Tuberculosis: current state of knowledge: an epilogue.

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), has developed various mechanisms to survive and cause disease in the human host. Incomplete understanding of the complex microbe-host interactions has hindered the identification of suitable biomarkers to expedite the development of diagnostic tools, drugs and vaccines. The field effectiveness of directly observed therapy-short course has been compromised by the intrinsic limitations of sputum microscopy and suboptimal adherence to the long duration of treatment amid the HIV-TB syndemic and various socioeconomic constraints. While molecular tools are transforming the diagnostic processes, especially for multi-drug-resistant (MDR)-TB, drug development and service provision for MDR-TB seriously lag behind. Inappropriate management of detected MDR-TB cases may amplify drug resistance, jeopardizing future control. Targeted screening and treatment of latent infection with M. tuberculosis with the currently available immunodiagnostic tools and treatment regimens aim more for personal protection than major epidemiological impact or elimination. The interferon-γ release assays (IGRA) are not affected by cross-reaction to the bacillus Calmette-Guérin (BCG) vaccine and are increasingly used for such screening before initiation of biologics for treatment of rheumatoid arthritis and other autoimmune disorders. BCG offers only partial and unreliable protection against pulmonary TB in adults, the crucial transmission link for this airborne infection. Systems biology and vaccinomics may speed up vaccine research. The successful development of a fully effective TB vaccine that targets both growing bacteria and non-growing persisters may reflect a major breakthrough, as natural infection does not induce sufficient immunity to prevent reinfection.