Modelling studies to estimate the prevalence of foot-and-mouth disease carriers after reactive vaccination.

Foot-and-mouth disease (FMD) is a highly contagious and economically significant viral disease of cloven-hoofed animals. Vaccination can be used to help restrict the spread of the infection, but evidence must be provided to show that the infection has been eradicated in order to regain the FMD-free status. While serological tests have been developed, which can identify animals that have been infected regardless of vaccination status, it is vital to know the probable prevalence of herds with FMD carriers and the within-herd prevalence of those carriers in order to design efficient post-epidemic surveillance strategies that establish freedom from disease. Here, we present the results of a study to model the expected prevalence of carriers after application of emergency vaccination and the impact of this on the sensitivity of test systems for their detection. Results showed that the expected prevalence of carrier-containing herds after reactive vaccination is likely to be very low, approximately 0.2%, and there will only be a small number of carriers, most likely one, in the positive herds. Therefore, sensitivity for carrier detection can be optimized by adopting an individual-based testing regime in which all animals in all vaccinated herds are tested and positive animals rather than herds are culled.

Use of laboratory data to reduce the time taken to detect new diseases: VIDA to FarmFile.

The analysis of laboratory data can provide information about the health of livestock populations; in Great Britain the Veterinary Investigation Diagnosis Analysis (VIDA) system has provided such data since 1975. However VIDA covers only known diagnoses, with limited epidemiological characterisation. The unexpected outbreak of bse showed that it was necessary to improve surveillance to detect new diseases, and a necessary update of the VIDA database for the millennium date change provided the opportunity. The information required to enhance the value of laboratory data was identified, a new form and database, 'FarmFile', were designed to record it, and they began to be used in 1999. The detection of new diseases depends on making comparisons with the expected or 'usual' levels of unexplained disease. The data are analysed quarterly to assess any changes in the levels of unexplained disease in different species, categorised in terms of clinical sign or body system, by comparison with previous years. No new diseases have been detected either through FarmFile or more traditional means since the new analyses started in earnest in 2004, but they have indicated that an unexplained event was not a new disease of concern, and developments continue to improve the system's sensitivity and specificity.

Clinical and laboratory investigations of the outbreaks of foot-and-mouth disease in southern England in 2007.

A case of foot-and-mouth disease (fmd) on a cattle farm in Normandy, Surrey, was confirmed on Friday August 3, 2007, the first case in the uk since 2001. The infection was detected nearby on a second farm on August 6. On September 12, fmd was confirmed on a farm approximately 20 km from Normandy in Egham, and this was followed by cases on five more farms in that area in the next three weeks. The majority of the infected farms consisted of multiple beef cattle holdings in semi-urban areas. In total, 1578 animals were culled on the infected farms, and fmd virus infection was confirmed in 278 of them by the detection of viral antigen, genome or antibodies to the virus, or by clinical signs. This paper describes the findings from animal inspections on the infected farms, including the estimated ages of the fmd lesions and the numbers of animals infected. It also summarises the test results from samples taken for investigation, including the detection of preclinically viraemic animals by using real-time reverse transcriptase-pcr.

A model (BSurvE) for estimating the prevalence of bovine spongiform encephalopathy in a national herd.

We developed the BSurvE spreadsheet model to estimate the true prevalence of bovine spongiform encephalopathy (BSE) in a national cattle population, and evaluate national BSE surveillance programs. BSurvE uses BSE surveillance data and demographic information about the national cattle population. The proportion of each cohort infected with BSE is found by equating the observed number of infected animals with the number expected, following a series of probability calculations and assuming a binomial distribution for the number of infected animals detected in each surveillance stream. BSurvE has been used in a series of international workshops, where analysis of national datasets demonstrated patterns of cohort infection that were consistent with infection-control activities within the country. The results also reflected the timing of known events that were high-risk for introduction of the infectious agent.

A model (BSurvE) for evaluating national surveillance programs for bovine spongiform encephalopathy.

Our BSurvE spreadsheet model estimates the BSE prevalence in a national cattle population, and can be used to evaluate and compare alternative strategies for a national surveillance program. Each individual surveillance test has a point value (based on demographic and epidemiological information) that reflects the likelihood of detecting BSE in an animal of a given age leaving the population via the stated surveillance stream. A target sum point value for the country is calculated according to a user-defined design prevalence and confidence level, the number of cases detected in animals born after the selected starting date and the national adult-herd size. Surveillance tests carried out on different sub-populations of animals are ranked according to the number of points gained per unit cost, and the results can be used in designing alternative surveillance programs.

