Bovine spongiform encephalopathy
Overview
Bovine spongiform encephalopathy (BSE), commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...

 that causes a spongy degeneration in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

. BSE has a long incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...

, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of four to five years, all breed
Breed
A breed is a group of domestic animals or plants with a homogeneous appearance, behavior, and other characteristics that distinguish it from other animals or plants of the same species. Despite the centrality of the idea of "breeds" to animal husbandry, there is no scientifically accepted...

s being equally susceptible. In the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

, the country worst affected, more than 180,000 cattle have been infected and 4.4 million slaughtered during the eradication program.

The disease may be most easily transmitted to human beings by eating food contaminated with the brain, spinal cord or digestive tract of infected carcasses.
Discussions
Encyclopedia
Bovine spongiform encephalopathy (BSE), commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...

 that causes a spongy degeneration in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

. BSE has a long incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...

, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of four to five years, all breed
Breed
A breed is a group of domestic animals or plants with a homogeneous appearance, behavior, and other characteristics that distinguish it from other animals or plants of the same species. Despite the centrality of the idea of "breeds" to animal husbandry, there is no scientifically accepted...

s being equally susceptible. In the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

, the country worst affected, more than 180,000 cattle have been infected and 4.4 million slaughtered during the eradication program.

The disease may be most easily transmitted to human beings by eating food contaminated with the brain, spinal cord or digestive tract of infected carcasses. However, it should also be noted that the infectious agent, although most highly concentrated in nervous tissue, can be found in virtually all tissues throughout the body, including blood. In humans, it is known as new variant Creutzfeldt–Jakob disease (vCJD or nvCJD), and by October 2009, it had killed 166 people in the United Kingdom, and 44 elsewhere Between 460,000 and 482,000 BSE-infected animals had entered the human food chain
Food chain
A food web depicts feeding connections in an ecological community. Ecologists can broadly lump all life forms into one of two categories called trophic levels: 1) the autotrophs, and 2) the heterotrophs...

 before controls on high-risk offal
Offal
Offal , also called, especially in the United States, variety meats or organ meats, refers to the internal organs and entrails of a butchered animal. The word does not refer to a particular list of edible organs, which varies by culture and region, but includes most internal organs other than...

 were introduced in 1989.

A British inquiry into BSE concluded that the epizootic
Epizootic
In epizoology, an epizootic is a disease that appears as new cases in a given animal population, during a given period, at a rate that substantially exceeds what is "expected" based on recent experience . Epidemic is the analogous term applied to human populations...

 was caused by cattle, who are normally herbivore
Herbivore
Herbivores are organisms that are anatomically and physiologically adapted to eat plant-based foods. Herbivory is a form of consumption in which an organism principally eats autotrophs such as plants, algae and photosynthesizing bacteria. More generally, organisms that feed on autotrophs in...

s, being fed the remains of other cattle in the form of meat and bone meal
Meat and bone meal
Meat and bone meal is a product of the rendering industry. It is typically about 48 - 52% protein, 33-...

 (MBM), which caused the infectious agent to spread. There are studies indicating that the cause of BSE may be from the contamination of MBM from sheep with scrapie
Scrapie
Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies , which are related to bovine spongiform encephalopathy and chronic wasting disease of deer. Like other spongiform encephalopathies, scrapie...

 that were processed in the same slaughterhouse. The epidemic was probably accelerated by the recycling of infected bovine tissues prior to the recognition of BSE. The origin of the disease itself remains unknown. The infectious agent is distinctive for the high temperatures at which it remains viable; this contributed to the spread of the disease in the United Kingdom, which had reduced the temperatures used during its rendering process. Another contributory factor was the feeding of infected protein supplements to very young calves.

This first reported case in North America was in December 1993 from Alberta, Canada.,
Another case reported later in May 2003. The first known U.S. occurrence came in December of the same year though it was later confirmed that it was a cow of Canadian origin and imported to the U.S. Canada announced two additional cases of BSE from Alberta in early 2005.
In June 2005 Dr. John Clifford, chief veterinary officer for the United States Department of Agriculture
United States Department of Agriculture
The United States Department of Agriculture is the United States federal executive department responsible for developing and executing U.S. federal government policy on farming, agriculture, and food...

 animal health inspection service confirmed a fully domestic case of BSE in Texas
Texas
Texas is the second largest U.S. state by both area and population, and the largest state by area in the contiguous United States.The name, based on the Caddo word "Tejas" meaning "friends" or "allies", was applied by the Spanish to the Caddo themselves and to the region of their settlement in...

