{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:34:27Z","timestamp":1785443667074,"version":"3.56.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Routine surveillance for antimalarial drug resistance is critical to sustaining the efficacy of artemisinin-based Combination Therapies (ACTs). <jats:italic>Plasmodium falciparum kelch-13 (Pfkelch-13)<\/jats:italic> and non-<jats:italic>Pfkelch-13<\/jats:italic> artemisinin <jats:italic>(<\/jats:italic>ART) resistance-associated mutations are uncommon in Africa. We investigated polymorphisms in <jats:italic>Plasmodium falciparum<\/jats:italic> actin-binding protein (Pfcoronin<jats:italic>)<\/jats:italic> associated with <jats:italic>in vivo<\/jats:italic> reduced sensitivity to ART in Nigeria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty-two <jats:italic>P. falciparum<\/jats:italic> malaria subjects who met the inclusion criteria were followed up in a 28-day therapeutic efficacy study of artemether-lumefantrine in Lagos, Nigeria. Parasite detection was done by microscopy and molecular diagnostic approaches involving PCR amplification of genes for <jats:italic>Pf<\/jats:italic>18S rRNA, <jats:italic>var<\/jats:italic>ATS, telomere-associated repetitive elements-2 (TARE-2). <jats:italic>Pfcoronin<\/jats:italic> and <jats:italic>Pfkelch-13<\/jats:italic> genes were sequenced bi-directionally while clonality of infections was determined using 12 neutral <jats:italic>P. falciparum<\/jats:italic> microsatellite <jats:italic>loci<\/jats:italic> and <jats:italic>msp2<\/jats:italic> analyses. Antimalarial drugs (sulfadoxine-pyrimethamine, amodiaquine, chloroquine and some quinolones) resistance variants (DHFR_51, DHFR_59, DHFR_108, DHFR_164, MDR1_86, MDR1_184, DHPS_581 and DHPS_613) were genotyped by high-resolution melting (HRM) analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 7 (26.92%) cases were identified either as early treatment failure, late parasitological failure or late clinical failure. Of the four post-treatment infections identified as recrudescence by <jats:italic>msp2<\/jats:italic> genotypes, only one was classified as recrudescence by multilocus microsatellites genotyping. Microsatellite analysis revealed no significant difference in the mean allelic diversity, <jats:italic>He<\/jats:italic>, (P = 0.19, Mann-Whitney test). Allele sizes and frequency per locus implicated one isolate. Genetic analysis of this isolate identified two new <jats:italic>Pfcoronin<\/jats:italic> SNVs (I68G and L173F) in addition to the P76S earlier reported. Linkage-Disequilibrium as a standardized association index, <jats:italic>I<jats:sub>A<\/jats:sub><jats:sup>S<\/jats:sup><\/jats:italic>, between multiple <jats:italic>P. falciparum<\/jats:italic> loci revealed significant LD (<jats:italic>I<jats:sub>A<\/jats:sub><jats:sup>S<\/jats:sup><\/jats:italic> = 0.2865, <jats:italic>P<\/jats:italic>=0.02, Monte-Carlo simulation) around the neutral microsatellite loci. The <jats:italic>pfdhfr\/pfdhps\/pfmdr1<\/jats:italic> drug resistance-associated haplotypes combinations, (108<jats:bold><jats:sub>T\/N<\/jats:sub><\/jats:bold>\/51<jats:bold><jats:sub>I\/<\/jats:sub><\/jats:bold>164<jats:bold><jats:sub>L<\/jats:sub><\/jats:bold>\/59<jats:bold><jats:sub>R<\/jats:sub><\/jats:bold>\/581<jats:bold><jats:sub>G<\/jats:sub><\/jats:bold>\/86<jats:bold><jats:sub>Y<\/jats:sub><\/jats:bold>\/184<jats:bold><jats:sub>F<\/jats:sub><\/jats:bold>), were observed in two samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>Pfcoronin<\/jats:italic> mutations identified in this study, with potential to impact parasite clearance, may guide investigations on emerging ART tolerance in Nigeria, and West African endemic countries.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1366563","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T04:36:09Z","timestamp":1713846969000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Detection of novel Plasmodium falciparum coronin gene mutations in a recrudescent ACT-treated patient in South-Western Nigeria"],"prefix":"10.3389","volume":"14","author":[{"given":"Olusola","family":"Ajibaye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yetunde Adeola","family":"Olukosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eniyou C.","family":"Oriero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Aigbiremo","family":"Oboh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bamidele","family":"Iwalokun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikechukwu Chidiebere","family":"Nwankwo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinaza Favour","family":"Nnam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olawunmi Victoria","family":"Adaramoye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somadina","family":"Chukwemeka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Okanazu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eniafe","family":"Gabriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel Oluwadare","family":"Balogun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Amambua-Ngwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S0962-8924(99)01673-6","article-title":"The kelch repeat superfamily of proteins: Propellers of cell function","volume":"10","author":"Adams","year":"2000","journal-title":"Trends Cell Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12936-020-03506-z","article-title":"Plasmodium falciparum multidrug resistance gene-1 polymorphisms in Northern Nigeria: implications for the continued use of artemether-lumefantrine in the region","volume":"19","author":"Adamu","year":"2020","journal-title":"Malaria J."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-019-3096-0","article-title":"Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria","volume":"19","author":"Ajibaye","year":"2020","journal-title":"Malar J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1093\/oxfordjournals.molbev.a026247","article-title":"Microsatellite markers reveal a spectrum of population structures in the malaria parasite plasmodium falciparum","volume":"17","author":"Anderson","year":"2006","journal-title":"Mol. 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