ABSTRACT
Atovaquone was the first hydroxynaphthoquinone suitable for the treatment of Plasmodium falciparum infection (Davies et al., 1989). Unfortunately, early treatment failure rates were as high as 30% (Looareesuwan et al., 1996; Chiodini et al., 1995); among those who had recrudescent infection, parasites were approximately 1000- to 10000-fold more resistant (Happi et al., 2006) than they had been pre-treatment. Accordingly, a partner drug was sought to reduce the rate of treatment failure and limit the emergence of resistance. In 1996 the highly synergistic combination atovaquone–proguanil was registered as an anti-malarial agent. Although safe and effective, atovaquone–proguanil is expensive compared with other anti-malarials, a factor that limits its use in endemicity.
