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.     

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.     

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.     

Big decisions based on small numbers: lessons from BSE.

The epidemic of bovine spongiform encephalopathy (BSE) has been the most expensive disaster ever to have befallen farming in the UK. It is believed to have led to a new form of spongiform encephalopathy in humans and as yet there is no way of knowing how many people will die of this disease. In order to curtail the BSE epidemic major decisions had to be made, often on the basis of inadequate scientific data. These data may have been derived from experiments using small sample numbers. Here we review some examples of where this has happened, sometimes with a beneficial outcome and sometimes with a misleading outcome. The identification of BSE as a new disease depended on precise neuropathological observation of a small number of cases rather than the obvious occurrence of large numbers of sick animals. Similarly, the recognition that BSE may have led to disease in humans was based on the neuropathological and clinical picture of new variant Creutzfeldt-Jakob disease (CJD) rather than on an increase in the number of cases of CJD in the UK. Early in the BSE epidemic the possibility that disease could be maternally transmitted from cow to calf was raised, mainly because of a belief that such transmission occurs in scrapie disease of sheep. But, we argue, the evidence for maternal transmission of scrapie, collected in the 1960s, was based on small numbers and is inadequate. Subsequent research has shown a very substantial genetic component in scrapie and epidemiological data show no excess risk in the offspring of affected ewes relative to the risk in the offspring of affected rams. An experiment to determine whether maternal transmission occurs in BSE was flawed and was unable to distinguish between maternal transmission and genetic susceptibility to environmental contamination. An assessment of the risk of BSE to humans depends on determining the levels of infectivity in tissues and transmissibility across species. Data on both of these are deficient, so it is not possible to predict how many people in the UK or elsewhere will become affected with new variant CJD in the next fifty years. The assessment of whether BSE could be transmitted to sheep and whether sheep therefore pose a risk to humans is hampered by a serious lack of evidence about the epidemiology of scrapie in the UK and elsewhere. The UK has paid a heavy price for the BSE epidemic but lessons should be learned from the experience. Every country should have a Specified Offals Ban even if it has no cases of BSE because, by the time it has, it will be too late. Furthermore, the occasional case of BSE should not be regarded as insignificant since it may be the harbinger of an epidemic in the making.     

Big decisions based on small numbers: Lessons from BSE

Summary

The epidemic of bovine spongiform encephalopathy (BSE) has been the most expensive disaster ever to have befallen farming in the UK. It is believed to have led to a new form of spongiform encephalopathy in humans and as yet there is no way of knowing how many people will die of this disease. In order to curtail the BSE epidemic major decisions had to be made, often on the basis of inadequate scientific data. These data may have been derived from experiments using small sample numbers. Here we review some examples of where this has happened, sometimes with a beneficial outcome and sometimes with a misleading outcome. The identification of BSE as a new disease depended on precise neuropathological observation of a small number of cases rather than the obvious occurrence of large numbers of sick animals. Similarly, the recognition that BSE may have led to disease in humans was based on the neuropathological and clinical picture of new variant Creutzfeldt‐Jakob disease (CJD) rather than on an increase in the number of cases of CJD in the UK. Early in the BSE epidemic the possibility that disease could be maternally transmitted from cow to calf was raised, mainly because of a belief that such transmission occurs in scrapie disease of sheep. But, we argue, the evidence for maternal transmission of scrapie, collected in the 1960s, was based on small numbers and is inadequate. Subsequent research has shown a very substantial genetic component in scrapie and epidemiological data show no excess risk in the offspring of affected ewes relative to the risk in the offspring of affected rams. An experiment to determine whether maternal transmission occurs in BSE was flawed and was unable to distinguish between maternal transmission and genetic susceptibility to environmental contamination. An assessment of the risk of BSE to humans depends on determining the levels of infectivity in tissues and transmissibility across species. Data on both of these are deficient, so it is not possible to predict how many people in the UK or elsewhere will become affected with new variant CJD in the next fifty years. The assessment of whether BSE could be transmitted to sheep and whether sheep therefore pose a risk to humans is hampered by a serious lack of evidence about the epidemiology of scrapie in the UK and elsewhere. The UK has paid a heavy price for the BSE epidemic but lessons should be learned from the experience. Every country should have a Specified Offals Ban even if it has no cases of BSE because, by the time it has, it will be too late. Furthermore, the occasional case of BSE should not be regarded as insignificant since it may be the harbinger of an epidemic in the making.     

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.     

