ISSN 1999-4915
www.mdpi.com/journal/viruses
Article
Molecular Modeling of Prion Transmission to Humans
Etienne Levavasseur 1, Nicolas Privat 1, Juan-Carlos Espinosa Martin 2,
Steve Simoneau 3, Thierry Baron 4, Benoit Flan 3, Juan-Maria Torres 2 and
Stéphane Haïk 1,5,6,* 1 Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC
Univ. Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM,
75013 Paris, France; E-Mails: etienne.levavasseur@inserm.fr (E.L.);
nicolas.privat@inserm.fr (N.P.) 2 Centro de Investigacion en Sanidad Animal,
Carretera de Algete a El Casar, 28130 Madrid, Spain; E-Mails:
espinosa.juan@inia.es (J.-C.E.M.); jmtorres@inia.es (J.-M.T.) 3 LFB
Biomédicaments, 91958 Les Ulis, France; E-Mails: simoneaus@lfb.fr (S.S.);
flan@lfb.fr (B.F.) 4 Agence nationale de sécurité sanitaire de l’alimentation,
de l’environnement et du travail (ANSES), Unité Maladies neurodégénératives,
69394 Lyon, France; E-Mail: thierry.baron@anses.fr 5 AP-HP, Hôpital de la
Pitié-Salpêtrière, Cellule nationale de référence des MCJ, F-75013 Paris, France
6 AP-HP, Hôpital de la Pitié-Salpêtrière, Neuropathologie, 75013 Paris,
France
* Author to whom correspondence should be addressed; E-Mail:
stephane.haik@courriel.upmc.fr; Tel.: +33-142-162-628; Fax: +33-142-161-899.
External Editor: Judd Aiken and Debbie McKenzie
Received: 24 July 2014; in revised form: 26 September 2014/ Accepted: 30
September 2014/ Published: 02 October 2014
Abstract:
Using different prion strains, such as the variant Creutzfeldt-Jakob
disease agent and the atypical bovine spongiform encephalopathy agents, and
using transgenic mice expressing human or bovine prion protein, we assessed the
reliability of protein misfolding cyclic amplification (PMCA) to model
interspecies and genetic barriers to prion transmission. We compared our PMCA
results with in vivo transmission data characterized by attack rates, i.e., the
percentage of inoculated mice that developed the disease. Using 19
seed/substrate combinations, we observed that a significant PMCA amplification
was only obtained when the mouse line used as substrate is susceptible to the
corresponding strain. Our results suggest that PMCA provides a useful tool to
study genetic barriers to transmission and to study the zoonotic potential of
emerging prion strains.
1. Introduction
Prion diseases are fatal transmissible disorders affecting humans and
animals. They are characterized by brain vacuolization, neuronal loss and
accumulation of PrPsc, an abnormal isoform of the host-encoded cellular prion
protein (PrPc). PrPsc has been proposed as the infectious agent, capable of
converting PrPc into PrPsc in an autocatalytical manner [1]. In humans, prion
diseases result from contamination, genetic inheritance or sporadic event. The
host susceptibility is influenced by the prion protein-encoding gene PRNP. For
example, the variant of Creutzfeldt-Jakob disease (vCJD), which has been
associated to the classical bovine spongiform encephalopathy (C-BSE) epidemics
in cattle through contaminated meat product consumption [2], has occurred so far
only in individuals homozygous for methionine at codon 129 of PRNP [3]. However,
this finding has been under debate [4,5]. Studies have investigated interspecies
and genotypic barriers [6,7] using an in vitro PrPsc amplification system named
protein misfolding cyclic amplification (PMCA) [8]. This method allows, in PCR
tubes, the amplification of minute amounts of PrPsc in infected tissues (seed)
in the presence of normal brain homogenate in excess (substrate), after cycles
of incubation and sonication. Then, the final product of the reaction can be
detected after proteinase K digestion by Western blot. While PMCA allows the
amplification of PrPsc, it has also been demonstrated that infectivity was
increased during the reaction [9], and that prion strain properties were
maintained throughout the reaction [10–12]. Brains from humans or transgenic
mice expressing a human PrP with methionine at codon 129 of PRNP provided the
best substrates to amplify vCJD and BSE PrPsc [6,7], suggesting that PMCA may
reproduce faithfully the genotypic transmission barrier. It was thus proposed as
a means to evaluate the zoonotic risk associated with emerging prion strains
(Nor98 in sheep, L-type BSE in cattle). Indeed, while classical BSE strain has
been recognized to be at the origin of vCJD in humans, L-BSE is considered to be
a sporadic form of prion disease in cattle, differing in many aspects
(epidemiology, neuropathology, biochemical features) from the C-BSE strain.
***Moreover, L-BSE has been transmitted more easily to transgenic mice
overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.
***It has been suggested that some sporadic CJD subtypes in humans may
result from an exposure to the L-BSE agent.
Lending support to this hypothesis, pathological and biochemical
similarities have been observed between L-BSE and an sCJD subtype (MV genotype
at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and
another sCJD subtype (MM genotype) [15].
Therefore, we investigated whether PMCA is reliable to model the genotypic
and interspecies barrier of transmission notably using L-BSE and C-BSE strains.
We assessed the seeding ability of PrPsc from human (vCJD) and animal (C-BSE,
L-BSE) prion strains to convert human or bovine PrPc. The aim of the study was
to compare, for each seed/substrate combination, the result obtained by PMCA
with the transmission efficiency previously observed in vivo.
snip...
Monday, November 3, 2014
***In addition, non-human primates are specifically susceptible for
atypical BSE as demonstrated by an approximately 50% shortened incubation time
for L-type BSE as compared to C-type. Considering the current scientific
information available, it cannot be assumed that these different BSE types pose
the same human health risks as C-type BSE or that these risks are mitigated by
the same protective measures.
BSE prions propagate as either variant CJD-like or sporadic CJD-like prion
strains in transgenic mice expressing human prion protein
*** Surprisingly, however, BSE transmission to these transgenic mice, in
addition to producing a vCJD-like phenotype, can also result in a distinct
molecular phenotype that is indistinguishable from that of sporadic CJD with
PrPSc type 2.
These data suggest that more than one BSEderived prion strain might infect
humans;
***it is therefore possible that some patients with a phenotype consistent
with sporadic CJD may have a disease arising from BSE exposure.
snip...
These studies further strengthen the evidence that vCJD is caused by a
BSE-like prion strain.
Also, remarkably, the key neuropathological hallmark of vCJD, the presence
of abundant florid PrP plaques, can be recapitulated on BSE or vCJD transmission
to these mice.
***However, the most surprising aspect of the studies was the finding that
an alternate pattern of disease can be induced in 129MM Tg35 mice from primary
transmission of BSE, with a molecular phenotype indistinguishable from that of a
subtype of sporadic CJD. This finding has important potential implications as it
raises the possibility that some humans infected with BSE prions may develop a
clinical disease indistinguishable from classical CJD associated with type 2
PrPSc. This is, in our experience, the commonest molecular sub-type of sporadic
CJD. In this regard, it is of interest that the reported incidence of sporadic
CJD has risen in the UK since the 1970s (Cousens et al., 1997)...
To date the OIE/WAHO assumes that the human and animal health standards set
out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE
which include the H-type and L-type atypical forms. This assumption is
scientifically not completely justified and accumulating evidence suggests that
this may in fact not be the case. Molecular characterization and the spatial
distribution pattern of histopathologic lesions and immunohistochemistry (IHC)
signals are used to identify and characterize atypical BSE. Both the L-type and
H-type atypical cases display significant differences in the conformation and
spatial accumulation of the disease associated prion protein (PrPSc) in brains
of afflicted cattle. Transmission studies in bovine transgenic and wild type
mouse models support that the atypical BSE types might be unique strains because
they have different incubation times and lesion profiles when compared to C-type
BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian
hamster the resulting molecular fingerprint had changed, either in the first or
a subsequent passage, from L-type into C-type BSE.
***In addition, non-human primates are specifically susceptible for
atypical BSE as demonstrated by an approximately 50% shortened incubation time
for L-type BSE as compared to C-type. Considering the current scientific
information available, it cannot be assumed that these different BSE types pose
the same human health risks as C-type BSE or that these risks are mitigated by
the same protective measures.
-------- Original Message --------
Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD
Date: Thu, 28 Nov 2002 10:23:43 -0000
From: "Asante, Emmanuel A" e.asante@ic.ac.uk
To: "'flounder@wt.net'" flounder@wt.net
Dear Terry,
I have been asked by Professor Collinge to respond to your request. I am a
Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have
attached a pdf copy of the paper for your attention.
Thank you for your interest in the paper.
In respect of your first question, the simple answer is, ***yes. As you
will find in the paper, we have managed to associate the alternate phenotype to
type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim
any further sub-classification in respect of Heidenhain variant CJD or Vicky
Rimmer's version. It will take further studies, which are on-going, to establish
if there are sub-types to our initial finding which we are now reporting. The
main point of the paper is that, as well as leading to the expected new variant
CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an
alternate phenotype which is indistinguishable from type 2 PrPSc.
I hope reading the paper will enlighten you more on the subject. If I can
be of any further assistance please to not hesitate to ask. Best wishes.
Emmanuel Asante
<>
____________________________________
Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial
College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44
(0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until
9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)
____________________________________
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection
against prion diseases is based on a certain numbers of hypotheses some of which
may turn out to be erroneous. In particular, a form of BSE (called atypical
Bovine Spongiform Encephalopathy), recently identified by systematic testing in
aged cattle without clinical signs, may be the origin of classical BSE and thus
potentially constitute a reservoir, which may be impossible to eradicate if a
sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases
constitute an unforeseen first threat that could sharply modify the European
approach to prion diseases.
Second threat
snip...
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC)
recently delivered a scientific opinion on any possible epidemiological or
molecular association between TSEs in animals and humans (EFSA Panel on
Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical
BSE prions as the only TSE agents demonstrated to be zoonotic so far
*** but the possibility that a small proportion of human cases so far
classified as "sporadic" CJD are of zoonotic origin could not be excluded.
Moreover, transmission experiments to non-human primates suggest that some TSE
agents in addition to Classical BSE prions in cattle (namely L-type Atypical
BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic
wasting disease (CWD) agents) might have zoonotic potential.
snip...
2014
***Moreover, L-BSE has been transmitted more easily to transgenic mice
overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.
***It has been suggested that some sporadic CJD subtypes in humans may
result from an exposure to the L-BSE agent. Lending support to this hypothesis,
pathological and biochemical similarities have been observed between L-BSE and
an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE
infected non-human primate and another sCJD subtype (MM genotype) [15].
snip...
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
4th MAD COW DISEASE U.S.A. CALIFORNIA ATYPICAL L-TYPE BASE BSE 2012
Saturday, August 4, 2012
*** Final Feed Investigation Summary - California atypical BASE BSE Case -
July 2012 (ATYPICAL L-TYPE BASE BSE)
Discussion: The C, L and H type BSE cases in Canada exhibit molecular
characteristics similar to those described for classical and atypical BSE cases
from Europe and Japan. *** This supports the theory that the importation of BSE
contaminated feedstuff is the source of C-type BSE in Canada. *** It also
suggests a similar cause or source for atypical BSE in these countries. ***
see page 176 of 201 pages...tss
I think they still test the lowest possible by oie standards, to keep them
in line for trade, which is about 40,000 a year, from 95 million or
so...tss
USDA NEVER GOT STARTED GOOD BEFORE SHUTTING DOWN $$$
Why is USDA "only" testing 40,000 samples a year? USDA's surveillance
strategy is to focus on the targeted populations where we are most likely to
find disease if it is present. This is the most effective way to meet both OIE
and our domestic surveillance standards. After completing our enhanced
surveillance in 2006 and confirming that our BSE prevalence was very low, we
concluded that 40,000 samples per year from these targeted, high risk
populations would far exceed these standards. In fact, this sampling is ten
times greater than OIE standards .
