title: Host-Directed Therapies for Tackling Multi-Drug Resistant Tuberculosis: Learning From the Pasteur-Bechamp Debates.
abstract: Tuberculosis remains a global emergency causing an estimated 1.5 million deaths annually. For several decades the major focus of tuberculosis treatment has been on antibiotic development targeting Mycobacterium tuberculosis. The lengthy tuberculosis treatment duration and poor treatment outcomes associated with multi-drug resistant tuberculosis (MDR-TB) are of major concern. The sparse new tuberculosis drug pipeline and widespread emergence of MDR-TB signal an urgent need for more innovative interventions to improve treatment outcomes. Building on the historical Pasteur-Bechamp debates on the role of the "microbe" vs the "host internal milieu" in disease causation, we make the case for parallel investments into host-directed therapies (HDTs). A range of potential HDTs are now available which require evaluation in randomized controlled clinical trials as adjunct therapies for shortening the duration of tuberculosis therapy and improving treatment outcomes for drug-susceptible tuberculosis and MDR-TB. Funder initiatives that may enable further research into HDTs are described.
authors.affiliation: Center for Clinical Microbiology, Division of Infection and Immunity, University College London (UCL) and NIHR Biomedical Research Centre, UCLHospitals NHS Foundation Trust, United Kingdom.
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.affiliation: Therapeutic Immunology, Departments of Laboratory Medicine and Microbiology, Tumour and Cell Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Maeurer
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D057285:Precision Medicine / Q000379:methods*; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents
keywords: host-directed therapy; multi-drug resistant tuberculosis; repurposed drugs; treatment; tuberculosis