Mad cow infected blood 'to kill 1,000’
Mad cow infected blood 'to kill 1,000’
Up to 1,000 people could die of the human form of “mad cow” disease through
infected blood given to them in British hospitals, ministers have been told.
By Rowena Mason, Political Correspondent
10:00PM BST 28 Apr 2013
Government experts believe there is still a risk of people contracting
variant Creutzfeldt-Jakob Disease (vCJD) through blood transfusions, as about
30,000 Britons are likely to be carrying the brain-wasting illness in a dormant
form — double the previous estimate.
They warn the current total death toll of 176 from vCJD could rise more
than five-fold as the infection has not been wiped out of the blood supply like
it has been in the food chain.
Frank Dobson, a former health secretary, tonight urged ministers to develop
a nationwide screening programme for blood donors to stop future infections of
vCJD, which has the potential to cause “horrendous deaths”.
People are no longer in danger of getting vCJD from eating British beef,
after ministers ordered the slaughter of millions of cows when the “mad cow”
disease scandal broke in 1989. Fears that hundreds of thousands of people could
contract the human form of bovine spongiform encephalopathy (BSE) proved
unfounded.
However, the Government acknowledges that one in 2,000 Britons – or
approximately 30,000 people- are already “silent” carriers of infectious
proteins that lead some people to develop vCJD.
A little-reported study last summer concluded the prevalence of this
“silent” vCJD is likely to be twice as high as previously thought.
These 30,000 carriers can unknowingly pass on the infectious proteins –
known as prions – to new potential sufferers through donated blood.
Because so little is known about vCJD, there is no telling which carriers
will go on to develop the disease or whether any new cases will actually
materialise at all.
There have been no new cases for two years and there are thought to be no
surviving sufferers of vCJD, which has always historically proved fatal.
However a new risk assessment published this month by the Government’s
Health Protection Analytical team reveals that infected blood donations could
cause up to 1,000 deaths in a high case scenario.
About half of the cases could develop in people who have already received
blood transfusions and up to 580 cases from people who are yet to be infected
with the disease. The central estimate of infections yet to occur is 205.
It suggests ministers could consider recruiting young blood donors born
after 1996 once they become eligible, as they will not have eaten infected beef.
“The number of “silent” vCJD infections associated with transfusion would
be much higher than the number of clinical cases,” it said. “It is therefore
important to maintain, and if possible enhance, measures to prevent onward
transmission of infection, notably the exclusion of recipients from donating
blood.”
Mr Dobson, the former Labour Health Secretary, said “everything humanly
possible should be done to develop a blood test”.
“There is no room at all for complacency,” he told The Daily Telegraph.
“With a blood test, you would be able to screen every potential donor. If that
screening showed the incidence was higher than thought then maybe you would do
it for the whole population.”
Professor John Collinge, an expert from University College London, whose
research unit has developed a blood test for vCJD, said there is an element of
“wishful thinking” within the Government, with officials hoping the problem has
gone away.
He said he is “sceptical of guesstimates” of future cases and believes
ministers need to start a study of vCJD in blood, rather than appendices, to get
a proper grip on the risk of infection through transfusions.
“The figure of one in 2,000 in the appendix study was pretty worrying,” he
said. “I was pretty alarmed by that. It’s clear there is a very substantial pool
of infection in the community. There needs to be blood testing to answer this
question of prevalance properly.”
Sir Paul Beresford, an MP and former Conservative environment minister,
also believes the Government must wake up to the potential for future vCJD
infections and is campaigning for more filtering of donated blood.
“If we’ve got it wrong our grandchildren are going to potentially have an
epidemic of vCJD that we can do nothing about but we can prevent it if we act
now,” he said.
“There’s some quite simple things they can do. For example, there’s a new
system that’s being developed that will filter red blood cells before
transfusion.
“[The system] is not adequate at the moment but the Government’s argument
is that there’s no sign of a risk because the number of people turning up with
vCJD is going down. But it can take 10, 15, 20, 25 years for this to pop up.”
A spokesman for the Department of Health said the Government continues to
encourage “people of all ages to give blood”, adding “we have one of the safest
blood supplies in the world”.
“Independent experts from the Advisory Committee on the Safety of Blood,
Tissues and Organs have used this study during their considerations of measures
to reduce the potential risk of transmission through blood transfusions,” she
said. “There is no evidence of any UK clinical cases of vCJD being linked to a
blood transfusion given after 1999.
“In fact there have been no new cases in the UK for more than two years.”
She said the study relates to people’s future potential to develop vCJD,
not actual new cases that have occured.
nothing like missing the bigger picture, but they been missing (ignroing)
it since 1985 $$$
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
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...
Thursday, August 12, 2010
Seven main threats for the future linked to prions
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...
Rural and Regional Affairs and Transport References Committee
The possible impacts and consequences for public health, trade and
agriculture of the Government's decision to relax import restrictions on beef
Final report June 2010
2.65 At its hearing on 14 May 2010, the committee heard evidence from Dr
Alan Fahey who has recently submitted a thesis on the clinical neuropsychiatric,
epidemiological and diagnostic features of Creutzfeldt-Jakob disease.48 Dr Fahey
told the committee of his concerns regarding the lengthy incubation period for
transmissible spongiform encephalopathies, the inadequacy of current tests and
the limited nature of our current understanding of this group of diseases.49
2.66 Dr Fahey also told the committee that in the last two years a link
has been established between forms of atypical CJD and atypical BSE. Dr Fahey
said that: They now believe that those atypical BSEs overseas are in fact
causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to
mad sheep disease or a different form. If you look in the textbooks it looks
like this is just arising by itself. But in my research I have a summary of a
document which states that there has never been any proof that sporadic
Creutzfeldt-Jakob disease has arisen de novo-has arisen of itself. There is no
proof of that. The recent research is that in fact it is due to atypical forms
of mad cow disease which have been found across Europe, have been found in
America and have been found in Asia. These atypical forms of mad cow disease
typically have even longer incubation periods than the classical mad cow
disease.50
Atypical BSE in Cattle
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.
