An Update on Scrapie (2008)
Scrapie is an always-fatal disease affecting the central nervous system (CNS) of sheep and goats. It is a member of a family of diseases called Transmissible Spongiform Encephalopathies (TSE's).
Other TSE's include bovine spongiform encephalopathy (BSE), better known as "mad cow" disease; chronic wasting disease (CWD) in deer and elk; transmissible spongiform encephalopathy in mink; feline spongiform encephalopathy in cats; and in humans: Kuru, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, and both classical (CJD) and new variant Creutzfeldt-Jakob disease (nvCJD).
TSE's cause sponge-like spaces in the brain of the affected animal. They affect the brain’s ability to control body functions and eventually cause death.
During the "mad cow" scare in Great Britain, scrapie was theoretically linked to "mad cow" disease which was linked to new variant CJD. It was proposed that cattle contracted BSE when they consumed meat and bone meal derived from scrapie-infected sheep carcasses and that humans developed nvCJD when they ingested BSE-infected beef.
The link between scrapie and mad cow disease has long since been discounted by scientists, as BSE is believed to be a new disease. The link between BSE and nvCJD has never been proven, despite its widespread acceptance as "fact." Alternative theories have never received the same consideration as the infected feed theory.
While scrapie has been recognized as a disease for more than 250 years in Europe and the United Kingdom and has been in the United States since 1947, there is still much we do not know about it and how it is transmitted. Research continues to increase our understanding of what causes scrapie, how scrapie is transmitted, how it can be detected in the live and asymptomatic animal, and how genetics affects an animal's susceptibility (and resistance) to the disease.
The exact cause of scrapie and other TSE's remains known. The causative agent has not been completely characterized. The popular theory is that the infective agent is a prion, an abnormally-shaped protein. Other theories maintain it is a virus with unusual characteristics or a virino ( a sub-viral particle).
The infective agent -- whatever it is -- is resistant to heat and other sterilization processes. It does not evoke an immune or inflammatory reaction in the host animal. It has a long incubation period. Infected sheep and goats usually do not show symptoms until 2 to 5 years after infection.
Symptoms can mimic other diseases, including ovine progressive pneumonia (OPP), pregnancy toxemia, listeriosis, rabies, toxins, and external parasites. Scrapie was so-named because affected sheep often scrape themselves against objects.
Scrapie is thought to be spread most commonly from dam to offspring via infected placenta and placental fluids. Genetically-susceptible ewes and lambs in the same lambing environment are considered at-risk for developing the disease. While rams and bucks can get scrapie, they are not believed to be involved in the transmission of the disease. Semen is not known to transmit infectivity.
Other oral routes of transmission are possible. It was recently learned that infective scrapie prions can be transmitted to lambs through the milk. Soil may also serve as a reservoir for the disease. In Iceland, scrapie has re-occurred on farms that were depopulated and disinfected, as long as 16 years after the last sheep left the farm.
Feed is not considered to be a significant factor in the transmission of scrapie. Scrapie is not known to pose a human health risk.
Organic farmer and scientist Mark Purdey (now deceased) hypothesized that BSE (and other TSE's) is the result of environmental pollutants and chemical inbalances. The prion protein needs copper to keep its structure. If copper is not available, the prion protein can take up manganese and unfold, causing disease.
In scrapie-infected areas of Iceland, researchers determined bioavailable manganese to be very high, whereas soluble and free copper were very low. In other studies, sheep infected with scrapie have been shown to have higher manganese levels in their blood before clinical symptoms developed, leading scientists to theorize that manganese levels could serve as a diagnostic marker for prion diseases.
Genetically-resistant sheep show similar high levels of manganese when challenged with the disease, suggesting that changes in blood manganese are a result of scrapie challenge and not a consequence of scrapie pathology. Purdey postulated that high levels of manganese and low levels of copper favor the occurrence of natural scrapie.
Scrapie is not a genetic disease; but a sheep's genotype (DNA) affects whether it will develop the disease if it is exposed to the infective agent. A simple blood or tissue test, done at any age, can be used to determine a sheep's resistance or susceptibility to scrapie. It is important to note that genetically-susceptible sheep are not carriers for the disease. Nor will they develop the disease if they are not exposed to the infective agent.
Sheep have one pair of genes that affect scrapie resistance and susceptibility, called PRNP. A lamb receives one copy of the gene from each of its parents. All genes are made up of codons. Four codons are known to affect scrapie resistance and susceptibility. As there are different strains of scrapie, codon 171 is the major one that determines scrapie resistance and susceptibility in the United States.
