scrapie

Pictures

Picture	Title	Caption	Copyright
Title Symptoms Caption Clinical appearance of a sheep with scrapie: area of alopecia and crusting of skin due to persistent rubbing of head against objects. The disease gets its name from this behaviour, which results from intense pruritis. Copyright Crown copyright 2004, Veterinary Laboratories Agency	Symptoms	Clinical appearance of a sheep with scrapie: area of alopecia and crusting of skin due to persistent rubbing of head against objects. The disease gets its name from this behaviour, which results from intense pruritis.	Crown copyright 2004, Veterinary Laboratories Agency
Title Clinical signs Caption Clinical signs. Sheep with scrapie with wool loss due to scraping. Copyright USDA	Clinical signs	Clinical signs. Sheep with scrapie with wool loss due to scraping.	USDA
Title Retracted nictitating membrane Caption Nictitating membrane of sheep retracted to show lymphoid tissue used for biopsy in preclinical testing. Copyright USDA	Retracted nictitating membrane	Nictitating membrane of sheep retracted to show lymphoid tissue used for biopsy in preclinical testing.	USDA
Title Histopathology Caption Histological section of the dorsal nucleus of the vagus nerve (medulla oblongata) from a sheep with scrapie showing vacuolation of neurons. This neuroanatomical location is the most common target site for such morphological changes in scrapie. (Haematoxylin and eosin stain). Copyright Crown copyright 2004, Veterinary Laboratories Agency	Histopathology	Histological section of the dorsal nucleus of the vagus nerve (medulla oblongata) from a sheep with scrapie showing vacuolation of neurons. This neuroanatomical location is the most common target site for such morphological changes in scrapie. (Haematoxylin and eosin stain).	Crown copyright 2004, Veterinary Laboratories Agency
Title Histopathology Caption Immunohistochemical preparation of the medulla oblongata from a sheep with scrapie: multifocal glial-associated disease-specific prion protein immunostaining. Copyright Crown copyright 2004, Veterinary Laboratories Agency	Histopathology	Immunohistochemical preparation of the medulla oblongata from a sheep with scrapie: multifocal glial-associated disease-specific prion protein immunostaining.	Crown copyright 2004, Veterinary Laboratories Agency
Title Histopathology Caption Immunohistochemistry of medulla oblongata in a sheep positive for PrPSc accumulation. Original image 40X. Copyright USDA	Histopathology	Immunohistochemistry of medulla oblongata in a sheep positive for PrPSc accumulation. Original image 40X.	USDA
Title Histopathology Caption Immunohistochemistry of medulla oblongata in a sheep negative for PrPSc accumulation. original image 40X. Copyright USDA	Histopathology	Immunohistochemistry of medulla oblongata in a sheep negative for PrPSc accumulation. original image 40X.	USDA
Title Histopathology Caption Immunohistochemistry of nictitating membrane in a sheep positive for PrPSc accumulation. Original image 40X. Copyright USDA	Histopathology	Immunohistochemistry of nictitating membrane in a sheep positive for PrPSc accumulation. Original image 40X.	USDA
Title Histopathology Caption Immunohistochemistry of nictitating membrane in a sheep negative for PrPSc accumulation. Original image 40X. Copyright USDA	Histopathology	Immunohistochemistry of nictitating membrane in a sheep negative for PrPSc accumulation. Original image 40X.	USDA

Identity

Preferred Scientific Name

• scrapie

International Common Names

• English: Paraplexia enzootica ovium; scrapie in goats; scrapie in sheep; spongiform encephalopathies; spongiform encephalopathy, scrapie; transmissible spongiform encephalopathies
• French: la tremblante; tremblante du mouton

Local Common Names

• Germany: Traberkrankheit
• Norway: Rida

English acronym

• TSE

Overview

Note: This datasheet covers 'classical' scrapie, not 'atypical' scrapie.

