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Molecular Epidemiology of Malaria in Cameroon. XXVIII. In vitro Activity of Dihydroartemisinin against Clinical Isolates of Plasmodium falciparum and Sequence Analysis of the P. falciparum ATPase 6 Gene

The Plasmodium falciparum ATPase 6 (Pfatp6), homolog of sarco-endoplasmic reticulum, calcium-dependent ATPase in malaria parasites, has been proposed to be the main target of artemisinins. Four distinct point mutations (L263E, E431K, A623E, and S769N) have been reported to be associated with artemisinin resistance. The Pfatp6 sequence polymorphism was determined to evaluate the prevalence of these mutations in fresh clinical isolates in Yaounde, Cameroon, and compare sequence data with in vitro response to dihydroartemisinin. Two major haplotypes were observed: the wild-type LEAS (n = 60, 62%) and a single mutant LKAS (n = 35, 36%). These amino acid substitutions did not influence the level of in vitro response to dihydroartemisinin (P > 0.05). Plasmodium falciparum isolates from Cameroon are highly sensitive in vitro to artemisinins. However, the relatively high prevalence of E431K may be a warning signal that warrants a regular monitoring of these molecular markers and/or in vitro activity of artemisinin derivatives.

Received September 26, 2008. Accepted for publication April 12, 2009.

Acknowledgments: We are grateful to Sisters Marie-Solange Oko and Pauline Ngono Mbia and their nursing and laboratory staff at the Catholic missionary Nlongkak dispensary in Yaounde for invaluable help in recruiting patients.

Financial support: This study was supported by the European Union (Redox Antimalarial Drug Discovery [READ-UP] project, contract no. 018602) and Technical Service Agreement, Global Malaria Programme, World Health Organization (Geneva, Switzerland).

Disclaimer: Pascal Ringwald is a staff member of the World Health Organization. This author alone is responsible for the views expressed in this publication, and they do not necessarily represent the decisions, policy, or views of the World Health Organization.

^* Address correspondence to Leonardo K. Basco, Unité de Recherche Maladies Infectieuses et Tropicales Emergentes, Institut de Recherche pour le Développement and Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la Lutte Contre les Endémies en Afrique Centrale, BP 288, Yaoundé, Cameroon. E-mail: lkbasco{at}yahoo.fr

Authors’ addresses: Rachida Tahar and Leonardo Basco, Unité de Recherche Maladies Infectieuses et Tropicales Emergentes, Institut de Recherche pour le Développement and Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la Lutte Contre les Endémies en Afrique Centrale, BP 288, Yaoundé, Cameroon, E-mails: rachida.tahar{at}ird.fr and lkbasco{at}yahoo.fr. Pascal Ringwald, Antimalarial Drug Resistance, Global Malaria Programme, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland, E-mail: ringwaldp{at}who.int.