Differential prevalence of plasmodium falciparum transporter polymorphisms and infection complexity in children with symptomatic and asymptomatic malaria in Tororo, Uganda.

Abstract

Malaria, particularly infection with Plasmodium falciparum, remains one of the most important infectious diseases in the world. A major challenge to the treatment and control of malaria has been resistance to most available antimalarial drugs. Polymorphisms in pfcrt and pfmdr1, genes encoding putative drug transporters, impact upon sensitivity of P. falciparum to multiple drugs. Considering the strong and, at times, reciprocal pressures of antimalarial drugs on parasite genetics and the impact of transporter polymorphisms on sensitivity to important ACT components. This study was aimed at determining the differential prevalence of P. falciparum transporter polymorphisms and complexity of infection in children with symptomatic and asymptomatic malaria in Tororo, Uganda. Two hundred and forty three children with documented fever (cases), and equal numbers randomly selected from the other clinical categories (controls) were studied. A multivariate analysis adjusting for age, COI, and parasite density was conducted, accounting for clustering with generalized estimating equations models fitted for each polymorphism, with robust standard errors. The prevalence of wild type genotypes was significantly higher in febrile compared to asymptomatic malaria infected children. There was no wild type genotype detected for pfcrt gene. Pfcrt mixed genotypes were significantly higher in febrile compared to asymptomatic malaria infected children. These results indicate that parasites with wild type genotypes associated with decreased sensitivity to both components of the Ugandan first-line malaria treatment artemether-lumefantrine were more likely than those with mutant genotypes to be associated with symptomatic malaria infection