194 
MALARIA 
finally the paroxysm may occur on a dif¬ 
ferent cycle day. Such anticipation or 
postponement of paroxysms, when occurring 
consistently, may have part basis in post- 
or pre-maturation of the cycle and part 
in some immunological factor, of which we 
are not yet cognizant, which results in the 
ultimate simplification of the pattern of 
the paroxysms. 
Some authors have stated that most 
malarial paroxysms occur in the morning 
and that this point is of value in differ¬ 
ential diagnosis. Craig (1909) noted that 
the paroxysms of quartan malaria usually 
occur during the afternoon or late morning. 
In our series of quartan infections, almost 
three-quarters of the paroxysms of arti¬ 
ficially inoculated patients occurred post 
meridian. The largest single group, on 
the basis of eight-hourly divisions com¬ 
prised over 33 per cent which took place 
between noon and 8 p.m. Of the naturally 
induced paroxysms, 94 per cent occurred 
post meridian and 52 per cent between noon 
and 8 p.m. Of considerable interest in this 
connection are the observations of Young, 
Coatney and Stubbs (1940). They found 
that the sporulation time of P. malariae 
could be altered by changing the hours of 
the patients’ activities and rest. 
Anemia. The development of anemia is 
much slower in quartan infections than in 
those due to P. falciparum or P. vivax. 
This may be due partly to the lower para¬ 
site densities usually characteristic of quar¬ 
tan malaria and partly to the tendency, as 
shown by the writer (1939a), of P. malariae 
to invade chiefly the mature cells, thus not 
interfering with the replacement. 
In our series it was noticeable that the 
rate of decline of the erythrocytes and 
hemoglobin was most rapid during the first 
and second months of clinical activity, and 
slowest in the case of the shortest clinical 
attacks. Of interest is the fact that in the 
case of patients with the infections of long¬ 
est duration, the erythrocyte count com¬ 
menced a sustained increase several months 
prior to the cessation of clinical activity. 
A marked increase in the mean erythrocyte 
level was noted during remissions. Those 
with the longest recurrences, who had had 
the shortest initial attack, experienced a 
greater diminution of erythrocytes during 
the recurrence than during the initial 
period of clinical activity. In general the 
trend of the hemoglobin fluctuations paral¬ 
leled that of the erythrocytes and the color 
index was less than unity. 
Splenomegaly. We have noted that the 
spleen does not attain the size in quartan 
infections that it may in P. vivax attacks. 
The period of detectable enlargement is 
proportional to the duration of the clinical 
attack and splenomegaly takes place more 
rapidly in the case of short clinical attacks 
and more slowly in the long incursions. No 
spleens have been noted to extend below the 
umbilicus. Enlargement of the spleen dur¬ 
ing the course of an infection is not neces¬ 
sarily consistently progressive to the maxi¬ 
mum but may be interrupted by contrac¬ 
tions. Splenomegaly developed very slowly 
in two naturally inoculated patients and 
was not detected in a small group of negro 
patients. 
Albuminuria and oedema. At some time 
during the course of the attack all of our 
patients developed some degree of albu¬ 
minuria and in the case of 14 it amounted 
to more than a trace; the clinical attack 
had to be interfered with in 12 of these. 
The tendency toward an appreciable degree 
of albuminuria was less marked in the 
naturally induced infections (due to fre¬ 
quency of quartan courses ?). Occasionally 
when the quantity of albumin has been re¬ 
corded as 4 plus we have noted erythro¬ 
cytes, even in large numbers; hyaline and 
granular casts have not been uncommon 
with lesser degrees of albuminuria. We 
have had no evidence of hemoglobinuria in 
our cases. 
Of 6 patients who showed varying degrees 
of oedema, 4 showed albuminuria to the 
extent of 4 plus. In the other 2 the albu¬ 
minuria did not exceed a trace. James 
(1910) cited the case of 2 patients in whom 
there was a marked oedema and clinical 
signs of acute diffuse nephritis. They gave 
a history of mild attacks of fever over a long 
period of time and had taken no quinine. 
Giglioli (1929), working in British Guiana, 
stated that untreated quartan malaria was 
