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.     

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.     

A Quantitative Assessment of the Prion Risk Associated with Wastewater from Carcass‐Handling Facilities

Wastewater from facilities processing livestock that may harbor transmissible spongiform encephalopathies (TSEs) infectivity is permitted under license for application to land where susceptible livestock may have access. Several previous risk assessments have investigated the risk of bovine spongiform encephalopathy (BSE) associated with wastewater effluents; however, the risk of exposure to classical scrapie and atypical scrapie has not been assessed. With the prevalence of certain TSEs (BSE in cattle and classical scrapie in sheep) steadily in decline, and with considerable changes in the structure of carcass‐processing industries in Great Britain, a reappraisal of the TSE risk posed by wastewater is required. Our results indicate that the predicted number of new TSE infections arising from the spreading of wastewater on pasture over one year would be low, with a mean of one infection every 1,000 years for BSE in cattle (769, 555,556), and one infection every 30 years (16, 2,500), and 33 years (16, 3,333) for classical and atypical scrapie, respectively. It is assumed that the values and assumptions used in this risk assessment remain constant. For BSE in cattle the main contributors are abattoir and rendering effluent, contributing 35% and 22% of the total number of new BSE infections. For TSEs in sheep, effluent from small incinerators and rendering plants are the major contributors (on average 32% and 31% of the total number of new classical scrapie and atypical scrapie infections). This is a reflection of the volume of carcass material and Category 1 material flow through such facilities.     

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.     

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.     

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.     

Comparison of the Historic Recycling Risk for BSE in Three European Countries by Calculating the Basic Reproduction Ratio R0

A deterministic model of BSE transmission is used to calculate the R(0) values for specific years of the BSE epidemics in the United Kingdom (UK), the Netherlands (NL), and Switzerland (CH). In all three countries, the R(0) values decreased below 1 after the introduction of a ban on feeding meat and bone meal (MBM) to ruminants around the 1990s. A variety of additional measures against BSE led to further decrease of R(0) to about 0.06 in the years around 1998. The calculated R(0) values were consistent with the observations made on the surveillance results for UK, but were partially conflicting with the surveillance results for NL and CH. There was evidence for a dependency of the BSE epidemic in NL and CH from an infection source not considered in the deterministic transmission model. Imports of MBM and feed components can be an explanation for this discrepancy, and the importance of imports for these observations is discussed.     

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.     

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.     

Annual Burden of Occupationally‐Acquired Influenza Infections in Hospitals and Emergency Departments in the United States

Infections among health‐care personnel (HCP) occur as a result of providing care to patients with infectious diseases, but surveillance is limited to a few diseases. The objective of this study is to determine the annual number of influenza infections acquired by HCP as a result of occupational exposures to influenza patients in hospitals and emergency departments (EDs) in the United States. A risk analysis approach was taken. A compartmental model was used to estimate the influenza dose received in a single exposure, and a dose–response function applied to calculate the probability of infection. A three‐step algorithm tabulated the total number of influenza infections based on: the total number of occupational exposures (tabulated in previous work), the total number of HCP with occupational exposures, and the probability of infection in an occupational exposure. Estimated influenza infections were highly dependent upon the dose–response function. Given current compliance with infection control precautions, we estimated 151,300 and 34,150 influenza infections annually with two dose–response functions (annual incidence proportions of 9.3% and 2.1%, respectively). Greater reductions in infectious were achieved by full compliance with vaccination and IC precautions than with patient isolation. The burden of occupationally‐acquired influenza among HCP in hospitals and EDs in the United States is not trivial, and can be reduced through improved compliance with vaccination and preventive measures, including engineering and administrative controls.     

