A Focus on Bovine Spongiform Encephalopathy

On this page... The Virus Theory Variant Creutzfedlt-Jakob Disease (vCJD) Transmissible Spongiform Encephalopathies The Prion Hypothesis Specified Risk Materials BSE Surveillance Feed Ban National Prion Research Program Advancing Prion Science: Guidance for the NPRP Findings of the IOM Committee on TSEs NPRP Research Recommendations Based on Findings USDA Research and Development International Research and Development Resources Bovine Spongiform Encephalopathy (BSE), commonly known as "mad cow disease", is a fatal neurodegenerative disease in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 4 years, usually affecting adult cattle at a peak age onset of four to five years, all breeds being equally susceptible. Post-mortem pathological tests of the brain tissue are the only existing methods to confirm BSE. Mad cow disease is believed to be linked to the variant Creutzfeldt-Jakob disease (vCJD), a fatal transmissible spongiform encephalopathy (TSE) disease found in humans. The relationship of the infective BSE agent and vCJD in humans is not completely understood and no direct correlation has been confirmed; however, a strong association exists between humans infected with vCJD and exposure to BSE-infected products. Understanding the TSE agent’s ability to cross species barriers and developing more sensitive antemortem diagnostic tests are two current areas of research. BSE was first identified in the United Kingdom (UK) in 1987. Between 1988 and 2002 more than 182,000 cases were found, accounting for 98% of the cases found world wide.9 Epidemiological studies have found that BSE is a feed-borne infection transmitted to animals through BSE-infected meat-and-bone meal in animal feed.18, 20 The exact origin of BSE in cattle is not known, but it is possible that it came from either scrapie in sheep; or a transmissible spongiform encephalopathy in another mammalian species; or a spontaneous mutation in cattle. Risk analysis studies on BSE transmission have initiated research to determine the following: risk materials and infectivity levels, infectious dose, route of infection, strain of the agent, genotype of the animals at risk, and the nature and size of species barriers.18 Transmissible Spongiform Encephalopathies BSE is one disease from a family of related but distinct, neuro-degenerative diseases called Transmissible Spongiform Encephalopathies (TSEs). TSEs are characterized by the long incubation period (with respect to the life expectancy of the host species) and by the existence of many different strains of infectious agents. Strains of TSE differ in their lesion profile, incubation period, pathogenicity, resistance to chemical and heat inactivation, and distribution in the infected organism. TSE agents are similar to conventional viruses in that they can compete for replication in a single host. This means that slow growing strains interfere with infection/replication of more rapid growing strains. Unlike traditional viruses, TSEs are resistant to most virus-inactivating treatments and do not provoke a systemic inflammatory response or antigenicity.8 The following is a list of different types of TSEs have been identified in animals and humans: chronic wasting disease (CWD) in elk and deer; transmissible mink encephalopathy (TME) in ranch-reared mink; feline spongiform encephalopathy (FSE) in cats and captive exotic felids; scrapie in sheep, goats, and moufflon;* kuru, Gerstmann-Straussler-Scheinker disease, fatal familial insomnia, Creutzfeldt-Jakob disease (CJD), and new variant Creutzfeldt-Jakob (vCJD) disease all found in humans. *The oldest TSE is scrapie. 3 Back to top Variant Creutzfedlt-Jakob Disease (vCJD) Two types of CJDs are known to exist: classical CJD new variant form, vCJD The vCJD was first diagnosed in 1996 in the UK by the National CJD Surveillance Unit. According to May 2007 statistical data, the total number of deaths in the United Kingdom from definite or probable vCJD cases is 160.5 Patients range in age from 12 to 74 years old and live an average of one year after showing clinical symptoms. The incubation period is believed to be 10 to 15 years, but could be longer. vCJD is linked to eating BSE contaminated beef products but the potential for transmission between people is not understood and extensive research is currently being conducted in order to understand the transmission, detection, and treatment. 