Evaluation of bovine spongiform encephalopathy (BSE) infection risk of cattle via sewage sludge from wastewater treatment facilities in slaughterhouses in Japan

Scattered SRM residues from BSE-infected cattle are possible to contaminate sewage during the slaughtering process in slaughterhouses. A proportion of the sludge discharged from wastewater treatment facilities at slaughterhouses has historically been processed into fertilizer. We therefore investigated the associated risk of BSE infection to cattle via sludge-derived fertilizer. Each stage of the process associated with BSE exposure was qualitatively evaluated and quantitative evaluations were subsequently performed using infectious dose as a unit of concern. Results of these qualitative evaluations indicated that installation of filter(s) at the drains to the wastewater treatment facilities has been undertaken by many slaughterhouses and has decreased the likelihood of SRM contamination of sewage. The level of sludge-derived fertilizer ingested by cattle was considered to be very low since the fertilizer is mixed with the ground soil, and the amount of soil ingested by cattle is likely to be small. Results from the quantitative analysis indicated the total infectious dose ingested by cattle in Japan from an infected cow has been estimated to be 5.5 x 10(-3) ID(50). Preventing scattering of SRM during the slaughtering process, installing filters to the drains with the removal of residues from the drain water and preventing the application of sludge-derived fertilizer to pasturelands would be effective to reduce the risk. Although the limited extent of available information, this study should provide useful indication for the development of an inclusive risk assessment for slaughterhouse sludge in the future.     

Meat and potential risks

By the term "meat" the consumer understands muscle meat, that is skeletal muscle. The german regulations, the "Leits?tze für Fleisch und Fleischerzeugnisse" as well as the Codex Alimentarius define meat in a much broader sense to include all edible parts of slaughtered or shot warm-blooded animals (skeletal muscles, fat, heart, gut, liver etc). Therefore, a differentiated procedure is required when the risk of BSE transmission by meat has to be estimated. This must be based on knowledge of occurrence, amount, and persistence of BSE agents in the organs of animals. The risk evaluation has to include further factors: differences between animal species, age of the animal at the time of slaughter, the possibility of contamination during the slaughtering and cutting process, and--as far as meat products are concerned--the processing technology. To date there are no indications for the existence of transmissible spongiform encephalopathy in pigs, poultry and fish, even though BSE has been transmitted to pigs experimentally by intracranial administration. Muscle meat of these species can be considered safe. Muscle meat of experimentally infected cattle in the preclinical stage and even of animals with clinically manifest BSE has not shown infectivity in homologous and autologous bioassays performed so far. This finding justifies the assumption that the risk of BSE exposure by the consumption of beef can be classified as extremely low. Nevertheless, the absence of a proof of infectivity can at present not be equated with absence of BSE agents. This is because of the limits of sensitivity of the bioassays and because muscle meat does contain non-muscle tissue such as connective tissue collagen, nerve and lymph tissue and blood vessels.     

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.     

Pathogenesis of experimental bovine spongiform encephalopathy (BSE): estimation of tissue infectivity according to incubation period

This paper reports the results of tissue infectivity assays of bovine spongiform encephalopathy (BSE) agent in orally exposed cattle at stages during the incubation period. Estimations of the titre of infectivity in central nervous system (CNS), certain peripheral nerve ganglia and distal ileum tissue were made according to time post exposure from the relationship between incubation period and dose for RIII mice and C57bl mice using data from titrations of brain material from cases of BSE. The rate of increase of infectivity in the bovine CNS was then estimated, taking into account these tissue infectivity titres, the variability of the brain titre of clinical field cases of BSE, and the probability density of the expected number of months before clinical onset of each infected bovine. The doubling time for CNS was shown to equal 1.2 months. The titre in the thoracic dorsal root ganglia (DRG) was, on average, approximately 1 log units less than CNS, and cervical DRG approximately 0.5 log less than thoracic DRG. The pattern of increase of infectivity in the distal ileum is that of an initial increase up to 14-18 months post exposure, followed by a decrease, which is likely to be highly variable between animals. These results will be informative for future risk assessments of BSE, especially in relation to reviewing current control measures.     

