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Bovine Spongiform Encephalopathy (BSE) Questions and Answers

What is BSE?

BSE (bovine spongiform encephalopathy) is a progressive neurological disorder of cattle; its symptoms are similar to a disease of sheep, called scrapie. BSE has been called "mad cow disease." BSE and scrapie both result from infection with a very unusual infectious agent. As of January 2004, more than 180,000 cases of BSE were confirmed in Great Britain in more than 35,000 herds of cattle. The epidemic peaked in January 1993 at almost 1,000 new cases per week. Although the origin of the disease is uncertain it may have resulted from the feeding of scrapie containing meat and bone meal (MBM) to cattle or from feeding cattle MBM derived from a cow or other animal that developed the disease due to a spontaneous mutation. There is strong evidence and general agreement that the outbreak was amplified by feeding meat-and-bone meal prepared from cattle to young calves.

What causes BSE?

The nature of the infectious agent that causes BSE and scrapie is unknown. Currently, the most accepted theory is that the agent is a modified form of a normal cell protein known as a prion. A prion is not a bacterium, parasite, or virus, and thus treatments usually used for treating or preventing bacterial infections (e.g. antibiotics) or viral infections are not effective against prions.

Where is the BSE agent found in cattle?

In cattle naturally infected with BSE, the BSE agent has been found in brain tissue, in the spinal cord, and in the retina of the eye. Additional experimental studies suggest that the BSE agent may also be present in the small intestine, tonsil, bone marrow, and dorsal root ganglia (lying along the vertebral column).

Which countries have reported BSE?

The vast majority of cases of BSE (more than 97% as of 2003) have been reported from the United Kingdom during an epidemic. However, endemic cases have also been reported in other European countries including: the Republic of Ireland, Switzerland, France, Liechtenstein, Luxembourg, Netherlands, Portugal and Denmark. The numbers of reported cases by country are available on the web site of the Office International des Epizooties. These numbers should be interpreted with caution, however, because the intensity and methods of surveillance probably vary over time and by country. In 2003 one case was reported in Canada and one in the United States (in a cow born in Canada).

How was BSE spread?

It is thought that BSE was spread via meat-and-bone meal fed to cattle. The practice of using this material as a source of protein in cattle feed has been common for several decades. In the late 1970s there was a change in the production (rendering) process used to make this meat and bone meal. One hypothesis has been that this change permitted the infectious agent of scrapie (a transmissible spongiform encephalopathy, or TSE, of sheep) to survive the rendering process, and get transmitted to other animals, such as cows, that are fed meat-and-bone meal nutritional supplements. An inquiry by the British government has however, concluded that scrapie infected MBM was not the source of BSE nor was the change in the rendering practices responsible for survival of the BSE agent. Rather, this inquiry has stated that BSE may have originated spontaneously as a result of a genetic mutation and was amplified by the feeding of contaminated MBM to cattle.

What has the British government done in response to the BSE epidemic?

In response to the BSE epidemic, the British Government instituted a series of measures to minimize the risk of disease transmission among both animals and humans. These included a ban on feeding ruminant protein (ruminants are animals, such as cows, sheep and goats) to ruminants (1988), removal of some "high risk" materials (such as brain, spinal cord and intestines) from cattle at slaughter (1989 and 1995), and a ban on cattle over 30 months of age from being used for food (1996). Following institution of these measures, Great Britain has seen a decrease in the number of cattle with BSE from a peak incidence of 36,682 confirmed cases in 1992 to 1044 confirmed in 2002.

Does BSE occur in the US?

According to the Animal Health and Plant Inspection Service (APHIS) of the United States Department of Agriculture, BSE has been detected in one cow in the United States. Following complications of pregnancy this cow was slaughtered December 9, 2003. As part of the APHIS ongoing surveillance of downer animals a brain sample was taken to test for the BSE agent. On December 25, 2003 it was confirmed that this animal tested positive for the BSE agent (on December 23, 2003 this was a "presumptive" case). Following this discovery the USDA and FDA announced additional measures to enhance the US protections against BSE (see: What measures has the US government taken to ensure that people are not exposed to the BSE agent in foods?).

What measures has the US government taken to ensure that people are not exposed to the BSE agent in foods?

