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Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study.

Publication ,  Journal Article
Taylor, SM; Antonia, A; Feng, G; Mwapasa, V; Chaluluka, E; Molyneux, M; ter Kuile, FO; Rogerson, SJ; Meshnick, SR
Published in: Infect Genet Evol
March 2012

Sulfadoxine-pyrimethamine (SP) has been widely deployed in Africa for malaria control and molecular evidence of parasite drug-resistance is prevalent. However, the temporal effects on the selection of Plasmodium falciparum are not well understood. We conducted a retrospective serial cross-sectional study between 1997 and 2006 to investigate changes in drug-resistant malaria among pregnant women delivering at a single hospital in Blantyre, Malawi. P. falciparum parasites were genotyped for parasite clone multiplicity and drug-resistance mutations, and the strength of selection upon mutant genotypes was quantified. Five mutations in the dihydrofolate reductase and dihydropteroate synthase genes began at moderate frequencies and achieved fixation by 2005; the frequency of the highly-SP-resistant "quintuple mutant" haplotype increased from 19% to 100%. The selective advantage of alleles and haplotypes were quantified with selection coefficients: Selection was positive on all mutant alleles and haplotypes associated with SP resistance, and the relative fitness of the quintuple mutant haplotype was 0.139 (95% C.I. 0.067-0.211), indicating a substantial positive selective advantage. Mutations that confer higher levels of resistance to SP did not emerge. SP-resistant haplotypes were rapidly selected for and fixed in P. falciparum populations infecting pregnant women while SP was widely deployed in Malawi. These results underscore the pressing need for new preventive measures for pregnancy-associated malaria and provide a real-world model of the selection landscape malaria parasites.

Duke Scholars

Published In

Infect Genet Evol

DOI

EISSN

1567-7257

Publication Date

March 2012

Volume

12

Issue

2

Start / End Page

282 / 290

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Tetrahydrofolate Dehydrogenase
  • Selection, Genetic
  • Retrospective Studies
  • Pregnancy Complications, Parasitic
  • Pregnancy
  • Plasmodium falciparum
  • Mutation
  • Microbiology
  • Malawi
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Taylor, S. M., Antonia, A., Feng, G., Mwapasa, V., Chaluluka, E., Molyneux, M., … Meshnick, S. R. (2012). Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study. Infect Genet Evol, 12(2), 282–290. https://doi.org/10.1016/j.meegid.2011.11.006
Taylor, Steve M., Alejandro Antonia, Gaoqian Feng, Victor Mwapasa, Ebbie Chaluluka, Malcolm Molyneux, Feiko O. ter Kuile, Stephen J. Rogerson, and Steven R. Meshnick. “Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study.Infect Genet Evol 12, no. 2 (March 2012): 282–90. https://doi.org/10.1016/j.meegid.2011.11.006.
Taylor SM, Antonia A, Feng G, Mwapasa V, Chaluluka E, Molyneux M, et al. Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study. Infect Genet Evol. 2012 Mar;12(2):282–90.
Taylor, Steve M., et al. “Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study.Infect Genet Evol, vol. 12, no. 2, Mar. 2012, pp. 282–90. Pubmed, doi:10.1016/j.meegid.2011.11.006.
Taylor SM, Antonia A, Feng G, Mwapasa V, Chaluluka E, Molyneux M, ter Kuile FO, Rogerson SJ, Meshnick SR. Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study. Infect Genet Evol. 2012 Mar;12(2):282–290.
Journal cover image

Published In

Infect Genet Evol

DOI

EISSN

1567-7257

Publication Date

March 2012

Volume

12

Issue

2

Start / End Page

282 / 290

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Tetrahydrofolate Dehydrogenase
  • Selection, Genetic
  • Retrospective Studies
  • Pregnancy Complications, Parasitic
  • Pregnancy
  • Plasmodium falciparum
  • Mutation
  • Microbiology
  • Malawi