so, USDA et al accidently find two atypical mad cows in Texas and Alabama
during the infamous enhanced BSE cover up back in 2004 and 2005, and then shut
the testing down to numbers so low, it’s almost impossible to find another mad
cow case, unless your country is to a point that mad cow disease can be found in
1 in 40,000, and STILL FIND MAD COW DISEASE, HOUSTON, WE HAVE A PROBLEM.
...
PLEASE UNDERSTAND, the USDA et al are lying about atypical BSE being a
spontaneous mutation, NOT caused by feed. spontaneous BSE has NEVER been proven
in any natural field case of BSE. feed is the most likely route. ...tss
"Government officials expressed confidence that contaminated food was not
the source, saying the animal had atypical L-type BSE, a rare variant not
generally associated with an animal consuming infected feed."
Emerg Infect Dis. 2006 December; 12(12): 1816–1821.
doi: 10.3201/eid1212.060965
PMCID: PMC3291375
Copyright notice
On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy
and Creutzfeldt-Jakob Disease
Paul Brown,* Lisa M. McShane,† Gianluigi Zanusso,‡ and Linda
Detwiler§
*Bethesda, Maryland, USA;
†National Institutes of Health, Bethesda, Maryland, USA;
‡University of Verona, Verona, Italy,
§Virginia-Maryland Regional College of Veterinary Medicine, College Park,
Maryland, USA
Corresponding author.
Address for correspondence: Paul Brown, 7815 Exeter Rd, Bethesda, MD 20814,
USA; email:
paulwbrown@comcast.net
SNIP...
Although the origin of the epidemic is thought to have been caused by a
species-crossing contamination by sheep scrapie during the course of rendering
and recycling carcass meat and bone meal as cattle feed, an alternative
hypothesis suggested an origin in a similarly recycled case of spontaneously
occurring disease in cattle. The pros and cons of these competing ideas have
been argued elsewhere (2,3), and neither will ever be convincingly proved or
disproved. Thus, the phenomenon of spontaneous disease remained in limbo until
the recent discovery of "atypical" strains of BSE reopened the question. In this
article we consider the importance of atypical BSE within the overall concept of
sporadic (spontaneous) disease and whether such cases, if they exist, could
account for at least some cases of apparently sporadic Creutzfeldt-Jakob (CJD)
in humans.
Other Sections▼
Sporadic BSE
Obviously, the ideal country in which to examine the question of sporadic
BSE would have a large national herd that was guaranteed never to have been
exposed to environmental sources of infection. Such an ideal will never be
realized. Until recently, the United States appeared to have at least approached
the ideal by having a large national herd, an adequate testing program, and an
apparently small risk for contamination by imported cattle or cattle feed. That
position was made vulnerable in late 2003 by the discovery of a case of BSE
imported from Canada and was eliminated altogether by the subsequent discovery
of 2 indigenously infected animals in widely separate regions of the country.
Although the 2 indigenous cases might represent sporadic disease, the continuing
identification of cases in western Canada, coupled with a history of substantial
numbers of cattle imported from Canada into the United States (both indigenous
US animals had the same molecular "signature" as the most recent Canadian case),
makes it difficult to ignore the possibility of undetected instances of feed
contamination from imported cattle and recycled infectious carcasses.
At present, the 2 best countries in which to undertake testing programs
would be Argentina and Australia; both have large national herds (≈50 million
and 30 million animals, respectively), and both are considered to be free of
orally acquired BSE infections, on the basis of importation history, nutritional
practices, and adequacy of surveillance (4). Even in these countries, however,
the discovery of a case of BSE could not be guaranteed to be spontaneous because
of the widespread global distribution of potentially infected cattle and cattle
feed and the vagaries of international trade: imperfect record keeping, lack of
compliance, and just plain deception.
As previously stated most of the characteristics of atypical BSE have not
been defined. In addition to the origin, the risk to other cattle by means of
natural transmission, the risk to humans and other animal species suck as
chickens and pigs is still unknown as is the distribution of infectivity
throughout the body of a bovine. There is little information on clinical
manifestation if it occurs at all in certain of the cases. Documented L cases
have been diagnosed from samples taken from older ‘’healthy’’ cattle presented
for routine slaughter.
While additional surveillance and research is being conducted, it is
important for policy make to consider the implications of atypical BSE. They may
need to rethink what populations are appropriate targets. It would probably be
unwise to prematurely lessen or discontinue the current BSE protection
measures.
SNIP...
Atypical BSE: What is it and what is the significance
Linda A. Detwiler, Paul Brown, Lisa M. McShane, and Gianluigi Zanusso
When atypical cases were first reported there was some speculation that
these may merely be protein accumulation disorders associated with old age. It
has now been shown that both the Land H types of atypical BSE are at least
experimentally transmissible. Homogenates from L cases have been transmitted to
bovinized transgenic mice, humanized transgenic mice, Cynomolgus monkeys and 1
breed of cattle (Buschmann et al. 2006; Book of abstracts (2006), International
Conference on Prion Diseases, Turin, Italy). H cases have been transmitted to
bovinized transgenic (Tgbov) and ovinized transgenic mice (Béringue et al.
2006). The incubation times for atypical L cases of BSE were shorter in the
Tgbov mice than classical BSE inoculated into Tgbov mice and the H cases had
longer incubations.
A variation or mutation of the classical BSE strain 􀂙 A different route of
exposure or exposure at an older age 􀂙 A strain of Scrapie transmitted to
cattle 􀂙 Sporadic or a spontaneous occurrence of BSE
At his point in time, there is no evidence to conclude that any of the
theories are or are not a possibility. There is considerable interest in the
sporadic theory. If a form of BSE were to ocnaturally, this may suggest that
certain control and prevention measure would have to remain in place
indefinitely. Proving or disproving the occurrence of a relatively rare sporadic
disease poses a significant challenge. It would require between 3 and 4.5
million tests performed on brain samples randomly taken from cattle over 7 years
of age in a country with no evidencrisk from orally acquired BSE. It is unlikely
that any country would have the will or resources to perform such a study.
Lacking this type of evidence, systematic surveillance over a long time period
may provide evidence about the nature of atypical BSE.
snip...see full text ;
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.
Wednesday, March 31, 2010
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.http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
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...
http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1 http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf
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... http://www.neuroprion.org/en/np-neuroprion.html
Saturday, June 25, 2011
Transmissibility of BSE-L and
Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
Transmissibility
of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus
Macaque
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 ;http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
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).http://www.cdc.gov/eid/content/13/12/1887.htm?s_cid=eid1887_e
PLoS One. 2012; 7(2): e31449.
