Scrapie is a fatal, degenerative disease

Disease

A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

 that affects the nervous system

Nervous system

The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...

s of sheep and goat

Goat

The domestic goat is a subspecies of goat domesticated from the wild goat of southwest Asia and Eastern Europe. The goat is a member of the Bovidae family and is closely related to the sheep as both are in the goat-antelope subfamily Caprinae. There are over three hundred distinct breeds of...

s. It is one of several transmissible spongiform encephalopathies (TSEs), which are related to bovine spongiform encephalopathy

Bovine spongiform encephalopathy

Bovine spongiform encephalopathy , commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of...

 (BSE or "mad cow disease") and chronic wasting disease

Chronic wasting disease

Chronic wasting disease is a transmissible spongiform encephalopathy of mule deer, whitetailed deer, elk , and moose. TSEs are caused by unusual infectious agents known as prions. To date, CWD has been found mainly in cervids...

 of deer. Like other spongiform encephalopathies, scrapie is caused by a prion

Prion

A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...

. Scrapie has been known since the 18th century (1732) and does not appear to be transmissible to human

Human

Humans are the only living species in the Homo genus...

s.

The name scrapie is derived from one of the clinical signs of the condition, wherein affected animals will compulsively scrape off their fleece 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 similar animals, and so one of the most common ways to contain scrapie (since it is incurable) is to quarantine and destroy 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 these are active areas of research. Recent studies suggest that prions may be spread through urine and persist in the environment for decades.

Scrapie usually affects sheep around 3–5 years of age. There appears to be the potential for transmission at birth and from contact with placental tissues. There is no evidence that scrapie is infectious to humans.

Uptake of prions

The protein enters through the intestines or through cuts in the skin. The prions cause normal proteins of the sheep to fold into the wrong shape. These proteins are gradually accumulated in the body, especially in nerve cells which subsequently die. When the prions are absorbed through the intestines, they first appear in the lymph nodes, especially in Peyer's patches at the small intestine

Small intestine

The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...

.

An experiment has shown that lambs risk being infected through milk from infected ewes. But the lambs in the experiment also infected each other, making it difficult to assess the risk of infection. The experiment did not continue long enough to show that the lambs developed symptoms, merely that the prion was present in the body.

Clinical signs and diagnosis

Changes are mild at first, there may be slight behavioural changes and maybe an increase in chewing movements. Ataxia and neurological signs then develop, and affected sheep struggle to keep up with the flock.

Some sheep scratch excessively and will show patches of wool loss and lesions on the skin. Scratching sheep over the rump area may lead to a nibbling reflex which is pathognomonic for the condition.

Signs that this is a chronic systemic disease appear later, with weight loss, anorexia, lethargy and possibly death.

Post-mortem examination is important for the diagnosis of scrapie. Histology of tissues will show accumulation of prion

Prion

A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...

 in the central nervous system and immunohistochemical staining and ELISA

ELISA

Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

 can also be used to demonstrate the protein. Sampling the third eyelid lymphoid tissue is also possible.

Treatment and preventive action

No treatment is available for affected sheep.

A test is now available which is performed by sampling a small amount of lymphatic tissue from the third eyelid.

In the United Kingdom

United Kingdom

The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

, the government has put in place a National Scrapie Plan, which encourages breeding from sheep that are genetically more resistant to scrapie. It is intended that this will eventually reduce the incidence of the disease in the UK sheep population. Scrapie occurs in Europe

Europe

Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 and North America

North America

North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...

, but to date Australia

Australia

Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...

 and New Zealand

New Zealand

New Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses and numerous smaller islands. The country is situated some east of Australia across the Tasman Sea, and roughly south of the Pacific island nations of New Caledonia, Fiji, and Tonga...

 (both major sheep-producing countries) are scrapie-free.

Breeds such as cheviot sheep

Cheviot sheep

The Cheviot is a breed of white faced sheep which gets its name from a range of hills in north Northumberland and the Scottish Borders. It is still common in this area of the United Kingdom, but also in north west Scotland, Wales and the south west of England as well as more rarely in Australia,...

 and suffolk

Suffolk (sheep)

Suffolk are a black-faced, open-faced breed of domestic sheep raised primarily for meat.-Ewes:They are mainly raised for wool and meat production especially when crossed with the progeny of a mountain ewe. For example, a purebred upland ewe such as a Welsh Mountain ewe might be bred with a breeding...

