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Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidity, how it reduces mortality is uncertain, and it has no proven benefit in HIV co-infected individuals. Further research on these aspects of its use, as well as alternative HDTs such as aspirin, thalidomide and other immunomodulatory drugs is needed. Based on new knowledge from pathogenesis studies, repurposed therapeutics which act upon small molecule drug targets may also have a role in TBM. Here we review existing literature investigating HDTs in TBM, and propose new rationale for the use of novel and repurposed drugs. We also discuss host variable responses and evidence to support a personalised approach to HDTs in TBM.<\/ns3:p>","DOI":"10.12688\/wellcomeopenres.16474.2","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T08:35:12Z","timestamp":1625128512000},"page":"292","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Host Directed Therapies for Tuberculous Meningitis"],"prefix":"10.12688","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8914-5094","authenticated-orcid":false,"given":"Angharad 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Davis<\/b>; \n<i>Posted: 19 May 2021<\/i>; Dear Reviewer 2,&nbsp;  Many thanks for your thorough review of the manuscript and your suggestion to add a section on TBM epidemiology and pathogenesis.  We agree that these are important areas, however since this manuscript forms a collection of published papers in a TBM supplement, many of which covered TBM epidemiology and pathogenesis in detail, the authors felt that this manuscript should maintain a narrow focus on the subject area, and therefore felt chapters on TBM epidemiology\/pathogenesis was beyond the scope of the article.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-292\/v2#referee-comment-4626","order":2,"name":"referee-comment-4626","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust through a UCL Wellcome Trust PhD Programme for Clinicians Fellowship to AGD [175479]; support for GT and JD [110179]; a Wellcome International Intermediate Fellowship to NTTT [206724]; a Wellcome Clinical PhD Fellowship to FVC [210772]; support for RJW [104803; 203135] and funding for the Francis Crick Institute [FC0010218]. \nRL is supported by a MRC CDA Fellowship [MRC\/R008922\/1]. \nDRB is supported by the National Institutes of Neurological Diseases and Stroke of the National Institutes of Health [R01NS086312]. \nRJW receives support from Francis Crick Institute, which is funded by UKRI [FC0010218]; Wellcome [FC0010218] and CRUK [FC0010218]. He also receives support from Meningitis Now and NIH [R01AI45436].\nNCB is supported by the National Institutes of Neurological Diseases and Stroke of the National Institutes of Health [K23NS110470]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}