Updated prediction for the BSE epidemic in dairy cattle in Japan

Following the detection of the first case of Bovine spongiform encephalopathy (BSE) in Japan in September 2001, nine million cattle were tested for BSE up to the end of 2008. As a result, a further 28 cases were detected in dairy cattle. Using the mathematical model previously developed and surveillance data up to the end of 2008, we estimated the prevalence of BSE-infected animals within each birth cohort for the years 1995–2001. We predicted historic and future trends in the number of BSE-infected animals to be culled and anticipated BSE cases from each birth cohort. The results indicate that more infected animals (428 (95% CI: 59–727)) than previously estimated would have been culled from 1995 to 2001, and more cases (53 (95% CI: 25–101)) than previously predicted would have been detected during this period with a higher peak in 2001, if a BSE surveillance program as comprehensive as the present one was applied. In and after 2009, 0–2 cases of BSE would likely to be detected. As previously predicted, the BSE epidemic should be eradicated by 2012.     

Adjusted incidence risks of BSE in risk subpopulations of cattle in Japan

Immediately after the detection of the first case of BSE in 2001, the Japanese government introduced active surveillance targeting fallen-stock and all cattle slaughtered for human consumption. By the end of 2004, four million animals were tested with rapid tests under the passive and active surveillance. As a result 13 additional cases were detected. I focused on the 1996 birth cohort, in which nine cases of BSE were detected during 2001–2004, and estimated the prevalence of BSE infection of that birth cohort using maximum-likelihood methods. Using the estimated prevalence of infection as an input variable, I calculated the adjusted incidence risk of BSE by different ages and risk subpopulations (clinical-suspects, fallen-stock, sick-slaughter and healthy-slaughter animals). The adjusted incidence risk of BSE in sick-slaughter animals (animals showing clinical signs not compatible with BSE when slaughtered for human consumption) was 18.7 and 4.5–78.4 times higher than the incidence risk in fallen-stock and healthy-slaughter animals, respectively.     

Simulation-based estimation of BSE infection in Japan

The first case of bovine spongiform encephalopathy (BSE) in Japan was found in September 2001. As a result, national BSE surveillance systems in slaughterhouses and farms were introduced between October 2001 and April 2004. All cattle, with the exception of those under 24 months of age that die at farms, now undergo compulsory testing when they die or are slaughtered. The removal of specified risk material (SRM) from all slaughtered cattle and a ban on the feeding of meat-and-bone meal to all farm animals were implemented in October 2001. However, infected cattle that died or were slaughtered before these measures were put into practice could have been a source of infection to other cattle through the rendering process. The slaughtered cattle could also have been a source of infection to humans via SRM that entered the food chain. The purpose of this study was to estimate the number of BSE-infected cattle that could have been a source of infection to cattle and humans before October 2001. Since all typical cases were dairy cattle, this study focused on the dairy cattle population. We developed a simulation model to obtain the year of death and the final disposition of infected cows born in each year from 1996 to 2001. In this model, the dairy cattle population was divided into birth cohorts, and parameters regarding its population dynamics were assumed to be constant. Using this model, the total number of infected cattle in each birth year was estimated by maximum likelihood estimation using data on the number of detected cases from 2002 to 2006. Finally, the number of infected cattle that died or were slaughtered each year was estimated by Monte-Carlo simulation using the same model with the total number of infected cattle estimated by maximum likelihood estimation. It was estimated that the majority of infected cattle that could have been sources of infection before 2001 were born in 1996. The total number born in 1996 was estimated to be 155 (95% confidence interval: 90-275). Of these 155 cattle, 56 died or were slaughtered before October 2001, after the accumulation of infectious agent in their bodies. Only 5 of these 56 cattle were estimated to have been slaughtered. Therefore, the number of infected cattle that could have served as a source of human infection would appear to have been a very limited subset of the BSE-infected cattle in Japan.     

A quantitative assessment of the BSE risk associated with fly ash and slag from the incineration of meat-and-bone meal in a gas-fired power plant in Denmark

It has been recommended that meat-and-bone meal (MBM) be incinerated at 850 °C for at least 2 s and the ashes and slag disposed of in controlled landfills, to dispose of animal-derived proteins. Most commonly, the MBM is incinerated in cement works or coal-fired power plants and the ashes and slag are incorporated into the cement or concrete.

