Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics [version 3; peer review: 3 approved]
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
F1000Research
Abstract
ENGLISH 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 <150 cells/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.
Description
CITATION: Cresswell, F. V., et al. 2019. Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics [version 3; peer review: 3 approved]. Wellcome Open Research, 4:164, doi:10.12688/wellcomeopenres.15506.3.
The original publication is available at https://wellcomeopenresearch.org
The original publication is available at https://wellcomeopenresearch.org
Keywords
Tuberculous meningitis -- Diagnosis, Pathogenic viruses, Pathogenic microorganisms -- Identification, Diagnostic microbiology
Citation
Cresswell, F. V., et al. 2019. Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics [version 3; peer review: 3 approved]. Wellcome Open Research, 4:164, doi:10.12688/wellcomeopenres.15506.3