朊病毒病及朊病毒的研究进展（一）

简要介绍了朊病毒病的基本特征、疾病谱、新发现的几种朊病毒病（致死性家族性失眠症、牛海绵状状脑病、新型克、雅二氏病等）及现毒病的诊断和防治方法,详细了阐述了现毒的基本概念、异常特性、支持朊病毒假说的语气及有特研究解决的问题等。     

基因研究发现人的克－雅氏病与疯牛病密切相关

基因研究发现人的克－雅氏病与疯牛病密切相关科学家戴维．克拉考尔及其合作者，在英国研究结果表明，与人的克罗伊茨费尔特－雅各布氏病和牛的疯牛病有联系的脑蛋白基因间有非常接近的相似性。这可能是人吃了疯牛病（牛海绵状脑病）患牛的肉得克－雅氏病，而吃了瘙痒病患...     

家畜海绵状脑病和痒病的发生与诊治

传染性海绵状脑病是由朊病毒引起人和动物的某组致死性中枢神经系统变性传染病,包括牛海绵状脑病、痒病、貂传染性脑病和人的克一雅氏病、库鲁病等。家畜共同特征是潜伏期长,可达几个月至几十年,进行性共济失调,震颤,姿势不稳,知觉过敏,家畜痴呆等神经症状,病程发展缓慢,但全部以死亡告终。     

朊病毒(Prion)——新的传染性病原体

朊病毒(或其类似物)能引起诸如牛海绵状脑病,绵羊痒病,传染性水貂脑病,麋、骡、鹿的慢性萎缩病以及人类的克—雅氏综合症(CJD)、格斯特曼—斯特拉斯勒综合症(GSS)及库鲁病,是一种新的传染性病原体。     

苔藓生物有望成为朊病毒的克星

可传播海绵状脑病是一类由朊病毒引起的神经性病变的总称,主要危害人类及其他多种动物,包括山羊、绵羊、牛、水貂、猫、狐猴等。目前发现有16种朊病毒病,其中人类朊病毒病有9种,动物朊病毒病有7种。引起该病的主要原因是细胞表达的正常朊蛋白发生空间结构变异并在神经中枢积聚后引起神经系统的病变,如疯牛病、痒病、     

牛海绵状脑病最新动态

牛海绵状脑病最新动态黄建珍，高彦生编译（广东拱北动植物检疫局珠海５１９０２０）牛海绵状脑病于１９８５年首次在英国发现，并一直困扰着英国的养牛业，使其蒙受巨大的经济损失。３月２０日，英国政府首次承认人吃了患牛的肉有可能会得克－雅氏病，这一消息在英国、欧...     

几种新的动物及动物与人共患病简介（一）

疯牛病 1 概念：“疯牛病”有多种名称，目前世界上广泛采用的病名是“传染性海绵状脑病”（TranSmissible spongifolm encephaiopathies TSE），简称“牛海绵状脑病”（BSE）。由于它是由“朊病毒”（又称“朊粒”）引起，所以，有的又叫“朊病毒病”或“朊粒病”（Prion diseases）。除此之外还有称为“传染性变性脑病”（TDE）、“传染性脑淀粉样变性”（TCA）、“亚急性海绵状脑病”（SSE）、“亚急性海绵状病毒性脑病”（SSVE）等的。严格意义上的“TSEs”应译为“可传递性海绵状脑病”。该病是人和动物共患、呈亚急性、渐进…     

疯牛病研究进展及世界各国的防制对策

传播性海绵状脑病（或称朊病毒疾病）是一类引起人和动物的神经组织退化的疾病．包括人的震颤病，雅克氏病（CJD），吉斯综合症（GSS）和致死性家族失眠症（FFI）以及动物的疯牛病、羊骚痒病。牛海绵状脑病（BSE），又称疯牛病，是牛的一种神经性、渐进性、致死性疾病，病原为朊病毒，是一种无核酸的蛋白性侵染颗粒。动物采食含有朊病毒的肉骨粉可引起该病的发生。     

