Current status and future landscape of diagnosing tuberculosis infection

Interferon-γ release assays (IGRAs), such as QuantiFERON-TB Gold (QFT) or T-SPOT.TB, are frequently used as tools for the diagnosis of tuberculosis (TB) infection in the 21st century. QFT-Plus recently emerged as the fourth generation of QFT assays and has replaced QFT In-Tube. However, IGRAs have several problems regarding the identification of active, latent, and cured TB infection, and the time-consuming diagnosis of TB infection because of the overnight incubation of clinical specimens or complexity of measuring the level of interferon (IFN)-γ. To easily diagnose TB infection and quickly compare it with conventional IGRAs, many in vitro tests are developed based on assays other than enzyme-linked immunosorbent assay or enzyme-linked immunospot, such as the fluorescent lateral flow assay that requires less manual operation and a shorter time. Simplified versions of IGRAs are emerging, including QIAreach QuantiFERON-TB. On the other hand, to distinguish active TB from latent or cured TB infection, new immunodiagnostic biomarkers beyond IFN-γ are evaluated using QFT supernatants. While IFN-γ or IFN-γ-related chemokine such as IFN-γ induced protein 10 is a potential biomarker in patients with active TB, interleukin-2 or latency-associated antigen such as heparin-binding hemagglutinin may be useful to distinguish active TB from latent or cured TB infection. There are no potential biomarkers to fully distinguish the time-phase of TB infection at present. It is necessary to discover new immunodiagnostic biomarkers to facilitate decisions on treatment selection for active or latent TB infection.