Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Unit
2011 Annual Report
1a.Objectives (from AD-416) Obj. 1. Assess the cross species
transmissibility of transmissible spongiform encephalopathies (TSEs) in
livestock and wildlife. Obj. 2. Investigate the pathobiology of TSEs in natural
and secondary hosts. Obj. 3. Investigate pathogenesis and ante mortem detection
of bovine spongiform encephalopathy (BSE). Obj. 4. Develop a method to detect
central nervous system (CNS) tissue contamination on carcasses. Obj. 5. Discover
effective methods to inactivate TSE agents in agricultural settings.
1b.Approach (from AD-416) Studies are focused on the four animal
Transmissible Spongiform Encephalopathy (TSE) agents found in the United States:
bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; chronic
wasting disease (CWD) of deer, elk, and moose; and transmissible mink
encephalopathy (TME). These agents will be tested for cross-species
transmissibility into various livestock and cervid species using both oral and
intracerebral inoculation. Sites of accumulation, routes of infection, methods
of isolate differentiation, and in the case of BSE, genetics of susceptibility
and ante-mortem diagnostics, will be investigated. Existing technology developed
at the National Animal Disease Center and those used in the meat packing
industry for the detection of fecal contamination on carcasses will be adapted
to detect CNS tissue contamination on carcasses. Methods of TSE inactivation
will be evaluated for efficacy in agricultural settings.
3.Progress Report This is the final report for project 3625-32000-086-00D,
terminated in September 2011 and replaced by 3625-32000-103-00D. The project
plan involved 5 objectives.
In Objective 1, Assess cross-species transmissibility of transmissible
spongiform encephalopathies (TSEs) in livestock and wildlife, numerous
experiments assessing the susceptibility of various TSEs in different host
species were conducted. Most notable is deer inoculated with scrapie, which
exhibits similarities to chronic wasting disease (CWD) in deer suggestive of
sheep scrapie as an origin of CWD.
In Objective 2, Investigate the pathobiology of TSEs in natural and
secondary hosts, deer were inoculated with CWD-infected blood. Several animals
developed clinical signs, a result consistent with CWD infectivity in blood.
Also, biochemical strain typing commonly used for rodent models of TSE was
investigated to assess the importance of genetic variability in natural hosts
and how to apply these methods to natural hosts.
Objective 3, Investigate pathogenesis and antemortem detection of bovine
spongiform encephalopathy (BSE), involves several different research areas. Our
results in genetic susceptibility of BSE support the now widely accepted
conclusion that atypical BSE is a spontaneous TSE in cattle. This has important
implications for the ruminant feed ban, food safety, and our understanding of
the origins of BSE. Also as part of Obj. 3, we identified the first recognized
case of genetic BSE where a natural case of BSE was identified in an animal
containing a polymorphism analogous to a human polymorphism that causes a
genetic TSE. Bovine spongiform encephalopathy has long been believed to only be
a feed-borne disease. Together, our results show for the first time the presence
of three different etiologies for BSE as are known to occur in humans. As part
of our investigation, classical, and atypical BSE isolates were inoculated into
cattle. Upon completion, this work will represent the first thorough comparison
of domestic and international BSE isolates, including both classical and
atypical BSE. An antemortem diagnostic technique based upon retinal function was
developed and is routinely applied to experimental animals on site. This
technique detects a TSE before the onset of clinical signs. Work is ongoing to
increase the number of animals containing the E211K polymorphism, a potential
cause of genetic BSE; this will provide the only means by which to prove the
novel allele may cause BSE. The unusual E211K BSE material has also been
successfully amplified in one of these animals.
Objective 4, Develop a method to detect CNS tissue contamination on
carcasses, resulted in a successful method that may be applied through
adaptation of existing technology currently used to detect fecal contamination
on carcasses.
In Objective 5, Determine effective methods to inactivate TSE agents in
agricultural settings, compounds applicable to agricultural settings were
evaluated; the results are being prepared for publication. As part of this
objective, a natural host model for assessing inactivation was developed.
Despite experimental success the model is not suitable due to incubation time.
4.Accomplishments 1. Deer inoculated with domestic isolates of sheep
scrapie. Scrapie-affected deer exhibit 2 different patterns of disease
associated prion protein. In some regions of the brain the pattern is much like
that observed for scrapie, while in others it is more like chronic wasting
disease (CWD), the transmissible spongiform encephalopathy typically associated
with deer. This work conducted by ARS scientists at the National Animal Disease
Center, Ames, IA suggests that an interspecies transmission of sheep scrapie to
deer may have been the origin of CWD. This is important for husbandry practices
with both captive deer, elk and sheep for farmers and ranchers attempting to
keep their herds and flocks free of CWD and scrapie.
2. Demonstrated transmissibility of K211 BSE, a rare genetic form of bovine
spongiform encephalopathy (BSE), to cattle. Cattle containing the rare K211 PRNP
gene have been produced in-house and used in this study conducted by ARS
scientists at the National Animal Disease Center, Ames, IA. These animals have
been inoculated with both K211 BSE and classical BSE. The K211 BSE is
transmissible and progresses far more rapidly in K211 cattle than does classical
BSE. Because of their genetic susceptibility to BSE, K211 PRNP cattle have a
very rapid incubation time and may be more susceptible to TSEs, which are two
characteristics that make them highly desirable for future studies of antemortem
diagnostics and residual infectivity or risk materials after decontamination.
The possibility remains that K211 BSE transmitted to conventional cattle will
result in a disease phenotype similar to classical BSE. If this turns out to be
true, then it will be very important in that it suggests a very rare genetic
form of BSE could have been the original source of brain material responsible
for the U.K. BSE epidemic. Current human and animal feed bans regarding
specified risk materials from cattle protect humans and animals from a
recurrence of such an epidemic.
Review Publications Hamir, A.N., Greenlee, J.J., Stanton, T.B., Smith,
J.D., Doucette, S., Kunkle, R.A., Stasko, J.A., Richt, J.A., Kehrli, Jr., M.E.
2011. Experimental inoculation of raccoons (Procyon lotor) with Spiroplasma
mirum and transmissible mink encephalopathy (TME). Canadian Journal of
Veterinary Research. 75(1):18–24.
Hamir, A.N., Greenlee, J.J., Nicholson, E.M., Kunkle, R.A., Richt, J.A.,
Miller, J.M., Hall, M. 2011. Experimental transmission of chronic wasting
disease (CWD) from elk and white-tailed deer to fallow deer by intracerebral
route: final report. Canadian Journal of Veterinary Research. 75(2):152-156.
Smith, J.D., Hamir, A.N., Greenlee, J.J. 2011. Cartilaginous metaplasia in
the sclera of Suffolk sheep. Veterinary Pathology. 48(4):827-829.
Loiacono, C.M., Beckwith, N., Kunkle, R.A., Orcutt, D., Hall, S.M. 2010.
