SOME PATHOLOGIC ASPECTS OF HUMAN 
MALARIA 
By PAUL R. CANNON 
DEPARTMENT OF PATHOLOGY, UNIVERSITY OF CHICAGO, CHICAGO, ILL. 
Human malaria is a type of infectious 
disease in which the duration, severity and 
outcome are affected by a number of vari¬ 
ables, such as the species of parasite, the 
variations in its biologic properties, the 
length of infection, the age and race of the 
host, the differing grades and kinds of re¬ 
sistance, the effects of relapse, the kinds 
and amounts of therapy used and the con¬ 
comitant influences of intercurrent and 
terminal infections. It is apparent from a 
consideration of these facts that malaria 
can no more develop according to a simple 
pathologic pattern than can tuberculosis, 
syphilis or any other infectious disease 
with a variable clinical course. Rather than 
attempting to describe pathologic details, 
therefore, this discussion will be directed 
toward those general pathologic aspects 
of malarial infection which have a direct 
relationship to infectious disease as a 
whole. 
A satisfactory understanding of any in¬ 
fectious process requires the study of 
properly fixed and stained necropsy mate¬ 
rial from all stages of the disease. It is be¬ 
cause of this requirement that the story 
of the pathologic effects in human malaria 
is as yet incomplete. There are several 
reasons for this. Very few patients die 
from tertian or quartan infections; further¬ 
more, in estivo-autumnal infections death 
does not usually occur for days or weeks, 
and the pathologic picture is that of the 
end stage, with this frequently obscured by 
a terminal infection. Too frequently, also, 
necropsies are performed hours after death, 
thus interfering with satisfactory fixation 
and staining of the tissues. Correct inter¬ 
pretation as to the site and extent of dis¬ 
tribution of malarial pigment in cells and 
organs has also been hampered by the wide¬ 
spread use of formalin-fixation, with the 
attendant uncertainty caused by the pres¬ 
ence in cells of the confusing “formalin 
pigment.” It is because of these difficulties 
that, although a great deal is known about 
the pathology of human malaria, many of 
the current ideas about its earlier phases 
are inferential or derived from experi¬ 
mental sources. 
The essential facts about the pathology 
of human malaria may be summarized 
briefly as follows (Dock 1894; Barker 1895; 
Craig 1938; Councilman and Abbott 1885; 
Seyfarth 1926): 
1. Malarial parasites, after their initial 
entrance into red blood cells and their con¬ 
sequent dissemination throughout the body, 
go through the characteristic cycles of 
asexual development which produce, in 
large measure, the symptoms of the disease. 
The ultimate course of events depends upon 
the ability of the host to prevent the con¬ 
tinued accumulation of the parasites and 
the ensuing parasitization of other red blood 
corpuscles. Under ordinary circumstances, 
as with tertian or quartan parasites, the 
defensive mechanisms of the infected indi¬ 
vidual soon come into action and, in time, 
the parasites disappear from the blood 
stream, tending to become localized pre¬ 
dominantly in three organs, viz., the liver, 
the spleen (Clark 1928) and the bone mar¬ 
row. In those instances where the para¬ 
sites continue to multiply in the tissues, as 
in infection with Plasmodium falciparum, 
localization in these organs, although oc¬ 
curring to some extent, fails to counterbal¬ 
ance the unrestricted reproduction of the 
parasites and the infection may ultimately 
become overwhelming and lethal. 
2. The selective localization of parasites 
in the liver, spleen and bone marrow oc¬ 
curs because of anatomic and physiologic 
characteristics peculiar to these organs 
