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A classical type of bovine spongiform encephalopathy (C-BSE), recognized in 1987, had a large impact on public health due to its zoonotic link to variant Creutzfeldt-Jakob disease by the human consumption of dietary products contaminated with the C-BSE prion. Thus, a number of countries implemented BSE surveillance using rapid post-mortem test kits that were approved for detection of the C-BSE prion in the cattle brain. However, as atypical BSE (L- and H-BSE) cases emerged in subsequent years, the efficacy of the kits for the detection of atypical BSE prions became a matter of concern. In response to this, laboratories in the European Union and Canada evaluated the kits used in their countries. Here, we carried out an evaluation study of NippiBL®, a kit currently used for BSE screening in Japan. By applying the kit to cattle brains of field cases of C-BSE and L-BSE, and an experimental case of H-BSE, we showed its comparable sensitivities to C, L-, and H-BSE prions, and satisfactory performance required by the European Food Safety Authority. In addition to NippiBL®, two kits (TeSeE® and FRELISA®) formerly used in Japan were effective for detection of the L-BSE prion, although the two kits were unable to be tested for the H-BSE prion due to the discontinuation of domestic sales during this study. These results indicate that BSE screening in Japan is as effective as those in other countries, and it is unlikely that cases of atypical BSE have been overlooked.

Using a stochastic simulation model, we estimated the effectiveness of the three BSE interventions (SRM removal, post-mortem testing and cohort culling) in Japan, in terms of the amount of bovine ID50 that would be prevented from entering the human food supply and the number of life years that would be saved from resulting vCJD cases. The average reduction of the BSE load on the human food supply under SRM removal was 97% over the period from 2002 to 2009. The average reduction of the BSE load under most-mortem testing was 83% over the period from 2002 to 2007. The risk reducing effect of the three interventions combined was 99%. The maximum number of life years saved by the three interventions combined was 40.84 in 2006., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We estimated the infection prevalence of BSE in Japanese cattle born in the period 2000-2012, using maximum likelihood methods and BSE surveillance data of these birth cohorts. From this, we predicted the number of infected cattle and test positives in years 2004-2020. Assuming that the infection prevalence decayed exponentially over time from 2000, the infection prevalence of the 2000 birth cohort was estimated to be 0.00058 which declined exponentially by 0.115 times per year in the following years. The number of infected cattle was calculated to have peaked in 2005 and would be zero by 2020. The number of test positives was calculated to have peaked in 2005 and would be zero by 2012. The number of BSE cases actually detected was within the 95% confidence interval of the predicted numbers. The detectable prevalence (predicted number of test positives/number of cattle tested) was predicted to be highest in 2005. In this year it was predicted that one animal out of 160,000 tested would test positive. The detectable prevalence would decline exponentially to zero in the subsequent years., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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 (R(0) ) 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., (© 2012 Society for Risk Analysis.)

L-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE. To characterize the Japanese L-type BSE prion, we conducted a comparative study of the Japanese and foreign L-type BSE isolates. The L-type BSE isolates of Japan, Germany, France and Canada were intracerebrally inoculated into bovinized prion protein-overexpressing transgenic mice (TgBoPrP). All the examined L-type BSE isolates were transmitted to TgBoPrP mice, and no clear differences were observed in their biological and biochemical properties. Here, we present evidence that the Japanese and Canadian L-type BSE prions are identical to those from the European cases.

Despite various measures taken by the Japanese government to protect the cattle population from exposure to the bovine spongiform encephalopathy (BSE) agent, the first case of BSE was detected in September 2001. Subsequently, BSE surveillance was enhanced, involving mandatory reporting and investigation of all clinical BSE suspects, and testing of fallen stock and all cattle slaughtered for human consumption. Tests on over nine million cattle led to the detection of 35 additional cases by the end of May 2009. Using the surveillance data and other information as input variables, models were developed to explore the possible source of introduction of BSE into Japan, evaluate the effectiveness of control measures, estimate the prevalence of BSE in different birth cohorts, predict a future BSE epidemic, and simulate the impact of changes in surveillance strategies. Despite difficulties associated with the availability and uncertainty of some of the input variables, these models provided an objective insight into the BSE situation in Japan.

