1. Thank you for viewing this presentation. We would like to remind you that this material is the property of the author. It is provided to you by the ERS for your personal use only, as submitted by the author.  2012 by the author

2. Christoph Lange IGRAs for the diagnosis of tuberculosis:... is the party over?

3. Incidence of tuberculosis in Germany Robert-Koch-Institute 2011

4. Robert-Koch-Institute 2020? 20 10 20 11 20 12 20 13 20 14 20 15 20 16 20 17 20 18 Incidence of tuberculosis in Germany

5. Global incidence of tuberculosis WHO 2010

6. 8. position of leading causes of deaths 1/3 of the world´s population could be infected > 80% can be cured prevention can be > 90% effective Tuberculosis WHO 2011

7. Lin P et al. J Immunol 2010 Clearance Pulmonary TB Low grade TB “percolating“ Dormant infection Septic TB Miliary TB Extrapulmonary TB LTBI active TB Spectrum of M. tuberculosis infection

9. x Prevention Diagnosis Treatment

11. v Pirquet C; Wien Med Wschr 1907 An allergy-test for the diagnosis of tuberculosis

12. v Pirquet C; Wien Med Wschr 1907 An allergy-test for the diagnosis of tuberculosis

14. TB cowboys

15. Proteom of M. tuberculosis und M. bovis BCG Jungblut PR et al.; Mol Microbiol 1999 M. tuberculosisM. bovis BCG

18. LTBI is defined by a positive reaction in the TST or IGRA

20. The risk for tuberculosis Horseburgh et al. NEJM 2011

21. The risk of tuberculosis in TST +ve individuals Comstock GW et al.; Am J Epidemiol 1974

22. Diel R et al.; AJRCCM 2011 Contact tracing

23. Aichelburg MC et al.Clin Infect Dis 2009 HIV-seropositives

24. Kim SH et al. Am J Transplant 2011 Transplantation

25. Leung CC et al. AJRCCM 2010 Silicosis

26. Diel R et al. Eur Respir J 2011 NPV of the TST and IGRAs for the development of tuberculosis TestNPV TST99.7 QFT-G-IT99.8 T-Spot.TB97.8

27. Diel R et al. Eur Respir J 2011 PPV and NPV of the TST and IGRAs for the development of tuberculosis TestPPVNPV TST2.3-3.399.7 QFT-G-IT2.8-14.399.8 T-Spot.TB3.3-10.097.8

28. Unadjusted cumulative incidence risk ratios for positive vs negative IGRA test results including studies with possible bias Rangaka M et al. Lancet 2011

29. Unadjusted incidence rates by test result Rangaka M et al. Lancet 2011

30. „Intention to test is intention to treat“

31. IsoniazidRifampicin Prevention of tuberculosis

32. Sterling T et al. NEJM 2011

34. FZB Retreat Nov. 201134 www.tb-net.org

35. What is the predictive value of IGRAs for the diagnosis of tuberculosis? n = 3449 22 european centers Update May 2012: n= 4500

36. APC T cell cytokine induction cytokine induction cytokine induction ELISAELISPOT assaySkin test IGRA IFN-  release assay PPD ESAT-6/CFP-10/TB7.7 Negative controls Positive control IGRAs and skin-testing in immunocompromised patients: a multicenter study

37. What is the predictive value of IGRAs for the diagnosis of TB in immunosuppressed individuals? Patientgrouptotal chronic renal failure275 control225 HIV infected patient786 rheumatoid arthritis206 solid organ transplant recipient197 stem cell transplant recipient103 total1792 19 european centers