NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
90
Report on Kála-ázar.
in the high hæmoglobin value, and in the comparatively slight
reduction of the specific gravity. Moreover, in the first two
respects they also agree very closely with some examinations
of the blood in cases of chronic malaria recorded in a paper
in the Indian Medical Gazette of 1883 by Dr. Waddell, which
are the only figures on the subject that I could find in the
limited literature which I have been able to consult.
It is then evident that the type of anæmia in kála-azár is
precisely similar in all its details to that met with in ordinary
chronic malaria. Let us now see if it resem bles that found in
anchylostomiasis.
In anchylostomiasis, which is the disease produced by an-
chyl ostoma sucking small quantities of
blood out of the mucous membrane of
the intestine and not simply the pre-
sence of anchyl ostoma, which may not have been present in
sufficient numbers, or long enough, to produce any disease
whatever), the essential symptom is anæmia. We have just
seen that in kála-ázar also anæmia is a constant and marked
symptom, and it will be obvious that if the two diseases are
essentially the same, except that the latter is more frequently
complicated by malaria, as was maintained by Dr. Giles, then
the blood changes must be also similar, or nearly so while if
the disease is a mixture of malaria and anchylostomiasis, then
the blood changes should present a gradual series interme-
diate between the two primary conditions. Let us see if this
is the case or not, Taking the different observations in the
same order as before, it has been found that the hmoglobin
in twelve cases averaged 15.16 per cent., showing that the
anæmia was more marked than it was in the kála-ázar cases.
The number of red corpuscles in eleven cases averaged
1,145,000, or 42.9 per cent., and the hæmoglobin value in
nine cases averaged only .31, showing that the hæmoglobin was
reduced more than twice as much as the number of the red
corpuscles, and this was a constant feature in the disease, for
the highest figure met with was .39, which is much lower than
The blood changes in
anchylostomiasis.
Blood changes in kála-ázar and anchylostomiasis.
91
the lowest figure obtained in any uncomplicated case of kála
-ázar, so that this alone serves to absolutely differentiate the
two forms of anæmia, and consequently also the two diseases
from one another. Again, the number of white corpuscles in
ten cases averaged 5,333, and their ratio to the number of red
w a s a s 1 i s t o 5 2 4 , s h o w i n g t h a t , a l t h o u g h t h e y a r e a c t u a l l y
reduced in number, as compared with the standard of healthy
Assamese people, yet relatively to the red corpuscles, they
are increased in number, or, in other words, they are not
reduced in as great proportion as are the latter. This again
is in marked contrast to the state of affairs in kála-ázar, in
which in the intervals between the fever, when the tempera
-ture is not raised, they are much reduced, both actually and
relatively, to the red corpuscles.
Once more, the specific gravity of the blood is always very
much reduced in anchylostomiasis, varying from 1,038 down
to as low as 1,030, and the average of eight cases was only
1,034. This is partly due to the greater degree of anæmia in
the series of cases of anchylostomiasis as compared with
those of kála-ázar; but if cases of the two diseases present
- i n g t h e s a m e d e g r e e o f a n æ m i a b e t a k e n , t h e s p e c i f i c g r a v i t y
of the blood is still found to be much lower in the anchylosto
-miasis ones than it is in the kála-ázar cases. Here, again,
this point is of the greatest importance, as it serves to differen
-tiate the two diseases, and as the estimation can be made in
two minutes with very little practice, it is likely to prove of
practical importance, for the treatment of the two different
types of anæmia should be quite different.
The type of the anæmia produced by anchylostomiasis
then differs so materially from that found in kála-ázar, as to
absolutely differentiate the two diseases from one another.
It has already been mentioned that a small percentage of
kála-ázar cases were found to be compli-
cated by a sufficiently large number of
anchylostoma to constitute them a factor in the production of
the anæmia met with in these cases, and it may be said at
N 2
Mixed cases.
