Bovine spongiform encephalopathy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

Bovine spongiform encephalopathy is a transmissible spongiform encephalopathy of cattle associated with abnormal prion proteins in the brain. Affected animals develop excitability and salivation followed by ataxia. This disorder has been associated with consumption of scrapie infected ruminant derived protein. This condition may be transmitted to humans, where it is referred to as variant or new variant CREUTZFELDT-JAKOB SYNDROME. Publius Flavius Vegetius Renatus records cases of a disease with similar characteristics in the 4th and 5th Century AD. The origin of the disease itself remains unknown. The current scientific view is that infectious proteins called prions developed through spontaneous mutation, probably in the 1970s, and there is a possibility that the use of organophosphorus pesticides increased the susceptibility of cattle to the disease. Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989. It is believed that the disease may be transmitted to human beings who eat infected carcasses. In humans, it is known as new variant Creutzfeldt-Jakob disease (vCJD or nvCJD), and by June 2007, it had killed 165 people in Britain, and six elsewhere with the number expected to rise because of the disease’s long incubation period. Based on the biochemical signatures of the disease-associated prion protein, Bovine spongiform encephalopahty (BSE) may be classified as either classic or atypical. Atypical BSE may further be classified into H- and L-types. Due to the accumulation of amyloid protein in the brain in cattles with L-type BSE, its also known as bovine amyloidotic spongiform encephalopathy (BASE). It is understood that Bovine spongiform encephalopathy (BSE) is caused by a misfolded prion protein. Misfolded prion proteins carry the disease between individuals and cause deterioration of the brain. BSE is a type of transmissible spongiform encephalopathy (TSE). Bovine spongiform encephalopathy (BSE) may be caused by different strains including the classic BSE strain (which is responsible for the outbreak in the United Kingdom) and two atypical strains (H and L strains). Bovine spongiform encephalopathy must be differentiated from other diseases that cause hyperesthesia, nervousness, reluctance to be milked, aggression, low head carriage, tremors, ataxia, disrupted milk production, and weight loss in animals, such as scrapes, rabies, encephalitic listeriosis, hypomagnesemia, lead poisoning, downer cow syndrome, nervous ketosis, polioencephalomalacia, ingestion of plant or fungal tremoragens, intracranial abscess or tumors, trauma to the spinal column, and other viral and bacterial neuroinfectious diseases. Following an epizootic of BSE in Britain, 165 people (up until 2007) acquired and died of a disease with similar neurological symptoms subsequently called vCJD, or (new) variant Creutzfeldt-Jakob disease. It is estimated that 400,000 cattle infected with BSE entered the human food chain in the 1980s. Although the BSE epizootic was eventually brought under control by culling all suspect cattle populations, people are still being diagnosed with vCJD each year. It is notable that there are no cases reported in Australia and New Zealand where cattle are mainly fed outside on grass pasture and, mainly in Australia, non-grass feeding is done only as a final finishing process before the animals are processed for meat. The most potent risk factor in the development of bovine spongiform encephalopathy is the consumption of meat-and-bone meal (MBM) by cattle. There is insufficient evidence to recommend routine screening for bovine spongiform encephalopathy (BSE). The symptoms of bovine spongiform encephalopathy typically develop 2-8 years after exposure to prions. Prognosis is generally poor, and death occurs approximately 3 months after the appearance of the first clinical signs. Bovine spongiform encephalopathy is primarily diagnosed based on the clinical presentation. However, postmortem examination should be performed for the definitive diagnosis. The postmortem investigation might be done with either western blot, ELISA, rapid test for BSE (ID-Lelystad), or histopathology. The confirmation of the diagnosis is possible either with the detection of PrPBSE in the brain tissue (either by western blot, ELISA, or ID-Lelystad), or vacuolation of neurons and neuropil in the histopathologic examination of medulla oblongata specimen. The most common symptoms of bovine spongiform encephalopathy include hyperesthesia, nervousness, reluctance to be milked, aggression, low head carriage, tremors, ataxia, disrupted milk production, and weight loss in animals. Common physical examination findings of bovine spongiform encephalopathy include ataxia, tremor, abnormal head carriage, hyperesthesia, excessive licking, loss of weight, recumbency, and abnormal ear position. Laboratory findings consistent with the diagnosis of bovine spongiform encephalopathy include the detection of PrPBSE in the brain tissue (either by western blot, ELISA, or ID-Leystad), the detection of Scrapie-Associated Fibrils in the brain tissue (by electron microscopy), and specific histopathologic findings such as vacuolation of neurons and neuropil. There are no ECG findings associated with bovine spongiform encephalopathy. There are no x-ray findings associated with bovine spongiform encephalopathy. There are no echocardiography/ultrasound findings associated with bovine spongiform encephalopathy. There are no CT scan findings associated with bovine spongiform encephalopathy. T2-weighted (T2W) MRI may be helpful in the diagnosis of bovine spongiform encephalopathy. Findings on T2W-MRI suggestive of bovine spongiform encephalopathy include T2W-MRI hyperintensity in the thalamic nuclei. There are no other imaging findings associated with bovine spongiform encephalopathy. There are no other diagnostic studies associated with bovine spongiform encephalopathy. There is no treatment for bovine spongiform encephalopathy. There are no recommended therapeutic interventions for the management of bovine spongiform encephalopathy. Surgical intervention is not recommended for the management of bovine spongiform encephalopathy. Effective measures for the primary prevention of bovine spongiform encephalopathy include control measures such as surveillance, banning specified risk materials, culling sick animals, and excluding all animals more than 30 months of age from the human food and animal feed supplies. There are no established measures for the secondary prevention of bovine spongiform encephalopathy.

