Transmissible spongiform encephalopathies (TSEs) are a group of progressive and fatal conditions that are associated with
prions
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It i ...
and affect the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
and
nervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
of many
animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
s, including
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
s,
cattle
Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult mal ...
, and
sheep
Sheep or domestic sheep (''Ovis aries'') are domesticated, ruminant mammals typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus ''Ovis'', in everyday usage it almost always refers to domesticated s ...
. According to the most widespread hypothesis, they are transmitted by
prion
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...
s, though some other data suggest an involvement of a ''
Spiroplasma
''Spiroplasma'' is a genus of Mollicutes, a group of small bacteria without cell walls. ''Spiroplasma'' shares the simple metabolism, parasitic lifestyle, fried-egg colony morphology and small genome of other ''Mollicutes'', but has a distinctiv ...
'' infection.
Mental and physical abilities deteriorate and many tiny holes appear in the
cortex
Cortex or cortical may refer to:
Biology
* Cortex (anatomy), the outermost layer of an organ
** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain''
*** Motor cortex, the regions of the cerebral cortex i ...
causing it to appear like a sponge when brain tissue obtained at
autopsy
An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any di ...
is examined under a
microscope
A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisibl ...
. The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen chronically.
TSEs of humans include
Creutzfeldt–Jakob disease
Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes, ...
,
Gerstmann–Sträussler–Scheinker syndrome
Gerstmann–Sträussler–Scheinker syndrome (GSS) is an extremely rare, usually familial, fatal neurodegenerative disease that affects patients from 20 to 60 years in age. It is exclusively heritable, and is found in only a few families all over ...
,
fatal familial insomnia
Fatal insomnia is an extremely rare genetic (and even more rarely, sporadic) disorder that results in trouble sleeping as its hallmark symptom. The problems with sleeping typically start out gradually and worsen over time. Eventually, the patien ...
, and
kuru
Kuru may refer to:
Anthropology and history
* Kuru (disease), a type of transmissible spongiform encephalopathy associated with the cannibalistic funeral practices of the Fore people
* Kuru (mythology), part of Meithei mythology
* Kuru Kingdom, ...
, as well as the recently discovered
variably protease-sensitive prionopathy
Variably protease-sensitive prionopathy (VPSPr) (formerly known as Protease Sensitive Prionopathy) is a sporadic prion protein disease first described in an abstract for a conference on prions in 2006, and this study was published in a 2008 report ...
and familial spongiform encephalopathy. Creutzfeldt-Jakob disease itself has four main forms, the sporadic (sCJD), the hereditary/familial (fCJD), the iatrogenic (iCJD) and the variant form (vCJD). These conditions form a spectrum of diseases with overlapping signs and symptoms.
TSEs in non-human mammals include
scrapie
Scrapie () is a fatal, degenerative disease affecting the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), and as such it is thought to be caused by a prion. Scrapie has been known since ...
in sheep,
bovine spongiform encephalopathy
Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is an incurable and invariably fatal neurodegenerative disease of cattle. Symptoms include abnormal behavior, trouble walking, and weight loss. Later in the course of t ...
(BSE) in cattle – popularly known as "mad cow disease" – and
chronic wasting disease
Chronic wasting disease (CWD), sometimes called zombie deer disease, is a transmissible spongiform encephalopathy (TSE) affecting deer. TSEs are a family of diseases thought to be caused by misfolded proteins called prions and include similar dis ...
(CWD) in deer and elk. The
variant form of Creutzfeldt–Jakob disease in humans is caused by exposure to
bovine spongiform encephalopathy
Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is an incurable and invariably fatal neurodegenerative disease of cattle. Symptoms include abnormal behavior, trouble walking, and weight loss. Later in the course of t ...
prions.
Unlike other kinds of infectious disease, which are spread by agents with a
DNA or
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
genome (such as
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
or
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
), the infectious agent in TSEs is believed to be a
prion
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...
