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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. ISSN 0066-4804
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Official URL: http://dx.doi.org/10.1128/AAC.00431-08
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 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: |
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| Volume: | Vol.52 | ||||
| Number: | No.11 | ||||
| Page Range: | pp. 3883-3888 | ||||
| Identification Number: | 10.1128/AAC.00431-08 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| URI: | http://wrap.warwick.ac.uk/id/eprint/46258 |
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