{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:33:48Z","timestamp":1740166428872,"version":"3.37.3"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Antimicrob Resist Infect Control"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>To carry out a whole genome sequencing (WGS)-based investigation on the emergence and spread of the largest multidrug-resistant tuberculosis (MDR TB) outbreak that has been thriving among HIV-negative patients, Tunisia, since the early 2000s.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed phylogeographic analyses and molecular dating based on a WGS dataset representing 68 unique <jats:italic>Mycobacterium tuberculosis<\/jats:italic> isolates, covering almost the entire MDR TB outbreak for the time period 2001\u20132016.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The data indicate that the ancestor of the MDR TB outbreak emerged in the region of Bizerte, as early as 1974 (95% CI 1951\u20131985), from where it spread to other regions by 1992 (95% CI 1980\u20131996). Analysis of a minimum spanning tree based on core genome Multilocus Sequence Typing (cgMLST) uncovered the early spill-over of the fitness-compensated MDR TB strain from the prison into the general population. Indeed, cases with history of incarceration were found to be directly or indirectly linked to up to 22 new outbreak cases (32.35%) among the non-imprisoned population. By around 2008, the MDR TB outbreak strain had acquired additional resistance, leading to an XDR phenotype.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>WGS allowed refining our understanding of the emergence and evolution of the largest MDR TB outbreak in Tunisia, whose causative strain has been circulating silently for almost 26\u00a0years before. Our study lends further support to the critical role of prisons-related cases in the early spread of the outbreak among the general population. The shift to an XDR phenotype of such an epidemic clone prompts an urgent need to undertake drastic control measures.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13756-023-01360-7","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T05:02:26Z","timestamp":1707886946000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7881-9348","authenticated-orcid":false,"given":"Naira","family":"Dekhil","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9194-0070","authenticated-orcid":false,"given":"Helmi","family":"Mardassi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"1360_CR1","unstructured":"World Health Organization. Global tuberculosis reports [Internet]. 2022 [cited 2022 Oct 31]. Available from: https:\/\/www.who.int\/teams\/global-tuberculosis-programme\/tb-reports."},{"key":"1360_CR2","unstructured":"WHO announces updated definitions of extensively drug-resistant tuberculosis [Internet]. [cited 2023 Nov 15]. Available from: https:\/\/www.who.int\/news\/item\/27-01-2021-who-announces-updated-definitions-of-extensively-drug-resistant-tuberculosis."},{"key":"1360_CR3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1183\/09031936.00027612","volume":"40","author":"R Loddenkemper","year":"2012","unstructured":"Loddenkemper R, Sotgiu G, Mitnick CD. Cost of tuberculosis in the era of multidrug resistance: will it become unaffordable? Eur Respir J. 2012;40:9\u201311.","journal-title":"Eur Respir J"},{"key":"1360_CR4","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1126\/science.abd1072","volume":"369","author":"Q Abdool Karim","year":"2020","unstructured":"Abdool Karim Q, Abdool Karim SS. COVID-19 affects HIV and tuberculosis care. Science. 