1. TB Testing Current Thinking
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TB Testing
Current Thinking
Darlene Morse, RN, M. Ed., CHES, CIC
Public Health Nurse Program Manager
Bureau of Infectious Disease Control
Division of Public Health Services
© 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries.
The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION. 1

2. History of Mantoux Skin Testing
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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
© 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries.
The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

3. Purified Protein Derivative--PPD
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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 hours
Problem with nontuberculosis mycobacteria or vaccination with Bacille Calmette-Guérin (BCG) vaccine
Live attenuated strain of Mycobacterium bovis
© 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries.
The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

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

8. An induration of 5 or more millimeters is considered positive in
-HIV-infected persons
-A recent contact of a person with TB disease
-Persons with fibrotic changes on chest radiograph consistent with prior TB
-Patients with organ transplants
-Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for 1 month or longer, taking TNF-a antagonists)
An induration of 10 or more millimeters is considered positive in
-Recent immigrants (< 5 years) from high-prevalence countries
-Injection drug users
-Residents and employees of high-risk congregate settings
-Mycobacteriology laboratory personnel
-Persons with clinical conditions that place them at high risk
-Children < 4 years of age
- Infants, children, and adolescents exposed to adults in high-risk categories
An induration of 15 or more millimeters is considered positive in any person, including persons with no known risk factors for TB. However, targeted skin testing programs should only be conducted among high-risk groups.

9. Interferon-Gamma Release Assays (IGRAs)
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
© 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries.
The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION. 9

10. Differences in Current IGRAs
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Differences in Current IGRAs
QFT-GIT
T-Spot
Measurement
IFN-γ concentration
Number of IFN-γ producing cells (spots)
Possible Results
Positive, Negative, indeterminate
Positive, negative, indeterminate, borderline
© 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries.
The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION. 10

11. Overall Sensitivity
T-Spot
90%
QFT-GIT
80%
TST

12. Overall Specificity IGRAs
>95% in low-TB incidence settings, not affected by BCG vaccine
TST
97% in populations not vaccinated by BCG
~60% in populations receiving BCG (varies by timing of BCG administration)

13. Limitations of IGRA accuracy
Testing cut offs were designed to maximize sensitivity/specificity
No gold standard for LTBI (or Cx neg 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

14. 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

15. 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

16. 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)

17. Dorman, S. E. , Belknap, R. , Graviss, E. A. , Schluger, N
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
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

18. 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?

19. 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, Morbidity and Mortality Weekly Report, 59(RR05), p Centers for Disease Control and Prevention. Accessed at:
Nayak, S. & Acharjya, B. (2012). Mantoux test and its interpretation. Indian Dermatology Online Journal, 3(1), p Accessed at:

20. Infectious Disease Investigation Unit
4/19/2017 2:38 AM
For More Information
Darlene Morse, RN
Infectious Disease Investigation Unit
© 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries.
The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.