PATHOLOGIC ASPECTS OF HUMAN MALARIA 
219 
is noteworthy is the vascular injury, as re¬ 
vealed by generalized fatty degeneration, 
hemorrhages into the brain, purpura, etc. 
Such a condition should certainly predis¬ 
pose to loss of fluid elements of the blood 
similar to that in shock, and as it does par¬ 
ticularly in the algid forms of pernicious 
malaria. There is also evidence of hemo- 
concentration in pernicious malaria at 
times, which might also lead as aforemen¬ 
tioned, to an increased tendency to blockage 
of capillaries. 
A factor not adequately considered in the 
genesis of capillary occlusion in pernicious 
malaria is that of agglutination of parasi¬ 
tized red blood cells, although Cropper, 
many years ago (1908), in smears taken 
from the blood of a patient two hours be¬ 
fore death from pernicious malaria de¬ 
scribed the clumping of red cells in masses, 
a phenomenon which he said “so far as I 
know has not been previously observed in 
peripheral blood, though it is commonly 
seen in the brain and other organs affected 
in pernicious attacks after death. ... I 
would conjecture that such masses must 
occur in the internal organs in intense in¬ 
fections, but that as a rule they are not seen, 
being eliminated and filtered out from the 
blood in the spleen or liver, thus giving rise 
not only to enlarged spleen but also to 
bilious, remittent attacks and malarial hep¬ 
atitis. Where, however, other organs such 
as the brain, the kidney, the pancreas or 
intestinal walls are affected, cerebral symp¬ 
toms, etc., develop.” 
Dudgeon and Clarke, more recently 
(1917), refer repeatedly to the presence of 
“agglutinated” red blood cells in thrombi 
seen in the brain, kidneys and suprarenals 
of patients dying of pernicious malaria. 
These observations merit more investi¬ 
gation in the light of Knisely’s recent dem¬ 
onstration by cinematophotography that, in 
severe infections of rhesus monkeys with 
P. knowlesi, erythrocytes actually aggluti¬ 
nate in the circulating blood stream follow¬ 
ing which the agglutinated masses, while 
passing through the liver, are quickly en¬ 
gulfed by macrophages. 
Evidence further substantiating this 
viewpoint is presented in the following 
case of pernicious malaria (Case #3883, 
Department of Pathology, The University 
of Chicago). 
The pathologic findings in this patient 
are of particular value because she had 
probably had no previous malarial infec¬ 
tion ; the present infection was unsuspected 
and no anti-malarial treatment was given; 
furthermore, necropsy was performed two 
hours after death. The patient, a woman 
50 years of age, developed symptoms of 
epigastric pain, nausea and vomiting, fol¬ 
lowed by irregular fever, rapid pulse and 
moderate leukopenia. She had recently 
been on a boat trip to Central America and 
these symptoms first appeared about 8 days 
after her return. The total duration of 
illness from the first chill until death was 
9 days. Figs. 1-6 inclusive furnish evi¬ 
dence of the unequal distribution and con¬ 
centration of the malarial parasites in 
various organs. Fig. 5 is especially inter¬ 
esting in that it shows intravascular ag¬ 
glutination of parasitized erythrocytes. 
Fig. 3 also shows the accumulation of para¬ 
sitized erythrocytes in a mucosal capillary 
of the ileum with an adjacent venule con¬ 
taining no parasitized red blood cells. Such 
an appearance can be explained by the 
gradual “screening out” of parasitized 
erythrocytes as they pass through capil¬ 
laries, with non-parasitized ones thus com¬ 
prising the bulk of the venous outflow. 
Such an agglomeration cannot be readily 
explained by chance, but could be due, in 
the lungs, to a similar adherence of parasi¬ 
tized erythrocytes on their passage through 
intra-alveolar capillaries and their occa¬ 
sional outflow into pulmonary veins. 
These evidences of intravascular ag¬ 
glomeration are to be expected, if malaria 
is a type of infectious disease which follows 
the general pattern of infectious processes. 
Agglutination of bacteria in the tissues is 
a recognized phenomenon (Sullivan, Neck- 
ermann and Cannon 1934). It is due, 
presumably, to the deposition of antibody- 
protein on the surface of the antigenic par¬ 
ticles, thus changing their surface proper- 