Our goal was to assess with a Monte Carlo simulation model the bovine spongiform encephalopathy (BSE) risk to cattle and humans posed by the ash and slag. The results will be used by decision makers to evaluate the need for disposal of the fly ash in controlled landfills and the feasibility of use of the ash by the phosphate and fertilizer industries.

We assumed that all specified risk material (SRM) and MBM produced in Denmark would be incinerated in this gas-fired power plant. Based on observations in 2001, we assumed that, on average, six (range: 0–15) clinical BSE cases each year were rendered into MBM and incinerated. In addition, SRM or carcasses from 0 to 31 (median = 10) BSE-infected-but-undetected animals/BSE case were also incinerated.

The simulations were run on a 1-week basis. Our results suggest that if the slag is collected and re-incinerated the median BSE infectivity remaining in the fly ash per week would be 3.1E−11 cattle ID₅₀. A cattle ID₅₀ is the amount of infectivity that will cause infection in 50% of cattle exposed to it. During the weeks when BSE was infected in the SRM-MBM, the median infectivity in the fly ash was estimated as 8.7E−10 cattle ID₅₀ and 2.9E−12 human ID₅₀. The 95th percentiles were 2.1E−08 cattle ID₅₀ and 5.8E−10 human ID₅₀, respectively. One ton of fly ash would contain ≤1.8E−07 cattle ID₅₀ 95% of the time. These are the potential exposures of the cattle or human populations. The potential exposures of individuals are far less.     

Questionnaire analysis of BSE cases in France detected by active surveillance and the reasons for non-notification

A mandatory reporting system (MRS) was set up in France in December 1990 to detect animals showing clinical signs of bovine spongiform encephalopathy (BSE). Since June 2000, four active surveillance programmes dedicated to fallen stock and slaughtered cattle have been implemented to reinforce the MRS. The clinical status of the cases detected through these programmes was investigated to understand why the MRS had failed to detect them. Up to September 1, 2002, 181 cases had been analysed (126 fallen stock and 55 slaughtered cattle). Almost all the fallen stock cases were animals which had been showing clinical signs, and two thirds of them had shown signs which should have led to a suspicion of BSE. No clinical signs had been reported for two thirds of the slaughtered cattle cases and 10 (8 per cent) of the fallen stock cases.     

Imported and indigenous BSE cases in Germany

Bovine spongiform encephalopathy (BSE) is a transmissible fatal neurodegenerative disease in cattle with an average incubation time of five years. The first BSE case in an indigenous cow was detected in Germany in November 2000. This was almost eight years after the huge BSE epidemic in the United Kingdom had peaked, and several years after many EU member states had seen their first BSE case. In the 1990s, BSE had been diagnosed in six imported animals in Germany. However, after the implementation of an active surveillance programme using BSE rapid testing systems, 399 indigenous German BSE cases have been found up to the end of July 2006. The birth cohorts of 1995-1997 contribute to the vast majority of the first 250 German cases that were diagnosed between 2000 and 2003. However, the most recent German BSE cases belong primarily to the birth cohorts 1998-2000 which is indicative of a recycling of BSE infectivity at that time. Moreover, there were two BSE cases in cattle born in spring 2001, i.e. after the meat and bone meal feed ban had come into effect on 2nd December 2000. In this article, we describe the dynamics of the German BSE epidemic and compare these data with those of other countries that observed larger numbers of cases.     

Prevalence of BSE in cattle found dead, euthanased or emergency slaughtered on farms in western France in 2000, 2001 and 2002

The overall trend and the trend within birth cohorts of the prevalence of bovine spongiform encephalopathy (BSE) in cattle found dead, euthanased or emergency slaughtered on farms in the Bretagne, Basse Normandie and Pays de la Loire regions of France, during the periods from August 7 to December 22 in 2000, 2001 and 2002, were analysed by non-conditional logistic regression, adjusted for the region and for the type of animals. The overall prevalence of BSE during these three periods decreased from 2.71 per 1000 in 2000 to 1.41 per 1000 in 2001 and 0.42 per 1000 in 2002. The prevalence within birth cohorts started to decrease for the cohort born between July 1, 1995 and June 30, 1996 (cohort 95/96) and the trend was reinforced for cohort 96/97, suggesting that the exposure of animals to the BSE agent had started to decrease for animals born after July 1995, that is, one year before the ban on specified risk materials in meat and bone meal was implemented in France. However, considering that most of the animals would have been infected at between six and 18 months of age, the decrease may have been due, at least partly, to this control measure.     

