CLINICAL TRIAL OF ORAL ARTESUNATE WITH OR WITHOUT HIGH-DOSE PRIMAQUINE FOR THE TREATMENT OF VIVAX MALARIA IN THAILAND

UDOMSAK SILACHAMROON Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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SRIVICHA KRUDSOOD Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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SOMBAT TREEPRASERTSUK Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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POLRAT WILAIRATANA Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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KOBSIRI CHALEARMRULT Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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HLA YIN MINT Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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PANNAMAS MANEEKAN Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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NICHOLAS J. WHITE Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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VICTOR R. GOURDEUK Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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GARY M. BRITTENHAM Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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SORNCHAI LOOAREESUWAN Department of Clinical Tropical Medicine and Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust, Mahidol University Oxford Tropical Medicine Research Programme Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Sickle Cell Disease, Howard University, Washington, District of Columbia; College of Physicians and Surgeons, Columbia University, Harkness Pavilion, New York, New York

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We studied prospectively 801 Thai patients admitted to the Bangkok Hospital for Tropical Diseases with acute, symptomatic Plasmodium vivax malaria to determine the optimum duration of treatment with oral artesunate and the safety, tolerability, and effectiveness of a high dose of primaquine in prevention of relapse. Patients were randomly assigned to one of four treatment groups: 1) a five-day course of artesunate (Group A5); 2) a seven-day course of artesunate (Group A7); 3) a five-day course of artesunate plus a 14-day course of high-dose primaquine (0.6 mg/kg, maximum dose = 30 mg) (Group A5 + P); and 4) a seven-day course of artesunate plus a 14-day course of high-dose primaquine (Group A7 + P). During 28 days of observation, P. vivax reappeared in the blood of 50% of those who received artesunate alone (Groups A5 and A7), compared with none of those who received primaquine (Groups A5 + P and A7 + P; P < 0.0001). Adverse effects were confined to the 13 patients with a deficiency for glucose-6-phosphate dehydrogenase; high-dose primaquine (0.6 mg/kg of base a day) had to be stopped in four (31%) patients because of a significant decrease in the hematocrit. The combination of five days of artesunate and 14 days of primaquine is a highly effective and generally well-tolerated treatment regimen for vivax malaria in Thailand.

Author Notes

Reprint requests: Prof. S. Looareesuwan, E-mail: tmslr@mahidol.ac.th.
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