The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved]
Tuberculous meningitis (TBM) results from dissemination of M. 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wellcome
2019-11-01
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| Series: | Wellcome Open Research |
| Online Access: | https://wellcomeopenresearch.org/articles/4-167/v1 |
| _version_ | 1818285213621420032 |
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| author | James A Seddon Lillian Tugume Regan Solomons Kameshwar Prasad Nathan C Bahr Tuberculous Meningitis International Research Consortium |
| author_facet | James A Seddon Lillian Tugume Regan Solomons Kameshwar Prasad Nathan C Bahr Tuberculous Meningitis International Research Consortium |
| author_sort | James A Seddon |
| collection | DOAJ |
| description | Tuberculous meningitis (TBM) results from dissemination of M. 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 of M. 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. |
| first_indexed | 2024-12-13T01:05:08Z |
| format | Article |
| id | doaj.art-4f9fa8cb4dac49b2b1b1746133f4624f |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-13T01:05:08Z |
| publishDate | 2019-11-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-4f9fa8cb4dac49b2b1b1746133f4624f2022-12-22T00:04:34ZengWellcomeWellcome Open Research2398-502X2019-11-01410.12688/wellcomeopenres.15535.117007The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved]James A Seddon0Lillian Tugume1Regan Solomons2Kameshwar Prasad3Nathan C Bahr4Tuberculous Meningitis International Research ConsortiumDepartment of Infectious Diseases, Imperial College London, London, W2 1PG, UKInfectious Diseases Institute, Makerere University, Kampala, UgandaDepartment of Paediatrics and Child Health, Stellenbosch University, Cape Town, South AfricaDepartment of Neurology, All India Institute of Medical Sciences, New Delhi, IndiaDepartment of Infectious Diseases, University of Kansas, Kansas City, KS, USATuberculous meningitis (TBM) results from dissemination of M. 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 of M. 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.https://wellcomeopenresearch.org/articles/4-167/v1 |
| spellingShingle | James A Seddon Lillian Tugume Regan Solomons Kameshwar Prasad Nathan C Bahr Tuberculous Meningitis International Research Consortium The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved] Wellcome Open Research |
| title | The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved] |
| title_full | The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved] |
| title_fullStr | The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved] |
| title_full_unstemmed | The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved] |
| title_short | The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved] |
| title_sort | current global situation for tuberculous meningitis epidemiology diagnostics treatment and outcomes version 1 peer review 2 approved |
| url | https://wellcomeopenresearch.org/articles/4-167/v1 |
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