The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and TSE prion disease
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE TSE
prion disease
C-TYPE BSE BOVINE SPONGIFORM ENCEPHALOPATHY
C-BSE i.e. what is considered for whatever purposes, the U.K. strain of
BSE, which has been linked to the nvCJD, now called vCJD in humans...tss)
C-BSE HAS BEEN DOCUMENTED IN THE USA
BSE 1st reported 1984 – 1985 ?
Ministry of Agriculture, Fisheries and Food
Central Veterinary laboratory New Haw Weybridge Surrey KT153NB
Telex 262318
Telephone By fleet (09323) 41111 Ext.
Director A J Stevens MA BVSc MRCVS DipBact
Mr J M Watkin-Jones
VI Centre
Winchester
YOUR reference C 1-9
Our reference VLO 12467/85/1509
Date 19 September 1985
VLO12467 A
PATHOLOGY REPORT
Gross observations: Received in formalin a well preserved bovine brain, 2
pieces of spinal cord and pieces of kidney all grossly normal.
Miscroscopic observations:
Cerebrum - mild multifocal (4 foci) non-suppurative perivascular
infiltration and focal gliosis.
Thalamus - NVL
Cerebellum - NVL
Corpora quadrigemina - mild neuropil vacuolation
Medulla - moderate neuronal and neuropil vacuolation of the reticular
formation
Spinal cord - mild neuropil vacuolation of the lumbar dorsal horns.
Kidney - chronic mild/moderate non-suppurative interstitial reaction with
tubular regeneration and fibrosis.
Also a mild peracute multi focal tubular necrosis with focal hyaline
droplet change.
DIAGNOSIS:
1. Moderate spongiform encephalopathy - acute.
2. Mild renal nephrosis - peracute
REMARKS:
These acute changes suggest a toxicity of some description. The
non-suppurative reactions are far more chronic, mild and non-specific.
Pathologist: Carol Richardson
85/9.19/1.1
---------------extract 1. of the DFAL "Early days"----------------
THE EARLY DAYS
This is a Draft Factual Account of the actions of MAFF and DH in relation
to events up to the decision to establish the Southwood Working Party. SCDFA
refers to the Slaughter and Compensation Draft Factual Account (DFA 6), CVLDFA
refers to the CVL Draft Factual Account (DFA 4) and the RFBDFA refers to the
Ruminant Feed Ban Part 1 Draft Factual Account (DFA 7), all of which should be
read in conjunction with this document.
1. On 22 December 1984, Mr David Bee, a veterinarian, was called to examine
Cow 133, belonging to farmer Mr Peter Stent of Pitsham Farm in Sussex. She had
an arched back and had lost weight. Mr Bee returned to the farm on numerous
occasions to see more cattle with unusual symptoms.
2. On 11 February 1985, Cow 133 died, having developed head tremor and lack
of co-ordination. By the end of April 1985, five more cows had died on the farm.
3. During Spring 1985 Mr Bee contacted Mr Watkin-Jones of the local
Veterinary Investigation Centre (VIC) at Winchester, Hampshire, regarding the
problems at Pitsham farm. The animals were showing aggression and were difficult
to milk. Mr Bee said that they had a peculiar gait and arched backs.
4. In April 1985, veterinarian Mr Colin Whitaker was called to Plurenden
Manor Farm, Kent, to examine some of Mr R Sternberg's cows showing symptoms
including changes of behaviour, aggression and lack of co-ordination.
5. On 2 September 1985 a cow with these symptoms was sent from Pitsham Farm
to Winchester VIC for slaughter. The VIC sent the brain and other specimens to
the Central Veterinary Laboratory (CVL) at Weybridge, Surrey. This was the
fourth Stent cow to be referred to the CVL, however the previous three referrals
had not included brain samples.
6. The samples, received on 10 September 1985, were first examined by Ms
Carol Richardson, who was the pathologist on duty. This, the subsequent
examinations of these samples, and the conflict of evidence about the
conclusions reached, are dealt with in the CVL DFA.
7. When Mr Watkin-Jones forwarded Mrs Richardson's report to Mr David Bee,
Mr Stent's vet, he wrote:
"I enclose a histological report carried out by my colleague Carol
Richardson. I have discussed her findings with her at some length and she
comments that the pathological changes found would be consistent with bacterial
toxin."
8 Ms Richardson did not remember having a conversation about the case with
Mr Watkin-Jones.
9 Mr Bee did not accept this diagnosis. He believed there had been a fungal
toxin in the cattle feed. He told the BSE Inquiry that on 4 October 1985, 'a
fungal toxin called citrinin had been found in the feed. In any case, by this
time, new cases had ceased to develop. I imagined that the problem had run its
course'.
10 On 28 June 1986 Mr Jeffrey examined tissue sections taken from the brain
of a nyala which had been kept at Marwell Zoo. This examination, and subsequent
consideration of the nyala, are described in the CVL DFA.
11. Since his first callout in April 1985, Mr Whitaker had seen several
more strange cases at Plurenden Manor Farm. Cattle had been exhibiting symptoms
which included changes in character and in behaviour. The cattle became more
nervous and aggressive. They also experienced a gradual deterioration of
voluntary physical control, including lack of co-ordination and ataxia
(inability to move). Mr Whitaker sought assistance from the local VIC at Wye. On
referrals from Wye VIC by Mr Carl Johnson, three brain samples from the herd of
Mr R. Sternberg of Plurenden Manor Farm were received at CVL (two on 27 November
1986 and one on 23 December 1986).
12. BSE was first recognised as a new disease by pathologists at the CVL in
December 1986, and by 19 December 1986 CVL had identified possible repercussions
for the export trade and for humans.
see much more here on this history of the first documented and or
recognized BSE cases here ;
BSE DRAFT FACTUAL ACCOUNTS (they did away with that history a while back,
here some parts of it...tss)
==============atypical TSE prion strains and variants==============
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.
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...
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...
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.
2013
Thursday, February 14, 2013
Unique Properties of the Classical Bovine Spongiform Encephalopathy Strain
and Its Emergence From H-Type Bovine Spongiform Encephalopathy Substantiated by
VM Transmission Studies
Saturday, January 05, 2013
Immunohistochemical Detection of Disease- Associated Prion Protein in the
Peripheral Nervous System in Experimental H-Type Bovine Spongiform
Encephalopathy
Atypical Bovine Spongiform Encephalopathy (BSE): transmissibility and
phenotypes in humans
Classical BSE is known to cause the so-called "new variant CJD" in humans,
but the transmission risk and potential features in humans of the recently
discovered atypical BSE strains (L type and H-type) were unknown. Bioassays in
humanized Tg mice conducted in our laboratory and others' have shown that the
BSE-L strain is more virulent than the classic BSE strain (BSE-C) in Tg mice
expressing human PrP-129M. We have succeeded recently to transmit BSE-H to the
humanized Tg mice as well, albeit at lower efficiency. We found that BSE-H
isolates from the USA, Germany, and Poland all exhibited limited transmission in
the humanized Tg mice. The USA BSE-H isolate also led to two divergent
phenotypes in the humanized mice, which is reminiscent of BSE-C. We have also
recently demonstrtaed that a BSE isolate carrying a genetic mutation in the PrP
gene is infectious, which provides the first evidence that animals can deveop a
transmissible genetic prion disease.
2012
Friday, March 09, 2012
Experimental H-type and L-type bovine spongiform encephalopathy in cattle:
observation of two clinical syndromes and diagnostic challenges Research article
MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...
***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate
Model
***Infectivity in skeletal muscle of BASE-infected cattle
***feedstuffs- It also suggests a similar cause or source for atypical BSE
in these countries.
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans.
The present study demonstrated successful intraspecies transmission of
H-type BSE to cattle and the distribution and immunolabeling patterns of PrPSc
in the brain of the H-type BSE-challenged cattle. TSE agent virulence can be
minimally defined by oral transmission of different TSE agents (C-type, L-type,
and H-type BSE agents) [59]. Oral transmission studies with H-type BSEinfected
cattle have been initiated and are underway to provide information regarding the
extent of similarity in the immunohistochemical and molecular features before
and after transmission.
In addition, the present data will support risk assessments in some
peripheral tissues derived from cattle affected with H-type BSE.
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by
plaques and glial- and stellate-type prion protein deposits
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.
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*
Author Affiliations
Edited by Stanley B. Prusiner, University of California, San Francisco, CA,
and approved December 23, 2003 (received for review September 9, 2003)
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.
Footnotes
∥ To whom correspondence should be addressed. E-mail:
salvatore.monaco@mail.univr.it.
† C.C. and G.Z. contributed equally to this work.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: TSE, transmissible spongiform encephalopathy, BSE, bovine
spongiform encephalopathy; CJD, Creutzfeldt-Jakob disease; vCJD, variant CJD;
sCJD, sporadic CJD; PrP, prion protein, PrPSc pathological PrP; BASE, bovine
amyloidotic spongiform encephalopathy.
Copyright © 2004, The National Academy of Sciences
Research Article
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate
Emmanuel E. Comoy mail,
Cristina Casalone, Nathalie Lescoutra-Etchegaray, Gianluigi Zanusso, Sophie
Freire, Dominique Marcé, Frédéric Auvré, Marie-Magdeleine Ruchoux, Sergio
Ferrari, Salvatore Monaco, Nicole Salès, Maria Caramelli, Philippe Leboulch,
Paul Brown, Corinne I. Lasmézas, Jean-Philippe Deslys
Abstract
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.
snip...
