title: Emergence of atovaquone-proguanil resistance during treatment of Plasmodium falciparum malaria acquired by a non-immune north American traveller to west Africa.
abstract: The importation of drug-resistant malaria is a growing public health problem in non-endemic countries. The combination of atovaquone and proguanil (Malarone) has become established as an agent of choice to prevent and treat chloroquine-resistant Plasmodium falciparum malaria in travelers. We describe the first reported case in North America of genetically confirmed atovaquone/proguanil-resistant P. falciparum malaria. Polymerase chain reaction and sequence analysis of the primary and recrudescent isolates confirmed the acquisition of a point mutation (Tyr268Ser) in the cytochrome b gene of the recrudescent isolate known to confer high-level resistance to atovaquone. Suboptimal therapy may have played a contributory role in the emergence of resistance.
authors.affiliation: Department of Pediatrics, Medicine, Medical Microbiology & Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Kuhn
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D053626:Atovaquone; D002170:Canada / Q000208:ethnology; D045303:Cytochromes b / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D009285:Naphthoquinones / Q000008:administration & dosage / Q000627:therapeutic use*; D010963:Plasmodium falciparum / Q000201:enzymology; D002727:Proguanil / Q000008:administration & dosage / Q000627:therapeutic use*; D012807:Sierra Leone
chemical_list: D000962:Antimalarials; D009285:Naphthoquinones; D045303:Cytochromes b; D002727:Proguanil; D053626:Atovaquone