604 Malaria 



The erythrocytic phase 



General features. The erythrocytic phase in a natural infection 

 normally is initiated by merozoites derived from E-E schizonts. Once 

 inside the red corpuscle, the young parasite usually develops a vacuole 

 which displaces the nucleus to the periphery, producing a "signet-ring" 

 stage. The ring, or young trophozoite, soon begins to grow. Binary fission 

 of ring stages has been suggested for P. vivax (3) and P. falciparum (50), 

 but this interpretation is not generally accepted. During growth, hemo- 

 globin is split into its protein component, which is used as food, and 

 hematin (76). As indicated by chemical and spectroscopic examination 

 (38, 47, 102), hematin is deposited in the retractile pigment granules of 

 erythrocytic stages. As estimated in infections of Macaca mulatta with 

 P. knowlesi, the hematin from about three-fourths of the corpuscular 

 hemoglobin is converted into pigment by the average parasite (74). 



Nuclear division begins toward the end of the growth period. The 

 result is a multinucleate schizont, which undergoes merogony. The 

 resulting merozoites, with some residual cytoplasm containing the pig- 

 ment, are released into the blood stream. The pigment and other residual 

 material are ingested by phagocytes. Hence, the presence of pigment in 

 such cells indicates a malarial infection with a current or recently termi- 

 nated erythrocytic phase. The liberated merozoites which do not undergo 

 phagocytosis enter fresh red corpuscles, or sometimes reticulocytes, and 

 repeat the cycle of growth and merogony. The time required ranges from 

 about 24 to 72 hours in different species, with some variation among 

 strains of a single species. Length of the cycle in the St. Elizabeth strain 

 of P. vivax has averaged 43.4 hours; in the New Hebrides strain, 45.7 

 hours; and in the Baltimore strain, 41.5 hours (123). 



During growth of the parasite, the corpuscle may undergo changes 

 which vary with the species of Plasmodium. Invaded corpuscles may 

 become enlarged, be distorted, become paler than the normal corpuscle, 

 undergo changes in reaction to the usual blood stains, or may show little 

 or no effect. Invaded corpuscles also tend to clump together in certain 

 malarial infections, such as P. knowlesi in monkeys (60). At the begin- 

 ning of the patent period, each corpuscle invaded by P. knowlesi becomes 

 coated with a thin self-adherent precipitate. As a result, such corpuscles 

 stick together. Since this coating substance is selectively ingested by 

 phagocytes, parasitized cells are rapidly ingested at this stage. As the 

 parasite-density increases, a fluffy precipitate forms, binding both invaded 

 and normal corpuscles into large masses. The blood now becomes thick 

 and sludge-like. Resistance of the larger masses causes the blood to flow 

 more slowly through the capillaries. Some of the smaller clumps, con- 

 taining both normal and invaded corpuscles, are ingested at this stage. 

 Later on, many of the larger clumps are broken up against the forks of 



