Title
**Plasmodium falciparum** strains harboring dihydrofolate reductase with the I164L mutation are absent in Malawi and Zambia even under antifolate drug pressure **Plasmodium falciparum** strains harboring dihydrofolate reductase with the I164L mutation are absent in Malawi and Zambia even under antifolate drug pressure
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Washington, D.C. ,
Subject
Human medicine
Source (journal)
Antimicrobial agents and chemotherapy. - Washington, D.C.
Volume/pages
52(2008) :11 , p. 3883-3888
ISSN
0066-4804
ISI
000260305600008
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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.
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