, thus being composed solely of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
material. Misshapened prion proteins carry the disease between individuals and cause deterioration of the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
. TSEs are unique diseases in that their
aetiology
Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...
may be genetic, sporadic, or infectious via ingestion of infected foodstuffs and via
iatrogenic
Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence. "Iatrogenic", ''Merriam-Webster.com'', Merriam-Webster, Inc., accessed 2 ...
means (e.g., blood transfusion). Most TSEs are sporadic and occur in an animal with no prion protein mutation. Inherited TSE occurs in animals carrying a rare
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
prion
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
, which expresses prion proteins that contort by themselves into the disease-causing
conformation. Transmission occurs when healthy animals consume tainted tissues from others with the disease. In the 1980s and 1990s, bovine spongiform encephalopathy spread in
cattle
Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult mal ...
in an epidemic fashion. This occurred because cattle were fed the
processed remains of other cattle, a practice now banned in many countries. In turn, consumption (by humans) of bovine-derived foodstuff which contained prion-contaminated tissues resulted in an outbreak of the
variant form of Creutzfeldt–Jakob disease in the 1990s and 2000s.
Prions cannot be transmitted through the air, through touching, or most other forms of casual contact. However, they may be transmitted through contact with infected tissue, body fluids, or contaminated medical instruments. Normal
sterilization procedures such as boiling or irradiating materials fail to render prions non-infective. However, treatment with strong, almost undiluted bleach and/or sodium hydroxide, or heating to a minimum of 134 °C, does destroy prions.
Classification
Features
The degenerative tissue damage caused by human prion diseases (CJD, GSS, and kuru) is characterised by four features: spongiform change,
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
al loss,
astrocytosis
Astrogliosis (also known as astrocytosis or referred to as reactive astrogliosis) is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, a ...
, and
amyloid
Amyloids are aggregates of proteins characterised by a Fibril, fibrillar morphology of 7–13 Nanometer, nm in diameter, a beta sheet (β-sheet) Secondary structure of proteins, secondary structure (known as cross-β) and ability to be Staining, ...
plaque formation. These features are shared with prion diseases in animals, and the recognition of these similarities prompted the first attempts to transmit a human prion disease (kuru) to a
primate
Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...
in 1966, followed by CJD in 1968 and GSS in 1981. These neuropathological features have formed the basis of the
histological
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
diagnosis of human prion diseases for many years, although it was recognized that these changes are enormously variable both from case to case and within the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
in individual cases.
The clinical signs in humans vary, but commonly include personality changes, psychiatric problems such as
depression, lack of coordination, and/or an unsteady gait (
ataxia
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
). Patients also may experience involuntary jerking movements called
myoclonus
Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...
, unusual sensations,
insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
, confusion, or memory problems. In the later stages of the disease, patients have severe mental impairment (
dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
) and lose the ability to move or speak.
Early neuropathological reports on human prion diseases suffered from a confusion of nomenclature, in which the significance of the diagnostic feature of spongiform change was occasionally overlooked. The subsequent demonstration that human prion diseases were transmissible reinforced the importance of spongiform change as a diagnostic feature, reflected in the use of the term "spongiform encephalopathy" for this group of disorders.
Prions appear to be most infectious when in direct contact with affected tissues. For example, Creutzfeldt–Jakob disease has been transmitted to patients taking injections of
growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
harvested from human
pituitary gland
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...
s, from cadaver
dura allografts and from instruments used for
brain surgery
Neurosurgery or neurological surgery, known in common parlance as brain surgery, is the medical specialty concerned with the surgical treatment of disorders which affect any portion of the nervous system including the brain, spinal cord and peri ...
(Brown, 2000) (prions can survive the "
autoclave
An autoclave is a machine used to carry out industrial and scientific processes requiring elevated temperature and pressure in relation to ambient pressure and/or temperature. Autoclaves are used before surgical procedures to perform sterilizat ...
" sterilization process used for most surgical instruments). It is also believed that dietary consumption of affected animals can cause prions to accumulate slowly, especially when
cannibalism
Cannibalism is the act of consuming another individual of the same species as food. Cannibalism is a common ecological interaction in the animal kingdom and has been recorded in more than 1,500 species. Human cannibalism is well documented, b ...
or similar practices allow the proteins to accumulate over more than one generation. An example is
kuru
Kuru may refer to:
Anthropology and history
* Kuru (disease), a type of transmissible spongiform encephalopathy associated with the cannibalistic funeral practices of the Fore people
* Kuru (mythology), part of Meithei mythology
* Kuru Kingdom, ...
