Mapping of aPlasmodium falciparum pfcrtK76T Mutation: A Useful Strategy for Controlling Chloroquine Resistance in Madagascar

Association of Plasmodium Falciparum Chloroquine Resistance Transporter Variant T76 With Age-Related Plasma Chloroquine Levels

“…Correspondingly, the proportion of children harboring at least one clone with pfcrt K76 was highest in children without detectable levels of CQ. This observation supports the view that the pfcrt polymorphism at position 76 is in fact a significant factor of CQ resistance, as shown in previous studies from Cameroon, 13 Mali, 8 Mozambique, 10 Nigeria, 20 Sudan, 12 Uganda, 9,21 Madagascar, 22 Laos, 11,23 Papua New Guinea, 14,24 and Thailand. 14,23 The proportion of children infected with parasite clones carrying the pfcrt T76 variant decreased significantly with age and correlated with the age-associated decrease in CQ levels.…”

Genetic Structure ofPlasmodium falciparumand Elimination of Malaria, Comoros Archipelago

“…However, the study of Pfcrt and Pfdhfr resistance–associated mutations differed markedly, explainable only by contrasting levels of drug selective pressure among islands. Indeed, the prevalence of the K76T mutation on the Pfcrt gene was high in both Grande Comore and Moheli as found in previous studies ( 32 , 33 ) but substantively lower in Anjouan and significantly higher in Mayotte where chloroquine use was massive during 1975–2007 ( 7 , 34 ). Similarly, the prevalence of Pfdhfr triple mutants was higher in Moheli than in Anjouan and the prevalence of Pfdhfr double or triple mutants higher in Marseille than in Grande Comore.…”

Mechanisms of Resistance of Malaria Parasites to Antifolates

“…Parasite drug resistance and transmission patterns are remarkably varied not just across Africa but within regions and even within villages. With the mounting evidence that the flow of some drug-resistance alleles through the P. falciparum population may be in part "clonal" (Ariey et al, 2002;Cortese et al, 2002;Wootton et al, 2002;Nair et al, 2003;Roper et al, 2003Roper et al, , 2004), today's treatment policy decisions are likely to have global impact on the next generation of malaria therapy. A single country's choice regarding first-line malaria therapy may well have a ripple effect for the region or the continent, if not the world, and should be placed in this larger context.…”