NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
Pathology and nature of kála-ázar.
report, namely, great wasting of the extremities, and upper
parts of the body contrasting markedly
with the enlargement of the abdomen, due
to the greatly increased size of the liver and
spleen, and in some cases dropsy of the feet, legs, and rarely of
the abdomen. Anæmia may also be noted in the mucous
membranes. The comparatively dark skin is often a note
-worthy feature, and on cutting into the body, the marked
absence of subcutaneous fat, in which respect the disease
differs from that of anchylostomiasis, concerning which
Lutz writes—"In most cases subcutaneous fat is well
developed, sometimes remarkably so," as is also the case in
"the chlorotic anæmia so often seen in England.
The pericardium contained from I to 5 ounces of fluid
in one-fourth of the cases, while I once
found 12 oz. present. Signs of recent in
-flammation of the serous membrane were
also occasionally met with.
The heart was nearly always much smaller than normal,
the average being only 6 oz., as against, a little over 8 oz., in
healthy people who had died from accidental causes. This
point struck me very much at first, and is again in
marked contrast, as has already been mentioned in the clini
- c a l s e c t i o n , w i t h w h a t i s m e t w i t h i n c a s e s o f a n c h y l o s t o m i a s i s ,
in which the heart is usually dilated and often also hypertro
- p h i e d t o s u c h a n e x t e n t a s t o c a u s e v e r y e v i d e n t p a l p i t a t i o n .
The difference is due to the more or less constant presence of
fever in kála-ázar cases, which, besides causing granular de
-generation of the heart muscle, followed by fatty changes, also
allows of no rest during which hypertrophy may take
place. This is borne out by the fact that in one or two very
chronic cases of the disease with prolonged. intervals between
the fever, slight enlargement was met with. In several cases
I found distinct fatty degeneration of the cardiac muscle, but
in some cases this was absent The heart muscle was usually
of nearly normal colour and consistency, and no signs of en-
docarditis were seen.
101
External appear-
ances of the body.
Cardio vascular sys-
tem.
Report on Kála- ázar.
The arteries of the brain were in several cases found to be
in a state of advanced fatty degeneration, which probably also
affected the other arteries of the body, and accounted for the
frequency of the slight epistaxis, which has been previously
n o t e d .
One or both pleural cavities often contained a small quan
-tity of clear fluid, and in one man who
died of pleurisy, 6th were found in his chest.
The bases of the lungs were almost invariably found to be
congested, especially in the cases who died during the rainy
season of actual fever. During the onset of the cold weather,
deaths were frequent from lung complications, which compris
- e d p n e u m o n i a , p l e u r i s y , a n d a l s o i n o n e c a s e g a n g r e n e o f t h e
lung. Œderna of the lungs also caused the death of one of the
dropsical type of cases.
The stomach was in two or three, cases very small, and its
mucous membrane thick and rough with
projecting ridges. This condition I have
also met with after death by accident in healthy persons, so
its occurrence in ká la-á zar is probably accidental, especially as
symptoms of inflammation of the organ, such as vomitting, are
very rare in this disease, while chronic dyspepsia is common
enough among natives. In one case ulceration was found,
but, as a rule, the mucous membrane appeared to the
naked eye to be normal. In one case also, marked pigmen
- t a t i o n o f t h e s p a c e s b e t w e e n t h e r u g s o f t h e s t o m a c h a n d
on the valvulæ conniventes only of the duodenum was
found—a distribution which suggested a deposition of the
pigment from the blood stream, rather than its formation
in situ, as a result of chronic inflammation. The case was
a very long standing one.
The small intestine was often thinner than normal, espe
-cially in the more chronic cases which had died of asthenia
accompanied by diarrhœa, and in these instances it was often ,
also pigmented, more especially in the upper part, but extend
-ing down to the ileo-cæcal valve, and usually less marked on
The respiratory sys
-tem.
Digestive system;
Pathology and nature of kála-ázar.
the peyers patches than elsewhere, causing them to stand out
in contrast to their surroundings. These changes were cer
- t a i n l y t h e r e s u l t o f c h r o n i c i n f l a m m a t i o n o f t h e s m a l l i n t e s t i n e s ,
which, doubtless, plays an important part in the pathology
of the disease. The mesenteric glands have also been found
in one or two cases to be pigmented.
