174 
MALARIA 
ruptly change to a tertian or double quar¬ 
tan, or the latter may similarly become a 
simple quartan. Such changes are attribu¬ 
table to the partial suppression of the cor¬ 
responding parasite generation. The na¬ 
ture of the mechanism, particularly the 
manner by which its action is limited to 
one of the parasite generations, is not un¬ 
derstood. Conversely, one may observe the 
introduction of new cycles in a tertian or 
quartan series, changing the attack to a 
quotidian. The effect of the new genera¬ 
tion may be manifested either gradually 
or abruptly. 
The paroxysm of intermittent fever pre¬ 
sents a succession of well defined stages. 
It may or may not be initiated by a cold 
stage, otherwise known as a chill or rigor. 
This stage is not, however, observed at the 
onset of primary infections, and it may not 
be evident until the disease has continued 
for one or two weeks. The cold stage is 
initiated by a sensation of chilliness, rap¬ 
idly progressing to shivering, often to an 
extreme degree. The skin is pale and 
bloodless, while the nails and lips are livid, 
the pulse is weak and rapid, and breathing 
is fast and shallow. Nausea is experienced 
and vomiting may be distressing. Convul¬ 
sions are not infrequent in children. The 
patient will usually request all available 
cover. Before the end of this period, which 
may last from 1-3 hours, the temperature 
is already above normal, and the patient 
experiences a brief interval of comfort. 
The temperature continues to rise and may 
attain considerable elevation, persisting for 
1-2 hours. The face is flushed, the skin 
hot and dry, the pulse is full and bound¬ 
ing, the head usually aches and some de¬ 
lirium may be evident. The bed clothes 
are discarded. The stage of fever is ter¬ 
minated by the appearance of a profuse 
perspiration, during which the tempera¬ 
ture rapidly falls to normal or below. The 
patient may feel exhausted, but after a 
brief sleep awakes refreshed and tranquil. 
This stage may last from 2 to 4 hours. 
The paroxysms of quartan last longer 
than those of vivax, and leave the patient 
with a sense of prostration not usually 
observed after the latter. In the intervals 
between paroxysms vivax patients will go 
about their usual pursuits. Some sporula- 
tion will have taken place before the onset 
of the rigor, but in general the rigor coin¬ 
cides with the time of sporulation. Most 
of the merozoites will have entered fresh 
erythrocytes before the end of the hot 
stage. 
Although, as shown, the initiation of 
symptoms coincides with the maturation of 
certain minimal numbers of parasites, the 
manner in which this process initiates the 
paroxysms has not been satisfactorily eluci¬ 
dated. Brown (1912) observed that a solu¬ 
tion of alkaline hematin injected intra¬ 
venously into rabbits produced a paroxysm 
characterized by a short prodromal stage, 
a stage of chill and rising temperature, 
and a hot stage. He concluded that the 
human paroxysm is, at least in part, refer¬ 
able to the toxic action of this pigment. In 
this connection it may also be mentioned 
that the studies of Sinton and Ghosh 
(Ghosh and Nath 1934) indicate that the 
haemazoin of P. knowlesi, whose pigment 
has been studied most intensively, appears 
to be identical with hematin. The rise in 
the plasma potassium level which occurs at 
the time of sporulation of the parasite 
has been studied by Zwemer, Sims and 
Coggeshall (1940). It is not clear whether 
the rise is attributable to the release of po¬ 
tassium from parasitized erythrocytes or 
has been liberated from body cells in gen¬ 
eral. That the high potassium values may 
be causably associated with the rigors is 
indicated by the observation of Beeson and 
Hoagland (1940) that the intravenous in¬ 
jection of 10 cc of a 10 per cent solution 
of calcium chloride will effect an almost 
instantaneous cessation of the rigor. In 
view of the relation of the adrenal cortex 
to the maintenance of a potassium equili¬ 
brium, continuation of these studies may 
have extremely significant results. Abrami 
and Senevet (1919) suggest that the par¬ 
oxysm, in part at least, is an anaphylactic 
reaction, resulting from the sudden libera¬ 
tion into the plasma of the protein of burst 
parasites. They point out a parallelism 