This study will contribute to a correct definition of specified risk
material (SRM) in atypical BSE. The incumbent of this position will develop new
and transfer existing, ultra-sensitive methods for the detection of atypical BSE
in tissue of experimentally infected cattle.
P.4.23
Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3,
Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5,
Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto
Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany;
4National Veterinary Research Institute, Poland; 5Kansas State University
(Previously at USDA National Animal Disease Center), USA
Background: Classical BSE is a world-wide prion disease in cattle, and the
classical BSE strain (BSE-C) has led to over 200 cases of clinical human
infection (variant CJD). Atypical BSE cases have been discovered in three
continents since 2004; they include the L-type (also named BASE), the H-type,
and the first reported case of naturally occurring BSE with mutated bovine PRNP
(termed BSE-M). The public health risks posed by atypical BSE were largely
undefined.
Objectives: To investigate these atypical BSE types in terms of their
transmissibility and phenotypes in humanized mice. Methods: Transgenic mice
expressing human PrP were inoculated with several classical (C-type) and
atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation
time, characteristics and distribution of PrPSc, symptoms, and histopathology
were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected
with minimal spongiosis and an average incubation time of 20-22 months, whereas
only one of the C-type BSE-inoculated mice developed prion disease after more
than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse
brains was biochemically different from bovine BASE or sCJD. PrPSc was also
detected in the spleen of 22% of BASE-infected humanized mice, but not in those
infected with sCJD. Secondary transmission of BASE in the humanized mice led to
a small reduction in incubation time.*** The atypical BSE-H strain is also
transmissible with distinct phenotypes in the humanized mice, but no BSE-M
transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than
classical BSE, has a lymphotropic phenotype, and displays a modest transmission
barrier in our humanized mice. 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.
P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN
HUMANIZED MOUSE MODELS
Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina
Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi
Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case
Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto
Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany;
4National Veterinary Research Institute, Poland; 5Kansas State University,
Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous
address: USDA National Animal Disease Center, Ames, IA 50010, USA
Classical BSE is a world-wide prion disease in cattle, and the classical
BSE strain (BSE-C) has led to over 200 cases of clinical human infection
(variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have
been discovered in three continents since 2004. The first case of naturally
occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006
in the USA. The transmissibility and phenotypes of these atypical BSE
strains/isolates in humans were unknown. We have inoculated humanized transgenic
mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M
isolate. We have found that the atypical BSE-L strain is much more virulent than
the classical BSE-C. *** The atypical BSE-H strain is also transmissible in the
humanized transgenic mice with distinct phenotype, but no transmission has been
observed for the BSE-M isolate so far.
III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE,
DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)
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.
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate
Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1,
Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1,
Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4,
Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4,
Jean-Philippe Deslys1
1 Institute of Emerging Diseases and Innovative Therapies, CEA,
Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del
Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps
Florida, Jupiter, Florida, United States of America, 5 Genetics Division,
Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts,
United States of America
Abstract Top Background Human variant Creutzfeldt-Jakob Disease (vCJD)
results from foodborne transmission of prions from slaughtered cattle with
classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which
remain mostly asymptomatic in aging cattle, were recently identified at
slaughterhouses throughout Europe and North America, raising a question about
human susceptibility to these new prion strains.
Methodology/Principal Findings Brain homogenates from cattle with
classical BSE and atypical (BASE) infections were inoculated intracerebrally
into cynomolgus monkeys (Macacca fascicularis), a non-human primate model
previously demonstrated to be susceptible to the original strain of cBSE. The
resulting diseases were compared in terms of clinical signs, histology and
biochemistry of the abnormal prion protein (PrPres). The single monkey infected
with BASE had a shorter survival, and a different clinical evolution,
histopathology, and prion protein (PrPres) pattern than was observed for either
classical BSE or vCJD-inoculated animals. Also, the biochemical signature of
PrPres in the BASE-inoculated animal was found to have a higher proteinase K
sensitivity of the octa-repeat region. We found the same biochemical signature
in three of four human patients with sporadic CJD and an MM type 2 PrP genotype
who lived in the same country as the infected bovine.
Conclusion/Significance Our results point to a possibly higher degree of
pathogenicity of BASE than classical BSE in primates and also raise a question
about a possible link to one uncommon subset of cases of apparently sporadic
CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of
atypical strains should temper the urge to relax measures currently in place to
protect public health from accidental contamination by BSE-contaminated
products.
Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire
S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle
to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017
Editor: Neil Mabbott, University of Edinburgh, United Kingdom
Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20,
2008
Copyright: © 2008 Comoy et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Funding: This work has been supported by the Network of Excellence
NeuroPrion.
Competing interests: CEA owns a patent covering the BSE diagnostic tests
commercialized by the company Bio-Rad.
* E-mail: emmanuel.comoy@cea.fr
snip...
In summary, we have transmitted one atypical form of BSE (BASE) to a
cynomolgus macaque monkey that had a shorter incubation period than monkeys
infected with classical BSE, with distinctive clinical, neuropathological, and
biochemical features; and have shown that the molecular biological signature
resembled that seen in a comparatively uncommon subtype of sporadic CJD. We
cannot yet say whether BASE is more pathogenic for primates (including humans)
than cBSE, nor can we predict whether its molecular biological features
represent a clue to one cause of apparently sporadic human CJD. However, the
evidence presented here and by others justifies concern about a potential human
health hazard from undetected atypical forms of BSE, and despite the waning
epizoonosis of classical BSE, it would be premature to abandon the precautionary
measures that have been so successful in reversing the impact of cBSE. We would
instead urge a gradual, staged reduction that takes into account the evolving
knowledge about atypical ruminant diseases, and both a permanent ban on the use
of bovine central nervous system tissue for either animal or human use, and its
destruction so as to eliminate any risk of environmental contamination.