4 See figures for the total number of vCJD cases Worldwide.23 Back to top The Prion Hypothesis TSEs are sometimes referred to as prion diseases. Prion proteins, PrP, now widely accepted as the infectious agents, normally exist in the plasma membrane of mammalian neurons but appear to become infectious upon conformational changes in their structure. Prion is an abbreviation for 'proteinaceous infectious particle' and it lacks a nucleic acid, distinguishing it from a virus. The 'protein only' hypothesis states that a modified form of the prion protein triggers the infectious neurodegenerative diseases. It was controversial when first proposed because all other infectious diseases are caused by organisms which contain genetic material (DNA or RNA). Prion proteins are thought to exist in two different conformations and are designated as follows: the benign cellular form, PrPc; and the infectious “scrapie” form, PrPsc.1 PrPc is encoded by the PRNP gene on chromosome 20 in humans.14 Certain conditions cause the PrPc structure to fold abnormally and it is the misfolded protease-resistant form, PrPsc, that accumulates in the brain causing neuronal death. The infectious nature appears to be caused by the abnormally folded protein (PrPsc), either alone or with other unknown elements, triggering a conformational change in the normal cellular prions (PrPc). A genetic factor, such as a mutation in the PrP protein gene, may be involved.10 Experiments with transgenic mice have demonstrated that disease susceptibility is positively correlated with PrP expression; and, the PrP sequence may be partly responsible for the species barrier. More knowledge of the PrP three-dimensional structure is essential to understanding is transition to PrPSc and its infectivity in TSEs.1 TSE research has made large advances in the past ten years but much remains to be discovered. The functions of PrPc in the absence of TSE and its role in the pathogenesis of TSE are not completely understood. It involves complex interactions of the infectious agent with different target cells and extracellular environments. Finding cellular receptors of the PrP may help provide answers.8 Back to top The Virus Theory More than ten years ago the virus theory was challenged by the research of Stanley Prusiner who won the Nobel Prize in 1997 for his discovery of prions. Now recent findings are questioning the currently accepted prion theory by suggesting that the causative TSE agent is a 25-nm virion particle rather than the abnormal PrP protein which has been detected in the brains of infected humans and animals. This is not the first time virus-like particles have been identified in TSE-infected brains. In 1968 they were identified within experimental mouse scrapie, by 1971 in natural sheep scrapie, and then finally in human CJD brain samples. 22 Critics of Prusiner’s prion hypothesis suggest he failed to prove that abnormal prion proteins are infective. A January 2007 published research study has demonstrated the infectivity of small 25-nm virion particles. Dr. Manuelidis and her Yale colleagues examined two types of infected cells representing two types of TSE strains, both scrapie (sheep) and Creutzfeldt-Jackob (human) disease agents. They found that only the infected cells contained small virus-like arrays; the uninfected controls had no comparable particles. These particles are consistent with the virion shape, size, and viral components, and they closely resemble those found in 1968. The Yale team used antibody binding studies to determine that the small 25-nm particles are structurally independent and have no relation to the abnormal PrP proteins. It is also unlikely that an identical virus-like structure would act as a contaminant. 22 A more detailed molecular analysis of these virus-like particles is recommended to substantiate their causal nature; however, this study provides some evidence that virions, not abnormal PrP proteins, are the causal TSE agent that induces PrP brain pathology. The findings appear online in the Proceedings of the National Academy of Sciences. Back to top Specified Risk Materials Specified risk materials (SRM) is the general term designated for infective tissues that transmit the disease. The BSE infective agent has been found to concentrate in specific tissues of BSE-infected cattle and these tissues are all part of the central nervous system, as BSE has not been shown to infect muscle. The World Organization for Animal Health (OIE) has established recommendations and guidelines for SRM removal based on the level of risk. In both the United States (U.S.) and Canada, considered low risk countries, SRMs are defined as: skull, brain, trigeminal ganglia (nerves attached to brain and close to the skull exterior), eyes, spinal cord, distal ileum, and the dorsal root ganglia (nerves attached to the spinal cord and close