The Basic Facts

Transmissible Spongiform Encephalopathies (TSEs) are a class of brain diseases, some of which affect humans while others affect animals. TSEs are associated with the accumulation of abnormal prion protein (PrP) in the brain.This abnormal protease-resistant protein is referred to as PrPRes(protease resistant protein) or PrPSc (PrP Scrapie).

All mammals produce normal PrP in cells of the central nervous system and other tissues. Changes in normal PrP are believed to lead to an altered protein referred to by some scientists as a “prion” (proteinacious infectious particle). Scientists believe that when abnormal PrP comes in contact with normal PrP, it distorts the normal protein structure. Scientists do not know what factors trigger this conversion. Some believe the abnormal PrP itself causes the conversion, while others believe a virus-like entity may be involved. Most scientists agree that the accumulation of abnormal PrP in brain cells results in altered function and eventual death or loss of function of cells. 1, ^13-16

CJD

Creutzfeldt-Jacob Disease (CJD) and variant Creutzfeldt-Jacob Disease (vCJD) are different diseases.Each has its own unique clinical and histopathological features. CJD was first characterized in the 1920s, and the Centers for Disease Control and Prevention (CDC) report the rate of CJD cases in the United States remains consistent with the rate in many other countries, which is approximately one case per million people each year. It is important to note that this incidence rate represents an average over time. Because age is a key factor in evaluating CJD distribution, and because the disease tends to strike people over the age of 55, the actual rate is higher for older people. ^{2, 15,24}

vCJD

Variant Creutzfeldt-Jakob disease (vCJD): is a human TSE identified in 1996 for the disease believed to be linked with BSE. Research from the U.K. supports an association between BSE and vCJD, in that vCJD likely developed as a result of people consuming products contaminated with central nervous system tissue of BSE-infected cattle.

Variant CJD was first documented in the United Kingdom in 1996. Surveillance by the CDC, in cooperation with state health departments and the National Prion Disease Pathology Surveillance Center, shows that no domestic cases of vCJD have been detected in the U.S. ^{2, 15} Scientists have concluded that the patients in the United States and Canada contracted vCJD in the U.K.²²

BSE

BSE, which is commonly referred to as "mad cow disease," has been detected in cattle in the U.K. and other European countries. 

The USDA, Food and Drug Administration (FDA) and many arms of the livestock industry have taken steps for a decade to prevent BSE from spreading in the U.S. ³  

The disease agent for BSE, to date, only has been found in brain tissue, the spinal cord and retina of naturally infected cattle.^{1, 4, 9}

However, evaluation of experimentally inoculated cattle has found BSE infectivity in additional nervous and other tissues, specifically the dorsal root ganglia (nervous tissues connected to the spinal cord) and trigeminal ganglia (nervous tissue connected to the brain), as well as distal ileum (tissues in the intestines), tonsil, and the third eyelid (nictating membrane). This research involved a series of experiments in which calves were either intracranially injected with or fed relatively large amounts of heavily infected brain from clinical BSE cases.

Examination of the animals fed BSE-infected brain showed infectivity in the distal ileum six to eight months after exposure and in other central nervous tissues 30 months or more after exposures. Reports on the research state that muscle meat and other tissues were tested for infectivity and no infectivity was found to date. ^20,31,34

CWD

Chronic Wasting Disease is a contagious fatal TSE in cervids (members of the deer and elk family). Research to date has shown CWD appears to be different from BSE. While the possibility of human infection remains a concern, it is important to note there have been no verified cases of humans contracting CWD.Centers for Disease Control and Prevention (CDC) and the National Prion Disease Pathology Surveillance Center (NPDPSC) investigations of unusually young CJD victims who consumed venison found “no strong evidence for a causal link.” ²⁹

For more information on CWD, please visit these websites:

Chronic Wasting Disease Alliance

www.usda.aphis.gov

Colorado Division of Wildlife

Scrapie

Scrapie affects sheep and goats and has been found in many sheep-producing countries throughout the world for over 250 years. It is not known to have public health implications.

Diagnostic Testing for TSEs

There currently is no practical test available that can accurately diagnose TSEs in living humans or animals (with the exception of scrapie in sheep and goats). Confirmed diagnoses must be made post-mortem by examining brain tissue through a microscope or by using other test methods that can identify the abnormal form of prion protein (PrPSc or PrPRes). The following are current types of diagnostic tests.

Histopathology: Examination of sections of brain tissue under a microscope to detect spongiform patterns characteristics of specific types of TSEs. Electron microscopes can be used to detect the presence of prion-associated fibrils (see definition of Scrapie Associated Fibrils). Histopathology tests take from two to five days to complete.

Immunohistochemistry: A laboratory methodology that involves microscopic examination of brain tissue that has been reacted with antibodies for proteins. The antibodies are linked to enzymes that show a chemical reaction (called staining) that can detect the abnormal form of prion protein found in TSEs. Immunohistochemistry is the test performed on all cattle brain samples collected in the USDA’s BSE surveillance program. Immunohistochemistry testing requires two to three days to complete.

Immunoblot/Western Blot: A biochemical technique in which brain tissue is homogenized and treated with a protease enzyme that destroys normal prion protein but not the abnormal protein. The brain sample is separated by gel electrophoresis (a method that separates protein molecules on the basis of size, electric charge, and other physical properties). Abnormal prion protein molecules can be detected immunologically using antibodies linked to an enzyme that results in a chemical reaction (staining). Immunoblot tests typically take one to two days to complete.There is a modified Western Blot approved for use in the Europe and other countries that takes 6-8 hours to complete.

ELISA (Enzyme-Linked Immunosorbent Assay): A process in which brain tissue is homogenized, normal prion protein is destroyed by a protease enzyme, and any remaining abnormal prion protein is bound to the surface of a clear, microtiter well. Abnormal proteins are detected immunologically using antibodies linked to an enzyme and exposed to a chemical substrate, which provides a signal in the form of a color change or light emission. An electronic instrument called a spectrophotometer picks up the signal. Positive tests for TSEs using the ELISA method usually are confirmed through immunohistochemistry or Western Blot testing. ELISA tests for TSEs typically can be completed in about four hours.