The total number of cattle and calves in the U.S. on January 1, 2014, was
87.73 million head, down 1.8% from January 2013 and 9.2% lower than at the last
cyclical peak in 2007. This is the lowest January cattle inventory since 1951,
_supposedly_, due to the drought, but I have my concern with that. the 2004
enhanced BSE surveillance program was shut down after finding two mad cows
(atypical's), and in my opinion, that's why they shut it down. also, Dr. Paul
Brown from the cdc said he trusted nothing from them after the Texas 2nd mad cow
was covered up for months and months, on what was suppose to be a 48 hour turn
around on testing. he said this ;
"Everything they did on the Texas cow makes everything USDA did before 2005
suspect," Brown said. (see link below).
the rest is history ;
An Arizona meat processing company and its owner pled guilty in February
2007 to charges of theft of Government funds, mail fraud, and wire fraud. The
owner and his company defrauded the BSE Surveillance Program when they falsified
BSE Surveillance Data Collection Forms and then submitted payment requests to
USDA for the services. In addition to the targeted sample population (those
cattle that were more than 30 months old or had other risk factors for BSE), the
owner submitted to USDA, or caused to be submitted, BSE obex (brain stem)
samples from healthy USDA-inspected cattle. As a result, the owner fraudulently
received approximately $390,000. Sentencing is scheduled for May 2007.
snip...
Topics that will be covered in ongoing or planned reviews under Goal 1
include:
soundness of BSE maintenance sampling (APHIS),
implementation of Performance-Based Inspection System enhancements for
specified risk material (SRM) violations and improved inspection controls over
SRMs (FSIS and APHIS),
snip...
The findings and recommendations from these efforts will be covered in
future semiannual reports as the relevant audits and investigations are
completed.
4 USDA OIG SEMIANNUAL REPORT TO CONGRESS FY 2007 1st Half
Office of the United States Attorney District of Arizona FOR IMMEDIATE
RELEASE For Information Contact Public Affairs February 16, 2007 WYN HORNBUCKLE
Telephone: (602) 514-7625 Cell: (602) 525-2681
CORPORATION AND ITS PRESIDENT PLEAD GUILTY TO DEFRAUDING GOVERNMENT’S MAD
COW DISEASE SURVEILLANCE PROGRAM
PHOENIX -- Farm Fresh Meats, Inc. and Roland Emerson Farabee, 55, of
Maricopa, Arizona, pleaded guilty to stealing $390,000 in government funds, mail
fraud and wire fraud, in federal district court in Phoenix. U.S. Attorney Daniel
Knauss stated, “The integrity of the system that tests for mad cow disease
relies upon the honest cooperation of enterprises like Farm Fresh Meats. Without
that honest cooperation, consumers both in the U.S. and internationally are at
risk.
WE can only hope that this is a single incident. BUT i have my doubts. I
remember when the infamous TOKEN Purina Feed Mill in Texas was feeding up to 5.5
grams of potentially and probably tainted BANNED RUMINANT feed to cattle, and
the FDA was bragging at the time that the amount of potentially BANNED product
was so little and the cattle were so big ;
"It is important to note that the prohibited material was domestic in
origin (therefore not likely to contain infected material because there is no
evidence of BSE in U.S. cattle), fed at a very low level, and fed only once. The
potential risk of BSE to such cattle is therefore exceedingly low, even if the
feed were contaminated."
On Friday, April 30 th , the Food and Drug Administration learned that a
cow with central nervous system symptoms had been killed and shipped to a
processor for rendering into animal protein for use in animal feed. ... FDA's
investigation showed that the animal in question had already been rendered into
"meat and bone meal" (a type of protein animal feed). Over the weekend FDA was
able to track down all the implicated material. That material is being held by
the firm, which is cooperating fully with FDA.
WE now know all that was a lie. WE know that literally Thousands of TONS of
BANNED and most likely tainted product is still going out to commerce. WE know
now and we knew then that .005 to a gram was lethal. WE know that CWD infected
deer and elk, scrapie infected sheep, BSE and BASE infected cattle have all been
rendered and fed back to livestock (including cattle) for human and animal
consumption.
Paul Brown, known and respected TSE scientist, former TSE expert for the
CDC said he had ''absolutely no confidence in USDA tests before one year ago'',
and this was on March 15, 2006 ;
"The fact the Texas cow showed up fairly clearly implied the existence of
other undetected cases," Dr. Paul Brown, former medical director of the National
Institutes of Health's Laboratory for Central Nervous System Studies and an
expert on mad cow-like diseases, told United Press International. "The question
was, 'How many?' and we still can't answer that."
Brown, who is preparing a scientific paper based on the latest two mad cow
cases to estimate the maximum number of infected cows that occurred in the
United States, said he has "absolutely no confidence in USDA tests before one
year ago" because of the agency's reluctance to retest the Texas cow that
initially tested positive.
USDA officials finally retested the cow and confirmed it was infected seven
months later, but only at the insistence of the agency's inspector general.
"Everything they did on the Texas cow makes everything USDA did before 2005
suspect," Brown said. ...snip...end
CDC - Bovine Spongiform Encephalopathy and Variant Creutzfeldt ... Dr. Paul
Brown is Senior Research Scientist in the Laboratory of Central Nervous System
... Address for correspondence: Paul Brown, Building 36, Room 4A-05, ...
PAUL BROWN COMMENT TO ME ON THIS ISSUE
Tuesday, September 12, 2006 11:10 AM
"Actually, Terry, I have been critical of the USDA handling of the mad cow
issue for some years, and with Linda Detwiler and others sent lengthy detailed
critiques and recommendations to both the USDA and the Canadian Food Agency."
OR, what the Honorable Phyllis Fong of the OIG found ;
Finding 2 Inherent Challenges in Identifying and Testing High-Risk Cattle
Still Remain
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
Tuesday, August 12, 2014
MAD COW USDA TSE PRION COVER UP or JUST IGNORANCE, for the record AUGUST
2014
Thursday, October 02, 2014
[Docket No. APHIS-2013-0064] Concurrence With OIE Risk Designations for
Bovine Spongiform Encephalopathy
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
***P.170: Potential detection of oral transmission of H type atypical BSE
in cattle using in vitro conversion
Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food
Inspection Agency; Lethbridge, AB Canada
Keywords: Atypical BSE, oral transmission, RT-QuIC
The detection of bovine spongiform encephalopathy (BSE) has had a
significant negative impact on the cattle industry worldwide. In response,
governments took actions to prevent transmission and additional threats to
animal health and food safety. While these measures seem to be effective for
controlling classical BSE, the more recently discovered atypical BSE has
presented a new challenge. To generate data for risk assessment and control
measures, we have challenged cattle orally with atypical BSE to determine
transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon
presentation of clinical symptoms, animals were euthanized and tested for
characteristic histopathological changes as well as PrPSc deposition.
The H-type challenged animal displayed vacuolation exclusively in rostral
brain areas but the L-type challenged animal showed no evidence thereof. To our
surprise, neither of the animals euthanized, which were displaying clinical
signs indicative of BSE, showed conclusive mis-folded prion accumulation in the
brain or gut using standard molecular or immunohistochemical assays. To confirm
presence or absence of prion infectivity, we employed an optimized real-time
quaking induced conversion (RT-QuIC) assay developed at the Rocky Mountain
Laboratory, Hamilton, USA.
Detection of PrPSc was unsuccessful for brain samples tests from the orally
inoculated L type animal using the RT-QuIC. It is possible that these negative
results were related to the tissue sampling locations or that type specific
optimization is needed to detect PrPSc in this animal. We were however able to
consistently detect the presence of mis-folded prions in the brain of the H-type
inoculated animal. Considering the negative and inconclusive results with other
PrPSc detection methods, positive results using the optimized RT-QuIC suggests
the method is extremely sensitive for H-type BSE detection. This may be evidence
of the first successful oral transmission of H type atypical BSE in cattle and
additional investigation of samples from these animals are ongoing.
P.169: PrPSc distribution in brain areas of a natural German H-type BSE
case
Anne Balkema-Buschmann, Grit Priemer, Markus Keller, and Martin H Groschup
Friedrich Loeffler Institut, Institute for Novel and Emerging Infectious
Diseases; Greifswald, Insel Riems, Germany
Keywords: BSE H-type, brain, muscle
Ten years after the initial description of atypical BSE cases of the H-type
and L-type, the distribution of PrPSc in different brain areas and peripheral
tissues of natural cases of these BSE forms is still not fully understood.
Intracerebral challenge experiments have been performed with both atypical BSE
forms in cattle, and the distribution of the abnormal prion protein and
infectivity has been analysed in a variety of tissues, confirming the general
restriction to the central nervous system as it was already generally
acknowledged for classical BSE, but showing a slightly earlier and stronger
involvement of the peripheral nervous system and the skeletal muscle.
www.landesbioscience.com Prion 105
However, data from cattle orally challenged with atypical BSE, which might
mimic the natural situation, are not yet available. Unfortunately, for most
natural cases of atypical BSE, only the obex region is available for further
analysis. The PrPSc distribution in the brains of natural L-type BSE cases in
Italy has been described in some detail, but comparably few such data are yet
available for natural H-type cases. Here we describe the analysis of different
brain areas and muscle samples of a natural H-type BSE case diagnosed in Germany
in 2014, and compare these data with those obtained from the respective samples
collected from cattle challenged intracerebrally with H-type BSE.
P.159: Transgenic mice overexpressing rabbit prion protein are susceptible
to BSE, BASE and scrapie prion strains but resistant to CWD and atypical
scrapie
Natalia Fernández-Borges,1 Enric Vidal,2 Belén Pintado,4 Hasier Eraña,1
Montserrat Ordóñez,3 Mercedes Márquez,5 Francesca Chianini,6 Dolors Fondevila,5
Manuel A Sánchez-Martín,7 Olivier Andréoletti,8 Mark P Dagleish,6 Martí
Pumarola,5 and Joaquín Castilla1,3 1CIC bioGUNE; Parque tecnológico de Bizkaia;
Derio; Bizkaia, Spain; 2Centre de Recerca en Sanitat Animal (CReSA); UAB-IR TA,
Campus de la Universitat Autònoma de Barcelona; Bellaterra; Barcelona,
Catalonia, Spain; 3IKERBASQUE; Basque Foundation for Science; Bilbao, Bizkaia,
Spain; 4Centro Nacional de Biotecnología (CNB), Campus de Cantoblanco;
Cantoblanco; Madrid, Spain; 5Department of Animal Medicine and Surgery;
Veterinary faculty; Universitat Autònoma de Barcelona (UAB); Bellaterra
(Cerdanyola del Vallès); Barcelona, Catalonia, Spain; 6Moredun Research
Institute; Bush Loan, Penicuik, Scotland, UK; 7Unidad de Generación de OMGs.
S.E.A. Department of Medicine; University of Salamanca; Salamanca, Spain; 8Ecole
Nationale du Veterinaire; Service de Pathologie du Bétail; Toulouse,
France
Interspecies transmission of prions is a well established phenomenon, both
experimentally and in field conditions. Upon passage through new hosts prion
strains have proven their capacity to change their properties. It is, in fact, a
source of strain diversity which needs to be considered when assessing the
potential risks associated with consumption of prion contaminated protein
sources.