92
Report on Kála-ázar.
once that they presented blood changes which were exactly
intermediate between those met with in the two contributing
diseases, thus showing that the worms had in these instances
been present in sufficient numbers and for a long enough period
to bring about characteristic alterations in the blood. Thus,
in five such cases, which were met with out of a total of 77
examined, or 6.49 per cent., the hæmoglobin value averaged
.43, which is just intermediate between the same figures for
the anchylostomiasis and kála-ázar, respectively, as were also
the other figures which will be found in the table on page 95,
and thus served as a test as to whether any number of the
worms, which might be met with in a given case, had been a
factor in the production of the anæmia or not, for, if they had
materially assisted in the production of the anæmia, then the
type of the blood changes found would show the charac-
teristic variation from that which is typical of kála-ázar.
Further, I have even been able to correctly suspect the
presence of anchylostoma in active numbers in an early case
of kála-ázar before anæmia was a marked symptom, and
when there was clinically no suspicion of them. I have,
moreover, been able, by an examination of the blood, to
diagnose from each other with certainty cases of both
kála-ázar and anchylostomiasis, which I had previously
either been unable to differentiate without it, or in which I
had even made a wrong diagnosis by the ordinary methods
in spite of considerable experience, for cases do not very infre-
quently occur in which kála-ázar very closely stimulates
anchylostomiasis, and this doubtless accounts for the former
confusion between the two diseases. Thus, on one of the tea
gardens, when working with Dr. Price, we picked out three
cases, one typical of kála-ázar, the second of anchylostomia-
sis, whilst the third man in some respects resembled the latter
disease, but he had an enlarged spleen, and dropsy of the legs
and abdomen, with only slight fullness of the face, and, on the
whole, we thought was probably suffering from kála-ázar. The
following table gives the blood changes which were found in
Blood changes in kála-ázar and anchylostomiasis.
93
them, from which it will be seen that the third and doubtful
case resembles the second in type, although not in degree,
or anchylostomiasis, one, so closely as to remove at once all
doubt as to the diagnosis, and the subsequent course of the
case, with a re-examination of the blood after an interval of two
months, proved it to be undoubtedly anchylostomiasis:
———
H æ m o - g l o b i n p e r c e n t .
Red cor-
puscles per
c. m.
White
corpuscles
per c. m.
Ratio of
red to
white.
H æ m o - g l o b i n v a l u e .
Kála-ázar case
28
1 , 6 0 0 , 0 0 0
1 , 8 0 0
1:945
. 8 4
Anchylostomiasis case
15
2,560,000
7,500
1:330
.28
Doubtful case
33
5 , 2 3 0 , 0 0 0
9,250
1:561
. 3 1
Again, not long after, on returning to Nowgong I found
in the dispensary, what I had no hesitation in saying was a
typical case of anchylostomiasis in a girl of 17, who had
marked anæmia, a "pearly white" conjunctiva, and no enlarge
-ment of the spleen or liver. As up to this time (and the same
remained true to the end of my investigation) I had failed to
find a single case of pure anchylostomiasis among the indige
-nous Assamese people, except on tea gardens, or in those who
had worked on tea gardens, or on the Assam-Bengal Railway,
in spite of visits paid to several of the dispensaries and
villages of the Nowgong district, after due notice, for the
purpose of seeing cases both of this disease and of kálá-ázar,
I was therefore much interested in this case, and as thymol
had been given the day before, I immediately examined the
stools passed during the preceding 24 hours before enquir
-ing into the history of the case, and was surprised to find
no worms. The blood was therefore examined, and the
hæmoglobin value proved to be .57, and the ratio of white
to red corpuscles 1 to 1,403, the red corpuscles numbered
3,650,000, and the hæmoglobin was 42 per cent., all these figures
being typical of kála-ázar as opposed to anchylostomiasis.
The history showed that she had lost four relatives of
kála-ázar, and had only one left alive, and that she had
94
Repot on Kála-ázar.
suffered from repeated attacks of fever during the last two
years, including four attacks during the rains of 1895, and
for six weeks of this year up to a short time before admission.
When seen, however, she had no fever, and only suffered
from anæmia, being in a fair way to recover, which she
subsequently did. Here, then the blood examination recti
-fied an actual mistake in diagnosis, for the case was one of
nearly recovered kála-ázar.
It only remains to consider the constancy of the typical
blood changes in kála-ázar, and any circumstances which
may modify them. It may be said that the hæmoglobin
value of uncomplicated cases of kála-ázar never falls below
.5 , as compared wi t h t hat of . 65 for a heal t hy nat i ve of Assam,
although it may rise considerably above the latter figure.
