Harold OchollaMark D. PrestonMwapatsa MipandoAnja T.R. JensenSusana CampinoBronwyn MacinnisDaniel AlcockAnja TerlouwIssaka ZongoJean Bosco OudraogoAbdoulaye A. DjimdeSamuel AssefaOgobara K. DoumboSteffen BorrmannAlexis NzilaKevin MarshRick M. FairhurstFrancois NostenTim J.C. AndersonDominic P. KwiatkowskiAlister CraigTaane G. ClarkJacqui MontgomeryMalawi-Liverpool-Wellcome Trust Clinical Research ProgrammeUniversity of MalawiLiverpool School of Tropical MedicineLondon School of Hygiene & Tropical MedicineWellcome Trust Sanger InstituteWellcome Trust Centre for Human GeneticsKobenhavns UniversitetCopenhagen University HospitalInstitut de Recherche en Sciences de la SantéUniversity of BamakoUniversitat TubingenKing Fahd University of Petroleum and MineralsWellcome Trust Research Laboratories NairobiNational Institute of Allergy and Infectious DiseasesTexas Biomedical Research InstituteNuffield Department of Clinical MedicineMahidol UniversityKEMRI/CDC LaboratoriesPennsylvania State University2018-11-092018-11-092014-01-01Journal of Infectious Diseases. Vol.210, No.12 (2014), 1991-200015376613002218992-s2.0-84924468292https://repository.li.mahidol.ac.th/handle/20.500.14594/34876© The Author 2014. Background: Selection by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum and continues to produce ever-changing landscapes of genetic variation. Methods: We performed whole-genome sequencing of 69 P. falciparum isolates from Malawi and used population genetics approaches to investigate genetic diversity and population structure and identify loci under selection. Results. High genetic diversity (π = 2.4 × 10^-4), moderately high multiplicity of infection (2.7), and low linkage disequilibrium (500-bp) were observed in Chikhwawa District, Malawi, an area of high malaria transmission. Allele frequency-based tests provided evidence of recent population growth in Malawi and detected potential targets of host immunity and candidate vaccine antigens. Comparison of the sequence variation between isolates from Malawi and those from 5 geographically dispersed countries (Kenya, Burkina Faso, Mali, Cambodia, and Thailand) detected population genetic differences between Africa and Asia, within Southeast Asia, and within Africa. Haplotype-based tests of selection to sequence data from all 6 populations identified signals of directional selection at known drugresistance loci, including pfcrt, pfdhps, pfmdr1, and pfgch1. Conclusions: The sequence variations observed at drug-resistance loci reflect differences in each country's historical use of antimalarial drugs and may be useful in formulating local malaria treatment guidelines.Mahidol UniversityMedicineArticleSCOPUS10.1093/infdis/jiu349