Rabbits were considered for decades a prion resistant species until proven
recently otherwise. To determine the extent of rabbit susceptibility to prions
and to assess their effects on the passage of different prion strains through
this species, a transgenic mouse model overexpressing rabbit PrPC was developed
(TgRab). Intracerebral challenges with prion strains originating from a variety
of species including field isolates (SSBP1 scrapie, Nor98-like scrapie, BSE,
BASE and CWD), experimental murine strains (ME7 and RML), experimentally
obtained strains (sheepBSE) and strains obtained by in vitro crossing of the
species barrier using saPMCA (BSE-RabPrPres, SSBP1-RabPrPres and CWD-RabPrPres)
have been performed.
Interestingly, on first passage, TgRab were susceptible to the majority of
prions tested with the exception of SSBP1 scrapie, CWD and Nor98 scrapie.
Furthermore TgRab were capable of propagating strain-specific features such as
differences in incubation periods, brain lesion and PrPd deposition profiles and
PK resistant western blotting band patterns. Our results confirm previous
studies shattering the myth that rabbits are resistant to prion infection and
this should be taken into account when choosing protein sources to feed rabbits.
P.168: Evolution of the biological properties of L-BSE after passage in
sheep with susceptible and resistant PrP genotypes
Michele A Di Bari, Umberto Agrimi, Claudia D’Agostino, Geraldina Riccardi,
Stefano Marcon, Elena Esposito, Paolo Frassanito, Flavio Torriani, Shimon
Simson, and Romolo Nonno Istituto Superiore di Sanità (ISS) Department of
Veterinary Public Health and Food Safety; Rome, Italy
Background. Cattle L-BSE was efficiently transmitted to sheep with
susceptible (QQ171) and resistant (QR171) PrP genotypes. 1 Notably, the PrPSc
signature of L-BSE was preserved in QQ171 sheep but not in QR171 sheep.2
Notwithstanding, bioassay in transgenic mice expressing bovine or ovine (ARQ)
PrPC showed that L-BSE strain was preserved in both, QQ171 and QR171
sheep-passaged L-BSE.3
Here we studied the biological properties of sheep-passaged L-BSE by
bioassay in bank voles and transgenic mice expressing the ovine VRQ PrP (tg338),
both characterized by a comparatively low susceptibility to cattle L-BSE.
Material and Methods. Voles and tg338 mice were intracerebrally inoculated
with cattle L-BSE and sheep-passaged (QQ171 and QR171) L-BSE isolates. Survival
time, lesion profiles, Pet-blot and WB analysis were used for strain typing.
Results. Cattle L-BSE transmitted quite inefficiently to tg338 mice, with
survival time >400 days post-infection (d.p.i.), while sheep-passaged inocula
were much more efficient and all gave terminal disease by ~140 d.p.i. However,
after sub-passage all inocula converged to a survival time of ~145 d.p.i.. and
showed overlapping pathological phenotypes.
In voles, cattle L-BSE transmitted with very long survival times (~800
d.p.i.) and was accompanied by an upward shift of the PrPSc type. Again, all
sheep-passaged L-BSE isolates transmitted much more efficiently, with similar
survival times of ~360 d.p.i.. Upon second passage, three different strains were
isolated in vole, characterized by distinct pathological phenotypes. This
divergence is epitomized by the different survival times of vole-adapted L-BSE
strains, which were ~400 d.p.i. for cattle L-BSE, ~130 d.p.i. for QQ171-passaged
L-BSE and ~225 d.p.i. for QR171-passaged L-BSE.
Conclusions. These findings, along with previously published data,3 show
that the original L-BSE strain was recovered after passage in sheep when
bioassay was performed in animal models expressing bovine or ovine PrPC. In
contrast, strain changes were observed in both, QQ171- and QR171-passaged L-BSE
by bioassay in vole, a species with divergent PrP sequence compared to
ruminants. Importantly, QQ171- and QR171-passaged L-BSE were characterised by
different PrPSc types and, accordingly, showed different biological properties
when transmitted to voles, but not when transmitted to other animal models.
Overall, our work support the hypothesis that prion isolates are likely
composed of multiple prion components, emphasizes the role of host PrP
polymorphisms on strain selection and mutation, and highlights the risk for new
potentially zoonotic strains that could emerge from prion evolution in animal
reservoirs.
P.172: BSE exposure risk from bovine intestine and mesentery
Fulvio Barizzone,1 Herbert Budka,2 Christine Fast,3 John N Griffin,4
Giuseppe Ru,5 Pietro Stella1 and Olivier Andréoletti6 1European Food Safety
Authority; Parma, Italy; 2Institute of Neuropathology; University Hospital
Zurich; Zurich, Switzerland; 3Friedrich-Loeffler-Institut; Institute of Novel
and Emerging Infectious Diseases; Isle of Riems, Germany; 4Department of
Agriculture, Food and the Marine; Backweston, Celbridge, Co. Kildare, Ireland;
5Istituto Zooprofilattico Sperimentale del Piemonte; Liguria e Valle d’Aosta;
Biostatistics Epidemiology and Analysis of Risk (BEAR) unit; Turin, Italy; 6UMR
Interactions Hôtes Agents Pathogènes; Ecole Nationale Vétérinaire INR A; ENVT;
Toulouse, France
Keywords: Bovine Spongiform Encephalopathy (BSE), cattle, intestine,
mesentery, specified risk material (SRM), quantitative risk assessment
(QRA)
Bovine intestines and mesenteries in the European Union (EU) are considered
among the tissues potentially containing the highest level of BSE infectivity
and have to be removed from the food and feed chain. A quantitative assessment
of the BSE infectious load potentially entering the food and feed chain yearly
in the European Union (EU) was developed. The evolution of the BSE infectious
titre and of the weight of the structures accumulating infectivity was
considered. The number of BSE infected cattle entering undetected in the food
and feed chain yearly was estimated. A model (TSEi) was developed to estimates
the evolution of the BSE infectious load in animals and the total yearly
infectious load that could enter the food and feed chain. In a BSE infected
bovine, the distribution of infectivity in intestines and mesentery varies with
the age. Up to 36 months of age the infectivity is mainly associated (on average
more than 90%) with the last 4 metres of small intestine and the caecum, over 36
and under 60 months of age, there is an inter-individual variability, from 60
months of age the infectivity is mainly associated (on average more than 90%)
with the mesenteric nerves and the celiac and mesenteric ganglion complex. The
total amount of infectivity peaks, about 15 BoID50, in animals younger than 18
months, it declines to 8-9 BoID50 (24–48 months of age) and it drops to 0.7
BoID50 in animals older than 60 months. The ileocaecal plate is the most
infectious part of the intestine and it can be used to estimate the potential
maximum level of exposure for an individual consumer.
In the EU, between 2007 and 2012, the yearly amount of BSE infectivity
associated with intestine and mesentery from animals entering the food and feed
chain was reduced by a factor of 10 (from about 23,000 to about 2,000 BoID50).
However, the maximum level of exposure to the BSE agent from intestine
remained stable (on average about 1.5-1.6 BoID50 per meter).
In case of re-emergence of BSE in the EU there would be an increase of the
potential maximum level of exposure to BSE from intestine. According to the TSEi
model the removal of the last four metres of the small intestine and of the
caecum from the food and feed chain would result in a major reduction of the BSE
exposure risk associated with intestine and mesentery in cattle.
P.131: Transmission of sheep-bovine spongiform encephalopathy in pigs
Carlos Hedman,1 Belén Marín,1 Fabian Corbière,3 Hicham Filali,1 Francisco
Vázquez, José Luis Pitarch,1 William Jirón,1 Rodrigo S Hernandez,1 Bernardino
Moreno,1 Martí Pumarola,2 Olivier Andréoletti,3 Juan José Badiola,1 and Rosa
Bolea1 1University of Zaragoza; Zaragoza, Spain; 2University of Barcelona;
Barcelona, Spain; 3Institut National de la Recherche (INR A); Toulouse,
France
Introduction. The transmissible spongiform encephalopathies (TSE) don´t
occur in swine in natural conditions. However, the bovine spongiform
encephalopathy (BSE) agent, inoculated by 3 simultaneous routes in pigs, is able
to reproduce a neurological disease in these animals. On the other hand, the BSE
agent after passage in sheep under experimental conditions (sheep- BSE) exhibits
altered pathobiologic properties. This new agent is able to cross the cattle-pig
transmission barrier more efficiently than BSE. The potential propagation of TSE
in animals from the human food chain, including pigs, needs to be assessed
regarding the risk for human infection by animals other than TSE-infected
ruminants. The aim of this work was to determine the susceptibility of pigs to
the Sheep-BSE agent and describe the pathological findings and PrPSc deposition
in different tissues.
Material and Methods. Seven minipigs were challenged intracerebrally with
sheep-BSE agent. Clinical observation and postmortem histopathology,
immunohistochemistry (antibody 2G11) and Western blotting were performed on
central nervous system (CNS), peripheral nervous system (PNS) and other
tissues.
Results. One pig was culled in an early incubation stage, and remaining six
were culled at the presence of clinical sings. Pigs developed a clinical disease
with locomotor disorders in an average time of 23 months post inoculation,
showing clinical findings in most of them earlier than those described in the
BSE in pigs experimental infection. TSE wasn´t confirmed in the preclinical pig.
In clinical pigs, the entire cerebral cortex showed severe neuropil vacuolation,
extensive and severe vacuolar changes affecting the thalamus, hippocampus and
cerebellum. PrPSc was found in CNS of all clinical pigs (6/6). Intracellular
(intraneuronal and intraglial) and neuropil-associated PrPSc deposition was
consistently observed in the brainstem, thalamus, and deeper layers of the
cerebral cortex. Also, PrPSc was observed in PNS, mainly in the myenteric plexus
and also in nerves belonging to the skeleton muscle. Moreover, the glycosylation
profile showed a 3 band pattern with a predominant monoglycosylated band in
positive pig samples.
This features concern on the potential risk of utilization of meat and
bound meal of small ruminants in feeding pigs.
P.177: Elements modulating the prion species barrier and its passage
consequences
Juan-Carlos Espinosa,1 Patricia Aguilar-Calvo,1 Ana Villa-Diaz,1 Olivier
Andréoletti,2 and Juan María Torres1 1Centro de Investigación en Sanidad Animal
(CISA-INI A); Valdeolmos, Madrid, Spain; 2UMR INR A-ENVT 1225; Interactions Hôte
Agent Pathogène; École Nationale Vétérinaire de Toulouse; Toulouse, France
The phenotypic features of Transmissible Spongiform Encephalopathy (TSE)
strains may be modified during passage across a species barrier. In this study
we investigated the biochemical and biological characteristics of Bovine
Spongiform Encephalopathy (BSE) infectious agent after transmission in both
natural host species (cattle, sheep, pigs, and mice) and in transgenic mice
overexpressing the corresponding cellular prion protein (PrPC) in comparison
with other non-BSE related prions from the same species. After these passages,
most characteristics of the BSE agent remained unchanged. BSE-derived agents
only showed slight modifications in the biochemical properties of the
accumulated PrPSc, which were demonstrated to be reversible upon re-inoculation
into transgenic mice expressing bovine-PrPC. Transmission experiments in
transgenic mice expressing bovine, porcine or human-PrP revealed that all
BSE-derived agents were transmitted with no or a weak transmission barrier. In
contrast, a high species barrier was observed for the non-BSE related prions
that harboured an identical PrP amino acid sequence such as sheep-scrapie, mouse
RML or human sCJD isolates, supporting the theory that the prion transmission
barrier is modulated by strain properties (presumably conformation-dependent)
rather than by PrP amino acid sequence differences between host and donor.
