216 
MALARIA 
as a particular type of infectious process 
which follows the characteristic pattern of 
any disseminative type of infection. It may 
thus be compared to septicemia, pyemia, 
tuberculosis, syphilis, typhoid fever, plague, 
undulant fever and the like. 
In the natural history of all of these dis¬ 
eases, certain general principles may be de¬ 
duced as follows: 
1. They may all, initially, be generalized 
infections, with the infectious agents widely 
disseminated through the blood stream. An 
essential difference is that the bacteria are 
carried in the blood plasma whereas the 
malaria parasites are carried within the red 
blood corpuscles (Ratcliffe 1928). 
2. The clinical severity depends upon the 
parasitizing potentialities of the infectious 
agents and the ability of the invaded host 
to restrict their development, their toxic 
effects and their tissue localization. Such 
terms as virulence, invasiveness and toxico- 
genicity describe the bacterial proclivities, 
whereas, in malaria, the varying effects are 
commonly supposed to be due to the dif¬ 
fering potencies of the “toxins” liberated 
with the merozoites at each segmentation. 
In both types of infection humoral and 
cellular mechanisms of defense determine 
the varying grades of natural and acquired 
resistance. In tertian and quartan malaria, 
for example, the parasitizing abilities of 
the microorganisms are usually counter¬ 
balanced by the resistance of the host; in 
pernicious malaria, on the other hand, the 
invasive potentialities of the parasites not 
infrequently overcome the resistive capacity 
of the host. But whether the infection is 
bacterial or malarial, the question whether 
it will be non-lethal or lethal depends upon 
the ability of the infected person to convert 
a generalizing, progressive type of infection 
into a localized, regressive one. The most 
important problem which confronts the 
host in any type of infectious disease, there-' 
fore, is either that of confining the initial 
infection to a localized area, or, if this is 
not immediately possible, of mobilizing de¬ 
fensive mechanisms which may ultimately 
localize the infectious agents. An adequate 
comprehension of this process in malaria, as 
revealed by pathologic facts, should aid 
materially in the better understanding of 
the genesis of the disease and the signifi¬ 
cance of its clinical symptoms. 
The similarity in the pathologic course 
of events in benign malaria and in typhoid 
fever is striking. In both infections there 
is the initial distribution of the infective 
agents throughout the body, followed by 
their predominant localization in the liver, 
spleen and bone marrow. This localization, 
in malaria, is evidenced by the greater de¬ 
position of malarial pigment, whereas, in 
typhoid fever, it is characterized by the 
presence of “focal necroses.” In both in¬ 
fections there is hypertrophy and hyper¬ 
plasia of the reticuloendothelial elements; 
in both, the usual blood response is a 
leukopenia. In both, injury to erythrocytes 
and increased erythrophagocytosis lead to 
secondary anemia; in each there is a char¬ 
acteristic increase in the number of mono¬ 
nuclear leukocytes in the blood. It is not 
surprising, therefore, that in the past the 
two diseases were so frequently confused, 
and that the term “typhomalaria” was used 
so commonly to describe symptoms which 
might pertain to either disease alone or to 
their concomitant occurrence. 
Pernicious malaria, on the other hand, 
may more appropriately be compared with 
those fulminant and overwhelming bacterial 
or viral infections in which death occurs 
speedily because of the unusual virulence 
of the invading agents, as, for example, in 
hemorrhagic smallpox, measles, scarlet 
fever, meningocoeeemia, streptococcic bac- 
teriemia, etc. Under these conditions an 
unusually invasive type of microorganism 
presumably overcomes the resistance of the 
host because the defensive mechanisms of 
the latter are unable to localize it. So, in 
infection with P. falciparum, the effects 
are particularly serious because (1) of its 
greater ability to multiply and (2) of its 
greater toxicogenicity. This species at¬ 
tains a higher concentration in the blood, 
has a shorter incubation period and thereby 
causes an earlier manifestation of symp¬ 
toms. This may be due to the fact that 
it produces more merozoites per schizont 
