{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:24:41Z","timestamp":1793384681358,"version":"4.5.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["K43TW011006"],"award-info":[{"award-number":["K43TW011006"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R03AI164123"],"award-info":[{"award-number":["R03AI164123"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    Tuberculous meningitis (TBM) remains a major cause of morbidity and mortality in children with tuberculosis (TB), yet there are currently no estimates of the global burden of pediatric TBM. Due to frequent non-specific clinical presentation and limited and inadequate diagnostic tests, children with TBM are often diagnosed late or die undiagnosed. Even when diagnosed and treated, 20% of children with TBM die. Of survivors, the majority have substantial neurological disability with significant negative impact on children and their families. Surveillance data on this devastating form of TB can help to quantify the contribution of TBM to the overall burden, morbidity and mortality of TB in children and the epidemiology of TB more broadly. Pediatric TBM usually occurs shortly after primary infection with\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    and reflects ongoing TB transmission to children. In this article we explain the public health importance of pediatric TBM, discuss the epidemiology within the context of overall TB control and health system functioning and the limitations of current surveillance strategies. We provide a clear rationale for the benefit of improved surveillance of pediatric TBM using a TB care cascade framework to support monitoring and evaluation of pediatric TB, and TB control more broadly. Considering the public health implications of a diagnosis of TBM in children, we provide recommendations to strengthen pediatric TBM surveillance and outline how improved surveillance can help us identify opportunities for prevention, earlier diagnosis and improved care to minimize the impact of TBM on children globally.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2022.751133","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T06:57:31Z","timestamp":1647500251000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Tuberculous Meningitis in Children: A Forgotten Public Health Emergency"],"prefix":"10.3389","volume":"13","author":[{"given":"Karen","family":"du Preez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen E.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Donald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan S.","family":"Solomons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Simon","family":"Schaaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Starke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke C.","family":"Hesseling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Seddon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1164\/art.1947.56.2.75","article-title":"Tuberculous meningitis in children; with special reference to serous meningitis; tuberculous meningitis","volume":"56","author":"Lincoln","year":"1947","journal-title":"Am Rev Tuberc."},{"key":"B2","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/S1473-3099(14)70852-7","article-title":"Treatment outcomes of childhood tuberculous meningitis: a systematic review and meta-analysis","volume":"14","author":"Chiang","year":"2014","journal-title":"Lancet Infect Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1017\/s0012162201002493","article-title":"Long-term follow up of childhood tuberculous meningitis","volume":"44","author":"Schoeman","year":"2002","journal-title":"Dev Med Child Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"857","DOI":"10.3390\/microorganisms9040857","article-title":"Defeating paediatric tuberculous meningitis: applying the WHO \u201cdefeating meningitis by 2030: global roadmap\u201d","volume":"9","author":"Basu Roy","year":"2021","journal-title":"Microorganisms."},{"key":"B5","volume-title":"Global Tuberculosis Report 2020","year":"2020"},{"key":"B6","first-page":"392","article-title":"The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era","volume":"8","author":"Marais","year":"2004","journal-title":"Int J Tuberc Lung Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1086\/595012","article-title":"High incidence of tuberculosis among HIV-infected infants: evidence from a South African population-based study highlights the need for improved tuberculosis control strategies","volume":"48","author":"Hesseling","year":"2009","journal-title":"Clin Infect Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e898","DOI":"10.1016\/S2214-109X(17)30289-9","article-title":"The global burden of tuberculosis mortality in children: a mathematical modelling study","volume":"5","author":"Dodd","year":"2017","journal-title":"Lancet Glob Health."},{"key":"B9","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S0022-3476(60)80132-1","article-title":"Tuberculous meningitis in children. A review of 167 untreated and 74 treated patients with special reference to early diagnosis","volume":"57","author":"Lincoln","year":"1960","journal-title":"J Pediatr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"628","DOI":"10.5588\/ijtld.11.0648","article-title":"Value of different staging systems for predicting neurological outcome in childhood tuberculous meningitis","volume":"16","author":"van Toorn","year":"2012","journal-title":"Int J Tuberc Lung Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1016\/S0140-6736(06)68507-3","article-title":"Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness","volume":"367","author":"Trunz","year":"2006","journal-title":"Lancet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/1471-2334-14-91","article-title":"Efficacy of isoniazid prophylactic therapy in prevention of tuberculosis in children: a meta-analysis","volume":"14","author":"Ayieko","year":"2014","journal-title":"BMC Infect Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/S0140-6736(20)30166-5","article-title":"The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis","volume":"395","author":"Martinez","year":"2020","journal-title":"Lancet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e0182185","DOI":"10.1371\/journal.pone.0182185","article-title":"Child contact management in high tuberculosis burden countries: a mixed-methods systematic review","volume":"12","author":"Szkwarko","year":"2017","journal-title":"PLoS ONE."