Abstract
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.
Highlights
Tuberculosis (TB) is one of the oldest communicable infectious diseases, spreads predominantly from person-person through inhalation of infected respiratory droplets
Human serves as a natural reservoir for M. tuberculosis (MTB) and its ability to establish latent infection has enabled the spread of infection to large number of people around the globe [1]
Rapid and accurate detection of drug-resistant MTB is critical for the effective early treatment of TB patients and to achieve the goals of World Health Organization (WHO) “End TB Strategy” which targets for 90% reduction in TB related deaths and 80% reduction in TB incidence by 2030 [1]
Summary
Tuberculosis (TB) is one of the oldest communicable infectious diseases, spreads predominantly from person-person through inhalation of infected respiratory droplets. It facilitates screening of clinical specimens with a lower number of bacilli and it would improve MTB detection in sputum samples of children, patients co-infected with HIV, smear-negative pulmonary TB, and extrapulmonary TB cases [2] It overcomes false-negative results seen in XpertMTB/RIF assay due to certain silent mutations in RIF genes. Unlike other molecular tests that are designed to target a limited number of target regions, WGS provides whole genome sequence of M. tuberculosis and single nucleotide polymorphisms (SNPs) responsible for specific resistance [18] This has certain additional advantages; allows species identification, screening of a sample for all types of mutations, detection of drug resistance, and predicting the organism evolution [2]. The WHO document provides detailed key global indicators and milestones for the post-2015 tuberculosis strategy
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