{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:46:02Z","timestamp":1768571162717,"version":"3.49.0"},"posted":{"date-parts":[[2025,11,13]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Malaria is a common disease in Mali associated with high morbidity and mortality. To improve malaria control, it is important to evaluate how current interventions affect the genetic make-up of circulating parasites. We analyzed the genomes of recently collected\n                  <jats:italic>Plasmodium falciparum<\/jats:italic>\n                  isolates across Mali to understand transmission dynamics, parasite relatedness, and selection pressures affecting parasite populations.\n                <\/jats:p>\n                <jats:p>\n                  We sequenced clinical isolates (n=458) collected in 2023 from 13 heath districts across Mali using molecular inversion probe (MIP) panels targeting key drug resistance mutations and common SNPs across the\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  genomes. We also MIP sequenced polymorphisms in the human \u03b2-globin gene in study participants to assess sickle haemoglobin mutation. We performed complexity of infection (COI), identity-by-descent (IBD), principal component (PCA), selection signal, and haplotype analyses.\n                <\/jats:p>\n                <jats:p>\n                  The prevalence of polygenomic infections ranged from 13.0% in the north, dominated by the Sahara Desert, to 44.0% in the south, with tropical wet and dry climates. Parasites collected from the same district showed low levels of genetic relatedness with a mean IBD of &lt;0.2. There was a network of parasite connectivity between sites across the country, and IBD between districts was inversely correlated with geographical distance separating them (\n                  <jats:italic>P=0.006, R=-0.28<\/jats:italic>\n                  ). The strongest selection signal was detected around the\n                  <jats:italic>chloroquine-resistance transporter<\/jats:italic>\n                  (\n                  <jats:italic>pfcrt<\/jats:italic>\n                  ) gene. PCA in monogenomic samples (n=242) separated a cluster of parasites (n=56) from the main population showing a specific selection signal around\n                  <jats:italic>acetyl-coA synthetase<\/jats:italic>\n                  (\n                  <jats:italic>pfacs8)<\/jats:italic>\n                  . The ACS8 Y40F mutation, associated with sickle haemoglobin and also known as\n                  <jats:italic>Pfsa1<\/jats:italic>\n                  , was detected in all the samples from this cluster. Higher prevalence of PfCRT K76T mutation (55.8%, n=104) and sickle cell trait (8.4%, n=83) were measured in samples carrying\n                  <jats:italic>Pfsa1<\/jats:italic>\n                  compared to wild type (26.6%, n=342 and 1.3%, n=237; respectively,\n                  <jats:italic>P&lt;0.005<\/jats:italic>\n                  , Chi-square test). Samples carrying both\n                  <jats:italic>Pfsa1<\/jats:italic>\n                  and PfCRT K76T exhibited higher IBD across chromosomes, and one major haplotype was identified around\n                  <jats:italic>pfcrt<\/jats:italic>\n                  in 80% of K76T mutants, in which 64% of\n                  <jats:italic>Pfsa1<\/jats:italic>\n                  was detected.\n                <\/jats:p>\n                <jats:p>\n                  Our nationwide genomic profiling of malaria parasites in Mali reveals clear selective sweeps linked to drug pressure and host genetics highly contributing to shaping the genetic make-up of parasite populations, and confirms the association of\n                  <jats:italic>Pfsa1<\/jats:italic>\n                  with sickle haemoglobin. The\n                  <jats:italic>Pfsa1<\/jats:italic>\n                  \u2013PfCRT 76T linkage highlights a critical axis of parasite adaptation that warrants close surveillance.\n                <\/jats:p>","DOI":"10.1101\/2025.11.11.25339971","type":"posted-content","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T03:10:33Z","timestamp":1763089833000},"source":"Crossref","is-referenced-by-count":0,"title":["Genome-wide SNP genotyping of\n                  <i>Plasmodium falciparum<\/i>\n                  isolates across Mali reveals major impacts of\n                  <i>Pfsa1<\/i>\n                  and PfCRT K76T selections on parasite populations"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7406-9508","authenticated-orcid":false,"given":"Karamoko","family":"Niar\u00e9","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7739-4437","authenticated-orcid":false,"given":"Antoine","family":"Dara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9kou","family":"Sissoko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Crudale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7146-6439","authenticated-orcid":false,"given":"Aminatou","family":"Kon\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hinda","family":"Doucour\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Sanogo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mady","family":"Cissoko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2024-577X","authenticated-orcid":false,"given":"Mahamadou S.","family":"Sissoko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1395-0051","authenticated-orcid":false,"given":"Mamadou","family":"T\u00e9k\u00e9t\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aissata","family":"Kon\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bintou","family":"Diarra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maimouna","family":"Demb\u00e9l\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boi","family":"Kon\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0591-0850","authenticated-orcid":false,"given":"Jonathan J.","family":"Juliano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6899-8204","authenticated-orcid":false,"given":"Jeffrey