HUMORAL IMMUNITY IN MALARIA 
253 
or without luetic infections and negative 
malaria complement fixation tests before 
induced therapeutic malarial infections de¬ 
velop the maximum titer of complement¬ 
fixing antibodies about 3 weeks after the 
onset of the central acute attack. In paret¬ 
ics the antibodies persist from 2 to 5 months 
after the disappearance of parasites from 
the blood smears, an important considera¬ 
tion, as these studies were conducted with a 
strain of malaria characterized by infre¬ 
quent relapses. It is possible that serum 
from patients in endemic areas of malaria 
would be positive for even longer periods. 
The value of this test as a diagnostic proce¬ 
dure depends upon its being positive in 
chronic infections without detectable para¬ 
sites in the peripheral blood stream. Strat- 
man-Thomas and Dulaney (1940) have 
employed the above described antigen and 
technique for diagnostic purposes with 
promising results. Although the test has 
yet to be completely evaluated, preliminary 
observations indicate that it may be an im¬ 
portant aid not only for diagnostic pur¬ 
poses but more important as a means of 
studying parasitic activity and host re¬ 
sponse. 
Agglutinins 
The specific agglutination of malarial 
parasites by an immune serum was origi¬ 
nally demonstrated in 1938 by Eaton with 
P. knowlesi. This observation has been 
confirmed by Somogyi (1939) and Singh 
and Singh (1940). Recently in a prelimi¬ 
nary publication Mulligan and Russell 
(1940) reported the specific agglutination 
of P. gallmaceum sporozoites in dilutions 
of homologous immune serum as high as 
1: 8000. Thus the discovery of agglutinins 
in malarial infections adds more evidence 
to the belief that the immune response 
within a host differs little whether the 
pathogen is a virus, bacterium, or a pro¬ 
tozoan. 
It is possible to detect agglutinins in P. 
knowlesi infections about the time that an 
acute infection is being transformed into 
a chronic one. Although only weakly posi¬ 
tive at this stage, the reaction becomes pro¬ 
gressively stronger so that finally a demon¬ 
strable effect may be obtained in serum 
diluted 1:1000. Only the mature parasites 
located within red cells that presumably 
have more permeable cell membranes, or 
parasites artificially released from the red 
cells, have the capacity of being agglutin¬ 
ated by an immune serum. Other related 
findings indicate that the agglutination 
phenomenon in malaria is a true antigen- 
antibody reaction. Unlike the complement 
fixation reaction where the antigen is un¬ 
able to distinguish between antibodies pro¬ 
duced by closely related parasites, the 
agglutination reaction is very specific. 
This test might possess important practical 
applications if it were possible to obtain 
sufficient organisms. Unfortunately, the 
reaction with schizonts is very unstable, 
and only viable organisms can be used. 
The specific agglutination of P. knowlesi 
parasites by the homologous immune serum 
is strong presumptive evidence that the 
parasites are sensitized in vivo and thus 
rendered highly susceptible to phagocytosis 
by the macrophagic cells of the host. As 
mentioned above, the cellular defense 
mechanism undoubtedly plays the final role 
in the concentration and destruction of the 
malaria parasite. In the initial stages of 
the fight, however, the host’s attempt to 
recover from an infection may be depen¬ 
dent upon specific antibodies. At least a 
highly active macrophage system is effective 
only against an infection originally respon¬ 
sible for its activation (Taliaferro, this vol¬ 
ume p. 239). 
Precipitins 
Several investigators (Pewny 1918; Zie- 
mann 1924; Taliaferro and Taliaferro 
1928; and Row 1931) have attempted to 
demonstrate specific precipitins in malaria 
immune serum, and although suggestive, 
none of the reported results appear to be 
entirely conclusive. The work of the Talia- 
ferros was the most extensive, as they tried 
75 separate parasite antigens. The best 
antigen was prepared from infected pla¬ 
centas by removing and drying the para¬ 
sites, then digesting with 0.05 N HC1, and 
