Interferon-Gamma Release Assays (IGRAs) as Alternatives to TB Skin Test
The QuantiFERON-TB Gold (QFT-G) test is the recommended alternative to tuberculin skin testing (TST) for detecting Mycobacterium tuberculosis infection, as it offers higher specificity, requires only one patient visit, and is not affected by prior BCG vaccination. 1
Advantages of IGRAs Over TST
- IGRAs such as QFT-G measure the release of interferon-gamma in blood samples after stimulation with M. tuberculosis-specific antigens (ESAT-6 and CFP-10), providing results within 24 hours without requiring a follow-up visit 1
- Unlike TST, QFT-G is not affected by prior BCG vaccination and has minimal cross-reactivity with most non-tuberculous mycobacteria, resulting in higher specificity 1, 2
- QFT-G eliminates reader bias and errors associated with TST placement and reading 1
- QFT-G does not trigger an anamnestic response (boosting), which can occur with repeated TST administration 1
Available IGRA Options
- QuantiFERON-TB Gold In-Tube (QFT-GIT): FDA-approved blood test that uses peptides representing ESAT-6, CFP-10, and TB7-7 as TB-specific antigens 1, 3
- T-SPOT.TB: Another commercially available IGRA that enumerates cells releasing IFN-γ after stimulation with similar antigens (available in Europe but mentioned in US guidelines) 1
Clinical Scenarios Where IGRAs Are Particularly Beneficial
- Patients with previous BCG vaccination, as IGRAs eliminate false positives due to cross-reactivity 4, 3
- Immunocompromised patients, such as those with chronic inflammatory diseases on immunosuppressive therapy, where TST may have reduced sensitivity 1, 5
- Patients requiring TB screening before starting biologic DMARDs or other immunosuppressive therapies 1
- Dialysis patients who often have high rates of anergy with TST 1
- Patients who may have difficulty returning for TST reading after 48-72 hours 1
Limitations of IGRAs
- Blood specimens must be processed within 12 hours after collection 1
- Laboratory experience with the assay may be limited in some settings 1
- Test reproducibility is lower when measured IFN-γ levels are near the cut-off point 1
- Substantial amounts of IFN-γ in the nil sample (negative control) can invalidate results 1
- May be more expensive than TST 1
Implementation Considerations
- QFT-G requires phlebotomy and proper handling of blood specimens 1
- Results can be available in less than 24 hours after testing 1
- No need for a second patient visit to read results as with TST 1
- IGRAs show moderate concordance with TST (kappa values ranging from 0.33 to 0.60 in various studies) 1, 4, 3
- In populations with routine BCG vaccination, IGRAs are particularly valuable due to their higher specificity 3
Special Populations
- In transplant candidates, QFT-G may more accurately determine the risk for latent TB infection compared to TST 6
- For patients with chronic inflammatory diseases such as rheumatoid arthritis or lupus, IGRAs may be more reliable than TST, especially when patients are on immunosuppressive therapy 5, 4
- For international travelers returning from TB-endemic areas, either TST or IGRA can be used for screening 1
By ordering a QuantiFERON-TB Gold test as part of your patient's lab work, you can effectively screen for TB infection with greater specificity and convenience than the traditional tuberculin skin test.