PERSON TO PERSON TRANSMISSION OF THE TSE PRION DISEASE, never say never. as the disease mutates, it becomes more virulent in some cases, and cwd is efficiently transmitted from cervid to cervid. there are now multiple strains of CWD in cervids, as with the TSE prion disease in bovine, sheep and goats, and we now have the atypical TSE in these species, that have mutated, and some strains _have_ become more virulent. we now have younger humans dying from the TSE prion disease, with shorter incubation period, and that are much younger. human to human casual transmission of the TSE prion disease...again, never say never. ...TSS
A Kiss of a Prion: New Implications for Oral Transmissibility
Bianca Da Costa Dias and Stefan F. T. Weiss + Author Affiliations
School of Molecular and Cell Biology University of the Witwatersrand,
Johannesburg South Africa Reprints or correspondence: Prof Stefan F. T. Weiss
School of Molecular and Cell Biology University of the Witwatersrand Private Bag
3 2050 Wits Johannesburg South Africa (stefan.weiss@wits.ac.za). There is no
doubt about it: prions-infectious particles composed mainly if not entirely of
misfolded protein (scrapie-type prion protein [PrPSc]), which are the causative
agents of transmissible spongiform encephalopathies (TSE) such as scrapie,
variant Creutzfeldt-Jakob Disease (vCJD), and bovine spongiform encephalopathy
(BSE)-are transmissible [1–3]. These agents may be introduced via intracerebral,
intravenous, intraperitoneal, or intraventricular infection, and recent research
indicates that oral transmission may also occur. The last mode of transmission
is of particular interest because it indicates that the consumption of meat and
other products derived from animals experiencing prion disorders may pose a real
risk to humans. Recent reports suggest that, in addition to meat, bodily fluids
such as blood, saliva, feces, and milk may well be risk factors for possible
transmission of TSEs to humans. Successful oral transmission among different
animal species (interspecies) has been demonstrated. However, species
specificity, the “ species barrier,” and the mode of transmission must be taken
into account and may explain why cattle, sheep, goats, mink, and mice are
successfully orally infected with bovine scrapie-type prion protein (bovPrPSc),
whereas the ingestion of bovPrPSc by pigs, poultry, and cervids such as elk and
deer fails to cause disease [1]. Humans are also thought to be susceptible to
oral infection by bovPrPSc by means of contaminated bovine products (eg, meat
pies), and this is believed to be the manner in which the zoonotic disease vCJD
originated [4].
But where do prions hide in the body? They replicate primarily in the
central nervous system, particularly in the brain and the lymphoreticular system
[4], as well as in other tissues such as muscle [5]. Furthermore, the presence
of these infectious agents in bodily excretions and secretions is a major cause
for concern, because it enhances the risks of transmissibility. Prions have been
identified in feces of asymptomatic deer [6] and in the blood, saliva, and urine
of deer with chronic wasting disease [7, 8]. PrPSc has also been detected in the
salivary glands of scrapie-affected sheep [9].
The report by Maddison et al [10] in this issue of theJournal describes for
the first time, to our knowledge, the secretion of prions into the oral cavity
of sheep. The authors used silicon dioxide (SiO2) to concentrate prions, in
conjunction with serial protein misfolding cyclic amplification, or sPMCA, a
method to amplify and detect the presence of very low concentrations of PrPSc.
Serial protein misfolding cyclic amplification has numerous applications, such
as the sensitive detection of pathological prions [11], later application for in
vitro generation of prions [12], and detection of prions in body fluids such as
blood from scrapie-infected hamsters [13]; the last example succeeded even in
the presymptomatic phase [14]. Maddison et al [10] used this technique to
demonstrate that prions are present in buccal swab samples obtained from sheep
with preclinical scrapie infections.
However, one must pose the following question: how do ingested infectious
PrPSc prions reach the mucus and saliva? After oral ingestion, prions are
thought to be taken up first by Peyer patches before they disseminate through
gut-associated lymphoid tissues, the lymphoreticular system, the vagus nerve,
and the enteric nervous system, after which they enter the central nervous
system [15]. Internalization of prions in the intestine is thought to be
performed by M-(microfold) cells [16] and by enterocytes, which internalize
bovPrPSc dependent on the prion receptor LRP/LR [17].
Maddison et al [10] suggest, according to their data, that prions are able
to spread from the small intestine to the oral salivary glands and epithelia
within a period of 9 months. This route explains the occurrence of prions in
saliva and the shedding of prions into the oral cavity.
The transmissibility of scrapie among sheep (intraspecies) is well
recognized. It must be emphasized that horizontal transfer (from one individual
to another) of scrapie is the main route of infection, because vertical
transmission of disease from mother to offspring via milk or placental tissue
occurs infrequently. Thus, in view of the report by Maddison et al, the oral
transmissibility of prions among sheep may serve as a major route for horizontal
scrapie transfer. This occurrence is plausible because sheep often lick each
other. Maddison et al [10] indicate that, because of the similarities in prion
tissue distribution, their implications for the oral transmission of ovine
scrapie might be true for other prion diseases, such as cervid chronic wasting
disease and human vCJD. If this is true for humans, a kiss of a prion may
sometimes have lethal consequences.
Next Section Acknowledgments We thank the Deutsche Forschungsgemeinschaft
(DFG) grant WE 2664/2–1, Germany and the National Research Foundation (NRF),
South Africa, for financial support. We thank Professor Juergen Richt, Kansas
State University, United States, for a critical reading of this paper.
Previous SectionNext Section Footnotes Potential conflicts of interest:
none reported.
Financial support: Deutsche Forschungsgemeinschaft, Germany (grant WE
2664/2–1) and the National Research Foundation, South Africa.
we are (in my opinion), exposed to the TSE prion in so many different ways
in every day life, the potential for exposure and then becoming infected via
taking care of a loved one with TSE prion disease, in my opinion risk factor
there from is minimal, if proper precautions are taken, and even if they were
not, the chance of becoming infected from a kiss, or casual contact is low, but
I do not think it is zero, actually, far from it. I put this all together for a
documentation of the known facts to date, of the potential casual human to human
transmission. I did not put it together to scare anyone. with aerosol
transmission of the TSE prion a reality now, infectivity in urine and feces and
transmission there from being reality now with the TSE prion disease, I don’t
see how anyone can rule _out_ the potential for transmission of the TSE prion
via a kiss (a vehicle for transmission of the TSE prion via saliva), or even for
a cut or open wound (all a cut is and transmission there from, is an crude
inoculation of sorts, and inoculation has been proven to be an efficient mode of
transmission for the TSE prion disease), even the eye, from either one of the
body fluids now that how proven to be infections. I can’t see why we have such
safety protocols for laboratory workers working with the TSE prion disease, but
yet the same officials will say it’s o.k. for the public, friends, and or family
members to do just the opposite with their loved ones when succumbing to the CJD
TSE prion disease. don’t get me wrong, I did it too, and would probably do it
again as far as kissing my mom. but science is science, and the transmission
studies speak for themselves with the bodily fluids. simply put, which is all I
was saying, we can’t say never, and or that none of these cases to date, have
not been, and or will not be, a potential vehicle for transmission. I believe,
and this is my opinion, that more concern for casual transmission with body
fluids and materials there from, should be put forth to families with their
loved ones, and I think that the safety protocols there from should be revised,
to match that of the laboratory settings. again, this is my opinion. your
opinion, and or others here, may read the same science and feel different out
the findings. ...take care, kind regards, terry
SUBSTANCE DATA SHEET
HUMAN PRION AGENTS
FOR USE IN RESEARCH LABORATORIES
SECTION I - INFECTIOUS AGENT
Name: Creutzfeldt-Jakob agent, Kuru agent
Synonym or Cross Reference:: Subacute spongiform encephalopathy,
Creutzfeldt-Jakob disease (CJD), Kuru, Transmissible Spongiform Encephalopathy
(TSE).
Characteristics: Filterable, self-replicating agent, slow infectious
pathogen, prion protein (PrP)
SECTION II - RECOMMENDED PRECAUTIONS
Containment Requirements: Biosafety level 3 facilities, practices and
containment equipment for activities involving these agents; also listed under
biosafety level 2 with special precautions; level of containment will depend on
the nature of the manipulations and the amount of sera, bio/necropsy materials
handled
Protective Clothing: Gown and gloves when handling potentially infectious
materials; eye protection may also be indicated
Other Precautions: Extreme care must be taken to avoid accidental
autoinoculation or other parenteral inoculations of infectious tissues and
fluids
SECTION III - HANDLING INFORMATION
Spills: Allow any potential aerosols to settle; wearing protective
clothing, gently cover spill with paper towel and apply 1N sodium hydroxide,
starting at perimeter and working towards the center; allow sufficient contact
time (1 hour) before clean up
Disposal: Decontaminate before disposal; steam sterilization (132·C for 1
hour), disinfection with 1N sodium hydroxide for 1 hour, incineration
Storage: In sealed containers that are appropriately labeled
The main precaution to be taken by laboratorians working with
prion-infected or contaminated material is to avoid accidental puncture of the
skin.3 Persons handling contaminated specimens should wear cut-resistant gloves
if possible. If accidental contamination of unbroken skin occurs, the area
should be washed with detergent and abundant quantities of warm water (avoid
scrubbing); brief exposure (1 minute to 1N NaOH or a 1:10 dilution of bleach)
can be considered for maximum safety.6 Additional guidance related to
occupational injury are provided in the WHO infection control guidelines.6
Unfixed samples of brain, spinal cord, and other tissues containing human prions
should be processed with extreme care in a BSL-2 facility utilizing BSL-3
practices.