Published online 2012 February 21. doi: 10.1371/journal.pone.0031449
PMCID: PMC3283643
Copyright Suardi 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.
Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform
Encephalopathy
Silvia Suardi,#1 Chiara Vimercati,#1 Cristina Casalone,#2 Daniela
Gelmetti,3 Cristiano Corona,2 Barbara Iulini,2 Maria Mazza,2 Guerino Lombardi,3
Fabio Moda,1 Margherita Ruggerone,1 Ilaria Campagnani,1 Elena Piccoli,1 Marcella
Catania,1 Martin H. Groschup,4 Anne Balkema-Buschmann,4 Maria Caramelli,2
Salvatore Monaco,5 Gianluigi Zanusso,5 and Fabrizio Tagliavini1*
1Instituto Di Ricoveroe Cura a Carattere Scientifico (IRCCS), Foundation
“Carlo Besta” Neurological Institute, Milano, Italy
2Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle
d'Aosta, Torino, Italy
3Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna,
Brescia, Italy
4Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany
5Policlinico G.B. Rossi, University of Verona, Verona, Italy
Jason Bartz, Editor
Creighton University, United States of America
#Contributed equally.
* E-mail: ftagliavini@istituto-besta.it
Conceived and designed the experiments: SS CV C. Casalone DG C. Corona GL
SM M. Caramelli GZ FT. Performed the experiments: SS CV DG C. Corona BI MM FM MR
IC EP M. Catania. Analyzed the data: SS CV C. Casalone DG C. Corona GL SM MHG AB
M. Caramelli GZ FT. Contributed reagents/materials/analysis tools: SS CV C.
Casalone DG C. Corona GL SM MHG AB M. Caramelli GZ FT. Wrote the paper: SS CV C.
Casalone DG C. Corona GL SM MHG AB M.Caramelli GZ FT.
Received December 13, 2011; Accepted January 8, 2012.
Abstract
The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE
is caused by a prion strain whose biological properties differ from those of
typical BSE, resulting in a clinically and pathologically distinct phenotype.
Whether peripheral tissues of BASE-affected cattle contain infectivity is
unknown. This is a critical issue since the BASE prion is readily transmissible
to a variety of hosts including primates, suggesting that humans may be
susceptible. We carried out bioassays in transgenic mice overexpressing bovine
PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from
cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for
inoculation transmitted disease, although the attack rate differed between
experimental and natural cases (~70% versus ~10%, respectively). This difference
was likely related to different prion titers, possibly due to different stages
of disease in the two conditions, i.e. terminal stage in experimental BASE and
pre-symptomatic stage in natural BASE. The neuropathological phenotype and
PrPres type were consistent in all affected mice and matched those of Tgbov XV
mice infected with brain homogenate from natural BASE. The immunohistochemical
analysis of skeletal muscles from cattle with natural and experimental BASE
showed the presence of abnormal prion protein deposits within muscle fibers.
Conversely, Tgbov XV mice challenged with lymphoid tissue and kidney from
natural and experimental BASE did not develop disease. The novel information on
the neuromuscular tropism of the BASE strain, efficiently overcoming species
barriers, underlines the relevance of maintaining an active surveillance.
snip...
Introduction
In 2004 an atypical form of bovine spongiform encephalopathy (BSE) termed
BASE or BSE-L was identified in Italy through active surveillance [1] and
subsequently recognized in different European countries, North America, Canada
and Japan [1]–[6]. BASE affects relatively old cattle (all cases were older than
9 years) and differs from BSE with regard to the neuropathological phenotype,
the biochemical profile of the disease-associated prion protein (PrPSc) and the
biological properties of the agent strain [1], [3], [7]. The neuropathological
hallmark of BASE is the presence of PrP amyloid plaques and the preferential
involvement of olfactory areas, hippocampus and thalamus with a relatively low
involvement of the brainstem, as opposed to classical BSE. The molecular
signature of BASE is a PrPSc type distinguished by a protease-resistant core
(PrPres) of lower molecular mass than BSE-PrPSc, with predominance of the
monoglycosylated protein band by western immunoblot.
Intra-species transmission revealed that the clinical picture of BASE
differs substantially from that of BSE, being characterized by mental dullness
and amyotrophy rather than hyper-reactivity and aggressiveness [8], [9]. As a
consequence, the recognition of BASE in vivo can be difficult and may represent
a major challenge for passive surveillance. Transmission studies to transgenic
mice overexpressing bovine PrP (Tgbov mice) showed that the BASE strain is more
aggressive than the BSE strain [10]. Furthermore, Tg mice overexpressing human
PrP as well as non-human primates are more susceptible to infection with BASE
than with BSE [11]–[14]. Overall these data raise concern about the potential
risk of transmission of BASE to humans and it is urgent to determine the
presence and distribution of infectivity in peripheral tissues of BASE-affected
cattle. To investigate this issue, we inoculated Tgbov mice with different
peripheral tissues from experimentally and naturally BASE-affected cattle and
found that various skeletal muscles contained infectivity and PrP-immunoreactive
deposits within individual fibers.
snip...
Discussion
This is the first report on the occurrence and distribution of infectivity
in peripheral tissues of BASE-affected cattle. We found that different skeletal
muscles (i.e., M. longissimus dorsi, M. intercostalis and M. gluteus) from
experimental and natural BASE carried infectivity, whereas spleen, cervical
lymph node and kidney did not, as highly susceptible Tgbov XV mice did not
develop disease up to 850 days after challenge. Noteworthy, all BASE muscles
used for inoculation transmitted disease, although the attack rate differed
between experimental and natural cases. This difference is likely related to
different prion titers in the two conditions, possibly due to different stages
of disease. In fact, the experimentally infected cattle was sacrificed at the
terminal stage when clinical signs were severe [8], while the cattle with
natural BASE was identified through active surveillance at a pre-symptomatic
stage.
Infectivity in skeletal muscles has been detected in various natural and
experimental prion diseases, including sheep affected by classical and Nor/98
atypical scrapie [17], deer with chronic wasting disease [18] and rodent models
of scrapie [19]. A large pathogenesis study on BSE-infected cattle in the UK
failed to detect infectivity in muscle tissue at any time during the course of
the disease by inoculation of inbred mice [20]. However, in a subsequent study
with Tgbov XV mice, M. semitendinosus from a field case of clinically
symptomatic BSE transmitted disease to one out of ten inoculated rodents. This
low amount of infectivity was tentatively related to the terminal nerve fibres
[21].
A major clinical feature of cattle experimentally infected with BASE is
amyotrophy, as a result of motor neuron disease [8]. Although we were unable to
detect PrPSc in the peripheral nerves of infected cattle and follow the kinetics
of PrP spreading through the neural pathway, a study of intra-species
transmission of a Japanese case of BASE showed that PrPres was first detectable
by immunoblot in the nerve roots and subsequently in the peripheral nerves [22].
