Chapter 7 - Voluntary Scrapie Flock Certification Program
7.1 The Disease

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Note: The use of the term "scrapie" refers to classical scrapie only; certification does not cover "atypical" scrapie, which is clinically, pathologically, biochemically and epidemiologically unrelated to classical scrapie.

Etiology

  • 1. Scrapie, a fatal disease, affects the central nervous system of sheep and goats and belongs to the family of diseases known as the transmissible spongiform encephalopathies (TSEs). While the precise cause of these diseases is still a subject of significant research, abnormal prion protein is associated with the presence of disease. This abnormal prion protein converts normal host prion proteins into the abnormal form. The accumulation of this abnormal prion protein is believed to cause the clinical signs of the disease.

Susceptible Species

  • 2. Scrapie is a naturally occurring disease of domestic and wild (mouflon) sheep and goats.

Distribution

  • 3. The disease was first reported in sheep over 250 years ago, and in Canada in 1938. Scrapie has been diagnosed in both sheep and goats in Canada, with the majority of cases identified in Ontario and Quebec. Scrapie is currently recognized in many small ruminant-raising countries all over the world. New Zealand and Australia are notable as countries recognized free from the disease.

Epidemiology

  • 4. The primary method of infection for most animals is through exposure to scrapie-infected sheep or goats and their scrapie-contaminated environment. It is thought that scrapie is most commonly spread from infected females to lambs or kids at birth through contact with the placenta and placental fluids, which contain large quantities of infectious scrapie prions. Healthy animals become infected by eating or licking contaminated materials in the lambing or kidding environment. Newborn lambs and kids sharing the same contaminated environment (lambing pen) are extremely susceptible to infection. Adult animals sharing the same environment are also at risk.

Transmission of scrapie between animals has been documented in the absence of lambing, and infectious prions have been found in feces, saliva and milk from both clinically and sub-clinically infected animals. As a result, pasture previously grazed by infected small ruminants or buildings previously inhabited by them may represent a transmission risk. Further, animals incubating the disease and even animals that never develop clinical signs may be a source of infection to others.

Abnormal prion proteins are extremely resilient with regards to traditional approaches to disinfection, as they are very resistant to both chemical and physical inactivation and stable over a wide pH and temperature range. While they undergo a significant decrease in infectivity titre with time, they have been demonstrated to persist in the environment for years. Reports indicate that environmental contamination as much as 16 years earlier can result in the reintroduction of scrapie infection.

There is no evidence to date that implicates semen in the transmission of scrapie. Several separate research studies on the potential of scrapie transmission by embryos have produced conflicting results. The research in this area has been assessed and the World Organisation for Animal Health (OIE) Terrestrial Animal Health Code currently states that when authorizing import or transit of in-vivo sheep-derived embryos, no scrapie-related conditions should be required, regardless of the scrapie risk status of the sheep and goat populations of the exporting country, zone or compartment. This applies as long as the embryos are handled in accordance with OIE embryo collection and processing requirements.

Genetic Effects

  • 5. Genetic makeup has been determined to be a significant factor in a sheep's susceptibility to infection with scrapie. At the present time, studies on goat genetics and scrapie susceptibility are more limited and less clear.

Current evidence indicates that there are different forms of the sheep prion protein. Some forms are highly susceptible to the structural transformation to the abnormal form found in scrapie, while others are resistant to this change. As in all mammals, sheep are diploid organisms, so that all cells contain two copies of each chromosome and, thus, two copies of the gene that codes for the normal prion protein. Genes are made up of codons. A codon is a stretch of DNA that determines which particular amino acid will be included at a particular location of a protein (in this case, the prion protein). The prion protein is composed of 256 amino acids; therefore, there are 256 codons determining these amino acids. In the literature concerning susceptibility to various strains of scrapie, three codons are discussed: 171, 154 and 136. In North America, two of these codons are given primary importance: 171 and 136. The presence of an arginine (R) at codon 171 of the prion protein confers resistance to the infectious scrapie prion protein. The presence of glutamine (Q) or histidine (H) – treated the same as a Q at codon 171 – is associated with susceptibility to the infectious scrapie prion protein. An alanine (A) at codon 136 confers resistance to the scrapie prion protein, while the presence of valine (V) at codon 136 confers greater susceptibility. V at site 136 is linked with Q at site 171, such that R cannot be found at site 171 in combination with V at site 136.

