{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:45:39Z","timestamp":1792788339184,"version":"4.5.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":86,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The European and Developing Countries Clinical Trials Partnership","award":["RIA2016V-1631"],"award-info":[{"award-number":["RIA2016V-1631"]}],"id":[{"id":"https:\/\/ror.org\/031jv9v19","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The effectiveness of current drug-resistant tuberculosis (DR-TB) regimens is limited by the absence of rapid diagnostics that comprehensively predict resistance to included drugs. Next-generation sequencing (NGS), through culture-free targeted sequencing (tNGS) and culture-based whole-genome sequencing (cWGS) of the\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      complex (MTBC), offers a powerful framework for precision diagnosis, surveillance, and trial applications. We evaluated two novel assays enabling high-resolution tNGS and enrichment-based direct WGS (dWGS) on respiratory samples, focusing on analytical sensitivity, DR and genotyping concordance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>tNGS Deeplex Myc-TB XL tNGS (Genoscreen, beta-testing) and dWGS QIAseq xHYB MTB (Qiagen) were evaluated on 96 MTBC\u2013positive decontaminated sputum samples from a vaccine trial, spanning a wide range of bacillary loads. DNA was extracted using a host-depletion protocol and quantified by MTBC-specific real-time PCR. Libraries were sequenced on Illumina platforms and analysed using assay-specific pipelines. Associations between genome copy (gc) number and sequencing coverage were assessed. DR concordance was benchmarked against cWGS and the WHO mutation catalogue across first-, second-line, newer, and repurposed drugs. WGS-based phylogenetic trees were constructed using Ridom SeqSphere\u2009+\u2009.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bacillary loads ranged from\u2009&lt;\u200910 to\u2009&gt;\u20091,000 MTBC gc\/\u00b5L. tNGS generated interpretable resistance profiles in 96.6% of specimens, achieving a limit of detection (LoD) of\u2009~\u200910 gc, with 100% positive agreement for all evaluated drugs and 100% negative agreement except for isoniazid\/ethionamide (\u2265\u200997%). dWGS yielded data suitable for DR analysis in 75% of samples, with a LoD of\u2009~\u2009100gc. No false negatives were observed for most drugs; one fluoroquinolone-resistant case was missed due to low-frequency variant thresholds, and resistance to delamanid and clofazimine was misclassified in one case each owing to interpretation rules. Negative agreement was 100% except for rifampicin (\u2265\u200997%). Lineage assignment was concordant with cWGS for both approaches, and dWGS supported transmission analysis in 65% of samples with adequate genome coverage, confirming the cluster detected by cWGS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this predominantly drug-susceptible TB cohort, tNGS showed high overall agreement with cWGS for DR profiling with a LoD within the range of low-complexity automated assays used for initial diagnosis. dWGS, while requiring higher DNA input, enables robust culture-free genome-wide analysis, including transmission inference and exploration of candidate DR loci. Bacillary load\u2013guided integration of both approaches may optimize DR-TB clinical management and genomic surveillance. Larger studies are needed to validate clinical and epidemiological predictive performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>This trial was registered on April 19, 2018, on the ClinicalTrials.gov database under the title: Study to Evaluate H56:IC31 in Preventing Rate of TB Recurrence, with the identifier NCT03512249.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13073-026-01726-7","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T03:52:08Z","timestamp":1784605928000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Towards culture-free sequencing of Mycobacterium tuberculosis: evaluating new targeted and whole-genome approaches for genotyping and drug resistance profiling"],"prefix":"10.1186","volume":"18","author":[{"given":"Ilaria","family":"Iannucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Di Marco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiarash","family":"Moghaddasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Miotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"POR TB study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro H.","family":"Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Churchyard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas