{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:17:15Z","timestamp":1791566235529,"version":"4.3.4"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["5D43TW011817"],"award-info":[{"award-number":["5D43TW011817"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005815","name":"Firland Foundation","doi-asserted-by":"publisher","award":["20240005"],"award-info":[{"award-number":["20240005"]}],"id":[{"id":"10.13039\/100005815","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Tuberc."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Whole-genome sequencing (WGS) data on resistance patterns in western Kenya remain limited. We evaluated resistant patterns of\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      complex (MTBC) isolates from western Kenya based on routine line probe assay (LPA) and\/or phenotypic drug-susceptibility testing (DST) using targeted WGS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross-sectional study, 1,053 archived MTBC isolates from 12 counties in western Kenya were analyzed. An enriched subset of 316 isolates was selected for WGS, of which 290 produced high-quality genomes. Genomic data were analyzed to determine lineage distribution and identify drug resistance mutations using WHO mutation catalogue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Out of the 1,053 isolates, 127 (12%) showed resistance to at least one anti-TB drug. Isoniazid resistant-rifampicin susceptible (Hr-TB) isolates were the most common (52; 40%), followed by rifampicin-resistant (33;26%) and multidrug-resistant (23;18%). The predominance of Hr-TB is consistent with reports from Kenya and other high-burden settings. Enriched WGS subset identified resistance-associated mutations in 43\/290 (14%) isolates, with similar resistance patterns. Rifampicin resistance was mainly associated with\n                      <jats:italic>rpoB<\/jats:italic>\n                      (S450L), while isoniazid resistance was dominated by\n                      <jats:italic>katG<\/jats:italic>\n                      S315\u2005T and\n                      <jats:italic>inhA<\/jats:italic>\n                      promoter mutations. Resistant isolates were mainly concentrated in Kisii, Migori, Homa Bay, and Siaya, predominantly within Lineages 4 and 3. Discordance was observed between routine testing and WGS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.026); approximately 86% of discordant isolates carrying mutations of uncertain significance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Western Kenya shows geographic DR-TB heterogeneity with predominant Hr-TB, which rifampicin-based diagnostics risk under-detection. Despite observed discordance, Integrating WGS with routine testing will strengthen surveillance, improve isoniazid resistance detection, and support appropriate treatment management in high-burden settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/ftubr.2026.1855780","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T08:25:57Z","timestamp":1781166357000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomic characterization of drug-resistant Mycobacterium tuberculosis complex in western Kenya reveals predominance of isoniazid resistance and discordance with routine susceptibility testing"],"prefix":"10.3389","volume":"4","author":[{"given":"Susan","family":"Musau","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Nairobi","place":["Nairobi, Kenya"]},{"name":"Tuberculosis and HIV Co-Infection Training 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