Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle.

The dose-response of cattle exposed to the bovine spongiform encephalopathy (BSE) agent is an important component of modelling exposure risks for animals and humans and thereby, the modulation of surveillance and control strategies for BSE. In two experiments calves were dosed orally with a range of amounts of a pool of brainstems from BSE-affected cattle. Infectivity in the pool was determined by end-point titration in mice. Recipient cattle were monitored for clinical disease and, from the incidence of pathologically confirmed cases and their incubation periods (IPs), the attack rate and IP distribution according to dose were estimated. The dose at which 50 % of cattle would be clinically affected was estimated at 0.20 g brain material used in the experiment, with 95 % confidence intervals of 0.04-1.00 g. The IP was highly variable across all dose groups and followed a log-normal distribution, with decreasing mean as dose increased. There was no evidence of a threshold dose at which the probability of infection became vanishingly small, with 1/15 (7 %) of animals affected at the lowest dose (1 mg).

[1]  H. Schwarzenbacher,et al.  A major genetic component of BSE susceptibility , 2006, BMC Biology.

[2]  M. Simmons,et al.  BSE immunohistochemical patterns in the brainstem: a comparison between UK and Italian cases , 2006, Acta Neuropathologica.

[3]  A. Buschmann,et al.  Highly bovine spongiform encephalopathy-sensitive transgenic mice confirm the essential restriction of infectivity to the nervous system in clinically diseased cattle. , 2005, The Journal of infectious diseases.

[4]  J. Wilesmith,et al.  Estimation of the age-dependent risk of infection to BSE of dairy cattle in Great Britain. , 2004, Preventive veterinary medicine.

[5]  T. Konold,et al.  Clinical findings in 78 suspected cases of bovine spongiform encephalopathy in Great Britain , 2004, Veterinary Record.

[6]  S. Prusiner 1 An Introduction to Prion Biology and Diseases , 2004 .

[7]  G. Wells,et al.  Animal Models of Transmissible Spongiform Encephalopathies: Experimental Infection, Observation and Tissue Collection , 2004 .

[8]  M. Stack Western Immunoblotting Techniques for the Study of Transmissible Spongiform Encephalopathies , 2004 .

[9]  J. Collinge,et al.  Bioassay for prions , 2003 .

[10]  R. Curnow,et al.  Repeated challenge with prion disease: The risk of infection and impact on incubation period , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  L. Terry,et al.  Detection of disease-specific PrP in the distal ileum of cattle exposed orally to the agent of bovine spongiform encephalopathy , 2003, Veterinary Record.

[12]  G. Dell’Omo,et al.  Early behavioural changes in mice infected with BSE and scrapie: automated home cage monitoring reveals prion strain differences , 2002, The European journal of neuroscience.

[13]  C. Henry,et al.  Clinical features of variant Creutzfeldt‐Jakob disease , 2002, Reviews in medical virology.

[14]  A. Aguzzi,et al.  Chronic Subclinical Prion Disease Induced by Low-Dose Inoculum , 2002, Journal of Virology.

[15]  I. Zerr,et al.  Clinical diagnosis and differential diagnosis of CJD and vCJD , 2002, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[16]  S. Trapmann,et al.  Rapid test for the preclinical postmortem diagnosis of BSE in central nervous system tissue , 2001, Veterinary Record.

[17]  W. Cooley,et al.  Evaluation of a rapid western immunoblotting procedure for the diagnosis of bovine spongiform encephalopathy (BSE) in the UK. , 2001, Journal of comparative pathology.

[18]  D. Taylor,et al.  Relative efficiency of transmitting bovine spongiform encephalopathy to RIII mice by the oral route , 2001, Veterinary Record.

[19]  A. McLean,et al.  Scrapie infections initiated at varying doses: an analysis of 117 titration experiments. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[20]  U. Braun,et al.  Bovine spongiform encephalopathy: Diagnostic approach and clinical findings , 1998 .