Detection of PrPSc in formalin-fixed, paraffin embedded tissue by Western blot
differentiates classical scrapie, Nor98 scrapie, and bovine spongiform
encephalopathy. Journal of Veterinary Diagnostic Investigation. 22(5):684-689.
Hamir, A.N., Kehrli, Jr., M.E., Kunkle, R.A., Greenlee, J.J., Nicholson,
E.M., Richt, J.A., Miller, J.M., Cutlip, R.C. 2011. Experimental interspecies
transmission studies of the transmissible spongiform encephalopathies to cattle:
comparison to bovine spongiform encephalopathy in cattle. Journal of Veterinary
Diagnostic Investigation. 23(3):407-420.
Nicholson, E.M. 2011. Enrichment of PrPSc in formalin-fixed,
paraffin-embedded tissues prior to analysis by Western blot. Journal of
Veterinary Diagnostic Investigation. 23(4):790-792.
Atypical H-Type Bovine Spongiform Encephalopathy in a Cow Born after the
Reinforced Feed-Ban on Meat-and-Bone-Meal
Claudia Guldimann1, Michaela Gsponer1, Cord Drögemüller2, Anna Oevermann1
and Torsten Seuberlich1,*
+ Author Affiliations
1NeuroCentre, National and OIE Reference Laboratory for BSE and Scrapie
2Institute of Genetics, Vetsuisse Faculty, University of Berne, Berne,
Switzerland
ABSTRACT
The significance of atypical bovine spongiform encephalopathies (BSE) in
cattle for controlling the BSE epidemic is poorly understood. Here we report a
case of atypical H-type BSE born after the implementation of the reinforced
feed-ban in Europe. This supports an etiology of H-type BSE unrelated to that of
classical BSE.
FOOTNOTES ↵* Corresponding author. Mailing address: NeuroCentre, DCR-VPH,
Bremgartenstrasse 109a, CH-3001 Berne, Switzerland. Phone: 41 31 631 2206. Fax:
41 31 631 2538. E-mail: torsten.seuberlich@vetsuisse.unibe.ch Copyright © 2012,
American Society for Microbiology. All Rights Reserved.
snip...
In contrast, the animal described here was 6.5 years old, CNS specific
neurological signs were not observed, and spongiform lesions as well as PrPd
deposits in the brain were minimal. All this supports that it was in an early,
preclinical stage of the disease. In this regard it is important to point out
that these minimal lesions and PrPd deposits were found in the grey matter
structures of the obex region of the medulla oblongata, the midbrain and the
thalamus. These findings are essentially similar to those in preclinical C-type
BSE (1,12,13,22) and support that sampling of the obex region in surveillance
schemes implemented for C98 type BSE might be similarly suitable for detection
of naturally occurring H-type BSE.
The main disease-control measure of C-type BSE is the ban on mammalian MBM
in ruminant feed. This feed-ban was enforced in Switzerland and the European
Union in the early 1990s and considerably reduced the number of newly infected
cattle. However, the recycling of the C-type BSE agent in the cattle population
was not blocked until the MBM feed-ban was reinforced in 2001, now excluding the
use of animal proteins in feed of all farmed animals (10).
It remains unknown, whether H-type BSE similarly transmits orally in the
cattle population with MBM as a vehicle or not. If oral transmission occurs and
is the sole etiology, the reinforced MBM feed-ban should be an appropriate
measure to prevent the spread of H-type BSE also and no cases should be born
after its implementation, i.e., after 2001 in Switzerland and Germany.
To our knowledge, this is the first report of an H-type BSE affected animal
being born after the reinforced MBM feed-ban in the respective country.
Therefore, this case provides further evidence that the etiology of H-type BSE
may be unrelated to the ingestion of prion contaminated meat-and-bone meal.
Taken together, this supports the widely expressed postulate that H-type BSE
originates from a spontaneous misfolding of cellular PrP with a pathophysiology
similar to sporadic Creutzfeld-Jakob disease in humans (7,20).
Alternatively, other yet unknown routes of transmission or genetic
determinants must be considered. This said, H-type BSE might persist after
eradication of C-type BSE. What are the implications of this scenario? Studies
in mice provided experimental evidence that H-type BSE may shift its disease
phenotype to that of C-type BSE (3) upon transmission. It has therefore been
hypothesized that the C-type BSE epidemic originated from spontaneously
occurring H-type BSE cases. If this was the case there would be a constant risk
that C-type BSE re-emerges in the cattle population once the feed-ban is
discontinued. Consequently, some measures of disease control would need to be
maintained indefinitely. Since the standards for the determination of a
countries’ BSE risk status currently do not differentiate between BSE subtypes
(28), BSE risk assessments will certainly need to take such considerations into
account. This highlights the need for continuing research into the relationship
between classical and atypical BSE variants to provide the scientific basis for
future disease surveillance and control policies.
re-Atypical H-Type Bovine Spongiform Encephalopathy in a Cow Born after the
Reinforced Feed-Ban on Meat-and-Bone-Meal
please note, one decade (10 years), post USA mad cow partial and voluntary
mad cow feed ban of August 4, 1997, the USA was still feeding cows to cows, with
some 10,000,000 pounds of banned blood laced meat and bone meal fed out into
commerce in 2007. 2006 was a banner year for mad cow protein into commerce as
well.
please see banned mad cow feed in commerce USA 1997 to 2007 ;
2007
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN
COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
PRODUCT
Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried,
Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
Firm initiated recall is ongoing.
REASON
Blood meal used to make cattle feed was recalled because it was cross-
contaminated with prohibited bovine meat and bone meal that had been
manufactured on common equipment and labeling did not bear cautionary BSE
statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI
___________________________________
PRODUCT
Custom dairy premix products:
MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX
Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL
PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST
PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN
Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J -
PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN,
BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT
Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with
commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm
initiated recall is complete.
REASON
Products manufactured from bulk feed containing blood meal that was cross
contaminated with prohibited meat and bone meal and the labeling did not bear
cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
please see 2006 and more here ;
Saturday, August 4, 2012
Final Feed Investigation Summary - California BSE Case - July 2012
Wednesday, May 30, 2012
PO-028: Oral transmission of L-type bovine spongiform encephalopathy
(L-BSE) in primate model Microcebus murinus
Wednesday, May 2, 2012
ARS FLIP FLOPS ON SRM REMOVAL FOR ATYPICAL L-TYPE BASE BSE RISK HUMAN AND
ANIMAL HEALTH
Wednesday, July 28, 2010
re-Freedom of Information Act Project Number 3625-32000-086-05, Study of
Atypical BSE UPDATE July 28, 2010
Sent: Wednesday, July 28, 2010 11:42 AM
Subject: re-Freedom of Information Act Project Number 3625-32000-086-05,
Study of Atypical BSE UPDATE
Greetings again Ms Williams et al at FOIA USDA,
Thank You again for your kind reply on this important information. However,
I am concerned that you may not be aware of new transmission studies. You (USDA
et al) state Ma'am ;
================================================
The SCA with Italy was mainly to confirm our respective country’s
diagnostic tests would detect the various atypical BSE cases as seen in each
country), in the meantime, the Italians have published their transmissibility
and pathogenesis work on their BASE cases in the following article:
Lombardi G, Casalone C, A DA, Gelmetti D, Torcoli G, Barbieri I, Corona C,
Fasoli E, Farinazzo A, Fiorini M, Gelati M, Iulini B, Tagliavini F, Ferrari S,
Caramelli M, Monaco S, Capucci L, Zanusso G (2008) Intraspecies transmission of
BASE induces clinical dullness and amyotrophic changes. PLoS Pathog
4:e1000075
The above mentioned paper concludes, “In all experimentally infected
animals, no PrP**TSE was detected in peripheral tissues, including cervical and
mesenteric lymph nodes, spleen, thymus, liver, lung, peripheral nerves and
forelimb and limb muscles, either by standard Western blot analysis or following
phosphotungstic acid precipitation.“
It is not necessary to change SRM removal due to any different tissue
infectivity distribution between classical BSE and atypical BSE. At this time,
there is no scientific evidence to suggest a need for expanding the list of
tissues included in the Specified Risk Material (SRM) ban as a result of
published studies on atypical BSE.
