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Intensity of malaria transmission and the evolution of drug resistance

Hastings, Ian ORCID: and Watkins, W. M. (2005) 'Intensity of malaria transmission and the evolution of drug resistance'. Acta Tropica, Vol 94, Issue 3, pp. 218-229.

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The intensity of malaria transmission varies both naturally and as a consequence of human public health intervention. The relationship between transmission intensity and the rate at which antimalarial drug resistance evolves affects the design of surveillance programmes, and the likely impact of malaria control programmes. Several theoretical studies have investigated this relationship and their key results are summarised and interpreted. The most important result is that transmission intensity does not directly affect the evolution of resistance. It exerts its influence through three clinical/epidemiological "mediators" (clonal multiplicity, the threat of infection, level of human immunity) which ultimately determine the dynamics of resistance via five "effector" variables: sexual recombination, intrahost dynamics, community drug use, proportion of malaria infections treated, and the number of parasites per host. We argue that the evolution of resistance is likely to be a two-stage process: mutations encoding drug tolerance preceding those encoding resistance. The evolution of drug tolerance is determined solely by the level of drug use in the community which is likely to have an extremely weak relationship with transmission intensity. The evolution of resistance is more complex and affected by all five effectors. The most likely scenarios are that resistance evolves faster in areas of high transmission if encoded by a single gene but if encoded by two or more genes it evolves fastest in areas of high or low transmission, with a minimum at intermediate levels of transmission. (c) 2005 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: drug resistance malaria epidemiology intensity of transmission elimination half-life plasmodium-falciparum pyrimethamine-sulfadoxine antimalarial-drugs selective pressure parasites spread mutations model chloroquine
Subjects: 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
Digital Object Identifer (DOI):
Depositing User: Sarah Lewis-Newton
Date Deposited: 13 Oct 2011 09:45
Last Modified: 19 Sep 2019 11:29


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