Scrapie (sheep, goats)

Scrapie is a fatal, degenerative neurological disease affecting sheep and goats, belonging to a group of disorders known as transmissible spongiform encephalopathies or prion diseases. First recognized in Great Britain over 250 years ago, scrapie is the oldest known transmissible spongiform encephalopathy and has been studied extensively as a model for understanding this unique class of infectious agents. The disease is caused by abnormal prion proteins that accumulate in the brain and other tissues, causing progressive neurological deterioration over months to years. The name derives from the characteristic behavior of affected sheep that scrape against fences, posts, and other objects due to intense itching.

Scrapie occurs in sheep and goat populations worldwide, with some countries having achieved eradication or freedom from the disease through intensive surveillance and control programs. The prevalence varies considerably between regions and is influenced by the genetic makeup of local sheep populations, as certain genotypes confer resistance while others increase susceptibility. The disease typically appears in adult animals between two and five years of age, though the incubation period can extend much longer. Because the clinical phase is relatively brief compared to the long incubation period, the number of subclinically infected animals in an affected flock typically far exceeds the number showing clinical signs.

The economic and welfare impact of scrapie extends beyond direct animal losses to include trade restrictions, costs of eradication programs, and the challenge of breeding for resistant genotypes while maintaining other desirable production traits. Affected flocks may face movement restrictions, mandatory testing, and potential depopulation depending on regulatory requirements. The association of scrapie with other prion diseases, particularly bovine spongiform encephalopathy and its human variant Creutzfeldt-Jakob disease, has heightened concerns about transmissible spongiform encephalopathies in food animals despite the lack of evidence that classical scrapie poses a risk to human health.

There is no treatment or cure for scrapie, and the disease is invariably fatal once clinical signs develop. Prevention focuses on genetic selection for resistant genotypes, testing and removal of infected animals, and biosecurity measures to prevent introduction of infection into naive flocks. Regulatory programs in many countries require reporting of suspected cases and may mandate testing, quarantine, and control measures in affected flocks. Understanding scrapie is essential for sheep and goat producers not only because of its direct impacts but also because of its regulatory significance and implications for breeding and management decisions.

Scrapie is caused by prions, which are abnormal forms of a naturally occurring protein called the prion protein or PrP. The normal cellular prion protein, designated PrPC, is found on cell surfaces throughout the body but particularly in nervous tissue. In scrapie and other prion diseases, the normal protein becomes misfolded into an abnormal form designated PrPSc that is resistant to degradation and accumulates in tissues. The abnormal prion protein acts as a template, inducing normal prion proteins to misfold into the abnormal form, creating a self-propagating cycle that eventually causes neurological disease. Unlike conventional infectious agents, prions contain no nucleic acids and replicate solely through protein misfolding.

Genetic susceptibility plays a crucial role in scrapie, with specific variations in the prion protein gene strongly influencing whether an animal will develop disease following exposure. In sheep, polymorphisms at codons 136, 154, and 171 of the prion protein gene determine susceptibility. Animals with the ARR/ARR genotype, indicating arginine at codon 171 on both chromosomes, are highly resistant to classical scrapie, while those with VRQ alleles are highly susceptible. Intermediate genotypes show varying degrees of susceptibility. This genetic component has enabled breeding programs to reduce scrapie risk through selection for resistant genotypes. In goats, genetic susceptibility is less well characterized but certain polymorphisms have been associated with increased or decreased risk.

Environmental and management factors influence scrapie transmission and persistence within flocks. The primary transmission route is from infected ewes to lambs during the birth process, with placental tissues and birth fluids containing high concentrations of infectious prions. The agent persists in the environment for extended periods, remaining infectious in soil and on pastures where infected animals have lambed. Horizontal transmission between animals can occur through exposure to contaminated environments, though this is generally less efficient than vertical transmission at birth. Common grazing areas, shared lambing facilities, and contaminated equipment can spread infection within and between flocks.

