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Estimating the human health risk from possible BSE infection of the British sheep flock

Abstract

Following the controversial failure of a recent study1 and the small numbers of animals yet screened for infection2, it remains uncertain whether bovine spongiform encephalopathy (BSE) was transmitted to sheep in the past via feed supplements and whether it is still present. Well grounded mathematical and statistical models are therefore essential to integrate the limited and disparate data, to explore uncertainty, and to define data-collection priorities. We analysed the implications of different scenarios of BSE spread in sheep for relative human exposure levels and variant Creutzfeldt–Jakob disease (vCJD) incidence. Here we show that, if BSE entered the sheep population and a degree of transmission occurred, then ongoing public health risks from ovine BSE are likely to be greater than those from cattle, but that any such risk could be reduced by up to 90% through additional restrictions on sheep products entering the food supply. Extending the analysis to consider absolute risk, we estimate the 95% confidence interval for future vCJD mortality to be 50 to 50,000 human deaths considering exposure to bovine BSE alone, with the upper bound increasing to 150,000 once we include exposure from the worst-case ovine BSE scenario examined.

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Figure 1: Epidemiological inputs to transmission model.
Figure 2: Epidemiological characteristics of BSE transmission scenarios in sheep.
Figure 3: Impact of risk-reduction measures.

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References

  1. Frankish, H. Samples blunder renders sheep-BSE study useless. Lancet 358, 1436 (2001)

    Article  CAS  Google Scholar 

  2. Beckett, M. House of Commons Hansard Debates, 22 October 2001 373 (2001) 〈http://www.parliament.the-stationery-office.co.uk/pa/cm200102/cmhansrd/cm011022/debindx/11022-x.htm〉.

  3. Det Norske Veritas Assessment of Exposure to BSE Infectivity in the UK Sheep Flock Report no. C782506 (The Meat and Livestock Commission, London, 1998)

    Google Scholar 

  4. Hadlow, W. J., Kennedy, R. C. & Race, R. E. Natural infection of Suffolk sheep with scrapie virus. J. Infect. Dis. 146, 657–664 (1982)

    Article  CAS  Google Scholar 

  5. van Keulen, L. J. M., Schreuder, B. E. C., Vromans, M. E. W., Langeveld, J. P. M. & Smits, M. A. Scrapie-associated prion protein in the gastrointestinal tract of sheep with natural scrapie. J. Comp. Pathol. 121, 55–63 (1999)

    Article  CAS  Google Scholar 

  6. van Keulen, L. J. M., Schreuder, B. E. C., Vromans, M. E. W., Langeveld, J. P. M. & Smits, M. A. Pathogenesis of natural scrapie in sheep. Arch. Virol. Suppl. 16, 57–71 (2000)

    Google Scholar 

  7. Andreoletti, O. et al. Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J. Gen. Virol. 81, 3115–3126 (2000)

    Article  CAS  Google Scholar 

  8. Foster, J. D., Parnham, D. W., Hunter, N. & Bruce, M. Distribution of the prion protein in sheep terminally infected with BSE following experimental oral transmission. J. Gen. Virol. 82, 2319–2326 (2001)

    Article  CAS  Google Scholar 

  9. Jeffrey, M. et al. Oral inoculation of sheep with the agent of bovine spongiform encephalopathy (BSE). 1. Onset and distribution of disease-specific PrP accumulation in brain and viscera. J. Comp. Pathol. 124, 280–289 (2001)

    Article  CAS  Google Scholar 

  10. Fraser, H., Bruce, M. E., Chree, A., McConnell, I. & Wells, G. A. H. Transmission of bovine spongiform encephalopathy and scrapie to mice. J. Gen. Virol. 73, 1891–1897 (1992)

    Article  Google Scholar 

  11. Wells, G. A. H. et al. Infectivity in the ileum of cattle challenged orally with bovine spongiform encephalopathy. Vet. Rec. 135, 40–41 (1994)

    Article  CAS  Google Scholar 

  12. Hart, R. J., Church, P. N., Kempster, A. J., Matthews, K. R. Audit of Bovine and Ovine Slaughter and By-products Sector (Ruminant Products Audit) (Leatherhead Food Research Association, London, 1997).

  13. Hunter, N. PrP genetics in sheep and the implications for scrapie and BSE. Trends Microbiol. 5, 331–334 (1997)

    Article  CAS  Google Scholar 

  14. Hunter, N., Goldmann, W., Marshall, E. & O'Neill, G. Sheep and goats: natural and experimental TSEs and factors influencing incidence of disease. Arch. Virol. Suppl. 16, 181–188 (2000)

    Google Scholar 

  15. Jeffrey, M. et al. Frequency and tissue distribution of infection-specific PrP in tissues of clinical scrapie and cull sheep obtained from scrapie affected farms in Shetland. J. Comp. Pathol. (submitted).