Publius Flavius Vegetius Renatus records cases of a disease with similar characteristics in the 4th and 5th Century AD. The origin of the disease itself remains unknown. The current scientific view is that infectious proteins called prions developed through spontaneous mutation, probably in the 1970s, and there is a possibility that the use of organophosphorus pesticides increased the susceptibility of cattle to the disease. Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989. It is believed that the disease may be transmitted to human beings who eat infected carcasses. In humans, it is known as new variant Creutzfeldt-Jakob disease (vCJD or nvCJD), and by June 2007, it had killed 165 people in Britain, and six elsewhere with the number expected to rise because of the disease’s long incubation period.

Based on the biochemical signatures of the disease-associated prion protein, Bovine spongiform encephalopahty (BSE) may be classified as either classic or atypical. Atypical BSE may further be classified into H- and L-types. Due to the accumulation of amyloid protein in the brain in cattles with L-type BSE, its also known as bovine amyloidotic spongiform encephalopathy (BASE).

It is understood that Bovine spongiform encephalopathy (BSE) is caused by a misfolded prion protein. Misfolded prion proteins carry the disease between individuals and cause deterioration of the brain. BSE is a type of transmissible spongiform encephalopathy (TSE).

Bovine spongiform encephalopathy (BSE) may be caused by different strains including the classic BSE strain (which is responsible for the outbreak in the United Kingdom) and two atypical strains (H and L strains).

Bovine spongiform encephalopathy must be differentiated from other diseases that cause hyperesthesia, nervousness, reluctance to be milked, aggression, low head carriage, tremors, ataxia, disrupted milk production, and weight loss in animals, such as scrapes, rabies, encephalitic listeriosis, hypomagnesemia, lead poisoning, downer cow syndrome, nervous ketosis, polioencephalomalacia, ingestion of plant or fungal tremoragens, intracranial abscess or tumors, trauma to the spinal column, and other viral and bacterial neuroinfectious diseases.

Following an epizootic of BSE in Britain, 165 people (up until 2007) acquired and died of a disease with similar neurological symptoms subsequently called vCJD, or (new) variant Creutzfeldt-Jakob disease. It is estimated that 400,000 cattle infected with BSE entered the human food chain in the 1980s. Although the BSE epizootic was eventually brought under control by culling all suspect cattle populations, people are still being diagnosed with vCJD each year. It is notable that there are no cases reported in Australia and New Zealand where cattle are mainly fed outside on grass pasture and, mainly in Australia, non-grass feeding is done only as a final finishing process before the animals are processed for meat.

The most potent risk factor in the development of bovine spongiform encephalopathy is the consumption of meat-and-bone meal (MBM) by cattle.

There is insufficient evidence to recommend routine screening for bovine spongiform encephalopathy (BSE).

