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Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 431-437
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

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Antimalarial Drug Susceptibility and Point Mutations Associated with Drug Resistance in 248 Plasmodium falciparum Isolates Imported from Comoros to Marseille, France in 2004–2006

Philippe Parola*, Bruno Pradines, Fabrice Simon, Marie-Paule Carlotti, Philippe Minodier, Marie-Pierre Ranjeva, Sékéné Badiaga, Lionel Bertaux, Jean Delmont, Marc Morillon, Ramatou Silai, Philippe Brouqui, AND Daniel Parzy
Service des Maladies Infectieuses et Tropicales, Hôpital Nord, Assistance Publique–Hôpitaux de Marseille, Marseille, France; Unité de Recherche en Physiologie et Pharmacocinétique Parasitaires, et Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Medecine Tropicale du Service de Sante des Armées, Marseille, France; Service de Pathologies Infectieuses et Tropicales, et Laboratoire de Biologie, Hôpital d’Instruction des Armées Laveran, Marseille, France; Service des Urgences, Hôpital Nord, Marseille, France; Unité de Pharmacologie Clinique et d’Evaluation Thérapeutique, Hôpital Timone, Assistance Publique–Hôpitaux de Marseille, Marseille, France; Centre de Formation et Recherche en Médecine et Santé Tropicales, Faculté de Médecine Secteur Nord, Marseille, France; Programme National de Lutte Contre le Paludisme, Moroni, Union des Comores

A total of 248 Plasmodium falciparum isolates were sampled in travelers with malaria who came to Marseille, France from Comoros to investigate in vitro activities of antimalarial drugs and molecular markers of drug resistance. Of the 248 isolates, 126 were maintained in culture. Of these, 53% were resistant to chloroquine, and 3% had reduced susceptibility to quinine, mefloquine, and atovaquone; 1% had reduced susceptibility to halofantrine and dihydroartemisinin; 7% had reduced susceptibility to monodesethylamodiaquine; 37% had reduced susceptibility to cycloguanil; and none had reduced susceptibility to lumefantrine. Resistance-associated point mutations were screened in 207 isolates. No mutations in the cytochrome b gene were found. Of the 207 isolates, 119 (58%) had a mutation in the P. falciparum dihydrofolate reductase (Pfdhfr) gene at codon 108, 6 (5%) had mutations in both Pfdhfr codon 108 and the P. falciparum dihydropteroate synthase codon 437, and 115 (56%) had the chloroquine resistance–associated K76T mutation in the P. falciparum chloroquine resistance transporter gene. This study represents a unique opportunity to improve surveillance of P. falciparum drug resistance in Comoros with consequences for treatment and chemoprophylaxis guidelines.


Received March 15, 2007. Accepted for publication June 13, 2007.

Acknowledgments: We thank E. Baret, N. Benoit, P. Bigot, J. Cren, and J. Mosnier for technical support, and Dr. P. Newton for editing the paper and helpful comments.

Financial support: This study was supported by the Programme Hospitalier de Recherche Clinique Régional 2003, Assistance Publique–Hôpitaux de Marseille; the French Ministry of Health (grant to the National Reference Centre of Malaria, Institut de Veille Sanitaire) and the French Armed Forces Health Service.

Disclosure: None of the authors has any conflicts of interest.

* Address correspondence to Philippe Parola, Service des Maladies Infectieuses et Tropicales, Hôpital Nord, Assistance Publique–Hôpitaux de Marseille, 13015 Marseille, France. E-mail: philippe.parola{at}medecine.univ-mrs.fr

Authors’ addresses: Philippe Parola, Jean Delmont, and Philippe Brouqui, Service des Maladies Infectieuses et Tropicales, Hôpital Nord, Assistance Publique–Hôpitaux de Marseille, 13015 Marseille, France, Telephone: 33-4-91-96-89-35, Fax: 33-4-91-96-89-38. Bruno Pradines, Unité de Recherche en Biologie et Epidémiologie Parasi-taires, Institut de Medecine Tropicale du Service de Sante des Armees, Boulevard Charles Livon, 13007 Marseille, France, Telephone: 33-4-91-15-01-10, Fax: 33-4-91-15-01-64. Fabrice Simon, Service de Pathologies Infectieuses et Tropicales, Hôpital d’Instruction des Armées Laveran, 13013 Marseille, France, Telephone: 33-4-91-61-72-48, Fax: 33-4-91-61-75-04. Marie-Paule Carlotti and Daniel Parzy, Unité de Recherche en Physiologie et Pharmacocinétique Parasitaires, Institut de Medecine Tropicale du Service de Sante des Armees, Boulevard Charles Livon, 13007 Marseille, France, Telephone: 33-4-91-15-01-14, Fax: 33-4-91-15-01-64. Philippe Minodier and Sékéné Badiaga, Service des Urgences, Hôpital Nord, Assistance Publique–Hôpitaux de Marseille, 13015 Marseille, France, Telephone: 33-4-91-96-83-84, Fax: 33-4-91-96-87-65. Marie-Pierre Ran-jeva, Unité de Pharmacologie Clinique et d’Evaluation Thérapeu-tique, Hôpital Timone, Assistance Publique–Hôpitaux de Marseille, Boulevard Jean Moulin, 13005 Marseille, Telephone: 33-4-91-38-80-01, Fax: 33-4-91-47-21-40. Marc Morillon, Laboratoire de Biologie, Hôpital d’Instruction des Armées Laveran, 13013 Marseille, France, Telephone: 33-4-91-61-71-10, Fax: 33-4-91-61-71-12. Ramatou Silai, Programme National de Lutte Contre le Paludisme, Moroni, Coulée, B 2108, Union des Comores, Telephone: 269-752-110.




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