Bovine Spongiform Encephalopathy Although the eventual total number of
variant CJD cases resulting from BSE transmission to humans is unknown, a review
of the epidemiological data from the United Kingdom indicates that BSE
transmission to humans is not efficient.9 The most prudent approach is to study
BSE prions at a minimum in a BSL-2 facility utilizing BSL-3 practices. When
performing necropsies on large animals where there is an opportunity that the
worker may be accidentally splashed or have contact with high-risk materials
(e.g., spinal column, brain) personnel should wear full body coverage personal
protective equipment (e.g., gloves, rear closing gown and face shield).
Disposable plasticware, which can be discarded as a dry regulated medical waste,
is highly recommended. Because the paraformaldehyde vaporization procedure does
not diminish prion titers, BSCs must be decontaminated with 1N NaOH and rinsed
with water. HEPA filters should be bagged out and incinerated. Although there is
no evidence to suggest that aerosol transmission occurs in the natural disease,
it is prudent to avoid the generation of aerosols or droplets during the
manipulation of tissues or fluids and during the necropsy of experimental
animals. It is further strongly recommended that impervious gloves be worn for
activities that provide the opportunity for skin contact with infectious tissues
and fluids.
The main precaution to be taken when working with prion-infected or
contaminated material is to avoid puncture of the skin. If accidental
contamination of skin occurs, the area is swabbed with In sodium hydroxide
(NaOH) for 5 minutes and then washed with copious amounts of water. Unfixed
samples of brain, spinal cord, and other tissues containing human prions should
be processed with extreme care at BSL 3.
Prions are characterized by extreme resistance to conventional inactivation
procedures including irradiation, boiling, dry heat, and chemicals (formalin,
betapropiolactone, alcohols). Sterilization of rodent brain extracts with high
titers of prions requires autoclaving at 132C for 4.5 hours. Denaturing organic
solvents such as phenol or chaotropic reagents such as guanidine isothiocyanate
or alkali such as NaOH can also be used for sterilization. Disposable
plasticware, which can be discarded as a dry waste, is highly recommended.
Although there is no evidence to suggest that aerosol transmission occurs
in the natural disease, it is prudent to avoid the generation of aerosols or
droplets during the manipulation of tissues or fluids and during the necropsy of
experimental animals. Formaldehyde-fixed and paraffin-embedded tissues,
especially of the brain, remain infectious. Some investigators recommend that
formalin-fixed tissues from suspected cases of prion disease be immersed for 30
min in 96% formic acid or phenol before histopathologic processing, but such
treatment may severely distort the microscopic neuropathology.
another interesting aspect of the TSE prion disease is KURU ;
Figure 25. All cooking. including that of human flesh from diseased
kinsmen. was done in pits with steam made by pouring water over the hot stones,
or cooked in bamboo cylinders in the hot ashes. Children participated in both
the butchery and the handling of cooked meat, rubbing their soiled hands in
their armpits or hair, and elsewhere on their bodies. They rarely or never
washed. Infection with the kuru virus was most probably through the cuts and
abrasions of the skin. or from nose-picking, rye (eye...tss) rubbing, or mucosal
injury.
These detailed descriptions will be published elsewhere but have reaffirmed
the oral histories of endocannibalism in the Fore recorded previously12,22–24
and that this practice ceased abruptly at the time of Australian administrative
control over the kuru areas. Although isolated events might have occurred for a
few years after this prohibition, we are confident that new exposures of
individuals to kuru at mortuary feasts would not have occurred after 1960. Not
only have no cases of kuru been recorded in people born after 1959 (and only
nine were recorded in those born after 1956); but also all the 11 last recorded
cases of kuru that we report here were born before 1950. If any source of
infection remained, whether from surreptitious cannibalism, possible ground
contam-ination with human prions at sites where food was prepared, or other
lateral routes, we would expect individuals born after this period to have
kuru—especially since children are thought to have had shorter incubation
periods than adults. However, no such cases have been observed. Additionally,
although a fraction of hamster-adapted scrapie prions have been shown to survive
in soil for at least 3 years,25 the mortuary feast practices (during which the
entire body would be consumed) were undertaken so that any substantial
contamination of soil would not have occurred, and traditional bamboo knives and
leaf plates were burned after the feast. Furthermore, no clusters of kuru cases,
as seen earlier in the epidemic,26 have been recorded for many years....
Kuru: The Science and the Sorcery
Special Jury Prize Winner, Pacific International Documentary Film Festival
2011.
This is the true story of one of the most incredible and challenging
medical detective stories of the 20th Century; a history of human tragedy,
adventure and discovery. It is the story of the Fore, a Papuan community
immersed in cannibalistic mortuary practices and sorcery in one of the most
remote regions on the planet, and the tragic disease that threatened to wipe out
their entire population.
In 1961, a young Australian medical researcher, Michael Alpers, puts up his
hand to work on a new and strange disease in the Eastern Highlands of Papua New
Guinea. There, he teams up with an American outer, Dr Carleton Gajdusek, who has
been in the local Fore region since 1957. For Michael it is the beginning of a
lifelong obsession.
Together, they are amidst a major epidemic. It is killing over 200 people a
year with devastating effects. It mainly targets women and children. The local
people, the Fore, call the disease kuru, their word for shivering. They believe
it is caused by sorcery.
Michael and Carleton are baffled by the disease. There are no scientific
disciplines to guide them as they attempt to unravel its mysteries. By pure
chance, a link is made to a strange transmissible animal disease in sheep,
Scrapie. The two kuru researchers embark on a 10-year experiment to see if the
fatal degenerative brain disease in humans could be transmissible like
Scrapie.
The decision is made to perform an autopsy on a kuru victim and inoculate
the kuru material into a chimpanzee. Kigea, ayoung girl in the village is
identified as being in the early stages of kuru. Kigea’s family, gives Michael
permission to perform an autopsy upon her death.
A brain sample taken from Kigea after her death is flown to the USA and
injected into a chimpanzee called Daisy. While Michael follows the progress of
the transmission experiment, he starts to collate all the recorded data on kuru
and begins to suspect cannibalism as the cause of the spreadof the
disease.
Within two years, he diagnoses Daisy with kuru. This is a defining moment.
It confirms kuru is transmissible and can cross the species barrier. The
revelation, together with epidemiological data collated with anthropologist
Shirley Lindenbaum, links the Fore’s mortuary feasts (consumption of dead
relatives) to the transmission of kuru. Cannibalism is the cause, and its origin
is linked to a rare disease called Creutzfeldt Jakob Disease(CJD), but the story
of kuru is far from over.
The infecting agent is the first new pathogen – prions – to be discovered
in over 100 years. Research results in two Nobel prizes: it’s discoveries
turning scientific understanding upside down, causing rifts in the beliefs ofthe
science community.
Then Mad Cow Disease (Bovine Spongiform Encephalopathy or BSE) reared its
head in the mid 1980s, and 10 years later the human variant CJD. All eyes turned
to kuru, the only model of a prion epidemic in human populations. Many unknowns
still surround prion diseases: there is no cure for kuru, or any of the prion
diseases. The effects are devastating and unprecedented incubation periods can
extend beyond 50 years.
Michael is the key and heart to this story, providing unique access to the
Fore people, and the world’s other leading authorities on the matter; including
Americans Prof. DC Gajdusek (Nobel Prize 1976), Prof. Stan Prusiner (Nobel Prize
1997), Prof Shirley Lindenbaum (Anthropologist) and British Prof. John Collinge
(Director, MRC Prion Unit, UK).
Kuru: The Science and the Sorcery combines history, science and
anthropology to tell a unique and ongoing ‘history of science’ documentary
spanning five decades. It intertwines the thinking of great minds, locally and
internationally, to reveal how this rare disease in the remote highlands of PNG
exploded to international attention and how Prion research has now revealed we
are all descendants of a remote past of cannibal practices.
Kuru: The Science and the Sorcery Australian scientist Michael Alpers
dedicated over 50 years to researching Kuru, an obscure and incurable brain
disease unique to the Fore people of New Guinea. Kuru was once thought to be a
psychosomatic illness, an infection, a genetic disorder, even a sorcerer's
curse, but Alpers' findings pointed to cannibalism as the culprit. Yet a recent
discovery has proven to be even more disturbing: the malady is linked to mad cow
disease and its human equivalent, variant CJD. With a decades-long incubation
period, could a larger outbreak be on its way?
human flesh taste very sweet
KURU EPIDEMIOLOGICAL PATROLS
Michael Alpers
First Reports
People of the Kuru region part 1
boy playing with animal bladder, blowing it up like a balloon. ...
