User:Tambler6666/Transmissible spongiform encephalopathy
I added information about plants carrying and transmitting prion diseases and edited some grammatical errors.
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== Infectivity ==
Scrapie was suspected to be infectious among sheep in the earliest days from which reliable reports are available. However, it wasn't until the 1930s that the inoculation experiments of Jean Cuillé and Paul-Louis Chelle convincingly demonstrated the infectivity of scrapie (see History, below). In 1959, William Hadlow recognized striking similarities between scrapie and the kuru cases described in humans by [[D. Carleton Gajdusek]]. The shared features of these human and nonhuman diseases prompted Gajdusek to conduct a series of experiments in which he demonstrated that human spongiform encephalopathies are transmissible to nonhuman [[Primate|primates]]. His research group reported the transmissibility of kuru in 1966, Creutzfeldt-Jakob disease (CJD) in 1968, and Gerstmann–Sträussler–Scheinker syndrome (GSS) in 1981. These experiments showed that human spongiform encephalopathies, like those in nonhuman species, can be infectious; because the diseases have an unusually long incubation period following exposure to the infectious agent, the agent was sometimes referred to as a 'slow virus'. The infectious agent was not shown with reasonable certainty to be primarily a protein until the work of [[Stanley Prusiner]] gave rise to the prion concept in 1982.
Infectious prion diseases in humans are uncommon and decreasing in incidence. [[Iatrogenesis|Iatrogenic]] versions have been recognized since the 1980's: Creutzfeldt–Jakob disease has been inadvertently transmitted to patients via injections of [[growth hormone]] harvested from human [[Cadaver|cadaveric]] [[Pituitary gland|pituitary glands]], via cadaveric [[Dura mater|dural]] allografts, and (more rarely) via corneal transplants, transfusion of blood products, and exposure to contaminated instruments used for [[brain surgery]]. Prions can survive heating in the [[autoclave]], a method used for the conventional sterilization of surgical instruments. For this reason, special precautions need to be taken to ensure the complete sterility of [[Neurosurgery|neurosurgical]] instruments.
Dietary consumption of affected animal parts can transmit prion disease, especially in nonhuman species in which infectious prion diseases are relatively common. In these instances, how the agent gains wider access to the body is not entirely clear; besides the apparent transmission of prions via the [[alimentary tract]], transmissible spongiform encephalopathies may be naturally acquired when prion-containing material comes in contact with damaged tissues such as the gums, skin, or [[conjunctiva]]. '''Early studies suggest that plants can be vessels for prion transmission if an infected plant is consumed. It was demonstrated in certain plant species, such as those that animals feed on, like [[alfalfa]] and [[barley]], among others. The roots can absorb prions released into the soil from previously deceased, infected animals and transfer them throughout the plant. In turn, this can infect the animal that consumes the prion-containing species.'''
In humans, infection via consumption is very rare, two well-known examples being kuru and variant Creutzfeldt-Jakob disease (vCJD). Kuru is a (now extinct) prion disease that reached epidemic proportions in the mid-20th century in the [[Fore (people)|Fore]] people of [[Papua New Guinea]]. Until the practice was abandoned in the mid-20th century, the Fore people would [[Human cannibalism|consume their dead]] as a funerary ritual. With the cessation of [[Cannibalism in Oceania|ritual cannibalism]], new cases of Kuru slowly ceased to appear. A more well-known infectious human prion disease is vCJD, a [[Zoonosis|zoonotic]] prion disease that is caused by the consumption of tissues from cows with bovine spongiform encephalopathy (BSE). Cows are thought to have acquired BSE by consuming food that contained meat products derived from animals with prion disease, possibly sheep with scrapie. Fortunately, vCJD has largely been eliminated by efforts to exclude tainted meat products from the food chain. Regulations in many developed countries now ban the use of [[Rendering (industrial)|rendered]] [[ruminant]] proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other animals.
Prions cannot be transmitted through the air, through touching, or by most other forms of casual contact. However, they may be transmitted through contact with infected tissue, bodily fluids, or contaminated medical instruments. Normal [[Sterilization (microbiology)|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.
