Presence Of Bovine Spongiform Encephalopathy Research Articles

BSE can propagate in sheep co-infected or pre-infected with scrapie

To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotypes either at the same time as subcutaneous challenge with scrapie, or three months later. In addition, VRQ/VRQ sheep naturally infected with scrapie after being born into a scrapie-affected flock were challenged subcutaneously with BSE at eight or twenty one months-of-age. Sheep were analysed by incubation period/attack rate, and western blot of brain tissue determined the presence of BSE or scrapie-like PrPSc. Serial protein misfolding cyclic amplification (sPMCA) that can detect very low levels of BSE in the presence of an excess of scrapie agent was also applied to brain and lymphoreticular tissue. For VRQ/ARQ sheep challenged with mixed infections, scrapie-like incubation periods were produced, and no BSE agent was detected. However, whilst ARQ/ARQ sheep developed disease with BSE-like incubation periods, some animals had a dominant scrapie western blot phenotype in brain, but BSE was detected in these sheep by sPMCA. In addition, VRQ/VRQ animals challenged with BSE after natural exposure to scrapie had scrapie-like incubation periods and dominant scrapie PrPSc in brain, but one sheep had BSE detectable by sPMCA in the brain. Overall, the study demonstrates for the first time that for scrapie/BSE mixed infections, VRQ/ARQ sheep with experimental scrapie did not propagate BSE but VRQ/VRQ sheep with natural scrapie could propagate low levels of BSE, and whilst BSE readily propagated in ARQ/ARQ sheep it was not always the dominant PrPSc strain in brain tissue. Indeed, for several animals, a dominant scrapie biochemical phenotype in brain did not preclude the presence of BSE prion.

Absence of classical and atypical (H- and L-) BSE infectivity in the blood of bovines in the clinical end stage of disease as confirmed by intraspecies blood transfusion.

While the presence of bovine spongiform encephalopathy (BSE) infectivity in the blood of clinically affected sheep has been proven by intraspecies blood-transfusion experiments, this question has remained open in the case of BSE-affected cattle. Although the absence of infectivity can be anticipated from the restriction of the agent to neuronal tissues in this species, evidence for this was still lacking. This particularly concerns the production and use of medicinal products and other applications containing bovine blood or preparations thereof. We therefore performed a blood-transfusion experiment from cattle in the clinical end stage of disease after experimental challenge with either classical (C-BSE) or atypical (H- and l-) BSE into calves at 4–6 months of age. The animals were kept in a free-ranging group for 10 years. Starting from 24 months post-transfusion, a thorough clinical examination was performed every 6 weeks in order to detect early symptoms of a BSE infection. Throughout the experiment, the clinical picture of all animals gave no indication of a BSE infection. Upon necropsy, the brainstem samples were analysed by BSE rapid test as well as by the highly sensitive Protein Misfolding Cyclic Amplification (PMCA), all with negative results. These results add resilient data to confirm the absence of BSE infectivity in the donor blood collected from C-, H- and l-BSE-affected cattle even in the final clinical phase of the disease. This finding has important implications for the risk assessment of bovine blood and blood products in the production of medicinal products and other preparations.

Household behavior with respect to meat consumption in the presence of BSE and CWD

AbstractIn this study, Canadian household meat consumption behavior in exotic (deer and elk meat) and traditional meats (beef, pork, chicken, turkey, bison, and seafood) is examined. This research introduces some differences in public response to transmissible spongiform encephalopathies (TSE) risks across consumer segments from different sources of meat supply, including hunted meat. The analysis uses a combination of survey and household meat purchase data that include a balanced household panel of 2,393 households per year across time. A two‐step estimation procedure is used with a probit model in the first step (consume or not) and a doublelog–translog two‐stage demand system in the second step (level of consumption). It is assumed and tested that household sociodemographics, consumers’ risk perceptions/attitudes, and media coverage of bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) are underlying demand shifters in consumers’ daily meat purchase decision. The results suggest that households who obtain venison from hunting show the highest confidence in venison safety. Exotic meat preferences negatively affect traditional meat consumption in the daily diets of households who purchase traditional meats from stores and obtain venison from hunting. In response to the media coverage of BSE and CWD, exotic meat eaters are less sensitive to animal disease media information than the general population.

