{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T01:23:19Z","timestamp":1794360199880,"version":"4.9.0"},"reference-count":26,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Stop TB Partnership and USAID for the New Diagnostics Working Group","award":["STBP\/USAID\/GSA\/2024-06"],"award-info":[{"award-number":["STBP\/USAID\/GSA\/2024-06"]}]},{"DOI":"10.13039\/100032626","name":"Unitaid","doi-asserted-by":"crossref","award":["2019-32-FIND MDR"],"award-info":[{"award-number":["2019-32-FIND MDR"]}],"id":[{"id":"10.13039\/100032626","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Glob Health"],"accepted":{"date-parts":[[2025,10,8]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early and accurate diagnosis of drug-resistant tuberculosis (DR-TB) is essential for improving treatment outcomes. Phenotypic drug susceptibility testing (pDST) is comprehensive but slow, while rapid molecular assays provide resistance information for a limited number of drugs. Targeted next-generation sequencing (tNGS) offers the potential for broad and rapid resistance detection, but its integration into diagnostic algorithms has been hindered by uncertainty about its placement within existing workflows.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study evaluated the extent to which two tNGS solutions\u2014Deeplex Myc-TB (GenoScreen) and TB Drug Resistance Test (Oxford Nanopore Technologies, ONT)\u2014provided interpretable drug resistance results that could inform regimen design, in comparison to other WHO-recommended molecular assays and pDST. Data were collected from three high-burden DR-TB settings under the Seq&amp;Treat study. Sequencing success rates and drug resistance detection were analysed based on: (1) the initial Xpert MTB\/RIF result (very low, low, medium, high), (2) resistance results for drugs in WHO-recommended regimens and (3) performance relative to other WHO-endorsed assays. The potential impact of different algorithms on the estimates was also considered. Key factors influencing successful tNGS adoption within diagnostic pathways were identified, leveraging insights from the Seq&amp;Treat diagnostic accuracy study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sequencing success rates were 88.5% (GenoScreen) and 93.1% (ONT) across 763 samples. While tNGS provided complete resistance data for 73%\u201386% of drugs in recommended regimens, pDST achieved 92%\u201393%. Both tNGS solutions matched or exceeded the sensitivity of WHO-recommended molecular assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study highlights the critical role of tNGS as a centralised tool for comprehensive drug resistance testing to inform DR-TB treatment decisions following initial screening assays. By complementing existing molecular tests with tNGS, diagnostic workflows can be optimised to ensure timely and comprehensive resistance detection. These findings support policy updates to integrate tNGS into global TB diagnostic algorithms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04239326\">NCT04239326<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjgh-2025-019135","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:40:25Z","timestamp":1762324825000},"page":"e019135","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Targeted next-generation sequencing for drug-resistant tuberculosis diagnosis: implementation considerations for bacterial load, regimen selection and diagnostic algorithm placement"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct04239326","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04239326","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04239326","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0099-903X","authenticated-orcid":false,"given":"Sophia B","family":"Georghiou","sequence":"first","affiliation":[{"name":"FIND, Geneva, Switzerland"},{"name":"End TB Dx Consulting LLC, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nestani","family":"Tukvadze","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia"},{"name":"Swiss Tropical and Public Health Institute, Allschwil, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"PD Hinduja National Hospital and Medical Research Centre, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaheed Vally","family":"Omar","sequence":"additional","affiliation":[{"name":"National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9727-6465","authenticated-orcid":false,"given":"Andrea Maurizio","family":"Cabibbe","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marva","family":"Seifert","sequence":"additional","affiliation":[{"name":"FIND, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swapna","family":"Uplekar","sequence":"additional","affiliation":[{"name":"FIND, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7696-3776","authenticated-orcid":false,"given":"Nazir","family":"Ismail","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Ruhwald","sequence":"additional","affiliation":[{"name":"FIND, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Suresh","sequence":"additional","affiliation":[{"name":"FIND, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E","family":"Colman","sequence":"additional","affiliation":[{"name":"FIND, Geneva, Switzerland"},{"name":"University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"2025120102300971000_10.11.e019135.1","unstructured":"World Health Organization . Global tuberculosis report 2024. Geneva, 2024. Available: https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports\/global-tuberculosis-report-2024"},{"key":"2025120102300971000_10.11.e019135.2","unstructured":"World Health Organization . The end tb strategy. Geneva, 2015. 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Rapid communication: key changes to the treatment of drug-resistant tuberculosis. Geneva, 2022. Available: https:\/\/www.who.int\/publications\/i\/item\/WHO-UCN-TB-2022-2"},{"key":"2025120102300971000_10.11.e019135.8","unstructured":"World Health Organization . Use of targeted next-generation sequencing to detect drug-resistant tuberculosis: rapid communication, july 2023. Geneva, 2023. Available: https:\/\/apps.who.int\/iris\/rest\/bitstreams\/1521320\/retrieve"},{"key":"2025120102300971000_10.11.e019135.9","unstructured":"World Health Organization . World health organization operational handbook on tuberculosis. In: Module 3: Diagnosis. Rapid Diagnostics for Tuberculosis Detection. 3rd edn. Geneva: Web Annex A. Information Sheets, 2024. 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Technical report on critical concentrations for drug susceptibility testing of isoniazid and the rifamycins (rifampicin, rifabutin and rifapentine). Geneva, 2021. Available: https:\/\/apps.who.int\/iris\/rest\/bitstreams\/1330649\/retrieve"},{"key":"2025120102300971000_10.11.e019135.13","unstructured":"World Health Organization . Technical report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis. Geneva; 2018. Available: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/260470\/WHO-CDS-TB-2018.5-eng.pdf?sequence=1&isAllowed=y"},{"key":"2025120102300971000_10.11.e019135.14","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts378"},{"key":"2025120102300971000_10.11.e019135.15","unstructured":"World Health Organization . Catalogue of mutations in mycobacterium tuberculosis complex and their association with drug resistance. Geneva, 2021. 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