title: Plasmodium falciparum drug resistance in Madagascar: facing the spread of unusual pfdhfr and pfmdr-1 haplotypes and the decrease of dihydroartemisinin susceptibility.
abstract: The aim of this study was to provide the first comprehensive spatiotemporal picture of Plasmodium falciparum resistance in various geographic areas in Madagascar. Additional data about the antimalarial resistance in the neighboring islands of the Comoros archipelago were also collected. We assessed the prevalence of pfcrt, pfmdr-1, pfdhfr, and pfdhps mutations and the pfmdr-1 gene copy number in 1,596 P. falciparum isolates collected in 26 health centers (20 in Madagascar and 6 in the Comoros Islands) from 2006 to 2008. The in vitro responses to a panel of drugs by 373 of the parasite isolates were determined. The results showed (i) unusual profiles of chloroquine susceptibility in Madagascar, (ii) a rapid rise in the frequency of parasites with both the pfdhfr and the pfdhps mutations, (iii) the alarming emergence of the single pfdhfr 164L genotype, and (iv) the progressive loss of the most susceptible isolates to artemisinin derivatives. In the context of the implementation of the new national policy for the fight against malaria, continued surveillance for the detection of P. falciparum resistance in the future is required.
authors.affiliation: Unité de Recherche sur le Paludisme, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
authors.forename: Valérie
authors.initials: V
authors.lastname: Andriantsoanirina
authors.forename: Arsène
authors.initials: A
authors.lastname: Ratsimbasoa
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.forename: Martial
authors.initials: M
authors.lastname: Jahevitra
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rabearimanana
authors.forename: Rogelin
authors.initials: R
authors.lastname: Radrianjafy
authors.forename: Voahangy
authors.initials: V
authors.lastname: Andrianaranjaka
authors.forename: Tantely
authors.initials: T
authors.lastname: Randriantsoa
authors.forename: Marie Ange
authors.initials: MA
authors.lastname: Rason
authors.forename: Magali
authors.initials: M
authors.lastname: Tichit
authors.forename: Léon Paul
authors.initials: LP
authors.lastname: Rabarijaona
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Rémy
authors.initials: R
authors.lastname: Durand
authors.forename: Didier
authors.initials: D
authors.lastname: Ménard
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D006239:Haplotypes; D008270:Madagascar; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011739:Pyrimethamine / Q000494:pharmacology; D013413:Sulfadoxine / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D002738:Chloroquine; D004094:Dihydropteroate Synthase; D004338:Drug Combinations; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011739:Pyrimethamine; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; C513498:Mdr1 protein, Plasmodium falciparum; C001205:fanasil, pyrimethamine drug combination; C039060:artenimol
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