Drug-Resistant Malaria Parasites Introduced into Madagascar from Comoros Islands

Abstract

To determine risk for drug-resistant malaria parasites entering Madagascar from Comoros Islands, we screened travelers. For the 141 Plasmodium falciparum isolates detected by real-time PCR, frequency of mutant alleles of genes associated with resistance to chloroquine and pyrimethamine was high. International-level antimalarial policy and a regional antimalarial forum are needed.

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

“…These findings are consistent with those presented in our previous report, in which we indicated that resistant P. falciparum parasites were introduced into Madagascar by travelers coming from the Comoros Islands (18). Resistant parasites were highly prevalent in the north/central western part of Madagascar in 2006 (Ͼ50%), and we observed their rapid spread along the north-to-south axis, reaching first the southwest (10-fold increase in 3 years) and then the eastern part of the country (1.5-fold increase in the central east and 3-fold increase in the southeast).…”

“…Indeed, the prevalence of the clinical failure of treatment with amodiaquine, SP and the combination artesunate and amodiaquine was Ͻ5%, while the rate of failure of treatment with CQ was 44% (19). However, the recent demonstration of the introduction of multidrug-resistant P. falciparum parasites into Madagascar from the Comoros Islands (18) and the emergence of the uncommon dihydrofolate reductase I164L genotype in P. falciparum parasites (17) suggest that the situation is currently changing in Madagascar.…”

Origins of the Recent Emergence of Plasmodium falciparum Pyrimethamine Resistance Alleles in Madagascar

“…These findings point to the existence of an efficient westward gene flow route across Asia, resulting in import into the Comoros (and other East African areas) of the pfdhfr triple and quadruple mutants and of the CVIET P. falciparum crt (pfcrt) chloroquine resistance-conferring allele (4). The data reported here add support to our recent findings demonstrating the invasion of multidrug-resistant parasites into Madagascar from the Comoros Islands (17) and confirm the hypothesis that the Comoros Islands is a port of entry of antimalarial drug-resistant malaria parasites into the southwestern Indian Ocean. We have witnessed the rapid spread of the mutant with the pfdhfr triple mutation of the SEA lineage since 2006 along the north-to-south axis and its current widespread distribution in Madagascar.…”

“…We have witnessed the rapid spread of the mutant with the pfdhfr triple mutation of the SEA lineage since 2006 along the north-to-south axis and its current widespread distribution in Madagascar. The present data, along with data from our previous studies (17,18), show that the invasion of parasites harboring the pfdhfr triple-mutation allele into Madagascar is probably a recent event which is still in progress and confirm that gene flow is the major force driving this haplotype across continents and countries (1). Because of the massive use of SP in IPTp and because of human population movements, the prevalence of the pfdhfr triple-mutation allele may continue to increase in Madagascar, as it is not yet as high as the prevalence in the Comoros Islands or many other African countries.…”

“…However, recent studies performed in Madagascar have shown that the situation is deteriorating and have demonstrated the introduction of P. falciparum multidrug-resistant parasites into Madagascar from the Comoros Islands (17), the rapid rise in the frequency of P. falciparum parasites with both pfdhfr and dhps mutations, and the alarming emergence of the single pfdhfr 164L allele from isolates collected during the last 3 years (2).…”