NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
Treatment of KáLa-ázar.
79
dose of quinine from two or three to ten or more grains three
times a day has been followed by a rapid cessation of the
fever, at least for a time. On the other hand, it is equally
certain that such large doses, as 10 or even 20 grains
three times a day, may fail to stop the fever in some of the
worst cases, and I find that in these the proportion of the
white corpuscles is usually very much reduced, and often
also the power of digestion and absorption by the intes
- t i n a l t r a c t , i n c l u d i n g p o s s i b l e e v e n s u c h d r u g s a s q u i n i n e ,
is very much diminished. That the latter is not, however,
the whole explanation, is proved by the fact that I recently
gave 15 grains of quinine daily, by the hypodermic method,
to a boy of ten years old in the chronic stage of the disease,
without stopping the fever; and what was even more remarkable
was the fact that he never suffered from the least buzzing in
the ears or from headache, or was in any way inconvenienced
by the treatment, with the exception of some pain over the seat
of the injections. This alone affords strong confirmation of the
malarious nature of the disease, as anyone who has treated
many cases of non-malarial remittent or continued fevers,
knows that much distress may follow the use of even ordinary
doses of quinine in them. To sum up, it may be said that
in the earlier stages large doses of quinine may be given with
the greatest advantage; but in the later ones it may fail to
check the fever even when given in heroic quantities.
Having thus cleared the ground, it may be stated that the
first indication is to give quinine in full doses, and ifit does not
control the fever rapidly, push it until it does, or until symptoms
of cinchonism appear, which I have never yet seen occur in
kála-ázar. If very full doses still fail to stop the fever, then I
hold that enough of the malarial antidote cannot be introduced
into the system through the digestive tract, and hence the
drug must be given hypodermically; just as in some of the most
acute cases of the Italian, and also of the Indian jungle, fevers,
if the drug is not thus given, the patient will be lost before
enough can be introduced by the mouth to inhibit or dest
roy
80
Report on Kála-ázar.
the malarial organisms before they kill the patient. The only
instance that I know of in which this method of using the
drug has been given any trial in kála-ázar, is by Dr. Dodds
Price, and he did not meet with much success with it;
but when it is mentioned that he only used it in two and a
half-grain doses, it will be evident that there is still scope
for a fuller trial of it in larger doses than this. Unfortunately,
owing partly to my having been on tour nearly the whole
of the cold weather, and to the impossibility I found of getting
early acute cases during this season of the year, when, as has
been before mentioned, fresh cases seldom occur, I have not
been able to test this line of treatment, so can only commend
it for trial as being that which is likely to give the best results.
Either the soluble bi-sulphate of quinine may be used, or
the ordinary drug dissolved in sufficient dilute hydrochloric
acid, and then diluted to a strength of one in four may be
injected into the back or loins.
(2) When once the fever has been stopped, it must not be
lost sight of that the patient will most likely have had 25 per
cent. or more of his blood destroyed by it, although this may
not appear in the state of his mucous membranes, and can
only be revealed by the hæmoglobinometer. He must then
remain under treatment until this has been repaired, and now
quinine, in small doses to ward off a recurrence of the fever,
combined with arsenic and, if desired, some iron (although
the former is of much greater use in the anæmia due to
malaria than the latter, for reasons which will be pointed out
in the next section), together with some nux vomica and some
bitter tonic to strengthen the heart and digestion (both of which
also will have suffered in the previous fever), will be indicat-
ed, and this tonic should be continued for at least a month
if the fever has been at all severe. By this time the patient
should be quite restored to health ; and if he be warned
to come again directly fever recommences, it should be possible
to prevent him from ever reaching that chronic condition
which is so very difficult to rescue him from. If only cases
Treatment of Kála-ázar.
could be got at in the early stage and treatment systematic
- a l l y c a r r i e d o u t o n t h e s e l i n e s , I f e e l s u r e t h e d i s e a s e
would have a very much lower mortality than it has
at present.
Treatment in the later
stages.
