Tuberculosis: An Overview of the Immunogenic Response, Disease Progression, and Medicinal Chemistry Efforts in the Last Decade toward the Development of Potential Drugs for Extensively Drug-Resistant Tuberculosis Strains

Abstract

Tuberculosis (TB) is a slow growing, potentially debilitating disease that has plagued humanity for centuries and has claimed numerous lives across the globe. Concerted efforts by researchers have culminated in the development of various strategies to combat this malady. This review aims to raise awareness of the rapidly increasing incidences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, highlighting the significant modifications that were introduced in the TB treatment regimen over the past decade. A description of the role of pathogen–host immune mechanisms together with strategies for prevention of the disease is discussed. The struggle to develop novel drug therapies has continued in an effort to reduce the treatment duration, improve patient compliance and outcomes, and circumvent TB resistance mechanisms. Herein, we give an overview of the extensive medicinal chemistry efforts made during the past decade toward the discovery of new chemotypes, which are potentially active against TB-resistant strains.

Pediatric Tuberculosis Management: A Global Challenge or Breakthrough?

“…Consequently, researchers and clinicians are constantly seeking innovative methods of synthesizing novel antitubercular agents that can find use as therapeutic and/or prophylactic drugs, particularly for pediatric patients. The repurposing of existing bioactive molecules for use as antitubercular agents and the identification of chemotypes that are being evaluated for their efficacy in in vivo studies are also being explored for the same purpose [ 251 , 252 , 253 ].…”

Comprehensive Coverage on Anti‐mycobacterial Endeavour Reported in 2021

“…[5] With the complexity of disease, there has been challenges to mitigate TB considering emergence of multi-drug resistant (MDR-TB) and extensive drug resistant (XDR-TB) strains, being the potential threat to public health. [6] MDR-TB results due to resistance against first line agents including isoniazid and rifampicin, wherein 71 % cases of MDR-TB arise due to rifampicin. [4] As per the recent guidelines from WHO, [7] second line injectables such as amikacin, capreomycin or kanamycin and fluoroquinolones (such as levofloxacin) have been used for the treatment of MDR-TB.…”

“…The standard four drugs such as isoniazid, rifampicin, ethambutol and pyrazinamide have been associated with prolonged drug treatment (6‐9 months), expensive drugs, adverse reactions, poor compliance of patients, polypharmacy and drug‐drug interactions [5] . With the complexity of disease, there has been challenges to mitigate TB considering emergence of multi‐drug resistant (MDR‐TB) and extensive drug resistant (XDR‐TB) strains, being the potential threat to public health [6] . MDR‐TB results due to resistance against first line agents including isoniazid and rifampicin, wherein 71 % cases of MDR‐TB arise due to rifampicin [4] .…”

Capacity and Readiness Assessment of Healthcare Facilities for Digital Health Interventions Against Tuberculosis and HIV in Addis Ababa, Ethiopia

“…There have been decades of investments made in the prevention and control of tuberculosis (TB) and human immunodeficiency virus (HIV), the two infectious diseases of global importance. Several studies have confirmed that TB and HIV will continue to pose major challenges without the deployment of innovative prevention and treatment strategies for everyone who needs them (17)(18)(19)(20)(21). For countries like Ethiopia that are overwhelmed by the dual burden of the two diseases, advancing the diagnosis, care, and treatment programs are essential to meeting global targets such as the 2035 End TB Strategy and the 2030 end AIDS epidemic (22)(23)(24)(25)(26).…”