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Why has the dihydrofolate reductase 164 mutation not consistently been found in Africa yet?

Nzila, Alexis, Ochong, Edwin, Nduati, E., Gilbert, K., Winstanley, P., Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192 and Marsh, Kevin (2005) 'Why has the dihydrofolate reductase 164 mutation not consistently been found in Africa yet?'. Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol 99, Issue 5, pp. 341-346.

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Abstract

Resistance to the antifolate sulfadoxine-pyrimethamine (SP), the current mass-treatment antimalarial drug, is associated with selection of point mutations in dihydrofolate reductase and dihydropteroate synthase. Among these mutations, the leucine 164 dihydrofolate reductase mutation (Leu-164) is associated with higher levels of SP resistance; this mutation is also associated with a decrease in the efficacy of chlorproguanil/dapsone, a newly developed antifolate antimalarial drug. Leu-164 has been detected in Southeast Asia and South America, regions where SP is no longer effective. Surprisingly, this mutation has not yet been detected in Africa, using the standard protocol based on PCR-RFLP, despite high SP resistance. In this paper, we discuss briefly the reasons why Leu-164 has not yet been selected in Africa and we propose a means that may slow down the selection of this mutation. (c) 2004 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: malaria plasmodium falciparum dihydrofolate reductase drug resistance antifolate africa uncomplicated falciparum-malaria pyrimethamine-sulfadoxine resistance dihydropteroate synthetase genes dihydrofolate-reductase gene kenyan plasmodium-falciparum drug-resistance chlorproguanil-dapsone antibiotic-resistance point mutations in-vitro
Subjects: QV Pharmacology > QV 38 Drug action.
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
QX Parasitology > Protozoa > QX 135 Plasmodia
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1016/j.trstmh.2004.07.002
Depositing User: Sarah Lewis-Newton
Date Deposited: 19 Oct 2011 13:45
Last Modified: 06 Feb 2018 13:03
URI: http://archive.lstmed.ac.uk/id/eprint/1970

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