eprintid: 10097379 rev_number: 16 eprint_status: archive userid: 608 dir: disk0/10/09/73/79 datestamp: 2020-05-14 09:16:18 lastmod: 2021-12-05 01:05:20 status_changed: 2020-05-14 09:16:18 type: article metadata_visibility: show creators_name: Seddon, JA creators_name: Tugume, L creators_name: Solomons, R creators_name: Prasad, K creators_name: Bahr, NC creators_name: Aarnoutse, RE creators_name: Anderson, STB creators_name: Bang, ND creators_name: Boulware, DR creators_name: Boyles, T creators_name: te Brake, LHM creators_name: Chandra, S creators_name: Chow, FC creators_name: Cresswell, FV creators_name: van Crevel, R creators_name: Davis, AG creators_name: Dian, S creators_name: Donovan, J creators_name: Dooley, KE creators_name: Figaji, A creators_name: Rizal, AG creators_name: Garg, RK creators_name: Gibb, DM creators_name: Hamers, RL creators_name: Hiep, NTT creators_name: Imran, D creators_name: Imron, A creators_name: Jain, SK creators_name: Jain, SK creators_name: Jeejeebhoy, B creators_name: Kalita, J creators_name: Kumar, R creators_name: Kumar, V creators_name: van Laarhoven, A creators_name: Lai, RPJ creators_name: Manesh, A creators_name: Marais, S creators_name: Mave, V creators_name: Meintjes, G creators_name: Meya, DB creators_name: Misra, UK creators_name: Modi, M creators_name: Ordonez, AA creators_name: Phu, NH creators_name: Pradhan, S creators_name: Proust, AM creators_name: Ramakrishnan, L creators_name: Rohlwink, U creators_name: Ruslami, R creators_name: Schoeman, JF creators_name: Sharma, K creators_name: Siddiqi, O creators_name: Solomons, RS creators_name: Thuong, NTT creators_name: Thwaites, GE creators_name: van Toorn, R creators_name: Tucker, EW creators_name: Wasserman, SA creators_name: Wilkinson, RJ title: The current global situation for tuberculous meningitis: Epidemiology, diagnostics, treatment and outcomes ispublished: pub divisions: UCL divisions: B02 divisions: D65 divisions: J38 keywords: Tuberculosis, Meningitis, Tuberculous meningitis, diagnosis, TBM note: © 2019 Seddon JA et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: 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. date: 2019-11-05 date_type: published official_url: https://doi.org/10.12688/wellcomeopenres.15535.1 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1781084 doi: 10.12688/wellcomeopenres.15535.1 lyricists_name: Gibb, Diana lyricists_id: MGIBB48 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Wellcome Open Research volume: 4 article_number: 167 citation: Seddon, JA; Tugume, L; Solomons, R; Prasad, K; Bahr, NC; Aarnoutse, RE; Anderson, STB; ... Wilkinson, RJ; + view all <#> Seddon, JA; Tugume, L; Solomons, R; Prasad, K; Bahr, NC; Aarnoutse, RE; Anderson, STB; Bang, ND; Boulware, DR; Boyles, T; te Brake, LHM; Chandra, S; Chow, FC; Cresswell, FV; van Crevel, R; Davis, AG; Dian, S; Donovan, J; Dooley, KE; Figaji, A; Rizal, AG; Garg, RK; Gibb, DM; Hamers, RL; Hiep, NTT; Imran, D; Imron, A; Jain, SK; Jain, SK; Jeejeebhoy, B; Kalita, J; Kumar, R; Kumar, V; van Laarhoven, A; Lai, RPJ; Manesh, A; Marais, S; Mave, V; Meintjes, G; Meya, DB; Misra, UK; Modi, M; Ordonez, AA; Phu, NH; Pradhan, S; Proust, AM; Ramakrishnan, L; Rohlwink, U; Ruslami, R; Schoeman, JF; Sharma, K; Siddiqi, O; Solomons, RS; Thuong, NTT; Thwaites, GE; van Toorn, R; Tucker, EW; Wasserman, SA; Wilkinson, RJ; - view fewer <#> (2019) The current global situation for tuberculous meningitis: Epidemiology, diagnostics, treatment and outcomes. Wellcome Open Research , 4 , Article 167. 10.12688/wellcomeopenres.15535.1 <https://doi.org/10.12688/wellcomeopenres.15535.1>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10097379/1/61a843b7-5179-41f7-b6e5-6b99fcea30a3_15535_-_james_seddon.pdf