{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:06:16Z","timestamp":1788307576187,"version":"build-2803163510"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Non-sputum-based tools are essential complements to the current tuberculosis diagnosis strategy. We aim to determine whether dual-gene qPCR melting curve detection of salivary exosomes\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      DNA can diagnose paucibacillary tuberculosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed the exosomal nucleic acid (ExoNA)-based saliva tuberculosis diagnostic, a rapid, non-sputum diagnostic method for tuberculosis by integrating enrichment of salivary exosomes, nucleic acid extraction, and dual-target qPCR melting curve analysis. In a pilot clinical study, adults with suspected pulmonary tuberculosis were enrolled to evaluate diagnostic performance against multiple reference standards. Subgroup analysis was performed in patients with negative smear microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Salivary exosomal DNA was identified as the predominant form of detectable\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      DNA in saliva. ExoNA-based salivary tuberculosis diagnostic reduced the turnaround time from 16\u00a0h to 3h, and reached a limit of detection of 10 CFU\/mL. In total, 130 patients with suspected pulmonary tuberculosis were included. Of them, 36\u00b79% (48\/130) were asymptomatic, and 80\u00b78% (105\/130) had negative smear microscopy results. The ExoNA-based Saliva TB assay had sensitivity of 81.2% (95% CI 53.7%-95.0%) and specificity of 82.8% (95% CI 63.5%-93.5%) against microbiological reference standards (n=45), while sensitivity of 68.4% (95% CI 54.6%-79.7%) and specificity of 82.9% (95% CI 67.4%-92.3%) under extended microbiological reference standards (n=98). In the subset of 105 patients with negative smear microscopy, the sensitivities remained within the range of 67.5% to 75.0% across different reference standards, and specificities ranged from 82.1% to 82.9%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ExoNA-based saliva tuberculosis assay demonstrates favorable diagnostic performance in patients with suspected pulmonary tuberculosis, with the advantages of non-invasive nature, easy sampling, and rapid detection. Multicenter validation in more heterogeneous populations is necessary prior to clinical use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1811140","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T04:19:26Z","timestamp":1780287566000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Salivary exosomal Mycobacterium tuberculosis DNA enables sensitive detection of paucibacillary tuberculosis: a molecular diagnosis study"],"prefix":"10.3389","volume":"16","author":[{"given":"Jun","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xubin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Clinic and Research Center of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]},{"name":"Division of Infectious Diseases, Department of Medicine, Karolinska Institute","place":["Stockholm, Sweden"]},{"name":"Department of Infectious Diseases, Karolinska University Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewen","family":"Tang","sequence":"additional","affiliation":[{"name":"Shanghai Liquidbio Bio-tech Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Diagnostics, Tulane University School of Medicine","place":["New Orleans, LA, United States"]},{"name":"Department of Medicine, Tulane University of Medicine","place":["New Orleans, LA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Tang","sequence":"additional","affiliation":[{"name":"Shanghai Liquidbio Bio-tech Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Liquidbio Bio-tech Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhi","family":"Lei","sequence":"additional","affiliation":[{"name":"Shanghai Liquidbio Bio-tech Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Liquidbio Bio-tech Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]},{"name":"Clinic and Research Center of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.00421-22","article-title":"Accuracy of tongue swab testing using Xpert MTB-RIF Ultra for tuberculosis diagnosis","author":"Andama","year":"2022"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2024.102554","article-title":"Detection of Mycobacterium tuberculosis complex in saliva by quantitative PCR: A potential alternative specimen for pulmonary tuberculosis diagnosis","volume":"148","author":"Ayalew","year":"2024","journal-title":"Tuberculosis (Edinburgh Scotland)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/jex2.100","article-title":"Optimization of extracellular vesicle isolation and their separation from lipoproteins by size exclusion chromatography","volume":"2","author":"Benayas","year":"2023","journal-title":"J. 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