How to use: interferon γ release assays for tuberculosis

Diagnosis and treatment of latent tuberculosis infection (LTBI) is important to reduce risk of progression to active tuberculosis (TB) disease. For the past century the tuberculin skin test (TST) has been used as a measure of exposure to Mycobacterium tuberculosis (MTB), but this test has limitations in test performance, sensitivity and specificity. Interferon γ release assays (IGRA), like TST, measure host immune response to MTB. IGRA are designed to be more specific for the diagnosis of LTBI than TST in patients with previous BCG or exposure to non-tuberculous mycobacteria, detecting interferon γ generated by T cells in response to antigens more specific to MTB. Although developed as an alternative to TST, recent data, particularly in children, suggest IGRA have their own limitations. Superiority to TST as a diagnostic test in children has not been demonstrated. Neither test discriminates between current or past MTB infection, or between latent infection and active disease. This article reviews the current literature on sensitivity and specificity of IGRA in the diagnosis of LTBI, and summarises current NICE recommendations for the use of IGRA in combination with TST. Although not developed for this purpose, in clinical practice IGRA have also been used as a diagnostic test for active TB. The gold standard for diagnosis of active TB disease is microbiological confirmation by culture of MTB. This article discusses the utility of IGRA as an adjunct to diagnosis of active TB disease, but emphasises that IGRA do not have sufficient sensitivity or specificity to exclude or confirm active TB disease.