Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling.

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3–4 weeks before onset of vaccine meningitis may be a risk factor in some cases.

水痘疫苗脑膜炎是一种罕见的疫苗接种延迟不良事件。已在12名儿童中诊断出水痘疫苗脑膜炎，其中3名儿童免疫功能低下。我们现在报告另外两例在接受过两次免疫且免疫功能正常的儿童中发生的疫苗脑膜炎病例，并对之前的第三例进行进一步检测。我们使用了三种方法来诊断或研究水痘疫苗脑膜炎病例，这些方法以前都未用于该疾病。其中包括对脑脊液进行宏基因组新一代测序和细胞因子多重分析，以及对白细胞进行免疫外显子组分析。在一个新病例中，通过对脑脊液进行宏基因组新一代测序确诊，检测到了水痘疫苗病毒和人疱疹病毒7的DNA。我们对两例病例的脑脊液进行了细胞因子多重分析，发现十种生物标志物升高：干扰素γ、白细胞介素IL - 1RA、IL - 6、IL - 8、IL - 10、IL - 17F、趋化因子CXCL - 9、CXCL - 10、CCL - 2和G - CSF。在第二个新病例中，我们对一组356个基因进行了免疫外显子组测序，但未发现错误。在对所有14例病例进行回顾后，我们得出结论：（i）这种不良事件没有常见的解释，但（ii）在疫苗脑膜炎发病前3 - 4周口服皮质类固醇冲击治疗可能在某些病例中是一个危险因素。