Bovine Spongiform Encephalopathy --About the Disease--

1. Bovine Spongiform Encephalopathy--About the Disease--

2. BSE or mad cow disease • Chronic, afebrile, degenerative disease affecting the central nervous system of cattle • Long incubation period: 3 to 8 years • Family of transmissible spongiform encephalopathies: • Chronic wasting disease of deer and elk • Five rare diseases in humans: kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia (FFI), and new variant Creutzfeldt-Jakob disease (nvCJD) • Scrapie

3. Prion--Current and most accepted theory: • agent is a modified form of a normal protein known as prion protein (misfolded protein and stable) • the normal prion protein changes into a pathogenic (harmful) form that then damages the central nervous system of cattle (this is not yet understood) • Possibly originated (transmission): • Changes in rendering operations in the early 1980's: removal of a solvent-extraction process that included a steam-heat treatment may have played a part • Feeding cattle meat-and-bone meal that contained scrapie-infected sheep products • Then amplified and spread when young calves were fed rendered, prion-infected, bovine meat-and-bone meal • A ban on feeding animal protein of ruminant origin to ruminants was enacted in Great Britain in July 1988

4. Transmission continued: • No evidence that BSE spreads horizontally • Maternal transmission may occur at an extremely low level • Host Range • Via the oral route, BSE has been successfully transmitted to cattle, sheep, and goats, mice, and mink • Agent isolated from several feline cases using strain typing in mice is indistinguishable from BSE in cattle, which suggests that FSE is actually BSE in exotic and domestic cats • Humans • Wild Ruminants

5. Affected animals may display: • Changes in temperament and sensation • Abnormalities of posture and movement • More specifically: • Apprehension, nervousness or aggression • Incoordination, especially hind-limb ataxia, tremor, difficulty in rising • Hyperaesthesia to sound and touch • Decreased milk production or loss of body condition, or both, despite continued appetite • No gross lesions • BSE agent is not found in meat (like steaks, roasts or ground beef) or milk

6. Diagnosis • Field: clinical signs—observed for 2 weeks and if improvement or recovery hasn’t taken place, BSE suspected • Laboratory: histopathological examination of brain tissue • Diagnosis may also be made by the detection of scrabie-associated febriles (SAF's) using electron microscopy • Immunohistochemistry and the Western blot technique if the brain has been frozen or autolytozed • Differential Diagnoses • Rabies, listeriosis, nervous ketosis, milk fever, grass tetany, lead poisoning

7. No treatment or vaccine • Control and Eradication • Implementation of import regulations prohibiting live ruminants and ruminant products (especially meat, bone meal, and offal) from countries where BSE may exist • Prohibition of feeding ruminant proteins to ruminants • Active surveillance effort focused on high-risk cattle for the early detection of BSE • Culling sick animals • UK excludes all animals more than 30 months of age from the human food and animal feed supplies • BSE testing of all cattle more than 30 months of age destined for human consumption • No beef imported from UK since 1985

8. --US Measures--

9. U.S. agencies have acted quickly with precautionary steps to prevent BSE in cattle or vCJD in humans from occurring in this country: • Prohibiting importation of live ruminant animals and most ruminant products from all of Europe (USDA) • Examining U.S. cattle exhibiting abnormal neurological behavior to test for BSE (USDA) • Prohibiting the use of most mammalian protein in the manufacture of animal feeds given to ruminant animals (FDA) • Recommending that animal tissues used in drug products should not come from a country with BSE (FDA) • Issuing guidelines asking blood centers to exclude potential donors who have spent six or more cumulative months in the U.K. between 1980 and 1996 from donating blood (FDA) • Conducting regular surveillance for any cases of vCJD among humans (CDC) • Conducting research on BSE, CJD, vCJD and related neurological diseases (NIH)