, which reached epidemic proportions in the mid-20th century in the
Fore people of
Papua New Guinea
Papua New Guinea (abbreviated PNG; , ; tpi, Papua Niugini; ho, Papua Niu Gini), officially the Independent State of Papua New Guinea ( tpi, Independen Stet bilong Papua Niugini; ho, Independen Stet bilong Papua Niu Gini), is a country i ...
, who used to consume their dead as a funerary ritual. Laws in developed countries now ban the use of
rendered ruminant
Ruminants (suborder Ruminantia) are ungulate, hoofed herbivorous grazing or browsing mammals that are able to acquire nutrients from plant-based food by Enteric fermentation, fermenting it in a specialized stomach prior to digestion, principally ...
proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other ruminants.
There exists evidence that prion diseases may be transmissible by the airborne route.
Note that not all
encephalopathies
Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
are caused by prions, as in the cases of
PML (caused by the
JC virus
''Human polyomavirus 2'', commonly referred to as the JC virus or John Cunningham virus, is a type of human polyomavirus (formerly known as papovavirus). It was identified by electron microscopy in 1965 by ZuRhein and Chou, and by Silverman and ...
),
CADASIL
CADASIL or CADASIL syndrome, involving cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is the most common form of hereditary stroke disorder, and is thought to be caused by mutations of the ''Notch 3'' ge ...
(caused by abnormal NOTCH3 protein activity), and
Krabbe disease
Krabbe disease (KD) (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare and often fatal lysosomal storage disease that results in progressive damage to the nervous system. KD involves dysfunctional metabolism of ...
(caused by a deficiency of the
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
galactosylceramidase).
Progressive Spongiform Leukoencephalopathy (PSL)—which is a spongiform encephalopathy—is also probably not caused by a prion, although the adulterant that causes it among
heroin
Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...
smokers has not yet been identified.
This, combined with the highly variable nature of prion disease pathology, is why a prion disease cannot be diagnosed based solely on a patient's symptoms.
Cause
Genetics
Mutations in the
PRNP
Major prion protein (PrP), is encoded in the human by the ''PRNP'' gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the bod ...
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
cause prion disease. Familial forms of prion disease are caused by inherited mutations in the PRNP gene. Only a small percentage of all cases of prion disease run in families, however. Most cases of prion disease are sporadic, which means they occur in people without any known risk factors or gene mutations. In rare circumstances, prion diseases also can be transmitted by exposure to prion-contaminated tissues or other biological materials obtained from individuals with prion disease.
The PRNP gene provides the instructions to make a protein called the
prion protein
Major prion protein (PrP), is encoded in the human by the ''PRNP'' gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the bod ...
(PrP). Under normal circumstances, this protein may be involved in transporting copper into cells. It may also be involved in protecting brain cells and helping them communicate. 24 Point-
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s in this gene cause cells to produce an abnormal form of the prion protein, known as PrP
Sc. This abnormal protein builds up in the brain and destroys nerve cells, resulting in the signs and symptoms of prion disease.
Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent.
In some people, familial forms of prion disease are caused by a new mutation in the PRNP gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children.
Protein-only hypothesis
Protein could be the infectious agent, inducing its own replication by causing conformational change of normal cellular PrP
C into PrP
Sc. Evidence for this hypothesis:
:*Infectivity titre correlates with PrP
Sc levels. However, this is disputed.
:*PrP
Sc is an isomer of PrP
C
:*Denaturing PrP removes infectivity
;*PrP-null mice cannot be infected
;*PrP
C depletion in the neural system of mice with established neuroinvasive prion infection reverses early spongeosis and behavioural deficits, halts further disease progression and increases life-span
Multi-component hypothesis
While not containing a nucleic acid genome, prions may be composed of more than just a protein. Purified PrP
C appears unable to convert to the infectious PrP
Sc form, unless other components are added, such as RNA and lipids.
These other components, termed cofactors, may form part of the infectious prion, or they may serve as catalysts for the replication of a protein-only prion.
Viral hypothesis
This hypothesis postulates that an as of yet undiscovered infectious viral agent is the cause of the disease. Evidence for this hypothesis is as follows:
:*Incubation time is comparable to a
lentivirus
''Lentivirus'' is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Lent ...
