NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
10
communities " fever" is only too familiar, and., even when a man is seriously ill,
he often thinks it unnecessary to call in medical advice though this may be
available.
It has been supposed that the patient himself must be struck by the extra
- o r d i n a r y c h a n g e i n h i s u r i n e ; a n d n o d o u b t h e i s , i f h e k n o w s t h a t t h e d i s e a s e
from which he is suffering is Black-water Fever ; but in a district where it is
not believed to exist, and among a community who have only heard vaguely of
the dread. disease, a man may overlook the condition of his urine and. not suspect
that he is suffering from Black-water Fever.
All these points are well exemplified in the case we have referred to from
Pu r u l i a . I t wa s o n l y b e c a u s e h e wa s t r a v e l l i n g t o Ca l c u t t a a t t h e t i me a n d wa s
taken to the General Hospital that this man came under observation ; also in spite
of passing through a typical attack of the disease he did. not know that he had
Black-water Fever, and. had. he been in his own district the attack would certain
- l y h a v e g o n e u n - r e c o r d e d , f o r h e a n d o n e o t h e r E u r o p e a n w e r e l i v i n g a l o n e i n
a remote part, many miles from the nearest civil station.
Black-water Fever therefore does occur in. India ; but it is evidently con
- f i n e d t o c e r t a i n l o c a l i z e d t r a c t s , a n d t h e r e c a n b e n o d o u b t , a s h a s b e e n m a i n t a i n e d ,
that it is rare in the practice of the average Indian physician. In this fact lies
one of the most powerful arguments for the view of the malarial origin of Black-
water Fever, yet based on the grounds of geographical distribution .
The areas we have especially mentioned as centres of Black-water Fever
are all tracts at once differentiated from the usual conditions in India by the
intensity of their malaria. Assam, the Duars, and the Darjeeling Terai we shall
consider in detail later. It is only necessary in. the present connection to say
that they are notoriously malarious districts.
The Jeypore District is a hilly intensely malarious tract, where the European
and native residents alike suffer severely from malaria.
Canara, on the west coast of India, is also a hilly district with a heavy rain
- f a l l , a n d i t i s i n t e r e s t i n g t o n o t e t h a t b e f o r e t h e o c c u r r e n c e o f B l a c k - w a t e r F e v e r
was actually recorded by Christie, Stephens and. Christophers, judging from
physical and other features, had already indicated this district as one likely
to yield cases of Black-water Fever.
Chota Nagpur is an extensive tract of hill country largely occupied by abori
- g i n a l t r i b e s , m e n t i o n e d b y H i r s c h a s o n e o f t h e m o s t m a l a r i a l p a r t s o f I n d i a .
Later on in this memoir we shall be able to picture what residence in such
districts entails to the European and even to the native of India.
11
But these conditions are not general throughout India in spite of an impression
to the contrary among those who are unfamiliar with life in this country.
Malaria exists as a rule, it is true, but. in a degree in no way comparable to its
intensity in the Black-water Fever districts. Europeans also, for reasons into
which we need not enter here, are usually but little exposed to such infection as
exists.
Thus one of us, as a result of experience, found it quite unnecessary to adopt
special precautions against malaria while living in the outskirts of Madras ; nor
did those living in the neighbourhood suffer, though a certain amount of infec
-tion, by no means great, was to be found in the bazaars. This condition is expe
- r i e n c e d i n C a l c u t t a , B o m b a y , a n d m o s t I n d i a n s t a t i o n s a n d i s m e t w i t h e v e n i n
rural districts, for one of us passed two years in a portion of Assam (Cachar)
without contracting malaria, although no special care was taken to avoid it ;
but on moving to Tezpur, a Black-water Fever district, he suffered severely until
from necessity he adopted the practice of taking quinine daily. Again in many
large tracts of India malaria may be very rife, but only at certain seasons. Thus
at Mian Mir which is one of the most notoriously malarious stations of the Punjab,
malaria is only really prevalent for two or three months in the autumn ; and
this remark applies more or less to the whole north-west, where rainfall is scanty
and there is a long period of drought associated with a cold season.
