Bovine Spongiform Encephalopathy Agent Research Articles

From Chemical Drug to Immunotherapy: New Approaches for the Treatment of Prion Diseases

Transmissible spongiform encephalopathies (TSEs) also called prion diseases are fatal neurodegenerative disorders of humans and animals which are unique as their origin can be infectious, genetic or sporadic. More than 80% of TSE patients have sporadic cases, 15% have familial forms and 5% iatrogenic forms. In humans, TSEs are represented by Creutzfeldt Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia and Kuru. In animals, the prominent prion diseases are scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) of cattle and chronic wasting disease (CWD) of deer and elk. A critical event in TSEs is the accumulation in the central nervous system (CNS) of an abnormally folded protein, PrPSc, the protease-resistant isoform of a normal cellular protein encoded by the host and called PrPC. Until now, PrPSc isoform represented not only the best molecular marker of prion diseases but also a favorite target for therapeutic strategies. During the last decade studies on prion diseases have taken a new dimension with the BSE crisis in Europe and the emergence of a new variant of Creutzfeldt-Jakob disease (vCJD) linked to the BSE agent. Currently, no effective therapy exists for patients suffering from a clinically manifest prion disease. In addition, the multiplicity of TSEs origins and clinical forms emphasizes the difficulties of a therapeutic intervention. Indeed, it is likely that sporadic CJD which are diagnosed lately during the course of the disease request the development of a therapeutic approach that is different from that of familial prion diseases due to mutation in the PrP gene. Diagnosis, origin and stages of the disease are critical factors that should orient studies towards the development of adapted therapeutic approaches. In this article, we will review the anti-prion drugs that were identified up to now. Keywords: immunotherapy, prion diseases, transmissible spongiform encephalopathies, gerstmann, straussler, scheinker syndrome

Prise en charge des suspicions de maladie de Creutzfeldt-Jakob en réanimation

Creutzfeldt-Jakob disease is a neurodegenerative disease whose main characteristic is dementia. It has three epidemiological forms: the main one, sporadic, the familial form associated with mutation of the gene encoding the prion protein and iatrogenic forms. This transmissible spongiform subacute encephalopathy is a rare disease with an incidence of one case per million inhabitants per year. The disease’s neuropathological characteristics are the presence of spongiosis, neuronal death and gliosis and the accumulation of the host-encoded protein, partly resistant to proteases. The new variant of Creutzfeldt-Jakob disease was described in Great-Britain in 1996 in young patients with no medical history to suggest a iatrogenic or familial origin. Hyperdense signals to cerebral MRI have been described in post-thalamic areas and can be a helpful diagnostic feature in cases with a suggestive clinical picture. This form was quickly suspected to be the consequence of infection in man with the bovine spongiform encephalopathy agent. To date, 130 cases have been recorded. The agent distribution in humans is largely peripheral. The safety of transplants, drugs, transfusion and regulations on the safety of hospitals need to be reassessed. From public health point of view, it is essential that all cases are identified.

Studies of the transmissibility of the agent of bovine spongiform encephalopathy to pigs.

Studies to test the transmissibility of the bovine spongiform encephalopathy (BSE) agent to pigs began in 1989. Parenteral inoculation of the agent by three routes simultaneously (intracranially, intravenously and intraperitoneally) produced disease with an incubation period range of 69-150 weeks. Pre-clinical pathological changes were detected in two pigs killed electively at 105 and 106 weeks post-inoculation. Infectivity was detected by bioassay in inbred mice in the CNS of those pigs that developed spongiform encephalopathy. Infectivity was also found in the stomach, jejunum, distal ileum and pancreas of terminally affected pigs. These findings show that pigs are susceptible to BSE. In contrast, disease failed to occur in pigs retained for 7 years after exposure by feeding BSE-affected brain on three separate days, at 1-2 week intervals. The amounts fed each day were equivalent to the maximum daily intake of meat and bone meal in rations for pigs aged 8 weeks. No infectivity was found in tissues assayed from the pigs exposed orally. This included tissues of the alimentary tract. It is suggested that these pigs did not become infected. The relatively high oral exposure used in these experiments compared with feed-borne exposure in the field may explain the absence of an epidemic of spongiform encephalopathy in domestic pigs concurrent with the BSE epidemic in the UK.

Risk management of transmissible spongiform encephalopathies in Asia.

