Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics [version 3; peer review: 3 approved]

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dc.contributor.authorCresswell, Fiona V.en_ZA
dc.contributor.authorDavis, Angharad G.en_ZA
dc.contributor.authorSharma, Kusumen_ZA
dc.contributor.authorRoy, Robindra Basuen_ZA
dc.contributor.authorGaniem, Ahmad Rizalen_ZA
dc.contributor.authorKagimu, Enocken_ZA
dc.contributor.authorSolomons, Reganen_ZA
dc.contributor.authorWilkinson, Robert J.en_ZA
dc.contributor.authorBahr, Nathan C.en_ZA
dc.contributor.authorThuong, Nguyen Thuy Thuongen_ZA
dc.contributor.authorTuberculous Meningitis International Research Consortiumen_ZA
dc.date.accessioned2022-01-19T10:31:57Z
dc.date.available2022-01-19T10:31:57Z
dc.date.issued2019
dc.descriptionCITATION: 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.
dc.descriptionThe original publication is available at https://wellcomeopenresearch.org
dc.description.abstractENGLISH 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.en_ZA
dc.description.urihttps://wellcomeopenresearch.org/articles/4-164
dc.description.versionPublisher's version
dc.format.extent27 pagesen_ZA
dc.identifier.citationCresswell, 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
dc.identifier.issn2398-502X (online)
dc.identifier.otherdoi:10.12688/wellcomeopenres.15506.3
dc.identifier.urihttp://hdl.handle.net/10019.1/124112
dc.language.isoen_ZAen_ZA
dc.publisherF1000Researchen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculous meningitis -- Diagnosisen_ZA
dc.subjectPathogenic virusesen_ZA
dc.subjectPathogenic microorganisms -- Identificationen_ZA
dc.subjectDiagnostic microbiologyen_ZA
dc.titleRecent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics [version 3; peer review: 3 approved]en_ZA
dc.typeArticleen_ZA
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