 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" allele

Allele

An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

s, 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

Smalahove

Smalahove is a Western Norwegian traditional dish made from a sheep's head, originally eaten before Christmas. The name of the dish comes from the combination of the Norwegian words hove and smale. Hove is a dialectal form of hovud, meaning head, and smale is one word for sheep...

 and smokie.

In 2010, A team from New York described detection of PrP^Sc even when initially present at only one part in a hundred thousand million (10⁻¹¹) in brain tissue. The method combines amplification with a novel technology called Surround Optical Fiber Immunoassay (SOFIA)

Surround Optical Fiber Immunoassay (SOFIA)

Surround Optical Fiber Immunoassay is an ultra-sensitive, in vitro diagnostic platform incorporating a surround optical fiber assembly that captures fluorescence emissions from an entire sample. The technology's defining characteristics are its extremely high limit of detection, sensitivity and...

 and some specific antibodies against PrP^Sc. After amplifying and then concentrating any PrP^Sc, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a micro-capillary tube. This tube is placed in a specially constructed apparatus so that it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser. The technique allowed detection of PrP^Sc 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. The researchers 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 PrP^Sc 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 that prions

Prion

A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...

 (PrP^SC) that infect sheep and goats with the fatal
transmissible encephalopathy

Encephalopathy

Encephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...

 known as scrapie

Scrapie

Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies , which are related to bovine spongiform encephalopathy and chronic wasting disease of deer. Like other spongiform encephalopathies, 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 excrements.

Confirmatory tesing for scrapie can only be achieved by applying Immunohistochemistry

Immunohistochemistry

Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...

 (IHC) of disease-associated prion protein (PrP^Sc) to tissues collected postmortem, including obex

Obex

The obex is the point in the human brain at which the fourth ventricle narrows to become the central canal of the spinal cord.The obex occurs in the caudal medulla.The decussating of sensory fibers happens at this point....

, 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.
Natural transmission

Transmission (medicine)

In medicine and biology, transmission is the passing of a communicable disease from an infected host individual or group to a conspecific individual or group, regardless of whether the other individual was previously infected...

 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, and notably the soil.

Prion concentration in birth fluids does not alter the infectivity

Infectivity

In epidemiology, infectivity refers to the ability of a pathogen to establish an infection. More specifically, infectivity is a pathogen's capacity for horizontal transmission that is, how frequently it spreads among hosts that are not in a parent-child relationship...

 of the prions. Even when
placentas have little PrPS^C (Prion protein - scrapie) kids born to naturally or experimentally infected does become
infected. PrP^SC are shed at a higher percent, 52%- 72% in in sheep placentas then goat
placenta at 5-10% in study trials at the USDA Agricultural Research Service by Dr. O’Rourke.

Fecal concentration of PrP^SC has been reported in the feces

Feces

Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...

 of sheep both in
the terminal and the early preclinical stages of the disease suggesting that prions are likely
to be shed into the environment throughout the pathogenesis

Pathogenesis

The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...

. 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.
Ruminants have specialized Peyer's patches that throughout the length of the ileum

Ileum

The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...

 amount
to approximately 100,000 follicles and all of these could be infected and shedding prions in to
the lumen

Lumen (anatomy)

A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...

.
Scrapie prions have been found in the Peyer's patches of naturally infected nonclinical lambs as young as 4 months of age.

Risk of exposure through contaminated soil via placentas or feces

Ingestion of soil by grazing sheep has been measured in two soil types, at two stocking rates
and over two grazing seasons. Animals ingested up to 44g soil per kg of body weight between
May and November. Rainfall and stocking rate emerged as factors influencing ingestion. The
effect of soil type and herbage on offer was less evident.

