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.     

BSE situation and establishment of Food Safety Commission in Japan

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 high-risk 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.     

The price of the precautionary principle: Cost-effectiveness of BSE intervention strategies in the Netherlands

Since 1996, bovine spongiform encephalopathy (BSE) in cattle has been linked to a new variant of Creutzfeldt-Jakob disease (vCJD), a fatal brain disease in man. This paper assessed the cost-effectiveness of BSE control strategies instituted by the European Commission. In a Monte Carlo simulation model, a non-intervention baseline scenario was compared to three intervention strategies: removal of specified risk materials from slaughter animals, post-mortem testing for BSE and the culling of feed and age cohorts of BSE cases. The food risk in the baseline scenario ranged from 16.98 lost life years in 2002 to 2.69 lost life years in 2005. Removing specified risk materials removal practices, post-mortem testing and post-mortem testing plus cohort culling reduced this risk with 93%, 82.7% and 83.1%. The estimated cost-effectiveness of all BSE measures in the Netherlands ranged from 4.3 million euros per life year saved in 2002 to 17.7 million euros in 2005. It was discussed that the cost-effectiveness of BSE control strategies will further deviate from regular health economics thresholds as BSE prevalence and incidence declines.     

Estimating the prevalence of BSE in dairy birth cohorts and predicting the incidence of BSE cases in Japan

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.     

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.     

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.     

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.     

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.     

Sensitivity and specificity of a commercial BSE kit for the detection of ovine scrapie

To examine the sensitivity of a commercially available bovine spongiform encephalopathy (BSE) kit (NippIBL) for the detection of ovine scrapie, 50 scrapie‐positive ovine samples from the UK, and 54 scrapie‐negative ovine samples from Japan were obtain and tested using this kit. The sensitivity and specificity of NippIBL for ovine samples were 96% and 100%, respectively. The detection limit of the abnormal isoform of prion protein (PrP^Sc) of NippIBL was examined using diluted scrapie‐positive samples. The sensitivity of NippIBL to ovine scrapie was 3–10 times superior to that of another commercial BSE diagnosis kit. Thus, the NippIBL kit proved more effective for the detection of ovine scrapie.     

Age-period-cohort analysis of the Bovine Spongiform Encephalopathy (BSE) epidemic in Switzerland

Cattle born after animal-feed control measures were implemented in 1990 have become BSE cases in Switzerland, indicating sub-optimal effectiveness of these measures. To evaluate these measures, the incidence of BSE cases in Switzerland recorded through clinical case reporting from January 1991 to June 2000 (categorized into age groups and birth cohorts of 6-month duration) was analyzed by Poisson log-linear regression using an age–period–cohort model. The incidence was maximum in the cattle cohort born from October 1989 to March 1990, and dropped to zero in the cohort born from April to September 1991. A second peak was observed in a cohort born from April to September 1994. The first drop of incidence is interpreted as a result of initial implementation of the feed ban in 1990. The second peak might be related to exposure of cattle to feed intended for pigs and poultry.     

Frequencies of PRNP gene polymorphisms in Vietnamese dairy cattle for potential association with BSE

Summary Since 2004, significant associations between bovine spongiform encephalopathy (BSE) susceptibility in cattle and frequencies of insertion/deletion (ins/del; indel) polymorphisms within the bovine prion protein gene (PRNP) have been reported. In this study, we investigated the frequencies of indel polymorphisms within two variable sites, a 23-bp indel polymorphism in the promoter region (23indel) and a 12-bp indel polymorphism in intron 1 region (12indel), in the PRNP in 206 Vietnamese dairy cattle and seven Japanese BSE-affected cattle. In Vietnamese dairy cattle, the frequency distributions of del allele and del/del genotypic polymorphisms in the 23indel site, which are thought to be associated with BSE susceptibility, were significantly higher, whereas the frequencies of del allelic and del/del genotypic polymorphisms in the 12indel site, which have been reported to confer BSE susceptibility, were significantly lower. We have provided evidence that Vietnamese dairy cattle have a unique genetic background in the PRNP gene in comparison with cattle or sires previously reported in other countries.     