Risk factors for scrapie include introduction of infected animals through purchase or breeding stock exchange, genetic susceptibility within the flock, exposure to contaminated environments, and management practices that facilitate transmission. Flocks that purchase animals without testing or consideration of genetics face introduction risks. Closed flocks with susceptible genotypes can maintain infection for generations once introduced. Lambing on contaminated pastures or in facilities where infected animals have lambed perpetuates transmission. The long incubation period means that infected animals may be sold or moved before showing clinical signs, spreading infection to new premises.

The pathophysiology of scrapie involves progressive accumulation of abnormal prion protein in lymphoid tissues early in infection, followed by spread to the central nervous system. In susceptible animals, prions typically first replicate in gut-associated lymphoid tissue following oral exposure or in local lymph nodes following exposure through other routes. The agent then spreads through the peripheral nervous system to the spinal cord and brain. Accumulation of PrPSc in neural tissue causes neuronal death, astrocyte proliferation, and the characteristic spongiform vacuolation that gives this group of diseases its name. Clinical signs emerge when sufficient neural damage has accumulated, typically years after initial infection.

The clinical signs of scrapie develop insidiously over weeks to months, typically in animals between two and five years of age, though cases in younger and older animals occur. Early warning signs are often subtle and may be attributed to other causes or go unnoticed entirely. Initial signs frequently include subtle changes in behavior such as nervousness, increased excitability, or conversely unusual dullness and depression. Affected animals may become separated from the flock, show reluctance to be herded, or display unusual responses to handling. Changes in gait, including high-stepping or bunny-hopping movements, may be observed before more obvious neurological signs develop.

The most characteristic and recognizable sign of scrapie is intense pruritus causing affected sheep to rub, scratch, and scrape against fences, posts, buildings, and any available surface, hence the disease name. This itching is so intense that sheep may cause significant wool loss and skin damage over the shoulders, flanks, and rump. When the lumbar area is scratched or rubbed, affected sheep often display a characteristic nibbling response, extending the neck and rhythmically moving the lips as if nibbling or chewing. This positive nibble reflex is highly suggestive of scrapie when present in combination with other clinical signs. Not all scrapie cases display prominent pruritus, and some animals may show primarily neurological signs without obvious scratching behavior.

Behavioral changes in scrapie-affected animals reflect progressive brain dysfunction and may include altered temperament ranging from increased nervousness and aggression to depression and lethargy. Affected sheep may show abnormal responses to stimuli, startling easily or failing to respond appropriately to normal cues. Some animals develop a fixed stare with dilated pupils. Teeth grinding is common and may indicate discomfort. Affected animals often show decreased appetite and progressive weight loss despite apparent feed availability. The behavioral changes tend to progress over the course of the disease, with animals becoming increasingly debilitated.

Physical examination of scrapie-affected animals reveals a constellation of findings related to progressive neurological deterioration. Weight loss is common and may be severe in advanced cases, with affected animals showing poor body condition despite adequate nutrition being available. The wool coat may appear rough, dull, or tattered, with areas of wool loss from rubbing. Skin lesions from self-trauma may be present. Neurological examination typically reveals ataxia affecting the hindquarters initially and progressing to involve all limbs. Tremors, particularly of the head and neck, are frequently observed. Weakness progresses to recumbency in terminal stages. Vision may be impaired. Swallowing difficulties may develop.

The progression of scrapie symptoms follows a characteristic pattern of gradual deterioration over weeks to several months. Early signs of subtle behavior changes and mild ataxia progress to more obvious pruritus, weight loss, and coordination problems. As the disease advances, affected animals become increasingly debilitated, with worsening ataxia, weakness, and inability to keep up with the flock. Terminal animals become recumbent and unable to rise, often dying from secondary complications such as predation, exposure, or starvation if not euthanized. The entire clinical course from first detectable signs to death typically spans two to six months, though some animals progress more rapidly or slowly.

