Quantifying Levels of Peste Des Petits Ruminants (PPR) Virus in Excretions from Experimentally Infected Goats and Its Importance for Nascent PPR Eradication Programme.

Following the successful eradication of rinderpest, the World Organization of Animal Health (OIE) and the Food and Agriculture Organisation (FAO) have set a goal to globally eradicate Peste des petits ruminants (PPR) by 2030. To support the eradication programme we have quantified the levels of PPR virus (PPRV) nucleic acid excreted in body fluids (blood, feces, saliva, nasal and eye swabs) of PPRV-infected goats to ascertain which days post-infection animals are potentially infectious, and hence direct quarantine activities. The data will also indicate optimal sample strategies to assess presence of PPR infection in the naturally infected herd. Peak PPRV nucleic acid detection in different bodily fluids was between 5 and 10 days post-infection. As such, this period must be considered the most infectious period for contact transmission, although high viral load was observed through RNA detection in nasal excretions from two days post-infection until at least two weeks post-infection. Percentage sample positivity was low both in eye swabs and saliva samples during the early stage of infection although RNA was detected as late as two weeks post-infection. From the individual animal data, PPRV was detected later post-infection in fecal material than in other body fluids and the detection was intermittent. The results from this study indicate that nasal swabs are the most appropriate to sample when considering molecular diagnosis of PPRV.

Assessing the variability in transmission of bovine tuberculosis within Spanish cattle herds.

In Spain, despite years of efforts to eradicate bovine tuberculosis (bTB), the disease is still endemic, with some areas of high prevalence. In this context, the surveillance and control plans may need to be re-evaluated, and understanding the dynamics of bTB spread within Spanish herds may help to develop new strategies for reducing the time for detection of infected herds and for the elimination of bTB from the herds already infected. Here, we developed a compartmental stochastic model to simulate bTB within-herd transmission, fed it with epidemiological data from 22 herds (obtained from a previous work) and carried out parameter inference using Approximate Bayesian Computing methods We also estimated the "Within-herd transmission potential Number" (Rh), i.e. the average number of secondary cases generated by a single animal infected introduced into a totally susceptible herd, considering different scenarios depending on the frequency of controls. The median global values obtained for the transmission parameters were: for the transmission coefficient (ß), 0.014 newly infected animals per infectious individual per day (i.e. 5.2 per year), for the rate at which infected individuals become infectious (α), 0.01 per day (equivalent to a latent period of 97 days), and for the rate at which infected individuals become reactive to the skin test (α1), 0.08 per day (equivalent to a period of 12 days for an infected animal to become reactive). However, the results also evidenced a great variability in the estimates of those parameters (in particular ß and α) among the 22 herds. Considering a 6-month interval between tests, the mean Rh was 0.23, increasing to 0.82 with an interval of 1 year, and to 2.01 and 3.47 with testing intervals of 2 and 4 years, respectively.

Inferring within-herd transmission parameters for African swine fever virus using mortality data from outbreaks in the Russian Federation.

Mortality data are routinely collected for many livestock and poultry species, and they are often used for epidemiological purposes, including estimating transmission parameters. In this study, we infer transmission rates for African swine fever virus (ASFV), an important transboundary disease of swine, using mortality data collected from nine pig herds in the Russian Federation with confirmed outbreaks of ASFV. Parameters in a stochastic model for the transmission of ASFV within a herd were estimated using approximate Bayesian computation. Estimates for the basic reproduction number varied amongst herds, ranging from 4.4 to 17.3. This was primarily a consequence of differences in transmission rate (range: 0.7-2.2), but also differences in the mean infectious period (range: 4.5-8.3 days). We also found differences amongst herds in the mean latent period (range: 5.8-9.7 days). Furthermore, our results suggest that ASFV could be circulating in a herd for several weeks before a substantial increase in mortality is observed in a herd, limiting the usefulness of mortality data as a means of early detection of an outbreak. However, our results also show that mortality data are a potential source of data from which to infer transmission parameters, at least for diseases which cause high mortality.

Survival of African Swine Fever Virus in Excretions from Pigs Experimentally Infected with the Georgia 2007/1 Isolate.

