A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing

In this article the development and parameterization of a quantitative assessment is described that estimates the amount of TSE infectivity that is present in a whole animal carcass (bovine spongiform encephalopathy [BSE] for cattle and classical/atypical scrapie for sheep and lambs) and the amounts that subsequently fall to the floor during processing at facilities that handle specified risk material (SRM). BSE in cattle was found to contain the most oral doses, with a mean of 9864 BO ID₅₀s (310, 38840) in a whole carcass compared to a mean of 1851 OO ID₅₀s (600, 4070) and 614 OO ID₅₀s (155, 1509) for a sheep infected with classical and atypical scrapie, respectively. Lambs contained the least infectivity with a mean of 251 OO ID₅₀s (83, 548) for classical scrapie and 1 OO ID₅₀s (0.2, 2) for atypical scrapie. The highest amounts of infectivity falling to the floor and entering the drains from slaughtering a whole carcass at SRM facilities were found to be from cattle infected with BSE at rendering and large incineration facilities with 7.4 BO ID₅₀s (0.1, 29), intermediate plants and small incinerators with a mean of 4.5 BO ID₅₀s (0.1, 18), and collection centers, 3.6 BO ID₅₀s (0.1, 14). The lowest amounts entering drains are from lambs infected with classical and atypical scrapie at intermediate plants and atypical scrapie at collection centers with a mean of 3 × 10^?7 OO ID₅₀s (2 × 10^?8, 1 × 10^?6) per carcass. The results of this model provide key inputs for the model in the companion paper published here.     

The BSE Risk of Processing Meat and Bone Meal in Nonruminant Feed: A Quantitative Assessment for the Netherlands

The total ban on use of meat and bone meal (MBM) in livestock feed has been very successful in reducing bovine spongiform encephalopathy (BSE) spread, but also implies a waste of high-quality proteins resulting in economic and ecological loss. Now that the BSE epidemic is fading out, a partial lifting of the MBM ban might be considered. The objective of this study was to assess the BSE risk for the Netherlands if MBM derived from animals fit for human consumption, i.e., category 3 MBM, would be used in nonruminant feed. A stochastic simulation model was constructed that calculates (1) the probability that infectivity of undetected BSE-infected cows ends up with calves and (2) the quantity of infectivity ( Q_inf ) consumed by calves in case of such an incident. Three pathways were considered via which infectivity can reach cattle: (1) cross-contamination in the feed mill, (2) cross-contamination on the primary farm, and (3) pasture contamination. Model calculations indicate that the overall probability that infectivity ends up with calves is 3.2%. In most such incidents the Q_inf is extremely small (median = 6.5 × 10⁻¹² ID₅₀; mean = 1.8 × 10⁻⁴ ID₅₀), corresponding to an average probability of 1.3 × 10⁻⁴ that an incident results in ≥1 new BSE infections. Cross-contamination in the feed mill is the most risky pathway. Combining model results with Dutch BSE prevalence estimates for the coming years, it can be concluded that the BSE risk of using category 3 MBM derived from Dutch cattle in nonruminant feed is very low.     

Transmissible Spongiform Encephalopathy Risk Assessment: The UK experience

Transmissible spongiform encephalopathy (TSE) risk assessments undertaken in the United Kingdom have mainly had the objective of determining the risks posed to humans from exposure to the causal agents associated with bovine spongiform encephalopathy (BSE) and variant Creutzfeld-Jakob disease (vCJD). In this article, I examine 19 of these risk assessments published to date and consider how their results might be influenced by underlying model assumptions and methodology. Three separate aspects common to all the assessments are infective load estimation, exposure pathway identification, and risk estimation. These are each discussed in detail.     

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.     

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.     

Complementary Approach of Data Analysis and Modeling to Estimate the Pattern of the BSE Epidemic: The Example of France

Clinical surveillance was the only way to detect bovine spongiform encephalopathy (BSE) until July 2000 in France. From the 103 cases identified as such between 1991 and June 2000, we used a back-calculation method to reconstruct the longitudinal trend of BSE infections. Between July 1987 and June 1997, an estimated 51,300 (CI =[24,300-84,700]) cattle were infected in France. The comprehensive surveillance of BSE with rapid tests, set up in France since 2001 at the abattoir and fallen plant, allowed study of the relative exposure of the successive birth cohorts with nonconditional logistic regression models adjusted for possible confounding variables. The results were in agreement with those of the back-calculation model, estimating a decrease of the BSE exposure from the birth cohort July 1995-June 1996 that matched with the decrease of the infection after June 1996. In view of the long incubation period of BSE, it is not possible to precisely assess the impact of any control measure before several years. Modeling was therefore used to estimate prospectively the efficiency of the ban of meat and bone meal extended to all farm species in November 2000. Using parameters about age at infection and incubation time estimated earlier, we assessed the minimum time to first detection if infections still occurred. We have waited up to June 2007 to know if less than 100 infections occurred among French cattle during the 6 months following January 2001.     

