Rare, highly pyrimethamine-resistant alleles of the Plasmodium falciparum dihydrofolate reductase gene from 5 African sites


Bates, SJ; Winstanley, PA; Watkins, WM; Alloueche, A; Bwika, J; Happi, TC; Kremsner, PG; Kublin, JG; Premji, Z; Sibley, CH; (2004) Rare, highly pyrimethamine-resistant alleles of the Plasmodium falciparum dihydrofolate reductase gene from 5 African sites. The Journal of infectious diseases, 190 (10). p. 1783. ISSN 0022-1899 DOI: https://doi.org/10.1086/425078

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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 13-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.

Item Type: Article
Keywords: Dihydropteroate-synthetase genes, chlorproguanil-dapsone, treatment, antimalarial-drug-resistance, thymidylate synthase, gene, sulfadoxine-pyrimethamine, point mutations, malaria, parasites, in-vitro, comparative efficacy, molecular markers
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 15499534
Web of Science ID: 224700800010
URI: http://researchonline.lshtm.ac.uk/id/eprint/14086

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