snip...
Moreover, in the paper by Buschmann A, Groschup MH (2005,) Highly bovine
spongiform encephalopathy-sensitive transgenic mice confirm the essential
restriction of infectivity to the nervous system in clinically diseased cattle.
J Infect Dis 192:934-942; the authors, when speaking about the classical BSE
food-borne epidemic in Europe, concluded their “results provide further
indication that the pathogenesis of BSE in cattle is fundamentally different
from that in sheep and mice, due to an exclusive intraneuronal spread of
infectivity from the gut to the central nervous system.”
end...
================================================
Again, in my opinion, the USDA is cherry picking the science they want to
use, and in doing so, I believe they are putting human lives at risk.
I disagree for the following reasons. New studies indeed show that ;
July 10, 2010
see full text ;
Wednesday, July 28, 2010
re-Freedom of Information Act Project Number 3625-32000-086-05, Study of
Atypical BSE UPDATE July 28, 2010
USDA TRIPLE BSE MAD COW FIREWALL, SRM, FEED, AND SURVEILLANCE
2012
***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...
MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...
***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate
Model
***Infectivity in skeletal muscle of BASE-infected cattle
***feedstuffs- It also suggests a similar cause or source for atypical BSE
in these countries.
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans.
The present study demonstrated successful intraspecies transmission of
H-type BSE to cattle and the distribution and immunolabeling patterns of PrPSc
in the brain of the H-type BSE-challenged cattle. TSE agent virulence can be
minimally defined by oral transmission of different TSE agents (C-type, L-type,
and H-type BSE agents) [59]. Oral transmission studies with H-type BSEinfected
cattle have been initiated and are underway to provide information regarding the
extent of similarity in the immunohistochemical and molecular features before
and after transmission.
In addition, the present data will support risk assessments in some
peripheral tissues derived from cattle affected with H-type BSE.
Friday, May 11, 2012
Experimental H-type bovine spongiform encephalopathy characterized by
plaques and glial- and stellate-type prion protein deposits
***support risk assessments in some peripheral tissues derived from cattle
affected with H-type BSE
Thursday, June 21, 2012
Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy
Associated with E211K Prion Protein Polymorphism
Justin J. Greenlee1*, Jodi D. Smith1, M. Heather West Greenlee2, Eric M.
Nicholson1
1 National Animal Disease Center, United States Department of Agriculture,
Agricultural Research Service, Ames, Iowa, United States of America, 2 Iowa
State University, Ames, Iowa, United States of America
Abstract
The majority of bovine spongiform encephalopathy (BSE) cases have been
ascribed to the classical form of the disease. Htype and L-type BSE cases have
atypical molecular profiles compared to classical BSE and are thought to arise
spontaneously. However, one case of H-type BSE was associated with a heritable
E211K mutation in the prion protein gene. The purpose of this study was to
describe transmission of this unique isolate of H-type BSE when inoculated into
a calf of the same genotype by the intracranial route. Electroretinograms were
used to demonstrate preclinical deficits in retinal function, and optical
coherence tomography was used to demonstrate an antemortem decrease in retinal
thickness. The calf rapidly progressed to clinical disease (9.4 months) and was
necropsied. Widespread distribution of abnormal prion protein was demonstrated
within neural tissues by western blot and immunohistochemistry. While this
isolate is categorized as BSE-H due to a higher molecular mass of the
unglycosylated PrPSc isoform, a strong labeling of all 3 PrPSc bands with
monoclonal antibodies 6H4 and P4, and a second unglycosylated band at
approximately 14 kDa when developed with antibodies that bind in the C-terminal
region, it is unique from other described cases of BSE-H because of an
additional band 23 kDa demonstrated on western blots of the cerebellum. This
work demonstrates that this isolate is transmissible, has a BSE-H phenotype when
transmitted to cattle with the K211 polymorphism, and has molecular features
that distinguish it from other cases of BSE-H described in the literature.
snip...
Most significantly it must be determined if the molecular phenotype of this
cattle TSE remains stable when transmitted to cattle without the E211K
polymorphism as several other isolates of atypical BSE have been shown to adopt
a molecular profile consistent with classical BSE after passage in transgenic
mice expressing bovine PrPC [40] or multiple passages in wild type mice [23].
Results of ongoing studies, namely passage of the E211K Htype isolate into
wild-type cattle, will lend further insight into what role, if any, genetic and
sporadic forms of BSE may have played in the origins of classical BSE. Atypical
cases presumably of spontaneous or, in the case of E211K BSE-H, genetic origins
highlight that it may not be possible to eradicate BSE entirely and that it
would be hazardous to remove disease control measures such as prohibiting the
feeding of meat and bone meal to ruminants.
P.4.23
Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw
Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1
1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale,
Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research
Institute, Poland; 5Kansas State University (Previously at USDA National Animal
Disease Center), USA
Background: Classical BSE is a world-wide prion disease in cattle, and the
classical BSE strain (BSE-C) has led to over 200 cases of clinical human
infection (variant CJD). Atypical BSE cases have been discovered in three
continents since 2004; they include the L-type (also named BASE), the H-type,
and the first reported case of naturally occurring BSE with mutated bovine PRNP
(termed BSE-M). The public health risks posed by atypical BSE were largely
undefined.