PrPres deposition in skeletal muscles has been found in a variety of prion
diseases, including experimental scrapie in hamsters [23], natural scrapie in
sheep [24], and mouse and primate models of BSE and CJD [25]–[27]. These reports
agree that PrPres in muscle tissue is associated with terminal nerve
endings.
In our study, immunohistochemistry showed the presence of amorphous or
granular, small PrP deposits in different skeletal muscles from both
experimental and natural BASE-affected cattle. PrP aggregates were found in
isolated muscle fibers with a scattered distribution which was at variance with
the topology of PrPres reported in the previous studies [23], [24], [26], [27].
Noteworthy, identical results were obtained using two different fixatives and
immunostaining protocols. Since PrPC is expressed in bovine muscles and skeletal
muscles are intrinsically capable of propagating prions [19], [28], we argue
that PrPSc deposition in BASE muscles might be the result of a primary PrP
replication through a neural-independent pathway. This possibility has been
previously considered in a patient affected by sporadic CJD and inclusion body
myositis where PrPC to PrPSc conversion occurred in skeletal muscle [29].
The limited number and irregular distribution of PrP positive fibers within
a muscle sample accounts for the absence of a detectable PrPres signal on
Western blot. The inhomogeneous distribution of PrPres and infectivity among
different muscles of the same animal and within the same muscle has been
previously observed in mice and in primates infected with different prion
strains. These findings have been tentatively related to biochemical differences
in skeletal muscles of different body regions and/or number of nerve endings
[19], [25], [26].
In the present study, Tgbov XV mice challenged with BASE muscles reproduced
the monoglycosylated-dominant PrPres type of BASE as well as a histopathological
lesion profile and pattern of PrPres deposition that matched those observed in
mice challenged with BASE brain. These findings indicate that, in Tgbov XV mice,
muscle and brain tissues maintain the same biological properties of the BASE
strain.
Although serial transmission studies in Tgbov XV mice showed that the BASE
prion is capable to replicate in the spleen converting, in part, into a BSE-like
strain (personal observation), we did not detect infectivity in lymph node and
spleen from cattle with experimental and natural BASE. This observation opposes
the possibility that the BASE agent might re-circulate, potentially as BSE-like
strain, in different hosts. Kidney is an edible organ and infectivity found in
urine is kidney-associated [30]. Lack of transmission from kidney of natural and
experimental BASE is an important issue, since infectivity in kidney has been
demonstrated by bioassay in human prion diseases [31], and PrPSc has been
observed in kidney of scrapie infected sheep and CWD affected deer
[32]–[34].
The present data offer novel information on the tropism of the BASE agent
and highlight relevant public health issues. While the transmission barrier for
classical BSE is high in most species, BASE prions are readily transmissible to
a variety of mammals including non-human primates [11]–[13], [35]. Accordingly,
the possibility of spreading of BASE prions through skeletal muscle to other
species should be taken into account and evaluated in risk analysis studies.
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"
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...
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)
http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf
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.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
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...
see follow-up here about North America BSE Mad Cow TSE prion risk factors,
and the ever emerging strains of Transmissible Spongiform Encephalopathy in many
species here in the USA, including humans ;
PLoS One. 2012; 7(2):
e31449.
Published online 2012 February 21. doi:
10.1371/journal.pone.0031449
PMCID: PMC3283643
Infectivity in
Skeletal Muscle of Cattle with Atypical Bovine Spongiform
Encephalopathy
The present data offer novel information on the tropism of
the BASE agent and highlight relevant public health issues. While the
transmission barrier for classical BSE is high in most species, BASE prions are
readily transmissible to a variety of mammals including non-human primates
[11]–[13], [35]. Accordingly, the possibility of spreading of BASE prions
through skeletal muscle to other species should be taken into account and
evaluated in risk analysis studies.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283643/?tool=pubmed
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie
to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek
DC. Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK National Institute of Neurological
Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey
(Macaca fascicularis) with an incubation period of more than 5 yr from the time
of intracerebral inoculation of scrapie-infected mouse brain. The animal
developed a chronic central nervous system degeneration, with ataxia, tremor and
myoclonus with associated severe scrapie-like pathology of intensive astroglial
hypertrophy and proliferation, neuronal vacuolation and status spongiosus of
grey matter. The strain of scrapie virus used was the eighth passage in Swiss
mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral
passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton,
Berkshire). http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE
TRANSMISSION TO CHIMPANZEES
IN CONFIDENCEhttp://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html
AUGUST 4, 1997 PARTIAL AND VOLUNTARY MAD COW FEED BAN WAS
NOTHING MORE THAN INK ON PAPER.
ONE DECADE, POST PARTIAL AND VOLUNTARY MAD
COW FEED BAN.
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, 2007http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm
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
______________________________http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html
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
###http://www.fda.gov/bbs/topics/ENFORCE/2006/ENF00964.html
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
###http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html
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
###http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html
please see full text
;http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html
Research Project: Study of Atypical Bse
Location: Virus and Prion Diseases of Livestock
Project Number:
3625-32000-073-07
Project Type: Specific C/A
Start Date: Sep 15,
2004
End Date: Sep 14, 2007
Objective:
The objective of this
cooperative research project with Dr. Maria Caramelli from the Italian BSE
Reference Laboratory in Turin, Italy, is to conduct comparative studies with the
U.S. bovine spongiform encephalopathy (BSE) isolate and the atypical BSE
isolates identified in Italy. The studies will cover the following areas: 1.
Evaluation of present diagnostics tools used in the U.S. for the detection of
atypical BSE cases. 2. Molecular comparison of the U.S. BSE isolate and other
typical BSE isolates with atypical BSE cases. 3. Studies on transmissibility and
tissue distribution of atypical BSE isolates in cattle and other species.
Approach:
This project will be done as a Specific Cooperative
Agreement with the Italian BSE Reference Laboratory, Istituto Zooprofilattico
Sperimentale del Piemonte, in Turin, Italy. It is essential for the U.S. BSE
surveillance program to analyze the effectiveness of the U.S diagnostic tools
for detection of atypical cases of BSE. Molecular comparisons of the U.S. BSE
isolate with atypical BSE isolates will provide further characterization of the
U.S. BSE isolate. Transmission studies are already underway using brain
homogenates from atypical BSE cases into mice, cattle and sheep. It will be
critical to see whether the atypical BSE isolates behave similarly to typical
BSE isolates in terms of transmissibility and disease pathogenesis. If
transmission occurs, tissue distribution comparisons will be made between cattle
infected with the atypical BSE isolate and the U.S. BSE isolate. Differences in
tissue distribution could require new regulations regarding specific risk
material (SRM) removal.
