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.     

Monte Carlo simulation of surveillance strategies for scrapie in Norwegian sheep

Our aim was to compare the efficiency of different surveillance strategies for detecting scrapie-infected sheep flocks in the Norwegian population using simulation modelling.The dynamic Monte Carlo simulation model has the flock as the unit. The input parameters include properties of the sheep population (number of flocks, flock size, age distribution, reasons for culling, breeds, prion protein-allele distribution); properties of scrapie (genotype-dependent infection rate and incubation periods, and age- and genotype-dependent prevalence of scrapie); properties of the surveillance strategy (selection of sheep for examination, period in which infected sheep are detectable, and properties of the diagnostic tests). For simplification, the prion protein-alleles were grouped into three allele groups: VRQ, ARR, and ARQ' (ARQ' represents ARQ, ARH and AHQ).Through either abattoir surveillance or surveillance of fallen stock, 70% of the detected sheep (compared to 33% in the underlying population). The model output was sensitive to the susceptibility of infection for the genotype ARQ'/ARQ'. The effect was large for abattoir surveillance (increased susceptibility increased the efficiency of abattoir surveillance).     

A comparison of the active surveillance of scrapie in the European Union

The abattoir and the fallen stock surveys constitute the active surveillance component aimed at improving the detection of scrapie across the European Union. Previous studies have suggested the occurrence of significant differences in the operation of the surveys across the EU. In the present study we assessed the standardisation of the surveys throughout time across the EU and identified clusters of countries with similar underlying characteristics allowing comparisons between them. In the absence of sufficient covariate information to explain the observed variability across countries, we modelled the unobserved heterogeneity by means of non-parametric distributions on the risk ratios of the fallen stock over the abattoir survey. More specifically, we used the profile likelihood method on 2003, 2004 and 2005 active surveillance data for 18 European countries on classical scrapie, and on 2004 and 2005 data for atypical scrapie separately. We extended our analyses to include the limited covariate information available, more specifically, the proportion of the adult sheep population sampled by the fallen stock survey every year. Our results show that the between-country heterogeneity dropped in 2004 and 2005 relative to that of 2003 for classical scrapie. As a consequence, the number of clusters in the last two years was also reduced indicating the gradual standardisation of the surveillance efforts across the EU. The crude analyses of the atypical data grouped all the countries in one cluster and showed non-significant gain in the detection of this type of scrapie by any of the two sources. The proportion of the population sampled by the fallen stock appeared significantly associated with our risk ratio for both types of scrapie, although in opposite directions: negative for classical and positive for atypical. The initial justification for the fallen stock, targeting a high-risk population to increase the likelihood of case finding, appears compromised for both types of scrapie in some countries.     

Swiss scrapie surveillance. II. Epidemiologic aspects of the detection of neurological diseases in sheep and goats

Monitoring of transmissible spongiform encephalopathy (TSE) in Swiss sheep and goats is based on the examination of animals from different sources. In this study, frequencies and proportions of the different diagnoses were compared between routinely submitted sheep and goats, notified scrapie suspects as well as fallen stock. Meningitis/ encephalitis cases were significantly more frequent (OR = 2.2) in the scrapie suspect group when compared to the routine submissions. Metabolic-toxic encephalopathy was seen more frequently within the fallen stock. Rare neurological diagnoses were more frequent among scrapie suspects and routine submissions when compared to fallen stock. Listeriosis was diagnosed equally frequent among the scrapie suspects and routine submissions but less frequent in fallen stock. Scrapie prevalence among the fallen stock and the routine submissions was 0 (zero), with 95% certainty that prevalence is < 1%. The examined animals are representative for most of the Swiss regions with considerable sheep and goat production. Continuation of the detailed neuropathological examination of small ruminants from these three groups, substituted by actively testing a sufficiently large sample of fallen stock and possibly also healthy-slaughtered adult sheep and goats for transmissible spongiform encephalopathies would ensure a good surveillance within the small ruminant population.     

A Bayesian hierarchical analysis to compare classical and atypical scrapie surveillance data; Wales 2002-2006

We describe the application of Bayesian hierarchical models (BHM) to the analysis of risk of sheep scrapie using data from multiple surveillance sources. More specifically, we analysed data from the test results of three surveillance sources on classical and atypical scrapie in Wales for the period 2002-2006. For each form of scrapie, a BHM was fitted to assess the occurrence of spatial patterns of risk shared by the multiple surveillance sources and the association between covariates and disease. We defined a shared-component model whereby the two types of data sources: exhaustive lists (e.g. reports of clinical cases) and sample-based data sources (e.g. abattoir survey) shared a common spatial pattern of risks at parish level. This shared component was adjusted by a risk-gradient parameter that moderated the individual contribution of the datasets. For both forms of scrapie, the risk-gradient was not significantly different indicating that the sensitivity of the two types of dataset was similar for the two diseases. The spatial patterns of the combinations of data sources appeared similar within disease. However, our results suggest that classical and atypical scrapie differ in their spatial patterns and disease determinants. The joint approach permitted inference from all the available evidence and resulted in robust and less biased estimates of risk, particularly for atypical scrapie where the number of observations was very limited.     