The symptoms of bovine spongiform encephalopathy typically develop 2-8 years after exposure to prions. Prognosis is generally poor, and death occurs approximately 3 months after the appearance of the first clinical signs.

Bovine spongiform encephalopathy is primarily diagnosed based on the clinical presentation. However, postmortem examination should be performed for the definitive diagnosis. The postmortem investigation might be done with either western blot, ELISA, rapid test for BSE (ID-Lelystad), or histopathology. The confirmation of the diagnosis is possible either with the detection of PrPBSE in the brain tissue (either by western blot, ELISA, or ID-Lelystad), or vacuolation of neurons and neuropil in the histopathologic examination of medulla oblongata specimen.

The most common symptoms of bovine spongiform encephalopathy include hyperesthesia, nervousness, reluctance to be milked, aggression, low head carriage, tremors, ataxia, disrupted milk production, and weight loss in animals.

Common physical examination findings of bovine spongiform encephalopathy include ataxia, tremor, abnormal head carriage, hyperesthesia, excessive licking, loss of weight, recumbency, and abnormal ear position.

Laboratory findings consistent with the diagnosis of bovine spongiform encephalopathy include the detection of PrPBSE in the brain tissue (either by western blot, ELISA, or ID-Leystad), the detection of Scrapie-Associated Fibrils in the brain tissue (by electron microscopy), and specific histopathologic findings such as vacuolation of neurons and neuropil.

There are no ECG findings associated with bovine spongiform encephalopathy.

There are no x-ray findings associated with bovine spongiform encephalopathy.

There are no echocardiography/ultrasound findings associated with bovine spongiform encephalopathy.

There are no CT scan findings associated with bovine spongiform encephalopathy.

T2-weighted (T2W) MRI may be helpful in the diagnosis of bovine spongiform encephalopathy. Findings on T2W-MRI suggestive of bovine spongiform encephalopathy include T2W-MRI hyperintensity in the thalamic nuclei.

There are no other imaging findings associated with bovine spongiform encephalopathy.

There are no other diagnostic studies associated with bovine spongiform encephalopathy.

There is no treatment for bovine spongiform encephalopathy.

There are no recommended therapeutic interventions for the management of bovine spongiform encephalopathy.

Surgical intervention is not recommended for the management of bovine spongiform encephalopathy.

Effective measures for the primary prevention of bovine spongiform encephalopathy include control measures such as surveillance, banning specified risk materials, culling sick animals, and excluding all animals more than 30 months of age from the human food and animal feed supplies.

There are no established measures for the secondary prevention of bovine spongiform encephalopathy.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

Publius Flavius Vegetius Renatus records cases of a disease with similar characteristics in the 4th and 5th Century AD. The origin of the disease itself remains unknown. The current scientific view is that infectious proteins called prions developed through spontaneous mutation, probably in the 1970s, and there is a possibility that the use of organophosphorus pesticides increased the susceptibility of cattle to the disease. Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989. It is believed that the disease may be transmitted to human beings who eat infected carcasses. In humans, it is known as new variant Creutzfeldt-Jakob disease (vCJD or nvCJD), and by June 2007, it had killed 165 people in Britain, and six elsewhere with the number expected to rise because of the disease’s long incubation period.

• Publius Flavius Vegetius Renatus records cases of a disease with similar characteristics in the 4th and 5th Century AD.^[1]

• A British inquiry into BSE concluded that the epidemic was caused by feeding cattle, who are normally herbivores, the remains of other cattle in the form of meat and bone meal (MBM), which caused the infectious agent to spread.^[2][3] The origin of the disease itself remains unknown. The current scientific view is that infectious proteins called prions developed through spontaneous mutation, probably in the 1970s, and there is a possibility that the use of organophosphorus pesticides increased the susceptibility of cattle to the disease.^[4] The infectious agent is distinctive for the high temperatures it is able to survive; this contributed to the spread of the disease in Britain, which had reduced the temperatures used during its rendering process.^[2] Another contributory factor was the feeding of infected protein supplements to very young calves.^[2][5]

• It is believed that the disease may be transmitted to human beings who eat infected carcasses.^[6] In humans, it is known as new variant Creutzfeldt-Jakob disease (vCJD or nvCJD), and by June 2007, it had killed 165 people in Britain, and six elsewhere^[7] with the number expected to rise because of the disease’s long incubation period. Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989.^[8]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

Based on the biochemical signatures of the disease-associated prion protein, Bovine spongiform encephalopahty (BSE) may be classified as either classic or atypical. Atypical BSE may further be classified into H- and L-types. Due to the accumulation of amyloid protein in the brain in cattles with L-type BSE, its also known as bovine amyloidotic spongiform encephalopathy (BASE).