African swine fever virus (ASFV) causes a lethal haemorrhagic disease of swine which can be transmitted through direct contact with infected animals and their excretions or indirect contact with contaminated fomites. The shedding of ASFV by infected pigs and the stability of ASFV in the environment will determine the extent of environmental contamination. The recent outbreaks of ASF in Europe make it essential to develop disease transmission models in order to design effective control strategies to prevent further spread of ASF. In this study, we assessed the shedding and stability of ASFV in faeces, urine and oral fluid from pigs infected with the Georgia 2007/1 ASFV isolate. The half-life of infectious ASFV in faeces was found to range from 0.65 days when stored at 4°C to 0.29 days when stored at 37°C, while in urine it was found to range from 2.19 days (4°C) to 0.41 days (37°C). Based on these half-lives and the estimated dose required for infection, faeces and urine would be estimated to remain infectious for 8.48 and 15.33 days at 4°C and 3.71 and 2.88 days at 37°C, respectively. The half-life of ASFV DNA was 8 to 9 days in faeces and 2 to 3 days in oral fluid at all temperatures. In urine, the half-life of ASFV DNA was found to be 32.54 days at 4°C decreasing to 19.48 days at 37°C. These results indicate that ASFV in excretions may be an important route of ASFV transmission.

Mass vaccination, immunity and coverage: modelling population protection against foot-and-mouth disease in Turkish cattle.

Foot-and-mouth disease (FMD) in Turkey is controlled using biannual mass vaccination of cattle. However, vaccine protection is undermined by population turnover and declining immunity. A dynamic model of the Turkish cattle population was created. Assuming biannual mass vaccination with a single-dose primary course, vaccine history was calculated for the simulated population (number of doses and time since last vaccination). This was used to estimate population immunity. Six months after the last round of vaccination almost half the cattle aged < 24 months remain unvaccinated. Only 50% of all cattle would have received > 1 vaccine dose in their life with the last dose given ≤ 6 months ago. Five months after the last round of vaccination two-thirds of cattle would have low antibody titres (< 70% protection threshold). Giving a two-dose primary vaccination course reduces the proportion of 6-12 month old cattle with low titres by 20-30%. Biannual mass vaccination of cattle leaves significant immunity gaps and over-reliance on vaccine protection should be avoided. Using more effective vaccines and vaccination strategies will increase population immunity, however, the extent to which FMD can be controlled by vaccination alone without effective biosecurity remains uncertain.

A Comparison of Dynamics in Two Models for the Spread of a Vector-Borne Disease.

In 2007, bluetongue virus (BTV) was introduced to both Denmark (DK) and the United Kingdom (UK). For this reason, simulation models were built to predict scenarios for future incursions. The DK and UK models have a common description of within-herd dynamics, but differ greatly in their descriptions of between-herd spread, one using an explicit representation of vector dispersal, the other a transmission kernel. Here, we compare model predictions for the dynamics of bluetongue in the UK, based on the 2007 incursion and vaccination rollout in 2008. We demonstrate how an agent-based model shows greater sensitivity to the level of vaccine uptake and has lower variability compared with a kernel-based model. However, a model using a transmission kernel requires less detailed data and is often faster.

Experimental pig-to-pig transmission dynamics for African swine fever virus, Georgia 2007/1 strain.

African swine fever virus (ASFV) continues to cause outbreaks in domestic pigs and wild boar in Eastern European countries. To gain insights into its transmission dynamics, we estimated the pig-to-pig basic reproduction number (R 0) for the Georgia 2007/1 ASFV strain using a stochastic susceptible-exposed-infectious-recovered (SEIR) model with parameters estimated from transmission experiments. Models showed that R 0 is 2·8 [95% confidence interval (CI) 1·3-4·8] within a pen and 1·4 (95% CI 0·6-2·4) between pens. The results furthermore suggest that ASFV genome detection in oronasal samples is an effective diagnostic tool for early detection of infection. This study provides quantitative information on transmission parameters for ASFV in domestic pigs, which are required to more effectively assess the potential impact of strategies for the control of between-farm epidemic spread in European countries.

Thermal inactivation of foot and mouth disease virus in extruded pet food.

