Host Directed Therapies for Tuberculous Meningitis

Area of Science:

• Immunology
• Infectious Diseases
• Pharmacology

Background:

• Tuberculous meningitis (TBM) involves a harmful host immune response, leading to significant morbidity and mortality.
• Dexamethasone is the only current host directed therapy (HDT) proven to reduce TBM mortality, but its effects on morbidity and mechanism of action remain unclear.
• Dexamethasone has shown no benefit in HIV-coinfected individuals, highlighting the need for alternative or adjunctive therapies.

Purpose of the Study:

• To review the existing literature on host directed therapies (HDTs) for TBM.
• To explore novel and repurposed drugs as potential HDTs for TBM, informed by new pathogenesis insights.
• To discuss personalized approaches to HDTs in TBM, considering variable host responses.

Main Methods:

• Literature review of existing studies on HDTs in TBM.
• Analysis of new knowledge from TBM pathogenesis research.
• Discussion of potential novel and repurposed therapeutic agents.

Main Results:

• Dexamethasone improves TBM mortality but not morbidity, with uncertain mechanisms and no benefit in HIV coinfection.
• Alternative HDTs like aspirin and thalidomide, alongside other immunomodulatory drugs, require further investigation.
• Repurposed therapeutics targeting small molecule drug targets show potential for TBM treatment.

Conclusions:

• Current HDTs for TBM, like dexamethasone, have limitations and require further research.
• Novel and repurposed drugs, informed by pathogenesis, offer promising avenues for TBM treatment.
• Personalized treatment strategies for HDTs in TBM are warranted due to variable host responses.