By:
Amy Cummings
Microbiology 1913
Mrs. Anita Hampton
Georgia
Perimeter College
Summer
2004
Prions are proteins that are found in the nerve cells of all
mammals. Numerous prions are in each nerve
cell, but no one knows for sure what the prion protein does. The brain of a human or animal infected with
a prion “disease” has many abnormally-shaped prions. One hypothesis states that when a person or
animal ingests an abnormally-shaped prion from contaminated food the
abnormally-shaped prion gets absorbed into the bloodstream and crosses into the
nervous system. The abnormal prion
touches a normal prion and changes the normal prion’s shape into an abnormal
one, thereby destroying the normal prion’s original
function. Both abnormal prions then contact and change
the shapes of other normal prions in the nerve cell. The nerve cell tries to get rid of the
abnormal prions by clumping them together in small sacs that merge with its
lysosome. However, the nerve cells
cannot digest the abnormal prions, and they accumulate in the lysosomes. The lysosomes grow and engorge the nerve
cell, which eventually lysis. Next, the
abnormal prions are released to infect other cells. Large, sponge-like holes are left where the
cells lysed. Numerous nerve cell deaths
lead to loss of brain function, and the person eventually dies. (howstuffworks.com/mad-cow-disease4.htm)
Prions first came to public attention in the mid 1980s in the form
of the bovine spongiform encephalopathy (BSE, or “mad cow disease”) epidemic in
the United Kingdom. Mad cow disease is a
prion disease in cattle. There is a
theory that mad cow disease came from feed contaminated with scrapie, the long
established sheep prion disease. In the
1980’s, producers of cattle feed (which often included ground meat and bone
meal byproducts from sheep) changed the way they processed feed. The change somehow allowed the scrapie
disease agent to survive the cattle feed production process, leading to the
silent spread of the mad cow disease epidemic.
The best known of the human prion diseases is Creutzfeldt-Jakob
disease (CJD). This is a rapidly progressive, fatal,
neurodegenerative disorder. The onset of
symptoms of this disease usually occurs at about age 60. It is believed to be caused by an abnormal
isoform of a cellular glycoprotein, the prion protein. CJD is
classified as a transmissible spongiform encephalopathy (TSE). Spongiform refers to the characteristic
appearance of infected brains, which become filled with holes until they
resemble sponges under a microscope. Other human TSEs include
kuru, fatal familial insomnia (FFI), and Gerstmann-Straussler-Scheinker disease
(GSS). Kuru was identified in people of
an isolated tribe in Papua New Guinea and has now almost disappeared. Family familial insomnia and
Gerstmann-Straussler-Scheinker are extremely rare hereditary diseases, found in
just a few families around the world.
There are three major
categories of CJD:
1. One type is the sporadic CJD, this disease appears even though the person has no known risk
factors for the disease. This is by far the most common type of CJD and
accounts for at least 85 percent of cases.
2. Another
type is hereditary CJD, in this case the person has a
family history of the disease and/or tests positive for a genetic mutation
associated with CJD. These inherited forms of
CJD include the Gerstmann-Straussler-Scheinker syndrome and fatal familial
insomnia that were mentioned earlier. About 5 to 10 percent of cases of CJD in the
United States are hereditary.
3. Last there is acquired CJD, these diseases can occur
from contamination through certain medical procedures of the brain or nervous
tissue, and they are called iatrogenic
CJD. Iatrogenic transmission of the
CJD agent has been reported in over 250 patients worldwide. These cases have been linked to the use of
contaminated human growth hormone, dura mater and corneal grafts, or
neurosurgical equipment. There were six
cases linked to the use of contaminated equipment. Of these, four were associated with
neurosurgical instruments, and two with stereotactic EEG depth electrodes. All of these equipment-related cases occurred
before the routine implementation of sterilization procedures currently used in
health care facilities. No such cases
have been reported since 1976, and no iatrogenic CJD cases associated with
exposure to the CJD agent from surfaces such as floors, walls, or countertops
have been identified.
o
Another acquired CJD is called the panencephalopathic form. This occurs primarily in Japan and has a
relatively long course, with symptoms often progressing for several years.
o
Over
the last few years, another type of Acquired CJD called variant (vCJD) has been identified in young people, which I will
discuss shortly.