The average weight of an adult sheep is 249.4 pounds. If an adult sheep ate 400g/kg of soil
as predicted by D. McGrath et al. then the average sheep would ingest approximately 45,000 g over
6 months or 251g per day. Assuming the soil was contaminated with prions (PrP^SC) from feces
or birth fluids then potentially the sheep would be infected. The concentration of the prions is
uncertain however as concentration is not directly proportionate

Proportionality

Proportionality may refer to:*Proportionality , the relationship of two variables whose ratio is constant*Proportionality , A legal principle under municipal law in which the punishment of a certain crime should be in proportion to the severity of the crime itself, and under international law an...

 to infectivity.

Factors affecting Prion infectivity in the soil: Factors affecting prion infectivity in the soil have been shown to include the length of time in the soil and the binding abilities of the soil.

'Length of time': For a detailed risk assessment

Risk assessment

Risk assessment is a step in a risk management procedure. Risk assessment is the determination of quantitative or qualitative value of risk related to a concrete situation and a recognized threat...

 of scrapie-contaminated soil it was of
major importance to analyze whether the detectable PrP^Sc in the
soil extracts still exhibited oral infectivity after incubation times up
to 29 months. A bioassay

Bioassay

Bioassay , or biological standardization is a type of scientific experiment. Bioassays are typically conducted to measure the effects of a substance on a living organism and are essential in the development of new drugs and in monitoring environmental pollutants...

 with Syrian hamsters

Golden Hamster

The golden hamster or Syrian hamster, Mesocricetus auratus, is a very well known member of the rodent subfamily Cricetinae, the hamsters. In the wild they are now considered vulnerable. Their numbers have been declining due to loss of habitat and deliberate destruction by humans. However, they are...

 was performed by feeding the animals with
contaminated soil or aqueous

Aqueous solution

An aqueous solution is a solution in which the solvent is water. It is usually shown in chemical equations by appending aq to the relevant formula, such as NaCl. The word aqueous means pertaining to, related to, similar to, or dissolved in water...

 soil extracts that had been collected after soil incubation
for 26 and 29 months, respectively. Hamsters fed with contaminated soil exhibited first scrapie-
associated symptoms at 13,166 days (95% CI)after the first application. The hamsters
reached the terminal stage of scrapie at 162,612 days (95% CI) after the first feeding. This
indicates substantial amounts of persistent infectivity in soil that had been incubated for 26 and
29 months. In Iceland, in 1978, a program was implemented to eradicate scrapie and affected flocks were culled

Culling

Culling is the process of removing animals from a group based on specific criteria. This is done either to reinforce certain desirable characteristics or to remove certain undesirable characteristics from the group...

, premises were disinfected, sheep houses were burnt and after 2-3 years, the premises were restocked with lambs from scrapie free areas. Between 1978 and 2004, scrapie recurred on 33 farms.
Nine recurrences occurred 14-21 years after culling as a result of environmental contamination.

'Soil types' : the binding abilities of different soil types have been shown to enhance disease
penetrance. Soil containing the common clay mineral montmorillonite

Montmorillonite

Montmorillonite is a very soft phyllosilicate group of minerals that typically form in microscopic crystals, forming a clay. It is named after Montmorillon in France. Montmorillonite, a member of the smectite family, is a 2:1 clay, meaning that it has 2 tetrahedral sheets sandwiching a central...

 (Mte) and
kaolinite

Kaolinite

Kaolinite is a clay mineral, part of the group of industrial minerals, with the chemical composition Al2Si2O54. It is a layered silicate mineral, with one tetrahedral sheet linked through oxygen atoms to one octahedral sheet of alumina octahedra...

 (Kte) binds more effectively with the prions (PrP^SC) than soil that contains quartz

Quartz

Quartz is the second-most-abundant mineral in the Earth's continental crust, after feldspar. It is made up of a continuous framework of SiO4 silicon–oxygen tetrahedra, with each oxygen being shared between two tetrahedra, giving an overall formula SiO2. There are many different varieties of quartz,...