Studies of embryo transfer from cattle clinically affected by bovine spongiform encephalopathy (BSE)

Semen from 13 bulls, eight with clinical bovine spongiform encephalopathy (BSE), was used to artificially inseminate (AI) 167 cows with clinical BSE, and their resultant embryos were collected non-surgically seven days after AI. The viable and non-viable embryos with intact zonae pellucidae were washed 10 times (as recommended by the International Embryo Transfer Society) then frozen. Later, 587 of the viable embryos were transferred singly into 347 recipient heifers imported from New Zealand, and 266 live offspring were born of which 54.1 per cent had a BSE-positive sire and a BSE-positive dam. The recipients were monitored for clinical signs of BSE for seven years after the transfer, and the offspring were monitored for seven years after birth. Twenty-seven of the recipients and 20 offspring died while being monitored but none showed signs of BSE. Their brains, and the brains of the recipients and offspring killed after seven years, were examined for BSE by histopathology, PrP immunohistochemistry, and by electron microscopy for scrapie-associated fibrils. They were all negative. In addition, 1020 non-viable embryos were sonicated and injected intracerebrally into susceptible mice (20 embryos per mouse) which were monitored for up to 700 days, after which their brains were examined for spongiform lesions. They were all negative. It is concluded that embryos are unlikely to carry BSE infectivity even if they have been collected at the end-stage of the disease, when the risk of maternal transmission is believed to be highest.     

Potential Risk Factors Associated with Bovine Spongiform Encephalopathy in Cattle from Schleswig‐Holstein,Germany

Since the first detection of bovine spongiform encephalopathy (BSE) in homebred cattle in Germany on 26 November 2000, 382 cases have been confirmed until 30 September 2005. Thirty‐two of these cases were reported from the Federal State of Schleswig‐Holstein (SH). There are hypotheses on the routes of infection for German cattle, but only few efforts have been made to assess potential risk factors by epidemiological studies. The purpose of this study was to identify potential risk factors at the farm level for the occurrence of BSE in cattle in SH. By applying the method of indirect standardization, the prevalence of various structural and management parameters of BSE‐affected farms in SH was compared with the prevalence of these parameters in a standard population of cattle farms from SH. The data describing the standard population were obtained by a cross‐sectional study performed in SH in 2003. Data of the BSE case population were available from the central German BSE case database. A possible association of the occurrence of BSE with the feeding of milk replacers to calves was observed. There was a clear indication that the occurrence of BSE was associated with the presence of pigs and/or poultry on the farm. This finding suggests that cross‐contamination of feed or cross‐exposition may have occurred in SH. The results obtained using the indirect standardization analysis were validated by multiple logistic regression. This study indicates that the feedborne path has been the principal route of transmission for the BSE agent in SH.     

Spatial heterogeneity of the risk of BSE in France following the ban of meat and bone meal in cattle feed

In France, meat-and-bone meal (MBM) has been prohibited for cattle feeding since 1990, but bovine spongiform encephalopathy (BSE) cases, called 'NAIF', appeared in animals born after this feed ban. Furthermore, in 1996 a new measure was taken: removal of cadavers and specified risk materials (SRM) from the processing of MBM dedicated to animal feed. Nevertheless, BSE cases (called 'super-NAIF') appeared in cattle born after this measure was in force. We analysed the spatial distribution of 445 'NAIF' and 58 'super-NAIF' cases detected in France from July 1, 2001 to July 31, 2003. The detection of BSE was based both on the mandatory reporting system (MRS) and the systematic test screening of cattle at the abattoir and at the fallen-animal plant with rapid tests. The background population was based on the adult-cow census. The disease mapping of the BSE risk was based on the standardised incidence ratio (stochastic Poisson process). A spatial component, which takes into account the spatial dependence between the geographical units by a notion of adjacency was used to eliminate the over-dispersion in the risk assessment. The geographical units were defined by hexagons with a side of 23km (France had 1264 hexagons). The parameters were estimated by a Metropolis Gibbs sampling algorithm using the Markov-chain Monte Carlo methods. The BSE cases were not randomly distributed. Furthermore, the areas at risk for the 'super-NAIF' matched part of the areas at risk for the 'NAIF' cases-which suggests that it might be a common source of contamination.     

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.     

Effectiveness of the BSE interventions in Japan

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.     

Potential risk factors associated with bovine spongiform encephalopathy in cattle from Schleswig-Holstein, Germany

Since the first detection of bovine spongiform encephalopathy (BSE) in homebred cattle in Germany on 26 November 2000, 382 cases have been confirmed until 30 September 2005. Thirty-two of these cases were reported from the Federal State of Schleswig-Holstein (SH). There are hypotheses on the routes of infection for German cattle, but only few efforts have been made to assess potential risk factors by epidemiological studies. The purpose of this study was to identify potential risk factors at the farm level for the occurrence of BSE in cattle in SH. By applying the method of indirect standardization, the prevalence of various structural and management parameters of BSE-affected farms in SH was compared with the prevalence of these parameters in a standard population of cattle farms from SH. The data describing the standard population were obtained by a cross-sectional study performed in SH in 2003. Data of the BSE case population were available from the central German BSE case database. A possible association of the occurrence of BSE with the feeding of milk replacers to calves was observed. There was a clear indication that the occurrence of BSE was associated with the presence of pigs and/or poultry on the farm. This finding suggests that cross-contamination of feed or cross-exposition may have occurred in SH. The results obtained using the indirect standardization analysis were validated by multiple logistic regression. This study indicates that the feedborne path has been the principal route of transmission for the BSE agent in SH.     