As identical results were observed with prions propagated either in natural
hosts or in transgenic mouse models, we postulate that the species barrier and
its passage consequences are uniquely governed by the host PrPC sequence and not
influenced by the PrPC expression level or genetic factors other than the PrPC
amino acid sequence. All these findings unequivocally demonstrate that the
species barrier and its passage consequences are uniquely driven by the PrPC
sequence, and not by other host genetic factors, demonstrating the validity of
transgenic PrP animals as models for studies of the species barrier.
The results presented herein reinforce the idea that the BSE agent is
highly promiscuous, infecting other species, maintaining its properties in the
new species, and even increasing its capabilities to jump to other species
including humans. These data are essential for the development of an accurate
risk assessment for BSE.
P.150: Zoonotic potential of L-type BSE prions: A new prion disease in
humans?
Emilie Jaumain,1 Stéphane Haïk,2 Isabelle Quadrio,3 Laetitia Herzog,1
Fabienne Reine,1 Armand Perret-Liaudet,3 Human Rezaei,1 Hubert Laude,1 Jean-Luc
Vilotte,4 and Vincent Béringue1 1INR A (Institut National de la Recherche
Agronomique); UR892; Virologie Immunologie Moléculaires; Jouy-en-Josas, France;
2IN SERM; Equipe maladie d’Alzheimer et maladies à Prions; CRicm; UMRS 1127; CNR
S; UPMC. R.; ICM, Hôpital de la Salpêtrière; Paris, France; 3Neurobiologie, CMRR
, Gériatrie, Hospices Civils de Lyon, Université Lyon 1-CNR S UMR5292-IN SERM
U1028; Lyon, France; 3INR A; UMR1313; Génétique Animale et Biologie Intégrative;
Jouy-en-Josas, France
Two novel prion strains, referred to as BSE-L and BSE-H, have been
recognized in bovines through active prion surveillance programs, both being
distinct from the epizootic, ‘classical’, BSE strain (C-BSE). Both H and L-types
have been detected worldwide as rare cases occurring in aged animals. Like C-BSE
prions, H- and L-types prions can propagate with relative ease in foreign
species or in transgenic mouse lines expressing heterologous PrP sequences. A
prion exhibiting biological properties similar to C-BSE agent sometimes emerged
from these cross-species transmissions. Previously, L-type prions were shown to
transmit to transgenic mice expressing human PrP with methionine at codon 129
with higher efficacy than C-BSE prions. Here, we examined whether L-type prions
propagate without any apparent transmission barrier in these mice and whether
such ‘humanised’ L-type prions share biological properties with CJD prions.
L-type prions and a panel of human CJD cases with various genotypes at codon 129
and electrophoretic PrPres signatures were serially transmitted by intracerebral
route to human PrP mice. The biological phenotypes induced by these agents were
compared by all the standard methods currently used to distinguish between prion
strains. At each passage, L-type prions were also transmitted back to bovine PrP
mice to assess whether the agent has evolved upon passaging on the human PrP
sequence. L-type prions transmitted to human PrP mice at 100% attack rate,
without notable alteration in the mean incubation times over 5 passages. At each
passage, ‘humanized’ L-type prions were able to transmit back to bovine PrP
transgenic mice without apparent transmission barrier, as based on the survival
time and the restoration of a L-type BSE phenotype. Comparison of mean
incubation times on primary and subsequent passages in human PrP mice showed no
overlap between L-type and sporadic CJD agents. While the electrophoretic
signature and regional distribution of PrPres in L-type diseased mouse brains
resembled that seen after transmission of MM2 CJD strain type, both agents
exhibited distinct resistance of the associated PrPres molecules to protease
denaturation.
In summary, L-type prions can be passaged on the human PrP sequence without
any obvious transmission barrier. The phenotype obtained differs from the
classical CJD prion types known so far. Careful extrapolation would suggest that
the zoonotic transmission of this agent could establish a new prion disease type
in humans.
Protein Structure and Biology
P.200: Clinical expression of BSE in mouse models is unrelated to hallmarks
of prion diseases
Christelle Jas-Duval,1,2 Jacqueline Mikol,1 Sophie Luccantoni-Freire,1
Christine Defer,2 Jean-Jacques Huart,2 Paul Brown,1 Jean-Philippe Deslys,1 and
Emmanuel E Comoy1 1CEA, Institute of Emerging Diseases and Innovative Therapies
(iMETI), Division of Prions and Related Diseases (SEPIA); Fontenay-aux-Roses,
France; 2EFS-Nord de France; Lille, France
Background. In 1997, we demonstrated that intracerebral inoculation of
cattle BSE to C57Bl/6 mice induced neurological disease, even though half of the
recipient animals were devoid of PrPres (Lasmezas et al., 1997). PrPres appeared
with shortening incubation periods after subsequent passages, suggesting that
detectable PrPres should be considered as an indicator of strain virulence
rather than as a specific (and required) marker of prion diseases. Subsequent
blood risk studies showed that cynomolgus macaques exposed to vCJD-contaminated
blood products developed either classical vCJD or a novel neurological disease
without detectable PrPres, In our continuing studies of this phenomenon, we now
report the results of intravenous inoculations of several different wild-type
mouse strains with bovine or primate BSE source material.
Materials and Methods. Brains from one bovine and one cynomolgus monkey
showing clinical signs of BSE were sonicated and ultracentrifuged at 188,000 g
for 1 hour. Resulting pellets and supernatants (equivalent to 2 mg of brain /
mouse) were intravenously injected to PrP+/+ Swiss, PrP+/- and PrP+/+ C57Bl/6N
mice, totalling 12 separate bioassays. PrPres was detected using conventional
ELISA, western blotting and IHC procedures. Pathology was studied on
formalin-fixed brain tissues.
Results. The transmission rate of BSE in those 12 experiments ranged from
0% (PrP+/- C57Bl/6N—cattle BSE—supernatant or pellet: no clinical sign, no
spongiosis and no PrPres) to 100% (Swiss—primate BSE—supernatant or pellet: all
mice exhibited clinical signs, spongiosis and PrPres). Overall, transmission was
more efficient in (1) Swiss than C57Bl/6 mice, (2) PrP+/+ than PrP+/- mice, (3)
primate than cattle BSE and (4) pellets than supernatant preparations. Among the
8 models exhibiting partial transmission ratios, 29 mice showed clinical
neurological signs, of which only one-third (10) had detectable spongiosis and
PrPres. The other animals exhibited only PrPres (7), only spongiosis (5) or
neither (7).
Conclusion. Our results suggest that clinical neurotoxicity, spongiosis,
and accumulation of PrPres are three interconnected but disparate phenomena.
Spongiosis and PrPres are specific but not systematic hallmarks of the onset of
prion diseases, notably upon first passage of non-adapted prion strains in a new
host. These results question the universality of current human diagnostic
criteria and the real prevalence of disease linked to BSE exposure.
Monday, June 23, 2014
PRION 2014 TYPICAL AND ATYPICAL BSE AND CJD REPORT UPDATES
Bovine Spongiform Encephalopathy BSE (typical and atypical strains) USDA
*** Saturday, November 2, 2013 ***
Exploring the risks of a putative transmission of BSE to new species
Wednesday, September 25, 2013
Presence of subclinical infection in gene-targeted human prion protein
transgenic mice exposed to atypical BSE
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.
www.landesbioscience.com
please see ;
Thursday, August 15, 2013
The emergence of novel BSE prions by serial passages of H-type BSE in
bovinized mice
Saturday, August 14, 2010 BSE
*** Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY
Sunday, September 1, 2013
*** Evaluation of the Zoonotic Potential of Transmissible Mink
Encephalopathy
We previously described the biochemical similarities between PrPres derived
from L-BSE infected macaque and cortical MM2 sporadic CJD: those observations
suggest a link between these two uncommon prion phenotypes in a primate model
(it is to note that such a link has not been observed in other models less
relevant from the human situation as hamsters or transgenic mice overexpressing
ovine PrP [28]). We speculate that a group of related animal prion strains
(L-BSE, c-BSE and TME) would have a zoonotic potential and lead to prion
diseases in humans with a type 2 PrPres molecular signature (and more
specifically type 2B for vCJD)
snip...
Together with previous experiments performed in ovinized and bovinized
transgenic mice and hamsters [8,9] indicating similarities between TME and
L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME
outbreaks in North America and Europe during the mid-1900s.
Saturday, November 2, 2013
*** APHIS Finalizes Bovine Import Regulations in Line with International
Animal Health Standards while enhancing the spread of BSE TSE prion mad cow type
disease around the Globe ***
Singeltary Response to USDA, and USDA RESPONSE TO SINGELTARY ON HARVARD BSE
RISK ASSESSMENT
Owens, Julie
From: Terry S. Singeltary Sr. [flounder9@verizon.net]
Sent: Monday, July 24, 2006 1:09 PM
To: FSIS RegulationsComments
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine
Spongiform Encephalopathy (BSE) Page 1 of 98
FSIS, USDA, REPLY TO SINGELTARY
USDA FDA TRIPLE MAD COW BSE FIREWALL
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN
COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
PRODUCT
Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried,
Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
Firm initiated recall is ongoing.
REASON
Blood meal used to make cattle feed was recalled because it was cross-
contaminated with prohibited bovine meat and bone meal that had been
manufactured on common equipment and labeling did not bear cautionary BSE
statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI
___________________________________
PRODUCT
Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot-
Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M
CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B
DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal,
JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT
Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral,
BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC
LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall #
V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with
commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm
initiated recall is complete.
REASON
Products manufactured from bulk feed containing blood meal that was cross
contaminated with prohibited meat and bone meal and the labeling did not bear
cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
Sunday, December 15, 2013
*** FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE ***
Tuesday, August 12, 2014 Maine Firm Recalls Ribeye and Carcass Products
That May Contain Specified Risk Materials
Class II Recall
Health Risk: Low
August 29, 2014
MAINE, August 29, 2014 – Bubier Meats, an establishment in Greene, Maine is
recalling approximately 25,192 pounds of fresh beef products because the dorsal
root ganglia may not have been completely removed, which is not compliant with
federal regulations that require their removal in cattle 30 months of age and
older, the Maine Meat and Poultry Inspection (MMPI) program announced today.
The products subject to recall include:
• Quartered beef carcasses that were stamped with the Maine mark of
inspection and establishment number “EST. 4.” with the following ship dates:
11/13/13, 11/26/13, 1/2/14, 1/21/14, 2/5/14, 2/19/14, 3/5/14, 3/19/14, 4/2/14,
4/30/14, 5/12/14, 5/28/14, 6/11/14, 6/25/14, 7/9/14, 7/23/14, 8/6/14, 8/20/14.
Bubier Meats advises that the quartered carcasses were distributed to Maine
retail stores, Rosemont Market locations in Portland and Yarmouth, and Maine
Meat in Kittery Maine, on various dates between November, 2013 and August, 2014.
All products would have been processed into smaller cuts with no identifying
consumer packaging. Such smaller cuts may include bone-in ribeye roasts, prime
rib roasts, T-bone steaks, porterhouse steaks, wing steaks, bone-in ribeye
steaks, bone-in sirloin steaks and neck bones.