Demographic characteristics of scrapie-affected holdings identified by active and passive surveillance schemes in Great Britain: 2002–2005

Several surveillance techniques have been used to quantify the prevalence of both classical and atypical scrapie in British sheep, namely the recording of clinical suspects (RC) and the testing of animals slaughtered at abattoir (AS) or reported as fallen stock (FS). Any estimate of prevalence based on a particular source is likely to have been affected by demographic differences in the populations sampled. In this study, the demographic characteristics of scrapie-affected holdings detected by each of the surveillance streams (RC, AS, FS) in Great Britain were compared. Analyses of all three streams indicated that the probability of an affected holding being detected by a particular stream differed by geographical area, the number of animals brought onto the holding, the type of scrapie identified (classical vs. atypical) and the year. More detailed analysis of AS and FS suggested that the annual and regional differences between these surveys could be explained by differences in sampling effort.     

A Bayesian zero-truncated approach for analysing capture-recapture count data from classical scrapie surveillance in France

Capture-recapture (CR) methods are used to study populations that are monitored with imperfect observation processes. They have recently been applied to the monitoring of animal diseases to evaluate the number of infected units that remain undetected by the surveillance system. This paper proposes three bayesian models to estimate the total number of scrapie-infected holdings in France from CR count data obtained from the French classical scrapie surveillance programme. We fitted two zero-truncated Poisson (ZTP) models (with and without holding size as a covariate) and a zero-truncated negative binomial (ZTNB) model to the 2006 national surveillance count dataset. We detected a large amount of heterogeneity in the count data, making the use of the simple ZTP model inappropriate. However, including holding size as a covariate did not bring any significant improvement over the simple ZTP model. The ZTNB model proved to be the best model, giving an estimation of 535 (CI(95%) 401-796) infected and detectable sheep holdings in 2006, although only 141 were effectively detected, resulting in a holding-level prevalence of 4.4‰ (CI(95%) 3.2-6.3) and a sensitivity of holding-level surveillance of 26% (CI(95%) 18-35). The main limitation of the present study was the small amount of data collected during the surveillance programme. It was therefore not possible to build complex models that would allow depicting more accurately the epidemiological and detection processes that generate the surveillance data. We discuss the perspectives of capture-recapture count models in the context of animal disease surveillance.     

Swiss scrapie surveillance. I. Clinical aspects of neurological diseases in sheep and goats

Small ruminants infected with scrapie show a large range of often unspecific clinical symptoms. The most-often described signs, locomotion, sensibility and behavioural disorders and emaciation, rarely occur together, and cases have been described in which only one of those signs was detectable.Thus, formulating a well-circumscribed definition of a clinical suspect case is difficult. Most animals with CNS-effecting diseases such as listeriosis, polioencephalomacia, cerebrospinal nematidiasis and enterotoxemia will, in a thorough neurological examination, show at least some scrapie-like symptoms. Among the 22 neurological field cases examined in this study, a goat with cerebral gliomatosis and hair lice showed the closest similarity to clinical scrapie. The unilateral deficiency of the cerebral nerves has potential as an clinical exclusion criterion for scrapie. However, the laboratory confirmation--or exclusion--of scrapie remains important. It thus needs to be realized that a consistent and thorough examination of neurologically diseased small ruminants (including fallen stock) is the backbone of a good surveillance system for these diseases. This should be a motivation for submitting adult sheep and goats for neuropathological examination.     