Emergency symptoms requiring immediate veterinary evaluation include sudden onset or rapid progression of neurological signs, recumbency or inability to rise, severe weight loss, and extensive self-inflicted wounds from scratching. While scrapie itself is not treatable, veterinary evaluation is essential to confirm the diagnosis, rule out other potentially treatable conditions, and implement appropriate regulatory notification and control measures. Animals with advanced disease should be humanely euthanized to prevent suffering and to enable diagnostic testing. Any sheep or goat with progressive neurological disease and pruritus should be treated as a suspect scrapie case pending diagnostic evaluation.

Clinical diagnosis of scrapie requires recognition of the characteristic combination of progressive neurological signs, pruritus, and weight loss in adult sheep or goats. The nibble reflex test, performed by scratching or rubbing the lumbar region and observing for lip movements and neck extension, is a useful field test though not definitive. History should include flock origin, introduction of new animals, previous scrapie cases in the flock or in source flocks, and the genotype status if known. Physical and neurological examination documents the extent of disease and rules out other obvious conditions. Clinical signs alone cannot provide definitive diagnosis, and laboratory confirmation is required.

Laboratory testing for scrapie has evolved significantly with advances in understanding of prion diseases. Definitive diagnosis has traditionally required histopathological examination of brain tissue for the characteristic spongiform changes and immunohistochemical detection of PrPSc in brain tissue, necessitating postmortem examination. Third eyelid biopsy for immunohistochemical detection of PrPSc in lymphoid tissue allows live animal testing and has been used in surveillance programs, though sensitivity is not perfect and negative results do not guarantee freedom from infection. Rectal biopsy examining gut-associated lymphoid tissue provides another live animal testing option. Genetic testing to determine prion protein genotype identifies animals at high or low risk but does not diagnose infection.

Necropsy examination of animals that die or are euthanized with suspected scrapie should include careful removal of the brain for diagnostic testing. Gross findings at necropsy are typically nonspecific, with affected animals showing poor body condition and muscle wasting. The brain appears grossly normal in most cases, though some atrophy may be present in advanced cases. Histopathological examination reveals the characteristic spongiform vacuolation of grey matter, neuronal degeneration, and astrogliosis. Immunohistochemistry demonstrates accumulation of PrPSc in brain tissue. These findings combined with compatible clinical history confirm the diagnosis.

Differential diagnosis for scrapie includes other causes of neurological disease, pruritus, and wasting in sheep and goats. External parasites including lice and mange mites cause intense pruritus and wool loss without neurological signs. Listeriosis causes acute neurological disease with brainstem signs but without chronic progression. Louping ill and other viral encephalitides produce acute neurological disease. Cerebral abscess or parasitic cyst causes focal neurological signs. Pregnancy toxemia in late-gestation ewes produces neurological signs with metabolic derangements. Chronic wasting conditions such as caseous lymphadenitis, Johne's disease, and internal parasitism cause weight loss without neurological involvement. The combination of progressive neurological disease, pruritus, and chronic wasting is most consistent with scrapie.

There is no treatment for scrapie, and the disease is invariably fatal. Once clinical signs develop, the disease progresses inexorably to death over weeks to months regardless of any intervention. No drugs or therapies have been shown to slow progression, improve clinical signs, or extend survival. Experimental treatments targeting prion replication have shown some promise in laboratory settings but are not available or practical for use in livestock. The appropriate response to clinically affected animals is humane euthanasia to prevent further suffering and enable diagnostic testing for regulatory purposes.

Emergency care for animals with suspected scrapie focuses on isolation to prevent transmission and humane management pending diagnostic confirmation. Affected animals should be separated from the flock, particularly from pregnant or lambing ewes, to minimize exposure of other animals to potentially infectious materials. Animals in the early stages of disease may be maintained with supportive care while diagnostic arrangements are made, but prolonged treatment attempts are not appropriate given the invariably fatal outcome. Pain and distress management through appropriate husbandry and potentially anti-inflammatory medication may be considered for animal welfare while awaiting disposition.