Now in the few cases of anchylostomiasis on which I have
made post-mortems, I have found the intestine to be sometimes
slightly thicker than normal, but not thinner, and I have not
seen any pigmentation of the mucous membrane. As the point
seemed to be an important one, and my experience was too
limited to allow of any safe generalizations being made from it, I
wrote to Dr. Sandwith on the subject, and am much indebted to
him for his kind reply to this and other questions. He writes
—
"The stomach contains no pigment or thickening, but I have once
or twice found hæmorrhage in the stomach as described by Giles.
I cannot explain this. The intestines and mesenteric glands are
neither of them pigmented."
In his paper on anchylostomiasis in Egypt, he also writes:
"I have not observed the constant changes in the mucous mem
-brane of the stomach described by Giles."
The pi gment at i on, . whi ch I have met wi t h i n t r ue cases of
kála-ázar, is moreover of such a distribution and so closely
set, that it could not possibly be due to the remains of the
small hæmorrhages caused by the bites of the anchylostoma
worms; although it might possibly arise from inflammation of
the intestines set up by these parasites, this must be rarely the
case, or it would have been seen by Dr. Sandwith in Cairo.
Most, then, of the cases in which Dr. Giles saw these
changes during his investigation of kála-ázar in Assam, must
have been true cases of the disease, and not, as he thought,
due to anchylostomiasis. His description of the exact
changes which he found, however, is not sufficiently minute
or systematic to allow of accurate comparison with those
which I met with.
The large intestines showed ulcerations in a very few
103
104
Report on Kála-ázar.
cases, and congested patches and thickening or even œdema
of the mucous, membrane rather more frequently, and in one
or two cases some pigmentation.
The anchylostoma were very carefully counted in each
case, and the amount of damage done by them minutely
scrutinised by the help of a magnifying glass, which was very
often necessary in order to enable it to be distinguished. In
4 out of the 25 autopsies, no anchylostoma were found; in 7
more, less than 10 were present, in 5 there were from 11 to
20, in 5 from 21 to 30, and in the other 4 cases, 48, 50, 80, and
103, respectively, the average of the whole being 21.48. In 7
healthy persons, who had died from accidental causes, on the
other hand, the numbers present were 11, 10, 11, 13, 24, 34,
61, and 72, respectively, with an average of 32. The slightly
smaller numbers in the former series is doubtless due to the
fact that some of the kála-ázar cases, but by no means all,
had been given thymol during life. In four cases, on the
other hand, in which the anæmia was really due to anchylos
-tomiasis, as proved by the character of the blood changes,
the numbers found were- 350, 40, and 249, giving an
average of 200. Dr. Sandwith, in post-mortems o n 1 8 c a s e s ,
which had not had the benefit of the: thymol treatment, found
in six of them less than to worms, in three others 20, 40, and
5o worms, but in the other nine numbers varying from 170
to 381, terminating with the maximum record of 863. Thus,
it is evident that, although in some cases very few worms may
be found after death; yet in a series of cases a very different
record is obtained from that met with in kála-ázar, and the
evidence here given, together with that detailed in the clinical
section, and the figures obtained by Dr. Dobson, prove incon
- t e s t a b l y , a p a r t a l t o g e t h e r f r o m t h e a b s o l u t e s c i e n t i f i c p r o o f
afforded by the differences in the blood changes given in Section
IV, that the anchylostoma worms are not present in the majority
of kála-ázar cases in larger numbers than they are in the
healthy people of Assam, much less are they present in
sufficiently larger numbers in this disease, than they are in
Pathology and nature of kála-ázar.
105
healthy people, to constitute them an important factor in the
production of the affection.
