228 
MALARIA 
tissue respiration and stimulates compen¬ 
sating mechanisms such as respiration and 
heart rate. The dilution of the blood 
plasma may also affect tissue metabolism 
and encourage edema. 
Reticulocytes are usually found in the 
blood in proportions slightly higher than 
normal during the course of malarial in¬ 
fection and usually are increased greatly 
after the acute stage of the disease has 
passed. The maturation of reticulocytes 
after discharge from the bone marrow into 
the circulation has been questioned by 
Mermod and Dock (1935). These authors 
found that reticulocytes were less resistant 
than mature erythrocytes to certain he¬ 
molysins such as saponin, and stated that 
reticulocytes did not participate in carry¬ 
ing oxygen to the tissues because they used 
oxygen themselves. The question as to 
whether, as they state, reticulocytosis is a 
necessary evil preceding erythrocyte regen¬ 
eration or is a direct evidence of regenera¬ 
tion must await further investigation. The 
attention which reticulocytes have received 
recently in relation to their infection by 
malaria parasites deserves special com¬ 
ment. It has been definite established that 
P. vivax has greater affinity for reticulo¬ 
cytes than for mature erythrocytes. A 
number of workers have also shown that 
P. falciparum, is apparently indifferent to 
the stage of erythrocyte which it invades, 
and Kitchen (1939b) has produced evidence 
that P. maXariae prefers mature erythro¬ 
cytes to reticulocytes. 
White Blood Cells 
Attention has already been called to the 
stimulation of the monocytes of the blood 
as part of the reticulo-endothelial system. 
Mulligan (1929), using supravital stains 
demonstrated that the reticulo-endothelial 
cells in the peripheral blood were increased 
in both acute and chronic malaria. In 
acute malaria both the younger monocytes 
and the older clasmatocytes were markedly 
increased. In chronic malaria the increase 
in monocytes was similar to that in acute 
cases but the increase in clasmatocytes was 
less. It is probable that these increases in 
circulating mononuclear cells reflect the in¬ 
creased activity of the reticulo-endothelial 
system rather than increased leucopoietic 
activity of the bone marrow. 
Reticulo-Endothelial System 
The stimulation of the reticulo-endo¬ 
thelial system throughout the body in ma¬ 
laria has received great attention and is 
manifested histologically by both a hyper¬ 
plasia of the system, chiefly of the spleen, 
bone marrow and liver, and an increased 
phagocytic activity of the individual mac¬ 
rophages. Increase in phagocytic activity 
of the individual macrophages is at first 
gradual, but Cannon and Taliaferro 
(1931), Taliaferro and Cannon (1936) 
and Taliaferro and Mulligan (1937) have 
demonstrated that in bird and monkey 
malaria there is a marked increase in phag¬ 
ocytic activity at the time of the sudden 
decrease of the parasites. They interpreted 
this as an immune reaction of the opsonic 
type and regarded it as the principal im¬ 
mune phenomenon in malaria (Taliaferro, 
this volume, p. 239). The recent demon¬ 
stration of positive complement fixation 
reactions (Coggeshall and Eaton 1938a), 
agglutination reactions (Eaton 1938), and 
protective substances (Coggeshall and 
Kumm 1937) indicates the presence of 
humoral antibodies which may also have 
their source in the reticuloendothelial cells 
(Taliaferro, this volume, p. 239). 
It is apparent that in malaria all of the 
functions of the reticulo-endothelial system 
are probably brought into play. These 
functions include phagocytosis, the forma¬ 
tion of bilirubin from hemoglobin, and the 
formation of various immune substances. 
In addition, the apparent absence of para¬ 
sites from the blood for the first few days 
following infection with sporozoites (Boyd 
and Stratman-Thomas 1934c) indicates that 
the reticuloendothelial system may serve as 
an incubator for the development of mero- 
zoites from sporozoites and may hold the 
secret to true chemoprophylaxis in malaria. 
Circulation 
The effect of malaria on the circulation 