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.     

A quantitative assessment of the risk of exposure to bovine spongiform encephalopathy via meat-and-bone meal in Japan

The feeding of meat-and-bone meal (MBM) derived from cattle infected with bovine spongiform encephalopathy (BSE) is a major source of BSE infection. The risks of BSE infection via MBM in Japan were examined quantitatively to estimate infectivity to cattle via MBM derived from a single clinically infected animal being rendered. Three routes of exposure were modeled: (i) feeding cattle concentrates containing MBM as an ingredient, (ii) feeding cattle concentrates contaminated with MBM from non-ruminant feed at feed plants and (iii) directly feeding MBM in supplemental form to cattle on farms. The effectiveness of measures designed to restrict the feeding of ruminants with ruminant MBM (feed restriction) as well as differences in the risk of exposure among regions were examined using the model.

The model revealed that the median total infectivity fed to dairy cattle via MBM derived from one infected animal was approximately 0.49 cattle oral ID₅₀ (5th percentile = 0.43 ID₅₀, 95th percentile = 0.54 ID₅₀). This value was reduced by 55% after the addition of MBM to cattle concentrates was restricted in 1996. The risk of exposure in dairy cattle was twice that in beef cattle. Comparisons of regional differences in exposure risk indicated that the risk was highest in a region where 14 of the 20 BSE cases reported to date were born. Our model suggested that the routes of exposure via MBM were unlikely to result in increased propagation of BSE in Japan. Furthermore, despite some regional variation, the risk of exposure declined further after the feed restriction was imposed in 1996.     

日本疯牛病防制给我们的启示与借鉴

2001年8月6日日本千叶县1头六岁奶牛发生疯牛病。疯牛病发生以后,日本政府高度重视对疯牛病的防制,采取了果断而有效的防制措施,迅速清除传染源,切断传播途径,使疯牛病得到了有效控制。总结日本对疯牛病的防制经验,对我们做好动物疫病的防制工作,是很好的借鉴,并能从中得到启示。2001年8月6日,日本千叶县一饲养户的1头六岁奶牛因不能站立,被送到屠宰场屠宰。该牛一个月前出现运动失调,容易跌倒等症状,与疯牛病很相似。经屠宰场采集延髓送日本动物卫生研究所进行检测,千叶县家畜保健卫生所进行实验室病性鉴定,日本动研所用免疫组织化学法复检…     

Targeted surveillance to assess the presence of BSE in the age risk population of cattle slaughtered in Bursa, Turkey: preliminary results of an immunohistochemical detection study for the 2004-2005 period

Bovine spongiform encephalopathy (BSE), a member of the transmissible spongiform encepahlopathies, has been a notifiable disease in Turkey since 1997. In 2002, the BSE status of Turkey was assessed by the EU Scientific Steering Committee as "it is likely but not confirmed".This study presents the results of a targeted surveillance study to assess the presence of BSE in the age risk population of Bursa, Turkey. In the assessment procedure, the immunohistochemical detection of protease-resistant prion protein (PrP-Sc) was aimed at and applied to 420 brain tissues of cattle slaughtered in Bursa at an age of 30-months and older. None of the samples were positive for BSE.     

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.     

百色市狂犬病综合防治措施的效果评价

为有效防控狂犬病,百色市开展疫情专项调查和防治研究,发现狂犬病病死率和死亡人数仍居人类各种法定报告传染病之首,死亡人数与动物发病数呈正相关关系;监测貌似健康犬狂犬病带毒率为1.9%,流行毒株属基因Ⅰ型,Ⅰ亚群;使用国产兽用狂犬病活疫苗（FlurryHEP株）免疫期为半年,注射进口兽用狂犬病灭活疫苗（PV株）免疫有效期为一年;“专题讲座＋发送短息”宣传方式效果好;采取“栓养、免疫、监测、扑灭、宣传”等综合防治措施效果显著。