Briefly stated then we may assert that the great majority of Europeans in.
India are not exposed to Black-water Fever conditions, assuming that these are
life in an intensely malarious district. An objection has been raised in
regard to the British soldier, who is frequently exposed to malarious conditions
and often suffers severely from the effects of residence in a malarious station,
but apparently does not suffer from Black-water Fever. The British soldier,
however, is under continual medical inspection and is almost certain if he suffers
much from malaria to be invalided or drafted to some healthier place long
before the necessary condition of pre-disposition has been reached.
It is evident therefore, after a full consideration of the facts, that the argu
- m e n t s r a i s e d a g a i n s t t h e t h e o r y a s t o t h e m a l a r i a l o r i g i n o f B l a c k - w a t e r F e v e r
based upon the geographical distribution of that disease are no longer tenable
in so far as they relate to India ; for an examination of the real facts shows that
where in India there is intense malaria Black-water Fever is also found.
ASSOCIATION OF BLACK-WATER FEVER WITH MALARIA.
That it is among communities living under constant liability to attacks of
malaria that Black-water Fever is found to exist is very generally admitted ; but
it has been urged that this association of the two diseases is only accidental,
12
due merely to the fact that the conditions favourable for the occurrence and
propagation of malaria are also suitable for the existence of the special parasite,
which has been suggested as the cause of Black-water Fever. It is a very
important matter then to decide whether the association of the two diseaes is
mer e concur r ence or an act ual r el at i onshi p. St ephens, suppor t i ng t he vi ew of
the malarial origin of Black-water Fever, brings forward direct evidence for such
real relationship based on the results of the examination of the blood and tissues
in Black-water Fever. He tabulates the results obtained by competent observers
in ninety-five cases, and shows that in 95 per cent. of those observed the day
before the attack malarial parasites were present. He also points out that the
failure to find parasites in cases of Black-water Fever seen at a latter stage in
no way invalidates the fact that an initial malarial infection is almost always
present. Both he and Christophers had previously called attention to the
subsidiary signs of malarial infection almost invariably present in Black-water
Fever even when parasites were absent. Thus provided the case be seen fairly
early although no parasites may be detected careful search will frequently demon
-strate the presence of pigmented leucocytes, undeniable evidence of very recent
infection: moreover a differential count of the leucocytes will usually show the
large mononuclear increase commonly met with in malarial bloods. With few ex
-ceptions also examination of the tissues of fatal cases has nearly always shown
the presence of parasites or pigmented leucocytes, the latter being so distributed
as to point to very recent infection.
In accord with such observations are others of a clinical nature, and it is
significant that in Italy where the study of malaria has been carried on with great
thoroughness and minuteness, hœmoglobinuria of malarial origin has been fully,
recognised. Marchi afava and Bi gnami , di scussi ng cases of hœmogl obi nuri a, draw
attention to the fact that these conditions should be included under post-malarial
phenomena, that is those which occur not only after the cessation of the fever but
even when parasites have entirely disappeared.
In regard to the disease in the tropics one is forced also to the conclusion that
if Black-water Fever is not caused by malaria it is closely bound up with it, so much
so that, whenever a case is seen under conditions suitable for accurate observation,
it is almost invariably found that the attack has been associated with an im-
mediately preceding attack of malaria. Panse's cases are exceedingly convincing
in this respect ; studying patients in Europe, who suffered from relapses after
return from Black-water Fever districts, he frequently saw the onset of Black-
water Fever in the course of the malarial attack for which the patient had been
admitted, and with the progress of the case noted the more or less rapid dis
- a p p e a r a n c e o f t h e ma l a r i a l p a r a s i t e s .
13
In addition to these there are other facts of a more general nature which must
be given due consideration.
A most noticeable feature of Black-water Fever is that it occurs only in those
who have been resident for some considerable time under Black-water Fever
conditions ; fresh arrivals are never attacked. Berenger Feraud (44), in 185
cases, has seen only one under three months' resident, the remaining 184
occurring as follows :—
Under 1 year
..
