{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T07:43:47Z","timestamp":1774079027714,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"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":[[2012,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Interferon-\u03b3 (IFN-\u03b3) release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate factors influencing results of IFN-\u03b3 release assays in children using a large European data set.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Pediatric Tuberculosis Network European Trials group pooled and analyzed data from five sites across Europe comprising 1,128 children who were all investigated for latent tuberculosis infection by tuberculin skin test and at least one IFN-\u03b3 release assay. Multivariate analyses examined age, bacillus Calmette-Gu\u00e9rin (BCG) vaccination status, and sex as predictor variables of results. Subgroup analyses included children who were household contacts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A total of 1,093 children had a QuantiFERON-TB Gold In-Tube assay and 382 had a T-SPOT.TB IFN-\u03b3 release assay. Age was positively correlated with a positive blood result (QuantiFERON-TB Gold In-Tube: odds ratio [OR], 1.08 per year increasing age [P &amp;lt; 0.0001]; T-SPOT.TB: OR, 1.14 per year increasing age [P &amp;lt; 0.001]). A positive QuantiFERON-TB Gold In-Tube result was shown by 5.5% of children with a tuberculin skin test result less than 5 mm, by 14.8% if less than 10 mm, and by 20.2% if less than 15 mm. Prior BCG vaccination was associated with a negative IFN-\u03b3 release assay result (QuantiFERON-TB Gold In-Tube: OR, 0.41 [P &amp;lt; 0.001]; T-SPOT.TB: OR, 0.41 [P &amp;lt; 0.001]). Young age was a predictor of indeterminate IFN-\u03b3 release assay results, but indeterminate rates were low (3.6% in children &amp;lt; 5 yr, 1% in children &amp;gt; 5 yr).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data show that BCG vaccination may be effective in protecting children against Mycobacterium tuberculosis infection. To restrict use of IFN-\u03b3 release assays to children with positive skin tests risks underestimating latent infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201201-0026oc","type":"journal-article","created":{"date-parts":[[2012,6,15]],"date-time":"2012-06-15T02:00:33Z","timestamp":1339725633000},"page":"378-384","source":"Crossref","is-referenced-by-count":85,"title":["Identifying Predictors of Interferon-\u03b3 Release Assay Results in Pediatric Latent Tuberculosis: A Protective Role of Bacillus Calmette-Gu\u00e9rin?: A pTB-NET Collaborative Study"],"prefix":"10.1093","volume":"186","author":[{"given":"Robindra Basu","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Paediatric Allergy and Infectious Diseases, Imperial College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Sotgiu","sequence":"additional","affiliation":[{"name":"Epidemiology and Biostatistics Unit, Department of Biomedical Sciences, University of Sassari, Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neus","family":"Altet-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Unitat de Prevenci\u00f3 i Control de la Tuberculosi, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Tsolia","sequence":"additional","affiliation":[{"name":"National and Kapodistrian Second Department of Paediatrics, P. and A. Kyriakou Children\u2019s Hospital, University of Athens School of Medicine, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezia","family":"Ruga","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, University Hospital, Padua, Italy; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Velizarova","sequence":"additional","affiliation":[{"name":"Bulgaria University Pediatric Clinic of Lung Diseases, Hospital St. Sofia, Medical University, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Kampmann","sequence":"additional","affiliation":[{"name":"Department of Paediatric Allergy and Infectious Diseases, Imperial College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,8,15]]},"reference":[{"key":"2026032101011143400_bib1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.prrv.2010.09.006","article-title":"Immunology and pathogenesis of childhood TB","volume":"12","author":"Jones","year":"2011","journal-title":"Paediatr Respir Rev"},{"key":"2026032101011143400_bib2","first-page":"426","article-title":"Adult-to-child transmission of tuberculosis: household or community contact?","volume":"7","author":"Schaaf","year":"2003","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101011143400_bib3","first-page":"392","article-title":"The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era","volume":"8","author":"Marais","year":"2004","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101011143400_bib4","first-page":"1091","article-title":"Guidance for national tuberculosis programmes on the management of tuberculosis in children. Chapter 1. Introduction and diagnosis of tuberculosis in children","volume":"10","author":"World Health Organization Stop TB Partnership Childhood TB Subgroup","year":"2006","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101011143400_bib5","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1016\/j.rmed.2006.08.006","article-title":"The history of tuberculosis","volume":"100","author":"Daniel","year":"2006","journal-title":"Respir