Proc Natl Acad Sci U S A. 2004 March 2; 101(9): 3065–3070. Published online
2004 February 17. doi: 10.1073/pnas.0305777101 PMCID: PMC365745 Medical Sciences
Identification of a second bovine amyloidotic spongiform encephalopathy:
Molecular similarities with sporadic Creutzfeldt-Jakob disease
Cristina Casalone,*† Gianluigi Zanusso,†‡ Pierluigi Acutis,* Sergio
Ferrari,‡ Lorenzo Capucci,§ Fabrizio Tagliavini,¶ Salvatore Monaco,‡ and Maria
Caramelli*
Abstract
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are
mammalian neurodegenerative disorders characterized by a posttranslational
conversion and brain accumulation of an insoluble, protease-resistant isoform
(PrPSc) of the host-encoded cellular prion protein (PrPC). Human and animal TSE
agents exist as different phenotypes that can be biochemically differentiated on
the basis of the molecular mass of the protease-resistant PrPSc fragments and
the degree of glycosylation. Epidemiological, molecular, and transmission
studies strongly suggest that the single strain of agent responsible for bovine
spongiform encephalopathy (BSE) has infected humans, causing variant
Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE
agent, which circumvents the so-called ”species barrier” between cattle and
humans and adapts to different mammalian species, has raised considerable
concern for human health. To date, it is unknown whether more than one strain
might be responsible for cattle TSE or whether the BSE agent undergoes
phenotypic variation after natural transmission. Here we provide evidence of a
second cattle TSE. The disorder was pathologically characterized by the presence
of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid
deposition in typical BSE cases, and by a different pattern of regional
distribution and topology of brain PrPSc accumulation. In addition, Western blot
analysis showed a PrPSc type with predominance of the low molecular mass
glycoform and a protease-resistant fragment of lower molecular mass than
BSE-PrPSc. Strikingly, the molecular signature of this previously undescribed
bovine PrPSc was similar to that encountered in a distinct subtype of sporadic
Creutzfeldt-Jakob disease.
snip...
Phenotypic Similarities Between BASE and sCJD. The transmissibility of CJD
brains was initially demonstrated in primates (27), and classification of
atypical cases as CJD was based on this property (28). To date, no systematic
studies of strain typing in sCJD have been provided, and classification of
different subtypes is based on clinical, neuropathological, and molecular
features (the polymorphic PRNP codon 129 and the PrPSc glycotype) (8, 9, 15,
19). The importance of molecular PrPSc characterization in assessing the
identity of TSE strains is underscored by several studies, showing that the
stability of given disease-specific PrPSc types is maintained upon experimental
propagation of sCJD, familial CJD, and vCJD isolates in transgenic PrP-humanized
mice (8, 29). Similarly, biochemical properties of BSE- and vCJD-associated
PrPSc molecules remain stable after passage to mice expressing bovine PrP (30).
Recently, however, it has been reported that PrP-humanized mice inoculated with
BSE tissues may also propagate a distinctive PrPSc type, with a
”monoglycosylated-dominant” pattern and electrophoretic mobility of the
unglycosylated fragment slower than that of vCJD and BSE (31). Strikingly, this
PrPSc type shares its molecular properties with the a PrPSc molecule found in
classical sCJD. This observation is at variance with the PrPSc type found in
M/V2 sCJD cases and in cattle BASE, showing a monoglycosylated-dominant pattern
but faster electrophoretic mobility of the protease-resistant fragment as
compared with BSE. In addition to molecular properties of PrPSc, BASE and M/V2
sCJD share a distinctive pattern of intracerebral PrP deposition, which occurs
as plaque-like and amyloid-kuru plaques. Differences were, however, observed in
the regional distribution of PrPSc. While in M/V2 sCJD cases the largest amounts
of PrPSc were detected in the cerebellum, brainstem, and striatum, in cattle
BASE these areas were less involved and the highest levels of PrPSc were
recovered from the thalamus and olfactory regions.
In conclusion, decoding the biochemical PrPSc signature of individual
human and animal TSE strains may allow the identification of potential risk
factors for human disorders with unknown etiology, such as sCJD. However,
although BASE and sCJD share several characteristics, caution is dictated in
assessing a link between conditions affecting two different mammalian species,
based on convergent biochemical properties of disease-associated PrPSc types.
Strains of TSE agents may be better characterized upon passage to transgenic
mice. In the interim until this is accomplished, our present findings suggest a
strict epidemiological surveillance of cattle TSE and sCJD based on molecular
criteria.
FC5.1.1
Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD,
and GSS Blood Specimens: the Baxter Study
Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5;
Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama,
USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General
Hospital, UK; 5Baxter BioSience, Austria
Background: Rodent and sheep models of Transmissible Spongiform
Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical
and clinical phases of disease. Results in a (presumably more appropriate)
non-human primate model have not been reported.
Objective: To determine if blood components (red cells, white cells,
platelets, and plasma) from various forms of human TSE are infectious.
Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and
intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic
Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob
disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma
samples from chimpanzees infected with either sCJD or
Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a
period of 5 years, and all dying or sacrificed animals had post-mortem
neuropathological examinations and Western blots to determine the presence or
absence of the misfolded prion protein (PrPTSE).
Results: No transmissions occurred in any of the animals inoculated with
blood components from patients with sporadic or variant CJD. All donor
chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their
pre-clinical phase plasmapheresis, several months earlier than the expected
onset of illness. One monkey inoculated with purified leukocytes from a
pre-clinical GSS chimpanzee developed disease after 36 months.
Conclusion: No infectivity was found in small volumes of blood components
from 4 patients with sporadic CJD and 3 patients with variant CJD. ***However, a
single transmission from a chimpanzee-passaged strain of GSS shows that
infectivity may be present in leukocytes, and the shock of general anaesthesia
and plasmspheresis appears to have triggered the onset of illness in
pre-clinical donor chimpanzees.
Saturday, September 5, 2009
TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS
snip...
Saturday, September 5, 2009
TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS
snip...
But the first thing is our own study, and as I mentioned, it's a Baxter
primate study, and those are the major participants. And the goal was twofold,
and here is the first one: to see whether CJD, either sporadic or familial --
actually it turns out to be the familial CJD is incorrect. It really should be
the Fukuoka strain of Gerstmann-Straussler-Scheinker disease. So it's really GSS
instead of familial CJD -- when passaged through chimps into squirrel monkeys
using purified blood components, very pure blood components.