Risk-based surveillance for H5N1 avian influenza virus in wild birds in Great Britain.

Recent outbreaks of the H5N1 strain of avian influenza in Europe have highlighted the need for continuous surveillance and early detection to reduce the likelihood of a major outbreak in the commercial poultry industry. In Great Britain (gb), one possible route by which H5N1 could be introduced into domestic poultry is through migratory wild birds from Europe and Asia. Extensive monitoring data on the 24 wild bird species considered most likely to introduce the virus into GB, and analyses of local poultry populations, were used to develop a risk profile to identify the areas where H5N1 is most likely to enter and spread to commercial poultry. The results indicate that surveillance would be best focused on areas of Norfolk, Suffolk, Lancashire, Lincolnshire, south-west England and the Welsh borders, with areas of lower priority in Anglesey, south-west Wales, north-east Aberdeenshire and the Firth of Forth area of Scotland. These areas have significant poultry populations including a large number of free-range flocks, and a high abundance of the 24 wild bird species.

Descriptive spatial analysis of scrapie-affected flocks in Great Britain between January 1993 and December 2002.

The spatial distribution of sheep flocks in Great Britain with confirmed clinical scrapie between January 1993 and December 2002 inclusive was investigated by using kernel density estimation and a cluster scan test statistic. Six statistically significant clusters were identified: three were lower risk, and were centred on the north-western coast of Scotland, the north-western coast of Wales and the South Yorkshire/Pennine region; three were of higher risk, and were centred in the central south, North Yorkshire and north Cumbria. General knowledge and the results of previous epidemiological studies were used to generate biologically plausible hypotheses that might explain these findings. They included aspects of flock management and disease transmission, and factors associated with the identification of cases, including their detection, recognition and, in particular, reporting levels, as well as diagnosis and animal movements.

Trends in age at detection in cases of bovine spongiform encephalopathy in Belgium: an indicator of the epidemic curve.

There were 118 cases of bovine spongiform encephalopathy (BSE) in Belgium before January 1, 2004. Trends in their age at detection were analysed and attempts were made to use this parameter as a predictor of the current status of the BSE epidemic in the country. The following variables were considered: date of birth, breed, date of detection, mode of detection, and the number and age of animals slaughtered and rendered each month. Age at detection as a function of date of birth was a very poor epidemiological indicator. It was concluded that the increasing age of BSE cases when they were detected was due to the depletion of cases, as a result of there being no new infections, and that it is a reliable indicator of a decrease in the epidemic curve in Belgium. By means of a simulation it is shown how age distribution at the time of detection closely follows the epidemic curve and data from Great Britain are used to illustrate the point.

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.

Area-level risks for BSE in British cattle before and after the July 1988 meat and bone meal feed ban.

In this paper we investigate area-level risk factors for BSE for the cattle population present in Great Britain between 1986 and 1997. By dividing this population into two birth cohorts, those born before the July 1988 ban on feeding ruminant-derived meat and bone meal to ruminants and those born after, second-order regional influences are distinguished from the strong first-order south-to-north gradient of area-level BSE risk using Bayesian hierarchical models that account for structured (spatially correlated) and unstructured heterogeneity in the data. For both cohorts area-level risk of BSE was increased by a more southerly location and greater numbers of dairy cattle, relative to non-dairy cattle. For the cohort of cattle born after the July 1988 ban on feeding ruminant-derived meat and bone meal area-level BSE risk was additionally associated with greater numbers of pigs, relative to cattle. These findings support the role of low level cross-contamination of cattle feed by pig feed as an influence on BSE incidence risk as the epidemic evolved. Prior to the 1988 meat and bone meal ban unexplained BSE risk was relatively uniformly distributed across the country whereas after the ban there were spatially aggregated areas of unexplained risk in the northern and eastern regions of England suggesting that local influences allowed BSE control measures to be less-successfully applied in these areas, compared with the rest of the country. We conclude that spatially localised influences were operating in divergent ways during the two phases of the epidemic.

The neuropathology and epidemiology of bovine spongiform encephalopathy.

