Scrapie is a neurological disease affecting sheep and goats. It is the archetypal example of transmissible spongiform encephalopathies (TSEs) and is caused by a prion, an unconventional infectious agent. This misfolded protein aggregates in the central nervous system. Scrapie is the oldest known prion disease, recognized for centuries, with descriptions dating back more than 250 years. The name comes from the compulsive scraping behavior affected animals exhibit due to intense itching.
What Exactly is a Prion Disease?
Prion diseases are neurodegenerative disorders affecting both humans and animals. They are unique because the infectious agent is a protein without genetic material like DNA or RNA. This infectious particle is a misfolded version of the cellular prion protein (PrPC), which naturally exists on the surface of cells, particularly neurons. The misfolded, disease-causing form is called PrPSc (“Sc” for scrapie).
The mechanism centers on PrPSc, which acts as a template to force normal PrPC proteins to change into the abnormal form. This conversion is self-propagating, leading to an exponential accumulation of misfolded proteins. These abnormal prions are resistant to degradation by enzymes, heat, and disinfectants, allowing them to persist and aggregate in tissues. The buildup of PrPSc in the brain causes vacuolation—small holes that give the tissue a sponge-like appearance, known as spongiform change. This progressive destruction of neural tissue causes severe neurological symptoms and ultimately leads to death.
Scrapie: Clinical Manifestation
Scrapie affects sheep and goats, with clinical signs typically appearing after a prolonged incubation period of two to five years. Once symptoms begin, the disease progresses rapidly, usually leading to death within one to six months. The most characteristic clinical sign is intense pruritus, or itching, which causes the animal to compulsively rub and scrape its body against objects like fences or posts.
The persistent scraping leads to wool loss and skin lesions. Other symptoms indicate damage to the central nervous system, including progressive loss of coordination (ataxia), which manifests as a high-stepping gait or “bunny-hopping” movement in the hind limbs. Infected animals often exhibit behavioral changes, such as increased excitability, tremors, and significant weight loss despite a normal appetite. In the final stages, animals become recumbent and unable to stand.
How Scrapie Spreads
Scrapie is an infectious disease that spreads through both horizontal and vertical transmission. The most significant source of infection is the birthing process, where infectious prions are shed in high concentrations in the placenta and birth fluids of infected ewes and does. Lambs and kids become infected primarily by ingesting this contaminated material from their mother or the environment immediately after birth.
Horizontal spread occurs when susceptible animals contact the contaminated environment. Prions are shed in feces, urine, and saliva, leading to widespread contamination of pastures and housing areas. The infectious prion protein is remarkably durable, remaining biologically active in the soil and on surfaces for years. This environmental persistence makes decontamination extremely difficult and poses a persistent risk of re-infection, which is a major factor in the difficulty of eradicating the disease.
The Family of Prion Diseases
Scrapie is categorized with other significant prion diseases that affect various mammalian species. These include Bovine Spongiform Encephalopathy (BSE), known as “Mad Cow Disease” in cattle, and Chronic Wasting Disease (CWD) in deer and elk. The most well-known human prion disease is Creutzfeldt-Jakob Disease (CJD), which can occur sporadically, be inherited, or be acquired.
The link between these animal and human diseases became clear with the emergence of a new variant of CJD (vCJD) in humans, which was determined to be caused by consuming beef products contaminated with the BSE agent. While Scrapie itself has not been epidemiologically linked to human disease, the existence of BSE and vCJD underscores the potential for prions to cross species barriers. The study of Scrapie, as the historical prototype, continues to provide foundational insights into the biology of prions and the mechanisms that govern their infectivity.