3:00 Afternoon Refreshment
Break, Poster and Exhibit Viewing in the Exhibit
Hall
3:30
Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse
Models
Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western
Reserve
University
Bovine Amyloid Spongiform Encephalopathy (BASE) is
an atypical BSE strain
discovered recently in Italy, and similar or different
atypical BSE cases
were also reported in other countries. The infectivity and
phenotypes of
these atypical BSE strains in humans are unknown. In
collaboration with
Pierluigi Gambetti, as well as Maria Caramelli and her
co-workers, we have
inoculated transgenic mice expressing human prion protein
with brain
homogenates from BASE or BSE infected cattle. Our data shows that
about half
of the BASE-inoculated mice became infected with an average
incubation time
of about 19 months; in contrast, none of the BSE-inoculated
mice appear to
be infected after more than 2 years. ***These results indicate
that BASE is
transmissible to humans and suggest that BASE is more virulent
than
classical BSE in humans.
6:30 Close of Day One
Tuesday, March 2,
2010
Animal Proteins Prohibited in Ruminant Feed/Adulterated/Misbranded
Rangen Inc 2/11/10 USAhttp://madcowfeed.blogspot.com/2010/03/animal-proteins-prohibited-in-ruminant.html
Monday, March 1, 2010
ANIMAL PROTEIN
I.E. MAD COW FEED IN COMMERCE A REVIEW 2010http://madcowfeed.blogspot.com/2010/03/animal-protien-ie-mad-cow-feed-in.html
Tuesday, September 14, 2010
Feed Safety
and BSE/Ruminant Feed Ban Support Project (U18)http://madcowfeed.blogspot.com/2010/09/feed-safety-and-bseruminant-feed-ban.html
Friday, October 8, 2010
Scientific
reasons for a feed ban of meat-and-bone meal, applicable to all farmed animals
including cattle, pigs, poultry, farmed fish and pet
foodhttp://madcowfeed.blogspot.com/2010/10/scientific-reasons-for-feed-ban-of-meat.html
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.http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
O.4.3
Spread of BSE
prions in cynomolgus monkeys (Macaca fascicularis) after oral
transmission
Edgar Holznagel1, Walter Schulz-Schaeffer2, Barbara Yutzy1,
Gerhard Hunsmann3, Johannes Loewer1 1Paul-Ehrlich-Institut, Federal Institute
for Sera and Vaccines, Germany; 2Department of Neuropathology, Georg-August
University, Göttingen, Germany, 3Department of Virology and Immunology, German
Primate Centre, Göttingen, Germany
Background: BSE-infected cynomolgus
monkeys represent a relevant animal model to study the pathogenesis of variant
Creutzfeldt-Jacob disease (vCJD).
Objectives: To study the spread of BSE
prions during the asymptomatic phase of infection in a simian animal
model.
Methods: Orally BSE-dosed macaques (n=10) were sacrificed at
defined time points during the incubation period and 7 orally BSE-dosed macaques
were sacrificed after the onset of clinical signs. Neuronal and non-neuronal
tissues were tested for the presence of proteinase-K-resistant prion protein
(PrPres) by western immunoblot and by paraffin-embedded tissue (PET) blot
technique.
Results: In clinically diseased macaques (5 years p.i. + 6
mo.), PrPres deposits were widely spread in neuronal tissues (including the
peripheral sympathetic and parasympathetic nervous system) and in lymphoid
tissues including tonsils. In asymptomatic disease carriers, PrPres deposits
could be detected in intestinal lymph nodes as early as 1 year p.i., but CNS
tissues were negative until 3 – 4 years p.i. Lumbal/sacral segments of the
spinal cord and medulla oblongata were PrPres positive as early as 4.1 years
p.i., whereas sympathetic trunk and all thoracic/cervical segments of the spinal
cord were still negative for PrPres. However, tonsil samples were negative in
all asymptomatic cases.
Discussion: There is evidence for an early spread
of BSE to the CNS via autonomic fibres of the splanchnic and vagus nerves
indicating that trans-synaptical spread may be a time-limiting factor for
neuroinvasion. Tonsils were predominantly negative during the main part of the
incubation period indicating that epidemiological vCJD screening results based
on the detection of PrPres in tonsil biopsies may mostly tend to underestimate
the prevalence of vCJD among humans.
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.http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
P03.137
Transmission of BSE to
Cynomolgus Macaque, a Non-human Primate; Development of Clinical Symptoms and
Tissue Distribution of PrPSC
Yamakawa, Y1; Ono, F2; Tase, N3; Terao, K3;
Tannno, J3; Wada, N4; Tobiume, M5; Sato, Y5; Okemoto-Nakamura, Y1; Hagiwara, K1;
Sata, T5 1National Institure of Infectious diseases, Cell biology and
Biochemistry, Japan; 2Corporation for Production and Research Laboratory
Primates., Japan; 3National Institure of Biomedical Innovation, Tsukuba Primate
Reserch Center, Japan; 4Yamauchi Univ., Veterinary Medicine, Japan; 5National
Institure of Infectious diseases, Pathology, Japan
Two of three
cynomolgus monkeys developed abnormal neuronal behavioral signs at 30-(#7) and
28-(#10) months after intracerebral inoculation of 200ul of 10% brain
homogenates of BSE affected cattle (BSE/JP6). Around 30 months post inoculation
(mpi), they developed sporadic anorexia and hyperekplexia with squeal against
environmental stimulations such as light and sound. Tremor, myoclonic jerk and
paralysis became conspicuous during 32 to 33-mpi, and symptoms become worsened
according to the disease progression. Finally, one monkey (#7) fell into total
paralysis at 36-mpi. This monkey was sacrificed at 10 days after intensive
veterinary care including infusion and per oral supply of liquid food. The other
monkey (#10) had to grasp the cage bars to keep an upright posture caused by the
sever ataxia. This monkey was sacrificed at 35-mpi. EEG of both monkeys showed
diffuse slowing. PSD characteristic for sporadic CJD was not observed in both
monkeys. The result of forearm movement test showed the hypofunction that was
observed at onset of clinical symptoms. Their cognitive function determined by
finger maze test was maintained at the early stage of sideration. However, it
was rapidly impaired followed by the disease progression. Their autopsied
tissues were immunochemically investigated for the tissue distribution of PrPSc.
