Ten years of BSE in Switzerland. The development of an extraordinary disease

The first case of bovine spongiform encephalopathy (BSE) in Switzerland was diagnosed in November 1990. BSE is--in particular considering its eradication--different from many other livestock diseases. Strict disease control measures were taken from the very beginning by the Swiss authorities in order to protect public as well as animal health. In addition, BSE has stimulated enormous media interest and public concern. The occurrence of the born after the ban (BAB) cases, increasing questions about the zoonotic potential of the disease and trade restrictions against Switzerland led to the "BSE-crisis". In 1999, Switzerland internationally took a leading role in the surveillance of BSE by active investigation of targeted risk population.     

Model calculation to explain the BSE-incidence in Germany

The future development of BSE-incidence in Germany is investigated using a simple epidemiological model calculation. Starting point is the development of the incidence of confirmed suspect BSE-cases in Great Britain since 1988, the hitherto known mechanisms of transmission and the measures taken to decrease the risk of transmission as well as the development of the BSE-incidence in Germany obtained from active post mortem laboratory testing of all cattle older then 24 months. The risk of transmission is characterized by the reproduction ratio of the disease. There is a shift in time between the risk of BSE transmission and the BSE incidence caused by the incubation time of more than 4 years. The observed decrease of the incidence in Germany from 2001 to 2003 is not a consequence of the measures taken at the end of 2000 to contain the disease. It can rather be explained by an import of BSE contaminated products from countries with a high BSE incidence in the years 1995/96 being used in calf feeding in Germany. From the future course of the BSE-incidence in Germany after 2003 a quantification of the recycling rate of BSE-infected material within Germany before the end of 2000 will be possible by use of the proposed model if the active surveillance is continued.     

Direct Costs of Bovine Spongiform Encephalopathy Control Measures in Germany

On 26 November 2000, the first autochthonous case of bovine spongiform encephalopathy (BSE) was detected in Germany. Since then, a total of 413 BSE cases have been confirmed, resulting in the culling and destruction of 17 313 heads of cattle. In view of the possible risks for human and animal health, Germany has adopted EU regulations along with some additional requirements concerning active surveillance and response measures after detecting a BSE‐positive animal. In this study, we used a stochastic model to estimate the costs incurred by the ensuing legislative amendments responding to BSE between November 2000 and December 2010. The total costs were estimated to range between 1847 and 2094 million Euros. They peaked in 2001 (about 394 million Euros) and declined since. About 54% of the costs (approximately 1000 million Euros) were incurred by the extension of the feed ban for animal protein to all farmed livestock. Active surveillance accounted for 21% (405 million Euros), the incineration of animal protein for 13% (249 million Euros) and the removal of specified risk material for 11% (225 million Euros). Only 1% of the costs was related to response measures after detecting a BSE‐positive animal, including indemnity payments for culled cattle and confiscated carcasses at the slaughterhouse.     

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.     

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.     

Analyzing BSE surveillance in low prevalence countries

If the prevalence of bovine spongiform encephalopathy (BSE) varies among cohorts within a population, stratified analysis of BSE surveillance data may allow identification of differences in BSE exposure that are important with respect to the design and evaluation of disease prevention and control measures. In low BSE prevalence populations, however, surveillance at levels that meet or exceed international guidelines may provide insufficient statistical power to distinguish prevalence levels among cohorts. Furthermore, overstratification to account for hypothetical variability in the population may inflate uncertainty in BSE risk estimates.     

Risk assessment as an indicator for the distribution of BSE in the world

For a long time, BSE was considered a problem of the UK exclusively. Even after the detection of BSE cases in countries outside the UK, the risk of having BSE was categorically denied by many other countries. Only after the introduction of active surveillance did several "BSE free" countries detect BSE in their country. However, before the detection of the first cases in several of these countries, a risk assessment (GBR) conducted by the Scientific Steering Committee of the EU showed that a risk could be present. There remain many countries with an unknown BSE risk. In order to minimise import risks from these countries, further risk assessment is needed to evaluate the real BSE distribution worldwide.     

