TY - JOUR

T1 - Prediction of Plasmodium falciparum resistance to sulfadoxine/ pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes

T2 - A comparative study between sites of differing endemicity

AU - Alifrangis, Michael

AU - Enosse, Sonja

AU - Khalil, Insaf F.

AU - Tarimo, Donath S.

AU - Lemnge, Martha M.

AU - Thompson, Richardo

AU - Bygbjerg, Ib C.

AU - Rønn, Anita M.

PY - 2003/12/1

Y1 - 2003/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=1342332265&partnerID=8YFLogxK

M3 - Journal article

AN - SCOPUS:1342332265

VL - 69

SP - 601

EP - 606

JO - Journal. National Malaria Society

JF - Journal. National Malaria Society

SN - 0002-9637

IS - 6

ER -