Fitness consequences of Plasmodium falciparum pfmdr1 polymorphisms inferred from ex vivo culture of Ugandan parasites. Polymorphisms in the Plasmodium falciparum multidrug resistance-1 (pfmdr1) gene impact upon sensitivity to multiple antimalarials. In Africa, polymorphisms at N86Y and D1246Y are common, with varied impacts on sensitivity to different drugs. To gain insight into the fitness consequences of these polymorphisms, we cultured parasites isolated from children with malaria in Tororo, Uganda, where the multiplicity of infection is high, and used pyrosequencing to follow polymorphism prevalences in culture over time.Overall, consistent trends in the direction of selection were seen, although differences were not statistically significant. Our results suggest fitness advantages for parasites with pfmdr1 mutant 86Y and wild type D1246, highlighting the complex interplay between drug resistance and fitness in malaria parasites.
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