Bovine spongiform encephalopathy (BSE), defined originally from its characteristic neuropathology, retains a place of particular interest in the scrapie-like or prion disease group, presenting uniquely an example of such diseases occurring as a nationwide food-borne epidemic in Great Britain. Comprehensive monitoring of the epidemic, both pathologically and epidemiologically, has facilitated our present understanding of the disease. BSE presents the classical neuropathological features of the transmissible spongiform encephalopathies. Although particularly similar to natural scrapie of sheep, BSE has, unlike scrapie, a stereotypic lesion profile from which it has been concluded that host and agent factors, including probably the strain of agent, which influence the profile, are constant in this disease. Neuronal loss in BSE may make an important but hitherto inapparent contribution to functional deficits. Preliminary ultrastructural studies have confirmed light microscopic features of brain changes in BSE but have as yet not established significant new findings. Immunohistochemical studies of PrP accumulation reveal distinctive forms and distributions of immunolabelling, confirming features reported previously in experimental models of scrapie, including perineuronal and perineuritic "synapse-like" reactivity. The histopathological diagnosis of BSE, validated on a single section of the medulla for the statutory diagnosis of large numbers of cases, is supplemented where necessary by fibril (SAF) examination which performs similarly to the histological diagnosis in the majority of cases. Epidemiological studies of BSE have supported the pathological findings that there is no detectable variation in susceptibility within the cattle population. The detailed monitoring of the epidemic has revealed the expected effects on the incidence as a result of statutory measures intended to prevent food-borne exposure after July 1988. The main effect has been a reduction in the national incidence during 1993 which has been continued into 1994. Analytical studies have not revealed any means of transmission, other than the food-borne source, capable of maintaining the epidemic in Great Britain. An international comparison of risk factors for the occurrence of BSE indicates that an epidemic of similar magnitude outside the British Isles is unlikely.

Bovine spongiform encephalopathy: a neuropathological perspective.

The occurrence of bovine spongiform encephalopathy (BSE), recognition that it is a new scrapie-like disease epidemic in domestic cattle in the United Kingdom and concern of a remote zoonotic potential has, in four years, produced a plethora of documented information. While much of this information has been communicated outwith the scientific literature, this review attempts to summarise, from a neuropathological viewpoint, the main findings to emerge. The initial studies established the nosological homology of BSE with the subacute spongiform encephalopathies or "prion" diseases of animals and man. Epidemiological data are consistent with an extended common source epidemic originating from an abrupt change, commencing in 1981-82, in the exposure of domestic cattle to a scrapie-like agent in meat and bone meal incorporated into commercial animal feedstuffs. It is currently proposed that the method of production of meat and bone meal has contributed vital factors to the change in exposure. Invariability of the distribution pattern of vacuolar pathology in the natural disease and on primary transmission to cattle suggests a uniformity of the pathogenesis of BSE. Studies in mice suggest uniformity also of the biological properties of different BSE isolates but indicate that the properties differ from those of sheep scrapie isolates. Human health risks, although perceived to be negligible, have been addressed by various strategies including statutory measures and long term monitoring.

Analysis of dam-calf pairs of BSE cases: confirmation of a maternal risk enhancement.

We investigate whether a calf born to a dam that develops bovine spongiform encephalopathy (BSE) (prior or subsequent to the birth) is itself at an enhanced risk of developing BSE. Analyses utilize the main database on reported BSE cases in the British cattle herd maintained by the Central Veterinary Laboratory in Weybridge to trace the dams of BSE-affected animals born following the ruminant feed ban in July 1988. The data reveal a significantly enhanced risk of disease in calves born to BSE-affected dams, with the risk being greatest when birth occurs after the onset of clinical signs of disease in the dam. The dependence of the maternally enhanced risk on the maternal incubation stage at birth argues for a significant component of direct maternal transmission of the aetiological agent of BSE, and offers little support for the hypothesis of genetic predisposition. Using a statistical likelihood model, we obtain estimates of the rate of direct maternal transmission by maternal incubation stage; however, biases in the available data make these values minimum estimates.

Bovine spongiform encephalopathy. Epidemiology, low dose exposure and risks.

BSE has occurred in the U.K. as an extended common source epidemic since 1985/86. The vehicle of infection was concentrated feeds containing meat and bone meal produced by the rendering of ovine, bovine and other animal wastes. The epidemic was probably initiated in 1981/82 when a sudden decline in the use of solvents in rendering allowed a low incidence of scrapie-like infection to occur in cattle. However, the presence in feed of bovine material that, from 1984/85 (or earlier), was increasingly infected with a cattle-adapted strain of agent amplified the epidemic greatly. Nevertheless, the incidence of BSE cases nationally has been low because of the generally low effective exposure of cattle to infection in feed. This, and a combination of risk factors that were probably unique to the U.K. can explain why relatively few cases of BSE have occurred in other countries. The feeding of ruminant-derived protein to all species of ruminants was banned in Great Britain in 1988, and in Northern Ireland in 1989. A more selective approach was subsequently adopted to minimize the risks of BSE infection of other species, including man. This was based on excluding from food a small number of bovine offals whose use and predicted infectivity titers would constitute the greatest potential source of infection. Recent studies of BSE support the basis of the specified bovine offals ban and suggest that more tissues were restricted than may have been necessary.

