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The impact of antimalarial drug resistance mutations on parasite fitness, and its implications for the evolution of resistance

Hastings, Ian ORCID: https://orcid.org/0000-0002-1332-742X and Donnelly, Martin ORCID: https://orcid.org/0000-0001-5218-1497 (2005) 'The impact of antimalarial drug resistance mutations on parasite fitness, and its implications for the evolution of resistance'. Drug Resistance Updates, Vol 8, Issue 1-2, pp. 43-50.

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Abstract

It is widely assumed in genetics that most mutations disrupt metabolism to some extent, and are consequently likely to be disadvantageous for the organisms that inherit them. This may apply to mutations encoding drug resistance in malaria, where the mutation may be disadvantageous in the absence of the drug, imposing a genetic 'cost' of resistance. We review several lines of evidence suggesting that such costs do occur, that they may be relatively large, and review their likely impact on the evolution of drug resistance in the malaria parasite Plasmodium falciparum. (c) 2005 Elsevier Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: malaria drug-resistance mutations costs evolution plasmodium-falciparum malaria elimination half-life chloroquine resistance pyrimethamine-sulfadoxine dihydrofolate-reductase dihydropteroate synthase combination chemotherapy genetic redundancy spread malawi Animals Antimalarials/therapeutic use* Drug Resistance/genetics* Evolution, Molecular Humans Malaria/drug therapy* Mutation Plasmodium falciparum*/drug effects Plasmodium falciparum*/enzymology Plasmodium falciparum*/genetics Tetrahydrofolate Dehydrogenase/genetics Antimalarials dihydrofolate reductase type II Tetrahydrofolate Dehydrogenase
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials
QV Pharmacology > QV 38 Drug action.
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Groups (2002 - 2012) > Vector Group
Digital Object Identifer (DOI): https://doi.org/10.1016/j.drup.2005.03.003
Depositing User: Sarah Lewis-Newton
Date Deposited: 12 Oct 2011 14:47
Last Modified: 06 Feb 2018 13:02
URI: http://archive.lstmed.ac.uk/id/eprint/1880

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