People of the Kuru region part 2
Monday, November 19, 2012
Prion in Saliva of Bovine Spongiform Encephalopathy–Infected Cattle
Aerosols
Prion transmission is usually not considered to be airborne like influenza
or chicken pox. But we and others recently have found that prions can also be
efficiently transmitted to mice through aerosols [5], [6]. Although
aerosol-transmitted prions have never been found under natural conditions, this
finding highlights the necessity of revising the current prion-related biosafety
guidelines and health standards in diagnostic and scientific laboratories being
potentially confronted with prion-infected materials.
Thursday, December 29, 2011
Aerosols An underestimated vehicle for transmission of prion diseases?
PRION
please see more on Aerosols and TSE prion disease here ;
Monday, November 26, 2012
Aerosol Transmission of Chronic Wasting Disease in White-tailed Deer
Simultaneous Onset of Alzheimer's Disease in a Husband and Wife in Their
Mid Fifties: What do We Really Know?
Jonathan Heath1, Lindsay Goicochea2, Mark Smith3, Rudy Castellani4.
1Department of Pathology, University of Maryland; 2University; 3Case Western
Reserve University; 4University of Maryland, Baltimore, Maryland
Whereas the genetic factors influencing the development and expression of
Alzheimer's disease are well characterized, environmental factors are currently
thought to play a marginal role. Such factors as prior closed head injury,
post-menopausal estrogen deficiency, aluminum exposure, smoking, diabetes,
atherosclerotic cardiovascular disease, and diet, among others, confer only a
modest increased risk if any, and are only tangentially considered in the major
pathogenic cascades that are presently hypothesized. We present the simultaneous
onset of Alzheimer's disease in a husband and wife, with both subjects
experiencing cognitive dysfunction within the same month. Both subjects were in
their mid-fifties at the time of presentation, both subjects showed
progressively neurological decline with prominent memory loss, both subjects
experienced myoclonus late in their disease course prompting referral to the
National Prion Disease Pathology Surveillance Center, and both subjects expired
12 years after onset, within two months of each other. Review of the family
pedigree revealed no family history of dementia or other neurologic illnesses in
multiple first degree relatives. The only historical finding of note was that
both subjects had moved out of their home briefly while it was being remodeled,
and both became symptomatic shortly after moving back in. At autopsy, the
subjects had classic advanced Alzheimer's disease, with Braak stage VI pathology
that was otherwise identiical in quantity and distribution of amyloid-beta,
cerebral amyloid angiopathy, and neurofibrillary degeneration. While no specific
toxin or other environmental cause was discerned, these two cases raise the
issue of epigenetic factors in Alzheimer's disease that may be more robust than
current literature indicates.
NEUROLOGY 1998;50:684-688 © 1998 American Academy of Neurology
Creutzfeldt-Jakob disease in a husband and wife
P. Brown, MD, L. Cervenáková, MD, L. McShane, PhD, L. G. Goldfarb, MD, K.
Bishop, BS, F. Bastian, MD, J. Kirkpatrick, MD, P. Piccardo, MD, B. Ghetti, MD
and D. C. Gajdusek, MD From the Laboratory of CNS Studies (Drs. Brown,
Cervenáková, Goldfarb, and Gajdusek), NINDS, and Biometric Research Branch (Dr.
McShane), NCI, National Institutes of Health, Bethesda, MD; the Department of
Obstetrics (K. Bishop), Gynecology and Reproductive Sciences, University of
Texas Houston Health Science Center, Houston, TX; the Department of Pathology
(Dr. Bastian), University of South Alabama Medical Center, Mobile, AL; the
Department of Pathology (Dr. Kirkpatrick), The Methodist Hospital, Houston, TX;
and the Department of Pathology (Drs. Piccardo and Ghetti), Indiana University
School of Medicine, Indianapolis, IN.
Address correspondence and reprint requests to Dr. Paul Brown, Building 36,
Room 5B21, National Institutes of Health, Bethesda, MD 20892.
A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a
1.5-year clinical course. Four and a half years later, his then 55-year-old
widow died from CJD after a 1-month illness. Both patients had typical clinical
and neuropathologic features of the disease, and pathognomonic
proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in
both brains. Neither patient had a family history of neurologic disease, and
molecular genetic analysis of their PrP genes was normal. No medical, surgical,
or dietary antecedent of CJD was identified; therefore, we are left with the
unanswerable alternatives of human-to-human transmission or the chance
occurrence of sporadic CJD in a husband and wife.
--------------------------------------------------------------------------------
Received May 5, 1997. Accepted in final form September 10, 1997.
SEE CJD IN MAN AND HIS CAT ;
[Image] Research letters Volume 352, Number 9134 [Image] 3 October 1998
[Previous] [Next]
[Image][Image]
Simultaneous occurrence of spongiform encephalopathy in a man and his cat
in Italy
[Image]
Gianluigi Zanusso, Ettore Nardelli, Anna Rosati, GianMaria Fabrizi, Sergio
Ferrari, Antonella Carteri, Franco De Simone, Nicola Rizzuto, Salvatore
Monaco
Transmissible spongiform encephalopathies (TSE) encompass inherited,
acquired, and sporadic mammalian neurological disorders, and are characterised
by the conversion of the cellular prion protein (PrP) in an insoluble and
protease-resistant isoform (PrPres). In human TSE, four types of PrPres have
been identified according to size and glycoform ratios, which may represent
different prion strains. Type-1 and type-2 PrPres are associated with sporadic
Creutzfeldt-Jakob disease (CJD), type 3 with iatrogenic CJD, and type 4 with
variant CJD.1,2 There is evidence that variant CJD is caused by the bovine
spongiform encephalopathy (BSE)-prion strain.2-4 The BSE strain has been
identified in three cats with feline spongiform encephalopathy (FSE), a prion
disease which appeared in 1990 in the UK.5 We report the simultaneous occurrence
of sporadic CJD in a man and a new variety of FSE in his cat.
A 60-year-old man, with no unusual dietary habits, was admitted in
November, 1993, because of dysarthria, cerebellar ataxic gait, visual agnosia,
and myoclonus. An electroencephalogram (EEG) showed diffuse theta-delta
activity. A brain magnetic resonance imaging scan was unremarkable. 10 days
later, he was speechless and able to follow only simple commands. Repeat EEGs
showed periodic triphasic complexes. 2 weeks after admission, he was mute,
akinetic, and unable to swallow. He died in early January, 1994.
His 7-year-old, neutered, female shorthaired cat presented in November,
1993, with episodes of frenzy, twitching of its body, and hyperaesthesia. The
cat was usually fed on canned food and slept on its owner's bed. No bites from
the cat were recalled. In the next few days, the cat became ataxic, with
hindquarter locomotor dysfunction; the ataxia got worse and there was diffuse
myoclonus. The cat was killed in mid-January, 1994.
No pathogenic mutations in the patient's PrP gene were found. The patient
and the cat were methionine homozygous at codon 129. Histology of the patient's
brain showed neocortical and cerebellar neuronal loss, astrocytosis, and
spongiosis (figure A). PrP immunoreactivity showed a punctate pattern and
paralleled spongiform changes (figure B). The cat's brain showed mild and focal
spongiosis in deeper cortical layers of all four lobes (figure C), vacuolated
cortical neurons (figure D), and mild astrogliosis. The cerebellar cortex and
the dentate nucleus were gliosed. Immunoreactive PrP showed a punctate pattern
in neocortex, allocortex, and caudate nucleus (figure E). Western blot analysis
of control and affected human and cat brain homogenates showed 3 PrP bands of
27-35 kDa. After digestion with proteinase K and deglycosylation, only samples
from the affected patient and cat showed type-1 PrPres, with PrP glycoform
ratios comparable to those observed in sporadic CJD1 (details available from
author).
[Image]
Microscopic sections of patient and cat brains
A: Occipital cortex of the patient showing moderate spongiform degeneration
and neuronal loss (haematoxylin and eosin) and B: punctate perineuronal pattern
of PrP immunoreactivity; peroxidase immunohistochemistry with monoclonal
antibody 3F4. C: cat parietal cortex showing mild spongiform degeneration
(haematoxylin and eosin).D: vacuolated neurons (arrow, haematoxylin and eosin),
E: peroxidase immunohistochemistry with antibody 3F4 shows punctate perineuronal
deposition of PrP in temporal cortex.
This study shows a spatio-temporal association between human and feline
prion diseases. The clinical features of the cat were different from previously
reported cases of FSE which were characterised by gradual onset of behavioural
changes preceding locomotor dysfunction and ataxia.5 Neuropathological changes
were also at variance with the diffuse spongiosis and vacuolation of brainstem
neurons, seen in FSE.5 The synaptic pattern of PrP deposition, similar in the
cat and in the patient, was atypical for a BSE-related condition. Evidence of a
new type of FSE was further provided by the detection of a type-1 PrPres, other
than the BSE-associated type 4.2 Taken together, our data suggest that the same
agent strain of sporadic CJD was involved in the patient and in his cat.
