PATHOLOGIC ASPECTS OF HUMAN MALARIA 
215 
(Cannon, Sullivan and Neckermann 1932). 
They differ particularly from other organs 
in possessing blood sinuses in addition to 
ordinary capillaries; this changes the char¬ 
acter of the blood flow. These sinuses, and 
the loose tissues around them, are lined 
with or contain potentially phagocytic cells 
along or between which the parasitized 
erythrocytes must pass. While doing so the 
parasitized cells are very likely to come into 
contact with phagocytes and be engulfed. 
Proof of this is seen in benign malaria, 
where these macrophages become engorged 
with parasites and pigment but eventually 
cleanse the blood of infected red blood cells. 
In malignant malaria, on the other hand, 
such phagocytosis, for various reasons, is 
presumably less effective, and the infection 
progresses at times to the lethal stage. 
Phagocytosis, therefore, stands out as the 
determining element in the progress of 
malaria infection and in the resulting 
pathologic picture of the disease. 
3. Because of this selective localization 
of the parasites, these three organs under¬ 
go hypertrophy, hyperplasia and pigmenta¬ 
tion, all characteristic features of the 
pathologic response; and in these processes 
additional pathologic complications may 
ensue, as, for example, fatty and toxic 
changes in the liver, hemorrhages or infarc¬ 
tions of the spleen, and focal necrosis of the 
spleen and bone marrow. The main reac¬ 
tion between tissues and parasites in all 
organs, however, is essentially mesenchymal 
and the parenchymal lesions which may 
occur are presumably secondary and for the 
most part incidental. 
4. Participation of lymphoid tissues is 
active in all three organs, although most 
evident in the spleen, as seen by the pro¬ 
liferative reactions of the splenic corpuscles 
and by the toxic necrosis, pigmentation, and 
“depletion” of the lymphoid structures. 
It is probable, therefore, that, as emphasized 
in the studies of simian malaria by Talia¬ 
ferro and associates (1936; 1937; this vol¬ 
ume p. 239), the lymphoid tissues constitute 
an important part of the reaction to malarial 
infection and act as a sort of “backlog” or 
mesenchymal reserve from which mono¬ 
nuclear phagocytes may be derived. 
5. The parasitization of the red blood 
cells and their dissolution during the course 
of schizogony leads to the anemia, so im¬ 
portant a feature of malaria. This varies 
in severity from the comparatively mild 
forms in chronic benign malaria to the ful¬ 
minating types seen in pernicious malaria 
or in blackwater fever (Whipple 1927). 
The influence of the infection upon the bone 
marrow is further reflected in the failure 
of the polymorphonuclear leukocytes to en¬ 
ter the blood stream, so that the usual blood 
picture is that of a leukopenia with a rela¬ 
tive lymphocytosis. The large mononuclear 
elements, however, are frequently increased 
in the blood and at times may comprise 
twenty-five per cent or more of the colorless 
corpuscles. 
6. Parasitic localizations in organs other 
than the liver, spleen and bone marrow are 
exceptional, and when they occur, as in 
pernicious malaria, are supposed to be due 
to embolic occlusions of capillaries and 
arterioles. These embolic occlusions ap¬ 
parently follow no general rule, although 
they are seen more frequently in the brain, 
heart and gastrointestinal tract. They may 
occur, however, in almost any organ of 
the body, as for example in the kidneys, 
pancreas, abdominal fat, thyroid glands, 
lungs or suprarenals. 
7. Because of these vascular disturbances, 
widespread toxic and necrotizing lesions 
may develop. These include the so-called 
ring hemorrhages of the brain, the peri¬ 
vascular areas of necrosis, the so-called 
malarial granulomas, the degenerative 
changes in the cells of the nervous tissues, 
the toxic changes in the tubules of the kid¬ 
neys, particularly as seen in blackwater 
fever, and the hemorrhagic and necrotizing 
lesions in the myocardium, suprarenals 
and elsewhere (Dudgeon and Clarke 1917; 
Gaskell and Millar 1919-20; Allen 1926). 
Consideration of these pathologic facts 
suggests the similarity of malaria to bac¬ 
terial infections and engenders the hope 
that common pathologic principles may 
govern both types of infection. Looked at 
from the standpoint of an infectious dis¬ 
ease, malaria, on the basis of an evaluation 
of its pathologic effects, may be considered 
