{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:45:58Z","timestamp":1793652358041,"version":"4.5.1"},"reference-count":120,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T00:00:00Z","timestamp":1572912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R007942\/1"],"award-info":[{"award-number":["MR\/R007942\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Research Foundation of South Africa","award":["109437"],"award-info":[{"award-number":["109437"]}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    Tuberculous meningitis (TBM) results from dissemination of\n                    <ns3:italic>M. tuberculosis<\/ns3:italic>\n                    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\u2013Gu\u00e9rin (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\n                    <ns3:italic>M. tuberculosis<\/ns3:italic>\n                    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.\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.15535.1","type":"journal-article","created":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T10:18:08Z","timestamp":1572949088000},"page":"167","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":118,"title":["The current global situation for tuberculous meningitis: epidemiology, diagnostics, treatment and outcomes"],"prefix":"10.12688","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-2302","authenticated-orcid":false,"given":"James 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Thakur, Department of Neurology, Columbia University Irving Medical Center, New York City, NY, USA, 09 Dec 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-167\/v1#referee-response-36945","order":0,"name":"referee-response-36945","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17007.r37823, Tamilarasu Kadhiravan, Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, Puducherry, India, 17 Feb 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-167\/v1#referee-response-37823","order":1,"name":"referee-response-37823","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust through funding to the Tuberculous Meningitis International Research Consortium. \n\nJAS is supported by a Clinician Scientist Fellowship jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC\/DFID Concordat agreement [MR\/R007942\/1]. RS is supported by the National Research Foundation of South Africa [109437].","order":2,"name":"grant-information","label":"Grant Information"},{"value":"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.","order":0,"name":"copyright-info","label":"Copyright"}]}}