It is not known whether atypical strains of BSE have been circulating for
years, or represent new forms of disease, and continuing research is clearly
needed to answer both this and the equally important question about a possible
relationship to at least certain forms of what are presently regarded as
sporadic cases of human disease (sCJD) [4], [23]. Moreover, the BASE strain has
been described to evolve naturally towards BSE after successive transmissions in
inbred mice [6]. The stability and pathogenicity of this strain in humans
remains to be determined, and it is worth recalling that the stability of the
cBSE/vCJD strain, which retains its specific molecular signature in different
infected hosts, is the exception rather than the rule. As has been previously
observed [24]–[26], one patient (Case No. 4, cf. figure 5 sample MM2#4)
exhibited both types of PrP, i.e. type 2 typical of the MM2 subtype and type 1
observed in the MM1 subtype. On the one hand, this demonstrates the interest of
such a simple biochemical test to refine PrP analysis, and on the other hand it
raises a question about the existence of different PrPres signatures in the same
patient, i.e., different prion strains linked to multiple infections or to
variants selected by the host.
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.
snip...
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
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.
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus
Macaque
"BSE-L in North America may have existed for decades"
Wednesday, May 19, 2010
Molecular, Biochemical and Genetic Characteristics of BSE in Canada
>>> The occurrence of atypical cases of BSE in countries such as
Canada with low BSE prevalence and transmission risk argues for the occurrence
of sporadic forms of BSE worldwide. <<<
RE-Molecular, Biochemical and Genetic Characteristics of BSE in
Canada
Posted by flounder on 19 May 2010 at 21:21 GMT
Greetings,
>>> The occurrence of atypical cases of BSE in countries such as
Canada with low BSE prevalence and transmission risk argues for the occurrence
of sporadic forms of BSE worldwide. <<<
In my opinion ;
THE statement above is about as non-scientific as a statement can be. There
is no proof what-so-ever that any of the atypical BSE cases or atypical scrapie
cases anywhere on the globe was a spontaneous case without any route and source
of the TSE agent. This is a myth. The USDA and the OIE are trying to make the
atypical BSE cases and they have already made the atypical Scrapie cases a legal
trading commodity, without any transmission studies first confirming that in
fact these atypical TSE will not transmit via feed. I suppose it is a human
transmission study in progress. IT's like what happened in England with c-BSE
and the transmission to humans via nvCJD never happened to the OIE and the USDA.
Canada does not have a low prevalence of BSE either, they have a high
prevalence. WHO knows about North America ? it's just that the U.S.A. try's much
harder at concealing cases of mad cow disease. THIS was proven with the first
stumbling and staggering mad cow in Texas, that was Wisk away to be rendered
without any test at all. Then, you had the second case of mad cow disease that
the USDA et al was almost as successful with as the first one, but the O.I.G.
stepped in and demanded testing over seas, this after many scientist around the
globe spoke out. Finally, after an act of Congress, the second case of mad cow
disease in Texas was confirmed. all this was done for a reason, and that reason
was the OIE USDA BSE MRR policy. Again, This study reeks of TRADE policy
wrangling. There is NO proof that the atypical TSE are spontaneous. please show
me these transmission studies ? on the other hand, we now know that the L-type
atypical BSE is much more virulent than the typical C-BSE, and we now know that
the H-type atypical BSE will transmit to humans. WHY can it not be that these
atypical cases are simply from feed that had different strains of TSE ? WHY is
it that no one will comment on the studies that was suppose to show infectivity
of tissues from atypical BSE ? WHY is it I had to file a FOIA on that issue?
L-type atypical BSE (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. SEE
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw
Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1
et al 2009 ;
Friday, March 09, 2012
Experimental H-type and L-type bovine spongiform encephalopathy in cattle:
observation of two clinical syndromes and diagnostic challenges
Research article
Experimental H-type and L-type bovine spongiform encephalopathy in cattle:
observation of two clinical syndromes and diagnostic challenges
Timm Konold, Gemma E Bone, Derek Clifford, Melanie J Chaplin, Saira
Cawthraw, Michael J Stack and Marion M Simmons
BMC Veterinary Research 2012, 8:22 doi:10.1186/1746-6148-8-22
Published: 8 March 2012
Abstract (provisional)
Background
The majority of atypical bovine spongiform encephalopathy (BSE) cases so
far identified worldwide have been detected by active surveillance. Consequently
the volume and quality of material available for detailed characterisation is
very limiting. Here we report on a small transmission study of both atypical
forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and
research, and to generate clinical, molecular and pathological data in a
standardised way to enable more robust comparison of the two variants with
particular reference to those aspects most relevant to case ascertainment and
confirmatory diagnosis within existing regulated surveillance programmes.
Results
Two groups of four cattle, intracerebrally inoculated with L-type or H-type
BSE, all presented with a nervous disease form with some similarities to
classical BSE, which progressed to a more dull form in one animal from each
group. Difficulty rising was a consistent feature of both disease forms and not
seen in two BSE-free, non-inoculated cattle that served as controls. The
pathology and molecular characteristics were distinct from classical BSE, and
broadly consistent with published data, but with some variation in the
pathological characteristics. Both atypical BSE types were readily detectable as
BSE by current confirmatory methods using the medulla brain region at the obex,
but making a clear diagnostic distinction between the forms was not consistently
straightforward in this brain region. Cerebellum proved a more reliable sample
for discrimination when using immunohistochemistry.
Conclusions
The prominent feature of difficulty rising in atypical BSE cases may
explain the detection of naturally occurring cases in emergency slaughter cattle
and fallen stock. Current confirmatory diagnostic methods are effective for the
detection of such atypical cases, but consistently and correctly identifying the
variant forms may require modifications to the sampling regimes and methods that
are currently in use.
======================================================================
One H-type BSE-inoculated steer (H3) had a ‘panic attack’ at 19 mpi: it
panicked during cleaning of the pen, ran into the hay rack and the wall of the
pen, slipped after circling in the pen and fell to the floor in lateral
recumbency with its legs thrashing for approximately 90 seconds. It subsequently
remained still in the same position for approximately 5 minutes before righting
itself. The steer eventually got up 3 minutes later rising with its forelimbs
first.
======================================================================
IN THE USA, that H-type BSE mad cow would have gone to the NSLP, thanks to
the USDA, and your children and my children and grandchildren were exposed to
the most high risk cattle i.e. dead stock downer cows, the most high risk for
mad cow disease. NOW, the argument (via industry), about non-ambulatory one
minute, but get up and walk the next, has been, ship those stumbling and
staggering highly suspect cow the render, before the beast falls again.
sometimes, they even help them up with a fork lift or stun gun. THIS is a
perfect example of what I have been saying all along, cattle that fall and break
a leg, are suspect mad cows, and should be treated as such. ...TSS
========================================================================
Postmortem test findings Vacuolar lesions consistent with TSE were observed
throughout the neuraxis in both the Htype and L-type BSE cases. At the obex, the
neuroanatomical distribution of vacuolation, and its appearance, were not
distinguishable from C-type BSE (Figure 2). However, the amount of vacuolation,
relative to observations in positive control animals challenged with C-type BSE
by the same route (data from previous studies [9]), appeared to be increased in
more rostral brain areas, noticeably the frontal cortex.
SNIP...
At the obex, the amount and distribution of immunolabelling made it
difficult to see obvious differences between these cases and C-type BSE, but
close examination revealed phenotypespecific features in this area too,
specifically labelling in white matter tracts (Figure 4a) in the H-type BSE
cases, and small aggregated forms of immunolabelling (Figure 4b) throughout the
reticular formation in L-type BSE cases.
========================================================================
THUS THE OBEX ONLY DIAGNOSTIC CRITERIA BY THE USDA ET AL, when they weren’t
testing perfectly healthy brains. ...TSS
=========================================================================
SNIP...
PrP genotyping revealed that all cattle had six octapeptide repeats and no
novel polymorphisms were detected. The only mutations detected were ‘silent’ in
that they do not affect the PrP protein sequence. The lack of wild type
sequences and the comparatively high number of cattle with the P113 silent
mutation (found in only three of 118 Holstein-Friesians examined in the UK [35])
was unusual but may be due to the breed studied; its occurrence was higher in a
study of predominantly beef breeds in the United States [36].
SNIP...
Conclusions
Cattle experimentally infected by intracerebral inoculation with L-type or
H-type BSE present with two clinical phenotypes, either dull or nervous forms,
which may be less clinically overt than classical BSE although difficulty in
rising is consistently displayed. This may explain the detection of naturally
occurring cases in apparently healthy or emergency slaughter cattle and fallen
stock. Current screening and confirmatory diagnostic methods are effective for
the detection of such atypical cases, but consistently and correctly identifying
and discriminating the variant forms may require modifications to the sampling
regimes and methods that are currently in use.
1992
IN CONFIDENCE
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367)
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
IBNC BSE or IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC)
1992
NEW BRAIN DISORDER
3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?
THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF
CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS
SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN HISTOPATHOLOGY AND
INCUBATION PERIODS BETWEEN THE TWO. MUST EMPHASISE THAT THIS IS _NOT_ BSE.
4. IS THIS NEW BRAIN DISORDER A THREAT ?
WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN
ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE,
AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE
AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED. ...
Tuesday, November 17, 2009
SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM
THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1
NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS
"All of the 15 cattle tested showed that the brains had abnormally
accumulated PrP"
2009
''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$
1995
page 9 of 14 ;
30. The Committee noted that the results were unusual. the questioned
whether there could be coincidental BSE infection or contamination with scrapie.
Dr. Tyrell noted that the feeling of the committee was that this did not
represent a new agent but it was important to be prepared to say something
publicly about these findings. A suggested line to take was that these were
scientifically unpublishable results but in line with the policy of openness
they would be made publicly available and further work done to test their
validity. Since the BSE precautions were applied to IBNC cases, human health was
protected. Further investigations should be carried out on isolations from
brains of IBNC cases with removal of the brain and subsequent handling under
strict conditions to avoid the risk of any contamination.