Objectives: To investigate these atypical BSE types in terms of their
transmissibility and phenotypes in humanized mice. Methods: Transgenic mice
expressing human PrP were inoculated with several classical (C-type) and
atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation
time, characteristics and distribution of PrPSc, symptoms, and histopathology
were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected
with minimal spongiosis and an average incubation time of 20-22 months, whereas
only one of the C-type BSE-inoculated mice developed prion disease after more
than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse
brains was biochemically different from bovine BASE or sCJD. PrPSc was also
detected in the spleen of 22% of BASE-infected humanized mice, but not in those
infected with sCJD. Secondary transmission of BASE in the humanized mice led to
a small reduction in incubation time.*** The atypical BSE-H strain is also
transmissible with distinct phenotypes in the humanized mice, but no BSE-M
transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than
classical BSE, has a lymphotropic phenotype, and displays a modest transmission
barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg
mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN
HUMANIZED MOUSE MODELS
Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina
Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi
Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case
Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto
Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany;
4National Veterinary Research Institute, Poland; 5Kansas State University,
Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous
address: USDA National Animal Disease Center, Ames, IA 50010, USA
Classical BSE is a world-wide prion disease in cattle, and the classical
BSE strain (BSE-C) has led to over 200 cases of clinical human infection
(variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have
been discovered in three continents since 2004. The first case of naturally
occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006
in the USA. The transmissibility and phenotypes of these atypical BSE
strains/isolates in humans were unknown. We have inoculated humanized transgenic
mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M
isolate. We have found that the atypical BSE-L strain is much more virulent than
the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the
humanized transgenic mice with distinct phenotype, but no transmission has been
observed for the BSE-M isolate so far.
III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE,
DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease
(CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk
Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE,
or less virulent than cBSE? just curious.....''
Professor Kong reply ;
.....snip
''As to the H-BSE, we do not have sufficient data to say one way or
another, but we have found that H-BSE can infect humans. I hope we could publish
these data once the study is complete. Thanks for your interest.''
Best regards,
Qingzhong Kong, PhD Associate Professor Department of Pathology Case
Western Reserve University Cleveland, OH 44106 USA
END...TSS
Thursday, December 04, 2008 2:37 PM
"we have found that H-BSE can infect humans."
personal communication with Professor Kong. ...TSS
BSE-H is also transmissible in our humanized Tg mice.
The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
let's take a closer look at this new prionpathy or prionopathy, and then
let's look at the g-h-BSEalabama mad cow.
This new prionopathy in humans? the genetic makeup is IDENTICAL to the
g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like
this, ......wait, it get's better. this new prionpathy is killing young and old
humans, with LONG DURATION from onset of symptoms to death, and the symptoms are
very similar to nvCJD victims, OH, and the plaques are very similar in some
cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets
even better, the new human prionpathy that they claim is a genetic TSE, has no
relation to any gene mutation in that family. daaa, ya think it could be related
to that mad cow with the same genetic make-up ??? there were literally tons and
tons of banned mad cow protein in Alabama in commerce, and none of it
transmitted to cows, and the cows to humans there from ??? r i g h t $$$
ALABAMA MAD COW g-h-BSEalabama
In this study, we identified a novel mutation in the bovine prion protein
gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United
States of America. This mutation is identical to the E200K pathogenic mutation
found in humans with a genetic form of CJD. This finding represents the first
report of a confirmed case of BSE with a potential pathogenic mutation within
the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most
likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K
mutation.
her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS
Pathog. 4, e1000156; 2008).
This raises the possibility that the disease could occasionally be genetic
in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the
UK epidemic had most likely originated from such a mutation and argued against
the scrapierelated assumption. Such rare potential pathogenic PRNP mutations
could occur in countries at present considered to be free of BSE, such as
Australia and New Zealand. So it is important to maintain strict surveillance
for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many
countries still feed ruminant proteins to pigs). Removal of specified risk
material, such as brain and spinal cord, from cattle at slaughter prevents
infected material from entering the human food chain. Routine genetic screening
of cattle for PRNP mutations, which is now available, could provide additional
data on the risk to the public. Because the point mutation identified in the
Alabama animals is identical to that responsible for the commonest type of
familial (genetic) CJD in humans, it is possible that the resulting infective
prion protein might cross the bovine–human species barrier more easily. Patients
with vCJD continue to be identified. The fact that this is happening less often
should not lead to relaxation of the controls necessary to prevent future
outbreaks.
Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary
Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen
A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier
Hall, Manhattan, Kansas 66506-5601, USA
NATURE|Vol 457|26 February 2009
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)
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.
Saturday, May 26, 2012
Are USDA assurances on mad cow case 'gross oversimplification'?
SNIP...
What irks many scientists is the USDA’s April 25 statement that the rare
disease is “not generally associated with an animal consuming infected feed.”
The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown,
one of the world’s experts on this type of disease who retired recently from the
National Institutes of Health. "(The agency) has no foundation on which to base
that statement.”
“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an
official with the USDA during the Clinton Administration now at Mississippi
State.
In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the
origins of atypical cases of BSE,” she said
The argument about feed is critical because if feed is the cause, not a
spontaneous mutation, the California cow could be part of a larger outbreak.
SNIP...
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
in the url that follows, I have posted
SRM breaches first, as late as 2011.
then
MAD COW FEED BAN BREACHES AND TONNAGES OF MAD COW FEED IN COMMERCE up until
2007, when they ceased posting them.
then,
MAD COW SURVEILLANCE BREACHES.
Friday, May 18, 2012
Update from APHIS Regarding a Detection of Bovine Spongiform Encephalopathy
(BSE) in the United States Friday May 18, 2012
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
OR-10 15:25 - 15:40 VARIABLY PROTEASE-SENSITIVE PRIONOPATHY IS
TRANSMISSIBLE IN BANK VOLES Nonno
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1
1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze
Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve
University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases. In BvI109, 3 VPSPr cases (2 VV and 1
MM) showed positive transmission until now. Overall, 5 voles were positive with
survival time between 281 and 596 d.p.i.. In contrast to what observed in
BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern,
characterized by low molecular weight PrPres. These PrPres fragments were
positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84,
suggesting that they are cleaved at both the C-terminus and the N-terminus.
Second passages are in progress from these first successful transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109. The
discovery of previously unrecognized prion diseases in both humans and animals
(i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases
might be wider than expected and raises crucial questions about the epidemiology
and strain properties of these new forms. We are investigating this latter issue
by molecular and biological comparison of VPSPr, GSS and Nor98.
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)
There have been two molecular types of "atypical" BSE isolates described in
the literature so far:
(i) a type with a lower molecular mass of the unglycosylated isoform also
called the L-type and
(ii) a type with a higher molecular mass of the unglycosylated isoform,
also called the H-type.
The L-type has been found in cattle in Italy (10), Japan (11), Germany (12)
and Belgium (13).
So far, the H-type has been described in cattle from France (14), Germany
(12) and the United States (15).
The U.S. cases were animals born and raised in the U.S. (Texas, Alabama).
Unusual cases of BSE are an
unexpected finding since it was previously believed that BSE disease in
cattle is caused by a single strain of
infectious agent, which has been shown to be very consistent and uniform in
appearance, even after
transmission to other species. The reports of unusual phenotypes of BSE in
cattle suggest that different PrPSc
phenotypes exist in cattle with BSE.
There are several hypotheses which can explain these findings:
(i) there are variants of the BSE agent with different molecular features
in cattle;
(ii) cattle may have been infected by another source of an infectious prion
agent (e.g. scrapie or CWD); or
(iii) a rare sporadic or genetic form of TSE disease could exist in cattle
as described for humans.
