A model (BSurvE) for estimating the prevalence of bovine spongiform encephalopathy in a national herd

We developed the BSurvE spreadsheet model to estimate the true prevalence of bovine spongiform encephalopathy (BSE) in a national cattle population, and evaluate national BSE surveillance programs. BSurvE uses BSE surveillance data and demographic information about the national cattle population. The proportion of each cohort infected with BSE is found by equating the observed number of infected animals with the number expected, following a series of probability calculations and assuming a binomial distribution for the number of infected animals detected in each surveillance stream. BSurvE has been used in a series of international workshops, where analysis of national datasets demonstrated patterns of cohort infection that were consistent with infection-control activities within the country. The results also reflected the timing of known events that were high-risk for introduction of the infectious agent.     

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.     

Comparison of BSE prevalence estimates from EU countries for the period July to December 2001 to the OIE and EU GBR classifications

Consequent upon the bovine spongiform encephalopathy (BSE) crisis, the European Union (EU) Commission enacted various decisions, which demanded that all bovine animals over 30 months of age should be examined by one of the approved rapid tests when slaughtered for human consumption. All cattle over 24 months of age subject to 'special emergency slaughtering' or died on the farm or in transit or suspect of BSE infection should also be examined by one of the approved rapid tests. According to a specific commission decision, Sweden and Finland were to test only a sample of bovine animals over 30 months of age subject to normal slaughter. Testing commenced on 1 January 2001. The authors evaluate the results of more than 5 million tests performed in the second semester 2001 from across the EU. The prevalence of BSE in the risk categories considered (emergency slaughter, fallen stock and healthy slaughtered), and the probability distribution of true-positive, false-positive and false-negative results are estimated by second-order Bayesian analysis. The results of the validation of tests performed in the EU are also considered by estimation of the probability distribution of their sensitivity and specificity. The prevalence of infection estimated in the cattle population of each EU country is compared against the criteria given in the OIE Terrestrial Animal Health Code and is also used to evaluate the consistency of the results of EU Geographical BSE Risk with the actual infection levels in the countries. Finally, the capability of the two current approaches to BSE surveillance (i.e. the testing of all slaughtered and dead cattle as applied in the EU and a surveillance system targeted at animals in risk categories only) to detect the infection in a given population are discussed.     

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.     

Breed predisposition for BSE: epidemiological evidence in Bavarian cattle

We present epidemiological data from Bavaria that indicates that animals of the Brown Swiss (BS) cattle breed might be more susceptible to BSE than animals from other breeds, both in terms of disease prevalence and length of the incubation period. BS animals were disproportionately represented among the BSE cases (BS represented about 9% of the susceptible population but 27% of actual cases). BS were slaughtered at a higher age (5.8 years vs. 5.0 years for other breeds), and there is a higher prevalence of feeding proprietary feeds to BS calves than calves from other breeds. There was no difference in the recorded feeding practice of BSE-positive animals from BS or other breeds. These results would lead to expect a higher prevalence of BSE in the BS population, with BS BSE animals being of equal age or older than BSE animals from other breeds. In contrast, median age at BSE detection was significantly lower in BS animals than in other breeds (61.4 vs. 68.8 months). There was no difference in the identification categories of BSE between BS animals and animals of other breeds that could explain this difference in age. BS cattle are reported to have more octapeptid repeats in the prion protein gene than other breeds, which could account for shorter incubation periods and higher susceptibility. These observations suggest that BS animals and their tissues should be used in further studies into genetic determinants of BSE susceptibility in cattle.     

Modelling the expected numbers of preclinical and clinical cases of bovine spongiform encephalopathy in Switzerland.

The objective of this study was to model the expected numbers of cattle incubating bovine spongiform encephalopathy (BSE) and the numbers of clinical cases of BSE in the Swiss cattle population between 1984 and 2005. The results were compared with the observed number of clinical BSE cases and with the results of a culling and testing scheme on herdmates of cattle with BSE. The age distribution of the Swiss cattle population, the age-at-death distribution of the first 235 BSE cases and exposure information were used to calculate the expected number of infected cattle in each birth cohort and the resulting numbers of clinical cases and survivors incubating the disease for each year. The model which did not assume any under-reporting of cases fitted the observed epidemic curve of clinical cases reasonably well, and predicted that the Swiss BSE epidemic would come to an end between 2003 and 2005. The age of survivors incubating BSE is increasing. The higher than expected incidence of subclinical cases observed in animals from the culling scheme is most probably the result of the heterogeneous distribution of infected animals and affected herds in the population. The results of the model need to be taken into account when designing surveillance and testing schemes for BSE.     

