Plasmodium falciparum drug resistance in Madagascar: facing the spread of unusual pfdhfr and pfmdr-1 haplotypes and the decrease of dihydroartemisinin susceptibility.
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.
Andriantsoanirina
Valérie
V
Unité de Recherche sur le Paludisme, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
Ratsimbasoa
Arsène
A
Bouchier
Christiane
C
Jahevitra
Martial
M
Rabearimanana
Stéphane
S
Radrianjafy
Rogelin
R
Andrianaranjaka
Voahangy
V
Randriantsoa
Tantely
T
Rason
Marie Ange
MA
Tichit
Magali
M
Rabarijaona
Léon Paul
LP
Mercereau-Puijalon
Odile
O
Durand
Rémy
R
Ménard
Didier
D
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*
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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