Quantitative Microbial Risk Assessment of Cryptosporidiosis and Giardiasis from Very Small Private Water Supplies

This article reports a quantitative microbial risk assessment of the risk of Giardia and Cryptosporidium in very small private water supplies. Both pathogens have been implicated in causing outbreaks of waterborne disease associated with such supplies, though the risk of endemic disease is not known. For exposure assessments, we used existing data to derive regression equations describing the relationships between the concentration of these pathogens and Escherichia coli in private water supplies. Pathogen concentrations were then estimated using national surveillance data of E. coli in private water supplies in England and France. The estimated risk of infection was very high with the median annual risk being of the order of 25–28% for Cryptosporidium and 0.4% to 0.7% for Giardia, though, in the poorer quality supplies the risk could be much higher. These risks are substantially greater than for public water supplies and well above the risk considered tolerable. The observation that observed infection rates are generally much lower may indicate increased immunity in people regularly consuming water from private supplies. However, this increased immunity is presumed to derive from increased disease risk in young children, the group most at risk from severe disease.     

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.     

Cryptosporidiosis Susceptibility and Risk: A Case Study

Regional estimates of cryptosporidiosis risks from drinking water exposure were developed and validated, accounting for AIDS status and age. We constructed a model with probability distributions and point estimates representing Cryptosporidium in tap water, tap water consumed per day (exposure characterization); dose response, illness given infection, prolonged illness given illness; and three conditional probabilities describing the likelihood of case detection by active surveillance (health effects characterization). The model predictions were combined with population data to derive expected case numbers and incidence rates per 100,000 population, by age and AIDS status, borough specific and for New York City overall in 2000 (risk characterization). They were compared with same-year surveillance data to evaluate predictive ability, assumed to represent true incidence of waterborne cryptosporidiosis. The predicted mean risks, similar to previously published estimates for this region, overpredicted observed incidence-most extensively when accounting for AIDS status. The results suggest that overprediction may be due to conservative parameters applied to both non-AIDS and AIDS populations, and that biological differences for children need to be incorporated. Interpretations are limited by the unknown accuracy of available surveillance data, in addition to variability and uncertainty of model predictions. The model appears sensitive to geographical differences in AIDS prevalence. The use of surveillance data for validation and model parameters pertinent to susceptibility are discussed.     

Effectiveness and Efficiency of Controlling Campylobacter on Broiler Chicken Meat

Campylobacter bacteria are an important cause of foodborne infections. We estimated the potential costs and benefits of a large number of possible interventions to decrease human exposure to Campylobacter by consumption of chicken meat, which accounts for 20-40% of all cases of human campylobacteriosis in the Netherlands. For this purpose, a farm-to-fork risk assessment model was combined with economic analysis and epidemiological data. Reduction of contamination at broiler farms could be efficient in theory. However, it is unclear which hygienic measures need to be taken and the costs can be very high. The experimental treatment of colonized broiler flocks with bacteriophages has proven to be effective and could also be cost efficient, if confirmed in practice. Since a major decrease of infections at the broiler farm is not expected in the short term, additional measures in the processing plant were also considered. At this moment, guaranteed Campylobacter-free chicken meat at the retail level is not realistic. The most promising interventions in the processing plant are limiting fecal leakage during processing and separation of contaminated and noncontaminated flocks (scheduling), followed by decontamination of the contaminated flock. New (faster and more sensitive) test methods to detect Campylobacter colonization in broilers flocks are a prerequisite for successful scheduling scenarios. Other methods to decrease the contamination of meat of colonized flocks such as freezing and heat treatment are more expensive and/or less effective than chemical decontamination.     

Assessing the export trade risk of bluetongue virus serotypes 4 and 8 in France

Bluetongue (BT) causes an economic loss of $3 billion every year in the world. After two serious occurrences of BT (bluetongue virus [BTV] occurrence in 2006 and 2015), France has been controlling for decades, but it has not been eradicated. As the largest live cattle export market in the world, France is also one of the major exporters of breeding animals and genetic materials in the world. The biosafety of its exported cattle and products has always been a concern. The scenario tree quantitative model was used to analyze the risk of BTV release from French exported live cattle and bovine semen. The results showed that with the increase in vaccination coverage rates, the risk decreased. If the vaccine coverage is 0%, the areas with the highest average risk probability of BTV-4 and BTV-8 release from exported live cattle were Haute-Savoie and Puy-de-Dôme, and the risk was 2.96 × 10^–4 and 4.25 × 10^–4, respectively. When the vaccine coverage was 90%, the risk probability of BTV-4 and BTV-8 release from exported live cattle was 2.96 × 10^–5 and 4.24 × 10^–5, respectively. The average probability of BTV-8 release from bovine semen was 1.09 × 10^–10. Sensitivity analysis showed that the probability of false negative polymerase chain reaction (PCR) test and the probability of BT infection in the bull breeding station had an impact on the model. The identification of high-risk areas and the discovery of key control measures provide a reference for decision makers to assess the risk of French exports of live cattle and bovine semen.     

