Malaria 603 



ameter and at maturity, on the eighth or ninth day, measures 35-60[jl 

 (95, 100). Merogony results in about 1,000 merozoites, averaging I.Ijjl in 

 diameter (98). Some of these merozoites presumably enter red corpuscles 

 at the end of the prepatent period. The E-E cycle is continued in the 

 liver, where schizonts have been found in the fourth month of infection 

 and after a month of latency (97). Thus, for the first time in the history 

 of malaria, a complete description of the life-cycle became available for 

 a species parasitic in a mammal (96). Preliminary observations (95, 99) 

 have indicated that the E-E cycle of P. vivax closely resembles that of 

 P. cynomolgi. 



The E-E stages of avian parasites have been observed mainly in 

 lymphoid-macrophage (reticulo-endothelial) cells. E-E stages of P. elonga- 

 tum develop primarily in wandering lymphoid-macrophage cells. Such 

 species as P. gaUinaceinn (53) and P. relictum (31) are found principally 

 in cajjillary endothelial cells, KiipfFer cells of the liver, and other fixed 

 cells lining sinuses of the bone marrow, lungs, and spleen. P. mexicanum 

 of lizards develops in both fixed and wandering cells (113). Two varieties 

 of E-E schizonts are found in P. relictum and P. gallinaceiini. Micro- 

 schizonts may produce about a thousand micromerozoites which are be- 

 lived to enter erythrocytes. Macroschizonts produce fewer and larger 

 macromerozoites which apparently invade lymphoid-macrophage cells 

 and continue the E-E cycle. 



This E-E phase in malaria offers a logical explanation for prepatent 

 and postpatent periods, latency, and repopulation of the blood in re- 

 lapses. The direct invasion of tissue cells other than erythrocytes by the 

 inoculated sporozoites leads to a pre-erythrocytic cycle of growth and 

 merogony. This explains the failure to demonstrate parasites in the 

 blood during the prepatent period. However, the development of E-E 

 stages does not depend exclusively upon the introduction of sporozoites 

 in avian malaria. Inoculation of blood containing trophozoites of 

 P. galUnaceum, for example, may be followed by the appearance of E-E 

 stages in lymphoid-macrophage cells after 4-6 days (116). In fact, inocula- 

 tion of a single trophozoite into a chick has produced infections showing 

 E-E stages (39). Factors which eliminate erythrocytic stages, as the 

 primary attack passes into a latent phase in relapsing malarias, usually 

 do not eliminate the E-E stages. Accordingly, the E-E cycle continues 

 throughout latency and may persist for a long time, as indicated by 

 occasional relapse after a prolonged latency. It is more likely that 

 invasion of the blood is attempted periodically, only to fail under the 

 action of a stimulated malaricidal mechanism, than that the production 

 of "micromerozoites" destined for red corpuscles is completely suppressed 

 during latency. Sooner or later, however, the blood is repopulated in 

 relapsing malaria. The most logical explanation for the occurrence of 

 relapses is based upon immunological relationships (Chapter XIV). 



