Global scenario and recent advances in molecular diagnosis and management of drug-resistant tuberculosis

Tuberculosis (TB) is one of the oldest communicable bacterial diseases, spreads predominantly by inhalation of infected respiratory droplets. It is a curable and preventable disease yet remains the leading infectious cause of human death worldwide. The TB burden is high among developing nations of Asia and Africa. Major obstacles in controlling TB are patient’s non-compliance to the anti-tubercular therapy, co-infection with Human immunodeficiency virus (HIV), low socioeconomic status, crowded living condition, inadequate rapid diagnostic testing facilities especially in resource-poor developing countries, delay in diagnosis and initiation of therapy, and the emergence of drug-resistant strains of Mycobacterium tuberculosis (MTB).  Multidrug-resistant (MDR-TB), extensively drug-resistant (XDR-TB), and total drug-resistant (TDR-TB) MTB strains are difficult to treat and are associated with frequent treatment failures and high mortality. The recent advent of molecular techniques including nucleic acid amplification tests (NAATs) and whole-genome sequencing (WGS) have significantly ameliorated the rapid detection of TB cases and drug-resistant MTB. This, in turn, enabled the early initiation of therapy and development of novel treatment plans which is crucial for the global TB elimination target. The World Health Organization (WHO) 2020 guideline prioritizes the use of newer drugs as part of all-oral regimens for the treatment of MDR-TB. Apart from the use of newer drug delivery methods, host factors including immune functions and cytokine responses as well as mycobacterial enzymatic pathways are targeted in TB drug development. Adjuvant therapy employing host-directed approaches is increasingly studied through the time-tested pathogen-targeted approach remains the mainstay in the current treatment of MDR-TB.