Bovine spongiform encephalopathy in ruminants and the new variant of Creutzfeldt-Jakob disease in humans]

The feeding of meat and bone meal which was contaminated with bovine spongiform encephalopathy (BSE) infectivity led to a huge epidemic in the British cattle population. After the emergence of a new variant form of Creutzfeldt-Jakob diseases (nvCJD) in 1996, European consumers lost confidence in beef meat. Given the coincidence by time and place and disease and agent specific characteristics, it must be assumed that nvCJD is caused by the transmission of BSE agent to man. This article gives an overview over the characteristics and diagnosis of transmissible spongiform encephalopathies, namely BSE and nvCJD, in animals and man.     

Animal-derived feedstuffs as possible vectors for bovine encephalopathy (BSE) in Germany. Part 2: Assessment of vector risk for compounded feed

Specific conditions and practices of cattle feeding in Germany have to be taken into account for assessing the risk of feed born transmission of bovine spongiform encephalopathy, especially regarding the situation before the year 2000 when specific directives were introduced for feed production. The present retrospective epidemiological study includes data on feed production and the estimated amount of animal derived feedstuffs for the production of compounded feed for cattle. Risk assessment was performed based on the 'reproduction rate' (R0), that is defined as the estimated number of infections resulting from the processing of brain and spinal cord of BSE affected cattle that is recycled to bovines via feed. Under the conditions as given in Germany until the year 2000 the reproduction rate of BSE via the inclusion of animal derived feedstuffs in compounded feed production for cattle was estimated to be 1.1. Thus, it can be expected that BSE could be reproduced in the system, but with comparatively low efficiency. The expected incidence of BSE should be considerably lower compared to the situation during the 90th in the UK, due to the markedly lower recycling rate of animal protein in cattle feeding. Animal fat could have been a significant factor for BSE transmission due to contamination by proteinaceous brain and spinal cord material during the production process. The relative significance of fat containing feedstuffs for BSE transmission could have been higher in Germany compared to the situation in the UK where meat and bone meal was produced under different conditions and frequently used in higher proportions as an ingredient for compounded feed for ruminants.     

Disposal of animal byproducts,dead and slaughtered animals

The current state of epidemiological knowledge about BSE clearly indicates that certain practices in carcass rendering had a significant impact on maintenance and spreading of BSE in the cattle population. This awareness did not come up spontaneously. As a reflection community legislation continuously developed and still does. The decisive move was done in the year 2000 by eliminating ruminant tissues with a high infectious potential with regard to BSE (specified risk material--SRM) from the human and animal feed chains. This step as well as the subsequent feed ban for all farm animals dramatically changed the logistical as well as the economical preconditions of the rendering industry. In fact the basic treatment (pressure cooking) remained almost unchanged. But instead of physically recycling the products they are nowadays predominantly used as an energy source in industry. In case of products that originate from the treatment of SRM burning is mandatory. These changes require a well adapted and intensified official supervision.     

Geographical BSE risk assessment and its impact on disease detection and dissemination

Bovine Spongiform Encephalopathy (BSE) rapidly evolved into an issue of major public concern particularly when, in 1996, evidence was provided that this disease had crossed the species barrier and infected humans in the UK with what has become known as "variant Creutzfeldt Jakob Disease" (vCJD). The aim of this paper is to describe the European Geographical BSE risk assessment (GBR) that was successfully used for assessing the qualitative likelihood that BSE could be present in a country where it was not yet officially recognized. It also discusses how this can lead to risk-based and therefore preventive management of BSE at national and international levels. The basic assumption of the GBR method is that the BSE agent is initially introduced into a country's domestic cattle production system through the importation of contaminated feedstuffs or live cattle. This is referred to as an "external challenge". The ability of the system to cope with such a challenge is, in turn, referred to as its "stability": a stable system will not allow the BSE agent to propagate and amplify following its introduction, while an unstable system will. The BSE-status of a country assessed by this system was used by the European Commission as the basis for trade legislation rules for cattle and their products. The GBR was an invaluable tool in evaluating the potential global spread of BSE as it demonstrated how a disease could be transferred through international trade. This was shown to be a critical factor to address in reducing the spread and amplification of BSE throughout the world. Furthermore, GBR resulted in the implementation of additional measures and management activities both to improve surveillance and to prevent transmission within the cattle population.