title: Molecular surveillance of mutations in the cytochrome b gene of Plasmodium falciparum in Gabon and Ethiopia.
abstract: BACKGROUND
  Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone) and inhibits the cytochrome bc1 complex of the electron transport chain in Plasmodium spp. Molecular modelling showed that amino acid mutations are clustered around a putative atovaquone-binding site resulting in a reduced binding affinity of atovaquone for plasmodial cytochrome b, thus resulting in drug resistance.
  
  
  METHODS
  The prevalence of cytochrome b point mutations possibly conferring atovaquone resistance in Plasmodium falciparum isolates in atovaquone treatment-naïve patient cohorts from Lambaréné, Gabon and from South Western Ethiopia was assessed.
  
  
  RESULTS
  Four/40 (10%) mutant types (four different single polymorphisms, one leading to an amino acid change from M to I in a single case) in Gabonese isolates, but all 141/141 isolates were wild type in Ethiopia were found.
  
  
  CONCLUSIONS
  In the absence of drug pressure, spontaneous and possibly resistance-conferring mutations are rare.
authors.affiliation: Department of Medical Laboratory Technology, Faculty of Health Sciences, Haramaya University, Haramaya, Ethiopia. tamiratgw2002@yahoo.com <tamiratgw2002@yahoo.com>
authors.forename: Tamirat
authors.initials: T
authors.lastname: Gebru
authors.forename: Asrat
authors.initials: A
authors.lastname: Hailu
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Jürgen F J
authors.initials: JF
authors.lastname: Kun
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
mesh_terms: D000818:Animals; D053626:Atovaquone / Q000494:pharmacology; D003062:Codon; D045303:Cytochromes b / Q000235:genetics*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D002727:Proguanil / Q000494:pharmacology
chemical_list: D003062:Codon; D004338:Drug Combinations; C109496:atovaquone, proguanil drug combination; D045303:Cytochromes b; D002727:Proguanil; D053626:Atovaquone