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Antimicrobial Agents and Chemotherapy, November 2009, p. 4588-4597, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00610-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Plasmodium falciparum Drug Resistance in Madagascar: Facing the Spread of Unusual pfdhfr and pfmdr-1 Haplotypes and the Decrease of Dihydroartemisinin Susceptibility{triangledown}

Valérie Andriantsoanirina,1 Arsène Ratsimbasoa,2 Christiane Bouchier,3 Martial Jahevitra,1 Stéphane Rabearimanana,1 Rogelin Radrianjafy,1 Voahangy Andrianaranjaka,1 Tantely Randriantsoa,1 Marie Ange Rason,1 Magali Tichit,3 Léon Paul Rabarijaona,4 Odile Mercereau-Puijalon,5 Rémy Durand,6 and Didier Ménard1,5*

Unité de Recherche sur le Paludisme, Institut Pasteur de Madagascar, Antananarivo, Madagascar,1 Departement de Santé Publique, Faculté de Médecine, Université d'Antananarivo, Antananarivo, Madagascar,2 Génopôle de l'Ile de France, Plate-Forme Génomique, Institut Pasteur, Paris, France,3 Section Survie de l'Enfant, United Nations Children's Fund, Antananarivo, Madagascar,4 Unité d'Immunologie Moléculaire des Parasites, CNRS URA 2581, Institut Pasteur, Paris, France,5 Laboratoire de Parasitologie-Mycologie, AP-HP Hôpital Avicenne, Bobigny, France6

Received 5 May 2009/ Returned for modification 26 July 2009/ Accepted 13 August 2009

The aim of this study was to provide the first comprehensive spatiotemporal picture of Plasmodium falciparum resistance 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 of pfcrt, pfmdr-1, pfdhfr, and pfdhps mutations and the pfmdr-1 gene copy number in 1,596 P. falciparum isolates 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 the pfdhfr and the pfdhps mutations, (iii) the alarming emergence of the single pfdhfr 164L 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 of P. falciparum resistance in the future is required.


* Corresponding author. Mailing address: Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, CNRS URA 2581, 28 rue du Roux, Paris 75724 Cedex 15, France. Phone: 331 40 61 35 55. Fax: 331 45 68 85 88. E-mail: dmenard{at}pasteur.fr

{triangledown} Published ahead of print on 24 August 2009.


Antimicrobial Agents and Chemotherapy, November 2009, p. 4588-4597, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00610-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.