{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:15:16Z","timestamp":1772244916824,"version":"3.50.1"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Worldwide, tuberculosis (TB) affects about one million children every year. The burden of the disease is higher in developing countries. However, there is limited information on the lineages and drug sensitivity patterns of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic>) infecting children in these countries, including Ethiopia. Thus, this study aimed to characterize the different lineages of the <jats:italic>M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic> complex causing childhood pulmonary tuberculosis and evaluate the drug-sensitivity patterns to the first-line anti-TB drugs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Method<\/jats:title>\n<jats:p>A total of 54 stored cultures were used in this study. The region of difference 9 (RD9) based polymerase chain reaction (PCR) and spoligotyping were employed for the identification of the isolates at the species and lineages level respectively. Lineage identification was done by using the pre-existing database. Identification of clustering of the spoligotype patterns was by using the SPOLIDB3-based model. The result was retrieved by the most probable family format. Furthermore, the phenotypic, and genotypic drug-sensitivity test (DST) was performed using Mycobacterium Growth Indicator Tube (MGIT\u2122 960) and GenoTypeMTBDR<jats:italic>plus<\/jats:italic> assay respectively. Data analysis was done using SPSS version 27 software.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Result<\/jats:title>\n<jats:p>Spoligotyping produced 39 interpretable results for <jats:italic>M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic>. The majority (74.4%) of them were clustered into 7 groups, while the rest (25.6%) were single. The Euro-American (EA) lineage was the predominant lineage (64.1%) followed by the East-African Indian (EAI) (30.8%) and M. Africanum (5.1%) lineages. The most predominant subtypes were SIT37 (15.4%), SIT149 (12.8%), SIT25 (7.7%), and SIT53 (7.7%). Furthermore, of the identified SITs, T1 and CAS families consisted of 38.5% and 28.2% of the lineages respectively. Drug susceptibility was 91.9% by phenotypic method and 97.4% by molecular assay. The overall prevalence of any resistance was 7.8% and there was a single MDR-TB.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Many of the isolates belong to the modern lineages (Euro American) representing the most common circulating strains in the country. More importantly, despites the tiny isolates tested, drug resistance is low. To fully describe the molecular epidemiology of MTBC lineages in children, we recommend a prospective large-scale study.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0284363","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T17:33:18Z","timestamp":1690565598000},"page":"e0284363","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic diversity and drug sensitivity profile of Mycobacterium tuberculosis among children in Ethiopia"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1918-0668","authenticated-orcid":true,"given":"Hilina","family":"Mollalign","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muluwork","family":"Getahun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0166-682X","authenticated-orcid":true,"given":"Getu","family":"Diriba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayinalem","family":"Alemu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4134-6329","authenticated-orcid":true,"given":"Dawit","family":"Chala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Begna","family":"Tulu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gobena","family":"Ameni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"issue":"11","key":"pone.0284363.ref001","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1016\/j.rmed.2006.08.006","article-title":"The history of tuberculosis","volume":"100","author":"TM Daniel","year":"2006","journal-title":"Respir Med"},{"key":"pone.0284363.ref002","volume-title":"World Health Organization, Global Tuberculosis Report","author":"WHO","year":"2020"},{"issue":"8","key":"pone.0284363.ref003","doi-asserted-by":"crossref","first-page":"e453","DOI":"10.1016\/S2214-109X(14)70245-1","article-title":"Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study","volume":"2","author":"PJ Dodd","year":"2014","journal-title":"The Lancet Global Health"},{"key":"pone.0284363.ref004","volume-title":"After years of neglect, growing attention to TB in children in Asia Pacific","author":"S Shukla","year":"2015"},{"issue":"4","key":"pone.0284363.ref005","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.ajme.2018.05.002","article-title":"Risk factors associated with paediatric tuberculosis in an endemic setting","volume":"54","author":"CJ Attah","year":"2018","journal-title":"Alexandria Journal of Medicine"},{"issue":"2","key":"pone.0284363.ref006","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1136\/thx.2010.141309","article-title":"Impact of tuberculosis exposure at home on mortality in children under 5 years of age in Guinea-Bissau","volume":"66","author":"VF Gomes","year":"2011","journal-title":"Thorax"},{"key":"pone.0284363.ref007","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1155\/2011\/239042","article-title":"Mycobacterium tuberculosis Complex Genotype Diversity and Drug Resistance Profiles in a Pediatric Population in Mexico","volume":"2011","author":"M Mac\u00edas Parra","year":"2011","journal-title":"Tuberculosis Research and Treatment"},{"key":"pone.0284363.ref008","first-page":"153","article-title":"Epidemiology and disease burden of tuberculosis in children: a global perspective","volume":"7","author":"J Seddon","year":"2014","journal-title":"Infect Drug Resist"},{"issue":"1","key":"pone.0284363.ref009","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s41479-016-0019-5","article-title":"Drug-resistant tuberculosis and advances in the treatment of childhood tuberculosis","volume":"8","author":"JA Seddon","year":"2016","journal-title":"Pneumonia"},{"issue":"5","key":"pone.0284363.ref010","doi-asserted-by":"crossref","first-page":"e1350","DOI":"10.1542\/peds.2006-0519","article-title":"A refined symptom-based approach to diagnose pulmonary tuberculosis in children","volume":"118","author":"BJ Marais","year":"2006","journal-title":"Pediatrics"},{"key":"pone.0284363.ref011","unstructured":"(GLI) Gli: Mycobacteriology Laboratory Manual,advancing TB diagnosis; 1985."