scrapie scrapie scrapie (/ˈskreɪpi/) is a fatal, degenerative disease affecting the nervous systems of sheep and goats. it is one of several transmissible spongiform encephalopathies (tses), and as such it is thought to be caused by a prion. scrapie has been known since at least 1732 and does not appear to be transmissible to humans. however, new studies suggest a link between scrapie and sporadic cjd. ewe with scrapie with weight loss and hunched appearance same ewe as above with bare patches on rear end from scraping the name scrapie is derived from one of the clinical signs of the condition, wherein affected animals will compulsively scrape off their fleeces against rocks, trees or fences. the disease apparently causes an itching sensation in the animals. other clinical signs include excessive lip smacking, altered gaits and convulsive collapse. scrapie is infectious and transmissible among conspecifics, so one of the most common ways to contain it (since it is incurable) is to quarantine and kill those affected. however, scrapie tends to persist in flocks and can also arise apparently spontaneously in flocks that have not previously had cases of the disease. the mechanism of transmission between animals and other aspects of the biology of the disease are only poorly understood, and are active areas of research. recent studies suggest prions may be spread through urine and persist in the environment for decades. scrapie usually affects sheep around three to five years of age. the potential for transmission at birth and from contact with placental tissues is apparent. regulation the disease has been notifiable in the eu since 1993, but unlike bse, there was no evidence as of 1999 to suggest that scrapie is a risk to human health. in july 2003, a canadian food inspection agency officer said that while scrapie shows up every year on canadian farms, "we've had a lot of experience with scrapie and there's never been a link between scrapie and human illness." as of 2004, the usda made no mention of scrapie in its sheep and goats death loss circular. historically, scrapie had been considered to be an animal health issue. however, between 1996 and 1999 the uk spongiform encephalopathy advisory committee had been considering the control and eradication of scrapie in the uk also with public health in mind because of concern over five issues: meat and bone meal (mbm), which was suspected to be the source of the bse in cattle outbreak in the late 1990s, had also been fed to sheep and goats. bse had been transmitted to sheep following experimental oral exposure. transmissible spongiform encephalopathy (tse) infection was widespread through the carcasses of the sheep, unlike cattle infection which is limited to neural tissues. scrapie in sheep was underreported and it might be masking bse – were it present in sheep. specified risk material (srm) measures may not be adequate to control human exposure. cause scrapie and other transmissible spongiform encephalopathies are caused by prion disease. prions were determined to be the infectious agent because transmission is difficult to prevent with heat, radiation and disinfectants, the agent does not evoke any detectable immune response, and it has a long incubation period of between 18 months and 5 years. the agent is thought to be much smaller than the smallest known virus. prions multiply by causing normally folded proteins of the same type to take on their abnormal shape, which then go on to do the same, in a kind of chain reaction. these abnormal proteins are gradually accumulated in the body, especially in nerve cells, which subsequently die. transmission and pathogenesis the primary mode of transmission is from mother to lamb through ingestion of placental or allantoic fluids. the agent can also enter through cuts in the skin. an experiment has shown lambs risk being infected through milk from infected ewes, but the lambs in the experiment also infected each other, making the risk of infection difficult to assess. the experiment did not continue long enough to show if the lambs developed symptoms, but merely that the abnormal prion was present in their bodies. the pathogenesis of scrapie involves the lymphatic system. once the agent is absorbed through the intestines, misfolded prions first appear and accumulate in the lymph nodes, especially in peyer's patches at the small intestine. eventually, the infection invades the brain, often through the spinal cord or the medulla oblongata by creeping up the sympathetic and parasympathetic nervous system, respectively. clinical signs and diagnosis changes are mild at first; slight behavioral changes and an increase in chewing movements may occur. ataxia and neurological signs then develop, and affected sheep struggle to keep up with the flock. the signs and effects of scrapie typically appear 2-5 years after infection but may appear afterwards. once the onset of clinical signs has occurred, sheep typically live for 1-6 months. in some cases, they may live longer, but death is an inevitable consequence of the condition. signs of scrapie vary between infected individual animals and develop slowly. due to the nerve cell damage caused by the condition, affected animals may exhibit behavioral changes, tremor, pruritus, and locomotor incoordination. some sheep scratch excessively and show patches of wool loss and lesions on the skin. scratching sheep over the rump area may lead to a nibbling reflex, which is characteristic for the condition. signs of a chronic systemic disease appear later, with weight loss, anorexia, lethargy, and death. post mortem examination is important for the diagnosis of scrapie. histology of tissues shows accumulation of prions in the central nervous system, and immunohistochemical staining and elisa can also be used to demonstrate the protein. treatment and preventive action no treatment is available for affected sheep. a test performed by sampling a small amount of lymphatic tissue from the third eyelid is now available. in the uk, the blair ministry implemented in 2001 a national scrapie plan, which encouraged breeding from sheep that are genetically more resistant to scrapie. this is intended to eventually reduce the incidence of the disease in the uk sheep population. scrapie occurs in europe and north america, but to date, australia and new zealand (both major sheep-producing countries) are scrapie-free. in 2003, there was pressure