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Antifolate Resistance in Plasmodium falciparum: Multiple Origins and Identification of Novel dhfr Alleles

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dc.contributor.author Andrea M McCollum, Amanda C Poe, Mary Hamel, Curtis Huber, Zhiyong Zhou, Ya Ping Shi, Peter Ouma, John Vulule, Peter Bloland, Laurence Slutsker, John W Barnwell, Venkatachalam Udhayakumar, Ananias A Escalante
dc.date.accessioned 2021-01-08T07:43:11Z
dc.date.available 2021-01-08T07:43:11Z
dc.date.issued 2006
dc.identifier.uri https://repository.maseno.ac.ke/handle/123456789/3484
dc.description.abstract BackgroundSulfadoxine-pyrimethamine has been widely used as first-line therapy for uncomplicated malaria throughout sub-Saharan Africa. Recent studies conducted in Asia and Africa suggest the triple-mutant dhfr genotype (51I/59R/108N) may have been generated as a single event in Southeast Asia, with subsequent spread of the single lineage to the African continent, but this hypothesis needs further validation MethodsDirect sequencing of polymerase chain reaction (PCR) products, pyrosequencing, and cloning of PCR products were utilized to identify mutations in dhfr. To investigate the evolutionary history of dhfr alleles, we assayed microsatellite loci flanking dhfr along chromosome 4 ResultsA total of 15 of 479 samples from western Kenya showed the presence of I164L, in 5 different genotypes. We document C50R in 2 of our samples. Using microsatellite markers, we show 2 haplotypes for both the 51I/108N/164L and 51I/59R/108N/164L genotypes. Our results also show multiple lineages for the triple-mutant dhfr genotype in Africa ConclusionsThese findings highlight the importance of local characterization of alleles before molecular surveillance of drug-resistant alleles is considered in different endemic settings and populations en_US
dc.publisher The University of Chicago Press en_US
dc.title Antifolate Resistance in Plasmodium falciparum: Multiple Origins and Identification of Novel dhfr Alleles en_US
dc.type Article en_US


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