Plasmodium falciparumDrug Resistance in Madagascar: Facing the Spread of Unusualpfdhfrandpfmdr-1Haplotypes and the Decrease of Dihydroartemisinin Susceptibility

Abstract
The aim of this study was to provide the first comprehensive spatiotemporal picture ofPlasmodium falciparumresistance 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 ofpfcrt,pfmdr-1,pfdhfr, andpfdhpsmutations and thepfmdr-1gene copy number in 1,596P. falciparumisolates 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 thepfdhfrand thepfdhpsmutations, (iii) the alarming emergence of the singlepfdhfr164L 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 ofP. falciparumresistance in the future is required.