Epidemiological surveillance has identified cases of atypical bovine spongiform encephalopathy (BSE) and scrapie in livestock, as well as chronic wasting disease (CWD) in cervids, highlighting the zoonotic potential of prion diseases and their impact on animal and human health.
== Other hypotheses ==
The infectious protein hypothesis has become the prevailing explanation for the causation of prion diseases. However, in the years following the recognition of their infectivity, other hypotheses regarding the infectious agent have been proposed. These include unorthodox forms of carbohydrates, lipids, [[Nucleic acid|nucleic acids]], or unusual or cryptic infectious agents. With respect to causation by nucleic acid-based infectious agents, a hypothesis championed by [[Laura Manuelidis]] invokes a cryptic [[Virus|viral agent]], and another proposed by [[Frank O. Bastian]] holds that ''[[Spiroplasma]]'' infection, specifically ''[[Spiroplasma mirum]]'', is a cause of transmissible spongiform encephalopathies. However, no alternative hypothesis has garnered sufficient support to displace the prion paradigm.
== Diagnosis ==
The variable presentation of prion diseases and their rapid progression following the appearance of signs and symptoms present a special challenge for diagnosis. Because the early signs of disease can mimic those in other brain disorders, the diagnosis of prion disease is often delayed. Upon clinical examination, sporadic CJD (the most frequent human prion disease) is suspected when the patient presents with rapidly progressing deterioration of cognition and movement. The diagnosis can be supported by the following tests: 1) [[Electroencephalogram]](EEG) - in CJD, the pattern of brain waves changes over the course of the disease, one typical abnormality being periodic sharp and slow wave complexes in the electrical signal; 2) [[Cerebrospinal fluid]] (CSF) tests, in particular, measurement of the [[14-3-3]] protein, [[tau protein]], and [[neurofilament light chain]], all of which increase in prion diseases; 3) [[Magnetic resonance imaging]](MRI) can detect characteristic changes in the structure of the brain; and 4) Real-time Quaking Induced Conversion ([[RT-QuIC]]) is used to detect the presence of abnormal PrP in the CSF. Although many of the changes detected by these tests occur in other diseases, combining the test results can establish the presence of prion disease with high [[Sensitivity and specificity]]. [[False positive]] diagnoses, though rare, are still possible; therefore, definitive diagnosis of prion diseases requires direct examination of brain tissue.
== Treatment ==
There are currently no known ways to cure or prevent prion disease. [[Symptomatic treatment|Supportive care]] is the only option for easing the burden of the disease in affected individuals. Certain medications''',''' such as '''[[Pentosan polysulfate|PSPs]],''' [[tetracycline]]''',''' and '''[[Doxycycline|doxycycline,]] have''' been studied experimentally to treat CJD''',''' but their results vary and are generally disappointing. PRN100, a [[Monoclonality|monoclonal]] antibody''',''' has been overlooked as an emerging treatment that has '''been''' shown to lengthen the lifespan of lab mice to '''a''' normal lifespan, their effectiveness in humans '''is''' still being studied.
== Epidemiology ==
Prion diseases are unique in medicine in that they can be sporadic, genetic, or infectious in origin. There are a number of different prion diseases of humans and nonhuman species, each with its own characteristics (such as the primary [[Host (biology)|host]] species, [[Incidence (epidemiology)|incidence]], disease course, and pathology). In humans, the most common prion disease is CJD, which is estimated to occur worldwide in 1 to 2 persons per million per year. Of these, approximately 85% are sporadic, 10-15% are genetic, and less than 1% are acquired by infection. The incidence of sCJD increases with age, and it is most likely to appear between the ages of 55 and 75.Although there may be subtle sex differences, males and females appear to be affected at a similar rate. Analyses in several countries suggest that the incidence of sCJD has risen in recent years. This increase may be due in part to improved detection of the disease, although the growing elderly population is also a possible factor. Much less common sporadic prion diseases include sporadic fatal insomnia (sFI) and variably protease'''-'''sensitive prionopathy (VPSPr).