It is unknown whether these TSE occurred as the result of horizontal
transmission in either direction, infection from an unknown common source, or
the chance occurrence of two sporadic forms.
1 Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypic
variablity in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996; 39: 767-78
[PubMed].
2 Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis
of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996;
383: 685-90 [PubMed].
3 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate
that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501
[PubMed].
4 Hill AF, Desbruslais M, Joiner S, et al. The same prion strain causes
vCJD and BSE. Nature 1997; 389: 448-50 [PubMed].
5 Pearson GR, Wyatt JM, Henderson JP, Gruffydd-Jones TJ. Feline spongiform
encephalopathy: a review. Vet Annual 1993; 33: 1-10.
------------------------------------------------------------------------
Sezione di Neurologie Clinica, Dipartimento di Scienze Neurologiche e della
Visione, Università di Verona, Policlinico Borgo Roma, 37134 Verona, Italy (S
Monaco; e mail rizzuto@Gorgorna.univr.it); and Istituto Zooprofilattico
Sperimentale della Lombardia e dell' Emilia, Brescia
=======================================
Terry S. Singeltary Sr. wrote:
######## Bovine Spongiform Encephalopathy #########
Greetings list members,
ODD that some FELINE in Italy seem to have this same or maybe very similar
phenotype of TSE;
In October 1998 the simultaneous occurrence of spongiform encephalopathy in
a man and his pet cat was reported. The report from Italy noted that the cat did
not display the same clinical features as FSE cases previously seen. Indeed, the
presence of a new type of FSE was suggested. The man was diagnosed as having
sporadic CJD, and neither case (man nor cat) appeared to be affected by a
BSE-related condition.
Case‐to‐case transmission in humans: case reports and series in which
spread through everyday human contact is suggested There are six reports in
which this possible mode of transmission is considered. The most recent is that
of a couple from the USA who had been married for 30 years.47 The husband died
at age 53. He had no relevant family history, but had had a rotator cuff repair
one year before disease onset. His wife developed symptoms four and half years
after her husband's death. She was morbidly obese and had had a previous
hysterectomy, hernia repair and cholecystectomy. Both occasionally ate brains in
the form of ‘kizka’, a type of sausage.
Immunocytochemistry confirmed pathogenic prion protein deposition in brain
tissue from both husband and wife. Full sequencing of the open reading frame of
the PRNP failed to demonstrate any pathogenic mutations. Another suspected
conjugal case has recently been shown not to be CJD. The histopathological
specimens did not stain for prion protein despite the microscopic appearance of
spongiform change.48
Sporadic CJD has been described in two co‐workers who shared a school wing
for 9 months.49 The first was a 48‐year‐old Californian‐born man of Hispanic
American descent who had had a traumatic leg amputation at age 23, but was
otherwise well. The second was a 48‐year‐old Chilean‐born male who had a blood
transfusion 6 months before onset of symptoms, and was known to eat lambs'
brains. The first patient developed symptoms 5 months after the last contact
with his colleague and was confirmed to have spCJD 2 months after this. The
second patient developed symptoms months later and died 9 months after the last
contact with his colleague.
An English woman, who died of CJD, histologically confirmed at post mortem,
was known to have contact with several affected members of a family with
familial CJD and was related to them by marriage.39 She had known one of the
family, who later died of CJD and had afternoon tea with her at family
gatherings, twice a year, for 20 years, as well as visiting in her final
illness. The woman herself died 12 years later. There is another similar case of
probable CJD, reported in a Chilean woman who died 13 years after contact with a
family with familial CJD. No details of contact are given. A third case of death
from CJD in someone related in marriage to a family with familial CJD has been
reported in France, in a Tunisian family. No details are given with regards to
family history or contact.21 What is notable about these last three incidents of
supposed infection by social contact is that all have occurred in association
with familial CJD. Although these patients were not known to have been
genetically related to their spouses, the possibility that they came from the
same gene pool cannot be dismissed.
Science
Coincident Scrapie Infection and Nephritis Lead to Urinary Prion
Excretion
Seeger, Harald; Heikenwalder, Mathias; Zeller, Nicolas; Kranich, Jan;
Schwarz, Petra; Gaspert, Ariana; Seifert, Burkhardt; Miele, Gino; Aguzzi,
Adriano
Date of publication 2005 Language English Notes Includes references Medium
text Pagination p. 324-326. Journal Title Science ISSN 0036-8075 Volume/Issue
2005 Oct. 14, v. 310, no. 5746 Abstract Prion infectivity is typically
restricted to the central nervous and lymphatic systems of infected hosts, but
chronic inflammation can expand the distribution of prions. We tested whether
chronic inflammatory kidney disorders would trigger excretion of prion
infectivity into urine. Urinary proteins from scrapie-infected mice with
lymphocytic nephritis induced scrapie upon inoculation into noninfected
indicator mice. Prionuria was found in presymptomatic scrapie-infected and in
sick mice, whereas neither prionuria nor urinary PrP[superscript Sc] was
detectable in prion-infected wild-type or PrP[superscript C]-overexpressing
mice, or in nephritic mice inoculated with noninfectious brain. Thus, urine may
provide a vector for horizontal prion transmission, and inflammation of
excretory organs may influence prion spread.
--------------------------------------------------------------------------------
Source: Information Systems Division, National Agricultural Library (United
States of America) NAL/USDA 10301 Baltimore Avenue Beltsville, Md. 20705 Email:
access@nal.usda.gov; URL: http://www.nal.usda.gov/
--------------------------------------------------------------------------------
AGRIS 2013 - FAO of the United Nations
Research Article
Detection of Prion Protein in Urine-Derived Injectable Fertility Products
by a Targeted Proteomic Approach
Alain Van Dorsselaer mail, * E-mail: neil.cashman@vch.ca (NRC);
vandors@unistra.fr (AVD)
Affiliation: Laboratoire de Spectrométrie de Masse Bio-Organique,
Université de Strasbourg, IPHC, CNRS, UMR7178, Strasbourg, France
X Christine Carapito, Affiliation: Laboratoire de Spectrométrie de Masse
Bio-Organique, Université de Strasbourg, IPHC, CNRS, UMR7178, Strasbourg, France
X François Delalande, Affiliation: Laboratoire de Spectrométrie de Masse
Bio-Organique, Université de Strasbourg, IPHC, CNRS, UMR7178, Strasbourg, France
X Christine Schaeffer-Reiss, Affiliation: Laboratoire de Spectrométrie de
Masse Bio-Organique, Université de Strasbourg, IPHC, CNRS, UMR7178, Strasbourg,
France
X Daniele Thierse, Affiliation: Laboratoire de Spectrométrie de Masse
Bio-Organique, Université de Strasbourg, IPHC, CNRS, UMR7178, Strasbourg, France
X Hélène Diemer, Affiliation: Laboratoire de Spectrométrie de Masse
Bio-Organique, Université de Strasbourg, IPHC, CNRS, UMR7178, Strasbourg, France
X Douglas S. McNair, Affiliation: Cerner Corporation, Kansas City,
Missouri, United States of America
X Daniel Krewski, Affiliation: McLaughlin Centre for Population Health Risk
Assessment, University of Ottawa, Ontario, Canada
X Neil R. Cashman mail
snip...
Conclusions/Significance The presence of protease-sensitive prion protein
in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP
suggests that prions may co-purify in these products. Intramuscular injection is
a relatively efficient route of transmission of human prion disease, and young
women exposed to prions can be expected to survive an incubation period
associated with a minimal inoculum. The risks of urine-derived fertility
products could now outweigh their benefits, particularly considering the
availability of recombinant products.
Citation: Van Dorsselaer A, Carapito C, Delalande F, Schaeffer-Reiss C,
Thierse D, et al. (2011) Detection of Prion Protein in Urine-Derived Injectable
Fertility Products by a Targeted Proteomic Approach. PLoS ONE 6(3): e17815.
doi:10.1371/journal.pone.0017815
Editor: Jean-Luc Darlix, Institut National de la Santé et de la Recherche
Médicale, France
Received: November 12, 2010; Accepted: February 10, 2011; Published: March
23, 2011
Discussion Using classical proteomic analyses, prion protein was detected
for the first time in two u-hCG preparations, and was among 33 different
non-gonadotropin proteins identified as contaminants of these pharmaceutical
products. In contrast, r-hCG preparations were negative for prion
proteins.
In one of the two u-hCG products tested, human prion protein was among the
ten major contaminants. The fact that prion protein sequences were identified in
several spots on our 2D electrophoresis gels is likely due to the presence of
heterogeneous glycosylation and degraded prion protein forms. It is also worth
noting that in the u-hCG preparation of manufacturer A, plasminogen was
identified among the urinary impurities; plasminogen has been identified as a
binding protein for disease-associated prion protein [17].
Both hMG and hMG-HP were tested using 2D gel electrophoresis. The results
confirmed that the two hMGs tested were less pure than hMG-HP and contained a
large number of total proteins (mainly represented by urinary impurities).