from previously-sinistered canadian husbandry practitioners on the chretien government and their cfia to implement their own national scrapie plan. breeds such as cheviot and suffolk are more susceptible to scrapie than other breeds. specifically, this is determined by the genes coding for the naturally occurring prion proteins. the most resistant sheep have a double set of arr alleles, while sheep with the vrq allele are the most susceptible. a simple blood test reveals the allele of the sheep, and many countries are actively breeding away the vrq allele. out of fear of bse, many european countries banned some traditional sheep or goat products made without removing the spinal cord, such as smalahove and smokie. in 2010, a team from new york described detection of prpsc even when initially present at only one part in a hundred billion (10−11) in brain tissue. the method combines amplification with a novel technology called surround optical fiber immunoassay and some specific antibodies against prpsc. the technique allowed detection of prpsc after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. the researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. the animals' brains were analysed once any symptoms became apparent. they could therefore compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals' lives, and from uninfected animals. the results showed very clearly that prpsc could be detected in the blood of animals long before the symptoms appeared. after further development and testing, this method could be of great value in surveillance as a blood- or urine-based screening test for scrapie. transmission/exposure pathways various studies have indicated prions (prpsc) that infect sheep and goats with the fatal transmissible encephalopathy known as scrapie, are able to persist in soil for years without losing their pathogenic activity. dissemination of prions into the environment can occur from several sources: mainly, infectious placenta or amniotic fluid of sheep and possibly environmental contamination by saliva or excrement. confirmatory testing for scrapie can only be achieved by applying immunohistochemistry of disease-associated prion protein (prpsc) to tissues collected post mortem, including obex (a brainstem structure), retropharyngeal lymph node and palatine tonsil. a live animal diagnostic, not confirmatory, test was approved in 2008 for immunochemistry testing on rectal biopsy-derived lymphoid tissue by usda. human prion protein, residues 125–228, created from protein database (pdb) entry 1qm3. the coloring illustrates the subdomains, that are proposed to initiate the conversion from the normal cellular to the scrapie form by slow motions. natural transmission of scrapie in the field seems to occur via the alimentary tract in the majority of cases, and scrapie-free sheep flocks can become infected on pastures where outbreaks of scrapie had been observed before. these findings point to a sustained contagion in the environment, notably in the soil. prion concentration in birth fluids does not alter the infectivity of the prions. naturally or experimentally infected does and ewes transmit the infection to the lambs, even when placentas have little prpsc. prpsc is shed at a higher percentage in sheep placentas (52–72%) than in goat placenta (5–10%) in study trials at the usda agricultural research service. detectable prpsc has been reported in the feces of sheep both in the terminal and the early preclinical stages of the disease, suggesting the prions are likely to be shed into the environment throughout the course of the disease. several sources of prions in feces could be postulated, including environmental ingestion and swallowing infected saliva; however, the most likely source is shedding from the gut-associated lymphoid tissue. ruminant animals have specialized peyer's patches that, throughout the length of the ileum, amount to about 100,000 follicles, and all of these could be infected and shedding prions into the lumen. scrapie prions have been found in the peyer's patches of naturally infected asymptomatic lambs as young as four months of age. exposure through contaminated vaccines contaminated louping-ill vaccine. also known as the 1935 moredun louping-ill vaccine disaster. more than 1,500 sheep developed scrapie following vaccination. "an investigation into the etiology of scrapie followed the vaccination of sheep for louping-ill virus with formalin-treated extracts of ovine lymphoid tissue unknowingly contaminated with scrapie prions (gordon 1946). two years later, more than 1500 sheep developed scrapie from this vaccine." "this vaccine was manufactured using formalised sheep brains contaminated with scrapie agent" "at the 1946 national veterinary medical association of great britain and ireland annual congress, w. s. gordon, phd, presented evidence of scrapie transmission by way of a vaccine for louping-ill." "dr. gordon developed an effective vaccine to prevent louping-ill during 1931-32. after four years of field trials, his vaccine was produced in three batches for widespread use in 1935. the vaccine was made from brain, spinal cord, and spleen tissues taken from sheep five days after they had received an intracerebral inoculation of louping-ill virus. formalin was added to the 10% saline suspension to inactivate the virus. during 1935 and 1936, no ill effects were noted in inoculated animals. then two owners reported scrapie in their blackface sheep who had been inoculated with louping-ill vaccine (batch 2) two and a half years earlier. scrapie had not been seen in the blackface breed before this. upon investigation dr. gordon discovered that 8 lambs used to make batch 2 had been born to ewes who had been exposed to scrapie; some of the ewes developed scrapie in 1936-7. dr. gordon hypothesized that an "infective agent of scrapie" was present in the lambs' tissues used to make batch 2 and that this agent "could withstand a concentration of formalin...which inactivated the virus of louping ill; it could be transmitted by subcutaneous inoculation; it had an incubative period of two years or longer." a four-and-a-half-year experiment involving 788 sheep was initiated by the animal disease research association in 1938. the researchers found that 60% of normal sheep inoculated intracerebrally with saline suspensions of brain and spinal cord tissue taken from sheep with scrapie developed scrapie within