. . . . . .
. .
..
. . . . 10
Second year
.
.
. .
. .
. .
. .
. . . . . 42
Third year ..
. .
. .
. .
. .
. . . . 7 9
Fourth year ..
.
0
..
. .
. .
..
. . . . 37
Fifth year . .
..
..
.
.
. .
. .
. . 9
At some later date
. .
.
.
. .
..
. . 8
This feature of the disease is of the greatest importance from an aetiologi
- c a l p o i n t o f v i e w . I t h a s b e e n a r g u e d t h a t i f B l a c k - w a t e r F e v e r w e r e a s p e c i f i c
disease it would not select persons just at this period of their residence. It is
suggested on the other hand that this peculiar incidence is explicable as due
merely to the accumulating chances of infection as time goes on. Such a view,
however, seems improbable in the face of the very remarkable uniformity in the
length of residence necessary before infection takes place. Later on we shall
see that in some countries at any rate this peculiar incidence cannot be explained
as a result of concomitant circumstances.
Quite a different state of things is found in malaria in which disease it is
customary for new-comers to a badly malarious country to contract infection
very shortly after their arrival ; and the same holds good in regard to suscept
- i b l e a n i m a l s b r o u g h t i n t o c o u n t r i e s w h e r e . p i r o p l a s m o s i s i s e n d e m i c .
Again Black-water Fever cannot be a complication of a mere attack of
malaria for there are no grounds for the belief that any single attack of malaria,
however sever e, can gi ve r i se t o hæmogl obi nur i a except i n a subj ect who has been
for some time resident under Black-water Fever conditions.
Another well recognised fact in regard to Black-water Fever is that it attacks
only certain susceptible races whilst the indigenous inhabitants of the countries
where the disease is prevalent apparently do not suffer. Thus in Africa besides
Europeans, Syrian hawkers, Indians, and even Negroes who have not been born
and bred under these conditions are liable to attacks.
These facts are in exact accordance with what we know of malaria in such coun
-tries as Tropical Africa, where the adult among the indigenous population pos
- s e s s e s a n i m m u n i t y a c q u i r e d b y r e p e a t e d i n f e c t i o n i n c h i l d h o o d . T h e
227 H. D.
14
non-occurrence of Black-water Fever among these people suggests either an
intimate relation of such immunity to malaria, or the assumption of an exact
parallel in the course of infection by some other parasite. That a man may
develop Black-water Fever, even for the first time, after his return to Europe, is a
fact generally recognised ; and many cases occur too long after leaving a district to
make it likely that the disease has been merely incubating. Of all diseases known
to us malaria exemplifies this peculiarity most, and that Black-water Fever also
shows it is a point not to be lightly dismissed. Panse's observations previously
quoted show that such attacks are invariably preceded by an active malarial infec
-tion ; and it is of course possible to explain attacks under such circumstances by
suggesting that the malaria has lowered the patient's resistance to the latent cause-
of Black-water Fever, which then asserts itself : or that the latter has stimulated
the malarial parasite into activity. In either case we must allow that Black-
water Fever, like malaria, can remain dormant in the system
THE PLACE OF QUININE IN THE MALARIAL HYPOTHESIS OF THE ORIGIN OF
BLACK-WATER FEVER.
There is no incompatibility between the view which asserts that quinine
administration, may produce Black-water Fever and the malarial hypothesis, if
we admit that the drug is only a determining cause, acting in conjunction with a
condition induced by previous intense malaria. The malaria hypothesis certainly
explains more readily than any other the undoubted action frequently exerted by
quinine in the precipitation of an attack of hæmoglobinuria.
Thus far we have summarized the recorded facts relating to the remoter
causes which act in the production. of Black-water Fever.
As to the mechanism and the exact process concerned in the terrific destruc
- t i o n o f r e d c e l l s w e h a v e n o c e r t a i n k n o w l e d g e ; b u t a s m a y b e e x p e c t e d t h i s h a s
been the subject of much speculation and conjecture.
