Scrapie: Introduction
(Tremblante du mouton, Rida) |  |
| Scrapie is a fatal neurologic disease that produces subacute spongiform encephalopathy in adult sheep. Similar diseases are found naturally in goats and with an increasing incidence in indigenous populations of deer and elk in North America (see
chronic wasting disease,
Chronic Wasting Disease: Introduction). Feedstuff derived from sheep meat and bonemeal that had been inadequately treated during manufacture was formerly thought to be the source of bovine spongiform encephalopathy (BSE,
Bovine Spongiform Encephalopathy: Introduction) and the newly recognized transmissible spongiform encephalopathies seen in captive wild ruminants, domestic cats, and captive wild Felidae. |
| Etiology, Transmission, and Pathogenesis: |
| Two possible structures for the causal neuropathogen have been proposed: 1) the prion—a small exogenous particle consisting of prion protein (PrP), which is an abnormal, proteinase-resistant form of a host cellular protein, that can act as a catalyst to convert more of the host’s protein to the abnormal form, and 2) the virino—a hybrid particle consisting largely of a small agent-specific core of nontranslated nucleic acid (which exists only to replicate itself )
associated with host cellular proteins (which may include PrP). Whatever the nature of the infectious agent, one of its most striking features is its resistance to conventional physical and chemical treatments that destroy bacteria, spores, fungi, and viruses. |
| In the course of the disease, the cellular form of PrP undergoes a conformational change, resulting in increased β-sheet folding and subsequent appearance of scrapie-associated fibrils (SAF). Amino acid substitutions in 3 regions of the host PrP gene govern disease susceptibility and influence how rapidly the disease progresses. |
| Scrapie is frequently transmitted in family lines in flocks, which indicates that some form of maternal transmission may occur at a pre- or postnatal stage. The infected placenta may also be eaten by other sheep or contaminate pastures, which may account for horizontal transmission. In some cases, abnormal PrP can be detected in biopsied tonsils in sheep ≤6 mo old. Subsequently, the agent is detectable at increasing titers in lymphoreticular tissues and after ~2 yr in the CNS,
where lesions develop; clinical signs follow typically at 3½ yr. |
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| Clinical Findings: |
| The onset is insidious. Behavioral changes may include increased excitability, nervousness, or aggressiveness, particularly elicited by sudden noise or movement. Fine tremors of the head and neck (tremblante du mouton) and occasional convulsions may be seen. Lack of limb coordination with a tendency to move at a trot or hop like a rabbit is characteristic. |
| Water metabolism is altered; affected sheep drink small quantities frequently, and urination may be abnormal with voiding of small quantities of urine. Intense pruritus, which often begins over the rump and can also include the head, is common although it is not seen in all cases. The fleece is dry, separable, and brittle, resulting in loss of fleece over large areas. Other areas may be rubbed raw. In some cases, the pruritus makes it difficult for the animal to feed and rest
normally, which is a major factor in emaciation and weakness. In less well-defined cases, pressure to the base of the tail can often elicit a nibbling response. Different breeds of sheep may not show the full range of clinical signs, and sheep may die without clinical signs. |
Lesions:
| Pathologic lesions are restricted to microscopic changes in the CNS. Single or multiple vacuoles surrounded by a zone of cytoplasmic degeneration may be present in neurons of the medulla, pons, midbrain, and spinal cord. Spongiform changes may also affect the surrounding neuropil. In scrapie-affected brains, abnormal PrP accumulates in various patterns, including deposits in the cytoplasm and cell membrane of neurons and astrocytes in the medulla oblongata and pons, with
amyloid staining in the walls of blood vessels and perivascularly in the thalamus of many infected sheep. The medulla at the level of obex is the earliest site of accumulation, and deposits in the dorsal motor nucleus of the vagus suggest that the agent gains access to the brain from the peripheral innervation of the GI tract. |
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| Diagnosis: |
| This is based on clinical signs and microscopic examination of the CNS. Further confirmation is provided by immunoblotting to detect abnormal PrP or by electron microscopy to detect abnormal SAF. Subclinical disease can also be detected from biopsied tonsils, which can be positive for abnormal PrP in sheep <1 yr old incubating the disease. |
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| Epidemiology and Control: |
| The prevalence of scrapie in sheep is unknown. However, the incidence is probably moderate in Great Britain and lower in most other countries in Europe and North America. |
| There is no treatment, although the disease was eradicated from Australia and New Zealand by compulsory slaughter of imported sheep and flockmates shortly after release from quarantine. After the disease first appeared in the USA (in 1947), the Scrapie Eradication Program was established. This involved identification of affected animals and destruction of all sheep in the flock as well as other exposed flocks. This procedure was modified in 1983 to destroy mainly bloodline
animals because of the strong familial occurrence of the disease. The current program in the USA is based on active, passive, and slaughter surveillance with removal of genetically susceptible sheep from flocks in which scrapie is detected. An eradication scheme has begun in the UK based on PrP gene susceptibility. It aims to replace scrapie-susceptible PrP alleles with more resistant ones, thereby controlling and eventually eliminating the disease from the national flock. |
| Goats can be infected by contact with scrapie-infected sheep, either directly or by exposure to contaminated pastures. |
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