Bovine Spongiform Encephalopathy Risk Assessment Research Articles

Elements Modulating the Prion Species Barrier and Its Passage Consequences

The specific characteristics of Transmissible Spongiform Encephalopathy (TSE) strains may be altered during passage across a species barrier. In this study we investigated the biochemical and biological characteristics of Bovine Spongiform Encephalopathy (BSE) after transmission in both natural host species (cattle, sheep, pigs and mice) and in transgenic mice overexpressing the corresponding cellular prion protein (PrPC) in comparison with other non-BSE related prions from the same species. After these passages, most features of the BSE agent remained unchanged. BSE-derived agents only showed slight modifications in the biochemical properties of the accumulated PrPSc, which were demonstrated to be reversible upon re-inoculation into transgenic mice expressing bovine-PrPC. Transmission experiments in transgenic mice expressing bovine, porcine or human-PrP revealed that all BSE-derived agents were transmitted with no or a weak transmission barrier. In contrast, a high species barrier was observed for the non-BSE related prions that harboured an identical PrP amino acid sequence, supporting the theory that the prion transmission barrier is modulated by strain properties (presumably conformation-dependent) rather than by PrP amino acid sequence differences between host and donor.As identical results were observed with prions propagated either in natural hosts or in transgenic mouse models, we postulate that the species barrier and its passage consequences are uniquely governed by the host PrPC sequence and not influenced by other host genetic factors. The results presented herein reinforce the idea that the BSE agent is highly promiscuous, infecting other species, maintaining its properties in the new species, and even increasing its capabilities to jump to other species including humans. These data are essential for the development of an accurate risk assessment for BSE.

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.

Bovine spongiform encephalopathy and its management in Israel

Following the outbreak of BSE in the UK in the mid-1980s, Israel banned the importation of live cattle and meat and bone meal from the UK. The appearance of its first and only domestic case in 2002 prompted the implementation of several additional protective measures, including improvements to the active surveillance system and the removal of high risk materials. A geographic bovine spongiform encephalopathy risk assessment conducted the same year concluded that it was likely and confirmed at a lower level that domestic cattle were infected with BSE (Level III). However, no other cases have been detected in the country. The government has followed a sound risk management and risk communication plan to avoid negative reactions from the public.

BSE Risk Assessment as a Basis for Updating French Screening Policy

The current French bovine spongiform encephalopathy (BSE) surveillance system, based on rapid testing of all cattle over 24 months of age and on clinical diagnosis, detects all clinical cases and some preclinical cases of BSE. Several indicators point to a marked shrinkage of the French BSE epidemic in recent years, owing to risk reduction measures. Meat and bone meal, the only known vector of the BSE agent, was banned in feed for all farmed species in November 2000. Thus the surveillance system may be relaxed. The objective of this risk assessment study was to provide information for decisionmakers on the minimum age at which healthy and high-risk cattle now need to be screened with rapid tests. For this purpose, we used the back-calculation method to project the course of the BSE epidemic. We examined the predicted patterns of the number and age distribution of cases of BSE that would be detected by the different existing surveillance streams. Various theoretical sensitivities of rapid tests were explored. Assuming that feed-borne sources of infection no longer exist, and that BSE does not occur spontaneously, our models suggest that it would have been possible to raise the minimum age for rapid tests to 66 months in early 2006, whereas theoretical reasoning, based on the assumption that the total meat and bone meal ban was effective in November 2001, suggests that this age cutoff could only be raised to 48 months in early 2006. These results only apply to cattle born and bred in France. If the situation remains unchanged, the age cutoff could be raised incrementally each year.

