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Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics

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...

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Autores principales: Cresswell, Fiona V, Davis, Angharad G., Sharma, Kusum, Basu Roy, Robindra, Ganiem, Ahmad Rizal, Kagimu, Enock, Solomons, Regan, Wilkinson, Robert J., Bahr, Nathan C, Thuong, Nguyen Thuy Thuong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000 Research Limited 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739117/
https://www.ncbi.nlm.nih.gov/pubmed/33364436
http://dx.doi.org/10.12688/wellcomeopenres.15506.3
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author Cresswell, Fiona V
Davis, Angharad G.
Sharma, Kusum
Basu Roy, Robindra
Ganiem, Ahmad Rizal
Kagimu, Enock
Solomons, Regan
Wilkinson, Robert J.
Bahr, Nathan C
Thuong, Nguyen Thuy Thuong
author_facet Cresswell, Fiona V
Davis, Angharad G.
Sharma, Kusum
Basu Roy, Robindra
Ganiem, Ahmad Rizal
Kagimu, Enock
Solomons, Regan
Wilkinson, Robert J.
Bahr, Nathan C
Thuong, Nguyen Thuy Thuong
author_sort Cresswell, Fiona V
collection PubMed
description 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.
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spelling pubmed-77391172020-12-23 Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics Cresswell, Fiona V Davis, Angharad G. Sharma, Kusum Basu Roy, Robindra Ganiem, Ahmad Rizal Kagimu, Enock Solomons, Regan Wilkinson, Robert J. Bahr, Nathan C Thuong, Nguyen Thuy Thuong Wellcome Open Res Review 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. F1000 Research Limited 2021-01-28 /pmc/articles/PMC7739117/ /pubmed/33364436 http://dx.doi.org/10.12688/wellcomeopenres.15506.3 Text en Copyright: © 2021 Cresswell FV et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Cresswell, Fiona V
Davis, Angharad G.
Sharma, Kusum
Basu Roy, Robindra
Ganiem, Ahmad Rizal
Kagimu, Enock
Solomons, Regan
Wilkinson, Robert J.
Bahr, Nathan C
Thuong, Nguyen Thuy Thuong
Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics
title Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics
title_full Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics
title_fullStr Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics
title_full_unstemmed Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics
title_short Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics
title_sort recent developments in tuberculous meningitis pathogenesis and diagnostics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739117/
https://www.ncbi.nlm.nih.gov/pubmed/33364436
http://dx.doi.org/10.12688/wellcomeopenres.15506.3
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