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

Abstract : 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<0.0001, Mann-Whitney). All resistant isolates came from areas with uncontrolled use of artemisinin derivatives. This rise in resistance indicates the need for increased vigilance and a coordinated and rapid deployment of drug combinations.
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https://hal-riip.archives-ouvertes.fr/pasteur-00590989
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Submitted on : Thursday, May 5, 2011 - 11:32:31 PM
Last modification on : Monday, January 13, 2020 - 5:08:06 PM

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Ronan Jambou, Eric Legrand, Makhtar Niang, Nimol Khim, Pharath Lim, et al.. Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6.. The Lancet, Elsevier, 2005, 366 (9501), pp.1960-3. ⟨10.1016/S0140-6736(05)67787-2⟩. ⟨pasteur-00590989⟩

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