The risk of importing foot and mouth disease, a highly contagious viral disease of livestock, severely restricts trade and investment opportunities in many developing countries where the virus is present. This study was designed to investigate the inactivation of foot and mouth disease virus (FMDV) by heat treatments used in extruded commercial pet food manufacture. If extrusion could be shown to reliably inactivate the virus, this could potentially facilitate trade for FMDV-endemic countries. The authors found that there was no detectable virus following: i) treatment of FMDVspiked meat slurry at 68°C for 300 s; ii) treatment of FMDV-spiked slurry and meal mix at 79°C for 10 or 30 s, or iii) treatment of homogenised bovine tongue epithelium, taken from an FMDV-infected animal, at 79°C for 10 s. This corresponds to an estimated 8 log10 reduction in titre (95% credible interval: 6 log10 -13 log10). Furthermore, the authors found that the pH of the slurry and meal mix was sufficient to inactivate FMDV in the absence of heat treatment. This demonstrates that heat treatments used in commercial pet food manufacture are able to substantially reduce the titre of FMDV in infected raw materials.

En raison du risque d'introduction de la fièvre aphteuse, une maladie virale très contagieuse affectant le bétail, les échanges internationaux et les possibilités d'investissement de nombreux pays en développement sont soumis à des restrictions majeures. La présente étude vise à déterminer si les traitements thermiques appliqués lors de la fabrication industrielle d'aliments extrudés destinés aux animaux de compagnie sont efficaces pour inactiver le virus de la fièvre aphteuse dans ces produits. Si la procédure d'extrusion avait pour propriété démontrée d'inactiver le virus de manière fiable, les pays où le virus de la fièvre aphteuse est présent à l'état endémique pourraient accéder plus facilement aux échanges internationaux. Les auteurs n'ont pas trouvé de virus détectable à l'issue des opérations suivantes : i) traitement à 68 °C pendant 300 s d'une bouillie de viandes à laquelle avait été ajoutée une quantité connue de virus de la fièvre aphteuse ; ii) traitement à 79 °C pendant 10 ou 30 s d'un mélange de bouillie et de pâté auquel avait été ajoutée une quantité connue de virus de la fièvre aphteuse ; iii) traitement à 79 °C pendant 10 s d'un échantillon homogénéisé d'épithélium lingual prélevé d'un bovin atteint de fièvre aphteuse. Ces résultats correspondent à une réduction estimée du titre de 8 log10 (intervalle de confiance à 95 % : 6 log10 ­13 log10). En outre, les auteurs ont constaté que le pH du mélange de bouillie et de pâté était de nature à inactiver le virus de la fièvre aphteuse, en l'absence de traitement thermique. Ces résultats démontrent que les traitements thermiques utilisés lors de la fabrication industrielle d'aliments pour animaux de compagnie permettent de réduire de manière importante les titres du virus de la fièvre aphteuse dans les matières premières infectées.

El riesgo de importar fiebre aftosa, enfermedad vírica muy contagiosa que afecta al ganado vacuno, restringe sobremanera el comercio y las oportunidades de inversión en muchos países en desarrollo en los que el virus está presente. Los autores describen un estudio encaminado a analizar el método de inactivación del virus por calor que se emplea en la fabricación industrial de piensos extrusionados para animales de compañía. Si quedaba demostrado que la extrusión es un método fiable para inactivar el virus de la fiebre aftosa, ello podría abrir perspectivas comerciales a todos aquellos países donde dicho virus es endémico. Los autores observaron que no había presencia detectable de virus después de: i) mantener a 68°C durante 300 segundos una emulsión cárnica enriquecida con virus de la fiebre aftosa; ii) mantener a 79°C durante 10 o 30 segundos una emulsión y una mezcla de harinas enriquecidas con el virus; o iii) mantener a 79°C durante 10 segundos un homogenado de epitelio lingual bovino procedente de un animal infectado por el virus. Ello corresponde a una reducción estimada de la titulación de log10 8 (intervalo de confianza al 95%: log10 6 ­ log10 13). Además, los autores observaron que, en ausencia de tratamiento térmico, el pH de la emulsión y la mezcla de harinas bastaba para inactivar el virus de la fiebre aftosa, lo que demuestra que los tratamientos térmicos utilizados en la fabricación industrial de piensos pueden reducir sustancialmente el título de virus de la fiebre aftosa en materias primas infectadas.

Randomised field trial to evaluate serological response after foot-and-mouth disease vaccination in Turkey.

