Diagnostic tests for tuberculosis infection and predictive indicators of disease progression: Utilizing host and pathogen biomarkers to enhance the tuberculosis elimination strategies.

Tuberculosis (TB) remains the leading cause of death worldwide from a single infectious disease. An estimated quarter of the world's population, about 2 billion people, has an immune response to Mycobacterium tuberculosis (Mtb) without clinical, microbiological, or radiological signs of TB disease. This condition is known as TB infection (TBI) and carries a lifelong risk of reactivation with 5%-10% of individuals eventually developing TB disease during their lifetime. Interferon-γ release assay and skin-tests are World Health Organization (WHO)-approved tests for TBI diagnosis and allow to identify those needing TB preventive therapy. The WHO End TB Strategy proposes several approaches to mitigate the global burden of TB. Achieving the goal of TB elimination requires improved early diagnosis of TBI individuals at risk of developing TB disease, provision of preventive therapy, and development of new diagnostic tests to address the current limitations. This review provides an update on the tests currently used for TBI diagnosis and offers an overview of experimental tests based on either host response analysis or pathogen detection. Additionally, we briefly report experimental tests, such as those based on host RNA signatures, which can help identifying TBI individuals at high risk of progressing toward TB disease. Although these experimental tests show promise, further investigation and randomized clinical trials are required to establish reliable proof-of-concept.