The Role of TB Biomarkers in Diagnosis, Prognosis and Prevention of Tuberculosis

Abstract

This chapter focuses on how biomarkers of tuberculosis can be utilized in the diagnosis, prognosis and treatment monitoring of TB. Tuberculosis biomarkers are measurable molecular indicators present and/or whose levels are altered in disease states. Found in blood, urine, bronchoalveolar lavage or sputum, biomarkers can originate from the bacteria (e.g. Ag85, lipoarabinomannan (LAM) and bacterial DNA) or from the host (e.g. cytokines/chemokines, metabolites, transcriptomics, mixed signatures and other proteins). Despite the lack of tuberculous specificity, Ag85 can facilitate early detection of mycobacterial infection, giving room for early commencing of treatment and, hence, better disease prognosis. Findings indicate that latent TB Infection (LTBI) can be diagnosed by Interferon Gamma Release Assay (IGRA) and piRNAs but is distinctively detected by TAM-TB (based on Ki-67, HLA-DR and SD38) and the CD4+; CCR6+, CXCR3+ and CCR4 signatures. Active Tuberculosis (ATB) in children can be diagnosed early by pyridoxate, quinolinate and N-acetylneuraminate metabolites signature, while gamma-glutamylalanine, pyridoxate, glutamine and gamma-glutamylglycine metabolites identify treatment response in this population. Lipopolysaccharide-binding protein (LBP), MMP-7 and C-reactive protein signature can reliably differentiate Extrapulmonary TB (EPTB) from Pulmonary TB (PTB) and health controls among juveniles. Irrespective of age, Mannose-binding lectin (MBL) can distinguish EPTB from PTB, since the later has significantly higher MBL than PTB and Controls. RISK11 has excellent diagnostic and prognostic capabilities in identifying ambulatory People living with HIV/AIDS+Active TB (PLWH+ATB) patients and the likelihood that latent conditions will advance to incident TB. Furthermore, IFN-α, IL-1α, IFN-γ, sCD40L, MMP-2, MMP-9 and IFN-α2 are the most reliable biosignature for the diagnosis of smear-negative TB. Neutrophil-driven IFN types 1 and 2 have the ability to monitor treatment course and predict prognosis since the INF levels reduce with effective treatment. Transthyretin, neopterin and C-reactive protein signature can be used to detect immune response to TB infection, prognosis and monitoring treatment course since the biomarkers levels decrease with a decrease in disease activity. IL-17 and Th-17 are crucial for vaccine-mediated protection against tuberculosis. Encouraging the elucidation, adoption and integration of biomarker-based technology into healthcare systems can facilitate individual and public health gain, as well as saving on tuberculosis-associated economic loss.