. Dr. Clifford would not identify the ranch, calling that "privileged information." The 12 year old animal was alive at the time when Oprah Winfrey
Oprah Winfrey
Oprah Winfrey is an American media proprietor, talk show host, actress, producer and philanthropist. Winfrey is best known for her self-titled, multi-award-winning talk show, which has become the highest-rated program of its kind in history and was nationally syndicated from 1986 to 2011...

 raised concerns about cannibalistic feeding practices on her show which aired April 16, 1996.

Cause

The infectious agent in BSE is believed to be a specific type of misfolded
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....

 protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 called a prion
Prion
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...

. Prion proteins carry the disease between individuals and cause deterioration of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

. BSE is a type of transmissible spongiform encephalopathy
Transmissible spongiform encephalopathy
Transmissible spongiform encephalopathies , also known as prion diseases, are a group of progressive conditions that affect the brain and nervous system of many animals, including humans. According to the most widespread hypothesis they are transmitted by prions, though some other data suggest an...

 (TSE). TSEs can arise in animals that carry an allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

 which causes previously normal protein molecules to contort by themselves from an alpha helical arrangement to a beta pleated sheet, which is the disease-causing shape
Conformational isomerism
In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted exclusively by rotations about formally single bonds...

 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
Senile plaques
Senile plaques are extracellular deposits of amyloid in the gray matter of the brain. The deposits are associated with degenerative neural structures and an abundance of microglia and astrocytes...

 fibers, leading to the microscopic appearance of "holes" in the brain, degeneration of physical and mental abilities, and ultimately death.

Different hypotheses exist for the origin of prion proteins in cattle. Two leading hypotheses suggest that it may have jumped species from the disease scrapie
Scrapie
Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies , which are related to bovine spongiform encephalopathy and chronic wasting disease of deer. Like other spongiform encephalopathies, scrapie...

 in sheep, or that it evolved from a spontaneous form of "mad cow disease" that has been seen occasionally in cattle for many centuries. Publius Flavius Vegetius Renatus records cases of a disease with similar characteristics in the 4th and 5th century AD. The British Government enquiry took the view the cause was not scrapie as had originally been postulated, and was some event in the 1970s that it was not possible to identify.

Findings published in PLoS Pathogens (September 12, 2008) suggest that mad cow disease also is caused by a genetic mutation within a gene called Prion Protein Gene. The research shows, for the first time, that a 10-year-old cow from Alabama
Alabama
Alabama is a state located in the southeastern region of the United States. It is bordered by Tennessee to the north, Georgia to the east, Florida and the Gulf of Mexico to the south, and Mississippi to the west. Alabama ranks 30th in total land area and ranks second in the size of its inland...

 with an atypical form of bovine spongiform encephalopathy had the same type of prion protein gene mutation as found in human patients with the genetic form of Creutzfeldt–Jakob disease, also called genetic CJD for short. Besides having a genetic origin, other human forms of prion diseases can be sporadic, as in sporadic CJD, as well as foodborne. That is, they are contracted when people eat products contaminated with mad cow disease. This form of Creutzfeldt-Jakob disease is called variant CJD.

Epidemic in British cattle

Cattle are normally herbivore
Herbivore
Herbivores are organisms that are anatomically and physiologically adapted to eat plant-based foods. Herbivory is a form of consumption in which an organism principally eats autotrophs such as plants, algae and photosynthesizing bacteria. More generally, organisms that feed on autotrophs in...

s, eating grass
Grass
Grasses, or more technically graminoids, are monocotyledonous, usually herbaceous plants with narrow leaves growing from the base. They include the "true grasses", of the Poaceae family, as well as the sedges and the rushes . The true grasses include cereals, bamboo and the grasses of lawns ...

. In modern industrial cattle-farming, various commercial feeds are used, which may contain ingredients including antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s, hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s, pesticide
Pesticide
Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...

s, fertilizer
Fertilizer
Fertilizer is any organic or inorganic material of natural or synthetic origin that is added to a soil to supply one or more plant nutrients essential to the growth of plants. A recent assessment found that about 40 to 60% of crop yields are attributable to commercial fertilizer use...

s, and protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 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
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 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 required said animal by-products to undergo a high temperature steam boiling process, this requirement had been eased in the United Kingdom 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."

The first confirmed animal to fall ill with the disease occurred in 1986 in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

, lab tests the following year indicated the presence of BSE; it was only in November 1987 that the British Ministry of Agriculture accepted it had a new disease on its hands. Subsequently, 165 people (up until October 2009) 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 the UK — one each in the Republic of Ireland
Republic of Ireland
Ireland , described as the Republic of Ireland , is a sovereign state in Europe occupying approximately five-sixths of the island of the same name. Its capital is Dublin. Ireland, which had a population of 4.58 million in 2011, is a constitutional republic governed as a parliamentary democracy,...

, Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...

 and the United States of America. There is also some concern about those who work with (and therefore inhale) cattle meat and bone meal
Meat and bone meal
Meat and bone meal is a product of the rendering industry. It is typically about 48 - 52% protein, 33-...

, such as horticulturists
Horticulture
Horticulture is the industry and science of plant cultivation including the process of preparing soil for the planting of seeds, tubers, or cuttings. Horticulturists work and conduct research in the disciplines of plant propagation and cultivation, crop production, plant breeding and genetic...

, who use it as fertilizer. Up to date statistics on all types of CJD are published by the National Creutzfeldt-Jakob Disease Surveillance Unit (NCJDSU) in Edinburgh.

For many of the vCJD patients, direct evidence exists that they had consumed tainted beef
Beef
Beef is the culinary name for meat from bovines, especially domestic cattle. Beef can be harvested from cows, bulls, heifers or steers. It is one of the principal meats used in the cuisine of the Middle East , Australia, Argentina, Brazil, Europe and the United States, and is also important in...

, 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
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...

 tissue with hamburger
Hamburger
A hamburger is a sandwich consisting of a cooked patty of ground meat usually placed inside a sliced bread roll...

 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 fewer 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 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.

In 2004, researchers reported evidence of a second contorted shape of prions in a rare minority of diseased cattle. If valid, this would imply 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
Structural biology
Structural biology is a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations in their structures affect their function...

. 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.

Alan Colchester, a professor of neurology at the University of Kent
University of Kent
The University of Kent, previously the University of Kent at Canterbury, is a public research university based in Kent, United Kingdom...

, and Nancy Colchester, writing in the September 3, 2005 issue of the medical journal The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...

, proposed a theory that the most likely initial origin of BSE in the United Kingdom was the importation from the Indian subcontinent of bone meal which contained CJD infected human remains. The government of India vehemently responded to the research calling it "misleading, highly mischievous; a figment of imagination; absurd," further adding that India maintained constant surveillance and had not had a single case of either BSE or vCJD. The authors responded in the January 22, 2006 issue of The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...

 that their theory is unprovable only in the same sense as all other BSE origin theories are and that the theory warrants further investigation.

Epizootic in the United Kingdom

During the course of the investigation into the BSE epizootic, an enquiry was also made into the activities of the Department of Health
Department of Health (United Kingdom)
The Department of Health is a department of the United Kingdom government with responsibility for government policy for health and social care matters and for the National Health Service in England along with a few elements of the same matters which are not otherwise devolved to the Scottish,...

 and its Medicines Control Agency. On May 7, 1999, in his written statement to the BSE Inquiry, David Osborne Hagger reported on behalf of the Medicines Control Agency that in a previous enquiry the Agency had been asked to:
"... identify relevant manufacturers and obtain information about the bovine material contained in children’s vaccines, the stocks of these vaccines and how long it would take to switch to other products." It was further reported that the: "... use of bovine insulin in a small group of mainly elderly patients was noted and it was recognised that alternative products for this group were not considered satisfactory." A medicines licensing committee report that same year recommended that: "... no licensing action is required at present in regard to products produced from bovine material or using prepared bovine brain in nutrient media and sourced from outside the United Kingdom, the Channel Isles and the Republic of Ireland provided that the country of origin is known to be free of BSE, has competent veterinary advisers and is known to practise good animal husbandry." In 1990 the British Diabetic Association became concerned regarding the safety of bovine insulin and the government licensing agency assured them that: "... there was no insulin sourced from cattle in the Britain or Ireland and that the situation in other countries was being monitored." In 1991 a European Community Commission: "... expressed concerns about the possible transmission of the BSE/scrapie agent to man through use of certain cosmetic treatments." Sources in France reported to the British Medicines Control Agency: "... that there were some licensed surgical sutures derived from French bovine material." Concerns were also raised: "... regarding a possible risk of transmission of the BSE agent in gelatin products."

Epidemiology

Country BSE cases vCJD cases
Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...

5 0
Belgium
Belgium
Belgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...

133 0
Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...

17 1
Czech Republic
Czech Republic
The Czech Republic is a landlocked country in Central Europe. The country is bordered by Poland to the northeast, Slovakia to the east, Austria to the south, and Germany to the west and northwest....

28 0
Denmark
Denmark
Denmark is a Scandinavian country in Northern Europe. The countries of Denmark and Greenland, as well as the Faroe Islands, constitute the Kingdom of Denmark . It is the southernmost of the Nordic countries, southwest of Sweden and south of Norway, and bordered to the south by Germany. Denmark...

14 0
Falkland Islands
Falkland Islands
The Falkland Islands are an archipelago in the South Atlantic Ocean, located about from the coast of mainland South America. The archipelago consists of East Falkland, West Falkland and 776 lesser islands. The capital, Stanley, is on East Falkland...

