BCG Vaccination Does Not Cause False Positive IGRA Results
BCG vaccination does not affect IGRA test results for tuberculosis infection, making IGRAs the preferred test for TB screening in BCG-vaccinated individuals. 1 Unlike tuberculin skin tests (TST), which can show false positive results due to BCG vaccination, IGRAs specifically detect Mycobacterium tuberculosis infection without cross-reactivity to BCG vaccine antigens.
Why IGRAs Are Not Affected by BCG Vaccination
IGRAs (Interferon-Gamma Release Assays) measure immune response to antigens specific to Mycobacterium tuberculosis that are not present in:
- BCG vaccine strains
- Most non-tuberculous mycobacteria
This is because IGRAs use antigens from the RD1 genomic region of M. tuberculosis, which includes:
- ESAT-6 (Early Secretory Antigenic Target-6)
- CFP-10 (Culture Filtrate Protein-10)
These antigens are absent in all BCG vaccine strains, which explains why IGRAs maintain high specificity regardless of BCG vaccination status 2.
Evidence Supporting IGRA Specificity in BCG-Vaccinated Individuals
The CDC guidelines clearly state that the specificity of IGRAs using ESAT-6 or CFP-10 does not differ significantly between BCG-vaccinated and non-vaccinated individuals 2. This is further supported by European consensus statements indicating that IGRAs "are most notably not confounded by prior BCG vaccination" 2.
Multiple studies demonstrate:
- IGRAs show better correlation with TB exposure than TST in BCG-vaccinated populations 2
- IGRAs better discriminate between M. tuberculosis and environmental mycobacteria 2
- The CDC recommends using IGRAs for testing individuals who have received BCG to increase diagnostic specificity 1
Comparing TST and IGRA in BCG-Vaccinated Individuals
The differences between these tests are significant:
| Test Feature | TST | IGRA |
|---|---|---|
| Affected by BCG | Yes - can cause false positives | No - maintains specificity |
| Specificity in BCG-vaccinated | ~85-86% | ~99% for QFT-GIT, ~88% for T-SPOT.TB [2] |
| Cross-reactivity | Reacts to BCG and some NTM | Minimal cross-reactivity |
| Visit requirements | Two visits (placement and reading) | Single visit |
Clinical Implications and Recommendations
When testing BCG-vaccinated individuals for latent TB infection:
Use IGRAs as first-line tests - The CDC recommends IGRAs for BCG-vaccinated individuals to improve specificity and treatment acceptance 1
Consider age-specific recommendations:
- For children under 5 years: TST may be preferred
- For children over 5 years and adults: IGRAs are appropriate 1
In BCG-vaccinated populations:
- Positive TST results may persist for up to 10 years after vaccination 2
- TST results may be falsely positive due to BCG, especially with recent vaccination
Potential Pitfalls and Caveats
While IGRAs are not affected by BCG vaccination, be aware of these limitations:
Certain NTM infections may cause false positive IGRAs:
- M. kansasii
- M. marinum
- M. szulgai These species share RD1 region homology with M. tuberculosis 3
Indeterminate results can occur in approximately 15% of IGRA tests 4, particularly in:
- Immunocompromised patients
- Improper specimen handling
- Technical laboratory issues
Agreement between TST and IGRA is generally poor in BCG-vaccinated populations due to false-positive TST results 2, 5
In conclusion, IGRAs maintain their specificity regardless of BCG vaccination status and are the preferred test for TB screening in BCG-vaccinated individuals to avoid false positive results that commonly occur with TST.