Despite years of biannual mass vaccination of cattle, foot-and-mouth disease (FMD) remains uncontrolled in Anatolian Turkey. To evaluate protection after mass vaccination we measured post-vaccination antibodies in a cohort of cattle (serotypes O, A and Asia-1). To obtain results reflecting typical field protection, participants were randomly sampled from across Central and Western Turkey after routine vaccination. Giving two-doses one month apart is recommended when cattle are first vaccinated against FMD. However, due to cost and logistics, this is not routinely performed in Turkey, and elsewhere. Nested within the cohort, we conducted a randomised trial comparing post-vaccination antibodies after a single-dose versus a two-dose primary vaccination course. Four to five months after vaccination, only a third of single-vaccinated cattle had antibody levels above a threshold associated with protection. A third never reached this threshold, even at peak response one month after vaccination. It was not until animals had received three vaccine doses in their lifetime, vaccinating every six months, that most (64% to 86% depending on serotype) maintained antibody levels above this threshold. By this time cattle would be >20 months old with almost half the population below this age. Consequently, many vaccinated animals will be unprotected for much of the year. Compared to a single-dose, a primary vaccination course of two-doses greatly improved the level and duration of immunity. We concluded that the FMD vaccination programme in Anatolian Turkey did not produce the high levels of immunity required. Higher potency vaccines are now used throughout Turkey, with a two-dose primary course in certain areas. Monitoring post-vaccination serology is an important component of evaluation for FMD vaccination programmes. However, consideration must be given to which antigens are present in the test, the vaccine and the field virus. Differences between these antigens affect the relationship between antibody titre and protection.

Veterinary and human vaccine evaluation methods.

Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines.

Retrospective evaluation of foot-and-mouth disease vaccine effectiveness in Turkey.

Foot-and-mouth disease (FMD) is present in much of Turkey and its control is largely based on vaccination. The arrival of the FMD Asia-1 serotype in Turkey in 2011 caused particular concern, spreading rapidly westwards across the country towards the FMD free European Union. With no prior natural immunity, control of spread would rely heavily on vaccination. Unlike human vaccines, field protection is rarely evaluated directly for FMD vaccines. Between September 2011 and July 2012 we performed four retrospective outbreak investigations to assess the vaccine effectiveness (VE) of FMD Asia-1 vaccines in Turkey. Vaccine effectiveness is defined as the reduction in risk in vaccinated compared to unvaccinated individuals with similar virus exposure in the field. The four investigations included 12 villages and 1230 cattle >4 months of age. One investigation assessed the FMD Asia-1 Shamir vaccine, the other three evaluated the recently introduced FMD Asia-1 TUR 11 vaccine made using a field isolate of the FMD Asia-1 Sindh-08 lineage that had recently entered Turkey. After adjustment for confounding, the TUR 11 vaccine provided moderate protection against both clinical disease VE=69% [95% CI: 50%-81%] and infection VE=63% [95% CI: 29%-81%]. However, protection was variable with some herds with high vaccine coverage still experiencing high disease incidence. Some of this variability will be the result of the variation in virus challenge and immunity that occurs under field conditions. In the outbreak investigated there was no evidence that the Asia-1 Shamir vaccine provided adequate protection against clinical FMD with an incidence of 89% in single vaccinated cattle and 69% in those vaccinated two to five times. Based on these effectiveness estimates, vaccination alone is unlikely to produce the high levels of herd immunity needed to control FMD without additional control measures.

Does covering of farm-associated Culicoides larval habitat reduce adult populations in the United Kingdom?

Culicoides biting midges (Diptera: Ceratopogonidae) are the biological vectors of a range of internationally important arboviruses of livestock, including bluetongue virus (BTV) and the recently emerging Schmallenberg virus (SBV). Culicoides species in the subgenus Avaritia (in the UK: Culicoides obsoletus Meigen, Culicoides scoticus Downes & Kettle, Culicoides dewulfi Goetghebuer and Culicoides chiopterus Meigen) have been implicated in BTV transmission in northern Europe and to a varying degree utilise cattle dung as a larval development substrate. The collection of cattle dung into heaps on farms provides a localised source of Culicoides emergence in close proximity to livestock. This study assesses the impact of covering dung heaps prior to the onset of adult Culicoides activity with the aim of reducing recruitment to the local adult populations at four livestock farms in England. Light suction trap catches of adult Culicoides from these farms were compared with those from four untreated control farms from a wide geographic range across the UK. It was demonstrated that implementing control of emergence from dung heaps did not have a significant impact upon the local adult subgenus Avaritia abundance at the treated farm holdings and that the onset of Culicoides activity was similarly unaffected. Use of this method in isolation is unlikely to have an effect in reducing the risk of BTV and SBV transmission. The implications of these results for control of farm-associated Culicoides in Europe are discussed.

