{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:25:37Z","timestamp":1783441537459,"version":"3.54.6"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032626","name":"Unitaid","doi-asserted-by":"publisher","award":["2019-32-FIND"],"award-info":[{"award-number":["2019-32-FIND"]}],"id":[{"id":"10.13039\/100032626","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>South Africa faces emerging resistance to tuberculosis drugs like bedaquiline. Phenotypic drug-susceptibility testing (DST), the current reference standard for bedaquiline DST, has long turnaround times. Targeted next-generation sequencing (tNGS) offers a comprehensive alternative, potentially delivering faster results. However, these advantages must be weighed against differences in cost and test accuracy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a decision tree model to evaluate the cost-effectiveness of tNGS against the standard of care (SOC) in South Africa across different levels of tNGS decentralization. Key outcomes included survival rates, time to a correct resistance profile, infectious time, and disability-adjusted life years (DALYs). Sensitivity analyses assessed the impact of drug-resistance prevalence, tNGS sensitivity, and improved DST access on overall cost-effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>tNGS averted 408 DALYs and correctly identified 90.7% of resistance profiles as compared to 87.7% with SOC. Based on model assumptions for South Africa, tNGS had a reduced turnaround time and averted 97 years of infectious time. Centralized tNGS was cost-saving relative to SOC; however, decentralization of tNGS resulted in higher costs per DALY averted ($671\u2013$2454). tNGS performance, relative to the SOC, improved at higher bedaquiline resistance and with increased sensitivity. Any increase in DST access through tNGS would improve cost-effectiveness in decentralized scenarios.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>tNGS could be cost-saving (centralized) or cost-effective (decentralized) in South Africa and has the potential to improve patient outcomes by returning a greater number of correct results in a shorter time. This analysis should be replicated across other settings to evaluate the broader feasibility of tNGS for DST.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf495","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T11:58:35Z","timestamp":1757073515000},"page":"e119-e125","source":"Crossref","is-referenced-by-count":4,"title":["Cost-effectiveness of Targeted Next-Generation Sequencing for Tuberculosis Drug-resistance Testing as an Alternative to the Standard of Care in South Africa"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3947-6900","authenticated-orcid":false,"given":"Alexandra","family":"de Nooy","sequence":"first","affiliation":[{"name":"Department of Global Health, Amsterdam University Medical Center , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaheed Vally","family":"Omar","sequence":"additional","affiliation":[{"name":"Centre for Tuberculosis, National & WHO Supranational TB Reference Laboratory, National Institute for Communicable Diseases, a division of the National Health Laboratory Service , Johannesburg ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Ockhuisen","sequence":"additional","affiliation":[{"name":"Department of Global Health, Amsterdam University Medical Center , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-8525","authenticated-orcid":false,"given":"Alice","family":"Zwerling","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa , Ottawa, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7429-0715","authenticated-orcid":false,"given":"Suvesh","family":"Shrestha","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa , Ottawa, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2645-058X","authenticated-orcid":false,"given":"Anita","family":"Suresh","sequence":"additional","affiliation":[{"name":"Sequencing Unit, FIND , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7247-4190","authenticated-orcid":false,"given":"Shaukat","family":"Khan","sequence":"additional","affiliation":[{"name":"Impact Unit, FIND , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7696-3776","authenticated-orcid":false,"given":"Nazir","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Infectious Diseases, University of the Witwatersrand , Johannesburg ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyra","family":"Grantz","sequence":"additional","affiliation":[{"name":"Impact Unit, FIND , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Girdwood","sequence":"additional","affiliation":[{"name":"Impact Unit, FIND , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4682-4999","authenticated-orcid":false,"given":"Brooke E","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Global 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