Ten years of BSE surveillance in Italy: neuropathological findings in clinically suspected cases

Between 2001 and 2010, 244 clinically suspected cases of bovine spongiform encephalopathy (BSE) were reported in Italy. This report summarizes the neuropathological findings in cattle displaying clinical signs consistent with a diagnosis of BSE. All animal specimens were submitted for confirmatory testing; samples testing negative underwent neuropathological examination to establish the differential diagnosis. Immunohistochemistry for scrapie prion protein (PrPSc) at the level of frontal cortex was carried out to exclude atypical BSE. Neuropathological changes were detected in 34.9% of cases; no histological lesions were found in 52.3% of subjects; 12.8% of samples were found unsuitable for analysis. BSE was detected in one case, but no cases of atypical BSE were observed. This study identified the diseases most commonly encountered in the differential diagnosis of BSE; furthermore, it demonstrated that the surveillance system is necessary for monitoring neuropathological disease in cattle and for the detection of BSE cases.     

Bovine spongiform encephalopathy (BSE) safety measures in Japan

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.     

BSE--present and future legal requirements

After BSE had first been recorded in November 2000 in a bovine animal born in Germany, national measures had immediately been taken and a great number of decisions taken at Community level resulting in substantial risk minimization. On 1 July 2001, Regulation No. 999/2001/EC came into force compiling all protection measures against BSE under Community law, including supplementary transitional measures. On the basis of the current legal situation, the evolving further development of key protection measures is described in the following.     

Diagnosis of bovine spongiform encephalopathy: a review

Cows affected with bovine spongiform encephalopathy (BSE) display chronic neurological signs consisting of behavioural changes, abnormalities of posture and movement, and/or hyperaesthesia. At present, there are no laboratory test available to diagnose BSE in the live animal. In this article, we describe the post-mortem diagnostic examination of brains from BSE-suspected cattle as currently performed at ID-Lelystad. The routine laboratory diagnosis of BSE consists of histopathological examination of the brain and detection of the modified prion protein, PrP(BSE), in brain tissue. These tests, however, have the disadvantage of being laborious and time consuming, so that results are available only after several days. Recently, at ID-Lelystad a new post-mortem test has been developed that enables screening of larger volumes of brain samples for PrP(BSE) within 1 day. This BSE test is especially suited for slaughterline monitoring. A preliminary validation study has shown that both sensitivity and specificity are 100% compared to the gold diagnostic standard of histopathology.     

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.     

新型克-雅氏病是人的牛海绵状脑病

本文在概述人朊病毒的基础上，重点阐述新型克－雅氏病与早先已知的各种人朊病毒病的区别和它是由牛海绵状脑病朊病毒引起的证据，并对牛海绵状脑病并非源于痒病而是原于牛散发性朊病毒病、影响新型克－雅氏病流行规模的主要因素和该病的主要预防措施等问题进行了讨论。     

Atypical BSE in Germany--proof of transmissibility and biochemical characterization

Intensive active surveillance has uncovered two atypical German BSE cases in older cattle which resemble the two different atypical BSE phenotypes that have recently been described in France (designated H-type) and Italy (designated L-type or BASE). The H-type is characterized by a significantly higher molecular size, but a conventional glycopattern of the proteinase K treated abnormal prion protein (PrP(Sc)), while the L-type PrP(Sc) has only a slightly lower molecular size and a distinctly different glycopattern. In this paper we describe the successful transmission of both German atypical BSE cases to transgenic mice overexpressing bovine PrP(C). Upon challenge with the L-type, these mice developed BSE after a substantially shorter incubation period than any classical BSE transmission using these mice to date. In contrast, the incubation period was distinctly prolonged when these mice were challenged with the H-type. PrP(Sc) accumulated in the brains of these mice were of the same atypical BSE type that had been used for the transmission. These atypical cases suggest the possible existence of sporadic BSE cases in bovines. It is thus feasible that the BSE epidemic in the UK could have also been initiated by an intraspecies transmission from a sporadic BSE case.     

TSE eradication in small ruminants--quo vadis?