The problem was discovered by MMPI during a review of company slaughter
logs. Dorsal root ganglia, branches of the nervous system located in the
vertebral column are considered specified risk materials (SRMs) and must be
removed from cattle 30 months of age and older in accordance with federal
regulations. SRMs are tissues that may contain the infective agent in cattle
infected with Bovine Spongiform Encephalopathy (BSE), as well as materials that
are closely associated with these potentially infective tissues. Although BSE is
extremely rare (only 4 US cows have been identified to date) it remains a human
health concern. Therefore, federal regulations prohibit SRMs from use as human
food to minimize potential human exposure to the BSE agent.
Every animal received ante-mortem inspection by MMPI inspection personnel,
who observed each animal at rest and in motion. All animals appeared healthy
with no indication that any of the cattle slaughtered displayed any signs of
BSE.
MMPI and Bubier Meats have received no reports of adverse reactions due to
consumption of these products. Anyone concerned about a reaction should contact
a healthcare provider.
MMPI routinely conducts recall effectiveness checks to verify recalling
firms notify their customers of the recall and that steps are taken to make
certain that the product is no longer available to consumers.
Consumers and media with questions about the recall should contact
establishment manager Tobie Bubier at 207-946-5015.
Consumers with food safety questions can “Ask Karen,” the FSIS virtual
representative available 24 hours a day at askkaren.gov (http://www.askkaren.gov/)or via
smartphone at m.askkaren.gov (http://m.askkaren.gov). “Ask Karen” live chat
services are available Monday through Friday from 10 a.m. to 4 p.m. ET. The
toll-free USDA Meat and Poultry Hotline 1-888-MPHotline (1-888-674-6854) is
available in English and Spanish and can be reached from l0 a.m. to 4 p.m.
(Eastern Time) Monday through Friday. Recorded food safety messages are
available 24 hours a day.
> MMPI and Bubier Meats have received no reports of adverse reactions
due to consumption of these products.
come back and tell us that in about 50 years...*** vCJD can have an
incubation period of over 30 years. ..TSS
Tuesday, August 19, 2014
Former Rancho Employees Charged With 11 Felonies processed meat from 101
condemned cattle, including 79 with “cancer eye''
Saturday, June 14, 2014
Rep. Rosa DeLauro (D-CT) Calls for Briefing on Beef Recalled for Mad Cow
Potential Rep. Rosa DeLauro (D-CT)
Thursday, June 12, 2014
Missouri Firm Recalls Ribeye and Carcass Products That May Contain
Specified Risk Materials 4,012 pounds of fresh beef products because the dorsal
root ganglia may not have been completely removed
*** Because typical clinical signs of BSE cannot always be observed in
nonambulatory disabled cattle, and because evidence has indicated these cattle
are more likely to have BSE than apparently healthy cattle, FDA is designating
material from nonambulatory disabled cattle as prohibited cattle materials.
Friday, March 21, 2014
Rancho Dead Stock Cancer Downers Recall Explained FSIS March 20 2014
?
“As of March 20, 2014, FSIS has completed all checks (effectiveness checks
and disposition verification checks) for recalls 002-2014 and 013-2014 regarding
Rancho Feeding Corporation. FSIS has determined that based on the number of
successful checks (see Directive 8080.1, Attachment 1, Table 3) where businesses
were notified of the recall and removed affected products from commerce that the
recall activities were effective.”
Thursday, March 20, 2014
JACK IN THE BOX NOW CAUGHT UP IN MASSIVE RANCHO DEAD STOCK DOWNER CANCER
COW RECALL
Thursday, March 6, 2014
TEXAS RECALL LIST MASSIVE FROM DEAD STOCK DOWNER CANCER COWS OFFAL from
Class I Recall 002-2014 and 013-2014 Health Risk: High Jan 13, 2014 and Feb 8,
2014 shipped to Texas, Florida, and Illinois UPDATE FEBRUARY 14, 2014
Thursday, February 27, 2014
BEEF, CANCER, PRIONS, AND OTHER DANGEROUS AND DEADLY PATHOGENS, APPARENTLY,
IT'S WHAT'S FOR DINNER
Thursday, November 28, 2013
Department of Justice Former Suppliers of Beef to National School Lunch
Program Settle Allegations of Improper Practices and Mistreating Cows
seems USDA NSLP et al thought that it would be alright, to feed our
children all across the USA, via the NSLP, DEAD STOCK DOWNER COWS, the most high
risk cattle for mad cow type disease, and other dangerous pathogens, and they
did this for 4 years, that was documented, then hid what they did by having a
recall, one of the largest recalls ever, and they made this recall and masked
the reason for the recall due to animal abuse (I do not condone animal abuse),
not for the reason of the potential for these animals to have mad cow BSE type
disease (or other dangerous and deadly pathogens). these TSE prion disease can
lay dormant for 5, 10, 20 years, or longer, WHO WILL WATCH OUR CHILDREN FOR THE
NEXT 5 DECADES FOR CJD ???
Saturday, September 21, 2013
Westland/Hallmark: 2008 Beef Recall A Case Study by The Food Industry
Center January 2010 THE FLIM-FLAM REPORT
DID YOUR CHILD CONSUME SOME OF THESE DEAD STOCK DOWNER COWS, THE MOST HIGH
RISK FOR MAD COW DISEASE ??? this recall was not for the welfare of the animals.
...tss you can check and see here ; (link now dead, does not work...tss)
try this link ;
Sunday, November 13, 2011
*** California BSE mad cow beef recall, QFC, CJD, and dead stock downer
livestock
Thursday, February 13, 2014
HSUS VS USDA ET AL BAN DOWNER CALVES FOR HUMAN CONSUMPTION (*veal) and
potential BSE risk factor there from
Saturday, November 10, 2012
Wisconsin Firm Recalls Beef Tongues That May Contain Specified Risk
Materials Nov 9, 2012 WI Firm Recalls Beef Tongues
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK
MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
Sunday, October 18, 2009
Wisconsin Firm Recalls Beef Tongues That Contain Prohibited Materials SRM
WASHINGTON, October 17, 2009
Thursday, October 15, 2009
Nebraska Firm Recalls Beef Tongues That Contain Prohibited Materials SRM
WASHINGTON, Oct 15, 2009
Thursday, June 26, 2008
Texas Firm Recalls Cattle Heads That Contain Prohibited Materials
Tuesday, July 1, 2008
Missouri Firm Recalls Cattle Heads That Contain Prohibited Materials
SRMs
Friday, August 8, 2008
Texas Firm Recalls Cattle Heads That Contain Prohibited Materials SRMs
941,271 pounds with tonsils not completely removed
Saturday, April 5, 2008
SRM MAD COW RECALL 406 THOUSAND POUNDS CATTLE HEADS WITH TONSILS
KANSAS
Wednesday, April 30, 2008
Consumption of beef tongue: Human BSE risk associated with exposure to
lymphoid tissue in bovine tongue in consideration of new research findings
Wednesday, April 30, 2008
Consumption of beef tongue: Human BSE risk associated with exposure to
lymphoid tissue in bovine tongue in consideration of new research findings
Friday, October 15, 2010
BSE infectivity in the absence of detectable PrPSc accumulation in the
tongue and nasal mucosa of terminally diseased cattle
SPECIFIED RISK MATERIALS SRMs
MAD COW USDA TSE PRION COVER UP or JUST IGNORANCE, for the record AUGUST
2014
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by
plaques and glial- and stellate-type prion protein deposits
Wednesday, April 25, 2012
4th MAD COW DISEASE U.S.A. CALIFORNIA ATYPICAL L-TYPE BSE 2012
RESPONSE TO PUBLIC COMMENTS
Bovine Spongiform Encephalopathy Update, October 31, 2005
INTRODUCTION The United States Department of Agriculture’s Food Safety and
Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington,
D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform
Encephalopathy Update, October 31, 2005 (report and model located on the FSIS
website:
Comments on technical aspects of the risk assessment were then submitted to
FSIS. Comments were received from Food and Water Watch, Food Animal Concerns
Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S.
Singeltary. This document provides itemized replies to the public comments
received on the 2005 updated Harvard BSE risk assessment. Please bear the
following points in mind:
IN SHORT, AND IN A NUT SHELL ;
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate
declarations made by the official Veterinary Services of Member Countries. The
OIE is not responsible for inaccurate publication of country disease status
based on inaccurate information or changes in epidemiological status or other
significant events that were not promptly reported to the Central Bureau,
IT is of my opinion, that the OIE and the USDA et al, are the soul reason,
and responsible parties, for Transmissible Spongiform Encephalopathy TSE prion
diseases, including typical and atypical BSE, typical and atypical Scrapie, and
all strains of CWD, and human TSE there from, spreading around the globe.
I have lost all confidence of this organization as a regulatory authority
on animal disease, and consider it nothing more than a National Trading
Brokerage for all strains of animal TSE, just to satisfy there commodity. AS i
said before, OIE should hang up there jock strap now, since it appears they will
buckle every time a country makes some political hay about trade protocol,
commodities and futures. IF they are not going to be science based, they should
do everyone a favor and dissolve there organization.
JUST because of low documented human body count with nvCJD and the long
incubation periods, the lack of sound science being replaced by political and
corporate science in relations with the fact that science has now linked some
sporadic CJD with atypical BSE and atypical scrapie, and the very real threat of
CWD being zoonosis, I believed the O.I.E. has failed terribly and again, I call
for this organization to be dissolved. ...
Tuesday, July 17, 2012
O.I.E. BSE, CWD, SCRAPIE, TSE PRION DISEASE Final Report of the 80th
General Session, 20 - 25 May 2012
USA CJD TSE PRION UNIT, TEXAS, SURVEILLANCE UPDATE NOVEMBER 2014
National Prion Disease Saturday, August 14, 2010 BSE
Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr
PRIONPATHY
Pathology Surveillance Center Cases Examined1 (October 7, 2014)
***6 Includes 11 cases in which the diagnosis is pending, and 19
inconclusive cases;
***7 Includes 12 (11 from 2014) cases with type determination pending in
which the diagnosis of vCJD has been excluded.
***The sporadic cases include 2660 cases of sporadic Creutzfeldt-Jakob
disease (sCJD),
***50 cases of Variably Protease-Sensitive Prionopathy (VPSPr)
***and 21 cases of sporadic Fatal Insomnia (sFI).
CONFIRMED HUMAN BSE AKA MAD COW DISEASE vCJD TEXAS USA
Monday, June 02, 2014 Confirmed Variant CJD Case in Texas
SO, 4 months after the fact and still no word on this case. no information
what so ever. the silence is deafening $$$
Monday, November 3, 2014
The prion protein protease sensitivity, stability and seeding activity in
variably protease sensitive prionopathy brain tissue suggests molecular overlaps
with sporadic Creutzfeldt-Jakob disease
Tuesday, November 04, 2014
Towards an Age-Dependent Transmission Model of Acquired and Sporadic
Creutzfeldt-Jakob Disease
Thursday, August 12, 2010
Seven main threats for the future linked to prions
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases
constitute an unforeseen first threat that could sharply modify the European
approach to prion diseases.
Second threat
snip...
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
*** but the possibility that a small proportion of human cases so far
classified as "sporadic" CJD are of zoonotic origin could not be excluded.
Moreover, transmission experiments to non-human primates suggest that some TSE
agents in addition to Classical BSE prions in cattle (namely L-type Atypical
BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic
wasting disease (CWD) agents) might have zoonotic potential.
snip...
