Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 144 No. 3334 (2014)

Contact tracing investigation after professional exposure to tuberculosis in a Swiss hospital using both tuberculin skin test and IGRA

  • Carlo Balmelli
  • Frédéric Zysset
  • Alberto Pagnamenta
  • Patrick Francioli
  • Catherine Lazor-Blanchet
  • Giorgio Zanetti
  • Jean-Pierre Zellweger
Cite this as:
Swiss Med Wkly. 2014;144:w13988


SETTING: A 950 bed teaching hospital in Switzerland.

AIM: To describe the result of a contact investigation among health care workers (HCW) and patients after exposure to a physician with smear-positive pulmonary tuberculosis in a hospital setting using standard tuberculin skin tests (TST) and Interferon-gamma release assay (IGRA).

METHOD: HCW with a negative or unknown TST at hiring had a TST two weeks after the last contact with the index case (T0), repeated six weeks later if negative (T6). All exposed HCW had a T-SPOT.TB at T0 and T6. Exposed patients had a TST six weeks after the last contact, and a T-SPOT.TB if the TST was positive.

RESULTS: Among 101 HCW, 17/73 (22%) had a positive TST at T0. TST was repeated in 50 at T6 and converted from negative to positive in eight (16%). Twelve HCW had a positive T-SPOT.TB at T0 and ten converted from negative to positive at T6. Seven HCW with a positive T-SPOT.TB reverted to negative at T6 or at later controls, most of them with test values close to the cut-off. Among 27 exposed patients tested at six weeks, ten had a positive TST, five of them confirmed by a positive T-SPOT.TB.

CONCLUSIONS: HCW tested twice after exposure to a case of smear-positive pulmonary TB demonstrated a possible conversion in 10% with T-SPOT and 16% with TST. Some T-SPOT.TB reverted from positive to negative during the follow-up, mostly tests with a value close to the cut-off. Due to the variability of the test results, it seems advisable to repeat the test with values close to the cut-off before diagnosing the presence of a tuberculous infection.