The earlier writers held that Black-water Fever occurred only when, the red cell
destruction, usual to a malarial attack, exceeded a certain point. It was thought
that the liver, being then, unable to cope with the excessive amount of hæmoglobin
liberated allowed a portion of this to pass unchanged into the urine. Modifications
of this view are that Black-water Fever is the result of a peculiar virulence of the
malarial parasite brought about by certain conditions, such for example as their
transmission through a particular species of anopheles (Daniels) ; or that it is due
to an excess of toxines liberated by the parasite possibly under stimulation of
quinine (Grocco) (45).
15
The view that asserts Black-water Fever to be a specific disease and draws an
analogy between it and the piroplasmoses hypothecates that, instead of the red
cells being destroyed by the malarial parasites or their toxines, the effect is brought
about by a special parasite.
The act i on of qui ni ne i n l i ber at i ng hæmogl obi n f r om t he r ed bl ood cor puscl es has
been urged, and as Stephens and Christophers pointed out solutions above a certain
strength possess the power to hæmolise red cells. Marchoux (46) moreover asserts
that quinine is not excreted during the actual period of Black-water Fever ; but that
its presence may be demonstrated in the urine as that condition subsides. Bensaude
(63) believes that quinine has no action on intact red cells ; but that on the breaking
up of these cells, it may act on the liberated hæmoglobin converting it into meth
æ - m o g l o b i n , w h i c h i s a t o n c e e x c r e t e d b y t h e k i d n e y s a s a f o r e i g n s u b s t a n c e . H e
suggest s t hat t he haemogl obi næmi a r esul t i ng f r om an or di nar y at t ack of mal ar i a
does not usually produce hæmoglobinuria, normal haemoglobin being readily ab
-sorbed, but that with the presence of quinine in. the blood the reaction
referred to takes pl ace, and met-hæmogl obi nur-a resul ts.
A theory advanced by Thayer (47) in 1898, and subsequently adopted by
many others as a possible explanation of the mechanism of blood destruction,
assumed that the red cells became less resistant than normal to changes in
the osmotic tension of the plasma, and thus became liable to undergo solution.
Stephens and Christophers, investigating the condition of the red cells in
regard to their behaviour in different strengths of salt solution (isotonic
point), found that during an attack of Black-water Fever they might show an
even increased resistance to solution ; though the examination of tho red
cells of persons living under Black-water Fever conditions frequently show
ed them to possess less than the normal resistance. They conclude, therefore,
that the apparent raised resistance observed in Black-water Fever might be due to
the destruction of the weaker cells in the course of the disease, with the result
that only the most resistent cells remain after an attack. Certain French
workers have suggested, as an explanation of the phenomena observed in
Black-water Fever, the occurrence of what they termed " demineralisation of the
plasma," a condition in which they assume a reduction in the amount of salts
normally found in solution in the plasma, the resulting alterations in osmotic
conditions giving rise to destruction of the red corpuscles. More recently McCay
(48) has brought forward an interesting hypothesis based on the observation that,
after the administration of even a single dose of quinine sulphate, he finds a reduc
- t i on i n t he sal t - cont ent s ( hæmosozi c val ue) of t he pl asma. Thi s he ascr i bes
to the action of the acid radical and not to the alkaloid, as his observations
caused him to believe that the administration of quinine hydrochloride does
16
not produce the same effect. In the main his theory regarding Black-water
Fever is in agreement with that of the French observers previously alluded
to, the process of destruction being supposed to be the result of the " demineralisa
- t i o n o f t h e p l a s m a . " B u t u p t o t h e p r e s e n t n o o b s e r v e r h a s g i v e n s u f f i c i e n t d a t a
to enable an opinion to be formed as to the part played, if any, by osmotic variations
in the production of Black-water Fever.