Unfortunately, cases are very rarely seen in the early stage
in dispensaries, and only too often on
tea gardens, they do not attend suffi
-ciently regularly, or are treated as ordinary fever cases until
they pass insensibly into the chronic stage. It is in these latter
places, however, that the line of treatment above laid down
could best be given a fair trial; but even then some would
necessarily be seen in the later stages of the disease. Here
again, the principles of treatment are the same as before,
but they hold out much less hope, and require some modi
-fication. Quinine should be given in large doses, and its
effect carefully watched. It will nearly always be found
to reduce the height of the fever, even when it does not
stop it altogether, and this is a considerable gain; for it
has been found that, if the temperature can be kept down
to 100° or 102° F., there is a much less rapid deterioration
of the blood than there is if it rises to 103° or 104°F. If,
however, large doses for ten days or a fortnight fail to
materially check the fever, it will be better to give smaller
doses combined with arsenic and strychnine; and in this
chronic stage, the best results have been obtained by
pushing the arsenic until thirty minims are taken in the
day. In doing so, looseness of the bowels must be care
-fully watched for, as this symptom will be a contra-indi
-cation to this line of treatment. If looseness of the bowels
has already started, the case will be a well nigh hopeless
one, but full doses of bismuth and salol have more effect
than any other drugs in controlling it, while a simple and
easily digested diet will be essential. In the class of cases
in which, after the fever has stopped for the time being, the
patient remains very wasted, and does not appear to be
able to digest his food, or to gain flesh, bone marrow in
M
82
Report on Kála-ázar.
tabloids will be indicated, and will be of the greatest service
in restoring the nutrition of the body if only fever remains
in abeyance. It will, however, be of little use as long as
there is fever of a marked degree, but a temperature running
up t o 101º F. , or s o occas i onal l y, wi l l not be a cont r a- i ndi cat i on
to its use.
A nutritious and easily digested diet will be of the first
importance, especially in the later stages of the disease. The
craving for meat has already been mentioned, and should,
when possible, be satisfied. All indigestible food should be
prohibited, as it is very likely to start uncontrollable diarrhœa.
From what has been written, it will be evident that I look
upon the disease in its earliest stages as curable by sufficiently
vigorous and constant anti-malarial treatment; but that it
is rarely that cases are seen early and often enough to
allow of this being carried out, even in in-door dispensaries,
while it is almost impossible in the case of out-door ones,
although much relief is doubtless given by them; while no
known treatment will save more than a small proportion of
the chronic cases. The disease is then essentially one in
which prevention is better than cure, and in which any
measures which would limit in the smallest degree the
prevalence and spread of the disease, will save infinitely
more lives than all the dispensaries in the province put
together.
(83)
SECTION IV.
THE BLOOD CHANGES IN KÁLA-ÁZAR AND ANCHYLOSTO-
MIASIS.
Although anæmia is the essential symptom of anchylosto
-miasis, and one of the main symptoms of kála-ázar, yet the
changes in the blood might be expected to be different in the
two cases, because the anæmia is produced in entirely different
ways in the two diseases. Thus, in the case of the former
disease, the anmia is brought about by the sucking of the
blood out of the mucous membrane of the small intestine by a
large number, usually from 500 to 1,000, or even 3,000, of very
small worms, which gain access to the intestinal tract in the
water and food, but cannot increase in number while in the
body. In the case of kála-ázar, on the other hand, as has
been shown in Section III, page 45, the anæmia is in direct
proportion to the fever, and is doubtless due to the blood being
destroyed inside the body by the malarial organisms, which
cause the fever. In the former case, all the constituents of
the blood are equally lost to the economy, although they
cannot all be replaced with the same rapidity. In the latter
case, the corpuscular elements of the blood only are destroyed,
while the albuminous fluid in which they float is not directly
affected, and what is of even more importance, the haemo
-globin, or coloring element, is not lost to the system, but, as
will be proved in Section V, is stored up in the liver, spleen,
etc., and is available for stocking fresh red corpuscles, as
these are renewed by the recuperative powers of the tissues.
