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 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.     

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.     

Questionnaire analysis of BSE cases in France detected by active surveillance and the reasons for non-notification

A mandatory reporting system (MRS) was set up in France in December 1990 to detect animals showing clinical signs of bovine spongiform encephalopathy (BSE). Since June 2000, four active surveillance programmes dedicated to fallen stock and slaughtered cattle have been implemented to reinforce the MRS. The clinical status of the cases detected through these programmes was investigated to understand why the MRS had failed to detect them. Up to September 1, 2002, 181 cases had been analysed (126 fallen stock and 55 slaughtered cattle). Almost all the fallen stock cases were animals which had been showing clinical signs, and two thirds of them had shown signs which should have led to a suspicion of BSE. No clinical signs had been reported for two thirds of the slaughtered cattle cases and 10 (8 per cent) of the fallen stock cases.     

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.     

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.     

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.     

Imported and indigenous BSE cases in Germany

Bovine spongiform encephalopathy (BSE) is a transmissible fatal neurodegenerative disease in cattle with an average incubation time of five years. The first BSE case in an indigenous cow was detected in Germany in November 2000. This was almost eight years after the huge BSE epidemic in the United Kingdom had peaked, and several years after many EU member states had seen their first BSE case. In the 1990s, BSE had been diagnosed in six imported animals in Germany. However, after the implementation of an active surveillance programme using BSE rapid testing systems, 399 indigenous German BSE cases have been found up to the end of July 2006. The birth cohorts of 1995-1997 contribute to the vast majority of the first 250 German cases that were diagnosed between 2000 and 2003. However, the most recent German BSE cases belong primarily to the birth cohorts 1998-2000 which is indicative of a recycling of BSE infectivity at that time. Moreover, there were two BSE cases in cattle born in spring 2001, i.e. after the meat and bone meal feed ban had come into effect on 2nd December 2000. In this article, we describe the dynamics of the German BSE epidemic and compare these data with those of other countries that observed larger numbers of cases.     

Animal feeding and feed legislation after the detection of the first indigenous BSE cases in Germany

In Great Britain, even the earliest tangible signs indicating the epidemiologic significance of meat and bone meal in the spreading of BSE soon gave rise to increasingly rigorous legislative measures regulating animal feedstuffs. In 1994 a ban on the feeding of animal proteins to ruminants was implemented throughout the entire EU. But until the first BSE cases were actually confirmed in locally raised cattle (November 2000), feeding practice and legislation more or less in Germany remained unaffected by the efforts undertaken in Great Britain. This situation was suddenly changed on 1 December, 2000, when the so-called "Verfütterungsverbot" was put into effect, a law which drastically extended bans regarding the feedstuffs (including fishmeal and animal fats) as well as the species concerned (all animals used in food production). In 2001 the "contamination" phenomenon (ingredients of animal origin were detected in mixed feeds) became a vital issue for the feed industry; through the media, the subject "feedstuff safety" gained a previously unseen level of public awareness. Those circles concerned with mixed feed production and animal husbandry were increasingly confronted with the consequences of the "Verfütterungsverbot" (availability and pricing of substitute ingredients; the demand for amino acids and inorganic sources of phosphorus; problems finding adequate substitutes for animal fats; poor digestibility of alternative components such as indigenous legumes or vegetable fats in calf diets; lower utilization rate of original phosphorus in mixed feeds with negative consequences for skeletal development). With the conditional approval of fishmeal (except in feeds for ruminants) the situation has eased again to a certain degree; on the EU level there are increasing signals pointing toward a political intention to reinstate the utilization of by-products of slaughtered animals qualified for human consumption (with the exception of fallen/dead animals and specific risk material) in poultry and swine feeding. In Germany, at least, the question of animal fat utilization for food-producing animals is still unsolved.     

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.     

Prognosis for presumed feline vaccine-associated sarcoma after excision: 61 cases (1986-1996)

OBJECTIVE: To evaluate time to first recurrence (TFR) and overall survival in cats with presumed vaccine-associated sarcomas (VAS) treated with excision. DESIGN: Retrospective study. ANIMALS: 61 cats with presumed VAS. PROCEDURE: Medical records of cats that received excision as the only initial treatment for presumed VAS were reviewed to evaluate prognosis. Overall survival curves and TFR were determined. RESULTS: Median TFR was 94 days. Median TFR for tumors treated with excision performed at a referral institution (274 days) was significantly longer than that for tumors excised by a referring veterinarian (66 days). Radical first excision yielded significantly longer median TFR (325 days) than did marginal first excision (79 days). Cats with tumors located on the limbs had longer median TFR (325 days) than cats with tumors located in other sites (66 days). Median overall survival time was 576 days. Significant differences in survival times between groups were not detected. Few cats (13.8%) receiving only surgical treatment had long-term (> 2 years) survival. CONCLUSIONS AND CLINICAL RELEVANCE: Radical first excision of presumed VAS is essential for extended TFR. Current recommendations for vaccination of the distal portions of the extremities are appropriate, because this practice permits radical excision of tumors (amputation) that develop at vaccination sites; however, surgery alone is seldom curative.     

BSE infection in bovine PrP transgenic mice leads to hyperphosphorylation of tau-protein

We observed the changes in the central nervous system (CNS) of transgenic mice expressing bovine prion protein (Bo-PrP) as a contribution to our knowledge of the pathogenesis of bovine spongiform encephalopathy (BSE). The main result was the detection of hyperphosphorylated tau. This protein was detected for the first time, using immunohistochemical techniques, in the neurons and glial cells of mice experimentally infected with BSE. The results highlighted the involvement of tau protein in the pathogenesis of BSE and the close link between hyperphosphorylated tau deposits and prion protein. Ultrastructural examination revealed a novel arrangement of intraneuronal tau deposits not hitherto reported.     

Prevalence of Cryptosporidium infection in calves in France

Two multicentre surveys were conducted in France to estimate the prevalence of Cryptosporidium infection in calves using qualitative ELISA for detection of Cryptosporidium coproantigens and oocysts. The first survey involved 4-12-day-old calves in six dairy-calf distribution centres, collecting calves from seven Administrative Regions (Aquitaine, Bretagne, Franche-Comté, Lorraine, Normandie, Nord, Pays de Loire). For each region, 20 calves were selected every month for 12 consecutive months (October 1995-September 1996). Prevalence of Cryptosporidium infection was 17.9% (Confidence Intervals (C.I.) 95%=[16.1%; 19.8%]) among the 1628 selected calves, of which only 5.3% had diarrhoea. The second survey conducted between November 1995 and May 1996 involved 4-21-day-old calves examined by veterinary practitioners who selected 189 livestock farms of dairy- or suckler-type in ten Administrative Departments (Allier, Cantal, Creuse, Doubs, Ille-et-Vilaine, Maine-et-Loire, Manche, Pas-de-Calais, Sa?ne-et-Loire, Vendée). Cryptosporidia were detected in 105 (55.6%) of the farms. Among the 440 calves examined, of which 398 (90.5%) presented diarrhoea, cryptosporidia were found in 191 animals, i.e. a prevalence of 43.4% (C.I. 95%=[38. 8%; 48.0%]). Breed of calves and type of housing had very little impact on prevalence in this survey. Some regional variations could be noticed, even if cryptosporidia infection is widespread. Monthly variations could be related to seasonal peaks in calving with a lower infection rate during summer.