2016 OPAM Mid-Year Educational Conference, Sponsored by AOCOPM Sunday, March 13, 2016

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1 Learning Objectives Tuberculosis Case Discussions: Evaluation for Tuberculosis Infection Melissa C. Overman, DO, MPH, CHES, FAOCOPM Describe appropriate technique for TST placement, reading and interpretation Describe the different indications for TST and IGRA screening tests Describe appropriate IGRA interpretation, including results for low-risk populations. Identify four tuberculosis resources for your own clinical practice. Case 1 The School Bus Driver Variables 62 yo BF, US born (South Carolina), had an employment TST as she wants to drive the school bus for the local school district. TST is reported as 10-15mm. She is asymptomatic and has a completely negative CXR. Clinical Otherwise healthy No medications No known exposure to TB Reactor or Converter Practical Aplisol or Tubersol Placement technique Reading and Interpretation Documentation Tuberculin reactor- an individual with a + skin test reaction (based on risk factors) with no clear documentation or history of being skin tested in the last two years. Convertor any individual with a negative skin test documented as baseline but who developed positive reaction with increase in reaction size of >10 mm within the past two years. Tuberculin Skin Testing Immune Response to Tuberculin In 1890, Robert Koch announced a cure for tuberculosis - 8 years after discovering the cause of TB Cure consisted of subcutaneous doses of tuberculin Subsequently found to be ineffective Ultimately became a widely-used diagnostic test for TB infection A positive test is result of a delayed-type hypersensitivity (DTH) response Reaction characterized by edema and formation of induration - measure in mm Reaction generally complete in hours DTH response detectable 2-10 weeks after initial infection V-1

2 Mantoux Skin Testing Method Aplisol and Tubersol Developed by Charles Mantoux in This is the standard tuberculin skin test. Intradermal injection of 0.1 ml of 5 TU PPD tuberculin Two PPD antigen products licensed by FDA: Tubersol Aplisol San Diego VAMC (2009) 2.2 (avg) to 14 in retested with QFT 83% negative 8 retested with both PPD 87.5% (+) with Aplisol 100% (-) with Tubersol Children s Rehab Hospital (2006) 1203 tested in annual screen 24 (2%) (+) with Aplisol 23 retested with Tubersol 74% were (-) Produce wheal 6 mm to 10 mm in diameter Take Home Message (CDC) pick one and stick with it Needle Too Deep Needle Too Shallow V-2

3 Reading a TST Two-step TST Testing False (+) TST False (-) TST Case 2 Foreign-born College Student 28yo male graduate student arrived from India two weeks ago for classes. School required screening TST placed and read as 15mm. Asymptomatic and CXR negative. No HIV risk factors elicited. Variables Testing Alternatives Clinical Otherwise healthy No medications No known exposure to TB History of BCG vaccine Practical BCG and Testing for MTB Testing Alternatives Interpretation of IGRA Blood Assay for M.Tuberculosis (BAMT) Interferon gamma Release Assay (IGRA) QuantiFERON-TB Gold T-Spot.TB Bacillus Calmette-Guerin (BCG) vaccine Utilized in many countries to prevent serious extrapulmonary tuberculosis, especially meningitis, in infants. Used in the US for Bladder CAtreatment Mycobacterium bovis Previous BCG vaccination is not a C/I totst Advantages Single patient visit Less reader bias Not affected by BCG or most other mycobacterium, except M. kansasii, M. marinum, M. szulgai Disadvantages More expensive Venipuncture required Specimen management Sensitivity and Specificity V-3

4 IGRA Interpretation Case 3 HCW with Negative IGRA 48yo BF works as floor nurse at local hospital. She is subject to annual tuberculosis screening by her employer documented negative TSTs positive IGRA. No known exposure. Repeat IGRA was negative. IGRA Reversion Among HCW 2 Studies Clinical Resources Central Arkansas Veterans Healthcare System 2303 HCW tested: 2232 (96.9%) negative 69 (3%) positive Repeat Test of Negatives: 71 (3.2%) converted (only 2 w/ TST conversion) 31 (45%) reverted (80% with previous neg TST) Cross-sectional multi-site study 2122 HCW completed Baseline test reversion 29/54 (53.7%) TST 67/118 (56.8%) QFT-GIT 92/144 (63.9%) T-SPOT Conversions 21/2293 (0.9%) TST 138/2263 (6.1%) QFT-GIT 177/2137 (8.3%) T-SPOT Short-Term IGRA Variability Repeatability and Reproducibility State Tuberculosis Programs Regional Tuberculosis Centers: Consultation Webinars Publications CDC: Mantoux tuberculin skin test poster TSTin3D.com Questions? Melissa C. Overman, DO, MPH, CHES, FAOCOPM melissa.overman@dhec.sc.gov V-4

5 References Centers for Disease Control and Prevention. Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005.MMWR 2005;54(No.RR-17). Centers for DiseaseControland Prevention. UpdatedGuidelinesfor UsingInterferon Gamma ReleaseAssays to Detect Mycobacterium tuberculosis Infection United States, MMWR 2010;59(No. RR-5). Dorman, S.E., Belknap, R., et al. (2014). Interferon-γ release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States. American Journal of Respiratory and Critical Care Medicine, 189(1): Gillenwater, K.A., Sapp, S.C., et al. (2006). Increase intuberculinskintest converters amonghealth care workers after achangefrom TubersoltoAplisol. AmericanJournalof Infection Control,34: Joshi, M., Monson, T.P., et al. (2014). IFN-γ release assay conversions and reversions. Challenges with serial testingin U.S. health careworkers. Annalsof theamericanthoracicsociety, 11(3): Mehta, S.R., MacGruder, C., et al. (2009). Differences in tuberculin reactivity as determined in a veterans administration employee health screening program. Clinical and Vaccine Immunology, 16(4): Public Health Image Library. V-5