疯牛病的传染途径及防控措施

疯牛病学名牛海绵状脑病,是一种由朊病毒引起的致死性人畜共患神经退行性疾病。病牛脑组织呈海绵状病变,传染给人类后可导致人类疯牛病——"克-雅病"。目前该病发病地区日益扩大,病例数上升,危害极大。从病原、临床症状、传染途径及防控措施4个方面对疯牛病以及人类感染朊病毒后所得"克-雅病"进行了总结。     

疯牛病与动物性饲料

牛海绵状脑病（BSE）又称疯牛病，是由非常规致病因子引起的一种亚急性海绵状脑病，也是危害牛中枢神经系统的传染性疾病，染上这种病的牛、脑神经会逐渐变成海绵状，随着大脑功能的退化，病牛会神经错乱，行动失控，最终死亡，食用被疯牛病污染了的牛肉、牛脑髓的人，有可能染上致命的“克－雅氏症”（CJD），脑部也会变成海绵状，最终因神经错乱而死亡。据欧盟委员会提供了数字，迄今欧盟国家总区发现约18万头患上疯牛病的牛，而因身染“克－雅氏症”致死的患者已达84人。英国科学家曾估计，仅在英国有可能感染上“克－雅氏症”的人高达百万之多，由于这种病有10年至30年的潜伏期，专家估计还要过10年才会出“克－雅氏症”大流行。     

Transmissible spongiform encephalopathies in humans

Transmissible spongiform encephalopathies (TSE) are dementing diseases and have been known to affect humans for over 90 years. The most common of these is the sporadic form of Creutzfeldt-Jakob disease (sCJD), followed by its familial (fCJD) and an iatrogenic (iCJD) form. 1996 a variant of CJD (vCJD) has been described in the UK, of which so far 131 cases have been observed worldwide. Specific biochemical and neuropathological signatures allow to distinguish between vCJD and sCJD and lead to the hypothesis that vCJD is due to transmission of BSE prions to humans. Although promising therapeutical approaches are being investigated, human TSE remain untreatable entities. Thus preventive measures are essential. In Switzerland the population has been exposed to BSE prions, too, but no case of vCJD as described in the UK has been observed until now. Since 2001, however, a so far unexplained increase of sCJD cases is being observed.     

Prions as the driving force in transmissible spongiform encephalopathies

Transmissible spongiform encephalopathies are degenerative disorders affecting the central nervous system (CNS) occurring in a variety of species. The causative agent is thought to be composed of an abnormal form of the host encoded prion protein (PrPC), termed PrPSc. The conformational change of PrPC into PrPSc can occur spontaneously, however, it can also be induced by PrPSc. Prion diseases such as bovine spongiform encephalopathy (BSE), scrapie and variant Creutzfeldt-Jakob-Disease (vCJD) are most likely caused by peripheral uptake of prions. The process by which prions proceed to the CNS following peripheral uptake is referred to as neuroinvasion. Infection with prions is thought to occur in two phases: After ingestion prions first replicate in lymphatic tissue and then gain access to the CNS via peripheral nerves. Studies looking at the biochemical and clinical characteristics of BSE and vCJD demonstrated that BSE is most likely responsible for vCJD in humans.     

The price of the precautionary principle: Cost-effectiveness of BSE intervention strategies in the Netherlands

Since 1996, bovine spongiform encephalopathy (BSE) in cattle has been linked to a new variant of Creutzfeldt-Jakob disease (vCJD), a fatal brain disease in man. This paper assessed the cost-effectiveness of BSE control strategies instituted by the European Commission. In a Monte Carlo simulation model, a non-intervention baseline scenario was compared to three intervention strategies: removal of specified risk materials from slaughter animals, post-mortem testing for BSE and the culling of feed and age cohorts of BSE cases. The food risk in the baseline scenario ranged from 16.98 lost life years in 2002 to 2.69 lost life years in 2005. Removing specified risk materials removal practices, post-mortem testing and post-mortem testing plus cohort culling reduced this risk with 93%, 82.7% and 83.1%. The estimated cost-effectiveness of all BSE measures in the Netherlands ranged from 4.3 million euros per life year saved in 2002 to 17.7 million euros in 2005. It was discussed that the cost-effectiveness of BSE control strategies will further deviate from regular health economics thresholds as BSE prevalence and incidence declines.     

