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Available from: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.cdc.gov\/tb\/publications\/factsheets\/testing\/IGRA.htm\" xlink:type=\"simple\">http:\/\/www.cdc.gov\/tb\/publications\/factsheets\/testing\/IGRA.htm<\/ext-link>"},{"issue":"1","key":"ref8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1128\/CMR.00034-13","article-title":"Gamma interferon release assays for detection of Mycobacterium tuberculosis infection","volume":"27","author":"M Pai","year":"2014","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0378-1119(98)00134-6","article-title":"Host vector system for high-level expression and purification of recombinant, enzymatically active alanine dehydrogenase of Mycobacterium tuberculosis","volume":"212","author":"B Hutter","year":"1998","journal-title":"Gene"},{"issue":"Pt 3","key":"ref10","first-page":"669","article-title":"Properties of the 40 kDa antigen of Mycobacterium tuberculosis, a functional L-alanine dehydrogenase","volume":"343","author":"B Hutter","year":"1999"},{"issue":"4","key":"ref11","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.jmb.2008.01.091","article-title":"Three-dimensional structures of apo- and holo-L-alanine dehydrogenase from Mycobacterium tuberculosis reveal conformational changes upon coenzyme binding","volume":"377","author":"D Agren","year":"2008","journal-title":"J Mol Biol"},{"issue":"6","key":"ref12","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/gene.2013.26","article-title":"Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India","volume":"14","author":"S Dhanasekaran","year":"2013","journal-title":"Genes Immun"},{"issue":"9","key":"ref13","doi-asserted-by":"crossref","first-page":"e46041","DOI":"10.1371\/journal.pone.0046041","article-title":"Potential role of M. tuberculosis specific IFN-gamma and IL-2 ELISPOT assays in discriminating children with active or latent tuberculosis","volume":"7","author":"E Chiappini","year":"2012","journal-title":"Plos One"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1128\/JB.05914-11","article-title":"ald of Mycobacterium tuberculosis encodes both the alanine dehydrogenase and the putative glycine dehydrogenase","volume":"194","author":"MM Giffin","year":"2012","journal-title":"J Bacteriol"},{"issue":"5","key":"ref15","doi-asserted-by":"crossref","first-page":"e0155522","DOI":"10.1371\/journal.pone.0155522","article-title":"Role of Alanine Dehydrogenase of Mycobacterium tuberculosisduring Recovery from Hypoxic Nonreplicating Persistence","volume":"11","author":"MM Giffin","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1684\/ecn.2017.0391","article-title":"Interferon Gamma Release Assay in response to PE35\/PPE68 proteins: a promising diagnostic method for diagnosis of latent tuberculosis","volume":"28","author":"S Mahmoudi","year":"2017","journal-title":"Eur Cytokine Netw"},{"issue":"3","key":"ref17","doi-asserted-by":"crossref","first-page":"e17813","DOI":"10.1371\/journal.pone.0017813","article-title":"Whole-blood flow-cytometric analysis of antigen-specific CD4 T cell cytokine profiles distinguishes active tuberculosis from non-active states","volume":"6","author":"U Sester","year":"2011","journal-title":"PLoS One"},{"issue":"8","key":"ref18","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1111\/j.1469-0691.2009.03104.x","article-title":"Detection of interleukin-2 in addition to interferon-gamma discriminates active tuberculosis patients, latently infected individuals, and controls","volume":"16","author":"R Biselli","year":"2010","journal-title":"Clin Microbiol Infect"},{"issue":"3","key":"ref19","first-page":"275","article-title":"IFN-\u03b3 and IL-2 Responses to Recombinant AlaDH against ESAT-6\/CFP-10 Fusion Antigens in the Diagnosis of Latent versus Active Tuberculosis Infection","volume":"42","author":"B Movahedi","year":"2017","journal-title":"Iran J Med Sci"},{"issue":"RR-6","key":"ref20","first-page":"1","article-title":"American Thoracic Society","volume":"9","year":"2000","journal-title":"MMWR Recomm Rep"},{"issue":"RR-5","key":"ref21","first-page":"1","article-title":"IGRA Expert Committee; Centers for Disease Control and Prevention (CDC). 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NICE guidelines. 2016; Available from: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/nice.org.uk\/guidance\/ng33\" xlink:type=\"simple\">nice.org.uk\/guidance\/ng33<\/ext-link>."},{"key":"ref26","article-title":"Centers for Disease Control and Prevention (CDC), developed in partnership with the New Jersey Medical School Global Tuberculosis Institute","year":"2013","journal-title":"Latent Tuberculosis Infection: A Guide for Primary Health Care Providers"},{"issue":"4857","key":"ref27","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1126\/science.3287615","article-title":"Measuring the Accuracy of Diagnostic Systems","volume":"240","author":"JA Swet","year":"1988","journal-title":"Science"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev-immunol-032712-095939","article-title":"The Immune Response in Tuberculosis","volume":"31","author":"A O'Garra","year":"2013","journal-title":"Annu 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