title: Estimating the temporal relationship between PrPSc detection and incubation period in experimental bovine spongiform encephalopathy of cattle.
abstract: This study examines tissues from sequential-kill, time-course pathogenesis studies to refine estimates of the age at which disease-specific PrP (PrP(Sc)) can first be detected in the central nervous system (CNS) and related peripheral nervous system ganglia of cattle incubating bovine spongiform encephalopathy (BSE). Such estimates are important for risk assessments of the age at which these tissues should be removed from cattle at slaughter to prevent human and animal exposure to BSE infection. Tissues were examined from cattle dosed orally with 100 or 1 g BSE-infected brain. Incubation period data for the doses were obtained from attack rate and the sequential-kill studies. A statistical model, fitted by maximum likelihood, accounted for the differences in the lognormal incubation period and the logistic probability of infection between different dose groups. Initial detection of PrP(Sc) during incubation was invariably in the brainstem and the earliest was at 30 and 44 months post-exposure for the 100 g- and 1 g-dosed sequential-kill study groups, respectively. The point at which PrP(Sc) in 50 % of the animals would be detected by immunohistochemistry applied to medulla-obex was estimated at 9.6 and 1.7 months before clinical onset for the 100 g- and 1 g-dosed cattle, respectively, with a low probability of detection in any of the tissues examined at more than 12 months before clinical onset. PrP(Sc) was detected inconsistently in dorsal root ganglia, concurrent with or after detection in CNS, and not at all in certain sympathetic nervous system ganglia.
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Arnold
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: J B M
authors.initials: JBM
authors.lastname: Ryan
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: T
authors.initials: T
authors.lastname: Konold
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Simmons
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: Y I
authors.initials: YI
authors.lastname: Spencer
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: A
authors.initials: A
authors.lastname: Wear
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: M
authors.initials: M
authors.lastname: Chaplin
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: M
authors.initials: M
authors.lastname: Stack
authors.affiliation: Canadian Food Inspection Agency, Winnipeg Laboratory, Winnipeg, MB R3E 3M4, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Czub
authors.affiliation: Health Canada, Health Products and Food Branch, Tunney's Pasture, Ottawa, ON K1A 0K9, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Mueller
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: P R
authors.initials: PR
authors.lastname: Webb
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: A
authors.initials: A
authors.lastname: Davis
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: J
authors.initials: J
authors.lastname: Spiropoulos
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: J
authors.initials: J
authors.lastname: Holdaway
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: S A C
authors.initials: SAC
authors.lastname: Hawkins
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Austin
authors.affiliation: Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: G A H
authors.initials: GAH
authors.lastname: Wells
mesh_terms: D000818:Animals; D002417:Cattle; D002490:Central Nervous System / Q000737:chemistry / Q000473:pathology; D016643:Encephalopathy, Bovine Spongiform / Q000175:diagnosis* / Q000503:physiopathology*; D005725:Ganglia, Autonomic / Q000737:chemistry / Q000473:pathology; D005727:Ganglia, Spinal / Q000737:chemistry / Q000473:pathology; D007120:Immunochemistry; D018620:PrPSc Proteins / Q000302:isolation & purification*; D013997:Time Factors
chemical_list: D018620:PrPSc Proteins