},{"key":"B15","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jinf.2004.02.010","article-title":"Tuberculous meningitis and miliary tuberculosis: the rich focus revisited","volume":"50","author":"Donald","year":"2005","journal-title":"J Infect."},{"key":"B16","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/s0041-3879(48)80033-4","article-title":"The time-table of tuberculosis","volume":"29","author":"Wallgren","year":"1948","journal-title":"Tubercle."},{"key":"B17","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/0002-9343(50)90212-9","article-title":"Course and prognosis of tuberculosis in children","volume":"9","author":"Lincoln","year":"1950","journal-title":"Am J Med."},{"key":"B18","first-page":"225","article-title":"Tuberculosis exposure in HIV-exposed infants in a high-prevalence setting","volume":"12","author":"Cotton","year":"2008","journal-title":"Int J Tuberc Lung Dis."},{"key":"B19","first-page":"627","article-title":"Childhood tuberculosis: the hidden epidemic","volume":"8","author":"Donald","year":"2004","journal-title":"Int J Tuberc Lung Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1136\/thoraxjnl-2016-209421","article-title":"The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis","volume":"72","author":"Dodd","year":"2017","journal-title":"Thorax."},{"key":"B21","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nrneurol.2017.120","article-title":"Tuberculous meningitis","volume":"13","author":"Wilkinson","year":"2017","journal-title":"Nat Rev Neurol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1111\/tmi.13059","article-title":"Human immunodeficiency virus in patients with tuberculous meningitis: systematic review and meta-analysis","volume":"23","author":"Pormohammad","year":"2018","journal-title":"Trop Med Int Health."},{"key":"B23","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/S1474-4422(05)01013-6","article-title":"Tuberculous meningitis: many questions, too few answers","volume":"4","author":"Thwaites","year":"2005","journal-title":"Lancet Neurol."},{"key":"B24","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/oxfordjournals.bmb.a069392","article-title":"The diagnosis of tuberculous meningitis","volume":"10","author":"Smith","year":"1954","journal-title":"Br Med Bull."},{"key":"B25","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/S1474-4422(13)70168-6","article-title":"Tuberculous meningitis: more questions, still too few answers","volume":"12","author":"Thwaites","year":"2013","journal-title":"Lancet Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"CD013359","DOI":"10.1002\/14651858","article-title":"Xpert MTB\/RIF and Xpert MTB\/RIF ultra assays for active tuberculosis and rifampicin resistance in children","volume":"8","author":"Kay","year":"2020","journal-title":"Cochrane Database Syst Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1111\/tmi.13525","article-title":"Diagnostic accuracy of Xpert MTB\/RIF for tuberculous meningitis: systematic review and meta-analysis","volume":"26","author":"Hernandez","year":"2021","journal-title":"Trop Med Int Health."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1542\/peds.2008-1353","article-title":"Twenty years of pediatric tuberculous meningitis: a retrospective cohort study in the western cape of South Africa","volume":"123","author":"van Well","year":"2009","journal-title":"Pediatrics."},{"key":"B29","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1111\/dmcn.13054","article-title":"Clinical characteristics and neurodevelopmental outcomes of children with tuberculous meningitis and hydrocephalus","volume":"58","author":"Rohlwink","year":"2016","journal-title":"Dev Med Child Neurol."},{"key":"B30","volume-title":"Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children","year":"2006"},{"key":"B31","volume-title":"Rapid Communication on Updated Guidance on the Management of Tuberculosis in Children and Adolescents","year":"2021"},{"key":"B32","first-page":"134","article-title":"Epidemiology of tuberculosis in the child","volume":"57","author":"Styblo","year":"1982","journal-title":"Bull Int Union Tuberc."},{"key":"B33","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/0962-8479(92)90039-M","article-title":"Childhood tuberculosis and tuberculous meningitis: high incidence rates in the Western Cape of South Africa","volume":"73","author":"Berman","year":"1992","journal-title":"Tuber Lung Dis."},{"key":"B34","first-page":"1","article-title":"The natural history of tuberculosis in children. A study of child contacts in the brompton hospital child contact Clinic from 1930 to 1952","volume":"42","author":"Davies","year":"1961","journal-title":"Tubercle."},{"key":"B35","first-page":"292","article-title":"Tuberculosis in children","volume":"11","author":"Drolet","year":"1925","journal-title":"Am Rev Tuberc."},{"key":"B36","first-page":"48","article-title":"Surveillance of tuberculosis","volume":"58","author":"Shimao","year":"1983","journal-title":"Bull Int Union Tuberc."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e28","DOI":"10.1016\/S2214-109X(18)30474-1","article-title":"Global shortages of BCG vaccine and tuberculous meningitis in children","volume":"7","author":"du Preez","year":"2019","journal-title":"Lancet Glob Health."