Scrapie is a fatal neurodegenerative disease of sheep and goats. It is part of a group of diseases classified as transmissible spongiform encephalopathies (TSEs). These diseases include bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in elk and deer, transmissible mink encephalopathy, and Creutzfeldt-Jakob disease (vCJD) in humans. The infectious agent is thought to be a prion, an agent smaller than the smallest known virus. Scrapie has a long history with the first descriptions dating back over 250 years. Despite this long history, many factors of the disease are still not fully understood, including a complete characterization of the infectious agent, routes of transmission and pathogenesis. Recent evidence linking vCJD in humans to BSE in cattle has increased attention for all TSEs, including scrapie. There are many laboratories in several different countries actively conducting research on scrapie and other TSEs. There is no evidence to date that scrapie is a risk to human health (Brown et al., 1987; Harries et al., 1988; Kondo and Kuriowa, 1982; WHO, 1999).

Scrapie was first described in the UK in 1732 (McGowan, 1922; Pattison, 1988) and recognized as an infectious disease in 1936 (Chelle, 1942; Poser, 2002). The extremely long incubation period of two to five years was noted as long ago as 1913 (Stockman, 1913). Pattison was the first to show transmission of scrapie to another species, a goat, in 1957 (Pattison, 1957; Pattison and Millson, 1961). In 1961 Chandler showed transmission to mice (Chandler, 1961). Pattison in 1965 showed that the scrapie agent was able to withstand a high degree of heat and high concentrations of formaldehyde (Pattison, 1965; Stamp et al., 1959). In 1966 Alper and colleagues first suggested that the scrapie agent was able to replicate despite apparently lacking nucleic acid (Alper et al., 1966). Prusiner in 1982 proposed that the scrapie agent was a nucleic acid-free proteinaceous infectious molecule or prion (Prusiner, 1982). Later work by Prusiner and colleagues showed that the prion protein (PrP) was a component of the normal cell and was encoded by the host genome (Oesch et al., 1985). The incubation time of scrapie was thought to be controlled by a single gene, Sip (scrapie incubation period) (Dickinson and Outram, 1988). The gene encoding PrP was subsequently found to be congruent to Sip in sheep (Moore et al., 1998). Prion protein is a normal cellular protein in many mammalian cell types (Prusiner, 1998). The normal cellular form undergoes a conformational change to a protease-resistant protein (PrP^Sc). The abnormal protein form of the host cellular protein is thought to act as a catalyst to convert more of the host’s protein to the abnormal form. Prusiner was awarded the 1997 Nobel Prize in Physiology or Medicine for his work on the infectious nature of prions. Soto and colleagues provided strong evidence that PrP^Sc is the infective agent of scrapie in a series of experiments reporting reversal of infectivity in PrP^Sc (Soto et al., 2000).

While scrapie has a long history and attempts have been made over the years to control and eradicate the disease, it remains endemic in many countries.

Scrapie has been recognized as a disease of sheep for more than 250 years. It is one of a small number of diseases known as the transmissible spongiform encephalopathies, along with:

Host Animals

Hosts/Species Affected

Genetic variations among sheep influence infectivity and the incubation period of scrapie. Amino acid changes in at least three locations on the PrP gene, codons 136, 154, and 171, have been shown to confer increased or decreased susceptibility to scrapie (Belt et al., 1995; Billinis et al., 2004; Clouscard et al., 1995; Elsen et al., 1999; Goldmann et al., 1991; Goldmann et al., 1990; Goldmann et al., 1994a,b; Hunter and Cairns, 1998; Hunter et al., 1997a,b,c; Hunter et al., 1991; Hunter et al., 1996; Hunter et al., 1992; Hunter et al., 1993; Hunter et al., 1994; Ikeda et al., 1995; Thorgeirsdottir et al., 1999; Tranulis et al., 1999; Westaway et al., 1994). The incidence of scrapie in various breeds of sheep has been associated with some of those polymorphisms (Bossers et al., 1996; Dickinson et al., 1968; Goldmann et al., 1991; Goldmann et al., 1990; Goldmann et al., 1994a; Hunter et al., 1991; Hunter et al., 1996; Hunter et al., 1992; Hunter et al., 1993; Hunter et al., 1997a,b; Hunter et al., 1994; Laplanche et al., 1993a; O'Rourke et al., 1997). At codon 136, the amino acid valine (V) has been linked to scrapie susceptibility while an alanine (A) was linked to resistance (Hunter et al., 1996; Hunter et al., 1994). At codon 171, glutamine (Q) or histidine (H) have been linked to scrapie susceptibility while an arginine (R) has been linked to resistance (Hunter, 1997; Ikeda et al., 1995; O'Rourke et al., 1996; Westaway et al., 1994). At codon 154, histidine (H) was linked to susceptibility while arginine (R) was linked to resistance (Laplanche et al., 1993a). Variation at codon 154 was shown to modulate incubation time in some breeds and may decrease susceptibility in other breeds (Dawson et al., 1998; Thorgeirsdottir et al., 1999). With very few exceptions, naturally infected sheep of a number of breeds in the USA, UK, Europe and Japan carry either 136 Valine (136 Valine/Valine or 136 Valine/Alanine) or 171 Glutamine/Glutamine (QQ) (Belt et al., 1995; Clouscard et al., 1995; Hunter et al., 1993; Hunter et al., 1994; Ikeda et al., 1995; Laplanche et al., 1993; Laplanche et al., 1993; O'Rourke et al., 1996; Westaway et al., 1994). There has been only one report of a scrapie-affected Suffolk carrying 171 Arginine/Arginine (RR) (Ikeda et al., 1995) and four published reports of scrapie-affected Suffolks with 171 Glutamine/Arginine (QR) (Hunter et al., 1997c; Ikeda et al., 1995).

PrP genotyping can be used as an aid in the control of scrapie. Several researchers have proposed breeding stock of resistant PrP genotypes and selection to produce progeny with reduced risk of disease (Dawson et al., 1998; Drögemüeller et al., 2001; Parry, 1979; Schreuder et al., 1997). The genotype of the fetus was found to be a factor in the deposition of PrPSc in the placenta (Andréoletti et al., 2002; Tuo et al., 2002). The fetal ARR allele was found to be associated with a lack of PrPSc deposition. Fetuses homozygous for ARQ were also shown to lack PrPSc in the placenta.

There are research efforts currently underway in several countries examining the possibility of a carrier state for scrapie; animals that become infected and shed the scrapie agent, but do not progress to develop clinical disease. Studies thus far have failed to detect such animals (Elsen et al., 1999), USDA-ARS, Pullman, WA, unpublished results.

Polymorphisms of the gene encoding the PrP protein have been found at many codons in the goat (Billinis et al., 2002; Goldmann et al., 1996), but only a couple have been associated with scrapie to date (Billinis et al., 2002; Goldmann et al., 1998; Goldmann et al., 1996). Research is continuing in this area and should provide more insight as more scrapie cases in goats are detected.

Other risk factors include sanitation issues such as not disposing of placental tissues and contaminated bedding after lambing. Farms that employed breeding and lambing management practices with lambing occurring in group pens were found more likely to report scrapie than farms where lambing occurred on pasture or in individual pens (Elsen et al., 1999; McLean et al., 1999).

Systems Affected

Distribution

The spread of sheep scrapie in Europe has been reported to have resulted from the importation of certain breeds of sheep such as the Merino from Spain (Parry and Oppenheimer, 1983; Stockman, 1913). The disease was spread through the movement of scrapie-infected preclinical sheep (Brash, 1952; Bull and Murnane, 1958; Cooper, 1973; Parry and Oppenheimer, 1983; Merwe, 1966). Scrapie was imported into Canada from the UK in 1938 (Schofield, 1938). The first case of scrapie in the USA was diagnosed in 1947 in a Michigan flock (USDA, 2005). The flock owner had imported sheep of British origin through Canada for several years. The incidence within a flock can be variable with reports in UK ranging from 0.37% to 20% (Hoinville et al., 2000; Hoinville et al., 1999; Schreuder et al., 1993; Sigurdarson, 1991).