Based on the biochemical signatures of the disease-associated prion protein, Bovine spongiform encephalopahty (BSE) may be classified as either classic or atypical. Atypical BSE may further be classified into H- and L-types. Due to the accumulation of amyloid protein in the brain in cattles with L-type BSE, its also known as bovine amyloidotic spongiform encephalopathy (BASE). ^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

It is understood that Bovine spongiform encephalopathy (BSE) is caused by a misfolded prion protein. Misfolded prion proteins carry the disease between individuals and cause deterioration of the brain. BSE is a type of transmissible spongiform encephalopathy (TSE).

The normal physiologic functions of prion protein (PrPC) can be understood as follows:^[1]

• Protection against oxidative stress
• Neuroprotection
• Neuronal differentiation
• Neuronal excitability
• Myelin maintenance
• Regulation of circadian rhythm
• Iron homeostasis
• Regulation of signaling pathways (e.g., ERK1/2, PI3K-Akt, cAMP-PKA, etc.)

It is understood that Bovine spongiform encephalopathy (BSE) is caused by a misfolded prion protein. Misfolded prion proteins carry the disease between individuals and cause deterioration of the brain. BSE is a type of transmissible spongiform encephalopathy (TSE).^[2] TSEs can arise in animals that carry an allele which causes normal prions to contort by themselves from an alpha-helical arrangement to a beta-pleated sheet, which is the disease-causing shape for the particular protein. Transmission can occur when healthy animals come in contact with tainted tissues from others with the disease. In the brain, these proteins cause native cellular prion protein to deform into the infectious state, which then goes on to deform further prion protein in an exponential cascade. This results in protein aggregates, which then form dense plaque fibers, leading to the microscopic appearance of “holes” in the brain, degeneration of physical and mental abilities, and ultimately death.

Different theories exist for the origin of prion proteins in cattle. Two leading theories suggest that it may have jumped species from the disease scrapie in sheep, or that it evolved from a spontaneous form of “mad-cow disease” which has been seen occasionally in cattle for many centuries.^[3] The British Government enquiry took the view the cause was not scrapie as had originally been postulated, and was some event in the 1970s which was not possible to identify.^[4]

Genes that might be involved in the pathogenesis of bovine spongiform encephalopathy (BSE) include:^[5]

• PRNP gene
• SPRN gene

Conditions associated with bovine spongiform encephalopathy include:

• Variant Creutzfeldt-Jakob disease (vCJD)

There is no characteristic finding of BSE on gross pathological examination.^[6]

On microscopic histopathological analysis, microcavitation or vacuolization of the neuropil in grey matter nuclei of the brainstem, and intracytoplasmic vacuolization of the neural perikarya and axons of the brainstem nuclei (which gives the impression of “spongy brain”) are characteristic findings of BSE, which usually involve the brainstem, bilateral and symmetrical.^[6][7]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

Bovine spongiform encephalopathy (BSE) may be caused by different strains including the classic BSE strain (which is responsible for the outbreak in the United Kingdom) and two atypical strains (H and L strains).

Bovine spongiform encephalopathy (BSE) may be caused by different strains including the classic BSE strain (which is responsible for the outbreak in the United Kingdom) and two atypical strains (H and L strains).^[1]

• Classic BSE strain has been causally linked to variant Creutzfeldt-Jakob disease (vCJD) in humans.

• Atypical BSE strains (H-type and L-type BSE) usually occur spontaneously (although might be transmitted through feed or the environment).

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

Bovine spongiform encephalopathy must be differentiated from other diseases that cause hyperesthesia, nervousness, reluctance to be milked, aggression, low head carriage, tremors, ataxia, disrupted milk production, and weight loss in animals, such as scrapes, rabies, encephalitic listeriosis, hypomagnesemia, lead poisoning, downer cow syndrome, nervous ketosis, polioencephalomalacia, ingestion of plant or fungal tremoragens, intracranial abscess or tumors, trauma to the spinal column, and other viral and bacterial neuroinfectious diseases.