Sheep that are RR at codon 171 are very resistant to scrapie. Sheep that are QQ are the most susceptible to scrapie and almost all known cases of scrapie have been QQ sheep. Sheep that are QR are usually resistant to scrapie. Some states have programs to help producers get their rams tested for scrapie resistance/susceptibility. RR rams (or ewes) will not produce any offspring that are susceptible to scrapie.
So far, there doesn't appear to be any negative correlation between scrapie resistance/susceptibility and any important production traits. Resistant genotypes have not been identified in goats yet.
Live animal testing
For many years, the only way to detect scrapie was to perform a necropsy and examine the brain tissue of the dead animal. It wasn't until 1998 that a pre-clinical test for live animals was developed. The third eyelid test extracts lymph tissue from the third eyelid. Prions collect in the lymphoid tissue in the sheep's third eyelid.
In early 2008, rectal biopsies were approved as another live animal test for scrapie. As compared to the third eyelid test, rectal biopsies are easier to perform, have less complications, and are just as accurate.
Also in 2008, a company in Europe announced the detection of exogenous prions in the blood plasma of asymptomatic scrapie-infected sheep. Amorfix Life Science, Ltd. is currently in discussions with potential partners to get regulatory approval and commercialize the test. A simple blood test to detect scrapie would aid greatly in the worldwide eradication of scrapie.
The incidence of scrapie in the United States is considered low. Slaughter surveillance studies conducted from February 2001 to March 2002 revealed a scrapie incidence of only 2/10 of one percent in the U.S. sheep population (1 in 500 sheep). States east of the Mississippi River have a higher incidence of scrapie (0.52 percent) than other regions in the U.S. While scrapie can affect any breed of sheep or goat, it is most commonly diagnosed in black-faced sheep and their crosses.
Though goats are just as susceptible to scrapie as sheep, only 21 goats have ever been diagnosed with scrapie in the U.S. Surveillance of scrapie incidence in goats is currently underway. None of the first 685 goats in the surveillance study (from Texas) have tested positive for scrapie. However, in December 2007, a 3-year old Nubian goat from a farm in Michigan tested positive for scrapie. Four additional goats were diagnosed with scrapie. It is not known how the original goat contracted the disease. Sheep had previously been kept on a farm where the goat was kept, but the goat did not have any direct contact with sheep. Goat-to-goat transmission most likely occurred.
The goal of the National Scrapie Eradication Program is to eliminate scrapie from U.S. sheep and goats by 2010 and for the United States to be recognized as "scrapie-free" by 2017. Australia and New Zealand are the only countries considered to be scrapie-free.
Towards this goal, all sheep and goats (with few exceptions) are required to carry official (USDA) scrapie ID (usually ear tags) when they leave their farm of origin. Scrapie ID allows trace-back of infected animals and identification of infected, source, and exposed flocks. To get free ear tags and the applicator to apply them, sheep and goat producers need to contact their area USDA-APHIS office. In Maryland and Delaware, call (410) 349-9708.
There is also a voluntary scrapie flock certification program which enables sheep and goat producers to have their flocks declared "scrapie-free" after five years of scrapie-free monitoring. Participating flocks are the only source of scrapie-free and scrapie-monitored sheep in the U.S. Other countries have similar programs for verifying scrapie-free breeding stock.
Current scrapie eradication efforts seem to be paying off. According to USDA-APHIS, the incidence of scrapie in cull sheep sampled at slaughter has been going down each year since 2003. As of October 30, 2007, the incidence of scrapie in black and moddled-faced sheep was 0.27% as compared to 1% five years ago.
Scrapie eradication requires cooperation of all segments of the sheep and goat industry. Scrapie costs the U.S. sheep and goat industry millions of dollars in lost revenue. The cost would be even greater if scrapie was ever found to cross the species barrier.
Last year, the first case of Nor98 atypical scrapie was diagnosed in a sheep in the United States. Four additional cases have followed. Nor98 is so-named because it was first discovered in 1998 in Norway. It has been diagnosed in sheep and goats in numerous countries in Europe, though fewer than 300 cases have been reported worldwide.
Nor98 differs from classical scrapie. It occurs mostly in sheep that are over 5 years of age. Twenty-five percent of the cases occur in sheep that are over 10 years of age. Nor98 seldom occurs in more than one sheep in a flock, unless it is a very large flock.
It is not known if and how Nor 98 is transmitted. It may occur sporadically. Horizontal transmission has not been ruled out. Nor98 can affect sheep that are genetically resistant to classical scrapie. The distribution of prions in sheep affected with Nor98 is different from classical scrapie. The current live animal tests do not detect Nor98.
Nor98 complicates scrapie eradication efforts. The World Organization for Animal Health has not yet decided how Nor98 will affect international trade.
Distribution of genotypes at codon 171 in US sheep (source: USDA APHIS, 2003)
This article was written in 2008 by Susan Schoenian.