Two-hit in vitro T-Cell Stimulation Detection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana

Abstract

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb). The pathogen is transmitted via aerosols from tuberculosis patients with cavernous disease to close contacts (HCs), who have a high risk of becoming Mtb infected. A minor subset of Mtb infected HCs will develop active tuberculosis whereas the majority will control the pathogen by immune surveillance and remain latently Mtb infected (LTBI) (1). IFN-γ producing CD4+Thelper cells are central for protection of LTBI against progression to active disease. Thelper cells induce a delayed type hypersensitivity reaction against mycobacterial antigens (i.e., Mtb purified protein derivative; PPD) and this recall immune response forms the basis of the tuberculin skin test (TST) for detection of previous Mtb infection. The TST test has been used for more than a century to diagnose Mtb infection. In several regions where tuberculosis is endemic the TST is still applied but replacement by more specific immunological in vitro tests (i.e., IFN-γ release assays, IGRAs) is ongoing (2).