Bovine spongiform encephalopathy must be differentiated from other diseases that cause hyperesthesia, nervousness, reluctance to be milked, aggression, low head carriage, tremors, ataxia, disrupted milk production, and weight loss in animals, such as scrapes, rabies, encephalitic listeriosis, hypomagnesemia, lead poisoning, downer cow syndrome, nervous ketosis, polioencephalomalacia, ingestion of plant or fungal tremoragens, intracranial abscess or tumors, trauma to the spinal column, and other viral and bacterial neuroinfectious diseases.^[1][2][3]

• In contrast to the other diseases in the differential diagnosis, BSE is typically characterized with slower onset of symptoms with progressive and fatal clinical course.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

Following an epizootic of BSE in Britain, 165 people (up until 2007) acquired and died of a disease with similar neurological symptoms subsequently called vCJD, or (new) variant Creutzfeldt-Jakob disease. It is estimated that 400,000 cattle infected with BSE entered the human food chain in the 1980s. Although the BSE epizootic was eventually brought under control by culling all suspect cattle populations, people are still being diagnosed with vCJD each year. It is notable that there are no cases reported in Australia and New Zealand where cattle are mainly fed outside on grass pasture and, mainly in Australia, non-grass feeding is done only as a final finishing process before the animals are processed for meat.

• Cattle, like most other food animals, are normally herbivores. In nature, cattle eat grass or grains. In modern industrial cattle-farming, various commercial feeds are used, which may contain ingredients including antibiotics, hormones, pesticides, fertilizers, and protein supplements.

• The use of meat and bone meal, produced from the ground and cooked left-overs of the slaughtering process as well as from the cadavers of sick and injured animals such as cattle, sheep, or chickens, as a protein supplement in cattle feed was widespread in Europe prior to about 1987. Worldwide, soya bean meal is the primary plant-based protein supplement fed to cattle. However, soya beans do not grow well in Europe, so cattle raisers throughout Europe turned to the less expensive animal by-product feeds as an alternative.

• A change to the rendering process in the early 1980s may have resulted in a large increase of the infectious agents in the cattle feed. A contributing factor was suggested to have been a change in British laws that allowed a lower temperature sterilization of the protein meal. While other European countries like Germany required said animal byproducts to undergo a high temperature steam boiling process, this requirement had been eased in Britain as a measure to keep prices competitive.

• Later the British Inquiry dismissed this theory saying “changes in process could not have been solely responsible for the emergence of BSE, and changes in regulation were not a factor at all.”^[1]

• Following an epizootic of BSE in Britain, 165 people (up until 2007) acquired and died of a disease with similar neurological symptoms subsequently called vCJD, or (new) variant Creutzfeldt-Jakob disease. This is a separate disease from ‘classical’ Creutzfeldt-Jakob disease, which is not related to BSE and has been known about since the early 1900s.

• Three cases of vCJD occurred in people who had lived in or visited Britain — one each in Ireland, Canada and the United States. There is also some concern about those who work with (and therefore inhale) cattle meat and bone meal, such as horticulturists, who use it as fertilizer. Up to date statistics on all types of CJD are published by the UK CJD Surveillance Centre in Edinburgh.

• For many of the vCJD patients, direct evidence exists that they had consumed tainted beef, and this is assumed to be the mechanism by which all affected individuals contracted it. Disease incidence also appears to correlate with slaughtering practices that led to the mixture of nervous system tissue with hamburger and other beef.

• It is estimated that 400,000 cattle infected with BSE entered the human food chain in the 1980s. Although the BSE epizootic was eventually brought under control by culling all suspect cattle populations, people are still being diagnosed with vCJD each year (though the number of new cases currently has dropped to less than 5 per year). This is attributed to the long incubation period for prion diseases, which are typically measured in years or decades. As a result the full extent of the human vCJD outbreak is still not fully known.

