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Antimicrobial Agents and Chemotherapy, November 2008, p. 3883-3888, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00431-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Plasmodium falciparum Strains Harboring Dihydrofolate Reductase with the I164L Mutation Are Absent in Malawi and Zambia Even under Antifolate Drug Pressure

Edwin Ochong,¹ David J. Bell,¹ David J. Johnson,¹ Umberto D'Alessandro,³ Modest Mulenga,⁴ Sant Muangnoicharoen,¹ Jean-Pierre Van Geertruyden,³ Peter A. Winstanley,² Patrick G. Bray,² Stephen A. Ward,¹ and Andrew Owen^2*

Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L35QA,¹ Department of Pharmacology and Therapeutics, 70 Pembroke Place, University of Liverpool, Liverpool, L69 3GF, United Kingdom,² Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium,³ Tropical Diseases Research Center (TDRC), Ndola, Zambia⁴

Received 1 April 2008/ Returned for modification 26 June 2008/ Accepted 29 July 2008

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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* Corresponding author. Mailing address: Department of Pharmacology and Therapeutics, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, United Kingdom. Phone: 44 (0) 151 794 5919. Fax: 44 (0) 151 794 5656. E-mail: aowen{at}liv.ac.uk

Published ahead of print on 25 August 2008.

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Antimicrobial Agents and Chemotherapy, November 2008, p. 3883-3888, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00431-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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