210 
MALARIA 
(1932) was unable to demonstrate a hyper- 
laetacidemia in the blood of blaekwater 
fever patients. Cort (1929) referring to 
the hemoglobinuria, suggested that a spe¬ 
cific factor was indicated by the evidence, 
“supposedly a malaria parasite, but a vari¬ 
ety capable of elaborating a potent hemoly¬ 
sin.” Numerous writers have felt that the 
hemoglobinuric attack was an anaphylactic 
manifestation. Many other hypotheses, 
largely speculative in nature, have been 
offered to account for the phenomenon. 
For a synopsis of these the reader is re¬ 
ferred to Stephens’ (1937) very useful 
summary. 
Pathogenesis. The crux in the patho¬ 
genesis of blaekwater fever is the intra¬ 
vascular hemolysis, whatever its cause. 
Whether it occurs in the peripheral circu¬ 
lation or, as advocated by Yorke, Murga- 
troyd and Owen (1930), in the sinuses of 
the spleen and liver, is still an open ques¬ 
tion. Lytic substances have not been 
demonstrated in the serum or plasma of 
blaekwater fever patients. The last named 
authors consider that several hemolytic 
crises rather than an isolated hemolytic 
episode are involved in the erythrocytic 
destruction. They also note that but a 
small proportion of the released hemo¬ 
globin is found in the plasma. Fairley and 
Bromfield (1934) observed that in any 
intravenous hemolysis only a very small 
amount of the liberated oxyhemoglobin 
finds its way into the urine. They felt that 
the factor which provokes the hemolysis 
acts on the oxyhemoglobin to convert it 
largely into methemoglobin since the latter 
could not be demonstrated in washed cor¬ 
puscles of these patients and yet was the 
predominant pigment in the plasma. The 
latter workers concluded that much of the 
hemoglobin was taken care of by the 
reticulo-endothelial system and subse¬ 
quently the liver. In their cases there was 
evident a hyperbilirubinemia. Also in two 
patients studied for this purpose, a five to 
sevenfold concentration of bilirubin was 
found in the gall-bladder. As Ross (1932) 
said, it is possible that the relationship 
between the amount of hemoglobin con¬ 
verted into bilirubin and the amount ex¬ 
creted by the kidneys may vary in different 
individuals. He also noted that the libera¬ 
tion of hemoglobin in malaria is not usually 
followed by hemoglobinuria. If a renal 
threshold for hemoglobin exists and it “is 
not reached, the hemoglobin will be dis¬ 
posed of solely by the reticulo-endothelial 
system, whereas if it is exceeded both this 
and the kidney undertake the duty of dis¬ 
posing of the excess.” The rapidity and 
degree of hemolysis would obviously influ¬ 
ence this mechanism and the resulting 
symptoms. 
Onset and symptoms. Although Thom¬ 
son (1924) considered that there were 
premonitory symptoms evident in black- 
water fever and Manson-Bahr (1931) de¬ 
scribed a “pre-blackwater” state, Yorke, 
Murgatroyd and Owen (1930), as well as 
Ross (1932), could not support this opin¬ 
ion. It is quite possible that in some in¬ 
stances symptoms due to a concurrent 
malarial infection have been mistaken for 
premonitory symptoms of blaekwater fever. 
In the majority of instances, the hemo- 
globinurie paroxysm is ushered in by a 
rigor which varies widely in its severity. 
Similarly its duration may vary from a 
fraction of an hour to as much as four 
hours. In a study of 162 patients with black- 
water fever, Ross (1932) observed rigor to 
be present in 114, or 70 per cent. In about 
11 per cent of these the rigor did not occur 
until after the appearance of hemoglobi¬ 
nuria. Multiple rigors are not uncommon. 
Stephens and Stott (1915) noted that the 
mode in the time incidence of rigors in 
their patients occurred between 9 a.m. and 
12 m. Ross’ (1932) experience was the 
same. 
The constant accompanying symptom of 
the hemoglobinuric attack is fever, the 
duration of which varies with the course 
of the illness. The intimate association of 
pyrexia and the attack is of interest inas¬ 
much as Barratt and Yorke (1914) showed 
that the injection of red cell stromata (but 
seldom hemoglobin) intravenously into 
rabbits usually caused convulsions and 
death. Fever may not commence to rise 