To obtain data concerning the survival of embryos and calves derived from somatic cell nuclear transfer (SCNT) in Japan, a nationwide survey was carried out in April, 2009. As a result, data concerning 3264 embryo transfers (ETs) with SCNT embryos which produced 301 calves were accumulated and their survival was analyzed. The present survey revealed that survival rates of transferred bovine embryos and produced calves derived from SCNT had not improved over a decade (1998-2007). A remarkable feature of the pregnancies with SCNT embryos was a high incidence of spontaneous abortions. When the decade was divided by the occurrence of bovine spongiform encephalopathy (BSE) in 2001, significant decreases in the 'after BSE' period (2002-2007) were observed in the percentages of calves born (P<0.01), calves living at birth (P<0.05), calves living for 24 h (P<0.05) and 6 months (P<0.01). Abortions that occurred during 61-99 days after ETs were significantly increased (P<0.01) in the 'after BSE' period. Certain kinds of regeneration that occurred in oocytes during the 15-20 h of storage of bovine ovaries at 10-15 °C as a part of BSE inspection might have had some negative effects on SCNT embryos when these oocytes were used as recipients of SCNT., (© 2011 The Authors. Journal compilation © 2011 Japanese Society of Animal Science.)

In spite of much analysis of the impact of bovine spongiform encephalopathy (BSE) on consumer perceptions and meat purchases, there has been little explicit analysis of the level of BSE knowledge. In this study the role of knowledge about BSE was examined in Canada, the United States, and Japan. In addition, the level of knowledge was linked to human health concerns regarding BSE and whether there is agreement with paying a premium for beef with BSE animal tests. From a public policy perspective, understanding whether higher or lower knowledge is linked to public concern and desire for market intervention might help in the design of risk communication in any future animal disease outbreak. Should lack of knowledge about the disease be related to a public desire for market intervention (animal testing, for example), then an increase in detailed information about how humans might contract the disease might change public pressure for intervention. As compared to U.S. and Canadian respondents, Japanese respondents are more knowledgeable regarding the ways in which humans might be exposed to the human variant of BSE (variant Creutzfeldt-Jakob disease, vCJD) and are more concerned about the disease. However, U.S. respondents are more willing to pay a premium for beef tested to ensure that it will not result in vCJD. Japanese respondents who are more knowledgeable about BSE are more concerned about the risk of BSE to human health. In Canada, subjects who are more knowledgeable about the ways in which humans attain vCJD are less concerned about the risk of BSE to human health. Knowledge of the ways in which humans develop vCJD does not significantly influence concerns about the risk of BSE to human health in the United States or willingness to pay for BSE-tested beef in any of the three countries. The links between knowledge and concerns about BSE and between knowledge and agreement with paying premiums for BSE-tested beef were estimated for each country using ordered probit regressions.

On 10 September 2001, the first case of bovine spongiform encephalopathy (BSE) in Japan was confirmed in a five-year-old dairy cow born in Hokkaido and raised in Chiba prefecture. Subsequently, BSE surveillance was enhanced. As a result, 35 additional cases were detected by the end of March 2009, with two to ten cases being detected each year up to the end of 2007. The epidemic appeared to peak in 2006. Cases are detected mostly in dairy cattle; in cattle born in 1996 and 2000; and in cattle born in Hokkaido. Two were atypical cases of BSE and the remainder classical cases. This paper describes and discusses the demographic structure of dairy and beef cattle, surveillance programmes in place and the epidemiological features of the BSE epidemic in Japan.

Cattle slaughtered in Japan for human consumption, regardless of their age, have been tested for bovine spongiform encephalopathy (BSE) since October 2001. Beginning in April 2004, all fallen stock from 24 months of age also have been tested. We evaluated the impact of potential changes to the current BSE surveillance programs for both slaughter cattle and fallen stock using a simple stochastic model. We calculated the probability that a BSE-infected dairy cow, Wagyu beef animal, Wagyu-Holstein cross steer or heifer, or Holstein steer slaughtered for human consumption or arising as fallen stock would be tested and detected. Four surveillance strategies were explored for cattle slaughtered for human consumption, with the minimum age at testing set at 0, 21, 31, or 41 months. Three surveillance strategies were explored for fallen stock, with the minimum age at testing set at 24, 31, or 41 months. Increasing the minimum age of testing from 0 to 21 months for both dairy cattle and Wagyu beef cattle had very little impact on the probability that a BSE-infected animal slaughtered for human consumption would be detected. Although increasing the minimum age at testing from 21 to 31 or 41 months would lead to fewer slaughtered animals being tested, the impact on the probability of detecting infected animals would be insignificant. The probability of infected Wagyu-Holstein crosses and Holstein steers being detected at slaughter or as fallen stock would be very low under all surveillance strategies.

