Scope of IGRA Gold in Diagnosis of Tuberculosis
Interferon-Gamma Release Assays (IGRAs) may be used as aids in diagnosing both latent Mycobacterium tuberculosis infection and active tuberculosis, serving as valuable tools for surveillance and identifying persons likely to benefit from treatment. 1
Overview of IGRAs
- IGRAs detect sensitization to M. tuberculosis by measuring interferon-gamma (IFN-γ) release in response to antigens representing M. tuberculosis, providing an alternative to the traditional tuberculin skin test (TST) 1
- Currently, two FDA-approved commercial IGRAs are available: QuantiFERON-TB Gold In-Tube test (QFT-GIT) and T-SPOT.TB test (T-Spot) 2
- IGRAs were developed after recognizing that IFN-γ plays a critical role in regulating cell-mediated immune responses to M. tuberculosis infection 1
Advantages of IGRAs over TST
- IGRAs use M. tuberculosis-specific antigens (ESAT-6 and CFP-10) that are absent from BCG vaccine strains and most nontuberculous mycobacteria, significantly improving specificity 1, 2
- Only one patient visit is required for IGRAs, eliminating the need for return visits for test reading 2
- IGRAs are not affected by prior BCG vaccination, making them particularly valuable in vaccinated populations 2, 3
- IGRAs avoid subjective interpretation issues associated with TST reading 1
Clinical Applications
- CDC recommends that IGRAs may be used in all situations where TST is recommended, including contact investigations and evaluation of recent immigrants 2
- IGRAs are particularly valuable for testing persons who have received BCG vaccination or who are unlikely to return for TST reading 2
- In immunocompromised patients, using both TST and IGRA can increase sensitivity for detecting latent TB infection 2
- IGRAs can be used to aid in diagnosing tuberculids (cutaneous manifestations of TB) when PCR of skin biopsies is negative 4
Limitations and Considerations
- Sensitivity and specificity of IGRAs vary across different clinical contexts and populations 2, 3
- False-positive IGRA results can occur due to sensitization to certain nontuberculous mycobacteria (M. kansasii, M. szulgai, and M. marinum) that contain ESAT-6 and CFP-10 1
- Severe diabetes mellitus may influence IGRA results, potentially leading to false negatives 5
- For IGRAs to measure IFN-γ response accurately, a fresh blood specimen containing viable white blood cells is needed 1
Implementation Approaches
- A two-step approach may be used, where TST is performed first, followed by IGRA to increase overall diagnostic accuracy 2
- IGRAs can be used together with TST to increase sensitivity in certain high-risk populations 2
- In low TB incidence countries, detection and management of latent TB infection using IGRAs is a key component of TB control 2
Future Directions
- Research is ongoing to develop IGRAs that can distinguish between active TB and latent TB infection, which current IGRAs cannot differentiate 6
- Investigations into the prognostic value of IGRAs for predicting progression to active TB are underway 6
- Newer generation tests like QuantiFERON-TB Gold Plus (QFT-Plus) have shown high sensitivity and specificity comparable to existing IGRAs 5