Molecular characterization of the cytochrome b gene and in vitro atovaquone susceptibility of Plasmodium falciparum isolates from Kenya

Antimicrob Agents Chemother. 2015 Mar;59(3):1818-21. doi: 10.1128/AAC.03956-14. Epub 2015 Jan 12.

Abstract

The prevalence of a genetic polymorphism(s) at codon 268 in the cytochrome b gene, which is associated with failure of atovaquone-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 Y268N mutant alleles, only mixtures of a mutant allele(s) with the wild type. There was a correlation between parasite 50% inhibitory concentration (IC50) and parasite genetic polymorphism; mutant alleles had higher IC50s than the wild type.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Antimalarials / pharmacology*
  • Atovaquone / pharmacology*
  • Codon / genetics
  • Cytochromes b / genetics*
  • DNA, Protozoan / genetics
  • Drug Combinations
  • Kenya
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / parasitology
  • Microbial Sensitivity Tests / methods
  • Mutation / genetics
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics*
  • Polymorphism, Genetic / genetics
  • Proguanil / pharmacology
  • Protozoan Proteins / genetics

Substances

  • Antimalarials
  • Codon
  • DNA, Protozoan
  • Drug Combinations
  • Protozoan Proteins
  • atovaquone, proguanil drug combination
  • Cytochromes b
  • Proguanil
  • Atovaquone