Characteristics of Plasmodium falciparum dhfr haplotypes that confer pyrimethamine resistance, Kilifi, Kenya, 1987-2006

  • Laura K. Certain
  • , Marnie Briceño
  • , Steven M. Kiara
  • , Alexis M. Nzila
  • , William M. Watkins
  • , Carol Hopkins Sibley

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.Weobserved no triple-mutant alleles with haplotypes related to those of the Africa-derived wild-type and double-mutant alleles.

Original languageEnglish
Pages (from-to)1743-1751
Number of pages9
JournalJournal of Infectious Diseases
Volume197
Issue number12
DOIs
StatePublished - 15 Jun 2008
Externally publishedYes

Bibliographical note

Funding Information:
Received 15 October 2007; accepted 28 December 2007; electronically published 12 May 2008. Potential conflicts of interest: none reported. Presented in part: 18th Annual Parasitology Conference, Seattle, WA, 18 May 2006. Financial support: National Institutes of Health (grant AI 55604 to C.H.S.). Reprints or correspondence: Prof. C. H. Sibley, Dept. of Genome Sciences, University of Washington, Box 355065, Seattle, WA 98105-5065 ([email protected]).

ASJC Scopus subject areas

  • General Medicine

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