rarely shews any lesions. The heart, kidneys, brain,
gall-bladder, urinary bladder, pancreas, suprarenals, testicles, lymphatic glands and
muscles shew, as a rule, no macroscopic changes.
The parasites are found constantly in immense numbers in the cells of the
liver, spleen and bone-marrow, in granulation tissue in the intestine and in the skin.
They were present in large numbers in a lymphatic gland draining an area in
which a skin lesion was present, but not in glands where no such condition existed.
Bodies are, in some cases at least, fairly numerous in patches in the testicle.
In the kidneys they do not appear to be numerous. They are present in some
CASE 1.— Advanced case of the disease. Spleen reaching to umbilicus. Papules and small ulcers. Diarrhœa.
CASE 2.—Well developed disease. Spleen well below the costal margin.
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cases in the lungs. In the blood of the large veins they appear to be fairly
numerous included in various types of cells.
The Clinical and Pathological nature of the disease.
In the first report I drew attention to certain very constant clinical features
in cases of systemic infection by the parasite. These were—
(1) A great enlargement of the spleen.
(2)Emaciation.
(3)An irregular high temperature.
(4)Abdominal symptoms.
I have since been able to add the following which appear to be equally charac-
teristic.
(5)A tendency to noma and local gangrenes.
(6)The frequent presence of a papular eruption and small or large ulcers
of the skin.
(7)The occurrence of hæmorrhages.
Enlarged spleen.—Enlargement of this organ has been very constant. In
Madras, bodies are almost always found on puncture in spleens which are so
enlarged as to project several inches below the costal margin. On the other
hand, in a few cases the spleen has been only moderately enlarged. In two cases
there was a high temperature and severe constitutional disturbance associated
with considerable enlargement of the spleen. Bodies were found, but were
extremely scanty in both cases.
Emaciation.—Although emaciation is generally present, it is not invariably
so, and death may occur from several causes connected with the disease without
wasting being a prominent sign.
Temperature.—An irregular temperature has been noted as a feature of the
disease. This is almost always present in the final stages. But even when
splenic enlargement is considerable and emaciation marked, a high temperature
may be absent, or slight rises only above the normal may occur. The most
frequent type of temperature is that shewing irregular rises to 102° or 103° F.; at
times a temperature of 104º or even 105° is reached. The two charts which
accompany this report, for which I am indebted to Major Robertson, I.M.S.,
are typical of the disease as most frequently seen. There appears to be an
acute form of the disease. In two cases in which the spleen reached half way to
the umbilicus there was high fever which afterwards fell to normal as in enteric
fever. In both cases it was very noticeable that the bodies were present in
very small numbers in blood drawn from the spleen. Major Robertson, I.M.S.,
informs me that such cases are frequently readmitted to hospital with similar
attacks.
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Abdominal symptoms. —The constancy with which abdominal symptoms
supervene has been already commented upon. These were shewn in the first
report to depend upon the formation of extensive ulcers in the large gut. Of the
seven autopsies, in five there was ulceration of the large intestine, and in one
gangrene of the cæcum. In one case only was the mucous membrane of the large
intestine normal. The dangerous nature of intestinal conditions is well shewn in
the autopsies recorded, where three out of seven deaths were directly due to
perforation of the gut. Healing of the ulcers appears to take place, since in
one case, only numerous pigmented and depressed scars were present.
In the first report it was shown that the above lesions were associated with
the presence of the parasites, often in very large numbers. In autopsy 6, single
bodies were found scattered through the organised granulation tissue, and in the
young tissue about the crypts, large cells were found as in autopsy 3. Bodies
which appeared to be multiple division forms appeared more common in the
granulation tissue from the intestine of case 3 than in the spleen, but the rapid
changes in the tissues of the intestine leading to fragmentation of the nuclei
render it difficult to be sure of such forms.
The amœba coli is by no means uncommon and is found in the granulation
tissue in the intestines and in the walls of abcesses in the liver. How far the
intestinal condition is due to the presence of this organism it is impossible at
present to say. Amœbæ were found in cases 2, 3 and 5. Small amœbæ with a
single chromatin mass were seen in the intestine as well as large forms in which
the chromatin mass has undergone division. In the liver abscesses large circular
forms were seen. The intestinal forms were identical with those seen in a typical
case of severe dysentery in a European. I have not been able after long search
to find any forms transitional between the amœba and the parasites under discus-
sion. In two deaths from typical dysentery in which the amœba coli was present,
the new parasite was not found in the spleen.
The occurrence of noma and local gangrenes. —Of the seven cases recorded,
two died of cancrum oris, one of noma of the vulva, and one of gangrene of the
cæcum. In two of these cases emaciation was not present and the body
appeared well nourished. In one case there was, in addition to the noma, a large-
ulcer of phagedenic type which had exposed the bones of the foot.
Noma undoubtedly plays a most important part in bringing about death
from this disease. Noma and perforation of the large intestine would appear
indeed from our cases to be the chief causes of death in infection by the
parasite.
Skin eruption and the occurrence of ulcers: Ulcers. —Shortly after the
discovery by Wright of the bodies in tropical ulcer, Major Donovan, 6
reported the
presence of the parasite in small ulcers which are often found about the knees
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and elbows of cases of the disease. I have examined scrapings and small pieces
of tissue snipped from such ulcers in three advanced cases of the disease and have
found bodies in small numbers in each case. The ulcers usually seen are small,
from 2 to 10 m.m. in diameter. They are covered with a thick raised scab and
the base of the ulcer is usually depressed and devoid of granulations. The edges
are usually thickened. The origin of the ulcers is doubtful. I have always failed
to detect sarcoptes in them and they appear to arise from ulceration of a papular
eruption which is generally found along with them.
In some cases larger ulcers are seen about the legs. They vary from the
size of a shilling to extensive raw surfaces several inches in diameter. In autopsy
7, ulcers of this nature in section shewed scattered bodies throughout the
tissues of their bases, and in the healthy skin in the immediate neighbourhood
Very scanty bodies were also seen in snippings taken from such ulcers in a similar
case (Pl. II, fig. 12).
In the granulation tissue surrounding the caseous mass in the dermis of
case 5, bodies were present in considerable numbers, and large numbers of bodies
were found in sections of a femoral gland above this lesion.
I have examined a number of large and small ulcers in the out-patient depart-
ment, but so far have never detected bodies where there was no general infection
with the new parasite.
Papular eruption.—It is common in cases of the disease especially in the
advanced stages to find a scanty or profuse papular eruption about the thighs,
Scarpa's triangle, and the scrotum. Similar papules are less frequently seen on
the trunk, arms and neck. Some of these appear to ulcerate and form small
ulcers covered with a raised scab, which are evidently slow to heal and chronic
in nature. An unulcerated papule from a case shewed, in section, bodies in small
numbers scattered through the dermis. Since we have been unable to find
bodies in normal skin, it is possible that the eruption is an integral part of the
disease. It appears distinct from the scabies seen on the hands of many of the
cases, and the papule examined shewed a deeper lesion than in this condition.
With regard to the skin lesions in general I am unable to say whether they
are due to the disease or other causes. The lesions have no very marked charac-
ters by which they may be detected or differentiated from those occurring in
natives not suffering from the disease. On the other hand, the presence of the
parasites in them is important.
Hæmorrhages.—Small petechial hæmorrhages are of fairly constant occur-
rence in fatal cases. They are especially frequent in the serous membranes,
peritoneum, pleura and meninges. Larger extravasations of blood in similar posi
-tions and into the mucous membranes appear also to be not infrequent. In one
case death occurred from a large hæmorrhage under the dura mater.
