TY - JOUR
T1 - Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine- sulfadoxine use and resistance
AU - Plowe, C. V.
AU - Cortese, J. F.
AU - Djimde, A.
AU - Nwanyanwu, O. C.
AU - Watkins, W. M.
AU - Winstanley, P. A.
AU - Estrada-Franco, J. G.
AU - Mollinedo, R. E.
AU - Avila, J. C.
AU - Cespedes, J. L.
AU - Carter, D.
AU - Doumbo, O. K.
N1 - Funding Information:
Financial support: Department of Medicine, School of Medicine, University of Maryland; Laboratory of Parasitic Diseases, NIH; US Agency for International Development through its Health and Human Resources Analysis for Africa (HHRAA) Program, the USAID Mission in Bamako, Mali and support of the Community Health Sciences Unit, Lilongwe, Malawi; UNDP/World Bank/WHO Special Programme for Research in Tropical Diseases (TDR CHEMAL #910151); Wellcome Trust, London (grant 045010); Pan American Health Organization (grant HPD-HD-G-USA-1035); and Ministry of Health, Bolivia.
PY - 1997
Y1 - 1997
N2 - To assess the relationship between mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) and clinical pyrimethamine-sulfadoxine resistance, polymerase chain reaction surveys and analyses for new mutations were conducted in four countries with increasing levels of pyrimethamine-sulfadoxine resistance: Mali, Kenya, Malawi, and Bolivia. Prevalence of mutations at DHFR codon 108 and a new mutation at DHPS 540 correlated with increased pyrimethamine-sulfadoxine resistance (P < .05). Mutations at DHFR 51, DHFR 59, and DHPS 437 correlated with resistance without achieving statistical significance. Mutations at DHFR 164 and DHPS 581 were common in Bolivia, where pyrimethamine-sulfadoxine resistance is wide-spread, but absent in African sites. Two new DHFR mutations, a point mutation at codon 50 and an insert at codon 30, were found only in Bolivia. DHFR and DHPS mutations occur in a progressive, stepwise fashion. Identification of specific sets of mutations causing in vivo drug failure may lead to the development of molecular surveillance methods for pyrimethamine-sulfadoxine resistance.
AB - To assess the relationship between mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) and clinical pyrimethamine-sulfadoxine resistance, polymerase chain reaction surveys and analyses for new mutations were conducted in four countries with increasing levels of pyrimethamine-sulfadoxine resistance: Mali, Kenya, Malawi, and Bolivia. Prevalence of mutations at DHFR codon 108 and a new mutation at DHPS 540 correlated with increased pyrimethamine-sulfadoxine resistance (P < .05). Mutations at DHFR 51, DHFR 59, and DHPS 437 correlated with resistance without achieving statistical significance. Mutations at DHFR 164 and DHPS 581 were common in Bolivia, where pyrimethamine-sulfadoxine resistance is wide-spread, but absent in African sites. Two new DHFR mutations, a point mutation at codon 50 and an insert at codon 30, were found only in Bolivia. DHFR and DHPS mutations occur in a progressive, stepwise fashion. Identification of specific sets of mutations causing in vivo drug failure may lead to the development of molecular surveillance methods for pyrimethamine-sulfadoxine resistance.
UR - http://www.scopus.com/inward/record.url?scp=0030720799&partnerID=8YFLogxK
U2 - 10.1086/514159
DO - 10.1086/514159
M3 - Artículo
SN - 0022-1899
VL - 176
SP - 1590
EP - 1596
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -