{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:15:49Z","timestamp":1781075749397,"version":"3.54.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Study on Influencing Factors and Countermeasures of Quality Management of Vaccine Clinical Trials","award":["Z20201489"],"award-info":[{"award-number":["Z20201489"]}]},{"name":"Anhui Zhifei Longcom Biopharmaceutical Co, Ltd, China"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>This study aimed to evaluate the safety and diagnostic performance of recombinant fusion protein early secretory antigenic target protein 6\u2013culture filtrate protein 10 (EC) in a community-based population aged \u22656 months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a 2-stage trial in a community-based population. The first stage used a randomized, double-blind, controlled design (n = 500), while the second stage used a nonrandomized, open design (n = 7000). Stage 1 participants underwent tuberculosis-specific enzyme-linked immunospot assay (T-SPOT.TB), tuberculin skin test (TST), and EC skin test (ECST). Stage 2 participants only received the ECST. The purposes of the first and second stage were to evaluate the diagnostic performance and safety of the ECST, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At the first stage, the sensitivity of ECST and TST was 89.41% (95% confidence interval [CI], 80.85%\u201395.04%) and 85.88% (95% CI, 76.64%\u201392.49%), respectively. The specificity of the ECST and TST was 96.98% (95% CI, 94.79%\u201398.43%%) and 61.06% (95% CI, 56.07%\u201365.87%), respectively. The consistency between ECST and T-SPOT.TB was higher than that between TST and T-SPOT.TB (\u03ba = 0.85 and 0.28, respectively). At the second stage, the incidence of adverse drug reactions (ADRs) was 11.75%, with 0.67% graded \u22653. The incidence of ADRs varied among age groups (&amp;lt;18 years, 2.89%; 18\u201364 years, 11.51%; \u226565 years, 16.98%) and was significantly higher in individuals with pulmonary tuberculosis (46.58%), human immunodeficiency virus infection (33.33%), diabetes mellitus (15.56%), close contacts of patients with tuberculosis (14.35%), and those with allergic histories (11.93%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ECST has a satisfactory safety and diagnostic performance profile and is suitable for screening Mycobacterium tuberculosis infection in the community-based population aged \u22656 months.<\/jats:p>\n                  <jats:p>Clinical Trials Registration. NCT05746611.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf332","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T12:57:08Z","timestamp":1750856228000},"page":"882-891","source":"Crossref","is-referenced-by-count":4,"title":["Safety and Diagnostic Performance of Recombinant Fusion Protein ESAT6-CPF10 Skin Test in A Large Population: A Phase 4 Clinical Trial"],"prefix":"10.1093","volume":"232","author":[{"given":"Junji","family":"Chen","sequence":"first","affiliation":[{"name":"Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention Institute of Vaccine Clinical Research, , Nanning, Guangxi Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Anhui Zhifei Longcom Biopharmaceutical Co, Ltd , Hefei, Anhui Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Anhui Zhifei Longcom Biopharmaceutical Co, Ltd , Hefei, Anhui Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Mo","sequence":"additional","affiliation":[{"name":"Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention Institute of Vaccine Clinical Research, , Nanning, Guangxi Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanting","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Anhui Zhifei Longcom Biopharmaceutical Co, Ltd , Hefei, Anhui Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangli","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Anhui Zhifei Longcom Biopharmaceutical Co, Ltd , Hefei, Anhui Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangyong","family":"Wu","sequence":"additional","affiliation":[{"name":"Liuzhou Center for Disease Control and Prevention Institute of Vaccine Clinical Research, , Liuzhou, Guangxi Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingjin","family":"Huang","sequence":"additional","affiliation":[{"name":"Liujiang District Center for Disease Control and Prevention Institute of Vaccine Clinical Research, , Liuzhou, Guangxi Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Anhui Zhifei Longcom Biopharmaceutical Co, Ltd , Hefei, Anhui Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Anhui Zhifei Longcom Biopharmaceutical Co, Ltd , Hefei, Anhui Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"2025101515154003600_jiaf332-B1","volume-title":"Global tuberculosis report 2023","author":"World Health Organization (WHO).","year":"2023"},{"key":"2025101515154003600_jiaf332-B2","doi-asserted-by":"crossref","first-page":"e1002152","DOI":"10.1371\/journal.pmed.1002152","article-title":"The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling","volume":"13","author":"Houben","year":"2016","journal-title":"PLoS Med"},{"key":"2025101515154003600_jiaf332-B3","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/S0140-6736(17)32130-X","article-title":"Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"390","author":"GBD 2016 DALYs and HALE