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J Gen Virol 88 (2007), 3198-3208; DOI 10.1099/vir.0.82987-0

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Estimating the temporal relationship between PrPSc detection and incubation period in experimental bovine spongiform encephalopathy of cattle

M. E. Arnold1, J. B. M. Ryan1, T. Konold1, M. M. Simmons1, Y. I. Spencer1, A. Wear1, M. Chaplin1, M. Stack1, S. Czub2,{dagger}, R. Mueller3, P. R. Webb1, A. Davis1,{ddagger}, J. Spiropoulos1, J. Holdaway1, S. A. C. Hawkins1, A. R. Austin1,§ and G. A. H. Wells1

1 Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK
2 Canadian Food Inspection Agency, Winnipeg Laboratory, Winnipeg, MB R3E 3M4, Canada
3 Health Canada, Health Products and Food Branch, Tunney's Pasture, Ottawa, ON K1A 0K9, Canada

Correspondence
M. E. Arnold
m.arnold{at}vla.defra.gsi.gov.uk

This study examines tissues from sequential-kill, time-course pathogenesis studies to refine estimates of the age at which disease-specific PrP (PrPSc) 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 PrPSc 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 PrPSc 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. PrPSc was detected inconsistently in dorsal root ganglia, concurrent with or after detection in CNS, and not at all in certain sympathetic nervous system ganglia.

{dagger}Present address: National and OIE BSE Reference Laboratories, Animal Diseases Research Institute, Canadian Food Inspection Agency, Township Road 9-1, Lethbridge, AB T1J 3Z4, Canada.

{ddagger}Present address: Pathology, Infectious Disease and Biosecurity, School of Veterinary Science, University of Queensland, St Lucia, QLD 4072, Australia.

§Present address: Oak Farm, Harpsden Bottom, Henley-on-Thames, Oxon RG9 4HY, UK.

Appendices A (including Supplementary Table S1 and Supplementary Fig. S1), B and C are available with the online version of this paper.




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