10. BSE and vCJD

11. vCJD may be acquired from eating food products containing the BSE agent • specific foods associated with this transmission are unknown • Strong epidemiologic and laboratory evidence for a causal association • Absence of confirmed cases of vCJD in geographic areas free of BSE supports a causal association

12. JAVMA Articles

13. Canada • Single case of BSE discovered in a 6- to 8-year-old Alberta cow • Likely caused by exposure to BSE-contaminated feed early in the animal's life, prior to a 1997 ban • January 2003 cow condemned for slaughter, but not high priority because not showing signs of BSE • May 2003, World Reference Lab in UK confirmed BSE • Launch investigation: 18 farms quarantined and 2700 cattle depopulated and tested • No other diseased animals found • October 2003, wrap up investigation

14. More cases discovered in Dec 2004 • US still considers Canada minimal risk so allow imports of live cattle less than 30 months of age and certain other commodities • Standards to be deemed minimal-risk: • Prohibition on specified-risk materials in human food • Surveillance for BSE at levels that meet or exceed international guidelines • Appropriate epidemiologic investigations, risk assessment, and risk mitigation measures imposed as necessary • In January 05, R-CALF-USA filed a lawsuit against the USDA in U.S. District Court, in an attempt to stop the reopening of the border • Still battling as of Aug 06

15. Canada • Older cattle present a greater risk for spreading the disease • Prions have had sufficient time to accumulate in many tissues • Cattle less than 30 months old, prions have been found to concentrate predominantly in the intestines • Dairy cow identified in 2006 under the national BSE surveillance program • Cow was born after the implementation of Canada's feed ban in 1997 • Investigation Overview: • Presume that this animal was exposed to feed containing a low level of infectivity during its first year of life, but impossible to determine the exact source of exposure • Major rations could have become contaminated during manufacture or distribution

16. New BSE rule by Dept of Agriculture: Bovine Spongiform Encephalopathy; Minimal-Risk Regions and Importation of Commodities • Establishes regulations to govern the importation of certain live cattle, bison, sheep, and goats into the United States from Canada • Only an accredited veterinarian, or a federal or state veterinary medical officer, may remove government seals on vehicles transporting feeder cattle, bison, sheep, or goats • Veterinarian, or a state or USDA representative, must issue “Permit for Movement of Restricted Animals” • For a permit to be issued: • Vehicle must be sealed • Only Canadian animals can be shipped in the vehicle • Canadian animals will be branded and cannot be mixed with U.S. animals going to slaughter

17. U.S. • Dec 03—First case, Washington State • routinely test downer cattle for BSE • implementing a national animal identification system to track animal movement. • ordered U.S. slaughterhouses not to process nonambulatory or "downer cattle" and to adopt processing techniques to prevent contaminating meat with bovine nerve tissue • skull, brain, trigeminal ganglia, eyes, vertebral column, spinal cord, and dorsal root ganglia from cattle more than 30 months of age cannot be used for human food; the use of small intestine of cattle of all ages is also prohibited • recall on Dec. 23 of some 10,000 pounds of raw meat distributed by Vern's Moses Lake Meats in Washington state, where the infected cow was processed. • Records show the cow was born in Alberta Canada, April 1997, meaning she was born prior to the implementation of the August 1997 ban on ruminant feed containing animal protein

18. March 06—Case in Alabama • Cow was believed to be about 10 years old, indicating that it was born prior to the implementation of the Food and Drug Administration's 1997 animal feed ban • Did not enter the human food or animal feed supplies • Investigation unable to locate the herd of origin • Two confirmatory tests that the USDA uses to determine whether an animal is infected with BSE: • Western blot test • Immunohistochemistry test

19. USDA • Approved laboratories to help with testing: • California Animal Health and Food Safety Laboratory System at University of California-Davis • Colorado State University Veterinary Diagnostic Laboratory • Texas Veterinary Medical Diagnostic Laboratory in College Station • Wisconsin Animal Health Laboratory in Madison • Washington State University Animal Disease Diagnostic Laboratory • Athens Diagnostic Laboratory at University of Georgia College of Veterinary Medicine • Veterinary Diagnostic Laboratory at Cornell University's New York State College of Veterinary Medicine • Presumptive positive results from a rapid test must be confirmed with the immunohistochemistry test • USDA has designated as the official test • Confirmatory testing will take place at the USDA's National Veterinary Services Laboratories in Ames, Iowa, the national reference laboratory for BSE.

