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.     

Application of one-list capture-recapture models to scrapie surveillance data in Great Britain

In this paper, we apply one-list capture-recapture models to estimate the number of scrapie-affected holdings in Great Britain. We applied this technique to the Compulsory Scrapie Flocks Scheme dataset where cases from all the surveillance sources monitoring the presence of scrapie in Great Britain, the abattoir survey, the fallen stock survey and the statutory reporting of clinical cases, are gathered. Consequently, the estimates of prevalence obtained from this scheme should be comprehensive and cover all the different presentations of the disease captured individually by the surveillance sources. Two estimators were applied under the one-list approach: the Zelterman estimator and Chao's lower bound estimator. Our results could only inform with confidence the scrapie-affected holding population with clinical disease; this moved around the figure of 350 holdings in Great Britain for the period under study, April 2005-April 2006. Our models allowed the stratification by surveillance source and the input of covariate information, holding size and country of origin. None of the covariates appear to inform the model significantly.     

Descriptive epidemiology of scrapie in Great Britain: results of a postal survey

In 1998, a questionnaire was sent to 11,554 British sheep farmers to determine how many believed that scrapie cases had occurred in their flock; 61.4 per cent of them responded anonymously. The results indicated that 14.9 per cent of farmers with more than 30 breeding ewes thought that they had ever experienced scrapie in their flock and 2.7 per cent thought that they had had cases in the past 12 months. A comparison of these results with the number of farmers reporting suspect scrapie cases to MAFF, in accordance with the statutory requirement, suggests that only 13 per cent of farmers who suspect that they may have cases of scrapie are currently reporting them. Scrapie occurred in all regions of the country but there was an apparent regional variation. Larger farms and those with purebred sheep appeared to be at greater risk of having cases. Other differences between affected and unaffected farms included lambing practices and sheep purchasing policy. On the majority of farms the first case occurred in a purchased animal. The survey also revealed a need for the provision of further information about scrapie to farmers.     

A case study of capture-recapture methodology using scrapie surveillance data in Great Britain

We applied capture–recapture methodology (CRC) to data from three surveillance sources (statutory notification, abattoir survey (AS) and fallen stock (FS) survey) to estimate the number of holdings infected with scrapie in Great Britain and to assess the sensitivity of the surveillance network. Between January 1, 2002 and March 31, 2003, 144 holdings were identified by the three sources. Using CRC modelling techniques, we estimated a minimum lower bound for the total number of holdings infected as 642. A biologically plausible positive dependence between the statutory reporting and the fallen stock survey was found statistically significant. The sensitivity of the three sources combined was very low. The integration of the three overlapping sources provided a better understanding of the interactions within the surveillance network. However, the scarcity of the data and reduced overlapping among sources only allowed for very cautious inferences to be drawn about the true proportion of scrapie affected holdings in the national population. Future surveys and surveillance activities should be planned such that the resulting data can be used more effectively as part of CRC modelling approaches.     

A stochastic model to estimate the prevalence of scrapie in Great Britain using the results of an abattoir-based survey

In 1997/1998, an abattoir survey was conducted to determine the likely exposure of the human population to transmissible spongiform encephalopathy (TSE) infection in sheep submitted for slaughter in Great Britain. The survey examined brain material from 2809 sheep processed through British abattoirs. Sampling was targeted by age: 45% of animals tested were ≥15 months old. All samples of adequate quality (98%) were tested for signs of scrapie infection using histopathology and scrapie-associated fibril (SAF) detection and 500 were tested using immunohistochemistry (IHC). No conclusive positive animals were found using either histology or IHC. Ten animals were positive by SAF. Standard statistical analyses suggest (with 95% confidence) that the prevalence of detectable (by histopathology) infection in the slaughter population was ≤0.11%. However, the incubation period of scrapie is long (usually around 2–3 years) and none of the tests used in the survey is capable of detecting scrapie infection in the early stages of infection. We present an age-structured stochastic model incorporating parameters for the incubation period of scrapie, prevalence of infection by age and test sensitivity. Using the model, we demonstrate that the negative results obtained for all samples using IHC and histopathology are consistent with a true prevalence of infection in the slaughter population of up to 11%. This suggests that up to 300 of the animals tested might have been infected but the infection was not sufficiently advanced in these animals to be detectable by IHC or histopathology. The survey was designed to detect a prevalence of 1% with a precision of ±0.5% and a confidence level of 95% in each age group assuming that diagnostic tests were 100% specific and sensitive from a known stage in the incubation period. The results of the model demonstrate that to estimate a true prevalence of scrapie infection of 1% with an accuracy of ±0.5% would have required a far larger sample size. An accurate estimate of the required sample size is complicated by uncertainty about test sensitivity and the underlying infection dynamics of scrapie. A pre-requisite for any future abattoir survey is validation of the diagnostic tests used in relation to both stage of incubation and genotype. Sampling in the <15-month age group was of no value in this survey because the diagnostic tests used were thought to be ineffective in most of the animals in this age group.     

Analysis of data from the passive surveillance of scrapie in Great Britain between 1993 and 2002

Reports of clinical scrapie in Great Britain between January 1, 1993 and December 31, 2002 were reviewed. Scrapie was confirmed in 4142 sheep on 1099 holdings. The cumulative case and holding incidence risks decreased in 2001, probably owing to the outbreak of foot-and-mouth disease, although there were regional variations. Sheep aged between three and four years old constituted the largest affected group. In the period between 1998 and 2002, 51.3 per cent of the cases had the genotype ARQ/VRQ, 19.3 per cent were ARQ/ARQ and 18.9 per cent were VRQ/VRQ; Swaledale, Shetland and Welsh mountain sheep were the most common pure breeds reported. The areas at highest risk were the Shetland Islands, followed by the south and east of England.     