  16. Baylis, M., Houston, F., Goldmann, W., Hunter, N. & McLean, A. R. The signature of scrapie: differences in the PrP genotype profile of scrapie-affected and scrapie-free UK sheep flocks. Proc. R. Soc. Lond. B 267, 2029–2035 (2000)

    Article  CAS  Google Scholar 

  17. Hunter, N. et al. Is scrapie solely a genetic disease? Nature 386, 137 (1997)

    Article  ADS  CAS  Google Scholar 

  18. Anderson, R. M. et al. Transmission dynamics and epidemiology of BSE in British cattle. Nature 382, 779–788 (1996)

    Article  ADS  CAS  Google Scholar 

  19. Ferguson, N. M., Donnelly, C. A., Woolhouse, M. E. J. & Anderson, R. M. The epidemiology of BSE in cattle herds in Great Britain II: Model construction and analysis of transmission dynamics. Phil. Trans. R. Soc. Lond. B 352, 803–838 (1997)

    Article  ADS  CAS  Google Scholar 

  20. Donnelly, C. A. & Ferguson, N. M. Statistical Aspects of BSE and vCJD—Models for Epidemics (Chapman & Hall and CRC, London, 2000)

    MATH  Google Scholar 

  21. Woolhouse, M. E. J. et al. Population dynamics of scrapie in a sheep flock. Phil. Trans. R. Soc. Lond. B 354, 751–756 (1999)

    Article  CAS  Google Scholar 

  22. Gravenor, M. B., Cox, D. R., Hoinville, L. J., Hoek, A. & McLean, A. R. The flock-to-flock force of infection for scrapie in Britain. Proc. R. Soc. Lond. B 268, 587–592 (2001)

    Article  CAS  Google Scholar 

  23. Hoinville, L. J. A review of the epidemiology of scrapie in sheep. Rev. Sci. Techn. Office Int. Epizooties 15, 827–852 (1996)

    Article  CAS  Google Scholar 

  24. Hoinville, L. J., Hoek, A., Gravenor, M. B. & McLean, A. R. Descriptive epidemiology of scrapie in Great Britain: results of a postal survey. Vet. Rec. 146, 455–461 (2000)

    Article  CAS  Google Scholar 

  25. Ghani, A. C., Ferguson, N. M., Donnelly, C. A. & Anderson, R. M. Predicted vCJD mortality in Great Britain. Nature 406, 583–584 (2000)

    Article  ADS  CAS  Google Scholar 

  26. d'Aignaux, J. N. H., Cousens, S. N., Smith, P. G. Predictability of the UK variant Creutzfeldt–Jakob disease epidemic. Science 294, 1729–1731; published online 25 October 2001 (10.1126/science.1064748).

  27. Valleron, A.-J., Boelle, P.-Y., Will, R. & Cesbron, J.-Y. Estimation of epidemic size and incubation time based on age characteristics of vCJD in the United Kingdom. Science 294, 1726–1728 (2001)

    Article  ADS  CAS  Google Scholar 

  28. Hill, A. F. et al. Molecular screening of sheep for bovine spongiform encephalopathy. Neurosci. Lett. 255, 159–162 (1998)

    Article  CAS  Google Scholar 

  29. Maissen, M., Roeckl, F., Glatzel, M., Goldmann, W. & Aguzzi, A. Plasminogen binds to disease-associated prion protein of multiple species. Lancet 357, 2026–2028 (2001)

    Article  CAS  Google Scholar 

  30. Hagenaars, T. J., Ferguson, N. M., Donnelly, C. A. & Anderson, R. M. Persistence patterns of scrapie in a sheep flock. Epidemiol. Infect. 127, 157–167 (2001)

    Article  CAS  Google Scholar 

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Acknowledgements

This work was funded by the Food Standards Agency. N.M.F. and A.C.G. acknowledge funding from The Royal Society. C.A.D., T.J.H. and R.M.A. acknowledge funding from the Wellcome Trust. We are very grateful to M. Bruce, S. Bellworthy and M. Jeffrey for access to pre-publication data on infectivity. We also thank L. Hoinville, J. Wilesmith and R. Will for access to data. We thank N. Hunter, L. Green, J. Anderson, A. James, A. Bromley, H. Mason, P. Comer and members of the Spongiform Encephalopathy Advisory Committee for discussions.

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Correspondence to N. M. Ferguson.

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Supplementary information

41586_2002_BFnature709_MOESM1_ESM.pdf

Supplementary chapters: Sheep demography, Infectivity of infected animals, Epidemiology of TSEs in sheep, Human consumption of ovine material, Epidemiological model of sheep TSEs, Human exposure and impact of risk reduction strategies, Absolute risk estimates: vCJD epidemic projection. Contains 13 supplementary tables, 4 supplementary figures and references. (PDF 432 kb)

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Ferguson, N., Ghani, A., Donnelly, C. et al. Estimating the human health risk from possible BSE infection of the British sheep flock. Nature 415, 420–424 (2002). https://doi.org/10.1038/nature709

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