Severe spongiform change in the brain together with heavy accumulation of PrPSc
having the type 2B/4 glycoform profile confirmed successful transmission of BSE
to Cynomolgus macaques. Granular and linear deposition of PrPSC was detected by
IHC in the CNS of both monkeys. At cerebral cortex, PrPSC was prominently
accumulated in the large plaques. Sparse accumulation of PrPSc was detected in
several peripheral nerves of #7 but not in #10 monkey, upon the WB analysis.
Neither #7 nor #10 monkey accumulated detectable amounts of PrPSc in their
lymphatic organs such as tonsil, spleen, adrenal grands and thymus although
PrPSc was barely detected in the submandibular lymph node of #7 monkey. Such
confined tissue distribution of PrPSc after intracerebral infection with BSE
agent is not compatible to that reported on the Cynomolgus macaques infected
with BSE by oral or intra-venous (intra-peritoneal) routs, in which PrPSc was
accumulated at not only CNS but also widely distributed lymphatic
tissues.
P04.27
Experimental BSE Infection of Non-human Primates:
Efficacy of the Oral Route
Holznagel, E1; Yutzy, B1; Deslys, J-P2;
Lasmézas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5;
Motzkus, D6; Hunsmann, G6; Löwer, J1 1Paul-Ehrlich-Institut, Germany;
2Commissariat à l´Energie Atomique, France; 3Instituto Superiore di Sanità ,
Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August
University, Germany; 6German Primate Center, Germany
Background: In 2001,
a study was initiated in primates to assess the risk for humans to contract BSE
through contaminated food. For this purpose, BSE brain was titrated in
cynomolgus monkeys.
Aims: The primary objective is the determination of
the minimal infectious dose (MID50) for oral exposure to BSE in a simian model,
and, by in doing this, to assess the risk for humans. Secondly, we aimed at
examining the course of the disease to identify possible
biomarkers.
Methods: Groups with six monkeys each were orally dosed with
lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second
titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05,
and 0.005 mg).
Results: In an ongoing study, a considerable number of
high-dosed macaques already developed simian vCJD upon oral or intracerebral
exposure or are at the onset of the clinical phase. However, there are
differences in the clinical course between orally and intracerebrally infected
animals that may influence the detection of biomarkers.
Conclusions:
Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route
using less than 5 g BSE brain homogenate. The difference in the incubation
period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years).
However, there are rapid progressors among orally dosed monkeys that develop
simian vCJD as fast as intracerebrally inoculated animals.
The work
referenced was performed in partial fulfilment of the study “BSE in primates“
supported by the EU (QLK1-2002-01096).http://www.neuroprion.org/resources/pdf_docs/conferences/prion2007/abstract_book.pdf
Simian vCJD can be easily triggered in
cynomolgus monkeys on the oral route using less than 5 g BSE brain
homogenate.http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
WE know now, and we knew decades ago, that 5.5
grams of suspect feed in TEXAS was enough to kill 100 cows.
look at the
table and you'll see that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of
the cows to come down with BSE;
Risk of oral infection with bovine
spongiform encephalopathy agent in primates
Corinne Ida Lasmézas,
Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold,
Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès,
Gerald Wells, Paul Brown, Jean-Philippe Deslys Summary The uncertain extent of
human exposure to bovine spongiform encephalopathy (BSE)--which can lead to
variant Creutzfeldt-Jakob disease (vCJD)--is compounded by incomplete knowledge
about the efficiency of oral infection and the magnitude of any bovine-to-human
biological barrier to transmission. We therefore investigated oral transmission
of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain
homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological
disease 60 months after exposure, whereas the other remained free of disease at
76 months. On the basis of these findings and data from other studies, we made a
preliminary estimate of the food exposure risk for man, which provides
additional assurance that existing public health measures can prevent
transmission of BSE to man.
snip...
BSE bovine brain
inoculum
100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01
mg
Primate (oral route)* 1/2 (50%)
Cattle (oral route)* 10/10
(100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%)
RIII mice (ic
ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)
PrPres biochemical
detection
The comparison is made on the basis of calibration of the
bovine inoculum used in our study with primates against a bovine brain inoculum
with a similar PrPres concentration that was inoculated into mice and cattle.8
*Data are number of animals positive/number of animals surviving at the time of
clinical onset of disease in the first positive animal (%). The accuracy of
bioassays is generally judged to be about plus or minus 1 log. ic
ip=intracerebral and intraperitoneal.
Table 1: Comparison of transmission
rates in primates and cattle infected orally with similar BSE brain
inocula
Published online January 27, 2005http://www.thelancet.com/journal/journal.isa
It is clear that the designing scientists must
also have shared Mr Bradley̢۪s surprise at the results because all the dose
levels right down to 1 gram triggered infection.http://web.archive.org/web/20040523230128/www.bseinquiry.gov.uk/files/ws/s145d.pdf
it is clear that the designing scientists must
have also shared Mr Bradleyâs surprise at the results because all the dose
levels right down to 1 gram triggered infection.http://web.archive.org/web/20030526212610/http://www.bseinquiry.gov.uk/files/ws/s147f.pdf
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 $$$
LET'S take a closer look at this new prionpathy or prionopathy, and then
let's look at the g-h-BSEalabama mad cow. This new prionopathy in humans? the
genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_
mad cow in the world to date like this, ......wait, it get's better. this new
prionpathy is killing young and old humans, with LONG DURATION from onset of
symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and
the plaques are very similar in some cases too, bbbut, it's not related to the
g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that
they claim is a genetic TSE, has no relation to any gene mutation in that
family. daaa, ya think it could be related to that mad cow with the same genetic
make-up ??? there were literally tons and tons of banned mad cow protein in
Alabama in commerce, and none of it transmitted to cows, and the cows to humans
there from ??? r i g h t $$$ 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.
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)
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
SEE FULL TEXT OF ALL THIS HERE ;
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
Friday, December 23, 2011
Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate
Model
Volume 18, Number 1—January 2012 Dispatch
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.
October 2009 O.11.3 Infectivity in skeletal muscle of BASE-infected cattle
Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1,
Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3,
Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5,
Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta" Neurological
Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS
Torino, Italy; 5University of Verona, Italy
Background: BASE is an atypical form of bovine spongiform encephalopathy
caused by a prion strain distinct from that of BSE. Upon experimental
transmission to cattle, BASE induces a previously unrecognized disease phenotype
marked by mental dullness and progressive atrophy of hind limb musculature.
Whether affected muscles contain infectivity is unknown. This is a critical
issue since the BASE strain is readily transmissible to a variety of hosts
including primates, suggesting that humans may be susceptible.
Objectives: To investigate the distribution of infectivity in peripheral
tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice
expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and
i.p. with 10% homogenates of a variety of tissues including brain, spleen,
cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from
cattle intracerebrally infected with BASE. No PrPres was detectable in the
peripheral tissues used for inoculation either by immunohistochemistry or
Western blot.