2020;369:366\u20138. https:\/\/doi.org\/10.1126\/science.abd1072.","journal-title":"Science"},{"key":"1360_CR5","doi-asserted-by":"publisher","first-page":"e0153983","DOI":"10.1371\/journal.pone.0153983","volume":"11","author":"N Dekhil","year":"2016","unstructured":"Dekhil N, Meftahi N, Mhenni B, Ben Fraj S, Haltiti R, Belhaj S, et al. MDR-TB outbreak among HIV-negative tunisian patients followed during 11 years. PLoS ONE. 2016;11:e0153983.","journal-title":"PLoS ONE"},{"key":"1360_CR6","doi-asserted-by":"publisher","first-page":"957","DOI":"10.3201\/eid1106.041365","volume":"11","author":"H Mardassi","year":"2005","unstructured":"Mardassi H, Namouchi A, Haltiti R, Zarrouk M, Mhenni B, Karboul A, et al. Tuberculosis due to resistant Haarlem strain Tunisia. Emerg Infect Dis. 2005;11:957\u201361.","journal-title":"Emerg Infect Dis"},{"key":"1360_CR7","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1093\/jac\/dkv345","volume":"71","author":"N Meftahi","year":"2016","unstructured":"Meftahi N, Namouchi A, Mhenni B, Brandis G, Hughes D, Mardassi H. Evidence for the critical role of a secondary site rpoB mutation in the compensatory evolution and successful transmission of an MDR tuberculosis outbreak strain. J Antimicrob Chemother. 2016;71:324\u201332.","journal-title":"J Antimicrob Chemother"},{"key":"1360_CR8","doi-asserted-by":"publisher","first-page":"547","DOI":"10.3201\/eid2503.181370","volume":"25","author":"I Bouzouita","year":"2019","unstructured":"Bouzouita I, Cabibbe AM, Trovato A, Daroui H, Ghariani A, Midouni B, et al. Whole-genome sequencing of drug-resistant mycobacterium tuberculosis strains, Tunisia, 2012\u20132016. Emerg Infect Dis. 2019;25:547\u201350.","journal-title":"Emerg Infect Dis"},{"key":"1360_CR9","doi-asserted-by":"publisher","first-page":"7119","DOI":"10.1038\/ncomms8119","volume":"6","author":"V Eldholm","year":"2015","unstructured":"Eldholm V, Monteserin J, Rieux A, Lopez B, Sobkowiak B, Ritacco V, et al. Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain. Nat Commun. 2015;6:7119.","journal-title":"Nat Commun"},{"key":"1360_CR10","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S1473-3099(12)70277-3","volume":"13","author":"TM Walker","year":"2013","unstructured":"Walker TM, Ip CL, Harrell RH, Evans JT, Kapatai G, Dedicoat MJ, et al. Whole-genome sequencing to delineate mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis. 2013;13:137\u201346.","journal-title":"Lancet Infect Dis"},{"key":"1360_CR11","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1126\/science.1124410","volume":"312","author":"S Gagneux","year":"2006","unstructured":"Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, Bohannan BJM. The competitive cost of antibiotic resistance in mycobacterium tuberculosis. Science. 2006;312:1944\u20136. https:\/\/doi.org\/10.1126\/science.1124410.","journal-title":"Science"},{"key":"1360_CR12","doi-asserted-by":"crossref","unstructured":"Warren R, de Kock M, Engelke E, Myburgh R, Gey van Pittius N, Victor T, et al. Safe mycobacterium tuberculosis DNA extraction method that does not compromise integrity. J Clin Microbiol. 2006; 44: 254\u20136.","DOI":"10.1128\/JCM.44.1.254-256.2006"},{"key":"1360_CR13","unstructured":"NextSeq 500 system WGS solution."},{"key":"1360_CR14","first-page":"220","volume":"103","author":"MA Skhairia","year":"2021","unstructured":"Skhairia MA, Dekhil N, Mhenni B, Fradj SB, Mardassi H. Successful expansion of Mycobacterium tuberculosis Latin American and mediterranean sublineage (L4.3\/LAM) in Tunisia mainly driven by a single, long-established clonal complex. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. 2021;103:220\u20135.","journal-title":"Int J Infect Dis IJID Off Publ Int Soc Infect Dis."},{"key":"1360_CR15","unstructured":"Andrews S. FastQC A Quality control tool for high throughput sequence data [Internet]. 2010 [cited 2019 May 8]. Available from: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"1360_CR16","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114\u201320.","journal-title":"Bioinformatics"},{"issue":"14","key":"1360_CR17","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Durbin R. Fast and accurate short read alignment with Burrows\u2013Wheeler transform. Bioinformatics. 2009;25(14):1754\u201360.","journal-title":"Bioinformatics"},{"key":"1360_CR18","unstructured":"NovoAlign [Internet]. [cited 2019 May 8]. Available from: http:\/\/www.novocraft.com\/products\/novoalign\/"},{"key":"1360_CR19","unstructured":"Ponstingl H, Ning Z. <p>SMALT\u2014a new mapper for DNA sequencing reads<\/p>. F1000Research [Internet]. 2010 [cited 2019 May 8];1. Available from: https:\/\/f1000research.com\/posters\/327."