PATHOLOGIC ASPECTS. OF HUMAN MALARIA 
217 
than do either P. vivax or P. malariae. It 
is also more toxic, in the sense that it causes 
graver symptoms, a severer anemia, greater 
damage to the central nervous system, more 
regressive changes in the infected erythro¬ 
cytes (the so-called “brassy” cells) and 
more severe degenerative changes in such 
parenchymatous organs as the heart, liver, 
kidneys and suprarenals. It may also lead 
to widespread fatty degeneration of blood 
vessel walls, leukopenia, vascular hemor¬ 
rhages, and purpuric lesions. 
In both types of fulminating infection, 
the adverse effects may be explained on the 
basis of unrestricted parasitic growth in 
“virgin soil.” This conclusion is sup¬ 
ported by the statement of Marchiafava 
(1931) that “only recent infections or 
early relapses develop into pernicious ma¬ 
laria. ” According to him “it is especially 
in organisms virgin to the malarial infec¬ 
tion that the estivo-autumnal parasites 
multiply more acutely, reaching at times 
enormous numbers; and, developing greater 
virulence, give rise to pernicious symptoms. 
And, on the other hand, with the persis¬ 
tence of infection in the organism, this 
acquires a relative and partial immunity, 
an immunity against the pernicious feature 
of the infection, such as we see exemplified 
every day among the inhabitants of malari¬ 
ous communities.” He states, furthermore, 
that the hyperplasia of the spleen in per¬ 
nicious malaria is always acute, with the 
pulp soft and almost fluid and that the 
spleen never shows evidence of a chronic 
hyperplasia. 
In all of these infectious processes, 
therefore, the primary pathologic effects are 
centered in the activities of the system of 
macrophages or, in other words, in the 
reticuloendothelial system. The contribu¬ 
tion of myeloid elements to the circulating 
blood may or may not be a significant part 
of the bone marrow response, but the fixed 
tissue reticular cells of the marrow act to 
engulf the foreign elements circulating in 
the blood. In the liver, spleen and bone 
marrow, which have been aptly called the 
“primary blood filters,” the first clash be¬ 
tween invader and invaded occurs, and 
here the immediate outcome of the infection 
is determined. If the disease is fulminating 
or malignant, death may occur because these 
organs are unable to localize the develop¬ 
ing infection. In more favorable cases, on 
the other hand, localization is accomplished 
and, in the hypertrophied macrophages of 
the splenic cords, the Kupffer cells of the 
liver and the reticular cells of the bone 
marrow, are seen the malarial and blood 
pigments as the characteristic effects of the 
successful struggle. All other pathologic 
effects of malarial infection, therefore, may 
be regarded as departures from the pri¬ 
mary purpose of blood cleansing and organ 
localization, and depend for the most part 
on local peculiarities, massiveness of infec¬ 
tion, embolic accident or pure chance. 
One may ask the question: Why does 
malaria show such a definite predilection 
for the reticuloendothelial system? It is 
equally proper to ask, however, why in 
bacterial septicemia, typhoid fever, undu- 
lant fever, miliary tuberculosis and in 
acute syphilis, the same predilection is 
manifested? Why, for example, in tertian 
and quartan malaria and in bacterial septi¬ 
cemia, are such organs as the myocardium, 
thyroid gland, pancreas, suprarenals, lungs, 
brain, kidneys and gastrointestinal tract so 
rarely affected? The answer requires a 
true understanding of the conditions which 
influence the removal of infective agents 
from the circulating blood; this, in turn, 
requires a more detailed consideration of 
two fundamental problems, viz., the essen¬ 
tial nature of endothelium and the dynam¬ 
ics of capillary blood flow. 
There has long been confusion regarding 
the essential nature of endothelium and its 
part in the localization of infectious disease. 
This is due to the fact that many persons 
have believed that all cells lining blood ves¬ 
sels are, by definition, endothelial cells, and 
that because some are actively phagocytic, 
all are likewise so. The popularity of the 
term “reticuloendothelial system” has also 
encouraged many to believe that all endo¬ 
thelium is actively or potentially phago¬ 
cytic and that from it arise the circulating 
mononuclear leukocytes of the blood. 
