title: Prevalent pfmdr1 n86y mutant Plasmodium falciparum in Madagascar despite absence of pfcrt mutant strains.
abstract: We assessed the status of point mutations associated with chloroquine resistance in pfcrt codon 76 and in pfmdr1 codon 86 among Plasmodium falciparum isolates from symptomatic patients in 3 sites in Madagascar. The in vitro susceptibility of P. falciparum isolates to quinoline-containing drugs was also determined. All isolates (N = 117) successfully typed were pfcrt wild-type, except one from Tsiroanomandidy (1 of 27). However, 67.5% (95% CI: 58.2-75.9%) of these isolates contained mutant pfmdr1 86Y. The pfmdr1 N86Y mutation is associated with higher mefloquine susceptibility, but it did not affect the sensitivity of parasites to chloroquine or quinine. Our findings demonstrate that pfmdr1 mutant P. falciparum are prevalent in Madagascar and confirm the low prevalence of pfcrt mutant P. falciparum after 60 years of chloroquine use. They provide additional field-based evidence for increased mefloquine susceptibility in pfmdr1 mutant P. falciparum and are suggestive of the intrahost selection of pfmdr1 mutant parasites.
authors.affiliation: Unité de Recherche sur le Paludisme, Antananarivo, Institut Pasteur de Madagascar, Madagascar. mieange@pasteur.mg
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Rason
authors.forename: Herilalaina B
authors.initials: HB
authors.lastname: Andrianantenaina
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ariey
authors.forename: Andrianirina
authors.initials: A
authors.lastname: Raveloson
authors.forename: Olivier
authors.initials: O
authors.lastname: Domarle
authors.forename: Milijaona
authors.initials: M
authors.lastname: Randrianarivelojosia
mesh_terms: D000655:Amodiaquine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D006801:Humans; D020128:Inhibitory Concentration 50; D008270:Madagascar / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology*; D015767:Mefloquine / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*; D011803:Quinine / Q000494:pharmacology; D012424:Rural Population
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D002738:Chloroquine; D016054:DNA, Protozoan; D015767:Mefloquine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D011803:Quinine; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C047386:desethylamodiaquine