A questionnaire-based survey was distributed to the Office International des Epizooties (OIE: World organisation for animal health) Member Countries in Asia to assess the use of risk management for transmissible spongiform encephalopathies. The author presents a summary of 16 responses received in July 2002. The survey revealed that import risk analysis on bovine spongiform encephalopathy (BSE) is not routinely carried out in ten countries, indicating an urgent need for further training courses. Although the number of ruminants imported from Europe is relatively small, significant quantities of feedstuffs of ruminant origin have been imported into Asia, which may mean that the BSE agent could have reached domestic cattle in most countries. The external challenge has been considerably reduced in recent years as most countries in Asia banned the importation of feedstuffs from countries with BSE, but a few weak spots which enable imports of risk materials still persist. Recycling of BSE through rendering plants is unlikely but cannot be totally excluded in some countries such as the People's Republic of China, India, Japan, Pakistan and Taipei China. Therefore, much more stringent management at slaughterhouses and rendering plants, as well as extensive surveillance programmes, are required in those countries. Bovine spongiform encephalopathy is not notifiable in six countries, indicating a total absence of risk management of BSE in those countries. Immediate actions by these governments to declare BSE a notifiable disease are considered necessary. Numbers of specimens tested for BSE are still very small in most countries in Asia, indicating a pressing need to upgrade surveillance programmes by introducing modern (economically affordable) diagnostic methods and by conducting practical training courses on epidemiological surveillance systems. With the exception of Japan, very little work has been performed on scrapie in Asia although the disease has been routinely monitored in the People's Republic of China, India, Myanmar, Pakistan and Taipei China.

Assessment of the risk factors related to bovine spongiform encephalopathy.

The Office International des Epizooties (OIE: World organisation for animal health) recommends that all OIE Member Countries determine the status of bovine spongiform encephalopathy (BSE) in their cattle populations by conducting a risk assessment and meeting certain BSE surveillance criteria. The OIE has identified and listed the factors and criteria for this in the International Animal Health Code. The factors to be assessed include the consumption of meat-and-bone meal (MBM) by cattle, the importation of cattle and MBM which are potentially infected or contaminated with the BSE agent, the livestock population structure, the rendering processes and the animal feeding practices. In this paper, the authors present an overview of these risk factors and criteria, detailing the relevant components of each. In the second part of this paper, the authors provide a risk assessment to demonstrate the application of the OIE BSE guidelines. This is a probabilistic risk assessment of the factors related to BSE for Canada which conforms to the OIE approach to import risk analysis. The steps include the hazard identification, release, exposure and consequence assessments and the risk estimation. A scenario tree for the release and exposure assessments was used to model the events emanating from the initiating failure event of importing cattle potentially infected with BSE. The consequence assessment describes the costs and losses associated with the introduction and establishment of BSE in other countries. The risk estimate, integrating the release, exposure and consequence assessments, indicates a negligible probability that BSE was introduced and established in Canada; nevertheless, the economic consequences would have been extreme.

The potential for transmissible spongiform encephalopathies in non-ruminant livestock and fish.

Pigs and poultry in the United Kingdom have undeniably been exposed to the bovine spongiform encephalopathy (BSE) agent. They consumed the same ruminant protein that gave rise to the BSE epidemic in cattle, but there has been no evidence of an epidemic in these species. Experimental investigations have shown pigs to be susceptible to infection by multiple parenteral challenge, but resistant to oral exposure with BSE-infected cattle brain. Current but incomplete evidence suggests that they are also resistant to oral challenge with sheep scrapie. Studies in domestic chickens indicate that they are resistant to both parenteral and oral challenge. Unfortunately, no published data exists on the susceptibility of fish to infection. Incidental findings in the brains of unexposed pigs are described that could otherwise give rise to concerns aboutthe presence of a transmissible spongiform encephalopathy in pig populations around the world.

Rendering practices and inactivation of transmissible spongiform encephalopathy agents.

The authors describe the historic form of rendering and provide details on present-day practice. Possible future directions for the rendering industry are considered. The role of rendered meat-and-bone meal (MBM) as a dietary supplement in propagating the United Kingdom (UK) epidemic of bovine spongiform encephalopathy (BSE) is discussed, together with the role of MBM in spreading BSE outside the UK. Evidence that customarily used rendering processes did not substantially inactivate the agents of BSE or scrapie is presented. In addition, the influence that the abandonment of solvent extraction (as an adjunct to rendering) in the UK might have had on BSE infectivity levels in MBM is discussed. The BSE-related safety of tallow and by-products of tallow are considered. Data that associate the BSE agent with a new variant form of Creutzfeldt-Jakob disease in humans, predominantly but not exclusively, in the UK, are also discussed.