Descriptive analysis of the results of an anonymous postal survey of the occurrence of scrapie in Great Britain in 2002

An anonymous postal survey was conducted in 2002 to estimate the proportion of farms in Great Britain affected with scrapie and to gather information on the likely risk factors for the occurrence of the disease; the response rate was 53 per cent. The survey showed that 1 per cent of the respondents thought they had had scrapie in their flock in the previous 12 months, and that 12 per cent thought they had had scrapie in the past. The results of the survey were consistent with the results of a similar survey carried out in 1998, and with notification patterns, but in 1998 approximately 3 per cent of farmers reported having had scrapie in the previous 12 months. It is not clear whether the apparent decrease in the prevalence of scrapie is real or whether it may be due to factors such as sampling biases, or to the increasing knowledge of the signs of scrapie shown by the respondents in 2002.     

The evolution of the prevalence of classical scrapie in sheep in Great Britain using surveillance data between 2005 and 2012

After the decline of the Bovine Spongiform Encephalopathy (BSE) epidemic in Great Britain (GB), scrapie remains the most prevalent animal Transmissible Spongiform Encephalopathy (TSE) present in GB. A number of control measures have been implemented for classical scrapie, and since 2005 there has been a large reduction in the number of observed cases. The objective of this study is to estimate two measures of disease frequency using up to date surveillance data collected during and after the implementation of different control measures established since 2004, and breeding for resistance schemes that ran from 2001 until 2009. This would enable an assessment of the effectiveness of both the breeding for resistance programme and the compulsory eradication measures in reducing the prevalence of scrapie in GB. Evaluation of the sensitivity of the rapid post-mortem test for scrapie indicated that it detected scrapie in the last 25% of the incubation period. A back-calculation model was developed to estimate the prevalence of infection at animal and flock-level. The results of the model indicated a mean drop of infection prevalence of 31% each year, leading to a 90% drop in infection prevalence between 2005, with an estimate of 5737 infected sheep in GB in 2012.     

Selection of Swaledale sheep of reduced susceptibility to experimental scrapie

A flock of 294 Swaledale sheep was injected with brain tissue from different sources so as to include strains of natural scrapie currently affecting the Swaledale breed. Discounting intercurrent deaths, 85 per cent of the flock developed clinical scrapie within an observation period of 2557 days (seven years). Scrapie cases fell into distinct early and late groups, occurring at (mean +/- sem) 287 +/- 7 days and 1207 +/- 38 days after injection, respectively. Breeding groups were formed from the survivors after the early cases had occurred and successive lamb crops were produced. Two groups of progeny and two groups of controls were injected with scrapie. The incidence of scrapie in the progeny (27 per cent) was much lower than in the controls (64 per cent). The incidence in the progeny was also assessed in relation to the response of their parents: it was high (about 40 per cent) when one or both parents developed late scrapie but otherwise very low (about 5 per cent). Hence the progeny of surviving parents had a greatly reduced susceptibility to the strains of scrapie used. Seventy-two of these selected progeny formed a nucleus flock which is being bred at Redesdale. The next stage of the experiment is to assess the effect of selected rams in recorded flocks with a high incidence of natural scrapie.     

A questionnaire survey of the prevalence of scrapie in sheep in Britain

An anonymous, self-administered questionnaire has been used in two independent surveys to try to determine the prevalence of scrapie in the national sheep flock. The disease was recorded in 35 counties in England and Wales. About a third (26.5 and 37.3 percent) of respondents owning 100 or more sheep indicated that they had seen sheep with scrapie in their flocks. The incidences of clinical cases recorded in affected flocks in the two surveys were 0.5 and 1.1 cases/100 ewes/year. At present there is no control over the disposal of these animals. If as has been suggested, an increase in the prevalence of scrapie was a contributory factor in the emergence of bovine spongiform encephalopathy, it would seem logical that measures should be introduced to monitor the prevalence and incidence of scrapie and to control the disposal of clinical cases.     

Genetic susceptibility to scrapie in sheep: a clinically relevant theme in veterinary medical education

RATIONALE FOR THIS STUDY: This article describes and evaluates two molecular biology practical classes based around the theme of genetic susceptibility to scrapie in sheep. These practical classes allow students to experience a range of molecular biology techniques in the context of a clinically based genetic disease. METHODOLOGY: The two molecular biology practical classes described are evaluated in terms of their perceived usefulness to study by first-year veterinary medicine students. The students' ratings are then assessed in relation to the approaches to studying (i.e., deep, strategic, and surface). These dimensions of learning are measured using the 52-item Approaches to Studying Inventory (ASI). RESULTS: The overall ratings from students in relation to both the practical classes were found to be positive. The scrapie genotyping practical was the highest-ranking laboratory-based practical in the first-year curriculum. Ratings in terms of usefulness to studies for both practical classes were found to be significantly higher for students with higher deep learning scores. CONCLUSION: The practical classes described here provide a clinically relevant scenario within which molecular biology concepts and methods can be illustrated to veterinary students. The positive correlation with deep learning is more evident for the scrapie genotyping practical than for the DNA extraction practical. This may reflects the complexity of the former, which is greater both technically and conceptually.