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We sequenced 187 <jats:italic>Plasmodium falciparum<\/jats:italic> samples from two sites in the Ethiopian highlands, Gondar (<jats:italic>n<\/jats:italic>\u2009=\u2009159) and Ziway (<jats:italic>n<\/jats:italic>\u2009=\u200928), using a multiplexed droplet digital PCR (ddPCR)\u2010based amplicon sequencing method targeting 35 microhaplotypes and drug resistance loci. Here, we characterize the parasite population structure and genetic relatedness. We identify moderate parasite diversity (mean H<jats:sub>E<\/jats:sub>: 0.54) and low infection complexity (74.9% monoclonal). A significant percentage of infections share microhaplotypes, even across transmission seasons and sites, indicating persistent local transmission. We identify multiple clusters of clonal or near\u2010clonal infections, highlighting high genetic relatedness. Only 6.3% of individuals diagnosed with <jats:italic>P. falciparum<\/jats:italic> reported recent travel. Yet, in clonal or near\u2010clonal clusters, infections of travellers were frequently observed first in time, suggesting that parasites may have been imported and then transmitted locally. 31.1% of infections are <jats:italic>pfhrp2\u2010<\/jats:italic>deleted and 84.4% <jats:italic>pfhrp3\u2010<\/jats:italic>deleted, and 28.7% have <jats:italic>pfhrp2<\/jats:italic>\/<jats:italic>3<\/jats:italic> double deletions. Parasites with <jats:italic>pfhrp2\/3<\/jats:italic> deletions and wild\u2010type parasites are genetically distinct. Mutations associated with resistance to sulphadoxine\u2013pyrimethamine or suggested to reduce sensitivity to lumefantrine are observed at near\u2010fixation. In conclusion, genomic data corroborate local transmission and the importance of intensified control in the Ethiopian highlands.<\/jats:p>","DOI":"10.1111\/mec.17292","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T07:34:08Z","timestamp":1707550448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i>Plasmodium falciparum<\/i> transmission in the highlands of Ethiopia is driven by closely related and clonal parasites"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2681-1114","authenticated-orcid":false,"given":"Aurel","family":"Holzschuh","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Eck Institute for Global Health University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalemwork","family":"Ewnetu","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology University of Gondar  Gondar Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise","family":"Carlier","sequence":"additional","affiliation":[{"name":"Trinity Centre for Global Health Trinity College Dublin  Dublin Ireland"},{"name":"Noul Inc.  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