Risk of introduction of BSE into Japan by the historical importation of cattle from the United Kingdom and Germany

All cattle of UK and German origin imported to Japan since 1980 and slaughtered before 2002 were traced (n = 33 and 15 respectively) and the probability that none, one, two or three of these imported cattle had developed BSE (reached the end or last stage of incubation period) at the year of slaughter/death was calculated. The predicted risk that BSE was introduced into Japan by imported cattle was 0.18. Among cattle imported from these countries in various years, cattle imported from the UK in 1987 and 1988 presented the highest risk, while the risk that BSE entered Japan by live cattle imported from the UK in 1982 and from Germany in 1993 was negligible. Because there was no effective system to avoid the recycling of the BSE agent, those infected cattle imported from the UK in 1987 and 1988 most probably entered the feed chain in Japan in 1992 and 1993.     

BSE infectivity in jejunum, ileum and ileocaecal junction of incubating cattle

ABSTRACT: To establish bovine spongiform encephalopathy (BSE) public health protection measures it is important to precisely define the cattle tissues considered as specified risk materials (SRM). To date, in pre-clinical BSE infected cattle, no evidence of the BSE agent had been found in the gut outside of the ileal Peyer's Patches. This study was undertaken to determine when and where the pathological prion protein (PrPSc) and/or BSE infectivity can be found in the small intestine of cattle 4 to 6 months of age, orally challenged with BSE. Samples of the jejunum, the ileum and the ileocaecal junction from 46 BSE infected cattle, culled from 1 up to 44 months post infection (mpi) were examined by immunohistochemistry. Samples from cattle 8 mpi to 20 mpi were additionally studied by PTA Western blot, rapid tests, and by mouse (TgbovXV) bioassay. In doing so nearly all of the cattle, from 4 up to 44 mpi, had detectable amounts of PrPSc and/or infectivity in the distal ileum. In the distal ileum clear time-dependent variations were visible concerning the amount of PrPSc, the tissue structures affected, and the cells involved. BSE infectivity was found not only in the ileum and ileocaecal junction but also in the jejunum. The systematic approach of this study provides new data for qualitative and quantitative risk assessments and allows defining bovine SRM more precisely.     

Impact of BSE on livestock production system

The small number of BSE cases diagnosed in Italy from January 2001 to 12 September 2001 (a total of 28, one every 9000 head) does not allow for a statistical analysis of the relationship between this disease and the livestock systems. However, some indications can be noted: (a) only dairy cattle, which represent three-quarters of the cattle raised in Italy, are involved; (b) 58% of the cases belong to medium-large farms that breed 27% of all head; (c) 13 out of 28 cases are 5-year-old animals and 26 out of 28 are between 5 and 7 years of age; (d) 15 of 28 cases come from Lombardia, where 27% of Italian dairy cattle are raised. The following factors may have affected the livestock system: (1) trends of beef meat consumption; (2) changes in livestock management; (3) changes in animal feeding; (4) possible effects on selection. A strong decline in beef meat consumption (4 kg/year) has been observed in the UK and other European countries since 1996 (the year of the discovery of the relationship between BSE and nvCJD). In Italy, from January 2001 the consumption of beef meat has declined as well as slaughter: a drop of 31% in the total slaughtered head in the period January-February, a drop of 14% in January-May. A fall in the price of calves has promoted, in some dairy farms, the start of the production of light beef less than one year old (advantages in the marketing of meat favour this initiative), a phenomenon which is not yet well established. Traceability and certification of meat have improved, thanks to breeders' associations and interprofessional agreements. The breeders associations have also started insurance initiatives against BSE risks. In Italy the employment of plant protein meals would increase the total feedstuff consumption by about 7%. Direct effects of BSE could slow down the genetic progress (GP) of cattle populations within breed and country. Indirect effects on GP may also happen as a consequence of an increase in the replacement rate (rr). This increase in rr reduced the generation interval and will therefore proportionally increase GP. Some important questions for the livestock production system are: Does the vertical transmission of BSE exist? Is there a genetic basis favouring the disease and is it inheritable? Are in vivo diagnostic tests possible? Are vaccination schemes against BSE possible and useful or is it better to pursue eradication?     