So this addresses the question that was raised just recently about whether
or not red cell infectivity that's been found in rodents is really in the red
cells or is it contaminated.
We prepared these samples with exquisite care, and they are
ultra-ultra-ultra purified. There's virtually no contamination of any of the
components that we looked at ? platelets, red cells, plasma, white cells -- with
any other component.
These are a sort of new set of slides, and what I've tried to do is make
them less complicated and more clear, but I'm afraid I haven't included the
build. So you'll just have to try and follow what I explain with this little red
pointer.
There were three initial patients. Two of them had sporadic CJD. One of
them had Gerstmann-Straussler-Scheinker syndrome. Brain tissue from each
individual patient was inoculated intracerebrally into a pair of chimpanzees.
All right?
From those chimps, either plasma or ultra purified -- in fact, everything
is ultra-purified. I'll just talk about purified plasma, purified white cells --
were inoculated intracerebrally and intravenously to get the maximum amount of
infective load into a pair of squirrel monkeys.
The same thing was done for each of these three sets. This monkey died
from non-CJD causes at 34 months post inoculation.
Let me go back for a second. I didn't point out the fact that these were
not sacrificed at this point. These chimpanzees were apheresed at 27 weeks when
they were still asymptomatic. In this instance, we apheresed them terminally
when they were symptomatic.
And before I forget, I want to mention just a little sidelight of this.
Chimpanzees in our experience -- and I think we may be the only people that have
ever inoculated chimpanzees, and that's no longer a possibility, so this was 20,
30 years ago -- the shortest incubation period of any chimpanzee that we have
ever seen with direct intracerebral inoculation is 13 months.
So we chose 27 weeks, which is about seven months, and incidentally
typically the incubation period is more like 16 or 18 months. The shortest was
13 months. We chose the 27th week, which is about six and a half months,
thinking that this would be about halfway through the incubation period, which
we wanted to check for the presence or absence of infectivity.
But within four weeks after the apheresis, which was conducted under
general anesthesia for three or four hours apiece, every single one of the six
chimpanzees became symptomatic. That is another experiment that I would love to
conclude, perhaps because this is simply not heard of, and it very much smells
like we triggered clinical illness. We didn't trigger the disease, but it
certainly looks like we triggered symptomatic disease at a point that was much
earlier than one would have possibly expected.
Maybe it will never be done because it would probably open the floodgates
of litigation. There's no end of little things that you can find out from CJD
patients after the fact. For example, the neighbor's dog comes over, barks at a
patient, makes him fall down, and three weeks later he gets CJD. So you have a
lawsuit against the neighbor.
I mean, this is not an unheard of matter, but I do think that physical
stress in the form of anesthesia and four hours of whatever goes on with
anesthesia, low blood pressure, sometimes a little hypoxemia looks like it's a
bad thing.
So here we have the 31st week. All of the chimps are symptomatic, and here
what we did was in order to make the most use of the fewest monkeys, which is
always a problem in primate research, we took these same three patients and
these six chimps. Only now we pooled these components; that is to say, we pooled
the plasma from all six chimps. We pooled ultra-purified white cells from all
six chimps because here we wanted to see whether or not we could distinguish a
difference between intracerebral route of infection and intravenous route of
infection.
With respect to platelets and red blood cells, we did not follow that. We
inoculated both intracerebral and intravenously, as we had done earlier because
nobody has any information on whether or not platelets and red cells are
infectious, and so we wanted again to get the maximum.
This is an IV versus IC goal. This one, again, is just getting the maximum
load in to see whether there is, in fact, any infectivity in pure platelets, in
pure red cells.
And of all of the above, the only transmission of disease related to the
inoculation was in a squirrel monkey that received pure leukocytes from the
presymptomatic apheresis. So that goes some way to address the question as to
whether or not it's a matter of contamination. To date the red cells have not
been -- the monkeys that receive red cells have not been observed for more than
a year because that was a later experiment.
So we still can't say about red cells, but we're about four and a half
years down the road now, and we have a single transmission from purified
leukocytes, nothing from plasma and nothing from platelets.
That was the first part of the experiment. The second part was undertaken
with the cooperation of Bob Will and others supplying material to us. These were
a couple of human, sporadic cases of CJD and three variant cases of CJD from
which we obtained buffy coat and plasma separated in a normal way. That is,
these are not purified components.
The two cases of sporadic CJD, the plasma was pooled from both patients.
The buffy coat was pooled from both patients, and then inoculated
intracerebrally and intravenously into three squirrel monkeys each. This is a
non-CJD death five years after inoculation. The other animals are still alive.
For variant CJD we decided not to pool. It was more important to eliminate
the possibility that there was just a little bit of infectivity in one patient
that would have been diluted to extinction, if you like, by mixing them if it
were to so occur with two patients, for example, who did not have infectivity.
So each one of these was done individually, but the principle was the same:
plasma and buffy coat for each patient was inoculated into either two or three
squirrel monkeys. This is, again, a non-CJD related death.
In addition to that, we inoculated rain as a positive control from the two
sporadic disease cases of human -- from the two human sporadic cases at ten to
the minus one and ten to the minus three dilutions. We have done this many, many
times in the past with other sporadic patients. So we knew what to expect, and
we got exactly what we did expect, namely, after an incubation period not quite
two years, all four monkeys developed disease at this dilution and at the minus
three dilution, not a whole lot of difference between the two.
Now, these are the crucial monkeys because each one of these monkeys every
three to four months was bled and the blood transfused into a new healthy
monkey, but the same monkey all the time. So this monkey, for example, would
have received in the course of 21 months about six different transfusions of
blood from this monkey into this monkey, similarly with this pair, this pair,
and this pair. So you can call these buddies. This is sort of the term that was
used. These monkeys are still alive.
In the same way, the three human variant CJD specimens, brain, were
inoculated into four monkeys, and again, each one of these monkeys has been
repeatedly bled at three to four month intervals and that blood transfused into
a squirrel monkey, the same one each time. Ideally we would love to have taken
bleeding at three months and inoculated a monkey and then let him go, watch him,
and then done the same thing at six months. It would have increased the number
of monkeys eightfold and just unacceptably expensive. So we did the best we
could.
