Stratification by interferon-γ release assay level predicts risk of incident TB

Abstract

Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

Diagnostic Challenge of Tuberculosis Heterogeneity

“…76 Similarly, a population-based study of almost 45,000 individuals from Norway also showed that quantitative IFN-γ concentrations greater than 4 IU/mL were associated with increased risk of TB. 77 Collectively, these studies show that elevated systemic inflammation and in particular type I/II IFN responses and complement pathway activation can reveal a state of immunological activation that occurs in asymptomatic individuals who either have radiographic evidence of TB pathology or are at very high risk of imminent incident TB disease.…”

Clinical Development of New TB Vaccines: Recent Advances and Next Steps

“…Clinical relevance of the POI efficacy signal is suggested by similar 45% efficacy of BCG revaccination against the exploratory endpoint, IGRA conversion >4.0 IU/mL interferon-gamma (Nemes et al, 2018a). IGRA conversion to above the 4.0 IU/mL threshold was associated with much higher risk of progression to TB disease in two diverse populations, i.e., South African infants (40-fold) (Andrews et al, 2017), and Norwegian adults (30-fold) (Winje et al, 2018), compared to those who remained IGRA-negative.…”

“…How can a new TB vaccination strategy offer protection both to "most of those at risk, " as well as "those most at risk, " given current limitations of predictive and diagnostic tests? Large cohort studies have identified proteomic and transcriptomic (Suliman et al, 2018b;Zak et al, 2016;Warsinske et al, 2018) host blood biomarkers and high IGRA conversion threshold values (interferon-gamma >4.0 IU/mL) (Winje et al, 2018;Andrews et al, 2017) that predict which infected individuals have highest risk of progression to TB disease. However, it is highly unlikely that pre-vaccination screening, even to identify IGRA-positive people, would be feasible in high TB incidence developing countries with limited resources and constrained health system capacity.…”

Escaping the Plato's cave of latent tuberculosis testing: a path for developers of predictive tests for risk of tuberculosis

“…Until we have proven efficacy and WHO endorsement of new ITTs, we will have to make do with the current diagnostic portfolio and incremental improvements hereof [2]. Recent findings from large prospective cohorts in Norway [18] and South Africa [19] suggest superior risk stratification in algorithms incorporating the magnitude of the interferon (IFN)-γ response in the IGRA [20] and serial IGRA testing. Other approaches seek to improve the TST and IGRA technologies, such as field-friendly specific skin tests including C-Tb based on the antigens used in IGRAs [21], and lateral flow or quantitative RT-PCR based tests using highly expressed markers like IFN-γ-inducible protein 10 as an alternative to IFN-γ [22], potentially combined with novel antigens to improve sensitivity in high-risk groups such as young children and people living with HIV [23,24].…”