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Two oral regimens comprising a single dose of 20 mg/kg of artemisinin followed by three days of quinine, 10 mg/kg three times a day (AQ), or doxycycline, 4 mg/kg once a day (AD), were compared with a standard seven-day course of oral quinine, 10 mg/kg three times a day (Q), in the treatment of uncomplicated falciparum malaria. Of 161 treated patients, 157 could be included in the analysis. The mean ± SD parasite clearance time was 43 ± 14 hr for AQ and 41 ± 19 hr for AD, and significantly longer for quinine: 66 ± 24 hr (P = 0.0001). Treatment failure occurred in one Q and in 3 AD patients. The recrudescence rate was 16% for Q, 28% for AQ, and significantly worse for AD: 67% (P = 0.0001). Adverse effects were mainly limited to cinchonism. The conclusion is that a seven-day course of quinine is still effective in the initial treatment of uncomplicated falciparum malaria in Vietnam, but one should pay attention to possible recrudescence. The addition of a single 20 mg/kg per os dose of artemisinin allows for shortening the duration of treatment, with faster parasite clearance, comparable efficacy, and better tolerance, but with no reduction of recrudescence. The combination of artemisinin with three days of doxycycline is also not effective in preventing recrudescence.