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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
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
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
Insert 5 tuberculin
units (TU) – 0.1 ml
of PPD
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.
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
Differences in Current IGRAs
QFT-GIT
Measurement IFN-γ
concentration
Possible
Results
T-Spot
Number of
IFN-γ
producing
cells (spots)
Positive,
Positive,
Negative,
negative,
indeterminate indeterminate,
borderline
Overall Sensitivity
T-Spot
QFT-GIT
TST
90%
80%
80%
Overall Specificity
IGRAs
TST
>95% in low-TB
incidence settings, not
affected by BCG
vaccine
97% in populations not
vaccinated by BCG
~60% in populations
receiving BCG (varies
by timing of BCG
administration)
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
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
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
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)
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
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?
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/
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