Genetic (heritable) human prion diseases are caused by changes in the PRNP gene, which codes for PrP. Three main categories of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). Of these, the most frequently occurring type is gCJD, whereas FFI is extremely rare.In addition to the mutations in PRNP that cause disease, there are [[Polymorphism (biology)|variations]] in the PRNP gene that can increase or decrease the likelihood of developing all three aetiological subtypes of prion disease (genetic, infectious''',''' and sporadic).
Infectious prion diseases in humans are very rare, historically accounting for less than 1% of cases; they include kuru, iatrogenic CJD (iCJD)''',''' and variant CJD (vCJD). Humans have been exposed to prions via contaminated foodstuffs, human cadaver-derived biologics (cadaveric hormones or cadaveric tissue grafts), or contaminated surgical instruments. From 1957 until 2004, more than 2700 cases of kuru among the Fore people of Papua New Guinea were documented. With the cessation of [[endocannibalism]] beginning in the 1950s, the number of cases began to decline, and today the disease is considered to be eradicated.
Of the approximately 500 cases of known iatrogenic CJD, most have been recipients of cadaveric pituitary hormones (200 cases, mostly in France) or cadaveric dura mater grafts (over 200 cases, mostly in Japan). The rest of the iCJD cases have been very uncommon; these have involved [[Corneal transplant|corneal transplants]] (2-10 cases), [[intracranial]] exposure to contaminated EEG electrodes (2 cases), exposure to contaminated surgical instruments (4 cases), or transfusion of blood (3 cases).
The variant form of CJD resulted from exposure of humans to prion-infected meat from cows with BSE. As of 2021, a total of 232 cases of vCJD had been reported worldwide. Of these, most were in the United Kingdom (178 cases) and France (28 cases), with the remaining 26 cases appearing in various other countries. All but one of these vCJD patients had a specific [[Polymorphism (biology)|polymorphism]] (MM) at codon 129 of the PRNP gene, underscoring the importance of this gene locus as a modifier of susceptibility to prion disease. Removal of cattle with prion disease from the food chain has brought the vCJD crisis to an end, although there is still some concern that people with certain polymorphisms of PRNP may yet develop disease after a longer incubation period. In general, an improved understanding of prions and their transmissibility has greatly reduced the risk of infectious human prion diseases.
In nonhuman species, the epidemiology of prion diseases differs from that in humans in that most cases are infectious in origin. Scrapie can be transmitted among sheep and goats in captivity, and chronic wasting disease (CWD) is unusual in that it is spreading both in captive and wild cervid populations, especially in North America. CWD was first identified in captive cervids in Colorado (USA) in 1967, and its distribution has since expanded to include many areas of North America as well as other countries. CWD is highly infectious, and it is transmissible via direct contact between animals or by contact with prion-contaminated materials. Infected animals can shed prions in saliva, feces, and urine into the environment, and the prions can remain infectious for years thereafter.
Other nonhuman prion diseases '''have mostly''' resulted from feeding animals prion-contaminated food; in addition to BSE, these include transmissible mink encephalopathy, exotic ungulate spongiform encephalopathy''',''' and feline spongiform encephalopathy. In the 1980s and 1990s, bovine spongiform encephalopathy (BSE, or "mad cow disease") spread in cattle at an epidemic rate, mostly in the UK. How the first cases of BSE arose is not known, but the epidemic was driven by feeding cattle meat and bone meal that contained the processed remains of infected animals. The bovine epidemic peaked in 1992 at 37,000 confirmed cases; as a result of a ban on feeding meat and bone meal to cattle, the numbers declined to single digits after 2011. Human consumption of meat from BSE-infected cattle caused an outbreak of variant CJD (see above). In the case of some newly emerging (or newly discovered) nonhuman prion diseases, such as CWD in Scandinavia and a prion disease of camels, the origins are sometimes unknown. While the transmission of prion disease from nonhumans to humans appears to be uncommon, the potential for zoonotic infection was highlighted by the BSE epidemic, and this possibility remains a concern among public health specialists.{{Dashboard.wikiedu.org draft template/about this sandbox}}
== Article Draft ==
=== Lead ===
=== Article body ===
=== References ===
[[Category:Wikipedia Student Program]]
Scrapie was suspected to be infectious among sheep in the earliest days from which reliable reports are available. However, it wasn't until the 1930s that the inoculation experiments of Jean Cuillé and Paul-Louis Chelle convincingly demonstrated the infectivity of scrapie (see History, below). In 1959, William Hadlow recognized striking similarities between scrapie and the kuru cases described in humans by [[D. Carleton Gajdusek]]. The shared features of these human and nonhuman diseases prompted Gajdusek to conduct a series of experiments in which he demonstrated that human spongiform encephalopathies are transmissible to nonhuman [[Primate|primates]]. His research group reported the transmissibility of kuru in 1966, Creutzfeldt-Jakob disease (CJD) in 1968, and Gerstmann–Sträussler–Scheinker syndrome (GSS) in 1981. These experiments showed that human spongiform encephalopathies, like those in nonhuman species, can be infectious; because the diseases have an unusually long incubation period following exposure to the infectious agent, the agent was sometimes referred to as a 'slow virus'. The infectious agent was not shown with reasonable certainty to be primarily a protein until the work of [[Stanley Prusiner]] gave rise to the prion concept in 1982.
