Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp.
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.
Cattamanchi
Adithya
A
Department of Medicine, San Francisco General Hospital University of California, San Francisco, San Francisco, California 94143, USA.
Kyabayinze
Daniel
D
Hubbard
Alan
A
Rosenthal
Philip J
PJ
Dorsey
Grant
G
D000655:Amodiaquine / Q000627:therapeutic use; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D000077332:Artesunate; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000235:genetics*; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology / Q000473:pathology; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics*; D011739:Pyrimethamine / Q000627:therapeutic use; D012008:Recurrence; D012717:Sesquiterpenes / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D017211:Treatment Failure; D014454:Uganda / Q000453:epidemiology
D000953:Antigens, Protozoan; D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D004338:Drug Combinations; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D012717:Sesquiterpenes; C065974:merozoite surface protein 2, Plasmodium; C072492:glutamate-rich protein, Plasmodium; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine