{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:04:15Z","timestamp":1793124255469,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>IFN-\u03b3 release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Gu\u00e9rin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P &amp;lt; 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative\/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201302-0365oc","type":"journal-article","created":{"date-parts":[[2013,12,3]],"date-time":"2013-12-03T16:35:29Z","timestamp":1386088529000},"page":"77-87","source":"Crossref","is-referenced-by-count":188,"title":["Interferon-\u03b3 Release Assays and Tuberculin Skin Testing for Diagnosis of Latent Tuberculosis Infection in Healthcare Workers in the United States"],"prefix":"10.1093","volume":"189","author":[{"given":"Susan E.","family":"Dorman","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Belknap","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Denver, Colorado"},{"name":"Denver Public Health Department, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Graviss","sequence":"additional","affiliation":[{"name":"Methodist Hospital Research Institute, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Reves","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Denver, Colorado"},{"name":"Denver Public Health Department, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Schluger","sequence":"additional","affiliation":[{"name":"C. P. Felton National Tuberculosis Center, International Center for AIDS Care and Treatment Programs, Mailman School of Public Health, Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Weinfurter","sequence":"additional","affiliation":[{"name":"Westat, Inc., Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Wang","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Cronin","sequence":"additional","affiliation":[{"name":"Maryland Department of Health and Mental Hygiene, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Hirsch-Moverman","sequence":"additional","affiliation":[{"name":"C. P. Felton National Tuberculosis Center, International Center for AIDS Care and Treatment Programs, Mailman School of Public Health, Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry D.","family":"Teeter","sequence":"additional","affiliation":[{"name":"Methodist Hospital Research Institute, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Parker","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Denver, Colorado"},{"name":"Denver Public Health Department, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise O.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles L.","family":"Daley","sequence":"additional","affiliation":[{"name":"Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, Colorado; and"},{"name":"University of Colorado School of Medicine, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2026032100333155200_bib1","first-page":"S221","article-title":"Centers for Disease Control and Prevention; endorsed by Council of Infectious Diseases Society of America and American Academy of Pediatrics. Targeted tuberculin testing and treatment of latent tuberculosis infection","volume":"161","author":"American Thoracic Society","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib2","first-page":"1","article-title":"Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005","volume":"54","author":"Jensen","year":"2005","journal-title":"MMWR Recomm Rep"},{"key":"2026032100333155200_bib3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1164\/ajrccm.159.1.9801120","article-title":"Interpretation of repeated tuberculin tests: boosting, conversion, and reversion","volume":"159","author":"Menzies","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.7326\/0003-4819-149-3-200808050-00241","article-title":"Systematic review: T-cell\u2013based assays for the diagnosis of latent tuberculosis infection: an update","volume":"149","author":"Pai","year":"2008","journal-title":"Ann Intern Med"},{"key":"2026032100333155200_bib5","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1086\/342333","article-title":"Risk of tuberculin skin test conversion among health care workers: occupational versus community exposure and infection","volume":"35","author":"Larsen","year":"2002","journal-title":"Clin Infect Dis"},{"key":"2026032100333155200_bib6","first-page":"1","article-title":"Updated guidelines for using interferon \u03b3 release assays to detect Mycobacterium tuberculosis infection\u2014United States, 2010","volume":"59","author":"Mazurek","year":"2010","journal-title":"MMWR Recomm Rep"},{"key":"2026032100333155200_bib7","doi-asserted-by":"crossref","first-page":"340","DOI":"10.7326\/0003-4819-146-5-200703060-00006","article-title":"Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research","volume":"146","author":"Menzies","year":"2007","journal-title":"Ann Intern Med"},{"key":"2026032100333155200_bib8","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S1473-3099(04)01206-X","article-title":"Interferon-\u03b3 assays in the immunodiagnosis of tuberculosis: a systematic review","volume":"4","author":"Pai","year":"2004","journal-title":"Lancet Infect Dis"},{"key":"2026032100333155200_bib9","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1126\/science.284.5419.1520","article-title":"Comparative genomics of BCG vaccines by whole-genome DNA