H.","family":"Diacon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Haterill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasmus","family":"Mortensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Nemes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issa","family":"Sabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Scriba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Skallerup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elana","family":"Van Brakel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Maurizio","family":"Cabibbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Maria","family":"Cirillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"1726_CR1","unstructured":"World Health Organization. Global tuberculosis report 2025. Available from: https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports\/global-tuberculosis-report-2025. Accessed 14 Jan 2026. Geneva; 2025."},{"key":"1726_CR2","unstructured":"World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment and care. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240107243. Accessed 14 Jan 2026. Geneva; 2025."},{"key":"1726_CR3","unstructured":"World Health Organization. Key updates to the treatment of drug-resistant tuberculosis: rapid communication, June 2024. Available from: https:\/\/www.who.int\/publications\/i\/item\/B09123. Accessed 14 Jan 2026. Geneva; 2024."},{"key":"1726_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2025.101516","volume":"60","author":"F Saluzzo","year":"2026","unstructured":"Saluzzo F, Cabibbe AM, Anthony R, Aubry A, Drobniewski F, Holicka Y, et al. Diagnostic algorithms for tuberculosis in Europe: insights from the European Reference Laboratory Network for Tuberculosis (ERLTB-Net). Lancet Reg Health Eur. 2026;60:101516.","journal-title":"Lancet Reg Health Eur"},{"issue":"9","key":"1726_CR5","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(9):533\u201345.","journal-title":"Nat Rev Microbiol"},{"key":"1726_CR6","unstructured":"World Health Organization. WHO consolidated guidelines on tuberculosis. Module 3: diagnosis. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240107984. Accessed 14 Jan 2026. Geneva; 2025."},{"key":"1726_CR7","unstructured":"World Health Organization. WHO operational handbook on tuberculosis. Module 3: diagnosis. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240110991. Accessed 15 Jan 2026. Geneva; 2025."},{"issue":"10","key":"1726_CR8","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/S2213-2600(13)70231-5","volume":"1","author":"JM Bryant","year":"2013","unstructured":"Bryant JM, Harris SR, Parkhill J, Dawson R, Diacon AH, van Helden P, et al. Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study. Lancet Respir Med. 2013;1(10):786\u201392.","journal-title":"Lancet Respir Med"},{"key":"1726_CR9","unstructured":"World Health Organization. The use of next-generation sequencing for the surveillance of drug-resistant tuberculosis: an implementation manual. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240078079. Accessed 14 Jan 2026. Geneva; 2023."},{"issue":"2","key":"1726_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2024.116249","volume":"109","author":"W Cloutier Charette","year":"2024","unstructured":"Cloutier Charette W, Rabodoarivelo MS, Point F, Knoblauch AM, Andrianomanana FR, Hall MB, et al. Concordance of targeted and whole genome sequencing for Mycobacterium tuberculosis genotypic drug susceptibility testing. Diagn Microbiol Infect Dis. 2024;109(2):116249.","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"1","key":"1726_CR11","doi-asserted-by":"publisher","first-page":"2001796","DOI":"10.1183\/13993003.01796-2020","volume":"57","author":"S Feuerriegel","year":"2021","unstructured":"Feuerriegel S, Kohl TA, Utpatel C, Andres S, Maurer FP, Heyckendorf J, et al. Rapid genomic first- and second-line drug resistance prediction from clinical Mycobacterium tuberculosis specimens using Deeplex-MycTB. Eur Respir J. 2021;57(1):2001796.","journal-title":"Eur Respir J"},{"issue":"3","key":"1726_CR12","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02338-2020","volume":"57","author":"A Jouet","year":"2021","unstructured":"Jouet A, Gaudin C, Badalato N, Allix-B\u00e9guec C, Duthoy S, Ferr\u00e9 A, et al. Deep amplicon sequencing for culture-free prediction of susceptibility or resistance to 13 anti-tuberculous drugs. Eur Respir J. 2021;57(3):2002338.","journal-title":"Eur Respir J"},{"key":"1726_CR13","volume-title":"Deeplex\u00ae Myc-TB user manual: from clinical sample to drug resistance profile","author":"Genoscreen","year":"2023","unstructured":"Genoscreen. Deeplex\u00ae Myc-TB user manual: from clinical sample to drug resistance profile. 5th ed. Lille: Genoscreen; 2023.","edition":"5th ed"},{"key":"1726_CR14","unstructured":"World Health Organization. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance, 2nd ed. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240082410. Accessed 14 Jan 2026. Geneva; 2023."