Infectious prion diseases in humans are uncommon and decreasing in incidence. [[Iatrogenesis|Iatrogenic]] versions have been recognized since the 1980's: Creutzfeldt–Jakob disease has been inadvertently transmitted to patients via injections of [[growth hormone]] harvested from human [[Cadaver|cadaveric]] [[Pituitary gland|pituitary glands]], via cadaveric [[Dura mater|dural]] allografts, and (more rarely) via corneal transplants, transfusion of blood products, and exposure to contaminated instruments used for [[brain surgery]]. Prions can survive heating in the [[autoclave]], a method used for the conventional sterilization of surgical instruments. For this reason, special precautions need to be taken to ensure the complete sterility of [[Neurosurgery|neurosurgical]] instruments.
Dietary consumption of affected animal parts can transmit prion disease, especially in nonhuman species in which infectious prion diseases are relatively common. In these instances, how the agent gains wider access to the body is not entirely clear; besides the apparent transmission of prions via the [[alimentary tract]], transmissible spongiform encephalopathies may be naturally acquired when prion-containing material comes in contact with damaged tissues such as the gums, skin, or [[conjunctiva]]. '''Early studies suggest that plants can be vessels for prion transmission if an infected plant is consumed. It was demonstrated in certain plant species, such as those that animals feed on, like [[alfalfa]] and [[barley]], among others. The roots can absorb prions released into the soil from previously deceased, infected animals and transfer them throughout the plant. In turn, this can infect the animal that consumes the prion-containing species.'''
In humans, infection via consumption is very rare, two well-known examples being kuru and variant Creutzfeldt-Jakob disease (vCJD). Kuru is a (now extinct) prion disease that reached epidemic proportions in the mid-20th century in the [[Fore (people)|Fore]] people of [[Papua New Guinea]]. Until the practice was abandoned in the mid-20th century, the Fore people would [[Human cannibalism|consume their dead]] as a funerary ritual. With the cessation of [[Cannibalism in Oceania|ritual cannibalism]], new cases of Kuru slowly ceased to appear. A more well-known infectious human prion disease is vCJD, a [[Zoonosis|zoonotic]] prion disease that is caused by the consumption of tissues from cows with bovine spongiform encephalopathy (BSE). Cows are thought to have acquired BSE by consuming food that contained meat products derived from animals with prion disease, possibly sheep with scrapie. Fortunately, vCJD has largely been eliminated by efforts to exclude tainted meat products from the food chain. Regulations in many developed countries now ban the use of [[Rendering (industrial)|rendered]] [[ruminant]] proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other animals.
Prions cannot be transmitted through the air, through touching, or by most other forms of casual contact. However, they may be transmitted through contact with infected tissue, bodily fluids, or contaminated medical instruments. Normal [[Sterilization (microbiology)|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.
