Hostname: page-component-f7d5f74f5-g2fc4 Total loading time: 0 Render date: 2023-10-03T04:44:51.536Z Has data issue: false Feature Flags: { "corePageComponentGetUserInfoFromSharedSession": true, "coreDisableEcommerce": false, "coreDisableSocialShare": false, "coreDisableEcommerceForArticlePurchase": false, "coreDisableEcommerceForBookPurchase": false, "coreDisableEcommerceForElementPurchase": false, "coreUseNewShare": true, "useRatesEcommerce": true } hasContentIssue false

Interferon-γ Release Assay vs. Tuberculin Skin Test for Tuberculosis Screening in Exposed Healthcare Workers: A Longitudinal Multicenter Comparative Study

Published online by Cambridge University Press:  16 February 2015

Jean-Christophe Lucet*
AP-HP, Bichat-Claude Bernard Hospital, Infection Control Unit, F-75018 Paris, France Université Paris Diderot, IAME, UMR 1137, F-75018 Paris, France
Dominique Abiteboul
AP-HP, Bichat-Claude Bernard Hospital, Department of Occupational Health, F-75018 Paris, France
Candice Estellat
AP-HP, Bichat-Claude Bernard Hospital, Département d’Epidémiologie et Recherche Clinique, URC Paris-Nord, F-75018 Paris, France INSERM, CiC-EC 1425, F-75018 Paris, France AP-HP, Bichat-Claude Bernard Hospital, Unité d’Immunologie “Auto-immunité et Hypersensibilités”, F-75018 Paris, France
Carine Roy
AP-HP, Bichat-Claude Bernard Hospital, Département d’Epidémiologie et Recherche Clinique, URC Paris-Nord, F-75018 Paris, France INSERM, CiC-EC 1425, F-75018 Paris, France
Sylvie Chollet-Martin
AP-HP, Bichat-Claude Bernard Hospital, Unité d’Immunologie “Auto-immunité et Hypersensibilités”, F-75018 Paris, France INSERM UMRS996, Université Paris-Sud, France
Florence Tubach
AP-HP, Bichat-Claude Bernard Hospital, Département d’Epidémiologie et Recherche Clinique, URC Paris-Nord, F-75018 Paris, France INSERM, CiC-EC 1425, F-75018 Paris, France Sorbonne Universités, UPMC Univ Paris 06, CIMI - Paris, F-75013, France
Guislaine Carcelain
Univ Paris Diderot, Sorbonne Paris Cité, ECEVE, UMR1123, Paris, F-75010France Inserm, U1135, CIMI, Paris, Paris, F-75013, France AP-HP, Hôpital Pitié-Salpêtrière, Département d’Immunologie, Paris, F-75013, France
Address all correspondence to Jean-Christophe Lucet, Hôpital Bichat-Claude Bernard, Bichat-Claude Bernard Hospital, 46 Rue Henri Huchard 75018 Paris, France (



Healthcare workers (HCWs), especially those caring for patients with tuberculosis (TB), are at high risk of acquiring that disease. The poor specificity of tuberculin skin testing (TST) prompted us to evaluate the effectiveness of the interferon-γ release assay (IGRA) in comparison with TST in a large prospective, multicenter, 1-year study of HCWs with occupational exposure to TB.


HCWs from high-risk units at 14 university hospitals were invited to participate and underwent both TST and IGRA (first Quantiferon TB Gold-IT®, QFT-G, then T-SPOT.TB® if QFT-G was indeterminate) at baseline and after 1 year. We collected demographic characteristics, country of birth, history of TB, immunosuppression, past exposure to TB, history of BCG vaccination, results of most recent TST, job category, and duration of current function.


