DISTINGUISHING RECRUDESCENCE FROM REINFECTION IN A LONGITUDINAL ANTIMALARIAL DRUG EFFICACY STUDY: COMPARISON OF RESULTS BASED ON GENOTYPING OF MSP-1, MSP-2, AND GLURP

ADITHYA CATTAMANCHI Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California; Department of Biochemistry, Makerere University Medical School, Kampala, Uganda; Department of Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, California

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DANIEL KYABAYINZE Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California; Department of Biochemistry, Makerere University Medical School, Kampala, Uganda; Department of Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, California

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ALAN HUBBARD Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California; Department of Biochemistry, Makerere University Medical School, Kampala, Uganda; Department of Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, California

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PHILIP J. ROSENTHAL Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California; Department of Biochemistry, Makerere University Medical School, Kampala, Uganda; Department of Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, California

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GRANT DORSEY Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California; Department of Biochemistry, Makerere University Medical School, Kampala, Uganda; Department of Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, California

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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.

Author Notes

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@itsa.ucsf.edu
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