Gametocytocidal activity in antimalarial drugs speeds the spread of drug resistance

Hastings, Ian ORCID: https://orcid.org/0000-0002-1332-742X (2006) 'Gametocytocidal activity in antimalarial drugs speeds the spread of drug resistance'. Tropical Medicine & International Health, Vol 11, Issue 8, pp. 1206-1217.

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Abstract

OBJECTIVE Antimalarial drugs kill the asexual parasites responsible for causing disease and some, notably chloroquine and the artemisinins, also kill the sexual transmission stages known as gametocytes. It is invariably argued by malariologists that gametocytocidal activity is beneficial because it reduces the rate at which resistance evolves by 'reducing the transmission of resistant parasites'. This seems dubious from a population genetics perspective, where intuition would lead to the opposite conclusion. The objective was to reconcile these differing views.
METHODS The effect of gametocytocidal drug activity was quantified mathematically and calibrated using field data.
RESULTS It appears to be a robust result that gametocytocidal activity actually promotes the spread of resistance through a population; the underlying reason is that gametocytocidal activity reduces transmission of drug-sensitive forms to a greater extent than the drug resistant, thereby increasing the spread of the latter. The increased rate of spread of resistance is quantified and appears to be small providing drug coverage is moderate or low.
CONCLUSIONS Citing reduced spread of resistance as a justification for deploying gametocytocidal antimalarials is unjustified; the deliberate use of a gametocytocidal antimalarial at high coverage to reduce transmission may ultimately be counterproductive through its rapid promotion of drug resistance.

Item Type:	Article
Uncontrolled Keywords:	plasmodium falciparum malaria drug resistance combination therapy gametocytocidal elimination half-life plasmodium-falciparum selective pressure malaria pyrimethamine chloroquine transmission infectivity artesunate primaquine
Subjects:	QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1111/j.1365-3156.2006.01668.x
Depositing User:	Ms Julia Martin
Date Deposited:	01 Mar 2011 16:13
Last Modified:	19 Sep 2019 11:29
URI:	https://archive.lstmed.ac.uk/id/eprint/1497

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