1. Molecular genotyping in a malaria treatment trial in Uganda - unexpected high rate of new infections within 2 weeks after treatment.
- Author
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Mugittu K, Priotto G, Guthmann JP, Kiguli J, Adjuik M, Snounou G, Beck HP, Mshinda H, Olliaro PL, and Taylor WR
- Subjects
- Animals, Artesunate, Child, Drug Combinations, Drug Therapy, Combination, Endemic Diseases, Genes, Protozoan genetics, Genotype, Humans, Merozoite Surface Protein 1 analysis, Parasitemia drug therapy, Parasitemia genetics, Polymerase Chain Reaction methods, Protozoan Proteins analysis, Recurrence, Uganda epidemiology, Antimalarials administration & dosage, Artemisinins administration & dosage, Malaria, Falciparum drug therapy, Malaria, Falciparum genetics, Malaria, Falciparum parasitology, Plasmodium falciparum genetics, Pyrimethamine administration & dosage, Sesquiterpenes administration & dosage, Sulfadoxine administration & dosage
- Abstract
Polymerase chain reaction (PCR) genotyping of malaria parasites in drug efficacy trials helps differentiate reinfections from recrudescences. A combination therapy trial of one (n = 115) or three (n = 117) days artesunate (1AS, 3AS 4 mg/kg/day) plus sulphadoxine-pyrimethamine (SP) vs. SP alone (n = 153) was conducted in Mbarara, a mesoendemic area of western Uganda. All paired recurrent Plasmodium falciparum parasitaemias on days 7, 14, 21 and 28 post-treatment were genotyped by PCR amplification and analysis of glutamate-rich protein (glurp) and merozoite surface proteins (msp) 1 and 2 genes to distinguish recrudescent from new infections. A total of 156 (1AS = 61, 3AS = 35, SP alone = 60) of 199 paired recurrent samples were successfully analysed and were resolved as 79 recrudescences (1AS = 32, 3AS = 8, SP = 39) and 77 as new infections (1AS = 29, 3AS = 27, SP = 21). The ratios of proportions of new to recrudescent infections were 0.2, 0.9, 1.4 and 1.9 on days 7, 14, 21 and 28, respectively (P < 0.001, chi(2) test for linear trend). Unexpected high new infection rates were observed early in follow-up on days 7 [5/26 (19.2%)] and 14 [24/51 (47.1%)]. These results impact significantly on resistance monitoring and point to the value of genotyping all recurrent infections in antimalarial trials.
- Published
- 2007
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