As to the lesions caused by the bites of the anchylostoma,
I was fortunate enough to get several autopsies within a very
few hours after death, when the large majority of the worms
were still adherent to the mucous membrane of the small
intestine. I was surprised to find that, although under many
of them a small hæmorrhage was easily seen, yet on close
examination it was found that at the point of attachment
of the majority of them, no hæmorrhage was visible, even
with a magnifying glass, but only a very small white dot or
circle. Doubtless, whenever they bite a new place, one of
these small hæmorrhages must be formed, which will certainly
take at least a week to be absorbed at the very lowest estima
-tion, so that it is evident that the worms usually remain
attached to the same place for at least that time, which is only
what might naturally be expected. Again, I found fresh blood
in only a minority of the worms which I examined under the
microscope, although it does not clot in the bodies of the
parasites, and would keep its natural appearance for some
time, which seems to show that the worms are not constantly
sucking blood out of the intestine, but only take sufficient
to nourish them, and to allow of the rapid formation
of ova; and as they are quite small and their food is of
the most nutritious kind, there is no necessity for their
taking more than a drop or two of blood a day, or for their
changing their feeding ground more than once a week,
perhaps, when the minute scar, which they make, begins
to contract around them. Now Dr. Braddon, of the Malay
Peninsula, in a criticism of Dr. Giles' report, estimates that,
even if it be allowed that a hundred parasites are present and
inflict several fresh bites daily, it would take a year to produce
such considerable erosion as would destroy even one-twentieth
of the digestive area of the small intestine alone. Yet Dr.
Giles writes that
—
"The mere loss of the nutritive matter required for the support P
106
Report on Kála-ázar.
of the parasites, is a quite small and quite unimportant factor in
the causation of the fatal symptoms produced by them . . . . The
real damage is mainly caused by the destruction of the digestive
powers."
The last sentence is a very true statement as applied to the
later stages of the more chronic cases of kála-ázar (only the
loss of the digestive powers is one of the effects of the fever,
and is not due at all to the very small number of anchylosto-
ma which are present in ordinary cases of the disease), but
is very wide of the mark as applied to anchylostomiasis.
Thus, Lutz writes of the latter-
"It may be said that adults, in the absence of any complication,
and in whom the disease runs a tolerably quick and uniform course,
do not begin to show symptoms until the number of anchylostoma
passes into the hundreds, so that when pronounced, general symptoms
are present, three to five hundred parasites may be set down as
present i n the duodenum. In severe cases I have found over a
thousand present, but in the Gotthardt epidemic, two or even three
thousand were found."
And he attributes the main symptoms to the loss of blood
brought about by the parasites, and traces the three stages
into which he divides the disease, namely, (1) stage of purely
local symptoms; (2) stage of simple anæmia, and (3)
dropsical stage, to the gradually produced anæmic condition
of the blood. With regard to the dyspeptic symptoms, he
writes —
"The gastric catarrh, occurring constantly in the advanced stage
of the disease, and leading in its train loss of appetite, diarrhœa, and
imperfect absorption, helps to bring about emaciation."
But that this even in the advanced stages of the disease
is not so fatal as Dr. Giles would have us believe, is quite
certain from the very low mortality of the affection when
properly treated, as has been shown in Section III. Some
other observations in connection with the subject of
anchylostomiasis, which do not come into my general argu-
ment on the nature of kála-ázar, will be given in an appendix
to this report.
Pathology and nature of kála ázar.
107
The liver.
This organ is much enlarged in kála-ázar, and averaged
in 21 adults 3lbs. 13oz.; and this in spite
of the emaciation of the great majorit
y o f t h e p a t i e n t s . I n f o u r a d u l t h e a l t h y p e o p l e , w h o d i e d f r o m
accidental causes, it averaged 2lbs. 5oz., but in four cases of
anchylostomiasis it only averaged 1lb. 14oz., which confirms
my clinical experience, and the statements of Lutz and Sand
- w i t h , t h a t t h e o r g a n i s e i t h e r n o r m a l o r s m a l l e r t h a n n o r m a l
in this disease. The average size of the organ in kála-ázar
cases given above, conveys but a feeble notion of the size to
which it may attain in this affection, for in the more chronic
cases I have found it to weigh over 5lbs. in two cases, over
6lbs. in one, while the maximum recorded was 7lbs. 2½oz.
