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Plasmodium falciparum strains harboring dihydrofolate reductase with the I164L mutation are absent in Malawi and Zambia even under antifolate drug pressure

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Ochong, Edwin, Bell, David J., Johnson, David J., D'Alessandro, Umberto, Mulenga, Modest, Muangnoicharoen, Sant, Van Geertruyden, Jean-Pierre, Winstanley, Peter, Bray, Patrick G., Ward, Stephen A. and Owen, Andrew (2008) Plasmodium falciparum strains harboring dihydrofolate reductase with the I164L mutation are absent in Malawi and Zambia even under antifolate drug pressure. Antimicrobial Agents and Chemotherapy, Vol.52 (No.11). pp. 3883-3888. doi:10.1128/AAC.00431-08

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Official URL: http://dx.doi.org/10.1128/​AAC.00431-08

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Abstract

The Plasmodium falciparum dihydrofolate reductase (PfDHFR) enzyme is the target of pyrimethamine, a component of the antimalarial pyrimethamine-sulfadoxine. Resistance to this drug is associated primarily with mutations in the Pfdhfr gene. The I164L mutant allele is of particular interest, because strains possessing this mutation are highly resistant to pyrimethamine and to chlorproguanil, a component of chlorproguanil-dapsone. A recent study from Malawi reported this mutation at a prevalence of 4.7% in parasites from human immunodeficiency virus-positive pregnant women by using a real-time PCR method. These observations have huge implications for the use of pyrimethamine-sulfadoxine, chlorproguanil-dapsone, and future antifolate-artemisinin combinations in Africa. It was imperative that this finding be rigorously tested. We identified a number of critical limitations in the original genotyping strategy. Using a refined and validated real-time PCR strategy, we report here that this mutation was absent in 158 isolates from Malawi and 42 isolates from Zambia collected between 2003 and 2005.

Item Type: Journal Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
ISSN: 0066-4804
Official Date: November 2008
Dates:
DateEvent
November 2008Published
Volume: Vol.52
Number: No.11
Page Range: pp. 3883-3888
DOI: 10.1128/AAC.00431-08
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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