An assessment of the long-term persistence of prion infectivity in aquatic environments.

The environment plays a key role in horizontal transmission of prion diseases, since prions are extremely resistant to classical inactivation procedures. In prior work, we observed the high stability of bovine spongiform encephalopathy (BSE) infectivity when these prions were incubated in aqueous media such as phosphate-buffered saline (PBS) or wastewater for nearly nine months. As a continuation of this experiment, the same samples were maintained in PBS or wastewater for five additional years and residual BSE infectivity was assessed in bovine PrPC transgenic mice. Over this long time period (more than six years), BSE infectivity was reduced by three and one orders of magnitude in wastewater and PBS respectively. To rule out a possible agent specific effect, sheep scrapie prions were subjected to the same experimental protocol, using eight years as the experimental end-point. No significant reduction in scrapie infectivity was observed over the first nine months of wastewater incubation while PBS incubation for eight years only produced a two logarithmic unit reduction in infectivity. By contrast, the dynamics of PrPRes persistence was different, disappearing progressively over the first year. The long persistence of prion infectivity observed in this study for two different agents provides supporting evidence of the assumed high stability of these agents in aquatic environments and that environmental processes or conventional wastewater treatments with low retention times would have little impact on prion infectivity. These results could have great repercussions in terms of risk assessment and safety for animals and human populations.

Mathematical Models for Estimating the Risks of Bovine Spongiform Encephalopathy (BSE).

When the bovine spongiform encephalopathy (BSE) epidemic first emerged in the United Kingdom in the mid 1980s, the etiology of animal prion diseases was largely unknown. Risk management efforts to control the disease were also subject to uncertainties regarding the extent of BSE infections and future course of the epidemic. As understanding of BSE increased, mathematical models were developed to estimate risk of BSE infection and to predict reductions in risk in response to BSE control measures. Risk models of BSE-transmission dynamics determined disease persistence in cattle herds and relative infectivity of cattle prior to onset of clinical disease. These BSE models helped in understanding key epidemiological features of BSE transmission and dynamics, such as incubation period distribution and age-dependent infection susceptibility to infection with the BSE agent. This review summarizes different mathematical models and methods that have been used to estimate risk of BSE, and discusses how such risk projection models have informed risk assessment and management of BSE. This review also provides some general insights on how mathematical models of the type discussed here may be used to estimate risks of emerging zoonotic diseases when biological data on transmission of the etiological agent are limited.

Risk assessment for transmission of variant Creutzfeldt-Jakob disease by transfusion of red blood cells in the United States.

BACKGROUND: Variant Creutzfeldt-Jakob disease (vCJD) is transmitted by blood transfusion. To mitigate the risk of transfusion-transmitted vCJD (TTvCJD), the US Food and Drug Administration has recommended deferral of potential at-risk blood donors, but some risk remains. We describe a quantitative risk assessment to estimate residual, postdeferral TTvCJD risk in the United States. STUDY DESIGN AND METHODS: We assumed that certain US donors may have acquired vCJD infection through dietary exposure to the agent of bovine spongiform encephalopathy during time spent in the United Kingdom, France, and other countries in Europe. Because of uncertainties regarding the prevalence of vCJD in the United Kingdom, we used both low and high UK prevalence estimates as model inputs. The model estimated the risk of infection from a transfusion in year 2011 and the cumulative risk from 1980 through 2011. The model was validated by comparing the model predictions with reported cases of vCJD. RESULTS: Using the low UK prevalence estimate, the model predicted a mean risk of 1 in 134 million transfusions, zero TTvCJD infections acquired in the year 2011, and zero cumulative clinical TTvCJD cases for the period spanning 1980 to 2011. With the high UK prevalence estimate, the model predicted a mean risk of 1 in 480,000 transfusions, six infections for 2011, and nine cumulative clinical cases from 1980 to 2011. CONCLUSIONS: Model validation exercises indicated that predictions based on the low prevalence estimate are more consistent with clinical cases actually observed to date, implying that the risk, while highly uncertain, is likely very small.

Laboratory activities involving transmissible spongiform encephalopathy causing agents: risk assessment and biosafety recommendations in Belgium.

Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed.

BSE and variant CJD: emerging science, public pressure and the vagaries of policy-making.

