Abstract |
The point mutations in the Plasmodium falciparum dihydrofolate reductase (dhfr) and the dihydropteroate synthase (dhps) genes that are linked to sulphadoxine-pyrimethamine (SP) resistance in vitro have been well characterised. To determine whether a few of these mutations could predict SP treatment failure in vivo, two mutations (Asn-108 and Arg-59) in the dhfr gene and one (Glu-540) in the dhps gene were analysed according to the risk of SP parasitological failure (RI-RIII) at day 28 in pre-treatment isolates in 79 Ugandan children aged 6-59 (mean = 18.4, S.D. = 8.8) months with uncomplicated falciparum malaria. Neither the dhfr-108 (P = 0.3) nor the dhps-540 (P = 0.6) or dhfr-108 + dhps-540 (P = 0.04) mutations were significantly associated with SP parasitological failure. However, the dhfr-108 + dhfr-59 (P = 0.04), the dhfr-59 + dhps-540 (P = 0.04) and the dhfr-108 + dhfr-59 + dhps-540 (P = 0.02) mutations significantly increased the risk for SP parasitological failure. Our findings confirm an earlier report that the dhfr-59 and the dhps-540 mutations could be useful genetic markers for rapid screening of populations at high risk of SP resistance.
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Authors | Ambrose O Talisuna, Anne Nalunkuma-Kazibwe, Peter Langi, Theonest K Mutabingwa, William W Watkins, Eric Van Marck, Thomas G Egwang, Umberto D'Alessandro |
Journal | Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
(Infect Genet Evol)
Vol. 4
Issue 4
Pg. 321-7
(Dec 2004)
ISSN: 1567-1348 [Print] Netherlands |
PMID | 15374529
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimalarials
- Drug Combinations
- Sulfadoxine
- Tetrahydrofolate Dehydrogenase
- Dihydropteroate Synthase
- Pyrimethamine
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Topics |
- Animals
- Antimalarials
(adverse effects, therapeutic use)
- Child, Preschool
- Dihydropteroate Synthase
(genetics)
- Drug Combinations
- Drug Resistance
- Follow-Up Studies
- Humans
- Infant
- Malaria, Falciparum
(drug therapy)
- Plasmodium falciparum
(enzymology, genetics)
- Point Mutation
- Pyrimethamine
(adverse effects, therapeutic use)
- Retrospective Studies
- Sulfadoxine
(adverse effects, therapeutic use)
- Tetrahydrofolate Dehydrogenase
(genetics)
- Time Factors
- Treatment Failure
- Uganda
(epidemiology)
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