That, again, is a non-CJD death, as is this.
This was of interest mainly to show that the titer of infectivity in brain
from variant CJD is just about the same as it from sporadic. We didn't do a
minus five and a minus seven in sporadic because we have an enormous experience
already with sporadic disease in squirrel monkeys, and we know that this is
exactly what happens. It disappears at about ten to the minus five. So the brain
titer in monkeys receiving human vCJD is identical to the brain titer in monkeys
that have been inoculated with sporadic CJD.
That's the experiment. All of the monkeys in aqua are still alive. They
are approaching a five-year observation period, and I think the termination of
this experiment will now need to be discussed very seriously in view of a
probable six-year incubation period in the U.K. case. The original plan was to
terminate the experiment after five years of observation with the understanding
that ideally you would keep these animals for their entire life span, which is
what we used to do when had unlimited space, money, and facilities. We can't do
that anymore.
It's not cheap, but I think in view of the U.K. case, it will be very
important to think very seriously about allowing at least these buddies and the
buddies from the sporadic CJD to go on for several more years because although
you might think that the U.K. case has made experimental work redundant, in
point of fact, anything that bears on the risk of this disease in humans is
worthwhile knowing, and one of the things we don't know is frequency of
infection. We don't know whether this case in the U.K. is going to be unique and
never happen again or whether all 13 or 14 patients have received blood
components are ultimately going to die. Let's hope not.
The French primate study is primarily directed now by Corinne Lasmezas. As
you know, the late Dominique Dromont was the original, originally initiated this
work, and they have very active primate laboratory in France, and I'm only going
to show two very simple slides to summarize what they did.
The first one is simply to show you the basis of their statement that the
IV route of infection looks to be pretty efficient because we all know that the
intracerebral route of infection is the most efficient, and if you look at this
where they inoculated the same infective load either intracerebrally or
intravenously, the incubation periods were not substantially different, which
suggests but doesn't prove, but doesn't prove that the route of infection is
pretty efficient.
Lower doses of brain material given IV did extend the incubation period
and presumably it's because of the usual dose response phenomenon that you see
in any infectious disease.
With a whopping dose of brain orally, the incubation period was even
lower. Again, just one more example of inefficiency of the route of infection
and the necessity to use more infective material to get transmissions.
And they also have blood inoculated IV which is on test, and the final
slide or at least the penultimate slide shows you what they have on test and the
time of observation, that taken human vCJD and like us inoculated buffy coat,
they've also inoculated whole blood which we did not do.
So to a great extent their studies are complementary to ours and makes it
all worthwhile.
We have about -- oh, I don't know -- a one to two-year lead time on the
French, but they're still getting into pretty good observation periods. Here's
three-plus years.
They have variant CJD adapted to the macaque. That is to say this one was
passaged in macaque monkeys, the cynomolgus, and they did the same thing. Again,
we're talking about a study here in which like ours there are no transmissions.
I mean, we have that one transmission from leukocytes, and that's it.
Here is a BSE adapted to the macaque. Whole blood, and then they chose to
inoculate leukodepleted whole blood, in both instances IV. Here they are out to
five years without a transmission.
And then finally oral dosing of the macaque, which had been infected with
-- which was infected with BSE, but a macaque passaged BSE, whole blood buffy
coat and plasma, all by the IC route, and they're out to three years.
So with the single exception of the leukocyte transmission from our chimp
that was inoculated with a sporadic case of CJD or -- excuse me -- with a GSS,
Gerstmann-Straussler, in neither our study nor the French study, which are not
yet completed have we yet seen a transmission.
And I will just close with a little cartoon that appeared in the
Washington Post that I modified slightly lest you get too wound up with these
questions of the risk from blood. This should be a "corrective."
(Laughter.)
DR. BROWN: Thanks.
Questions?
CHAIRPERSON PRIOLA: Yes. Any questions for Dr. Brown? Dr. Linden.
DR. LINDEN: I just want to make sure I understand your study design
correctly. When you mention the monkeys that have the IV and IC inoculations,
the individual monkeys had both or --
DR. BROWN: Yes, yes, yes. That's exactly right.
DR. LINDEN: So an individual monkey had both of those as opposed to some
monkeys had one and some had the other?
DR. BROWN: Correct, correct. Where IC and IV are put down together was IC
plus IV into a given monkey.
DR. LINDEN: Into a given monkey. Okay.
And the IC inoculations, where were those given?
DR. BROWN: Right parietal cortex, Southern Alabama.
(Laughter.)
DR. BROWN: Oh, it can't be that clear. Yeah, here, Pierluigi.
CHAIRPERSON PRIOLA: Dr. Epstein.
DR. BROWN: Pierluigi always damns me with feint praise. He always says
that's a very interesting study, but. I'm waiting for that, Pierluigi.
I think Jay Epstein --
DR. GAMBETTI: I will say that there's an interesting study and will say,
but I just --
(Laughter.)
DR. GAMBETTI: -- I just point of review. You talk about a point of
information. You say that -- you mention GSS, I guess, and the what, Fukuowa
(phonetic) --
DR. BROWN: Yes, Fukuoka 1.
DR. GAMBETTI: Fukuowa, and is that from the 102, if I remember correctly,
of the --
DR. BROWN: Yes, that is correct.
DR. GAMBETTI: Because that is the only one that also --
DR. BROWN: No, it's not 102. It's 101. It's the standard. It's a classical
GSS. Oh, excuse me. You're right. One, oh, two is classical GSS. It's been so
long since I've done genetics. You're right.
DR. GAMBETTI: Because that is the only one I know, I think, that I can
remember that has both the seven kv fragment that is characteristic of GSS, but
also the PrPsc 2730. So in a sense, it can be stretching a little bit compared
to the sporadic CJD.
DR. BROWN: Yeah, I think that's right. That's why I want to be sure that I
made you aware on the very first slide that that was not accurate, that it truly
was GSS.
There's a GSS strain that has been adapted to mice, and it's a hot strain,
and therefore, it may not be translatable to sporadic disease, correct. All we
can say for sure is that it is a human TSE, and it is not variant. I think
that's about it.
