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Two mutations in dihydrofolate reductase combined with one in the dihydropteroate synthase gene predict sulphadoxine-pyrimethamine parasitological failure in Ugandan children with uncomplicated falciparum malaria

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dc.contributor.author Talisuna, A. O. en_US
dc.contributor.author Nalunkuma-Kazibwe, A. en_US
dc.contributor.author Langi, P. en_US
dc.contributor.author Mutabingwa, T. K. en_US
dc.contributor.author Watkins, W. W. en_US
dc.contributor.author Van Marck, E. en_US
dc.contributor.author Egwang, T. G. en_US
dc.contributor.author D'Alessandro, U. en_US
dc.date.accessioned 2007-12-06T14:34:13Z
dc.date.available 2007-12-06T14:34:13Z
dc.date.issued 2004 en_US
dc.identifier.issn 1567-1348 en_US
dc.identifier.doi http://dx.doi.org/10.1016/j.meegid.2004.04.002
dc.identifier.other ITG-P1B en_US
dc.identifier.other ITG-PLA en_US
dc.identifier.other PARAS en_US
dc.identifier.other U-MALAR en_US
dc.identifier.other JIF en_US
dc.identifier.other DOI en_US
dc.identifier.other ABSTRACT en_US
dc.identifier.uri http://hdl.handle.net/10390/291
dc.description.abstract The point mutations in the Plasmodium falciparum dihydrofolate reductase (dhfr) and the dihydropteroate synthase (dhps) genes that are linked to sulphadoxine-pyrimethamine (SP) resistance in vitro have been well characterised. To determine whether a few of these mutations could predict SP treatment failure in vivo, two mutations (Asn-108 and Arg-59) in the dhfr gene and one (Glu-540) in the dhps gene were analysed according to the risk of SP parasitological failure (RI-RIII) at day 28 in pre-treatment isolates in 79 Ugandan children aged 6-59 (mean = 18.4, S.D. = 8.8) months with uncomplicated falciparum malaria. Neither the dhfr-108 (P = 0.3) nor the dhps-540 (P = 0.6) or dhfr-108 + dhps-540 (P = 0.04) mutations were significantly associated with SP parasitological failure. However, the dhfr-108 + dhfr-59 (P = 0.04), the dhfr-59 + dhps-540 (P = 0.04) and the dhfr-108 + dhfr-59 + dhps-540 (P = 0.02) mutations significantly increased the risk for SP parasitological failure. Our findings confirm an earlier report that the dhfr-59 and the dhps-540 mutations could be useful genetic markers for rapid screening of populations at high risk of SP resistance. en_US
dc.language English en_US
dc.subject Protozoal diseases en_US
dc.subject Malaria en_US
dc.subject Plasmodium falciparum en_US
dc.subject Antimalarials en_US
dc.subject Sulfadoxine-pyrimethamine en_US
dc.subject Drug resistance en_US
dc.subject Prediction en_US
dc.subject Risk populations en_US
dc.subject Screening en_US
dc.subject In vivo en_US
dc.subject Molecular markers en_US
dc.subject Point mutations en_US
dc.subject Dihydrofolate reductase gene en_US
dc.subject Dihydropteroate synthase gene en_US
dc.subject Uganda en_US
dc.subject Africa, East en_US
dc.title Two mutations in dihydrofolate reductase combined with one in the dihydropteroate synthase gene predict sulphadoxine-pyrimethamine parasitological failure in Ugandan children with uncomplicated falciparum malaria en_US
dc.type Article en_US
dc.citation.issue 4 en_US
dc.citation.jtitle Infection, Genetics and Evolution en_US
dc.citation.volume 4 en_US
dc.citation.pages 321-327 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/15374529
dc.citation.jabbreviation Infect Genet Evol en_US


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