Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease

Abstract

Tuberculosis (TB) remains a devastating disease, yet despite its enormous toll on global health, tools to control TB are insufficient and often outdated. TB Biomarkers (TB-BM) would constitute extremely useful tools to measure infection status and predict outcome of infection, vaccination or therapy. There are several types of TB-BM: Correlate of Infection; Correlate of TB Disease; Correlate of Increased Risk of Developing Active TB Disease; Correlate of the Curative Response to Therapy; and Correlate of Protection (CoP). Most TB-BM currently studied are host-derived BM, and consist of transcriptomic, proteomic, metabolomic, cellular markers or marker combinations ('signatures'). In particular, vaccine-inducible CoP are expected to be transformative in developing new TB vaccines as they will de-risk vaccine research and development (R&D) as well as human testing at an early stage. In addition, CoP could also help minimizing the need for preclinical studies in experimental animals. Of key importance is that TB-BM are tested and validated in different well-characterized human TB cohorts, preferably with complementary profiles and geographically diverse populations: genetic and environmental factors such as (viral) coinfections, exposure to non-tuberculous mycobacteria, nutritional status, metabolic status, age (infants vs children vs adolescents vs adults) and other factors impact host immune set points and host responses across different populations. In this study, we review the most recent advances in research into TB-BM for the diagnosis of active TB, risk of TB development and treatment-induced TB cure.

Contemporary Concise Review 2018: Respiratory infections and tuberculosis

“…Despite the introduction of IGRA using more specific antigens to avoid interference by prior BCG (Bacillus Calmette‐Guerin) vaccination, all existing tests for latent TB infection and predictive biomarkers for future disease development are subject to a generic limitation imposed on their positive predictive value by the generally low absolute disease risks . Shorter rifamycin‐based regimens (e.g.…”

Cell-Mediated Immune Responses to in vivo-Expressed and Stage-Specific Mycobacterium tuberculosis Antigens in Latent and Active Tuberculosis Across Different Age Groups

“…Among these 17 TNF-α+ cells clusters identified, those with CD8+TEMRA or CD8+CD4+ phenotypes, defined by the expression of multiple intracellular markers, were the most prominent in adult INTRODUCTION Tuberculosis (TB) kills more than 4,000 persons per day and is the most life-threatening disease caused by a single infectious agent, Mycobacterium tuberculosis (Mtb) (1). Although one fourth of the global population is estimated to be latently infected (2), none of the current immunodiagnostics can discriminate between recent and past Mtb infection, or predict risk of possible TB progression in LTBI (3)(4)(5). Although neonatal vaccination with Bacillus Calmette-Guérin (BCG), the only licensed TB vaccine, protects infants against severe forms of TB, it is unable to prevent active pulmonary TB in adults and adolescents, such that it has little impact on Mtb transmission (6).…”

Preventive therapy for tuberculosis in rheumatological patients undergoing therapy with biological drugs

“…The availability of non-anti-TNF targeted biologics that are not associated with an increased risk of TB reactivation, offers a great opportunity to tailor a therapy at low/absent TB risk in patients with RA, PsA, and AS [68,139]. New biomarkers for better evaluate TB status are needed [140].…”