Case-control study on feed risk factors for BSE cases born after the feed ban in France

In France, after the ban on meat and bone meal (MBM) in cattle feeding in June 1990, cases of Bovine Spongiform Encephalopathy (BSE) have continued to be detected in bovines born after that ban (called BAB cases). A case-control study was therefore carried out to determine the way these cases were contaminated. A multivariate conditional model was built adjusting for the production type of the animals and taking into account the herd size. The results confirmed that feeding cattle with proprietary concentrates was at risk for BSE, with an adjusted odds ratio of 6.8 (2.5; 18.7) for the consumption of less or three different proprietary concentrates and 17.6 (5.7; 54.8) for more than three, when comparing with no consumption of proprietary concentrates, considering feeding of bovines before the age of two. The results suggest that cross-contaminations by MBM in bovine concentrates have occurred after 1990. To a lesser extent, on-farm cross-contaminations, i.e. consumption by cattle of feedstuffs initially dedicated to other animals and which could legally contain MBM, have probably also existed, since the presence on farms of poultry fed purchased feed involved an increased risk of BSE with an odds ratio of 1.8 (1.1; 3.0). The use of milk replacers, which often incorporates animal fats, was also at risk with an odds ratio of 1.8 (1.0; 3.1).     

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.     

BSE, feed and cattle in Switzerland: is there a spatial relation?

Cross-contamination of cattle feed with meat and bone meal (MBM) allowed in feed for other species is regarded as the current hypothesis for the infection pathway of Bovine Spongiform Encephalopathy (BSE) cases occurring after the implementation of a ban on feeding MBM to cattle. This study was aimed at establishing a spatial relation between BSE cases in Switzerland and the findings of MBM in cattle feed. A cluster analysis and a cohort study were performed. Two hundred sixteen BSE cases born after December 1990 and detected until August 1st 2005, screening data of 504 feed producers between 1996 and 2001 and population data from the Swiss 2001 cattle census were included. The cluster analysis showed feed producer, positive for MBM contaminations in cattle feed, as possible cluster centres for BSE cases. In the cohort study, farms within a radius of 2 and 10 km around positive feed producers showed significantly higher odds to have a BSE case than the control group. The odds ratio and its 95% confidence interval were 2.23 (1.26-3.93) for the 2 km radius and 1.38 (1-1.9) for the 10 km radius. The results provide evidence for a spatial relation between cross-contamination and BSE occurrence. These findings support the hypothesis of cross-contamination to be an important route for BSE transmission after a feed ban.     

A spatio-temporal analysis of BSE cases born before and after the reinforced feed ban in France

A spatio-temporal analysis was carried out to see how the risk distribution of bovine spongiform encephalopathy (BSE) in France changed depending on the period of birth. The data concerned the 539 BSE cases born in France after the ban (BAB) of meat and bone meal (MBM) in 1990 and detected between July 1, 2001 and December 31, 2003, when the surveillance of BSE was comprehensive. Seventy-two of these cases were born after the reinforced (second) ban (BASB) in 1996, which involved the removal of BSE-risk materials and cadavers from the processing of MBM. The Ederer-Myers-Mantel (EMM) time and space cluster test was applied, after classifying the cases by trimester and region of birth, BAB or BASB status, and dairy or beef status. Then disease mapping was performed for four successive birth periods, three for the BAB cases (January 1991 through June 1994, July 1994 through June 1995, July 1995 through June 1996), and one for the BASB (July 1996 through October 1998). It was elaborated with the Bayesian graphical modelling methods and based on a Poisson distribution with spatial smoothing. The parameters were estimated by a Markov Chain Monte Carlo (MCMC) simulation method. The main finding was that the areas with the highest risk of BSE changed largely from one birth period to another; from the west, it reached the east of France for birth cohort 1994-1995 and the southwest for birth cohort 1995-1996. The EMM test identified a peak risk in this region both for dairy and beef cattle in the fall 1995. The spatial distribution of the risk for the BASB cases matched the spatial pattern of risk for the preceding BAB birth cohort quite well; this was in favour of a common origin of the infection of the BAB and BASB cases, despite the complementary control measures.     

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.     

