NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
2
of quinine in producing these attacks. Nevertheless it is stated that the
phenomenon is seen in malarial subjects, and the belief that malaria is in some way
concerned is clearly present ; Tomaselli definitely states that he considers a pre-
disposition the result of chronic malarial infection to be necessary before quinine
can have this action.
The later researches of Koch (7) show the same action of quinine in associa-
tion with the hæmoglobinuria of East Africa ; but Koch is especially concerned that
this condition is not malaria.
The idea then held was, it should be remembered, that a paroxysm of Black-
water Fever is a pernicious form of malarial attack ; and even at the present time
there is some confusion on this point, writers sometimes pointing out clinical dif-
ferences between an attack of malaria and one of Black-water Fever, as an arg
ument against the malarial origin of the latter.
Hence, when Koch finding few or no parasites in his cases comes to the con-
clusion that it is not malaria, we must interpret him as referring to the disease pro-
cess itself, with which he was concerned at the moment, and not with the conditions
which may have given rise to it. Koch's researches were the first to show definitely
that Black-water Fever is, in no sense, an attack of malaria ; though Grawitz and
Kohlstoch (20) had as early as 1892 given up the use of quinine in the treatment
of their cases, because on examination of the blood they could find no malarial
parasites. Since Koch, almost all those who have studied the disease have come to
the conclusion that Black-water Fever is a condition quite distinct from, and
dependent on, a different morbid process to that concerned in a malarial attack.
II.
THAT BLACK-WATER FEVER IS QUININE INTOXICATION.
That quinine under certain circumstances can induce attacks of Black-water
Fever is undoubted. It is usual, however, for Europeans in the tropics to take
quinine when they feel the onset of fever; and it is to be expected that in very many
cases of Black-water Fever there will be a history of previous quinine adminis-
tration ; but a large number of cases are recorded in which, time after time, a dose
of quinine has been followed with clockwork regularity by the appearance of
hæmoglobinuria.
Even under ordinary clinical conditions, it is the experience of most observers
that attacks of Black-water Fever have in most cases been induced by quinine, the
symptoms commencing within four or five hours of its administration. On the
other hand, a number of cases have been recorded in which the patient had not taken
quinine prior to his attack.
3
A study of recorded cases seem to point to the existence of two different
conditions under which this drug may act in the production of hæmoglobinuria.
In one class of case the drug may have even been frequently employed with
benefit in the treatment of malaria ; until perhaps one day, when a dose bas teen
taken for what has been supposed to be an actual or impending attack of malarial
fever, its administration is followed in the course of a few hours by the onset of
hæmoglobinuria. In these cases it frequently happens that subsequent doses
of quinine fail to produce a repetition of the symptoms ; this is the condition met
with in the majority of Black-water Fever cases.
In another category must be placed those much rarer cases where quinine even
in minute doses is invariably followed by the onset of hæmoglobinuria.
The view that quinine alone is sufficient to bring on attacks of the disease,
apart from an acquired predisposition, has been upheld by only a few observers.
Without exception, even those who have laid the greatest stress upon the part
played by this drug in the production of hæmoglobinuria, have taken care to qualify
their statements by pointing out that a special acquired predisposition is necessary.
So far as we are aware there is no record of any case in which the administra-
tion of quinine to healthy persons has produced hæmoglobinuria. The ordinary
effects of this drug upon the organism are well known and easily recognised ;
cinchonism or true quinine intoxication is a familiar phenomenon among these
who have to make frequent use of the remedy ; and its occurrence almost always
bears some direct relation to the amount absorbed ; hæmoglobinuria is not a
symptom of this condition, and has never to our knowledge been recorded as oc-
curring in the case of persons in whom the accidental administration of an overdose
has produced fatal results.
It is true that more or less concentrated solutions of quinine will in vitro pro-
duce hæmolysis of human blood corpuscles suspended in salt solution; but as will
be seen later, when we give our own observations, it does not excercise this effect
upon red cells suspended in human blood serum ; and there is no evidence to show
that quinine exerts a directly destructive effect upon normal human erythrocytes
within the body.
Obviously the action of quinine in these cases must be clearly distinguished
from that of such a substance as chlorate of potash, which, innocuous in small
doses, in larger quantities produces markedly toxic symptoms, prominent among
which is red cell destruction and hæmoglobinuria (methæmoglobinuria). Admin-
istered in poisonous doses, the action of this substance upon a person can be
foretold with certainty, quite apart from any consideration of such questions
as special predisposition, place of residence, country, or any other circumstance.
