Alternative BSE risk assessment methodology for beef and beef offal imported into Japan

The Food Safety Commission (FSC) of Japan, established in July 2003, has its own initiative to conduct risk assessments on food stuffs known as "self-tasking assessment". Within this framework, the FSC decided to conduct a risk assessment of beef and beef offal imported into Japan from countries with no previous BSE reports; thus, a methodology was formed to suit to this purpose. This methodology was partly based on the previous assessments of Japanese domestic beef and beef imported from U.S.A./Canada, but some modifications were made. Other organizations' assessment methods, such as those used for BSE status assessment in live cattle by the OIE and EFSA's GBR, were also consulted. In this review, the authors introduce this alternative methodology, which reflects (1) the risk of live cattle in the assessed country including temporal risks of BSE invasion and domestic propagation, with the assessment results verified by surveillance data, and (2) the risk of beef and beef offal consisting of cumulative BSE risk by types of slaughtering and meat production processes implemented and the status of mechanically recovered meat production. Other possible influencing factors such as atypical BSE cases were also reviewed. The key characteristic of the current assessment is a combination of the time-sequential risk level of live cattle and qualitative risk level of meat production at present in an assessed country.     

Temporal aspects of the epidemic of bovine spongiform encephalopathy in Great Britain: individual animal-associated risk factors for the disease

The objectives of this study were first to determine the cumulative incidence of bovine spongiform encephalopathy (BSE) in the British cattle population from July 1986 to June 1997, secondly, to identify individual animal-associated risk factors that influenced the age of onset of clinical signs in confirmed BSE cases, and, thirdly, to assess the effectiveness of the measures introduced to control BSE during the epidemic. The analyses were based on the population of British cattle at risk, derived from agricultural census data collected between 1986 and 1996, and BSE case data collected up to June 30, 1997. The unit of interest was individual adult cattle recorded on annual agricultural censuses between June 1986 and June 1996. Univariate and multivariate survival analysis techniques were used to characterise the age of onset of clinical signs. In total 167,366 cases of BSE were diagnosed in Great Britain up to June 30, 1997. The cumulative incidence of BSE between July 1986 and June 1997 was 1.10 (95 per cent confidence interval [CI] 1.09 to 1.10) cases per 100 adult cattle at risk. Cattle from the South east, South west and Eastern regions of England had 4.26 to 5.96 (95 per cent CI 4.15 to 6.14) times as great a monthly hazard of being confirmed with BSE as cattle from Scotland. Compared with cattle born before June 1985, those born between July 1987 and June 1988 had 22.5 (95 per cent CI 22.1 to 22.8) times the monthly hazard of being confirmed with BSE, whereas those born in the 12 months after July 1988 had only 7.39 (95 per cent CI 7.24 to 7.54) times the monthly hazard of being confirmed with BSE. This reduction in hazard was directly attributable to the ban on the use of ruminant protein as a feed instituted in July 1988. Successive cohorts from 1989 to 1991 experienced further reductions in the hazard of experiencing BSE. The additional decrease in hazard observed for the 1990 cohort may be attributed to the effect of the Specified Bovine Offal ban instituted in September 1990.     

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.     

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.     

Risk assessment and surveillance for bovine spongiform encephalopathy (BSE) in Argentina

An assessment was made of the risks of bovine spongiform encephalopathy (BSE) occurring in Argentina. Most of the factors associated with the origin and development of the BSE epidemic in the UK are essentially absent. For example, Argentina's large sheep and cattle industries are based on low-cost production systems using grass. Concentrated feeds are not used for sheep, rarely for beef cattle and to a comparatively modest extent for dairy cows. Particularly important are the facts that scrapie (and BSE) has never been reported in Argentina—very small amounts of waste tissues from sheep are rendered to produce meat and bone meal (MBM)—and MBM is not used in concentrated feeds for cattle. We conclude that Argentina has an exceptionally low risk of BSE due to scrapie. There is a very small risk of BSE having been introduced via live animals imported from countries with BSE, but this could only give rise to isolated cases because MBM is not fed to cattle.

A surveillance programme has been carried out based largely on a histological examination of brains from three categories of old dairy cows: animals reported on the suspicion of having neurological disease; animals in poor condition at slaughter; healthy animals randomly selected in the abattoir. No evidence of transmissible spongiform encephalopathy was seen in several sections from each of a total of 1019 brains. We conclude that, for most practical purposes, Argentina may be considered to be free from BSE.     