Non-gonadotropin proteins present in hMG-HP products were identified by MS,
resulting in 34 co-purified contaminants. Only gonadotropin proteins were seen
in all the recombinant preparations analyzed by 2D gel electrophoresis. Using
this 2D-gel/LC-MS/MS proteomic workflow, prion proteins were identified only in
u-hCG and not in hMG-HP preparations. In parallel, a targeted proteomic approach
(LC-SRM) was developed to detect human prion proteins which are sensitive to
proteases. The method was optimized to provide quantitative data in each
container of product. This is the most sensitive MS-based quantification
technique currently available with a limit of detection in the low femtomolar
range. This approach for prion protein detection, identification and
quantification was used on all gonadotropin pharmaceutical preparations included
in our study, including both urinary (hCG, hMG, hMG-HP) and recombinant
products.
All urine-derived preparations tested, produced by different manufacturers,
showed the presence of human prion proteins in varying amounts. These findings
demonstrate that the purification processes for different urine-derived
preparations are unable to remove prion proteins from the source material and
that the process controls employed do not permit the identification of this
contaminant.
Do the prion protein peptides detected in this study originate from
infectious prions? Preparation of tryptic peptides is preceded by solubilization
in 8M urea, which is adequate to disaggregate and denature the
disease-associated isoform of the prion protein rendering it susceptible to
trypsin digestion. It is also clear that native and diseased isoforms of the
prion protein share affinity for chromatography substrates utilized to purify
peptide hormones [3]. Finally, infectious prions can range down in size to
oligomers of a few dozen prion protein molecules [18], which would be
undetectable by existing biochemical methodologies including MS methods employed
in this study.
Although no cases of human prion disease due to the use of urinary
gonadotropins have been recognized to date, the epidemiological signal for
transmission may be difficult to detect. Each year, more than 300,000 young
women in the US and Canada are prescribed urine-derived gonadotropins for
infertility. Although the Food and Drug Administration and Health Canada once
considered these products to be in the lowest category of risk for prion disease
transmission, the discovery of full infectivity in the urine of nephritic
scrapie-infected mice in 2005 led to new requirements for product labeling and a
review of donor procedures and manufacturing processes. Additional recent
findings suggest that urinary prion excretion can occur without renal pathology
[6], [7]. These results warrant a reassessment as to whether the risks of
urine-derived fertility products could now outweigh their benefits, particularly
considering the availability of recombinant products that do not require human
urine as a substrate.
Although urinary gonadotropins have been previously characterized as safe
[19], [20], this opinion may be overly optimistic in view of the present
findings, supported by results from other recently published studies. Notably,
blood products were once also considered ‘safe’, based on the lack of detectable
prions in vCJD using an inadequately sensitive mouse bioassay [21]. In line with
recent published studies, the 2010 updated World Health Organization tables on
‘Tissue infectivity distribution in transmissible spongiform encephalopathy’
moved urine from the category of ‘Tissues with no detectable infectivity’ to the
category of ‘Lower-infectivity tissue’ (the latter category includes blood)
[22].
Current urine collection systems pool the urine of thousands of donors and,
unlike the blood collection system, do not allow for donor tracing. There is
also no mechanism of ensuring that the designated donor is actually the one who
provides the urine, as donation is normally done at home. However, even if donor
management and tracing were flawless, the fact that prionuria may exist well
before the onset of clinically overt prion disease, without being detectable by
current methods, remains a cause for concern. Furthermore, the now indisputable
detection of prions in urine of experimental animals, the lack of a species
barrier for human-to-human transmission, the relative efficiency of the
intramuscular injection route for prion transmission, and the young age of
fertility drug recipients all support application of the ‘precautionary
principle’ for urinary derived pharmaceuticals. As risk management paradigms
shift towards more proactive approaches intended to ‘anticipate and prevent’
emerging risks [23]–[26], a careful examination of the risk of transmission of
human prion disease through the use of urine-derived hormones and peptides would
appear to be warranted.
Friday, March 25, 2011
Detection of Prion Protein in Urine-Derived Injectable Fertility Products
by a Targeted Proteomic Approach
HD.13: CWD infection in the spleen of humanized transgenic mice
Liuting Qing and Qingzhong Kong Case Western Reserve University; Cleveland,
OH USA
Chronic wasting disease (CWD) is a widespread prion disease in free-ranging
and captive cervid species in North America, and there is evidence suggesting
the existence of multiple CWD strains. The susceptibility of human CNS and
peripheral organs to the various CWD prion strains remains largely unclear.
Current literature suggests that the classical CWD strain is unlikely to infect
human brain, but the potential for peripheral infection by CWD in humans is
unknown. We detected protease-resistant PrpSc in the spleens of a few humanized
transgenic mice that were intracerebrally inoculated with natural CWD isolates,
but PrpSc was not detected in the brains of any of the CWD-inoculated mice. Our
ongoing bioassays in humanized Tg mice indicate that intracerebral challenge
with such PrpSc-positive humanized mouse spleen already led to prion disease in
most animals. ***These results indicate that the CWD prion may have the
potential to infect human peripheral lymphoid tissues.
=====
HD.12: Comparative study of the distribution of the prion protein in the
squirrel monkey (Saimiri sciureus) following experimental challenge with variant
and sporadic CJD
Diane L. Ritchie,1 Paul Brown,2 Susan Gibson,3 Thomas R. Kreil,4 Christian
Abee3 and James W. Ironside1 1National CJD Surveillance Unit; Edinburgh, UK;
2Bethesda; Bethesda, MD USA; 3Deparment of Comparative Medicine; University of
South Alabama; Mobile, AL USA; 4Baxter Bioscience; Vienna, Austria
Introduction, Reports suggest that the number of tissues and organs showing
the presence of the abnormal prion protein (PrPTSE) in variant CJD (vCJD)
patients may be greater than previously thought. A limited peripheral
involvement in some cases of sporadic CJD (sCJD) has also been reported. This
accumulation of PrPTSE outside the brain has raised concerns about the possible
iatrogenic transmission risk of vCJD. The squirrel monkey (Saimiri sciureus) has
been shown to be highly susceptible to experimental challenge with human prion
disease. Neuropathological and biochemical analyses of CNS tissue have shown
that sCJD and vCJD can be distinguished in the squirrel monkey and that many of
the strain characteristics that define these agents are conserved after
transmission. Following on from these initial studies, immunohistochemistry and
western blot analysis were performed on a wide range of peripheral tissues
including, lymphoreticular tissues and peripheral neural tissue to establish the
full-body distribution of PrPTSE in this primate animal model. Materials and
Methods. Brain homogenates from sCJD or vCJD patients were inoculated into the
frontal cortex of squirrel monkeys. Animals were kept under constant clinical
surveillance. At post-mortem, formalin fixed CNS tissue and a wide range of
peripheral tissues were taken for immunohistochemical analysis together with
frozen tissues taken for the biochemical detection of PrPTSE. Results.
Immunohistochemical analysis showed no evidence of PrPTSE deposition in
peripheral tissues in either variant or sporadic CJD-infected animals. However,
western blot assays detected PrPTSE in the spleen of a proportion of the vCJD-
infected animals. The PrPTSE isotype resembled that detected in CNS tissue from
the vCJD- infected animals and from human vCJD cases. ***In addition, western
blot analysis detected PrPTSE in the spleen of a single animal following
challenge with sporadic CJD. The PrPTSE type in this animal resembled that found
in CNS tissue from the same animal, with a PrPTSE type similar to that found in
human sCJD type 1 cases. Conclusion. This study confirms the accumulation of
PrPTSE in the CNS and spleen of a proportion of squirrel monkeys infected
intra-cerebrally with human vCJD. Furthermore, this study extends the evidence
that there may be a peripheral involvement in some cases of sCJD. PrPTSE typing
confirms the conservation of PrPTSE type on transmission to the squirrel monkey
and suggests that there are no tissue-specific adaptations in the biochemical
phenotype of the agent strain following primate-to-primate transmission.
=====
Oral.15: Molecular barriers to zoonotic prion transmission: Comparison of
the ability of sheep, cattle and deer prion disease isolates to convert normal
human prion protein to its pathological isoform in a cell-free system
Marcelo A.Barria,1 Aru Balachandran,2 Masanori Morita,3 Tetsuyuki
Kitamoto,4 Rona Barron,5 Jean Manson,5 Richard Kniqht,1 James W. lronside1 and
Mark W. Head1 1National CJD Research and Surveillance Unit; Centre for Clinical
Brain Sciences; School of Clinical Sciences; The University of Edinburgh;
Edinburgh, UK; 2National and OIE Reference Laboratory for Scrapie and CWD;
Canadian Food Inspection Agency; Ottawa Laboratory; Fallowfield. ON Canada;
3Infectious Pathogen Research Section; Central Research Laboratory; Japan Blood
Products Organization; Kobe, Japan; 4Department of Neurological Science; Tohoku
University Graduate School of Medicine; Sendai. Japan; 5Neurobiology Division;
The Roslin Institute and R(D)SVS; University of Edinburgh; Easter Bush;
Midlothian; Edinburgh, UK
Background. Bovine spongiform encephalopathy (BSE) is a known zoonotic
prion disease, resulting in variant Creurzfeldt- Jakob disease (vCJD) in humans.
