IGRA is a whole-blood test that can help to diagnose M. tuberculosis infection. Like TST, it does not differentiate between TB infection and TB disease. IGRA measures the cell-mediated immune response of people with TB infection. T-cells of infected people are sensitized to TB and respond to stimulation with peptides simulating those expressed by TB bacteria by secreting a cytokine called interferon-gamma. IGRA uses peptides from proteins made almost exclusively by M. tuberculosis and other mycobacteria from the M. tuberculosis complex. These proteins are absent from BCG vaccines and from most non-tuberculous mycobacteria. Special blood collection tubes coated with peptides from the TB antigenic proteins are used to collect and incubate the blood. Interferon-gamma is released when the blood from infected individuals is incubated with the antigens; this is not the case for people without TB infection. An enzyme-linked immunosorbent assay test is used to detect and quantify the amount of interferon-gamma released.
The advantages of IGRA include that the test requires only a single visit, results are available within 24 hours, and prior BCG vaccination does not cause a false-positive result. Disadvantages include that the test is more expensive, it requires phlebotomy, the blood sample must be processed quickly, laboratory facilities are required, and (as for TST) accuracy may be limited in people living with HIV (62).
In practice, the availability and affordability of tests will determine the choice by clinicians and programme managers. TST may require significantly fewer resources than IGRA, and may be more familiar to practitioners in resource-constrained settings, but recurrent global shortages and stockouts of tuberculin PPD have reduced its use in scaling up the programmatic management of TPT. See also Table 4.1 in the WHO operational handbook on tuberculosis. Module 1: prevention – tuberculosis preventive treatment (15). Novel skin tests will be reviewed by WHO in 2022.