Descriptive spatial analysis of BSE in western France

The spatial heterogeneity of Bovine Spongiform Encephalopathy (BSE) was analysed on the 84 cases confirmed in western France (WF) between August and December 2000, when both the Mandatory Reporting System and an active surveillance on cattle at risk were running. Ninety-four percent of these cases were born between June 1993 and June 1996, and we analysed the location at birth. One disease mapping and two clustering methods (Scan of Kulldorff and the method of Besag and Newell) were used. In order to attenuate the contrasts artificially created by the standard disease mapping method (over-dispersion), we estimated the Standard Incidence Ratio (SIR) with a Bayesian method (Poisson-Gamma model) allowing a smoothing of the estimators. The geographical location of interest was the "canton", that divided the total area into 526 geographical units. The background population (2.6 million cattle) was obtained from the Agricultural Census 2000. We tested the hypothesis of a homogenous spatial distribution of the BSE risk where the expected number of BSE cases per unit area was obtained by applying the overall BSE rate in WF to each "canton", standardised on the type of breed, dairy versus beef suckler. The SIR ranged from 0.80 to 2.18 and the spatial distribution of BSE cases was significantly heterogeneous. Two spatial clusters were detected with the spatial scan statistics of Kulldorff and the method of Besag and Newell (18 to 20 observed BSE-cases per cluster with a radius of 45 km) centred on the "département" of C?tes-d'Armor and Mayenne. Another cluster was detected with the method of Besag and Newell (9 observed BSE-cases) in the "département" of Finistère. The results proved that the risk of BSE is linked to the geographical location in the area of the study.     

Poultry, pig and the risk of BSE following the feed ban in France--a spatial analysis

A spatial analysis was carried out in order to analyse the reason why the risk of Bovine Spongiform Encephalopathy (BSE) was spatially heterogeneous in France, during the period following the feed ban of Meat and Bone Meal to cattle. The hypothesis of cross-contamination between cattle feedstuff and monogastric feedstuff, which was strongly suggested from previous investigations, was assessed, with the assumption that the higher the pig or poultry density is in a given area, the higher the risk of cross-contamination and cattle infection might be. The data concerned the 467 BSE cases born in France after the ban of meat and bone meal (July 1990) and detected between July 1st, 2001 and December 31, 2003, when the surveillance system was optimal and not spatially biased. The disease mapping models were elaborated with the Bayesian graphical modelling methods and based on a Poisson distribution with spatial smoothing (hierarchical approach) and covariates. The parameters were estimated by a Markov Chain Monte Carlo simulation method. The main result was that the poultry density did not significantly influence the risk of BSE whereas the pig density was significantly associated with an increase in the risk of 2.4% per 10 000 pigs. The areas with a significant pig effect were located in regions with a high pig density as well as a high ratio of pigs to cattle. Despite the absence of a global effect of poultry density on the BSE risk, some areas had a significant poultry effect and the risk was better explained in some others when considering both pig and poultry densities. These findings were in agreement with the hypothesis of cross-contamination, which could take place at the feedstuff factory, during the shipment of food or on the farm. Further studies are needed to more precisely explore how the cross-contamination happened.     

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.     

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.     

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.     

Geographical clustering of cases of bovine spongiform encephalopathy (BSE) born in Switzerland after the feed ban

Over one-third of the cases of BSE in Switzerland have been born after the feed ban of December 1, 1990. Evidence for the geographical clustering of these cases emerged in two distinct regions. All the 354 BSE cases recorded until June 30, 2000 (set A), and the 376 cases recorded up to May 14, 2001 (set B), were georeferenced to the centres of the communities in which the herds of origin were located, and control populations were georeferenced to the centres of the communities in which these herds were located at the time of the census. The latitudes and longitudes of these centres were used in the statistical analysis of the spatial clustering. The Cuzick-Edwards test and the spatial scan statistics were applied to assess the significance of the clusters, while controlling for the spatial distribution of the underlying cattle population. There was global clustering of the cases born after the ban, and distinct and significant (P<0.05) spatial clusters were repeatedly identified in the two case datasets, and in several control populations (all cases born before the feed ban on a random sample of control farms) in terms of cattle density by region or cow density by region. Differential reporting was excluded as the underlying reason for the observed clusters.     

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.     

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.     