},{"key":"1360_CR20","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A Mckenna","year":"2010","unstructured":"Mckenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The genome analysis toolkit: a mapreduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297\u2013303.","journal-title":"Genome Res"},{"key":"1360_CR21","unstructured":"Picard tools\u2014by broad institute [Internet]. [cited 2019 May 8]. Available from: https:\/\/broadinstitute.github.io\/picard\/."},{"key":"1360_CR22","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1128\/JCM.00567-14","volume":"52","author":"TA Kohl","year":"2014","unstructured":"Kohl TA, Diel R, Harmsen D, Rothg\u00e4nger J, Walter KM, Merker M, et al. Whole-genome-based mycobacterium tuberculosis surveillance: a standardized, portable, and expandable approach. J Clin Microbiol. 2014;52:2479\u201386.","journal-title":"J Clin Microbiol"},{"key":"1360_CR23","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/s41579-019-0214-5","volume":"17","author":"CJ Meehan","year":"2019","unstructured":"Meehan CJ, Goig GA, Kohl TA, Verboven L, Dippenaar A, Ezewudo M, et al. Whole genome sequencing of mycobacterium tuberculosis: current standards and open issues. Nat Rev Microbiol. 2019;17:533\u201345.","journal-title":"Nat Rev Microbiol"},{"key":"1360_CR24","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1093\/sysbio\/syv068","volume":"65","author":"T-H To","year":"2016","unstructured":"To T-H, Jung M, Lycett S, Gascuel O. Fast dating using least-squares criteria and algorithms. Syst Biol. 2016;65:82\u201397.","journal-title":"Syst Biol"},{"key":"1360_CR25","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1093\/bioinformatics\/btu033","volume":"30","author":"A Stamatakis","year":"2014","unstructured":"Stamatakis A. RAxML 8 version: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014;30:1312\u20133.","journal-title":"Bioinformatics"},{"issue":"W1","key":"1360_CR26","doi-asserted-by":"publisher","first-page":"W293","DOI":"10.1093\/nar\/gkab301","volume":"49","author":"I Letunic","year":"2021","unstructured":"Letunic I, Bork P. Interactive tree of life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 2021;49(W1):W293\u20136.","journal-title":"Nucleic Acids Res"},{"key":"1360_CR27","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3390\/antibiotics11020133","volume":"11","author":"A Ushtanit","year":"2022","unstructured":"Ushtanit A, Kulagina E, Mikhailova Y, Makarova M, Safonova S, Zimenkov D. Molecular determinants of ethionamide resistance in clinical isolates of mycobacterium tuberculosis. Antibiotics. 2022;11:133.","journal-title":"Antibiotics"},{"key":"1360_CR28","unstructured":"CDCTB. Dear colleague letter [Internet]. Cent. Dis. Control Prev. 2022 [cited 2023 Nov 15]. Available from: https:\/\/www.cdc.gov\/tb\/publications\/letters\/2022\/surv-def-xdr.html."},{"key":"1360_CR29","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1093\/molbev\/msz131","volume":"36","author":"SA Ishikawa","year":"2019","unstructured":"Ishikawa SA, Zhukova A, Iwasaki W, Gascuel O. A fast likelihood method to reconstruct and visualize ancestral scenarios. Mol Biol Evol. 2019;36:2069\u201385. https:\/\/doi.org\/10.1093\/molbev\/msz131.","journal-title":"Mol Biol Evol"},{"key":"1360_CR30","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3389\/fpubh.2019.00087","volume":"7","author":"MJ van der Werf","year":"2019","unstructured":"van der Werf MJ, K\u00f6dm\u00f6n C. Whole-genome sequencing as tool for investigating international tuberculosis outbreaks: a systematic review. Front Public Health. 2019;7:87.","journal-title":"Front Public Health"},{"key":"1360_CR31","doi-asserted-by":"publisher","first-page":"e1001387","DOI":"10.1371\/journal.pmed.1001387","volume":"10","author":"A Roetzer","year":"2013","unstructured":"Roetzer A, Diel R, Kohl TA, R\u00fcckert C, N\u00fcbel U, Blom J, et al. Whole genome sequencing versus traditional genotyping for investigation of a mycobacterium tuberculosis outbreak: a longitudinal molecular epidemiological study. PLoS Med. 2013;10:e1001387.","journal-title":"PLoS Med"},{"key":"1360_CR32","doi-asserted-by":"publisher","first-page":"16644","DOI":"10.7554\/eLife.16644","volume":"5","author":"V Eldholm","year":"2016","unstructured":"Eldholm V, Rieux A, Monteserin J, Lopez JM, Palmero D, Lopez B, et al. Impact of HIV co-infection on the evolution and transmission of multidrug-resistant tuberculosis. Elife. 