DR. CLIFFORD: "Basically the IHC test, besides looking at location of the
brain stem you're also doing a staining technique to identify abnormal prion
proteins. In this case they had some staining, but the staining did not match up
with what they would typically see in a BSE case. It didn't have the normal
distribution it would see within the samples. So basically that's why the
request for doing additional testing, and that's why we're sending it to
Weybridge as well."
DR. CLIFFORD: "There was some staining present. But it did not match a
normal pattern, and we're taking through that to do additional tests in
additional parts of the brain stem to try to see if we can find a normal
staining pattern as well as sending that sample to Weybridge to run against
their IHC."
Atypical BSE
Atypical BSE, is a rare type of “madcow” disease that is not linked to the
consumption of contaminated feed.The second (Texas) and third (Alabama)
announced cases of U.S. BSE were atypical. ...
Subject: BSE, BOVINE - USA: ATYPICAL STRAIN Date: June 1, 2006 at 11:09 am
PST BSE, BOVINE - USA: ATYPICAL STRAIN
**********************************
A ProMED-mail post
ProMED-mail, a program of the International Society for Infectious Diseases
Date: 31 May 2006 From: Terry S. Singletary and Mary Marshall
Source: Rapid City Journal [edited]
The 2 cases of bovine spongiform encephalopathy found in U.S. cattle over
the past year came from a rare strain of BSE found largely in Europe that
scientists are only beginning to identify, according to research by a French
scientist.
Researchers in France and Italy who presented their work at an
international conference in London reported 2 rare strains of bovine spongiform
encephalopathy that are harder to detect and affect mainly older cattle.
Thierry Baron of the French Food Safety Agency presented research
indicating that a 12-year-old Texas cow testing positive for BSE in June 2005,
and the 10-year-old Alabama cow that tested positive in March [2006?], showed
identical testing patterns to a small number of BSE cases in France, Sweden and
Poland.
Animal scientists are calling such strains "atypical" BSE, which is
different from the "typical" BSE caused by cattle eating feed with ruminant
offal contaminated with a BSE protein.
They don't know whether the atypical strains are caused by something else
or simply appear spontaneously in older, susceptible cattle.
Art Davis, a U.S. Department of Agriculture (USDA) scientist for the Animal
and Plant Health Inspection Service (APHIS) at the National Veterinary Services
Laboratory in Ames, Iowa, said in his presentation Sunday at the London
conference that the Texas and Alabama test results showed completely different
prion patterns than the Washington state case discovered in December 2003.
"The classical lesions were not there," Davis said of the cases. The
Washington state cow originated in Alberta, Canada, near where several other BSE
cases have been found.
The "typical" BSE strain caused a mad cow disease epidemic in Great Britain
beginning in the mid-1980s that killed 184 000 cattle and more than 100 people
who contracted a human form of the disease caused by eating contaminated beef
products.
The scientific evidence shows that in almost all cattle cases, the fatal
neurological disorder was contracted through contaminated meat and bone meal fed
to the cow, typically at a young age.
However, scientists finding atypical cases of BSE are beginning to question
if there has been a change in the abnormal protein that causes BSE or if cattle
might be susceptible to a sporadic BSE affecting older cattle.
Danny Matthews, head of transmissible spongiform encephalopathies at
England's Veterinary Laboratories Agency, said recent research on atypical cases
of BSE raises questions over whether older cattle can sporadically get the
disease or if there are more strains of BSE than previously understood.
Scientists might also be facing something new, such as "son of BSE," he said.
"We don't fully understand what atypical BSE means," Matthews said. "Is it
spontaneous or another source causing it? Time will tell."
Although the test patterns in the U.S. cases and atypical cases in Europe
closely matched, Baron said there were no known links among any of the positive
animals. The French Food Safety Agency sent a researcher to the United States to
study the positive Texas case and compare its results to known cases in France
that did not match the typical BSE positive tests.
"You could place them side-by-side and not tell the difference," Baron
said.
Baron also raised the prospect that the disease could be sporadic in at
least a small number of older cattle. He said, however, such a conclusion would
be hard to determine because of the small number of cattle with this atypical
strain globally.
Dr. Sam Holland, South Dakota's state veterinarian, said there are many
strains of BSE and varying degrees of infectiousness of the agent.
"What if the scenario is there is an atypical prion out there that is much
less infective, has a longer incubation period and has not been recognized as
part of the Great Britain BSE experience identified in 1985 and '86?" Holland
said. "There could be others out there that we haven't recognized yet."
He said it is possible the atypical strains are not caused by contaminated
feed and that it still makes sense to continue the ban on ruminant offal in
cattle feed to prevent the spread of typical BSE and eventually to eliminate
that disease.
"Based on what we know about BSE, it makes good sense to -- number one --
keep some surveillance in place; number 2, watch what we import and restrict
shipments and movements from places that have had those syndromes; and, number
3, with what we know about BSE, it seems to be very prudent to keep our ruminant
offal ban in place," Holland said.
"At least for typical BSE's, it seems to be very effective. It's probably
reasonable to continue the ruminant offal ban even after the last typical BSE
case has been eliminated."
Editor's note: DTN, a private company based in Omaha, Neb., provides
information to agriculture, energy trading markets and other weather-sensitive
industries. The Rapid City Journal received a copy of DTN's story and expanded
on it.
[Byline: Chris Clayton]
-- Terry S. Singletary and Mary Marshall
[An atypical form has been found in sheep with scrapie. Other countries
have indicated an atypical form of BSE. It seems logical that the US would have
an a atypical form as well. The case might even be made that new variant CJD is
an atypical form of CJD. Clearly there is more to the TSE diseases than we fully
comprehend. - Mod.TG]
[see also: 2005 ---- Scrapie, atypical, ovine - Falkland Islands
20051120.3371 2004 ---- Scrapie, atypical, sheep - UK and Ireland 20041210.3274
Scrapie, atypical, sheep - UK (02) 20040409.0965 Scrapie, atypical, sheep -
UK20040408.0952 BSE, atypical - France: OIE 20040201.0391 Scrapie, atypical,
sheep - France: OIE 20040201.0390 BSE - France: distinct molecular phenotypes
20040107.0076 2003 ---- Scrapie - Norway: new phenotype 20031117.2857 BSE -
Japan (08): 9th case, lab findings 20031115.2838 BSE, atypical case - Italy: OIE
20031022.2649 BSE - Italy: atypical, suspected 20031012.2576 BSE - Japan (06):
atypical 20031009.2547 BSE - Japan (05): atypical 20031008.2526 BSE - Japan
(04): atypical 20031007.2511 2002 ---- BSE? Sheep - USA (Vermont) 20020412.3937
2000 ---- BSE? sheep - USA (Vermont) (06) 20000724.1223 BSE? sheep - USA
(Vermont) 20000717.1184 1996 ---- CJD sporadic vs variant differences
19960526.0990] ...............tg/pg/lm
*##########################################################*
************************************************************
END...TSS
2012
==============================================
Saturday, August 4, 2012
Final Feed Investigation Summary - California BSE Case - July 2012
=============================================
SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE
INVESTIGATION JULY 2012
Summary Report BSE 2012
Executive Summary
Saturday, August 4, 2012
Update from APHIS Regarding Release of the Final Report on the BSE
Epidemiological Investigation
CENSORSHIP IS A TERRIBLE THING $$$
Canada has had a COVER-UP policy of mad cow disease since about the 17th
case OR 18th case of mad cow disease. AFTER THAT, all FOIA request were ignored
$$$
THIS proves there is indeed an epidemic of mad cow disease in North
America, and it has been covered up for years and years, if not for decades, and
it’s getting worse $$$
Thursday, February 10, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011
and how to hide mad cow disease in Canada Current as of: 2011-01-31
Wednesday, August 11, 2010
REPORT ON THE INVESTIGATION OF THE SIXTEENTH CASE OF BOVINE SPONGIFORM
ENCEPHALOPATHY (BSE) IN CANADA
Thursday, August 19, 2010
REPORT ON THE INVESTIGATION OF THE SEVENTEENTH CASE OF BOVINE SPONGIFORM
ENCEPHALOPATHY (BSE) IN CANADA
Friday, March 4, 2011
Alberta dairy cow found with mad cow disease
Reasons for the New Regulation Order No. 23 (as well as amending Order No.
