Diagnosis and Management of Tuberculosis Infection

Overview of IGRAs

The Centers for Disease Control and Prevention recommends that IGRAs may be used in all situations where the tuberculin skin test is recommended, including contact investigations and evaluation of recent immigrants, as they detect sensitization to M. tuberculosis by measuring interferon-gamma release in response to antigens representing M. tuberculosis 1, 2
IGRAs measure host immune response to M. tuberculosis, similar to the tuberculin skin test, but with improved specificity, and two FDA-approved commercial IGRAs are currently available: QuantiFERON-TB Gold In-Tube test and T-SPOT.TB test 1, 2

IGRAs are not affected by prior BCG vaccination, improving specificity in vaccinated populations, and they require only one patient visit, eliminating the need for return visits for test reading 3
IGRAs use M. tuberculosis-specific antigens that are absent from BCG vaccine strains and most nontuberculous mycobacteria, reducing false-positive results 4

Sensitivity and specificity of IGRAs vary across different clinical contexts and populations, with a strength of evidence that is not clearly defined 5, 1

IGRAs may be used as aids in diagnosing M. tuberculosis infection, both latent infection and infection manifesting as active tuberculosis, particularly for surveillance purposes and to identify persons likely to benefit from treatment 2
The CDC recommends using IGRAs in individuals who have received BCG vaccination or are unlikely to return for TST reading, and in immunocompromised patients, using both TST and IGRA can increase sensitivity for detecting LTBI 3

Guidelines recommend a two-step approach to IGRA use, where TST is used first, followed by IGRA, either when TST is negative or positive, to increase sensitivity and specificity 5
IGRAs can also be used together with TST to increase sensitivity, or as a replacement for TST in certain situations 5

In high TB incidence settings, IGRAs are most useful for screening high-risk groups, and in low TB incidence countries, detection and management of LTBI using IGRAs is a key component of TB control 5
IGRAs may be affected by the presence of certain nontuberculous mycobacteria, and high-dose steroids can suppress TST reactions, making IGRA testing less affected by steroid therapy 4, 3