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.

Between October 2001 and December 2006 an estimated total of 6 million cattle in Japan were tested for BSE, with 31 returning a positive result. Exploratory mapping, the space-time scan statistic, and ordinal logistic regression have been used to describe the epidemiology of the 24 cases identified in the prefecture of Hokkaido, and to quantify the risk factors for the disease. Two birth cohort groups were affected: cattle born during a period of seven months in 1996, and cattle born between 1999 and 2001. The descriptive spatial analyses showed that eight of the 10 cases born in 1996 were born in areas with a relatively high density of dairy farms in the east of Hokkaido, but that the 14 later cases were more widely distributed throughout the prefecture, with equal numbers of cases in the east and the west. These findings provide indirect evidence of a single localised contamination of the cattle feed supply in 1996, and recycling of the infection after 1999.

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.

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.

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.

Following the detection of the first case of BSE in Japan in September 2001, four million cattle were subjected to a rapid test for BSE up to the end of 2004. A further 10 cases were detected in the dairy cattle population and two cases in Holstein steers. We focused on the dairy population and estimated the prevalence of BSE infected animals within each birth cohort for the years 1992-2001 using Bayesian inference. From this we were able to predict historic and future trends in the number of infected animals culled from each cohort and whether or not they could be detected using a rapid test. Assuming that BSE infectivity entered Japan in 1995, 225 (95%CI: 111-418) infected animals were predicted to have been culled from 1995 to 2001, of which 116 (56-219) would have been slaughtered for human consumption, and 33 (12-65) cases would have been detected during this period if a BSE surveillance program as comprehensive as the one in place as of April 2004 was applied. Assuming that BSE infectivity entered Japan in 1992, 905 (366-4633) infected animals were predicted to have been culled from 1992 to 2001, of which 694 (190-2473) would have been slaughtered for human consumption, and 201 (53-693) cases would have been detected during this period. Assuming the April 2004 level of surveillance continues and that the feed ban introduced in 2001 is completely effective, 18 (3-111) BSE cases are likely to be detected in the future. The BSE epidemic in Japan most likely reached a peak between 1998 and 2001 and should be eradicated around 2012.

Since the first identification of bovine spongiform encephalopathy (BSE) in Japan in September 2001, a series of safety measures was introduced by the Ministry of Agriculture, Forestry and Fisheries, the Ministry of Health, Labour and Welfare and the Food Safety Commission of the Cabinet Office. These measures included blanket BSE testing and removal of specified risk materials at slaughterhouses, surveillance of risk animals and a ban on the use of meat-and-bone meals and traceability on all farms. The Japanese experience over the past five years has shed light on several issues in countries that have a low BSE incidence.

The objectives of this study were 1) to investigate the effect of changes in carcass market prices due to bovine spongiform encephalopathy (BSE) occurrences on estimates of genetic parameters and economic weights for carcass traits; and 2) to compare direct and indirect approaches for prediction of genetic merit of Japanese Black cattle for profitability of their progeny. The direct approach utilized estimated breeding values of carcass prices, whereas in the indirect approach, selection indices were constructed as products of economic weights and breeding values of component traits. Data were composed of 80,191 carcass records divided into 5 periods based on changes in carcass prices as a result of occurrences of BSE in Japan and the United States. The periods ranged from a period before occurrence of BSE in Japan to a period of beef import restrictions and a rise in prices. Carcass traits analyzed included HCW, LM area, rib thickness, subcutaneous fat thickness, and marbling score (MS). Price traits included carcass unit price and carcass sale price. Estimates of heritability for price traits were moderate (0.32 to 0.46) and slightly sensitive to changes in carcass market prices. Genetic correlations of HCW and LM area with price traits increased and that between MS and carcass sale price decreased with period, whereas estimates of genetic correlation between MS and carcass unit price were high in all periods (0.96 to 0.98). Economic weights for carcass traits varied with periods because carcass prices were highly sensitive to economic importance of traits. Nevertheless, correlations between within-period breeding values for price traits estimated using direct and indirect approaches were high (0.92 to 0.99). This result indicates that selection realized by direct and indirect approaches will provide very similar results. A comparison among within-approach breeding values estimated in different periods showed that the largest differences in breeding values of sires for price traits were between the periods after occurrences of BSE in Japan and in the United States. Economic effects of BSE occurrences influenced the importance of carcass traits and economic merits of price traits through a change of carcass prices from period to period, irrespective of the approach taken in determining the genetic merit of breeding animals for profitability of their progeny.

