How to use: interferon γ release assays for tuberculosis

Abstract

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.

Advances in Diagnosis and Treatment of Latent Tuberculosis Infection

“…These in vitro blood tests assess the immunologic reaction of cytokines (interferon-␥) to specific antigens to M. tuberculosis. 26 The QuantiFERON-TB test (QFT) and the QFT Gold test (QFT-G) ( 29,30 In 2008, the T.SPOT TB test (Oxford Immunotec, Abingdon, UK) was developed, requiring 5 mL of peripheral mononuclear cells for the enzyme-linked immunospot to evaluate the response to M. tuberculosis-specific antigens (CFP-10, ESAT-6) when compared with control media. 31 Results for the QFT-G In-Tube and T-SPOT.TB tests are recorded with qualitative (positive, negative, or indeterminate) and quantitative values within a period of 24 hours.…”

“…31 Results for the QFT-G In-Tube and T-SPOT.TB tests are recorded with qualitative (positive, negative, or indeterminate) and quantitative values within a period of 24 hours. 28,30 Key differences between the TST and IGRA as diagnostic measures for LTBI 21,23,30,32,33 are listed in Table 2.…”

“…47,48 However, if IGRAs produce an indeterminate or invalid result, whether low mitogen or high Nil (negative control), the tests should be repeated and reviewed by a TB specialist. 30 …”

Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

“…Both tests are approved by the U.S. Food and Drug Administration (FDA), Health Canada, and Conformité Européenne marked for use in Europe. Figure 3 provides an overview of the immunological basis of commercial IGRAs (28).…”

No added value of interferon-γ release to a prediction model for childhood tuberculosis

“…IGRAs are known to be at least as sensitive but more specific than TST for detecting sensitisation to M. tuberculosis [8]. Neither TST nor IGRAs have been demonstrated to be superior in the diagnosis of latent TB infection in children nor for the prediction of active TB disease; importantly, neither can differentiate M. tuberculosis infection from active TB disease [5,9,10]. However, as has been suggested in previous reports, the use of IGRAs with other predictors might modify its predictive accuracy and offer utility in combination [9,11,12].…”