C
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fine capillaries throughout the whole area of the section including the dermis
beneath the unulcerated epidermis. In the vessels above the size of capillaries,
large cells containing from 6 to 12 bodies were occasionally seen.
3. Thin slices of the caseous nodule and the surrounding tissue described in
autopsy 5 were fixed in absolute alcohol, cut in paraffin, and stained with Roma-
nowski's stain. The central caseous mass was seen to consist of necrotic cells of
several varieties, chiefly small lymphoid cells and large mononuclear elements. A
certain number of polymorphonuclear cells were present, but they did not form the
great majority of cells as in ordinary pus. The necrotic area was surrounded by
granulation tissue which extended to a distance of a few millimetres between the
layers of dense fibrous tissue, which surrounded the whole. Bodies were found
readily in the granulation tissue, and wherever an infiltration of healthy tissues
with cells was taking place. As many as ten, and in some cases more, bodies
were to be seen in each field of the microscope. In the young granulation tissue
composed of lymphoid cells and larger mononuclear cells the parasites were seen
in every case lying embedded singly in the latter type of cell. In the capillaries
in the neighbourhood, bodies were seen lying singly, or in twos and threes, in the
endothelium cells. In the smaller vessels in the neighbourhood of the granulation
tissue, large cells containing numerous parasites were seen. These were similar
to the cells seen in the liver and spleen. They were most often attached by one
side to the vessel wall whilst the mass of the cell projected into the lumen of
the vessel (Pl. II. fig. 9). In the somewhat larger vessels they were often much
more free in the lumen. In a sweat gland which had been invaded by the granula-
tion tissue, many cells, each containing several bodies, were seen. These lay in
close connection with the coils of the gland, apparently in fine capillaries
which surrounded the coil. In adipose tissue which had been invaded by granula-
tion tissue, single bodies lying in the endothelium cells of capillaries were readily
seen. In parts of the section remote from the granulation tissue, bodies could not
be found either in the capillaries or larger vessels. In the capillaries of healthy
adipose tissue no bodies were to be made out. In these sections all stages
between unaltered endothelium cells containing a single body, and large cells partially
detached from the vessel wall and containing many bodies, could be made out.
4. Sections of apparently normal skin from the thigh of the same case were
carefully searched, but no bodies were found. In the neighbourhood of the pale
cicatrix-like areas already noted, many large cells loaded with pigment of the
same nature as the epithelial pigment were seen in the tissues and occasionally in
the smaller vessels.
5. Areolar tissue from the skin and subperitoneal tissue were spread upon
slides and stained by the Romanowski method. The tissue elements were well
displayed, but no bodies were seen.
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6. Films from various sized chronic ulcers apart from general infection
have failed to shew parasites. In ulcers encroaching upon the skin, large cells with
single or double nuclei, and exactly resembling the smaller macrophages, are seen
filled with balls of a greenish pigment which appear to be derived from the skin.
LYMPHATIC GLANDS.—A femoral lymphatic gland taken from the right groin
in case 5, cut in paraffin and stained by Romanowski's method shewed, in the lymph
sinuses lying around the cortical masses of lymphoid tissue, many large cells
crowded with the parasitic bodies. Similar cells containing pigment of the same
nature as that seen in sections of the skin were also present in the same position,
and in some cases cells contained both pigment and parasites (Pl. I. fig. 6).
Many of the cells shewed the necrotic changes and central vacuolisation to be
described later (Pl. II. fig. 6). In some cases they appeared to be on the point of
dissolution. Many of the stroma cells of both the cortex and medulla, but especially
the former, contained small groups of the bodies (Pl. I. fig. 5). Sections of a
femoral lymphatic gland from case 6, in which no skin lesion was present, shewed
no bodies.
INTESTINE.—Very thin sections of the intestine in autopsies 3 and 6 shewed
single bodies lying in the organised granulation tissue. In almost every case
they could be demonstrated as lying in what appeared to be the cytoplasm of
endothelium cells of fine capillaries. In the younger granulation tissue, and es-
pecially that infiltrating between the crypts of Lieberkuhn, the bodies were seen in
large cells resembling stroma cells, and in macrophages. The number of bodies
in different pieces of tissue from the same case varied very much.