Medical management is not applicable to scrapie due to the lack of effective treatments. Any medications administered would be purely palliative and would not affect disease outcome. No withdrawal time considerations are relevant because affected animals should not enter the food chain regardless of treatment status. Carcasses of scrapie-affected animals require special handling and disposal as discussed in regulatory requirements, as prions are highly resistant to standard disinfection and rendering procedures and persist in the environment.

Supportive care for animals with scrapie is limited to providing comfortable conditions and adequate nutrition while diagnostic and regulatory processes proceed. Good quality feed and water should be available, recognizing that affected animals may have difficulty eating due to neurological impairment. Protection from environmental extremes and from aggressive flock mates prevents additional suffering. Soft bedding prevents pressure sores in recumbent animals. However, supportive care should not be prolonged as the animal's condition will inevitably deteriorate and euthanasia is the most humane outcome.

Flock-level management following diagnosis of scrapie depends on regulatory requirements and program options available in the jurisdiction. In the United States, the Scrapie Eradication Program provides options including flock certification programs and cleanup plans for affected flocks. Options may include genetic testing and selective removal of susceptible animals, depopulation of the entire flock, or other approved approaches. Movement restrictions apply to affected and exposed flocks. Indemnity payments may be available for animals destroyed as part of official eradication efforts. Owners should work closely with regulatory veterinarians to understand options and obligations.

The decision to euthanize suspected scrapie cases should be made promptly once the clinical picture is clear. Prolonging the life of affected animals serves no therapeutic purpose and only extends suffering while potentially increasing environmental contamination. Euthanasia should be performed by approved methods that do not damage the brain, as diagnostic testing requires intact brain tissue. Proper carcass disposal according to regulatory requirements prevents environmental contamination with prions. Documentation of clinical findings, diagnostic submissions, and disposal should be maintained for regulatory records.

Recovery from scrapie does not occur because the disease is invariably fatal and progressive. Once clinical signs develop, affected animals deteriorate over a period of weeks to months until death occurs or humane euthanasia is performed. No spontaneous recovery has ever been documented in natural scrapie cases. The pathological changes in the brain are irreversible, and the abnormal prion protein continues to accumulate even if transmission to new cells could somehow be stopped. Any discussion of recovery must therefore focus on flock-level recovery following detection and control of scrapie rather than individual animal outcomes.

The timeline for flock recovery following scrapie detection depends on the control approach implemented and the genetic makeup of the flock. Flocks that elect depopulation can restock after appropriate premises cleanup, though prions persist in the environment for years. Flocks pursuing genetic cleanup through testing and selective removal may require several years to eliminate susceptible genotypes while maintaining flock size and production. Certification programs require extended periods of surveillance and testing before freedom from infection can be verified. Throughout this period, movement restrictions and testing requirements apply.

Post-diagnosis management focuses on preventing additional cases and eventually achieving documented freedom from infection. Rigorous identification and genotyping of all animals enables informed culling decisions. Removal of all susceptible genotypes eliminates the substrate for disease maintenance. Lambing management that prevents exposure of newborn lambs to potentially contaminated environments interrupts transmission. Environmental management including pasture rest and facility decontamination where feasible reduces residual contamination. Testing of animals leaving the flock through slaughter surveillance documents absence of infection.

Prognostic factors for flock recovery include the genetic makeup of the flock, availability of resistant breeding stock, regulatory requirements, and the owner's commitment to the eradication process. Flocks with a high proportion of resistant genotype animals can transition relatively quickly to a resistant population. Those dominated by susceptible genotypes face more challenging decisions about breeding stock sourcing. The availability of genetic testing and certified resistant rams facilitates transition. Success requires sustained commitment over multiple years of controlled breeding and surveillance.