},{"issue":"10","key":"1726_CR15","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.00382-23","volume":"61","author":"BC Mann","year":"2023","unstructured":"Mann BC, Jacobson KR, Ghebrekristos Y, Warren RM, Farhat MR. Assessment and validation of enrichment and target capture approaches to improve Mycobacterium tuberculosis WGS from direct patient samples. J Clin Microbiol. 2023;61(10):e0038223.","journal-title":"J Clin Microbiol"},{"issue":"6","key":"1726_CR16","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00744-21","volume":"6","author":"N Lozano","year":"2021","unstructured":"Lozano N, Lanza VF, Su\u00e1rez-Gonz\u00e1lez J, Herranz M, Sola-Campoy PJ, Rodr\u00edguez-Grande C, et al. Detection of minority variants and mixed infections in Mycobacterium tuberculosis by direct whole-genome sequencing on noncultured specimens using a specific-DNA capture strategy. mSphere. 2021;6(6):e00744-21.","journal-title":"mSphere"},{"issue":"5","key":"1726_CR17","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1128\/JCM.02483-16","volume":"55","author":"AA Votintseva","year":"2017","unstructured":"Votintseva AA, Bradley P, Pankhurst L, Del Ojo Elias C, Loose M, Nilgiriwala K, et al. Same-day diagnostic and surveillance data for tuberculosis via whole-genome sequencing of direct respiratory samples. J Clin Microbiol. 2017;55(5):1285\u201398.","journal-title":"J Clin Microbiol"},{"key":"1726_CR18","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.585","volume":"2","author":"EL Doughty","year":"2014","unstructured":"Doughty EL, Sergeant MJ, Adetifa I, Antonio M, Pallen MJ. Culture-independent detection and characterisation of Mycobacterium tuberculosis and M. africanum in sputum samples using shotgun metagenomics on a benchtop sequencer. PeerJ. 2014;2:e585.","journal-title":"PeerJ"},{"issue":"7","key":"1726_CR19","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1128\/JCM.00486-15","volume":"53","author":"AC Brown","year":"2015","unstructured":"Brown AC, Bryant JM, Einer-Jensen K, Holdstock J, Houniet DT, Chan JZ, et al. Rapid whole-genome sequencing of Mycobacterium tuberculosis isolates directly from clinical samples. J Clin Microbiol. 2015;53(7):2230\u20137.","journal-title":"J Clin Microbiol"},{"issue":"4","key":"1726_CR20","doi-asserted-by":"publisher","first-page":"e175","DOI":"10.1016\/S2666-5247(20)30060-4","volume":"1","author":"GA Goig","year":"2020","unstructured":"Goig GA, Cancino-Mu\u00f1oz I, Torres-Puente M, Villamayor LM, Navarro D, Borr\u00e1s R, et al. Whole-genome sequencing of Mycobacterium tuberculosis directly from clinical samples for high-resolution genomic epidemiology and drug resistance surveillance: an observational study. Lancet Microbe. 2020;1(4):e175.","journal-title":"Lancet Microbe"},{"issue":"7","key":"1726_CR21","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae320","volume":"11","author":"S Vasanthaiah","year":"2024","unstructured":"Vasanthaiah S, Verma R, Kumar A, Bandari AK, George J, Rastogi M, et al. Culture-free whole genome sequencing of Mycobacterium tuberculosis using ligand-mediated bead enrichment method. Open Forum Infect Dis. 2024;11(7):ofae320.","journal-title":"Open Forum Infect Dis"},{"key":"1726_CR22","unstructured":"QIAGEN. QIAseq\u00ae xHYB Mycobacterium tuberculosis Panel Library Kit Handbook. Available from:\u00a0https:\/\/www.qiagen.com\/us\/products\/next-generation-sequencing\/metagenomics\/targeted-metagenomics\/qiaseq-xhyb-mycobacterium-tuberculosis-panel. Accessed 14 Jan 2026.: QIAGEN; 2024."},{"issue":"7","key":"1726_CR23","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/S1473-3099(24)00814-4","volume":"25","author":"\u00c1 Borges","year":"2025","unstructured":"Borges \u00c1, Russell M, Tait D, Scriba TJ, Nemes E, Skallerup P, et al. Immunogenicity, safety, and efficacy of the vaccine H56:IC31 in reducing the rate of tuberculosis disease recurrence in HIV-negative adults successfully treated for drug-susceptible pulmonary tuberculosis: a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Infect Dis. 2025;25(7):751\u201363.","journal-title":"Lancet Infect Dis"},{"key":"1726_CR24","unstructured":"National Center for Biotechnology Information. Culture-based Whole-genome sequencing data previously published. Sequence Read Archive. Accession Number: PRJNA1171160.\u00a0Available from:\u00a0https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA1171160\/. Accessed 15 Jan 2026. 2024."},{"key":"1726_CR25","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.5895","volume":"6","author":"TA Kohl","year":"2018","unstructured":"Kohl TA, Utpatel C, Schleusener V, De Filippo MR, Beckert P, Cirillo DM, et al. MTBseq: a comprehensive pipeline for whole genome sequence analysis of Mycobacterium tuberculosis complex isolates. PeerJ. 