Coulthart Michael B, Geschwind Michael D, Qureshi Shireen, Phielipp Nicolas, Demarsh Alex, Abrams Joseph Y, Belay Ermias, Gambetti Pierluigi, Jansen Gerard H, Lang Anthony E, Schonberger Lawrence B
1 Canadian Creutzfeldt-Jakob Disease Surveillance System, Centre for Foodborne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Ottawa, ON K1A 0K9, Canada
2 Memory and Aging Center, Box 1207, University of California, San Francisco (UCSF), San Francisco, CA 94143-1207, USA.
Brain. 2016 Oct;139(Pt 10):2609-2616. doi: 10.1093/brain/aww206.
As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease-the human form of a prion disease of cattle, bovine spongiform encephalopathy-have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980-96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. We report results of a quantitative analysis of country-specific relative risks of infection for three individuals diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were born and raised in Saudi Arabia, but had histories of residence and travel in other countries. To calculate country-specific relative probabilities of infection, we aligned each patient's life history with published estimates of probability distributions of incubation period and age at infection parameters from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The distributions were then partitioned into probability density fractions according to time intervals of the patient's residence and travel history, and the density fractions were combined by country. This calculation was performed for incubation period alone, age at infection alone, and jointly for incubation and age at infection. Country-specific fractions were normalized either to the total density between the individual's dates of birth and symptom onset ('lifetime'), or to that between 1980 and 1996, for a total of six combinations of parameter and interval. The country-specific relative probability of infection for Saudi Arabia clearly ranked highest under each of the six combinations of parameter × interval for Patients 1 and 2, with values ranging from 0.572 to 0.998, respectively, for Patient 2 (age at infection × lifetime) and Patient 1 (joint incubation and age at infection × 1980-96). For Patient 3, relative probabilities for Saudi Arabia were not as distinct from those for other countries using the lifetime interval: 0.394, 0.360 and 0.378, respectively, for incubation period, age at infection and jointly for incubation and age at infection. However, for this patient Saudi Arabia clearly ranked highest within the 1980-96 period: 0.859, 0.871 and 0.865, respectively, for incubation period, age at infection and jointly for incubation and age at infection. These findings support the hypothesis that human infection with bovine spongiform encephalopathy occurred in Saudi Arabia.
截至2016年年中,12个国家报告了231例变异型克雅氏病(牛海绵状脑病这种牛朊病毒病的人类形式)。几乎无一例外,这些受影响个体在人类接触牛海绵状脑病全球风险最高的时期(1980 - 1996年)有在英国或其他西欧国家长期居住的经历。然而,其他人类感染的地理聚集区仍有可能存在,确定这些区域可能有助于预测该流行病的未来走向。我们报告了对在美国和加拿大被诊断为变异型克雅氏病的三名个体进行的特定国家感染相对风险的定量分析结果。这三人都在沙特阿拉伯出生并长大,但有在其他国家居住和旅行的经历。为了计算特定国家的感染相对概率,我们将每位患者的生活史与来自英国171例变异型克雅氏病病例队列的潜伏期和感染年龄参数概率分布的已发表估计值进行比对。然后根据患者居住和旅行史的时间间隔将这些分布划分为概率密度分数,并按国家对密度分数进行合并。此计算分别针对单独的潜伏期、单独的感染年龄以及潜伏期和感染年龄联合进行。特定国家的分数要么相对于个体出生日期和症状出现日期之间的总密度(“一生”)进行归一化,要么相对于1980年至1996年之间的总密度进行归一化,总共得到参数和时间间隔的六种组合。在患者1和患者2的参数×时间间隔的六种组合中的每一种情况下,沙特阿拉伯的特定国家感染相对概率显然最高,患者2(感染年龄×一生)和患者1(潜伏期和感染年龄联合×1980 - 1996年)的值分别在0.572至0.998之间。对于患者3,使用一生时间间隔时,沙特阿拉伯的相对概率与其他国家的相对概率没有那么明显的差异:潜伏期、感染年龄以及潜伏期和感染年龄联合的相对概率分别为0.394、0.360和0.378。然而对于该患者,在1980 - 1996年期间沙特阿拉伯显然排名最高:潜伏期、感染年龄以及潜伏期和感染年龄联合的相对概率分别为0.859、0.871和0.865。这些发现支持了人类在沙特阿拉伯感染牛海绵状脑病的假设。