Scrapie is endemic in many European countries and has been reported in several countries throughout most other continents (Detwiler and Baylis, 2003; OIE, 2000). Scrapie in goats has been reported in many countries (Andrews et al., 1992; Brotherston et al., 1968; Capucchio et al., 1998; Chelle, 1942; Fankhauser et al., 1982; Harcourt, 1974; Hourrigan et al., 1979; Leontides et al., 2000; Stemshorn, 1975; Toumazos, 1991; Toumazos and Alley, 1989). Only Australia and New Zealand are recognized as being free of scrapie.

Scrapie has been a notifiable disease within the EU since 1993, and many countries of the EU as well as the USA and Canada use active surveillance programs where slaughter surveillance combined with mandatory identification provides information on national and regional prevalence(CFIA, 2005; European Commission, 2001; USDA, 2005). Many countries lack a surveillance program, so their scrapie status is unknown. There is no preclinical screening test that reliably detects all scrapie-infected sheep so determining the scrapie status of countries is difficult. Passive surveillance, or data collected from disease observations on an ad hoc basis, is not adequate for detecting all cases of scrapie. Australia and New Zealand appear to have successfully eliminated scrapie after the introduction of the disease from imported sheep by the complete depopulation of all imports and all contact sheep (Detwiler and Baylis, 2003).

For current information on disease incidence, see OIE's WAHID Interface.

Distribution Table

The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Pathology

Pathologic lesions are restricted to microscopic changes in the CNS. Grossly, sheep and goats may show a loss of body condition and there may be wool loss in sheep that are pruritic and scraping.

Diagnosis

Clinical diagnosis

A preemptive diagnosis of scrapie may be made from clinical signs combined with history. Diagnosis cannot be confirmed without laboratory tests.

Lesions

Microscopic changes in the CNS are degenerative and unaccompanied by inflammation. Single or multiple vacuoles surrounded by a zone of cytoplasmic degeneration may be present in the neurons of the medulla, pons, midbrain, and spinal cord. The surrounding neuropil may also be affected by spongiform changes (Brown et al., 1999; Fraser, 1976; Wells and McGill, 1992; Wood et al., 1997). The vacuolation is not completely diagnostic since it may also be present to a lesser extent in the brains of healthy sheep (Fraser, 1976; Zlotnik and Rennie, 1958). Astrocyte proliferation precedes the vacuolization of neurons and demyelination does not occur (Dandoy-Dron et al., 1998).

Differential diagnosis

Scrapie may be confused with other neurological diseases or other diseases that cause progressive loss of condition or pruritus with skin lesions. Major differentials (OIE, 2000; Radostits et al., 2000) include:

Viral encephalomyelitides (pseudorabies or Aujeszky’s disease, rabies, maedi visna)
Bacterial meningoencephalomyelitides (listeriosis)
Pregnancy toxemia (ketosis)
Hypocalcemis-hypomagnesemia
Toxins (mercury, lead, organophosphates, plant toxins)
Mange, lice, bacterial dermatitis

Laboratory diagnosis

There are no serological tests available for scrapie. No immune response or inflammatory response has been detected (Kasper et al., 1982; Porter et al., 1973). PrP^Sc from postmortem brainstem or lymphoid tissues may be detected by Western immunoblot analysis (Farquhar et al., 1989; Stack et al., 1996; Wadsworth et al., 2001) and immunohistochemistry (IHC) (Miller et al., 1993; Miller et al., 1994; O'Rourke et al., 1998; Keulen et al., 1996; Keulen et al., 1995). Transmission to mice by injecting suspect tissue can be used to assay infectivity (OIE, 2000).

Other diagnostic tests

Tonsil biopsies with subsequent staining for PrPSc by IHC can be used for preclinical scrapie screening (Schreuder et al., 1998; Schreuder et al., 1996). In the most susceptible genotypes, PrPSc was found in the tonsils of sheep at four to five months of age (Schreuder et al., 1998). Preclinical antemortem testing is also available detecting PrPSc by IHC in nictitating membrane lymphoid biopsies (Bender et al., 2004; Ikegami et al., 1991; O'Rourke et al., 2000; O'Rourke et al., 1998; Thuring et al., 2000). The third eyelid lymphoid tissue can be used for diagnosis in sheep over 14 months of age and was recognized in 2001 as an official preclinical screening test for scrapie in the USA. Biopsy of the rectoanal-associated lymphoid tissue and with PrP^Sc by IHC can also be used to identify pre-clinical infection (Gonzalez et al., 2005).