Med"},{"key":"2026032101011143400_bib6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1097\/MCP.0b013e32832a0adc","article-title":"T-cell interferon-\u03b3 release assays for the rapid immunodiagnosis of tuberculosis: clinical utility in high-burden vs. low-burden settings","volume":"15","author":"Dheda","year":"2009","journal-title":"Curr Opin Pulm Med"},{"key":"2026032101011143400_bib7","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1183\/09031936.00115110","article-title":"Interferon \u03b3 release assays for the diagnosis of latent M. tuberculosis infection: a systematic review and meta-analysis","volume":"37","author":"Diel","year":"2011","journal-title":"Eur Respir J"},{"key":"2026032101011143400_bib8","doi-asserted-by":"crossref","first-page":"814943","DOI":"10.1155\/2011\/814943","article-title":"Pathogenesis, immunology, and diagnosis of latent Mycobacterium tuberculosis infection","volume":"2011","author":"Ahmad","year":"2011","journal-title":"Clin Dev Immunol"},{"key":"2026032101011143400_bib9","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1097\/QCO.0b013e32813e3fd8","article-title":"T cell\u2013based diagnosis of childhood tuberculosis infection","volume":"20","author":"Lalvani","year":"2007","journal-title":"Curr Opin Infect Dis"},{"key":"2026032101011143400_bib10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.prrv.2010.09.009","article-title":"Immune-based diagnostics for TB in children: what is the evidence?","volume":"12","author":"Ling","year":"2011","journal-title":"Paediatr Respir Rev"},{"key":"2026032101011143400_bib11","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1097\/INF.0b013e318214b915","article-title":"The utility of an interferon \u03b3 release assay for diagnosis of latent tuberculosis infection and disease in children: a systematic review and meta-analysis","volume":"30","author":"Machingaidze","year":"2011","journal-title":"Pediatr Infect Dis J"},{"key":"2026032101011143400_bib12","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.5588\/ijtld.10.0631","article-title":"Interferon-\u03b3 release assays and childhood tuberculosis: systematic review and meta-analysis","volume":"15","author":"Mandalakas","year":"2011","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101011143400_bib13","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":"2026032101011143400_bib14","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1136\/thx.2005.048033","article-title":"Performance of a whole blood interferon \u03b3 assay for detecting latent infection with Mycobacterium tuberculosis in children","volume":"61","author":"Connell","year":"2006","journal-title":"Thorax"},{"key":"2026032101011143400_bib15","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S0140-6736(06)69064-8","article-title":"Blood tests for diagnosis of tuberculosis","volume":"368","author":"Kampmann","year":"2006","journal-title":"Lancet"},{"key":"2026032101011143400_bib16","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.5588\/ijtld.10.0770","article-title":"Tuberculin skin test and QuantiFERON assay in young children investigated for tuberculosis in South Africa","volume":"15","author":"Moyo","year":"2011","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101011143400_bib17","doi-asserted-by":"crossref","first-page":"e419","DOI":"10.1542\/peds.2008-1722","article-title":"Performance of commercial blood tests for the diagnosis of latent tuberculosis infection in children and adolescents","volume":"123","author":"Bergamini","year":"2009","journal-title":"Pediatrics"},{"key":"2026032101011143400_bib18","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.diagmicrobio.2009.11.002","article-title":"QuantiFERON-TB Gold In-Tube as help for the diagnosis of tuberculosis in a French pediatric hospital","volume":"66","author":"Grare","year":"2010","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2026032101011143400_bib19","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1097\/INF.0b013e3181a16394","article-title":"The likelihood of an indeterminate test result from a whole-blood interferon-\u03b3 release assay for the diagnosis of Mycobacterium tuberculosis infection in children correlates with age and immune status","volume":"28","author":"Haustein","year":"2009","journal-title":"Pediatr Infect Dis J"},{"key":"2026032101011143400_bib20","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1016\/S0140-6736(10)60393-5","article-title":"New vaccines for tuberculosis","volume":"375","author":"Kaufmann","year":"2010","journal-title":"Lancet"},{"key":"2026032101011143400_bib21","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S0140-6736(06)68507-3","article-title":"Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness","volume":"367","author":"Trunz","year":"2006","journal-title":"Lancet"},{"key":"2026032101011143400_bib22","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/S0140-6736(05)67534-4","article-title":"Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study","volume":"366","author":"Soysal","year":"2005","journal-title":"Lancet"},{"key":"2026032101011143400_bib23","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1542\/peds.2005-2095","article-title":"Comparison of enzyme-linked immunospot assay and tuberculin skin test in healthy children exposed to Mycobacterium