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.     

Risk of introduction of BSE into Sweden by import of cattle from the United Kingdom

All cattle of United Kingdom origin imported to Sweden since 1980 were traced (n=94) and the probability that none of these imported cattle had clinical signs of bovine spongiform encephalopathy (BSE) at the year of slaughter (death) was calculated. If BSE had been introduced by live-animal imports, the consequences of such an event also was evaluated. The potential of the recently introduced surveillance system of high-risk cattle to detect such an event also was evaluated.We found that BSE most probably has not been introduced to Sweden by live-animal imports. We also found that, if this event had occurred and assuming a worst-case scenario that the animal was not prevented from being rendered, the rendering system (during certain periods) would not have prevented further spread of infection. Finally, we found that the BSE surveillance of high-risk cattle has not been in place long enough to verify that this event has not occurred (as of December 2001).     

Bovine spongiform encephalopathy: epidemiological studies

This study, initiated in June 1987, describes the epidemiology of bovine spongiform encephalopathy (BSE), a recently described novel neurological disease of domestic cattle first identified in Great Britain in November 1986. Records suggested that the earliest suspected cases occurred in April 1985. There was variability in the presenting signs and the disease course, but the majority of cases developed behavioural disorders, gait ataxia, paresis and loss of bodyweight; pruritus was not a predominant sign. The form of the epidemic was typical of an extended common source in which all affected animals were index cases. The use of therapeutic or agricultural chemicals on affected farms presented no common factors. Specific genetic analyses eliminated BSE from being exclusively determined by simple mendelian inheritance. Neither was there any evidence that it was introduced into Great Britain by imported cattle or semen. The study supports previous evidence of aetiological similarities between BSE and scrapie of sheep. The findings were consistent with exposure of cattle to a scrapie-like agent, via cattle feedstuffs containing ruminant-derived protein. It is suggested that exposure began in 1981/82 and that the majority of affected animals became infected in calfhood.     

Targeted surveillance to assess the prevalence of BSE in high-risk populations in western France and the associated risk factors

A pilot study was set up for the first time in France in August 2000, to obtain more precise estimates on the BSE epidemic in France. Three categories of cattle at risk of BSE (found dead on-farm, euthanased and emergency slaughtered) were sampled exhaustively from August 7 to December 22, 2000, in the three regions assumed to be the most affected with BSE in France (Basse-Normandie, Bretagne and Pays de la Loire). The samples were checked by using Prionics tests, and positive samples were confirmed by Western blot or immunohistochemistry. The overall prevalence of positive cattle was 0.16 per cent. Multifactorial logistic regression showed that there was a significantly higher prevalence among cattle from the birth cohorts July 1993 to June 1994 and July 1994 to June 1995, than among those born before July 1993, and among the categories 'euthanased' and 'emergency slaughtered' than among the category 'dead on-farm, and a higher prevalence in the regions Pays de la Loire and Bretagne than in Basse-Normandie. No significant differences in the prevalence of BSE were observed between dairy, beef suckler and mixed herds.     

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.     

Epidemiological study on BSE outbreak in Japan

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

Animal-derived feeds as possible vectors for bovine spongiform encephalopathy (BSE) in Germany. 1. Comparative risk assessment for a single animal food of animal origin

The occurrence of BSE cases in Germany after the ban of meat and bone meal for ruminant feed in 1994 requires a detailed investigation of animal derived feedstuffs regarding their specific risks as vectors for the disease. Accepting the theory that BSE is a prion transmitted disease, the theoretical infectious potential was calculated for animal derived feedstuffs. This calculation was based on the assumption, that risk material (brain, spinal cord) of one clinically diseased cattle was rendered in the process as established in Germany (133 degrees C, 3 bar, 20 min) or, alternatively, that one diseased animal was slaughtered resulting in normal processing of the by-products for human food production. From this risk assessment it became obvious that meat and bone meal was one, but probably not the most important source for the spreading of BSE. Taking into account the high sensitivity of calves it can be speculated that certain products, e.g. from bone processing (bone meal) and fat melting (mixed animal fats), commonly used for the formulation of milk replacers, might have been more important as pathways. As it can't be excluded retrospectively that infected meat and bone meal was imported from the UK, this non-calculable influence may have been related to the significance of the other products. The calculation model underlines that efficient removal of specified risk material (brain, spinal cord) and adequate processing (133 degrees C, 3 bar, 20 min) or alternatively other equivalent treatments of fats are prerequisites for minimising the risk of feed borne transmission of BSE by animal derived feedstuffs. The epidemiological consequences are part of a subsequent paper.     