Rapid immuno- or ligand binding assays that are currently approved by the EU for active surveillance for small ruminant TSEs (European Commission, 2001) are:

Bio-Rad TeSeE rapid test

Bio-Rad TeSeE Sheep/Goat rapid test

Enfer TSE Kit version 2.0

Enfer TSE Version 3

IDEXX HerdChek BSE-Scrapie Antigen Test Kit, EIA

Prionics-Check Western Small Ruminant test

Prionics Check LIA Small Ruminants

(Commission Regulation (EC) No 162/2009) 

Also approved by the EFSA BIOHAZ Panel and awaiting statutory incorporation to the EU approved list is the Prionics Check Prio STRIP SR (EFSA Panel on Biological Hazards, 2012).

At this time only IHC of brain or lymphoid tissues has been approved for diagnosis of scrapie in the USA.

List of Symptoms/Signs

Disease Course

The majority of cases of scrapie in sheep occur in animals between three to five years of age. It is generally thought that transmission is most efficient during lambing (Dickinson et al., 1974; Hourrigan et al., 1979). Horizontal transmission of scrapie has been shown in field conditions with unrelated sheep (Brotherston et al., 1968; Dickinson et al., 1974; Hourrigan et al., 1979) and in heavily infected flocks (Matthews et al., 1999; Ryder et al., 2004; Woolhouse et al., 1998). Horizontal transmission to goats reared with infected sheep has also been documented (Billinis et al., 2002; Brotherston et al., 1968; Dickinson et al., 1974; Toumazos and Alley, 1989). The placenta and possibly the placental fluids are thought to be a source of infection. Infection is thought to occur orally among newborn lambs and any cohort adult sheep or lambs that may come in contact with the infected material (Dickinson et al., 1974; Hourrigan et al., 1979). PrP^Sc has been found in the placenta (Andréoletti et al., 2002; Onodera et al., 1993; Race et al., 1998; Tuo et al., 2002; Tuo et al., 2001), and various other tissues (Andréoletti et al., 2000; Heggebø et al., 2000; Jeffrey et al., 2001a,b; Race et al., 1998; Keulen et al., 1996; Keulen et al., 1999). These studies did not include tests for infectivity. Infectivity of the placenta was shown in an oral dosing experiment in 1972 where placenta was given to sheep and goats (Pattison et al., 1972). Experimental transmission of scrapie to sheep and goats using infected brain tissue has also been shown (Foster et al., 2001; Pattison and Millson, 1961). There have been unsuccessful attempts to identify the scrapie agent in blood (Hadlow et al., 1974; Hadlow et al., 1982; Hadlow et al., 1980; Pattison and Millson, 1962a,b), but in 2002 the transmission of scrapie was achieved with whole blood transfusion and a buffy coat transfusion (Hunter et al., 2002).
Studies on the spread of scrapie infectivity have suggested that after oral intake, PrP^Sc first accumulates in Peyer’s patches of the small intestine, gut-associated lymphoid tissues (GALT) and ganglia of the enteric nervous system (Beekes and McBride, 2000; Beekes et al., 1998; Heggebø et al., 2000; Kimberlin and Walker, 1989; Keulen et al., 1999). PrP^Sc then moves onward to the tonsil, spleen, retropharyngeal lymph nodes, mesenteric lymph nodes, and peripheral nervous tissue (Mabbott and Bruce, 2001; Maignien et al., 1999; Press et al., 2004). PrP^Sc eventually spreads to most lymph nodes and the central nervous system (CNS). PrP^Sc can be found in the lymphoreticular system tissues for months before it is found in the brain (Eklund et al., 1967; Hadlow et al., 1974; Hadlow et al., 1982; Hadlow et al., 1980; Hadlow et al., 1979).
Early clinical signs may include subtle behavioural changes such as staring or fixed gaze, teeth grinding (bruxism), fine tremor, and hyperaesthesia to sound or sudden movements. Affected animals may later become intolerant to exercise and develop ataxia. The ataxia can include awkwardness at turning, swaying of the hindquarters and some gait abnormalities such as a high stepping gait in the forelimbs or a bunny hopping gait in the hindlimbs. Some sheep have intense pruritis that leads to compulsive rubbing, nibbling at the skin, or scraping against fixed objects. This may lead to wool loss especially over the hindquarters and lateral thorax. This clinical sign is also the origin of the term ‘scrapie’. A characteristic lip smacking or nibbling reflex can often be elicited by scratching over the lumbar region. In later stages there can be significant weight loss even without a noticeable decrease in appetite, weakness, recumbency, and death. (Bradley, 1997; Dickinson, 1976; Kimberlin, 1981; Palmer, 1976; Parry and Oppenheimer, 1983; Radostits et al., 2000). Affected animals may live one to six months after onset of clinical signs (Capucchio et al., 2001; Foster et al., 2001a,b,c; USDA, 2005). It is also important to note that some scrapie-infected sheep may appear healthy if left undisturbed, but the stress of transport, shearing, or pregnancy may bring on clinical signs (Detwiler and Baylis, 2003).