The accuracy of the National Equine Database in relation to vector-borne disease risk modelling of horses in Great Britain.

REASONS FOR PERFORMING THE STUDY: The National Equine Database (NED) contains information on the size and distribution of the horse population, but the data quality remains unknown. These data could assist with surveillance, research and contingency planning for equine infectious disease outbreaks. OBJECTIVES: 1) To assess the extent of obsolete and missing data from NED, 2) evaluate the extent of spatial separation between horse and owner location and 3) identify relationships between spatial separation and land use. METHODS: Two questionnaires were used to assess data accuracy in NED utilising local authority passport inspections and distribution of questionnaires to 11,000 horse owners. A subset of 1010 questionnaires was used to assess horse-owner geographic separation. RESULTS: During 2005-2010, 17,048 passports were checked through local authority inspections. Of these, 1558 passports (9.1%; 95% confidence interval [CI] 8.7-9.5%) were noncompliant, with 963 (5.6%; 95% CI 5.3-6.0%) containing inaccurate information and 595 (3.5%; 95% CI 3.2-3.8%) classified as missing. Of 1382 questionnaires completed by horse owners, 380 passports were obsolete (27.5%; 95% CI 25.2-29.9%), with 162 (11.7%; 95% CI 10.0-13.4%) being retained for deceased horses and 218 (15.8%; 95% CI 13.9-17.7%) having incorrect ownership details. Fifty-three per cent (95% CI 49.9-56.1%) of owners kept their horse(s) at home and 92% (95% CI 90.3-93.7%) of horses resided within 10 km of their owners. CONCLUSIONS AND POTENTIAL RELEVANCE: Data from a small sample survey suggest the majority of data on NED are accurate but a proportion of inaccuracies exist that may cause delay in locating horses and contacting owners during a disease outbreak. The probability that horses are located in the same postcode sector as the owner's home address is larger in rural areas. Appropriate adjustment for population size, horse-owner spatial separation and land usage would facilitate meaningful use of the national horse population derived from NED for risk modelling of incursions of equine diseases into Great Britain.

Investigating incursions of bluetongue virus using a model of long-distance Culicoides biting midge dispersal.

Bluetongue virus (BTV) is an economically important pathogen of ruminants that is the aetiological agent of the haemorrhagic disease bluetongue. Bluetongue virus is biologically transmitted by Culicoides biting midges (Diptera: Ceratopogonidae), and long-range dispersal of infected vector species contributes substantially to the rapid spread of the virus. The range of semi-passive flights of infected Culicoides on prevailing winds has been inferred to reach several hundred kilometres in a single night over water bodies. In this study, an atmospheric dispersion model was parameterized to simulate Culicoides flight activity based on dedicated entomological data sets collected in the UK. Five outbreaks of BTV in Europe were used to evaluate the model for use as an early warning tool and for retrospective analyses of BTV incursions. In each case, the generated predictions were consistent with epidemiological observations confirming its reliability for use in disease outbreak management. Furthermore, the model aided policy makers to predict, contain and eradicate BTV outbreaks in the UK during 2007 and 2008.

Comparison of pre-emptive and reactive strategies to control an incursion of bluetongue virus serotype 1 to Great Britain by vaccination.

Bluetongue (BT) is a disease of ruminants caused by bluetongue virus (BTV), which is spread between its hosts by Culicoides midges. Vaccination is the most effective way to protect susceptible animals against BTV and was used reactively to control the recent northern European outbreak. To assess the consequences of using vaccination pre-emptively we used a stochastic, spatially explicit model to compare reactive and pre-emptive vaccination strategies against an incursion of BTV serotype 1 (BTV-1) into Great Britain. Both pre-emptive and reactive vaccination significantly reduced the number of affected farms and limited host morbidity and mortality. In addition, vaccinating prior to the introduction of disease reduced the probability of an outbreak occurring. Of the strategies simulated, widespread reactive vaccination resulted in the lowest levels of morbidity. The predicted effects of vaccination were found to be sensitive to vaccine efficacy but not to the choice of transmission kernel.