microarray","volume":"284","author":"Behr","year":"1999","journal-title":"Science"},{"key":"2026032100333155200_bib10","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/S0140-6736(03)12950-9","article-title":"Comparison of T-cell\u2013based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak","volume":"361","author":"Ewer","year":"2003","journal-title":"Lancet"},{"key":"2026032100333155200_bib11","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1378\/chest.08-2048","article-title":"Comparative performance of tuberculin skin test, QuantiFERON-TB-Gold In-Tube assay, and T-SPOT.TB test in contact investigations for tuberculosis","volume":"135","author":"Diel","year":"2009","journal-title":"Chest"},{"key":"2026032100333155200_bib12","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00420-010-0571-x","article-title":"Serial testing with the interferon-\u03b3 release assay in Portuguese healthcare workers","volume":"84","author":"Torres Costa","year":"2011","journal-title":"Int Arch Occup Environ Health"},{"key":"2026032100333155200_bib13","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1086\/657336","article-title":"Questionable effectiveness of the QuantiFERON-TB Gold test (Cellestis) as a screening tool in healthcare workers","volume":"31","author":"Gandra","year":"2010","journal-title":"Infect Control Hosp Epidemiol"},{"key":"2026032100333155200_bib14","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1128\/CVI.05058-11","article-title":"Within-subject variability of Mycobacterium tuberculosis\u2013specific \u03b3 interferon responses in German health care workers","volume":"18","author":"Ringshausen","year":"2011","journal-title":"Clin Vaccine Immunol"},{"key":"2026032100333155200_bib15","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/1471-2334-10-220","article-title":"Predictors of persistently positive Mycobacterium tuberculosis\u2013specific interferon-\u03b3 responses in the serial testing of health care workers","volume":"10","author":"Ringshausen","year":"2010","journal-title":"BMC Infect Dis"},{"key":"2026032100333155200_bib16","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1017\/S0950268809002751","article-title":"Estimation of incidence of tuberculosis infection in health-care workers using repeated interferon-\u03b3 assays","volume":"137","author":"Yoshiyama","year":"2009","journal-title":"Epidemiol Infect"},{"key":"2026032100333155200_bib17","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1164\/rccm.201305-0831OC","article-title":"Challenges with QuantiFERON-TB Gold assay for large-scale, routine screening of U.S. healthcare workers","volume":"188","author":"Slater","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib18","first-page":"A1010","article-title":"Evaluation of new interferon-\u03b3 release assays in the diagnosis of latent tuberculosis infection in US health care workers: baseline results [abstract]","volume":"179","author":"Dorman","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib19","first-page":"A4101","article-title":"Diagnosis of latent tuberculosis infection in US health care workers: reproducibility, repeatability and 6 month follow-up with interferon \u03b3 release assays [abstract]","volume":"179","author":"Belknap","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib20","first-page":"A2263","article-title":"Interferon-\u03b3 release assays in the serial testing for latent tuberculosis infection in US healthcare workers [abstract]","volume":"181","author":"Belknap","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib21","first-page":"A1187","article-title":"Re-running QuantiFERON TB Gold In-Tube samples as a strategy for identifying false positive results [abstract]","volume":"183","author":"Belknap","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib22"},{"key":"2026032100333155200_bib23","first-page":"519","article-title":"[Experiences with the intracutaneous Mendel-Mantoux tuberculin test in routine screening in a public health office][article in German]","volume":"59","author":"Daniello","year":"1997","journal-title":"Gesundheitswesen"},{"key":"2026032100333155200_bib24","author":"QuantiFERON-TB Gold Package Insert"},{"key":"2026032100333155200_bib25","author":"T-SPOT"},{"key":"2026032100333155200_bib26","first-page":"65","article-title":"A simple sequentially rejective multiple test procedure","volume":"6","author":"Holm","year":"1979","journal-title":"Scand J Stat"},{"key":"2026032100333155200_bib27","author":"World Health Organization","year":"2010"},{"key":"2026032100333155200_bib28","doi-asserted-by":"crossref","first-page":"163","DOI":"10.5588\/ijtld.11.0364","article-title":"Serial testing of Malaysian health care workers with QuantiFERON\u00ae-TB Gold In-Tube","volume":"16","author":"Rafiza","year":"2012","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032100333155200_bib29","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1745-6673-7-6","article-title":"Interferon-\u03b3 release assays for the tuberculosis serial testing of health care workers: a systematic review","volume":"7","author":"Ringshausen","year":"2012","journal-title":"J Occup Med Toxicol"},{"key":"2026032100333155200_bib30","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1164\/rccm.200604-472OC","article-title":"Serial testing of health care workers for tuberculosis using interferon-\u03b3 