Comparative Prevalence of Resistance-Associated Genetic Polymorphisms in Parasites Infecting Humans and Mosquitoes in Uganda.

Controlling malaria in high transmission areas, such as much of sub-Saharan Africa, will require concerted efforts to slow the spread of drug resistance and to impede malaria transmission. Understanding the fitness costs associated with the development of drug resistance, particularly within the context of transmission, can help guide policy decisions to accomplish these goals, as fitness constraints might lead to decreased transmission of drug-resistant strains. To determine if resistance-mediating polymorphisms impact on development at different parasite stages, we compared the genotypes of parasites infecting humans and mosquitoes from households in Uganda. Genotypes at 14 polymorphic loci in genes encoding putative transporters ( and and folate pathway enzymes ( and were characterized using ligase detection reaction-fluorescent microsphere assays. In paired analysis using the Wilcoxon signed-rank test, prevalences of mutations at 12 loci did not differ significantly between parasites infecting humans and mosquitoes. However, compared with parasites infecting humans, those infecting mosquitoes were enriched for the 86Y mutant allele ( = 0.0001) and those infecting s.s. were enriched for the 86Y ( = 0.0001) and 76T ( = 0.0412) mutant alleles. Our results suggest modest directional selection resulting from varied fitness costs during the life cycle. Better appreciation of the fitness implications of drug resistance mediating mutations can inform optimal malaria treatment and prevention strategies.