Seasonal carriage of pfcrt and pfmdr1 alleles in Gambian Plasmodium falciparum imply reduced fitness of chloroquine-resistant parasites.
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.
Ord
Rosalynn
R
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Alexander
Neal
N
Dunyo
Sam
S
Hallett
Rachel
R
Jawara
Musa
M
Targett
Geoffrey
G
Drakeley
Christopher J
CJ
Sutherland
Colin J
CJ
D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002648:Child; D002738:Chloroquine / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D005714:Gambia; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000187:drug effects / Q000378:metabolism*; D016017:Odds Ratio; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D015800:Protozoan Proteins / Q000187:drug effects / Q000378:metabolism*; D012621:Seasons
D000962:Antimalarials; D002738:Chloroquine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum