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J Infect Dis. 2007 Dec 1;196(11):1613-9. Epub 2007 Oct 25.

Seasonal carriage of pfcrt and pfmdr1 alleles in Gambian Plasmodium falciparum imply reduced fitness of chloroquine-resistant parasites.

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1
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.

Abstract

BACKGROUND:

Observations in natural Plasmodium falciparum populations after removal of failing drugs suggest that there is a fitness cost of drug resistance.

METHODS:

To examine the effect of transient removal of drug pressure, we analyzed seasonal changes in the prevalence of chloroquine (CQ)-resistant parasite genotypes in The Gambia. Parasite isolates from 441 children presenting with uncomplicated falciparum malaria over 5 seasons (1998-2002) were linked to weekly rainfall data.

RESULTS:

The prevalence of CQ-resistant parasites increased slightly over 5 years, with the 76T allele of pfcrt (odds ratio [OR] per year, 1.16; P=.03) and the 86Y allele of pfmdr1 (OR per year, 1.18; P=.02) becoming significantly more common. However, intraseasonal analysis showed that these alleles decreased in prevalence each dry season. Wild-type parasites with respect to both loci predominated as transmission began each year, with resistant parasites becoming more common as drug use increased. This pattern was seen for both pfcrt-76T (OR per week, 1.09; P=.001) and pfmdr1-86Y (OR per week, 1.07; P=.001) and could not be explained by seasonal changes in the clonal complexity of infections.

CONCLUSIONS:

The fitness cost of CQ resistance works against the persistence of resistant parasites through the dry season.

PMID:
18008244
DOI:
10.1086/522154
[Indexed for MEDLINE]
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