A Quantitative Risk Assessment for Bovine Spongiform Encephalopathy in Japan

A predictive case‐cohort model was applied to Japanese data to analyze the interaction between challenge and stability factors for bovine spongiform encephalopathy (BSE) for the period 1985–2020. BSE risk in cattle was estimated as the expected number of detectable cases per year. The model was comprised of a stochastic spreadsheet calculation model with the following inputs: (1) the origin and quantity of live cattle and meat and bone meal imported into Japan, (2) the age distribution of native cattle, and (3) the estimated annual basic reproduction ratio (R₀) for BSE. The estimated probability of having zero detectable cases in Japan in 2015 was 0.90 (95% CI 0.83–0.95). The corresponding value for 2020 was 0.99 (95% CI 0.98–0.99). The model predicted that detectable cases may occur in Japan beyond 2015 because of the assumption that continued transmission was permitted to occur (albeit at a very low level) after the 2001 ban on the importation and domestic use of all processed animal proteins for the production of animal feed and for fertilizer. These results reinforce the need for animal health authorities to monitor the efficacy of control measures so that the future course of the BSE epidemic in Japan can be predicted with greater certainty.     

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.     

Preventive Health Behavior and Adaptive Accuracy of Risk Perceptions

This study examined the relation between health behavior and risk perceptions in the context of an acute livestock epidemic. Participants in a longitudinal web-based survey ( N = 195) were asked to report their meat consumption and their perceived risk in relation to bovine spongiform encephalopathy (BSE) and other related livestock diseases. Cross-sectional analyses at both measurement points (T1 and T2) showed that participants with low levels of preventive nutrition (high meat consumption) felt more at risk for BSE-related diseases than those reporting comparable higher levels of preventive behavior (low meat consumption), indicating relative accuracy. These results suggest that people recognize when their behavior is risky. More importantly, perceived risk also showed adaptive accuracy from a change perspective: increases in preventive nutrition from T1 to T2 were significantly associated with decreases in perceived risk between T1 and T2. Possible foundations and implications of an adaptive accuracy of risk perceptions are discussed.     

Optimal Tracking and Testing of U.S. and Canadian Herds for BSE: A Value-of-Information (VOI) Approach

The U.S. Department of Agriculture (USDA) tests a subset of cattle slaughtered in the United States for bovine spongiform encephalitis (BSE). Knowing the origin of cattle (U.S. vs. Canadian) at testing could enable new testing or surveillance policies based on the origin of cattle testing positive. For example, if a Canadian cow tests positive for BSE, while no U.S. origin cattle do, the United States could subject Canadian cattle to more stringent testing. This article illustrates the application of a value-of-information (VOI) framework to quantify and compare potential economic costs to the United States of implementing tracking cattle origins to the costs of not doing so. The potential economic value of information from a tracking program is estimated to exceed its costs by more than five-fold if such information can reduce future losses in export and domestic markets and reduce future testing costs required to reassure or win back customers. Sensitivity analyses indicate that this conclusion is somewhat robust to many technical, scientific, and market uncertainties, including the current prevalence of BSE in the United States and/or Canada and the likely reactions of consumers to possible future discoveries of BSE in the United States and/or Canada. Indeed, the potential value of tracking information is great enough to justify locating and tracking Canadian cattle already in the United States when this can be done for a reasonable cost. If aggressive tracking and testing can win back lost exports, then the VOI of a tracking program may increase to over half a billion dollars per year.     

Consumption of Bovine Spongiform Encephalopathy (BSE) Contaminated Beef and the Risk of Variant Creutzfeldt‐Jakob Disease

To date, the variant Creutzfeldt‐Jakob disease (vCJD) risk assessments that have been performed have primarily focused on predicting future vCJD cases in the United Kingdom, which underwent a bovine spongiform encephalopathy (BSE) epidemic between 1980 and 1996. Surveillance of potential BSE cases was also used to assess vCJD risk, especially in other BSE‐prevalent EU countries. However, little is known about the vCJD risk for uninfected individuals who accidentally consume BSE‐contaminated meat products in or imported from a country with prevalent BSE. In this article, taking into account the biological mechanism of abnormal prion PrP^res aggregation in the brain, the probability of exposure, and the expected amount of ingested infectivity, we establish a stochastic mean exponential growth model of lifetime exposure through dietary intake. Given the findings that BSE agents behave similarly in humans and macaques, we obtained parameter estimates from experimental macaque data. We then estimated the accumulation of abnormal prions to assess lifetime risk of developing clinical signs of vCJD. Based on the observed number of vCJD cases and the estimated number of exposed individuals during the BSE epidemic period from 1980 to 1996 in the United Kingdom, an exposure threshold hypothesis is proposed. Given the age‐specific risk of infection, the hypothesis explains the observations very well from an extreme‐value distribution fitting of the estimated BSE infectivity exposure. The current BSE statistics in the United Kingdom are provided as an example.     

