{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:08:21Z","timestamp":1788761301517,"version":"build-2803163510"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Paucibacillary pulmonary tuberculosis (PTB) is diagnostically challenging because molecular assays are inherently insensitive at sub-threshold bacillary loads. The incremental value of T-SPOT.TB\u2014a host immune-response assay (an ELISPOT-based interferon-\u03b3 release assay, IGRA)\u2014combined with molecular testing in this setting is not well established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this single-center, STARD 2015-compliant prospective diagnostic-accuracy study at a regional general hospital (January 2021\u2013December 2023), adults with suspected smear-negative PTB underwent simultaneous GeneXpert MTB\/RIF, in-house IS6110 TB-DNA real-time PCR, and T-SPOT.TB. Each participant was classified as PTB or non-PTB by a blinded three-member panel using a reference standard with two PTB-confirmation routes\u2014microbiological (positive mycobacterial culture) or clinical (compatible clinicoradiological presentation plus documented response to standard anti-TB therapy at 6 months); participants meeting neither route were non-PTB. Performance was quantified by sensitivity, specificity, predictive values, likelihood ratios, and balanced accuracy ([sensitivity + specificity]\/2). Paired comparisons used the McNemar exact test with Bonferroni correction. No a priori sample-size calculation was performed; analyses are exploratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 78 participants [PTB\n                      <jats:italic>n<\/jats:italic>\n                      = 44 (microbiological\n                      <jats:italic>n<\/jats:italic>\n                      = 33, clinical\n                      <jats:italic>n<\/jats:italic>\n                      = 11); non-PTB\n                      <jats:italic>n<\/jats:italic>\n                      = 34], T-SPOT.TB had the highest individual sensitivity (79.5%; 95% CI 65.5\u201388.8%) and balanced accuracy (0.780; 0.681\u20130.872), versus GeneXpert (29.5%; 0.618) and TB-DNA PCR (31.8%; specificity 100%; 0.659). Under a parallel (any-positive) rule, TB-DNA PCR + T-SPOT.TB showed the highest balanced accuracy observed in this cohort (0.826; 0.734\u20130.907; sensitivity 88.6%, specificity 76.5%; the sensitivity gain over T-SPOT.TB alone did not reach statistical significance, exact McNemar p = 0.125). The triple combination did not improve discrimination (0.796). T-SPOT.TB was the sole positive assay in 21\/44 (47.7%) confirmed PTB cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this exploratory single-center cohort, T-SPOT.TB contributed unique diagnostic information (47.7% exclusive detection) not captured by molecular assays. TB-DNA PCR + T-SPOT.TB showed the highest observed balanced accuracy, but, given the single-center design and absence of a priori powering, this is hypothesis-generating and requires confirmation in adequately powered, multicenter studies before any clinical recommendation. Where available, Xpert MTB\/RIF Ultra is the preferred first-line molecular assay and should be prioritized, in combination with T-SPOT.TB, in future prospective evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1819718","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:34:33Z","timestamp":1788759273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Triple-modality diagnosis of paucibacillary pulmonary tuberculosis: comparative accuracy of GeneXpert MTB\/RIF, TB-DNA PCR, and T-SPOT.TB"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaohong","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Yichun University, Yichun","place":["Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Second Affiliated Hospital of Yichun University, Yichun","place":["Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Yichun University, Yichun","place":["Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Yichun Vocational Technical College, Yichun","place":["Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Yichun University, Yichun","place":["Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Ji","sequence":"additional","affiliation":[{"name":"Jiangxi Vocational College of Technology, Ganzhou","place":["Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Guo","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Yichun University, Yichun","place":["Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","unstructured":"Global Tuberculosis Report.\n          \n          2024"},{"key":"B2","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1186\/s12879-020-05515-4","article-title":"Risk factors for recurrent tuberculosis after successful treatment in a high burden setting: a cohort study.","volume":"20","author":"Cudahy","year":"2020","journal-title":"BMC Infect Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/S0140-6736(07)60316-X","article-title":"Progress in tuberculosis control and the evolving public-health system in China.","volume":"369","author":"Wang","year":"2007","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1056\/NEJMoa0907847","article-title":"Rapid molecular detection of tuberculosis and rifampin resistance.","volume":"363","author":"Boehme","year":"2010","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3068","DOI":"10.1128\/JCM.00718-11","article-title":"Cepheid