In three cases only was it under 2½lbs., and they had suffered
much from diarrhœa during life. Its appearance on section
varied a good deal, as it was usually of a mottled yellow
and red colour, which was distributed in a manner precisely
similar to that figured in Dr. Drury's paper in the transactions
of the first Indian Medical Congress on "a peculiar form of
fatty degeneration in malarious poisoning." In addition to
this there were often darker patches, most frequently seen
just under the capsule of the organ, which were due to the
deposition of pigment, and in other cases this was indicated
by a general darkening of the whole cut section of the organ,
giving it a dirty brownish appearance. In one or two very
chronic cases it was of quite a dark hue, while in one case,
which ran rather a rapid course and finished with a tempera
- t u r e o f 1 0 5°F . , i t o n l y p r e s e n t e d a n a p p e a r a n c e o f g r e a t
congestion. In one case, well marked cirhosis of the liver
was present, but I was unable to absolutely exclude alcohol
as a factor in its production, and although Kelsch and Keiner
describe a form of the disease as occurring in chronic malaria,
yet most cases of kála-ázar certainly run too rapid a course
to allow of its production in a marked degree. The organ
is, however, frequently harder than normal, and some excess of
interlobular tissue may often be seen under the microscope.
P 2
108
Report on Kála-ázar.
The gall bladder was normal, and contained bile, which was
often of a rather dark colour.
The spleen is always enlarged, and usually markedly so. It
averaged 2lbs. 5oz. in 21 cases in adults.
The lowest weight was 14 oz. in an acute
case; it was between one and two pounds in five cases; between
two and three in seven cases, and over three in seven others,
the maximum being 3lbs. 14oz. If the great wasting of the
body be taken into account, the relative enlargement of the
organ would be much greater than these figures indicate.
Except in the most acute cases, the organ is harder than
normal, especially in its peripheral portions, and under the
microscope an excess of fibrous tissue is found. The organ is
also usually of a dark-red colour, which, in the peripheral parts,
often gives it an almost black appearance, which is again due
to the deposition of pigment in the organ. In four healthy
adults, who died from accidental causes, the organ averaged
1lb., varying from 8oz. to 1lb. 8oz., and in four anchylos
- t o m i a s i s c a s e s , i t o n l y a v e r a g e d 1 0 ½ o z . , b e i n g u n d e r o n e
pound in each case, in which respect, once more, my observa
- t i o n s a r e i n a c c o r d w i t h t h e m u c h m o r e e x t e n s i v e e x p e r i e n c e
of both Lutz and Sandwith, in showing that in this disease,
except when it is complicated by malaria, the spleen is either
of normal size or it is diminished in bulk.
The kidneys presented no pathological changes to the
naked eye, except for the occasional occurrence of small
cysts, such as will be met with in any series of post-mortems,
but their colour was often rather darker than normal, instead
of being lighter, as might have been expected in a disease in
which anæmia is such a constant feature; but this was subse
- quently found to be due to the constant presence of pigmenta
- t i o n o f t h e o r g a n s . T h e i r w e i g h t w a s a l s o l e s s t h a n n o r m a l ,
but this again was only in proportion to the general wasting
of the body, and was in marked contrast to the enlargement
of the liver and spleen. The suprarenal bodies were also
carefully examined, but nothing abnormal was found in them.
The spleen.
Pathology and nature of kála-ázar.
The thoracic duct was also dissected out in all the earlier
cases, but was always found to be patent, so that the emacia-
tion was not due to any obstruction of this channel of absorp
-tion.
The cerebro-spinal
system.
A small quantity of fluid was often found beneath the
arachnoid, or in the ventricles of the brain,
which probably filled the vacancy formed
by slight atrophy of the organ. On sec
-tion the brain and spinal cord were normal. Pigmentation
was always found to be well marked on the under-surface of
the medulla oblongata, which in a few cases extending over
the pons as far even as the optic commissure, and over the
upper surface of the cerebellum. At first this was looked
on as constant and important sign of the disease, but it was
subsequently found that it was also to be met with under
the medulla in healthy persons, and even in anchylostomiasis,
so that it must be a normal condition in the natives of this
country, although I have not seen it mentioned in any book
on pathology. It extends down over the anterior sur
-face of the cervical portion of spinal cord. In one case
hæmorrhage beneath the arachnoid was the immediate cause
of death; but this was in a mixed case, and was, I think, due
rather to the blood changes brought about by the anchylos
-tomiasis factor than dependent on the fever of kála-ázar, as
I met with a similar hæmrnorrhage between the anterior surface
of the bladder and the peritoneum in a case of pure anchylos
-tomiasis.
