Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6

Artemisinin derivatives are an essential component of treatment against multidrug-resistant Plasmodium falciparum malaria. We aimed to investigate in-vitro resistance to artemisinin derivatives in field isolates. In-vitro susceptibility of 530 P falciparum isolates from three countries (Cambodia, Fr...

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Bibliographic Details
Published in:The Lancet (British edition) 2005-12, Vol.366 (9501), p.1960-3
Main Authors: Jambou, Ronan, Legrand, Eric, Niang, Makhtar, Khim, Nimol, Lim, Pharath, Volney, Béatrice, Ekala, Marie Thérèse, Bouchier, Christiane, Esterre, Philippe, Fandeur, Thierry, Mercereau-Puijalon, Odile
Format: Article
Language:English
Subjects:
Animals
Antimalarials
Artemisinins
Drug Resistance, Multiple
Genotype
Humans
Life Sciences
Microbiology and Parasitology
Parasitic Sensitivity Tests
Parasitology
Plasmodium falciparum
Point Mutation
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Summary:Artemisinin derivatives are an essential component of treatment against multidrug-resistant Plasmodium falciparum malaria. We aimed to investigate in-vitro resistance to artemisinin derivatives in field isolates. In-vitro susceptibility of 530 P falciparum isolates from three countries (Cambodia, French Guiana, and Senegal) with different artemisinin use was assessed with an isotopic microtest. Artemether IC50 up to 117 and 45 nmol/L was seen in French Guiana and Senegal, respectively. DNA sequencing in a subsample of 60 isolates lends support to SERCA-PfATPase6 as the target for artemisinins. The S769N PfATPase6 mutation, noted exclusively in French Guiana, was associated with raised (>30 nmol/L) artemether IC50s (p
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(05)67787-2