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.     

TSE surveillance in small ruminants and pigs: a pilot study

Switzerland is controlling Transmissible Spongiform Encephalopathies (TSE) in cattle (BSE) and small ruminants (scrapie). Since BSE is potentially transmissible to sheep, goats or pigs through feeding of contaminated meat and bone meal, implementation of an active surveillance programme for TSE in these species is discussed. The aim of this pilot study was to obtain preliminary data on the prevalence ofTSE and other neurological disorders in these populations. For that purpose, a total of 398 perished and 825 slaughtered adult small ruminants and pigs was examined for the presence of neuropathological changes. None of these animals revealed positive for TSE. However, the investigations demonstrated that perished sheep and goats exhibited a higher prevalence of relevant neuropathological changes when compared with slaughtered animals. From these results, it is concluded that perished small ruminants are probably a risk population for TSE and should be considered as target populations for an active surveillance programme.     

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.     

Temporal and spatial patterns of the clinical surveillance of BSE in France,analysed from January 1991 to May 2002 through a vigilance index

Between 1991 and mid 2000, the surveillance of Bovine Spongiform Encephalopathy (BSE) in France was based solely on clinical surveillance through a Mandatory Reporting System. Since 2000, the implementation of active surveillance programmes using rapid tests, as a complementary tool targeted at dead and slaughtered cattle has shown that part of the BSE cases were not detected with the clinical surveillance. In order to obtain a better knowledge of the strength of the clinical surveillance, we analysed a vigilance index defined as the ratio of negative clinical suspicions to the cattle population in the region and period of interest. The temporal analysis of the vigilance index showed that it did not vary much between 1991 and 1999, increased sharply since 2000, and then decreased partly in 2001. The geographical analysis of the variations of the vigilance index was performed at the department level by comparing the observed number of negative clinical suspicions per department to the expected number, computed on the basis of the national average index and standardised on the production type of the cattle - dairy versus beef suckling cattle. As assumed, the data followed a Poisson distribution. We observed a high geographical variation of the vigilance index: ten departments out of 91 presented a significantly higher vigilance index than the national one, and four a significantly lower vigilance index. The vigilance index showed that the clinical surveillance was heterogeneous during the past twelve years, both in time and geographic location, in a range of one to ten. So the apparent trend in the BSE epidemic during this period as well as the differences in the spatial incidence of BSE have to be analysed with caution.     

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.     

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.     

The unrecognised French BSE epidemic

In France, implementation of systematic screening programs in 2000, as a complement to the mandatory reporting of animals with clinical signs of BSE (passive surveillance), revealed certain limitations of the mandatory system. Indeed, systematic screening showed that some BSE cases were not detected by the clinical surveillance system, implying considerable BSE case under-reporting throughout the epidemic. As the most likely explanation for variant Creutzfeldt-Jakob disease (vCJD) is exposure to the aetiologic agent of BSE, it is essential to reconstruct the French BSE epidemic pattern accounting for this under-reporting. We estimated age- and year-specific incidence rates of BSE by using a back-calculation method. This approach relies on the principle that the number of clinical BSE cases is the consequence of the number of BSE-infected animals after a known incubation time, defined as the time between infection and clinical onset. We generalized this model to take into account epidemiological characteristics of BSE, such as French cattle mortality, BSE case reporting probability, and age-dependent susceptibility and/or exposure to the BSE agent. We confirmed that the average BSE incubation period is five years and that the peak risk of bovine infection occurs between 6 and 12 months of age. The results also showed that the proportion of underreporting is the most influential parameter in the model, and that BSE was substantially underreported until rapid tests were introduced. Indeed, only 103 BSE cases were detected by passive surveillance up to June 2000, while we estimated that there was 301 200 (95% confidence interval (CI) [27 600-837 600]) cattle infected by the BSE agent. Despite uncertainty over the beginning of the epidemic, we showed that the French BSE epidemic in the late 1980s was completely undetected, and only the second wave, after 1990, was observed.     

