{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:05:06Z","timestamp":1790867106594,"version":"4.1.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zoonoses and Emerging Livestock Systems (ZELS) program","award":["BB\/L018977\/1"],"award-info":[{"award-number":["BB\/L018977\/1"]}]},{"DOI":"10.13039\/501100002142","name":"Animal Health and Veterinary Laboratories Agency","doi-asserted-by":"publisher","award":["TBSE3294"],"award-info":[{"award-number":["TBSE3294"]}],"id":[{"id":"10.13039\/501100002142","id-type":"DOI","asserted-by":"publisher"}]},{"name":"biotechnology and biologic sciences research council"},{"DOI":"10.13039\/501100000278","name":"department for international development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000269","name":"economic & social research council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"medical research council"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Previous work has shown differential predominance of certain<jats:italic>Mycobacterium tuberculosis (M<\/jats:italic>.<jats:italic>tb)<\/jats:italic>lineages and sub-lineages among different human populations in diverse geographic regions of Ethiopia. Nevertheless, how strain diversity is evolving under the ongoing rapid socio-economic and environmental changes is poorly understood. The present study investigated factors associated with<jats:italic>M<\/jats:italic>.<jats:italic>tb<\/jats:italic>lineage predominance and rate of strain clustering within urban and peri-urban settings in Ethiopia.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>Pulmonary Tuberculosis (PTB) and Cervical tuberculous lymphadenitis (TBLN) patients who visited selected health facilities were recruited in the years of 2016 and 2017. A total of 258<jats:italic>M<\/jats:italic>.<jats:italic>tb<\/jats:italic>isolates identified from 163 sputa and 95 fine-needle aspirates (FNA) were characterized by spoligotyping and compared with international<jats:italic>M<\/jats:italic>.<jats:italic>tb<\/jats:italic>spoligotyping patterns registered at the SITVIT2 databases. The molecular data were linked with clinical and demographic data of the patients for further statistical analysis.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>From a total of 258<jats:italic>M<\/jats:italic>.<jats:italic>tb<\/jats:italic>isolates, 84 distinct spoligotype patterns that included 58 known Shared International Type (SIT) patterns and 26 new or orphan patterns were identified. The majority of strains belonged to two major<jats:italic>M<\/jats:italic>.<jats:italic>tb<\/jats:italic>lineages, L3 (35.7%) and L4 (61.6%). The observed high percentage of isolates with shared patterns (n = 200\/258) suggested a substantial rate of overall clustering (77.5%). After adjusting for the effect of geographical variations, clustering rate was significantly lower among individuals co-infected with HIV and other concomitant chronic disease. Compared to L4, the adjusted odds ratio and 95% confidence interval (AOR; 95% CI) indicated that infections with L3<jats:italic>M<\/jats:italic>.<jats:italic>tb<\/jats:italic>strains were more likely to be associated with TBLN [3.47 (1.45, 8.29)] and TB-HIV co-infection [2.84 (1.61, 5.55)].<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusion<\/jats:title><jats:p>Despite the observed difference in strain diversity and geographical distribution of<jats:italic>M<\/jats:italic>.<jats:italic>tb<\/jats:italic>lineages, compared to earlier studies in Ethiopia, the overall rate of strain clustering suggests higher transmission and warrant more detailed investigations into the molecular epidemiology of TB and related factors.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0253480","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T17:35:17Z","timestamp":1626111317000},"page":"e0253480","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Epidemiology of Mycobacterium tuberculosis lineages and strain clustering within urban and peri-urban settings in Ethiopia"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5604-9706","authenticated-orcid":true,"given":"Hawult","family":"Taye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kassahun","family":"Alemu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adane","family":"Mihret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5276-7236","authenticated-orcid":true,"given":"Sosina","family":"Ayalew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Hailu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L. N.","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziv","family":"Shkedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8028-1150","authenticated-orcid":true,"given":"Abraham","family":"Aseffa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The ETHICOBOTS consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,12]]},"reference":[{"key":"pone.0253480.ref001","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.3389\/fmicb.2018.02820","article-title":"A New Phylogenetic Framework for the Animal-Adapted Mycobacterium tuberculosis Complex","volume":"9","author":"D. Brites","year":"2018","journal-title":"Front Microbiol"},{"key":"pone.0253480.ref002","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-3-319-64371-7_5","article-title":"Biological and Epidemiological Consequences of MTBC Diversity","volume":"1019","author":"M. Coscolla","year":"2017","journal-title":"Adv Exp Med Biol"},{"issue":"4","key":"pone.0253480.ref003","doi-asserted-by":"crossref","first-page":"e1008728","DOI":"10.1371\/journal.pgen.1008728","article-title":"Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: Evidence for coevolution?","volume":"16","author":"M.L. McHenry","year":"2020","journal-title":"PLoS Genet"},{"key":"pone.0253480.ref004","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.3389\/fimmu.2017.01948","article-title":"The Troika host\u2013pathogen\u2013extrinsic factors in tuberculosis: modulating inflammation and clinical outcomes","volume":"8","author":"H.N. Bastos","year":"2018","journal-title":"J Frontiers in immunology"},{"issue":"1590","key":"pone.0253480.ref005","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1098\/rstb.2011.0316","article-title":"Host-pathogen coevolution in human tuberculosis","volume":"367","author":"S. Gagneux","year":"2012","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"pone.0253480.ref006","doi-asserted-by":"crossref","first-page":"550760","DOI":"10.3389\/fmicb.2020.550760","article-title":"Lineage-Specific Proteomic Signatures in the Mycobacterium tuberculosis Complex Reveal Differential Abundance of Proteins Involved in Virulence, DNA Repair, CRISPR-Cas, Bioenergetics and Lipid Metabolism","volume":"11","author":"S.A. Yimer","year":"2020","journal-title":"Front Microbiol"},{"issue":"12","key":"pone.0253480.ref007","first-page":"1314","volume":"23","author":"D. Mekonnen","year":"2019","journal-title":"Genomic diversity and transmission dynamics of M. tuberculosis in Africa: a systematic review and meta-analysis"},{"key":"pone.0253480.ref008","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.meegid.2018.12.030","article-title":"Evolution Macro-geographical specificities of the prevailing tuberculosis epidemic as seen through SITVIT2, an updated version of the Mycobacterium tuberculosis genotyping database","volume":"72","author":"D. Couvin","year":"2019","journal-title":"J Infection, Genetics"},{"issue":"1","key":"pone.0253480.ref009","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens7010017","article-title":"Mycobacterium tuberculosis Molecular Determinants of Infection, Survival Strategies, and Vulnerable Targets","volume":"7","author":"D.M. Ferraris","year":"2018","journal-title":"Pathogens"},{"issue":"4","key":"pone.0253480.ref010","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00250-13","article-title":"Clade-specific virulence patterns of Mycobacterium tuberculosis complex strains in human primary macrophages and aerogenically infected mice","volume":"4","author":"N. Reiling","year":"2013","journal-title":"mBio"},{"issue":"4","key":"pone.0253480.ref011","first-page":"e1008728","article-title":"Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity","volume":"16","author":"M.L. McHenry","year":"2020","journal-title":"Evidence for coevolution?"},{"issue":"4","key":"pone.0253480.ref012","doi-asserted-by":"crossref","DOI":"10.1128\/CMR.00021-18","article-title":"Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection","volume":"31","author":"P.K. Drain","year":"2018","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"pone.0253480.ref013","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41426-018-0106-1","article-title":"E.A. Graviss Risk factors for extrapulmonary dissemination of tuberculosis and associated mortality during treatment for extrapulmonary tuberculosis","volume":"7","author":"X. Qian","year":"2018","journal-title":"Emerg Microbes Infect"},{"issue":"3","key":"pone.0253480.ref014","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3201\/eid1903.120256","article-title":"Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia","volume":"19","author":"R. Firdessa","year":"2013","journal-title":"Emerg Infect Dis"},{"issue":"10","key":"pone.0253480.ref015","doi-asserted-by":"crossref","first-page":"e0240257","DOI":"10.1371\/journal.pone.0240257","article-title":"genetic diversity and drug sensitivity patterns of Mycobacterium tuberculosis strains isolated from tuberculous meningitis patients at a tertiary care hospital in South India","volume":"15","author":"K. Krishnakumariamma","year":"2020","journal-title":"PloS