Epidemiological surveillance has identified cases of atypical bovine spongiform encephalopathy (BSE) and scrapie in livestock, as well as chronic wasting disease (CWD) in cervids, highlighting the zoonotic potential of prion diseases and their impact on animal and human health.
== Other hypotheses ==
The infectious protein hypothesis has become the prevailing explanation for the causation of prion diseases. However, in the years following the recognition of their infectivity, other hypotheses regarding the infectious agent have been proposed. These include unorthodox forms of carbohydrates, lipids, [[Nucleic acid|nucleic acids]], or unusual or cryptic infectious agents. With respect to causation by nucleic acid-based infectious agents, a hypothesis championed by [[Laura Manuelidis]] invokes a cryptic [[Virus|viral agent]], and another proposed by [[Frank O. Bastian]] holds that ''[[Spiroplasma]]'' infection, specifically ''[[Spiroplasma mirum]]'', is a cause of transmissible spongiform encephalopathies. However, no alternative hypothesis has garnered sufficient support to displace the prion paradigm.
== Diagnosis ==
The variable presentation of prion diseases and their rapid progression following the appearance of signs and symptoms present a special challenge for diagnosis. Because the early signs of disease can mimic those in other brain disorders, the diagnosis of prion disease is often delayed. Upon clinical examination, sporadic CJD (the most frequent human prion disease) is suspected when the patient presents with rapidly progressing deterioration of cognition and movement. The diagnosis can be supported by the following tests: 1) [[Electroencephalogram]](EEG) - in CJD, the pattern of brain waves changes over the course of the disease, one typical abnormality being periodic sharp and slow wave complexes in the electrical signal; 2) [[Cerebrospinal fluid]] (CSF) tests, in particular, measurement of the [[14-3-3]] protein, [[tau protein]], and [[neurofilament light chain]], all of which increase in prion diseases; 3) [[Magnetic resonance imaging]](MRI) can detect characteristic changes in the structure of the brain; and 4) Real-time Quaking Induced Conversion ([[RT-QuIC]]) is used to detect the presence of abnormal PrP in the CSF. Although many of the changes detected by these tests occur in other diseases, combining the test results can establish the presence of prion disease with high [[Sensitivity and specificity]]. [[False positive]] diagnoses, though rare, are still possible; therefore, definitive diagnosis of prion diseases requires direct examination of brain tissue.
== Treatment ==
There are currently no known ways to cure or prevent prion disease. [[Symptomatic treatment|Supportive care]] is the only option for easing the burden of the disease in affected individuals. Certain medications''',''' such as '''[[Pentosan polysulfate|PSPs]],''' [[tetracycline]]''',''' and '''[[Doxycycline|doxycycline,]] have''' been studied experimentally to treat CJD''',''' but their results vary and are generally disappointing. PRN100, a [[Monoclonality|monoclonal]] antibody''',''' has been overlooked as an emerging treatment that has '''been''' shown to lengthen the lifespan of lab mice to '''a''' normal lifespan, their effectiveness in humans '''is''' still being studied.
== Epidemiology ==
Prion diseases are unique in medicine in that they can be sporadic, genetic, or infectious in origin. There are a number of different prion diseases of humans and nonhuman species, each with its own characteristics (such as the primary [[Host (biology)|host]] species, [[Incidence (epidemiology)|incidence]], disease course, and pathology). In humans, the most common prion disease is CJD, which is estimated to occur worldwide in 1 to 2 persons per million per year. Of these, approximately 85% are sporadic, 10-15% are genetic, and less than 1% are acquired by infection. The incidence of sCJD increases with age, and it is most likely to appear between the ages of 55 and 75.Although there may be subtle sex differences, males and females appear to be affected at a similar rate. Analyses in several countries suggest that the incidence of sCJD has risen in recent years. This increase may be due in part to improved detection of the disease, although the growing elderly population is also a possible factor. Much less common sporadic prion diseases include sporadic fatal insomnia (sFI) and variably protease'''-'''sensitive prionopathy (VPSPr).