Classical bovine spongiform encephalopathy (BSE) was first recognized in 1987 in the United Kingdom and ultimately spread to cattle across Europe and to the Middle East, North America and Japan through the movement of infected animals and contaminated meat and bone meal. The human expression of BSE, variant Creutzfeldt-Jakob Disease (vCJD), likewise was first identified in the UK and now has been observed in many countries due to human exposure to BSE contaminated products or to vCJD contaminated human tissues through transplantation and injection. BSE provides an example of an emerging infectious disease that demonstrates the challenges of policy-making in the face of rapidly changing science and public outrage pushing for action. Lessons learned through the BSE epidemic include: (1) beware of facts as new science continues to emerge; (2) complex issues rarely have simple solutions; (3) evaluate epidemics from a macro-epidemiologic perspective to understand their complexity and devise effective risk management strategies; (4) options always exist for prevention/control; (5) risk communications play a vital role before and during an emerging disease epidemic; and (6) risk management progress involves both science and politics. Adoption of One Health approaches involving systems thinking and shared leadership hold the most promise for effectively managing complex emergency global health issues like BSE.

Toxics, Toyotas, and terrorism: the behavioral economics of fear and stigma.

Economists have traditionally viewed the behavioral response to risk as continuous and proportional. In contrast, psychologists have often contended that people have little control over their response to risk that is dichotomous, nonproportional, visceral, and fear based. In extreme cases, this automatic response results in the stigmatization of a product, technology, or choice, which seemingly cannot be eliminated or reduced. In resolving these contrasting perspectives, we review four recent studies that blend behavioral economics and psychology. Together, they provide evidence for a dual-process decision model for risk that incorporates both reason and fear. They show consumers' responses to perceived risk as a mix of proportional and dichotomous (safe/unsafe) responses that are relatively more continuous in situations where deliberation is possible, and more dichotomous in emotional or stressful circumstances. These findings reconcile mixed results in past studies, and, more importantly, the dual-process model allows a clear definition of stigma, and suggests new ways to mitigate stigma and to help manage potentially damaging overreactions to it.

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.

Do beef risk perceptions or risk attitudes have a greater effect on the beef purchase decisions of Canadian consumers?

Cluster analysis is applied in this study to group Canadian households by two characteristics, their risk perceptions and risk attitudes toward beef. There are some similarities in demographic profiles, meat purchases, and bovine spongiform encephalopathy (BSE) media recall between the cluster that perceives beef to be the most risky and the cluster that has little willingness to accept the risks of eating beef. There are similarities between the medium risk perception cluster and the medium risk attitude cluster, as well as between the cluster that perceives beef to have little risk and the cluster that is most willing to accept the risks of eating beef. Regression analysis shows that risk attitudes have a larger impact on household-level beef purchasing decisions than do risk perceptions for all consumer clusters. This implies that it may be more effective to undertake policies that reduce the risks associated with eating beef, instead of enhancing risk communication to improve risk perceptions. Only for certain clusters with higher willingness to accept the risks of eating beef might enhancing risk communication increase beef consumption significantly. The different role of risk perceptions and risk attitudes in beef consumption needs to be recognized during the design of risk management policies.

The economic impacts of chronic wasting disease and bovine spongiform encephalopathy in alberta and the rest of Canada.

Input-output analysis was used to calculate the economic impacts from potential prion diseases outbreaks in Alberta and the rest of Canada. Both chronic wasting disease (CWD) and bovine spongiform encephalopathy (BSE) have the capacity not only to affect the farmed cervid and cattle industries, but also to impact all industries with direct and indirect links to these sectors. Cervid sector shocks yield small spillover effects on the economies of Alberta as well as that of all of Canada. In contrast, the cattle sector generates larger multiplier effects in both specifically Alberta region and all of Canada. The industries that consistently experience the largest impacts from prion disease outbreaks in both Alberta and remainder of Canada economic regions are agricultural sectors, mining and energy sectors, and industries dedicated to trade, transportation, and warehousing.

Assessment of enzymatic methods in the δ18O value determination of the L-tyrosine p-hydroxy group for proof of illegal meat and bone meal feeding to cattle.

The δ(18)O value of the p-hydroxy group of L-tyrosine depends on the biosynthesis by plants or animals, respectively. In animal proteins it reflects the diet and is therefore an absolute indicator for illegal feeding with meat and bone meal. The aim of this investigation was to perform the positional (18)O determination on L-tyrosine via a one-step enzymatic degradation. Proteins from plants, herbivores, omnivores, and carnivores were characterized by their δ(13)C, δ(15)N, and δ(18)O values, the latter for normalizing the positional δ(18)O values. Their L-tyrosine was degraded by tyrosine phenol lyase to phenol, analyzed as (2,4,6)-tribromophenol. Degradation by tyrosine decarboxylase yielded tyramine. The δ(18)O values of both analytes corresponded to the trophic levels of their sources but were not identical, probably due to an isotope effect on the tyrosine phenol lyase reaction. Availability of the enzyme, easy control of the reaction, and isolation of the analyte are in favor of tyrosine decarboxylase degradation as a routine method.