to the vertebral column) of cattle aged 30 months or older. In the U.S., tonsils are removed from cattle of all ages. SRMs must be removed at slaughter and disposed as inedible material. The dorsal root ganglia must be removed during the deboning process and in animal older than 30 months, the vertebral column (excluding the vertebrae of the tail, the transverse processes of the lumbar and thoracic vertebrae, and the wings of the sacrum) is removed to be certain the dorsal root ganglia is extracted in its entirety.7 In the United Kingdom, and other countries classified as moderate to high risk, the OIE code recommends SRM removal as follows: tonsils and intestines in cattle at all ages; and, brains, eyes, spinal cord, skull and vertebral column form animals over twelve months of age. The removal of SRMs is believed by many experts to be the single most important action in protecting the public health.21 Back to top BSE Surveillance An active BSE surveillance program has existed in the United States since May 1990, in order to safeguard the American cattle population. The U.S. surveillance program is an interagency effort coordinated by the USDA Animal and Plant Health Inspection Service (APHIS) and includes both active and passive surveillance. It is designed to prevent infection and transmission of foreign animal diseases like BSE, or any TSE, from infecting U.S. cattle. In addition, measures are in place to quickly detect and respond to an outbreak. The BSE surveillance program was enhanced when the first BSE outbreak occurred in the United States in 2003. 6 Surveillance tests are not food safety tests and can only be used for the purpose of statistical analysis. Current detection methodology is limited and OIE suggest that the likelihood of detecting BSE in cattle varies depending on the characteristics of the subpopulation. The closer the animal is to exhibiting clinical BSE symptoms, the better the likelihood of detection. Currently, positive cases have been detected three months prior to clinical signs; however, given that the incubation period is about 4 years long much time exists when infected cattle are tested and false negatives result. According to European data, it is 100 times more likely that BSE will be detected in cattle exhibiting clinical signs of BSE, than in downers on farms; and is 5,000 to 10,000 more times than in healthy 30 month old cattle at slaughter. Another estimate is that the current test methodology has a false negative test rate of 92%, meaning in a population of 100 clinically normal BSE infected adult cattle, 92 would test negative even though infected. 6 The U.S. surveillance strategy is to regionally represent the distribution of adult cattle across the nation. The regions are based on the movement of cattle going to slaughter. Each region has different surveillance goals and is treated as an individual country. A scientific approach allows for uniform surveillance across the nation while representing regional differences. Nationally, 12, 500 samples are tested in order to detect one BSE-infected cattle per million. This approach is widely accepted around the world. The U.S. has an adult cattle population of 45 million so if it is assumed that one per million is BSE-infected, than forty-five U.S. cattle would be infected. However, in the accuracy of random sampling of adult animals, three million cattle would need to be tested in order to obtain a 95 percent confidence level. 6 The U.S. has an active targeted surveillance plan rather than a random sampling strategy in order to establish a more efficient and effective survey. APHIS focuses on the higher risk population of cattle, which are not going to slaughter. BSE-infected cattle have never been detected under the age of 20 months and 88% of the U.S. slaughter population is under this age. The higher risk population is those most likely to have been exposed to the BSE and it is this population where the disease will more likely be detected. European surveillance testing has defined non-ambulatory cattle as high risk. A survey conducted by the American Association of Bovine Practitioners estimated that 195,000 non-ambulatory cattle exist in the U.S. If it is assumed that 45 BSE-infected cattle can potentially be detected in a high risk population of 195,000, the level of disease that is detected is 0.023 percent. According to a statistical analysis formulation by Cannon and Roe, a sample size of 12,500 is necessary to detect BSE at a prevalence of 0.023 percent. The national sample size of 12,500 established to detect one BSE-infected cattle per million is based upon scientific risk analysis