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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

Ochong, Edwin, Bell, David J., Johnson, David, D'Alessandro, U., Mulenga, M., Muangnoicharoen, Sant, Van Geertruyden, J. P., Winstanley, P. A., Bray, Patrick, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 and Owen, A. (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, Issue 11, pp. 3883-3888.

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Official URL: http://aac.asm.org/

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: Article
Subjects: WC Communicable Diseases > Tropical and Parasitic Diseases > WC 755 Epidemiology
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
QV Pharmacology > QV 38 Drug action.
QV Pharmacology > QV 4 General works
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
QX Parasitology > QX 4 General works
QX Parasitology > Protozoa > QX 135 Plasmodia
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
WA Public Health > WA 105 Epidemiology
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1128/AAC.00431-08
Depositing User: Mary Creegan
Date Deposited: 30 Mar 2010 10:37
Last Modified: 06 Feb 2018 13:00
URI: http://archive.lstmed.ac.uk/id/eprint/887

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