Analyzing BSE Transmission to Quantify Regional Risk

As a result of consumer fears and political concerns related to BSE as a risk to human health, a need has arisen recently for more sensitive methods to detect BSE and more accurate methods to determine BSE incidence. As a part of the development of such methods, it is important to be able to identify groups of animals with above-average BSE risk. One of the well-known risk factors for BSE is age, as very young animals do not develop the disease, and very old animals are less likely to develop the disease. Here, we analyze which factors have a strong influence on the age distribution of BSE in a population. Building on that, we develop a simple set of calculation rules for classifying the BSE risk in a given cattle population. Required inputs are data on imports and on the BSE control measures in place over the last 10 or 20 years.     

The Impact of Social Amplification and Attenuation of Risk and the Public Reaction to Mad Cow Disease in Canada

Following the detection of bovine spongiform encephalopathy (BSE) in Canada, and subsequently in the United States, confidence in the safety of beef products remained high. Consumers actually increased their consumption of beef slightly after the news of an increased risk from mad cow disease, which has been interpreted as public support for beef farmers and confidence in government regulators. The Canadian public showed a markedly different reaction to the news of domestic BSE than the furious and panicked responses observed in the United Kingdom, Germany, and Japan. Using the social amplification of risk framework, we show that, while other countries displayed social amplification of risk, Canada experienced a social attenuation of risk. The attenuated reaction in Canada toward mad cow disease and increased human health risks from variant Creutzfeldt-Jakob disease (vCJD) was due to the social context at the time when BSE was discovered domestically. Mortality, morbidity, and psychosocial impacts resulting from other major events such as severe acute respiratory syndrome (SARS), West Nile virus (WNV), and the U.S.-Iraq war made the theoretical risks of BSE and vCJD a lower priority, reducing its concern as a risk issue.     

Why Reduced-Form Regression Models of Health Effects Versus Exposures Should Not Replace QRA: Livestock Production and Infant Mortality as an Example

Do pollution emissions from livestock operations increase infant mortality rate (IMR)? A recent regression analysis of changes in IMR against changes in aggregate “animal units” (a weighted sum of cattle, pig, and poultry numbers) over time, for counties throughout the United States, suggested the provocative conclusion that they do: “[A] doubling of production leads to a 7.4% increase in infant mortality.” Yet, we find that regressing IMR changes against changes in specific components of “animal units” (cattle, pigs, and broilers) at the state level reveals statistically significant negative associations between changes in livestock production (especially, cattle production) and changes in IMR. We conclude that statistical associations between livestock variables and IMR variables are very sensitive to modeling choices (e.g., selection of explanatory variables, and use of specific animal types vs. aggregate “animal units). Such associations, whether positive or negative, do not warrant causal interpretation. We suggest that standard methods of quantitative risk assessment (QRA), including emissions release (source) models, fate and transport modeling, exposure assessment, and dose-response modeling, really are important—and indeed, perhaps, essential—for drawing valid causal inferences about health effects of exposures to guide sound, well-informed public health risk management policy. Reduced-form regression models, which skip most or all of these steps, can only quantify statistical associations (which may be due to model specification, variable selection, residual confounding, or other noncausal factors). Sound risk management requires the extra work needed to identify and model valid causal relations.     

Quantitative Assessment of the Health Risk for Livestock When Animal Viruses Are Applied in Human Oncolytic Therapy: A Case Study for Seneca Valley Virus

Some viruses cause tumor regression and can be used to treat cancer patients; these viruses are called oncolytic viruses. To assess whether oncolytic viruses from animal origin excreted by patients pose a health risk for livestock, a quantitative risk assessment (QRA) was performed to estimate the risk for the Dutch pig industry after environmental release of Seneca Valley virus (SVV). The QRA assumed SVV excretion in stool by one cancer patient on Day 1 in the Netherlands, discharge of SVV with treated wastewater into the river Meuse, downstream intake of river water for drinking water production, and consumption of this drinking water by pigs. Dose–response curves for SVV infection and clinical disease in pigs were constructed from experimental data. In the worst scenario (four log₁₀ virus reduction by drinking water treatment and a farm with 10,000 pigs), the infection risk is less than 1% with 95% certainty. The risk of clinical disease is almost seven orders of magnitude lower. Risks may increase proportionally with the numbers of treated patients and days of virus excretion. These data indicate that application of wild‐type oncolytic animal viruses may infect susceptible livestock. A QRA regarding the use of oncolytic animal virus is, therefore, highly recommended. For this, data on excretion by patients, and dose–response parameters for infection and clinical disease in livestock, should be studied.     