149) of the State Committee for Veterinary Medicine name BSE as the reason for
new import requirement. The legal title for Order No. 23 is "On Urgent Measures
Aimed at Prevention and Elimination of BSE and Other Prion Infections in
Cattle”. Neither Order explains how the threat of introduction of BSE can be
addressed through the inspection of producers of all products of animal origin
including fish, dairy products, poultry and pork. It is not clear what other
concerns are addressed through the proposed inspections. Formal Notification of
Trading Partners On August 3rd, Ukraine's Notification and Enquiry Point issued
a legal Notification G/SPS/N/UKR/3/Rev.1 found on the Official WTO Website
(Committee on Sanitary and Phytosanitary Measures)
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Unit
2011 Annual Report
1a.Objectives (from AD-416) Obj. 1. Assess the cross species
transmissibility of transmissible spongiform encephalopathies (TSEs) in
livestock and wildlife. Obj. 2. Investigate the pathobiology of TSEs in natural
and secondary hosts. Obj. 3. Investigate pathogenesis and ante mortem detection
of bovine spongiform encephalopathy (BSE). Obj. 4. Develop a method to detect
central nervous system (CNS) tissue contamination on carcasses. Obj. 5. Discover
effective methods to inactivate TSE agents in agricultural settings.
1b.Approach (from AD-416) Studies are focused on the four animal
Transmissible Spongiform Encephalopathy (TSE) agents found in the United States:
bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; chronic
wasting disease (CWD) of deer, elk, and moose; and transmissible mink
encephalopathy (TME). These agents will be tested for cross-species
transmissibility into various livestock and cervid species using both oral and
intracerebral inoculation. Sites of accumulation, routes of infection, methods
of isolate differentiation, and in the case of BSE, genetics of susceptibility
and ante-mortem diagnostics, will be investigated. Existing technology developed
at the National Animal Disease Center and those used in the meat packing
industry for the detection of fecal contamination on carcasses will be adapted
to detect CNS tissue contamination on carcasses. Methods of TSE inactivation
will be evaluated for efficacy in agricultural settings.
3.Progress Report This is the final report for project 3625-32000-086-00D,
terminated in September 2011 and replaced by 3625-32000-103-00D. The project
plan involved 5 objectives.
In Objective 1, Assess cross-species transmissibility of transmissible
spongiform encephalopathies (TSEs) in livestock and wildlife, numerous
experiments assessing the susceptibility of various TSEs in different host
species were conducted. Most notable is deer inoculated with scrapie, which
exhibits similarities to chronic wasting disease (CWD) in deer suggestive of
sheep scrapie as an origin of CWD.
In Objective 2, Investigate the pathobiology of TSEs in natural and
secondary hosts, deer were inoculated with CWD-infected blood. Several animals
developed clinical signs, a result consistent with CWD infectivity in blood.
Also, biochemical strain typing commonly used for rodent models of TSE was
investigated to assess the importance of genetic variability in natural hosts
and how to apply these methods to natural hosts.
Objective 3, Investigate pathogenesis and antemortem detection of bovine
spongiform encephalopathy (BSE), involves several different research areas. Our
results in genetic susceptibility of BSE support the now widely accepted
conclusion that atypical BSE is a spontaneous TSE in cattle. This has important
implications for the ruminant feed ban, food safety, and our understanding of
the origins of BSE. Also as part of Obj. 3, we identified the first recognized
case of genetic BSE where a natural case of BSE was identified in an animal
containing a polymorphism analogous to a human polymorphism that causes a
genetic TSE. Bovine spongiform encephalopathy has long been believed to only be
a feed-borne disease. Together, our results show for the first time the presence
of three different etiologies for BSE as are known to occur in humans. As part
of our investigation, classical, and atypical BSE isolates were inoculated into
cattle. Upon completion, this work will represent the first thorough comparison
of domestic and international BSE isolates, including both classical and
atypical BSE. An antemortem diagnostic technique based upon retinal function was
developed and is routinely applied to experimental animals on site. This
technique detects a TSE before the onset of clinical signs. Work is ongoing to
increase the number of animals containing the E211K polymorphism, a potential
cause of genetic BSE; this will provide the only means by which to prove the
novel allele may cause BSE. The unusual E211K BSE material has also been
successfully amplified in one of these animals.
Objective 4, Develop a method to detect CNS tissue contamination on
carcasses, resulted in a successful method that may be applied through
adaptation of existing technology currently used to detect fecal contamination
on carcasses.
In Objective 5, Determine effective methods to inactivate TSE agents in
agricultural settings, compounds applicable to agricultural settings were
evaluated; the results are being prepared for publication. As part of this
objective, a natural host model for assessing inactivation was developed.
Despite experimental success the model is not suitable due to incubation time.
4.Accomplishments 1. Deer inoculated with domestic isolates of sheep
scrapie. Scrapie-affected deer exhibit 2 different patterns of disease
associated prion protein. In some regions of the brain the pattern is much like
that observed for scrapie, while in others it is more like chronic wasting
disease (CWD), the transmissible spongiform encephalopathy typically associated
with deer. This work conducted by ARS scientists at the National Animal Disease
Center, Ames, IA suggests that an interspecies transmission of sheep scrapie to
deer may have been the origin of CWD. This is important for husbandry practices
with both captive deer, elk and sheep for farmers and ranchers attempting to
keep their herds and flocks free of CWD and scrapie.
