{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:27:01Z","timestamp":1782707221376,"version":"3.54.5"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Extrapulmonary tuberculosis (EPTB) is characterized by atypical clinical symptoms, difficult diagnosis, and high mortality, so it is very important to know the prevalence and drug resistance (DR) status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study analyzed 427 isolates of EPTB from a Chinese hospital. Drug susceptibility testing for widely used anti-TB drugs was performed. All isolates were subjected to whole-genome sequencing (WGS) to explore the molecular characteristics of resistance and to perform phylogenetic analysis. Clinical characteristics and DR patterns associated with\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      (MTB) lineages were evaluated using chi-square analysis, and associations with DR-EPTB were assessed using multinomial logistic regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The number of EPTB strains exhibited a general upward trend, and most EPTB cases in this study were accompanied by PTB. The predominant types were tuberculosis of urinary system (29.98%), tuberculous meningitis (23.65%), and lymph node tuberculosis (22.72%). Quadratic regression revealed a decline in urinary system cases and an increase in lymph node cases. Lineage 2 accounted for 83.60% of isolates and was significantly associated with isoniazid (INH) and streptomycin (STR) resistance. Overall resistance rates were 13.58% for INH and 7.73% for rifampicin (RIF). Male sex was associated with higher DR risk (aOR = 1.63, p = 0.046). Common resistance mutations included\n                      <jats:italic>katG<\/jats:italic>\n                      Ser315Thr,\n                      <jats:italic>rpoB<\/jats:italic>\n                      Ser450Leu, and\n                      <jats:italic>gyrA<\/jats:italic>\n                      mutations. The clustering rate was 19.67%, indicating limited recent transmission.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The predominance of lineage 2 and high rates of anti-tuberculosis drug resistance indicate that EPTB remains a clinically and epidemiologically significant problem.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1692783","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T06:30:40Z","timestamp":1765434640000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Deciphering the population dynamics and drug-resistance characteristics of extrapulmonary tuberculosis: genomic and clinical insights from a Chinese hospital"],"prefix":"10.3389","volume":"15","author":[{"given":"Shiwei","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyi","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.ijregi.2022.06.005","article-title":"Genetic diversity and drug resistance profiles of Mycobacterium tuberculosis complex isolates from patients with extrapulmonary tuberculosis in Ghana and their associated host immune responses","volume":"4","author":"Addo","year":"2022","journal-title":"IJID Reg."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5511","DOI":"10.2147\/IDR.S415906","article-title":"Phenotypic drug resistance pattern and mutation characteristics of mycobacterium tuberculosis from different body fluids among extra pulmonary patients presented in selected hospitals in addis ababa, Ethiopia","volume":"16","author":"Alehegn","year":"2023","journal-title":"Infect. Drug Resist."},{"key":"B3","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jiph.2019.07.001","article-title":"Pulmonary vs. extra-pulmonary tuberculosis hospitalizations in the US [1998-2014","volume":"1","author":"Banta","year":"2020","journal-title":"J. Infect. Public Health"},{"key":"B4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13244-022-01172-0","article-title":"Extrapulmonary tuberculos\u0131s: an old but resurgent problem","volume":"1","author":"Baykan","year":"2022","journal-title":"Insights Imaging"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2101","DOI":"10.1111\/crj.12779","article-title":"Prevalence and risk factors of drug-resistant extrapulmonary tuberculosis","volume":"6","author":"Boonsarngsuk","year":"2018","journal-title":"Clin. Respir. J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1007\/s00439-020-02120-y","article-title":"Mendelian susceptibility to mycobacterial disease: recent discoveries","author":"Bustamante","year":"2020","journal-title":"Hum. Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"405","DOI":"10.2147\/CLEP.S65331","article-title":"Long-term mortality in patients with pulmonary and extrapulmonary tuberculosis: a Danish nationwide cohort study","volume":"6","author":"Christensen","year":"2014","journal-title":"Clin. Epidemiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13073-015-0164-0","article-title":"Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences","volume":"1","author":"Coll","year":"2015","journal-title":"Genome Med."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001721","article-title":"A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics","volume":"8","author":"Consortium","year":"2022","journal-title":"PloS Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/1465-9921-6-134","article-title":"The Beijing genotype and drug resistant tuberculosis in the Aral Sea region of Central Asia","volume":"1","author":"Cox","year":"2005","journal-title":"Respir. Res."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1234785","article-title":"The impact of the COVID-19 pandemic on the global tuberculosis epidemic","volume":"14","author":"Falzon","year":"2023","journal-title":"Front. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"6099","DOI":"10.1038\/s41467-021-26248-1","article-title":"Population structure, biogeography and transmissibility of Mycobacterium tuberculosis","volume":"1","author":"Freschi","year":"2021","journal-title":"Nat. Commun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/nrmicro.2018.8","article-title":"Ecology and evolution of Mycobacterium tuberculosis","volume":"4","author":"Gagneux","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"B14","first-page":"1761","article-title":"Extrapulmonary tuberculosis: an overview","volume":"9","author":"Golden","year":"2005","journal-title":"Am. Fam Physician"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1347.e1","DOI":"10.1016\/j.cmi.2020.12.006","article-title":"Extrapulmonary tuberculosis among migrants in Europe, 1995 to 2017","volume":"9","author":"Hayward","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"B16","doi-asserted-by":"publisher","first-page":"13959","DOI":"10.1038\/s41598-020-70613-x","article-title":"Xpert MTB\/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting","volume":"1","author":"Hoel","year":"2020","journal-title":"Sci. Rep."