Scrapie susceptibility as defined by the codons 171 and 136 is as follows:
Sheep's Genotype (136, 171) Susceptibility to classical scrapie
AA RR Negligible
AA QR Very low
AV QR Intermediate
AA QQ
AV QQ
VV QQ
High

It is still not definitively known whether animals with less susceptible genotypes do not become infected with the scrapie agent or whether they are merely protected from developing the clinical signs of scrapie.

The vast majority of positive cases of scrapie that have been genotyped in North America have been determined to be homozygotes for QQ at codon 171. Small numbers of QRs around the world have tested positive for scrapie. In these cases, the amino acids at codon 136 are examined and heterozygotes for A and V at codon 136 appear to indicate greater susceptibility among the QR population. Although no cases of scrapie with 171RR genotype have been reported in North America, a couple of cases have been reported in Europe.

Recent science indicates that the genotype of the fetus influences the migration and accumulation of abnormal prion in the placenta of an infected ewe. The placenta of a 171QQ infected ewe carrying a 171QQ fetus accumulates large quantities of abnormal prion, which is then shed during birth or abortion. However, the abnormal prion does not accumulate in the placenta of a fetus with a 171QR or 171RR genotype. This means that use of a 171RR ram can prevent the shedding of abnormal prion at lambing, even from infected ewes.

It is important for producers to understand that scrapie genotyping is not disease testing. A 171QQ sheep does not automatically have scrapie, just as there is no absolute guarantee that a 171RR sheep cannot get scrapie. The CFIA does not intend to mandate the Canadian sheep flock to breed for scrapie resistance; rather, scrapie genotyping is a tool that can be used in an overall plan to manage the risk of scrapie on a particular premises. Whether or not a particular producer can or should use scrapie genotyping is a decision to be made based on individual factors such as breed, the prevalence of 171RR within the flock, the management of the ewe flock and the current status of other breeding indices.

Clinical Signs

  • 6. Clinical signs of scrapie rarely develop before the age of 18 months and are highly variable. The majority of cases are diagnosed in animals two to five years of age. As many animals do not show overt clinical signs until late in the course of the disease, significant transmission of the scrapie agent occurs prior to any visible indications of a disease problem. Clinical signs vary considerably, with wasting and debility with or without tremors and a lack of coordination being more prominent features throughout the clinical course of cases of scrapie in Canada. Animals can also just have a poor coat or be found dead.

    The predominant nervous signs of scrapie are as follows:

    • tremors and a lack of coordination;
    • a change in mental status (apprehension, teeth grinding and aggression); and
    • altered sensation (pruritus or itchiness, loss of wool, excoriation and inflammation of the skin, nibble reflex and excessive licking).

Differential Diagnosis

  • 7. Differential diagnosis to consider in the initial clinical stages of scrapie includes the following:
    • ectoparasites (lice, mites);
    • hypomagnesaemia;
    • pregnancy toxemia (ovine ketosis);
    • rabies;
    • listeriosis;
    • maedi-visna;
    • pseudorabies (Aujeszky's disease);
    • sarcocystosis.

Laboratory Diagnosis

  • 8. Scrapie is diagnosed through the detection of the abnormal prion protein in brain or lymphoid tissue. Tissues to submit for post-mortem diagnosis include the obex of the brain and the retro-pharyngeal lymph nodes. Abnormal prion protein has been detected in young animals, but is only consistently detected in animals over 12 months of age. Typically, a preliminary test is administered (enzyme-linked immunosorbent assay [ELISA]), and if this identifies the potential presence of scrapie, it is followed by confirmatory testing using immunohistochemistry and/or Western blot.

Detection of abnormal prions by live animal testing with either third eyelid biopsy or recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy has highspecificity; however, it has lower sensitivity with false negatives occurring. To maximize sensitivity, third eyelid testing should be applied to ewes over 14months of age with the genotype 171QQ. Similarly, RAMALT testing should be applied to ewes over 12 months of age with the genotype 171QQ, and does over 12 months of age. Lymphoid tissue testingis a useful screening tool for the presence of infection in a flock, but it is not a reliable indicator of individual freedom from disease.

Scrapie genotyping is not testing for disease; it is a screening test that indicates a sheep's relative susceptibility for scrapie. When one is trying to find infection, sheep with the highest susceptibility are the subpopulation in which one is most likely to discover the disease.

Immunity

  • 9. No immune response to scrapie prion protein has been detected.

Public Health

  • 10. Scrapie is not considered to pose a risk to human health.
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