Adaptive changes in Plasmodium transmission strategies following chloroquine chemotherapy.
Buckling, A., Crooks, L., and Read A. 1999. Plasmodium chabaudi: Effect of antimalarial drugs on gametocytogenesis. Experimental Parasitology 93, 45–54. The proportion of asexual blood-stage malaria parasites that develop into transmission stages (gametocytes) can increase in response to stress. We investigated whether stress imposed by a variety of antimalarial drugs administered before or during infection increased gametocyte production (gametocytogenesis) in vivo in the rodent malaria parasite, Plasmodium chabaudi. All methods of drug treatment greatly reduced the numbers of asexual parasites produced during an infection but resulted in either no reduction in numbers of gametocytes or a smaller reduction than that experienced by asexuals. We used a simple model to estimate temporal variation in gametocyte production. Temporal patterns of gametocytogenesis did not greatly differ between untreated and prophylaxis infections, with rates of gametocytogenesis always increasing as the infection progressed. In contrast, administration of drugs 5 days after infection stimulated increased rates of gametocytogenesis early in the infection, resulting in earlier peak gametocyte densities relative to untreated infections. Given the correlation between gametocyte densities and infectivity to mosquito vectors, and the high frequency of subcurative drug therapy and prophylaxis in human populations, these data suggest that antimalarial drugs may frequently have only a small effect on reducing malaria transmission and may help to explain the rapid spread of drug-resistant genotypes. q 1999 Academic Press Index Descriptors and Abbreviations: Apicomplexan parasite; Plasmodium chabaudi; malaria; gametocytogenesis; gametocytes; postinfection (pi); antimalarial chemotherapy; antimalarial prophylaxis; quinine, pyrimethamine, chloroquine; red blood cells (rbc); dimethyl sulfoxide (DMSO); standard error of the mean (SEM); analysis of variance (ANOVA).