Atovaquone and proguanil hydrochloride followed by primaquine for treatment of Plasmodium vivax malaria in Thailand

Chloroquine-resistant Plasmodium vivax malaria has been reported in several geographical areas. The P. vivax life-cycle includes dormant hepatic paras ites (hypnozoites) that cause relapsing malaria weeks to years after initia l infection. Curative therapy must therefore target both the erythrocytic a nd hepatic stages of infection. Between July 1997 and June 1998, we conduct ed an open-label study in Thailand to evaluate the efficacy and tolerabilit y of a sequential regimen of combination atovaquone (1000 mg) and proguanil hydrochloride (400 mg), once daily for 3 days, followed by primaquine (30 mg daily for 14 days) for treatment of vivax malaria. All 46 patients who c ompleted the 3-day course of atovaquone-proguanil cleared their parasitaemi a within 2-6 days. During a 12-week follow-up period in 35 patients, recurr ent parasitaemia occurred in 2. Both recurrent episodes occurred 8 weeks af ter the start of therapy, consistent with relapse from persistent hypnozoit es rather than recrudescence of persistent blood-stage parasites. The dosin g regimen was well tolerated. Results of this trial indicate that atovaquon e-proguanil followed by primaquine is safe and effective for treatment of v ivax malaria.