In contrast, classical scrapie in sheep is thought to offer little or no danger
to human health. However, a widening range of prion diseases have been
recognized in cattle, sheep and deer. The risks posed by individual animal prion
diseases to human health cannot be determined a priori and are difficult to
assess empirically. The fundamemal event in prion disease pathogenesis is
thought to be the seeded conversion of normal prion protein (PrPC) to its
pathological isoform (PrPSc). Here we report the use of a rapid molecular
conversion assay to test whether brain specimens from different animal prion
diseases are capable of seeding the conversion of human PrPC ro PrPSc. Material
and Methods. Classical BSE (C-type BSE), H-type BSE, L-type BSE, classical
scrapie, atypical scrapie, chronic wasting disease and vCJD brain homogenates
were tested for their ability to seed conversion of human PrPC to PrPSc in
protein misfolding cyclic amplification (PMCA) reactions. Newly formed human
PrPSc was detected by protease digestion and western blotting using the antibody
3F4. Results. C-type BSE and vCJD were found to efficiently convert PrPC to
PrPSc. Scrapie failed to convert human PrPC to PrPSc. Of the other animal prion
diseases tested only chronic wasting disease appeared to have the capability ro
convert human PrPC to PrPSc. The results were consistent whether the human PrPC
came from human brain, humanised transgenic mouse brain or from cultured human
cells and the effect was more pronounced for PrPC with methionine at codon 129
compared with that with valine. Conclusion. Our results show that none of the
tested animal prion disease isolates are as efficient as C-type BSE and vCJD in
converting human prion protein in this in vitro assay. ***However, they also
show that there is no absolute barrier ro conversion of human prion protein in
the case of chronic wasting disease.
=====
Invited.16: Studies of chronic wasting disease transmission in cervid and
non-cervid species
Edward A, Hoover,1 Candace K. Mathiason,1 Davin M. Henderson,1 Nicholas J.
Haley,1 Davis M. Seelig,1 Nathaniel D. Denkers,1 Amy V. Nalls,1 Mark D. Zabe,1
Glenn C. Telling,1 Fernando Goni2 and Thomas Wisniewski,2 1Prion Research
Center; Colorado State University; Fort Collins, CO USA; 2New York University
School of Medicine; New York, NY USA
How and why some misfolded proteins become horizontally transmitted agents
and occasionally cross species barriers are issues fundamental to understanding
prion disease. Chronic wasting disease (CWD) of cervids is perhaps a prototype
of horizontal prion transmission, encompassing efficient mucosal uptake,
lymphoid amplification, neuroinvasion, peripheralization, and dissemination via
mucosal excretion. Efficient mucosal transmission of CWD in deer has been
demonstrated by oral, nasal, aerosol, and indirect contact exposure. In
addition, other studies (Mathiason CK, et al.) reported at the symposium support
a significant role for pre- and/or postnatal transmission of CWD from doe to
offspring. Accumulating, yet still incomplete, evidence also suggests that the
period of relatively covert CWD infection may be longer than originally thought.
Given the above, minimally invasive sensitive assays based on body fluids from
live animals would aid substantially in understanding the biology of CWD. We
have been applying seeded realtirne quaking-induced amplification of recombinant
PrP substrates (i.e., RT-QuIC methodology) to: (1) investigate antemortem CWD
detection, and (2) model PrP-based species barriers and trans-species
adaptation-topics we previously explored using sPMCA and in vivo bioassays. At
this symposium, we report sensitive and specific detection CWD prions in saliva,
urine, blood (Mathiason lab), and rectal and pharyngeal lymph node samples
(Haley NJ, et al.) from pre-symptomatic and symptomatic experimentally and
naturally exposed deer. Other ongoing studies are employing RT-QuIC methodology
to model amplification barriers among CWD, FSE, BSE, and CJD prions using
cervine, feline, bovine, human, and promiscuous rPrP substrates and the above
species prion seeds, cellular co-factors, and transgenic mice. Finally, in
collaboration with the Wisniewski laboratory, we are conducting of experimental
CWD vaccination studies in deer employing oral administration of an attenuated
Salmonella vector expressing cervid PrP epitopes.
=====
AD.06: Detecting prions in the brain and blood of TSE-infected deer and
hamsters
Alan Elder,1 Davin Henderson,1 Anca Selariu,1 Amy Nalls,1 Byron Caughey,2
Richard Bessen,1 Jason Bartz3 and Candace Mathiason1 1Colorado State University;
Fort Collins, CO USA; 2NIH Rocky Mountain Laboratories; Hamilton, MT USA;
3Creighton University; Omaha, NE USA
While large quantities of protease resistant prion protein (PrPres) can be
demonstrated by western blot or IHC in lymphoid biopsies or post-mortem brain
tissues harvested from prion-infected animals, these conventional assays are
less reliable as means to detect the small quantities of prions thought to be
present in bodily fluids or associated with early and asymptomatic phases of TSE
disease. The Real Time-Quaking Induced Conversion (RT-QuIC) assay is capable of
detecting prions at concentrations below the level of sensitivity of
conventional assays and provides a real-time fluorescent readout negating the
use of proteases. We have made modifications to the RT-QuIC assay to utilize it
for the detection of PrPres in brain and blood harvested from various species
infected with prions. In this study, we analyzed CWD-infected deer and
CWD/TME-infected hamster whole blood to determine the effect of: (1) various
anticoagulants, (2) freezing and (3) NaPTA precipitation. Brain tissue and blood
collected from naive deer and hamsters served as negative controls. We were able
to demonstrate amplifiable prions in (1) brain and blood samples harvested from
CWD/TME-infected animals, (2) heparinized blood, (3) frozen vs. fresh blood and
(4) NaPTA treated samples. The RT-QuIC assay is able to detect PrPres in various
species of animals and shows promise as an antemortem diagnostic tool for
blood-borne TSEs.
=====
Oral.08: Mother to offspring transmission of chronic wasting disease in
Reeve's Muntjac deer
Amy Nalls,1 Erin McNulty,1 Jenny Powers,2 Davis Seelig,1 Clare Hoover,1
Nicholas Haley,1 Jeanette Hayes-Klug,1 Kelly Anderson,1 Paula Stewart,3 Wilfred
Goldmann,3 Edward A. Hoover1 and Candace K. Mathiason1 1Colorado State
University; Fort Collins, CO USA; 2National Park Service; Fort Collins, CO USA;
3The Roslin Institute and Royal School of Veterinary Studies; Edinburgh, UK
To investigate the role mother to offspring transmission plays in chronic
wasting disease (CWD), we have developed a cervid model employing the Reeve's
muntjac deer (Muntiacus reevesi). Eight muntjac doe were orally inoculated with
CWD and tested PrPCWD lymphoid positive by 4 mo post infection. Fourteen fawns
were born to these eight CWD-infected doe-3 were born viable, 6 were born
non-viable and 5 were harvested as fetuses from early or end-stage CWD-infected
doe. All three viable fawns have demonstrated CWD IHC lymphoid biopsy positivity
between 43 d post birth and 11 mo post birth. Two of these three CWD positive
viable offspring have developed clinical signs consistent with TSE disease
(28-33 mo post birth). Moreover, CWD prions have been detected by sPMCA in 11 of
16 tissues harvested from 6 full-term non-viable fawns and in 7 of 11 fetal
tissues harvested in utero from the second and third trimester fetuses.
Additional tissues and pregnancy related fluids from doe and offspring are being
analyzed for CWD prions. In summary, using the muntjac deer model we have
demonstrated CWD clinical disease in offspring born to CWD-infected doe, and in
utero transmission of CWD from mother to offspring. These studies provide basis
to further investigate the mechanisms of maternal transfer of prions.
=====
AD.63: Susceptibility of domestic cats to chronic wasting disease
Amy V.Nalls,1 Candace Mathiason,1 Davis Seelig,2 Susan Kraft,1 Kevin
Carnes,1 Kelly Anderson,1 Jeanette Hayes-Klug1 and Edward A. Hoover1 1Colorado
State University; Fort Collins, CO USA; 2University of Minnesota; Saint Paul, MN
USA
Domestic and nondomestic cats have been shown to be susceptible to feline
spongiform encephalopathy (FSE), almost certainly caused by consumption of
bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and
free-ranging nondomestic felids scavenge cervid carcasses, including those in
areas affected by chronic wasting disease (CWD), we evaluated the susceptibility
of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5
cats each were inoculated either intracerebrally (IC) or orally (PO) with
CWD-infected deer brain. At 40 and 42 mo post-inoculation, two IC-inoculated
cats developed signs consistent with prion disease, including a stilted gait,
weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail
tremors, and ataxia, and progressed to terminal disease within 5 mo. Brains from
these two cats were pooled and inoculated into cohorts of cats by IC, PO, and
intraperitoneal and subcutaneous (IP/SC) routes. Upon subpassage, feline-adapted
CWD (FelCWD) was transmitted to all IC-inoculated cats with a decreased
incubation period of 23 to 27 mo. FelCWD was detected in the brains of all the
symptomatic cats by western blotting and immunohistochemistry and abnormalities
were seen in magnetic resonance imaging, including multifocal T2 fluid
attenuated inversion recovery (FLAIR) signal hyper-intensities, ventricular size
increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4
IP/SQ and 2 of 4 PO inoculared cats have developed abnormal behavior patterns
consistent with the early stage of feline CWD. These results demonstrate that
CWD can be transmitted and adapted to the domestic cat, thus raising the issue
of potential cervid-to- feline transmission in nature.
