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PREVALENT PFMDR1 N86Y MUTANT PLASMODIUM FALCIPARUM IN MADAGASCAR DESPITE ABSENCE OF PFCRT MUTANT STRAINS

We assessed the status of point mutations associated with chloroquine resistance in pfcrt codon 76 and in pfmdr1 codon 86 among Plasmodium falciparum isolates from symptomatic patients in 3 sites in Madagascar. The in vitro susceptibility of P. falciparum isolates to quinoline-containing drugs was also determined. All isolates (N = 117) successfully typed were pfcrt wild-type, except one from Tsiroanomandidy (1 of 27). However, 67.5% (95% CI: 58.2–75.9%) of these isolates contained mutant pfmdr1 86Y. The pfmdr1 N86Y mutation is associated with higher mefloquine susceptibility, but it did not affect the sensitivity of parasites to chloroquine or quinine. Our findings demonstrate that pfmdr1 mutant P. falciparum are prevalent in Madagascar and confirm the low prevalence of pfcrt mutant P. falciparum after 60 years of chloroquine use. They provide additional field-based evidence for increased mefloquine susceptibility in pfmdr1 mutant P. falciparum and are suggestive of the intrahost selection of pfmdr1 mutant parasites.

Received December 19, 2006. Accepted for publication January 31, 2007.

Acknowledgments: The authors thank the Direction Provinciale de la Santé de Toamasina and the Service de Santé de District de Santé de Tsiroanomandidy for their collaboration. We also thank the medical team of the Groupe de Recherche sur le Paludisme de l’Institut Pasteur de Madagascar for sample collection.

Financial support: This study was supported financially by the French Government (FSP/RAI), the European Union (RESMALCHIP QLTR-2001-01503), the Institut Pasteur, and the IAEA in Vienna (RAF 6/025).

Disclaimer: We declare that we have no commercial or other association potentially posing a conflict of interest concerning the work reported in this paper.

^* Address correspondence to Milijaona Randrianarivelojosia, BP 1274, Antananarivo 101, Madagascar. E-mail: milijaon{at}pasteur.mg

Authors’ addresses: Marie-Ange Rason, Herilalaina B. Andrianantenaina, Frédéric Ariey, Olivier Domarle, and Milijaona Randrianarivelojosia, Unité de Recherche sur le Paludisme, BP 1274, Institut Pasteur de Madagascar, Antananarivo (101), Madagascar, Telephone: +261 20 22 412 72, Fax: +261 20 22 415 34, E-mails: mieange{at}pasteur.mg, milijaon{at}pasteur.mg, and domarle{at}pasteur.mg. (Current address for Frédéric Ariey, Institut Pasteur de Cambodge, 5 Boulevard Monivong, BP 983 Phnom Pehn, Cambodge, E-mail: fariey{at}pasteur-kh.org). Andrianirina Raveloson, Service de Lutte Contre le Paludisme, Ministère de la Santé et du Planning Familial, Antananarivo, Madagascar, E-mail: a_raveloson{at}hotmail.com.

Reprint requests: Milijaona Randrianarivelojosia, Unité de Recherche sur le Paludisme, BP 1274 Antananarivo (101), Institut Pasteur de Madagascar, E-mail: milijaon{at}pasteur.mg.