Case-control study of cases of bovine spongiform encephalopathy born after July 31, 1996 (BARB cases) in Great Britain.

This paper reports the results of a case-control study of the bovine spongiform encephalopathy (BSE) cases born in Great Britain after the statutory reinforcement of the ban (BARB) on the feeding of mammalian-derived meat and bone meal on 31 July 1996. A total of 499 suspect clinical cases of BSE, born after 31 July 1996, and reported negative by July 31, 1996 and were compared with the set of 164 confirmed Great BARB cases in Great Britain detected by both passive and active surveillance. Animal-level risk factors (age and type of feed offered) and herd-level risk factors (herd size and type, number of prereinforced feed ban BSE cases born on the holding, the presence of other domestic species and waste management) were obtained for the analysis. BARB cases were 2.56 times (95 per cent CI 1.29 to 5.07) more likely to be exposed to homemix or a combination of homemix and proprietary feeds were 0.59 times (95 per cent CI 0.50 to 0.69) as less likely to be exposed to the unit increases in the number of prereinforced feed ban BSE cases diagnosed on the natal holding. A supplementary spatial analysis of these cases revealed three areas of excess BARB density: Northwest and Southwest of Wales and Northeast of Scotland.

Descriptive epidemiological features of cases of bovine spongiform encephalopathy born after July 31, 1996 in Great Britain.

This paper describes the results of analyses of the epidemiological features of the 164 cases of bovine spongiform encephalopathy (BSE) in Great Britain that were born after the introduction of the reinforced legislation introduced on August 1, 1996 (BARB cases) and that were detected before December 31, 2008. This additional control measure prohibited the use of mammalian meat and bone meal (MMBM) in feed for farm animals to prevent further exposure of cattle to the BSE agent. There was a pronounced reduction in the risk of infection, by three orders of magnitude, for cattle born after July 31, 1996 compared with that for cattle born earlier, and a statistically significant exponential reduction in the estimated prevalence between successive annual birth cohorts after this date. There was no evidence that a significant number of these cases occurred as a result of a maternally associated risk factor, infection from environmental contamination (other than from feedstuffs) or as a result of a genetically based aetiology. The epidemiological features were consistent with an exogenous feedborne source as a result of a reliance on imported feedstuffs in Great Britain and the later introduction of a ban on the use of MMBM in other EU member states on January 1, 2001.

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.

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.

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.

The importance of the PrP genotype in active surveillance for ovine scrapie.

Surveillance activities for ovine scrapie have expanded in the 21st century, following concerns about the potential for a hidden epidemic of bovine spongiform encephalopathy in European sheep populations. Large-scale surveys have been used to estimate the prevalence of scrapie infection. In this study we analyse data from the surveys in Great Britain between 2002 and 2004. When we estimate genotype-specific prevalences for each of the two screening tests used a difference is observed. One test underestimates the number of positive cases in genotypes classically considered to be at a low relative risk of developing clinical disease (ARR- and AHQ-containing genotypes). By comparison, the other test underestimates the number of positive cases in genotypes classically considered to be at an increased relative risk of developing clinical disease (VRQ-containing genotypes). These findings have implications for surveillance, disease control, and diagnostic test evaluation.

A comparison of predictions made by three simulation models of foot-and-mouth disease.

AIMS: To describe results of a relative validation exercise using the three simulation models of foot-and-mouth disease (FMD) in use by the quadrilateral countries (QUADS; Australia, Canada, New Zealand, and United States of America; USA). METHODS: A hypothetical population of farms was constructed and, following the introduction of an FMD-like disease into a single farm, spread of disease was simulated using each of the three FMD simulation models used by the QUADS countries. A series of 11 scenarios was developed to systematically evaluate the key processes of disease transmission and control used by each of the three models. The predicted number of infected units and the size of predicted outbreak areas for each scenario and each model were compared using the Kruskal-Wallis test. Agreement among the three models in terms of geographical areas predicted to become infected were quantified using Fleiss' Kappa statistic. RESULTS: Although there were statistically significant differences in model outputs in terms of the numbers of units predicted to become infected, the temporal onset of infection throughout the simulation period, and the spatial distribution of infected units, these differences were generally small and would have resulted in the same (or similar) management decisions being adopted in each case. CONCLUSIONS: Agreement among the three models in terms of the numbers of premises predicted to become infected, the temporal onset of infection throughout the simulation period, and the spatial distribution of infected premises provides evidence that each of the model developers are consistent in their approach to simulating the spread of disease throughout a population of susceptible individuals. This consistency implies that the assumptions taken by each development team are appropriate, which in turn serves to increase end-user confidence in model predictions. CLINICAL RELEVANCE: Relative validation is one of a number of steps that can be undertaken to increase end-user confidence in predictions made by infectious disease models.

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.

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.

Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle.

The dose-response of cattle exposed to the bovine spongiform encephalopathy (BSE) agent is an important component of modelling exposure risks for animals and humans and thereby, the modulation of surveillance and control strategies for BSE. In two experiments calves were dosed orally with a range of amounts of a pool of brainstems from BSE-affected cattle. Infectivity in the pool was determined by end-point titration in mice. Recipient cattle were monitored for clinical disease and, from the incidence of pathologically confirmed cases and their incubation periods (IPs), the attack rate and IP distribution according to dose were estimated. The dose at which 50 % of cattle would be clinically affected was estimated at 0.20 g brain material used in the experiment, with 95 % confidence intervals of 0.04-1.00 g. The IP was highly variable across all dose groups and followed a log-normal distribution, with decreasing mean as dose increased. There was no evidence of a threshold dose at which the probability of infection became vanishingly small, with 1/15 (7 %) of animals affected at the lowest dose (1 mg).

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.

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.

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.

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.