Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/3323
Title: 61. Maïga, O., Djimdé, A. A., Hubert, V., Renard, E., Aubouy, A., Kironde, F., . . . Clain, J. (2007). A shared Asian origin of the triple-mutant dhfr allele in plasmodium falciparum from sites across africa.
Authors: Maiga, O.
Djimde, A.A.
Hubert, V.
Renard, E.
Aubouy, A.
Kironde, F.
Nsimba, B.
Koram, K.A.
Doumbo, O.K.
Le Bras, J.
Clain, J.
Keywords: EMTREE medical terms: adult; Africa; allele; article; Asian; chromosome; dhfr gene; female; gene; gene locus; gene mutation; genetic recombination; genetic variability; haplotype; heterozygote; human; infection prevention; major clinical study; malaria; male; microsatellite marker; molecular evolution; mutant; nonhuman; parasite isolation; Plasmodium falciparum; priority journal; protozoal genetics; Thailand; wild type
Issue Date: 1-Jul-2007
Citation: Maïga, O., Djimdé, A. A., Hubert, V., Renard, E., Aubouy, A., Kironde, F., . . . Clain, J. (2007). A shared Asian origin of the triple-mutant dhfr allele in plasmodium falciparum from sites across africa. Journal of Infectious Diseases, 196(1), 165-172.
Abstract: Background. Usefulness 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. © 2007 by the Infectious Diseases Society of America. All rights reserved.
URI: http://hdl.handle.net/123456789/3323
ISSN: 00221899
Appears in Collections:Noguchi Memorial Institute for Medical Research

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