Impact: Economic

Scrapie is classified as a notifiable disease by the World Organization for Animal Health (OIE); transmissible diseases that are considered to be of socioeconomic and/or public health importance within countries and that are significant in the international trade of animals and animal products (OIE, 2005). The presence of scrapie in sheep-producing countries prevents the export of breeding stock, semen, and embryos to many other countries. For example the American Sheep Industry Association estimates that scrapie costs the industry over US $20 million each year in lost export sales, disposal costs for offal, and lost productivity (National Institute for Animal Agriculture, 2005).

Zoonoses and Food Safety

The European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC) reviewed the evidence for links between animal and human TSEs. They concluded that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent (EFSA Panel on Biological Hazards, 2011).

Disease Treatment

No effective treatment is available for scrapie, and the condition is fatal.

Prevention and Control

Until relatively recently, scrapie has been a difficult disease to control. The lack of a live animal test that would allow for large scale flock screening has meant that infected animals are not identified until clinical disease appears: epidemiological studies are also hampered.

The potential for PrP genotyping to control scrapie started to emerge in the 1990s when case control studies demonstrated clear linkage between scrapie risk and PrP genotype in several breeds of sheep in Britain (Hunter et al., 1997). The signi?cant polymor­phisms linked to disease risk are at codons 136 (alanine/valine), 154 (arginine/histidine), and 171 (glutamine/histidine/arginine) of the ovine PrP gene. Combinations of these poly­morphisms produce ?ve commonly seen PrP haplotypes or alleles – ARR, AHQ, ARH, ARQ and VRQ – not all breeds carry all alleles – with the potential to generate up to 15 genotypes.

Genotyping has been used in two main ways. Firstly, selective breeding programmes have operated in several EU Member States in the last decade, whereby rams are genotyped and then selected for breeding to reduce disease risk in their progeny. This programme requires negative selection of VRQ (and sometimes ARQ) carriers and positive selection for ARR. Secondly, whole flock genotypoing can be targeted at affected flocks, with selective culling of high risk genotypes and leaving a resistant population.

Application of a combination of these programmes in Great Britain since 2002 (Dawson et al., 2008), has seen a steady reduction in estimates of prevalence, as judged by ongoing active surveillance of fallen stock and healthy slaughter sheep. (see: AHVLA, Sheep TSE surveillance statistics (Great Britain).

