1. October 3, 2006

2. Serial Testing of Health Care Workers for Tuberculosis Using Interferon-γ Assay Madhukar Pai, et. al. American Journal of Respiratory and Critical Care Medicine, 2006, (174): 349-355. Discussion by:Anna Gushchin Mentor: Dr. David Paterson GHIG Journal Club October 3, 2006

3. Acknowledgements Dr. David Paterson –University of Pittsburgh, Department of Medicine, Division of Infectious Diseases. Dr. Anu Manandhar –Tilganga Eye Centre, Gaushala, Nepal. Dean Harvey –University of Pittsburgh, School of Medicine. You!

4. Outline Global TB Burden Current Diagnosis Methods Article Findings Discussion

5. Why TB? Estimated 1/3 of the world is affected –9 million cases every year 1. MMWR: March 24, 2006 (17,690 samples) –Multiple drug resistant TB MDR 20% –Extensive drug resistant TB XDR 2% How is this treated? –Isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin, cycloserine, capreomycin… 1) World Health Organization. Global Tuberculosis Control. Surveillance, Planning Financing WHO Report 2005. Geneva. (3,538) (70)

6. Before Treating, Must Detect PPD – (Purified Protein Derivative) –0.1 mL injection –48-72 hours later measure reaction Secondary confirmation may be necessary –1-2 weeks apart US CDC recommendations: –HCW: Every year –High Risk: Every 6 months

7. Question Which country currently has the highest voluntarily reported rate of XDR (extremely drug-resistant) TB? 2002-2004 Latvia 21% XDR What % of the population in India is estimated to be infected? 40%

8. Serial Testing of Health Care Workers for Tuberculosis Using Interferon-γ Assay Madhukar Pai, et. al. American Journal of Respiratory and Critical Care Medicine, 2006, (174): 349-355.

9. Questions Asked: Is IFN-γ release assay (IGRA) comparable to the Tuberculin Skin Test (TST) aka PPD? Are there advantages to using one technology over another? Can it be used successfully in an underserved population with a high burden of infection?

10. 1) Is IGRA comparable to TST? 353 medical and nursing students –216 completed the study Tested twice (6 months apart) –QFT (QuantiFERON) –TST Analysis: –Concordant/discordant

11. The Technology IGRA: –Unaffected by BCG vaccination –Single visit –No booster effects –Rapid test, 24 hours –Uses whole blood –Good detection of LTBI –98.2% Specificity –90% Sensitivity.

12. How do these tests work? TST Hypersensitivity response > Erythema IGRA

13. Results! N=216

14. Statistics Bottom line: compared the 4 subgroups for level of agreement (kappa coefficient)

15. Results +veConversionConversion 2 TST48 (22%)14 (9.5%) (10mm) 6 (4.1%) (6mm) QFT38 (18%)17 (11.6%) >0.35IU/ml 11 (7.5%) >0.70IU/ml Agreement 96%, Kappa = 0.70

16. Conclusions IGRA shows promise for serial testing IGRA is comparable with TST Must interpret results judiciously –Determine the threshold points for positive and negative results.

17. Study Strengths TST Same evaluator read TST results from “blinded” calipers. Used same PPD preparation. QFT Internal positive and negative controls. Colorimetric test (read by plate reader).

18. Limitations Small sample size BCG effect Isoniazid treatment in some* Not included other professionals

19. Limitations quantiFERON-TB Gold-in Tube: Cellestis –Refrigerated (2 year shelf life) –44 test/kit ($748.00) –After initial costs: $17/patient

20. Lessons Testing people is difficult if they do not come in. Cannot test immunocompromised. People more likely to come for one appointment.

22. What do you think? Is this a technology that should be implemented in hospitals in ______? How to present evidence for a New technology without a “gold standard”?