Results: Mice inoculated with BASE-brain homogenates showed clinical signs
of disease with incubation and survival times of 175±15 and 207±12 days. Five
out of seven mice challenged with skeletal muscle developed a similar
neurological disorder, with incubation and survival times of 380±11 and 410±12
days. At present (700 days after inoculation) mice challenged with the other
peripheral tissues are still healthy. The neuropathological phenotype and PrPres
type of the affected mice inoculated either with brain or muscle were
indistinguishable and matched those of Tgbov XV mice infected with natural BASE.
Discussion: Our data indicate that the skeletal muscle of cattle
experimentally infected with BASE contains significant amount of infectivity, at
variance with BSE-affected cattle, raising the issue of intraspecies
transmission and the potential risk for humans. Experiments are in progress to
assess the presence of infectivity in skeletal muscles of natural BASE.
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
Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject
PRO/AH/EDR>
Prion disease update 2010 (11) PRION DISEASE UPDATE 2010 (11)
Sunday, February 5, 2012
February 2012 Update on Feed Enforcement Activities to Limit the Spread of
BSE
Wednesday, March 7, 2012
Case-control study of cases of bovine spongiform encephalopathy born after
July 31, 1996 (BARB cases) in Great Britain Veterinary Record
doi:10.1136/vr.100097
Wednesday, March 7, 2012
The epidemiology of bovine spongiform encephalopathy in the Republic of
Ireland before and after the reinforced feed ban
Thursday, February 23, 2012
EIGHT FORMER SECRETARIES OF AGRICULTURE SPEAKING AT USDA'S 2012 AGRICULTURE
OUTLOOK FORUM INDUCTED INTO USA MAD COW HALL OF SHAME
Tuesday, February 14, 2012
White House budget proposes cuts to ag programs including TSE PRION disease
aka mad cow type disease
Thursday, February 16, 2012
Bovine Spongiform Encephalopathy BSE
31 USA SENATORS ASK PRESIDENT OBAMA TO HELP SPREAD MAD COW DISEASE 2012
> > > Ackerman says downed cattle are 50 times more likely to have
mad cow disease (also known as Bovine Spongiform Encephalopathy, or BSE) than
ambulatory cattle that are suspected of having BSE. Of the 20 confirmed cases of
mad cow disease in North America since 1993, at least 16 have involved downer
cattle, he said. < < <
don’t forget the children...
PLEASE be aware, for 4 years, the USDA fed our children all across the
Nation (including TEXAS) dead stock downer cows, the most high risk cattle for
BSE aka mad cow disease and other dangerous pathogens.
who will watch our children for CJD for the next 5+ decades ???
WAS your child exposed to mad cow disease via the NSLP ???
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
DID YOUR CHILD CONSUME SOME OF THESE DEAD STOCK DOWNER COWS, THE MOST HIGH
RISK FOR MAD COW DISEASE ???
you can check and see here ;
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE
RISE IN NORTH AMERICA
Sunday, February 12, 2012
National Prion Disease Pathology Surveillance Center Cases Examined1
(August 19, 2011) including Texas
atypical Nor-98 Scrapie has spread from coast to
coast in the USA 2012
NIAA
Annual Conference April 11-14, 2011San Antonio, Texas
DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever
many grains of salt you wish. ...tss)
The most frightening thing I have read all day is the report of Gambetti's
finding of a new strain of sporadic cjd in young people...Dear God, what in the
name of all that is holy is that!!! If the US has different strains of
scrapie.....why????than the UK...then would the same mechanisms that make
different strains of scrapie here make different strains of BSE...if the
patterns are different in sheep and mice for scrapie.....could not the BSE be
different in the cattle, in the mink, in the humans.......I really think the
slides or tissues and everything from these young people with the new strain of
sporadic cjd should be put up to be analyzed by many, many experts in
cjd........bse.....scrapie Scrape the damn slide and put it into
mice.....wait.....chop up the mouse brain and and spinal cord........put into
some more mice.....dammit amplify the thing and start the damned
research.....This is NOT rocket science...we need to use what we know and get
off our butts and move....the whining about how long everything takes.....well
it takes a whole lot longer if you whine for a year and then start the
research!!! Not sure where I read this but it was a recent press release or
something like that: I thought I would fall out of my chair when I read about
how there was no worry about infectivity from a histopath slide or tissues
because they are preserved in formic acid, or formalin or formaldehyde.....for
God's sake........ Ask any pathologist in the UK what the brain tissues in the
formalin looks like after a year.......it is a big fat sponge...the agent
continues to eat the brain ......you can't make slides anymore because the agent
has never stopped........and the old slides that are stained with Hemolysin and
Eosin......they get holier and holier and degenerate and continue...what you
looked at 6 months ago is not there........Gambetti better be photographing
every damned thing he is looking at.....
Okay, you need to know. You don't need to pass it on as nothing will come
of it and there is not a damned thing anyone can do about it. Don't even hint at
it as it will be denied and laughed at.......... USDA is gonna do as little as
possible until there is actually a human case in the USA of the nvcjd........if
you want to move this thing along and shake the earth....then we gotta get the
victims families to make sure whoever is doing the autopsy is credible,
trustworthy, and a saint with the courage of Joan of Arc........I am not
kidding!!!! so, unless we get a human death from EXACTLY the same form with
EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any
action........it is ALL gonna be sporadic!!!
And, if there is a case.......there is gonna be every effort to link it to
international travel, international food, etc. etc. etc. etc. etc. They will go
so far as to find out if a sex partner had ever traveled to the UK/europe, etc.
etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth.
They have all the cards, all the money, and are willing to threaten and carry
out those threats....and this may be their biggest downfall...
Thanks as always for your help. (Recently had a very startling revelation
from a rather senior person in government here..........knocked me out of my
chair........you must keep pushing. If I was a power person....I would be
demanding that there be a least a million bovine tested as soon as possible and
agressively seeking this disease. The big players are coming out of the woodwork
as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very
dumb....who's "will"! "Will be the burden to bare if there is any
coverup!"
again it was said years ago and it should be taken seriously....BSE will
NEVER be found in the US! As for the BSE conference call...I think you did a
great service to freedom of information and making some people feign
integrity...I find it scary to see that most of the "experts" are employed by
the federal government or are supported on the "teat" of federal funds. A scary
picture! I hope there is a confidential panel organized by the new government to
really investigate this thing.
You need to watch your back........but keep picking at them.......like a
buzzard to the bone...you just may get to the truth!!! (You probably have more
support than you know. Too many people are afraid to show you or let anyone else
know. I have heard a few things myself... you ask the questions that everyone
else is too afraid to ask.)
END...TSS
IN CONFIDENCE
Perceptions of unconventional slow virus in the USA
GAH WELLS
Report of a visit to the U.S.A. April-May 1989
3. Prof. A Robertson gave a brief account of BSE. The US approach was to
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 fantical incident to be avoided in the USA AT
ALL COSTS.
and they meant it !
Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health
Crisis
full text with source references ;
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.
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.
Response to Public Comments on the Harvard Risk Assessment of Bovine
Spongiform Encephalopathy Update, October 31, 2005
INTRODUCTION
The United States Department of Agriculture’s Food Safety and Inspection
Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to
present findings from the Harvard Risk Assessment of Bovine Spongiform
Encephalopathy Update, October 31, 2005 (report and model located on the FSIS
website:
Comments on technical aspects of the risk assessment were then submitted to
FSIS. Comments were received from Food and Water Watch, Food Animal Concerns
Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S.
Singeltary.
This document provides itemized replies to the public comments received on
the 2005 updated Harvard BSE risk assessment. Please bear the following points
in mind:
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
Subject: Bovine Spongiform Encephalopathy; Importation of Bovines and
Bovine Products APHIS-2008-0010-0008 RIN:0579-AC68
Comment from Terry Singeltary
Document ID: APHIS-2008-0010-0008 Document Type: Public Submission
This is comment on Proposed Rule: Bovine Spongiform Encephalopathy;
Importation of Bovines and Bovine Products
Docket ID: APHIS-2008-0010 RIN:0579-AC68
Topics: No Topics associated with this document
View Document:
More
Document Subtype: Public Comment
Status: Posted
Received Date: March 22 2012, at 12:00 AM Eastern Daylight Time
Date Posted: March 22 2012, at 12:00 AM Eastern Daylight Time
Comment Start Date: March 16 2012, at 12:00 AM Eastern Daylight Time
Comment Due Date: May 15 2012, at 11:59 PM Eastern Daylight Time
Tracking Number: 80fdd617
First Name: Terry
Middle Name: S.
Last Name: Singeltary
City: Bacliff
Country: United States
State or Province: TX
Organization Name: CJD TSE PRION
Submitter's Representative: CONSUMERS
Comment:
comment submission Document ID APHIS-2008-0010-0001 Greetings USDA, OIE et
al, what a difference it makes with science, from one day to the next. i.e. that
mad cow gold card the USA once held. up until that fateful day in December of
2003, the science of BSE was NO IMPORTS TO USA FROM BSE COUNTRY. what a
difference a day makes$ now that the shoe is on the other foot, the USDA via the
OIE, wants to change science again, just for trade $ I implore the OIE decision
and policy makers, for the sake of the world, to refuse any status quo of the
USA BSE risk assessment. if at al, the USA BSE GBR should be raise to BSE GBR
IV, for the following reasons. North America is awash with many different TSE
Prion strains, in many different species, and they are mutating and spreading.
IF the OIE, and whatever policy makers, do anything but raise the risk factor
for BSE in North America, they I would regard that to be highly suspicious. IN
fact, it would be criminal in my opinion, because the OIE knows this, and to
knowingly expose the rest of the world to this dangerous pathogen, would be
‘knowingly’ and ‘willfully’, just for the almighty dollar, once again. I warned
the OIE about all this, including the risk factors for CWD, and the fact that
the zoonosis potential was great, way back in 2002. THE OIE in collaboration
with the USDA, made the legal trading of the atypical Nor-98 Scrapie a legal
global commodity. yes, thanks to the OIE and the USDA et al, it’s now legal to
trade the atypical Nor-98 Scrapie strain all around the globe. IF you let them,
they will do the same thing with atypical BSE and CWD (both strains to date).
This with science showing that indeed these TSE prion strains are transmissible.
I strenuously urge the OIE et al to refuse any weakening to the USA trade
protocols for the BSE TSE prion disease (all strains), and urge them to
reclassify the USA with BSE GBR IV risk factor. SEE REFERENCE SOURCES IN
ATTACHMENTS
SEE Terry S. Singeltary Sr. Attachment WORD FILE ;
Sunday, March 11, 2012
APHIS Proposes New Bovine Spongiform Encephalopathy Import Regulations in
Line with International Animal Health Standards Proposal Aims to Ensure Health
of the U.S. Beef Herd, Assist in Negotiations
Bovine Spongiform Encephalopathy; Importation of
Bovines and Bovine Products APHIS-2008-0010-0008 RIN:0579-AC68
Monday,
March 26, 2012
CANINE SPONGIFORM ENCEPHALOPATHY: A NEW FORM OF ANIMAL
PRION DISEASE http://caninespongiformencephalopathy.blogspot.com/2012/03/canine-spongiform-encephalopathy-new.html
Ultrastructural findings in pigs experimentally
infected with bovine spongiform encephalopathy agent
Monday, December 21, 2009
Distinct Molecular
Signature of Bovine Spongiform Encephalopathy Prion in Pigs
PORCINE SPONGIFORM ENCEPHALOPATHY
PSE
7 OF 10 LITTLE PIGGIES WENT ON TO DEVELOP BSE;
1: J Comp
Pathol. 2000 Feb-Apr; 122(2-3): 131-43. Related
Articles,
Links
Click here to read
The neuropathology of
experimental bovine spongiform encephalopathy in the pig.
Ryder SJ,
Hawkins SA, Dawson M, Wells GA.
Veterinary Laboratories Agency Weybridge,
Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, UK.
In an
experimental study of the transmissibility of BSE to the pig, seven of 10 pigs,
infected at 1-2 weeks of age by multiple-route parenteral inoculation with a
homogenate of bovine brain from natural BSE cases developed lesions typical of
spongiform encephalopathy. The lesions consisted principally of severe neuropil
vacuolation affecting most areas of the brain, but mainly the forebrain. In
addition, some vacuolar change was identified in the rostral colliculi and
hypothalamic areas of normal control pigs. PrP accumulations were detected
immunocytochemically in the brains of BSE-infected animals. PrP accumulation was
sparse in many areas and its density was not obviously related to the degree of
vacuolation. The patterns of PrP immunolabelling in control pigs differed
strikingly from those in the infected animals.
