Federal disease control — Scrapie

Introduction

Scrapie is a naturally occurring disease of domestic and wild (mouflon) sheep and goats. The disease was first reported in sheep over 250 y ago and in Canada in 1938 (1). While the precise cause of the disease is still the subject of significant research, abnormal prion protein is associated with the presence of disease (2,3). Pregnancy appears to trigger the migration of abnormal prion protein to the reproductive tract (4,5,6,7). Birthing fluids and tissues, such as placenta, from infected females contain large quantities of the scrapie agent (8,4). 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 (4,8). Adult females sharing the same environment are also at risk but may require repeated exposure to a contaminated environment before becoming infected (4,7). Although scrapie is an infectious disease, it is not highly contagious. In contrast to some diseases, such as foot-and-mouth disease, casual contact between animals and inanimate objects, such as vehicle tires, people, or the wind, are not known to transmit scrapie (4,5,9,10,11).

Several separate research studies on the potential of scrapie transmission by embryos have produced conflicting results (12,13,14,15). At present, there is inadequate information to negate embryo transfer as a transmission risk or to provide advice on appropriate measures to mitigate this risk. There is no evidence to date that implicates semen in the transmission of scrapie.

Clinical signs of scrapie rarely develop before the age of 18 mo and are highly variable. The majority of cases are diagnosed in animals 2 to 5 y 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 (16,17,18,19,20,21).

The predominant nervous signs of scrapie are as follows (22):

• a change in mental status (apprehension, teeth grinding, aggression);

• altered sensation (pruritus or itchiness, loss of wool, excoriation and inflammation of the skin, nibble reflex, excessive licking);

• tremors; and

• abnormal posture and locomotion (ataxia, “bunny hopping,” recumbency).

Scrapie is a reportable disease in Canada. Anyone suspecting this disease must report this suspicion to a district veterinarian of the Canadian Food Inspection Agency. Diseases that may be confused with scrapie include heavy infestations of ectoparasites (lice & mites), photosensitization, pregnancy toxemia, listeriosis, rabies, maedi-visna, and poisonings (organophosphates and copper).

Role of genetics

Genetic makeup has been determined to be a significant factor in an animal's susceptibility to infection with scrapie. A gene that regulates the incubation period for scrapie (the amount of time to develop the disease) has been identified (23,24,25,26,27,28). The presence of specific amino acids at certain sites on the gene confer scrapie susceptibility. At the other end of the spectrum, the presence of other amino acids at the same sites on the gene appear to confer scrapie resistance. It is still not known whether animals with these latter genotypes do not become infected with the scrapie agent or whether they are merely protected from developing the clinical signs of scrapie (29,30).

The specific amino acids and the sites that appear to confer susceptibility verus resistance vary with the strain of scrapie agent involved and the breed of sheep (31). While the genetic profile for all sheep breeds present in North America has not been determined, all positive cases of scrapie that have been genotyped in North America have been determined to be homozygotes for glutamine (QQ) at codon 71 (Balachrandan A, Sutton D, personal communications).

A blood test (32,33,34,35) is commercially available in Canada to determine the genetic profile of an animal. It is possible to use genetic profile as a farm management tool. Selection of breeding rams may include examination of their genetic profile by blood test. Recent science indicates that the genotype of the fetus may influence the migration and accumulation of abnormal prion in the placenta of an infected ewe (36). A 171 QQ infected ewe carrying a 171 QQ fetus would result in the accumulation of large quantities of abnormal prion, which is then shed during birth or abortion. Theoretically, in a fetus with a genotype 171 QR or 171 RR, the abnormal prion does not accumulate in the placenta and associated fluids. This would mean that use of a 171 RR ram could prevent the shedding of abnormal prion at lambing, even from infected ewes. Heavy promotion of the use of 171 RR rams across Canada might be effective in minimizing the spread of scrapie, but it could result in a significant change in the genotypic profile of sheep in Canada; there might be impacts on secondary characteristics, such as carcass quality, or the unveiling of previously unidentified congenital problems (36).

Detection of infected animals

Routine methods of preventing a disease that is transmitted between animals are vaccination, quarantine, testing, and removal. Since the scrapie agent elicits no detectable immune response in the host, vaccinations and serological testing for presence of antibodies have not been possible to date. At this time, there is no treatment to cure an animal that has contracted the disease.

Scrapie is currently diagnosed by examining brain and other tissues (4,7,37,38,39,40,41,42,43). Lymphoid follicles on the third eyelid (nictitating membrane) may be harvested for testing. However, the abnormal prion protein is not found in this tissue in all scrapie agent-infected sheep. This possibility of a falsely negative test, combined with the fact that this tissue is relatively labor-intensive to harvest, limits the use of the third eyelid test in screening for the presence of disease in groups of animals. Determination of the negative disease status of individual animals is not possible with this test.

The lack of a preclinical screening test for live sheep and goats also presents a challenge to the development of an active surveillance program for scrapie. Brain samples from mature animals could be harvested at the time of slaughter, if this occurs in the presence of a trained individual; in order to support effective disease eradication, active surveillance is only useful when a trace back to the source of the infection (infected premises) is possible. The lack of identification in its small ruminant populations is a substantial obstacle that Canada currently faces in the development of active surveillance and effective eradication of scrapie.

Farm management measures

The lack of a useful preclinical diagnostic test for screening large numbers of live sheep and goats means that the current method of preventing the introduction of scrapie is to maintain a closed flock for females and embryos. If replacement ewes are required, they should be sourced from flocks not known to be affected by scrapie and that take measures to prevent the introduction of scrapie. The following are some preventive steps that a potential purchaser or new owner of purchased animals can take.

• 1. Purchase animals from premises known to be a minimal risk for scrapie.

• 2. Test for genetic scrapie susceptibility and avoid introducing scrapie-susceptible animals.

• 3. Limit introductions to males and semen.

• 4. Although feed has not been identified as a significant factor in the transmission of scrapie, comply with the feed ban. Feed or feed ingredients manufactured and distributed for the use of nonruminant species, such as pigs, poultry, dogs, or cats, should not be fed to sheep or goats.

Scrapie control at the national level

Due to the constraints on active surveillance outlined above, the national scrapie control program has been slow in detecting new infected premises. However, concerns over transmissible spongiform encephalopathies in general may provide the impetus for governments and industry to address such issues as identification and resource implementation, significant enhancements to the national control program.