Epidemiology of bovine spongiform encephalopathy and related diseases.

The occurrence of bovine spongiform encephalopathy in Great Britain, first detected in 1986, has necessarily stimulated a large research programme. Encompassed in this are studies of the epidemiology of the disease. These commenced in 1987 and are continuing. The ensuing results have been reported and reviewed during the course of the epidemic. This paper provides a brief overview of the results of the epidemiological studies, but concentrates on the more recent features of the epidemic which are important in assessing the future course of the disease.

Surveillance of BSE.

The current method used to identify suspect BSE cases is based on reporting cattle displaying clinical signs compatible with BSE. The reporting of such cases is dependent on the ability of farmers and veterinarians to recognise the disease symptoms and on the willingness to report such cases. Furthermore, it depends on the stage of the disease, because early clinical signs of BSE are not always typical. Histology and immunohistochemistry are established and reliable to confirm BSE in cattle, but the procedure is cumbersome, time consuming and therefore not suited for mass testing of animals. A targeted surveillance system using the Prionics-Western-Blot Test was initiated in Switzerland in 1999. Prionics-positive results are confirmed by histology or immunohistochemistry by the BSE-reference laboratory. This surveillance scheme has confirmed fallen stock and cows subjected to emergency slaughter as the major risk groups. Currently all cattle from these two categories are tested. As a further measure a random sample of cows from regular slaughtering is tested. This enables to determine the BSE status independent of the inaccuracies of a clinical case reporting system. This approach may be helpful to reliably assess the BSE situation in countries with low incidence in order to verify their BSE status and in countries which want to prove their BSE-free status.

Tuberculosis in badgers (Meles meles).

This review examines the incidence of tuberculosis in badgers, the pathogenesis and diagnosis of the disease in the badger, and the control prospects related to spread of tuberculosis from badgers to cattle.

Estimation of the age-dependent risk of infection to BSE of dairy cattle in Great Britain.

An important aspect of the bovine spongiform encephalopathy (BSE) epidemic has been an apparent age-dependent risk of infection, with younger cattle being more likely to become infected than older cattle. Our objective was to determine the age-dependent risk of infection of dairy cattle. We first reviewed unpublished data on the feeding patterns of proprietary concentrates for dairy-replacement cattle. These data showed that autumn- and spring-born cattle would receive different feeding patterns of proprietary concentrates, and so age-dependent risk of infection profiles were obtained separately for autumn- and spring-born cattle. We used back-calculation methods to analyse BSE-epidemic data collected in Great Britain between 1984 and 1996. Dairy cattle were most at risk in the first 6 months of life; adult cattle were at relatively low risk of infection. Between 6 and 24 months of age, risk profiles reflected feeding patterns of proprietary concentrates in each of the autumn- and spring-born cohorts.

Spatio-temporal epidemiology of foot-and-mouth disease in two counties of Great Britain in 2001.

The spatial, temporal, and spatio-temporal features of the 2001 British foot-and-mouth disease epidemic in selected areas within the counties of Cumbria and Devon, which experienced the greatest incidence of disease, are described using hazard functions, extraction mapping and the space-time K-function. In Cumbria, the hazard of foot-and-mouth disease infection peaked at 2.8% in the week commencing 8 March 2001 and farm holdings in this area continued to be identified with disease to 12 September 2001. In contrast, peak infection hazard in Devon was 0.7% in the week commencing 15 March 2001 and eradication of the disease was achieved in this area by 31 May 2001. Persistence of the disease in Cumbria was consistent with: (1) many cattle holdings infected early in the epidemic (creating a high environmental viral load), and (2) a relatively large amount of medium-to-long-distance spread of the virus associated with seasonal farming activities-compounded to some extent by the movement of people and vehicles between disaggregated farm land parcels. The interaction of disease risk in Cumbria showed that premises remained infectious for longer throughout May, June and July, consistent with delays in disease detection during this period.

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 > or =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 < or =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.