title: Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle - an update.
abstract: BACKGROUND
  To provide information on dose-response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of the bovine prion protein gene on disease incidence and revises estimates of effective oral exposure.
  
  
  RESULTS
  Following interim published results, two further cattle, one dosed with 100 mg and culled at 127 months post exposure and the other dosed with 10 mg and culled at 110 months post exposure, developed BSE. Both had a similar pathological phenotype to previous cases. Based on attack rate and incubation period distribution according to dose, the dose estimate at which 50% of confirmed cases would be clinically affected was revised to 0.15 g of the brain homogenate used in the experiment, with a 95% confidence interval of 0.03-0.79 g. Neither the full open reading frame nor the promoter region of the prion protein gene of dosed cattle appeared to influence susceptibility to BSE, but this may be due to the sample size.
  
  
  CONCLUSIONS
  Oral exposure of cattle to a large range of doses of a BSE brainstem homogenate produced disease in all dose groups. The pathological presentation resembled natural disease. The attack rate and incubation period were dependent on the dose.
authors.affiliation: Specialist Scientific Support Department, Animal Health and Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, UK. timm.konold@ahvla.gsi.gov.uk
authors.forename: Timm
authors.initials: T
authors.lastname: Konold
authors.forename: Mark E
authors.initials: ME
authors.lastname: Arnold
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Austin
authors.forename: Saira
authors.initials: S
authors.lastname: Cawthraw
authors.forename: Steve A C
authors.initials: SA
authors.lastname: Hawkins
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stack
authors.forename: Marion M
authors.initials: MM
authors.lastname: Simmons
authors.forename: A Robin
authors.initials: AR
authors.lastname: Sayers
authors.forename: Michael
authors.initials: M
authors.lastname: Dawson
authors.forename: John W
authors.initials: JW
authors.lastname: Wilesmith
authors.forename: Gerald A H
authors.initials: GA
authors.lastname: Wells
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001933:Brain Stem / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism* / Q000473:pathology / Q000635:transmission; D005838:Genotype; D055256:Infectious Disease Incubation Period; D008954:Models, Biological; D016366:Open Reading Frames; D010641:Phenotype; D011328:Prions / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D013997:Time Factors; D014020:Tissue Extracts / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D011328:Prions; D014020:Tissue Extracts