A shared Asian origin of the triple-mutant DHFR allele in plasmodium falciparum from sites across Africa.

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.

A shared Asian origin of the triple-mutant DHFR allele in plasmodium falciparum from sites across Africa.

Date

2007-07-01

Authors

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.

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

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.