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.     

Cryptosporidium and Dairy Cattle in the Catskill/Delaware Watershed: A Quantitative Risk Assessment

We carried out a study to estimate the public health risk posed by dairy cattle located in New York City's Catskill/Delaware watershed, as measured by daily C. parvum-like oocyst loading. A Monte Carlo simulation model that takes into account the nature of the dairy cattle population within the target area, age-specific incidence/prevalence rates, as well as differential fecal production and oocyst-shedding intensity rates was used to address the objectives. Additionally, the model was designed to distinguish between zoonotic and nonzoonotic species/genotypes of Cryptosporidium. Total estimated daily C. parvum-like oocyst shedding across all age/production categories was estimated at 4.15 x 10(10). The zoonotic C. parvum comprised 93.5% of this load. It was estimated that preweaned calves produce 99.5% of the total daily C. parvum ocyst burden. The recently described nonzoonotic C. bovis was estimated to have a daily load of 2.2 x 10(9) oocysts across all age/production strata. C. parvum deer-like genotype was estimated to have a total daily load of 1.3 x 10(9) oocysts. The results of this study support earlier assertions that strategies aimed at reducing the cryptosporidial risk posed by dairy cattle to public health will be most efficacious if aimed at preweaned calves.     

Quantitative Risk Assessment of Listeria monocytogenes in French Cold-Smoked Salmon: II. Risk Characterization

A model for the assessment of exposure to Listeria monocytogenes from cold-smoked salmon consumption in France was presented in the first of this pair of articles (Pouillot et al ., 2007, Risk Analysis, 27:683–700). In the present study, the exposure model output was combined with an internationally accepted hazard characterization model, adapted to the French situation, to assess the risk of invasive listeriosis from cold-smoked salmon consumption in France in a second-order Monte Carlo simulation framework. The annual number of cases of invasive listeriosis due to cold-smoked salmon consumption in France is estimated to be 307, with a very large credible interval ([10; 12,453]), reflecting data uncertainty. This uncertainty is mainly associated with the dose-response model. Despite the significant uncertainty associated with the predictions, this model provides a scientific base for risk managers and food business operators to manage the risk linked to cold-smoked salmon contaminated with L. monocytogenes. Under the modeling assumptions, risk would be efficiently reduced through a decrease in the prevalence of L. monocytogenes or better control of the last steps of the cold chain (shorter and/or colder storage during the consumer step), whereas reduction of the initial contamination levels of the contaminated products and improvement in the first steps of the cold chain do not seem to be promising strategies. An attempt to apply the recent risk-based concept of FSO (food safety objective) on this example underlines the ambiguity in practical implementation of the risk management metrics and the need for further elaboration on these concepts.     

上交所利率期限结构的三因子广义高斯仿射模型

本文以上交所债券价格隐含的利率期限结构数据作为分析对象,首先利用主成份分析法对利率期限结构的变化进行分析,发现需要两个至三个状态变量,利率模型才可能反映利率期限结构的变化。同时在以前的研究里,发现利率期限结构具有一定的可预测性,因此本文选择三因子广义高斯仿射模型描述上交所的利率期限结构。利用卡尔曼滤波法以及极大似然估计法,估计了连续时间的三因子广义高斯仿射模型,模型可以描述上交所利率期限结构的相对变化。     

中国股票市场行业与地区效应分析

根据国家行业分类,参照地区的远近和经济发达程度,把中国股票市场的股票划分为21个行业、12个地区。依据中国股票市场从1995年7月到2001年6月的股票回报率月数据,利用约束回归分析法对回报率的行业和地区效应进行了横截面和时间序列分析,表明中国股票市场具有明显的行业和地区效应,并且行业效应大于地区效应。