A Quantitative Assessment of the Risks from Illegally Imported Meat Contaminated with Foot and Mouth Disease Virus to Great Britain

Foot and mouth disease (FMD) is considered by many as the most important animal disease in the world. FMD is highly contagious and outbreaks incur significant costs as affected countries are severely limited in their ability to trade. A number of trade commodities may be contaminated with FMD virus (FMDV) including animal products, for example, meat. As a member of the European Union, Great Britain (GB) has put in place a number of regulations to prevent the importation of pathogens in imported meat products. However, the illegal importation of meat provides a route by which safety controls may be circumvented and meat from FMD affected areas may be imported. This study assesses the FMD infection risk posed to the livestock population of GB from the illegal importation of meat, and estimates the major contributors to this overall risk, through the development of a quantitative risk assessment model. From model results, the total amount of illegal meat entering GB each year is estimated on average to be 11,875 tonnes. with 90% certainty that this is between 4,398 and 28,626 tonnes per year; of which between 64.5 and 565 kg are contaminated with FMDV. This flow of illegal meat results in an estimate of a frequency of FMD infection in GB livestock of 0.015 cases of infected animals per year, with 90% certainty it is between 0.0017 and 0.053. Imports from the region Near and Middle East account for 47% of this risk, and 68% of the risk is attributed to bone-in and dried de-boned products.     

Risk of Legionellosis in residential areas around farms irrigating with municipal wastewater

The conservation of freshwater is of both global and national importance, and in the United States, agriculture is one of the largest consumers of this resource. Reduction of the strain farming puts on local surface or groundwater is vital for ensuring resilience in the face of climate change, and one possible option is to irrigate with a combination of freshwater and reclaimed water from municipal wastewater treatment facilities. However, this wastewater can contain pathogens that are harmful to human health, such as Legionella pneumophila, which is a bacterium that can survive aerosolization and airborne transportation and cause severe pneumonia when inhaled. To assess an individual adult's risk of infection with L. pneumophila from a single exposure to agricultural spray irrigation, a quantitative microbial risk assessment was conducted for a scenario of spray irrigation in central Illinois, for the growing seasons in 2017, 2018, and 2019. The assessment found that the mean risk of infection for a single exposure exceeded the safety threshold of 10^–6 infections/exposure up to 1 km from a low-pressure irrigator and up to 2 km from a high-pressure irrigator, although no median risk exceeded the threshold for any distance or irrigator pressure. These findings suggest that spray irrigation with treated municipal wastewater could be a viable option for reducing freshwater consumption in Midwest farming, as long as irrigation on windy days is avoided and close proximity to the active irrigator is limited.     

Risk Perception of the "Mad Cow Disease" in France: Determinants and Consequences

Since 1996, when bovine spongiform encephalopathy (BSE) was assessed as a possible human transmissible disease, a variant of Creutzfeldt-Jakob disease (vCJD), French people have entered into a long period of fear and avoidance of beef and bovine byproducts, which produced an unprecedented collapse in the beef market. This article deals with the perceived risk of the "mad cow disease" (MCD) in the French general population. Two surveys were conducted on a representative sample of the adult population, the first one in 2000 during the peak of the crisis and the second one 13 months later in a quieter period. The main assumption we made was that changes in beef consumption are strongly related to the perceived risk of MCD, which we defined as people's cognitive and affective responses to hazard. Our objective was to identify the determinants and consequences of this perceived risk and to compare them in different sociopolitical contexts. The results issued from a bivariate and multivariate analysis show that: (i) the distribution of most of the variables significantly related to the perceived risk identified in the first survey had changed in the second survey, in relation with the reduction of worry and the resumption of national beef consumption; (ii) the propensity for self-protection through avoiding or ceasing beef eating was more related to feelings of worry than to subjective vCJD risk assessments; and (iii) the main determinant of less avoidance to beef products was the preference for beef, a feeling identified prior to emergence of the risk of MCD, remaining unchanged in various contexts.