Where does BSE in the Netherlands come from?

It is only in the last 5 years that the Netherlands has been confronted with cases of bovine spongiform encephalopathy (BSE). The cases diagnosed to date have not been clearly linked to imports from the United Kingdom. This article describes the various possible explanations for the Dutch cases. The risk factors involved, have either a connection with imported BSE, local origin of BSE, or both. These factors can also be divided into introductory risk and propagation risk, terms that were also used in an EU risk assessment study. Research at ID-Lelystad since the early 1990s and at IKC-Ede has tried to assess the relative importance of the various risk factors, the results of which are discussed in this paper. The paper does not deal with the specifics of the cases diagnosed to date, because of the absence of an in-depth epidemiological investigation, but provides a general assessment of the risk factors that might have played a role. Important factors have been, in addition to the initial imports of cattle and meat and bone-meal from the UK, the continuing imports from other countries with covert BSE and the cross-contamination within the animal feed production lines. Emphasis is on the period of the early and mid-1990s, the period in which most calves with diagnosed BSE were born.     

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.     

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.     

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.     

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.     

BSE/TSE--the present epidemiologic and diagnostic situation

In 1992, 1994 and 1997, first BSE cases were diagnosed among imported cattle. The first domestic BSE case in Germany was confirmed on 26 November 2000. Altogether 192 cases (7 cases in 2000, 125 cases in 2001 and 60 cases in 2002) were reported (at the date: 7. August 2002). Comparing the BSE situation in Germany with other European countries under consideration of the surveillance schemes applied, Germany has a similar BSE incidence based on 100,000 adult cattle as France and Spain but a higher incidence than neighboring countries like The Netherlands, Austria and Denmark. At present, on average 2,3 cases per week are confirmed in Germany. With respect to the age distribution of the BSE cases, about 84% of all domestic cases confirmed originated out of the years 1995 and 1996 with a accumulation in 1996 (about 53% of all cases). Single BSE cases with the years of birth 1990, 1991 and 1993 demonstrate, that the BSE agent is circulating among the German cattle population at least since the beginning of the nineties. Between 1985 und 7 August 2002, scrapie was diagnosed in 26 sheep flocks in Germany, but alone during the year 2002 (until 7 August 2002) 11 scrapie affected sheep flocks were discovered.     

Risk factors for BSE-infections in Lower Saxony, Germany

In order to generate data on the cattle population and farm management in the state of Lower Saxony, Germany, a basic demographic survey was conducted. Afterwards these BSE-free farms as a reference population were compared with the population on BSE farms to identify risk factors for BSE infections. A variety of risk factors for BSE were reviewed, including the import of cattle from the United Kingdom, commercial foodstuff, dairy farming, herd size and cross-contamination with foodstuff for other farm animals. For the basic demographic survey of the reference, a questionnaire was mailed to a representative sample of cattle farms in Lower Saxony where BSE cattle had not occurred before the sample was taken. Distribution of risk factors within this reference population (n=731) and the BSE population (n=49) were compared following the concept of indirect standardisation in stratified populations. The size of farms was used as the stratification variable, with three strata. Under the same rate as in the reference population, the portion of Red Holstein cattle breed was four fold higher than in the BSE population (SER=4.03; p=0.0003). Milk replacer was fed 1.41 times more often on BSE farms (p=0.0478). However, the use of concentrated foodstuff for pigs (SER=0.21) was significantly less frequent in the BSE population than expected (p=0.0001), whereas the husbandry of sheep, goats or game animals seemed to increase the risk of BSE 2.85 times (p=0.0413). There were no significant differences between the two populations concerning the purchase of cattle (p=0.1514) and the use of concentrated feed for calves during the 1990s (p=0.6212). This is an epidemiological indication of increased susceptibility of Red Holstein cattle to BSE. However, this study did not confirm the assumption that the use of commercial foodstuff other than milk replacer or the purchase of cattle increases the risk of BSE infection. It nevertheless remains likely that commercial foodstuffs such as concentrated feed for calves were risk factors in Germany as well.