QuantiFERON-TB Gold and BCG Vaccination
No, prior BCG vaccination will not cause a positive QuantiFERON-TB Gold test. The test is specifically designed to avoid this problem by using antigens (ESAT-6 and CFP-10) that are absent from all BCG vaccine strains. 1
Why QuantiFERON-TB Gold Is Not Affected by BCG
The key advantage of QuantiFERON-TB Gold over the tuberculin skin test is that it uses synthetic peptides representing ESAT-6 and CFP-10 proteins, which are present in Mycobacterium tuberculosis but absent from all BCG vaccine strains. 1 This fundamental design difference eliminates the false-positive results that plague tuberculin skin testing in BCG-vaccinated populations.
The tuberculin skin test (TST) uses purified protein derivative (PPD) that contains antigens shared with BCG vaccine strains and nontuberculous mycobacteria, leading to false-positive reactions in vaccinated individuals. 1
In contrast, QuantiFERON-TB Gold measures interferon-gamma release only in response to M. tuberculosis-specific proteins that BCG lacks. 1
Clinical Evidence Supporting BCG Independence
Multiple studies and guidelines confirm this BCG independence:
CDC guidelines explicitly state that QuantiFERON-TB Gold is expected to be more specific for M. tuberculosis than tests using tuberculin PPD as antigen, specifically because ESAT-6 and CFP-10 are absent from all BCG vaccine strains. 1
In a study of 216 BCG-vaccinated Japanese nursing students at low risk for TB infection, QuantiFERON-TB Gold demonstrated 98.1% specificity, confirming minimal false-positive results from vaccination. 1
Research in BCG-vaccinated Greek army recruits showed significant discordance between TST (5.4% positive) and QuantiFERON-TB Gold (only 11.4% of TST-positive subjects were QFT-positive), with overall poor agreement (kappa = 0.02), demonstrating that BCG vaccination causes false-positive TST results but not false-positive QuantiFERON results. 2
A German contact investigation study found that QuantiFERON-TB Gold was unaffected by BCG vaccination status, while positive TST reactions were closely associated with prior BCG vaccination (OR 24.7). 3
Important Caveats
The only exception to BCG independence involves three rare nontuberculous mycobacteria: M. kansasii, M. szulgai, and M. marinum contain ESAT-6 and CFP-10 proteins and could theoretically cause false-positive QuantiFERON-TB Gold results if someone is sensitized to these organisms. 1 However, these infections are uncommon and unrelated to BCG vaccination.
Clinical Implications
QuantiFERON-TB Gold is the preferred test for BCG-vaccinated individuals when screening for latent TB infection. 1, 4
A positive QuantiFERON-TB Gold result in a BCG-vaccinated person should be interpreted as true M. tuberculosis infection, not vaccine effect. 1
Studies show that among BCG-vaccinated individuals with positive TST results, only 7.7-30% have positive QuantiFERON-TB Gold results, indicating that most positive TSTs in this population are false positives from vaccination. 5, 6