1 0
Finland
Finland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...

1 0
France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...

900 25
Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...

312 0
Greece
Greece
Greece , officially the Hellenic Republic , and historically Hellas or the Republic of Greece in English, is a country in southeastern Europe....

1 0
Hong Kong
Hong Kong
Hong Kong is one of two Special Administrative Regions of the People's Republic of China , the other being Macau. A city-state situated on China's south coast and enclosed by the Pearl River Delta and South China Sea, it is renowned for its expansive skyline and deep natural harbour...

2 0
Republic of Ireland
Republic of Ireland
Ireland , described as the Republic of Ireland , is a sovereign state in Europe occupying approximately five-sixths of the island of the same name. Its capital is Dublin. Ireland, which had a population of 4.58 million in 2011, is a constitutional republic governed as a parliamentary democracy,...

1,353 4
Israel
Israel
The State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...

1 56
Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...

138 2
Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

26 1
Liechtenstein
Liechtenstein
The Principality of Liechtenstein is a doubly landlocked alpine country in Central Europe, bordered by Switzerland to the west and south and by Austria to the east. Its area is just over , and it has an estimated population of 35,000. Its capital is Vaduz. The biggest town is Schaan...

2 0
Luxembourg
Luxembourg
Luxembourg , officially the Grand Duchy of Luxembourg , is a landlocked country in western Europe, bordered by Belgium, France, and Germany. It has two principal regions: the Oesling in the North as part of the Ardennes massif, and the Gutland in the south...

2 1
Netherlands
Netherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...

85 3
Oman
Oman
Oman , officially called the Sultanate of Oman , is an Arab state in southwest Asia on the southeast coast of the Arabian Peninsula. It is bordered by the United Arab Emirates to the northwest, Saudi Arabia to the west, and Yemen to the southwest. The coast is formed by the Arabian Sea on the...

2 0
Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...

21 0
Portugal
Portugal
Portugal , officially the Portuguese Republic is a country situated in southwestern Europe on the Iberian Peninsula. Portugal is the westernmost country of Europe, and is bordered by the Atlantic Ocean to the West and South and by Spain to the North and East. The Atlantic archipelagos of the...

875 2
Saudi Arabia
Saudi Arabia
The Kingdom of Saudi Arabia , commonly known in British English as Saudi Arabia and in Arabic as as-Sa‘ūdiyyah , is the largest state in Western Asia by land area, constituting the bulk of the Arabian Peninsula, and the second-largest in the Arab World...

0 1
Slovakia
Slovakia
The Slovak Republic is a landlocked state in Central Europe. It has a population of over five million and an area of about . Slovakia is bordered by the Czech Republic and Austria to the west, Poland to the north, Ukraine to the east and Hungary to the south...

15 0
Slovenia
Slovenia
Slovenia , officially the Republic of Slovenia , is a country in Central and Southeastern Europe touching the Alps and bordering the Mediterranean. Slovenia borders Italy to the west, Croatia to the south and east, Hungary to the northeast, and Austria to the north, and also has a small portion of...

7 0
Spain
Spain
Spain , officially the Kingdom of Spain languages]] under the European Charter for Regional or Minority Languages. In each of these, Spain's official name is as follows:;;;;;;), is a country and member state of the European Union located in southwestern Europe on the Iberian Peninsula...

412 5
Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....

1 0
Switzerland
Switzerland
Switzerland name of one of the Swiss cantons. ; ; ; or ), in its full name the Swiss Confederation , is a federal republic consisting of 26 cantons, with Bern as the seat of the federal authorities. The country is situated in Western Europe,Or Central Europe depending on the definition....

453 0
Thailand
Thailand
Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...

2
United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

183,841 175
United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

3 3
Total 188,579 280

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 E.U. 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 low 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 Argentina
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...

, Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...

, Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

, New Zealand
New Zealand
New Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses and numerous smaller islands. The country is situated some east of Australia across the Tasman Sea, and roughly south of the Pacific island nations of New Caledonia, Fiji, and Tonga...

, Uruguay
Uruguay
Uruguay ,officially the Oriental Republic of Uruguay,sometimes the Eastern Republic of Uruguay; ) is a country in the southeastern part of South America. It is home to some 3.5 million people, of whom 1.8 million live in the capital Montevideo and its metropolitan area...

, and Vanuatu
Vanuatu
Vanuatu , officially the Republic of Vanuatu , is an island nation located in the South Pacific Ocean. The archipelago, which is of volcanic origin, is some east of northern Australia, northeast of New Caledonia, west of Fiji, and southeast of the Solomon Islands, near New Guinea.Vanuatu was...

 where cattle are mainly fed outside on grass pasture and, mostly in Australia, non-grass feeding is done only as a final finishing process before the animals are slaughtered 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 United Kingdom anyone with possible vCJD symptoms must be reported to the Creutzfeldt-Jakob Disease Surveillance Unit. In the United States, the CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

 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.