31. Mr. Bradley informed the Committee that the CVO had informed the CMO
about the IBNC results and the transmission from retina and he, like the
Committee was satisfied that the controls already in place or proposed were
adequate. ...
snip... see full text
http://web.archive.org/web/20030327015011/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
Wednesday, July 28, 2010
Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA
Final report
IN CONFIDENCE
BSE ATYPICAL LESION DISTRIBUTION
http://web.archive.org/web/20041226015813/http://www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf
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
HARVARD BSE RISK ASSESSMENT AND REASSESSMENT OF SUPPRESSED HARVARD RISK
ASSESSMENT THAT WAS SO FLAWED $$$
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by
plaques and glial- and stellate-type prion protein deposits
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus
Macaque
"BSE-L in North America may have existed for decades"
Over the next 8-10 weeks, approximately 40% of all the adult mink on the
farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or
dead dairy cattle...
Thursday, June 24, 2010
Accumulation of L-type Bovine Prions in Peripheral Nerve Tissues Volume 16,
Number 7–July 2010
Dispatch
The L-type BSE prion is much more virulent in primates and in humanized
mice than is the classical BSE prion, which suggests the possibility of zoonotic
risk associated with the L-type BSE prion. These findings emphasize the critical
importance of understanding tissue distribution of L-type BSE prions in cattle
because, among the current administrative measures for BSE controls, the
specified risk materials removal policy plays a crucial role in consumer
protection.
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.
new url ;
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)
> atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate.
> but no transmission has been observed for the BSE-M isolate so far.
???
================================
h-type atypical BSE BOVINE SPONGIFORM ENCEPHALOPATHY
DOCUMENTED IN THE USA...TSS
h-genetic atypical BSE BOVINE SPONGIFORM ENCEPHALOPATHY
DOCUMENTED IN THE USA...TSS
Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy
Associated with E211K Prion Protein Polymorphism
Justin J. Greenlee1*, Jodi D. Smith1, M. Heather West Greenlee2, Eric M.
Nicholson1
1 National Animal Disease Center, United States Department of Agriculture,
Agricultural Research Service, Ames, Iowa, United States of America, 2 Iowa
State University, Ames, Iowa, United States of America
Abstract
The majority of bovine spongiform encephalopathy (BSE) cases have been
ascribed to the classical form of the disease. Htype and L-type BSE cases have
atypical molecular profiles compared to classical BSE and are thought to arise
spontaneously. However, one case of H-type BSE was associated with a heritable
E211K mutation in the prion protein gene. The purpose of this study was to
describe transmission of this unique isolate of H-type BSE when inoculated into
a calf of the same genotype by the intracranial route. Electroretinograms were
used to demonstrate preclinical deficits in retinal function, and optical
coherence tomography was used to demonstrate an antemortem decrease in retinal
thickness. The calf rapidly progressed to clinical disease (9.4 months) and was
necropsied. Widespread distribution of abnormal prion protein was demonstrated
within neural tissues by western blot and immunohistochemistry. While this
isolate is categorized as BSE-H due to a higher molecular mass of the
unglycosylated PrPSc isoform, a strong labeling of all 3 PrPSc bands with
monoclonal antibodies 6H4 and P4, and a second unglycosylated band at
approximately 14 kDa when developed with antibodies that bind in the C-terminal
region, it is unique from other described cases of BSE-H because of an
additional band 23 kDa demonstrated on western blots of the cerebellum. This
work demonstrates that this isolate is transmissible, has a BSE-H phenotype when
transmitted to cattle with the K211 polymorphism, and has molecular features
that distinguish it from other cases of BSE-H described in the literature.
snip...
Results and Discussion
Clinical Findings
A calf with the K211 allele was intracranially inoculated with Htype BSE
from the US 2006 BSE case that also had one K211 allele. This calf demonstrated
clinical signs at approximately 9.4 months (288 days) post-inoculation (PI).
Initial signs were nondescript: listlessness, head down in non-physiologic
position with drooping ears, and decreased feed consumption. Within a week,
clinical signs had progressed to the calf separating himself from others in the
pen, head pressing into the wall or gate, and intermittent reluctance to rise
with a stumbling gate for a brief time after rising. The calf began to
demonstrate a lip licking and accentuated chewing behavior that was not
associated with feeding. The lip-licking and chewing behaviors increased in
frequency and severity, and at the time of necropsy at approximately 9.8 months
PI (301 days), the calf was depressed, salivating excessively, and reluctant to
rise.
Progression to severe clinical signs of BSE occurred in this animal after
9.8 months, a faster onset than the 12–18 months described for other
experimental cases of H-type BSE [28,29,30,31]. Previous studies describe the
onset of clinical signs for BSE-H as early as 8 months PI [31], but more
commonly at 12 months PI [30] or later [28] with a 2–7 month progression of
disease to ataxia and inability to rise [28,30,31]. Our findings are similar to
other reports in that the earliest clinical signs appear to be vague: weight
loss, depression, and low head carriage. However, reports of clinical findings
in BSE-H are variable: from ataxia and myoclonus that progresses to an inability
to rise without nervousness or aggression [30] to a nervous disease form that is
characterized by overeactivity to external stimuli, apprehension and anxiety
[31]. This case of E211K BSE-H is different in that the most obvious outward
clinical signs were bizarre licking and chewing behaviors not described
elsewhere. While the calf affected with E211K was reluctant to rise, it was able
to rise when encouraged, however, this animal was younger and smaller than
cattle in other studies that had difficulty getting to their feet, which may
play a role in the difference reported.
snip...
Distribution and Characterization of Lesions in BSE-H
Vacuolar lesions typical of spongiform encephalopathy were present
throughout the brain of this calf. Spongiform change was most severe in the
piriform cortex and hippocampus, but present at all levels of brain examined.
The distribution of lesions suggests sampling at various levels of the brain,
including the obex, would be fruitful for diagnosis. Vacuolation scores ranged
from 1 to 3 (scale of 0 to 4), but the vast majority of regions were scored a 2
or higher, indicating definitive spongiform lesions (Fig. S1). Lesions
predominantly affected gray matter with little to no involvement of white
matter. Vacuoles were primarily present in the neuropil, but were also detected
within the cytoplasm of neurons (Fig. 3). At all levels of the spinal cord,
there were few inconclusive vacuoles present in the neuropil of the dorsal
horns.
Results of microscopic examination for vacuolar change indicate that
additional tools may be required to differentiate E211K BSE from classical BSE
or other isolates of BSE-H that have been described in the literature [30,31].
Similar to other reports, vacuolar change was generally observed in all brain
areas and moderate to severe vacuolar change was detected in cerebral cortex,
cerebellum, basal ganglia, thalamus, and brainstem [30,31]. However, there were
contrasts in the areas with the highest vacuolation scores. The highest levels
of spongiform change were evident in piriform cortex and hippocampus in this
case, whereas the highest levels were in thalamic nuclei and midbrain of other
reports [30]. Profiles developed using larger numbers of animals suggest that
BSE-H may be difficult to distinguish from classical BSE based on spongiform
change in the obex, but may have increased numbers of vacuoles in rostral brain
areas [31]. E211K BSE-H had the lowest scores in pontine and hypoglossal motor
nuclei, which was similar to previous reports of BSE-H [30]. In summary, it
appears that vacuolar change is variable amongst different isolates classified
as BSE-H. Caution should be used when considering the lesion profile of this
single animal as what role individual animal differences or the E211K
polymorphism play cannot be determined without further experimentation.
Microscopic evaluation of the brain of the US 2006 H-type BSE case was
limited to the obex and complicated by freeze artifact, precluding a definitive
microscopic interpretation [18]. Therefore, this is the first description of the
microscopic lesions in the CNS of a bovid affected with H-type BSE associated
with the E211K polymorphism. No amyloid plaques were present in the tissues from
the calf with E211K BSE-H, which is similar to one previous study of BSE-H [31],
but contrasts with another [30].
Immunohistochemical analysis for PrPSc demonstrated widespread
immunoreactivity throughout the brain, spinal cord, and retina with lesser
immunoreactivity in neurohypophysis and the trigeminal ganglia (Fig. S2).
Regardless of the brain region examined, PrPSc immunoreactivity was readily
apparent. Immunoreactivity was most intense in the brainstem and midbrain and
patterns of immunoreactivity were similar to those previously described
[1,18,26,30,31]with an intraglial distribution predominating. The predominant
patterns in the cortex were intraglial and stellate on a background of fine
punctate and granular particulate staining that was multifocally coalescing
(Fig. 4A). Perineuronal staining was also evident, but intraneuronal
immunoreactivity was rare. Immunoreactivity increased in intensity from frontal
cortex caudal to occipital cortex. In the white matter subjacent to the cortex,
there were rare coarse particulate foci of immunoreactivity that were most often
associated with glial cell margins (Fig. S3). This is in contrast to previous
studies where glial staining in the white matter was a more prominent feature in
BSE-H [31]. We did not see PrPSc immunoreactive plaques in the gray or white
matter, but other reports indicate that this occurs as a prominent [30] or
lesser [31] feature. Immunoreactivity in hippocampus, midbrain, and brainstem
was markedly intense and frequently formed coalescing aggregates (Fig. 4B).
