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Darlene Morse, RN, M. Ed., CHES, CIC Public Health Nurse Program Manager

Darlene Morse, RN, M. Ed., CHES, CIC Public Health Nurse Program Manager Bureau of Infectious Disease Control Division of Public Health Services. TB Testing Current Thinking. History of Mantoux Skin Testing. Originally developed by Dr. Robert Koch in 1890 What else was he known for?

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Darlene Morse, RN, M. Ed., CHES, CIC Public Health Nurse Program Manager

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  1. Darlene Morse, RN, M. Ed., CHES, CIC Public Health Nurse Program Manager Bureau of Infectious Disease Control Division of Public Health Services TB Testing Current Thinking

  2. History of Mantoux Skin Testing • Originally developed by Dr. Robert Koch in 1890 • What else was he known for? • Mantoux test (placing intradermally) developed • by Charles Mantoux and Clemens von Pirquetto in 1907 • Purified Protein Derivative (PPD) • Interpretation remains controversial

  3. Purified Protein Derivative--PPD • Delayed-type hypersensitivity (DTH) reaction to antigenic components in the tuberculin • DTH response is shown after infection with M. tuberculosis • Reaction to TST starts 5-6 hours after placement and reaches maximum 48-72 hours • Problem with nontuberculosis mycobacteria or vaccination with Bacille Calmette-Guérin (BCG) vaccine • Live attenuated strain of Mycobacterium bovis

  4. Insert 5 tuberculin units (TU) – 0.1 ml of PPD

  5. Released for use in 2001—Revised in 2005 2005-Two tests were approved by the FDA QuantiFERON™-TB Gold In-Tube test (QFT-GIT) T-Spot™ TB test (T-Spot) Blood tests that measures immune reactivity of M. tuberculosis and measures release of IFN-γ Interferon-Gamma Release Assays (IGRAs)

  6. Differences in Current IGRAs

  7. Overall Sensitivity

  8. Overall Specificity

  9. Limitations of IGRA accuracy • Testing cut offs were designed to maximize sensitivity/specificity • No gold standard for LTBI (or Cxneg active TB) this requires use of surrogate reference standards • Sensitivity: assessed in culture-positive patients • What is true for LTBI? • Specificity: assessed in people “unlikely” to have disease (no known exposure, low incidence setting) • Some “low risk” people might actually have been exposed to TB disease

  10. IGRA Limitations continued • IGRAs are indirect tests (measure immune response rather than detecting pathogens • Should we expect sensitivity in patients with culture + disease to be the same in patients with LTBI? • Host immunologic factors/status can alter test results • These same factors might allow progression of infection to disease… • Treatment can alter immunologic responses • Many published evaluations of IGRA performance have used different interpretive criteria than those approved by the FDA

  11. Routine testing with TST or IGRA is NOT Recommended • IGRAs can be used in place of (but not in addition to) TST in most situations • contact investigations • testing during pregnancy • screening of healthcare workers • those undergoing serial evaluation for TB infection • IGRAs preferred: • Persons who have received BCG (vaccine or CA therapy) • People who don’t return for readings

  12. TST Preferred • Children under 5 • Same day as a live virus vaccine is given or not until 4-6 weeks after the vaccine • MMR • Yellow fever vaccine • Small pox vaccine • (Use of IGRA in the setting of live virus vaccine has not been studied-but can be drawn the same day as live virus vaccine administration)

  13. Dorman, S. E., Belknap, R., Graviss, E. A., Schluger, N., Weinfurter, P., Wang, Y., Cronin, W., Hirsch-Moverman, Y., Teeter, L. D., Parker, M., Garrett, D. O. & Daley, C. L. (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), p. 77-87. Findings— After testing over 2418 healthcare workers in four large medical facilities. Using IGRA testing resulted in significantly higher conversion rates than the TST testing and the IGRA conversions appear to be falsely positive. Study did confirm using the IGRA with HCW’s with BCG vaccine history affirmed the use of IGRAs

  14. Questions Raised Why not do both tests together? Do health care workers need to be tested annually? Where do I find the Facility Risk Assessment? Where do I find the county data for my area? Other questions?

  15. References Mazaurek, G. H., Jereb, J., Vernon, A., Lobue, P., Goldberg, S. & Castro, K. (2010). Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection—United States, 2010. Morbidity and Mortality Weekly Report, 59(RR05), p. 1-25. Centers for Disease Control and Prevention. Accessed at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5905a1.htm Nayak, S. & Acharjya, B. (2012). Mantoux test and its interpretation. Indian Dermatology Online Journal, 3(1), p. 2-6. Accessed at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481914/

  16. For More Information Darlene Morse, RN Infectious Disease Investigation Unit 603-271-4494 Darlene.m.morse@dhhs.state.nh.us http://www.dhhs.nh.gov

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