The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, Edinburgh, United Kingdom.
Friedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases, Greifswald, Germany.
PLoS Pathog. 2021 Feb 18;17(2):e1009276. doi: 10.1371/journal.ppat.1009276. eCollection 2021 Feb.
Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by blood transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing infection, using BSE-infected sheep as a model. All components were capable of transmitting prion disease when donors were in the preclinical phase of infection, with the highest rates of infection in recipients of whole blood and buffy coat, and the lowest in recipients of plasma. Leucodepletion of components (<106 WBCs/unit) resulted in significantly lower transmission rates, but did not completely prevent transmission by any component. Donor PRNP genotype at codon 141, which is associated with variation in incubation period, also had a significant effect on transfusion transmission rates. A sensitive protein misfolding cyclic amplification (PMCA) assay, applied to longitudinal series of blood samples, identified infected sheep from 4 months post infection. However, in donor sheep (orally infected), the onset of detection of PrPSc in blood was much more variable, and generally later, compared to recipients (intravenous infection). This shows that the route and method of infection may profoundly affect the period during which an individual is infectious, and the test sensitivity required for reliable preclinical diagnosis, both of which have important implications for disease control. Our results emphasize that blood transfusion can be a highly efficient route of transmission for prion diseases. Given current uncertainties over the prevalence of asymptomatic vCJD carriers, this argues for the maintenance and improvement of current measures to reduce the risk of transmission by blood products.
变异型克雅氏病（vCJD）是人畜共患的牛海绵状脑病（BSE）感染导致的朊病毒病。有记录的 vCJD 通过输血传播的病例需要持续采取降低风险的措施来保护血液供应，例如白细胞去除（去除白细胞，WBC）。本研究旨在确定不稳定血液成分（红细胞、血小板、血浆）在人医中常用的输血传播朊病毒病的风险，以及白细胞去除在预防感染中的有效性，使用 BSE 感染绵羊作为模型。当供体处于感染的临床前阶段时，所有成分都能够传播朊病毒病，全血和血浆的受者感染率最高，而血浆的受者感染率最低。成分的白细胞去除（<106 WBC/单位）导致传播率显著降低，但不能完全防止任何成分的传播。供体 PRNP 基因在 141 密码子处的基因型与潜伏期的变化有关，对输血传播率也有显著影响。一种敏感的蛋白错误折叠循环扩增（PMCA）检测方法，应用于一系列纵向血液样本，可在感染后 4 个月从感染绵羊中识别出感染的绵羊。然而，在供体绵羊（经口感染）中，与受者（静脉感染）相比，血液中 PrPSc 的检测开始时间变化更大，且通常更晚。这表明感染途径和方法可能会深刻影响个体具有传染性的时间，以及可靠的临床前诊断所需的检测灵敏度，这两者对疾病控制都有重要影响。我们的结果强调了输血可能是朊病毒病的一种非常有效的传播途径。鉴于目前对无症状 vCJD 携带者的流行率存在不确定性，这就需要维持和改进当前降低血液制品传播风险的措施。