[21]  M. Beekes,et al.  Effect of repeated oral infection of hamsters with scrapie. , 1998, The Journal of general virology.

[22]  G. Wells,et al.  Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. , 1998, The Veterinary record.

[23]  M. Simmons,et al.  PATHOLOGICAL TEMPERAMENT CHANGES IN BOVINE ANIMALS , 1997 .

[24]  M. Simmons,et al.  THE TOPOGRAPHIC DISTRIBUTION PATTERN OF VACUOLATION IN THE CENTRAL NERVOUSSYSTEM OF CATTLE INFECTED ORALLY WITH BOVINE SPONGIFORM ENCEPHALOPATHY , 1997 .

[25]  A. Hofman,et al.  A new variant of Creutzfeldt-Jakob disease in the UK , 1996, The Lancet.

[26]  M. Simmons,et al.  BSE in Great Britain: consistency of the neurohistopathological findings in two random annual samples of clinically suspect cases , 1996, Veterinary Record.

[27]  J. Wilesmith,et al.  The Neuropathology and Epidemiology of Bovine Spongiform Encephalopathy , 1995, Brain pathology.

[28]  N. Hunter,et al.  Frequencies of PrP gene variants in healthy cattle and cattle with BSE in Scotland , 1994, Veterinary Record.

[29]  H. Fraser,et al.  Transmission of bovine spongiform encephalopathy and scrapie to mice. , 1992, The Journal of general virology.

[30]  J. Wilesmith,et al.  Bovine spongiform encephalopathy. Epidemiology, low dose exposure and risks. , 1994, Annals of the New York Academy of Sciences.

[31]  J. Wilesmith Epidemiology of bovine spongiform encephalopathy and related diseases. , 1993, Archives of virology. Supplementum.

[32]  J. Wilesmith,et al.  Bovine Spongiform Encephalopathy , 1994, Revue scientifique et technique.

[33]  H. Fraser,et al.  Transmission of bovine spongiform encephalopathy and scrapie to mice , 2007 .

[34]  W D Hueston,et al.  Bovine spongiform encephalopathy: case-control studies of calf feeding practices and meat and bonemeal inclusion in proprietary concentrates. , 1992, Research in veterinary science.

[35]  J. Ryan,et al.  Bovine spongiform encephalopathy: aspects of the clinical picture and analyses of possible changes 1986-1990 , 1992, Veterinary Record.

[36]  N. Hunter,et al.  Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon. , 1991, The Journal of general virology.

[37]  J. Gorham,et al.  Organ-specific modification of the dose-response relationship of scrapie infectivity. , 1990, The Journal of infectious diseases.

[38]  M. Dawson,et al.  Preliminary evidence of the experimental transmissibility of bovine spongiform encephalopathy to cattle , 1990, Veterinary Record.

[39]  R. Kimberlin,et al.  Pathogenesis of scrapie in mice after intragastric infection. , 1989, Virus research.

[40]  J. Ryan,et al.  Bovine spongiform encephalopathy: epidemiological studies , 1988, Veterinary Record.

[41]  R. Kimberlin,et al.  Incubation periods in six models of intraperitoneally injected scrapie depend mainly on the dynamics of agent replication within the nervous system and not the lymphoreticular system. , 1988, The Journal of general virology.

[42]  S. Prusiner,et al.  Measurement of the scrapie agent using an incubation time interval assay , 1982, Annals of neurology.

[43]  R. Kimberlin,et al.  Pathogenesis of mouse scrapie: effect of route of inoculation on infectivity titres and dose-response curves. , 1978, Journal of comparative pathology.

[44]  Outram Gw The pathogenesis of scrapie in mice. , 1976 .

[45]  G. Outram The pathogenesis of scrapie in mice. , 1976, Frontiers of biology.

[46]  H. Fraser,et al.  Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. , 1968, Journal of comparative pathology.

[47]  E. C. Fieller The Biological Standardization of Insulin , 1940 .