Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amodiaquine / therapeutic use
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Animals
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Antigens, Protozoan / genetics
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Antimalarials / therapeutic use*
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Artemisinins / therapeutic use
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Artesunate
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Child, Preschool
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DNA, Protozoan / genetics*
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Drug Combinations
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Drug Resistance
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Female
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Genotype
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Humans
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Infant
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Longitudinal Studies
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Malaria, Falciparum / drug therapy*
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Malaria, Falciparum / epidemiology
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Malaria, Falciparum / parasitology
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Malaria, Falciparum / pathology
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Male
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Merozoite Surface Protein 1 / genetics
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Plasmodium falciparum / genetics*
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Plasmodium falciparum / isolation & purification
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Polymerase Chain Reaction
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Protozoan Proteins / genetics*
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Pyrimethamine / therapeutic use
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Recurrence
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Sesquiterpenes / therapeutic use
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Sulfadoxine / therapeutic use
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Treatment Failure
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Uganda / epidemiology
Substances
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Antigens, Protozoan
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Antimalarials
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Artemisinins
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DNA, Protozoan
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Drug Combinations
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Merozoite Surface Protein 1
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Protozoan Proteins
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Sesquiterpenes
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merozoite surface protein 2, Plasmodium
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glutamate-rich protein, Plasmodium
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Amodiaquine
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fanasil, pyrimethamine drug combination
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Artesunate
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Sulfadoxine
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Pyrimethamine