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
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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. / Alifrangis, Michael; Enosse, Sonja; Khalil, Insaf F.; Tarimo, Donath S.; Lemnge, Martha M.; Thompson, Richardo; Bygbjerg, Ib C.; Rønn, Anita M.
I: American Journal of Tropical Medicine and Hygiene, Bind 69, Nr. 6, 01.12.2003, s. 601-606.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 203866800