In the 1990’s, an unusually large
number of people in Great Britain developed what appeared to be CJD, and
scientist began studying the evidence regarding a relationship between mad cow
disease and CJD. The outbreak was
alarming not only because so many people died of a presumably rare disease, but
also because of their relatively young ages — the youngest victim was only 19. Even more disturbing was the way they appeared
to have contracted the disease. All had
eaten meat from cattle suspected of having mad cow disease. Scientists eventually concluded that the new
ailment — named variant CJD (vCJD) — was a form of Creutzfeldt-Jakob disease
resulting from exposure to the mad cow disease. This conclusion was based on the facts that
the vCJD victims had lived in areas where outbreaks of mad cow disease had
occurred years earlier. No victims were
found in areas without mad cow disease outbreaks. Also, the time between the mad cow disease
outbreaks and the deaths of the victims equaled the time it takes for the CJD
to develop. Although there is very
strong evidence that the agent responsible for the human disease is the same
agent responsible for the mad cow disease outbreaks in cattle, the specific
foods that might be associated with the transmission of this agent from cattle
to humans are unknown.
The "classic"
CJD doesn't appear to be connected to mad cow disease, however, it's similar to
the vCJD in many ways.
Ø They are both thought to
occur when misshapen prion proteins attack brain cells.
Ø Both appear to have long
incubation periods, even as long as 10 to 15 years, before signs and symptoms appear.
Ø And both cause profound
mental and physical deterioration, resulting in death.
Although there are slight
variations in the way the signs and symptoms manifest themselves between the
“classic” CJD and the vCJD, the two forms of the disease are far more alike
than they are different. Everyone
affected with these diseases must eventually contend with grave mental and
physical problems. A few of the differences
are:
Ø It
often takes years or even decades after infection before someone with classic
CJD develops signs and symptoms of the disease.
Although it's too early to know for certain, scientists suspect that the
same is true of vCJD. That's why some
experts predict that an epidemic of vCJD is still to come.
Ø Both classic and variant CJD begin with personality changes such
as anxiety, depression, memory loss and impaired thinking. As the diseases progress, mental symptoms
become more severe. Ultimately, people
with both forms of CJD develop dementia — a mental disorder that robs them of
the ability to speak, think, reason, remember and move. With classic
CJD, the progression from initial personality changes to
complete dementia occurs quickly — usually within six months or less of the
onset of symptoms. In
the variant CJD, psychiatric symptoms are most prominent early on in the
disease, but dementia develops later in the course of the disease.
Ø Both types of CJD affect balance and coordination, leading to
stumbling, falls and difficulty walking, but these problems occur sooner in
vCJD than they do in classic CJD.
Ø Most people lapse into coma before succumbing to these invariably
fatal diseases. People with classic CJD
generally live an average of only seven months after signs and symptoms appear,
although some people may live as long as one or two years after the onset of
symptoms. Death is usually not a result
of the disease itself, but rather of complications such as heart failure,
respiratory failure and pneumonia. People
with vCJD tend to live slightly longer — about 12 to 14 months after signs and
symptoms appear.
Ø Other
signs and symptoms of classic CJD include blurred vision and eventual
blindness, involuntary muscle contractions, difficulty speaking, which may lead
to mumbling or speech that's difficult to understand, and difficulty swallowing.
Ø Additional signs and symptoms of vCJD include a sense that the
skin feels sticky, sensations of cold or pain, muscle paralysis, and tremors.
The
main indicators that lead to a diagnosis of CJD are: rapid dementia, unsteady
gait, and sudden jerky movements. There
is currently no single diagnostic test for CJD.
