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In Vitro Activity of Atovaquone Against the African Isolates and Clones of Plasmodium falciparum

The in vitro activity of atovaquone (566C80) was evaluated and compared with that of chloroquine, quinine, mefloquine, halofantrine, artemether, pyrimethamine, and cycloguanil against African isolates and clones of Plasmodium falciparum using an isotopic, semimicro, drug susceptibility test. Atovaquone was highly active against the chloroquine-susceptible L-3 (geometric mean 50% inhibitory concentration [IC₅₀] = 0.978 nM) and L-16 clones (mean IC₅₀ = 0.680 nM) and against the multidrug-resistant FCM 29 clone (mean IC₅₀ = 1.76 nM). Similar low IC₅₀ values for atovaquone were observed against the chloroquine-susceptible isolates (n = 35; geometric mean IC₅₀ = 0.889 nM) and the chloroquine-resistant parasites (n = 26; geometric mean IC₅₀ = 0.906 nM). The in vitro responses between atovaquone and the other antimalarial drugs were not correlated, indicating the absence of in vitro cross-resistance. The high in vitro activity of atovaquone without any in vitro evidence for cross-resistance with other antimalarial drugs against the naturally occurring malaria parasites is a factor that favors further development of the drug for clinical use.