DR. GAMBETTI: I agree, but this is also not perhaps the best --
DR. BROWN: No, it is not the best. We understand --
DR. GAMBETTI: -- of GSS either.
DR. BROWN: Yeah. If we had to do it over again, we'd look around for a --
well, I don't know. We'd probably do it the same way because we have two
sporadics already on test they haven't transmitted, and so you can take your
pick of what you want to pay attention to.
Jay?
DR. EPSTEIN: Yes, Paul. Could you just comment? If I understood you
correctly, when you did the pooled apheresis plasma from the six chimps when
they were symptomatic at 31 weeks, you also put leukocytes into squirrel monkeys
in that case separately IV and IC, but in that instance you have not seen an
infection come down in squirrel monkey, and the question is whether it's
puzzling that you got transmission from the 27-week asymptomatic sampling,
whereas you did not see transmission from the 31-week sampling in symptomatic
animals.
DR. BROWN: Yes, I think there are two or three possible explanations, and
I don't know if any of them are important. The pre-symptomatic animal was almost
symptomatic as it turned out so that we were pretty close to the period at which
symptoms would being, and whether you can, you know, make much money on saying
one was incubation period and the other was symptomatic in this particular case
because both bleedings were so close together. That's one possibility.
The other possibility is we're dealing with a very irregular phenomenon
and you're not surprised at all by surprises, so to speak so that a single
animal, you could see it almost anywhere.
The third is that we, in fact, did just what I suggested we didn't want to
do for the preclinical, namely, by pooling we got under the threshold. See?
You can again take that for what it's worth. It is a possible explanation,
and again, until we know what the levels of infectivity are and whether by
pooling we get under the threshold of transmission, we simply cannot make
pronouncements.
CHAIRPERSON PRIOLA: Dr. DeArmond.
DR. DeARMOND: Yeah, it was very interesting data, but the --
(Laughter.)
DR. BROWN: I just love it. Go ahead.
DR. DeARMOND: Two comments. The first one was that the GSS cases, as I
remember from reading your publications -- I think Gibbs was involved with them
-- when you transmitted the GSS into animals, into monkeys, perhaps I think it
was chimps, the transmission was more typical of CJD rather than GSS. There were
no amyloid plaques. It was vacuolar degeneration so that you may be transmitting
a peculiar form, as I criticized once in Bali and then you jumped all over me
about.
DR. BROWN: I may do it again.
DR. DeARMOND: Calling me a bigot and some other few things like that.
(Laughter.)
DR. BROWN: Surely not. I wouldn't have said that.
DR. DeARMOND: So there could be something strange about that particular --
DR. BROWN: Yeah. I think you and Pierluigi are on the same page here. This
may be an unusual strain from a number of points of view.
DR. DeARMOND: The other question though has to do with species barrier
because the data you're showing is kind of very reassuring to us that it's hard
to transmit from blood, but the data from the sheep and from the hamsters and
some of the work, I think, that has been done by others, that it's easy in some
other animals to transmit, hamster to hamster, mouse to mouse.
Could you comment on the --
DR. BROWN: That's exactly why we went to primates. That's exactly it,
because a primate is closer to a human than a mouse is, and that's just common
sense.
And so to try and get a little closer to the human situation and not
totally depend on rodents for transferrable data, that is why you would use a
primate. Otherwise you wouldn't use them. They're too expensive and they cause
grief to animal care study people and protocol makers and the whole thing.
Primate studies are a real pain.
DR. DeARMOND: But right now it's inconclusive and you need more time on
it.
DR. BROWN: I believe that's true. I think if we cut it off at six years
you could still say it was inconclusive, and cutting it off at all will be to
some degree inconclusive, and that's just the way it is.
DR. DeARMOND: So what has to be done? Who do you have to convince, or who
do we all have to convince to keep that going?
DR. BROWN: Thomas?
Without trying to be flip at all, the people that would be the first
people to try to convince would be the funders of the original study. If that
fails, and it might for purely practical reasons of finance, then we will have
to look elsewhere because I really don't want to see those animals sacrificed,
not those eight buddies. Those are crucial animals, and they don't cost a whole
lot to maintain. You can maintain eight -- well, they cost a lot from my point
of view, but 15 to $20,000 a year would keep them going year after year.
CHAIRPERSON PRIOLA: Dr. Johnson.
DR. JOHNSON: Yeah, Paul, I'm intrigued as you are by the shortening of the
incubation period. Have you in all of the other years of handling these animals
when they were transfused, when they were flown out to Louisiana at night -- a
lot of the stressful things have happened to some of these chimps. Have you ever
noticed that before or is this a new observation?
DR. BROWN: Brand new.
MR. JOHNSON: Brand new. Okay.
CHAIRPERSON PRIOLA: Bob, did you want to say something? Dr. Rohwer.
DR. ROHWER: The Frederick fire, wasn't that correlated with a lot of --
DR. BROWN: Not that I k now of, but you may --
DR. ROHWER: Well, that occurred shortly after I came to NIH, and what I
remember is that there were a whole bunch of conversions that occurred within
the few months following the fire. That was fire that occurred adjacent to the
NINDS facility, but in order to protect it, they moved the monkeys out onto the
tarmac because they weren't sure it wouldn't burn as well.
DR. BROWN: Well, if you're right, then it's not brand new, but I mean, I'm
not sure how we'll ever know because if I call Carlton and ask him, I'm not sure
but what I would trust the answer that he gives me, short of records.
You know, Carlot is a very enthusiastic person, and he might say, "Oh,
yeah, my God, the whole floor died within three days," but I would want to
verify that.
On the other hand, it may be verifiable. There possibly are records that
are still extant.
DR. ROHWER: Actually I thought I heard the story from you.
(Laughter.)
DR. BROWN: You didn't because it's brand new for me. I mean, either that
or I'm on the way
(Laughter.)
CHAIRPERSON PRIOLA: Dr. Bracey.
DR. BRACEY: I was wondering if some of the variability in terms of the
intravenous infection route may be related to intraspecies barriers, that is,
the genetic differences, the way the cells, the white leukocytes are processed,
whether or not microchimerism is established, et cetera.
