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U.S. Food & Drug
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Prions and Transmissible Spongiform Encephalopathies
| 1. Name of the Agent: | The prion. Prions are normal proteins of animal tissues that can misfold and become infectious: they are not cellular organisms or viruses. In their normal noninfectious state, these proteins may be involved in cell-to-cell communication. When these proteins become abnormally shaped i.e., infectious prions, they are thought to come into contact with a normally shaped protein and transform that protein into the abnormally shaped prion. This process causes a geometric increase of abnormally shaped prion proteins until the number of abnormally shaped protein causes overt illness. When consumed by animals, prions are thought to be absorbed into the body during digestion where they begin the process of changing their normal protein counterparts into abnormal proteins; however infectious prions from one species of animal have less of a potential of causing the abnormal shape in the normally shaped prion proteins of another species (the "species barrier"). While the "prion theory" of Transmissible Spongiform Encephalopathies (TSEs) is widely accepted, there are other theories of the cause of these illnesses. |
| 2. Nature of Acute Disease: | Prions are associated with a group of diseases called Transmissible Spongiform Encephalopathies (TSEs). In humans, the illness suspected of being foodborne is variant Creutzfeldt-Jakob disease (vCJD). The human disease vCJD and the cattle disease, bovine spongiform encephalopathy (BSE), also known as "mad cow" disease, appear to be caused by the same agent. Other similar but not identical TSE diseases exist in animals, but there is no known transmission of these TSEs to humans. Included among these is chronic wasting disease (CWD) of deer and elk, and the oldest known of these diseases - scrapie - which occurs in sheep and goats. No early acute clinical indications for TSEs have been described. After an extended incubation period of years, these diseases result in irreversible neurodegeneration. |
| 3. Nature of Disease: | The neurodegenerative phase of vCJD in humans typically involves the formation of "daisy-shaped" areas of damage in the central nervous system. There is also, in common with other TSEs, vacuolization (formation of holes) that gives brain tissue a spongy appearance when examined under a microscope. It is thought that the build-up of the abnormally shaped prion proteins causes the observed neurodegeneration. |
| 4. Diagnosis of Human Illness: | The most reliable means for diagnosing any TSE is the microscopic examination of brain tissue - a post-mortem procedure. Preliminary diagnoses of vCJD are based on patient history, clinical symptoms, electroencephalograms, and magnetic resonance imaging of the brain. |
| 5. Associated Foods: | The major concern for consumers is the potential contamination of meat products by BSE contaminated tissues or the inclusion of BSE contaminated tissues in foods, including dietary supplements. High risk tissues for BSE contamination include the cattle's skull, brain, trigeminal ganglia (nerves attached to the brain, eyes, tonsils, spinal cord, dorsal root ganglia (nerves attached to the spinal cord), and the distal ileum (part of the small intestine). The direct or indirect intake of high-risk tissues may have been the source of human illnesses in the United Kingdom and elsewhere. Bovine meat (if free of central nervous system tissue) and milk have, to date, shown no infectivity in test animals. Gelatin, derived from the hides and bones of cattle, appears to be very low risk , especially with adequate attention to the quality of source material and effectiveness of gelatin-making process. Based upon many studies, scientists have concluded that forms of CJD other than vCJD do not appear to be associated with the consumption of specific foods. |
| 6. Relative Frequency of Disease: | There is one reported human cases of vCJD in the United States in a woman that appears to have aquired the illness from consumption of contaminated food when growing up in the United Kingdom. In the U. K., there have been around 143 human cases of suspected or confirmed vCJD from 1993, when the illness was first recognized, through December 2003. There have been six reported cases of vCJD in France and one in Italy. Since 1986, more than 180,000 cases of BSE have occurred in the U.K.in cattle, particularly dairy cattle. BSE cases have also been identified in 20 European countries, Japan, Israel, and Canada. The feeding of rendered TSE-infected animal by-products to cattle is believed to have caused the epidemic of BSE. Practices such as this have now been prohibited, resulting in a dramatic decline in the number of cases. There is one reported case of BSE in the U.S. which appears to be the result of importing cattle from Canada that may have been exposed to feed which contained meat and bone meal from rendered cattle. |
