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

J Infect Dis. 2007 Dec 1;196(11):1613-9. doi: 10.1086/522154. Epub 2007 Oct 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Antimalarials / pharmacology*
  • Child
  • Chloroquine / pharmacology*
  • Drug Resistance, Microbial
  • Gambia
  • Humans
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / metabolism*
  • Multidrug Resistance-Associated Proteins / drug effects
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Odds Ratio
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics*
  • Protozoan Proteins / drug effects
  • Protozoan Proteins / metabolism*
  • Seasons*


  • Antimalarials
  • Mdr1 protein, Plasmodium falciparum
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • Chloroquine