BSE and CJD: Ethical issues and socio-economic impact

The outbreak of bovine spongiform encephalopathy (BSE) or "mad cow disease" in the United Kingdom and continental Europe continues to concern beef and dairy producers and the general public in the United States. This concern has increased recently because of the continued spread of the disease on the European continent and the development of a similar disease that has appeared in people, mostly in the U.K. The new disease known as variant Creutzfeldt-Jakob disease (vCJD) appears to be more closely related to BSE in its pathology than to traditional CJD. It is therefore assumed that vCJD has crossed the species barrier from cattle to Man.

BSE and CJD are prion diseases, a group of rapidly progressive, fatal, untreatable neurodegenerative syndromes characterized by the accumulation in the brain of a protease-resistant protein that is the main (or only) macromolecule of the transmissible agent. The prototypical prion disease of animals is scrapie, which has been long recognized in sheep and goats as a common and economically important disorder. Following 1988, BSE has given rise to considerable economic and political turmoil in the United Kingdom as it developed in more than 150 000 cattle. At the peak of the epidemic in 1993, approximately 700 cattle were newly affected each week. The epidemic has been linked to changes in the rendering of sheep or cattle carcasses for use as protein supplements to feed-meal, suggesting that inadequately inactivated scrapie agent from sheep, cattle or both was the initial cause. Following a legislation banning the feeding of ruminant offal to livestock, the rate of diagnosed BSE has decreased. It is still uncertain whether the origins of BSE lie in a mutant form of scrapie or if it developed naturally in cattle.

A number of human prion diseases exist including CJD, kuru, Gerstmann-Sträussler-Scheinker (GSS) syndrome and fatal familial insomnia (FFI). These diseases are rare and, until recently, were not considered of any great socio-economic significance. However, in the wake of the BSE crisis in the U.K. and the suspicion that contaminated beef may lie at the root of it, many people now fear that an epidemic may be imminent. The infectivity of prion diseases appears to reside in the prion protein designated PrPSc. PrPSc is the abnormal, protease-resistant isoform of a normal cellular membrane protein designated PrPC. Stanley B. Prusiner of the University of California at San Francisco has long contended that changes in conformation underlie the dramatic differences in the properties of the two isoforms; by abnormal molecular folding, PrPSc acquires protease resistance and a "catalytic" ability to recruit more conformational copies of itself from PrPC. PrPSc is remarkably resistant to many procedures that inactivate conventional infectious agents and, therefore, problems have been encountered in decontamination procedures of, for example, surgical instruments. Although 90% of prion disease cases arise sporadically and a further 10% arise where the family has some history of the disease, it is an unfortunate fact that about eighty cases of CJD have arisen iatrogenically, that is, as a result of exposure to medical treatment, facilities, or personnel. Cases of transmission by corneal transplant, transplant of dura mater, exposure to infected neurosurgical instruments and electroencephalogram probes, and transplantation of human growth hormone have been confirmed.

The indestructibility of prions creates real problems in sterilizing surgical instruments; it is basically impossible, and equipment has retained infectivity and caused infection in patients even after repeated "sterilizations." Currently in the U.K., scientists are considering making all surgical instruments disposable. Neurosurgical equipment is already disposed of after each patient. Since vCJD is carried heavily by the lymphoreticular (blood/lymph) systems, the tonsils, appendix, and most recently, the lymph nodes of vCJD patients have been found to be full of prions, unlike in patients with classical CJD. This has brought about the worrisome debate in the U.K. that all surgical equipment, not just neurosurgical, could be contaminated and has brought on calls to destroy all surgical equipment after use or to use disposable instruments only. The U.K. has also banned the reuse of contact "fitting" lenses by optometrists and opthamologists—hard lenses that are "sterilized" between patient use in clinics that fit contact lenses. The eye has a direct neural link with the brain and is one of the most highly infectious organs of the body in CJD and vCJD, after the brain and spinal cord. There is concern that these lenses could spread iatrogenic vCJD. Additionally "touch" tonometry has been banned in the UK, only the "air puff" method is allowed now. And, of course, ophthalmological surgery could be a prime candidate for this as well. However, nothing is being done in this regard in the U.S. to screen U.K. patients, or U.S. patients who have lived abroad.

A new fear is that blood supplies may be contaminated with prions and that Creutzfeldt-Jakob disease (CJD) will join hepatitis and AIDS in the public and medical consciousness as the next infectious disease epidemic which may be contracted through donated blood and tissue. In view of the theoretical risk of blood-borne transmission of CJD, some experts recommend that the following groups of people not donate blood: all people with CJD; first-degree relatives of CJD patients with familial disease (determined by genetic testing, by identifying two or more first-degree relatives with CJD or, if there is no information, by a precautionary assumption of familial disease); recipients of products derived from human pituitary glands; and recipients of corneal or dura-mater grafts.

The risk of transmission of CJD through blood, blood products, and organ or tissue transplants, is being addressed by, for example, the Laboratory Centre for Disease Control (LCDC) in Canada. They are planning to initiate an enhanced surveillance system for CJD throughout Canada. Cases will be reported to the surveillance system by specialists in neurology, neuropathology and geriatrics. Through record review, interview, genetic sequencing and neuropathological examination, extensive information about every person suspected of having CJD will be collected and compared with data from a control population to ascertain the relative risk of CJD associated with exposure to blood and blood products. In addition, Canada has been invited to participate in European Concerted Action on CJD, an international surveillance program for variant CJD coordinated by investigators in Edinburgh. This obviously has ethical implications for patient privacy and it is questionable if such extreme measures are really necessary. The prion agent is not new unlike HIV and other emerging agents and there is an absence of any recorded cases of CJD among people with hemophilia and recipients of multiple transfusions or people who abuse injection drugs. Also, a small case-controlled study in Britain revealed no risk for the subsequent development of CJD associated with receiving blood.

See also BSE and CJD: recent advances in research; Public health, current issues