Among 807 HCWs enrolled, current or past TST at baseline was positive (≥15 mm) in 282 (34.9%); the IGRA was positive in 113 (14.0%) and indeterminate in 3 (0.4%). After 1 year, 594 HCWs had both an IGRA and TST (or prior TST≥15 mm) at baseline and an IGRA and TST (if indicated). The conversion rate was 2.5% (9 of 367) with TST and 7.6% (45 of 594) with IGRA, with poor agreement between the 2 tests. Using only QFT-G, conversion (9.9%) and reversion (17.8%) rates were higher for baseline QFT-G positive quantitative values <1 IU/mL.


TST and the IGRA yielded discordant results. The value of IGRA in addition to TST remains undetermined; the two should be jointly interpreted in decision-making (clinical trial registration NCT00797836).

Infect Control Hosp Epidemiol 2015;00(0): 1–6

Original Articles
© 2015 by The Society for Healthcare Epidemiology of America. All rights reserved 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)



The QUANTIPS Study Group: B Ripault, P Rucay, A Chevallier (Hôpital universitaire, Angers), MF Maillard, D Emilie, A Gleaize (Hôpital Antoine Béclère, Clamart), D Abiteboul, F Brégent, S Chollet-Martin, P Nicaise (Hôpital Bichat-Cl. Bernard, Paris), C Pillier-Loriette, Y Taoufik, H Chavez (Hôpital Bicêtre, le Kremlin-Bicètre), A Sobazeck, A Trichard, M Labalette (Hôpital univesitaire, Lille) M Brabet, J-P Vendrell, E Tuaillon (Hôpital universitaire, Montpellier), V Naël, D Tripodi, M Audrain (Hôpital universitaire, Nantes), ML Lepori, AS Wasmer, G Faure, M De Carvalho (Hôpital universitaire, Nancy), N Coullaud, C Capitaine, E Ritter, S Benzaken (Hôpital universitaire, Nice), M Louet, F Désert (Hôpital Pitié-Salpetrière, Paris), G Coulombier, JM Gombert et A Barra (Hôpital universitaire, Poitiers), M Courgeon, C Vialard, B Sorel, C Laguitton, N Genetet et D Monnier (Hôpital universitaire, Rennes), M Bourgeois, M.A Touat, C Rabian (Hôpital Saint Louis, Paris), P Ochin (Hôpital Universitaire, Tourcoing)


