Deciphering Tuberculous Meningitis: From Clinical Challenges to Novel Models and Pathogenic Pathways
Mohamad Mosa Mubarak1,2, Shahnawaz Majeed1, Hadiya Amin Kantroo1,2
1Clinical Microbiology PK/PD Division, CSIR - Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, 190005, India.
Abstract:
During and after the COVID-19 pandemic, Tuberculosis (TB) has reestablished with higher figures due to interruptions in the Directly Observed Treatment Short course (DOTS) despite underreporting. The rising consequences would have extended to extra-pulmonary forms of TB as well, including Tuberculous Meningitis (TBM). Considering the fact that TBM is the most dangerous and worst form of TB, we found the need to scan the literature to highlight various aspects of TBM. Epidemiology of TBM is proportionally less frightening, but the consequent mortalities and morbidities are more alarming than pulmonary TB. Here, we address critical research gaps in Tuberculous Meningitis that warrant further investigations. The highlighted aspects encompass a comprehensive understanding of TBM's clinical presentation and improved diagnostic tools for timely detection, the exploration of innovative chemotherapies and surgical interventions, the unraveling of the role of the blood-brain barrier in disease onset, investigating of the contributions of various brain cells to TBM development, deciphering the complex inflammatory response, exploring the involvement of Matrix Metalloproteinases in tissue damage, delving into host-pathogen genetics influencing susceptibility, utilizing robust in-vivo and in-vitro models for mechanistic insights, and more importantly between TBM and SARS-COVID-19 are discussed. Addressing these gaps will substantially advance our understanding of TBM's complex pathogenesis, contributing to more effective diagnostic, therapeutic, and preventive strategies against this debilitating disease.
Insights
Tuberculosis meningitis (TBM) is a severe form of TB, with increased incidence post-COVID-19 due to treatment disruptions. Further research is crucial for better diagnostics and treatments for TBM.
Area of Science:
- Neurology
- Infectious Diseases
- Public Health
Background:
- COVID-19 pandemic disrupted Tuberculosis (TB) treatment, leading to increased TB incidence.
- Tuberculous Meningitis (TBM), a severe extra-pulmonary TB form, poses significant mortality and morbidity risks.
- Existing literature requires comprehensive review to address critical research gaps in TBM.
Purpose of the Study:
- To review and highlight key research gaps in Tuberculous Meningitis (TBM).
- To identify areas for further investigation in TBM's clinical presentation, diagnosis, and treatment.
- To explore TBM's pathogenesis, including the role of the blood-brain barrier, cellular contributions, inflammation, and host-pathogen genetics.
Main Methods:
- Literature scan focusing on TBM epidemiology, clinical aspects, and pathogenesis.
- Identification of research gaps in diagnostics, chemotherapy, surgical interventions, and molecular mechanisms.
- Exploration of TBM's interaction with SARS-COVID-19 and the utility of in-vivo/in-vitro models.
Main Results:
- TBM presents unique epidemiological challenges with high mortality and morbidity.
- Significant knowledge gaps exist in timely TBM diagnosis and effective therapeutic strategies.
- The role of the blood-brain barrier, brain cells, inflammation, Matrix Metalloproteinases, and host-pathogen genetics in TBM pathogenesis requires further elucidation.
Conclusions:
- Addressing identified research gaps is essential for advancing TBM understanding and management.
- Improved diagnostic tools and innovative treatments are needed for TBM.
- Further research into TBM pathogenesis, including its interplay with COVID-19, will enhance prevention and control strategies.
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