Genetic variation in the host and adaptive phenomena in Plasmodium falciparum infection.

The in vitro culture of Plasmodium falciparum, after synchronization, lends itself well to an analysis of the asexual schizogonic cycle. We have found in this system that DNA synthesis and RNA synthesis are associated mainly with the trophozoite stage, with the latter peaking slightly ahead of the former. Distinctive patterns of protein synthesis are seen at serial times along the cycle, with a number of 'stage-specific' bands identifiable on SDS gels. The fate of the infection can be influenced by the genotype of the host cell. Thus, glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes are invaded normally, but maturation of intracellular parasites is delayed and impaired. However, the parasites that do develop will then have a normal behaviour in their next rounds in G6PD-deficient cells, suggesting that an adaptive change has taken place. These results fit well with the relative protection against P. falciparum in vivo of girls heterozygous for G6PD deficiency but not of hemizygous G6PD-deficient boys.