Monday, June 17, 2013
Early detection of chronic wasting disease prions in urine of
pre-symptomatic deer by real-time quaking-induced conversion assay
Thursday, April 12, 2012
Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to
2010
Eurosurveillance, Volume 17, Issue 15, 12 April 2012
Research articles
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
Sunday, June 9, 2013
TSEAC March 14, 2013: Transmissible Spongiform Encephalopathies Advisory
Committee Meeting Webcast
Tuesday, May 21, 2013
CJD, TSE, PRION, BLOOD Abstracts of the 23rd Regional Congress of the
International Society of Blood Transfusion, Amsterdam, The Netherlands, June
2-5, 2013
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
Thursday, October 25, 2012
Current limitations about the cleaning of luminal endoscopes and TSE prion
risk factors there from
Article in Press
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to
Bramble et al
Evidence For CJD/TSE Transmission Via Endoscopes
From Terry S. Singletary, Sr flounder@wt.net 1-24-3
Tuesday, July 31, 2012
11 patients may have been exposed to fatal disease Creutzfeldt-Jakob
Disease CJD Greenville Memorial Hospital
Thursday, August 02, 2012
CJD case in Saint John prompts letter to patients Canada CJD case in Saint
John prompts letter to patients
Saturday, February 12, 2011
Another Pathologists dies from CJD, another potential occupational death ?
another happenstance of bad luck, a spontaneous event from nothing, or
friendly fire ???
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
Sunday, May 10, 2009
Meeting of the Transmissible Spongiform Encephalopathies Committee On June
12, 2009 (Singeltary submission)
Thursday, January 29, 2009
Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan,
1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number
2-February 2009 Research
Wednesday, August 20, 2008
Tonometer disinfection practice in the United Kingdom: A national survey
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007
(occupational exposure to prion diseases)
Monday, December 31, 2007
Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in
Endodontic Practice in Absence of Adequate Prion Inactivation
Subject: CJD: update for dental staff
Date: November 12, 2006 at 3:25 pm PST
1: Dent Update. 2006 Oct;33(8):454-6, 458-60.
CJD: update for dental staff.
Friday, July 19, 2013
Beaumont Hospital in Dublin assessing patients for CJD
Saturday, September 21, 2013
CJD CONFIRMED in patient at New Hampshire Department of Health and Human
Services (DHHS), Catholic Medical Center (CMC), and the Manchester Health
Department (MHD)
Thursday, September 26, 2013
Minimise transmission risk of CJD and vCJD in healthcare settings Guidance
Wednesday, June 19, 2013
Spreading of tau pathology in Alzheimer's disease by cell-to-cell
transmission
MAD COW TESTING ONLY CATCHES SOME MAD COWS
SPREADING IT ALL AROUND
Saturday, October 19, 2013
***A comparative study of modified confirmatory techniques and additional
immuno-based methods for non-conclusive autolytic Bovine spongiform
encephalopathy cases
Wednesday, September 25, 2013
Inspections, Compliance, Enforcement, and Criminal Investigations BSE TSE
PRION 2013
Wednesday, October 09, 2013
WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281
in compensation REVISED
Thursday, October 10, 2013
CJD REPORT 1994 increased risk for consumption of veal and venison and lamb
Monday, October 14, 2013
Researchers estimate one in 2,000 people in the UK carry variant CJD
proteins
Friday, August 16, 2013
*** Creutzfeldt-Jakob disease (CJD) biannual update August 2013 U.K. and
Contaminated blood products induce a highly atypical prion disease devoid of
PrPres in primates
WHAT about the sporadic CJD TSE proteins ?
WE now know that some cases of sporadic CJD are linked to atypical BSE and
atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all
it’s sub-types $$$
Sunday, August 11, 2013
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing
an extreme increase of 48% between 2008 and 2010
Sunday, July 21,
2013
Welsh Government and Food Standards Agency Wales
Joint Public Consultation on the Proposed Transmissible Spongiform
Encephalopathies (Wales) Regulations 2013 Singeltary Submission WG18417
Sunday, October 13, 2013
CJD TSE Prion Disease Cases in Texas by Year, 2003-2012
Tuesday, September 24, 2013
NORDION (US), INC., AND BIOAXONE BIOSCIENCES, INC., Settles $90M Mad Cow
TSE prion Contamination Suit Cethrin(R)
Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 1
of 15
Monday, October 21, 2013
WTO Mad cow disease (No 193)
Saturday, July 6, 2013
Small Ruminant Nor98 Prions Share Biochemical
Features with Human Gerstmann-Sträussler-Scheinker Disease and Variably
Protease-Sensitive Prionopathy
Research Article
Thursday, March 29, 2012
atypical Nor-98 Scrapie has spread from coast to
coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio,
Texas
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to
Sheep
Volume 17, Number 5-May 2011 However, work with
transgenic mice has demonstrated the potential susceptibility of pigs, with the
disturbing finding that the biochemical properties of the resulting PrPSc have
changed on transmission (40).
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and
Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
(hmmm, this is getting interesting now...TSS)
Sporadic CJD type 1 and atypical/ Nor98 scrapie are
characterized by fine (reticular) deposits,
see also ;
All of the Heidenhain variants were of the
methionine/ methionine type 1 molecular subtype.
see full text ;
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and
Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
Friday, March 09, 2012
Experimental H-type and L-type bovine spongiform
encephalopathy in cattle: observation of two clinical syndromes and diagnostic
challenges
Research article
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy
characterized by plaques and glial- and stellate-type prion protein deposits
Tuesday, August 22, 2006
BSE ATYPICAL TEXAS AND ALABAMA UPDATE JANUARY 20, 2007
2009 UPDATE ON ALABAMA MAD COW FOUND IN 2006
http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM
Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform
Encephalopathies (BSE): Public Health Risk Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE,
or less virulent than cBSE? just curious.....''
Professor Kong reply ;
.....snip
''As to the H-BSE, we do not have sufficient data to say one way or
another, but we have found that H-BSE can infect humans. I hope we could publish
these data once the study is complete. Thanks for your interest.''
Best regards,
Qingzhong Kong, PhD Associate Professor Department of Pathology Case
Western Reserve University Cleveland, OH 44106 USA
END...TSS
Thursday, December 04, 2008 2:37 PM
"we have found that H-BSE can infect humans."
personal communication with Professor Kong. ...TSS
BSE-H is also transmissible in our humanized Tg mice.
The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
please see below from PRION2013 ;
*** This study imply the possibility that the novel BSE prions with high
virulence in cattle will be emerged during intraspecies transmission.
AD.56: The emergence of novel BSE prions by serial passages of H-type BSE
in bovinized mice
Kentaro Masujin, Naoko Tabeta, Ritsuko Miwa, Kohtaro Miyazawa, Hiroyuki
Okada, Shirou Mohri and Takashi Yokoyama
National Institute of Animal Health; Tsukuba, Japan
H-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE,
and has been detected in several European countries, and North America.
Transmission studies of H-type BSE led to the emergence of the classical BSE
(C-BSE) phenotypes during passages in inbred wild type and bovinized
PrP-overexpressing transgenic mice. In this study, we conducted serial passages
of Canadian H-type BSE isolate in bovinized PrP-overexpressing transgenic mice
(TgBoPrP). H-type BSE isolate was transmitted to TgBoPrP with incubation periods
of 320 ± 12.2 d at primary passage. The incubation period of 2nd and 3rd passage
were constant (~= 220 d), no clear differences were observed in their biological
and biochemical properties. However, at the forth passage, 2 different BSE
phenotypes were confirmed; one is shorter survival times (109 ± 4 d) and the
other is longer survival times. TgBoPrP mice with longer incubation period
showed the H-type phenotype of PrPsc profile and pathology. However, those of
shorter incubation period were different phenotypes from previously existed BSE
prions (C-BSE, L-type BSE, and H-type BSE). *** This study imply the possibility
that the novel BSE prions with high virulence in cattle will be emerged during
intraspecies transmission.
please see ;
Thursday, August 15, 2013
The emergence of novel BSE prions by serial passages of H-type BSE in
bovinized mice
Wednesday, September 25, 2013
Presence of subclinical infection in gene-targeted human prion protein
transgenic mice exposed to atypical BSE
*** TESTING MAD COWS ONLY CONFIRMS _SOME_ MAD COWS ***
HOW MANY WERE MISSED, AND CONSUMBED ???