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.5588\/ijtld.16.0062","article-title":"IMCI indicators of childhood TBM at primary health care level in the western cape Province of South Africa","volume":"20","author":"Solomons","year":"2016","journal-title":"Int J Tuberc Lung Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"734","DOI":"10.119\/4\/73410.1542\/peds.2006-1796","article-title":"Association between passive smoking and infection with mycobacterium tuberculosis in children","volume":"119","author":"den Boon","year":"2007","journal-title":"Pediatrics."},{"key":"B40","doi-asserted-by":"publisher","first-page":"9","DOI":"10.5588\/ijtld.15.0471","article-title":"Counting children with tuberculosis: why numbers matter","volume":"19","author":"Seddon","year":"2015","journal-title":"Int J Tuberc Lung Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e432","DOI":"10.1016\/S2214-109X(14)70269-4","article-title":"What's in a number? Accurate estimates of childhood tuberculosis","volume":"2","author":"Cruz","year":"2014","journal-title":"Lancet Glob Health."},{"key":"B42","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.ijid.2016.10.016","article-title":"Quality of tuberculosis care in high burden countries: the urgent need to address gaps in the care cascade","volume":"56","author":"Cazabon","year":"2017","journal-title":"Int J Infect Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"S702","DOI":"10.1093\/infdis\/jix335","article-title":"The South African tuberculosis care cascade: estimated losses and methodological challenges","volume":"216","author":"Naidoo","year":"2017","journal-title":"J Infect Dis."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e1002149","DOI":"10.1371\/journal.pmed.1002149","article-title":"The tuberculosis cascade of care in India's public sector: a systematic review and meta-analysis","volume":"13","author":"Subbaraman","year":"2016","journal-title":"PLoS Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"177","DOI":"10.12688\/wellcomeopenres.15515.2","article-title":"Establishing the cascade of care for patients with tuberculous meningitis","volume":"4","author":"Imran","year":"2019","journal-title":"Wellcome Open Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"181","DOI":"10.12688\/wellcomeopenres.15591.1","article-title":"Tuberculous meningitis: new tools and new approaches required","volume":"4","author":"Seddon","year":"2019","journal-title":"Wellcome Open Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1186\/1471-2458-11-784","article-title":"High caseload of childhood tuberculosis in hospitals on Java Island, Indonesia: a cross sectional study","volume":"11","author":"Lestari","year":"2011","journal-title":"BMC Public Health."},{"key":"B48","doi-asserted-by":"publisher","first-page":"19","DOI":"10.5588\/pha.11.0010","article-title":"Incomplete registration and reporting of culture-confirmed childhood tuberculosis diagnosed in hospital","volume":"1","author":"du Preez","year":"2011","journal-title":"Public Health Action."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e023910","DOI":"10.1136\/bmjopen-2018-023910","article-title":"Tuberculosis notification in a private tertiary care teaching hospital in South India: a mixed-methods study","volume":"9","author":"Siddaiah","year":"2019","journal-title":"BMJ Open."},{"key":"B50","doi-asserted-by":"publisher","first-page":"15","DOI":"10.5588\/pha.12.0055","article-title":"The burden and outcomes of childhood tuberculosis in Cotonou, Benin","volume":"3","author":"Ade","year":"2013","journal-title":"Public Health Action."},{"key":"B51","doi-asserted-by":"publisher","first-page":"31900312","DOI":"10.1183\/13993003.00312-2019","article-title":"Unmasking the hidden tuberculosis mortality burden in a large post mortem study in maputo central hospital, Mozambique","volume":"54","author":"Garcia-Basteiro","year":"2019","journal-title":"Eur Respir J."},{"key":"B52","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12941-020-00363-1","article-title":"Anticipating the impact of the COVID-19 pandemic on TB patients and TB control programmes","volume":"19","author":"Togun","year":"2020","journal-title":"Ann Clin Microbiol Antimicrob."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1093\/cid\/cix602","article-title":"Excellent treatment outcomes in children treated for tuberculosis under routine operational conditions in Cape Town, South Africa","volume":"65","author":"Osman","year":"2017","journal-title":"Clin Infect Dis."},{"key":"B54","doi-asserted-by":"crossref","unstructured":"Impact of the COVID-19 Pandemic on TB Detection and Mortality in 2020","DOI":"10.1186\/s12941-020-00363-1"},{"key":"B55","doi-asserted-by":"publisher","first-page":"732","DOI":"10.5588\/ijtld.20.0267","article-title":"Bacille Calmette-Gu\u00e9rin (BCG) vaccine and the COVID-19 pandemic: responsible stewardship is needed","volume":"24","author":"Schaaf","year":"2020","journal-title":"Int J Tuberc Lung Dis."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.3390\/vaccines9111228","article-title":"Impact of COVID-19 disruptions on global BCG coverage and paediatric TB mortality: a modelling study","volume":"9","author":"Shaikh","year":"2021","journal-title":"Vaccines."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.751133\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T06:57:50Z","timestamp":1647500270000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.751133\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,17]]},"references-count":56,"alternative-id":["10.3389\/fneur.2022.751133"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2022.751133","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,17]]},"article-number":"751133"}}