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Genotyping frequently is used to distinguish recrudescent from new infections in antimalarial drug efficacy trials, but methodology and interpretation of results have not been standardized. We compared the utility of polymorphisms within 3 Plasmodium falciparum genes during a longitudinal trial in Kampala, Uganda. Merozoite surface protein-1 (msp-1) and merozoite surface protein-2 (msp-2) revealed greater diversity than glutamate-rich protein. Genotypes based on msp-1, msp-2, and all 3 genes combined were compared for 394 initial and subsequent isolates. Classification of most episodes as due to recrudescence or reinfection was straightforward. In 24% (msp-1), 16% (msp-2), and 62% (3 genes combined) of samples, subsequent episodes contained identical and new alleles, however. Our analysis suggested that such episodes should be classified as reinfections and not recrudescence. Comparing the 3 studied genes, msp-2 results were most accurate, and analysis of this single gene effectively distinguished recrudescence from reinfection in our study population.
Received July 26, 2002. Accepted for publication October 21, 2002.
Acknowledgments: We thank the clinical study team of B.M. Karakire, Marx Dongo, Sam Nsobya, Moses Kiggundu, Christopher Bongole, Regina Nakafero, Bridget K. Nzarubara, Pauline Byakika, and Sarah Kibirango; Sarah Staedke, for reviewing the manuscript; community leaders from the Kawempe Division of Kampala; and the study participants and their parents or guardians.
Financial support: This work was supported by the Fogarty International Center/National Institutes of Health (TW00007, TW01506, and AI43301), the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), and the Doris Duke Charitable Foundation Clinical Research Fellowship.
Authors’ addresses: Adithya Cattamanchi, Philip J. Rosenthal, and Grant Dorsey, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, P.O. Box 0811, San Francisco, CA 94143, Telephone: 415-206-8687, Fax: 415-648-8425. Daniel Kyabayinze, Department of Biochemistry, Makerere University Medical School, P.O. Box 7072, Kampala, Uganda. Alan Hubbard, Department of Biostatistics, School of Public Health, University of California, Berkeley, 735 University Hall, Berkeley, CA 94720, Telephone: 510-642-8365, Fax: 510-642-5815.
Reprint requests: Grant Dorsey, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, P.O. Box 0811, San Francisco, CA 94143, Telephone: 415-206-8687, Fax: 415-648-8425, E-mail: grantd{at}itsa.ucsf.edu
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