methods. In addition, the OIE has established international surveillance standards for the number of samples to be tested each year within a country. In the last five years, the U.S. has exceeded the OIE recommendation of 433 samples per year.6 Back to top Feed Ban The European Union (EU) introduced a ban on ruminant feedstuffs containing protein derived from mammalian tissues in 1994 as part of their BSE eradication program. Originally, feed-borne contamination as a vehicle of disease transmission was just scientific opinion, but now epidemiological evidence, as well as the effect of feed bans, proves this to be true. 9 During the slaughter process prior to the 1994 ban, ruminant tissues were rendered and processed for use in feedstuffs in the form of meat-and-bone meal (MBM). MBM is defined as processed mammalian tissue used directly or indirectly for animal feed. The 1994 ban concerned animal proteins of ruminant origin being fed to ruminants, so ruminant protein continued to be fed to non-ruminants. The continuation of BSE after the 1994 feed ban was blamed on unintentional cross contamination during feed production since most of the feed mill facilities produced both ruminant and non-ruminant feedstuffs. In 2000, the Scientific Steering Committee (SCC) of the European Union (EU) recognized that the cross contamination of mammalian MBM with all animal feedstuffs was unavoidable due to mixed-species feed mills and the lack of test methods to distinguish animal proteins of ruminant origin. In January 2001, EU legislation imposed a total ban which specified that processed proteins derived from all mammals, birds, and fish be prohibited for all farmed animals intended for the production of food.9 The SCC had various opinions on the total ban and provided four crucial conditions that, if followed and cross-contamination avoided or detected, would greatly reduce the risk of BSE transmission through recycled animal tissues in feed for non-ruminant farmed animals. The four conditions are as follows: raw material is fit for human consumption; SRMs and fallen stock be removed; pressure-cooking standards (133 C, 20 minutes, 3 bar) be followed; and control of the MBM ban to ruminants is implemented effectively. 9 In 2002, the EC issued an animal by-product regulation. Only materials from animals fit for human consumption following veterinarian inspection are allowed to be used in animal feed production. This regulation excludes fallen livestock and other condemned materials from the feed chain and it banned intra-species recycling. 9 EC legislation made developing rapid control methods for distinguishing and identifying animal proteins of different species a necessity in order to enforce the bans implemented.9 Currently, different methods are being considered for the identification of animal protein in feed; however, feed microscopy is the official analysis method of the EU. In January 2001, an EC project called STRATFEED was initiated in order to test several of these analytical techniques: classical microscopy; polymerase chain reaction (PCR); near infrared microscopy (NIRM); and near infrared spectroscopy (NIRS). The enzyme-linked immunoabsorbent assay (ELISA) is also an available test; but is not part of the STRATFEED project.9 Back to top National Prion Research Program “The Department of Defense (DOD) National Prion Research Program (NPRP) was established in FY02 by the Joint Appropriations Conference Committee Report No. 107-350, which provided $42.5 million for research on prion disease.” 13 This congressional research program is managed by the U.S. Army Medical Research and Materiel Command (USAMRMC) and is conducted according to a two-tier review model recommended to them in 1993 by the Institute of Medicine (IOM). In FY02 the primary goal of NPRP was to develop a rapid, sensitive and reproducible antemortem diagnostic test for the detection of prion disease and for use as a screening assay. The Integration Panel developed the FY02 NPRP investment strategy in June 2002 and the call for proposals was announced in August 2002. To support the proposal evaluation process, the USAMRMC had requested that the IOM Committee on Transmissible Spongiform Encephalophies assess prion detection and disease diagnosis, and provide expert advice to the National Prion Research Program (NPRP) for an effective research agenda. The IOM issued an interim report in February 2003, Advancing Prion Science: Guidance for the National Prion Research Program, and the Integration Panel used this report to support and recommend funding for 38 of the 136 proposals. The final version of this IOM report was issued in November 2003 and can be found at the National Academies Press. 