• The scientific consensus is that infectious BSE prion material is not destroyed through normal cooking procedures, meaning that contaminated beef foodstuffs prepared “well done” may remain infectious.^[2][3]

• In 2004 researchers reported evidence of a second contorted shape of prions in a rare minority of diseased cattle. In other words, this implies a second strain of BSE prion. Very little is known about the shape of disease-causing prions, because their insolubility and tendency to clump thwarts application of the detailed measurement techniques of structural biology. But cruder measures yield a “biochemical signature” by which the newly discovered cattle strain appears different from the familiar one, but similar to the clumped prions in humans with traditional CJD Creutzfeldt-Jakob Disease.

• The finding of a second strain of BSE prion raises the possibility that transmission of BSE to humans has been underestimated, because some of the individuals diagnosed with spontaneous or “sporadic” CJD may have actually contracted the disease from tainted beef. So far nothing is known about the relative transmissibility of the two disease strains of BSE prion.

• In 2005 a controversial paper in The Lancet introduced a theory that BSE might have originated in British cattle when they ate imported animal feed that included infected human remains from Hindu funeral ceremonies in India. [3] This paper is merely a conjecture, however, and the authors suggest only that further investigation should occur.
• In the UK, the country worst affected, 179,000 cattle were infected and 4.4 million killed as a precaution.^[4]

Country	BSE cases	vCJD cases	Country	BSE cases	vCJD cases
Austria	5	0	Belgium	125	0
Canada	10	1	Czech Rep	9	0
Denmark	15	0	Falkland Islands	1	0
Finland	1	0	France	900+	11
Germany	312	0	Greece	1	0
Hong Kong	2	0	Israel	1	0
Italy	117	1	Japan	26	1
Lichtenstein	2	0	Luxembourg	2	1
Netherlands	75	1	Oman	2	0
Poland	21	0	Portugal	875	2
Republic of Ireland	1353	4	Slovakia	15	0
Slovenia	7	0	Spain	412	2
Sweden	1	0	Switzerland	453	0
Thailand	n/a	2	UK	183823	160
US	3	3	Total	188535	170 (+ 6 results pending)

The table to the right summarizes reported cases of BSE and of vCJD by country. BSE is the disease in cattle, while vCJD is the disease in people.

The tests used for detecting BSE vary considerably as do the regulations in various jurisdictions for when, and which cattle, must be tested. For instance, in the EU the cattle tested are older (30 months+), while many cattle are slaughtered earlier than that. At the opposite end of the scale, Japan tests all cattle at the time of slaughter. Tests are also difficult as the altered prion protein has very small levels in blood or urine, and no other signal has been found. Newer tests are faster, more sensitive, and cheaper, so it is possible that future figures may be more comprehensive. Even so, currently the only reliable test is examination of tissues during an autopsy.

It is notable that there are no cases reported in Australia and New Zealand where cattle are mainly fed outside on grass pasture and, mainly in Australia, non-grass feeding is done only as a final finishing process before the animals are processed for meat.

As for vCJD in humans, autopsy tests are not always done and so those figures too are likely to be too low, but probably by a lesser fraction. In the UK anyone with possible vCJD symptoms must be reported to the UK Creutzfeldt-Jakob Disease Surveillance Unit and so it is unlikely that any cases would be missed. In the U.S., the CDC has refused to impose a national requirement that physicians and hospitals report cases of the disease. Instead, the agency relies on other methods, including death certificates and urging physicians to send suspicious cases to the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University in Cleveland, which is funded by the CDC.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

The most potent risk factor in the development of bovine spongiform encephalopathy is the consumption of meat-and-bone meal (MBM) by cattle.

The most potent risk factor in the development of bovine spongiform encephalopathy is the consumption of meat-and-bone meal (MBM) by cattle.^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

There is insufficient evidence to recommend routine screening for bovine spongiform encephalopathy (BSE).

There is insufficient evidence to recommend routine screening for bovine spongiform encephalopathy (BSE).

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

The symptoms of bovine spongiform encephalopathy typically develop 2-8 years after exposure to prions. Prognosis is generally poor, and death occurs approximately 3 months after the appearance of the first clinical signs.

• The symptoms of bovine spongiform encephalopathy typically develop 2-8 years after exposure to prions.^[1]

• Prognosis is generally poor, and death occurs approximately 3 months after the appearance of the first clinical signs.^[1]

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