Risk management of transmissible spongiform encephalopathies in Europe.

Bovine spongiform encephalopathy (BSE) was first described in the United Kingdom (UK) in November 1986. After the introduction of an active surveillance system, most countries in Europe have reported BSE cases in the cattle population. This indicates that the use of active surveillance in addition to passive surveillance is important to assess the true BSE status in a country. Scrapie, a transmissible spongiform encephalopathy (TSE) in sheep and goats, has been reported in countries throughout the world with a few notable exceptions. Concern was expressed that BSE could have been introduced into sheep and goats. Currently, distinguishing between scrapie and BSE in small ruminants is only possible through lengthy experiments in mice. Preliminary results of active surveillance, introduced in 2002, show that significant under-reporting occurred. The history of BSE in cattle shows that risk assessments concerning the risk in a given country were often ignored and subsequent risk management decisions were inaccurate, i.e. although the risk was probable, no measures were taken in terms of either animal or human health. Furthermore, the effect of the measures taken was often overestimated and these had to be amended several times. The most important action to prevent new cases of TSEs occurring is by banning the feeding meat-and-bone meal (MBM) to ruminants. Further measures to be considered are the exclusion of specified risk material and carcasses from rendering, the process parameters for rendering of animal waste and the prevention of cross-contamination of feed with MBM. The most important measures to protect the consumer are the ban on specified risk material, such as brain and spinal cord, which may contain particularly high concentrations of the BSE agent, and the ban on mechanically recovered meat. The most important measures taken in Europe and the scientific background thereof are described and discussed.

Detection of disease-specific PrP in the distal ileum of cattle exposed orally to the agent of bovine spongiform encephalopathy

The immunohistochemical localisation of the disease-specific protein, PrPSc, was examined in the distal ileum of cattle up to 40 months after they had been exposed orally to the agent of...

Failure of immunocompetitive capillary electrophoresis assay to detect disease-specific prion protein in buffy coat from humans and chimpanzees with Creutzfeldt-Jakob disease.

The emergence of a new environmentally caused variant of Creutzfeldt-Jakob disease (vCJD), the result of food-born infection by the causative agent of bovine spongiform encephalopathy (BSE), has stimulated research on a practical diagnostic screening test. The immunocompetitive capillary electrophoresis (ICCE) assay has been reported to detect disease-specific, proteinase-resistant prion protein (PrPres) in the blood of scrapie-infected sheep. We have applied this method to blood from CJD-infected chimpanzees and humans. The threshold of detection achieved with our ICCE was 0.6 nM of synthetic peptide corresponding to the prion protein (PrP) C-terminus, and 2 nM of recombinant human PrP at the optimized conditions. However, the test was unable to distinguish between extracts of leucocytes from healthy and CJD-infected chimpanzees, and from healthy human donors and patients affected with various forms of CJD. Thus, the ICCE assay as presently performed is not suitable for use as a screening test in human transmissible spongiform encephalopathies (TSEs).

Inactivation of TSE agents: safety of blood and blood-derived products

Evidence relating to whether the blood of individuals with sporadic Creutzfeldt-Jakob disease is infectious is discussed. The conclusion is that this is unproven. Similar consideration is given to the blood of individuals with variant Creutzfeldt-Jakob disease; it is concluded that there is no convincing evidence that the blood is infectious but reasons for caution are presented. There is discussion regarding factors that add to the safety of plasma-derived therapeutic products, including the capacity of the manufacturing processes to inactivate or remove infectivity by the chemical and physical processes involved. There is extended discussion regarding the inactivation of these types of agents and the few reliable options available in worst-case scenarios such as the processing of instruments used neurosurgically on known or suspected cases. The most effective method is exposure to 1 M sodium hydroxide during autoclaving at 121 °C. The inappropriateness of applying any of the most effective methods to blood and blood-products because they are harsh and denaturing is discussed. Nevertheless, such procedures have potential application to the plant used in the manufacture of plasma-products. Evidence is presented which suggests that even more modest treatments (the use of lower concentrations of sodium hydroxide at lower temperatures) are effective when applied to surfaces that are free from any tissue contamination, as is the case with plant used to manufacture plasma-derived products. This evidence has come from studies carried out by the gelatin manufacturers of Europe regarding the capability of their manufacturing systems to inactivate the causal agent of bovine spongiform encephalopathy.