TESTIS.—Sections of the testis from autopsy 5 shewed among the tubules
small areas in which an aggregation of nuclei was apparent. On closer examination
these nuclei were seen to be chiefly those of endothelium cells. In these areas
single bodies were present in considerable numbers lying in the cytoplasm of the
cells. In somewhat larger vessels, endothelium cells were seen containing
two or three bodies (Pl. I. fig. 3) and in the still larger vessels crowded cells were
frequent. The bodies were not present in the capillaries in all parts of the testis.
LUNG.—In autopsies 4 and 5, fairly numerous large crowded cells were seen
in films.
KIDNEY.—Films from autopsy 6 shewed occasional cells of endothelial
nature containing from 5 to 20 bodies. Only a small piece of kidney cortex was
reserved for sections and no bodies could be seen in this. The glomerular
capillaries were carefully searched but in vain. Sections of the cortex and
medulla of the kidney from case 1 were examined but no bodies were found.
LARGE VEINS.—Blood films made from the large veins, femoral, portal,
hepatic, some hours after death, shewed cells containing parasites which were first
thought to be peculiar forms of large mononuclear leucocytes. It seems certain that
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these cells are in reality endothelial in nature, since they resemble closely cells
seen forming the walls of small vessels exposed in tangential section. I have
thought it possible that they may become detached from the vessel wall after
death (Pl. II. fig. 6 and fig. 7).
SPLEEN AND LIVER.—In blood obtained from these organs by puncture, most
of the parasites are seen either free or included in a matrix. In sections of the
organs no such relation is to be made out and the parasites are seen lying in the
cytoplasm of cells. The cells are of two kinds.
Leucocytes. —Laveran and Mesnil, Ross and Manson and Low all call atten-
tion to the existence of phagocytosis and the presence of bodies in the large
mononuclear and polymorphonuclear leucocytes. In my first report I have
also considered the part played by the leucocytes in taking up the parasites.
The endothelium.—Marchand and Ledingham note the occurrence of the
parasite in very large cells in the spleen and bone-marrow. In my first report I
also made mention of these enormous cells, which appear to be of a similar nature
to the macrophages seen in fatal cases of malaria. The careful study of sec-
tions of the spleen and liver in cases of infection with the new parasite has
led me to conclude that the macrophages are derived from the vascular en-
dothelium and that they represent a final stage of endothelium cells which
have become more and more modified and distended with included parasites. It
is indeed easy to trace every gradation between flattened endothelium cells con-
taining a few bodies and the enormous swollen cells almost blocking the capillary
in which they lie. In both the liver and spleen, many more bodies are included in
cells of endothelial nature than in the leucocytes. In films this fact is masked
by the rupture of many of the more distended endothelial cells, and also by the
fact that many endothelium cells approximate in appearance to cells of large
mononuclear leucocyte type and may be readily classed in this group. Two cells,
in reality endothelial in nature, are figured by me as large mononuclear leucocytes
in my first report (fig. 22) and it is possible that others have erred similarly.
The following types of endothelium cell in which the parasite occurs may be
noted.
1. Endothelium cells but little modified. In films these have round, oval or
kidney-shaped nuclei and extensive protoplasm which is often arranged so as to
give the cells an elongated appearance. The protoplasm, as a rule, shews a
tendency to vacuolisation especially towards the free ends of the cells (Pl. II. fig. 6).
It also tends to become protruded in the form of buds. In sections they may be
quite flat or they may shew at one, or more rarely both ends, a swollen appearance.
They are applied closely to the capillary wall or stroma. They contain, as a rule,
from 6 to 12 bodies. Identical cells are seen in the capillaries of the testis and
of granulation tissne (Pl. II. fig. 8).