Does the Presence of Scrapie Affect the Ability of Current Statutory Discriminatory Tests To Detect the Presence of Bovine Spongiform Encephalopathy?

Current European Commission (EC) surveillance regulations require discriminatory testing of all transmissible spongiform encephalopathy (TSE)-positive small ruminant (SR) samples in order to classify them as bovine spongiform encephalopathy (BSE) or non-BSE. This requires a range of tests, including characterization by bioassay in mouse models. Since 2005, naturally occurring BSE has been identified in two goats. It has also been demonstrated that more than one distinct TSE strain can coinfect a single animal in natural field situations. This study assesses the ability of the statutory methods as listed in the regulation to identify BSE in a blinded series of brain samples, in which ovine BSE and distinct isolates of scrapie are mixed at various ratios ranging from 99% to 1%. Additionally, these current statutory tests were compared with a new in vitro discriminatory method, which uses serial protein misfolding cyclic amplification (sPMCA). Western blotting consistently detected 50% BSE within a mixture, but at higher dilutions it had variable success. The enzyme-linked immunosorbent assay (ELISA) method consistently detected BSE only when it was present as 99% of the mixture, with variable success at higher dilutions. Bioassay and sPMCA reported BSE in all samples where it was present, down to 1%. sPMCA also consistently detected the presence of BSE in mixtures at 0.1%. While bioassay is the only validated method that allows comprehensive phenotypic characterization of an unknown TSE isolate, the sPMCA assay appears to offer a fast and cost-effective alternative for the screening of unknown isolates when the purpose of the investigation was solely to determine the presence or absence of BSE.

The role of mathematical modelling in understanding the epidemiology and control of sheep transmissible spongiform encephalopathies: a review

To deal with the incompleteness of observations and disentangle the complexities of transmission much use has been made of mathematical modelling when investigating the epidemiology of sheep transmissible spongiform encephalopathies (TSE) and, in particular, scrapie. Importantly, these modelling approaches allow the incidence of clinical disease to be related to the underlying prevalence of infection, thereby overcoming one of the major difficulties when studying these diseases. Models have been used to investigate the epidemiology of scrapie within individual flocks and at a regional level; to assess the efficacy of different control strategies, especially selective breeding programmes based on prion protein (PrP) genotype; to interpret the results of scrapie surveillance; and to inform the design of surveillance programmes. Furthermore, mathematical modelling has played an important role when assessing the risk to human health posed by the possible presence of bovine spongiform encephalopathy in sheep. Here, we review the various approaches that have been taken when developing and analysing mathematical models for the epidemiology and control of sheep TSE and assess their impact on our understanding of these diseases. We also identify areas that require further work, discuss future challenges and identify data gaps.

Simulation of the options for a national control programme to eradicate scrapie from Great Britain

Because of the risk to public health posed by the potential presence of bovine spongiform encephalopathy (BSE) in sheep, there are plans to eradicate transmissible spongiform encephalopathies (TSEs) from the British sheep population. We used a mathematical model for the spread of scrapie between sheep flocks to assess the efficacy of five control strategies at eradicating the infection from the national flock. These range from ram-genotyping schemes through whole-flock genotyping with selective culling to whole-flock slaughter. The impact of control was considered under three scenarios for the long-term dynamics of scrapie in GB: two in which scrapie is ultimately eliminated (with different median extinction times) and one in which scrapie remains endemic. Results suggested that it is feasible to eradicate scrapie from the British sheep flock, but that any national control programme will take decades to eliminate the disease and be costly. The most-effective strategy, measured in terms of the probability of eradication and time taken for eradication, was predicted to be whole-flock culling, which was effective under all three scenarios for the long-term dynamics of scrapie. Strategies involving whole-flock genotyping with selective culling were also effective, though they were predicted to take longer to eradicate scrapie than whole-flock culling. Ram-genotyping schemes were effective in some instances, but not for the scenario where scrapie remained endemic in the national flock. At low levels of reporting of clinical disease (<20%) the probability of eradication within 100 years was predicted to be <100% and, consequently, low levels of reporting could compromise the effectiveness of a control programme. Moreover, the predicted time taken to eradicate scrapie would increase markedly if the reporting compliance decreased.