The vegetative and minimally conscious states: a review of the literature and preliminary survey of prevalence in Ireland.

BACKGROUND: In the absence of reliable, objective and direct measures of awareness, the diagnosis and prognosis of the vegetative and minimally conscious states are greatly complicated. This has led to an unacceptably high level of misdiagnosis. Although diagnosis and prognosis have typically relied on bedside behavioural measures, a number of recent studies on neuroimaging and neurophysiological methods offer the possibility of improvement in these areas. OBJECTIVES: We examined current clinical practice and possible future directions in the diagnosis, prognosis and treatment of disorders of consciousness, as well as the ethical and legal dilemmas associated with these disorders. We also summarise epidemiological data from three specialist rehabilitation hospitals in Ireland. CONCLUSIONS: We recommend an international agreement on standard behavioural assessment. This would enable greater consistency in diagnosis and prognostication, as well as improved accuracy of epidemiological data. Based on the current evidence, we advocate the introduction of neuroimaging and neurophysiological techniques into the standardised investigation profile. A more detailed epidemiological study is also required in Ireland.

Scaling from challenge experiments to the field: Quantifying the impact of vaccination on the transmission of bluetongue virus serotype 8.

Bluetongue (BT) is an economically important disease of ruminants caused by bluetongue virus (BTV) and transmitted by Culicoides biting midges. The most practical and effective way to protect susceptible animals against BTV is by vaccination. Data from challenge studies in calves and sheep conducted by Intervet International b.v., in particular, presence of viral RNA in the blood of challenged animals, were used to estimate vaccine efficacy. The results of the challenge studies for calves indicated that vaccination is likely to reduce the basic reproduction number (R(0)) for BTV in cattle to below one (i.e. prevent major outbreaks within a holding) and that this reduction is robust to uncertainty in the model parameters. Sensitivity analysis showed that the whether or not vaccination is predicted to reduce R(0) to below one depended on the following assumptions: (i) whether "doubtful" results from the challenge studies are treated as negative or positive; (ii) whether or not the probability of transmission from host to vector is reduced by vaccination; and (iii) whether the extrinsic incubation period follows a realistic gamma distribution or the more commonly used exponential distribution. For sheep, all but one of the vaccinated animals were protected and, consequently, vaccination will consistently reduce R(0) in sheep to below one. Using a stochastic spatial model for the spread of BTV in Great Britain (GB), vaccination was predicted to reduce both the incidence of disease and spatial spread in simulated BTV outbreaks in GB, in both reactive vaccination strategies and when an incursion occurred into a previously vaccinated population.

The impact of sheep breed on the risk of classical scrapie.

The risk of classical scrapie in sheep is associated with polymorphisms in the prion protein (PrP) gene. In recent years, large-scale selective breeding programmes for sheep at lower risk of disease have been undertaken across the European Union. We analysed large-scale datasets on scrapie and sheep demography to investigate additional effects of sheep breed on scrapie risk. There was evidence for variation between certain breeds in the scrapie risk of some PrP genotypes, which could be caused by innate breed differences or distinct scrapie strains circulating within them. While the PrP genotypes of cases are generally consistent across breeds, some exceptions provide evidence that scrapie strain may influence affected PrP genotypes to a greater extent than innate breed differences. There was a significant association between the breed-level incidence of scrapie and the frequency of susceptible PrP genotypes in breeds. Our results lend support to selective breeding programmes which aim to reduce the frequency of high-risk PrP genotypes with measures not varying by sheep breed.

Prevalence of sheep infected with classical scrapie in Great Britain, 1993-2007.

Extensive surveillance for classical scrapie has been carried out in Great Britain since 1993, the results of which can be used for monitoring the effect of control measures introduced since 2001. A back-calculation approach was used to estimate the prevalence of sheep infected with classical scrapie, which integrates data on reported clinical cases (1993-2007) and the results of fallen stock and abattoir surveys (2002-2007). The prevalence of classical scrapie in GB was fairly constant until 2003, although the estimates depended on assumptions made about the performance of diagnostic tests used in the surveys. If infected animals could be detected in the final quarter of the incubation period, the estimated prevalence was 0.6-0.7%, while if they could be detected in the final half of the incubation period, it was 0.3-0.4%. Between 2003 and 2007 the prevalence declined by around 40%, and the magnitude of the reduction was independent of assumptions made about the diagnostic tests.