Sunday, August 09, 2009
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
Tuesday, August 18, 2009
BSE-The Untold Story - joe gibbs and singeltary 1999 – 2009
Saturday, June 14, 2014
Rep. Rosa DeLauro (D-CT) Calls for Briefing on Beef Recalled for Mad Cow
Potential Rep. Rosa DeLauro (D-CT)
Thursday, June 12, 2014
Missouri Firm Recalls Ribeye and Carcass Products That May Contain
Specified Risk Materials 4,012 pounds of fresh beef products because the dorsal
root ganglia may not have been completely removed
Tuesday, November 04, 2014
The pathological and molecular but not clinical phenotypes are maintained
after second passage of experimental atypical bovine spongiform encephalopathy
in cattle
CHRONIC WASTING DISEASE CWD TSE PRION
>>> According to the Centers for Disease Control and Prevention
(CDC) and the World Health Organization, there is no evidence CWD can be
transmitted to humans, but it is still wise to not consume any part of an animal
that shows signs of CWD.
NOW, what is the latest on human risk factors to CWD strains ???
*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent
*** Here we report that a human prion strain that had adopted the cervid
prion protein (PrP) sequence through passage in cervidized transgenic mice
efficiently infected transgenic mice expressing human PrP,
*** indicating that the species barrier from cervid to humans is prion
strain-dependent and humans can be vulnerable to novel cervid prion strains.
PPo2-27:
Generation of a Novel form of Human PrPSc by Inter-species Transmission of
Cervid Prions
*** Our findings suggest that CWD prions have the capability to infect
humans, and that this ability depends on CWD strain adaptation, implying that
the risk for human health progressively increases with the spread of CWD among
cervids.
PPo2-7:
Biochemical and Biophysical Characterization of Different CWD Isolates
*** The data presented here substantiate and expand previous reports on the
existence of different CWD strains.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
***The presence and seeding activity of PrPTSE in skeletal muscle from
CWD-infected cervids suggests prevention of such tissue in the human diet as a
precautionary measure for food safety, pending on further clarification of
whether CWD may be transmissible to humans.
>>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO
CONVERSION OF THE HUMAN PRION PROTEIN<<<
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
Wednesday, January 01, 2014
Molecular Barriers to Zoonotic Transmission of Prions
*** chronic wasting disease, there was no absolute barrier to conversion of
the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay
when seeded with CWD, resembles that found in the most common human prion
disease, namely sCJD of the MM1 subtype.
PRION2013 CONGRESSIONAL ABSTRACTS CWD
Sunday, August 25, 2013
HD.13: CWD infection in the spleen of humanized transgenic mice
***These results indicate that the CWD prion may have the potential to
infect human peripheral lymphoid tissues.
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
***However, they also show that there is no absolute barrier to conversion of
human prion protein in the case of chronic wasting disease.
PRION2013 CONGRESSIONAL ABSTRACTS CWD
Sunday, August 25, 2013
***Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood,
and mother to offspring transmission
there is in fact evidence that the potential for cwd transmission to humans
can NOT be ruled out.
I thought your readers and hunters and those that consume the venison,
should have all the scientific facts, personally, I don’t care what you eat, but
if it effects me and my family down the road, it should then concern everyone,
and the potential of iatrogenic transmission of the TSE prion is real i.e.
‘friendly fire’, medical, surgical, dental, blood, tissue, and or products there
from...like deer antler velvet and TSE prions and nutritional supplements there
from, all a potential risk factor that should not be ignored or silenced. ...
the prion gods at the cdc state that there is ;
''no strong evidence''
but let's see exactly what the authors of this cwd to human at the cdc
state ;
now, let’s see what the authors said about this casual link, personal
communications years ago. see where it is stated NO STRONG evidence. so, does
this mean there IS casual evidence ????
“Our conclusion stating that we found no strong evidence of CWD
transmission to humans”
From: TSS (216-119-163-189.ipset45.wt.net)
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To:
Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam,
In the Archives of Neurology you quoted (the abstract of which was attached
to your email), we did not say CWD in humans will present like variant CJD.
That assumption would be wrong. I encourage you to read the whole article
and call me if you have questions or need more clarification (phone:
404-639-3091). Also, we do not claim that "no-one has ever been infected with
prion disease from eating venison." Our conclusion stating that we found no
strong evidence of CWD transmission to humans in the article you quoted or in
any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message-----
From:
Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease
2008 1: Vet Res. 2008 Apr 3;39(4):41
A prion disease of cervids: Chronic wasting disease
Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported
to the Surveillance Center***,
snip...
full text ;
***********CJD REPORT 1994 increased risk for consumption of veal and
venison and lamb***********
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL
REPORT AUGUST 1994
Consumption of venison and veal was much less widespread among both cases
and controls. For both of these meats there was evidence of a trend with
increasing frequency of consumption being associated with increasing risk of
CJD. (not nvCJD, but sporadic CJD...tss)
These associations were largely unchanged when attention was restricted to
pairs with data obtained from relatives. ...
Table 9 presents the results of an analysis of these data.
There is STRONG evidence of an association between ‘’regular’’ veal eating
and risk of CJD (p = .0.01).
Individuals reported to eat veal on average at least once a year appear to
be at 13 TIMES THE RISK of individuals who have never eaten veal.
There is, however, a very wide confidence interval around this estimate.
There is no strong evidence that eating veal less than once per year is
associated with increased risk of CJD (p = 0.51).
The association between venison eating and risk of CJD shows similar
pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK
OF CJD (p = 0.04).
There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY
OF LAMB EATING (p = 0.02).
The evidence for such an association between beef eating and CJD is weaker
(p = 0.14). When only controls for whom a relative was interviewed are included,
this evidence becomes a little STRONGER (p = 0.08).
snip...
It was found that when veal was included in the model with another
exposure, the association between veal and CJD remained statistically
significant (p = < 0.05 for all exposures), while the other exposures ceased
to be statistically significant (p = > 0.05).
snip...
In conclusion, an analysis of dietary histories revealed statistical
associations between various meats/animal products and INCREASED RISK OF CJD.
When some account was taken of possible confounding, the association between
VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS
STATISTICALLY. ...
snip...
In the study in the USA, a range of foodstuffs were associated with an
increased risk of CJD, including liver consumption which was associated with an
apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3
studies in relation to this particular dietary factor, the risk of liver
consumption became non-significant with an odds ratio of 1.2 (PERSONAL
COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
snip...see full report ;
Thursday, October 10, 2013
*************CJD REPORT 1994 increased risk for consumption of veal and
venison and lamb**************
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge
Spencers Lane BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third
annual report from the CJD Surveillance Unit. I am sorry that you are
dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the
Department of Health is committed to publishing their reports as soon as they
become available. In the circumstances it is not the practice to circulate the
report for comment since the findings of the report would not be amended. In
future we can ensure that the British Deer Farmers Association receives a copy
of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed
of the results of any research in respect of CJD. This report was entirely the
work of the unit and was produced completely independantly of the the
Department.
The statistical results reqarding the consumption of venison was put into
perspective in the body of the report and was not mentioned at all in the press
release. Media attention regarding this report was low key but gave a realistic
presentation of the statistical findings of the Unit. This approach to
publication was successful in that consumption of venison was highlighted only
once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed statistical
links between CJD and consumption of venison, would increase, and quite possibly
give damaging credence, to the whole issue. From the low key media reports of
which I am aware it seems unlikely that venison consumption will suffer
adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
iatrogenic human CWD as sporadic CJD, what if ???
*** our results raise the possibility that CJD cases classified as VV1 may
include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne
infection by type 1 prions from animals, e.g., chronic wasting disease prions in
cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have
been reported (40, 41). The results of the present study emphasize the need for
traceback studies and careful re-examination of the biochemical properties of
sCJD-VV1 prions. ***
snip...see full text ;
Thursday, January 2, 2014
*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant
Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ??? ***
*** We hypothesize that both BSE prions and CWD prions passaged through
felines will seed human recPrP more efficiently than BSE or CWD from the
original hosts, evidence that the new host will dampen the species barrier
between humans and BSE or CWD. The new host effect is particularly relevant as
we investigate potential means of trans-species transmission of prion disease.
Monday, August 8, 2011
*** Susceptibility of Domestic Cats to CWD Infection ***
Oral.29: Susceptibility of Domestic Cats to CWD Infection
Amy Nalls, Nicholas J. Haley, Jeanette Hayes-Klug, Kelly Anderson, Davis M.
Seelig, Dan S. Bucy, Susan L. Kraft, Edward A. Hoover and Candace K. Mathiason†
Colorado State University; Fort Collins, CO USA†Presenting author; Email:
ckm@lamar.colostate.edu
Domestic and non-domestic cats have been shown to be susceptible to one
prion disease, feline spongiform encephalopathy (FSE), thought to be transmitted
through consumption of bovine spongiform encephalopathy (BSE) contaminated meat.
Because domestic and free ranging felids scavenge cervid carcasses, including
those in CWD affected areas, we evaluated the susceptibility of domestic cats to
CWD infection experimentally. Groups of n = 5 cats each were inoculated either
intracerebrally (IC) or orally (PO) with CWD deer brain homogenate. Between
40–43 months following IC inoculation, two cats developed mild but progressive
symptoms including weight loss, anorexia, polydipsia, patterned motor behaviors
and ataxia—ultimately mandating euthanasia. Magnetic resonance imaging (MRI) on
the brain of one of these animals (vs. two age-matched controls) performed just
before euthanasia revealed increased ventricular system volume, more prominent
sulci, and T2 hyperintensity deep in the white matter of the frontal hemisphere
and in cortical grey distributed through the brain, likely representing
inflammation or gliosis. PrPRES and widely distributed peri-neuronal vacuoles
were demonstrated in the brains of both animals by immunodetection assays. No
clinical signs of TSE have been detected in the remaining primary passage cats
after 80 months pi. Feline-adapted CWD was sub-passaged into groups (n=4 or 5)
of cats by IC, PO, and IP/SQ routes. Currently, at 22 months pi, all five IC
inoculated cats are demonstrating abnormal behavior including increasing
aggressiveness, pacing, and hyper responsiveness.
*** Two of these cats have developed rear limb ataxia. Although the limited
data from this ongoing study must be considered preliminary, they raise the
potential for cervid-to-feline transmission in nature.
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.
www.landesbioscience.com
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
FELINE SPONGIFORM ENCEPHALOPATHY FSE
PRION CONFERENCE 2014 HELD IN ITALY RECENTLY CWD BSE TSE UPDATE
> First transmission of CWD to transgenic mice over-expressing bovine
prion protein gene (TgSB3985)
PRION 2014 - PRIONS: EPIGENETICS and NEURODEGENERATIVE DISEASES – Shaping
up the future of prion research
Animal TSE Workshop 10.40 – 11.05 Talk Dr. L. Cervenakova First
transmission of CWD to transgenic mice over-expressing bovine prion protein gene
(TgSB3985)
P.126: Successful transmission of chronic wasting disease (CWD) into mice
over-expressing bovine prion protein (TgSB3985)
Larisa Cervenakova,1 Christina J Sigurdson,2 Pedro Piccardo,3 Oksana
Yakovleva,1 Irina Vasilyeva,1 Jorge de Castro,1 Paula Saá,1 and Anton Cervenak1
1American Red Cross, Holland Laboratory; Rockville, MD USA; 2University of
California; San Diego, CA USA; 3Lab TSE/OBRR /CBER/FDA; Rockville, MD USA
Keywords: chronic wasting disease, transmission, transgenic mouse, bovine
prion protein
Background. CWD is a disease affecting wild and farmraised cervids in North
America. Epidemiological studies provide no evidence of CWD transmission to
humans. Multiple attempts have failed to infect transgenic mice expressing human
PRNP gene with CWD. The extremely low efficiency of PrPCWD to convert normal
human PrPC in vitro provides additional evidence that transmission of CWD to
humans cannot be easily achieved. However, a concern about the risk of CWD
transmission to humans still exists. This study aimed to establish and
characterize an experimental model of CWD in TgSB3985 mice with the following
attempt of transmission to TgHu mice.