Genetic selection for resistant genotypes represents the most powerful tool for scrapie prevention in sheep flocks. Breeding programs that incorporate prion protein genotype testing and selection for resistance can dramatically reduce or eliminate scrapie susceptibility over several generations. The target is to increase the frequency of the ARR allele while eliminating the VRQ and other susceptible alleles from the flock. Using only ARR/ARR rams ensures that all offspring carry at least one resistant allele. Over time, the flock can transition to predominantly or entirely resistant genotype composition. National programs in several countries have promoted or mandated selection for resistance, significantly reducing scrapie incidence.

Biosecurity measures prevent introduction of scrapie into naive flocks and limit spread within affected populations. The highest-risk practice is introducing sheep from flocks of unknown or positive scrapie status, particularly pregnant ewes or animals born to infected dams. Purchasing only from certified scrapie-free flocks or requiring genotype testing before purchase reduces introduction risk. Avoiding common grazing areas shared with flocks of unknown status prevents environmental exposure. Not sharing equipment, particularly lambing equipment, between flocks prevents mechanical transmission. Avoiding embryo transfer or artificial insemination from untested sources eliminates those transmission routes.

Nutritional management does not directly prevent scrapie, as the disease is caused by an infectious agent rather than nutritional deficiency. However, maintaining animals in good nutritional status supports overall health and immune function. Animals under nutritional stress may be more susceptible to clinical disease progression if infected. Good nutrition does not prevent infection or alter susceptibility in genetically susceptible animals, so nutritional management should complement rather than replace genetic and biosecurity approaches.

Management practices that reduce transmission focus on the perinatal period when most transmission occurs. Lambing areas should be kept as clean as possible, with prompt removal of placentas and birth fluids. Rotation of lambing pastures prevents buildup of environmental contamination. Avoiding situations where ewes lamb in close proximity to each other reduces exposure of lambs to infectious materials from unrelated dams. Fostering lambs onto ewes of unknown status should be avoided. Carcasses of all dead sheep should be properly disposed of rather than left on pastures.

Flock enrollment in official scrapie certification programs provides documented assurance of low risk and may be required for certain sales or movements. In the United States, the Voluntary Scrapie Certification Program and Scrapie Free Flock Certification Program provide pathways to certified status through testing and surveillance. Participation requires individual animal identification, regular inventory, and testing of animals that die or are culled. Export certification may require specific program enrollment. Buyers increasingly seek animals from certified flocks, providing market advantages to participants.

Daily management and monitoring in flocks at risk for or recovering from scrapie requires heightened awareness of clinical signs and rigorous record keeping. All animals should be observed regularly for early signs of disease including subtle behavior changes, poor condition, and scratching. The nibble reflex can be checked periodically on suspicious individuals. Body condition scoring helps identify animals losing weight before deterioration becomes severe. Any animal showing potential scrapie signs should be isolated and evaluated. Prompt removal of suspect cases reduces potential transmission to flock mates.

Housing and environmental management contribute to scrapie control through reducing environmental contamination and facilitating clean lambing. Indoor lambing facilities allow intensive management and cleanup between animals, though complete prion decontamination is difficult. Disposable bedding that can be properly disposed of is preferred over permanent fixtures. Lambing paddocks should be rested between seasons where possible. Equipment used in lambing should be cleaned between animals and between seasons. Pastures where known positive animals have lambed should be rested for extended periods, recognizing that complete decontamination of soil is not achieved by rest alone.

Herd health programs for scrapie incorporate genetic management, surveillance, and biosecurity. Genotype testing should be performed on all breeding stock with results recorded and used in mating decisions. Rams should be tested before use and only ARR/ARR rams used if transitioning to a resistant flock. Replacement ewes should preferentially be selected from resistant genotypes. Surveillance through testing of all deaths and culls documents ongoing freedom from disease. Biosecurity protocols should be written and followed consistently.

