{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:34:39Z","timestamp":1786995279775,"version":"build-2736575974"},"posted":{"date-parts":[[2025,6,23]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":89,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Antimalarial resistance, including reduced susceptibility to artemisinin-based combination therapies, is increasing in Africa. 157\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  isolates from Cibitoke, Burundi, were sequenced for ten resistance markers (including background loci associated with\n                  <jats:italic>kelch13<\/jats:italic>\n                  -mediated artemisinin partial resistance) using Nanopore sequencing.\n                  <jats:italic>Plasmepsin<\/jats:italic>\n                  -2 and\n                  <jats:italic>pfmdr1<\/jats:italic>\n                  copy number variations were assessed by digital PCR. No validated\n                  <jats:italic>pfkelch13<\/jats:italic>\n                  mutations linked to artemisinin partial resistance were detected. A novel\n                  <jats:italic>pfkelch13<\/jats:italic>\n                  mutation, A676T, was identified in one isolate, adjacent to the validated A675V mutation reported in neighboring East African countries. Mutant alleles were observed at several background loci previously implicated in artemisinin resistance in Southeast Asia, including\n                  <jats:italic>pffd<\/jats:italic>\n                  D193Y (7.0%),\n                  <jats:italic>pfmdr2<\/jats:italic>\n                  I492V (31.8%),\n                  <jats:italic>pfatg18<\/jats:italic>\n                  T38I (3.2%), and\n                  <jats:italic>pfarps10<\/jats:italic>\n                  V127M\/D128H (2.6%), while\n                  <jats:italic>pfpx1<\/jats:italic>\n                  (C1484F) and\n                  <jats:italic>pfmdr2<\/jats:italic>\n                  (T484I) remained wild type. However, their functional role in Africa remains uncertain. Sulfadoxine-pyrimethamine (SP) resistance was widespread. In single-clone infections, the quintuple\n                  <jats:italic>pfdhfr\/pfdhps<\/jats:italic>\n                  haplotype predominated (59.6%). Chloroquine resistance\u2013associated\n                  <jats:italic>pfcrt<\/jats:italic>\n                  IET triple mutant haplotypes at codons 74-76 were detected in 94.3% of isolates.\n                  <jats:italic>pfmdr1<\/jats:italic>\n                  haplotypes defined by codons 86, 184, and 1246 were dominated by NYD (56.3%) and NFD (40.4%). No\n                  <jats:italic>pfpm2<\/jats:italic>\n                  duplications were observed, while\n                  <jats:italic>pfmdr1<\/jats:italic>\n                  copy number amplification was rare (1.8%). These findings reveal a high prevalence of mutations associated with SP resistance, posing a threat to the efficacy of intermittent preventive treatment in pregnancy and seasonal malaria chemoprevention in Burundi. The identification of the\n                  <jats:italic>pfkelch13<\/jats:italic>\n                  A676T variant highlights the importance of continued genomic surveillance. However, the role of this mutation in artemisinin resistance remains to be determined.\n                <\/jats:p>","DOI":"10.1101\/2025.06.22.25330092","type":"posted-content","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T23:30:16Z","timestamp":1750721416000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Novel\n                  <i>Plasmodium falciparum Kelch13<\/i>\n                  A676T Variant and high Chloroquine and Sulfadoxine-Pyrimethamine Resistance in Cibitoke, Burundi"],"prefix":"10.64898","author":[{"given":"Tolulope","family":"Kayode","sequence":"first","affiliation":[{"name":"Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, Indiana, United States of America"},{"name":"Environmental Change Initiative, University of Notre Dame, Indiana, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-4999","authenticated-orcid":false,"given":"David","family":"Niyukuri","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Burundi, Bujumbura, Burundi,"},{"name":"South African DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2681-1114","authenticated-orcid":false,"given":"Aurel","family":"Holzschuh","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Allschwil, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-6813","authenticated-orcid":false,"given":"Gustavo","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, Indiana, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8027-8376","authenticated-orcid":false,"given":"Tiffany","family":"Huwe","sequence":"additional","affiliation":[{"name":"Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, Indiana, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3062-5901","authenticated-orcid":false,"given":"Anita","family":"Lerch","sequence":"additional","affiliation":[{"name":"Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, Indiana, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3715-7891","authenticated-orcid":false,"given":"Joseph","family":"Nyandwi","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Burundi, Bujumbura, Burundi,"},{"name":"National Institute of Public Health, Bujumbura, Burundi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9354-0414","authenticated-orcid":false,"given":"Cristian","family":"Koepfli","sequence":"additional","affiliation":[{"name":"Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, Indiana, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081711551350000_2025.06.22.25330092v2.1","unstructured":"World Malaria Report 2023. 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