Husbandry methods and good practice

Husbandry methods such as constructing lambing pens from straw bales and destroying them after each lambing, and moving sheep to clean paddocks in small groups will reduce the risk of cross contamination. Cross infection can be reduced by using several lambing areas separated from each other. Producers should pick up the placenta and clean bedding contaminated with placental fluids and tissues after lambing to minimize scrapie transmission. Intensive production methods appear to increase the spread of the disease.

Farm-level control

Scrapie infection can be minimized by maintaining a closed flock and only obtaining replacement ewes or breeding rams from scrapie-free flocks. Animals of resistant genotypes should be used for breeding to further minimize the risk of scrapie infection in a flock (CFIA, 2005; Dawson et al., 1998; European Commission, 2001; US Department of Agriculture, 2005).

Codon 136: sheep homozygous for alanine (AA) have been shown to be more resistant to scrapie than sheep homozygous for valine (VV) or heterozygous (AV) in European studies. AA sheep in Europe do have a lower incidence of scrapie but they are not completely resistant to scrapie. In sheep in the USA differences at codon 136 are less important than in European sheep, which may be due to differences in the strain of scrapie agent in the two regions.

Codon 154: changes at this codon, arginine (R) or histidine (H) appear to be less important than either the other two codons, and screening sheep for differences at this codon has little value for determining resistance.

Codon 171: amino-acid changes at this codon have a large effect on susceptibility in sheep in both the USA and Europe. Scrapie is very rare in sheep homozygous for arginine (RR) at this codon (a case in a Suffolk in Japan has been reported: Ikeda et al., 1995). The frequency of heterozygous (QR) sheep is low among sheep with scrapie, whereas the frequency of scrapie-infected sheep homozygous for glutamine (QQ) is high (Thomas, 2001).

Therefore the most susceptible genotypes are VV¹³⁶, RR¹⁵⁴, QQ¹⁷¹ and VA¹³⁶, RR¹⁵⁴, and QQ¹⁷¹. Scrapie frequently occurs in AA¹³⁶, RR¹⁵⁴, QQ¹⁷¹ in Suffolk sheep, whereas AA¹³⁶, RR¹⁵⁴, and RR¹⁷¹ confer resistance in all breeds.

National and international control policies

Many countries where scrapie is endemic, including the UK, USA, EU, Iceland and Canada have implemented national control programmes to eradicate scrapie (CFIA, 2005; DEFRA, 2001; European Commission, 2003a,b; Thorgeirsdottir et al., 2002; USDA, 2005). Some countries such as the UK and The Netherlands, and several countries of the EU use genetic selection as their primary means of scrapie control (Drögemüeller et al., 2001; Pluimers, 2004; Sipos et al., 2002). The UK government control programme (National Scrapie Plan or NSP) was launched in 2001 and proposes to increase the frequency of the ARR allele in the UK sheep population (DEFRA, 2001).

Regulation (EC) No 999/2001 of the European Parliament and the Council of the European Union lays down rules for the prevention, control and eradication of transmissible spongiform encephalopathies in animals. [See also, Summaries of EU legislation: Transmissible Spongiform Encephalopathies (TSEs)]

The Scrapie Flock Certification Programme in the USA assigns status to flocks having no evidence of scrapie, thereby providing a source of scrapie-free breeding animals (US Department of Agriculture, 2005). In the USA, sheep of high risk genotypes are also removed from the flock or their movement is restricted. Sheep from infected and source flocks are often depopulated in an effort to eliminate disease. Producers receive compensation by the Federal government for animals that must be removed from the flock. Iceland also uses a combination of genetic selection and depopulation of infected and source flocks for scrapie control (Thorgeirsdottir et al., 2002).

BSE of cattle has been linked to the practice of incorporating rendered ruminant byproducts into cattle feed. Meat- and bone meal-contaminated feeds have not been shown to be involved in scrapie transmission, but prohibiting the use of feeds that contain ruminant animal products in sheep and goats is a prudent measure. In the UK, a feed ban was issued in 1988 prohibiting the feeding of ruminant-derived meat and bone meal to ruminants (HMSO, 2002). This ban was adopted by the EU in 1994 and in the USA in 1997 (European Commission, 2001; FDA, 1997).

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