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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

Taylor, Steve M., Antonia, Alejandro, Feng, Gaoqian, Mwapasa, Victor, Chaluluka, Ebbie, Molyneux, Malcolm E, terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617, Rogerson, Stephen J. and Meshnick, Steven R. (2012) 'Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study'. Infection Genetics and Evolution, Vol 12, Issue 2, pp. 282-290.

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Abstract

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.

Item Type: Article
Subjects: QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
QX Parasitology > Protozoa > QX 135 Plasmodia
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WB Practice of Medicine > Therapeutics > WB 330 Drug therapy
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WQ Obstetrics > Pregnancy Complications > WQ 256 Infectious diseases
Digital Object Identifer (DOI): https://doi.org/10.1016/j.meegid.2011.11.006
Depositing User: Martin Chapman
Date Deposited: 07 Aug 2013 13:46
Last Modified: 31 May 2018 14:13
URI: http://archive.lstmed.ac.uk/id/eprint/3457

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