The impact of the genotype on the prevalence of classical scrapie at population level

ABSTRACT: Total number and genotypes of animals in holdings selected for the genotype & cull option in the Compulsory Scrapie Flock Scheme (CSFS) in Great Britain were extracted from the National Scrapie Plan data warehouse. The association between various genotype-related measures and scrapie prevalence infection was tested using zero-inflated negative binomial models with the counts of positive cases as dependent variable, and country, number of flocks in the scheme, flock size, surveillance source and the following genotype-related measurements: the centered-log ratios (clr) oof the 15 genotypes, of the proportions of the 5 alleles at codons 136, 154 and 171, of the proportions of the 5 NSP types, and two flock-susceptibility risk indicators, as explanatory variables. A total of 319341 genotyped animals from 168 holdings were included in the analysis. An increased proportion of the ARR/ARR genotype corresponded to a decrease in the number of scrapie cases. ARR/AHQ, AHQ/VRQ, ARH/VRQ and ARQ/VRQ genotypes, NSP type V, ARH, ARQ, AHQ and VRQ alleles and the low and high-susceptibility risk indicators are all associated with an increase risk in the number of scrapie cases.Regardless the management practices; the increased susceptibility that the non-ARR alleles confer on an individual could be extrapolated at the population level. Increasing prevalence of ARR allele reduces the overall risk of scrapie at population level. At genotype level, the VRQ/VRQ genotype, present a very low frequency in the study population, seems to play a residual effect in the overall risk of scrapie in a flock.     

The use of pestivirus antigen ELISA currently available for the detection of hairy shaker disease/border disease virus in sheep

AIMS: To estimate the number of cases of scrapie that would occur in sheep of different prion protein (PrP) genotypes if scrapie was to become established in New Zealand, and to compare the performance of two commercially available, rapid ELISA kits using ovine retro-pharyngeal lymph nodes (RLN) from non-infected and infected sheep of different PrP genotypes.

METHODS: Using published data on the distribution of PrP genotypes within the New Zealand sheep flock and the prevalence of cases of scrapie in these genotypes in the United Kingdom, the annual expected number of cases of scrapie per genotype was estimated, should scrapie become established in New Zealand, assuming a total population of 28 million sheep. A non-infected panel of RLN was collected from 737 sheep from New Zealand that had been culled, found in extremis or died. Brain stem samples were also collected from 131 of these sheep. A second panel of infected samples comprised 218 and 117 RLN from confirmed scrapie cases that had originated in Europe and the United States of America, respectively. All samples were screened using two commercial, rapid, transmissible spongiform encephalopathy ELISA kits: Bio-Rad TeSeE ELISA (ELISA-BR), and IDEXX HerdChek BSE-Scrapie AG Test (ELISA-ID).

RESULTS: If scrapie became established in New Zealand, an estimated 596 cases would occur per year; of these 234 (39%) and 271 (46%) would be in sheep carrying ARQ/ARQ and ARQ/VRQ PrP genotypes, respectively. For the non-infected samples from New Zealand the diagnostic specificity of both ELISA kits was 100%. When considering all infected samples, the diagnostic sensitivity was 70.4 (95% CI=65.3–75.3)% for ELISA-BR and 91.6 (95% CI=88.2–94.4)% for ELISA-ID. For the ARQ/ARQ genotype (n=195), sensitivity was 66.2% for ELISA-BR and 90.8% for ELISA-ID, and for the ARQ/VRQ genotype (n=107), sensitivity was 81.3% for ELISA-BR and 98.1% for ELISA-ID.

CONCLUSIONS: In this study, the ELISA-ID kit demonstrated a higher diagnostic sensitivity for detecting scrapie in samples of RLN from sheep carrying scrapie-susceptible PrP genotypes than the ELISA-BR kit at comparable diagnostic specificity.

CLINICAL RELEVANCE: The diagnostic performance of the ELISA-ID kit using ovine RLN merits the consideration of including this assay in the national scrapie surveillance programme in New Zealand.     

Neuropathological survey of fallen stock: active surveillance reveals high prevalence of encephalitic listeriosis in small ruminants

This paper describes the prevalence of brain lesions in the Swiss fallen stock population of small ruminants. 3075 whole brains (75% sheep, 25% goats) were collected as part of a year-long active survey of transmissible spongiform encephalopathies (TSEs) in small ruminants conducted by the Swiss authorities between July 2004 and July 2005. All fallen stock brains were systematically examined by histopathology to obtain reliable data on histologically identifiable brain lesions. Lesions were found in an unexpectedly high number of animals (8.1% of all examined brains). A wide spectrum of diseases was detected showing that this approach provides an excellent opportunity to screen for the prevalence of neurological diseases. Encephalitic listeriosis was by far the most frequent cause of CNS lesions in both species and its prevalence was unexpectedly high when compared to notified confirmed cases. In conclusion, the prevalence of listeriosis as estimated by passive surveillance based on the notification of clinical suspects has been underestimated in the past.     

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.     

Ovine scrapie. New tools for control of an old disease.