Trans-biopolitics: Complexity in interspecies relations.

This article introduces the concept of trans-biopolitics to account for complexity in the intermingling of animal and human bodies, with particular attention to diseases capable of crossing the species divide from animals to humans. While zoonotic diseases never disappeared, they had re-emerged as pressing concerns by the 21st century. The concept of trans-biopolitics takes into account the power relations inherent in human and nonhuman lives in contemporary global, industrial, and technological formations. More specifically, trans-biopolitics revolves around practices determining whose lives are possible or legitimate to prolong, whose bodies are sacrificed in order to preserve the vitality of other bodies, and whose bodies are sustained yet ultimately rendered insignificant. To illustrate, we examine connections between bovine spongiform encephalopathy and feline spongiform encephalopathy, to show how certain bodies (humans, livestock) are taken into consideration in terms of health and food regulations, whereas other bodies (pets) remain at the periphery. Acknowledging human-animal relations in contemporary technological and global contexts challenges us to rethink ways in which the politics of health continues to evolve.

Estimating the impact on the food chain of changing bovine spongiform encephalopathy (BSE) control measures: the BSE control model.

The decline in the bovine spongiform encephalopathy (BSE) epidemic in Great Britain (GB) demands a review of control strategies to ensure that they remain proportionate. Amongst controls that are subject to review are those intended to minimise the risk of BSE exposure of consumers through food. Such risk mitigation steps are costly, and the relative impact of each in terms of human exposure to BSE infectivity is not known. This risk assessment, termed the BSE Control Model, aims to estimate by use of stochastic simulation the impact of testing of cattle at slaughter and the removal of Specified Risk Materials (SRM) on potential BSE infectivity consumed. This paper describes the use of the model to investigate the effect of different risk management methods that have been or could be implemented between 2005 and 2010. Our results suggest that the amount of infectivity consumed in 2005 with the Over Thirty Month (OTM) rule in place was a mean of 0.03 bovine oral ID(50) (BO ID(50)). This is an extremely low amount, particularly considering that it would be spread over, on average, 236 infected carcases that would be further sub-divided into portions for human consumption. The highest contributor to the total amount of infectivity consumed per year is spinal contamination at carcase splitting (35%). In 2006 the OTM scheme was discontinued and head meat was again permitted into the food chain. These changes resulted in an increase in the amount of infectivity consumed, rising to an estimated 28 BO ID(50) in 2006, and 19 BO ID(50) in 2007. In 2008 the age at removal of vertebral column was raised from 24 to 30 months, and an estimated 24 BO ID(50) of infectivity was consumed. At the beginning of 2009 the age at testing of cattle was raised to 48 months for healthy slaughter, emergency slaughter and fallen stock. Under these conditions, an estimated mean of 24 BO ID(50) will be consumed in 2009, decreasing to 20 BO ID(50) in 2010. Even though presented in terms of bovine rather than human oral ID(50), such estimates represent an extremely low exposure of the British population. Considerable uncertainty would surround any attempt to try to convert such exposure into estimates of new cases of vCJD, but the most recent estimates of the size of the species barrier between cattle and humans (4000, EFSA, 2006) suggest that there would be few, if any, new cases of vCJD arising from such exposure levels.

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.

Risk of introduction of BSE into Japan by the historical importation of live cattle from the United Kingdom.

All cattle imported from the United Kingdom to Japan since 1980 and slaughtered before 2002 were traced (n=33), and the number of cattle that were possibly infected with BSE and entered the animal feed chain was calculated. Because there was no effective system to avoid recycling of the BSE agent via animal feed until the early 1990s, of the 33 cattle imported from the UK into Japan, most probably 7 or 8 were infected and entered the animal feed chain, 2 of which entered the animal feed chain in each of 1992 and 1993. In terms of infectivity, 400-550 cattle oral ID(50) of the BSE agent entered the feed chain in each of these years. The amount of infectivity that entered the feed chain in 1989, 1991 and 1995 was smaller but still substantial, suggesting that the BSE agent might have entered the Japanese feed chain in any of these years.

Mad cows and computer models: the U.S. response to BSE.