Materials and Methods. TgSB3985 mice and wild-type FVB/ NCrl mice were
intracranially injected with 1% brain homogenate from a CWD-infected Tga20 mouse
(CWD/Tga20). TgSB3985 and TgRM (over-expressing human PrP) were similarly
injected with 5% brain homogenates from CWD-infected white-tailed deer (CWD/WTD)
or elk (CWD/Elk). Animals were observed for clinical signs of neurological
disease and were euthanized when moribund. Brains and spleens were removed from
all mice for PrPCWD detection by Western blotting (WB). A histological analysis
of brains from selected animals was performed: brains were scored for the
severity of spongiform change, astrogliosis, and PrPCWD deposition in ten brain
regions.
Results. Clinical presentation was consistent with TSE. More than 90% of
TgSB3985 and wild-type mice infected with CWD/Tga20, tested positive for PrPres
in the brain but only mice in the latter group carried PrPCWD in their spleens.
We found evidence for co-existence or divergence of two CWD/ Tga20 strains based
on biochemical and histological profiles. In TgSB3985 mice infected with CWD-elk
or CWD-WTD, no animals tested positive for PrPCWD in the brain or in the spleen
by WB. However, on neuropathological examination we found presence of amyloid
plaques that stained positive for PrPCWD in three CWD/WTD- and two
CWD/Elk-infected TgSB3985 mice. The neuropathologic profiles in CWD/WTD- and
CWD/Elkinfected mice were similar but unique as compared to profiles of BSE,
BSE-H or CWD/Tg20 agents propagated in TgSB3985 mice. None of CWD-infected TgRM
mice tested positive for PrPCWD by WB or by immunohistochemical detection.
Conclusions. To our knowledge, this is the first established experimental
model of CWD in TgSB3985. We found evidence for co-existence or divergence of
two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice.
Finally, we observed phenotypic differences between cervid-derived CWD and
CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway
to characterize these strains.
PRION 2014 CONFERENCE
CHRONIC WASTING DISEASE CWD
A FEW FINDINGS ;
Conclusions. To our knowledge, this is the first established experimental
model of CWD in TgSB3985. We found evidence for co-existence or divergence of
two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice.
Finally, we observed phenotypic differences between cervid-derived CWD and
CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway
to characterize these strains.
We conclude that TSE infectivity is likely to survive burial for long time
periods with minimal loss of infectivity and limited movement from the original
burial site. However PMCA results have shown that there is the potential for
rainwater to elute TSE related material from soil which could lead to the
contamination of a wider area. These experiments reinforce the importance of
risk assessment when disposing of TSE risk materials.
The results show that even highly diluted PrPSc can bind efficiently to
polypropylene, stainless steel, glass, wood and stone and propagate the
conversion of normal prion protein. For in vivo experiments, hamsters were ic
injected with implants incubated in 1% 263K-infected brain homogenate. Hamsters,
inoculated with 263K-contaminated implants of all groups, developed typical
signs of prion disease, whereas control animals inoculated with non-contaminated
materials did not.
Our data establish that meadow voles are permissive to CWD via peripheral
exposure route, suggesting they could serve as an environmental reservoir for
CWD. Additionally, our data are consistent with the hypothesis that at least two
strains of CWD circulate in naturally-infected cervid populations and provide
evidence that meadow voles are a useful tool for CWD strain typing.
Conclusion. CWD prions are shed in saliva and urine of infected deer as
early as 3 months post infection and throughout the subsequent >1.5 year
course of infection. In current work we are examining the relationship of
prionemia to excretion and the impact of excreted prion binding to surfaces and
particulates in the environment.
Conclusion. CWD prions (as inferred by prion seeding activity by RT-QuIC)
are shed in urine of infected deer as early as 6 months post inoculation and
throughout the subsequent disease course. Further studies are in progress
refining the real-time urinary prion assay sensitivity and we are examining more
closely the excretion time frame, magnitude, and sample variables in
relationship to inoculation route and prionemia in naturally and experimentally
CWD-infected cervids.
Conclusions. Our results suggested that the odds of infection for CWD is
likely controlled by areas that congregate deer thus increasing direct
transmission (deer-to-deer interactions) or indirect transmission
(deer-to-environment) by sharing or depositing infectious prion proteins in
these preferred habitats. Epidemiology of CWD in the eastern U.S. is likely
controlled by separate factors than found in the Midwestern and endemic areas
for CWD and can assist in performing more efficient surveillance efforts for the
region.
Conclusions. During the pre-symptomatic stage of CWD infection and
throughout the course of disease deer may be shedding multiple LD50 doses per
day in their saliva. CWD prion shedding through saliva and excreta may account
for the unprecedented spread of this prion disease in nature.
P.28: Modeling prion species barriers and the new host effect using RT-QuIC
Kristen A Davenport, Davin M Henderson, Candace K Mathiason, and Edward A
Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA
The propensity for trans-species prion transmission is related to the
structural characteristics of the enciphering and heterologous PrP, but the
exact mechanism remains mostly mysterious.
Studies of the effects of primary or tertiary prion protein
www.landesbioscience.com Prion 37 structures on trans-species prion transmission
have relied upon animal bioassays, making the influence of prion protein
structure vs. host co-factors (e.g. cellular constituents, trafficking, and
innate immune interactions) difficult to dissect.
As an alternative strategy, we are using real-time quaking-induced
conversion (RT-QuIC) to investigate the propensity for and the kinetics of
trans-species prion conversion. RT-QuIC has the advantage of providing more
defined conditions of seeded conversion to study the specific role of native
PrP:PrPRES interactions as a component of the species barrier.
We are comparing chronic wasting disease (CWD) and bovine spongiform
encephalopathy (BSE) prions by seeding each prion into its native host recPrP
(full-length bovine recPrP, or white tail deer recPrP) vs. into the heterologous
species. Upon establishing the characteristics of intra-species and
inter-species prion seeding for CWD and BSE prions, we will evaluate the seeding
kinetics and cross-species seeding efficiencies of BSE and CWD passaged into a
common new host—feline—shown to be a permissive host for both CWD and BSE.
*** We hypothesize that both BSE prions and CWD prions passaged through
felines will seed human recPrP more efficiently than BSE or CWD from the
original hosts, evidence that the new host will dampen the species barrier
between humans and BSE or CWD. The new host effect is particularly relevant as
we investigate potential means of trans-species transmission of prion disease.
Tuesday, November 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison
in an Upstate New York community: risk behaviours and health outcomes 2005–2011
Sunday, August 24, 2014
USAHA 117TH ANNUAL MEETING USDA-APHIS–VS CWD Herd Certification Program
Goals TSE PRION October 17 – 23, 2013
SCRAPIE TSE PRION DISEASE
*** OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED, WISHES TO
CONTINUE SPREADING IT AROUND THE GLOBE
Monday, November 30, 2009
*** USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL
HEALTH CODE, DOES NOT SURPRISE ME $
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep
and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were
exposed to the infectious agents only by their nonforced consumption of known
infectious tissues. The asymptomatic incubation period in the one monkey exposed
to the virus of kuru was 36 months; that in the two monkeys exposed to the virus
of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the
two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively.
Careful physical examination of the buccal cavities of all of the monkeys failed
to reveal signs or oral lesions. One additional monkey similarly exposed to kuru
has remained asymptomatic during the 39 months that it has been under
observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie
by natural feeding to squirrel monkeys that we have reported provides further
grounds for concern that scrapie-infected meat may occasionally give rise in
humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is
transmissible to man. This has followed reports that the disease has been
transmitted to primates. One particularly lurid speculation (Gajdusek 1977)
conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and
transmissible encephalopathy of mink are varieties of a single "virus". The U.S.
Department of Agriculture concluded that it could "no longer justify or permit
scrapie-blood line and scrapie-exposed sheep and goats to be processed for human
or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is
emphasised by the finding that some strains of scrapie produce lesions identical
to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be
transmissible to man raises two considerations. First, the safety of laboratory
personnel requires prompt attention. Second, action such as the "scorched meat"
policy of USDA makes the solution of the acrapie problem urgent if the sheep
industry is not to suffer grievously.
snip...
76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes
of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey
(Macaca fascicularis) with an incubation period of more than 5 yr from the time
of intracerebral inoculation of scrapie-infected mouse brain. The animal
developed a chronic central nervous system degeneration, with ataxia, tremor and
myoclonus with associated severe scrapie-like pathology of intensive astroglial
hypertrophy and proliferation, neuronal vacuolation and status spongiosus of
grey matter. The strain of scrapie virus used was the eighth passage in Swiss
mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral
passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton,
Berkshire).
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2
December 2010
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
Thursday, December 23, 2010
Molecular Typing of Protease-Resistant Prion Protein in Transmissible
Spongiform Encephalopathies of Small Ruminants, France, 2002-2009
Volume 17, Number 1 January 2011
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform
encephalopathy following passage in sheep
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
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
*** Canada Increased Atypical Scrapie Detections
Press reports indicate that increased surveillance is catching what
otherwise would have been unreported findings of atypical scrapie in sheep. In
2009, five new cases have been reported in Quebec, Ontario, Alberta, and
Saskatchewan. With the exception of Quebec, all cases have been diagnosed as
being the atypical form found in older animals. Canada encourages producers to
join its voluntary surveillance program in order to gain scrapie-free status.
The World Animal Health will not classify Canada as scrapie-free until no new
cases are reported for seven years. The Canadian Sheep Federation is calling on
the government to fund a wider surveillance program in order to establish the
level of prevalence prior to setting an eradication date. Besides long-term
testing, industry is calling for a compensation program for farmers who report
unusual deaths in their flocks.
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.
P.5.21 Parallels between different forms of sheep scrapie and types of
Creutzfeldt-Jakob disease (CJD)
Wiebke M. Wemheuer1, Sylvie L. Benestad2, Arne Wrede1, Wilhelm E.
Wemheuer3, Tatjana Pfander1, Bjørn Bratberg2, Bertram Brenig3,Walter J.
Schulz-Schaeffer1 1University Medical Center Goettingen, Germany; 2Institute of
Veterinary Medicine Oslo, Norway; 3Institute of Veterinary Medicine Goettingen,
Germany
Background: Scrapie in sheep and goats is often regarded as the archetype
of prion diseases. In 1998, a new form of scrapie - atypical/Nor98 scrapie - was
described that differed from classical scrapie in terms of epidemiology, Western
blot profile, the distribution of pathological prion protein (PrPSc) in the body
and its stability against proteinase K. In a similar way, distinct disease types
exist in sporadic Creutzfeldt-Jakob disease (CJD). They differ with regard to
their clinical outcome, Western blot profile and PrPSc deposition pattern in the
central nervous system (CNS). Objectives: The comparison of PrPSc deposits in
sheep scrapie and human sporadic CJD.
