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Antimalarial drug treatment policy in sub-Saharan Africa is generally guided by the results of clinical drug efficacy studies in patients with uncomplicated Plasmodium falciparum malaria. The selection criteria used to enroll these patients often vary and may have a significant impact on treatment outcomes. In Kampala, Uganda, we investigated the impact of age, baseline temperature, and pre-treatment parasite density on estimates of treatment efficacy using a statistical modeling approach in 2,138 patients enrolled in six clinical trials involving seven different treatment regimens. Decreasing age, increasing temperature, and increasing parasite density were all independent predictors of an increased risk of treatment failure across all treatment groups. Compared with an unrestrictive approach to subject selection, enrolling only patients fulfilling selection criteria recommended by the World Health Organization (age < 5 years old, documented fever, and parasite density < 200,000/µL) increased the risk of treatment failure by 25–60% for the different treatment regimens. Caution should be taken when comparing results from drug efficacy studies with different subject selection criteria.
Received March 6, 2004. Accepted for publication May 28, 2004.
Acknowledgments: We thank the clinical study team of B. M. Karakire, Regina Nakafero, Christopher Bongole, Moses Kiggundu, Marx Dongo, Denise Njama, Authur Mpimbazia, Bridget Nzarubara, Pauline Byakika, Naome Kilama, Mary Kasanga, Sam Nsobya, Assay Balita, Annet Birabwa, Sara Kibirango, Kenneth Mwebaze, George Musoke, and Fred Kintu for their assistance in the study.
Financial support: This study was supported by the Fogarty International Center/National Institutes of Health (TW00007, TW01506 and AI43301) and the United Nations Development Program/World Bank/World Health Organization Special Program for Research and Training in Tropical Diseases.
Authors’ addresses: Grant Dorsey and Sarah G. Staedke, Department of Medicine, San Francisco General Hospital, University of California, Parnassus Avenue, Box 0811, San Francisco, CA, 94143, Telephone: 415-206-4680, Fax: 415-648-8425, E-mails: grantd{at}itsa.ucsf.edu and staedke{at}itsa.ucsf.edu. Anne F. Gasasira and Moses R. Kamya, Department of Medicine, Makerere University Medical School, Anatomy Building, Room C-443, Kampala, Uganda, Telephone: 256-41-251-387, Fax: 256-41-540-524, E-mails: a_gasasira{at}hotmail.com and mkamya{at}info.com.ug. Rhoderick Machekano and Alan Hubbard, Department of Biostatistics, School of Public Health, University of California, 735 U-Hall 7360, Berkeley, CA, 94172, Telephone: 510-642-8365, Fax: 510-642-5815, E-mails: rodmach{at}uclink.berkeley.edu and hubbard{at}stat.berkeley.edu.
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