Certain other theories have from time to time been put forward, the mention of
which serves to indicate the general confusion and uncertainty that has for long
existed regarding the process concerned in the blood destruction of Black-water
Fever. Thus Pellerin (49) advanced the view that the kidney was involved, the
h æ m o g l o b i n o b s e r v e d i n t h e u r i n e b e i n g d e r i v e d f r o m h æ m o r r h a g e s i n t o t h a t
organ or from the breaking down of infarcts ; and Plan has also cited as a possible
explanation a damaged condition of the kidneys in some way altering their relation
to the blood which, in the case of certain malarial subjects, might suffer injury and
b e d e p r i v e d o f i t s h æmo g l o b i n i n i t s p a s s a g e t h r o u g h t h e m. Y e r s i n ( 4 9 a ) announc
- i n g t h e d i s c o v e r y o f a b a c i l l u s i n t h e u r i n e s u g g e s t s i t s t o x i c e f f e c t s u p o n t h e
blood as a likely cause ; and Collet (49b), influenced perhaps by the fact that the
filtrate from cultures of the B. Megatherium may exci t e hæmogl obi nur i a when
injected into guinea-pigs, has mentioned possible infection by that organism as a
question to be considered.
But of the real mechanism of Black-water Fever we are still ignorant, though
certain observers, prominent among whom are the Italians, have definitely formu
- l a t e d t h e v i e w t h a t B l a c k - w a t e r F e v e r i s d u e t o t h e a c t i o n o f a s p e c i f i c h æ m o l y s i n ,
and one of them Casa grandi (50) states that he has succeeded in demonstrating in
malarial hæmoglobinuria such a hæmolysin masked by the presence of an anti
-hæmolysin. The study of the complex phenomena into which these researches
lead us is better discussed in relation to our own later investigation.
CHAPTER II.
NATURE OF THE DISEASE. SCOPE OF THE PRESENT ENQUIRY.
Black-water Fever is a disease localised to certain parts of the world ; it is Definition.
characterised by hæmoglobinuria. Apart from it hæmoglobinuria in man is rare,
being seen only in occasional cases of paroxysmal hæmoglobinuria or as a rare
complication in certain other diseases. On its importance as a bar to Colonial Importance
. expansion we need not comment, beyond saying that it is becoming more and more
recognised as a cause of death among Europeans in tropical countries. Few diseases
Clinica Features. have a more striking symptomatology, and an enormous literature has grown up Features.
dealing with the clinical features, diagnosis, and treatment of the condition.
Black-water Fever attacks as a rule men who have been more or less affected by the
ill health so frequent in tropical malarious countries, but sometimes the disease
strikes down a man who to his companions seems strong and robust.
There occur also in most cases what have been called prodromata. It is stated Prodromata.
by Nothnagel that these prodromata which resemble malaria differ in presenting a
more marked cold stage. Our own experience is that the prodromal fever can never
be differentiated from an ordinary malarial attack, which patients themselves
almost always consider it. Whether it is so in reality we must leave for further
discussion. In some Cases an intermission of the prodromal fever is followed by the
Black water which comes on as though it were the fever returning, while in others
no definite prodrome has been recognised.
Almost invariably a rigor followed shortly afterwards by the passage of hæmo- Onset.
globinous urine marks the onset of the disease. In the history of some cases it is
stated that abnormal urine was the first symptom, and that the rigor followed, but
this point we cannot ascertain with certainty. The urine first passed may be light
red in colour or quite dark. In an ordinary case it is lighter at first but soon Urine
becomes of a deep mahogany red colour or even nearly black, though even then it General.
appears claret coloured by transmitted light. With slight variations these characters
of the urine continue until hæmoglobinuria ceases or suppression supervenes. At the Temperature.
onset the temperature generally rises to 104° F. or even 105° F. and remains high
during the greater part of the paroxysm. But sometimes, especially in mild cases,
the disease runs an almost a febrile course. Throughout the attack there is often
extreme thirst, :and usually great nausea; and the bilious vomiting with the
jaundice has served to give the disease the name of " Bilious hæemoglobinuric General
Symptoms
. Fever."
(17)
227 H.D.