Genetic (heritable) human prion diseases are caused by changes in the PRNP gene, which codes for PrP. Three main categories of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). Of these, the most frequently occurring type is gCJD, whereas FFI is extremely rare.In addition to the mutations in PRNP that cause disease, there are [[Polymorphism (biology)|variations]] in the PRNP gene that can increase or decrease the likelihood of developing all three aetiological subtypes of prion disease (genetic, infectious''',''' and sporadic).
Infectious prion diseases in humans are very rare, historically accounting for less than 1% of cases; they include kuru, iatrogenic CJD (iCJD)''',''' and variant CJD (vCJD). Humans have been exposed to prions via contaminated foodstuffs, human cadaver-derived biologics (cadaveric hormones or cadaveric tissue grafts), or contaminated surgical instruments. From 1957 until 2004, more than 2700 cases of kuru among the Fore people of Papua New Guinea were documented. With the cessation of [[endocannibalism]] beginning in the 1950s, the number of cases began to decline, and today the disease is considered to be eradicated.
Of the approximately 500 cases of known iatrogenic CJD, most have been recipients of cadaveric pituitary hormones (200 cases, mostly in France) or cadaveric dura mater grafts (over 200 cases, mostly in Japan). The rest of the iCJD cases have been very uncommon; these have involved [[Corneal transplant|corneal transplants]] (2-10 cases), [[intracranial]] exposure to contaminated EEG electrodes (2 cases), exposure to contaminated surgical instruments (4 cases), or transfusion of blood (3 cases).
The variant form of CJD resulted from exposure of humans to prion-infected meat from cows with BSE. As of 2021, a total of 232 cases of vCJD had been reported worldwide. Of these, most were in the United Kingdom (178 cases) and France (28 cases), with the remaining 26 cases appearing in various other countries. All but one of these vCJD patients had a specific [[Polymorphism (biology)|polymorphism]] (MM) at codon 129 of the PRNP gene, underscoring the importance of this gene locus as a modifier of susceptibility to prion disease. Removal of cattle with prion disease from the food chain has brought the vCJD crisis to an end, although there is still some concern that people with certain polymorphisms of PRNP may yet develop disease after a longer incubation period. In general, an improved understanding of prions and their transmissibility has greatly reduced the risk of infectious human prion diseases.
In nonhuman species, the epidemiology of prion diseases differs from that in humans in that most cases are infectious in origin. Scrapie can be transmitted among sheep and goats in captivity, and chronic wasting disease (CWD) is unusual in that it is spreading both in captive and wild cervid populations, especially in North America. CWD was first identified in captive cervids in Colorado (USA) in 1967, and its distribution has since expanded to include many areas of North America as well as other countries. CWD is highly infectious, and it is transmissible via direct contact between animals or by contact with prion-contaminated materials. Infected animals can shed prions in saliva, feces, and urine into the environment, and the prions can remain infectious for years thereafter.
Other nonhuman prion diseases '''have mostly''' resulted from feeding animals prion-contaminated food; in addition to BSE, these include transmissible mink encephalopathy, exotic ungulate spongiform encephalopathy''',''' and feline spongiform encephalopathy. In the 1980s and 1990s, bovine spongiform encephalopathy (BSE, or "mad cow disease") spread in cattle at an epidemic rate, mostly in the UK. How the first cases of BSE arose is not known, but the epidemic was driven by feeding cattle meat and bone meal that contained the processed remains of infected animals. The bovine epidemic peaked in 1992 at 37,000 confirmed cases; as a result of a ban on feeding meat and bone meal to cattle, the numbers declined to single digits after 2011. Human consumption of meat from BSE-infected cattle caused an outbreak of variant CJD (see above). In the case of some newly emerging (or newly discovered) nonhuman prion diseases, such as CWD in Scandinavia and a prion disease of camels, the origins are sometimes unknown. While the transmission of prion disease from nonhumans to humans appears to be uncommon, the potential for zoonotic infection was highlighted by the BSE epidemic, and this possibility remains a concern among public health specialists.{{Dashboard.wikiedu.org draft template/about this sandbox}}
== Article Draft ==
=== Lead ===
=== Article body ===
=== References ===
[[Category:Wikipedia Student Program]]