BSE and scrapie diagnosis in Germany

The detection of pathological prion protein is considered as pathognomonic for the diagnosis of transmissible spongiform encephalopathies. According to the EU regulations cattle older than 30 months of age (Germany 24 months) and slaughtered for human consumption must be tested by using BSE rapid tests. Likewise must be fallen stock and clinically affected animals. This article gives an overview over the diagnostic hierarchy and organization of the diagnostic system for BSE and scrapie in Germany. All suspect cases found by rapid testing are reinvestigated and clarified by the National reference laboratory for these diseases which is part of the recently founded Institute of Novel and Emerging Infectious Diseases at the Federal Research Centre for Virus Diseases of Animals located on the isle of Riems. Until the end of 2001 130 BSE cases were confirmed out of 230 submissions.     

Breed predisposition for BSE: epidemiological evidence in Bavarian cattle

We present epidemiological data from Bavaria that indicates that animals of the Brown Swiss (BS) cattle breed might be more susceptible to BSE than animals from other breeds, both in terms of disease prevalence and length of the incubation period. BS animals were disproportionately represented among the BSE cases (BS represented about 9% of the susceptible population but 27% of actual cases). BS were slaughtered at a higher age (5.8 years vs. 5.0 years for other breeds), and there is a higher prevalence of feeding proprietary feeds to BS calves than calves from other breeds. There was no difference in the recorded feeding practice of BSE-positive animals from BS or other breeds. These results would lead to expect a higher prevalence of BSE in the BS population, with BS BSE animals being of equal age or older than BSE animals from other breeds. In contrast, median age at BSE detection was significantly lower in BS animals than in other breeds (61.4 vs. 68.8 months). There was no difference in the identification categories of BSE between BS animals and animals of other breeds that could explain this difference in age. BS cattle are reported to have more octapeptid repeats in the prion protein gene than other breeds, which could account for shorter incubation periods and higher susceptibility. These observations suggest that BS animals and their tissues should be used in further studies into genetic determinants of BSE susceptibility in cattle.     

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 ID₅₀ (BO ID₅₀). 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 ID₅₀ in 2006, and 19 BO ID₅₀ in 2007.In 2008 the age at removal of vertebral column was raised from 24 to 30 months, and an estimated 24 BO ID₅₀ 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 ID₅₀ will be consumed in 2009, decreasing to 20 BO ID₅₀ in 2010. Even though presented in terms of bovine rather than human oral ID₅₀, 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 clinical diagnosis of BSE

Diagnosis of Bovine spongiform encephalopathy (BSE) is confirmed by specified laboratory methods on brain material. On the other hand clinical signs of manifest BSE are quite obvious. The first part of this paper describes case histories, clinical signs, laboratory findings and the most common differential diagnoses. On the basis of the data of actual prevalence in Germany, the role of clinical examination in eradication of BSE is dealt in the second part. Clinical diagnosis is a very sensitive and specific method when there is a high prevalence. According to the data from December 2000 to November 2001 prevalence in Germany was beyond 1 BSE case per 100,000 cattle or 3 cases per 100,000 cows. This very low prevalence decreases rapidly sensitivity and specificity of the diagnosis made by clinical examination. Therefore the main focus of field-diagnostics has to be laid on specified laboratory diagnostic methods. On the other hand prevalence of BSE-positive cattle is distinctly higher in the group of animals slaughtered in cases of illness or emergency than in cattle slaughtered on the regulatory bases. Nevertheless every veterinary practitioner should be aware of the clinical picture of BSE, clinical examination-routine and differential diagnosis, because occurrence of BSE is still possible in any dairy herd. At the moment it is not possible to make any statement if eradication of BSE can be reached in future.     