The proportion of slaughtered cattle tested for BSE is much smaller in the U.S. than in Europe and Japan, leaving the U.S. heavily dependent on statistical models to estimate both the current prevalence and the spread of BSE. We examine the models relied on by USDA, finding that the prevalence model provides only a rough estimate, due to limited data availability. Reassuring forecasts from the model of the spread of BSE depend on the arbitrary constraint that worst-case values are assumed by only one of 17 key parameters at a time. In three of the six published scenarios with multiple worst-case parameter values, there is at least a 25% probability that BSE will spread rapidly. In public policy terms, reliance on potentially flawed models can be seen as a gamble that no serious BSE outbreak will occur. Statistical modeling at this level of abstraction, with its myriad, compound uncertainties, is no substitute for precautionary policies to protect public health against the threat of epidemics such as BSE.

Quantitative risk assessment for bovine spongiform encephalopathy in low- or zero-prevalence countries: the example of Norway.

A predictive case-cohort model is applied to Norwegian data to analyze the interaction between challenge and stability factors for bovine spongiform encephalopathy (BSE) during the period 1980-2010. For each year, the BSE risk in cattle is estimated as the expected number of cases. The age distribution of expected cases as well as the relative impact of different challenges is estimated. The model consists of a simple, transparent, and practical deterministic spreadsheet calculation model, in which the following country-specific inputs are entered: (i) annual imports of live cattle and meat and bone meal, (ii) age distribution of native cattle, and (iii) estimated annual basic reproduction ratio (R(0)) for BSE. Results for Norway indicate that the highest risk of BSE cases was in 1989, when a total BSE risk of 0.13 cases per year was expected. After that date, the year-to-year decrease in risk ranged between 3% and 47%, except for a secondary peak in 1994 at 0.06 cases per year. The primary peak was almost entirely (99%) attributable to the importation of 11 cattle from the United Kingdom between 1982 and 1986. The secondary peak, in 1994, originated mainly from the recycling of the U.K. imported cattle (92%). In 2006, the remaining risk was 0.0003 cases per year, or 0.001 per million cows per year, with a maximal age-specific incidence of 0.03 cases per million per year in 10-year-old cattle. Only 15% of the cases were expected in imported cattle. The probability of having zero cases in Norway in 2006 was estimated to be 99.97%. The model and results are compared to previous risk assessments of Norway by the EU.

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.

Influence of routine slaughtering on the evolution of BSE: example of British and French slaughterings.

The aim of this article is to build a methodology allowing the study and the comparison of the potential spread of BSE at the scale of countries under different routine slaughtering conditions in order to evaluate the risk of nonextinction due to this slaughtering. We first model the evolution in discrete time of the proportion of animals in the latent period and that of infectives, assuming a very large branching population not necessarily constant in size, two age classes, less than 1-year-old animals, and adult animals. We analytically derive a bifurcation parameter rho(0) allowing us to predict either endemicity or extinction of the disease, which has the meaning of an epidemiological reproductive rate. We show that the classical reproductive number R(0) cannot be used for prediction if the size of the population, when healthy, does not remain stable throughout time. We illustrate the qualitative results by means of simulations with either the British routine slaughtering probabilities or the French ones, the other conditions being assumed identical in both countries. We show that the French probabilities lead to a higher risk of spread of the disease than the British ones, this result being mainly due to a smaller value of the routine slaughtering probability of the adult animals in France than in Great Britain.

Exposure assessment of TSEs from the landspreading of meat and bone meal.

Recent changes in European legislation have meant that certain processed abattoir waste, which has been appropriately heat treated and ground to a specified particle size, can be spread on nonpasture agricultural land. This has opened the way for the potential landspreading of mammalian meat and bone meal (mMBM) derived from animals slaughtered for human consumption. This article reports on two separate case studies (Study 1 carried out in Great Britain (GB) and Study 2 carried out in Ireland) on the potential exposure to TSE infectivity following the spreading of abattoir waste (derived from animals slaughtered for human consumption) on nonpasture agricultural land. For Study 1, the average TSE infectivity on nonpasture agricultural land per year from sheep with scrapie was found to be higher (five orders of magnitude) than that estimated for BSE in cattle (3.9 x 10(-3) Ovine Oral ID(50)/ton of soil compared to 3.3 x 10(-8) Bovine Oral ID(50)/ton of soil). The mean estimate for BSE in sheep was 8.1 x 10(-6) Ovine Oral ID(50)/ton of soil. The mean level of infectivity in mMBM was assessed to be 1.2 x 10(-5) and 2.36 x 10(-5) ID(50)/ton of mMBM for Study 1 and 2, respectively. For Study 2 the spreading of mMBM was estimated to result in infectivity on nonpasture land of 1.62 x 10(-8) Bovine Oral ID(50)/m(3). The mean simulated probability of infection per year per bovine animal was 1.11 x 10(-9). Given the low infectivity density and corresponding low risks to bovines the spreading of mMBM could be considered a viable alternative for the utilization of mMBM.