4
But quinine never produces hæmoglobinuria except in the case of. persons
who are the subject of predisposition, acquired only after residence under
special circumstances, in certain places ; and even in such persons . the
occurrence of hæmogiobinuria can never be prognosticated with any certainty,.
save in a fractional percentage of ,cases. That cases do exist, in which this
acquired idiosyncrasy is so marked that even the most minute dose of quinine
is followed within a few hours by the passage of hæmoglobinuria urine has
been well established; and it is the recognition of this fact which has led to the
attempt to distinguish a special form of quinine hæmoglobinuria in contradistinc-
tion to the class of case in which the relation of quinine administration to the
onset of this symptom is not so evident, or in which quinine can be definitely ex-
cluded.
Many cases of Black-water Fever occurring without the administration of qui-
nine have now been recorded by A. Plehn (4) (twenty-two); Cardamatis (5) (thirty.
two) ; Theophanidis (5) (ten), Korylos (5) (three), Shropshire (8) (fifteen per cent
of apparently one hundred and seventy seven cases) and many other observers.
III.
THAT BLACK-WATER FEVER IS A DISTINCT DISEASE DUE TO SOME SPECIFIC ORGANISM.
As a result of the kindling of interest in Tropical Parasitology, which followed
upon Manson's and Ross's discovery of the mosquito cycle of the malarial parasite,.
protozoal infections in animals (such as the Piroplasmoses) have been brought
prominently before the minds of those engaged in tropical research. The import-
ance of not overlooking new human parasites was still further accentuated by the
discovery of the parasite of Kala-azar, and the danger of confusing diseases of some-
what like symptoms rendered very clear by the fact that up to this time infection
by the Leishman Donovan Body, had been everywhere classed as malaria.
Even in 1898 the apparent resemblance shown by Black-water Fever to the
hæmoglobinuria of animals associated with piroplasma infections naturally pre-
sented itself to anyone studying the disease. No one has succeeded, however, in-
spite of much attention, in finding in the blood or organs or Black-water Fever cases
a special parasite of this nature. Such a view of the origin of the disease is there-
fore at present not supported by any facts ; and it is even made somewhat impro-
bable by a study of all that is known of the condition, notably the amount of posi-
tive evidence pointing to a malarial origin, and the difficulty of fitting in a special
parasite view with what we know of the action of quinine in this disease. The
demonstration of the presence or absence of a special parasite is, however, of such
fundamental importance, that until absolutely disproved the possibility of its
presence must be given every consideration.
5
IV.
THAT BLACK-WATER FEVER IS THE RESULT OF AN INDUCED CONDITION BROUGHT
ABOUT BY REPEATED MALARIAL INFECTION LASTING OVER A CERTAIN TIME.
Most modern observers have accepted this view, first brought forward by
Stephens and Christophers (9) and later strongly supported by Panse (10).
These observers, while agreeing so far with Koch that the morbid process con-
cerned cannot be considered as one bearing any true resemblance to a malarial
attack, formed the conclusion that it was exposure to severe and long continued
malarial infection which brings about the condition of unstable equilibrium in the
blood necessary before quinine, or any other determining factor, can bring about
an attack of the disease.
Since then much confirmatory evidence has been amassed showing that Black
-water Fever is clinically most closely associated with malarial infection. But
this view of the origin of the disease is not universally accepted, and certain ob-
jections have been raised, more particularly by these who maintain that the .disease
is a specific one with no real relation to malaria. This being so it will be necessary
to pass in brief review the facts that have been ascertained in regard to the relation
of Black-water Fever to malaria, and to consider in detail the objections that have
been raised against the theory that it is of malarial origin.
GEOGRAPHICAL DISTRIBUTION.
The geographical distribution of Black-water Fever we now know to be very
wide. In Europe it is recorded from Italy, Sicily, Sardinia, Greece, and Spain,
from Mery in Russia along the banks of the Danube, in the Caucasus and from
Turkey. In Italy as Stephens (11) points out it occurs more especially in South
Calabria, where the mortality from malaria, according to Celli . , reaches 9 to 9.9
per 10,000, a rate double that in the Roman Campagna and more than ten times
that in Northern Italy.
In Asia the disease has been met with in Cochin China, Tonkin, and Siam, and
it occurs also in India, Burmah, the Straits Settlements, Java, Sumatra, New Guinea,
and the New Hebrides ; it has also been described as occurring among certain
communities in the more malarious parts of Palestine.
Throughout Tropical Africa it is the chief cause of mortality among Europeans ;
and it is found also in Madagascar, Burbon, Mauritius, Reunion, and the Comorro
Islands.