assay","volume":"174","author":"Pai","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib31","first-page":"1","article-title":"Serial testing with an interferon-\u03b3 release assay in German healthcare workers","volume":"5","author":"Schablon","year":"2010","journal-title":"GMS Krankenhaushyg Interdiszip"},{"key":"2026032100333155200_bib32","first-page":"84","article-title":"Use of interferon-\u03b3 release assays in a health care worker screening program: experience from a tertiary care centre in the United States","volume":"19","author":"Joshi","year":"2012","journal-title":"Can Respir J"},{"key":"2026032100333155200_bib33","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1164\/rccm.201107-1244OC","article-title":"Discordance among commercially available diagnostics for latent tuberculosis infection","volume":"185","author":"Mancuso","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib34","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1378\/chest.09-2350","article-title":"Evidence-based comparison of commercial interferon-\u03b3 release assays for detecting active TB: a metaanalysis","volume":"137","author":"Diel","year":"2010","journal-title":"Chest"},{"key":"2026032100333155200_bib35","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1164\/rccm.201203-0430OC","article-title":"Test variability of the QuantiFERON-TB Gold In-Tube assay in clinical practice","volume":"187","author":"Metcalfe","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib36","doi-asserted-by":"crossref","first-page":"e43790","DOI":"10.1371\/journal.pone.0043790","article-title":"Within-subject interlaboratory variability of QuantiFERON-TB Gold In-Tube tests","volume":"7","author":"Whitworth","year":"2012","journal-title":"PLoS One"},{"key":"2026032100333155200_bib37","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1128\/JCM.01136-11","article-title":"Preanalytical delay reduces sensitivity of QuantiFERON-TB Gold In-Tube assay for detection of latent tuberculosis infection","volume":"49","author":"Doberne","year":"2011","journal-title":"J Clin Microbiol"},{"key":"2026032100333155200_bib38","doi-asserted-by":"crossref","first-page":"e54748","DOI":"10.1371\/journal.pone.0054748","article-title":"Repeat IGRA testing in Canadian health care workers: conversions or unexplained variability?","volume":"8","author":"Zwerling","year":"2013","journal-title":"PLoS One"},{"key":"2026032100333155200_bib39","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S0140-6736(00)02742-2","article-title":"Specific immune-based diagnosis of tuberculosis","volume":"356","author":"Andersen","year":"2000","journal-title":"Lancet"},{"key":"2026032100333155200_bib40"},{"key":"2026032100333155200_bib41","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1086\/595695","article-title":"Comparison of QuantiFERON-TB Gold In-Tube test and tuberculin skin test for identification of latent Mycobacterium tuberculosis infection in healthcare staff and association between positive test results and known risk factors for infection","volume":"30","author":"Vinton","year":"2009","journal-title":"Infect Control Hosp Epidemiol"},{"key":"2026032100333155200_bib42","doi-asserted-by":"crossref","first-page":"e43014","DOI":"10.1371\/journal.pone.0043014","article-title":"TB screening in Canadian health care workers using interferon-\u03b3 release assays","volume":"7","author":"Zwerling","year":"2012","journal-title":"PLoS One"},{"key":"2026032100333155200_bib43","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1164\/rccm.200811-1704OC","article-title":"Within-subject variability and boosting of T-cell interferon-\u03b3 responses after tuberculin skin testing","volume":"180","author":"van Zyl-Smit","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100333155200_bib44","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.tube.2011.05.004","article-title":"Influence of previous tuberculin skin test on serial IFN-\u03b3 release assays","volume":"91","author":"Sauzullo","year":"2011","journal-title":"Tuberculosis (Edinb)"},{"key":"2026032100333155200_bib45","doi-asserted-by":"crossref","first-page":"e8517","DOI":"10.1371\/journal.pone.0008517","article-title":"Within-subject variability of interferon-\u03b3 assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review","volume":"4","author":"van Zyl-Smit","year":"2009","journal-title":"PLoS One"},{"key":"2026032100333155200_bib46","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1586\/eri.12.150","article-title":"IFN-\u03b3 release assay versus tuberculin skin test for monitoring TB infection in healthcare workers","volume":"11","author":"Nienhaus","year":"2013","journal-title":"Expert Rev Anti Infect Ther"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/189\/1\/77\/67246145\/ajrccm_189_1_77.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/189\/1\/77\/67246145\/ajrccm_189_1_77.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:34:17Z","timestamp":1774067657000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/189\/1\/77\/8506016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,1]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1,1]]},"published-print":{"date-parts":[[2014,1,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201302-0365oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,1]]},"published":{"date-parts":[[2014,1,1]]}}}