It has recently been found in some cases of pernicious
anæmia observed in England, that the mar-
row of the shafts of the long bones, which
in health consists of yellow fat, is converted into red marrow,
such as is normally met with in the loose cancellous tissue of
the end of the long bones, and which forms the bulk of that
of the short bones. This red marrow has the function of form-
ing red corpuscles of the blood. An examination was there-
fore made of the marrow in the shaft of the femur or humerus
109
The bone marrow.
110
Report on Kála-ázar.
in all my post-mortems, and it was found that in cases of
kála-ázar, the yellow marrow was always converted into the
red variety, often being of a dusky-red hue, and that this
change was in proportion to the length and chronicity of the
case. It was also much softer than usual, and nearly, or
quite, free from the small spiculæ of bone which are met with
in it normally. The cancellous tissue of the ends of the
bones was also sometimes looser than normal, showing that
a certain amount of the bone salts had been absorbed. Pig-
ment is also to be found in the marrow under the microscope.
These changes are doubtless of a compensatory nature, due to
the efforts on the part of the system, to repair the unusually
rapid deterioration of the blood, and hence their occurrence
in this disease is only further evidence of the destructive
effect of the fever on the blood. As the changes have been
fully described in the Journal of Pathology and Bacteriology,
Vol. II, No. 3, by Dr. Robert Muir, they need not be further
discussed here. Out of four healthy persons, who died from
accidental causes, on the other hand, in two the bone marrow
was quite yellow, and in the other two only faintly tinged with
red. In three cases of anchylostomiasis it was reddened, but
not to the same degree as in k á l a - á z a r , a n d D r . S a n d w i t h , w h o
examined it in a recent case at my suggestion, found it to be
of the colour of "strawberries and cream." I expect that slight
changes of this nature will be found to be very frequent in such
countries as India, where malaria and other diseases which
destroy the blood are so common, and where even in health
the demands on the system for the repair of the blood are much
greater than in temperate climates, so that its occurrence in
kála-ázar is probable of more pathological interest than of
diagnostic importance. Its discovery, however, suggested to
me the line of treatment by bone marrow tabloids, which pro-
mises to be of considerable value. These changes account for
the pains in the limbs, which have been noted to be such a
common feature of the disease.
The chief point to which attention was directed when
Pathology and nature of kála-ázar.
sections of the different organs were being prepared for exami
-nation under the microscope, in accordance
with my plan of work, as set forth in Sec
-tion II, was to determine if pigment was
present in the liver, spleen, and kidneys, and if so, whether it was
as marked and constant feature as Kelsch and Keiner have
shown it to be in the cases of chronic malaria, which they
examined in Algeria. It may at once be said that it was con
-stantly met with in the series of cases examined, and that it
was roughly in proportion to the chronicity of the case, being
easily seen in properly prepared specimens in the more acute
cases, while in the more chronic ones it was so marked as to
be visible to the naked eye in thin sections floated out in a
white vessel, especially in those cases which showed a dark
colour of the surface of a section of the organs in the post
-mortem room. The distribution was also similar to that
figured by the French authors in their work, so that it will not
be necessary to describe it in detail here. Its presence affords
complete proof of the malarial nature of the disease, and its
importance is enhanced by the complimentary results of the
analysis of the amount of iron in the liver to be immediately
mentioned. In one case, in which kála-ázar was complicated
by anchylostomiasis, the changes were less marked than
usual, probably owing to a portion of the deposited pigment
having been used up to re-stock the red corpuscles, the hæmo
-globin values of which were low in this instance, being only .4.
No other changes, besides those already mentioned, were met
with, which are regarded as being of sufficient importance to
require description here: suffice it to say that no changes were
seen, which were inconsistent with the malarial nature of the
disease, and it is also worthy of note that all the pathological
changes recorded in this section, as well as all the clinical
signs detailed in an earlier one, were found by Kelsch and
Keiner in cases of chronic malaria in Algeria, as recorded in
their Traite des maladies des pays chauds.
The foregoing description of the pathological changes met
The microscopical
anatomy.