While intraneuronal straining was rare in the cortex, it became the most obvious
pattern in the midbrain and brainstem nuclei (Fig. 4D) with notable exception of
the parasympathetic nucleus of the vagus nerve. Intraneuronal staining also was
readily apparent in spinal cord (Fig. S2). Immunoreactivity was scant in the
cerebellum where small, multifocal clumps of granular and particulate staining
occurred in the molecular and granular layers. The cerebellar white matter was
devoid of immunoreactivity except for in association with deep cerebellar nuclei
(Fig. S4), which is in contrast to other studies of BSE-H where the most
prominent staining of the cerebellum was in the white matter [31]. Considering
the strong immunoreactivity in other regions of the brain, the scant
immunoreactivity in cerebellum was surprising. This finding corroborates recent
studies examining PrPSc immunoreactivity in the brainstem and cerebellum of
cases of BSE-H where the cerebellum and caudal brainstem contained less PrPSc
than more rostral regions of the brainstem [31,38]The immunohistochemical
techniques used here failed to demonstrate PrPSc in other tissues examined. This
finding is consisent with other studies of atypical BSE that suggest that no
significant PrPSc depositions occur in peripheral tissues [39]. Other findings
of the lesions described contrast those described for wild-type cattle with
BSE-H [30] in that no PrPSc plaques were noted and that there is less
immunoreactivity in the cerebellum in this case. Whether the E211K polymorphism
influences lesion character or distribution when inoculated with other BSE
isolates will require further study.
snip...
The disease reported here was true to the molecular characterization of the
case diagnosed in 2006, which is the best approximation of H-type BSE that may
occur later in life in cattle with the E211K polymorphism. Based on the case
history of the original 2006 E211K BSE case and the fact that the vast majority
of naturally-occurring atypical BSE cases involve older cattle (.10 yrs of age),
we speculate that a pre-clinical period of at least 10 years will be required
for BSE-H to naturally occur in E211K cattle without prior exposure to
infectious material. While an inoculation study cannot definitely prove that the
U.S. 2006 BSEH case was due to the E211K polymorphism, i.e. an inherited TSE,
the results of this study do suggest that cattle with the K211 allele are
predisposed to rapid onset of BSE-H when exposed.
Most significantly it must be determined if the molecular phenotype of this
cattle TSE remains stable when transmitted to cattle without the E211K
polymorphism as several other isolates of atypical BSE have been shown to adopt
a molecular profile consistent with classical BSE after passage in transgenic
mice expressing bovine PrPC [40] or multiple passages in wild type mice [23].
Results of ongoing studies, namely passage of the E211K Htype isolate into
wild-type cattle, will lend further insight into what role, if any, genetic and
sporadic forms of BSE may have played in the origins of classical BSE. Atypical
cases presumably of spontaneous or, in the case of E211K BSE-H, genetic origins
highlight that it may not be possible to eradicate BSE entirely and that it
would be hazardous to remove disease control measures such as prohibiting the
feeding of meat and bone meal to ruminants.
snip...
Citation: Greenlee JJ, Smith JD, West Greenlee MH, Nicholson EM (2012)
Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy
Associated with E211K Prion Protein Polymorphism. PLoS ONE 7(6): e38678.
doi:10.1371/journal.pone.0038678
Editor: Corinne Ida Lasmezas, The Scripps Research Institute Scripps
Florida, United States of America
Received January 6, 2012; Accepted May 11, 2012; Published June 8, 2012
This is an open-access article, free of all copyright, and may be freely
reproduced, distributed, transmitted, modified, built upon, or otherwise used by
anyone for any lawful purpose. The work is made available under the Creative
Commons CC0 public domain dedication.
Funding: This research was funded in its entirety by congressionally
appropriated funds to the United States Department of Agriculture, Agriculture
Research Service. The funders of the work did not influence study design, data
collection and analysis, decision to publish, and preparation of the
manuscript.
Competing Interests: The authors have declared that no competing interests
exist. * E-mail: justin.greenlee@ars.usda.gov
see full text ;
Research Article
BSE Case Associated with Prion Protein Gene Mutation
Jürgen A. Richt mail,
S. Mark Hall
Abstract
Bovine spongiform encephalopathy (BSE) is a transmissible spongiform
encephalopathy (TSE) of cattle and was first detected in 1986 in the United
Kingdom. It is the most likely cause of variant Creutzfeldt-Jakob disease (CJD)
in humans. The origin of BSE remains an enigma. Here we report an H-type BSE
case associated with the novel mutation E211K within the prion protein gene
(Prnp). Sequence analysis revealed that the animal with H-type BSE was
heterozygous at Prnp nucleotides 631 through 633. An identical pathogenic
mutation at the homologous codon position (E200K) in the human Prnp has been
described as the most common cause of genetic CJD. This finding represents the
first report of a confirmed case of BSE with a potential pathogenic mutation
within the bovine Prnp gene. A recent epidemiological study revealed that the
K211 allele was not detected in 6062 cattle from commercial beef processing
plants and 42 cattle breeds, indicating an extremely low prevalence of the E211K
variant (less than 1 in 2000) in cattle.
Author Summary
Bovine spongiform encephalopathy (BSE or Mad Cow Disease), a transmissible
spongiform encephalopathy (TSE) or prion disease of cattle, was first discovered
in the United Kingdom in 1986. BSE is most likely the cause of a human prion
disease known as variant Creutzfeldt Jakob Disease (vCJD). In this study, we
identified a novel mutation in the bovine prion protein gene (Prnp), called
E211K, of a confirmed BSE positive cow from Alabama, United States of America.
This mutation is identical to the E200K pathogenic mutation found in humans with
a genetic form of CJD. This finding represents the first report of a confirmed
case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We
hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in
“the approximately 10-year-old cow” carrying the E221K mutation.
snip...
Discussion
Our results demonstrate for the first time a potential pathogenic mutation
(E211K) within the Prnp gene of a bovine with an H-type BSE phenotype at a
position representing the most common mutation in humans (E200K) associated with
genetic TSEs [7]. This mutation was not found in the Prnp gene of other North
American (1 H-type U.S.; 1 H-type and 1 L-type Canadian) and European (7 H-type
and 3 L-type cases) cattle [8] and a miniature zebu (H-type) [9] with atypical
BSE phenotypes. The functional significance of this finding, however, remains
unknown. Importantly, the penetrance of the E200K mutation in humans is very
high [7],[10]. The origin of atypical BSE cases still remains unexplained.
Several hypotheses have been considered including the existence of a previously
unrecognized “sporadic” form of a TSE in this species. The detection of the
E211K Prnp mutation, known to be pathogenic in humans, in a 10 year old hybrid
cow (Bos indicus×Bos taurus) with H-type BSE could provide additional support to
the following hypotheses: (i) that U.K. BSE has been acquired from a genetic
case or cases of cattle BSE, (ii) that all three etiological forms of human TSEs
(sporadic, genetic and infectious) are also present in cattle, and (iii) that
BSE started on the Indian subcontinent. However, more data are required to
support these hypotheses. It is well known, that large amounts of mammalian
protein material were imported from India to the U.K. during the relevant time
period (late 1970s and early 1980s) [3]. Therefore it could be speculated that
one possible route of contamination of U.K. cattle with BSE was through animal
feed containing imported meat and bone meal material contaminated with a case or
cases of genetic BSE.
Epidemiological investigations conducted by USDA personnel failed to reveal
any evidence of a feed source contaminated with TSE material fed to this animal
snip...end
Citation: Richt JA, Hall SM (2008) BSE Case Associated with Prion Protein
Gene Mutation. PLoS Pathog 4(9): e1000156.
doi:10.1371/journal.ppat.1000156
Editor: David Westaway, University of Alberta, Canada
Received: June 5, 2008; Accepted: August 15, 2008; Published: September 12,
2008
This is an open-access article distributed under the terms of the Creative
Commons Public Domain declaration which stipulates that, once placed in the
public domain, this work may be freely reproduced, distributed, transmitted,
modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: This work was supported by the USDA-ARS-National Animal Disease
Center (NADC) and USDA-APHIS-National Veterinary Services Laboratories (NVSL)
and by the NIAID-NIH PO1 AI 77774-01 “Pathogenesis, Transmission and Detection
of Zoonotic Prion Diseases”.
Competing interests: Patent pending: Dr. Jürgen A. Richt submitted a patent
application entitled “Novel Polymorphism in Bovine Prion Protein Gene Sequence”
(Docket Number 0078.06; Serial No. 11/787,784) on April 18, 2006.
* E-mail: jricht@vet.k-state.edu
Citation: Greenlee JJ, Smith JD, West Greenlee MH, Nicholson EM (2012)
Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy
Associated with E211K Prion Protein Polymorphism. PLoS ONE 7(6): e38678.
doi:10.1371/journal.pone.0038678
Editor: Corinne Ida Lasmezas, The Scripps Research Institute Scripps
Florida, United States of America
Received: January 6, 2012; Accepted: May 11, 2012; Published: June 8,
2012
This is an open-access article, free of all copyright, and may be freely
reproduced, distributed, transmitted, modified, built upon, or otherwise used by
anyone for any lawful purpose. The work is made available under the Creative
Commons CC0 public domain dedication.
Funding: This research was funded in its entirety by congressionally
appropriated funds to the United States Department of Agriculture, Agriculture
Research Service. The funders of the work did not influence study design, data
collection and analysis, decision to publish, and preparation of the
manuscript.
Competing interests: The authors have declared that no competing interests
exist.
* E-mail: justin.greenlee@ars.usda.gov
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.
let's take a closer look at this new prionpathy or prionopathy, and then
let's look at the g-h-BSEalabama mad cow.
This new prionopathy in humans? the genetic makeup is IDENTICAL to the
g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like
this, ......wait, it get's better. this new prionpathy is killing young and old
humans, with LONG DURATION from onset of symptoms to death, and the symptoms are
very similar to nvCJD victims, OH, and the plaques are very similar in some
cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets
even better, the new human prionpathy that they claim is a genetic TSE, has no
relation to any gene mutation in that family. daaa, ya think it could be related
to that mad cow with the same genetic make-up ??? there were literally tons and
tons of banned mad cow protein in Alabama in commerce, and none of it
transmitted to cows, and the cows to humans there from ??? r i g h t $$$
ALABAMA MAD COW g-h-BSEalabama
In this study, we identified a novel mutation in the bovine prion protein
gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United
States of America. This mutation is identical to the E200K pathogenic mutation
found in humans with a genetic form of CJD. This finding represents the first
report of a confirmed case of BSE with a potential pathogenic mutation within
the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most
likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K
mutation.
her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS
Pathog. 4, e1000156; 2008).
