MAD COW DISEASE:
Is there a human link? You decide

INTRODUCTION

Mad Cow Epidemic (Great Britain, 1986)

A fatal "spongiform encephalopathy"-like disease was identified in British cattle
  • The epidemic was thought to have been caused by feeding cattle with scrapie infected sheep offal (brain matter).
  • The infectious agent within the offal was hypothesized to be an abnormal protein or prion, which had led to scrapie in sheep and bovine spongiform encephalopathy (BSE) in cows.

    Specified Offals Ban of 1989

  • The introduction of legislative controls, and the restriction sheep-offal may have been too late.
  • It has been estimated that nearly 2 million cows infected with BSE would enter the food chain between 1983 and 1999 ( Dealer & Kent, 1995).
  • Although projections on the number of people who have consumed beef, and thus a possible exposure to BSE are theoretical, the numbers are disturbing, up to 34 million people (Dealer & Kent, 1995).

    European Community (EC) Regulations

  • 1990-94, EC prohibited the export of specified bovine offals to other European nations, and condemned their use as feeding supplements for cattle.
  • 1996, EC restricted the export of cattle from the UK.

    From scrapie in sheep, to BSE in cows; aren't humans the end of the food chain?

    PRION THEORY

    Transmissible spongiform encephalopathies are spread by an agent (prion) which, unlike any other known agent of disease, appears to lack informational nucleic acid (DNA or RNA).
  • Prusiner coined the term "prion" to emphasize the proteinaceous and infectious nature of the transmissible agent.
  • Prions are simply, a modified form of an endogenous and ubiquitous protein PrPc of unknown function, found in many mammalian species, including humans.
  • PrPc protein is encoded by the human prion protein gene (PRNP) on the short arm of chromosome 20.
  • Evidence for the infectious nature of the prion: PrP gene knockout mice do not develop infection / transgenic mice expressing PrPsc, develop CNS degeneration and neuropathology indistinguishable from scrapie infection.
  • The infectious protein, PrPsc, once transmitted, accumulates during the advanced stages of the disease.
  • PrPsc propagates by interacting with the normal protein, converting the normal PrPc protein through a postranslational process inducing the conversion of alpha helices into beta-pleated sheets.
  • The resultant conformational change imparts resistance to proteolysis.
  • New variant CJD, has a "suspicious signature" of its PrPsc protein, as determined by western blot. The western blot patterns are nearly identical to those found in cows infected with BSE. Illustrations of Prion Propagation and Conversion

    HISTOPATHOLOGY

    Stage 1 : Spongiform change
  • widespread vacuoles in dendrites (holes in the brain tissue)
    • Stage 2 : Neuronal degeneration
  • loss of dendritic spines and deafferentiation (brain messages are disconnected)
    • Stage 3 : Astrogliosis
  • proliferation of astrocytes (overgrowth of star-shaped nerve cells)

    • CLINICAL FEATURES

    Sporadic CJD Cases

  • disease onset usually occurs in individuals between 60 and 70 years of age
  • loss of memory
  • may develop behavioural changes in later stages of disease
  • dementia (irreversible intellectual deterioration and emotional disturbance)
  • vision and coordination abnormalities
  • death usually occurs at 6 months following diagnosis

    New Variant CJD Cases

  • all ten patients were under 50 years of age (average age 28 years)
  • only two out of the ten patients experienced memory impairment as part of initial clinical presentation
  • nine out of ten patients had behavioural changes as an early clinical feature
  • nine patients developed in ataxia (inability to coordinate muscular movements)
  • all patients developed progressive dementia
  • electroencephalogram (EEG, recording of the electrical activity of the brain) features in all ten patients were atypical of sporadic CJD cases
  • death usually occurred within 13 months
    For a glossary of medical and scientific terms relevant to CJD click here: glossary

    THE REAL QUESTION: "Should we be worried?"

    What people are most concerned about is whether or not a person can develop CJD from eating bovine spongiform encephalopathy (BSE, i.e. Mad Cow Disease) infected meat. Presented below are the sides of the ongoing debate. YOU DECIDE...

    Yes, there is a link

  • profile of the recent cases of CJD in the UK are unlike those previously observed (i.e. younger age with no genetic predisposition)
  • new variant CJD brain sections show the presence of amyloid plaques (aggregates of PrP protein) (similar to plaques seen in scrapie (sheep spongiform encephalopathy) but uncharacteristic of sporadic CJD)
  • experimental evidence of BSE transmission to mice and macaques by intracerebral injection (i.e. a species jump is possible)
  • western blot patterns of defective PrP in BSE are similar to that of new variant CJD

    No, there is no link

  • statistics show that there is a similar incidence (one per million) of CJD in other European countries without BSE-infected cattle
  • previous cases in young individuals may have been misdiagnosed
  • similar incidence of CJD cases in meat-eaters and vegetarians have been reported
  • there is no experimental evidence to show a definite link between BSE and CJD
  • health scare amplified by the media
    For official statistics from the UK Creutzfeldt-Jacob Surveillance Unit click here: statistics
    For the complete Lancet article published by the CJD Surveillance Unit in April, 1996 click here: Lancet

    CANADIAN CONCERNS

    The cattle epidemic and the new variant cases were all located in Great Britain. As Canadians, should we also be concerned about the risk of infection from BSE?

  • following the BSE epidemic in Britain, Canada banned the importation of beef and cattle from the UK in 1990
  • the Canadian beef industry enforces strict surveillance and control measures
  • as far as we know, milk does not contain infectious material, and is safe to drink
  • potentially infectious tissues (brain, spinal cord, spleen, thymus, etc.) is removed from slaughtered cattle

    For additional facts from the Beef Information Centre click here: BIC

    The authors: David Alvarez, Jeannie Choi & Alpa Popat

    References

    Almond JW, Will bovine spongiform encephalopathy transmit to humans? BMJ 1995; 311:1415-21.

    Armond L, Prusiner S, Etiology and Pathogenesis of Prion Diseases. AJP 1995; 146:790-805.

    Barlow RM, Middleton DJ, Dietary transmission of bovine spongiform encephalopathy to mice. Vet Rec 1990; 126:111-2.

    Beef Information Centre, http://www.corpinfohub.com/bic/bic.htm

    Collinge J, Sidle KC, Meads J, Ironside J and Hill AF. Molecular analysis of prion stain variation and the aetiology of 'new variant' CJD. Nature 1996; 383: 685-690.

    Dealer, SF., Kent, JT, BSE:an update on the statistical evidence. British Food Journal 1990; 97: 3-19

    Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC. Oral transmission of kuru, CJD, and scrapie to non-human primates. J Infect Dis 1980; 142:205-8.

    MacKnight C. Bovine spongioform encephalopathy and Creutzfeldt-Jakob disease: implications for physicians. Can Med Assoc J 1996; 155: 529-536.

    Prusiner,S, The Prion Diseases, http://www.nmla.com.umdibble/prion.html

    Will RG, Ironside JW, Zeider M, Cousens, SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A and Smith PG. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347: 921-25.