},{"issue":"7","key":"pone.0284363.ref012","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1128\/JCM.40.7.2339-2345.2002","article-title":"Rapid and simple approach for identification of Mycobacterium tuberculosis complex isolates by PCR-based genomic deletion analysis","volume":"40","author":"LM Parsons","year":"2002","journal-title":"J Clin Microbiol"},{"issue":"4","key":"pone.0284363.ref013","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":"1","key":"pone.0284363.ref014","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":"BMC Infectious Diseases"},{"issue":"3","key":"pone.0284363.ref015","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1073\/pnas.022618299","article-title":"Determinants of cluster distribution in the molecular epidemiology of tuberculosis","volume":"99","author":"M Murray","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pone.0284363.ref016","doi-asserted-by":"crossref","first-page":"e00744","DOI":"10.1002\/mbo3.744","article-title":"Spoligotype-based population structure of Mycobacterium tuberculosis in the Jimma Zone, southwest Ethiopia","volume":"8","author":"G Abebe","year":"2019","journal-title":"Microbiologyopen"},{"key":"pone.0284363.ref017","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.nmni.2017.02.003","article-title":"Mycobacterium tuberculosis in central Ethiopia: drug sensitivity patterns and association with genotype","volume":"17","author":"Z Bedewi","year":"2017","journal-title":"New Microbes New Infect"},{"key":"pone.0284363.ref018","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 Research International"},{"key":"pone.0284363.ref019","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1186\/s12889-015-2105-7","article-title":"Molecular typing and drug sensitivity testing of Mycobacterium tuberculosis isolated by a community-based survey in Ethiopia","volume":"15","author":"M Getahun","year":"2015","journal-title":"BMC public health"},{"issue":"7","key":"pone.0284363.ref020","doi-asserted-by":"crossref","first-page":"512","DOI":"10.3109\/00365548.2013.773068","article-title":"Molecular typing of mycobacteria isolated from extrapulmonary tuberculosis patients at Debre Birhan Referral Hospital, central Ethiopia","volume":"45","author":"L Garedew","year":"2013","journal-title":"Scandinavian Journal of Infectious Diseases"},{"issue":"1","key":"pone.0284363.ref021","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1186\/1756-0500-6-352","article-title":"Genotype diversity of Mycobacterium isolates from children in Jimma, Ethiopia","volume":"6","author":"B Workalemahu","year":"2013","journal-title":"BMC Research Notes"},{"key":"pone.0284363.ref022","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/1471-2180-10-195","article-title":"Molecular diversity of Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in Mozambique","volume":"10","author":"SO Viegas","year":"2010","journal-title":"BMC Microbiol"},{"issue":"10","key":"pone.0284363.ref023","doi-asserted-by":"crossref","first-page":"e0163994","DOI":"10.1371\/journal.pone.0163994","article-title":"Prevalence of Drug Resistance Mycobacterium Tuberculosis among Patients Seen in Coast Provincial General Hospital, Mombasa, Kenya","volume":"11","author":"IP Ombura","year":"2016","journal-title":"PLOS ONE"},{"issue":"47","key":"pone.0284363.ref024","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2017.22.47.17-00103","article-title":"Childhood multidrug-resistant tuberculosis in the European Union and European Economic Area: an analysis of tuberculosis surveillance data from 2007 to 2015","volume":"22","author":"C K\u00f6dm\u00f6n","year":"2017","journal-title":"Euro Surveill"},{"issue":"11","key":"pone.0284363.ref025","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.3201\/eid2311.170234","article-title":"Drug-Resistant Tuberculosis among Children, China, 2006\u20132015","volume":"23","author":"N-N Tao","year":"2017","journal-title":"Emerging infectious diseases"},{"issue":"6","key":"pone.0284363.ref026","doi-asserted-by":"crossref","first-page":"e0197737","DOI":"10.1371\/journal.pone.0197737","article-title":"Drug-resistance patterns of Mycobacterium tuberculosis strains and associated risk factors among multi drug-resistant tuberculosis suspected patients from Ethiopia","volume":"13","author":"EA Mesfin","year":"2018","journal-title":"PLOS ONE"},{"issue":"7","key":"pone.0284363.ref027","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1093\/jac\/dkr173","article-title":"Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: classical and new drugs","volume":"66","author":"PE Almeida Da Silva","year":"2011","journal-title":"J Antimicrob Chemother"},{"issue":"7","key":"pone.0284363.ref028","doi-asserted-by":"crossref","first-page":"e0133869","DOI":"10.1371\/journal.pone.0133869","article-title":"A Global Perspective on Pyrazinamide Resistance: Systematic Review and Meta-Analysis","volume":"10","author":"MG Whitfield","year":"2015","journal-title":"PLOS ONE"},{"issue":"10","key":"pone.0284363.ref029","first-page":"e86","article-title":"Molecular analysis of pyrazinamide resistance in Mycobacterium tuberculosis in Vietnam highlights the high rate of pyrazinamide resistance-associated mutations in clinical isolates","volume":"6","author":"NQ Huy","year":"2017","journal-title":"Emerg Microbes Infect"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0284363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T17:33:56Z","timestamp":1690565636000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0284363"}},"subtitle":[],"editor":[{"given":"Leonid","family":"Chindelevitch","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,28]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0284363","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,28]]}}}