Global, regional, and national burden of meningitis, its risk factors, and aetiologies, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023

1990 - 2023年全球、区域和国家的脑膜炎负担、危险因素及病因：《2023年全球疾病负担研究》的系统分析

Meningitis remains the leading infectious cause of neurological disabilities globally, disproportionately affecting children younger than 5 years and populations in the African meningitis belt. Whereas previous global estimates focused on ten pathogen categories, this study presents the most comprehensive analysis to date, assessing the meningitis burden attributable to 17 causative pathogens based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework. Although mortality and incidence have declined significantly since 1990, progress is insufficient to meet WHO 2030 targets. Despite marked progress in reducing bacterial meningitis via global vaccination campaigns, a substantial meningitis burden persists, attributable both to common pathogens such as S pneumoniae and N meningitidis and to emerging non-bacterial pathogens such as Candida spp and drug-resistant fungi. Achieving WHO goals will require sustained investment in surveillance, vaccination, maternal screening, and health-system strengthening, especially in high-burden settings.

脑膜炎仍然是全球神经系统残疾的主要感染性病因，对5岁以下儿童和非洲脑膜炎带地区的人群影响尤为严重。此前的全球评估聚焦于10种病原体类别，而本研究是迄今为止最全面的分析，依据《2023年全球疾病、伤害和危险因素研究》（GBD 2023）框架，评估了17种致病病原体导致的脑膜炎负担。尽管自1990年以来，脑膜炎的死亡率和发病率显著下降，但这一进展仍不足以实现世界卫生组织（WHO）2030年目标。尽管通过全球疫苗接种运动，在减少细菌性脑膜炎方面取得了显著进展，但脑膜炎负担仍然很重，这既归因于肺炎链球菌和脑膜炎奈瑟菌等常见病原体，也归因于念珠菌属和耐药真菌等新兴非细菌性病原体。要实现世卫组织的目标，需要持续投资于监测、疫苗接种、孕产妇筛查和卫生系统强化，特别是在负担较重的地区。

REF: GBD 2023 Meningitis & Antimicrobial Resistance Collaborators. Global, regional, and national burden of meningitis, its risk factors, and aetiologies, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet Neurol. 2026;25(5):451-468. doi:10.1016/S1474-4422(26)00101-8 PMID: 41911930

Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial

美国弗里德赖希共济失调患者个体化运动和补充烟酰胺腺嘌呤二核苷酸（NAD⁺）前体的安全性和有效性：一项单中心 2×2 析因随机对照试验

Friedreich's ataxia is a rare, chronic, progressive, neurodegenerative condition affecting multiple organ systems, including neurological, musculoskeletal, cardiac, and endocrine systems, and is marked by low cardiopulmonary fitness. We tested the effect of exercise and NAD+precursor supplementation with nicotinamide riboside, which have each shown benefits in animal and early clinical studies, on cardiopulmonary fitness in individuals with Friedreich's ataxia. The combination of nicotinamide riboside plus exercise for 12 weeks was safe and increased cardiopulmonary fitness in children and adults with Friedreich's ataxia. Longer studies are needed to establish whether adding nicotinamide riboside to exercise could be considered as part of a long-term, comprehensive treatment approach.

弗里德赖希共济失调是一种罕见的慢性进行性神经退行性疾病，会影响多个器官系统，包括神经系统、肌肉骨骼系统、心血管系统和内分泌系统，其特征是心肺功能低下。我们测试了运动以及补充烟酰胺核糖（一种烟酰胺腺嘌呤二核苷酸 [NAD+] 前体）对弗里德赖希共济失调患者心肺功能的影响，此前动物实验和早期临床研究均显示这两种干预手段有一定益处。对弗里德赖希共济失调患儿和成人进行为期 12 周的烟酰胺核糖补充联合运动干预是安全的，且能增强其心肺功能。需要开展更长期的研究，以确定在运动基础上添加烟酰胺核糖是否可作为长期综合治疗方案的一部分。

REF: Lin KY, Bucha A, McSweeney K, et al. Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial. Lancet Neurol. 2026;25(5):469-481. doi:10.1016/S1474-4422(26)00082-7 PMID: 42009009

Identification of genetic risk loci associated with aquaporin 4-positive neuromyelitis optica spectrum disorder: a genome-wide association study

与水通道蛋白4阳性视神经脊髓炎谱系疾病相关的遗传风险位点鉴定：一项全基因组关联研究

Little is known about the causes of serum aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (AQP4-positive NMOSD) or how its pathophysiology differs from other demyelinating autoimmune diseases, which limits therapeutic and preventative opportunities despite available diagnostic biomarkers. By performing a pan-ancestry genome-wide association study (GWAS), we aimed to deepen our understanding of the genetic architecture of AQP4-positive NMOSD and to explore shared heritability with other autoimmune diseases. AQP4-positive NMOSD is more genetically similar to systemic autoimmune diseases than to multiple sclerosis, despite sharing overlapping clinical phenotypes. Specifically, a polymorphism associated with reduced complement C4 was identified as the biggest disease genetic risk factor, which has been shown to facilitate the development of autoantibody-producing B cells. Our findings also support a pathogenic role of HLA-restricted CD4+T cells, owing to both a genome-wide significant association of HLA-DRB1*03:01 as well as heritable risk within the TYK2-STAT4 signalling pathway. Having already been shown to be a successful target for treating psoriatic arthritis and, potentially, systemic lupus erythematosus, we propose the TYK2-STAT4 pathway as a possible therapeutic target in AQP4-positive NMOSD.

关于血清水通道蛋白4（AQP4）抗体阳性的视神经脊髓炎谱系疾病（AQP4阳性NMOSD）的病因，以及其病理生理学与其他脱髓鞘自身免疫性疾病有何不同，人们知之甚少。尽管有可用的诊断生物标志物，但这限制了治疗和预防的机会。通过开展全血统全基因组关联研究（GWAS），我们旨在加深对AQP4阳性NMOSD遗传结构的理解，并探索其与其他自身免疫性疾病的共同遗传特性。尽管AQP4阳性NMOSD与多发性硬化症有重叠的临床表型，但其在遗传上与全身性自身免疫性疾病更为相似。具体而言，一种与补体C4降低相关的多态性被确定为最大的疾病遗传风险因素，已有研究表明该因素会促进产生自身抗体的B细胞的发育。我们的研究结果还支持HLA限制的CD4+T细胞的致病作用，这是因为HLA - DRB1*03:01具有全基因组显著关联性，并且TYK2 - STAT4信号通路存在可遗传风险。鉴于TYK2 - STAT4通路已被证明是治疗银屑病关节炎的有效靶点，并且可能也是治疗系统性红斑狼疮的靶点，我们提出将TYK2 - STAT4通路作为AQP4阳性NMOSD的一个潜在治疗靶点。

REF: Attfield KE, Armen AP, Kuttikkatte SB, et al. Identification of genetic risk loci associated with aquaporin 4-positive neuromyelitis optica spectrum disorder: a genome-wide association study. Lancet Neurol. 2026;25(5):482-491. doi:10.1016/S1474-4422(26)00084-0 PMID: 42009010