GeneXpert MTB\/RIF assay for Mycobacterium tuberculosis detection and rifampin resistance identification in patients with substantial clinical indications of tuberculosis and smear-negative microscopy results.","volume":"49","author":"Ioannidis","year":"2011","journal-title":"J Clin Microbiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/S1473-3099(17)30691-6","article-title":"Xpert MTB\/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study.","volume":"18","author":"Dorman","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"CD009593","DOI":"10.1002\/14651858.CD009593.pub5","article-title":"Xpert Ultra versus Xpert MTB\/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive pulmonary tuberculosis.","volume":"2","author":"Zifodya","year":"2021","journal-title":"Cochrane Database Syst Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1128\/JCM.02157-10","article-title":"Comparison of the Xpert MTB\/RIF test with an IS6110-TaqMan real-time PCR assay for direct detection of Mycobacterium tuberculosis in respiratory and nonrespiratory specimens.","volume":"49","author":"Armand","year":"2011","journal-title":"J Clin Microbiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.jinf.2018.07.002","article-title":"Xpert MTB\/RIF Ultra assay for the diagnosis of pulmonary tuberculosis in children: a multicentre comparative accuracy study.","volume":"77","author":"Sabi","year":"2018","journal-title":"J Infect"},{"key":"B10","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1183\/09031936.00115110","article-title":"Interferon-\u03b3 release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis.","volume":"37","author":"Diel","year":"2011","journal-title":"Eur Respir J"},{"key":"B11","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.eimc.2009.05.012","article-title":"Interferon gamma release assays: principles and practice.","volume":"28","author":"Lalvani","year":"2010","journal-title":"Enferm Infecc Microbiol Clin"},{"key":"B12","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.jinf.2011.06.010","article-title":"Diagnostic performance of T-SPOT.TB for extrapulmonary tuberculosis according to the site of infection.","volume":"63","author":"Cho","year":"2011","journal-title":"J Infect"},{"key":"B13","doi-asserted-by":"publisher","first-page":"6568","DOI":"10.4081\/idr.2016.6568","article-title":"Tuberculosis Biomarkers: From Diagnosis to Protection.","volume":"8","author":"Goletti","year":"2016","journal-title":"Infect Dis Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1164\/rccm.200604-465OC","article-title":"Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot.","volume":"174","author":"Jafari","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"h5527","DOI":"10.1136\/bmj.h5527","article-title":"STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies.","volume":"351","author":"Bossuyt","year":"2015","journal-title":"BMJ"},{"key":"B16","doi-asserted-by":"publisher","first-page":"CD009593","DOI":"10.1002\/14651858.CD009593.pub3","article-title":"Xpert \u00ae MTB\/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults.","volume":"2014","author":"Steingart","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"B17","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1183\/09031936.00114810","article-title":"Interferon-\u03b3 release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis.","volume":"37","author":"Sester","year":"2011","journal-title":"Eur Respir J"},{"key":"B18","doi-asserted-by":"publisher","first-page":"S1120","DOI":"10.1093\/infdis\/jir410","article-title":"Interferon-\u03b3 release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis.","volume":"204","author":"Metcalfe","year":"2011","journal-title":"J Infect Dis"},{"key":"B19","doi-asserted-by":"publisher","first-page":"16076","DOI":"10.1038\/nrdp.2016.76","article-title":"Tuberculosis.","volume":"2","author":"Pai","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1056\/NEJMra1405427","article-title":"Latent Mycobacterium tuberculosis infection.","volume":"372","author":"Getahun","year":"2015","journal-title":"N Engl J Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"15284","DOI":"10.1038\/srep15284","article-title":"Body fluid interferon-\u03b3 release assay for diagnosis of extrapulmonary tuberculosis in adults: a systematic review and meta-analysis.","volume":"5","author":"Zhou","year":"2015","journal-title":"Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1128\/CMR.00034-13","article-title":"Gamma interferon release assays for detection of Mycobacterium tuberculosis infection.","volume":"27","author":"Pai","year":"2014","journal-title":"Clin Microbiol Rev"},{"key":"B23","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/S1473-3099(14)71085-0","article-title":"Latent tuberculosis infection in rural China: baseline results of a population-based, multicentre, prospective cohort study.","volume":"15","author":"Gao","year":"2015","journal-title":"Lancet Infect Dis"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1819718\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:34:34Z","timestamp":1788759274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1819718\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":23,"alternative-id":["10.3389\/fmed.2026.1819718"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1819718","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"article-number":"1819718"}}