The USDA is responsible for the health of US livestock. To prevent BSE from entering the country, the USDA Animal and Plant Health Inspection Service (APHIS) has, since 1989, prohibited the importation of live ruminants from countries where BSE is known to exist in native cattle. On December 12, 1997, APHIS stopped the importation of live ruminants and most ruminant products, including meat, meat-and-bone meal, offals, glands, etc. from all of Europe. FDA is responsible for animal feeds in the US. In August 1997, FDA prohibited the use of most mammalian protein in the manufacture of animal feeds given to ruminants. Following the discovery of one cow with BSE in the US, the USDA and FDA have announced additional measures to enhance protections against the spread of BSE in US cattle and to minimize human exposure to bovine materials that may contain the BSE agent. USDA has issued an interim final rule (Federal Register January 12, 2004 Vol. 69, Number 7) removing downer animals and specified risk materials and tissues from the human food chain; requiring additional process controls for establishments using advanced meat recovery (AMR); holding meat from cattle that have been targeted for BSE surveillance testing until the test has confirmed negative; and prohibiting the air injection stunning of cattle. In January 2004, FDA proposed additional safeguards including: excluding brain, spinal cord, gut and eyes of older animals from human food and from rendered material in animal feeds, eliminating poultry litter, cow blood and processed plate waste as feed ingredients for cattle, labeling requirements for pet food, and additional control measures to prevent cross contamination of feed and feed ingredients at feed mills. In addition, since 1990, the USDA has led an interagency surveillance program for evidence of BSE in the US. USDA has tested 20,000 animals annually for each of the last 2 years, and approximately 75 percent of these were downers at slaughter. A BSE risk assessment performed by Harvard University's Center for Risk Analysis at the School of Public Health concluded that even if BSE were to occur in the US the measures already taken would largely prevent its spread to animals or humans, and the disease would gradually disappear over a number of years.

How is the BSE agent detected?

The presence of the BSE agent in tissues is generally determined by injecting animals, usually mice, with samples, then observing the mice to see if they die and have characteristic brain tissue changes. Mouse inoculation studies take a long time (up to 700 days) to detect the agent, and a negative result (that is, lack of brain tissue changes in the injected mice) may only mean that there was too little of the infectious agent to cause symptoms, not that the material was completely free of the infectious agent. It is also possible to detect the presence of the abnormal prion protein in tissues (such as brain) using special staining procedures although these methods do not allow an accurate assessment of infectivity of the infected material.

Does BSE or a similar disease occur in humans?

BSE belongs to a group of progressive degenerative neurological diseases known as transmissible spongiform encephalopathies (TSEs). TSE diseases are always fatal. The TSE diseases include scrapie, which affects sheep and goats; transmissible mink encephalopathy; feline (cat) spongiform encephalopathy; and chronic wasting disease of deer and elk. There are six TSE diseases that affect people: kuru, classical Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and sporadic fatal insomnia. The human diseases are very rare; for example, classical CJD has been well studied and occurs sporadically worldwide at a rate of about one case per one million people each year.

Questions and Answers on Variant CJD (vCJD)

What is the new variant form of CJD that the experts in the United Kingdom believe might be related to the BSE outbreak in cattle?

In contrast to the classic form of CJD, the new variant or variant form (vCJD) in the United Kingdom and France affects younger persons (average age at onset: 26 years), and has different clinical features from CJD. People with vCJD begin with serious psychiatric problems or problems with their senses (ears, eyes or smell). This first set of symptoms is followed weeks or months later by poor muscle coordination, muscle spasms, and mental confusion. The illness lasts for at least 6 months, and on average people with vCJD die approximately 13 months after their symptoms begin. When patients' brains are examined by autopsy, there are clear changes in brain tissue structure, including many "spongiform," or open spongy-looking areas, abnormal clumps of prion protein called plaques, and other areas with less prominent accumulations of abnormal prion protein.

Exactly how does this newly recognized variant of CJD differ from classical CJD?