2. Demonstrated transmissibility of K211 BSE, a rare genetic form of bovine
spongiform encephalopathy (BSE), to cattle. Cattle containing the rare K211 PRNP
gene have been produced in-house and used in this study conducted by ARS
scientists at the National Animal Disease Center, Ames, IA. These animals have
been inoculated with both K211 BSE and classical BSE. The K211 BSE is
transmissible and progresses far more rapidly in K211 cattle than does classical
BSE. Because of their genetic susceptibility to BSE, K211 PRNP cattle have a
very rapid incubation time and may be more susceptible to TSEs, which are two
characteristics that make them highly desirable for future studies of antemortem
diagnostics and residual infectivity or risk materials after decontamination.
The possibility remains that K211 BSE transmitted to conventional cattle will
result in a disease phenotype similar to classical BSE. If this turns out to be
true, then it will be very important in that it suggests a very rare genetic
form of BSE could have been the original source of brain material responsible
for the U.K. BSE epidemic. Current human and animal feed bans regarding
specified risk materials from cattle protect humans and animals from a
recurrence of such an epidemic.
Review Publications Hamir, A.N., Greenlee, J.J., Stanton, T.B., Smith,
J.D., Doucette, S., Kunkle, R.A., Stasko, J.A., Richt, J.A., Kehrli, Jr., M.E.
2011. Experimental inoculation of raccoons (Procyon lotor) with Spiroplasma
mirum and transmissible mink encephalopathy (TME). Canadian Journal of
Veterinary Research. 75(1):18–24.
Hamir, A.N., Greenlee, J.J., Nicholson, E.M., Kunkle, R.A., Richt, J.A.,
Miller, J.M., Hall, M. 2011. Experimental transmission of chronic wasting
disease (CWD) from elk and white-tailed deer to fallow deer by intracerebral
route: final report. Canadian Journal of Veterinary Research. 75(2):152-156.
Smith, J.D., Hamir, A.N., Greenlee, J.J. 2011. Cartilaginous metaplasia in
the sclera of Suffolk sheep. Veterinary Pathology. 48(4):827-829.
Loiacono, C.M., Beckwith, N., Kunkle, R.A., Orcutt, D., Hall, S.M. 2010.
Detection of PrPSc in formalin-fixed, paraffin embedded tissue by Western blot
differentiates classical scrapie, Nor98 scrapie, and bovine spongiform
encephalopathy. Journal of Veterinary Diagnostic Investigation. 22(5):684-689.
Hamir, A.N., Kehrli, Jr., M.E., Kunkle, R.A., Greenlee, J.J., Nicholson,
E.M., Richt, J.A., Miller, J.M., Cutlip, R.C. 2011. Experimental interspecies
transmission studies of the transmissible spongiform encephalopathies to cattle:
comparison to bovine spongiform encephalopathy in cattle. Journal of Veterinary
Diagnostic Investigation. 23(3):407-420.
Nicholson, E.M. 2011. Enrichment of PrPSc in formalin-fixed,
paraffin-embedded tissues prior to analysis by Western blot. Journal of
Veterinary Diagnostic Investigation. 23(4):790-792.
Tuesday, July 17, 2012
O.I.E. BSE, CWD, SCRAPIE, TSE PRION DISEASE Final Report of the 80th
General Session, 20 - 25 May 2012
CHRONIC WASTING DISEASE, CWD, AND THE DEER PENS AT THE FOOT HILLS CAMPUS
page 30,
*** Spraker suggested an interesting explanation for the occurrence of CWD.
The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr.
Bob Davis. At or about that time, allegedly, some scrapie work was conducted at
this site. When deer were introduced to the pens they occupied ground that had
previously been occupied by sheep.
(PLEASE NOTE SOME OF THESE OLD UK GOVERNMENT FILE URLS ARE SLOW TO OPEN,
AND SOMETIMES YOU MAY HAVE TO CLICK ON MULTIPLE TIMES, PLEASE BE PATIENT, ANY
PROBLEMS PLEASE WRITE ME PRIVATELY, AND I WILL TRY AND FIX OR SEND YOU OLD PDF
FILE...TSS)
IN CONFIDENCE
PERCEPTIONS OF UNCONVENTIONAL SLOW VIRUS DISEASES OF ANIMALS IN USA
GAH WELLS
REPORT OF A VISIT TO THE USA APRIL-MAY 1989
now, years later, see the latest studies here on scrapie and cwd ;
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed
deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture;
Agricultural Research Service, National Animal Disease Center; Ames, IA USA
Interspecies transmission studies afford the opportunity to better
understand the potential host range and origins of prion diseases. The purpose
of these experiments was to determine susceptibility of white-tailed deer (WTD)
to scrapie and to compare the resultant clinical signs, lesions, and molecular
profiles of PrPSc to those of chronic wasting disease (CWD). We inoculated WTD
intracranially (IC; n = 5) and by a natural route of exposure (concurrent oral
and intranasal (IN); n = 5) with a US scrapie isolate. All deer were inoculated
with a 10% (wt/vol) brain homogenate from sheep with scrapie (1ml IC, 1 ml IN,
30 ml oral). All deer inoculated by the intracranial route had evidence of PrPSc
accumulation. PrPSc was detected in lymphoid tissues as early as 7
months-post-inoculation (PI) and a single deer that was necropsied at 15.6
months had widespread distribution of PrPSc highlighting that PrPSc is widely
distributed in the CNS and lymphoid tissues prior to the onset of clinical
signs. IC inoculated deer necropsied after 20 months PI (3/5) had clinical
signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural
and lymphoid tissues. The results of this study suggest that there are many
similarities in the manifestation of CWD and scrapie in WTD after IC inoculation
including early and widespread presence of PrPSc in lymphoid tissues, clinical
signs of depression and weight loss progressing to wasting, and an incubation
time of 21-23 months. Moreover, western blots (WB) done on brain material from
the obex region have a molecular profile similar to CWD and distinct from
tissues of the cerebrum or the scrapie inoculum. However, results of microscopic
and IHC examination indicate that there are differences between the lesions
expected in CWD and those that occur in deer with scrapie: amyloid plaques were
not noted in any sections of brain examined from these deer and the pattern of
immunoreactivity by IHC was diffuse rather than plaque-like. After a natural
route of exposure, 100% of WTD were susceptible to scrapie. Deer developed
clinical signs of wasting and mental depression and were necropsied from 28 to
33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB.
Similar to IC inoculated deer, samples from these deer exhibited two different
molecular profiles: samples from obex resembled CWD whereas those from cerebrum
were similar to the original scrapie inoculum. On further examination by WB
using a panel of antibodies, the tissues from deer with scrapie exhibit
properties differing from tissues either from sheep with scrapie or WTD with
CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive
when probed with mAb P4, however, samples from WTD with scrapie are only weakly
immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from
sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from
WTD with scrapie are strongly positive. This work demonstrates that WTD are
highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is
differentiable from CWD.
