How should tuberculosis (TB) screening be approached in individuals who have received the Bacillus Calmette-Guérin (BCG) vaccine?

Tuberculosis Screening in BCG-Vaccinated Individuals

Prior BCG vaccination should not prevent tuberculin skin testing, and positive reactions (≥10 mm induration) should be interpreted as indicating true M. tuberculosis infection and managed accordingly, especially in individuals from high TB-prevalence countries or with other risk factors. 1

Key Principle: BCG History Does Not Contraindicate Testing

• Tuberculin skin testing is not contraindicated in BCG-vaccinated persons, and results should be used to support or exclude the diagnosis of M. tuberculosis infection. 1
• There is no reliable method to distinguish tuberculin reactions caused by BCG vaccination from those caused by natural M. tuberculosis infection. 1

Interpretation Thresholds Based on Risk Factors

Use ≥10 mm Induration as Positive in BCG-Vaccinated Individuals When:

• The person is a contact of someone with infectious TB, particularly if transmission to others has occurred 1
• The person was born in or has resided in a high TB-prevalence country 1
• The person has continuous exposure to high-prevalence populations (healthcare workers, homeless shelter staff, drug treatment center workers) 1
• The person is an injection drug user 1

Use ≥5 mm Induration as Positive in BCG-Vaccinated Individuals When:

• The person is HIV-infected (or consider treatment even if nonreactive to tuberculin due to potential anergy) 1
• The person is a recent close contact of an active TB case 1
• The person has fibrotic changes on chest radiograph consistent with prior TB 1

Rationale for Not Attributing Positive Tests to BCG

Several evidence-based reasons support treating positive reactions as true infection rather than vaccine effect: 1

• Tuberculin test conversion rates after BCG vaccination may be much less than 100% 1
• The mean reaction size among BCG recipients is often <10 mm 1
• Tuberculin sensitivity from BCG tends to wane over time after vaccination 1
• Reactions >20 mm of induration are unlikely to be caused by BCG 1
• Most BCG-vaccinated persons in the U.S. are from high-prevalence areas where the probability of true infection is substantial 1

Alternative Testing: Interferon-Gamma Release Assays (IGRAs)

IGRAs (such as QuantiFERON-TB Gold) are preferred over TST in BCG-vaccinated individuals because they eliminate false-positive results caused by BCG cross-reaction. 2

Advantages of IGRA Testing:

• Higher specificity than TST in BCG-vaccinated populations 2
• Measures interferon-gamma release to M. tuberculosis-specific antigens not found in BCG vaccines 2
• Requires only a single patient visit 2
• Eliminates reader bias and placement errors 2
• Does not trigger anamnestic (boosting) response 2

When to Prefer IGRA:

• Children <3 years old with BCG vaccination at birth (BCG interference is more significant in this age group) 3
• Serial testing situations where boosting phenomenon could complicate interpretation 2
• When BCG was administered recently or multiple times 1

Two-Step Testing for Serial Screening Programs

For BCG-vaccinated individuals entering serial testing programs (e.g., healthcare workers), two-step baseline testing should be performed to identify boosted reactions and prevent misclassification as new infections. 1, 4

Two-Step Protocol:

• Perform initial TST at baseline 1, 4
• If negative, repeat TST 1-3 weeks later 1, 4
• If second test is positive, classify as previously infected (boosted reaction), not new conversion 1, 4
• This prevents unnecessary contact investigations and inappropriate preventive therapy 1, 4

Defining True Conversion in BCG-Vaccinated Individuals:

• An increase in induration of ≥10 mm within 2 years indicates true skin test conversion from recent infection 1

Common Pitfalls to Avoid

• Do not assume large reactions are due to BCG vaccination – the probability that a positive reaction results from true M. tuberculosis infection increases with reaction size, contact history, and country of origin. 1
• Do not skip testing because of BCG history – this leads to missed diagnoses in high-risk populations. 1
• Do not use ≥15 mm threshold routinely – while reactions >20 mm are unlikely from BCG alone, the standard ≥10 mm threshold is appropriate for most BCG-vaccinated individuals with risk factors. 1
• Do not forget anergy testing in HIV-infected BCG recipients – they may be nonreactive despite true infection and should be considered for preventive therapy regardless of TST result. 1

Follow-Up After Positive Test

• Perform chest radiograph to exclude active TB disease 2, 5
• If chest radiograph is normal, treat for latent TB infection according to standard guidelines 1
• Evaluate family members and close contacts for TB infection 2