Scrapie

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Also known as: ‘’’’’TSE – Transmissible spongiform encephalopathy ‘’’’’’, ‘’’’’Paraplexia enzootica ovium’’’’’,

Introduction

Scrapie was first described in the UK in 1732 [1], [2], and recognised as an infectious disease in 1936 [3], [4],. It is a progressive, fatal and non-febrile neurological disorder affecting sheep and goats. It belongs to a group of diseases called transmissible spongiform encephalopathy (TSE) and other TSE’s include Creutzfeldt-Jakob disease in humans, BSE, chronic wasting disease (CWD) in elk and deer, transmissible mink encephalopathy and feline spongiform encephalopathy has been found within cats in the UK. The disease is believed to be caused by a conformational change in the prion (PrP). A prion is a protein that occurs normally in the nervous and lymphoreticular tissues. It is only when the prion changes conformation into a protease-resistant protein PrPsc that it causes degeneration of neurological tissue. The disease causes astrocyte proliferation and then vacuolization of neurons but demyelination does not occur [5].The abnormal protein is thought to act as a catalyst to convert more of the host’s protein into this abnormal form. The disease has been notifiable in the EU since 1993 but unlike BSE there is no evidence to suggest that scrapie is a risk to human health [6], [7],;[8], [9]. Studies on the spread of scrapie infectivity have suggested that after oral intake, PrPSc first accumulates in Peyer’s patches of the small intestine, gut-associated lymphoid tissues (GALT) and ganglia of the enteric nervous system Cite error: Invalid <ref> tag; invalid names, e.g. too many, [10],[11], [12]. PrPScthen moves onward to the tonsil, spleen, retropharyngeal lymph nodes, mesenteric lymph nodes, and peripheral nervous tissue [13], [14],[15]. PrPSc eventually spreads to most lymph nodes and the central nervous system (CNS). PrPSc can be found in the lymphoreticular system tissues for months before it is found in the brain [16]; [17]; [18]; [19]; [20]. Affected animals may live one to six months after onset of clinical signs [21]; [22] , [23],[24], [25]

The original source of disease is thought to have come from imported Merino sheep from Spain [26]; [27], and spread through the movement of of scrapie-infected preclinical sheep [28]; [29]; [30]; [26]; [31]. Scrapie is now endemic throughout Europe and most other continents [32]; [33]. It has also been reported in goats [34]; [35]; [36], [3]; [37];[38]; [39]; [40]; [41]; [42]; [43] Only Australia and New Zealand are recognized as being currently free of scrapie.

Signalment

Scrapie has a long incubation period of two to five years [27] and affects the majority of sheep between 3 and 5 years of age. It is able to withstand a high degree of heat and high concentrations of formaldehyde [44]; [45] and unlike BSE is influenced by breed and genetic variations among sheep influence infectivity and the incubation period of scrapie. Research has shown that 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 [46]; [47]; [48]; [49]; Cite error: Closing </ref> missing for <ref> tag; [50], [51] , [52],; [53],, [54],, [55],, [56], [57],; [58],; [59],[60],[61],[62],[63], [64],. The disease has been shown to be effectively transmitted during lambing [65]; [39] as placenta and possibly the placental fluids are thought to be a source of infection [66]; [67]; [68]; [69]; [70] and experimental studies have shown that oral dosing of infected placenta can spread the disease in sheep and goats [71].

Clinical Signs

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 (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 and may lead to wool loss (especially over the hindquarters and lateral thorax). 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. [72], [73]; [74]; [75], [26]; [76]. It is important to note that some scrapie-infected sheep may appear healthy until stressed by transport, shearing, or pregnancy [32].

Diagnosis

A pre-emptive diagnosis of scrapie may be made from the above clinical signs combined with history and confirmed with laboratory tests. As there is no immune or inflammatory response there are no serological test available for scrapie [77]; [78] Pathologic lesions are confined to the CNS. Histology (immunohistochemistry) usually shows vacuolation and an accumulation of prion proteins in various parts of the CNS (medulla, pons, midbrain, and spinal cord). However vacuolation is not completely diagnostic since it may also be present to a lesser extent in the brains of healthy sheep [79]; [80]. In most instances the abnormal prion is resistant to protein kinase digestion, a feature used in diagnostic techniques.

 PrPSc from post-mortem brainstem or lymphoid tissues may be detected by Western immunoblot analysis [81]; [82]; [83] and immunohistochemistry (IHC) [84] [85]; [86]; [87], [88] . Transmission to mice by injecting suspect tissue can be used to assay infectivity [33]tonsil [89]; [90] and lymphoid biopsies [91]; [92]; [93]; [86]; [94] stained for  PrPsc by using  IHC have been used for preclinical scrapie screening . 

Rapid tests for surveillance that have been approved by the EU include: Western blot test for the detection of the protease-resistant fragment PrPRes (Prionics Check test), Chemiluminescent ELISA test involving an extraction method and an ELISA technique, using an enhanced chemiluminescent reagent (Enfer test) and Sandwich immunoassay for PrPRes carried out following denaturation and concentration steps (Bio-Rad test)[95]

‘’’Differential diagnosis’’’: Viral encephalomyelitides (pseudorabies or Aujeszky’s disease, rabies, maedi visna), Bacterial meningoencephalomyelitides (listeriosis), Pregnancy toxemia (ketosis), Hypocalcemis-hypomagnesemia, Toxins (mercury, lead, organophosphates, plant toxins) and Mange, lice, bacterial dermatitis [33]; [76]

Treatment

Scrapie is a fatal condition and no effective treatment is currently available

Control

Good husbandry and hygiene around lambing can greatly reduce the infectious load . It is recommended that individual straw bale pens are used which can be destroyed after each lambing and that contaminated bedding and placenta should be destroyed immediately. Infection can be minimised 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 [96] [97]; [95]; [98]. Genetic resistance to scrapie depends on the prion genotype of the sheep and on the strain of scrapie present. Genotypes of sheep resistant to one strain of scrapie may be susceptible to another strain but on the whole the ARR allele confers resistance in all breeds. 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 [99] . Many countries use a combination of genetic selection, depopulation of infected sources and sourcing scrapie free flocks to control the spread of scrapie [98] and [100]

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) and was adopted by the EU in 1994 and USA in 1997 [95]; [101].

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