Pathogenesis of experimental bovine spongiform encephalopathy (BSE): estimation of tissue infectivity according to incubation periodMark Edward Arnold, Stephen Anthony Charles Hawkins, Robert Green, Ian Dexter and Gerald Arthur Henry Wells
Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, United Kingdom
Received 6 May 2008; accepted 23 October 2008; published online 28 October 2008
Abstract - This paper reports the results of tissue infectivity assays of bovine spongiform encephalopathy (BSE) agent in orally exposed cattle at stages during the incubation period. Estimations of the titre of infectivity in central nervous system (CNS), certain peripheral nerve ganglia and distal ileum tissue were made according to time post exposure from the relationship between incubation period and dose for RIII mice and C57bl mice using data from titrations of brain material from cases of BSE. The rate of increase of infectivity in the bovine CNS was then estimated, taking into account these tissue infectivity titres, the variability of the brain titre of clinical field cases of BSE, and the probability density of the expected number of months before clinical onset of each infected bovine. The doubling time for CNS was shown to equal 1.2 months. The titre in the thoracic dorsal root ganglia (DRG) was, on average, approximately 1 log units less than CNS, and cervical DRG approximately 0.5 log less than thoracic DRG. The pattern of increase of infectivity in the distal ileum is that of an initial increase up to 14–18 months post exposure, followed by a decrease, which is likely to be highly variable between animals. These results will be informative for future risk assessments of BSE, especially in relation to reviewing current control measures.
Key words: bovine spongiform encephalopathy / pathogenesis / modeling / infectivity titres / maximum likelihood estimation
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© INRA, EDP Sciences 2008