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Prion Diseases
Microbes and Society
Fall 2007
What is a Prion?
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Prion- small proteinaceous infectious particles which
resist inactivation by procedures that modify nucleic
acids
Disease causing prion is a modified form of a normal
cellular protein known as PrPc. This normal form is
protease sensitive so it does not accumulate.
The modified prion is known as PrPsc (for scrapie)
which is relatively resistant to proteases and
accumulates in cytoplasmic vesicles of diseased
individuals.
Appears that the acquisition of PrPsc allows for
conversion of PrPc into PrPsc and that leads to disease.
Transmissible Spongiform
Encephalopathies
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TSE’s are a family of rare
progressive
neurodegenerative disorders
that affect both humans and
animals. They are
distinguished by long
incubation periods,
characteristic spongiform
changes associated with
neuronal loss, and a failure to
induce inflammatory
response. (CDC)
TSE’s in Animals
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Scapie- sheep, first known TSE been around for
100’s of years. Sheep get it by ingestion off of
pasture or transplacental transmission
Mad Cow Disease or BSE- cows. First cases may
have occurred by feeding scrapie infected tissue
to cows
Chronic Wasting Disease (CWD)- deer, elk
Transmissible Mink Encephalopathies (TME)mink
Animal TSE’s and Society
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BSE in Great Britain cost millions of dollars,
loss of life, a crash in the beef industry and
fostered mistrust of the government. Others?
CWD- Mostly “scared” hunters. However has
the added cost of monitoring which cost $$$$
TME- found in ranched mink so has an impact
on fur sales
More TSE’s and Animals
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Scrapie
Packers and producers have had difficulty finding options for
disposal of sheep offal and dead sheep causing packers and
producers to incur significant increases in disposal costs.
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• Other countries have expressed concerns and have indicated that
they may prohibit or restrict certain ruminant products because the
United States has scrapie.
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• Domestic and international markets for U.S. sheep–derived meat
and bone meal have been adversely affected.
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The combination of all of these factors has led to the decision to
develop a strong scrapie eradication program in the United States
TSE’s and Humans
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Creutzfeldt-Jakob Disease (CJD)
Variant Creutzfeldt-Jakob Disease (vCJD)
Gerstmann-Straussler-Scheinker Syndrome
Fatal Familial Insomnia
Kuru
Classic CJD
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Classic CJD has been recognized since the early
1920s. The most common form of classic CJD
is believed to occur sporadically, caused by the
spontaneous transformation of normal prion
proteins into abnormal prions. This sporadic
disease occurs worldwide, including the United
States, at a rate of approximately one case per 1
million population per year, although rates of up
to two cases per million are not unusual.
vCJD
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There is now strong scientific evidence that the agent
responsible for the outbreak of prion disease in cows,
BSE, is the same agent responsible for the outbreak of
vCJD in humans. Both disorders are invariably fatal
brain diseases with unusually long incubation periods
measured in years, and are caused by an unconventional
transmissible agent.
However, risk of acquiring vCJD through infected cow
meat is still low. Why?
Comparison of classic CJD and
vCJD
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The median age at death for vCJD patients is 28
years, compared with 68 years for patients with
classic CJD.
The median duration of illness for vCJD is 14
months, compared to 5 months for classic CJD.
Kuru
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Kuru is a rare and fatal brain disorder that occurred at
epidemic levels during the 1950s-60s among the Fore
people in the highlands of New Guinea.
The disease was the result of the practice of ritualistic
cannibalism among the Fore, in which relatives
prepared and consumed the tissues (including brain) of
deceased family members.
Brain tissue from individuals with kuru was highly
infectious, and the disease was transmitted either
through eating or by contact with open sores or
wounds.
Inherited Human TSE’s
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Gerstmann-Straussler-Scheinker Syndrome- a
rare inherited dementia that presents in the later
years.
Fatal Familial Insomnia- an extremely rare
inherited prion disease that is characterized by
insomnia and ultimately death.
Treatment
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Nothing yet, but immune cells may be what
carries the protein to the lymph nodes and
eventually the brain.
Prevention- food animals have strict diets which
limit or prevent animals from ingesting CNS
material that may contain prions.