  1. Broekmans JF, Migliori GB, Rieder HL, Lees J, Ruutu P, Loddenkemper R, et al. European framework for tuberculosis control and elimination in countries with a low incidence: Recommendations of the World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Royal Netherlands Tuberculosis Association (KNCV) Working Group. Eur Respir J. 2002;19(4):765–75.
  2. Erkens CG, Kamphorst M, Abubakar I, Bothamley GH, Chemtob D, Haas W, et al. Tuberculosis contact investigation in low prevalence countries: a European consensus. Eur Respir J. 2010;36(4):925–49.
  3. Horsburgh CR, Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med. 2004;350(20):2060–7.
  4. Diel R, Loddenkemper R, Zellweger JP, Sotgiu G, D’Ambrosio L, Centis R, et al. Old ideas to innovate tuberculosis control: preventive treatment to achieve elimination. Eur Respir J. 2013;42(3):785–801.
  5. Moran-Mendoza O, Marion SA, Elwood K, Patrick D, FitzGerald JM. Risk factors for developing tuberculosis: a 12–year follow-up of contacts of tuberculosis cases. Int J Tuberc Lung Dis. 2010;14(9):1112–9.
  6. Fox GJ, Barry SE, Britton WJ, Marks GB. Contact investigation for tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2013;41(1):140–56.
  7. Ligue pulmonaire suisse et Office fédéral de la santé publique, editor. Manuel de la Tuberculose / Handbuch Tuberkulose. Berne: LPS / OFSP; 2011.
  8. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159–74.
  9. Tissot F, Zanetti G, Francioli P, Zellweger JP, Zysset F. Influence of bacille Calmette-Guerin vaccination on size of tuberculin skin test reaction: to what size? Clin Infect Dis. 2005;40(2):211–7.
  10. Marra F, Marra CA, Sadatsafavi M, Moran-Mendoza O, Cook V, Elwood RK, et al. Cost-effectiveness of a new interferon-based blood assay, QuantiFERON-TB Gold, in screening tuberculosis contacts. Int J Tuberc Lung Dis. 2008;12(12):1414–24.
  11. Diel R, Nienhaus A, Loddenkemper R. Cost-effectiveness of Interferon-{gamma} Release Assay Screening for Latent Tuberculosis Infection Treatment in Germany. Chest. 2007;131(5):1424–34.
  12. Diel R, Goletti D, Ferrara G, Bothamley G, Cirillo D, Kampmann B, et al. Interferon-{gamma} release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Respir J. 2011;37(1):88–99.
  13. Mulder C, van Deutekom H, Huisman EM, Toumanian S, Koster BF, Meijer-Veldman W, et al. Role of the QuantiFERON(R)-TB Gold In-Tube assay in screening new immigrants for tuberculosis infection. Eur Respir J. 2012;40(6):1443–9.
  14. Lee SW, Oh DK, Lee SH, Kang HY, Lee CT, Yim JJ. Time interval to conversion of interferon-gamma release assay after exposure to tuberculosis. Eur Respir J. 2011;37(6):1447–52.
  15. Anibarro L, Trigo M, Villaverde C, Pena A, Cortizo S, Sande D, et al. Interferon-gamma release assays in tuberculosis contacts: is there a window period? Eur Respir J. 2011;37(1):215–7.
  16. Sarivalasis A, Zellweger J, Faouzi M, Daher O, Deslarzes C, Bodenmann P. Factors associated with latent tuberculosis among asylum seekers in Switzerland: a cross-sectional study in Vaud County. BMC Infectious Diseases. 2012;12(1):285.
  17. van Zyl-Smit RN, Pai M, Peprah K, Meldau R, Kieck J, Juritz J, et al. Within-subject variability and boosting of T-cell interferon-gamma responses after tuberculin skin testing. Am J Respir Crit Care Med. 2009;180(1):49–58.
  18. Detjen AK, Loebenberg L, Grewal HM, Stanley K, Gutschmidt A, Kruger C, et al. Short-term Reproducibility of a Commercial Interferon-gamma Release Assay. Clin Vaccine Immunol. 2009.
  19. Beffa P, Zellweger A, Janssens JP, Wrighton-Smith P, Zellweger JP. Indeterminate test results of T-SPOT.TB performed under routine field conditions. Eur Respir J. 2008;31(4):842–6.
  20. Andersen P, Doherty TM, Pai M, Weldingh K. The prognosis of latent tuberculosis: can disease be predicted? Trends Mol Med. 2007;13(5):175–82.
  21. Zwerling A, van den Hof S, Scholten J, Cobelens F, Menzies D, Pai M. Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review. Thorax. 2011.
  22. Pai M. Serial testing with TB interferon-gamma release assays: toward a nuanced understanding. Chest. 2012;142(6):1366–7.
  23. Pai M, O’Brien R. Serial testing for tuberculosis: can we make sense of T cell assay conversions and reversions? PLoSMed. 2007;4(6):e208.
  24. Metcalfe JZ, Cattamanchi A, McCulloch CE, Lew JD, Ha NP, Graviss EA. Test variability of the QuantiFERON-TB gold in-tube assay in clinical practice. AJRCCM. 2013;187(2):206–11.
  25. Veerapathran A, Joshi R, Goswami K, Dogra S, Moodie EE, Reddy MV, et al. T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data. PLoSONE. 2008;3(3):e1850.
  26. Torres Costa J, Silva R, Ringshausen FC, Nienhaus A. Screening for tuberculosis and prediction of disease in Portuguese healthcare workers. J Occup Med Toxicol. 2011;6:19.
  27. Zellweger JP, Rieder HL. Serial screening for latent tuberculosis infection in healthcare workers in low-risk settings. Am J Respir Crit Care Med. 2014;189(1):3–4.
  28. Hill PC, Brookes RH, Fox A, Jackson-Sillah D, Jeffries DJ, Lugos MD, et al. Longitudinal Assessment of an ELISPOT Test for Mycobacterium tuberculosis Infection. PLoSMed. 2007;4(6):e192.
  29. Mack U, Migliori GB, Sester M, Rieder HL, Ehlers S, Goletti D, et al. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur Respir J. 2009;33(5):956–73.
  30. Zumla A, Atun R, Maeurer M, Mwaba P, Ma Z, O’Grady J, et al. Viewpoint: Scientific dogmas, paradoxes and mysteries of latent Mycobacterium tuberculosis infection. Trop Med Int Health. 2011;16(1):79–83.
  31. Landry J, Menzies D. Preventive chemotherapy. Where has it got us? Where to go next? Int J Tuberc Lung Dis. 2008;12(12):1352–64.
  32. Haldar P, Thuraisingam H, Patel H, Pereira N, Free RC, Entwisle J, et al. Single-step QuantiFERON screening of adult contacts: a prospective cohort study of tuberculosis risk. Thorax. 2012.
  33. Horsburgh CR, Jr., Goldberg S, Bethel J, Chen S, Colson PW, Hirsch-Moverman Y, et al. Latent TB infection treatment acceptance and completion in the United States and Canada. Chest. 2010;137(2):401–9.
  34. Hirsch-Moverman Y, Bethel J, Colson PW, Franks J, El-Sadr W. Predictors of latent tuberculosis infection treatment completion in the United States: an inner city experience. Int J Tuberc Lung Dis. 2010;14(9):1104–11.
  35. Anibarro L, Casas S, Paz-Esquete J, Gonzalez L, Pena A, Guerra MR, et al. Treatment completion in latent tuberculosis infection at specialist tuberculosis units in Spain. Int J Tuberc Lung Dis. 2010;14(6):701–7.
  36. Trajman A, Long R, Zylberberg D, Dion MJ, Al-Otaibi B, Menzies D. Factors associated with treatment adherence in a randomised trial of latent tuberculosis infection treatment. Int J Tuberc Lung Dis. 2010;14(5):551–9.
  37. Fresard I, Bridevaux PP, Rochat T, Janssens JP. Adverse effects and adherence to treatment of rifampicin 4 months vs isoniazid 6 months for latent tuberculosis: a retrospective analysis. Swiss Med Wkly. 2011;141:w13240.

Most read articles by the same author(s)