1. Pai, M, Zwerling, A, Menzies, D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med 2008;149:177184.CrossRefGoogle Scholar
2. Antoine, D, Belghiti, F, Guthmann, J, Campese, C, Lévy-Bruhl, D, Che, D. Les cas de tuberculose déclarés en France en 2012. BEH 2014:352359.Google Scholar
3. Zwerling, A, Benedetti, A, Cojocariu, M, et al. Repeat IGRA testing in Canadian health workers: conversions or unexplained variability? PloS One 2013;8:e54748.CrossRefGoogle ScholarPubMed
4. Dorman, SE, Belknap, R, Graviss, EA, et al. Interferon-γ release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States. Am J Respir Crit Care Med 2014;189:7787.Google ScholarPubMed
5. Pai, M, Denkinger, CM, Kik, SV, et al. Γ interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev 2014;27:320.CrossRefGoogle ScholarPubMed
6. Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med 2000;161:S221S247.Google Scholar
7. Ringshausen, FC, Schablon, A, Nienhaus, A. Interferon-γ release assays for the tuberculosis serial testing of health care workers: a systematic review. J Occup Med Toxicol Lond Engl 2012;7:6.CrossRefGoogle ScholarPubMed
8. Zwerling, A, Hof, S, van den, Scholten, J, Cobelens, F, Menzies, D, Pai, M. Interferon-γ release assays for tuberculosis screening of healthcare workers: a systematic review. Thorax 2012;67:6270.CrossRefGoogle ScholarPubMed
9. Drobniewski, F, Balabanova, Y, Zakamova, E, Nikolayevskyy, V, Fedorin, I. Rates of latent tuberculosis in health care staff in Russia. PLoS Med 2007;4:e55.CrossRefGoogle Scholar
10. Girardi, E, Angeletti, C, Puro, V, et al. Estimating diagnostic accuracy of tests for latent tuberculosis infection without a gold standard among healthcare workers. Euro Surveill Bull 2009:14.Google ScholarPubMed
11. Harada, N, Nakajima, Y, Higuchi, K, Sekiya, Y, Rothel, J, Mori, T. Screening for tuberculosis infection using whole-blood interferon-γ and Mantoux testing among Japanese healthcare workers. Infect Control Hosp Epidemiol 2006;27:442448.CrossRefGoogle ScholarPubMed
12. Lien, LT, Hang, NTL, Kobayashi, N, et al. Prevalence and risk factors for tuberculosis infection among hospital workers in Hanoi, Viet Nam. PloS One 2009;4:e6798.CrossRefGoogle Scholar
13. Campo, MT, del, Fouad, H, Solís-Bravo, MM, Sánchez-Uriz, MA, Mahíllo-Fernández, I, Esteban, J. Cost-effectiveness of different screening strategies (single or dual) for the diagnosis of tuberculosis infection in healthcare workers. Infect Control Hosp Epidemiol 2012;33:12261234.CrossRefGoogle Scholar
14. Demkow, U, Broniarek-Samson, B, Filewska, M, et al. Prevalence of latent tuberculosis infection in health care workers in Poland assessed by interferon-γ whole blood and tuberculin skin tests. J Physiol Pharmacol 2008;59(Suppl 6):209217.Google Scholar
15. Torres Costa, J, , R, Cardoso, MJ, et al. Tuberculosis screening in Portuguese healthcare workers using the tuberculin skin test and the interferon-γ release assay. Eur Respir J 2009;34:14231428.CrossRefGoogle ScholarPubMed
16. Hotta, K, Ogura, T, Nishii, K, et al. Whole blood interferon-γ assay for baseline tuberculosis screening among Japanese healthcare students. PloS One 2007;2:e803.CrossRefGoogle ScholarPubMed
17. Topić, RZ, Dodig, S, Zoricić-Letoja, I. Interferon-γ and immunoglobulins in latent tuberculosis infection. Arch Med Res 2009;40:103108.CrossRefGoogle ScholarPubMed
18. Vinton, P, Mihrshahi, S, Johnson, P, Jenkin, GA, Jolley, D, Biggs, B-A. 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. Infect Control Hosp Epidemiol 2009;30:215221.CrossRefGoogle ScholarPubMed
19. Larsen, NM, Biddle, CL, Sotir, MJ, White, N, Parrott, P, Blumberg, HM. Risk of tuberculin skin test conversion among health care workers: occupational versus community exposure and infection. Clin Infect Dis 2002;35:796801.CrossRefGoogle ScholarPubMed
20. Fong, KS, Tomford, JW, Teixeira, L, et al. Challenges of interferon-γ release assay conversions in serial testing of health-care workers in a TB control program. Chest 2012;142:5562.CrossRefGoogle Scholar
21. Gandra, S, Scott, WS, Somaraju, V, Wang, H, Wilton, S, Feigenbaum, M. Questionable effectiveness of the QuantiFERON-TB Gold Test (Cellestis) as a screening tool in healthcare workers. Infect Control Hosp Epidemiol 2010;31:12791285.CrossRefGoogle ScholarPubMed
22. Pai, M, Joshi, R, Dogra, S, et al. Serial testing of health care workers for tuberculosis using interferon-γ assay. Am J Respir Crit Care Med 2006;174:349355.CrossRefGoogle ScholarPubMed
23. Ringshausen, FC, Nienhaus, A, Schablon, A, Schlösser, S, Schultze-Werninghaus, G, Rohde, G. Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-γ responses in the serial testing of health care workers. BMC Infect Dis 2010;10:220.CrossRefGoogle ScholarPubMed