Establishment and maintenance of a longitudinal study of bovine spongiform encephalopathy (the ULiSES scheme)

This paper addresses the issues of tracing and compliance encountered in setting up and maintaining a UK-wide 5-year observational study of beef cattle. The 5-year prospective study was initiated in 1997 to investigate the occurrence of bovine spongiform encephalopathy (BSE) in a single herd of pedigree Aberdeen Angus cattle, in which BSE had been detected at low prevalence. The study was given the acronym ULiSES (University of Liverpool Spongiform Encephalopathy Scheme). All cattle present on the farm at the start of the scheme were registered as members of the study population (n=320), as were all calves subsequently born on the farm (n=350). Animals that were sold (n=291) were traced and monitored at destination farms. Farmers were requested to give advance notification of slaughter of any ULiSES animal and an attempt was made to collect post-mortem samples of nervous tissue, peripheral lymphoid tissue and striated muscle from all animals in the scheme at the time of slaughter, death or euthanasia. Sections of medulla were examined (by standard histopathological techniques) for the presence of spongiform change. Remaining samples were stored at −70°C for future investigation by alternative tests. At the halfway point of the scheme in October 1999, 75.2% (506/673) of the study population was still alive; 42% (284) of the population was still alive on the study farm and 33% (222) was distributed on other farms throughout the UK. Complete sets of specimens had been recovered from 77% (129/167) of dead animals. All brainstem sections were negative by histopathological examination. No suspect cases of BSE were reported in ULiSES animals.

Failure to recover specimens occurred principally in animals which had left the study farm. The main cause of specimen loss was a failure of compliance in a small number of individuals who had purchased large numbers of ULiSES animals, and subsequently slaughtered them without contacting the University. Despite this, farmer compliance was generally high. The ULiSES scheme shows the feasibility of a country-wide longitudinal observational study spanning a period of several years and indicates the large impact of small numbers of non-compliant individuals.     

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.     

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.     

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.     

Estimating the trend of the French BSE epidemic over six birth cohorts through the analysis of abattoir screening in 2001 and 2002

A bovine spongiform encephalopathy (BSE) testing programme at the abattoir started in 2001 in France. A total of 5 281 293 bovines were tested in 2001 and 2002; 87 were found positive in 2001--37 per million (95% CI 30-46)--, whereas only 71 in 2002--24 per million (95% CI 19-30). Logistic regression models were run to compare the prevalence of BSE on successive birth cohorts, using a pair-wise method of controlling for age at testing; the prevalence on the first one, determined on animals slaughtered in 2001, was compared to the prevalence on the following one determined on animals slaughtered in 2002. Five models were performed in order to compare the birth cohorts preceding and following the months of June 1993 (i.e. July 92-June 93 birth cohort compared to July 93-June 94 birth cohort) (8.5 years old cattle), June 1994 (7.5 years old cattle), June 1995 (6.5 years old cattle), June 1996 (5.5 years old cattle) and June 1997 (4.5 years old cattle). The models were adjusted for the production type of cattle and the test used. The results showed a significant increase (OR = 2.31, 95% CI 1.08-4.9) of the BSE prevalence between the July 93-June 94 and July 94-June 95 cohorts, and then a significant decrease over the next two birth cohorts; the July 95-June 96 birth cohort was significantly less affected than the July 94-June 95 one (OR = 0.46, 95% CI 0.27-0.78), and the July 96-June 97 birth cohort was significantly less affected than the July 95-June 96 one (OR = 0.17, 95% CI 0.07-0.37). The increase in BSE prevalence between the July 93-June 94 and July 94-June 95 cohorts was in agreement with modelling studies, but needs to be confronted to the data on fallen stock at the national level. The decrease in BSE prevalence on the birth cohorts born after June 1995 was in agreement with the findings on the fallen stock in the western part of France and matches the implementation of the removal of specified risk materials (SRM) and dead animals from the processing of meat and bone meal (MBM) since June 1996.     

Spatial analysis of bovine spongiform encephalopathy in Galicia, Spain (2000-2005)

In Spain, the first bovine spongiform encephalopathy (BSE) case was detected in 2000 in a cow born in the Galicia region (Northwestern Spain). From then and until October 2005, 590 cases were detected, 223 of them in Galicia.

In 1994, meat and bone meal (MBM) was banned on ruminant feed and, in 1996, an EU decision mandating an overall change in MBM processing was implemented. This decision was gradually applied in the territory and not enforced before July 1998. The objective of this study was to explore clustering of BSE cases and estimate the standard incidence ratio (SIR) of BSE in Galicia. Our study was based on the BSE cases detected during the surveillance period 2000–2005 in the Galicia region. These cases were divided, based on birth date, into two periods: animals born from 1994 to July 1998, and those born after July 1998. We tested the role of cross-contamination on the geographical SIR distribution for both periods. Hierarchical Bayesian models were used to model the overdispersion and lack of independence of the SIR estimates. The geographical distribution of the standard incidence ratio of BSE between both periods was different. In the second period, the SIR was reduced in some areas. The reduction in these areas could be attributable to the changes in the processing of MBM. We did not find any statistical link between the poultry population and the standard incidence ratio, but pig population had a positive effect.