Saturday, October 19, 2013
A comparative study of modified confirmatory techniques and additional
immuno-based methods for non-conclusive autolytic Bovine spongiform
encephalopathy cases
Friday, October 25, 2013
*** UK FSA TSE BSE Board meeting agenda: 5 November 2013 ***
P03.141
Aspects of the Cerebellar Neuropathology in
Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1;
Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary
Institute,
Norway Nor98 is a prion disease of old sheep and
goats. This atypical form of scrapie was first described in Norway in 1998.
Several features of Nor98 were shown to be different from classical scrapie
including the distribution of disease associated prion protein (PrPd)
accumulation in the brain. The cerebellum is generally the most affected brain
area in Nor98. The study here presented aimed at adding information on the
neuropathology in the cerebellum of Nor98 naturally affected sheep of various
genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical
(IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic
protein, amyloid, and cell markers for phagocytic cells were conducted. The type
of histological lesions and tissue reactions were evaluated. The types of PrPd
deposition were characterized. The cerebellar cortex was regularly affected,
even though there was a variation in the severity of the lesions from case to
case. Neuropil vacuolation was more marked in the molecular layer, but affected
also the granular cell layer. There was a loss of granule cells. Punctate
deposition of PrPd was characteristic. It was morphologically and in
distribution identical with that of synaptophysin, suggesting that PrPd
accumulates in the synaptic structures. PrPd was also observed in the granule
cell layer and in the white matter. The pathology features of Nor98 in the
cerebellum of the affected sheep showed similarities with those of sporadic
Creutzfeldt-Jakob disease in humans.
***The pathology features of Nor98 in the cerebellum
of the affected sheep showed similarities with those of sporadic
Creutzfeldt-Jakob disease in humans.
PR-26
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF
GSS
R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M.
Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1
Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public
Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della
Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of
Pathology, Oslo, Norway
Molecular variants of PrPSc are being increasingly
investigated in sheep scrapie and are generally referred to as "atypical"
scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98
seems to be the best identified. We studied the molecular properties of Italian
and Norwegian Nor98 samples by WB analysis of brain homogenates, either
untreated, digested with different concentrations of proteinase K, or subjected
to enzymatic deglycosylation. The identity of PrP fragments was inferred by
means of antibodies spanning the full PrP sequence. We found that undigested
brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa
(PrP11), truncated at both the C-terminus and the N-terminus, and not
N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP
(FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased
levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that
FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely
digested even at the highest concentrations, similarly to PrP27-30 associated
with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11
and a fragment of 17 kDa with the same properties of PrP11, that was tentatively
identified as a dimer of PrP11. Detergent solubility studies showed that PrP11
is insoluble in 2% sodium laurylsorcosine and is mainly produced from
detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie
isolates, we found that a sample with molecular and pathological properties
consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when
the brain was analysed by PrPSc immunohistochemistry. Taken together, our
results show that the distinctive pathological feature of Nor98 is a PrP
fragment spanning amino acids ~ 90-155. This fragment is produced by successive
N-terminal and C-terminal cleavages from a full-length and largely
detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK
digestion.
*** Intriguingly, these conclusions suggest that some
pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker
disease.
119
A newly identified type of scrapie agent can
naturally infect sheep with resistant PrP genotypes
Annick Le Dur*,?, Vincent Béringue*,?, Olivier
Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶,
Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,??
+Author Affiliations
*Virologie Immunologie Moléculaires and ?Génétique
Biochimique et Cytogénétique, Institut National de la Recherche Agronomique,
78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la
Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte
Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire
des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon,
France; **Pathologie Infectieuse et Immunologie, Institut National de la
Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology,
National Veterinary Institute, 0033 Oslo, Norway
***Edited by Stanley B. Prusiner, University of
California, San Francisco, CA (received for review March 21, 2005)
Abstract Scrapie in small ruminants belongs to
transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of
fatal neurodegenerative disorders that affect humans and animals and can
transmit within and between species by ingestion or inoculation. Conversion of
the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a
misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and
pathogenesis. The intensified surveillance of scrapie in the European Union,
together with the improvement of PrPSc detection techniques, has led to the
discovery of a growing number of so-called atypical scrapie cases. These include
clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual
pathological and PrPSc molecular features and "cases" that produced discordant
responses in the rapid tests currently applied to the large-scale random
screening of slaughtered or fallen animals. Worryingly, a substantial proportion
of such cases involved sheep with PrP genotypes known until now to confer
natural resistance to conventional scrapie. Here we report that both Nor98 and
discordant cases, including three sheep homozygous for the resistant PrPARR
allele (A136R154R171), efficiently transmitted the disease to transgenic mice
expressing ovine PrP, and that they shared unique biological and biochemical
features upon propagation in mice. *** These observations support the view that
a truly infectious TSE agent, unrecognized until recently, infects sheep and
goat flocks and may have important implications in terms of scrapie control and
public health.
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
Authors
Andreoletti O., Herva M. H., Cassard H., Espinosa J.
C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F.,
Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de
Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif
sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum,
0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly,
France.
Content
Atypical scrapie is a TSE occurring in small
ruminants and harbouring peculiar clinical, epidemiological and biochemical
properties. Currently this form of disease is identified in a large number of
countries. In this study we report the transmission of an atypical scrapie
isolate through different species barriers as modeled by transgenic mice (Tg)
expressing different species PRP sequence.
The donor isolate was collected in 1995 in a French
commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which
had all neuro-pathological and biochemical characteristics of atypical scrapie.
Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate
retained all the described characteristics of atypical scrapie.
Surprisingly the TSE agent characteristics were
dramatically different v/hen passaged into Tg bovine mice. The recovered TSE
agent had biological and biochemical characteristics similar to those of
atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent
than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able
to develop into this model, albeit with low attack rate on first passage.
Furthermore, after adaptation in the porcine mouse
model this prion showed similar biological and biochemical characteristics than
BSE adapted to this porcine mouse model. Altogether these data indicate.
(i) the unsuspected potential abilities of atypical
scrapie to cross species barriers
(ii) the possible capacity of this agent to acquire
new characteristics when crossing species barrier
These findings raise some interrogation on the
concept of TSE strain and on the origin of the diversity of the TSE agents and
could have consequences on field TSE control measures.
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep
Peripheral Tissues
RESEARCH
Emerging Infectious Diseases • www.cdc.gov/eid • Vol.
17, No. 5, May 2011
Experimental Oral Transmission of Atypical Scrapie to
Sheep
Marion M. Simmons, S. Jo Moore,1 Timm Konold, Lisa
Thurston, Linda A. Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen
A.C. Hawkins, Melanie J. Chaplin, and John Spiropoulos
To investigate the possibility of oral transmission
of atypical scrapie in sheep and determine the distribution of infectivity in
the animals’ peripheral tissues, we challenged neonatal lambs orally with
atypical scrapie; they were then killed at 12 or 24 months. Screening test
results were negative for disease-specifi c prion protein in all but 2
recipients; they had positive results for examination of brain, but negative for
peripheral tissues. Infectivity of brain, distal ileum, and spleen from all
animals was assessed in mouse bioassays; positive results were obtained from
tissues that had negative results on screening. These fi ndings demonstrate that
atypical scrapie can be transmitted orally and indicate that it has the
potential for natural transmission and iatrogenic spread through animal feed.
Detection of infectivity in tissues negative by current surveillance methods
indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and
potentially infectious material may be able to pass into the human food chain.
SNIP...
Although we do not have epidemiologic evidence that
supports the effi cient spread of disease in the fi eld, these data imply that
disease is potentially transmissible under fi eld situations and that spread
through animal feed may be possible if the current feed restrictions were to be
relaxed. Additionally, almost no data are available on the potential for
atypical scrapie to transmit to other food animal species, certainly by the oral
route. However, work with transgenic mice has demonstrated the potential
susceptibility of pigs, with the disturbing fi nding that the biochemical
properties of the resulting PrPSc have changed on transmission (40). The
implications of this observation for subsequent transmission and host target
range are currently unknown.
How reassuring is this absence of detectable PrPSc
from a public health perspective? The bioassays performed in this study are not
titrations, so the infectious load of the positive gut tissues cannot be
quantifi ed, although infectivity has been shown unequivocally. No experimental
data are currently available on the zoonotic potential of atypical scrapie,
either through experimental challenge of humanized mice or any meaningful
epidemiologic correlation with human forms of TSE. However, the detection of
infectivity in the distal ileum of animals as young as 12 months, in which all
the tissues tested were negative for PrPSc by the currently available screening
and confi rmatory diagnostic tests, indicates that the diagnostic sensitivity of
current surveillance methods is suboptimal for detecting atypical scrapie and
that potentially infectious material may be able to pass into the human food
chain undetected.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol.
17, No. 5, May 2011
Saturday, October
19, 2013
ACA Council Meets
to Endorse Several Proposed USAHA Resolutions (CWD TSE PRION DISEASE)
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
TSS