2018;6:e5895.","journal-title":"PeerJ"},{"key":"1726_CR26","unstructured":"Molzym. Ultra-Deep Microbiome Prep kit Handbook (Removal of Host DNA, Enrichment and Extraction of Microbial DNA for Next-Generation Sequencing). Available from:\u00a0https:\/\/www.molzym.com\/images\/downloads\/Manuals\/Ultra-Deep-Microbiome_Prep_G-020_V07.pdf. Accessed 14 Jan 2026. 2013."},{"issue":"10","key":"1726_CR27","doi-asserted-by":"publisher","first-page":"4565","DOI":"10.1128\/JCM.41.10.4565-4572.2003","volume":"41","author":"F Broccolo","year":"2003","unstructured":"Broccolo F, Scarpellini P, Locatelli G, Zingale A, Brambilla AM, Cichero P, et al. Rapid diagnosis of mycobacterial infections and quantitation of Mycobacterium tuberculosis load by two real-time calibrated PCR assays. J Clin Microbiol. 2003;41(10):4565\u201372.","journal-title":"J Clin Microbiol"},{"key":"1726_CR28","unstructured":"National Center for Biotechnology Information. Culture-free Whole-genome and targeted NGS sequencing data from this study. Sequence Read Archive. Accession number: PRJNA1392017. Available from:\u00a0https:\/\/dataview.ncbi.nlm.nih.gov\/object\/PRJNA1392017?reviewer=rp9i2vb2arvpc9o2hlb83olf8j. Accessed 14 Jan 2026. 2026."},{"key":"1726_CR29","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing, Version 4.5.2. Available from: https:\/\/www.r-project.org\/. Accessed 14 Jan 2026.: R Foundation for Statistical Computing; 2021."},{"key":"1726_CR30","doi-asserted-by":"crossref","unstructured":"Kohl T, Diel R, Harmsen D, Rothg\u00e4nger J, Meywald Walter K, Merker M, et al. Whole-Genome-Based Mycobacterium tuberculosis Surveillance: a Standardized, Portable, and Expandable Approach. J Clin Microbiol. 2014;52(7):2479\u201386.","DOI":"10.1128\/JCM.00567-14"},{"issue":"6","key":"1726_CR31","doi-asserted-by":"publisher","DOI":"10.1093\/gpbjnl\/qzae046","volume":"22","author":"J Qu","year":"2025","unstructured":"Qu J, Liu W, Chen S, Wu C, Lai W, Qin R, et al. Deep amplicon sequencing reveals culture-dependent clonal selection of Mycobacterium tuberculosis in clinical samples. Genomics Proteomics Bioinformatics. 2025;22(6):qzae046.","journal-title":"Genomics Proteomics Bioinformatics"},{"issue":"1","key":"1726_CR32","doi-asserted-by":"publisher","first-page":"7114","DOI":"10.1038\/s41467-024-51266-0","volume":"15","author":"C Mariner-Llicer","year":"2024","unstructured":"Mariner-Llicer C, Goig GA, Torres-Puente M, Vashakidze S, Villamayor LM, Saavedra-Cervera B, et al. Genetic diversity within diagnostic sputum samples is mirrored in the culture of Mycobacterium tuberculosis across different settings. Nat Commun. 2024;15(1):7114.","journal-title":"Nat Commun"},{"issue":"7","key":"1726_CR33","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1136\/thorax-2024-221409","volume":"79","author":"M Park","year":"2024","unstructured":"Park M, Satta G, Haldar P. Heteroresistance in tuberculosis: are we missing drug-resistant bacteria hiding in plain sight? Thorax. 2024;79(7):599\u2013600.","journal-title":"Thorax"},{"issue":"12","key":"1726_CR34","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1056\/NEJMc1413930","volume":"372","author":"E Sanchez-Padilla","year":"2015","unstructured":"Sanchez-Padilla E, Merker M, Beckert P, Jochims F, Dlamini T, Kahn P, et al. Detection of drug-resistant tuberculosis by Xpert MTB\/RIF in Swaziland. N Engl J Med. 2015;372(12):1181\u20132.","journal-title":"N Engl J Med"}],"container-title":["Genome Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13073-026-01726-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01726-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01726-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:20:14Z","timestamp":1792066814000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13073-026-01726-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1726"],"URL":"https:\/\/doi.org\/10.1186\/s13073-026-01726-7","relation":{},"ISSN":["1756-994X"],"issn-type":[{"value":"1756-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"assertion":[{"value":"15 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The trial was done in accordance with the Declaration of Helsinki, the International Council for Harmonisation Guideline for Good Clinical Practice (version E6, revision 2), and national Good Clinical Practice guidelines, and is registered with ClinicalTrials.gov, NCT03512249 (23). The study protocol was approved by the South Africa Health Products Regulatory Authority (Pretoria, South Africa; approval number 20180624), by the Tanzania Medicines and Medical Devices Authority (Dar es Salaam, Tanzania; approval number TFDA0019\/CTR\/00147\/18), and by all relevant institutional ethics committees in South Africa and Tanzania (23).All participants consented to participate in the trial and to the sample storage for biobank and TB research (23).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"152"}}