In the West Indies it was known to the early French observers ; and in Nicara
-gua, Costa Rica, French, British and Dutch Guiana, Brazil, Central America, and
Cuba it has been recognised for a considerable time ; while American physicians
227 H.D.
6
from some of the Southern States were among the first observers to describe the
disease, which has a wide distribution throughout the more malarious portions of
that country.
That this distribution of Black-water Fever agrees in the main with that of the
greatest intensity of malaria is evident; but it has been objected:
(1.) That in the case of many of these countries the disease has only recently
been introduced.
(2.) That the coincidence with malaria is not exact ; and more specially
that there are countries notoriously malarious in which Black-water
Fever is very rare, or does not exist.
The converse of this latter suggestion, namely, that Black-water Fever occurs
in comparatively non-malarious districts has not so far as we are aware been ad-
vanced.
(1) The belief that Black-water Fever had a peculiar and restricted distri-
bution has been emphasised in most text-books until quite recent years. To ex-
plain the constantly increasing area from which the disease is now being recorded
some writers have advanced the view that in many of these countries, as for ex-
ample India, the disease has only recently been introduced. This does not seem
to us a conclusion warranted by the facts.
In making an examination of the literature of Black-water Fever one cannot
help remarking that the recognition of its geographical distribution, as we now
know it, has been a very gradual process, in the history of which it is possible to
distinguish certain definite periods.
The first may be called the French Period, and dates from the time when Le-
beau (12), Daullé (13), and Le Roy de Mericourt (14) first described the disease
" Fievre Bilious Hæmaturique" as occurring in Madagascar and some of the ad-
j acent islands. Almost immediately other French physicians reported finding
the same type of fever in Senegambia, Senegal, Gaboon, Guiana, the Antilles,
and other parts of the West Indies.
Until 1858 nothing' was heard of hæmoglobinuric fever outside French pos-
sessions. But in that year Verratas (15) a Greek, described what he termed
" Quinine Hæmoglobinuria"; and two years later a similar communication was
made by another Greek, Papabasilos (16).
The American period commences from about 1860. The disease was first
described by Doctor Cummings (17) of Louisiana in 1859, and it was shortly
afterwards recognised in Alabama and Texas (1866). From this time onward it
was reported with increasing frequency from many parts of the Southern States
of North America.
7
The Italian period may be said to date from 1874 when Tomaselli (6) pub-
lished his classic monograph upon Quinine Intoxication, describing cases of
hæmoglobinuria seen by him in Sicily. Almost immediately, interest being
aroused, the disease was shown to occur also in Sardinia and Southern Italy.
About this time too the Dutch physicians (Jacobs) (18) in Java, Guinea
and New Guiana discovered the presence of the affection in those colonies.
From 1890 commences the German period, with Schellong's (19) well known
work in Kaiser Wilhelm's Land ; and from this time, co-incident possibly with
the stimulation of German colonial activity, we find numbers of investigators
belonging to that nation recording observations upon the disease from the Kam-
eroons, German East Africa, and New Guinea. Prominent among the names
of these workers are those of Grawitz and Kohlstock (20), Steudel (21), the two
Plehns (3 and 4), Ziemann (22), and Koch (7).
Up to comparatively recently little or nothing of the disease had been record-
ed from British dependencies although French observers had already reported it
from various parts of Africa, Asia, and America ; and though Crosse (22a) and
Manson (22 b) had called attention to the disease in 1892, and from time to time
a few isolated papers upon the subject had appeared in English medical journals,
no adequate account of the condition had yet found a place in textbooks avail-
able to the majority of British physicians practising abroad.
But in 1898 as an immediate result of Manson's and Ross's great discovery
a sudden and extraordinary awakening of interest in Tropical Disease was arous-
ed throughout the British Empire, and within the half dozen or so succeeding
years we find Black-water Fever recorded by British observers from British Cen-
tral Africa (Moffat) (23), Stephens and Christophers (9), Daniels (24), Hearsey
(25), India (Powell) (26), Seal (27), British Honduras (Brown) (28), Rhodesia,
Uganda (Moffat) (29), Nigeria (Hanley) (30), British East Africa (Daniels),
The Soudan (Ensor) (38), China (Wenyon) (31), British Malaya (Wright) (34),
Burmah (Finke) (35), Syria. (Cropper) (36), Masterman (37), and elsewhere. It is
obvious that a recent introduction of the disease into these countries is most
unlikely.
(2) In regard to the objection that the distribution of Black-water Fever is
more restricted than that of malaria, Stephens has pointed out that, in many
countries where malaria is known to occur, the inhabitants are not exposed to the
disease in an intense form ; and that if we consider the distribution of intense
malaria we shall find that it coincides very closely with that of Black-water Fever.