This raises the possibility that the disease could occasionally be genetic
in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the
UK epidemic had most likely originated from such a mutation and argued against
the scrapierelated assumption. Such rare potential pathogenic PRNP mutations
could occur in countries at present considered to be free of BSE, such as
Australia and New Zealand. So it is important to maintain strict surveillance
for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many
countries still feed ruminant proteins to pigs). Removal of specified risk
material, such as brain and spinal cord, from cattle at slaughter prevents
infected material from entering the human food chain. Routine genetic screening
of cattle for PRNP mutations, which is now available, could provide additional
data on the risk to the public. Because the point mutation identified in the
Alabama animals is identical to that responsible for the commonest type of
familial (genetic) CJD in humans, it is possible that the resulting infective
prion protein might cross the bovine–human species barrier more easily. Patients
with vCJD continue to be identified. The fact that this is happening less often
should not lead to relaxation of the controls necessary to prevent future
outbreaks.
Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary
Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen
A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier
Hall, Manhattan, Kansas 66506-5601, USA
NATURE|Vol 457|26 February 2009
> Epidemiological investigations conducted by USDA personnel failed to
reveal any evidence of a feed source contaminated with TSE material fed to this
animal
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY
(see mad cow feed in COMMERCE IN ALABAMA...TSS)
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
> Epidemiological investigations conducted by USDA personnel failed to
reveal any evidence of a feed source contaminated with TSE material fed to this
animal
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim
McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre,
Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of
Calgary, Canada
Background: Three BSE types (classical and two atypical) have been
identified on the basis of molecular characteristics of the misfolded protein
associated with the disease. To date, each of these three types have been
detected in Canadian cattle.
Objectives: This study was conducted to further characterize the 16
Canadian BSE cases based on the biochemical properties of there associated
PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and
relative proteinase K sensitivity of the PrPres from each of the 16 confirmed
Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type
and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and
changes in glycosylation similar to other atypical BSE cases. PK digestion under
mild and stringent conditions revealed a reduced protease resistance of the
atypical cases compared to the C-type cases. N terminal- specific antibodies
bound to PrPres from H type but not from C or L type. The C-terminal-specific
antibodies resulted in a shift in the glycoform profile and detected a fourth
band in the Canadian H-type 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.
> Epidemiological investigations conducted by USDA personnel failed to
reveal any evidence of a feed source contaminated with TSE material fed to this
animal
what about that ALABAMA MAD COW, AND MAD COW FEED THERE FROM IN THAT STATE
???
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY
*** (see mad cow feed in COMMERCE IN ALABAMA...TSS)
BANNED MAD COW FEED IN COMMERCE IN ALABAMA
Date: September 6, 2006 at 7:58 am PST PRODUCT
a) EVSRC Custom dairy feed, Recall # V-130-6;
b) Performance Chick Starter, Recall # V-131-6;
c) Performance Quail Grower, Recall # V-132-6;
d) Performance Pheasant Finisher, Recall # V-133-6.
CODE None RECALLING FIRM/MANUFACTURER Donaldson & Hasenbein/dba J&R
Feed Service, Inc., Cullman, AL, by telephone on June 23, 2006 and by letter
dated July 19, 2006. Firm initiated recall is complete.
REASON
Dairy and poultry feeds were possibly contaminated with ruminant based
protein.
VOLUME OF PRODUCT IN COMMERCE 477.72 tons
DISTRIBUTION AL
______________________________
PRODUCT Bulk custom dairy pre-mixes,
Recall # V-120-6 CODE None RECALLING FIRM/MANUFACTURER Ware Milling Inc.,
Houston, MS, by telephone on June 23, 2006. Firm initiated recall is complete.
REASON Possible contamination of dairy animal feeds with ruminant derived meat
and bone meal.
VOLUME OF PRODUCT IN COMMERCE 350 tons
DISTRIBUTION AL and MS
______________________________
PRODUCT
a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet, 50 lb.
bags, Recall # V-121-6;
b) Tucker Milling, LLC #31120, Game Bird Breeder Pellet, 50 lb. bags,
Recall # V-122-6;
c) Tucker Milling, LLC #31232 Game Bird Grower, 50 lb. bags, Recall #
V-123-6;
d) Tucker Milling, LLC 31227-Crumble, Game Bird Starter, BMD Medicated, 50
lb bags, Recall # V-124-6;
e) Tucker Milling, LLC #31120, Game Bird Breeder, 50 lb bags, Recall #
V-125-6;
f) Tucker Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags, Recall #
V-126-6;
g) Tucker Milling, LLC #30116, TM Broiler Finisher, 50 lb bags, Recall #
V-127-6
CODE All products manufactured from 02/01/2005 until 06/20/2006 RECALLING
FIRM/MANUFACTURER Recalling Firm: Tucker Milling LLC, Guntersville, AL, by
telephone and visit on June 20, 2006, and by letter on June 23, 2006.
Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated recall
is ongoing.
REASON Poultry and fish feeds which were possibly contaminated with
ruminant based protein were not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 7,541-50 lb bags
DISTRIBUTION AL, GA, MS, and TN
END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006
###
Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125
TONS Products manufactured from 02/01/2005 until 06/06/2006
Date: August 6, 2006 at 6:16 pm PST PRODUCT
a) CO-OP 32% Sinking Catfish, Recall # V-100-6;
b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall #
V-101-6;
c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;
d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6;
e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6;
f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50
lb. bag, Recall # V-105-6;
g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%,
Recall # V-106-6;
h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to
20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall #
V-107-6;
i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall #
108-6;
j) CO-OP LAYING CRUMBLES, Recall # V-109-6;
k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall #
V-110-6;
l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6;
m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 CODE
Product manufactured from 02/01/2005 until 06/06/2006
RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL,
by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is
complete.
REASON Animal and fish feeds which were possibly contaminated with ruminant
based protein not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 125 tons
DISTRIBUTION AL and FL
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE Sun Jul 16, 2006
09:22 71.248.128.67
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II
______________________________
PRODUCT
a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy Animals,
Recall # V-079-6;
b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net weight 50lb (22.6 kg),
Recall # V-080-6;
c) PRO-PAK, MARINE & ANIMAL PROTEIN CONCENTRATE FOR USE IN ANIMAL FEED,
Recall # V-081-6;
d) Feather Meal, Recall # V-082-6 CODE
a) Bulk
b) None
c) Bulk
d) Bulk
RECALLING FIRM/MANUFACTURER H. J. Baker & Bro., Inc., Albertville, AL,
by telephone on June 15, 2006 and by press release on June 16, 2006. Firm
initiated recall is ongoing.
REASON
Possible contamination of animal feeds with ruminent derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE 10,878.06 tons
DISTRIBUTION Nationwide
END OF ENFORCEMENT REPORT FOR July 12, 2006
###
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK
MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
Saturday, November 6, 2010
TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the
EU Berne, 2010 TAFS
INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a
non-profit Swiss Foundation
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
=========================================
IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS IBNC (just another mad cow BSE
TSE prion strain)
THEY KNEW 2 DECADES AGO the damn BSE mad cow testing were not finding cases
;
NEW BRAIN DISORDER
3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?
4. IS THIS NEW BRAIN DISORDER A THREAT ?
snip...
NEW BRAIN DISORDER
3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?
THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF
CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS
SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN THE HISTOPATHOLOGY
AND INCUBATION PERIODS BETWEEN THE TWO.
MUST EMPHASIZE THAT THIS IS NOT BSE.
4. IS THIS NEW BRAIN DISORDER A THREAT ?
WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN
ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE,
AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE
AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED.
http://web.archive.org/web/20040315054455/http://www.bseinquiry.gov.uk/files/yb/1992/10/26001001.pdf
BSE-NON-CONFIRMATION OF DISEASE
3. A question posed by Mr Whaley (para 2) is that classical lesions of BSE
may not occur in all cases. Supposing we had a strain variant that produced it's
lesions in the cerebrum these would not be detected by our current method. I
think this would be unlikely but not impossible - another reason why at least a
proportion of complete brains (or blocks) should be retained during the epidemic
so if the problem Mr Whaley indicates escalates, it can be investigated.
snip...
5. IF you had the information what benefit would there be ? what would you
do with it ?
CONCLUSION
I do not recommend any action. The situation should be accepted. I do not
think the VIS can do more at present. The situation should be kept under review
particularly if there is an escalation in numbers in this category.
R BRADLEY
15 MAY 1990
90/5.15/3.2
Tuesday, November 17, 2009
SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM
THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1
NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS
"All of the 15 cattle tested showed that the brains had abnormally
accumulated PrP"
Saturday, February 28, 2009
NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS
"All of the 15 cattle tested showed that the brains had abnormally
accumulated PrP"
2009
SEAC 102/2
2009
===========================================
PLEASE NOTE *
Over the next 8-10 weeks, approximately 40% of all the adult mink on the
farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or
dead dairy cattle...
Saturday, December 01, 2007
Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and
L-type Bovine Spongiform Encephalopathy in a Mouse Model
Volume 13, Number 12–December 2007 Research
Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and
L-type Bovine Spongiform Encephalopathy in a Mouse Model
Thierry Baron,* Anna Bencsik,* Anne-Gaëlle Biacabe,* Eric Morignat,*
andRichard A. Bessen†*Agence Française de Sécurité Sanitaire des Aliments–Lyon,
Lyon, France; and†Montana State University, Bozeman, Montana, USA
Abstract
Transmissible mink encepholapathy (TME) is a foodborne transmissible
spongiform encephalopathy (TSE) of ranch-raised mink; infection with a ruminant
TSE has been proposed as the cause, but the precise origin of TME is unknown. To
compare the phenotypes of each TSE, bovine-passaged TME isolate and 3 distinct
natural bovine spongiform encephalopathy (BSE) agents (typical BSE, H-type BSE,
and L-type BSE) were inoculated into an ovine transgenic mouse line (TgOvPrP4).
