title: Malarone treatment failure not associated with previously described mutations in the cytochrome b gene.
abstract: Malarone (atovaquone-proguanil) is an effective drug for the treatment and prophylaxis of multidrug-resistant falciparum malaria. However, first cases of resistance have been reported, which are associated with mutations at codon 268 of the parasite's cytochrome b gene. We report the first case of Malarone treatment failure from Central Africa.Drug concentration was well within curative range. Pre- and post-treatment Plasmodium falciparum isolates revealed codon 268 wild-type alleles, and no other mutations of the putative atovaquone-binding domain.These findings illustrate the spread of atovaquone-proguanil-resistance in Africa and question the usefulness of codon 268 as the only target for the surveillance of its emergence.
authors.affiliation: Institute of Tropical Medicine, Charité, Humboldt University, Berlin, Germany. ole.wichmann@charite.de
authors.forename: Ole
authors.initials: O
authors.lastname: Wichmann
authors.forename: Marion
authors.initials: M
authors.lastname: Muehlen
authors.forename: Holger
authors.initials: H
authors.lastname: Gruss
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.forename: Tomas
authors.initials: T
authors.lastname: Jelinek
mesh_terms: D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D053626:Atovaquone; D001682:Biological Availability; D045303:Cytochromes b / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D009285:Naphthoquinones / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D017354:Point Mutation; D002727:Proguanil / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D009285:Naphthoquinones; C109496:atovaquone, proguanil drug combination; D045303:Cytochromes b; D002727:Proguanil; D053626:Atovaquone