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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| Veröffentlicht in: | The Journal of infectious diseases Jg. 176; H. 6; S. 1590 |
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| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
United States
01.12.1997
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| ISSN: | 0022-1899 |
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| Abstract | 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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| AbstractList | 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.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. 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. |
| Author | Doumbo, O K Cespedes, J L Carter, D Cortese, J F Watkins, W M Djimde, A Plowe, C V Nwanyanwu, O C Winstanley, P A Estrada-Franco, J G Mollinedo, R E Avila, J C |
| Author_xml | – sequence: 1 givenname: C V surname: Plowe fullname: Plowe, C V organization: Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA – sequence: 2 givenname: J F surname: Cortese fullname: Cortese, J F – sequence: 3 givenname: A surname: Djimde fullname: Djimde, A – sequence: 4 givenname: O C surname: Nwanyanwu fullname: Nwanyanwu, O C – sequence: 5 givenname: W M surname: Watkins fullname: Watkins, W M – sequence: 6 givenname: P A surname: Winstanley fullname: Winstanley, P A – sequence: 7 givenname: J G surname: Estrada-Franco fullname: Estrada-Franco, J G – sequence: 8 givenname: R E surname: Mollinedo fullname: Mollinedo, R E – sequence: 9 givenname: J C surname: Avila fullname: Avila, J C – sequence: 10 givenname: J L surname: Cespedes fullname: Cespedes, J L – sequence: 11 givenname: D surname: Carter fullname: Carter, D – sequence: 12 givenname: O K surname: Doumbo fullname: Doumbo, O K |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/9395372$$D View this record in MEDLINE/PubMed |
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| DOI | 10.1086/514159 |
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| Snippet | To assess the relationship between mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) and clinical... |
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| SubjectTerms | 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 |
| Title | Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance |
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