I could, however, find very little in the way of examina
- t i o n s o f t h e b l o o d i n s u c h o f t h e l i t e r a t u r e o f a n c h y l o s t o m i a s i s
and malarial fevers as was available to me, so I determined to
make as complete an examination of it as possible in these
two diseases, and it was hoped that in this way it might be
determined in what respects the blood changes differed in the
two diseases, and if the differences were sufficiently marked
M 2
84
Report on Kála-ázar.
and characteristic to be of diagnostic value. For this purpose
the hæmoglobin was estimated by Dr. Gower's instrument,
and the red and white corpuscles counted by the hæmocy
-tometer of the same scientist, while in the later cases the
specific gravity of the blood was determined by the accurate
instrument of Dr. Lloyd Jones, as soon as this was ob
-tained from England. The coagulability of the blood was
also determined in a few cases by means of the instrument
of Professor Wright, of Netley. The results exceeded my most
sanguine expectations, and proved conclusively that the
anæmia of anchylostomiasis differs from that of kála-ázar in
every way it well could, while, on the other hand, that of Kál
a - á z a r
agrees in every detail with that of ordinary chronic
malaria, as met with in districts which were unaffected by
kála-ázar, for, as has been repeatedly said, this latter disease
cannot be distinguished from ordinary chronic malaria in the
affected districts. The evidence on which these statements
are based must be given in this section, and, although the
subject is a very complicated and technical one, an endeavour
will be made to discuss it as lucidly as possible. The blood
of healthy natives of Assam must first be described, as it has
been found to differ from the European standard, especially
in the case of the amount of hæmoglobin, which is much
lower in them than the standard of Dr. Gower's instrument.
Then the changes in the case of Kál á - á z a r ,
o r d i n a r y c h r o n i c
malaria, and anchylostomiasis, respectively, will be given, and
lastly the explanation of the differences will be pointed out.
In estimating the standard of the blood in the healthy
inhabitants of Assam, it was necessary to
The blood of heal- exclude both those who had any number
thy Assam ese.
of anchylostorna in their intestines, and
also those who had had any material amount of fever during
the last two years, for, as will be shown presently, both of these
classes, the latter to a much greater degree than the former, had
somewhat inferior blood. Now it must be constantly borne in
mind that the presence of anchylostoma in the intestines of
Blood changes in kálá-ázar and anchylostomiasis. 85
of a man does not prove that he is suffering from anchylosto-
miasis, for they must have done some definite injury before the
man can be said to be suffering from disease caused by the
presence of the worms, which is what is meant by the term.
It requires the presence of at least 500 anchylostoma for
a space of from six months to one year in a healthy person
to produce marked anæmia, but a smaller number than this
would doubtless suffice to bring about alterations in the stand-
ard of the blood sufficiently great to be indicated by the
delicate instruments which have been used in this research.
It was then of great importance, especially in view of the
frequent presence of the worms in cases of kála-ázar, to
determine what number of worms could be present without
causing any blood changes, for it is obvious that the system
which can withstand for even a few months the attack of
two or even three thousand of these worms, must be able
to so completely repair the loss caused by only a small
number of them, that no changes will appear in the blood.
To test these points, thymol was given to a series of 50 healthy
men in the Nowgong jail, and the blood of many of them was
also minutely examined. The results were as follows: taking
the hæmoglobin to represent the standard of the blood, for
this is its most essential element, and also that which is least
easily replaced, and consequently soonest becomes reduced
when there is any drain upon it, it was found that the average
amount of this constituent, according to the scale of Dr.
Gower's instrument, of seven men, who had no anchylostoma,
was 57.28 per cent., while that of 17 cases, who had anchy-
lostoma in numbers varying from 1 to 20, was 57.7, so that it
is obvious that these small numbers had no effect on the
blood what ever. Again, two men, one of whom had one anchy-
lostomum and 42 flukes, and the other 110 anchylostoma
and 104 flukes (amphistomum hominis), each had 57 per cent.
of hæmoglobin, so that even considerable numbers may be
present, and yet, at least for a time, the drain of blood
produced by them may be completely repaired. On the other
86
Report on Kála-ázar.
8 6
R e p o r t o n K á l a - á z a r . hand, one man, out of whom 293 anchylostoma were obtained,
had only 42 per cent., although he did not appear clinically
to be at all anæmic. Again, the average amount of hæmo
- g l o b i n i n 1 6 m e n , w h o h a d n o t s u f f e r e d f r o m m o r e t h a n o n e
week's fever in the last two years, was 60.8 per cent., while that
of 8 cases, who had had more than a week's fever in the same
time, was only 52.7, so that it is evident that comparatively
slight malarial fever, especially if it recurs at intervals, is a
much commoner and more important factor in causing
anæmia than is the presence of small numbers of anchy
-lostoma. If then only cases who have not had more than a
very few days' fever for two years, and who have not more
than 20 anchylostoma, be taken as healthy men, we shall
be on the safe side. The average amount of hæmoglobin
in 14 such natives in the Nowgong jail in the rainy season
was 62 per cent., while in 12 of them the average number of
red corpuscles in a cubic millimetre was 4,734,000, which is
very little below the European standard of five millions. It
will be noticed, however, that the hæmoglobin falls very much
below the standard of Dr. Gower's instrument, which is, I think,
rather a high one, for I well remember testing the blood
of myself and eight healthy students, when House Physician
to St. Mary's Hospital in London, and finding the average to
be only about 85 per cent., and that of seven healthy Euro
-peans in Assam during the rainy season I found to be but 71
per cent. The higher rate of Europeans over natives is, I
believe, due to the larger amount of animal food consumed
by the former, which contains more iron than vegetable food,
and that in a more assimilable form, for Ralph Stockman has
shown that the diet of Europeans contains only from 1/11t o 1 / 8
of a grain of iron a day, and the deterioration of the blood is
much greater in tropical than in temperate climates, and so
the need of iron is also greater.
Quite recently, however, I found that several of these
Europeans had from 8 to 10 per cent. more haemoglobin
towards the end of the cold weather than they had during
Blood changes in kála-ázar and anchylostomiasis.
87
the previous rainy season, and probably the natives vary to
some extent in the same way. This would partly explain
the low average obtained; but as all the observations on which
the figures given are based were made during the rainy
season, their relative value is not altered by this fact.
It follows from the greater deficiency of hæmoglobin in
proportion to the number of red corpuscles in the blood of
natives, that the amount of hæmoglobin in each corpuscle must
also be less than the normal standard, which may be represent
-ed by unity, and its amount may be estimated by simple rule of
three. The figure for a healthy native of Assam thus ob
-tained, which may best be termed the hæoglobin value,
works out t o be . 65. The i mport ance of t hi s fi gure wi l l be
immediately seen. Again, the number of white corpuscles
and their ratio to the red varies considerably in health, but
we may take the European standard to be 6,000 to 7,000
per cubic millimetre, or 1 white to 600 to 700 red, in accordance
with the authority of Hamilton. In eight healthy natives
the same figures averaged 7,325, and 1 to 684, respect
-ively, which agree with the European standard. Once more,
the specific gravity of the blood of six healthy natives
varied from 1,052 to 1,058, the average being 1,054.33,
These figures may be taken then to represent the composition
of the blood of healthy natives of Assam during the rainy
season, and will serve as a standard of comparison with those
met with in anchylostomiasis, chronic malaria, and kála-ázar.
The blood changes
in kála-ázar.