A","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0062-2283","authenticated-orcid":false,"given":"Abdoulaye A.","family":"Djimd\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025111508400432000_2025.11.11.25339971v1.1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4857.290"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.2","doi-asserted-by":"crossref","first-page":"9687","DOI":"10.1038\/s41598-018-28017-5","article-title":"Consistent signatures of selection from genomic analysis of pairs of temporal and spatial Plasmodium falciparum populations from The Gambia","volume":"8","year":"2018","journal-title":"Scientific Reports"},{"key":"2025111508400432000_2025.11.11.25339971v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy223"},{"issue":"7895","key":"2025111508400432000_2025.11.11.25339971v1.4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41586-021-04288-3","article-title":"Malaria protection due to sickle haemoglobin depends on parasite genotype","volume":"602","year":"2022","journal-title":"Nature"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.5","doi-asserted-by":"crossref","first-page":"180214","DOI":"10.1038\/sdata.2018.214","article-title":"Present and future K\u00f6ppen-Geiger climate classification maps at 1-km resolution","volume":"5","year":"2018","journal-title":"Scientific Data"},{"issue":"3","key":"2025111508400432000_2025.11.11.25339971v1.6","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.actatropica.2005.04.015","article-title":"Public health impact of drug resistant Plasmodium falciparum malaria","volume":"94","year":"2005","journal-title":"Acta Tropica"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.7","doi-asserted-by":"crossref","first-page":"e1005348","DOI":"10.1371\/journal.pcbi.1005348","article-title":"THE REAL McCOIL: A method for the concurrent estimation of the complexity of infection and SNP allele frequency for malaria parasites","volume":"13","year":"2017","journal-title":"PLoS Computational Biology"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.8","doi-asserted-by":"crossref","first-page":"8271","DOI":"10.1038\/s41598-022-11974-3","article-title":"Stratification at the health district level for targeting malaria control interventions in Mali","volume":"12","year":"2022","journal-title":"Scientific Reports"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.9","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s13071-022-05379-4","article-title":"Sub-national tailoring of seasonal malaria chemoprevention in Mali based on malaria surveillance and rainfall data","volume":"15","year":"2022","journal-title":"Parasites & Vectors"},{"key":"2025111508400432000_2025.11.11.25339971v1.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211803)"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.11","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s42003-023-04997-7","article-title":"Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique","volume":"6","year":"2023","journal-title":"Communications Biology"},{"key":"2025111508400432000_2025.11.11.25339971v1.12","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-4523-0"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.13","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1038\/s41467-022-29688-5","article-title":"Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183","volume":"13","year":"2022","journal-title":"Nature Communications"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.14","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s12936-021-03760-9","article-title":"Therapeutic efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015-2016","volume":"20","year":"2021","journal-title":"Malaria Journal"},{"key":"2025111508400432000_2025.11.11.25339971v1.15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2009.00641.x"},{"key":"2025111508400432000_2025.11.11.25339971v1.16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200101253440403"},{"key":"2025111508400432000_2025.11.11.25339971v1.17","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1746-3"},{"key":"2025111508400432000_2025.11.11.25339971v1.18","unstructured":"Garrison, E. , & Marth, G. (2012). Haplotype-based variant detection from short-read sequencing. In arXiv [q-bio.GN]. arXiv. http:\/\/arxiv.org\/abs\/1207.3907"},{"key":"2025111508400432000_2025.11.11.25339971v1.19","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.14.557461"},{"key":"2025111508400432000_2025.11.11.25339971v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2011.06.001"},{"key":"2025111508400432000_2025.11.11.25339971v1.21","doi-asserted-by":"publisher","DOI":"10.1101\/2023.11.07.23298207"},{"key":"2025111508400432000_2025.11.11.25339971v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2012.12.007"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s12936-020-03202-y","article-title":"Effect of routine seasonal malaria chemoprevention on malaria trends in children under 5 years in Dangassa, Mali","volume":"19","year":"2020","journal-title":"Malaria Journal"},{"key":"2025111508400432000_2025.11.11.25339971v1.24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062032"},{"issue":"4","key":"2025111508400432000_2025.11.11.25339971v1.25","first-page":"483","article-title":"Changes in the resistance of Plasmodium falciparum to chloroquine in Hainan, China","volume":"73","year":"1995","journal-title":"Bulletin of the World Health Organization"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.26","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1186\/1475-2875-13-452","article-title":"Artemisinin resistance \u2013 modelling the potential human and economic costs","volume":"13","year":"2014","journal-title":"Malaria Journal"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12936-022-04059-z","article-title":"Effect of three years\u2019 seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali","volume":"21","year":"2022","journal-title":"Malaria