I have only met with four exceptions to this rule, which,
however, puzzled me a good deal, until one day, when going
over my notes to see how often hæmorrhage from the nose,
which is so often met with in kála-ázar, was of sufficient
extent to be likely to affect the blood changes, and to make
them approximate towards the anchylostomiasis type, I found
only three such cases, and on looking up their blood analyses,
I found all three of them among the four exceptions above
mentioned out of over 50 estimations. This is a good
example of the value of minute notes of a series of cases
combined with special observations in elucidating a compli
-cated problem, for three out of the four exceptions were
at once explained, and the correctness of the observations
themselves was confirmed. The fourth was on a tea garden,
where I have found other cases complicated by anchylosto
-miasis, and, although no worms were expelled by thymol,
this is not surprising, as he had very likely had the drug on
a previous occasion, and I have found that it takes some
months after the parasites have been expelled before the blood
reaches the normal type again, so it is very probable that
he had suffered from the disease at some time previously to
his being attacked by kála-ázar.
Blood changes in kála-ázar and anchylostomiasis.
95
The following table shows at a glance the difference
in the average blood composition in healthy natives of Assam,
kála-ázar, ordinary chronic malaria, anchylostomiasis, and
mixed cases of kála-ázar and anchylostomiasis:
————
P e r c e n t a g e o f h æ m o - g l o b i n .
R e d c o r p u s c l e s p e r c u b i c m i l l i m e t r e .
W h i t e c o r p u s c l e s p e r c u b i c m i l l i m e t r e .
R a t i o o f w h i t e t o r e d c o r p u s c l e s .
S p e c i f i c g r a v i t y .
H æ m o g l o b i n v a l u e .
Healthy natives of Assam
6 2
4 , 7 3 4 , 0 0 0
7, 325
1 : 6 8 4
1 . 0 5 4
. 0 5
Kála-ázar cases
33.45
2 , 4 6 2 , 0 0 0
2, 600
1: 1, 170
1 . 0 4 8
. 6 5
Ordinary chronic malaria
3 1 . 6
2 , 0 0 0 , 0 0 0
1, 600
1: 1, 400
1 . 0 4 2
. 7 3
Anchylostomiasis
1 5 . 2
1 , 1 4 5 , 0 0 0
5, 338
1 : 5 2 4
1 . 0 3 4
. 3 1
Kála-ázar and anchylostomiasis
2 7 . 4
3 , 1 2 0 , 0 0 0
3, 200
1 : 9 7 5
1 . 0 3 9
. 4 3
The explanation and significance of these various changes
met with in the blood must now be given, as they may not
at first sight be evident. It will also be necessary to see if
there is any confirmation of my results to be found in such
literature as is at hand.
It will be evident from the facts given in the clinical
section of this report, that in kála-ázar the anæmia is
produced by the destruction of the blood corpuscles by the
fever, which, as will be proved later, is purely malarial, and is
caused by the plasmodium malariæ living on the red corpus
- c l e s , w h i c h t h e y d e s t r o y , w h i l e t h e w h i t e c o r p u s c l e s b e c o m e
gradually reduced, doubtless owing to the losses sustained by
them in their unremitting fight with these organisms, as is
shown by the constant occurrence of actual or relative leuco
- c y t o s i s d u r i n g f e v e r . T h e o t h e r e l e m e n t s o f t h e b l o o d a r e
not directly affected, but in the latter stages they suffer some
deterioration owing to the loss of digestive power, preventing
their daily expenditure being replaced, as it is in health. On
the other hand, the primary cause of the symptoms in
anchylostomiasis is the daily loss of the small quantities of
96
Report on Kála-ázar.
