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Bull World Health Organ. 1994;72(2):233-8.

Comparison of oral artesunate and quinine plus tetracycline in acute uncomplicated falciparum malaria.

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  • 1Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.


In Thailand Plasmodium falciparum malaria is highly resistant to available antimalarials. Investigations on the efficacy of existing antimalarials and of alternative drugs are urgently needed. Artesunate has been shown to be effective against falciparum malaria, but is associated with a high recrudescence rate. We have carried out a comparative clinical trial of the standard regimen of quinine + tetracycline versus oral artesunate at a 700-mg total dose given over 5 days to patients with acute uncomplicated falciparum malaria. The 64 male patients who took part in the study were randomized to receive either quinine-tetracycline (33 patients) or oral artesunate (31 patients). All the patients were admitted to the Bangkok Hospital for Tropical Diseases for 28 days. Oral artesunate had faster parasite and fever clearance times than the combination quinine-tetracycline, but the cure rate was not significantly different for the two regimens. However, the occurrence of adverse effects, such as tinnitus, was significantly higher in the quinine-tetracycline group. Surprisingly nausea and dizziness were rather common with artesunate. The possibility of neurological adverse effects for artesunate should also be borne in mind. Oral artesunate (700 mg given over 5 days) is effective and better tolerated than the combination quinine-tetracycline. The cure rate we obtained is higher than that reported in previous studies with 600 mg of oral artesunate given over 5 days. Oral artesunate can be considered as an alternative drug for multiple-drug-resistant falciparum malaria; however, adverse effects, particularly neurotoxicity, should be closely monitored before its widespread use can be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)


At the Bangkok Hospital for Tropical Diseases in Thailand, health workers collected blood samples from male patients with acute uncomplicated falciparum malaria so researchers could compare the efficacy of artesunate (700 mg over 5 days) with the standard antimalarial treatment (600 mg quinine at 8 hour intervals plus 250 mg tetracycline at 6 hour intervals for 7 days). All 31 patients in the artesunate group had a much more rapid initial response than the 33 in the quinine-tetracycline group (mean parasite clearance time [PCT] = 37 hours; mean fever clearance time [FCT] = 31 vs. 73 and 55 hours, respectively) (p = 0.000001 for PCT; p = 0.000041 for FCT). In both groups, the mean PCT and mean FCT did not differ with level of pretreatment parasitemia. The cure rates on day 28 did not differ significantly (96.7% for the artesunate group, 100% for the quinine-tetracycline group). Five men in the artesunate group and nine in the quinine-tetracycline group had Plasmodium vivax in the peripheral blood between days 13 and 24, suggesting that these two regimens are not effective during the intrahepatic stage of plasmodia. 29 patients in the quinine-tetracycline group had tinnitus, while no one in the artesunate group did (p = 0.000001). Nausea and dizziness were common in both groups (45% for the artesunate group and 60% for the quinine-tetracycline group; 52% and 48%, respectively). Vomiting was more common in the quinine-tetracycline group (91% vs. 26%; p = 0.000005). Seven patients in the artesunate group had bradycardia, mostly during days 2-7. Convulsions occurred in one patient in the artesunate group 21 days after the first dose. They may have been caused by malaria, but artemisinin compounds have had central nervous system effects. These findings suggest that 700 mg artesunate is an effective antimalarial in areas with multiple-drug resistant parasites. Health workers should monitor its side effects, especially neurotoxicity, closely.

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