A shared Asian origin of the triple-mutant dhfr allele in Plasmodium falciparum from sites across Africa

dc.contributor.authorMaïga, O.
dc.contributor.authorDjimdé, A.A.
dc.contributor.authorHubert, V.
dc.contributor.authorRenard, E.
dc.contributor.authorAubouy, A.
dc.contributor.authorKironde, F.
dc.contributor.authorNsimba, B.
dc.contributor.authorKoram, K.A.
dc.contributor.authorDoumbo, O.K.
dc.contributor.authorLe Bras, J.
dc.contributor.authorClain, J.
dc.date.accessioned2012-05-03T16:39:24Z
dc.date.accessioned2017-10-16T13:09:38Z
dc.date.available2012-05-03T16:39:24Z
dc.date.available2017-10-16T13:09:38Z
dc.date.issued2007
dc.description.abstractUsefulness of sulfadoxine-pyrimethamine as first-line therapy for uncomplicated Plasmodium falciparum malaria and intermittent preventive treatment in pregnancy throughout sub-Saharan Africa is compromised by the spread of dhfr alleles associated with pyrimethamine resistance. A predominant haplotype associated with the N51I+C59R+S108N triple-mutant dhfr allele has been reported recently in 4 African countries. A more comprehensive picture of the evolution of this mutant allele in Africa is lacking. METHODS: Seventy-five P. falciparum isolates carrying the wild-type dhfr allele and 204 carrying the triple-mutant dhfr allele from 11 African countries were selected. The genetic diversity of the chromosomes bearing these alleles was analyzed with 4 microsatellite markers closely linked to the dhfr gene. RESULTS: Seventy-three different 4-locus haplotypes carrying the wild-type dhfr allele were found. By contrast, 175 (85%) of 204 isolates carrying the triple-mutant dhfr allele shared a unique haplotype, identical to the one identified in Thailand. For the remaining triple-mutant isolates and one isolate with the quadruple-mutant dhfr allele N51I+C59R+S108N+I164L), haplotypes were closely related to the predominant haplotype by mutation or recombination. CONCLUSIONS: Migration of parasites carrying an ancestral triple-mutant dhfr allele drives the spread of dhfr alleles associated with pyrimethamine resistance throughout West and Central Africa.en_US
dc.identifier.urihttp://197.255.68.203/handle/123456789/1032
dc.language.isoenen_US
dc.publisherJournal of Infectious Diseases 196(1):165-72en_US
dc.titleA shared Asian origin of the triple-mutant dhfr allele in Plasmodium falciparum from sites across Africaen_US
dc.typeArticleen_US

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