13 Back to top Advancing Prion Science: Guidance for the NPRP The current disease theory of TSEs is that the infective agent is a misfolded three-dimensional configuration of a normal cell membrane protein known as a prion. It is transmitted by ingestion and possibly by blood transfer. No antemortem diagnostic tests, nor cures, nor treatments exist; and, the development of such measures are complicated by the lack of a fundamental understanding of the molecular mechanisms of prion replication, mechanisms of TSE pathogenesis, and the function of the normal cellular prion protein. The IOM committee recommends research in each of these areas in addition to the epidemiology and the natural history of TSEs. The recommendations in this report provide a framework for research in order to develop effective diagnostics and therapeutics. 14 Back to top Findings of the IOM Committee on TSEs The scientific community must first answer fundamental questions about TSEs and prions. This lack of knowledge is an impediment to developing diagnostics and therapeutics. There is a limited infrastructure in the U.S. in order to study TSEs and this also impedes the development of diagnostics and therapeutics. There are no available drugs or therapeutics to effectively treat TSEs. Existing diagnostic tests are far from being sensitive enough and marginal improvements will be insufficient. It is not known whether human blood infected with prion disease is a vehicle of disease transmission. Recent animal studies showed that a transfusion of infected sheep blood transmitted two different TSE agents to uninfected sheep. The United States would benefit from strengthening its TSE surveillance system. Human TSEs in the United States are underrecognized and underreferred for definitive diagnosis. U.S. measures to prevent BSE-infected tissue of cattle from entering the food chain are not completely error proof. A review of the U.S. policy on SRMs would be appropriate. No evidence, other than theoretical, exists to conclude that CWD is transmissible to humans. The committee advised people to avoid exposure to CWD-contaminated meat due to the wide range of venison processing practices and insufficient regulations. A small and unknown level of risk for acquiring a TSE exists for U.S. forces and their families who were stationed in Europe during the 1980s and 1990s. Back to top NPRP Research Recommendations Based on Findings Fund basic biomedical research on prion structure; prion replication; TSE pathogenesis; and physiological function/role of the normal cellular prion protein. pathogenesis; and physiological function/role of the normal cellular prion protein. Augment infrastructure for TSE research by training more investigators; providing longer research grants (i.e. 5-7 years) for research in animals; upgrading existing laboratories; and supporting new or established animal repositories. Develop of therapeutic agents, such as antibodies, to prevent or treat TSEs. Either block the conversion of the normal cellular prion protein to the abnormally folded form or disrupt TSE pathogenesis after conversion has occurred. Develop novel detection methods and reagents (antibodies, peptides, nucleic acids, synthetic derivatives, chimeric molecules) that detect or bind to prions instead of improving existing methods. Understand blood as a vehicle of transmission, especially the risk of prion transmission through human blood. Enhance the current TSE surveillance system through research that examines distribution; prevalence; natural history; exposure and transmission characteristics; host susceptibility; and host range of TSEs such as chronic wasting disease (CWD). Support efforts to identify and autopsy a greater number of suspected cases of TSEs. Improve rapid, accurate, and affordable screening assays for detecting central nervous system tissue in processed meat products, since prions reside mainly in the central nervous system (CNS) tissue. Evaluate whether the CWD infectious agent is transmissible to humans through CWD-contaminated meat and meat products. Monitor the occurrence of TSEs in the population of U.S. forces and their dependents stationed in Europe during the 1980s and 1990s through established data systems in the DOD and the Department of Veteran Affairs. Back to top USDA Research and Development The USDA/ARS is currently conducting several TSE research projects. The following are some of USDA’s research objectives:15 Develop diagnostic and surveillance tests for BSE, scrapie, and CWD. Characterize innate genetic resistance to BSE and CWD and develop