The Role of CEA (Center of Animal Encephalopathies) in the BSE Surveillance: BSE in Italy

Bovine spongiform encephalopathy (BSE) is a neurodegenerative disease that affects cattle, associated with the detection of a protease-resistant protein called PrPsc. BSE was detected first in the UK (Wells et al., 1987) and then described in many European countries, including Italy (Guarda et al., 1994). Exposure to the agent of BSE is the most probable cause of a new disease in man, variant Creutzfeldt–Jakob disease (Bruce et al., 1997; Hill et al., 1997). The evidence prompted public concern about the human risk in consumption of bovine-derived products and led to enhanced surveillance of BSE, which was in the early years based on the passive approach. This kind of surveillance identified the only two BSE cases in Italy up to 2001. The introduction in Italy of a system of active surveillance for BSE using the new rapid test in January 2001 has provided the opportunity to ascertain the presence of BSE in indigenous Italian cows. Between January and 5 September, 230 670 samples were examined by the national network of the Istituti Zooprofilattici and 26 positive BSE cases were detected, with a prevalence of 1.13 per 10 000 animals tested. Nine of these belonged to risk categories (3 fallen stock and 6 emergency slaughter) and 17 were regularly slaughtered cattle. The prevalence is 1.3 per animal tested. All the cases except two were born after the 1994 feed ban. The mean age at diagnosis was 6 years (range 4–13 years). The neuropathology of all 21 Italian BSE cases is chacterized by the same patterns of spongiosis (degree and distribution) and PrP immunopositivity as those reported in other European countries (Wells et al., 1992; Orge et al., 2001; Tegtmeier et al., 2001), although the histology, immunohistochemistry (IHC) and Western blot (WB) findings were limited to the same sample taken for the rapid test (a section of pons at the cerebellar peduncles and obex level). Conspicuous spongiosis in the neuropil of the grey matter and neuronal perikarya vacuolation were observed in all cases except for one that showed minimal spongiform changes. In all the other cases, severe vacuolar changes occurred in the neuropil, mainly in the solitary tract nucleus and in nucleus of the spinal tract of V; mild spongiosis was observed in the dorsal nucleus of the vagus nerve. Vacuolization of neuronal perikarya was predominantly observed in the vestibular nuclear complex, in the reticular formation and, to a lesser extent, in the dorsal nucleus of the vagus. Mild astrocytosis was visualized in each sample by

91. The safety of bovine gelatin with regard to the bovine spongiform encephalopathy agent

Fifteen roe deer were examined at necropsy from Northern Turkey in the period 2006–2010 for the helminth infections. Totally 6470 helminth specimens were collected and identified by morphological criteria. Twenty-five helminth species were identified (1 of the Class Trematoda, 1 of Cestoda and 23 of Nematoda). Dicrocoelium dendriticum (Prevalence 20%) was found in liver. Cysticercus tenuicollis (6.6%) was found in mesentery. Haemonchus contortus (53.3%), Ostertagia leptospicularis (73.3%), O. leptospicularis (minor morph: kolchida) (53.3%), Ostertagia ostertagi (26.6%), Spiculopteragia spiculoptera (66.6%), S. spiculoptera (minor morph: mathevossiani) (6.6%), Teladorsagia circumcincta (40.0%), T. circumcincta (minor morph: davtiani) (6.6%), T. circumcincta (minor morph: trifurcata) (6.6%), Trichostrongylus axei (66.6%) were found in abomasum. Trichostrongylus andreevi (6.6%), T. colubriformis (6.6%), T. longispicularis (26.6%), T. vitrinus (40.0%), T. capricola (6.6%), Cooperia oncophora (26.6%), C. punctata (6.6%), Nematodirus filicollis (66.6%), and Capillaria bovis (26.6%) were found in small intestine. Oesophagostomum venulosum (46.6%), Chabertia ovina (26.6%), and Trichuris ovis (13.3%) were found in large intestine. Dictyocaulus capreolus (6.6%) was found in lungs.

Variant Creutzfeldt-Jakob disease.

