Rare, Highly Pyrimethamine‐Resistant Alleles of thePlasmodium falciparumDihydrofolate Reductase Gene from 5 African Sites
Year: 2004
Type: article
Abstract: In eastern and southern Africa, there has been a rapid increase in the prevalence of alleles with mutations in the Plasmodium falciparum dihydrofolate reductase gene (dhfr) associated with increased risk of clinical failure of sulfadoxine-pyrimethamine (S/P). Molecular methods for surveillance of these mutations are now widespread, but the usual analysis detects only the most prevalent allele in a polyclonal sample. We used a yeast-expression system to identify rare, highly pyrimethamine-resistant alleles of dhfr in isolates from 5 African countries--Kenya, Tanzania, Malawi, Gabon, and Nigeria. Only the isolates from Nigeria yielded significant numbers of novel resistant alleles, and only 1 of the alleles from any location showed a >3-fold increase in resistance to S/P or to chlorproguanil-dapsone. Overall, these results suggest that dhfr alleles that confer high levels of resistance to antifolates are rare, even in eastern and southern Africa, where pyrimethamine has been intensively used.
DOI: 10.1086/425078
Institutions: University of Washington, University of Liverpool, London School of Hygiene & Tropical Medicine, Kenya Medical Research Institute, University of Ibadan, Institute for Advanced Medical Research and Training, Albert Schweitzer Hospital, University of Tübingen, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Muhimbili University of Health and Allied Sciences
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1996516048