Page 386 - Review of Medical Microbiology and Immunology ( PDFDrive )

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mebooksfree.com mebooksfree.com mebooksfree.com as an autosomal dominant trait. In these patients, 12 dif- 375 mebooksfree.com
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CHAPTER 44 Slow Viruses & Prions
or animal exposure. Vegetarians and meat eaters have the
ferent point mutations and several insertion mutations in
same rate. The rate of CJD is the same in countries whose
the prion protein gene have been found. One of these, a
animals have scrapie and those whose animals do not. There
point mutation in codon 102, is the same mutation found
is no evidence for person-to-person or transplacental
transmission.
in patients with GSS syndrome—another slow central
There is no increased risk for medical caregivers; there-
fore, gowns and masks are unnecessary. The standard pre-
tures of GSS syndrome are cerebellar ataxia and spastic
paraparesis. The hereditary forms of these diseases may be
cautions for obtaining infectious specimens should be
prevented by the detection of carriers and genetic
observed. It has been transmitted iatrogenically (e.g., in a nervous system disease of humans. The main clinical fea-
mebooksfree.com mebooksfree.com mebooksfree.com tious forms are kuru and probably variant CJD (see next mebooksfree.com
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counseling.
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corneal transplant, via intracerebral electrodes, in hor-
The origin of these spongiform encephalopathies is
mones extracted from human pituitaries, and in grafts of
cadaveric dura mater). There is only one confirmed case of
threefold: infectious, hereditary, and sporadic. The infec-
CJD being transmitted by blood transfusion, and intrave-
nous drug use does not increase the risk. Proper steriliza-
section). Transmission of the infectious agent was docu-
tion of CJD agent-contaminated material consists of either
mented by serial passage of brain material from a person
with CJD to chimpanzees. The hereditary form is best
autoclaving or treating with sodium hypochlorite.
illustrated by GSS syndrome (see preceding paragraph) and
The main clinical findings of CJD are dementia (includ-
by a disease called fatal familial insomnia. The term spo-
ing behavioral changes, memory loss, and confusion) and
myoclonic jerking. Additional findings include ataxia,
aphasia, visual loss, and hemiparesis. The symptoms typi-
of either an infectious or a hereditary cause.
cally appear gradually and progress inexorably. In the ter-
Fatal familial insomnia is a very rare disease character-
minal stage, the patient becomes mute and akinetic, then radic refers to the appearance of the disease in the absence
ized by progressive insomnia, dysautonomia (dysfunction
comatose. About 80% of those affected die within 1 year.
of the autonomic nervous system) resulting in various
mebooksfree.com mebooksfree.com mebooksfree.com Variant Creutzfeldt-Jakob mebooksfree.com mebooksfree.com
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Most cases occur in people who are 50 to 70 years of age.
symptoms, dementia, and death. A specific mutation in the
A presumptive diagnosis of CJD can be made pathologi-
prion protein is found in patients with this disease.
cally by detecting spongiform changes in a brain biopsy
specimen. Neuronal loss and gliosis are seen. Amyloid
plaques are also seen in some cases of CJD. In variant CJD,
Disease (vCJD)
“florid” plaques composed of flowerlike amyloid plaques
In 1996, several cases of CJD occurred in Great Britain due
surrounded by a halo of vacuoles are seen. Brain imaging
to ingestion of beef. These cases are a new variant of CJD
and the electroencephalogram may show characteristic
(vCJD, also called nvCJD) because they occurred in much
changes. There is no evidence of inflammation (i.e., no
neutrophils or lymphocytes are seen). The blood count and
pathologic findings different from those found in the typi-
routine spinal fluid test results are normal. The finding of a
cal form of the disease. None of those affected had con-
normal brain protein called 14-3-3 in the spinal fluid sup-
sumed cattle or sheep brains, but brain material may have
ports the diagnosis. younger people than usual and had certain clinical and
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mebooksfree.com mebooksfree.com mebooksfree.com whose native prion protein is homozygous for valine at mebooksfree.com
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been admixed into processed meats such as sausages.
The specific diagnosis of CJD is typically made by
Only people whose native prion protein is homozygous
immunohistochemistry in which labeled antiprion anti-
for methionine at amino acid 129 contract vCJD. People
bodies are used to stain the patient’s brain specimen.
Because we do not make antibodies to prion proteins, there
amino acid 129 or who are heterozygotic do not contract
are no serologic diagnostic tests. No antibodies are made in
vCJD. These findings indicate that prion proteins with
humans because humans are tolerant to our prion proteins.
methionine are more easily folded into the pathologic beta-
(The antibodies used in the immunohistochemical lab tests
pleated sheet form.
are made in other animals in which the human prions are
The prions isolated from the “variant CJD” cases in
immunogenic.) Unlike viruses, prions cannot be grown in
culture, so there are no culture-based diagnostic tests.
cow disease more than they resemble other prions, which is
Tonsillar tissue obtained from patients with variant CJD
was positive for prion protein using monoclonal antibody–
evidence to support the hypothesis that variant CJD origi-
nated by eating beef. There is no evidence that eating lamb
based assays. The use of tonsillar or other similar lymphoid humans chemically resemble the prions isolated from mad
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is associated with variant CJD. As of February 2009, vCJD
tissue may obviate the need for a brain biopsy. Pathologic
has been diagnosed in 209 people, 165 of whom have lived
prion proteins have also been detected in the olfactory epi-
thelium of patients with CJD.
in the United Kingdom. Three cases of vCJD have occurred
There is no treatment for CJD, and there is no drug or
acquired it in the United Kingdom. All cases of vCJD have
vaccine available for prevention.
occurred in individuals who lived or traveled in a country
Although most cases of CJD are sporadic, about 10%
where BSE has been detected.
are hereditary. The hereditary (familial) form is inherited
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