Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity
Research output: Contribution to journal › Journal article › Research › peer-review
Plasmodium falciparum resistance to sulfadoxine/pyrimethamine (S/P) is due to mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhfr) genes. Large-scale screening of the prevalence of these mutations could facilitate the surveillance of the level of S/P resistance in vivo. The prevalence of mutations in dhfr and dhps in relation to S/P efficacy was studied in four sites of differing endemicity in Sudan, Mozambique, and Tanzania. The sites were organized in order of increasing resistance and a significant increase in the prevalence of triple mutations in codons c51, c59, and c108 of dhfr was observed. A similar trend was observed when dhfr genotypes were combined with c437 of dhps. Since the differences in S/P resistance between the sites were minor, but nevertheless revealed major differences in dhfr genotype prevalence, the role of dhfr as a general molecular marker seems debatable. The differences may reflect variation in the duration and magnitude of S/P usage (or other antifolate drugs) between the sites. Thus, triple dhfr mutations may prove suitable only as a general guideline for detecting emerging S/P resistance in areas where S/P has been introduced recently. However, changes in susceptibility within the same area with moderate levels of resistance may be possible by longitudinal surveillance of a subset of dhfr/dhps mutations that has been associated with S/P resistance in vivo in a defined location.
Original language | English |
---|---|
Journal | American Journal of Tropical Medicine and Hygiene |
Volume | 69 |
Issue number | 6 |
Pages (from-to) | 601-6 |
Number of pages | 5 |
ISSN | 0002-9637 |
Publication status | Published - 2003 |
Bibliographical note
Keywords: Adolescent; Adult; Aged; Animals; Antimalarials; Biological Markers; Child; Dihydropteroate Synthase; Drug Combinations; Drug Resistance, Multiple; Endemic Diseases; Female; Humans; Malaria, Falciparum; Male; Middle Aged; Mutation; Parasitic Sensitivity Tests; Plasmodium falciparum; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Population Surveillance; Predictive Value of Tests; Prevalence; Pyrimethamine; Sulfadoxine; Tanzania; Tetrahydrofolate Dehydrogenase
ID: 8377887