1.1 The Disease

• Creutzfeldt-Jakob disease (CJD), Kuru, Gerstmann-Straussler-Scheinker (GSS), and fatal familial insomnia (FFI) in humans;
• Scrapie in sheep and goats;
• Transmissible mink encephalopathy (TME) in mink;
• Chronic wasting disease (CWD) of deer and elk; and
• Bovine spongiform encephalopathy (BSE) in cattle.

In addition, there are examples of TSEs that are thought to occur as the result of exposure to BSE infected bovine material, such as feline spongiform encephalopathy (FSE) and variant Creutzfeldt-Jakob disease (vCJD).

While a number of theories describe the etiology, the protein only or prion theory has emerged to dominate the literature. The prion theory takes advantage of the fact that a modified form of a normal, host encoded, membrane associated, prion protein is the only disease specific macromolecule consistently isolated in BSE-affected animals. The prion theory assigns infectivity to a structurally modified form of the prion protein (PrP) which in turn promotes the conversion of other prion molecules to the same, abnormal form. The accumulation of these abnormal isoforms (PrPsc) within the affected cell cytoplasm, interferes with normal cell function, contributes to the characteristic spongiform changes, and eventually results in cell death.

The PrPsc is extremely resistant to heat, ultraviolet and ionizing radiation, and a large range of chemical disinfectants. It is insoluble in detergent and has a predominately beta sheet structure making it relatively protease resistant-a characteristic that has been exploited in the development of rapid post-mortem diagnostic tests for the disease.

Until recently, bioassays demonstrated that, unlike scrapie, BSE was caused by a single strain or isoform. More recent findings are suggestive of the possible existence of more than one strain.

The World Organisation for Animal Health (OIE) lists the species susceptible to BSE as all members of the family Bovidae including cattle, bison and water buffalo.

Incubation Period

Modes of Transmission

According to the current scientific knowledge, BSE infectivity has been demonstrated in the following tissues, to varying degrees, which if fed to susceptible species could result in the transmission of the infective agent:

The following listed materials have been determined by the OIE not to be a source of BSE infectivity:

• gelatin and collagen prepared exclusively from hides and skins;
• milk and milk products;
• semen and in vivo derived embryos as detailed in 3.3 Premises Control Actions (2) and 3.3 Premises Control Actions (5);
• protein-free tallow (maximum level of insoluble impurities of 0.15% in weight) and derivatives made from this tallow;
• dicalcium phosphate (with no trace of protein or fat);
• hides and skins.

Horizontal and Vertical Transmission: BSE is not considered to be a contagious disease; however, other potential modes of transmission need to be considered.

• Horizontal transmission:
  The current body of scientific evidence concludes that horizontal transmission does not occur.

• Vertical transmission-from sire:
  Epidemiological studies have demonstrated that semen used for commercial artificial insemination and prepared in accordance with internationally recognized protocols is not associated with a risk of BSE transmission.

• Maternal transmission:
  Experiments have concluded that in vivo derived bovine embryos collected in accordance with internationally recognized protocols are not associated with a risk of BSE transmission.

  Although there is no direct evidence of BSE transmission from cow to calf, it is assumed that maternal transmission can occur. It is estimated that calves born to infected cows during the last one-sixth of the incubation period may become infected (less than 10% of the time). If maternal transmission occurs, it would be at a rate insufficient to initiate or to propagate the disease.

Vectors: There is no indication that insect or arthropod vectors are implicated in the transmission of BSE.

Fomites and Iatrogenic Transmission: In general, fomites associated with normal agricultural husbandry are not considered risks in BSE transmission. Nevertheless, iatrogenic transmission of TSE within the sheep and human populations has been well documented and supports the possibility of its occurrence in the cattle population. Veterinary instruments and procedures, which could result in the transmission of nervous or lymphoid tissue, should be considered in terms of their potential to transmit infection.

