Tests for Prior Tuberculosis Exposure
Two tests are used to detect prior exposure to tuberculosis: the Tuberculin Skin Test (TST), also called the Mantoux test, and Interferon-Gamma Release Assays (IGRAs), which include QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB. 1
Primary Testing Options
Tuberculin Skin Test (TST/Mantoux Test)
- The TST involves intradermal injection of purified protein derivative (PPD) tuberculin, with measurement of induration (not erythema) after 48-72 hours 1, 2
- An induration diameter ≥5 mm is considered positive for any contact of an infectious TB case 1
- The test detects a delayed-type hypersensitivity response indicating prior exposure to Mycobacterium tuberculosis or BCG vaccination 3, 4
Interferon-Gamma Release Assays (IGRAs)
- QuantiFERON-TB Gold (QFT-G) measures interferon-gamma release from lymphocytes when blood is incubated with M. tuberculosis-specific proteins ESAT-6 and CFP-10 1
- T-SPOT.TB (ELISPOT test) uses a similar principle but is formatted differently 1
- IGRAs are unaffected by BCG vaccination and most non-tuberculous mycobacteria, providing greater specificity than TST 1, 5
When to Use Each Test
IGRA is Preferred Over TST in:
- Patients with prior BCG vaccination, as TST produces false-positives in this population 1, 6
- Situations where patient return for TST reading (48-72 hours later) is unlikely 7
- Patients already on immunosuppressive therapy 7
- Foreign-born individuals from countries where BCG vaccination is routine 1
Either Test Can Be Used:
- The CDC states that QFT-G can be used in all circumstances where TST is currently used, including contact investigations 1
- QFT-G should be used in place of, not in addition to, TST 1
- A positive result from either test should prompt the same evaluation and management 1
Critical Testing Timing
Initial Testing
- Test all contacts without documented prior TB or latent TB infection (LTBI) at initial encounter, ideally within 7 days for high-priority contacts 1
Follow-Up Testing (The 8-10 Week Window)
- If the initial test is negative, repeat testing must occur 8-10 weeks after the last exposure using the same test type 1, 8
- This timing reflects the window period required for the immune system to mount a detectable response after M. tuberculosis exposure 1, 8
- A negative test obtained <8 weeks after exposure is unreliable for excluding infection 1, 8
Important Clinical Caveats
Do Not Retest These Groups:
- Persons with documented prior LTBI or TB disease do not need repeat testing after exposure 1, 7
- Instead, evaluate them clinically if TB disease is suspected 1
Test Limitations in Immunocompromised Patients:
- Both QFT-G and TST may be less sensitive in severely immunosuppressed adults, children <5 years, or patients about to receive TNF-α inhibitors 1
- A negative result alone should not exclude M. tuberculosis infection in these high-risk groups 1
BCG Vaccination Considerations:
- A positive TST in a BCG-vaccinated contact of an infectious TB case should be interpreted as evidence of recent M. tuberculosis infection, not just vaccine effect 1
- The distortion from BCG is almost insignificant in adults >30 years of age 1
- TST may be false-negative in patients on corticosteroids >1 month or immunomodulators >3 months 1
Two-Step Testing:
- The routine two-step TST procedure (used to detect boosting in serial testing programs) should typically NOT be used for contact investigations 1
- A contact whose second test is positive after an initial negative result should be classified as recently infected, not as a booster phenomenon 1