Objectives

There are few data available regarding the clinical course of tick-borne encephalitis virus (TBEV) vaccination breakthrough infections. The published studies suggest that vaccination breakthrough infections may have a more severe course than native TBEV infection in unvaccinated individuals—potentially due to antibody-dependent enhancement. Here we report a large analysis of vaccination breakthrough infections.

Methods

This retrospective analysis was based on a national surveillance dataset spanning the years 2001–2018. Variables reflecting disease severity, such as ‘CNS symptoms’, ‘myelitis’, ‘fatal outcome’ and ‘hospitalization’ were analysed as well as general epidemiological variables. Cases were categorized as ‘unvaccinated’ or ‘ever vaccinated’, the latter category including cases with at least one dose of a TBEV vaccine.

Results

A total of 6073 notified TBEV infection cases were included in our analysis. Sufficient data on vaccination status were available for 95.1% of patients (5777/6073); of these, 5298 presented with a native infection. A total of (334/5777) cases developed an infection despite having been vaccinated at least once. Comparing unvaccinated patients with those with at least one vaccination, we find an odds ratio (OR) 2.73, (95% confidence interval (CI) 0.79–9.50) regarding the variable fatal outcome that did not reach statistical significance. Analysing the clinical variables ‘CNS symptoms’ and ‘myelitis’, there is no difference between these groups (OR 0.86, 95% CI 0.68–1.08; and OR 1.30, 95% CI 0.74–2.27 respectively). Patients who were vaccinated and had an assumed protection at symptom onset (n = 100) had a higher risk for the development of myelitic symptoms (OR 2.21, 95% CI 1.01–4.86]) than unvaccinated patients.

Conclusion

Our findings could neither verify that vaccination breakthrough infections might cause a more severe disease than native infections nor prove a clear antibody-dependent enhancement phenomenon. It remains unclear whether the increased myelitis risk in a subgroup of vaccinated patients is a true effect or confounded.

中文翻译：

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传脑炎病毒疫苗的突破性感染在德国：2001年至2018年的回顾性分析。

目标

关于tick传脑炎病毒（TBEV）疫苗突破性感染的临床病程，几乎没有可用的数据。已发表的研究表明，在未接种疫苗的个体中，疫苗突破性感染的病程可能比天然TBEV感染更为严重-可能是由于抗体依赖性增强。在这里，我们报告了疫苗接种突破性感染的大量分析。

方法

这项回顾性分析基于2001年至2018年的国家监视数据集。分析了反映疾病严重程度的变量，例如“中枢神经系统症状”，“脊髓炎”，“致命结局”和“住院”，以及一般的流行病学变量。病例分为“未接种”或“曾经接种”，后一类包括至少接种一剂TBEV疫苗的病例。

结果

我们的分析总共包括6073例通报的TBEV感染病例。95.1％的患者可获得足够的疫苗接种状况数据（5777/6073）；其中有5298例是自然感染。尽管至少接种了一次疫苗，但总共（334/5777）例发生了感染。将未接种疫苗的患者与至少接种过一次疫苗的患者进行比较，我们发现未达到统计学意义的可变致命结果的比值比（OR）为2.73（95％置信区间（CI）为0.79–9.50）。分析临床变量“中枢神经系统症状”和“脊髓炎”后，这些组之间没有差异（OR 0.86，95％CI 0.68–1.08； OR 1.30，95％CI 0.74–2.27）。接种疫苗并假定在症状发作时有保护的患者（n = 100）与未接种疫苗的患者相比，发生骨髓炎症状的风险更高（OR 2.21，95％CI 1.01–4.86]。

结论

我们的发现既不能证明疫苗突破性感染比自然感染可能导致更严重的疾病，也不能证明有明显的抗体依赖性增强现象。尚不清楚在接种疫苗的亚组中增加的脊髓炎风险是真实的效果还是混淆的。