In 1996 the Spongiform Encephalopathy Advisory Committee (SEAC) of the UK announced the identification of 10 cases of variant CJD (vCJD, Lancet, 1996, 347: 921-25). Since then over 100 people have died of vCJD in the UK. The following features describe how vCJD cases differ from the sporadic or classical form of CJD (Lancet, 1996, 347: 921-25, Rev.Med.Virol. 2002;12: 143-50):

  • The affected individuals were much younger than the classical CJD patient. Typically, CJD patients are over 63 years old. The average patient with vCJD is 26 years old; patients ranged from 12-74 years old.
  • The course of vCJD averaged 13 months (range 6-40 months). Classical CJD cases average a 4 month duration.
  • In the vCJD cases, electroencephalographic (EEG) electrical activity in the brain, while abnormal (slowed), was not typical of classical CJD, which often has periodic bursts of increased electrical activity.
  • Although changes in brain tissue structure of patients with vCJD were recognizable as CJD, the pattern was different from classical CJD, with large aggregates of prion protein plaques often surrounded by vacuoles.

How did people get this new variant of CJD?

On March 20, 1996 a statement from the Spongiform Encephalopathy Advisory Committee (SEAC) of the United Kingdom indicated concern that before November 1989, when inclusion of certain cow and sheep by-products in human food was banned, the BSE agent may have been transmitted to people through contaminated food products. The SEAC said that food might account for the 10 vCJD cases described in 1996 (Lancet 1996; 347:921-5). The specific foods, if any that may be associated with the transmission of this agent from cattle to humans are unknown. However, the SEAC has indicated that milk and milk products are unlikely to pose any risk for human exposure to the BSE agent.

What is the evidence directly linking this newly recognized variant of CJD to BSE exposure?

There is strong epidemiologic and laboratory evidence suggesting that new variant CJD (vCJD) and BSE are caused by the same infectious agent. For instance, all cases of confirmed vCJD have occurred in people who have lived in geographic areas which have had BSE cases. The majority of cases of vCJD have occurred in the UK, which has had the largest number of cases of BSE in cattle. In addition, the time interval or "incubation period" between the most likely period for the initial exposure of the population to potentially BSE-contaminated food (1984-1986) and onset of initial vCJD cases (1994-1996), about 10 years, is similar to the known time intervals between exposure to the classical CJD agent and the development of CJD. An experimental study reported in June 1996, showed that three cynomolgus macaque monkeys that were injected with brain tissue from cattle with BSE later developed symptoms and changes in brain tissue that were strikingly similar to vCJD (Nature 1996;381:743-4). Another study published in 1996 showed that prion proteins obtained from 10 vCJD patients and BSE-infected animals had molecular characteristics that were similar to each other but distinct from prion proteins obtained from patients with classical CJD (Nature 1996;383:685-90). Furthermore, results of an ongoing experimental study involving injection of a panel of various strains of mice with the agent that causes BSE and vCJD suggested that these agents cause a similar disease in mice (Nature 1997;389:498-501). Histological analysis of mouse brains from this study showed no significant differences in the neuropathological changes observed in the BSE and vCJD-infected mice (Neuropathology and Applied Neurobiology 2003; 29:262-272). A study using transgenic mice (PNAS 1999; 96:15137-15242) also supports the hypothesis that the BSE agent from cattle causes vCJD.

How many cases of variant CJD have occurred?

Cases of variant CJD are very rare, and most have occurred in the United Kingdom. Information provided by the UK Creutzfeldt-Jakob Disease Surveillance Unit (February, 2004) indicates that there have been 146 cases of definite and probable vCJD in the United Kingdom. These cases have all been diagnosed since 1995. France has reported six cases. The Republic of Ireland, Italy, Canada and the US have each reported one case. The cases in Ireland, Canada and the US each occurred in individuals who had spent several years in the UK.

Could anyone in Europe diagnosed with the newly recognized variant of CJD (vCJD) have acquired this from vaccines?

In the UK the majority of cases of vCJD were born before 1980, and it is very unlikely that they received vaccines contaminated with the BSE agent (Vaccine 2000; 19:409-410). Surveillance of vCJD in the UK has identified three "risk factors," or characteristics common to most if not all of the people who had vCJD: i) residence in the UK; ii) a particular genetic susceptibility (met/met homozygosity at codon 129 of the PrP gene); and iii) age. Epidemiological evidence to date suggests that these cases of vCJD acquired the disease from eating beef products containing the BSE agent after 1980. To date (February 2004) there have been 156 reported cases of vCJD. Of these, 146 have occurred in the UK. Six cases of vCJD have been diagnosed in France, and one each in Canada, Ireland, Italy and the US. The cases in Canada, Ireland and the US each occurred in individuals who had spent several years in the UK.

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