Abstract |
Mutations in dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) are associated with in vitro resistance to sulfadoxine and pyrimethamine, respectively. The response of 75 patients to sulfadoxine-pyrimethamine was determined, and the genes of the corresponding Plasmodium falciparum isolates were sequenced. Of 12 different unmixed allelic combinations, the triple dhfr mutation Asn-108/Arg-59/Ile-51 was observed in all patients responding with early treatment failure. Some, but not all, patients with an adequate clinical response also harbored isolates with the triple dhfr mutation. Higher initial parasitemia and fever distinguished these 2 patient groups. The dhps genotype apparently had no influence on the clinical outcome. The other dhfr alleles with 1 or 2 mutations and the wild-type allele were found in patients with an adequate clinical response. The triple dhfr mutation is one of the genetic determinants associated with in vivo resistance to sulfadoxine-pyrimethamine.
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Authors | L K Basco, R Tahar, A Keundjian, P Ringwald |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 182
Issue 2
Pg. 624-8
(Aug 2000)
ISSN: 0022-1899 [Print] United States |
PMID | 10915101
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Drug Combinations
- fanasil, pyrimethamine drug combination
- Sulfadoxine
- Tetrahydrofolate Dehydrogenase
- Dihydropteroate Synthase
- Pyrimethamine
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Topics |
- Adolescent
- Adult
- Child
- Child, Preschool
- Dihydropteroate Synthase
(genetics)
- Drug Combinations
- Drug Resistance
(genetics)
- Genes, Protozoan
- Humans
- Malaria, Falciparum
(drug therapy, genetics)
- Middle Aged
- Molecular Sequence Data
- Mutation
- Pyrimethamine
(therapeutic use)
- Sulfadoxine
(therapeutic use)
- Tetrahydrofolate Dehydrogenase
(genetics)
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