Practices in the United States relating to BSE

Soybean meal is cheap and plentiful in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

. The million and a half tons of cotton seed meal produced in the U.S. every year that is not suitable for humans or any other simple-stomach animal is even cheaper than soybean meal. It is just as nutritious and cattle eat it just as well as soybean meal. Historically, meat and bone meal, blood meal and meat scraps have almost always commanded a higher price as a feed additive than oil seed meals in the U.S. so there was not much incentive to use animal products to feed ruminants. As a result, the use of animal byproduct feeds was never common, as it was in Europe. However, U.S. regulations only partially prohibit the use of animal byproducts in feed. In 1997, regulations prohibited the feeding of mammalian byproducts to ruminant
Ruminant
A ruminant is a mammal of the order Artiodactyla that digests plant-based food by initially softening it within the animal's first compartment of the stomach, principally through bacterial actions, then regurgitating the semi-digested mass, now known as cud, and chewing it again...

s such as cows and goats. However, the byproducts of ruminants can still be legally fed to pets or other livestock including pigs and poultry, such as chickens. In addition, it is legal for ruminants to be fed byproducts from some of these animals. A proposal to end the use of cow blood, restaurant scraps, and poultry litter
Poultry litter
In agriculture, poultry litter or broiler litter is a material used as bedding in poultry operations to renderthe floor more manageable. Common litter materials are wood shavings, sawdust, peanut hulls, shredded sugar cane, straw, and other dry, absorbent, low-cost organic materials...

 (fecal matter, feathers) in January 2004 has yet to be implemented.

Regulatory failures

In February 2001, the USGAO
Government Accountability Office
The Government Accountability Office is the audit, evaluation, and investigative arm of the United States Congress. It is located in the legislative branch of the United States government.-History:...

 reported that the FDA, which is responsible for regulating feed, had not adequately enforced the various bans. Compliance with the regulations was shown to be extremely poor before the discovery of the Washington cow, but industry representatives report that compliance is now total. Even so, critics call the partial prohibitions insufficient. Indeed, U.S. meat producer Creekstone Farms
Creekstone Farms Premium Beef
Creekstone Farms Premium Beef, LLC is a beef processing company located in Arkansas City, KS. The company was founded in 1995 by John and Carol Stewart. Originally a purebred Black Angus farm in Campbellsburg, KY, Creekstone Farms entered the processing business in 2003 with the purchase of a ...

 alleges that the USDA
United States Department of Agriculture
The United States Department of Agriculture is the United States federal executive department responsible for developing and executing U.S. federal government policy on farming, agriculture, and food...

 is preventing BSE testing from being conducted.

The USDA has issued recalls of beef supplies that involved introduction of downer cows into the food supply. Hallmark/Westland Meat Packing Company
Hallmark/Westland Meat Packing Company
Hallmark/Westland Meat Packing Company was a California-based meat packaging company. It was forced into bankruptcy due to costs from a meat recall and ensuing litigation.-2008 recall:...

 was found to have used electric shocks to prod downer cows into the slaughtering system in 2007.
Possibly due to pressure from large agribusiness, the United States has drastically cut back on the number of cows inspected for BSE.

The ban on British beef

The BSE crisis led to the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...

 banning exports of British beef with effect from March 1996; the ban would last for 10 years before it was finally lifted on 1 May 2006, despite attempts in May 1996 by British prime minister John Major
John Major
Sir John Major, is a British Conservative politician, who served as Prime Minister of the United Kingdom and Leader of the Conservative Party from 1990–1997...

 to get the ban lifted.

If indeed a form of Bovine Spongiform Encephalopathy (BSE) exists in the United States, one might expect to see a rise in the number of cases of Creutzfeldt-Jakob disease (CJD). CJD, however, is not a reportable illness in the United States (Holman, 1995). Because the Centers for Disease Control (CDC) does not actively monitor the disease (Altman, 1996d) a rise similar to the one in the UK could be missed (Altman, 1996d). Already, a number of U.S. CJD clusters have been found. In the largest known U.S. outbreak of sporadic cases to date (Flannery, 1996) a fivefold expected rate was found to be associated with cheese consumption in Pennsylvania's Lehigh Valley (Little, 1993) A striking increase in CJD was also reported in Florida (Berger, 1994) and there is an anecdotal report of an cluster in Oregon (Boule, 1996). An analysis of death certificates in a number of states, though, showed an overall stable and typical CJD incidence rate from 1979 to 1993 (World, 1996). To track the disease, the CDC has just initiated a four-state study of death certificates (Altman, 1996a), but since it is considered well known that death-certificate diagnoses are not always accurate (Davanpour, 1993) the survey may not provide an accurate assessment.