Collaborators","year":"2017","journal-title":"Lancet"},{"key":"2025101515154003600_jiaf332-B4","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1016\/S0140-6736(15)60570-0","article-title":"WHO's new end TB strategy","volume":"385","author":"Uplekar","year":"2015","journal-title":"Lancet"},{"key":"2025101515154003600_jiaf332-B5","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1093\/cid\/ciaa519","article-title":"Predictors of discordant tuberculin skin test and QuantiFERON-TB Gold In-Tube results in eastern China: a population-based, cohort study","volume":"72","author":"Lu","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2025101515154003600_jiaf332-B6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.7326\/0003-4819-149-3-200808050-00241","article-title":"Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update","volume":"149","author":"Pai","year":"2008","journal-title":"Ann Intern Med"},{"key":"2025101515154003600_jiaf332-B7","doi-asserted-by":"crossref","first-page":"2\u2013","DOI":"10.1186\/s12995-015-0044-y","article-title":"Tuberculin skin test and Quantiferon test agreement and influencing factors in tuberculosis screening of healthcare workers: a systematic review and meta-analysis","volume":"10","author":"Lamberti","year":"2015","journal-title":"J Occup Med Toxicol"},{"key":"2025101515154003600_jiaf332-B8","doi-asserted-by":"crossref","first-page":"1498448","DOI":"10.3389\/fimmu.2025.1498448","article-title":"Screening and preclinical assessment of novel Mycobacterium tuberculosis recombinant antigens based tuberculin skin testing","volume":"16","author":"Ou","year":"2025","journal-title":"Front Immunol"},{"key":"2025101515154003600_jiaf332-B9","doi-asserted-by":"crossref","first-page":"e158","DOI":"10.1002\/hsr2.158","article-title":"How are high burden countries implementing policies and tools for latent tuberculosis infection? A survey of current practices and barriers","volume":"3","author":"Faust","year":"2020","journal-title":"Health Sci Rep"},{"key":"2025101515154003600_jiaf332-B10","first-page":"814","article-title":"Establishment of quality standards for recombinant Mycobacterium tuberculosis fusion protein","volume":"42","author":"Zhang","year":"2020","journal-title":"CJATB"},{"key":"2025101515154003600_jiaf332-B11","doi-asserted-by":"crossref","first-page":"e11277","DOI":"10.1371\/journal.pone.0011277","article-title":"First-in-man open clinical trial of a combined rdESAT-6 and rCFP-10 tuberculosis specific skin test reagent","volume":"5","author":"Bergstedt","year":"2010","journal-title":"PLoS One"},{"key":"2025101515154003600_jiaf332-B12","first-page":"2600","article-title":"Diaskintest\u2014screening method in mass examination of the child population for tuberculosis in Russia","volume":"44","author":"Aksenova","year":"2014","journal-title":"Eur Respir J"},{"key":"2025101515154003600_jiaf332-B13","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12879-023-08008-2","article-title":"Comparing the diagnostic performance of QuantiFERON-TB Gold Plus with QFT-GIT, T-SPOT.TB and TST: a systematic review and meta-analysis","volume":"23","author":"Zhang","year":"2023","journal-title":"BMC Infect Dis"},{"key":"2025101515154003600_jiaf332-B14","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1164\/rccm.200607-907ED","article-title":"Weighing gold or counting spots: which is more sensitive to diagnose latent tuberculosis infection?","volume":"174","author":"Barnes","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2025101515154003600_jiaf332-B15","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S1473-3099(21)00261-9","article-title":"The diagnostic performance of novel skin-based in-vivo tests for tuberculosis infection compared with purified protein derivative tuberculin skin tests and blood-based in vitro interferon-\u03b3 release assays: a systematic review and meta-analysis","volume":"22","author":"Krutikov","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"2025101515154003600_jiaf332-B16","volume-title":"WHO consolidated guidelines on tuberculosis. Module 3: diagnosis\u2014tests for tuberculosis infection","author":"World Health Organization (WHO).","year":"2022"},{"key":"2025101515154003600_jiaf332-B17","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1093\/cid\/ciab472","article-title":"Sensitivity, specificity, and safety of a novel ESAT6-CFP10 skin test for tuberculosis infection in China: 2 randomized, self-controlled, parallel-group phase 2b trials","volume":"74","author":"Xu","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2025101515154003600_jiaf332-B18","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.mimet.2012.06.001","article-title":"Use of ESAT-6-CFP-10 fusion protein in the bovine interferon-gamma ELISPOT assay for diagnosis of Mycobacterium bovis infection in cattle","volume":"90","author":"Parthasarathy","year":"2012","journal-title":"J Microbiol Methods"},{"key":"2025101515154003600_jiaf332-B19","doi-asserted-by":"crossref","first-page":"e0181622","DOI":"10.1128\/jcm.01816-22","article-title":"Evaluation of ESAT6-CFP10 skin test for Mycobacterium tuberculosis infection among persons living with HIV in China","volume":"61","author":"Lu","year":"2023","journal-title":"J Clin Microbiol"},{"key":"2025101515154003600_jiaf332-B20","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ijid.2022.11.014","article-title":"High accuracy of recombinant fusion protein early secretory antigenic