DR. BROWN: I don't think that processing is at fault, but the question,
the point that you raise is a very good one, and needless to say, we have
material with which we can analyze genetically all of the animals, and should it
turn out that we get, for example, -- I don't know -- a transmission in one
variant monkey and no transmissions in another and a transmission in three
sporadic monkeys, we will at that point genetically analyze every single animal
that has been used in this study, but we wanted to wait until we could see what
would be most useful to analyze.
but the material is there, and if need be, we'll do it.
CHAIRPERSON PRIOLA: Okay. Thank you very much, Dr. Brown.
I think we'll move on to the open public hearing section of the morning.
snip...
snip...
see full text ;
(Laughter.)
Saturday, January 20, 2007
Fourth case of transfusion-associated vCJD infection in the United Kingdom
(Laughter.)
Friday, June 29, 2012
Highly Efficient Prion Transmission by Blood Transfusion
(Laughter.)
Wednesday, August 24, 2011
All Clinically-Relevant Blood Components Transmit Prion Disease following
a Single Blood Transfusion: A Sheep Model of vCJD
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/all-clinically-relevant-blood.html
(Laughter.)
Wednesday, August 24, 2011
There Is No Safe Dose of Prions
(Laughter.)
Sunday, May 1, 2011
W.H.O. T.S.E. PRION Blood products and related biologicals May 2011
(Laughter.)
Monday, February 7, 2011
FDA’s Currently-Recommended Policies to Reduce the Possible Risk of
Transmission of CJD and vCJD by Blood and Blood Products 2011 ???
(Laughter.)
Sunday, August 01, 2010
Blood product, collected from a donors possibly at increased risk for vCJD
only, was distributed USA JULY 2010
(Laughter.)
atypical L-type BASE BSE California 2012
SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE
INVESTIGATION JULY 2012
Summary Report BSE 2012
Executive Summary
Saturday, August 4, 2012
*** Final Feed Investigation Summary - California BSE Case - July 2012
(see tons and tons of banned highly suspect mad cow feed in ALABAMA 2006,
and 2007, one decade post partial and voluntary mad cow feed ban in the USA, see
where 10,000,000 pounds of blood laced banned meat and bone meal was fed out
into commerce)
Saturday, August 4, 2012
Update from APHIS Regarding Release of the Final Report on the BSE
Epidemiological Investigation
Tuesday, November 02, 2010
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only)
diagnostic criteria CVL 1992
Saturday, December 15, 2012
Bovine spongiform encephalopathy: the effect of oral exposure dose on
attack rate and incubation period in cattle -- an update 5 December 2012
Thursday, February 14, 2013
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and
TSE prion disease
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
CJD Incidents Panel to be disbanded
The Creutzfeldt-Jakob Disease (CJD) Incidents Panel will be dissolved at
the end of March 2013. Subsequently, the following arrangements will apply:
From 1 April 2013, responsibility for investigating, assessing and managing
CJD incidents (and where appropriate notifying patients) will be with local
trusts, health boards and health protection teams in the same way as most other
incidents that place patients at risk; National guidance on CJD incident
management will be available to support this and will be published on the legacy
Health Protection Agency website [1]. Novel issues that arise with respect to
CJD risk management and infection control can be referred to the Advisory
Committee on Dangerous Pathogens (ACDP) Transmissible Spongiform Encephalopathy
(TSE) Risk Management Sub-Group; Long term public health surveillance of CJD
exposures will continue and trusts, health boards and health protection teams
are asked to continue reporting the occurrence of incidents to Public Health
England, in particular if they involve a patient notification exercise;
Infection control guidance from the Advisory Committee on Dangerous Pathogens
Transmissible Spongiform Encephalopathy Risk Management Subgroup (ACDP TSE RM
SG, formerly the TSE Working Group) to reduce the risk of spread of TSEs in
healthcare and community settings can be found at: http://www.dh.gov.uk/health/2012/11/acdp-guidance/.
Further/background information:
What is a CJD Incident? – A surgical incident has occurred when a patient
with, or at increased risk of, any human prion disease, including all forms of
CJD, has had an invasive procedure involving high or medium infectivity tissues
for CJD and where TSE instrument precautions were not taken. Patients
subsequently exposed to the implicated instruments may need to be informed that
they are at increased risk of CJD, depending on the specific circumstances.
Questions relating to the interpretation of the guidance should be sent to the
HPA/PHE CJD team either via the CJD mailbox cjd@hpa.org.uk (cjd@phe.gov.uk,
after 1 April 2013), or to: katy.sinka@hpa.org.uk, emma.hollis@phe.gov.uk.
Note
1. The guidance will be available on the HPA website: Topics › Infectious
Diseases › Infections A-Z › Creutzfeldt-Jakob Disease (CJD) › CJD Guidance and
Advice.
Sunday, February 10, 2013
Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection
report/CJD
Thursday, January 17, 2013
TSE guidance, surgical, dental, blood risk factors, Part 4 Infection
control of CJD, vCJD and other human prion diseases in healthcare and community
settings (updated January 2013)
Monday, December 10, 2012
Report on the monitoring of ruminants for the presence of Transmissible
Spongiform Encephalopathies (TSEs) in the EU in 2011 Final version 18 October
2012
Friday, August 24, 2012
Iatrogenic prion diseases in humans: an update
Friday, August 10, 2012
Incidents of Potential iatrogenic Creutzfeldt-Jakob disease (CJD) biannual
update (July 2012)
Thursday, July 05, 2012
Incidence of variant Creutzfeldt-Jakob disease diagnoses and deaths in the
UK January 1994 – December 2011
Thursday, April 12, 2012
Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to
2010
Eurosurveillance, Volume 17, Issue 15, 12 April 2012
Research articles
Wednesday, August 24, 2011
All Clinically-Relevant Blood Components Transmit Prion Disease following a
> Single Blood Transfusion: A Sheep Model of vCJD
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/all-clinically-relevant-blood.html