Transgenic mice were susceptible to infection with bovine-passaged TME, typical
BSE, and L-type BSE but not to H-type BSE. Based on survival periods, brain
lesions profiles, disease-associated prion protein brain distribution, and
biochemical properties of protease-resistant prion protein, typical BSE had a
distint phenotype in ovine transgenic mice compared to L-type BSE and bovine
TME.The similar phenotypic properties of L-type BSE and bovine TME in TgOvPrP4
mice suggest that L-type BSE is a much more likely candidate for the origin of
TME than is typical BSE.
snip...
Conclusion
These studies provide experimental evidence that the Stetsonville TME agent
is distinct from typical BSE but has phenotypic similarities to L-type BSE in
TgOvPrP4 mice. Our conclusion is that L-type BSE is a more likely candidate for
a bovine source of TME infection than typical BSE. In the scenario that a
ruminant TSE is the source for TME infection in mink, this would be a second
example of transmission of a TSE from ruminants to non-ruminants under natural
conditions or farming practices in addition to transmission of typical BSE to
humans, domestic cats, and exotic zoo animals(37). The potential importance of
this finding is relevant to L-type BSE, which based on experimental transmission
into humanized PrP transgenic mice and macaques, suggests that L-type BSE is
more pathogenic for humans than typical BSE (24,38).
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus
Macaque
"BSE-L in North America may have existed for decades"
Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Sophie Freire,1
Jürgen Richt,2 Justin Greenlee,3 Juan-Maria Torres,4 Paul Brown,1 Bob Hills5 and
Jean-Philippe Deslys1
1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Kansas State
University; Manhattan, KS USA; 3USDA; Ames, IA USA; 4INIA; Madrid, Spain;
5Health Canada; Ottawa, ON Canada†Presenting author; Email:
emmanuel.comoy@cea.fr
The epidemiology of Transmissible mink encephalopathy (TME) indicates an
alimentary origin. Several inter-species transmission experiments have not
succeeded in establishing with certainty any natural reservoir of this prion
strain, although both ovine and bovine sources have been suspected. Cattle
exposed to TME develop a spongiform encephalopathy that is distinct from
classical Bovine Spongiform Encephalopathy (c-BSE).
Inoculation of c-BSE to cynomolgus macaque provided early evidence of a
possible risk to humans, and remains an important model to define the risk of
both primary (oral transmission from cattle to primate) and secondary
(intravenous intra-species transmission) exposures. We have also evaluated the
transmissibility of other cattle prion strains to macaques, including L- and H-
atypical forms of BSE, namely BSE-L and BSE-H, and cattle-adapted TME.
BSE-L induced a neurological disease distinct from c-BSE. Peripheral
exposures demonstrate the transmissibility of BSE-L by oral, intravenous, and
intra-cerebral routes, with incubation periods similar to c-BSE. Cattle-adapted
TME also induced a rapid disease in cynomolgus macaque. The clinical features,
lesion profile, and biochemical signature of the induced disease was similar to
the features observed in animals exposed to BSE-L, suggesting a link between the
two prion strains. Secondary transmissions to a common host (transgenic mouse
overexpressing bovine PrP) of cattle-TME and BSE-L before or after passage in
primates induced diseases with similar incubation periods: like the c-BSE
strain, these cattle strains maintained their distinctive features regardless of
the donor species and passages.
If the link between TME and BSE-L is confirmed, our results would suggest
that BSE-L in North America may have existed for decades, and highlight a
possible preferential transmission of animal prion strains to primates after
passage in cattle.
=====================end...tss====================
link url not available, please see PRION 2011 ;
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
2012 atypical L-type BSE BASE California reports
SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE
INVESTIGATION JULY 2012
Summary Report BSE 2012
Executive Summary
Saturday, August 4, 2012
Update from APHIS Regarding Release of the Final Report on the BSE
Epidemiological Investigation
Saturday, August 4, 2012
*** Final Feed Investigation Summary - California BSE Case - July 2012
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
Sunday, December 2, 2012
CANADA 19 cases of mad cow disease SCENARIO 4: ‘WE HAD OUR CHANCE AND WE
BLEW IT’
Tuesday, July 14, 2009 U.S.
Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE
Red Book
Date: February 14, 2000 at 8:56 am PST
WHERE did we go wrong $$$
ALSO, SEE Scrapie Mission, Texas, did not produce _typical_ BSE... see page
17 here ;
3.57 The experiment which might have determined whether BSE and scrapie
were caused by the same agent (ie, the feeding of natural scrapie to cattle) was
never undertaken in the UK. It was, however, performed in the USA in 1979, when
it was shown that cattle inoculated with the scrapie agent endemic in the flock
of Suffolk sheep at the United States Department of Agriculture in Mission,
Texas, developed a TSE quite unlike BSE.339 The findings of the initial
transmission, though not of the clinical or neurohistological examination, were
communicated in October 1988 to Dr Watson, Director of the CVL, following a
visit by Dr Wrathall, one of the project leaders in the Pathology Department of
the CVL, to the United States Department of Agriculture.340 The results were not
published at this point, since the attempted transmission to mice from the
experimental cow brain had been inconclusive. The results of the clinical and
histological differences between scrapie-affected sheep and cattle were
published in 1995. Similar studies in which cattle were inoculated
intracerebrally with scrapie inocula derived from a number of scrapie-affected
sheep of different breeds and from different States, were carried out at the US
National Animal Disease Centre.341 The results, published in 1994, showed that
this source of scrapie agent, though pathogenic for cattle,
*** did not produce the same clinical signs of brain lesions characteristic
of BSE. ***
3.58 There are several possible reasons why the experiment was not
performed in the UK. It had been recommended by Sir Richard Southwood (Chairman
of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the
Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342
though it was not specifically recommended in the Working Party Report or indeed
in the Tyrrell Committee Report (details of the Southwood Working Party and the
Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89
and vol. 11: Scientists after Southwood respectively). The direct inoculation of
scrapie into calves was given low priority, because of its high cost and because
it was known that it had already taken place in the USA.343 It was also felt
that the results of such an experiment would be hard to interpret. While a
negative result 337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells,
G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice,
Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I.,
Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform
Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier,
Philosophical Transactions of the Royal Society of London, Series B, Biological
Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I.,
Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C.,
Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate
that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339
Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle
Experimentally Infected with the Scrapie Agent, American Journal of Veterinary
Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R.,
Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994)
Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases,
169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4 SCIENCE 84 would be
informative, a positive result would need to demonstrate that when scrapie was
transmitted to cattle, the disease which developed in cattle was the same as
BSE.344 Given the large number of strains of scrapie and the possibility that
BSE was one of them, it would be necessary to transmit every scrapie strain to
cattle separately, to test the hypothesis properly. Such an experiment would be
expensive. Secondly, as measures to control the epidemic took hold, the need for
the experiment from the policy viewpoint was not considered so urgent. It was
felt that the results would be mainly of academic interest.345 3.59
Nevertheless, from the first demonstration of transmissibility of BSE in 1988,
the possibility of differences in the transmission properties of BSE and scrapie
was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to
transmit BSE to hamsters had failed. Subsequent findings increased that
possibility.
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
snip...
PAGE 31
Appendix I
VISIT TO USA - DR A E WRATHALL - INFO ON BSE AND SCRAPIE
1. Dr Clark lately of the Scrapie Research Unit, Mission Texas has
successfully transmitted ovine and caprine scrapie to cattle. The experimental
results have not been published but there are plans to do this. This work was
initiated in 1978. A summary of it is:-
Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with a
2nd Suffolk scrapie passage:-
i/c 1ml i/m, 5ml; s/c 5ml; oral 30ml.
1/6 went down after 48 months with a scrapie/BSE-like disease.
Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat virus
2/6 went down similarly after 36 months.
Expt C Mice inoculated from brains of calves/cattle in expts A & B were
resistant, only 1/20 going down with scrapie and this was the reason given for
not publishing.
Diagnosis in A, B, C was by histopath. No reports on SAF were given.
Dr Warren Foote indicated success so far in eliminating scrapie in
offspring from experimentally- (and naturally) infected sheep by ET. He had
found difficulty in obtaining emhryos from naturally infected sheep (cf SPA).
3. Prof. A Robertson gave a brief account of BSE. The US approach was to
PAGE 32
accord it a very low profile indeed. Dr A Thiermann showed the picture in
the "Independent" with cattle being incinerated and thought this was a fanatical
incident to be avoided in the US at all costs. BSE was not reported in USA.
4. Scrapie incidents (ie affected flocks) have shown a dramatic increase
since 1978. In 1953 when the National Control Scheme was started there were
10-14 incidents, in 1978 - 1 and in 1988 so far 60.
5. Scrapie agent was reported to have been isolated from a solitary fetus.
6. A western blotting diagnostic technique (? on PrP} shows some promise.
7. Results of a questionnaire sent to 33 states on the subject of the
national sheep scrapie programme survey indicated;
17/33 wished to drop it 6/33 wished to develop it 8/33 had few sheep and
were neutral
Information obtained from Dr Wrathall's notes of a meeting of the U.S.
Animal Health Association at Little Rock, Arkansas Nov. 1988.
please see ;
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
=============================================
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
***The pathology features of Nor98 in the cerebellum of the affected sheep
showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
PR-26
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS
R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B.
Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto
Superiore di Sanità, Department of Food Safety and Veterinary Public Health,
Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna,
Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo,
Norway
Molecular variants of PrPSc are being increasingly investigated in sheep
scrapie and are generally referred to as "atypical" scrapie, as opposed to
"classical scrapie". Among the atypical group, Nor98 seems to be the best
identified. We studied the molecular properties of Italian and Norwegian Nor98
samples by WB analysis of brain homogenates, either untreated, digested with
different concentrations of proteinase K, or subjected to enzymatic
deglycosylation. The identity of PrP fragments was inferred by means of
antibodies spanning the full PrP sequence. We found that undigested brain
homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11),
truncated at both the C-terminus and the N-terminus, and not N-glycosylated.
After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and
N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11.
Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are
mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at
the highest concentrations, similarly to PrP27-30 associated with classical
scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment
of 17 kDa with the same properties of PrP11, that was tentatively identified as
a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in
2% sodium laurylsorcosine and is mainly produced from detergentsoluble,
full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a
sample with molecular and pathological properties consistent with Nor98 showed
plaque-like deposits of PrPSc in the thalamus when the brain was analysed by
PrPSc immunohistochemistry. Taken together, our results show that the
distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids
~ 90-155. This fragment is produced by successive N-terminal and C-terminal
cleavages from a full-length and largely detergent-soluble PrPSc, is produced in
vivo and is extremely resistant to PK digestion.
*** Intriguingly, these conclusions suggest that some pathological features
of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
A newly identified type of scrapie agent can naturally infect sheep with
resistant PrP genotypes
Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne
Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?,
Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,? +Author Affiliations
*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique,
Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France;
?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole
Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066
Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité
Agents Transmissibles Non Conventionnels, 69364 Lyon, France;
**Pathologie Infectieuse et Immunologie, Institut National de la Recherche
Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National
Veterinary Institute, 0033 Oslo, Norway
***Edited by Stanley B. Prusiner, University of California, San Francisco,
CA (received for review March 21, 2005)
Abstract
Scrapie in small ruminants belongs to transmissible spongiform
encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative
disorders that affect humans and animals and can transmit within and between
species by ingestion or inoculation. Conversion of the host-encoded prion
protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP
(PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified
surveillance of scrapie in the European Union, together with the improvement of
PrPSc detection techniques, has led to the discovery of a growing number of
so-called atypical scrapie cases. These include clinical Nor98 cases first
identified in Norwegian sheep on the basis of unusual pathological and PrPSc
molecular features and "cases" that produced discordant responses in the rapid
tests currently applied to the large-scale random screening of slaughtered or
fallen animals. Worryingly, a substantial proportion of such cases involved
sheep with PrP genotypes known until now to confer natural resistance to
conventional scrapie. Here we report that both Nor98 and discordant cases,
including three sheep homozygous for the resistant PrPARR allele (A136R154R171),
efficiently transmitted the disease to transgenic mice expressing ovine PrP, and
that they shared unique biological and biochemical features upon propagation in
mice. *** These observations support the view that a truly infectious TSE agent,
unrecognized until recently, infects sheep and goat flocks and may have
important implications in terms of scrapie control and public health.
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
Authors
Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon
S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J.
M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France;
ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex,
France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway,
INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.
Content
Atypical scrapie is a TSE occurring in small ruminants and harbouring
peculiar clinical, epidemiological and biochemical properties. Currently this
form of disease is identified in a large number of countries. In this study we
report the transmission of an atypical scrapie isolate through different species
barriers as modeled by transgenic mice (Tg) expressing different species PRP
sequence.
The donor isolate was collected in 1995 in a French commercial sheep flock.
inoculation into AHQ/AHQ sheep induced a disease which had all
neuro-pathological and biochemical characteristics of atypical scrapie.
Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate
retained all the described characteristics of atypical scrapie.
Surprisingly the TSE agent characteristics were dramatically different
v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and
biochemical characteristics similar to those of atypical BSE L in the same mouse
model. Moreover, whereas no other TSE agent than BSE were shown to transmit into
Tg porcine mice, atypical scrapie was able to develop into this model, albeit
with low attack rate on first passage.
Furthermore, after adaptation in the porcine mouse model this prion showed
similar biological and biochemical characteristics than BSE adapted to this
porcine mouse model. Altogether these data indicate.
(i) the unsuspected potential abilities of atypical scrapie to cross
species barriers
(ii) the possible capacity of this agent to acquire new characteristics
when crossing species barrier
These findings raise some interrogation on the concept of TSE strain and on
the origin of the diversity of the TSE agents and could have consequences on
field TSE control measures.
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease
Are Encoded by Distinct Prion Types
Wiebke M. Wemheuer,* Sylvie L. Benestad,† Arne Wrede,* Ulf Schulze-Sturm,*
Wilhelm E. Wemheuer,‡ Uwe Hahmann,* Joanna Gawinecka,§ Ekkehard Schu¨ tz,‡ Inga
Zerr,§ Bertram Brenig,‡ Bjørn Bratberg,† Olivier Andre´ oletti,¶ and Walter J.
Schulz-Schaeffer*
From the Prion and Dementia Research Unit,* Department of Neuropathology,
and the National Transmissible Spongiform Encephalopathies Reference Center,§
Department of Neurology, University Medical Center Goettingen, Goettingen,
Germany; the Department of Pathology,† National Veterinary Institute, Oslo,
Norway; the Institute of Veterinary Medicine,‡ Faculty for Agricultural
Sciences, University of Goettingen, Goettingen, Germany; and Animal Health,¶
Interactions Hôte Agent Pathogène, Ecole Nationale Ve´te´rinaire de Toulouse,
Toulouse, France
Transmissible spongiform encephalopathies such as scrapie in sheep,
Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in
cattle are characterized by the accumulation of a misfolded protein: the
pathological prion protein. Ever since bovine sporadic encephalopathy was
discovered as the likely cause of the new variant of CJD in humans, parallels
between human and animal transmissible spongiform encephalopathies must be
viewed under the aspect of a disease risk for humans. In our study we have
compared prion characteristics of different forms of sheep scrapie with those of
different phenotypes of sporadic CJD. The disease characteristics of sporadic
CJD depend considerably on the prion type 1 or 2. Our results show that there
are obvious parallels between sporadic CJD type 1 and the so-called
atypical/Nor98 scrapie. These parelleles apply to the deposition form of
pathological prion protein in the brain, detected by the paraffin-embedded-
tissue blot and the prion aggregate stability with regard to denaturation by the
chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2
and classical scrapie. The observed parallels between types of sporadic CJD and
types of sheep scrapie demonstrate that distinct groups of prion disease exist
in different species. This should be taken into consideration when discussing
interspecies transmission. (Am J Pathol 2009, 175:2566–2573; DOI:
10.2353/ajpath.2009.090623)
snip...
Discussion
In humans, different prion types are linked with clinically and
neuropathologically distinct prion diseases.8 The present work emphasizes that
the differences in deposition characteristics and stability with regard to
denaturation between atypical/Nor98 and classical scrapie also account for
different prion types. Moreover, the two scrapie types that have been
characterized show a number of striking similarities with human PrPSc types in
sporadic CJD. Hence, we propose that the existence of different PrPSc types
might be a common denominator of prion diseases in humans and animals. Since
these two prion types show an across-the-species comparability with similar
biochemical and pathological
characteristics, it is most likely that they exist due to a different
conformational pattern of the disease-related prion protein.
snip...
Conclusion
As the prion protein is a highly conserved protein in terms of evolution,
parallels between characteristics of prion types in TSEs of different species
are of interest. In the present study, we report previously unknown similarities
between sheep scrapie forms and human sporadic CJD types. We propose that the
observed similarities between sheep scrapie and sporadic CJD in humans justify
new interspecies groups of prion diseases in which prion types, not prion
strains, are the major determinant for prion disease forms. While epidemiology
implies that classical scrapie is not related to human TSEs,47 the
atypical/Nor98 scrapie risk for human transmission has not yet been elucidated.
Currently there is no compelling evidence that sCJD has a different origin than
sporadic genesis. However, the finding of prion types with an across-the-species
comparability might provide further understanding of the pathogenesis in prion
diseases. Prion Types Encode Interspecies TSEs 2571 AJP December 2009, Vol. 175,
No. 6
CHRONIC WASTING DISEASE CWD
P35
ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A
WISCONSIN STRAIN OF CWD
Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of
Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2
Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary
Research Institute, 4.Center for Prions and Protein Folding Diseases, 5
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
T6G 2P5
The identification and characterization of prion strains is increasingly
important for the diagnosis and biological definition of these infectious
pathogens. Although well-established in scrapie and, more recently, in BSE,
comparatively little is known about the possibility of prion strains in chronic
wasting disease (CWD), a disease affecting free ranging and captive cervids,
primarily in North America. We have identified prion protein variants in the
white-tailed deer population and demonstrated that Prnp genotype affects the
susceptibility/disease progression of white-tailed deer to CWD agent. The
existence of cervid prion protein variants raises the likelihood of distinct CWD
strains. Small rodent models are a useful means of identifying prion strains. We
intracerebrally inoculated hamsters with brain homogenates and phosphotungstate
concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD
endemic area) and experimentally infected deer of known Prnp genotypes. These
transmission studies resulted in clinical presentation in primary passage of
concentrated CWD prions. Subclinical infection was established with the other
primary passages based on the detection of PrPCWD in the brains of hamsters and
the successful disease transmission upon second passage. Second and third
passage data, when compared to transmission studies using different CWD inocula
(Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin
white-tailed deer population is different than the strain(s) present in elk,
mule-deer and white-tailed deer from the western United States endemic region.
PPo2-7:
Biochemical and Biophysical Characterization of Different CWD Isolates
Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin, Germany
Key words: CWD, strains, FT-IR, AFM
Chronic wasting disease (CWD) is one of three naturally occurring forms of
prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie
in sheep. CWD is contagious and affects captive as well as free ranging cervids.
