The effect of artemisinin, its derivatives and mefloquine against chloroquine-resistant strains of Plasmodium falciparum in vitro

Abstract

A 48 h in vitro test of the efficacy of artemisinin, dihydroartemisinin, artemether, mefloquine and chloroquine was carried out against 3 chloroquine-resistant strains of Plasmodium falciparum, strains K1 and T996 from Thailand and LS21 from India. A sigmoid E_max model was fitted to all in vitro inhibition data for each combination of drug and strain. Strains K1 and LS21 were strongly resistant to chloroquine, whereas T996 was partially resistant. Artemisinin, dihydroartemisinin and artemether were active against all strains, with complete growth inhibition at 10⁻⁷m. Artemether and dihydroartemisinin were both more potent than artemisinin, with 50% effective (EC₅₀) values of 0·57–1·6 nm and 0·36–3·1 nm respectively; the EC₅₀ of artemisinin was 1·5–6·1 nm for the 3 strains. The EC₅₀ values for mefloquine were 46–185 nm. At higher concentrations, strains K1 and LS21 were fully inhibited, while with strain T996 mefloquine did not fully inhibit even at the highest concentration, 1·28×10⁻⁶m. It is concluded that artemisinin and its derivatives were highly effective against the 3 chloroquine-resistant strains, one of which showed borderline resistance to mefloquine.