Paul-Ehrlich-Institut, Langen, Germany.
Emerg Infect Dis. 2013 May;19(5):712-20. doi: 10.3201/eid1905.120274.
Risk for human exposure to bovine spongiform encephalopathy (BSE)-inducing agent was estimated in a nonhuman primate model. To determine attack rates, incubation times, and molecular signatures, we orally exposed 18 macaques to 1 high dose of brain material from cattle with BSE. Several macaques were euthanized at regular intervals starting at 1 year postinoculation, and others were observed until clinical signs developed. Among those who received ≥5 g BSE-inducing agent, attack rates were 100% and prions could be detected in peripheral tissues from 1 year postinoculation onward. The overall median incubation time was 4.6 years (3.7-5.3). However, for 3 macaques orally exposed on multiple occasions, incubation periods were at least 7-10 years. Before clinical signs were noted, we detected a non-type 2B signature, indicating the existence of atypical prion protein during the incubation period. This finding could affect diagnosis of variant Creutzfeldt-Jakob disease in humans and might be relevant for retrospective studies of positive tonsillectomy or appendectomy specimens because time of infection is unknown.
我们通过非人类灵长类动物模型估计了人类接触牛海绵状脑病(BSE)诱导因子的风险。为了确定攻击率、潜伏期和分子特征,我们通过口服方式将 18 只猕猴暴露于 1 高剂量来自患有 BSE 的牛的脑组织中。自接种后 1 年开始,每隔一段时间就会对几只猕猴进行安乐死,而对其他猕猴则进行观察,直到出现临床症状。在接受≥5 g BSE 诱导剂的猕猴中,攻击率为 100%,并且可以从接种后 1 年起在周围组织中检测到朊病毒。总体中位潜伏期为 4.6 年(3.7-5.3)。然而,对于多次口服暴露的 3 只猕猴,潜伏期至少为 7-10 年。在出现临床症状之前,我们检测到一种非 2B 型特征,表明在潜伏期存在异常朊病毒蛋白。这一发现可能会影响人类变异型克雅氏病的诊断,并且可能与回顾性研究阳性扁桃体切除术或阑尾切除术标本有关,因为感染时间未知。