Methods: Tissues of the CNS of sheep with classical scrapie, sheep with
atypical/Nor98 scrapie and 20 patients with sporadic CJD were examined using the
sensitive Paraffin Embedded Tissue (PET) blot method. The results were compared
with those obtained by immunohistochemistry. With the objective of gaining
information on the protein conformation, the PrPSc of classical and
atypical/Nor98 sheep scrapie and sporadic CJD was tested for its stability
against denaturation with guanidine hydrochloride (GdnHCl) using a Membrane
Adsorption Assay.
Results: The PrPSc of atypical/Nor98 scrapie cases and of CJD prion type 1
patients exhibits a mainly reticular/synaptic deposition pattern in the brain
and is relatively sensitive to denaturation with GdnHCl. In contrast classical
scrapie cases and CJD prion type 2 patients have a more complex PrPSc deposition
pattern in common that consists of larger PrPSc aggregates and the PrPSc itself
is comparatively stable against denaturation.
Discussion: The similarity between CJD types and scrapie types indicates
that at least two comparable forms of the misfolded prion protein exist beyond
species barriers and can elicit prion diseases. It seems therefore reasonable to
classify classical and atypical/Nor98 scrapie - in analogy to the existing CJD
types - as different scrapie types.
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01
Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine
issue 2284. Subscribe and get 4 free issues. FOUR years ago, Terry Singeltary
watched his mother die horribly from a degenerative brain disease. Doctors told
him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit
her violent symptoms, and he demanded an autopsy. It showed she had died of
sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by
chance into a killer. But Singeltary thinks otherwise. He is one of a number of
campaigners who say that some sCJD, like the variant CJD related to BSE, is
caused by eating meat from infected animals. Their suspicions have focused on
sheep carrying scrapie, a BSE-like disease that is widespread in flocks across
Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no
evidence that it poses a risk to human health. But if the French finding means
that scrapie can cause sCJD in people, countries around the world may have
overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They
injected the brains of macaque monkeys with brain from BSE cattle, and from
French and British vCJD patients. The brain damage and clinical symptoms in the
monkeys were the same for all three. Mice injected with the original sets of
brain tissue or with infected monkey brain also developed the same
symptoms.
As a control experiment, the team also injected mice with brain tissue from
people and animals with other prion diseases: a French case of sCJD; a French
patient who caught sCJD from human-derived growth hormone; sheep with a French
strain of scrapie; and mice carrying a prion derived from an American scrapie
strain. As expected, they all affected the brain in a different way from BSE and
vCJD. But while the American strain of scrapie caused different damage from
sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been
epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute
for Animal Health in Edinburgh, who was a member of the same team as Deslys.
"You see about the same incidence of the disease everywhere, whether or not
there are many sheep, and in countries such as New Zealand with no scrapie." In
the only previous comparisons of sCJD and scrapie in mice, Bruce found they were
dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would
not necessarily see a relationship between the two with epidemiology if only
some strains affect only some people," says Deslys. Bruce is cautious about the
mouse results, but agrees they require further investigation. Other trials of
scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion
protein, and each type of protein can fold up two different ways. Kretschmar has
found that these six combinations correspond to six clinical types of sCJD: each
type of normal prion produces a particular pathology when it spontaneously
deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing
prion, the relationship between pathology and prion type should be different, as
it is in vCJD. "If we look at brain samples from sporadic CJD cases and find
some that do not fit the pattern," says Kretschmar, "that could mean they were
caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence
elsewhere. Singeltary and other US activists think that some of these people
died after eating contaminated meat or "nutritional" pills containing dried
animal brain. Governments will have a hard time facing activists like Singeltary
if it turns out that some sCJD isn't as spontaneous as doctors have
insisted.
Deslys's work on macaques also provides further proof that the human
disease vCJD is caused by BSE. And the experiments showed that vCJD is much more
virulent to primates than BSE, even when injected into the bloodstream rather
than the brain. This, says Deslys, means that there is an even bigger risk than
we thought that vCJD can be passed from one patient to another through
contaminated blood transfusions and surgical instruments.
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
Dietary Risk Factors for Sporadic Creutzfeldt-Jakob Disease: A
Confirmatory Case-Control Study
Conclusions—The a priori hypotheses were supported.
*Consumption of various meat products may be one method of transmission of
the infectious agent for sCJD.
Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
Transmissible Spongiform Encephalopathy TSE Prion Disease have now been
discovered in a wide verity of species across North America. typical C-BSE,
atypical L-type BASE BSE, atypical H-type BSE, atypical H-G BSE, of the bovine,
typical and atypical Scrapie strains, in sheep and goats, with atypical Nor-98
Scrapie spreading coast to coast in about 5 years. Chronic Wasting Disease CWD
in cervid is slowly spreading without any stopping it in Canada and the USA and
now has mutated into many different strains. Transmissible Mink Encephalopathy
TME outbreaks. These Transmissible Spongiform Encephalopathy TSE Prion Disease
have been silently mutating and spreading in different species in North America
for decades.
The USDA, FDA, et al have assured us of a robust Triple BSE TSE prion
Firewall, of which we now know without a doubt, that it was nothing but ink on
paper. Since the 1997 mad cow feed ban in the USA, literally tons and tons of
banned mad cow feed has been put out into commerce, never to return, as late as
December of 2013, serious, serious breaches in the FDA mad cow feed ban have
been documented. The 2004 enhanced BSE surveillance program was so flawed, that
one of the top TSE prion Scientist for the CDC, Dr. Paul Brown stated ; Brown,
who is preparing a scientific paper based on the latest two mad cow cases to
estimate the maximum number of infected cows that occurred in the United States,
said he has "absolutely no confidence in USDA tests before one year ago" because
of the agency's reluctance to retest the Texas cow that initially tested
positive. see ; http://www.upi.com/Health_News/2006/03/15/Analysis-What-that-mad-cow-means/UPI-12841142465253/
The BSE surveillance and testing have also been proven to be flawed, and
the GAO and OIG have both raised serious question as to just how flawed it has
been (see GAO and OIG reports). North America has more documented TSE prion
disease, in different documented species (excluding the Zoo BSE animals in the
EU), then any other place on the Globe. This does not include the very
likelihood that TSE prion disease in the domestic feline and canine have been
exposed to high doses of the TSE prion disease vid pet food. To date, it’s still
legal to include deer from cwd zone into pet food or deer food. Specified Risk
Material i.e. SRM bans still being breach, as recently as just last month.
nvCJD or what they now call vCJD, another case documented in Texas last
month, with very little information being released to the public on about this
case? with still the same line of thought from federal officials, ‘it can’t
happen here’, so another vCJD blamed on travel of a foreign animal disease from
another country, while ignoring all the BSE TSE Prion risk factors we have here
in the USA and Canada, and the time that this victim and others, do spend in the
USA, and exposed to these risk factors, apparently do not count in any way with
regard to risk factor. a flawed process of risk assessment.
sporadic CJD, along with new TSE prion disease in humans, of which the
young are dying, of which long duration of illness from onset of symptoms to
death have been documented, only to have a new name added to the pot of prion
disease i.e. sporadic GSS, sporadic FFI, and or VPSPR. I only ponder how a
familial type disease could be sporadic with no genetic link to any family
member? when the USA is the only documented Country in the world to have
documented two different cases of atypical H-type BSE, with one case being
called atypical H-G BSE with the G meaning Genetic, with new science now showing
that indeed atypical H-type BSE is very possible transmitted to cattle via oral
transmission (Prion2014). sporadic CJD and VPSPR have been rising in Canada,
USA, and the UK, with the same old excuse, better surveillance. You can only use
that excuse for so many years, for so many decades, until one must conclude that
CJD TSE prion cases are rising. a 48% incease in CJD in Canada is not just a
blip or a reason of better surveillance, it is a mathematical rise in numbers.
More and more we are seeing more humans exposed in various circumstance in the
Hospital, Medical, Surgical arenas to the TSE Prion disease, and at the same
time in North America, more and more humans are becoming exposed to the TSE
prion disease via consumption of the TSE prion via deer and elk, cattle, sheep
and goats, and for those that are exposed via or consumption, go on to further
expose many others via the iatrogenic modes of transmission of the TSE prion
disease i.e. friendly fire. I pondered this mode of transmission via the victims
of sporadic FFI, sporadic GSS, could this be a iatrogenic event from someone
sub-clinical with sFFI or sGSS ? what if?
Two decades have passed since Dr. Ironside first confirmed his first ten
nvCJD victims in 1995. Ten years later, 2005, we had Dr. Gambetti and his first
ten i.e. VPSPR in younger victims. now we know that indeed VPSPR is
transmissible. yet all these TSE prion disease and victims in the USA and Canada
are being pawned off as a spontaneous event, yet science has shown, the
spontaneous theory has never been proven in any natural case of TSE prion
disease, and scientist have warned, that they have now linked some sporadic CJD
cases to atypical BSE, to atypical Scrapie, and to CWD, yet we don’t here about
this in the public domain. We must make all human and animal TSE prion disease
reportable in every age group, in ever state and internationally, we must have a
serious re-evaluation and testing of the USA cattle herds, and we must ban
interstate movement of all cervids. Any voluntary effort to do any of this will
fail. Folks, we have let the industry run science far too long with regards to
the TSE prion disease. While the industry and their lobbyist continues to funnel
junk science to our decision policy makers, Rome burns. ...end
REFERENCES
[all scientific peer review studies and other scientific information I have
put into blogs, to shorten reference data. I DO NOT advertise or make money from
this, this information is for education use...lost my mom to the hvCJD, and just
made a promise, never forget, and never let them forget. ...TSS]
Sunday, June 29, 2014
Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
Self-Propagative
Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer
Disease
Received July 24, 2014; Accepted September 16, 2014; Published November 3,
2014
Singeltary comment ;
Mom DOD 12/14/97
Heidenhain Variant Creutzfeldt Jakob Disease Case Report
snip...
Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'
DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114
McCullough Bldg. Galveston, Texas 77555-0785
FAX COVER SHEET DATE: 4-23-98
TO: Mr. Terry Singeltary @ -------
FROM: Gerald Campbell FAX: (409) 772-5315 PHONE: (409) 772-2881 Number of
Pages (including cover sheet): Message:
*CONFIDENTIALITY NOTICE* T
his document accompanying this transmission contains confidential
information belonging to the sender that is legally privileged. This information
is intended only for the use of the individual or entry names above. If you are
not the intended recipient, you are hereby notified that any disclosure, copying
distribution, or the taking of any action in reliances on the contents of this
telefaxed information is strictly prohibited. If you received this telefax in
error, please notify us by telephone immediately to arrange for return of the
original documents.
--------------------------
Patient Account: 90000014-518 Med. Rec. No.: (0160)118511Q Patient Name:
POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C Attending
Dr.: Date / Time Admitted : 12/14/97 1228 Copies to: UTMB University of Texas
Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683
Pathology Report
FINAL AUTOPSY
DIAGNOSIS Autopsy' Office (409)772-2858
Autopsy NO.: AU-97-00435 AUTOPSY INFORMATION: Occupation: Unknown
Birthplace: Unknown Residence: Crystal Beach Date/Time of Death: 12/14/97 13:30
Date/Time of Autopsy: 12/15/97 15:00 Pathologist/Resident: Pencil/Fernandez
Service:
Private
Restriction: Brain only
FINAL AUTOPSY DIAGNOSIS I. Brain: Creutzfeldt-Jakob disease, Heidenhain
variant.
snip...see full text ;
TSS