one"},{"issue":"3","key":"pone.0253480.ref016","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1136\/thoraxjnl-2012-201824","article-title":"Ethnicity and mycobacterial lineage as determinants of tuberculosis disease phenotype","volume":"68","author":"M. Pareek","year":"2013","journal-title":"J Thorax"},{"issue":"11","key":"pone.0253480.ref017","doi-asserted-by":"crossref","first-page":"e0140625","DOI":"10.1371\/journal.pone.0140625","article-title":"Determinants of the Sympatric Host-Pathogen Relationship in Tuberculosis","volume":"10","author":"S. David","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"pone.0253480.ref018","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/1471-2334-14-309","article-title":"Increased level of acute phase reactants in patients infected with modern Mycobacterium tuberculosis genotypes in Mwanza, Tanzania","volume":"14","author":"R. Stavrum","year":"2014","journal-title":"BMC Infect Dis"},{"issue":"3","key":"pone.0253480.ref019","doi-asserted-by":"crossref","first-page":"e0193911","DOI":"10.1371\/journal.pone.0193911","article-title":"Genotyping and spatial analysis of pulmonary tuberculosis and diabetes cases in the state of Veracruz, Mexico","volume":"13","author":"F. Blanco-Guillot","year":"2018","journal-title":"PLoS One"},{"issue":"3","key":"pone.0253480.ref020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003318","article-title":"HIV Infection Disrupts the Sympatric Host\u2013Pathogen Relationship in Human Tuberculosis","volume":"9","author":"L. Fenner","year":"2013","journal-title":"PLoS Genet"},{"key":"pone.0253480.ref021","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.02219","article-title":"Genetic Resistance to Mycobacterium tuberculosis Infection and Disease","volume":"9","author":"M. M\u00f6ller","year":"2018","journal-title":"Front Immunol"},{"key":"pone.0253480.ref022","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.ebiom.2018.10.013","article-title":"The relationship between transmission time and clustering methods in Mycobacterium tuberculosis epidemiology","volume":"37","author":"C.J. Meehan","year":"2018","journal-title":"EBioMedicine"},{"issue":"10","key":"pone.0253480.ref023","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1111\/1469-0691.12253","article-title":"The re-emergence of tuberculosis: what have we learnt from molecular epidemiology?","volume":"19","author":"M. Borgdorff","year":"2013","journal-title":"J Clinical Microbiology Infection"},{"issue":"9","key":"pone.0253480.ref024","doi-asserted-by":"crossref","first-page":"e0198054","DOI":"10.1371\/journal.pone.0198054","article-title":"Molecular epidemiology and drug resistance patterns of Mycobacterium tuberculosis complex isolates from university students and the local community in Eastern Ethiopia","volume":"13","author":"A. Mekonnen","year":"2018","journal-title":"PLoS One"},{"issue":"6","key":"pone.0253480.ref025","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1111\/tmi.12875","article-title":"J.S. Michael Spoligotyping of Mycobacterium tuberculosis isolates at a tertiary care hospital in India","volume":"22","author":"S. Suzana","year":"2017","journal-title":"Trop Med Int Health"},{"issue":"1","key":"pone.0253480.ref026","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12879-017-2267-2","article-title":"Molecular typing of Mycobacterium tuberculosis complex isolated from pulmonary tuberculosis patients in central Ethiopia","volume":"17","author":"Z. Bedewi","year":"2017","journal-title":"BMC Infect Dis"},{"key":"pone.0253480.ref027","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12879-015-0846-7","article-title":"Investigation of the high rates of extrapulmonary tuberculosis in Ethiopia reveals no single driving factor and minimal evidence for zoonotic transmission of Mycobacterium bovis infection","volume":"15","author":"S. Berg","year":"2015","journal-title":"BMC Infect Dis"},{"issue":"4","key":"pone.0253480.ref028","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1128\/JCM.03566-14","article-title":"Mycobacterium tuberculosis lineage 7 strains are associated with prolonged patient delay in seeking treatment for pulmonary tuberculosis in Amhara Region, Ethiopia","volume":"53","author":"S.A. Yimer","year":"2015","journal-title":"J Clin Microbiol"},{"issue":"1","key":"pone.0253480.ref029","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s12879-018-3046-4","article-title":"Spoligotyping based genetic diversity of Mycobacterium tuberculosis in Ethiopia: a systematic review","volume":"18","author":"B. Tulu","year":"2018","journal-title":"J BMC infectious diseases"},{"issue":"2","key":"pone.0253480.ref030","doi-asserted-by":"crossref","first-page":"e0193083","DOI":"10.1371\/journal.pone.0193083","article-title":"Molecular