After BCG vaccination, is the tuberculin skin test (TST) reliable for detecting tuberculosis infection?

Tuberculin Skin Test Reliability After BCG Vaccination

The tuberculin skin test (TST) remains a valid and recommended screening tool after BCG vaccination, though it has reduced specificity compared to interferon-gamma release assays (IGRAs), which are preferred in BCG-vaccinated individuals. 1

Key Principle: TST Should Still Be Used

• Tuberculin skin testing is not contraindicated in BCG-vaccinated persons, and positive results should be used to support or exclude the diagnosis of M. tuberculosis infection. 1
• The CDC explicitly states that prior BCG vaccination should not prevent tuberculin skin testing, and positive reactions should be interpreted as indicating true M. tuberculosis infection, especially in individuals from high TB-prevalence countries or with other risk factors. 2

Understanding BCG's Impact on TST Specificity

The effect of BCG on TST varies dramatically based on age at vaccination and time since vaccination:

BCG Given in Infancy

• Only 8.5% of infants vaccinated with BCG will have false-positive TST ≥10 mm attributable to BCG. 3
• After 10 years from infant BCG vaccination, only 1% have false-positive TST results. 3
• BCG effect on TST is minimal when received in infancy, especially ≥10 years after vaccination. 3

BCG Given After Infancy

• 41.8% of individuals vaccinated after their first birthday have false-positive TST ≥10 mm. 3
• After 10 years, 21.2% still have false-positive results. 3
• BCG vaccination after infancy may influence TST results for up to 55 years after vaccination, though the effect is attenuated after 15 years. 4

Age-Dependent Effects in Children

• BCG vaccination affects TST responses in IGRA-negative children less than 5 years old but not in older children. 5
• In children over 5 years of age, BCG vaccination has little impact on TST size. 5

TST Interpretation Thresholds in BCG-Vaccinated Individuals

Use ≥10 mm induration as positive in BCG-vaccinated individuals who: 1, 2

• Are contacts of someone with infectious TB
• Were born in or have resided in a high TB-prevalence country
• Have continuous exposure to high-prevalence populations

Use ≥5 mm induration as positive in BCG-vaccinated individuals who: 2

• Are HIV-infected
• Are recent close contacts of an active TB case
• Have fibrotic changes on chest radiograph consistent with prior TB

Why IGRAs Are Preferred Over TST

Interferon-gamma release assays (IGRAs) should be the preferred test in BCG-vaccinated individuals because they eliminate the specificity problem entirely: 1

• IGRA specificity is 99% compared to TST specificity of 85% in the same populations, with the lower TST specificity directly attributable to false-positive results from BCG vaccination. 1, 6
• IGRAs use M. tuberculosis-specific antigens (ESAT-6 and CFP-10) that are absent from all BCG vaccine strains, making them completely unaffected by BCG vaccination regardless of when or how many times the vaccine was administered. 6
• IGRAs require only a single patient visit and eliminate reader bias. 7
• A positive IGRA result should never be attributed to BCG vaccination—it always indicates true M. tuberculosis infection. 6

Practical Algorithm for BCG-Vaccinated Individuals

1. First-line approach: Use IGRA testing (QuantiFERON-TB Gold or T-SPOT) rather than TST in BCG-vaccinated individuals. 1, 7

2. If TST is used instead:

   • Apply appropriate induration thresholds (≥10 mm for most, ≥5 mm for high-risk groups). 1, 2
   • Consider age at BCG vaccination and time elapsed since vaccination when interpreting results. 3, 4
   • In children <5 years old, be aware that BCG may cause false-positive results; in children >5 years old, BCG has minimal impact. 5

3. Two-step approach: Many international guidelines recommend TST followed by confirmatory IGRA if TST is positive in BCG-vaccinated individuals, because IGRA will be negative if the TST positivity is due to BCG alone. 6

4. If positive screening test: Perform chest radiograph to exclude active TB disease. 7, 2

5. If latent TB confirmed: Initiate appropriate treatment for latent TB infection and evaluate close contacts. 7, 2

Common Pitfalls to Avoid

• Do not dismiss positive TST results as "just BCG" in individuals from high TB-prevalence countries or with TB exposure—treat as true infection. 1, 2
• Do not assume BCG effect wanes after 10 years if vaccination occurred after infancy—effects can persist up to 55 years. 4
• Recognize that tuberculin reactivity caused by BCG can be boosted by repeated tuberculin skin testing, potentially prolonging reactivity. 1
• BCG-induced reactivity that has weakened might be boosted by administering a tuberculin skin test 1 week to 1 year after the initial test. 1

Bottom Line on Reliability

The TST is reliable for detecting TB infection in BCG-vaccinated individuals, but has reduced specificity leading to false-positive results. 1 The size of a tuberculin reaction in a BCG-vaccinated person is not a factor in determining whether the reaction is caused by M. tuberculosis infection or prior BCG vaccination. 1 Therefore, IGRAs are the preferred diagnostic approach in BCG-vaccinated populations to avoid unnecessary treatment of false-positive results while maintaining excellent sensitivity for true infection. 1