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237753","article-title":"The epidemiology of extrapulmonary tuberculosis in China: A large-scale multi-center observational study","volume":"8","author":"Kang","year":"2020","journal-title":"PloS One"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0011403","article-title":"Evaluation of Xpert MTB\/RIF assay for the diagnosis of extrapulmonary tuberculosis in Southwest China","volume":"6","author":"Li","year":"2023","journal-title":"PloS Negl. Trop. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ijid.2022.12.005","article-title":"Extrapulmonary tuberculosis in China: a national survey","volume":"128","author":"Li","year":"2023","journal-title":"Int. J. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2294858","DOI":"10.1080\/22221751.2023.2294858","article-title":"Genomic analysis of lineage-specific transmission of multidrug resistance tuberculosis in China","volume":"1","author":"Li","year":"2024","journal-title":"Emerg. Microbes Infect."},{"key":"B21","doi-asserted-by":"publisher","first-page":"100390","DOI":"10.1016\/j.jctube.2023.100390","article-title":"Clinical features, resistance patterns and treatment outcomes of drug-resistant extra-pulmonary tuberculosis: A scoping review","volume":"33","author":"Miiro","year":"2023","journal-title":"J. Clin. Tuberc Other Mycobact Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"151","DOI":"10.5588\/ijtld.18.0109","article-title":"Drug resistance in extra-pulmonary tuberculosis in South Korea: comparison with pulmonary tuberculosis","volume":"2","author":"Mok","year":"2019","journal-title":"Int. J. Tuberc Lung Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1080\/07391102.2023.2283159","article-title":"Exploring natural products library to identify potential inhibitors targeting isoniazid-resistant tuberculosis","volume":"2","author":"N","year":"2025","journal-title":"J. Biomol Struct. Dyn"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.12128","article-title":"Whole-genome comparative analysis at the lineage\/sublineage level discloses relationships between Mycobacterium tuberculosis genotype and clinical phenotype","volume":"9","author":"Negrete-Paz","year":"2021","journal-title":"PeerJ"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209650","article-title":"Extra-pulmonary tuberculosis: A retrospective study of patients in Accra, Ghana","volume":"1","author":"Ohene","year":"2019","journal-title":"PloS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1080\/17476348.2021.1927718","article-title":"Extrapulmonary tuberculosis","volume":"7","author":"Sharma","year":"2021","journal-title":"Expert Rev. Respir. Med."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202302076","article-title":"Whole genome sequencing of drug resistance Mycobacterium tuberculosis from extra-pulmonary sites","volume":"11","author":"Shi","year":"2023","journal-title":"Life Sci Alliance"},{"key":"B28","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1186\/s12879-020-05256-4","article-title":"Machine learning reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis","volume":"1","author":"Sibandze","year":"2020","journal-title":"BMC Infect. Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1128\/JCM.43.6.2996-2997.2005","article-title":"Extraction of Mycobacterium tuberculosis DNA: a question of containment","volume":"6","author":"Somerville","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01324-23","article-title":"Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistant Mycobacterium tuberculosis in China","volume":"5","author":"Song","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.3967\/bes2024.168","article-title":"Therapeutic strategies for tuberculosis: progress and lessons learned","volume":"11","author":"Sun","year":"2024","journal-title":"BioMed. Environ. Sci."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.29282","article-title":"Global frequency and clinical features of stroke in patients with tuberculous meningitis: A systematic review","volume":"9","author":"Sy","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1128\/JCM.02180-07","article-title":"Relationship between Mycobacterium tuberculosis genotype and the clinical phenotype of pulmonary and meningeal tuberculosis","volume":"4","author":"Thwaites","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.meegid.2016.09.004","article-title":"Overview on mechanisms of isoniazid action and resistance in Mycobacterium tuberculosis","volume":"45","author":"Unissa","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s11904-009-0019-7","article-title":"Tuberculous meningitis in HIV-infected individuals","volume":"3","author":"Vinnard","year":"2009","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1007\/s15010-022-01921-9","article-title":"Occurrence of extrapulmonary tuberculosis is associated with geographical origin: spatial characteristics of the Frankfurt TB cohort 2013-2018","volume":"3","author":"Wetzstein","year":"2023","journal-title":"Infection"},{"key":"B37","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nrneurol.2017.120","article-title":"Tuberculous meningitis","volume":"10","author":"Wilkinson","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"W587","DOI":"10.1093\/nar\/gkad359","article-title":"Tree Visualization By One Table (tvBOT): a web application for visualizing, modifying and annotating phylogenetic trees","author":"Xie","year":"2023","journal-title":"Nucleic Acids Res."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1692783\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T06:30:44Z","timestamp":1765434644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1692783\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":38,"alternative-id":["10.3389\/fcimb.2025.1692783"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1692783","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]},"article-number":"1692783"}}