Host Directed Therapies for Tuberculous Meningitis
Angharad Davis, Joseph Donovan, Marise Bremer, Ronald van Toorn, Johan F. Schoeman, Ariba Dadabhoy, Rachel Lai, Fiona V Cresswell, David R. Boulware, Robert J. Wilkinson, Nguyễn Thụy Thương Thương, Guy Thwaites, Nathan C. Bahr
Abstract
A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). 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.