The first concern is to rule out treatable forms of dementia such as
encephalitis or chronic meningitis. In
most CJD patients, the presence of 14-3-3 protein in the cerebrospinal fluid or
a typical electroencephalogram (EEG) pattern has been reported. However, the only way to confirm a diagnosis
requires a brain biopsy or autopsy. Both
brain biopsy and autopsy pose a small, but definite, risk that the surgeon or
others who handle the brain tissue may become accidentally infected by
self-inoculation. Because a correct diagnosis of CJD does not
help the patient, a brain biopsy is discouraged unless it is needed to rule out
a treatable disorder. Worldwide, doctors
typically only diagnose one case per million people each year, most commonly in
older adults.
There
is no treatment that can cure either type of CJD, and there is nothing that will
slow the progression of the disease.
Current treatment is aimed at alleviating symptoms and making the
patient as comfortable as possible.
Opiate drugs can help relive pain, and the drugs clonazepam and sodium
valproate may help relieve involuntary muscle jerks. During later stages of the disease, changing
the person’s position frequently can keep him or her comfortable and helps
prevent bedsores. A catheter can be used to drain urine if the patient cannot
control bladder function, and intravenous fluids and artificial feeding also
may be used. (Centers for Disease Control and Prevention (CDCP))
From 1995 through June
2002, a total of 124 human cases of vCJD were reported in the United Kingdom, 6
cases in France, and 1 case each in Ireland, Italy, and the United States. The case-patients from Ireland and the United
States had each lived in the United Kingdom for more than 5 years during the UK
“mad cow disease” epidemic. The best
estimate of the annual increase in the number of vCJD cases in the United
Kingdom since the outbreak began is 18% per year, which is equivalent to a
doubling every 4.2 years.
A growing number of cases
of vCJD are being linked to contaminated beef in Great Britain and in other
countries, including Spain, Portugal, France and Germany. Scientist have identified the presence of the mad
cow disease agent in the brain, spinal cord, retina, dorsal root ganglia,
distal ileum, and the bone marrow of cattle experimentally infected with this
agent by the oral route. In addition to
cattle, sheep are susceptible to experimental infection with the mad cow
disease agent by the oral route. There
is a theoretical risk that in countries where flocks of sheep and goats may
have been exposed to this agent through contaminated feed these animals might
have developed infections caused by the mad cow disease agent and that these
infections are being maintained in the flocks, even in the absence of continued
exposure to contaminated feed (for example, through maternal transmission). Regardless, as of July 2002, cattle remain the
only known food animal species with disease caused by the mad cow disease
agent.
In the United Kingdom,
the current risk of acquiring vCJD from eating beef and beef products appears
to be extremely small, perhaps about one case per 10 billion servings. In other countries of the world, this current
risk, if it exists at all, would not likely be any higher than that in the
United Kingdom. This is particularly true
if mad cow disease-related public health control measures are being well
implemented. Such as enhanced mad cow
disease surveillance, the culling of sick animals, and bans of specified risk
materials. The most stringent of these
control measures that have been applied in the United Kingdom is an “Over
Thirty Months Scheme” that excludes all animals older than 30 months from the
human food and animal feed chains. This
policy appears to be highly effective.
One way to reduce
the already very low risk of CJD transmission from one person to another is
that people should never donate blood, tissues, or organs if they have
suspected or confirmed CJD, or if they are at increased risk because of a
family history of the disease, a dura mater graft, or other factor. Remember that normal sterilization procedures
such as cooking, washing, and boiling do not destroy prions. Caregivers, health care workers, and undertakers
should take extra precautions when they are working with a person with CJD. Also, when traveling to Europe or other
areas with cases of mad cow disease one may wish to consider both avoiding beef
and beef products altogether. Selecting
solid pieces of muscle meat rather than beef products, such as burgers and
sausages, is also a good idea. These
choices might have a reduced opportunity for contamination with tissues that
may harbor the mad cow disease agent. There is no evidence that CJD is contagious
through casual contact with a CJD patient.
References
National Prion Disease Pathology Surveillance Center Website: http://www.cjdsurveillance.com/
Creutzfeldt-Jakob (CJD) Foundation Inc.
http://www.cjdfoundation.org
http://www.cjdfoundation.org
National Organization for Rare Disorders (NORD)
http://www.rarediseases.org
GOOD
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