target protein 6-culture filtrate protein 10 skin test for the detection of tuberculosis infection: a phase III, multi-centered, double-blind, hospital-based, randomized controlled trial","volume":"126","author":"Xia","year":"2023","journal-title":"Int J Infect Dis"},{"key":"2025101515154003600_jiaf332-B21","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s40291-015-0135-6","article-title":"Latent tuberculosis infection screening in immigrants to low-incidence countries: a meta-analysis","volume":"19","author":"Campbell","year":"2015","journal-title":"Mol Diagn Ther"},{"key":"2025101515154003600_jiaf332-B22","doi-asserted-by":"crossref","first-page":"e0003655","DOI":"10.1371\/journal.pgph.0003655","article-title":"Systematic review of the economic impact of novel Mycobacterium tuberculosis specific antigen-based skin tests for detection of TB infection compared with tuberculin skin test and interferon-gamma release assays","volume":"4","author":"Gosc\u00e9","year":"2024","journal-title":"PLoS Glob Public Health"},{"key":"2025101515154003600_jiaf332-B23","doi-asserted-by":"crossref","first-page":"e24507","DOI":"10.1016\/j.heliyon.2024.e24507","article-title":"Prospective cohort study on tuberculosis incidence and risk factors in the elderly population of eastern China","volume":"10","author":"Jiang","year":"2024","journal-title":"Heliyon"},{"key":"2025101515154003600_jiaf332-B24","volume-title":"Global tuberculosis report 2021","author":"World Health Organization (WHO).","year":"2021"},{"key":"2025101515154003600_jiaf332-B25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/oxfordjournals.aje.a121593","article-title":"The prognosis of a positive tuberculin reaction in childhood and adolescence","volume":"99","author":"Comstock","year":"1974","journal-title":"Am J Epidemiol"},{"key":"2025101515154003600_jiaf332-B26","doi-asserted-by":"crossref","first-page":"ofad228","DOI":"10.1093\/ofid\/ofad228","article-title":"A systematic review on the safety of Mycobacterium tuberculosis\u2013specific antigen-based skin tests for tuberculosis infection compared with tuberculin skin tests","volume":"10","author":"Hamada","year":"2023","journal-title":"Open Forum Infect Dis"},{"key":"2025101515154003600_jiaf332-B27","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1128\/CVI.00154-16","article-title":"Safety of recombinant fusion protein ESAT6-CFP10 as a skin test reagent for tuberculosis diagnosis: an open-label, randomized, single-center phase I clinical trial","volume":"23","author":"Li","year":"2016","journal-title":"Clin Vaccine Immunol"},{"key":"2025101515154003600_jiaf332-B28","doi-asserted-by":"crossref","first-page":"889.e9","DOI":"10.1016\/j.cmi.2016.07.015","article-title":"Recombinant fusion ESAT6-CFP10 immunogen as a skin test reagent for tuberculosis diagnosis: an open-label, randomized, two-centre phase 2a clinical trial","volume":"22","author":"Li","year":"2016","journal-title":"Clin Microbiol Infect"},{"key":"2025101515154003600_jiaf332-B29","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1001\/archinte.161.14.1760","article-title":"The effect of BCG vaccination on tuberculin reactivity and the booster effect among hospital employees","volume":"161","author":"Moreno","year":"2001","journal-title":"Arch Intern Med"},{"key":"2025101515154003600_jiaf332-B30","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1186\/s12879-024-10302-6","article-title":"Accuracy of ESAT6-CFP10 skin test compared with tuberculin skin test in a healthy population: a randomized, blind, parallel controlled phase III clinical study","volume":"24","author":"Ding","year":"2024","journal-title":"BMC Infect Dis"},{"key":"2025101515154003600_jiaf332-B31","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1093\/infdis\/jiz138","article-title":"The lung mucosa environment in the elderly increases host susceptibility to Mycobacterium tuberculosis infection","volume":"220","author":"Moliva","year":"2019","journal-title":"J Infect Dis"},{"key":"2025101515154003600_jiaf332-B32","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s11274-023-03636-x","article-title":"Clinical manifestations and immune response to tuberculosis","volume":"39","author":"Carabal\u00ed-Isajar","year":"2023","journal-title":"World J Microbiol Biotechnol"},{"key":"2025101515154003600_jiaf332-B33","doi-asserted-by":"crossref","first-page":"909S","DOI":"10.1378\/chest.126.4_MeetingAbstracts.909S-b","article-title":"The booster effect of a repeat Mantoux tuberculin skin test as a diagnostic criterion of tuberculosis in children","volume":"126","author":"Rivera","year":"2004","journal-title":"Chest"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf332\/63581094\/jiaf332.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/4\/882\/63581094\/jiaf332.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/4\/882\/63581094\/jiaf332.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T19:18:02Z","timestamp":1760555882000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/232\/4\/882\/8173866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,25]]},"references-count":33,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,6,25]]},"published-print":{"date-parts":[[2025,10,15]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf332","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10,15]]},"published":{"date-parts":[[2025,6,25]]}}}