加强肠道病毒基因组监测显示肠道病毒D68病例激增,约翰霍普金斯医疗系统,马里兰州,2024年
Enhanced genomic surveillance of enteroviruses reveals a surge in enterovirus D68 cases, the Johns Hopkins health system, Maryland, 2024.
作者信息
Fall Amary, Norton Julie M, Abdullah Omar, Pekosz Andrew, Klein Eili, Mostafa Heba H
机构信息
Division of Medical Microbiology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
出版信息
J Clin Microbiol. 2025 Jul 9;63(7):e0046925. doi: 10.1128/jcm.00469-25. Epub 2025 Jun 10.
This study reports increased Enterovirus D68 (EV-D68) circulation in 2024, re-establishing its biennial circulation cycle after its interruption during the COVID-19 pandemic. A total of 1,395 respiratory and cerebrospinal fluid (CSF) samples, positive for rhinovirus/enterovirus, collected from January to November 2024 were screened. EV-D68 was the predominant enterovirus detected (72.6% of EV-positive samples), with cases peaking in October, consistent with historical seasonal patterns. Demographically, children under 5 years were predominantly infected with EV-D68 (41.6% of cases). Phylogenetic analysis revealed the co-circulation of two EV-D68 subclades: B3 (71%) and A2 (29%). Subclade B3 was primarily associated with pediatric infections (median age: 5 years), while A2 was more common in adults (median age: 42 years). Comparative genomic analysis of the 2024 B3 genomes, along with genomes from 2018 and 2022, identified the emergence of four amino acid substitutions, including three in nonstructural proteins (3C: I597V; 3D: I950V, T2173A) and one in the structural protein VP2 (T145S). The six positive enterovirus CSF samples diagnosed in 2024 included six different types: EV-D68, E9, E30, E18, CV-A9, and CV-B1. Notably, the 2024 EV-D68 outbreak did not coincide with a reported increase in acute flaccid myelitis (AFM) cases. This study highlights the importance of EV-D68 genomic surveillance for monitoring EV-D68 evolution, given its association with severe respiratory disease and neurological complications. Enhanced surveillance is also critical for the early detection of the emergence of enteroviruses, such as EV-C105, identified in this study.IMPORTANCEEnteroviruses (EVs), a genus within the family, are small, single-stranded RNA viruses linked to a wide spectrum of diseases, including neurological conditions. Despite their prevalence, they remain understudied. EV-D68 and EV-A71 have raised global public health concerns due to outbreaks of acute flaccid myelitis (AFM) and encephalomyelitis in North America and Europe. EVs exhibit high genetic variability, and viral evolution has been associated with changes in neurovirulence. Notably, EV-D68 epidemics in 2014, 2016, and 2018 coincided with spikes in AFM cases. However, AFM reports from 2019 to 2022 were low, even with a significant increase in EV-D68 infections in 2022. We developed an EV-D68 genomic surveillance workflow to investigate genotype associations with severe disease. Our previous work linked amino acid substitutions in 2018 strains to increased disease severity. This study analyzes EV-D68 evolution in 2024 and documents the return of its biennial circulation pattern following disruption during the COVID-19 pandemic.
本研究报告称,肠道病毒D68(EV-D68)在2024年的传播有所增加,在新冠疫情期间中断后重新确立了其两年一次的传播周期。对2024年1月至11月收集的1395份鼻病毒/肠道病毒检测呈阳性的呼吸道和脑脊液(CSF)样本进行了筛查。EV-D68是检测到的主要肠道病毒(占EV阳性样本的72.6%),病例数在10月达到峰值,与历史季节性模式一致。从人口统计学角度来看,5岁以下儿童主要感染EV-D68(占病例的41.6%)。系统发育分析显示两个EV-D68亚分支共同传播:B3(71%)和A2(29%)。亚分支B3主要与儿科感染相关(中位年龄:5岁),而A2在成人中更常见(中位年龄:42岁)。对2024年B3基因组以及2018年和2022年的基因组进行比较基因组分析,确定出现了四个氨基酸替换,包括非结构蛋白中的三个(3C:I597V;3D:I950V、T2173A)和结构蛋白VP2中的一个(T145S)。2024年诊断出的六份肠道病毒阳性脑脊液样本包括六种不同类型:EV-D68、E9、E30、E18、CV-A9和CV-B1。值得注意的是,2024年的EV-D68疫情与急性弛缓性脊髓炎(AFM)病例报告增加并不一致。鉴于EV-D68与严重呼吸道疾病和神经系统并发症的关联,本研究强调了对EV-D68进行基因组监测以监测其进化的重要性。加强监测对于早期发现本研究中鉴定出的肠道病毒(如EV-C105)的出现也至关重要。重要性肠道病毒(EVs)是该科中的一个属,是与包括神经系统疾病在内的广泛疾病相关的小型单链RNA病毒。尽管它们很常见,但仍研究不足。EV-D68和EV-A71因在北美和欧洲爆发急性弛缓性脊髓炎(AFM)和脑脊髓炎而引起全球公共卫生关注。肠道病毒表现出高度的遗传变异性,病毒进化与神经毒力变化有关。值得注意的是,2014年、2016年和2018年的EV-D68疫情与AFM病例激增同时发生。然而,2019年至2022年的AFM报告较少,即使2022年EV-D68感染显著增加。我们开发了一种EV-D68基因组监测工作流程,以研究基因型与严重疾病的关联。我们之前的工作将2018年毒株中的氨基酸替换与疾病严重程度增加联系起来。本研究分析了2024年EV-D68的进化,并记录了其在新冠疫情期间中断后两年一次传播模式的恢复。