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.
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.
Authors: Md Tauqeer Alam; Dziedzom K de Souza; Sumiti Vinayak; Sean M Griffing; Amanda C Poe; Nancy O Duah; Anita Ghansah; Kwame Asamoa; Laurence Slutsker; Michael D Wilson; John W Barnwell; Venkatachalam Udhayakumar; Kwadwo A Koram Journal: J Infect Dis Date: 2011-01-15 Impact factor: 5.226
Authors: Sumiti Vinayak; Md Tauqeer Alam; Rithy Sem; Naman K Shah; Augustina I Susanti; Pharath Lim; Sinuon Muth; Jason D Maguire; William O Rogers; Thierry Fandeur; John W Barnwell; Ananias A Escalante; Chansuda Wongsrichanalai; Frederick Ariey; Steven R Meshnick; Venkatachalam Udhayakumar Journal: J Infect Dis Date: 2010-05-15 Impact factor: 5.226
Authors: Sumiti Vinayak; Md Tauqeer Alam; Tonya Mixson-Hayden; Andrea M McCollum; Rithy Sem; Naman K Shah; Pharath Lim; Sinuon Muth; William O Rogers; Thierry Fandeur; John W Barnwell; Ananias A Escalante; Chansuda Wongsrichanalai; Frederick Ariey; Steven R Meshnick; Venkatachalam Udhayakumar Journal: PLoS Pathog Date: 2010-03-26 Impact factor: 6.823
Authors: Patrícia Salgueiro; José L Vicente; Conceição Ferreira; Vânia Teófilo; André Galvão; Virgílio E do Rosário; Pedro Cravo; João Pinto Journal: BMC Infect Dis Date: 2010-06-09 Impact factor: 3.090