Data from: Validation and utilization of amended diagnostic criteria in Creutzfeldt-Jakob Disease surveillance

Objective: To validate an amended protocol for clinical diagnosis of sporadic Creutzfeldt-Jakob Disease (sCJD) including Real-Time Quaking-induced Conversion (RT-QuIC) and to observe its utilization in CJD surveillance. Methods: In the framework of a prospective epidemiological study, all neuropathological confirmed sCJD cases that received CSF RT-QuIC analysis during diagnostic work up (n=65) and a control group of non- CJD cases (n=118) were selected to investigate the accuracy of an amended diagnostic protocol. The patients had been referred to the German National Reference Center for Transmissible Spongiform Encephalopathies. The influence of the amended protocol on incidence figures was evaluated in the context of three years of surveillance activity (screened cases using 14-3-3 test: n=18.789, highly suspicious cases of CJD: n=704). Annual incidences were calculated using current criteria and the amended protocol. Results: The amended protocol showed a sensitivity of 97% and a specificity of 99%. When it was applied to all suspected cases that were referred to the reference center, the assessed incidence of CJD increased from 1.7 to 2.2 per million in 2016. Conclusion: CJD surveillance remains challenging as information from external healthcare institutions can be limited. RT-QuIC shows excellent diagnostic accuracy when applied in the clinical setting to symptomatic patients. Data for RT-QuIC alone, when applied as a general screening test, are not available yet. We propose an amended research protocol which improves early and accurate clinical diagnosis of sCJD during surveillance activities. The utilization of this protocol will probably lead to a significant increase of the incidence rate.【研究目的】验证一项纳入实时震颤诱导转化试验（Real-Time Quaking-induced Conversion, RT-QuIC）的散发性克雅氏病（sporadic Creutzfeldt-Jakob Disease, sCJD）改良临床诊断方案，并观察其在克雅氏病监测中的应用效果。 【研究方法】本研究为一项前瞻性流行病学研究，共纳入两类研究对象：一类为在诊断流程中接受脑脊液（Cerebrospinal Fluid, CSF）RT-QuIC检测的经神经病理确诊的散发性克雅氏病病例（n=65），另一类为非克雅氏病对照组病例（n=118），旨在评估该改良诊断方案的诊断准确性。所有研究对象均转诊至德国传染性海绵状脑病国家参考中心。结合三年的监测工作数据（其中接受14-3-3蛋白检测（14-3-3 test）的筛查病例共18789例，高度疑似克雅氏病的病例共704例），本研究评估了改良方案对发病统计数据的影响。研究分别采用现行诊断标准与改良方案计算年度发病率。 【研究结果】该改良诊断方案的灵敏度为97%，特异度为99%。将其应用至转诊至参考中心的所有疑似病例后，2016年克雅氏病的评估发病率从每百万人1.7例升至2.2例。 【研究结论】克雅氏病的监测工作仍具挑战性，因外部医疗机构提供的信息往往存在局限性。将RT-QuIC应用于有症状患者的临床场景时，展现出优异的诊断准确性。目前尚无将RT-QuIC作为通用筛查试验的相关研究数据。本研究提出一项改良研究方案，可在监测活动中优化散发性克雅氏病的早期精准临床诊断。该方案的应用或可使发病率出现显著提升。