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

Ronan Jambou (1) , Eric Legrand (2) , Makhtar Niang (1) , Nimol Khim (3) , Pharath Lim (3) , Béatrice Volney (2) , Marie Thérèse Ekala (4) , Christiane Bouchier (5) , Philippe Esterre (2) , Thierry Fandeur (3) , Odile Mercereau-Puijalon (4)

1 Institut Pasteur de Dakar
2 Institut Pasteur de la Guyane
3 Institut Pasteur du Cambodge
4 Immunologie moléculaire des parasites
5 Génomique (Plate-Forme) - Genomics Platform

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.

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Parasitology

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, 2005, 366 (9501), pp.1960-3. ⟨10.1016/S0140-6736(05)67787-2⟩. ⟨pasteur-00590989⟩