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.

Eight major policies were implemented by Japanese Government since Oct. 2001, to deal with bovine spongiform encephalopathy (BSE). These are; 1) Surveillance in farm by veterinarian, 2) Prion test at healthy 1.3mi cows/yr, by veterinarian, 3) Elimination of specified risk material (SRM), 4) Ban of MBM for production, sale use, 5) Prion test for fallen stocks, 6) Transparent information and traceability, 7) New Measures such as Food Safety Basic Law, and 8) Establish of Food Safety Commission in the Cabinet Office. At this moment, the extent of SRM risk has only been indicated by several reports employing tests with a limited sensitivity. There is still a possibility that the items in the SRM list will increase in the future, and this indiscriminately applies to Japanese cattle as well. Although current practices of SRM elimination partially guarantee total food safety, additional latent problems and imminent issues remain as potential headaches to be addressed. If the index of SRM elimination cannot guarantee reliable food safety, we have but to resort to total elimination of tissues from high risk-bearing and BSE-infected animals. However, current BSE tests have their limitations and can not yet completely detect highrisk and/or infected animals. Under such circumstances, tissues/wastes and remains of diseased, affected fallen stocks and cohort animals have to be eliminated to prevent BSE invading the human food chain systems. The failure to detect any cohort should never be allowed to occur, and with regular and persistent updating of available stringent records, we are at least adopting the correct and useful approach as a reawakening strategy to securing food safety. In this perspective, traceability based on a National Identification System is required.

To address the public concerns provoked by the first incidence of bovine spongiform encephalopathy (BSE) in Japan, the BSE screening tests in Japan are evaluated in use of modeling analysis in evidence-based diagnosis. Under the assumptions based on epidemiological statistics such as the annual number of screened cattle with 1,227,385, the annual incidence of BSE infection with four, and the sensitivity of 99.0% for both primary and secondary tests, it was estimated that, the current threshold of cut-off for the BSE positive would have 0.119 false negatives per year. The decrease of the sensitivity of ELISA down to 90.0% resulted in the increase up to 0.792 false negatives per year. Even with the 90.0% sensitivity, shifting the cut-off point from the current level to the best one remarkably reduced the false negatives per year down to 0.0004. Regarding false positives, with 99.7% specificity for both ELISA and the confirmatory tests revealed the risk of 0.03 false positives per year, while the cut-off shifting that can best minimize false negatives largely increased the false positives up to 11,013. Although it is confirmed the possibility of false negatives is very low, the current method of screening can be further improved by shifting the decision level of cut-off to define the BSE "positive". Such an improvement, however, raises an issue of trade-off : the less false negatives, the more false positives. We believe our approach can help the public perception of an optimum decision-making for BSE screening, considering the trade-off.

Prion disease is the new designation of a group of spongiform encephalopathies, all invariably fatal, which show similar clinical and neuropathological changes. They comprise a range of distinct diseases in both animals and man, and spontaneous, hereditary and transmissible forms are recognized. Until the sudden occurrence in the mid-1980s of an epizootic of a formerly unknown disease, popularly named 'mad cow disease', in cattle in the UK, very little attention had been paid to these rather obscure diseases. Concurrently it was asserted that the disease-causing agent appeared to be a ubiquitous mammalian brain constituent, and the disease mechanism a conformational change of its structure. These events have not only led to a new understanding of these extraordinary diseases, but have also provided insight into both neurodegeneration and disease mechanisms at the molecular level. Moreover, in 1997 the prion concept earned its originator the second Nobel price for medicine within this scientific field. In this introduction and overview of prion diseases, historical and philosophical perspectives are presented along with descriptions of the diseases in both animals and man. Epidemiology, genetics and transmissibility are also covered.