The term of 'TSE infections in small ruminants' summarises BSE as well as classical and the recently discovered atypical scrapie infections in sheep and goats.There are fundamental differences between the TSE infections in small and large ruminants. Other than in bovines the TSE pathogenesis in small ruminants implies that various peripheral tissues become infectious long before the onset of clinical symptoms. At least in sheep, classical scrapie is efficiently transmitted horizontally within affected flocks. On the other hand, BSE poses a distinctly higher zoonotic risk than scrapie. Therefore, regulatory measures for the protection of animals and humans from a BSE infection must be substantially different for large and small ruminants. While culling of the birth and feeding cohort of a BSE affected cattle is considered to be effective to prevent any further BSE cases in the affected herd, an effective BSE and classical scrapie eradication programme in small ruminants requires a much more stringent eradication strategy and the rendering of all susceptible animals. The situation became even more complicated when atypical scrapie cases with divergent transmission and pathogenesis characteristics and with a novel biochemical phenotype of the infectious agent came into play. The discovery of these atypical scrapie cases has initiated a discussion about the suitability of the current TSE eradication measures in sheep (which are selective breeding and genotype based culling), in particular when such cases were also found in sheep carrying the believed scrapie resistant genotypes.     

Review on the epidemiology and dynamics of BSE epidemics

The paper describes how the comprehensive surveillance of bovine spongiform encephalopathy (BSE) and studies carried out on these data has enhanced our knowledge of the epidemiology of BSE. Around 7, 000 BSE cases were detected through the screening of about 50 million cattle with rapid tests in Europe. It confirmed that the clinical surveillance had a poor capacity to detect cases, and also showed the discrepancy of this passive surveillance efficiency between regions and production types (dairy/beef). Other risk factors for BSE were being in a dairy herd (three times more than beef), having a young age at first calving (for dairy cattle), being autumn-born (dairy and beef), and being in a herd with a very high milk yield. These findings focus the risk on the feeding regimen of calves/heifers. Several epidemiological studies across countries suggest that the feedborne source related to meat and bone meal (MBM) is the only substantiated route of infection - even after the feed ban -, while it is not possible to exclude maternal transmission or milk replacers as a source of some infections. In most European countries, the average age of the cases is increasing over time and the prevalence decreasing, which reflects the effectiveness of control measures. Consistent results on the trend of the epidemic were obtained using back-calculation modelling, the R(0) approach and Age-Period-Cohort models. Furthermore, active surveillance also resulted in the finding of atypical cases. These are distinct from previously found BSE and classified in two different forms based on biochemical characteristics; their prevalence is very low (36 cases up to 1st September 2007), affected animals were old and some of them displayed clinical signs. The origin and possibility of natural transmission is unknown.     

Transmissible spongiform encephalopathies in sheep and goats

Scrapie has been known to occur in sheep and goats for over 250 years. Sheep and goats can be experimentally infected orally with BSE, however BSE infection can only be distinguished from scrapie using costly and extensive laboratory procedures. An overview of both the current state of knowledge on Transmissible Spongiform Encephalopathies (TSE) in small ruminants as well as the TSE monitoring and control strategies in place in Switzerland is presented.     

Area-level risks for BSE in British cattle before and after the July 1988 meat and bone meal feed ban

In this paper we investigate area-level risk factors for BSE for the cattle population present in Great Britain between 1986 and 1997. By dividing this population into two birth cohorts, those born before the July 1988 ban on feeding ruminant-derived meat and bone meal to ruminants and those born after, second-order regional influences are distinguished from the strong first-order south-to-north gradient of area-level BSE risk using Bayesian hierarchical models that account for structured (spatially correlated) and unstructured heterogeneity in the data. For both cohorts area-level risk of BSE was increased by a more southerly location and greater numbers of dairy cattle, relative to non-dairy cattle. For the cohort of cattle born after the July 1988 ban on feeding ruminant-derived meat and bone meal area-level BSE risk was additionally associated with greater numbers of pigs, relative to cattle. These findings support the role of low level cross-contamination of cattle feed by pig feed as an influence on BSE incidence risk as the epidemic evolved. Prior to the 1988 meat and bone meal ban unexplained BSE risk was relatively uniformly distributed across the country whereas after the ban there were spatially aggregated areas of unexplained risk in the northern and eastern regions of England suggesting that local influences allowed BSE control measures to be less-successfully applied in these areas, compared with the rest of the country. We conclude that spatially localised influences were operating in divergent ways during the two phases of the epidemic.     

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.