Origins of the recent emergence of Plasmodium falciparum pyrimethamine resistance alleles in Madagascar.

Valérie Andriantsoanirina (1) , Christiane Bouchier (2) , Magali Tichit (2) , Martial Jahevitra (1) , Stéphane Rabearimanana (1) , Rogelin Randrianjafy (1) , Arsène Ratsimbasoa (3) , Odile Mercereau-Puijalon (4) , Rémy Durand (5) , Didier Ménard (1)

1 Institut Pasteur de Madagascar
2 Génomique (Plate-Forme) - Genomics Platform
3 Ministère de la Santé, du Planning Familial et de la Protection Sociale
4 Immunologie moléculaire des parasites
5 Laboratoire de Parasitologie-Mycologie

The combination of sulfadoxine-pyrimethamine is recommended for use as intermittent preventive treatment of malaria during pregnancy and is deployed in Africa. The emergence and the spread of resistant parasites are major threats to such an intervention. We have characterized the Plasmodium falciparum dhfr (pfdhfr) haplotypes and flanking microsatellites in 322 P. falciparum isolates collected from the Comoros Islands and Madagascar. One hundred fifty-six (48.4%) carried the wild-type pfdhfr allele, 19 (5.9%) carried the S108N single-mutation allele, 30 (9.3%) carried the I164L single-mutation allele, 114 (35.4%) carried the N51I/C59R/S108N triple-mutation allele, and 3 (1.0%) carried the N51I/C59R/S108N/I164L quadruple-mutation allele. Microsatellite analysis showed the introduction from the Comoros Islands of the ancestral pfdhfr triple mutant allele of Asian origin and its spread in Madagascar. Evidence for the emergence on multiple occasions of the I164L single-mutation pfdhfr allele in Madagascar was also obtained. Thus, the conditions required to generate mutants with quadruple mutations are met in Madagascar, representing a serious threat to current drug policy.

Domains: Life Sciences [q-bio]

Valérie Andriantsoanirina, Christiane Bouchier, Magali Tichit, Martial Jahevitra, Stéphane Rabearimanana, et al.. Origins of the recent emergence of Plasmodium falciparum pyrimethamine resistance alleles in Madagascar.. Antimicrobial Agents and Chemotherapy, 2010, 54 (6), pp.2323-9. ⟨10.1128/AAC.01511-09⟩. ⟨pasteur-00835565⟩