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In Vitro Activity of Artemisinin Derivatives Against African Isolates and Clones of Plasmodium falciparum

The in vitro activities of chloroquine, quinine, melfoquine, halofantrine, artemisinin, arteether, artemether, and artelinate were evaluated against African clones and isolates of Plasmodium falciparum, using an isotopic, semimicro, drug susceptibility test. The chloroquine-resistant FCM 29 clone was 1.6 and 6.2 times more susceptible to artemisinin when compared with the chloroquine-susceptible, mefloquine-, and halofantrine-resistant L-3 and L-16 clones, respectively. Cross-resistance patterns between the standard antimalarial drugs and artemisinin were determined against 36 African isolates of P. falciparum obtained from imported cases of malaria in France. Chloroquine-resistant isolates (n = 21) were significantly more susceptible to artemisinin (50% inhibitory concentration [IC₅₀] 7.67 nM), arteether (IC₅₀ 3.88 nM), artemether (IC₅₀ 3.71 nM), and artelinate (IC₅₀ 3.46 nM), as compared with the 15 chloroquine-susceptible isolates (IC₅₀ 11.4, 5.66, 5.14, and 5.04 nM, respectively). Arteether, artemether, and artelinate were equally effective and twice as potent as artemisinin. A significant positive correlation was found between artemisinin and mefloquine (r = 0.424, P = 0.022), artemisinin and halofantrine (r = 0.569, P < 0.001), chloroquine and quinine (r = 0.651, P < 0.001), and mefloquine and halofantrine (r = 0.863, P < 0.001), suggesting in vitro cross-resistance among these drugs. The present in vitro findings require confirmation in clinical studies.

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