Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance

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 increasin...

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Bibliographic Details
Published in:The Journal of infectious diseases Vol. 176; no. 6; p. 1590
Main Authors: Plowe, C V, Cortese, J F, Djimde, A, Nwanyanwu, O C, Watkins, W M, Winstanley, P A, Estrada-Franco, J G, Mollinedo, R E, Avila, J C, Cespedes, J L, Carter, D, Doumbo, O K
Format: Journal Article
Language:English
Published: United States 01.12.1997
Subjects:
Africa - epidemiology
Amino Acid Sequence
Animals
Antimalarials - pharmacology
Antimalarials - therapeutic use
Base Sequence
Bolivia - epidemiology
Cloning, Molecular
Dihydropteroate Synthase - genetics
Dihydropteroate Synthase - metabolism
DNA, Protozoan - analysis
DNA, Protozoan - genetics
Drug Combinations
Drug Resistance
Humans
Malaria, Falciparum - drug therapy
Malaria, Falciparum - epidemiology
Malaria, Falciparum - genetics
Malaria, Falciparum - parasitology
Molecular Epidemiology
Molecular Sequence Data
Molecular Structure
Mutagenesis, Insertional
Plasmodium falciparum - drug effects
Plasmodium falciparum - enzymology
Plasmodium falciparum - genetics
Point Mutation
Polymerase Chain Reaction
Prevalence
Pyrimethamine - pharmacology
Pyrimethamine - therapeutic use
Sulfadoxine - pharmacology
Sulfadoxine - therapeutic use
Tetrahydrofolate Dehydrogenase - chemistry
Tetrahydrofolate Dehydrogenase - genetics
Tetrahydrofolate Dehydrogenase - metabolism
Bolivia
Africa
ISSN:0022-1899
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Summary: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 widespread, 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.
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ISSN:0022-1899
DOI:10.1086/514159