As long as there is no definite answer of whether CWD can breach the species
barrier to humans precautionary measures especially for the protection of
consumers need to be considered. In principle, different strains of CWD may be
associated with different risks of transmission to humans. Sophisticated strain
differentiation as accomplished for other prion diseases has not yet been
established for CWD. However, several different findings indicate that there
exists more than one strain of CWD agent in cervids. We have analysed a set of
CWD isolates from white-tailed deer and could detect at least two biochemically
different forms of disease-associated prion protein PrPTSE. Limited proteolysis
with different concentrations of proteinase K and/or after exposure of PrPTSE to
different pH-values or concentrations of Guanidinium hydrochloride resulted in
distinct isolate-specific digestion patterns. Our CWD isolates were also
examined in protein misfolding cyclic amplification studies. This showed
different conversion activities for those isolates that had displayed
significantly different sensitivities to limited proteolysis by PK in the
biochemical experiments described above. We further applied Fourier transform
infrared spectroscopy in combination with atomic force microscopy. This
confirmed structural differences in the PrPTSE of at least two disinct CWD
isolates. The data presented here substantiate and expand previous reports on
the existence of different CWD strains.
PPo2-22:
CWD Strain Emergence in Orally Inoculated White-tailed Deer (Odocoileus
virginianus) with Different PRNP Genotypes
Camilo Duque-Velasquez,1 Chad Johnson,2 Allen Herbst,1 Judd Aiken1 and
Debbie McKenzie1 1Centre for Prions and Protein Folding Diseases; University of
Alberta; Edmonton, Alberta Canada; 2Department of Soil Science; University of
Wisconsin; Madison, Wisconsin USA
Key words: CWD, strains, emergence
Chronic wasting disease (CWD) is a prion disease affecting captive and
free-ranging cervids in North America. We have previously demonstrated that
specific Prnp polymorphisms are linked to susceptibility/resistance to CWD
infection in free-ranging white-tailed deer populations. The “wild-type” alleles
(with glutamine at aa 95 and a Glycine at aa 96) were over-represented in the
infected deer while the polymorphisms at aa 95 (Q95H) and 96 (G96S) were
under-represented in the CWD-positive animals. Experimental oral infection of
white-tailed deer with known Prnp genotypes (with inocula from CWD-positive
wt/wt deer) confirmed this link between Prnp primary sequence and incubation
period. All orally infected animals became clinically positive for CWD. The
wt/wt had the shortest incubation period (693 dpi) and the Q95H/G96S the longest
(1596 dpi). Brain homogenates prepared from clinically affected deer of each
genotype were treated with proteinase K and resolved by western blot;
differences in the glycosylation pattern and PK resistance were observed and are
suggestive of different PrPSc isoforms. Subsequent experiments regarding
biochemical properties like detergent solubility, structural stability, host
range and the stability of these characteristics upon serial passages will allow
us to further define potential CWD strain emergence in white-tailed deer.
Wednesday, September 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
Chronic Wasting Disease CWD cervids interspecies transmission
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
David W. Colby1,* and Stanley B. Prusiner1,2
+ Author Affiliations
1Institute for Neurodegenerative Diseases, University of California, San
Francisco, San Francisco, California 94143 2Department of Neurology, University
of California, San Francisco, San Francisco, California 94143 Correspondence:
stanley@ind.ucsf.edu
SNIP...
Greetings,
I believe the statement and quote below is incorrect ;
"CWD has been transmitted to cattle after intracerebral inoculation,
although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This
finding raised concerns that CWD prions might be transmitted to cattle grazing
in contaminated pastures."
Please see ;
Within 26 months post inoculation, 12 inoculated animals had lost weight,
revealed abnormal clinical signs, and were euthanatized. Laboratory tests
revealed the presence of a unique pattern of the disease agent in tissues of
these animals. These findings demonstrate that when CWD is directly inoculated
into the brain of cattle, 86% of inoculated cattle develop clinical signs of the
disease.
"although the infection rate was low (4 of 13 animals [Hamir et al.
2001])."
shouldn't this be corrected, 86% is NOT a low rate. ...
kindest regards,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
MARCH 1, 2011
UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET
AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF
THE STUDIES ON CWD TRANSMISSION TO CATTLE ;
----- Original Message -----
From: David Colby
To: flounder9@verizon.net
Cc: stanley@XXXXXXXX
Sent: Tuesday, March 01, 2011 8:25 AM
Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 +
Author Affiliations
Dear Terry Singeltary,
Thank you for your correspondence regarding the review article Stanley
Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner
asked that I reply to your message due to his busy schedule. We agree that the
transmission of CWD prions to beef livestock would be a troubling development
and assessing that risk is important. In our article, we cite a peer-reviewed
publication reporting confirmed cases of laboratory transmission based on
stringent criteria. The less stringent criteria for transmission described in
the abstract you refer to lead to the discrepancy between your numbers and ours
and thus the interpretation of the transmission rate. We stand by our assessment
of the literature--namely that the transmission rate of CWD to bovines appears
relatively low, but we recognize that even a low transmission rate could have
important implications for public health and we thank you for bringing attention
to this matter.
Warm Regards, David Colby
--
David Colby, PhDAssistant ProfessorDepartment of Chemical
EngineeringUniversity of Delaware
====================END...TSS==============
SNIP...SEE FULL TEXT ;
============================================
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
Friday, November 23, 2012
sporadic Creutzfeldt-Jakob Disease update As at 5th November 2012 UK, USA,
AND CANADA
Tuesday, August 03, 2010
Variably protease-sensitive prionopathy: A new sporadic disease of the
prion protein
Monday, August 9, 2010
Variably protease-sensitive prionopathy: A new sporadic disease of the
prion protein or just more PRIONBALONEY ?
snip...see full text ;
O.K. let's compare some recent cases of this prionpathy in other countries
besides Gambetti's first 10 recently, that he claims is a spontaneous event,
from a genetic disorder, that is not genetic, but sporadic, that is related to
no animal TSE in North America, or the world. ...
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
Needless conflict
Journal name: Nature Volume: 485, Pages: 279–280 Date published: (17 May
2012) DOI: doi:10.1038/485279b Published online 16 May 2012
Creutzfeldt-Jakob Disease Surveillance in Texas
Sunday, July 11, 2010
CJD or prion disease 2 CASES McLennan County Texas population 230,213 both
cases in their 40s
see the continuing rise of sporadic CJD in Texas here ;
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE
RISE IN NORTH AMERICA
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)
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis,
Date aired: 27 Jun 2011
Friday, November 23, 2012
sporadic Creutzfeldt-Jakob Disease update As at 5th November 2012 UK, USA,
AND CANADA
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...
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...
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
Saturday, October 6, 2012
TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM
ENCEPHALOPATHIES 2011 Annual Report
re-Human Prion Diseases in the United States Posted by flounder on 01 Jan
2010 at 18:11 GMT
I kindly disagree with your synopsis for the following reasons ;
Tuesday, November 08, 2011
Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob
Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011
Original Paper
Conclusions:These findings raise doubt about the possibility of a reliable
CJD surveillance only based on mortality data.
Views & Reviews
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in
the United States
Ermias D. Belay, MD, Ryan A. Maddox, MPH, Pierluigi Gambetti, MD and
Lawrence B. Schonberger, MD
+ Author Affiliations
From the Division of Viral and Rickettsial Diseases (Drs. Belay and
Schonberger and R.A. Maddox), National Center for Infectious Diseases, Centers
for Disease Control and Prevention, Atlanta, GA; and National Prion Disease
Pathology Surveillance Center (Dr. Gambetti), Division of Neuropathology,
Institute of Pathology, Case Western Reserve University, Cleveland, OH.
Address correspondence and reprint requests to Dr. Ermias D. Belay, 1600
Clifton Road, Mailstop A-39, Atlanta, GA 30333.
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment
on the CDC's attempts to monitor the occurrence of emerging forms of CJD.
Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al.
JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL
TEXT
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North
America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember,
the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been
documented in North America, along with the typical scrapie's, and atypical
Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these
TSE in different species have been rendered and fed to food producing animals
for humans and animals in North America (TSE in cats and dogs ?), and that the
trading of these TSEs via animals and products via the USA and Canada has been
immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances
and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD
only theory in 2009. With all the science to date refuting it, to continue to
validate this old myth, will only spread this TSE agent through a multitude of
potential routes and sources i.e. consumption, medical i.e., surgical, blood,
dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and
the urgent need to make all human TSE in the USA a reportable disease, in every
state, of every age group, and to make this mandatory immediately without
further delay. The ramifications of not doing so will only allow this agent to
spread further in the medical, dental, surgical arena's. Restricting the
reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO
age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge,
Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al
and many more, that the world of TSE Transmissible Spongiform Encephalopathy is
far from an exact science, but there is enough proven science to date that this
myth should be put to rest once and for all, and that we move forward with a new
classification for human and animal TSE that would properly identify the
infected species, the source species, and then the route.
re-Human Prion Diseases in the United States Posted by flounder on 01 Jan
2010 at 18:11 GMT
I kindly disagree with your synopsis for the following reasons ;
Wednesday, May 16, 2012
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Proposal ID: 29403
Monday, August 20, 2012
CASE REPORTS CREUTZFELDT-JAKOB DISEASE: AN UNDER-RECOGNIZED CAUSE OF
DEMENTIA
Friday, October 05, 2012
Differential Diagnosis of Jakob-Creutzfeldt Disease
see the Duke, Pa, Yale, and Mexican study here, showing the misdiagnosis of
CJD TSE prion disease as Alzheimers ;
Monday, July 23, 2012
The National Prion Disease Pathology Surveillance Center July 2012
layperson
Terry S. Singeltary Sr.
mom dod 12/14/97 hvCJD confirmed...
posted by Terry S. Singeltary Sr. at
5:52 PM
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