Abstract |
Pyrimethamine, in combination with sulfadoxine, is currently one of the major alternative drugs used for the treatment of chloroquine-resistant Plasmodium falciparum malaria infections in Africa. The mechanism of pyrimethamine resistance has been strongly associated with a single, key point mutation in the dihydrofolate reductase- thymidylate synthase gene, resulting in the substitution of the wild-type allele Ser-108 by either Asn-108 or Thr-108. The pyrimethamine-resistant phenotype and/or genotype were determined in 273 Cameroonian clinical isolates obtained in Yaounde by in vitro assays and polymerase chain reaction-restriction fragment length polymorphism over a 5-year period. The in vitro assays showed that 42% (18 of 43) and 63% (69 of 110) of the isolates obtained in 1994-1995 and 1997-1998, respectively, were resistant to pyrimethamine (50% inhibitory concentration [IC50] > 100 nM). The polymerase chain reaction showed that 43% (55 of 127) and 59% (50 of 85) of the isolates in 1994-1995 and 1997-1998, respectively, had the mutant Asn-108 allele. The pyrimethamine-resistant genotype (Asn-108) corresponded with the pyrimethamine-resistant phenotype (IC50 > or = 100 nM) in a large majority (> 95%) of the isolates. The results of our study suggest an increasing prevalence of pyrimethamine resistance in Yaounde. Our study further suggests that pyrimethamine resistance can be monitored by a technique that can be adopted by malaria research centers in Africa.
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Authors | L K Basco, P Ringwald |
Journal | The American journal of tropical medicine and hygiene
(Am J Trop Med Hyg)
Vol. 61
Issue 5
Pg. 802-6
(Nov 1999)
ISSN: 0002-9637 [Print] United States |
PMID | 10586915
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimalarials
- DNA Primers
- DNA, Protozoan
- Drug Combinations
- fanasil, pyrimethamine drug combination
- Sulfadoxine
- Tetrahydrofolate Dehydrogenase
- Pyrimethamine
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Topics |
- Adolescent
- Adult
- Animals
- Antimalarials
(pharmacology)
- Cameroon
(epidemiology)
- Child
- DNA Primers
(chemistry)
- DNA, Protozoan
(chemistry)
- Drug Combinations
- Drug Resistance
(genetics)
- Electrophoresis, Agar Gel
- Humans
- Inhibitory Concentration 50
- Malaria, Falciparum
(drug therapy, epidemiology, parasitology)
- Phenotype
- Plasmodium falciparum
(drug effects, enzymology, genetics)
- Point Mutation
- Polymerase Chain Reaction
- Polymorphism, Restriction Fragment Length
- Pyrimethamine
(pharmacology)
- Scintillation Counting
- Sulfadoxine
(pharmacology)
- Tetrahydrofolate Dehydrogenase
(chemistry, genetics)
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