tuberculosis.","volume":"117","author":"Hill","year":"2006","journal-title":"Pediatrics"},{"key":"2026032101011143400_bib24"},{"key":"2026032101011143400_bib25"},{"key":"2026032101011143400_bib26","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2307\/2529310","article-title":"The measurement of observer agreement for categorical data","volume":"33","author":"Landis","year":"1977","journal-title":"Biometrics"},{"key":"2026032101011143400_bib27","doi-asserted-by":"crossref","first-page":"6116","DOI":"10.1016\/j.vaccine.2009.08.031","article-title":"BCG vaccination reduces risk of infection with Mycobacterium tuberculosis as detected by \u03b3 interferon release assay","volume":"27","author":"Eisenhut","year":"2009","journal-title":"Vaccine"},{"key":"2026032101011143400_bib28","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4161\/viru.1.2.11054","article-title":"Significance of reduced reactivity in ELISPOT assay to RD antigens of Mycobacterium tuberculosis in BCG vaccinated individuals exposed to a patient with tuberculosis","volume":"1","author":"Eisenhut","year":"2010","journal-title":"Virulence"},{"key":"2026032101011143400_bib29","doi-asserted-by":"crossref","first-page":"e16137","DOI":"10.1371\/journal.pone.0016137","article-title":"Secondary attack rate of tuberculosis in urban households in Kampala, Uganda","volume":"6","author":"Whalen","year":"2011","journal-title":"PLoS ONE"},{"key":"2026032101011143400_bib30","doi-asserted-by":"crossref","first-page":"e3407","DOI":"10.1371\/journal.pone.0003407","article-title":"Whole blood interferon-\u03b3 responses to Mycobacterium tuberculosis antigens in young household contacts of persons with tuberculosis in Uganda","volume":"3","author":"Lewinsohn","year":"2008","journal-title":"PLoS ONE"},{"key":"2026032101011143400_bib31","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1136\/thx.2009.127555","article-title":"A prospective large-scale study of methods for the detection of latent Mycobacterium tuberculosis infection in refugee children","volume":"65","author":"Lucas","year":"2010","journal-title":"Thorax"},{"key":"2026032101011143400_bib32","article-title":"CG117 tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control","author":"National Institute for Health and Clinical Excellence","year":"2011"},{"key":"2026032101011143400_bib33","article-title":"The Red Book\u2014report of the Committee on Infectious Diseases","author":"Committee on Infectious Diseases, American Academy of Pediatrics","year":"2009"},{"key":"2026032101011143400_bib34","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1097\/INF.0b013e318220c52a","article-title":"Interferon-\u03b3 release assay for the diagnosis of latent tuberculosis in children younger than 5 years of age","volume":"30","author":"Pavic","year":"2011","journal-title":"Pediatr Infect Dis J"},{"key":"2026032101011143400_bib35","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1097\/INF.0b013e3182272227","article-title":"Interferon-\u03b3 release assay performance for diagnosing tuberculosis disease in 0- to 5-year-old children","volume":"30","author":"Debord","year":"2011","journal-title":"Pediatr Infect Dis J"},{"key":"2026032101011143400_bib36","first-page":"174","article-title":"Concordance of a positive tuberculin skin test and an interferon \u03b3 release assay in bacille Calmette-Gu\u00e9rin vaccinated persons","volume":"15","author":"Mahan","year":"2011","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101011143400_bib37","doi-asserted-by":"crossref","first-page":"e1000199","DOI":"10.1371\/journal.pmed.1000199","article-title":"Sexual inequality in tuberculosis","volume":"6","author":"Neyrolles","year":"2009","journal-title":"PLoS Med"},{"key":"2026032101011143400_bib38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-9255-7-28","article-title":"Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent children","volume":"7","author":"Casimir","year":"2010","journal-title":"J Inflamm"},{"key":"2026032101011143400_bib39","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1164\/rccm.200207-682OC","article-title":"The epidemiology of severe sepsis in children in the United States","volume":"167","author":"Watson","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032101011143400_bib40","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.vaccine.2010.10.071","article-title":"Diphtheria\u2013tetanus\u2013pertussis vaccine administered simultaneously with measles vaccine is associated with increased morbidity and poor growth in girls: a randomised trial from Guinea-Bissau","volume":"29","author":"Agergaard","year":"2011","journal-title":"Vaccine"},{"key":"2026032101011143400_bib41","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"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/186\/4\/378\/67247119\/ajrccm_186_4_378.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/186\/4\/378\/67247119\/ajrccm_186_4_378.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:01:24Z","timestamp":1774069284000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/186\/4\/378\/8507650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2012,8,15]]},"published-print":{"date-parts":[[2012,8,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201201-0026oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,8]]},"published":{"date-parts":[[2012,8]]}}}