Abstract
The pathogenesis of Tuberculous meningitis (TBM) is poorly understood, but contemporary molecular biology technologies have allowed for recent improvements in our understanding of TBM. For instance, neutrophils appear to play a significant role in the immunopathogenesis of TBM, and either a paucity or an excess of inflammation can be detrimental in TBM. Further, severity of HIV-associated immunosuppression is an important determinant of inflammatory response; patients with the advanced immunosuppression (CD4+ T-cell count of <150cells/μL) having higher CSF neutrophils, greater CSF cytokine concentrations and higher mortality than those with CD4+ T-cell counts > 150 cells/μL. Host genetics may also influence outcomes with LT4AH genotype predicting inflammatory phenotype, steroid responsiveness and survival in Vietnamese adults with TBM. Whist in Indonesia, CSF tryptophan level was a predictor of survival, suggesting tryptophan metabolism may be important in TBM pathogenesis. These varying responses mean that we must consider whether a "one-size-fits-all" approach to anti-bacillary or immunomodulatory treatment in TBM is truly the best way forward. Of course, to allow for proper treatment, early and rapid diagnosis of TBM must occur. Diagnosis has always been a challenge but the field of TB diagnosis is evolving, with sensitivities of at least 70% now possible in less than two hours with GeneXpert MTB/Rif Ultra. In addition, advanced molecular techniques such as CRISPR-MTB and metagenomic next generation sequencing may hold promise for TBM diagnosis. Host-based biomarkers and signatures are being further evaluated in childhood and adult TBM as adjunctive biomarkers as even with improved molecular assays, cases are still missed. A better grasp of host and pathogen behaviour may lead to improved diagnostics, targeted immunotherapy, and possibly biomarker-based, patient-specific treatment regimens.
Highlights
The pathogenesis of Tuberculous meningitis (TBM) is poorly understood, but contemporary molecular biology technologies have allowed for recent improvements in our understanding of TBM
In this article we review important recently published studies that have informed our current understanding of TBM pathogenesis and diagnostics
In Vietnamese adults with TBM, leukotriene A4 hydrolase (LTA4H) genotype is a strong predictor of mortality though this finding was not duplicated in Indonesia
Summary
Tryptophan level was a predictor of survival, suggesting tryptophan metabolism may be important in TBM pathogenesis. Indonesian HIV-negative TBM patients showed a strong myeloid blood response and a remarkably broad lymphoid CSF response including innate lymphocytes, there was little correlation between blood and CSF compartments[20] These recent studies in Vietnamese and Indonesian adults with TBM, aimed at gaining insights into mechanisms of the inflammatory response in disease pathogenesis, used novel and high-resolution methods to look at lipid mediator profiles and immune cell populations. A later prospective study in Vietnam reported that in TBM HIV-uninfected adults, LTA4H genotype influences cytokine inflammatory response and correlates with TBM severity, Figure 216. Evidence from recent studies shows LTA4H genotype, CSF cytokines and CSF immune cells such as neutrophils are determinants of inflammatory state, which impacts both bacterial growth and host damage and leads to different outcomes.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