It has been stated that the distribution of Black-water Fever is not that of
any of the known varieties of the malarial parasite ; but it is difficult to see how
8
such a statement can be upheld for all we can say at present in regard to the dis-
tribution of the different varieties of malaria is that, as one approaches the tropics,
one finds infection with the malignant tertian form more and more frequent, a
statement which applies also to the frequency of Black-water Fever : and that
Blackwater Fever can arise from only one variety of the malarial parasite ,we
have at present no proof.
It is then only with the intensity of malaria that we are concerned, and the
only portion of the objection that seems to merit consideration is the statement
that there are certain countries which are intensely malarious in which Black-
water Fever either does not occur or is very infrequent. Though it is repeatedly
averred that this is the case, the basis of fact for such a statement is extremely
slight.
It has been stated that Black-water Fever is rare in Algeria ; but the brothers
Sergent (39) have within recent years recorded 31 cases with 22 deaths, and Coste
(40) has reported another 25 cases, proving that the condition is far more
frequent than has previously been supposed.
Black-water Fever is also stated not to occur in Egypt, a very malarious
country ; but it is significant that it is common in parts of Palestine ; and it is
being reported from the Soudan north of Fashoda.
The greatest stress of all is laid on India. It has been stated that, whilst
people in India are much subjected to malaria and are accustomed to take
quinine freely, there is no Black-water Fever ; and it is the same view which has
caused this country to be cited so frequently in the present connection.
Manson (42) emphasizing the objection to the malarial origin of the disease
says, speaking of Black-water Fever : " It is exceedingly common among the few
Europeans who live in Tropical Africa, it is practically unknown amongst the
many thousands of Englishmen who live in the fever haunts of India."
These views would no doubt be readily echoed by numbers of medical
men in India, who affirm, and we believe often quite rightly, that they have
never encountered the disease.
At first sight therefore it might appear that there were grounds for the asser-
tion that in India while severe malaria is common Black-water Fever is gene-
rally speaking rare or absent, and should this view prove on enquiry to be
correct, it is obvious that it would form a serious objection. to the theory based
upon the suggested intimate relations between these diseases. Before giving
weight to this objection it is necessary to consider the history of Black-water
Fever in India and to note the circumstances in which it has appeared.
9
Maclean (43) in his lectures upon the Diseases of Tropical Climates (1886) states,
with reference to the urine in certain cases of remittent fever, that " In some
cases recorded by me there was profuse secretion of bloody urine, which last-
ed until convalescence set in." But Powell (26) was the first actually to recog-
nise the disease, when he recorded the occurrence of a number of cases in Cachar.
A little later other cases were reported from Sylhet, the Darjeeling Terai,
Cachar, and the Duars. Stephens and Christophers, who described four cases
from the Duars, also note in their report to the Royal Society that cases had been
met with in other parts of India, including Hazaribagh, Meerut, Roorkee, and
Secunderabad, while the disease is common among the Europeans in the Jey-
pore Hills. They also mention that cases of the disease have been seen from time
to time in the hospitals of Calcutta and Madras, though these may have originated
in other places.
Since then Christie (32) has recorded three cases from Canara in the Born-
bay Presidency, and DeCruz (33) a further number of cases among both Europeans
and natives in the Jeypore district.
Nor are these the only places in which Black-water Fever may occur in India.
In our list of cases given in the present memoir we are able to record one
in a European from Purulia in Chota Nagpore ; and Colonel C. J. Bamber, I.M.S.,
has drawn our attention to the death of a European officer from Black-water
Fever in the Lower Godavery district, a reputedly malarious part of Southern
India. Doctor Gopal Chatterjee has also told us of two cases in Bengalis living
near Calcutta, where he states there are some very malarious villages. The
family in which both cases occurred had for some time been suffering from malaria,
and he had on several occasions found them to have malarial parasites in their
blood. Doctor Bramacheri has given us particulars of a case arising in a native
of the Burdwan district.
These represent, we feel sure, only a few of the districts in which the disease
may be occasionally met with. Many other likely areas probably have no Euro-
pean residents ; but in others where Europeans and educated natives reside we
suspect that careful enquiry would show the disease to exist.
A common belief, that a disease having such a striking symptomatology as
Black-water Fever can scarcely be overlooked, is not borne out by experience ; it is
only too frequently entirely unrecognised or confused with other diseases, when it
occurs in districts in which it has not previously been diagnosed. As a rule where
Black-water Fever occurs, men are for the most part living remote from civilization,
and the disease being a sudden one and soon over a case except under special
circumstances is often not seen by any medical man. Again in all such
227 H. D.