Molecular Characterization of the Cytochrome b Gene and In Vitro Atovaquone Susceptibility of Plasmodium falciparum Isolates from

The prevalence of a genetic polymorphism(s) at codon 268 in the cytochrome b gene, which is associated with failure of atova-quone-proguanil treatment, was analyzed in 227 Plasmodium falciparum parasites from western Kenya. The prevalence of the wild-type allele was 63%, and that of the Y268S (denoting a Y-to-S change at position 268) mutant allele was 2%. There were no pure Y268C or Y268Nmutant alleles, only mixtures of a mutant allele(s) with the wild type. There was a correlation between par-asite 50 % inhibitory concentration (IC50) and parasite genetic polymorphism; mutant alleles had higher IC50s than the wild type. Atovaquone-proguanil (AP) is a fixed-dose combination anti-malarial drug, mostly used for treatment and chemoprophy-laxis of falciparum malaria for international travelers (1). Use of atovaquone alone leads to high rates of treatment recrudescence (2), which is attributed to mutations in the cytochrome b gene (pfcytb) (3). Plasmodium falciparum atovaquone-resistant isolates have been described following atovaquone or AP treatment fail-ures (4–11) and in vitro drug susceptibility testing (5, 8, 10, 12). In vitro and in vivo resistance to atovaquone has been associated with point mutations at codon 268 in pfcytb (5, 9, 10, 13). These muta-tions include Y268S (denoting the Y-to-S change at position 268)