Epidemiological study on BSE outbreak in Japan

The aim of this study is to identify, as hypotheses, all feasible sources and routes of infection for the BSE cases in Japan, and to study the probability of each hypothesis. The strategy of this epidemiological study is as follows. 1) BSE risk status in Japan is tentatively divided into 3 stages, i.e., before 1996 April when administrative guidance for feed ban of cattle MBM introduced. After that to 2001 September, the first case of BSE in Japan, then, after 2001 October with real feed ban in the law. 2) Make hypotheses depending on the invasive risk scenarios and propagation risk of BSE in Japan, and they are checked by evidences, case control study or statistics. 3) Grouping of BSE cattle was conducted time sequentially and spatially; that is Group-A (1995-96, born in Hokkaido, Kanto), Group-B (1999 in Kyushu), Group-C (1999-2001 in Hokkaido), Group-D (young cattle born after real feed ban) and Pre-A, Post-D groups. As a result, a milk replacer was considered one of the most probable cause of group-A contamination, and group-C outbreak might be caused by an indigenous BSE propagation of group-A in Hokkaido. If the hypothesis of Holland animal fat as causative material was accepted, however, there are several unexplainable points. Collection of scientific evidences on animal fat impurity and age dependent susceptibility to BSE will be needed to clarify the true causative material.     

A method to identify BSE suspects in emergency slaughtered cattle during ante mortem examination

A method is presented by which a maximal number of BSE-infected cattle that had escaped the filter of clinical examination are identified during ante mortem examination. This approach might prove to be an efficient and cost-effective method for veterinary and non-veterinary meat inspectors to remove infected animals prior to slaughter. In a case-control study, the clinical signs of 224 randomly selected sick slaughtered animals were compared with the clinical signs of 26 sick slaughtered animals in which BSE infection was diagnosed using a rapid test post mortem. In addition, the clinical signs of the sick slaughtered BSE-positive animals were compared with the clinical signs of a group of BSE suspects identified during the same time period and in which BSE infection could be confirmed. As a result of this study a mathematical model was developed to identify BSE suspects. This model contains a total of 7 variables (clinical signs) that proved to be of importance. These signs were aggressive behaviour, grinding of teeth, protruding eyeballs, reduced rumination, inability to stand, overexcitability, and difficulty in standing up. The presented model has a sensitivity of 61.5% (16 out of 26 BSE-positive animals slaughtered while sick were identified) and a specificity of 99.6% when compared to a rapid test conducted post mortem.     

Simulating the BSE epidemic and multiplication factor in dairy herds in Japan

With the objective of evaluating the effectiveness of an administrative guidance on the use of ruminant meat-and-bone meal in ruminant feed, effective from April 1996 to September 2001, we developed a model to simulate the evolution of the BSE epidemic and to estimate the BSE multiplication factor (K) in the Japanese dairy population. The output that provided the best fit to the number of BSE cases both observed and predicted to date suggest that the probability that bovine MBM was fed back to cattle was 14.2-75.2% and 0.129-0.570% during the periods from 1992 to April 1996 and from April 1996 to October 2001, respectively. Given these estimates, the value of K would have peaked in 1995 at 40-48 and then declined to 0.32-0.67 between 1997 and 2001. These results suggest that the administrative guidance was effective in reducing the amount of MBM fed to cattle by a factor of 104-141 and was perhaps enough to drive the epidemic towards extinction.     

Analysis and prediction of the BSE incidence in Ireland

Our purpose was to report the statistical methodology that was used to describe the nature of bovine spongiform encephalopathy (BSE) propagation in the Irish cattle population, to predict the number of future cases and to assess the risk to humans in terms of the number of infected animals that were processed. We used a nonlinear Poisson-regression model for the available birth-cohort data and an iterative method to compute the parameter estimates. Standard errors for the estimates were computed from the nonlinear model and these were validated using a bootstrap procedure.

We illustrated the use of the model for prediction and risk assessment using the BSE incidence data between 1981 and 2000. The change in case ascertainment or reporting level was a crucial parameter that determined the observed pattern of clinical BSE. Significant propagation risk was detected from 1985 onwards, with peaks in 1986 and 1994. The trough in the propagation risk in 1990 coincided with a ban of the use of meat-and-bone meal for ruminant feed. Excluding the newly adopted active surveillance method in 2001, the predicted and observed data were comparable.     

Active surveillance of BSE in cattle in The Netherlands

Since January 2, 2001 a large-scale active surveillance programme for BSE started in the Netherlands in addition to the passive surveillance programme of cattle with clinical symptoms compatible with BSE. Based on decisions of the Council of European Ministers of Agriculture, the European Union launched an active surveillance system for BSE in cattle of 30 months and older. Until April 1, more than 100,000 head of cattle were tested in this scheme, including all cattle slaughtered and a large part of the cattle that died on the farm. Four animals were found positive in the active surveillance system and one cow from the passive surveillance tested positive for BSE during the first three months.