Characteristics of Plasmodium falciparum dhfr haplotypes that confer pyrimethamine resistance, Kilifi, Kenya, 1987--2006.
Resistance to the antimalarial drug sulfadoxine-pyrimethamine (SP) emerged in Plasmodium falciparum from Asia in the 1960s and subsequently spread to Africa. It is not known whether alleles that confer SP resistance also arose independently in Africa. We defined the coding region and microsatellite haplotypes of dhfr alleles in P. falciparum collected in Kilifi, Kenya, during 1987--2006, which spans the period when SP was first introduced. Isolates that carried a double-mutant or triple-mutant dhfr allele were detected at a low frequency, even during 1987--1988. Each of 2 double mutants carried a unique haplotype, and both were related to wild-type haplotypes from the same population. The number of isolates that carried a triple-mutant dhfr allele increased rapidly after introduction of SP and shared the haplotype of the triple mutant derived form Asia. We observed no triple-mutant alleles with haplotypes related to those of the Africa-derived wild-type and double-mutant alleles.
Certain
Laura K
LK
Department of Genome Sciences, University of Washington, Seattle, Washington 98105-5065, USA.
Briceño
Marnie
M
Kiara
Steven M
SM
Nzila
Alexis M
AM
Watkins
William M
WM
Sibley
Carol Hopkins
CH
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology; D018895:Microsatellite Repeats; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D011739:Pyrimethamine / Q000494:pharmacology*; D013997:Time Factors
D000962:Antimalarials; D011739:Pyrimethamine