title: Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria.
abstract: We report the first in vitro and genetic confirmation of Malarone (GlaxoSmithKline; atovaquone and proguanil hydrochloride) resistance in Plasmodium falciparum acquired in Africa. On presenting with malaria two weeks after returning from a 4-week visit to Lagos, Nigeria without prophylaxis, a male patient was given a standard 3-day treatment course of Malarone. Twenty-eight days later the parasitaemia recrudesced. Parasites were cultured from the blood and the isolate (NGATV01) was shown to be resistant to atovaquone and the antifolate pyrimethamine. The cytochrome b gene of isolate NGATV01 showed a single mutation, Tyr268Asn which has not been seen previously.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. quinton.fivelman@lshtm.ac.uk
authors.forename: Quinton L
authors.initials: QL
authors.lastname: Fivelman
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Butcher
authors.forename: Ipemida S
authors.initials: IS
authors.lastname: Adagu
authors.forename: David C
authors.initials: DC
authors.lastname: Warhurst
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Pasvol
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D053626:Atovaquone; D003062:Codon / Q000235:genetics; D045303:Cytochromes b / Q000037:antagonists & inhibitors / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D006801:Humans; D008131:London; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000201:enzymology / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use; D009549:Nigeria / Q000208:ethnology; D018512:Parasitemia / Q000188:drug therapy* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D002727:Proguanil / Q000494:pharmacology* / Q000627:therapeutic use; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D014195:Travel
chemical_list: D000962:Antimalarials; D003062:Codon; D004338:Drug Combinations; D009285:Naphthoquinones; D015800:Protozoan Proteins; C109496:atovaquone, proguanil drug combination; D045303:Cytochromes b; D002727:Proguanil; D053626:Atovaquone