| Polymorphisms in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine-pyrimethamine resistance in malaria-infected patients from Nigeria. | |
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MedLine Citation:
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PMID: 16023986 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes have been used as means to predict treatment failure to sulfadoxine-pyrimethamine (SP) and for monitoring/surveillance of resistance to the drug in many areas where malaria is endemic. However, patients responses to treatment are significantly dependent on factors like host immunity profile of treated patients. In order to investigate the relationship between molecular markers of SP resistance, host immunity and clinical outcome, the association between pre-treatment dhfr and dhps genotypes, age and treatment outcomes was evaluated in 109 children treated with SP for acute uncomplicated malaria in Ibadan, Nigeria. Seventy-three percent of the children were cured with the drug, while 27% failed treatment after 28 days of follow-up. All children infected with parasites harboring less than two dhfr/dhps mutations were cured with SP. The dhfr triple (Asn-108/Ile-51/Arg-59) mutants or the dhps double mutants (Gly-437/Glu-540) were independently associated with SP treatment failure in children aged less than 5 years, but not in older children. The dhfr and dhps quintuple mutant (dhfr triple mutant+dhps double mutant) was the genotype most strongly associated with SP treatment failure (OR=24.72, 95%CI=8.24-74.15) in both younger and older children. |
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Authors:
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C T Happi; G O Gbotosho; O A Folarin; D O Akinboye; B O Yusuf; O O Ebong; A Sowunmi; D E Kyle; W Milhous; D F Wirth; A M J Oduola |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Acta tropica Volume: 95 ISSN: 0001-706X ISO Abbreviation: Acta Trop. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-29 Completed Date: 2005-10-12 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0370374 Medline TA: Acta Trop Country: Netherlands |
Other Details:
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Languages: eng Pagination: 183-93 Citation Subset: IM |
Affiliation:
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Malaria Research Laboratories, Postgraduate Institute for Medical Research and Training (PIMRAT), College of Medicine, University of Ibadan, Ibadan, Nigeria. christianhappi@hotmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antimalarials / pharmacology, therapeutic use* Child Child, Preschool Dihydropteroate Synthase / genetics* Drug Combinations Drug Resistance / genetics* Female Humans Infant Malaria, Falciparum / drug therapy*, immunology Male Nigeria Plasmodium falciparum / drug effects, genetics*, isolation & purification Polymorphism, Genetic Pyrimethamine / pharmacology, therapeutic use* Sulfadoxine / pharmacology, therapeutic use* Tetrahydrofolate Dehydrogenase / genetics* Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
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R03TW006298-01A1/TW/FIC NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antimalarials; 0/Drug Combinations; 2447-57-6/Sulfadoxine; 37338-39-9/sulfadoxine-pyrimethamine; 58-14-0/Pyrimethamine; EC 1.5.1.-/dihydrofolate reductase type II; EC 1.5.1.3/Tetrahydrofolate Dehydrogenase; EC 2.5.1.15/Dihydropteroate Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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