intervention strategy. Characterize induced protection from BSE and CWD and develop an intervention strategy. Develop biological and biochemical detection method for the infectious agent in animal tissues and in the environment. Develop and validate live animal diagnostic test for scrapie. Identify transmission routes of scrapie through the reproductive tract, placenta and related blood supply and validate. Identify genetic markers that correlate with disease protection in sheep. Identify genetic markers for resistance to TSEs of cattle, deer, and elk. Develop assays for identification of transmission pathways through direct animal contact and environmental contamination. Collaborate with researchers in the UK to develop methods to characterize and differentiate known prion disease in ruminants and cervids such as BSE, scrapie, and CWD. Assess interspecies transmission of TSEs and determine parameters associated with TSE induction, especially in neonates. Identify different strains of TSEs. Correlate prion isoforms with ruminant and cervid susceptibility. Understand the pathobiology of TSE. Evaluate capillary immunoelectrophoresis assay (CIE) for Creutzfeld-jakob Disease in humans using scrapie as a model and validate this CIE assay for its sensitivity to detecting abnormal PrP in blood. Back to top International Research and Development EU Funded Research under the Framework Programmes Since 1990 the European Commission (EC) has had a TSE research program which grew rapidly after 1996 when the UK announced the link between exposure to BSE and the 10 cases of a new variant Creutzfeldt-Jakob Disease (vCJD) in humans. In 1996 the EC proposed a TSE Action Plan recommending research priorities. A total of 54 TSE projects funded by 50.7 million euros with multidisciplinary expertise of 120 laboratories were commissioned under the Action Plan and the Fourth Framework Programme. The Fifth Framework Programme from 1998-2002 funded approximately 26 TSE projects. In 2000, Research Council requested that the EC establish a TSE Expert Group in order to assess the state of TSE research; encourage scientific information sharing between researchers; and identify new research initiatives and monitor existing ones. As a result and in an effort to fill specific gaps, a specific call for TSE research proposals was given in 2001 resulting in 15 new TSE projects (part of the 26). These newly commissioned TSE projects began in 2002 with the launch of the Sixth Framework Programme. It is the objective of this program to develop methods of analysis, detection and control of prion type diseases with a focus on developing antemortem diagnostic tests for BSE and scrapie. 11 Some of the EU-funded TSE projects currently being conducted are focusing on the following specific objectives: 16 BSE Strain in Sheep Assess BSE vertical and horizontal transmission in sheep under natural conditions Determine the minimal infective BSE dose in sheep Evaluate strain detection in sheep that could be co-infected with scrapie and BSE. Evaluate serial trans-species transmission and its effect on the human species barrier BSE Transmission through Food and Blood Assess the risk of human to contract vCJD and the potential for human-human transmission Determine the infectious dose in contaminated food for a non-human primate and determine if the TSE-infected primate can transmit the disease through blood Prion Genome Binding Sites Identify possible genomic binding sites for PrP. Use DNA microarray technology to study PrP at the molecular level and develop a chip based screening test for PrP determination. Sensitive Diagnostic Markers and Methodology for Early Detection Using non-invasive technology, identify in viva diagnostic and prion disease progression markers using magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) in humans and animal models. Improve and validate an existing fluorescent immunoassay method, used in sheep blood analysis, for application in bovine and human prion diseases using blood, cerebrospinal fluid, and urine analysis. Improved methods must enable detection of PrPsc in the early stages of disease, prior to clinical symptoms. Understand the appearance of early disease markers and the neurodegeneration mechanism in neuronal cell cultures induced by BSE infection. Determine the molecular properties of the normal prion protein (PrPc) conformation and conformational transitions to the abnormal isoform, PrPsc in order to understand the steps of prion infection and pathogenicity. Use knowledge of the human genome sequence and population genetics to identify genes that may have a role in the pathogenesis of human