It has already been mentioned that in kála-ázar anæmia
is a constant and usually well-marked fea-
ture. It varies widely in its degree from
quite a slight one, which is not evident in
an ordinary clinical examination but is revealed by the hæmo
-globinometer, registering only from 35 per cent. to 50 per cent.,
down to extreme degrees in which only from 12 per cent. to
20 per cent. is found. On the average, however, it is not so
low as in anchylostomiasis, the average of 107 observations of
the former disease ( kála-ázar ) being 33.45 per cent., while
88
Report on Kála-ázar.
that of 12 cases of the latter was 15.16 per cent., while
Sandwith, of Cairo, found the average of 173 cases to be 26
per cent. The most important point, however, regarding the
anæmia of Kála-ázar is that in this disease the hæmoglobin
and the number of the red corpuscles are equally, or nearly
equally, reduced, so that the hæmoglobin value does not differ,
as a rule, very much from the normal. Thus, the number of
red corpuscles in 50 observations averaged 2,462,000 per cubic
millimetre, or 49.24 per cent., and the hæmoglobin value
wor ks out t o be . 65, whi ch, i t wi l l be s een, exact l y cor r es ponds
with what was found to be the normal figure for healthy
natives of Assam.
The number of white cor puscles differs very widely in
Kala azar from the normal, but it is complicated by the
occurrence of leucocytosis, or an excess of white corpus-
cles, actual or relative, during the presence of fever. In the
very early stages well-marked leucocytosis occurs, just as in
an attack of ordinary acute malarial fever, and I have seen
the white corpuscles number 23,000 per c.m., or 1 to 174 red,
in a case which I have very good reason for believing to be one
of a very early kála-ázar (see page 74). In all well marked
cases, on the other hand, during the absence of fever, the white
corpuscles are very much reduced, there not unfrequently
being only about 2,000, and, in spite of the red corpuscles also
being greatly reduced, there may be only 1 white to over 2,000
red. The average number in 36 observations made during
the absence of fever was 2,600 per c. m., or 1 to 1,I70 red.
Repeated estimations made in the same cases show, however,
that during the occurrence of fever, especially if the tempera-
ture is over 102°F., the white corpuscles will be present in
considerably larger numbers than they are in the same case in
the absence of fever. For instance, in one case, on a day
when the temperature was normal, 1 white to 1,225 white
corpuscles were found; but on another occasion, when the
temperature was 103.2, they were present in the proportion of
to 672, and many other similar instances might be given;
Blood changes in kála-ázar and anchylostomiasis.
89
but the reduction of the number of white corpuscles, except
when fever is present, is the most important and constant
change in them in kála-ázar.
The specific gravity of the blood is always reduced in
anæmia, chiefly, according to Lloyd Jones, in relation to
the diminution in the amount of hæmoglobin. In kála-ázar
the specific gravity of the blood is reduced, but only to a
comparatively slight extent, and it never reaches the extreme
degrees to which it is nearly always found to be reduced
in anchylostomiasis, and not unfrequently it is scarcely
removed from the normal limits, which are said by Lloyd
Jones to vary considerably. Thus, out of 34 observations, the
specific gravity of the blood was between 1,050 and 1,060 in
14 cases, while in 19 cases it was between 1,040 and 1,049,
while in only one, and that a case in the very last dropsical
stage, did it reach 1,039. The average was 1,048. Again, it
has been found that the specific gravity falls as the red cor
-puscles and hæmoglobin become reduced, and rises as they
increase in cases of recovery; but there was no constant
relation between the number of the red corpuscles and hæmo
-globin and the specific gravity of the blood, so that the altera
-tions in the composition of the plasma must influence its density.
The coagulability of the blood in kála-ázar was found
to be within the normal limits in a few cases in which it
was estimated by means of Professor Wright's instrument.
The blood changes in
Drdinary chronic malaria.
The average composition of the blood in five cases of
chronic malaria in Sylhet (including
three of the cases shown in the photo
-graph opposite page 29), which district
has not been affected by kála-ázar, was as follows: hæmoglobin
31.6 per cent., red corpuscles per cubic millimetre
2,000,000, the number of white corpuscles per cubic milli
- m e t r e 1 , 6 0 0 , 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 1 t o 1 , 4 0 0 s p .
gr. 1.042, and the hæmoglobin value .73.
These figures resemble those of kála-ázar both in the
great reduction of the white corpuscles as compared to the redN