| 7. Course of Disease and Complications: | Cases of vCJD usually present with psychiatric problems, such as depression. As the disease progresses, neurologic signs appear -- unpleasant sensations in the limbs and/or face. There are problems with walking and muscle coordination. Sometimes, late in the course of the disease, victims become forgetful and then experience severe problems with processing information and speaking. Patients are hospitalized and are increasingly unable to care for themselves until death occurs. |
| 8. Target Populations: | All cases of vCJD to date have occurred in individuals of a single human genotype that is methionine homozygous at codon 129 of the prion protein. About 40% of the total human population belongs to this methionine-methionine homozygous state. The susceptibility of other genotypes is not yet known. |
| 9. Food Analysis & Reconditioning: | No practical detection methods exist, at present. The abnormally shaped prions are resistant to most heat and chemical treatments, however certain food manufacturing processes (e.g. gelatin production) do result in significant decrease in prion infectivity through exclusion. There are no known means of reconditioning contaminated foods. The key to food protection is obtaining bovine meat and meat byproducts from animals not infected with BSE and protecting against contamination of food with high risk tissues, especially brain and spinal cord tissue. |
| 10. Selected Outbreaks: | Significant numbers of vCJD cases have occurred only in the United Kingdom; isolated cases have been reported in other countries. |
| 11. Education and Background Resources: | Literature references can be found at the links below. |
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CDC's Emerging Infectious Diseases |
The epidemic of bovine spongiform encephalopathy in the United Kingdom, that began in 1986 and during its course affected nearly 200,000 cattle, is waning. It leaves in its wake a human outbreak of variant Creutzfeldt-Jakob disease, most probably resulting from the consumption of beef products contaminated by central nervous system tissue. Although averaging only 10-15 cases a year since its first appearance in 1994, the future magnitude and geographic distribution of this illness cannot yet be predicted. The possibility that large numbers of apparently healthy persons might be incubating the disease raises concerns about iatrogenic transmissions through instrumentation (surgery and medical diagnostic procedures) and blood and organ donations. Government agencies in many countries continue to implement new measures to minimize this risk. |
| APHIS USDA Background document on BSE | BSE has had a substantial impact on the livestock industry in the United Kingdom. The disease also has been confirmed in native-born cattle in Belgium, Denmark, France, Germany, Italy, Ireland, Liechtenstein, Luxembourg, the Netherlands, Northern Ireland, Portugal, Spain, Switzerland, and Canada. The Animal and Plant Health Inspection Service (APHIS) of the U.S. Department of Agriculture (USDA) is enforcing import restrictions and conducting surveillance for BSE to prevent this serious disease from becoming established in the United States. APHIS surveillance detected the single BSE occurance in the U.S. |
| Centers for Disease Control and Prevention Background document on CJD |
Since 1996, evidence has been increasing for a causal relationship between ongoing outbreaks in Europe of a disease in cattle, called bovine spongiform encephalopathy (BSE, or "mad cow disease"), and a disease in humans, called variant Creutzfeldt-Jakob disease (vCJD). Both disorders are inevitably fatal brain diseases with unusually long incubation periods measured in years, and are caused by an unconventional transmissible agent. |
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Food and Drug Administration |
Rendered feed ingredients contaminated with an infectious agent are believed to have been the source of BSE infection in cattle in the United Kingdom. Some of the feed given to cattle included remnants of the slaughtering process, such as the brain and spinal cord, which harbor the agent that is believed to cause BSE. Although the material is cooked during the rendering process, the BSE agent can survive cooking. To prevent the establishment and amplification of BSE through feed in the United States, FDA implemented a final rule that, in most cases, prohibits the feeding of mammalian protein to ruminant animals. This rule, Title 21 Part 589.2000 of the Code of Federal Regulations, became effective on August 4, 1997. |
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Food and Drug Administration |
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Loci index for PrP of Homo sapiens |
Available from the GenBank Protein database, which contains the protein sequences for many organisms. |
| 12. Molecular Structural Data: | |
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PrP Protein in Humans |
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PrP Protein in Cattle |
mow@cfsan.fda.gov
January 2004 with periodic updates
