du Preez Karen, Jenkins Helen E, Martinez Leonardo, Chiang Silvia S, Dlamini Sicelo S, Dolynska Mariia, Aleksandrin Andrii, Kobe Julia, Graham Stephen M, Hesseling Anneke C, Starke Jeffrey R, Seddon James A, Dodd Peter J
Desmond Tutu Tuberculosis Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
Lancet Glob Health. 2025 Jan;13(1):e59-e68. doi: 10.1016/S2214-109X(24)00383-8.
Tuberculous meningitis is fatal if untreated and can lead to lifelong neurological sequelae. However, to our knowledge, there are no data on the number of children affected by this disease. We aimed to estimate the global disease burden and attributable mortality of childhood tuberculous meningitis by WHO regions, age groups, treatment status, and HIV status in 2019.
We developed a Bayesian mathematical model to estimate the number of children aged 0-14 years who developed tuberculous meningitis, died from tuberculous meningitis, and did not die from tuberculous meningitis but had neurological sequelae in 2019. We reviewed the literature and used meta-analyses to quantify key parameters used as model inputs: risk of tuberculous meningitis after Mycobacterium tuberculosis infection, tuberculous meningitis as a proportion of tuberculosis notification data (ie, routine surveillance data that countries report to WHO), and risk ratios for tuberculous-meningitis mortality by age group. We identified routine tuberculosis surveillance data from countries and literature that reported the proportion of notified childhood tuberculosis that was due to tuberculous meningitis. Country-level data were from Brazil; the USA; Ukraine; South Africa; and the European Centre for Disease Prevention and Control, which included 29 countries but was aggregated and considered as one site. We assumed tuberculosis notification was synonymous with detection and treatment, combined age-disaggregated risk ratios and published meta-analytic estimates of the case-fatality rate in children who received treatment to produce estimates of tuberculous-meningitis mortality by age group and HIV status, and assumed that untreated tuberculous meningitis was always fatal. We assumed similar age-disaggregated risk ratios for neurological sequelae among children who had treatment for tuberculous meningitis and lived as for children who died.
An estimated 24 000 (95% credible interval 22 300-25 700) children younger than 15 years developed tuberculous meningitis in 2019. Of these children, 13 000 (12 100-13 900) were estimated to have been diagnosed and treated for tuberculous meningitis. Most untreated children were younger than 5 years. Among the 24 000 children with tuberculous meningitis, 16 100 (14 900-17 300) were estimated to have died in 2019, of whom 1101 (6·8%) had HIV. 13 380 (83·1%) of 16 100 deaths were estimated to be in children younger than 5 years and 11 000 (68·3%) were estimated to be in children who did not receive tuberculous-meningitis treatment. Of the 7900 (5800-10 000) children who did not die, 5550 (5110-5980) were estimated to have neurological sequelae.
Our estimates of tuberculous meningitis in children younger than 15 years showed substantial mortality and morbidity. Improved diagnostics and strong health-care systems to facilitate early diagnosis are crucial to improve outcomes, and tuberculosis prevention should be a public health priority.
Fogarty International Center of the US National Institutes of Health.
结核性脑膜炎若不治疗会致命，并可导致终身神经后遗症。然而，据我们所知，尚无关于受此病影响儿童数量的数据。我们旨在按世界卫生组织区域、年龄组、治疗状况和艾滋病毒状况，估算2019年儿童结核性脑膜炎的全球疾病负担和归因死亡率。
我们开发了一个贝叶斯数学模型，以估算2019年0至14岁患结核性脑膜炎、死于结核性脑膜炎以及未死于结核性脑膜炎但有神经后遗症的儿童数量。我们查阅了文献并使用荟萃分析来量化用作模型输入的关键参数：结核分枝杆菌感染后患结核性脑膜炎的风险、结核性脑膜炎在结核病通报数据（即各国向世界卫生组织报告的常规监测数据）中所占比例，以及各年龄组结核性脑膜炎死亡率的风险比。我们从各国和文献中确定了报告了通报的儿童结核病中因结核性脑膜炎所致比例的常规结核病监测数据。国家层面的数据来自巴西、美国、乌克兰、南非以及欧洲疾病预防控制中心，后者包括29个国家，但数据进行了汇总并视为一个地点。我们假定结核病通报等同于检测和治疗，将按年龄分类的风险比与已发表的接受治疗儿童病死率的荟萃分析估计值相结合，以得出各年龄组和艾滋病毒状况的结核性脑膜炎死亡率估计值，并假定未治疗的结核性脑膜炎总是致命的。我们假定接受结核性脑膜炎治疗并存活的儿童与死亡儿童的神经后遗症按年龄分类的风险比相似。
估计2019年有24000名（95%可信区间22300 - 25700）15岁以下儿童患结核性脑膜炎。在这些儿童中，估计有13000名（12100 - 13900）被诊断患有结核性脑膜炎并接受了治疗。大多数未治疗的儿童年龄小于5岁。在24000名患结核性脑膜炎的儿童中，估计2019年有16100名（14900 - 17300）死亡，其中1101名（6.8%）感染了艾滋病毒。16100例死亡中估计有13380例（83.1%）发生在5岁以下儿童，11000例（68.3%）估计发生在未接受结核性脑膜炎治疗的儿童中。在7900名（5800 - 10000）未死亡的儿童中，估计有5550名（5110 - 5980）有神经后遗症。
我们对15岁以下儿童结核性脑膜炎的估计显示出很高的死亡率和发病率。改进诊断方法以及建立强大的医疗保健系统以促进早期诊断对于改善结局至关重要，结核病预防应成为公共卫生重点。
美国国立卫生研究院福格蒂国际中心。
