title: A stochastic model to estimate the prevalence of scrapie in Great Britain using the results of an abattoir-based survey.
abstract: 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.
authors.affiliation: Department of Epidemiology, VLA Weybridge, New Haw, Addlestone, Surrey KT15 3NB, UK. crw1005@cam.ac.uk
authors.forename: C R
authors.initials: CR
authors.lastname: Webb
authors.forename: J W
authors.initials: JW
authors.lastname: Wilesmith
authors.forename: M M
authors.initials: MM
authors.lastname: Simmons
authors.forename: L J
authors.initials: LJ
authors.lastname: Hoinville
mesh_terms: D000003:Abattoirs / Q000706:statistics & numerical data*; D000818:Animals; D001921:Brain / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000662:veterinary; D015233:Models, Statistical; D018622:PrP 27-30 Protein / Q000302:isolation & purification*; D012608:Scrapie / Q000453:epidemiology* / Q000473:pathology / Q000635:transmission; D012680:Sensitivity and Specificity; D012756:Sheep; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D018622:PrP 27-30 Protein