The prion hypothesis assigns infectivity to a structurally modified form of the prion protein which in turn promotes the conversion of other prion protein molecules to the same, abnormal form. The process involved in this conformational change is poorly described. The accumulation of these abnormal isoforms of the prion protein interferes with the normal function and appearance of the infected nerve cell. One of the major criticisms of the prion protein hypothesis is that in the absence of any nucleic acids, the strain variations observed in other TSE diseases are not explained. It is suspected that strain differences could be the result of mutations in the PrP gene resulting in tertiary conformational changes of the prion protein.

Ingested modified prion may be absorbed across the gut wall at Peyer’s patches. This would be consistent with the observation that there appears to be an age related susceptibility to the infectious agent. Young cattle are estimated to be as much as ten times more susceptible than adults. A number of researchers have calculated that susceptibility peaks at some point between 0.5 and 1.5 years of age and then steadily declines in the following years to a level approximating 10% of the peak value. BSE infectivity has not been detected in the blood of infected cattle, leading some investigators to speculate that neuroinvasion can occur directly via peripheral nerves or the lymphoreticular system, and then via the peripheral nerves. The debate continues around whether the spleen is a source of BSE infectivity. If there is infectivity in the blood or spleen it may occur at a level below the current detection limits.

Distribution of Infectivity

In excess of 18 months post infection, infectivity was detected in the following tissues: small intestine (distal ileum), brain, spinal cord, dorsal and trigeminal root ganglia. One study concluded bone marrow was slightly infectious when the animal was clinically affected; however, this finding has not been replicated. Despite numerous attempts, this experiment failed to find any consistent changes associated with the brains of affected animals more than three months before the onset of clinical signs.

Infectious Dose

Clinical Signs

The clinical signs can be grouped into three categories, with the predominant findings in each arranged in order of decreasing frequency.

• Disturbance of behaviour
  • Apprehension, fearfulness
  • Aggressiveness
  • Tremors: trembling and muscle twitching
• Disturbances of locomotion
  • Abnormal posture
  • Lack of co-ordination, primarily in the hind limbs
  • Recumbency in later stages
• Disturbance of sensitivity
  • Easily startled by minor disturbances such as noise or movement of people or animals
  • Hypersensitivity to light, touch and noise
• In addition there is often loss of body weight, condition and reduced milk production, despite continued appetite.

The duration of the clinical disease can range from less than two weeks to as long as one year. The majority of cases will require euthanasia within two months of onset.

Pathology

Mortality/Morbidity

Differential Diagnosis

• rabies
• listeriosis - bacterial encephalitis
• nervous ketosis
• hypomagnesemia (grass tetany)
• hypocalcemia
• thromboembolic meningoencephalitis
• spinal cord or brain abscess or neoplasia
• traumatic injury
• lead poisoning or other toxicity
• polioencephalomalacia

The Government of Canada has amended the Food and Drug Regulations and the Health of Animals Regulations to prevent SRM from entering the human food supply. The regulations establish a definition for SRM and prohibit the sale or import for sale of food products containing SRM under the Food and Drug Regulations from countries that are not BSE-free. Amendments to the Health of Animals Regulations require the removal of SRM from carcasses and prohibit the use and export of SRM in food for human consumption.

SRM is currently defined as the skull, brain, trigeminal ganglia (nerves attached to the brain), eyes, tonsils, spinal cord and dorsal root ganglia (nerves attached to the spinal cord) of cattle aged 30 months or older, and the distal ileum (portion of the small intestine) of cattle of all ages. Regulatory amendments have been initiated to move tonsils to the list of tissues to be removed from cattle of all ages.

The removal of SRM is internationally recognized as the most effective public health measure in preventing the transmission of BSE. Canada does not support the routine testing of healthy slaughter cattle as it is not as an efficient or cost effective measure to protect human health as the removal of SRM.

Because of BSE’s zoonotic potential, safety precautions to prevent exposure to the BSE agent should be taken by laboratory and field staff involved in the sampling of potentially infectious tissue (brain) from BSE suspect or equivalent risk animals as detailed in 6.2 Appendix 2-Sanitary Precautions/Disinfectants.