Abstract
Bacille Calmette-Guérin (BCG) is the only licenced tuberculosis (TB) vaccine, but has limited efficacy against pulmonary TB disease development and modest protection against extrapulmonary TB. Preventative antibiotic treatment for Mycobacterium tuberculosis (Mtb) infections in high-prevalence settings is unfeasible due to unclear treatment durability, drug toxicity, logistical constraints related to directly observed treatment strategy (DOTS) and the lengthy treatment protocols. Together, these factors promote non-adherence, contributing to relapse and establishment of drug-resistant Mtb strains. Although antibiotic treatment of drug-susceptible Mtb is generally effective, drug-resistant TB has a treatment efficacy below 50% and can, in a proportion, develop into progressive, untreatable disease. Other immune compromising co-infections and/or co-morbidities require more complex prevention/treatment approaches, posing huge financial burdens to national health services. Novel TB treatment strategies, such as host-directed therapeutics, are required to complement pathogen-targeted approaches. Pre-clinical studies have highlighted promising candidates that enhance endogenous pathways and/or limit destructive host responses. This review discusses promising pre-clinical candidates and forerunning compounds at advanced stages of clinical investigation in TB host-directed therapeutic (HDT) efficacy trials. Such approaches are rationalized to improve outcome in TB and shorten treatment strategies.
Highlights
Tuberculosis (TB) remains the leading cause of death by infection worldwide.[1]
While the outcome of some trials has been met with anticlimactic conclusions, emerging evidence outlined in this review suggests that the TB field is making steady progress in identifying beneficial host-directed therapeutic (HDT) across a broad range of drug classification and mechanistic activity
According to the therapies discussed in this review, we propose that certain HDTs will be of particular relevance to a specific TB infection/disease group
Summary
Tuberculosis (TB) remains the leading cause of death by infection worldwide.[1]. Despite introduction of directly observed treatment short-course (DOTS), the reduction in the global TB burden has been modest.
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