The true prevalence of prion diseases in the United States or any other country remains a mystery (Harrison, 1991). Compounding the uncertainty, autopsies are rarely performed on atypical dementias (Harrison, 1991), because medical professionals fear infection (Altman, 1996a). The officially reported rate in this country is less than 1 case in a million people per year (World, 1996). An informal survey of neuropathologists, however, registered a theoretical range of 2-12% of all dementias as actually CJD (Harrison, 1991). And hundreds of thousands of Americans suffer from severe dementias every year (Brayne, 1994; United, 1995). Two other studies average about a 3% CJD rate among dementia patients (Mahendra, 1987; Wade, 1987). A preliminary 1989 University of Pennsylvania study showed that 5% of patients diagnosed with dementia were actually dying from Creutzfeldt-Jakob disease, (Boller, 1989) implying CJD likely goes largely undiagnosed at present (Harrison, 1991).

The most common misdiagnosis of CJD is Alzheimer's disease (Harrison, 1991). CJD was even described by the top CJD researcher of the government of the United States (Wlazelek, 1990a) as "Alzheimer's in fast forward (Wlazelek, 1990b)." The symptoms and pathology of both diseases overlap (Brown, 1989). There can be spongy changes in Alzheimer's, for example, and senile plaques in CJD (Brown, 1989). The causes may overlap as well; epidemiological evidence suggests that people eating meat more than four times a week for a prolonged period have a three times higher chance of suffering a dementia than long-time vegetarians (Giem, 1993), although this result may be confounded by vascular factors (Van Duijn, 1996).

Paul Brown, medical director for the U.S. Public Health Service (Gruzen, 1996), said that the brains of the young people who died from the new CJD variant in the UK even look like Alzheimer's brains (Hager, 1996). Stanley Prusinger, the scientist who coined the term prion, speculates Alzheimer's may in fact turn out to be a prion disease (Prusiner, 1984). In younger victims the disease could look like multiple sclerosis or a severe viral infection, according to Alzheimer's expert Gareth Roberts (Brain, 1996).

An estimated two to three million Americans are afflicted by Alzheimer's (Scully, 1993); it is the fourth leading cause of death among the elderly in the U.S (Perry, 1995). Twenty percent or more of people clinically diagnosed with Alzheimer's disease are found at autopsy to not have had Alzheimer's at all (McKhann, 1984). At Yale, out of 46 patients clinically diagnosed with Alzheimer's, 6 were proven to be CJD at autopsy (Manuelidis, 1989). In another post-mortem study 3 out of 12 "Alzheimer" patients actually died from a spongiform encephalopathy (Teixeira, 1995).

Carleton Gajdusek, who was awarded a Nobel Prize for his work with prion diseases (Manuelidis, 1985), estimates that 1% of people showing up in Alzheimer clinics actually have CJD (Folstein, 1983). That means that hundreds of people (Hoyert, 1996; United, 1995) may already be dying from mad cow disease each year in the United States.

Regional exceptions to the UK export ban

It was successfully negotiated that beef from Wales was allowed to be exported to the Dutch market, which had formerly been an important market for Northern Irish beef. Of two approved export establishments in the United Kingdom in 1999, one was in Scotland - an establishment to which live beef was supplied from Northern Ireland. As the incidence of BSE was very low in Northern Ireland (partly due to the early adoption of an advanced herd tagging and computerization system in the region) - only six cases of BSE by 1999 - calls were made to remove the E.U. ban on exports with regard to Northern Irish beef.

Effect on the U.S. beef industry

Japan was the top importer of U.S. beef, buying 240,000 tons valued at $1.4 billion in 2003. After the discovery of the first case of BSE in the U.S. on December 23, 2003, Japan halted U.S. beef imports. In December 2005, Japan once again allowed imports of U.S. beef, but reinstated its ban in January 2006 after a technical violation of the U.S.-Japan beef import agreement: a vertebral column, which should have been removed prior to shipment, was included in a shipment of veal.

Tokyo yielded to U.S. pressure to resume imports, ignoring consumer worries about the safety of U.S. beef, said Japanese consumer groups. Michiko Kamiyama from Food Safety Citizen Watch and Yoko Tomiyama from Consumers Union of Japan
Consumers Union of Japan
or CUJ was founded in 1969 by Takeuchi Naokazu. CUJ is certified as a non-profit organization by Japan's NPO legislation. With offices in Nishi-Waseda, Tokyo, CUJ publishes "Consumer Report" as a member newsletter, as well as an online service in Japanese....

 said about this: "The government has put priority on the political schedule between the two countries, not on food safety or human health."