Sequential pressurized liquid extraction to determine brain-originating fatty acids in meat products as markers in bovine spongiform encephalopathy risk assessment studies

A new approach using sequential pressurized liquid extraction described recently [J. Poerschmann, R. Carlson, J. Chromatogr. A, 1127 (2006) 18–25] was applied to determine lipid markers originating from central nervous system (CNS) tissue of cows in heat-processed sausages. These studies are very important in quality control as well as risk assessment studies in the face of the bovine spongiform encephalopathy (BSE) crisis. Diagnostic CNS lipid markers, which should not be present in meat products without CNS addition, were recognized on complete transesterification as polar 2-hydroxy-fatty acids (2OH-24:0, 2OH-24:1, 2OH-22:0, 2OH-18:0, shorthand designation) as well as odd-numbered non-branched fatty acids beyond C 22. An array of other fatty acids including lignoceric acid (24:0), nervonic acid (24:1), arachidonic acid (20:4), and polyunsaturated nC 22-surrogates are strongly related to CNS lipids, but occur as traces in meat products without CNS addition as well, thus reducing their value as diagnostic markers. Samples including meat products without CNS addition, meat with 3% CNS addition, as well as pure CNS homogenates, were subjected to sequential PLE (pressurized liquid extraction) consisting of two steps: n-hexane/acetone 9:1 (v/v) extraction at 50 °C to remove neutral lipids, followed by chloroform/methanol 1:4 (v/v) extraction at 110 °C to isolate polar CNS lipids (two 10 min PLE cycles each). To enhance the fractionation efficiency, cyanopropyl modified silica as well as chemically not modified silica sorbent was used at the outlet of the PLE cartridge to retard polar lipids in the first extraction step. This method proved superior to widely distributed exhaustive lipid extraction followed by solid-phase extraction (SPE) using silica regarding lipid recoveries and clear-cut boundaries between lipid classes. Methodological studies showed that the alcoholysis using trimethylchlorosilane/methanol (1:9, v/v) is an excellent method for the complete transesterification of lipids and quantitative formation of methyl esters.

An evaluation of United Kingdom environmental bovine spongiform encephalopathy risk assessment

As a member of the group of diseases known as transmissible spongiform encephalopathies (TSEs), bovine spongiform encephalopathy (BSE) has been causally associated with a new variant of Creutzfeldt-Jakob disease (vCJD) in humans. Given the many uncertainties on the transmission and persistence of TSE pathogens in the environment, quantitative assessment of risks to humans and animals continues to remain a public health issue. This paper reviews quantitative BSE risk assessments undertaken in the United Kingdom since 1997 to address the potential for human exposure and theoretical health risks through environmental pathways. The review focuses on how model assumptions and methodology may influence the results.

Development of a risk assessment for BSE in the aquatic environment.

Bovine spongiform encephalopathy (BSE) is believed to be transmitted by the ingestion of proteinaceous agents called prions which accumulate in the brain and spinal cord of infected bovines. Concern has been expressed about the risks of transmission of BSE to humans through BSE prions discharged to the aquatic environment from rendering plants, abattoirs and landfills. The disease-related form of the prion protein is relatively resistant to degradation, and infectivity decays rather slowly in the environment. Levels of disinfection used for drinking water treatment would have little effect. This paper presents the assumptions which were used to model the risks from a rendering plant disposing of cull cattle carcasses in the catchment of a chalk aquifer which is used for a drinking water abstraction. The risk assessment approach focused on identifying the hydrogeological and physical barriers which would contribute to preventing BSE infectivity gaining entry to the aquifer. These barriers included inactivation of BSE agent by the rendering process, removal from the effluent by treatment at the plant, filtration and adsorption in the clay and chalk, and dilution in the ground water. The importance in environmental risk assessment of the cow-to-man species barrier is considered. Two key conclusions about the environmental behaviour of the BSE agent are that prion proteins are 'sticky' and bind to particulates, and that the millions of BSE prion molecules comprising a human oral ID50 are subject to some degree of dispersion and hence dilution in the environment. Assuming the rendering plant processes 2000 cull cattle carcasses per week, the risks to drinking water consumers were estimated to be remote. Indeed, even using worst case assumptions an individual would have to consume 21 d-1 of tap water for 45 million years to have a 50% chance of infection through drinking water drawn from the aquifer.