Record keeping for scrapie management must meet regulatory requirements and support flock management decisions. All animals must be individually identified and that identification maintained throughout the animal's life. Records should include date of birth, dam and sire identification, genotype test results, and disposition. Animals sold must be traceable in case disease is later identified in source or destination flocks. Testing results including third eyelid biopsies, postmortem examinations, and genotype tests should be maintained indefinitely. These records form the basis for regulatory compliance and certification program participation.

Economic considerations in scrapie management include the costs of genetic testing and selection, potential productivity impacts of prioritizing disease resistance over production traits, testing and surveillance costs, and market implications of scrapie status. Genetic testing costs have decreased substantially as technology has improved. Some correlation between certain resistant genotypes and reduced productivity has been reported in some breeds, though selection programs can maintain production while improving resistance. Certified flocks may command premium prices for breeding stock. Trade access may require documented scrapie-free status.

All sheep breeds are susceptible to scrapie, but the frequency of susceptible versus resistant prion protein genotypes varies substantially between breeds, creating breed-associated risk differences. Breeds with high frequencies of VRQ or other susceptible alleles have historically experienced higher scrapie incidence than breeds dominated by resistant genotypes. Suffolk sheep have historically had relatively high frequencies of susceptible genotypes in many populations and have been commonly affected by scrapie. Some hill breeds in the United Kingdom have also had high susceptible allele frequencies. Conversely, some breeds have naturally high frequencies of the ARR resistance allele.

Production type influences scrapie risk primarily through management practices and genetic selection history rather than inherent susceptibility. Breeds selected primarily for meat production may have different genotype frequencies than breeds selected for wool or dual-purpose use. Commercial flocks with frequent animal turnover and purchases from multiple sources face higher introduction risks than closed flocks. Purebred breeding flocks participating in certification programs may have lower prevalence due to testing and selection. Extensively managed flocks may have delayed disease detection compared to intensively observed flocks.

Genetic testing and selection have become central to scrapie risk management in sheep. The identification of prion protein gene polymorphisms and their relationship to disease susceptibility has enabled science-based breeding decisions. Testing is now widely available and relatively inexpensive, allowing even small-scale producers to make informed genetic selections. National and international breeding programs have promoted the ARR allele, shifting genotype frequencies toward resistance in many populations. Some breeds have achieved very high resistant allele frequencies through concerted selection efforts. Ongoing testing and selection pressure is needed to maintain gains and prevent re-emergence of susceptible genotypes.

Scrapie is one of several transmissible spongiform encephalopathies affecting animals and humans, and understanding these related conditions provides context for scrapie management and regulatory concern. Bovine spongiform encephalopathy in cattle and its associated variant Creutzfeldt-Jakob disease in humans heightened concerns about prion diseases in food animals. Chronic wasting disease affects deer and elk and is spreading in wild cervid populations. These diseases share the fundamental mechanism of prion protein misfolding but have distinct host ranges, transmission characteristics, and public health implications. Classical scrapie has not been associated with human disease despite centuries of exposure.

Conditions with similar clinical presentations to scrapie must be differentiated to ensure appropriate diagnosis and response. External parasite infestations including sheep scab, lice, and various mite species cause intense pruritus and wool loss without neurological involvement. Listeriosis produces acute neurological disease, typically with brainstem signs including facial paralysis and circling. Pregnancy toxemia in ewes causes neurological signs with characteristic metabolic derangements. Maedi-visna causes chronic wasting with respiratory involvement. Various encephalitides cause acute neurological disease. The chronic progressive nature of scrapie with combined neurological signs, pruritus, and wasting helps distinguish it from these conditions.

Atypical scrapie is a distinct form of ovine prion disease that differs from classical scrapie in several important respects. Atypical scrapie affects different prion protein genotypes, with ARR animals, which are resistant to classical scrapie, being susceptible to some atypical strains. The distribution of prion protein in the brain differs between typical and atypical forms. Atypical scrapie may arise spontaneously rather than through transmission in some cases. It is less clearly transmissible than classical scrapie. Regulatory approaches to atypical scrapie vary and may differ from classical scrapie management requirements.