A Comparison of Rapid Bovine Spongiform Encephalopathy Testing Methods on Autolyzed Bovine Brain Tissue

In 1999, the European Union (EU) approved 3 rapid methods for the testing of bovine brain samples for the presence of bovine spongiform encephalopathy (BSE). The evaluation that led to the approval did not include an analysis of autolyzed material. Member states of the EU have active surveillance programs for BSE, which target fallen stock as well as other categories of cattle. Autolysis is a common feature of fallen stock samples because there can be a considerable delay between death and collection of samples. Therefore, it is important to know whether these tests perform optimally on autolyzed samples. The Veterinary Laboratories Agency (VLA) selected 250 positive fallen stock samples. These had been detected during routine testing using the Prionics-Check Western blot and confirmed as BSE cases by immunohistochemistry or electron microscopy. Samples were graded according to the degree of autolysis and then tested by the 3 methods: Prionics-Check Western blot, Platelia test, and Enfer test. All 3 methods correctly classified the samples as positive BSE cases, therefore alleviating doubt about their ability to do so. Subsequent EU validation exercises, such as those conducted in 2002--2003, have included the testing of autolyzed material. It is important that all new methods be evaluated on autolyzed tissue before approval for official use.

The Role of CEA (Center of Animal Encephalopathies) in the BSE Surveillance: BSE in Italy

Bovine spongiform encephalopathy (BSE) is a neurodegenerative disease that affects cattle, associated with the detection of a protease-resistant protein called PrPsc. BSE was detected first in the UK (Wells et al., 1987) and then described in many European countries, including Italy (Guarda et al., 1994). Exposure to the agent of BSE is the most probable cause of a new disease in man, variant Creutzfeldt–Jakob disease (Bruce et al., 1997; Hill et al., 1997). The evidence prompted public concern about the human risk in consumption of bovine-derived products and led to enhanced surveillance of BSE, which was in the early years based on the passive approach. This kind of surveillance identified the only two BSE cases in Italy up to 2001. The introduction in Italy of a system of active surveillance for BSE using the new rapid test in January 2001 has provided the opportunity to ascertain the presence of BSE in indigenous Italian cows. Between January and 5 September, 230 670 samples were examined by the national network of the Istituti Zooprofilattici and 26 positive BSE cases were detected, with a prevalence of 1.13 per 10 000 animals tested. Nine of these belonged to risk categories (3 fallen stock and 6 emergency slaughter) and 17 were regularly slaughtered cattle. The prevalence is 1.3 per animal tested. All the cases except two were born after the 1994 feed ban. The mean age at diagnosis was 6 years (range 4–13 years). The neuropathology of all 21 Italian BSE cases is chacterized by the same patterns of spongiosis (degree and distribution) and PrP immunopositivity as those reported in other European countries (Wells et al., 1992; Orge et al., 2001; Tegtmeier et al., 2001), although the histology, immunohistochemistry (IHC) and Western blot (WB) findings were limited to the same sample taken for the rapid test (a section of pons at the cerebellar peduncles and obex level). Conspicuous spongiosis in the neuropil of the grey matter and neuronal perikarya vacuolation were observed in all cases except for one that showed minimal spongiform changes. In all the other cases, severe vacuolar changes occurred in the neuropil, mainly in the solitary tract nucleus and in nucleus of the spinal tract of V; mild spongiosis was observed in the dorsal nucleus of the vagus nerve. Vacuolization of neuronal perikarya was predominantly observed in the vestibular nuclear complex, in the reticular formation and, to a lesser extent, in the dorsal nucleus of the vagus. Mild astrocytosis was visualized in each sample by