65 nations implemented full or partial restrictions on importing U.S. beef products because of concerns that U.S. testing lacked sufficient rigor. As a result, exports of U.S. beef declined from 1,300,000 metric tons in 2003, (before the first mad cow was detected in the U.S.) to 322,000 metric tons in 2004. This has increased since then to 771,000 metric tons in 2007.

On December 31, 2006, Hematech, Inc, a biotechnology company based in Sioux Falls
Sioux Falls, South Dakota
Sioux Falls is the largest city in the U.S. state of South Dakota. Sioux Falls is the county seat of Minnehaha County, and also extends into Lincoln County to the south...

, South Dakota
South Dakota
South Dakota is a state located in the Midwestern region of the United States. It is named after the Lakota and Dakota Sioux American Indian tribes. Once a part of Dakota Territory, South Dakota became a state on November 2, 1889. The state has an area of and an estimated population of just over...

, announced that it had used genetic engineering and cloning technology to produce cattle that lacked a necessary gene for prion production - thus theoretically making them immune to BSE.

Clinical signs in cattle

Cows affected by BSE are usually apart from the herd and will show progressively deteriorating behavioural and neurological signs. One notable signs is an increase in aggression. Cattle will react excessively to noise or touch and will slowly become ataxic
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...

.

Systemic signs of disease such as a drop in milk production, anorexia
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...

 and lethargy are also present.

Diagnosis

There continues to be a very practical problem with diagnosis of BSE. It has an incubation period of months to years during which there are no symptoms, even though the pathway of converting the normal brain PrP protein into the toxic, disease-related PrPSc form has started. At present, there is virtually no way to detect PrPSc reliably except by examining postmortem brain tissue using neuropathological and immunohistochemical methods. Accumulation of the abnormally folded PrPSc form of the PrP protein is a characteristic of the disease, but it is present at very low levels in easily accessible body fluids like blood or urine. Researchers have tried to develop methods to measure PrPSc, but there are still no fully accepted methods for use in materials such as blood.

The traditional method of diagnosis relies on histopathological examination of the medulla oblongata
Medulla oblongata
The medulla oblongata is the lower half of the brainstem. In discussions of neurology and similar contexts where no ambiguity will result, it is often referred to as simply the medulla...

 of the brain, and other tissues, at post mortem. Immunohistochemistry
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...

 can be used to demonstrate prion protein accumulation.

In 2010, A team from New York described detection of PrPSc even when initially present at only one part in a hundred thousand million (10−11) in brain tissue. The method combines amplification with a novel technology called Surround Optical Fiber Immunoassay (SOFIA)
Surround Optical Fiber Immunoassay (SOFIA)
Surround Optical Fiber Immunoassay is an ultra-sensitive, in vitro diagnostic platform incorporating a surround optical fiber assembly that captures fluorescence emissions from an entire sample. The technology's defining characteristics are its extremely high limit of detection, sensitivity and...

 and some specific antibodies against PrPSc. After amplifying and then concentrating any PrPSc, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a micro-capillary tube. This tube is placed in a specially constructed apparatus so that it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser. The technique allowed detection of PrPSc after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. The animals’ brains were analysed once any symptoms became apparent. The researchers could therefore compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals’ lives, and from uninfected animals. The results showed very clearly that PrPSc could be detected in the blood of animals long before the symptoms appeared. After further development and testing, this method could be of great value in surveillance as a blood or urine-based screening test for BSE.

Control

A ban on feeding cattle meat and bone meat to cattle has resulted in a reduction in cases in countries where the disease was present. In disease-free countries, control relies on import control, feeding regulations and surveillance measures.

At the abattoir in the UK, the brain, spinal cord, trigeminal ganglia, intestines, eyes and tonsils from cows are classified as Specified Risk Material
Specified risk material
Specified risk material is the general term designated for tissues of ruminant animals that cannot be inspected and passed for human food because scientists have determined that BSE-causing prions concentrate there. The term was referred to in the United Kingdom's Specified Risk Material Order...

(SRM) and must be disposed of appropriately.