Ovine scrapie was described nearly 300 years ago and is endemic in many parts of the world. The recent emergence of a related bovine disease in the United Kingdom and Europe, with probable transmission to humans, has lent urgency to scrapie surveillance and control programs. The biology, genetics, diagnosis, and proposed routes of transmission can be understood in the context of the presumed causative agent, the prion protein. An integrated program of management and husbandry to reduce introduction and spread of the disease within a flock, diagnosis of preclinically infected sheep in both live animal and postmortem settings, and identification of breeding stock of low risk of scrapie are reviewed as the basis for scrapie eradication programs.     

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.     

Characteristics, prevalence and aetiology of lesions of the oral mucosa in adult sheep

A total of 214 sheep with lesions of the oral mucosa were recorded at the Veterinary Laboratories Agency regional laboratories between March 15, 2002 and February 28, 2003. Using denominator data from the scrapie abattoir survey a prevalence of 0.95 per cent (95 per cent CI 0.82 to 1.10 per cent) was recorded, and using the fallen stock survey a prevalence of 1.15 per cent (95 per cent CI 0.64 to 1.91 per cent) was recorded. The lesions varied widely and included dental pad lesions in 20 per cent of cases. In total, 248 sites were affected, the commonest being the lower gum below the incisors, which was affected in 100 sheep. Most of the lesions were 1 cm or less in diameter. Ninety per cent of the 251 lesions examined histologically were erosions, ulcers, healed ulcers, focal epithelial necrosis or haemorrhages, and the changes observed indicated that trauma was the most likely primary cause.     

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.     

Analysis of meat juice ELISA results and questionnaire data to investigate farm-level risk factors for Salmonella infection in UK pigs

The study set out to explore risk factors for Salmonella infection in pigs, based on seroprevalence amongst slaughtered pigs, using a large study population of holdings and a comprehensive list of farm characteristics. Farm data were collected from pig quality assurance schemes and supplemented by a postal questionnaire. These data were used with meat juice serology results from ongoing abattoir Salmonella surveillance, for a multivariable risk factor analysis, modelling the ELISA sample to positive ratio directly (ELISA ratio). The study population contained 566 farms, covering a geographically representative spread of farms within the United Kingdom, with a mean average of 224 sample results per holding over a 4-year period. The model highlighted that temporal factors (quarterly and yearly cycles) and monthly meteorological summaries for rainfall, sunshine and temperature were associated with Salmonella presence (P < 0.01). The ELISA ratio was found to be highest in autumn and lowest in spring and summer, whereas yearly averages showed a greater degree of variation than seasonal. Two feed variables (homemix and barley) were found to be protective factors, as was a conventional, rather than organic or freedom foods, farm enterprise type. The number of annual pig deliveries and dead stock collections, and the main cause of pig mortality on the farm were found to be associated with Salmonella infection. Scottish farms had a lower ELISA ratio than other regions, and an increased number of pig farms within a 10-km radius was associated with a higher ELISA ratio. The study demonstrated that the analysis of routinely collected data from surveillance and quality assurance schemes was cost-effective, with sufficient power to detect modest associations between Salmonella and exposure variables. The model results can be used to inform on-farm Salmonella control policies and could target-specific geographical regions and seasons to assist the efficiency of surveillance.     

Assessment of the utility of routinely collected cattle census and disposal data for syndromic surveillance

Census and disposal data provide a multipurpose source of information on cattle mortality. The retrospective analyses we conducted on the data gathered in the National Cattle Register produced relevant information for describing and modelling the cattle mortality baseline and evaluating the impact of the 2007-2008 Blue Tongue epidemic on the French cattle population. This work was conducted retrospectively but showed that monitoring cattle mortality near real time could help detecting unexpected events. We are thus currently working on a timely and automated system to monitor cadaver disposal requests received by rendering plants, thanks to a data interchange system recently implemented between the Ministry of Agriculture and the fallen stock companies. Besides technical and methodological challenges, using these data for surveillance purposes raises epidemiological questions that still need to be answered. The question remains notably as to whether an abnormal increased mortality is a sensitive and timely signal for detecting unexpected health events. It appears also very challenging to identify the most adequate surveillance scale (time, space and population) and the most adequate anomaly detection algorithms to apply when the characteristics of the signals to be detected (shape, amplitude, etc.) are not known a priori. In Human health, similar systems have not yet proven their ability to detect unexpected events earlier than classical surveillance systems currently in place, but they have already demonstrated their value for real time assessment of identified and potentially dangerous events. Combined with traditional surveillance systems, we think that monitoring routinely collected data could improve the surveillance of the animal population health. Even if not used for detection purposes, cattle mortality monitoring could be used to rapidly produce information on the impact and evolution of identified events, what would facilitate decision-making regarding management measures and improve the communication.     

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.