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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

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  • 1 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, Yaoundé, Cameroon; Antimalarial Drug Resistance, Global Malaria Programme, World Health Organization, Geneva, Switzerland

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.

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