blood which are sucked out by the worms; while, again in
the latter stages this may be supplementel bý some loss of
digestive power owing to the injury to the intestine which
may be produced by the worms. It is evident that in anch
y - l o s t o m i a s i s a l l t h e e l e m e n t s o f t h e b l o o d w i l l e q u a l l y b e l o s t
to the economy, including the albuminous parts, which are not
primarily affected in the case of kála-ázar. The different con
-stituents are not, however, equally readily renewed by the sys
- t e m . O n t h e c o n t r a r y , t h e w h i t e c o r p u s c l e s a r e m o r e e a s i l y
replaced than the red, so that in anchylostomiasis the former,
although actually reduced in number, might be expected to
become increased relatively to the red corpuscles; and this is
just what we have found to be the case. Much more important,
however, is the hæmoglobin, and this element of the blood, con
- t a i n i n g , a s i t d o e s , i r o n i n a n o r g a n i c c o m b i n a t i o n , i s m u c h l e s s
easily replaced. It has been shown by the analyses of the late
Dr. Bevan Rake, that after death from anchylostomiasis the
amount of iron in the liver is often much reduced. This is due
to the reserve iron in the liver being used up to stock the
newly-formed red corpuscles, as these are turned out by
the bone marrow. As soon as this reserve is exhausted, the
renewal of the hæmoglobin will be entirely dependent on the
amount of iron absorbed from the food through the digestive
canal. Now this has been shown by Dr. Ralph Stockman to
only amount to one-eighth of a grain daily in the case of a diet
containing animal food, and will be even less in a vegetable
one, such as the vast majority of the natives of India subsist
on. Consequently, there is soon a great difficulty in the
formation of enough hæmoglobin to put into the red corpus
-cles, which are being formed, and so a deficiency of hæmo
-globin relatively to the number of the red corpuscles gradually
ensues, and the hæmoglobin value sinks to half, or less than
half, that met with in health. Thus, the change in the com
-position of the blood, which we have seen actually occurs in
anchylostomiasis, is only what might have been expected to
result from a slight, but steady, daily loss of blood, and my
Blood changes in kála-ázar and anchylostomiasis. 97
observations confirm the opinion that this loss of blood is the
essential factor in the production of the anæmia. Again, the
much lower specific gravity of the blood, even when the
more intense anæmia is allowed for, which I have found in
anchylostomiasis as compared with kála-ázar, is easily explain
-ed by the loss of the albuminous elements in the former disease
being partly replaced by water, and hence the specific gravity
will fall, especially when the changes in the digestive system
prevent the absorption of a full amount of nourishment from
the elementary canal; while in kála-ázar this loss does not
occur, and the density of the blood remains nearer to the normal
being only affected by the loss of the red corpuscles and
hæmoglobin.
It remains to be explained how it is that the hæmoglobin
value of the blood in kála-ázar maintains its standard, as
compared with anchylostomiasis. It has already been men
-tioned that the red corpuscles are replaced by the action of
the bone marrow. In health it is only the marrow in the ends
of the long bones and in the cancellous tissue of the other
bones, which has the physiological function of forming new
red corpuscles to replace such as become worn out day by
day. It has been calculated that if the red marrow of all
the bones of the body could be massed together, it would
exceed in bulk the spleen itself, so that it can easily be seen
how important are its functions during health. In the case,
however, of such diseases as kála-ázar and anchylostomiasis,
in which the blood is daily being impaired, the work of renew
-ing the loss of the red corpuscles becomes doubly difficult. It
has, moreover, recently been shown by Robert Muir and others
that in the disease known as pernicious or essential an
æ - m i a ( u n d e r w h i c h t e r m s o m e a u t h o r s w o u l d i n c l u d e a l l e x t r e m e
forms of anæmia due to whatever cause, and therefore those
now under consideration), the marrow of the shafts of the long
bones, which in health consists only of fat, becomes converted
into red marrow, this being a compensatory change, or an
effort on the part of the system to cope with the excessive
9 8
Report on Kála-ázar.
demand for red corpuscles. This change I have found to
be a characteristic and constant one in all cases of kála-ázar,
and they are also met with, although in my experience not
quite to so marked a degree, in cases of anchylostomiasis,
being doubtless purely of a compensatory nature in each case.