PMID: 10684682 [PubMed -
indexed for MEDLINE]
IN CONFIENCE
EXPERIMENTAL PORCINE
SPONGIFORM ENCEPHALOPATHY
1. CMO should be aware that a pig inoculated
experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months
developed an illness, now confirmed as a spongiform encephalopathy. This is the
first ever description of such a disease in a pig, although it seems there are
no previous attempts at experimental inoculation with animal material. The
Southwood group had thought pigs would not be susceptible. Most pigs are
slaughtered when a few weeks old but there have been no reports of relevant
neurological illness in breeding sows or other elderly pigs. ...see full text
;
IN CONFIDENCE
So it is plausible
pigs could be pre-clinically affected with BSE but since so few are allowed to
reach adulthood this has not been recognized through clinical disease.
...
CONFIDENTIAL
EXPERIMENTAL PORCINE
SPONGIFORM ENCEPHALOPATHY
While this clearly is a cause for concern we
should not jump to the conclusion that this means that pigs will necessarily be
infected by bone and meat meal fed by the oral route as is the case with cattle.
...
CONFIDENTIAL
we cannot rule out the possibility that
unrecognized subclinical spongiform encephalopathy could be present
in British pigs though there is no evidence for this: only with
parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans
of sufficient concern to consider any action.
May I, at the outset, reiterate that we
should avoid dissemination of papers relating to this experimental finding to
prevent premature release of the information. ...
CONFIDENTIAL
3. It is particularly important that
this information is not passed outside the Department, until Ministers have
decided how they wish it to be handled. ...
CONFIDENTIAL
But it
would be easier for us if pharmaceuticals/devices are not directly mentioned at
all. ...
CONFIDENTIAL
Our
records show that while some use is made of porcine materials in medicinal
products, the only products which would appear to be in a hypothetically
''higher risk'' area are the adrenocorticotrophic hormone for which the source
material comes from outside the United Kingdom, namely America China Sweden
France and Germany. The products are manufactured by Ferring and Armour. A
further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use
of porcine skin - which is not considered to be a ''high risk'' tissue, but one
of its uses is described in the data sheet as ''in dural replacement''. This
product is sourced from the United Kingdom.....
FELINE SPONGIFORM ENCEPHALOPATHY FSE
EQUINE SPONGIFORM ENCEPHALOPATHY ESE
A CONTRIBUTION TO THE NEUROPATHOLOGY OF THE RED-NECKED OSTRICH (STRUTHIO
CAMELUS) - SPONGIFORM ENCEPHALOPATHY
4.21 Three cases of SE’s with an unknown infectious agent have been
reported in ostriches (Struthio Camellus) in two zoos in north west Germany
(Schoon @ Brunckhorst, 1999, Verh ber Erkeg Zootiere 33:309-314). These birds
showed protracted central nervous symptoms with ataxia, disturbances of balance
and uncoordinated feeding behaviour. The diet of these birds had included
poultry meat meal, some of which came from cattle emergency slaughter
cases.
SE1806
TRANSMISSION STUDIES OF BSE TO DOMESTIC FOWL BY ORAL EXPOSURE TO BRAIN
HOMOGENATE
1 challenged cock bird was necropsied (41 months p.i.) following a period
of ataxia, tremor, limb abduction and other neurological signs.
Histopathological examination failed to reveal any significant lesions of the
central or peripheral nervous systems...
1 other challenged cock bird is also showing ataxia (43 months p.i.).
snip...
94/01.19/7.1
A notification of Spongiform Encephalopathy was introduced in October 1996
in respect of ungulates, poultry and any other animal.
4.23 MAFF have carried out their own transmission experiments with hens. In
these experiments, some of the chickens exposed to the BSE agent showed
neurological symptoms. However MAFF have not so far published details of the
symptoms seen in chickens. Examination of brains from these chickens did not
show the typical pathology seen in other SE’s. 4.24 A farmer in Kent in November
1996 noticed that one of his 20 free range hens, the oldest, aged about 30
months was having difficulty entering its den and appeared frightened and tended
to lose its balance when excited. Having previously experienced BSE cattle on
his farm, he took particular notice of the bird and continued to observe it over
the following weeks. It lost weight, its balance deteriorated and characteristic
tremors developed which were closely associated with the muscles required for
standing. In its attempts to maintain its balance it would claw the ground more
than usual and the ataxia progressively developed in the wings and legs, later
taking a typical form of paralysis with a clumsy involuntary jerky motion.
Violent tremors of the entire body, particularly the legs, became common,
sparked off by the slightest provocation. This is similar to that seen in many
BSE cases where any excitement may result in posterior ataxia, often with
dropping of the pelvis, kicking and a general nervousness. Three other farmers
and a bird breeder from the UK are known to have reported having hens with
similar symptoms. The bird breeder who has been exhibiting his birds for show
purposes for 20 years noticed birds having difficulty getting on to their perch
and holding there for any length of time without falling. Even though the bird
was eating normally, he noticed a weight loss of more than a pound in a bird the
original weight of which was 5 pounds. 4.25 Histological examination of the
brain revealed degenerative pathological changes in hens with a minimal
vacuolation. The presence of PrP immunostaining of the brain sections revealed
PrP-sc positive plaques and this must be regarded as very strong evidence to
demonstrate that the hens had been incubating Spongiform Encephalopathy.
OPINION on : NECROPHAGOUS BIRDS AS POSSIBLE TRANSMITTERS OF TSE/BSE ADOPTED
BY THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 7-8 NOVEMBER 2002
OPINION
1. Necrophagous birds as possible transmitters of BSE. The SSC considers
that the evaluation of necrophagous birds as possible transmitters of BSE,
should theoretically be approached from a broader perspective of mammals and
birds which prey on, or are carrion eaters (scavengers) of mammalian species.
Thus, carnivorous and omnivorous mammals, birds of prey (vultures, falcons,
eagles, hawks etc.), carrion eating birds (crows, magpies etc.) in general could
be considered possible vectors of transmission and/or spread of TSE infectivity
in the environment. In view also of the occurrence of Chronic Wasting Disease
(CWD) in various deer species it should not be accepted that domestic cattle and
sheep are necessarily the only source of TSE agent exposure for carnivorous
species. While some information is available on the susceptibility of
wild/exotic/zoo animals to natural or experimental infection with certain TSE
agents, nothing is known of the possibility of occurrence of TSE in wild animal
populations, other than among the species of deer affected by CWD in the
USA.
1 The carrion birds are animals whose diet regularly or occasionally
includes the consumption of carcasses, including possibly TSE infected ruminant
carcasses.
C:\WINNT\Profiles\bredagi.000\Desktop\Necrophagous_OPINION_0209_FINAL.doc
Tuesday, April 24, 2012
MAD COW DISEASE USA 4TH CASE DOCUMENTED ATYPICAL BSE CALIFORNIA
USA MAD COW DISEASE
AND CJD THERE FROM SINGELTARY ET AL 1999 – 2012
TSS