prion diseases; and, to identify diagnostics and treatments. Monitor vCJD and develop risk factors. In order to do this: Identify all forms of CJD, including atypical phenotypes of sporadic CJD (sCJD) Identify all cases of vCJD in participating countries Conduct detailed population studies of PrP genotype to determine age and gender distributions within regions Examine risk factors surrounding vCJD UK Strategy for TSE Research (2004 -2007) Most TSE research in the UK is supported by five public funders: 7 Biotechnology and Biological Sciences Research Council (BBSRC) Department for Environment, Food and Rural Affairs (Defra) Department of Health (DH) Food Standards Agency (FSA) Medical Research Council (MRC) Recently, scientists consulted and drafted the “UK strategy for research and development on human and animal health aspects of Transmissible Spongiform Encephalopathies (TSEs) (2004-2007)”. This document highlights knowledge gaps in TSE/prion science and identifies key goals and research strategies to address these uncertainties.17 Department of Health Outlined the following key goals:17 Public health The surveillance of human TSE disease Epidemiological studies of human disease, especially those in the very young, the elderly and in at-risk populations. Research designed to protect the blood supply and the supply of blood products Research on the development of sensitive and specific diagnostic technologies Prevention of infection Research to accurately assess levels of infectivity in organs, tissues and body fluids Research on novel methods to decontaminate surgical instruments and other medical devices and the introduction of these into NHS practice Treatment The development and assessment of novel therapeutic compounds The assessment of these compounds in humans through clinical trials The Medical Research Council (MRC) Key Research Areas by MRC17 The biological and epidemiological relationship between CJD and BSE Epidemiological modelling of CJD The analysis, perception and communication of risk in relation to CJD Early disease progression and diagnosis in life including in vivo imaging approaches, with a focus on the development of non-invasive pre-clinical tests for human TSE diseases, particularly vCJD, e.g. a blood test or throat swab Integrated molecular, epidemiological and clinical approaches to understanding the cause or causes of sporadic CJD and the relationship with atypical dementias Molecular, genetic, cellular and functional approaches to elucidating mechanisms of TSEs transmission, PrP replication, pathogenesis and clinical progression, with a view to improving understanding of how TSEs cause disease, particularly during the very early stages The biological function of normal prion protein (PrP) The molecular structure of the prion proteins Development and improvement of animal models and cell culture systems Development of approaches to reduce secondary (iatrogenic) infection Rational approaches to developing therapy including vaccine based treatment approaches Biotechnology and Biological Sciences Research Council Key areas of TSE Research funded by BBSRC:17 The nature of the infectious agent. The normal function and structural biology of the prion protein (PrP). Molecular methods of strain differentiation. Molecular mechanisms and genetics of pathogenesis of both the CNS and PNS. Approaches underpinning the development of therapeutics. Epidemiology and modelling to underpin scrapie control Scrapie as a natural disease model in the target species. Establishing whether PrPSc is present in sub-clinical animals. Food Standards Agency (FSA) Key Research Areas funded by FSA:17 The development of rapid detection methods for TSE’S in ante and post-mortem food animals. The development of detection methods capable of differentiating between TSEs. The development of TSE detection methods for animal tissues and animal products (milk and dairy products). Determining relative infectivity of edible tissues and animal products from BSE infected cattle, sheep and goats. Determining the susceptibility of animal species to BSE infection with age and the effect of abnormal conditions on susceptibility (cattle, sheep and goats). Providing information on the transmissibility of BSE to food animal species (cattle, sheep, pigs, poultry, goats and fish). Collecting information with regard to TSEs on the routes and consumption patterns of animal products entering the food chain. Providing information on the risk of contamination of edible tissues with SRM caused by current stunning, slaughter and carcass dressing techniques and where necessary develop alternative lower risk techniques. Carrying