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

Scrapie and bovine spongiform encephalopathy (BSE) are major global concerns and the emergence of variant Creutzfeldt-Jakob disease (vCJD) has caused turmoil for blood transfusion services and hospitals worldwide. Recent reports of iatrogenic CJD (iCJD) cases following blood transfusions from Transmissible Spongiform Encephalopathies (TSE)-infected donors have fuelled this concern. Major diagnostic tests for BSE and scrapie are conducted post-mortem from animals in late stages of the disease. Although the lymphoreticular system is involved in the earlier pathogenesis of some forms of sheep scrapie and vCJD, which presents great opportunity for diagnostic development, other TSE diseases (some strains of scrapie, sporadic CJD (sCJD) and bovine BSE) do not present such a diagnostic opportunity. Thus, there is an urgent need for pre-mortem tests that differentiate between healthy and diseased individuals at early stages of illness, in accessible samples such as blood and urine using less invasive procedures. This review reports on the current state of progress in the development and use of prion and non-prion biomarkers in the diagnosis of TSE diseases. Some of these efforts have concentrated on improving the sensitivity of PrPSc detection to allow in vivo diagnosis at low abundances of PrPSc whilst others have sought to identify non-prion protein biomarkers of TSE disease, many of which are still at early stages of development. In this review we comment upon the limitations of prion based tests and review current research on the development of tests for TSE that rely on non-prion disease markers in body fluids that may allow preclinical disease diagnosis.     

使用含牛源蛋白的化妆品传播vCJD的风险评估

运用风险分析理论,以科学研究为基础,同时遵循客观实际,分别从危害确认、接触评估、危害评定及风险评定几方面对含有牛源性成份的化妆品能否传播人类变异型克雅氏症的风险进行了科学评估。结果认为,由于化妆品直接与皮肤接触,而朊蛋白可以被身体许多部位吸收,所以含有牛源性蛋白的化妆品是一个潜在的暴露源,使用含牛源性蛋白的化妆品存在感染人类变异型克雅氏症的风险。然而,由于风险评估中存在许多重要的变数,因而存在许多不确定性,关于发生该病的风险所做的任何定量评估都不是很准确的,防止疯牛病病原通过化妆品传播的最可靠的做法就是化妆品生产中禁止使用高风险性牛源蛋白。     

Geographical BSE risk assessment and its impact on disease detection and dissemination

Bovine Spongiform Encephalopathy (BSE) rapidly evolved into an issue of major public concern particularly when, in 1996, evidence was provided that this disease had crossed the species barrier and infected humans in the UK with what has become known as "variant Creutzfeldt Jakob Disease" (vCJD). The aim of this paper is to describe the European Geographical BSE risk assessment (GBR) that was successfully used for assessing the qualitative likelihood that BSE could be present in a country where it was not yet officially recognized. It also discusses how this can lead to risk-based and therefore preventive management of BSE at national and international levels. The basic assumption of the GBR method is that the BSE agent is initially introduced into a country's domestic cattle production system through the importation of contaminated feedstuffs or live cattle. This is referred to as an "external challenge". The ability of the system to cope with such a challenge is, in turn, referred to as its "stability": a stable system will not allow the BSE agent to propagate and amplify following its introduction, while an unstable system will. The BSE-status of a country assessed by this system was used by the European Commission as the basis for trade legislation rules for cattle and their products. The GBR was an invaluable tool in evaluating the potential global spread of BSE as it demonstrated how a disease could be transferred through international trade. This was shown to be a critical factor to address in reducing the spread and amplification of BSE throughout the world. Furthermore, GBR resulted in the implementation of additional measures and management activities both to improve surveillance and to prevent transmission within the cattle population.     