epidemiology and drug sensitivity pattern of Mycobacterium tuberculosis strains isolated from pulmonary tuberculosis patients in and around Ambo Town, Central Ethiopia","volume":"13","author":"M. Tilahun","year":"2018","journal-title":"PLoS One"},{"issue":"4","key":"pone.0253480.ref031","doi-asserted-by":"crossref","first-page":"e5068","DOI":"10.1371\/journal.pone.0005068","article-title":"The burden of mycobacterial disease in ethiopian cattle: implications for public health","volume":"4","author":"S. Berg","year":"2009","journal-title":"PLoS One"},{"issue":"4","key":"pone.0253480.ref032","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1128\/jcm.35.4.907-914.1997","article-title":"Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology","volume":"35","author":"J. Kamerbeek","year":"1997","journal-title":"J Clin Microbiol"},{"issue":"2","key":"pone.0253480.ref033","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2217\/fmb.10.165","article-title":"Genotyping of Mycobacterium tuberculosis: application in epidemiologic studies","volume":"6","author":"M. Kato-Maeda","year":"2011","journal-title":"Future Microbiol"},{"key":"pone.0253480.ref034","doi-asserted-by":"crossref","first-page":"101858","DOI":"10.1016\/j.tube.2019.101858","article-title":"Molecular epidemiology of M. tuberculosis in Ethiopia: A systematic review and meta-analysis","volume":"118","author":"D. Mekonnen","year":"2019","journal-title":"Tuberculosis (Edinb)"},{"issue":"12","key":"pone.0253480.ref035","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/S1473-3099(18)30625-X","article-title":"Global, regional, and national burden of tuberculosis, 1990\u20132016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study","volume":"18","author":"H.H. Kyu","year":"2018","journal-title":"J The Lancet Infectious Diseases"},{"issue":"5","key":"pone.0253480.ref036","first-page":"519","article-title":"Tuberculosis Burden in Ethiopia from 1990 to 2016: Evidence from the Global Burden of Diseases 2016 Study","volume":"28","author":"A. Deribew","year":"2018","journal-title":"Ethiop J Health Sci"},{"key":"pone.0253480.ref037","doi-asserted-by":"crossref","first-page":"174732","DOI":"10.1155\/2015\/174732","article-title":"Genetic Diversity of Mycobacterium tuberculosis Complex Isolated from Tuberculosis Patients in Bahir Dar City and Its Surroundings, Northwest Ethiopia","volume":"2015","author":"A. Nuru","year":"2015","journal-title":"Biomed Res Int"},{"issue":"7","key":"pone.0253480.ref038","doi-asserted-by":"crossref","first-page":"e0132400","DOI":"10.1371\/journal.pone.0132400","article-title":"Epidemiology of Peripheral Lymph Node Tuberculosis and Genotyping of M. tuberculosis Strains: A Case-Control Study","volume":"10","author":"C. Khandkar","year":"2015","journal-title":"PLoS One"},{"key":"pone.0253480.ref039","doi-asserted-by":"crossref","first-page":"238532","DOI":"10.1155\/2014\/238532","article-title":"Strain diversity of Mycobacterium tuberculosis isolates from pulmonary tuberculosis patients in Afar pastoral region of Ethiopia","volume":"2014","author":"M. Belay","year":"2014","journal-title":"Biomed Res Int"},{"issue":"3","key":"pone.0253480.ref040","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/ftx020","article-title":"Relapse, re-infection and mixed infections in tuberculosis disease","volume":"75","author":"A. McIvor","year":"2017","journal-title":"Pathog Dis"},{"issue":"12","key":"pone.0253480.ref041","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1128\/JCM.01467-14","article-title":"Genetic diversity and dynamic distribution of Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in Thailand","volume":"52","author":"P. Srilohasin","year":"2014","journal-title":"J Clin Microbiol"},{"issue":"9","key":"pone.0253480.ref042","doi-asserted-by":"crossref","first-page":"e744","DOI":"10.1371\/journal.pntd.0000744","article-title":"S. Gagneux Mycobacterium africanum\u2014review of an important cause of human tuberculosis in West Africa","volume":"4","author":"B.C. de Jong","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"pone.0253480.ref043","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/cid\/ciy938","article-title":"The importance of heterogeneity to the epidemiology of tuberculosis","volume":"69","author":"J.M. Trauer","year":"2018","journal-title":"J Clinical infectious diseases"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253480","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T21:10:04Z","timestamp":1672780204000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253480"}},"subtitle":[],"editor":[{"given":"Md Jamal","family":"Uddin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,12]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0253480","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,12]]}}}