Saturday, March 23, 2013
CJD Incidents Panel to be disbanded
Tuesday, March 05, 2013
A closer look at prion strains Characterization and important implications
Prion
7:2, 99–108; March/April 2013; © 2013 Landes Bioscience
Thursday, February 21, 2013
National Prion Disease Pathology Surveillance Center Cases Examined January
16, 2013
16 YEAR OLD SPORADIC FFI ?
Monday, January 14, 2013
Gambetti et al USA Prion Unit change another highly suspect USA mad cow
victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes
along with this BSe
Monday, December 31, 2012
Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State,
2006–2011-2012
Tuesday, December 25, 2012
CREUTZFELDT JAKOB TSE PRION DISEASE HUMANS END OF YEAR REVIEW DECEMBER 25,
2012
Tuesday, June 26, 2012
Creutzfeldt Jakob Disease Human TSE report update North America, Canada,
Mexico, and USDA PRION UNIT as of May 18, 2012
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the
rise in Canada and the USA
Wednesday, June 13, 2012
MEXICO IS UNDER or MIS DIAGNOSING CREUTZFELDT JAKOB DISEASE AND OTHER PRION
DISEASE SOME WITH POSSIBLE nvCJD
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion
poker goes up again $
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until
now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
The discovery of previously unrecognized prion diseases in both humans and
animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion
diseases might be wider than expected and raises crucial questions about the
epidemiology and strain properties of these new forms. We are investigating this
latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
Thursday, April 4, 2013
Variably protease-sensitive prionopathy in the UK: a retrospective review
1991–2008
Brain (2013) 136 (4): 1102-1115. doi: 10.1093/brain/aws366
Sunday, March 31, 2013
Creutzfeldt Jakob Disease CJD worlds youngest documented victim, 11 years
old, shall we pray
Wednesday, April 24, 2013
Dissociation between Transmissible Spongiform Encephalopathy (TSE)
Infectivity and Proteinase K-Resistant PrPSc Levels in Peripheral Tissue from a
Murine Transgenic Model of TSE Disease
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
(see video here)
U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?
(see video at bottom)
Sunday, September 6, 2009
MAD COW USA 1997
(SEE SECRET VIDEO)
Creutzfeldt-Jakob Disease Public Health Crisis
Sunday, August 09, 2009
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
BOUGHT AND PAID FOR BY YOUR LOCAL CATTLE DEALERS AND LOBBYIEST
EVERYWHERE...
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,
i pulled this comment off another board about the OIE and all it's lobby
groups...tss
Having been to their offices in Paris and talked personally with the Head
of the Animal Test Section, you would choke if you knew how many lobby groups
attend that office daily. There is a steady stream of paid lobby groups that
have one goal in life and that is to sway the Section Heads of each department
within the OIE to suit the needs of different juristictions around the world,
which curiously enough, also includes the USA and Canada. Anyone can go there
and chat with them - providing they can privide valid cause to be let in. To say
that the only goal of the OIE is animal health is actually only part of their
function. They are more than that and my discussions with Dr. Diaz there has
showed me that. But to blindly make a statement regarding what they do when you
have no idea what they actually do is like eating the skin of the orange and not
knowing what is actually under. Interstingly you state that the US Government
applied pressure (to the OIE) I assume and that is a great example of the lobby
groups doing their job. So, at the end of the day, one can safely assume that it
is the pressure applied by certain influential lobby groups that will determine
a likely aoutcome to an apparent OIE directive. Man alive, isn't it great to
live in a democracy wherein the people get to make the choices and not just some
"other" interested party or group - say like........Cargyll or Tyson for
example?
So, one last question, question?
Who wags the tail of that dog?? And for what reason other than one that is
purely associated with trade and international agreements and greed?
Location: Edmonton, Alberta, Canada
Occupation: CEO of BSE Prion Solutions Inc.
Interests: Prion Diseases and Live Animal Testing
end...tss
Tuesday, July 17, 2012
O.I.E. BSE, CWD, SCRAPIE, TSE PRION DISEASE Final Report of the 80th
General Session, 20 - 25 May 2012
Wednesday, May 25, 2011
O.I.E. Terrestrial Animal Health Standards Commission and prion (TSE)
disease reporting 2011
----- Original Message -----
From: Terry S. Singeltary Sr.
To: BSE-L@LISTS.AEGEE.ORG
Cc: trade@oie.int ; oie@oie.int ; f.diaz@oie.int ; scientific.dept@oie.int
; cjdvoice@yahoogroups.com ; BLOODCJD@YAHOOGROUPS.COM
Sent: Tuesday, May 24, 2011 2:24 PM
Subject: O.I.E. Terrestrial Animal Health Standards Commission and prion
(TSE) disease reporting 2011
Saturday, December 18, 2010
OIE Global Conference on Wildlife Animal Health and Biodiversity -
Preparing for the Future (TSE AND PRIONS) Paris (France), 23-25 February 2011
Monday, November 23, 2009
BSE GBR RISK ASSESSMENTS UPDATE NOVEMBER 23, 2009 COMMISSION OF THE
EUROPEAN COMMUNITIES AND O.I.E. COMMISSION DECISION of 11 November 2009 amending
the Annex to Decision 2007/453/EC as regards the BSE status of Chile, Colombia
and Japan (notified under document C(2009) 8590)
Tuesday, January 1, 2008
BSE OIE USDA
Subject: OIE BSE RECOMMENDATION FOR USA, bought and paid for by your local
cattle dealers i.e. USDA
Date: May 14, 2007 at 9:00 am PST
OIE BSE RECOMMENDATION FOR USA, bought and paid for by your local cattle
dealers i.e. USDA
STATEMENT BY DR. RON DEHAVEN REGARDING OIE RISK RECOMMENDATION
March 9, 2007
Tuesday, November 02, 2010
IN CONFIDENCE
The information contained herein should not be disseminated further except
on the basis of "NEED TO KNOW".
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only)
diagnostic criteria CVL 1992
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
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:
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
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Friday, April 19, 2013
APHIS 2013 Stakeholder Meeting (March 2013) BSE TSE PRION
TSS
posted by Terry S. Singeltary Sr. | 12:48 PM
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