Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics

Wellcome Open Research

article

Fiona V Cresswell¹  Angharad G. Davis⁴  Kusum Sharma⁷  Robindra Basu Roy¹  Ahmad Rizal Ganiem⁸  Enock Kagimu²  Regan Solomons⁹  Robert J. Wilkinson⁵  Nathan C Bahr^1,11  Nguyen Thuy Thuong Thuong^1,12 

[1] Clinical Research Department, London School of Hygiene and Tropical Medicine;Research Department, Infectious Diseases Institute;MRC-UVRI-London School of Hygiene and Tropical Medicine Uganda Research Unit;University College London;Francis Crick Institute;Department of Medicine, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town;Department of Medical Microbiology, Post-graduate Department of Medical Education and Research;Department of Neurology, Hasan Sadikin Hospital, Faculty of Medicine. Universitas Padjadjaran;Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University;Department of Infectious Diseases, Imperial College;Division of Infectious Diseases. Department of Medicine., University of Kansas;Oxford University Clinical Research Unit

关键词: Tuberculous meningitis;    TBM;    TB;    HIV;    pathogenesis;    diagnostics;   

DOI  :  10.12688/wellcomeopenres.15506.3

学科分类：内科医学

来源: Wellcome

【 摘 要 】

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. 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.

【 授权许可】

CC BY