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Therapeutic host-directed strategies to improve outcome in tuberculosis.

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.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Young C,Walzl G,Du Plessis N

doi

10.1038/s41385-019-0226-5

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

190-204

issue

2

eissn

1933-0219

issn

1935-3456

pii

10.1038/s41385-019-0226-5

journal_volume

13

pub_type

杂志文章,评审

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