Journal"},{"issue":"11","key":"2025111508400432000_2025.11.11.25339971v1.28","doi-asserted-by":"crossref","first-page":"6057","DOI":"10.3390\/ijms22116057","article-title":"Selection of pfcrt K76 and pfmdr1 N86 coding alleles after uncomplicated malaria treatment by artemether-lumefantrine in Mali","volume":"22","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"key":"2025111508400432000_2025.11.11.25339971v1.29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.12688\/wellcomeopenres.18681.1","article-title":"Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples","volume":"8","year":"2023","journal-title":"Wellcome Open Research"},{"key":"2025111508400432000_2025.11.11.25339971v1.30","doi-asserted-by":"publisher","DOI":"10.1111\/mec.15706"},{"key":"2025111508400432000_2025.11.11.25339971v1.31","doi-asserted-by":"crossref","first-page":"1526049","DOI":"10.3389\/fgene.2025.1526049","article-title":"Highly multiplexed molecular inversion probe panel in Plasmodium falciparum targeting common SNPs approximates whole-genome sequencing assessments for selection and relatedness","volume":"16","year":"2025","journal-title":"Frontiers in Genetics"},{"key":"2025111508400432000_2025.11.11.25339971v1.32","doi-asserted-by":"publisher","DOI":"10.1101\/2022.05.26.493561"},{"key":"2025111508400432000_2025.11.11.25339971v1.33","doi-asserted-by":"publisher","DOI":"10.1101\/2025.08.31.672853"},{"issue":"3","key":"2025111508400432000_2025.11.11.25339971v1.34","doi-asserted-by":"crossref","first-page":"e208","DOI":"10.1016\/S2352-3026(22)00004-7","article-title":"Estimating the risk of child mortality attributable to sickle cell anaemia in sub-Saharan Africa: a retrospective, multicentre, case-control study","volume":"9","year":"2022","journal-title":"The Lancet. Haematology"},{"issue":"3","key":"2025111508400432000_2025.11.11.25339971v1.35","first-page":"53","article-title":"Management of sickle cells disease by households in Bamako","volume":"24","year":"2009","journal-title":"Le Mali medical"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.36","doi-asserted-by":"crossref","first-page":"7268","DOI":"10.1038\/s41467-023-43087-4","article-title":"Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal","volume":"14","year":"2023","journal-title":"Nature Communications"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.37","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12936-018-2349-7","article-title":"hmmIBD: software to infer pairwise identity by descent between haploid genotypes","volume":"17","year":"2018","journal-title":"Malaria Journal"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.38","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41598-023-27417-6","article-title":"Protein KIC5 is a novel regulator of artemisinin stress response in the malaria parasite Plasmodium falciparum","volume":"13","year":"2023","journal-title":"Scientific Reports"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.39","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12936-015-1075-7","article-title":"Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa","volume":"15","year":"2016","journal-title":"Malaria Journal"},{"key":"2025111508400432000_2025.11.11.25339971v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70055-5"},{"key":"2025111508400432000_2025.11.11.25339971v1.41","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa527"},{"key":"2025111508400432000_2025.11.11.25339971v1.42","doi-asserted-by":"crossref","unstructured":"Tuteja, R . (2016). Emerging functions of helicases in regulation of stress survival in malaria parasite Plasmodium falciparum and their comparison with human host. Parasitology International, 65(6 Pt A), 645\u2013664.","DOI":"10.1016\/j.parint.2016.08.010"},{"key":"2025111508400432000_2025.11.11.25339971v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1005-2"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.44","doi-asserted-by":"crossref","first-page":"9522","DOI":"10.1038\/s41598-023-36002-w","article-title":"Genome-wide genetic variation and molecular surveillance of drug resistance in Plasmodium falciparum isolates from asymptomatic individuals in Ou\u00e9less\u00e9bougou, Mali","volume":"13","year":"2023","journal-title":"Scientific Reports"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.45","doi-asserted-by":"crossref","first-page":"11553","DOI":"10.1038\/ncomms11553","article-title":"Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies","volume":"7","year":"2016","journal-title":"Nature Communications"},{"key":"2025111508400432000_2025.11.11.25339971v1.46","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.14-0031"},{"issue":"1","key":"2025111508400432000_2025.11.11.25339971v1.47","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1038\/s41467-020-15779-8","article-title":"The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC","volume":"11","year":"2020","journal-title":"Nature Communications"},{"key":"2025111508400432000_2025.11.11.25339971v1.48","unstructured":"World Health Organization. (2012). WHO policy recommendation: seasonal malaria chemoprevention (SMC) for plasmodium falciparum malaria control in highly seasonal transmission areas of the Sahel sub-region in Africa (No. WHO\/HTM\/GMP\/2012.02). World Health Organization. https:\/\/iris.who.int\/handle\/10665\/337978"},{"key":"2025111508400432000_2025.11.11.25339971v1.49","unstructured":"World malaria report 2024. (n.d.). Retrieved January 17, 2025, from https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2024"},{"key":"2025111508400432000_2025.11.11.25339971v1.50","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.29.24306442"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.11.11.25339971","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:51:02Z","timestamp":1768510262000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.11.11.25339971"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":50,"URL":"https:\/\/doi.org\/10.1101\/2025.11.11.25339971","relation":{},"subject":[],"published":{"date-parts":[[2025,11,13]]},"subtype":"preprint"}}