It is in this way then that new red corpuscles are produced
in both diseases, but in the case of anchylostomiasis, there
soon becomes a dearth of hæmoglobin with which to stock
them. In kála-ázar, on the other hand, the hæmoglobin is not
lost to the economy, as it is in the former disease, for, when
the plasmodia destroy the red corpuscles, the colouring matter
becomes converted into pigment, and on the division of the
parasite into numerous small ones, and the breaking up of the
enclosing red corpuscle, such as occurs in the case of quoti
-dian fever every day at the time of the onset of the fever, this
pigment is set free in the blood, and gets filtered out by the
spleen, liver, and other organs, where it forms the pigmentary
deposits, which are of such a characteristic feature of chronic
malaria, and which will be shown in the next section, to be also
a marked and constant feature of kála-ázar. Thus, when in
this disease fresh red corpuscles are formed by the bone mar
-row, there is already a stock of iron in these organs in organic
combination, waiting to be used up to re-stock the red corpus
-cles, and this may even proceed until they contain more than
the normal amount, as shown by the frequent abnormally high
hæmoglobin value in kála-ázar. The ease with which the
hæmoglobin may be replaced constitutes the essential cause
of the difference of the type of the anæmia of kála-ázar from
that of anchylostomiasis, and thus we see every change which
I have found in the blood in either disease, is completely
accounted for by what we know of the causation and patho
-logy of them, and the complete differentiation of them as sepa
-rate and distinct diseases, which, however, sometimes compli
-cate each other, is placed on a firm basis.
It is also evident from the above that while iron will be
essential in the treatment of the anæmia of anchylostomiasis,
Blood changes in kála-ázar and anchylostomiasis. 99
it is much less important in that of the anæmia produced by
malarial fevers, for, in the latter case, there is plenty of iron
in an organic combination in the liver, etc., ready for use, but
here arsenic will be indicated to increase the output of red
corpuscles by the bone marrow, which explains the value of
this drug in malarial and so-called pernicious or essential
anæmia.
The question remains—can any confirmation of my results
be found in the scanty literature within my reach? I made a
search for such in Calcutta before beginning work, but only
found those by Dr. Waddell, which have been already
mentioned on page 90, and, with regard to anchylostomiasis,
I find, in Dr. Sandwith's valuable paper on this disease,
in the Indian Medical Gazette of July 1894, details as to
the estimation of the hæmoglobin and the number of the red
corpuscles in 173 cases; and working out the hæmoglobin
value from these figures, it agreed so closely with what I
had found it to be in my smaller number of cases, allowing for
the low blood standard of natives in Assam, that I considered
it to be quite unnecessary to spend more time in examining a
larger number. The differences in the type of anæmia in
chronic malaria and anchylostomiasis above described are then
confirmed by the results obtained by independent observers,
and the proof that the anæmia of kála-ázar differs essentially
from that met with in anchylostomiasis, while it conforms to
that caused by malarial fever, is placed on a sound basis
O
2
100
Report on Kála-ázar.
SECTION V.
THE PATHOLOGY AND NATURE OF KÁLA-ÁZAR.
In this section the pathological anatomy, both macroscopic,
as seen in the post-mortem room, and microscopic, as far as
this has been worked out by means of cutting sections of the
diseased organs, will first be given, and then the true nature
of the disease will be discussed in the light of all the facts
which have been adduced in the first five sections of this
report.
With regard to the pathology of the disease, again, but
little help is to be obtained in the literature of the subject, and
the value of that little is greatly diminished by the former
confusion between kála-ázar and anchylostomiasis. I much
regret that I have not been able to devote as much time to
the microscopical part of the work as I should like to have
done, owing to the pressing claims of the more immediately
practical work of studying the mode of spread and present
limits of the epidemic which has necessitated prolonged
tours; while at the time of writing I am anxious to submit
my report without delay, so as to allow of a full consideration
of my recommendation before the next cold weather arrives,
which is the only time for action being taken on them. As
I still have the material by me, I shall hope to go into this—
the more scientific side of the question—as soon as I shall
have any leisure time, and only the more important facts will
be given here.
The following description of the changes found post-
mortem is based on 25 autopsies on cases of kála-ázar, which
have been made by myself, with the exception of a few which
were kindly performed for me, in accordance with a
scheme I drew up, by Mr. McNaught and Dr. Dodds Price.
Four others on cases of anchylostomiasis, and seven
medico-legal ones were performed for the sake of control
observations.
These have been described in the clinical part of this