The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes

Wellcome Open Research

article

James A Seddon¹  Lillian Tugume³  Regan Solomons⁴  Kameshwar Prasad⁵  Nathan C Bahr⁶ 

[1] Department of Infectious Diseases, Imperial College London;Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University;Infectious Diseases Institute, Makerere University;Department of Paediatrics and Child Health, Stellenbosch University;Department of Neurology, All India Institute of Medical Sciences;Department of Infectious Diseases, University of Kansas

关键词: Tuberculosis;    Meningitis;    Tuberculous meningitis;    diagnosis;    TBM;   

DOI  :  10.12688/wellcomeopenres.15535.1

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Tuberculous meningitis (TBM) results from dissemination ofM. tuberculosis to the cerebrospinal fluid (CSF) and meninges. Ischaemia, hydrocephalus and raised intracranial pressure frequently result, leading to extensive brain injury and neurodisability. The global burden of TBM is unclear and it is likely that many cases are undiagnosed, with many treated cases unreported. Untreated, TBM is uniformly fatal, and even if treated, mortality and morbidity are high. Young age and human immunodeficiency virus (HIV) infection are potent risk factors for TBM, while Bacillus Calmette–Guérin (BCG) vaccination is protective, particularly in young children. Diagnosis of TBM usually relies on characteristic clinical symptoms and signs, together with consistent neuroimaging and CSF parameters. The ability to confirm the TBM diagnosis via CSF isolation ofM. tuberculosis depends on the type of diagnostic tests available. In most cases, the diagnosis remains unconfirmed. GeneXpert MTB/RIF and the next generation Xpert Ultra offer improved sensitivity and rapid turnaround times, and while roll-out has scaled up, availability remains limited. Many locations rely only on acid fast bacilli smear, which is insensitive. Treatment regimens for TBM are based on evidence for pulmonary tuberculosis treatment, with little consideration to CSF penetration or mode of drug action required. The World Health Organization recommends a 12-month treatment course, although data on which to base this duration is lacking. New treatment regimens and drug dosages are under evaluation, with much higher dosages of rifampicin and the inclusion of fluoroquinolones and linezolid identified as promising innovations. The inclusion of corticosteroids at the start of treatment has been demonstrated to reduce mortality in HIV-negative individuals but whether they are universally beneficial is unclear. Other host-directed therapies show promise but evidence for widespread use is lacking. Finally, the management of TBM within health systems is sub-optimal, with drop-offs at every stage in the care cascade.

【 授权许可】

CC BY