THE INFECTION IN THE INTERMEDIATE HOST: 
BLACKWATER FEVER 
By S. F. KITCHEN 
INTERNATIONAL HEALTH DIVISION, ROCKEFELLER FOUNDATION, TALLAHASSEE, FLA. 
This syndrome is now generally accepted 
to be intimately related to malaria although 
the exact nature of the relationship is still 
the cause of much controversy. 
Etiology. Forty years ago Marchiafava 
and Bignami (1901) speaking of instances 
of this disease, in some of which attacks 
malaria parasites could not be found, and 
some of which were cured and others pro¬ 
voked by quinine, stated: “But in all these 
cases, although occurring under the most 
varied conditions, the one fact which can 
be affirmed with certainty is the etiological 
importance of the malarial infection.” 
Stephens (1913), working in the Panama 
Canal Zone, offered statistical evidence sup¬ 
porting this relationship as regards inci¬ 
dence. Deeks and James (1911), studying 
blackwater fever in the same region, con¬ 
sidered malaria as “a predisposing factor 
of great importance” and showed that 
“hemoglobinuric fever prevails among all 
races in direct proportion to the amount 
of malaria among them”; they went further 
and concluded that the amount of black¬ 
water fever is in direct proportion to the 
intensity of estivo-autumnal malaria. Foy 
and Kondi (1937), working in Macedonia, 
also established a definite correlation be¬ 
tween malaria and blackwater fever in a 
malaria-sensitized population. Neverthe¬ 
less there are yet many points concerning 
hemoglobinuric fever that are obscure. 
On the other hand, however, we recog¬ 
nize several established facts regarding its 
etiology: (a) It occurs chiefly in non- 
immune persons who are relatively recent 
arrivals (usually a few months to a few 
years resident) in endemically malarious 
areas. Boss (1932) has shown that it is 
particularly prevalent in persons with oc¬ 
cupation in which the opportunity for con¬ 
stant exposure to infected mosquitoes is 
present. Residential environment is like¬ 
wise important in this connection, (b) In 
the case of those who develop blackwater 
fever there is usually, though not invari¬ 
ably, a history of repeated attacks of 
malaria. Ross (1932) concluded that fre¬ 
quency of previous malarial infection in 
patients with blackwater fever was a fac¬ 
tor of undoubted significance. Leishman 
(1912) stated that “there is certainly no 
direct relationship to the number or 
severity of the antecedent attacks of ma¬ 
laria. ” We have not observed any evidence 
of blackwater fever in over 200 patients 
with naturally induced P. falciparum in¬ 
fections ; most of these have been in colored 
persons and few have been reinfected 
James, Nicol and Shute (1932) reported 
two instances of hemoglobinuria in their 
induced P. falciparum infections. Accord¬ 
ing to Stephens (1913), it is usually during 
the second year of residence in the tropics 
that the greatest incidence of blackwater 
fever is noted and he considered this as 
evidence of the part played by repeated 
malarial infection. The disease has not 
been known to occur where malaria does 
not exist, (c) Negroes and other native 
races of endemic zones show a high degree 
of immunity to blackwater fever and this 
immunity is noticeably linked up with that 
to malaria. Furthermore, measures which 
decrease the incidence of malaria will do 
likewise for blackwater fever. 
The common association of blackwater 
fever and P. falciparum malaria has un¬ 
doubtedly led some workers, such as Robert¬ 
son and Moore (1923) and Thomson 
(1924), to regard the former disease either 
as a pernicious form of the latter or as the 
same disease. Marchiafava and Bignami 
(1901), however, had stated “that a special 
place should be reserved for hemoglobi- 