20. USDA • Sharp increase in testing to enhance surveillance plan: • The primary focus: continue to test those high risk cattle, but the number tested will greatly increase • A random sampling of at least 20,000 apparently healthy, older cows will also be tested • Older cattle will be tested at slaughter because BSE has a typical incubation period between 3 and 8 years

21. Safeguards • First rule will ban the following materials from FDA-regulated human food, (including dietary supplements) and cosmetics: • Any material from downer cattle • Any material from dead cattle (that die on the farm) • "Specified risk materials" that are known to harbor the highest concentrations of the infectious agent for BSE, such as the brain, skull, eyes, and spinal cord of cattle 30 months or older, and a portion of the small intestine and tonsils from all cattle, regardless of their age or health • The product known as mechanically separated beef, which may contain specified risk materials; however, meat obtained by Advanced Meat Recovery (an automated system for cutting meat from bones) may be used

22. Second rule: • eliminate the exemption in the feed rule that allows mammalian blood and blood products to be fed to other ruminants as a protein source (blood can carry some infectivity for BSE ) • ban the use of poultry litter as a feed ingredient for ruminant animals • concern is that when poultry feed is spilled in the chicken house, it will be collected as part of the poultry litter and added to ruminant feed • Poultry feed may legally contain protein that is prohibited in ruminant feed, such as bovine meat and bone meal • ban the use of plate waste as a feed ingredient for ruminants • Plate waste consists of uneaten meat and other meat scraps that are collected from large restaurant operations and rendered into meat and bone meal for animal feed • minimize the possibility of cross-contamination of ruminant and nonruminant feed by requiring equipment, facilities, or production lines to be dedicated to nonruminant animal feeds if they use protein that is prohibited in ruminant feed

23. FDA proposing new rule: • Prohibit the use of certain cattle-origin material in the feed of all animals—not just in the feed of ruminants • 21 CFR 589--old ruling on food

24. PRIONS

25. Mice Studies: • misfolded proteins that cause transmissible spongiform encephalopathies • infiltrate organs affected by chronic inflammation and proliferate • new finding raises the possibility that prions may spread to other tissues in cattle and other animals that have conditions such as pancreatitis and nephritis • investigated whether chronic inflammation influences prion pathogenesis, because studies have shown that B lymphocytes and other components of the immune system are involved in prion replication • When inflammation subsided, however, the prions disappeared • unclear what risk this poses to human health • USDA does not plan to impose additional restrictions on tissues that enter the food supply

26. CWD

27. TSE of deer and elk • Clinical Signs: • Weight loss over time • Decreased interactions with other animals, listlessness, lowering of the head, blank facial expression, and repetitive walking in set patterns • Excessive salivation and grinding of the teeth also are observed • No known relationship between CWD and any other TSE of animals or people • Definitive diagnosis is based on postmortem examination (necropsy) and testing • Emaciation • Aspiration pneumonia, which may be the actual cause of death, also is a common finding • Immunohistochemistry

28. Transmission • Study provides the first solid evidence that chronic wasting disease can be transmitted through environments contaminated by carcasses or excrement of infected animals • Spreading through direct interactions between animals • Might be passed in the blood and saliva of infected deer • Raise new questions about whether the disease can be spread by blood-sucking insects such as mosquitoes and ticks or social contact between animals • Infectious prions were discovered in the animals' tonsils as soon as three months after exposure to saliva or blood from an infected deer • Vertical Transmission (mother to offspring) is possible