. Enhanced transmissibility of soil-bound prions may explain the environmental spread of scrapie despite low levels shed into the environment. The mechanism by which Mte or other
soil components enhances the transmissibility of particle bound prions remains to be clarified.
Prion binding to Mte or other soil components may partially protect PrP^SC from denaturation

Denaturation

Denaturation may refer to:*Denaturation , a structural change in macromolecules caused by extreme conditions*Denaturation , transforming fissile materials so that they cannot be used in nuclear weapons...

or proteolysis

Proteolysis

Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...

 in the digestive tract allowing more disease agent to be taken up from the
gut. Adsorption of PrP^Sc soil may alter aggregation state of the protein, shifting the size
distribution toward more infectious prion protein particles thereby increasing the infectious
units. For prion disease to be transmitted via ingestion of prion contaminated soil, prions must also
remain infectious by the oral route of exposure. Researchers at the University of Wisconsin investigated the oral infectivity of Mte and soil bound prions. The effects of prion source (via infected brain homogenate and purified PrP^Sc) and dose on penetrance (proportion of animals eventually exhibiting clinical signs of scrapie) and incubation period (time to
onset of clinical symptoms) was evaluated. Approximately 38% of animals receiving 200ng of unbound clarified PrP^Sc orally exhibited clinical symptoms with an incubation period for infected animals of 203, 633 days. In contrast, all animals orally dosed with an equivalent amount of Mte-bound PrP^Sc manifested disease symptoms in 195,637 days. Animals orally receiving Mte soil alone or 10-fold less unbound clarified PrP^Sc (20ng) remained asymptomatic throughout the course of the experiment. These data established that the Mte-bound prions remain infectious via the oral route of exposure but that the agent binding Mte increases disease penetrance, enhancing the efficiency of oral transmission.

Transmission Summary

Prions (PrP^Sc) are shed from sheep and goats in birth fluids, feces and other excrements. The
concentration of the prions is uncertain however it is not directly proportionate to infectivity. Sheep
do ingest soil and therefore soil represents a plausible environmental reservoir of scrapie which
can persist in the environment for years. Longevity of the prions and the attachment of
soil particles likely influences the persistence and infectivity of prions in the environment.
Effective methods to inactivate prions in the soil are currently lacking and the effects of natural
degradation mechanisms on prion infectivity are largely unknown. An improved understanding
of the processes affecting the mobility, persistence and bioavailability

Bioavailability

In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...

 of prions in soil is needed
for the management of prion contaminated environments. A system for estimating the prion
binding capacity of soil on US farms using simple soil analysis may give us an estimate of the
prion risk in the environment and if prion binding is likely possibly the use of soil amendments
or top dressings may help to mitigate the infectious prions. Lichens, Lobaria pulmonaria

Lobaria pulmonaria

Lobaria pulmonaria is a large epiphytic lichen consisting of an ascomycete fungus and a green algal partner living together in a symbiotic relationship with a cyanobacterium—a symbiosis involving members of three kingdoms of organisms...

, may have potential for reducing the number of prions because some lichen species contain a protease

Protease

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

 enzyme that show promise in breaking down the prion. Further work to clone and characterize the protease, assess its effects on prion infectivity and determine which organism or organisms present in lichens produce or influence the protease activity is warranted and is currently under investigation.

See also

• Kuru
  Kuru (disease)
  Kuru is an incurable degenerative neurological disorder that is a type of transmissible spongiform encephalopathy, caused by a prion found in humans...
  
  
• Transmissible mink encephalopathy
  Transmissible mink encephalopathy
  Transmissible mink encephalopathy is rare sporadic disease that affects the central nervous system of ranch-raised mink. It is classified as a transmissible spongiform encephalopathy, believed to be caused by proteins called prions...
  
  
• Creutzfeldt-Jakob disease
  Creutzfeldt-Jakob disease
  Creutzfeldt–Jakob disease or CJD is a degenerative neurological disorder that is incurable and invariably fatal. CJD is at times called a human form of mad cow disease, given that bovine spongiform encephalopathy is believed to be the cause of variant Creutzfeldt–Jakob disease in humans.CJD...
  
  

External links

• Article about scrapie and the aforementioned diagnostic test
• UK government scrapie information
• UK government National Scrapie Plan
• Scrapie research at the Institute for Animal Health (UK)
• Sheep genetics research at the Institute for Animal Health (includes photo of a sheep with scrapie)
• Scrapie in the United States
• US Department of Agriculture video of infected sheep demonstrating Hopping Gait