The unrecognised French BSE epidemic

In France, implementation of systematic screening programs in 2000, as a complement to the mandatory reporting of animals with clinical signs of BSE (passive surveillance), revealed certain limitations of the mandatory system. Indeed, systematic screening showed that some BSE cases were not detected by the clinical surveillance system, implying considerable BSE case under-reporting throughout the epidemic. As the most likely explanation for variant Creutzfeldt-Jakob disease (vCJD) is exposure to the aetiologic agent of BSE, it is essential to reconstruct the French BSE epidemic pattern accounting for this under-reporting. We estimated age- and year-specific incidence rates of BSE by using a back-calculation method. This approach relies on the principle that the number of clinical BSE cases is the consequence of the number of BSE-infected animals after a known incubation time, defined as the time between infection and clinical onset. We generalized this model to take into account epidemiological characteristics of BSE, such as French cattle mortality, BSE case reporting probability, and age-dependent susceptibility and/or exposure to the BSE agent. We confirmed that the average BSE incubation period is five years and that the peak risk of bovine infection occurs between 6 and 12 months of age. The results also showed that the proportion of underreporting is the most influential parameter in the model, and that BSE was substantially underreported until rapid tests were introduced. Indeed, only 103 BSE cases were detected by passive surveillance up to June 2000, while we estimated that there was 301 200 (95% confidence interval (CI) [27 600-837 600]) cattle infected by the BSE agent. Despite uncertainty over the beginning of the epidemic, we showed that the French BSE epidemic in the late 1980s was completely undetected, and only the second wave, after 1990, was observed.     

人类朊病的研究进展

作者从流行病学、临床症状、诊断方法、治疗等方面对人类朊病克雅氏症（CJD）和新型克雅氏症（vCJD）的最新研究进展进行综述,为进一步研究该类疾病提供理论依据。     

Progress and limits of TSE diagnostic tools

Following the two "mad cow" crises of 1996 and 2000, there was an urgent need for rapid and sensitive diagnostic methods to identify animals infected with the bovine spongiform encephalopathy (BSE) agent. This stimulated research in the field of prion diagnosis and led to the establishment of numerous so-called "rapid tests" which have been in use in Europe since 2001 for monitoring at-risk populations (rendering plants) and animals slaughtered for human consumption (slaughterhouse). These rapid tests have played a critical role in the management of the mad cow crisis by allowing the removal of prion infected carcasses from the human food chain, and by allowing a precise epidemiological monitoring of the BSE epizootic. They are all based on the detection of the abnormal form of the prion protein (PrP(Sc) or PrP(res)) in brain tissues and consequently are only suitable for post-mortem diagnosis. Since it is now very clear that variant Creutzfeldt-Jakob disease (vCJD) can be transmitted by blood transfusion, the development of a blood test for the diagnosis of vCJD is a top priority. Although significant progress has been made in this direction, including the development of the protein misfolding cyclic amplification (PMCA) technology, at the time this paper was written, this objective had not yet been achieved. This is the most important challenge for the years to come in this field of prion research.     

Identification and characterization of two bovine spongiform encephalopathy cases diagnosed in the United States.

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy of cattle, first detected in 1986 in the United Kingdom and subsequently in other countries. It is the most likely cause of variant Creutzfeldt-Jakob disease (vCJD) in humans, but the origin of BSE has not been elucidated so far. This report describes the identification and characterization of two cases of BSE diagnosed in the United States. Case 1 (December 2003) exhibited spongiform changes in the obex area of the brainstem and the presence of the abnormal form of the prion protein, PrP(Sc), in the same brain area, by immunohistochemistry (IHC) and Western blot analysis. Initial suspect diagnosis of BSE for case 2 (November 2004) was made by a rapid ELISA-based BSE test. Case 2 did not exhibit unambiguous spongiform changes in the obex area, but PrP(Sc) was detected by IHC and enrichment Western blot analysis in the obex. Using Western blot analysis, PrP(Sc) from case 1 showed molecular features similar to typical BSE isolates, whereas PrP(Sc) from case 2 revealed an unusual molecular PrP(Sc) pattern: molecular mass of the unglycosylated and monoglycosylated isoform was higher than that of typical BSE isolates and case 2 was strongly labeled with antibody P4, which is consistent with a higher molecular mass. Sequencing of the prion protein gene of both BSE-positive animals revealed that the sequences of both animals were within [corrected] the range of the prion protein gene sequence diversity previously reported for cattle.