Case-control study of cases of bovine spongiform encephalopathy born after July 31, 1996 (BARB cases) in Great Britain

This paper reports the results of a case-control study of the bovine spongiform encephalopathy (BSE) cases born in Great Britain after the statutory reinforcement of the ban (BARB) on the feeding of mammalian-derived meat and bone meal on 31 July 1996. A total of 499 suspect clinical cases of BSE, born after 31 July 1996, and reported negative by July 31, 1996 and were compared with the set of 164 confirmed Great BARB cases in Great Britain detected by both passive and active surveillance. Animal-level risk factors (age and type of feed offered) and herd-level risk factors (herd size and type, number of prereinforced feed ban BSE cases born on the holding, the presence of other domestic species and waste management) were obtained for the analysis. BARB cases were 2.56 times (95 per cent CI 1.29 to 5.07) more likely to be exposed to homemix or a combination of homemix and proprietary feeds were 0.59 times (95 per cent CI 0.50 to 0.69) as less likely to be exposed to the unit increases in the number of prereinforced feed ban BSE cases diagnosed on the natal holding. A supplementary spatial analysis of these cases revealed three areas of excess BARB density: Northwest and Southwest of Wales and Northeast of Scotland.     

Cases of bovine spongiform encephalopathy born in Switzerland before and after the ban on the use of bovine specified risk material in feed

In Switzerland there was a reduction in the number of cases of bovine spongiform encephalopathy, observed in the birth cohorts from 1995 to 1996, but no further reduction in the following birth cohorts up to 1998. From the records of 34 cases born after April 30, 1996 (BAB96) and 174 cases born before April 30, 1996 and after December 1990 (BAB90), observed up to April 30, 2004, the risk factors at the farm level, possible routes of exposure and the geographical distribution of the cases were analysed to try to explain the observations. No evidence was found for a rate of exposure other than feed. There was some evidence that the risk factors at farm level were different between the BAB90 and BAB96 cases. A large proportion of the BAB96 cases was born in cantons that had reported only a few BAB90 cases, but a small cluster of the BAB96 cases was found in a region where there had been a cluster of BAB90 cases. The spatial distribution of these cases indicated that the risk of exposure to infection had been more randomly distributed than during the period up to April 1996. Farms with mixed livestock had a higher risk of having a case born after the ban on the feeding of specified risk material in 1996. In a regression model, a trend towards an association between cases of BSE and presence of small ruminants on the farm was observed for the BAB96 cases, and the presence of pigs and the pig:cattle ratio were significant for the BAB90 cases.     

Simulating the BSE epidemic and multiplication factor in dairy herds in Japan

With the objective of evaluating the effectiveness of an administrative guidance on the use of ruminant meat-and-bone meal in ruminant feed, effective from April 1996 to September 2001, we developed a model to simulate the evolution of the BSE epidemic and to estimate the BSE multiplication factor (K) in the Japanese dairy population. The output that provided the best fit to the number of BSE cases both observed and predicted to date suggest that the probability that bovine MBM was fed back to cattle was 14.2-75.2% and 0.129-0.570% during the periods from 1992 to April 1996 and from April 1996 to October 2001, respectively. Given these estimates, the value of K would have peaked in 1995 at 40-48 and then declined to 0.32-0.67 between 1997 and 2001. These results suggest that the administrative guidance was effective in reducing the amount of MBM fed to cattle by a factor of 104-141 and was perhaps enough to drive the epidemic towards extinction.     

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.     

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.     

Prevalence of BSE in cattle found dead, euthanased or emergency slaughtered on farms in western France in 2000, 2001 and 2002

The overall trend and the trend within birth cohorts of the prevalence of bovine spongiform encephalopathy (BSE) in cattle found dead, euthanased or emergency slaughtered on farms in the Bretagne, Basse Normandie and Pays de la Loire regions of France, during the periods from August 7 to December 22 in 2000, 2001 and 2002, were analysed by non-conditional logistic regression, adjusted for the region and for the type of animals. The overall prevalence of BSE during these three periods decreased from 2.71 per 1000 in 2000 to 1.41 per 1000 in 2001 and 0.42 per 1000 in 2002. The prevalence within birth cohorts started to decrease for the cohort born between July 1, 1995 and June 30, 1996 (cohort 95/96) and the trend was reinforced for cohort 96/97, suggesting that the exposure of animals to the BSE agent had started to decrease for animals born after July 1995, that is, one year before the ban on specified risk materials in meat and bone meal was implemented in France. However, considering that most of the animals would have been infected at between six and 18 months of age, the decrease may have been due, at least partly, to this control measure.