Summary. Variant Creutzfeldt–Jakob disease (CJD) is an emerging form of human prion disease caused by oral exposure to the bovine spongiform encephalopathy agent. Most cases have occurred in the UK, but smaller numbers of cases have been identified in 10 other countries worldwide. All confirmed cases belong to a single genetic subgroup defined by methionine homozygosity at codon 129 in the prion protein gene. Variant CJD has a widespread distribution of infectivity in the body, involving lymphoid tissues during at least the latter part of the incubation period. This is unlike other forms of human prion disease, and raised concerns that the transmissible agent might also be present in blood. To date, four probable cases of variant CJD infection have been identified following transfusion of packed red blood cells from asymptomatic donors who subsequently died from variant CJD. Recently, one case of likely transmission of variant CJD infection by UK factor VIII (FVIII) concentrates has been reported in an elderly haemophilic patient in the UK, who had been treated with FVIII produced from pooled plasma to which a donor who subsequently died from variant CJD had contributed. The recipient showed no signs or symptoms of variant CJD during life, but evidence of variant CJD infection was detected in his spleen following a postmortem examination. Continued surveillance is required to investigate the prevalence of secondary variant CJD infection in other patients with bleeding disorders who have been treated with UK-sourced pooled plasma products.

Biological and biochemical characterization of sheep scrapie in Japan.

Due to the apparent absence of an agent-specific nucleic acid genome, scrapie strains cannot be classified by genome characterization, which is commonly used for the classification of many viruses. However, scrapie strains can be distinguished to some extent by biological properties such as transmissibility to experimental animals and distribution of neuropathological lesions and by biochemical properties such as the molecular mass and relative protease-resistance of the disease-specific isoform of prion protein (PrP(Sc)). In order to preliminarily characterize the scrapie strains that are prevalent in Japan, we analyzed the transmissibility of sheep scrapie isolates to mice and the relative proteinase K (PK) resistance of the corresponding PrP(Sc). The results indicate that Japanese scrapie strains can be divided into at least three groups based on biological and biochemical properties. The first group includes isolates which cause disease in mice with an incubation period of approximately 400 days and possess PrP(Sc) with relatively high PK resistance. Isolates of the second group contain PrP(Sc) that is highly resistant to PK digestion but transmit poorly to mice. The final group consists of isolates that cause disease in mice with an incubation period of less than 300 days and are associated with PrP(Sc) with reduced PK resistance. Sheep scrapie has occurred sporadically in Japan since1982, with only approximately 60 officially reported cases so far. However, the diversity of scrapie strains in the field suggested by our data raises the concern that a scrapie strain similar to the parental agent of bovine spongiform encephalopathy could exist or emerge in Japan. Thus, continuous surveillance for scrapie will be required to prevent the further spread of scrapie, not only among the sheep population but also to other species, and to eliminate any potential risk of sheep scrapie to public health.

Bacterial target sites for biocide action

Although biocides have been used for a century, the number of products containing biocides has recently increased dramatically with public awareness of hygiene issues. The antimicrobial efficacy of biocides is now well documented; however, there is still a lack of understanding of their antimicrobial mechanisms of action. There is a wide range of biocides showing different levels of antimicrobial activity. It is generally accepted that, in contrast to chemotherapeutic agents, biocides have multiple target sites within the microbial cell and the overall damage to these target sites results in the bactericidal effect. Information about the antimicrobial efficacy of a biocide (i.e. the eta-value) might give some useful indications about the overall mode of action of a biocide. Bacteriostatic effects, usually achieved by a lower concentration of a biocide, might correspond to a reversible activity on the cytoplasmic membrane and/or the impairment of enzymatic activity. The bacteriostatic mechanism(s) of action of a biocide is less documented and a primary (unique?) target site within the cell might be involved. Understanding the mechanism(s) of action of a biocide has become an important issue with the emergence of bacterial resistance to biocides and the suggestion that biocide and antibiotic resistance in bacteria might be linked. There is still a lack of understanding of the mode of action of biocides, especially when used at low concentrations (i.e. minimal inhibitory concentration (MIC) or sublethal). Although this information might not be required for highly reactive biocides (e.g. alkylating and oxidizing agents) and biocides used at high concentrations, the use of biocides as preservatives or in products at sublethal concentrations, in which a bacteriostatic rather than a bactericidal activity is achieved, is driving the need to better understand microbial target sites. Understanding the mechanisms of action of biocides serves several purposes: (i) it will help to design antimicrobial formulations with an improved antimicrobial efficacy and (ii) it will ensure the prevention of the emergence of microbial resistance.

