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SULFADOXINE-PYRIMETHAMINE PLUS CHLOROQUINE OR AMODIAQUINE FOR UNCOMPLICATED FALCIPARUM MALARIA: A RANDOMIZED, MULTISITE TRIAL TO GUIDE NATIONAL POLICY IN UGANDA

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  • 1 Ministry of Health, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Makerere University Medical School, Kampala, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California; Institute of Public Health, Makerere University, Kampala, Uganda

The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine-pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-pyrimethamine and from 13% to 35% with amodiaquine plus sulfadoxine-pyrimethamine (risk differences 21–32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-pyrimethamine was significantly more efficacious; however, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.

Author Notes

Reprint requests: Nathan Bakyaita, Ministry of Health/UMSP, P.O. Box 7475, Kampala, Uganda, Telephone: Office +256 41 231563/9 Ext 249, Cell +256 77 601579, Fax: +256 41 540524, E-mail: nbakyaita@yahoo.com.
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