out risk analysis to assess the risk to the consumer from TSEs entering the food chain and the effect of any proposed risk reduction measures. The development of methods to detect SRM in food products. Undertaking studies on historic butchery practices, meat processing and the historic production and utilisation of mechanically recovered meat (MRM) in processed meat products, to determine the routes of BSE infectivity into the food chain and the risk to the consumer from this source of contamination. Department of Environment, Food, and Rural Affairs(DEFRA) Key Research Areas funded by DEFRA:17 The further development of diagnostic tests, both post and pre-mortem, to allow differentiation between strains of TSE and detection of disease at an earlier stage of the incubation period The improvement of methods for the detection of species specific compounds in animal feeds to support statutory controls Monitoring strain stability of BSE in cattle Epidemiological studies of BSE in cattle and TSEs in sheep aimed at ensuring that appropriate control measures are in place, and modelling to provide forecasts of the future course of the diseases To determine effective methods for inactivation and decontamination of the infectious agent to ensure safe treatment and disposal of risk materials Studies on the source of infection for BSE cases in cattle born after the augmented feed controls in August 1996 Determining demographic and genotype profiles of UK sheep flock and studies on transmission of TSE infection within and between flocks Investigation of effects of selective breeding programme on sheep production traits, conformation, survival, health and welfare Studies on the correlation of PrPSc detection and infectivity in tissues from infected animals together with relative sensitivity of different species Studies on the persistence, movement and transfer of infectivity/PrPSc in soils and the environment. Back to top Resources The following resources were used to develop this fact sheet. For a more in-depth list of online resources on BSE, visit the BSE Resource List. Prion Diseases Microbiology at Leicester. Bovine Spongiform Encephalopathy (BSE) Encyclopedia of Food Microbiology, Volume 1. Variant Creutzfeldt-Jakob Disease (Variant CJD) in Canada Health Canada. Creutzfeldt-Jakob Disease Statistics University of Edinburgh. National Creutzfeldt-Jakob Disease Surveillance Unit. BSE Surveillance USDA. Animal and Plant Health Inspection Service. FSIS Requirements Prohibiting Use of Specified Risk Materials (SRMs) for Human Food USDA. Food Safety and Inspection Service. The Transmissible Spongiform Encephalopathies Office International des Epizooties. Science and Technology Review, Volume 22(1), 2003. An Overview of Tests for Animal Tissues in Feeds Applied in Response to Public Health Concerns Regarding Bovine Spongiform Encephalopathy Office International des Epizooties. Science and Technology Review, Volume 22(1), 2003. On the trail of the Mystery Prion European Commission. EU-funded TSE Research in Europe European Commission. Prion-Related Neurodegenerative Disease Huntington's Outreach Project for Education at Stanford University. Department of Defense National Prion Research Program Department of Defense Congressional Directed Medical Research Programs. Advancing Prion Science: Guidance for the National Prion Research Program (2004) National Academies/Institute of Medicine/ Medical Follow-up Agency. National Academies Press. EU-funded TSE Research Programs Community Research and Development Information Service (CORDIS). UK Strategy for Research and Development on Human and Animal Health Aspects of Transmissible Spongiform Encephalopathies (2004 – 2007) Medical Research Council (United Kingdom). Bovine Spongiform Encephalopathy Office International des Epizooties. Science and Technology Review, Volume 22(1), 2003. Joint WHO/FAO/OIE Technical Consultation on BSE: public health, animal health and trade: Conclusions and Key Recommendations OIE Headquarters. Paris, June 2001. Manual on Bovine Spongiform Encephalopathy FAO. 1998. Food Directorate Policy on Specified Risk Material (SRM) in the Food Supply Health Canada. Cells Infected with Scrapie and Creutzfeldt-Jakob Disease Agents produce Intracellular 25-nm Virus-like Particles Proceedings of the National Academy of Sciences. January 2007. Variant Creutzfeldt-Jakob Disease Current Data, April 2007 University of Edinburgh. National Creutzfeldt-Jakob Disease Surveillance Unit. Back to top

This document was created by Tara Smith. Users are encouraged to provide feedback and comments. This document was created in Mar 2005; Updated in Nov 2007