Further reading

  • Altman, Lawrence K. "Four States Watching for Brain Disorder." New York Times, 9 April 1996a.
  • Altman, Lawrence K. "U.S. Officials Confident That Mad Cow Disease of Britain Has Not Occurred Here." New York Times, 27 March 1996d: 12A.
  • "Apocalypse Cow: U.S. Denials Deepen Mad Cow Danger." PR Watch, 3.1 (1996): 1-8
  • Berger, Joseph R., et al. "Creutzfeldt-Jakob Disease: A Ten-Year Experience." Neurology, 44 (1994): A260.
  • Bleifuss, Joel. "Killer Beef." In These Times, 31 May 1993: 12-15.
  • Boller, F., O. L. Lopez, and J. Moossy. "Diagnosis of Dementia." Neurology, 38 (1989): 76-79.
  • Boule, Margie. "Despite Anecdotal Evidence, Docs Say No Mad Cow Disease Here." Oregonian, 16 April 1996: C01.
  • "Brain Disease May Be Commoner Than Thought - Expert." Reuter Information Service, 15 May 1996.
  • Brayne, C. "How Common are Cognitive Impairment and Dementia?" Dementia and Normal Aging, Canbridge: University Press, 1994.
  • Brown, Paul. "Central Nervous System Amyloidoses." Neurology, 39 (1989): 1103-1104.
  • Davanpour, Zoreth, et al. "Rate of Creutzfeldt-Jakob Disease in USA." Neurology, 43 (1993): A316.
  • Flannery, Mary. "Twelve - Fifteen 'Mad Cow' Victims a Year in Area." Philadelphia Daily News, 26 March 1996: 03.
  • Folstein, M. "The Cognitive Pattern of Familial Alzheimer's Disease." Biological Aspects of Alzheimer's Disease. Ed. R. Katzman. Cold Spring Harbor Laboratory, 1983.
  • Gruzen, Tara. "Sheep Parts Fail to Cause Mad Cow Disease in U. S. Test." Seattle Times, 29 March 1996: A11.
  • Hager, Mary and Mark Hosenball. "'Mad Cow Disease' in the U.S.?" Newsweek, 8 April 1996:58-59.
  • Harrison, Paul J., and Gareth W. Roberts. "'Life, Jim, But Not as We Know It'? Transmissible Dementias and the Prion Protein." British Journal of Psychiatry, 158 (1991): 457-70.
  • Holman, R. C., et al. "Edidemiology of Creutzfeldt-Jakob Disease in the United States, 1979-1990." Neuroepidemiology, 14 (1995): 174-181.
  • Hoyert, Donna L. "Vital and Health Statistics. Mortality Trends for Alzheimer's Disease, 1979-1991." Washington: U.S. Dept. of Health and Human Services, 1996.
  • Little, Brian W., et al. "The Epidemiology of Creutzfeldt-Jakob Disease in Eastern Pennsylvania." Neurology, 43 (1993): A316.
  • Mahendra, B. Dementia, Lancaster: MTP Press Limited, 1987: 174.
  • Manuelidis, Elias E. "Presidential Address." Journal of Neuropathology and Experimental Neurology, 44 (1985): 1-17.
  • Manuelidis, Elias E. and Laura Manuelidis. "Suggested Links between Different Types of Dementias: Creutzfeldt-Jakob Disease, Alzheimer Disease, and Retroviral CNS Infections." Alzheimer Disease and Associated Disorders, 2 (1989): 100-109.
  • McKhann, Guy., et al. "Clinical Diagnosis of Alzheimer's Disease." Neurology, 34 (1984): 939.
  • Prusiner, S. "Some Speculations about Prions, Amyloid, and Alzheimer's Disease." New England Journal of Medicine, 310 (1984): 661-663.
  • Perry, R.T., et al. "Human Prion Protein Gene: Two Different 24 BP Deletions in an Atypical Alzheimer's Disease Family." American Journal of Medical Genetics, 60 (1995): 12-18.
  • Scully, R. E., et al. "Case Records of the Massachusetts General Hospital." New England Journal of Medicine, 29 April 1993: 1259-1263.
  • Teixeira, F., et al. "Clinico-Pathological Correlation in Dementias." Journal of Psychiatry and Neuroscience, 20 (1995): 276-282.
  • United States Department of Commerce. Statistical Abstract of the United States, Washington: Bureau of the Census, 1995.
  • Van Duijn, C. M. "Epidemiology of the Dementia: Recent Developments and New Approaches." Neuroepidemiology, 60 (1996): 478-488.
  • Wade, J. P. H., et al. "The Clinical Diagnosis of Alzheimer's Disease." Archives of Neurology, 44 (1987): 24-29.
  • Wlazelek, Ann. "Fatal Brain Disease Mystifies Experts." Morning Call, 23 September 1990a: B01.
  • Wlazelek, Ann. "Scientists Try to Track Fatal Disease; International Expert Visits Area to Study Unusual Incedence Rate." Morning Call, 27 September 1990b: B04.
  • "World Health Organization Consultatoin on Public Health Issues Related to Bovine Spongiform Encephalopathy and the Emergence of a New Variant of Creutzfeldt-Jakob Disease.", Morbidity and Mortality Weekly Report, 12 April 1996: 295-303.*/


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