BCG Vaccination Does NOT Cause Positive IGRA Results
No, BCG vaccination does not result in a positive Interferon-Gamma Release Assay (IGRA) report. This is the primary advantage of IGRAs over the tuberculin skin test (TST), which is frequently affected by prior BCG vaccination 1.
Why IGRAs Are Not Affected by BCG
IGRAs use highly specific M. tuberculosis antigens (ESAT-6 and CFP-10) that are absent from all BCG vaccine strains, making them unaffected by BCG vaccination regardless of when or how many times the vaccine was administered 1.
The CDC explicitly states that pooled IGRA specificity was 99% in populations unlikely to have M. tuberculosis infection, compared to only 85% for TST in the same populations, with the lower TST specificity directly attributable to false-positive results from BCG vaccination 1.
Multiple international guidelines confirm that the specificity of IGRAs does not differ significantly between BCG-vaccinated and non-vaccinated individuals when comparing cohorts with similar infection risks 1.
Clinical Evidence Supporting This Distinction
In BCG-vaccinated Greek army recruits with positive TST results (≥10mm), only 11.4% had positive IGRA results, demonstrating that the vast majority of positive TSTs in this population were false positives from BCG vaccination 2.
A study of 336 children found that the discordant pattern of IGRA-negative/TST-positive was significantly associated with BCG vaccination, confirming that BCG causes TST positivity but not IGRA positivity 3.
Among BCG-vaccinated foreign-born individuals with positive TST, patient characteristics (age, sex, country of origin) and TST size predicted IGRA positivity, indicating that positive IGRAs reflected true M. tuberculosis infection rather than BCG vaccination 4.
Important Caveats About IGRA Specificity
Three nontuberculous mycobacteria (M. kansasii, M. marinum, and M. szulgai) can cause false-positive IGRA results because they share the RD1 gene segment with M. tuberculosis 1, 5. However, this is rare and unrelated to BCG vaccination.
M. leprae also contains these antigens, but this is clinically uncommon and distinct from BCG cross-reactivity 1.
Why This Matters Clinically
The American Thoracic Society/CDC guidelines specifically recommend IGRAs for BCG-vaccinated persons to avoid the false-positive TST results that lead to unnecessary treatment 1, 6.
Many international guidelines (Germany, Italy, Spain, Netherlands, Canada for low-risk contacts) recommend a two-step approach: TST followed by confirmatory IGRA if TST is positive in BCG-vaccinated individuals, precisely because IGRA will be negative if the TST positivity is due to BCG alone 1.
In BCG-vaccinated children, IGRAs show better correlation with TB exposure than TST and are not confounded by vaccination history 1.
Practical Application
If a BCG-vaccinated person has a positive TST but negative IGRA, the TST positivity is almost certainly due to BCG vaccination rather than true M. tuberculosis infection 2.
If both tests are positive in a BCG-vaccinated person, the IGRA positivity indicates true M. tuberculosis infection (either latent or active disease requiring further evaluation) 4.
A positive IGRA result should never be attributed to BCG vaccination—it always indicates either true M. tuberculosis infection or, rarely, infection with M. kansasii, M. marinum, or M. szulgai 1, 5.