Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

Abstract

The identification of individuals with latent tuberculosis infection (LTBI) is useful for both fundamental understanding of the pathogenesis of disease and for clinical and public health interventions (i.e., to prevent progression to disease). Basic research suggests there is a pathogenetic continuum from exposure to infection to disease, and individuals may advance or reverse positions within the spectrum, depending on changes in the host immunity. Unfortunately, there is no diagnostic test that resolves the various stages within the spectrum of Mycobacterium tuberculosis infection. Two main immune-based approaches are currently used for identification of LTBI: the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA). TST can use either the conventional purified protein derivative or more specific antigens. Extensive research suggests that both TST and IGRA represent indirect markers of M. tuberculosis exposure and indicates a cellular immune response to M. tuberculosis . The imperfect concordance between these two tests suggests that neither test is perfect, presumably due to both technical and biological reasons. Neither test can accurately differentiate between LTBI and active TB. Both IGRA and TST have low sensitivity in a variety of immunocompromised populations. Cohort studies have shown that both TST and IGRA have low predictive value for progression from infection to active TB. For fundamental applications, basic research is necessary to identify those at highest risk of disease with a positive TST and/or IGRA. For clinical applications, the identification of such biomarkers can help prioritize efforts to interrupt progression to disease through preventive therapy.

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review

“…As a consequence, a large number of people need to be screened and treated to prevent one case of active TB [ 6 ]. Operational issues related to TST and IGRA may decrease screening uptake: The TST requires a second visit 48–72 h after the first visit to read the skin test induration (test result) and IGRA testing is generally costlier than TST and may not be as widely available in EU/EEA countries [ 61 ]. Patients with latent TB are asymptomatic and thus long treatment regimens ranging from 3 to 9 months lead to poor treatment completion [ 32 ].…”

Diagnosis for Latent Tuberculosis Infection: New Alternatives

“…Interestingly, the IGRA sensitivity is not compromised by diabetes in TB patients; in fact, the sensitivity of QTF was significantly higher in TB patients with diabetes in comparison to those with no diabetes (41). The technical variations that may affect IGRA results include those related to blood sampling (time, volume), tube shaking, incubation or processing delay (cell viability in blood may be affected), incubation duration, analytical errors, and manufacturing defects (5).…”

“…The identification of individuals in contact with active TB cases during the first 2 years of exposure is important for two reasons: first, because it allows the implementation of public health policies of disease control by identifying individuals with an increased risk of developing the active tuberculosis; in particular, those who acquired the infection recently (4,5); and second, because it can lead to a better understanding of the immune response during infection, which could be instrumental in the development of better therapeutic and prophylactic interventions.…”

Management of psoriatic patients in biologic treatment associated with infectious comorbidities

“…Retreatment with biological therapy should be considered case by case [17]. On the basis of clinical judgment, IGRA test (Interferon-Gamma Release Assay) could be performed every 12 months, and in case of positive results during treatment with tumor necrosis factor α (TNF-α), interleukins (IL)-12/23 or IL-17 blockers, it is necessary to consult an infectious diseases physician [18,19].…”