:*Strain variation of different isolates of PrP
Sc
:*An increasing titre of PrP
Sc as the disease progresses suggests a replicating agent.
Diagnosis
There continues to be a very practical problem with diagnosis of prion diseases, including BSE and CJD. They have an incubation period of months to decades during which there are no symptoms, even though the pathway of converting the normal brain PrP protein into the toxic, disease-related PrP
Sc form has started. At present, there is virtually no way to detect PrP
Sc reliably except by examining the brain using neuropathological and immunohistochemical methods after death. Accumulation of the abnormally folded PrP
Sc 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 PrP
Sc, but there are still no fully accepted methods for use in materials such as blood.
In 2010, a team from New York described detection of PrP
Sc even when initially present at only one part in a hundred billion (10
−11) in brain tissue. The method combines amplification with a novel technology called
Surround Optical Fiber Immunoassay (SOFIA)
Surround optical-fiber immunoassay (SOFIA) is an ultrasensitive, ''in vitro'' diagnostic platform incorporating a surround optical-fiber assembly that captures fluorescence emissions from an entire sample. The technology's defining characteristi ...
and some specific antibodies against PrP
Sc. After amplifying and then concentrating any PrP
Sc, 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 PrP
Sc 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 PrP
Sc could be detected in the blood of animals long before the symptoms appeared.
Epidemiology
Transmissible spongiform encephalopathies (TSE) are very rare but can reach epidemic proportions. It is very hard to map the spread of the disease due to the difficulty of identifying individual strains of the prions. This means that, if animals at one farm begin to show the disease after an outbreak on a nearby farm, it is very difficult to determine whether it is the same strain affecting both herds—suggesting transmission—or if the second outbreak came from a completely different source.
Classic Creutzfeldt-Jakob disease (CJD) was discovered in 1920. It occurs sporadically over the world but is very rare. It affects about one person per million each year. Typically, the cause is unknown for these cases. It has been found to be passed on genetically in some cases. 250 patients contracted the disease through iatrogenic
transmission
Transmission may refer to:
Medicine, science and technology
* Power transmission
** Electric power transmission
** Propulsion transmission, technology allowing controlled application of power
*** Automatic transmission
*** Manual transmission
*** ...
(from use of contaminated surgical equipment). This was before equipment sterilization was required in 1976, and there have been no other iatrogenic cases since then. In order to prevent the spread of infection, the World Health Organization created a guide to tell health care workers what to do when CJD appears and how to dispose of contaminated equipment. The Centers for Disease Control and Prevention (CDC) have been keeping surveillance on CJD cases, particularly by looking at death certificate information.
Chronic wasting disease (CWD) is a prion disease found in North America in deer and elk. The first case was identified as a fatal wasting syndrome in the 1960s. It was then recognized as a transmissible spongiform encephalopathy in 1978. Surveillance studies showed the endemic of CWD in free-ranging deer and elk spread in northeastern Colorado, southeastern Wyoming and western Nebraska. It was also discovered that CWD may have been present in a proportion of free-ranging animals decades before the initial recognition. In the United States, the discovery of CWD raised concerns about the transmission of this prion disease to humans. Many apparent cases of CJD were suspected transmission of CWD, however the evidence was lacking and not convincing.
In the 1980s and 1990s, bovine spongiform encephalopathy (BSE or "mad cow disease") spread in cattle at an epidemic rate. The total estimated number of cattle infected was approximately 750,000 between 1980 and 1996. This occurred because the cattle were fed processed remains of other cattle. Then human consumption of these infected cattle caused an outbreak of the human form CJD. There was a dramatic decline in BSE when feeding bans were put in place. On May 20, 2003, the first case of BSE was confirmed in North America. The source could not be clearly identified, but researchers suspect it came from imported BSE-infected cow meat. In the United States, the USDA created safeguards to minimize the risk of BSE exposure to humans.
Variant Creutzfeldt-Jakob disease (vCJD) was discovered in 1996 in England. There is strong evidence to suggest that vCJD was caused by the same prion as bovine spongiform encephalopathy. A total of 231 cases of vCJD have been reported since it was first discovered. These cases have been found in a total of 12 countries with 178 in the United Kingdom, 27 in France, five in Spain, four in Ireland, four in the United States, three in the Netherlands, three in Italy, two in Portugal, two in Canada, and one each in Japan, Saudi Arabia, and Taiwan.
History
In the 5th century
BCE
Common Era (CE) and Before the Common Era (BCE) are year notations for the Gregorian calendar (and its predecessor, the Julian calendar), the world's most widely used calendar era. Common Era and Before the Common Era are alternatives to the or ...
,
Hippocrates
Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history of ...
described a disease like TSE in cattle and sheep, which he believed also occurred in man.
Publius Flavius Vegetius Renatus
Publius (or Flavius) Vegetius Renatus, known as Vegetius (), was a writer of the Later Roman Empire (late 4th century). Nothing is known of his life or station beyond what is contained in his two surviving works: ''Epitoma rei militaris'' (also re ...
records cases of a disease with similar characteristics in the 4th and 5th centuries AD. In 1755, an outbreak of
scrapie
Scrapie () is a fatal, degenerative disease affecting the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), and as such it is thought to be caused by a prion. Scrapie has been known since ...
was discussed in the British House of Commons and may have been present in Britain for some time before that. Although there were unsupported claims in 1759 that the disease was contagious, in general it was thought to be due to inbreeding and countermeasures appeared to be successful. Early-20th-century experiments failed to show transmission of
scrapie
Scrapie () is a fatal, degenerative disease affecting the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), and as such it is thought to be caused by a prion. Scrapie has been known since ...
between animals, until extraordinary measures were taken such as the intra-ocular injection of infected nervous tissue. No direct link between
scrapie
Scrapie () is a fatal, degenerative disease affecting the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), and as such it is thought to be caused by a prion. Scrapie has been known since ...
and disease in man was suspected then or has been found since. TSE was first described in man by
Alfons Maria Jakob
Alfons Maria Jakob (2 July 1884 – 17 October 1931) was a German neurologist who worked in the field of neuropathology.
He was born in Aschaffenburg, Bavaria and educated in medicine at the universities of Munich, Berlin, and Strasbourg, whe ...
in 1921.
Daniel Carleton Gajdusek
Daniel Carleton Gajdusek ( ;Holley, Joe (December 16, 2008) "D. Carleton Gajdusek; Controversial Scientist", ''The Washington Post'', p. B5. September 9, 1923 – December 12, 2008) was an American physician and medical researcher who was the co ...
's discovery that Kuru was transmitted by cannibalism accompanied by the finding of scrapie-like lesions in the brains of Kuru victims strongly suggested an infectious basis to TSE. A paradigm shift to a non-nucleic infectious entity was required when the results were validated with an explanation of how a
prion
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...
protein might transmit spongiform encephalopathy. Not until 1988 was the neuropathology of spongiform encephalopathy properly described in cows. The alarming amplification of
BSE
BSE may refer to:
Medicine
* Bovine spongiform encephalopathy, also known as mad cow disease, a neurodegenerative disease of cattle
* Breast self-examination
Stock exchanges
* Bahrain Stock Exchange, Bahrain
* Baku Stock Exchange, Azerbaijan
* B ...
in the British cattle herd heightened fear of transmission to humans and reinforced the belief in the infectious nature of TSE. This was confirmed with the identification of a Kuru-like disease, called new variant
Creutzfeldt–Jakob disease
Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes, ...
, in humans exposed to
BSE
BSE may refer to:
Medicine
* Bovine spongiform encephalopathy, also known as mad cow disease, a neurodegenerative disease of cattle
* Breast self-examination
Stock exchanges
* Bahrain Stock Exchange, Bahrain
* Baku Stock Exchange, Azerbaijan
* B ...
. Although the infectious disease model of TSE has been questioned in favour of a
prion
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...
transplantation model that explains why cannibalism favours transmission, the search for a viral agent was, as of 2007, being continued in some laboratories.
References
* ''This entry incorporates public domain text originally from the National Institute of Neurological Disorders and Stroke,
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
br>
and the
U.S. National Library of Medicine
The United States National Library of Medicine (NLM), operated by the United States federal government, is the world's largest medical library.
Located in Bethesda, Maryland, the NLM is an institute within the National Institutes of Health. Its ...
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'
External links
*
{{Prion diseases
Transmissible spongiform encephalopathies,