2016;5:16644.","journal-title":"Elife"},{"key":"1360_CR33","doi-asserted-by":"publisher","first-page":"S86","DOI":"10.1086\/518665","volume":"196","author":"CD Wells","year":"2007","unstructured":"Wells CD, Cegielski JP, Nelson LJ, Laserson KF, Holtz TH, Finlay A, et al. HIV infection and multidrug-resistant tuberculosis\u2014the perfect storm. J Infect Dis. 2007;196:S86-107. https:\/\/doi.org\/10.1086\/518665.","journal-title":"J Infect Dis"},{"key":"1360_CR34","doi-asserted-by":"publisher","first-page":"5421","DOI":"10.1128\/aac.00695-11","volume":"55","author":"H Takiff","year":"2011","unstructured":"Takiff H, Guerrero E. Current prospects for the fluoroquinolones as first-line tuberculosis therapy. Antimicrob Agents Chemother. 2011;55:5421\u20139. https:\/\/doi.org\/10.1128\/aac.00695-11.","journal-title":"Antimicrob Agents Chemother"},{"key":"1360_CR35","doi-asserted-by":"publisher","first-page":"2446","DOI":"10.1128\/jcm.31.9.2446-2450.1993","volume":"31","author":"D Chevrel-Dellagi","year":"1993","unstructured":"Chevrel-Dellagi D, Abderrahman A, Haltiti R, Koubaji H, Gicquel B, Dellagi K. Large-scale DNA fingerprinting of mycobacterium tuberculosis strains as a tool for epidemiological studies of tuberculosis. J Clin Microbiol. 1993;31:2446\u201350.","journal-title":"J Clin Microbiol"},{"key":"1360_CR36","doi-asserted-by":"publisher","first-page":"e1000381","DOI":"10.1371\/journal.pmed.1000381","volume":"7","author":"I Baussano","year":"2010","unstructured":"Baussano I, Williams BG, Nunn P, Beggiato M, Fedeli U, Scano F. Tuberculosis incidence in prisons: a systematic review. PLoS Med. 2010;7:e1000381.","journal-title":"PLoS Med"},{"key":"1360_CR37","doi-asserted-by":"publisher","first-page":"452","DOI":"10.3201\/eid2103.140896","volume":"21","author":"FPC Sacchi","year":"2015","unstructured":"Sacchi FPC, Pra\u00e7a RM, Tatara MB, Simonsen V, Ferrazoli L, Croda MG, et al. Prisons as reservoir for community transmission of tuberculosis, Brazil. Emerg Infect Dis. 2015;21:452\u20135.","journal-title":"Emerg Infect Dis"},{"key":"1360_CR38","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1038\/s41591-021-01358-x","volume":"27","author":"SM Gygli","year":"2021","unstructured":"Gygli SM, Loiseau C, Jugheli L, Adamia N, Trauner A, Reinhard M, et al. Prisons as ecological drivers of fitness-compensated multidrug-resistant mycobacterium tuberculosis. Nat Med. 2021;27:1171\u20137.","journal-title":"Nat Med"}],"container-title":["Antimicrobial Resistance &amp; Infection Control"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13756-023-01360-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13756-023-01360-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13756-023-01360-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T16:10:29Z","timestamp":1708186229000},"score":1,"resource":{"primary":{"URL":"https:\/\/aricjournal.biomedcentral.com\/articles\/10.1186\/s13756-023-01360-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,14]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1360"],"URL":"https:\/\/doi.org\/10.1186\/s13756-023-01360-7","relation":{},"ISSN":["2047-2994"],"issn-type":[{"type":"electronic","value":"2047-2994"}],"subject":[],"published":{"date-parts":[[2024,2,14]]},"assertion":[{"value":"26 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No interventions have been performed for the specific need of this study. DNAs for WGS was obtained from the strain collection of the Unit of Typing & Genetics of Mycobacteria of the Institut Pasteur, Tunis, as part of its routine diagnostic activity permitted by the Tunisian Ministry of Health, in the context of the National TB program. Furthermore, analysis of this strain collection has been previously published []. Only fully anonymized data were processed, and hence no further ethical clearance was required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18"}}