Predicting the size of the vCJD epidemic in France

More than 5 years after the description of the first cases of variant Creutzfeldt-Jakob disease (vCJD), there is still great uncertainty about the size of the vCJD epidemic in the United Kingdom (UK), although the most recent predictions based on statistical modelling are more optimistic than the previous ones. The number of vCJD cases in France is far too small to attempt any direct modelling of the vCJD epidemic in the French population. Comparative assessment of the level of exposure to the bovine spongiform encephalopathy (BSE) agent in the UK and France could help to estimate the size of the vCJD epidemic in France. Data on imports of beef products from the UK between 1985 and 1996, BSE epidemic in French cattle, and travel of French people to the UK suggest that the French population was much less exposed to the BSE agent than the UK population. The France/UK ratio of vCJD incidence is currently approximately equal to 0.05. Further studies are needed to estimate accurately the exposure ratio between UK and France and to examine whether comparative data about exposure and incidence are fully consistent. The temporal pattern of exposure in UK and France, and possible differences in exposure to high risk bovine tissues because of food habits or risk reduction measures should be carefully considered. To cite this article: A. Alpérovitch, R.G. Will, C. R. Biologies 325 (2002) 33–36.

Neuropathology of variant Creutzfeldt-Jakob disease

The neuropathological features human prion diseases comprise spogiform change, neuronal loss, astrocytic and microglial proliferation and the accumulation of the abnormal isoform of prion protein (PrP RES) in the central nervous system. Variant Creutzfeldt-Jakob disease (CJD) is a novel human prion disease which appears to result from infection by the bovine spongiform encephalopathy (BSE) agent. The neuropathology of variant CJD shows morphological and immunocytochemical characteristics distinct from all other types of human prion disease, and is characterised by abundant florid and cluster plaques in the cerebrum and cerebellum, and widespread accumulation of PrP RES on immunocytochemistry. Spongiform change is most marked in the caudate nucleus and putamen, and the thalamus exhibits severe neuronal loss and gliosis, which is most marked in the posterior nuclei and correlates with the areas of high signal seen in the posterior thalamus on MRI examination of the brain. Western blot analysis of PrP RES on frozen brain tissue in variant CJD tissue shows a uniform isotype, with a glycoform ratio distinct from sporadic CJD. PrP RES accumulation is widespread in lymphoid tissues in vCJD. All cases of variant CJD are methionine homozygotes at codon 129 of the PrP gene. Histological and biochemical techniques will be required to identify cases of ‘human BSE’ in individuals who are MV or VV at codon 129 of the PrP gene. Continued surveillance is required to investigate this possibility in the UK and other countries where BSE has been reported. To cite this article: James W. Ironside, C. R. Biologies 325 (2002) 27–31.

BSE infection of the small short-lived primate Microcebus murinus

Eleven Microcebus murinus (lemur) primates were intracerebrally or orally infected by bovine spongiform encephalopathy (BSE) or macaque-adapted BSE (MBSE) brain homogenates. In many BSE and MBSE infected lemurs, but not in animals inoculated with normal bovine brain, persistent behavioral changes occurred as early as 3 months, and neurological signs as early as 13 months after infection. Immunohistochemical examination of animals sacrificed during the incubation period revealed an abnormal accumulation of ‘prion’ protein (PrP) in the intestinal wall, intestinal nervous plexus, mesenteric lymph nodes and spleen, and in the clinical stage, also in the brain. In MBSE-inoculated animals, proteinase K resistance of the PrP (PrPres) was confirmed by Western blot in the spleen and the brain. Obvious signs of neurodegeneration were observed in all infected animals characterized by hyperaggregated and paired-helical filaments-immunoreactive Tau proteins, β42-amyloid plaques and astrogliosis. Additionally, PrPres was present in the ganglion cells of the retina in diseased animals after either intracerebrally or oral infection by the BSE or MBSE agent. These results show that the microcebe is susceptible to the BSE infectious agent via intracerebral and oral routes with comparatively short incubation periods compared to simians, and could be a useful animal model to study the pathophysiology of disease transmission in primates. To cite this article: N. Bons et al., C. R. Biologies 325 (2002) 67–74.

Diagnosis and prevention of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease.

An outbreak of bovine spongiform encephalopathy (BSE) arose in the United Kingdom as a result of prions entering and being recycled through the ruminant food chain. Humans have since developed a variant form of Creutzfeldt-Jakob disease (vCJD), also mostly in the United Kingdom, that occurs in younger individuals and causes prominent psychiatric and/or behavioral manifestations early in disease. Laboratory studies now provide strong evidence that the causative agent of BSE in cattle and vCJD in humans share a common origin. Because of a lack of information regarding the incubation period of vCJD and the number of people who may have been exposed, the future scope of this disease remains unknown. Control of the current and any future outbreaks in cattle requires strict measures to prevent contamination of the animal food chain with prions of any species. Prevention of human exposure mandates the avoidance of neural tissue in all human foods.