White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection
Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion
Research Unit, National Animal Disease Center, USDA-ARS
Interspecies transmission studies afford the opportunity to better
understand the potential host range and origins of prion diseases. Previous
experiments demonstrated that white-tailed deer are susceptible to sheep-derived
scrapie by intracranial inoculation. The purpose of this study was to determine
susceptibility of white-tailed deer to scrapie after a natural route of
exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal
(1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep
clinically affected with scrapie. Non-inoculated deer were maintained as
negative controls. All deer were observed daily for clinical signs. Deer were
euthanized and necropsied when neurologic disease was evident, and tissues were
examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and
western blot (WB). One animal was euthanized 15 months post-inoculation (MPI)
due to an injury. At that time, examination of obex and lymphoid tissues by IHC
was positive, but WB of obex and colliculus were negative. Remaining deer
developed clinical signs of wasting and mental depression and were necropsied
from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and
WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal
and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work
demonstrates for the first time that white-tailed deer are susceptible to sheep
scrapie by potential natural routes of inoculation. In-depth analysis of tissues
will be done to determine similarities between scrapie in deer after
intracranial and oral/intranasal inoculation and chronic wasting disease
resulting from similar routes of inoculation.
see full text ;
Envt.06:
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Aru Balachandran,2
Jürgen Richt,3 Vincent Beringue,4 Juan-Maria Torres,5 Paul Brown,1 Bob Hills6
and Jean-Philippe Deslys1
1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Canadian Food
Inspection Agency; Ottawa, ON Canada; 3Kansas State University; Manhattan, KS
USA; 4INRA; Jouy-en-Josas, France; 5INIA; Madrid, Spain; 6Health Canada; Ottawa,
ON Canada
†Presenting author; Email: emmanuel.comoy@cea.fr
The constant increase of chronic wasting disease (CWD) incidence in North
America raises a question about their zoonotic potential. A recent publication
showed their transmissibility to new-world monkeys, but no transmission to
old-world monkeys, which are phylogenetically closer to humans, has so far been
reported. Moreover, several studies have failed to transmit CWD to transgenic
mice overexpressing human PrP. Bovine spongiform encephalopathy (BSE) is the
only animal prion disease for which a zoonotic potential has been proven. We
described the transmission of the atypical BSE-L strain of BSE to cynomolgus
monkeys, suggesting a weak cattle-to-primate species barrier. We observed the
same phenomenon with a cattleadapted strain of TME (Transmissible Mink
Encephalopathy). Since cattle experimentally exposed to CWD strains have also
developed spongiform encephalopathies, we inoculated brain tissue from
CWD-infected cattle to three cynomolgus macaques as well as to transgenic mice
overexpressing bovine or human PrP. Since CWD prion strains are highly
lymphotropic, suggesting an adaptation of these agents after peripheral
exposure, a parallel set of four monkeys was inoculated with CWD-infected cervid
brains using the oral route. Nearly four years post-exposure, monkeys exposed to
CWD-related prion strains remain asymptomatic. In contrast, bovinized and
humanized transgenic mice showed signs of infection, suggesting that CWD-related
prion strains may be capable of crossing the cattle-to-primate species barrier.
Comparisons with transmission results and incubation periods obtained after
exposure to other cattle prion strains (c-BSE, BSE-L, BSE-H and cattle-adapted
TME) will also be presented, in order to evaluate the respective risks of each
strain.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2
Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch
Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and
Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany
†Presenting author; Email: dausm@rki.de
Chronic wasting disease (CWD) is a contagious, rapidly spreading
transmissible spongiform encephalopathy (TSE) occurring in cervids in North
America. Despite efficient horizontal transmission of CWD among cervids natural
transmission of the disease to other species has not yet been observed. Here, we
report a direct biochemical demonstration of pathological prion protein PrPTSE
and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected
cervids. The presence of PrPTSE was detected by Western- and postfixed frozen
tissue blotting, while the seeding activity of PrPTSE was revealed by protein
misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal
muscles of CWD-infected WTD was estimated to be approximately 2000- to
10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE
was located in muscle- associated nerve fascicles but not, in detectable
amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal
muscle from CWD-infected cervids suggests prevention of such tissue in the human
diet as a precautionary measure for food safety, pending on further
clarification of whether CWD may be transmissible to humans.
Sunday, January 22, 2012
Chronic Wasting Disease CWD cervids interspecies transmission
Friday, August 24, 2012
Diagnostic accuracy of rectal mucosa biopsy testing for chronic wasting
disease within white-tailed deer (Odocoileus virginianus) herds in North America
Saturday, September 01, 2012
Resistance of Soil-Bound Prions to Rumen Digestion
Monday, September 17, 2012
Rapid Transepithelial Transport of Prions Following Inhalation
Thursday, September 27, 2012
Genetic Depletion of Complement Receptors CD21/35 Prevents Terminal Prion
Disease in a Mouse Model of Chronic Wasting Disease
CDC
October 2012
Synopsis Occurrence, Transmission, and Zoonotic Potential of Chronic
Wasting Disease
Controlling the spread of CWD, especially by human action, is a more
attainable goal than eradication. Human movement of cervids has likely led to
spread of CWD in facilities for captive animals, which has most likely
contributed to establishment of new disease foci in free-ranging populations
(Figure 1, panel A). Thus, restrictions on human movement of cervids from
disease-endemic areas or herds continue to be warranted. Anthropogenic factors
that increase cervid congregation such as baiting and feeding should also be
restricted to reduce CWD transmission. Appropriate disposal of carcasses of
animals with suspected CWD is necessary to limit environmental contamination
(20), and attractive onsite disposal options such as composting and burial
require further investigation to determine contamination risks. The best options
for lowering the risk for recurrence in facilities for captive animals with
outbreaks are complete depopulation, stringent exclusion of free-ranging
cervids, and disinfection of all exposed surfaces. However, even the most
extensive decontamination measures may not be sufficient to eliminate the risk
for disease recurrence (20; S.E. Saunders et al. unpub. data)
UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET
AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF
THE STUDIES ON CWD TRANSMISSION TO CATTLE ;
CWD to cattle figures CORRECTION
Greetings,
I believe the statement and quote below is incorrect ;
"CWD has been transmitted to cattle after intracerebral inoculation,
although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This
finding raised concerns that CWD prions might be transmitted to cattle grazing
in contaminated pastures."
Please see ;
Within 26 months post inoculation, 12 inoculated animals had lost weight,
revealed abnormal clinical signs, and were euthanatized. Laboratory tests
revealed the presence of a unique pattern of the disease agent in tissues of
these animals. These findings demonstrate that when CWD is directly inoculated
into the brain of cattle, 86% of inoculated cattle develop clinical signs of the
disease.
" although the infection rate was low (4 of 13 animals [Hamir et al.
2001]). "
shouldn't this be corrected, 86% is NOT a low rate. ...
kindest regards,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Thank you!
Thanks so much for your updates/comments. We intend to publish as rapidly
as possible all updates/comments that contribute substantially to the topic
under discussion.
re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author
Affiliations
1Institute for Neurodegenerative Diseases, University of California, San
Francisco, San Francisco, California 94143 2Department of Neurology, University
of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu
Mule deer, white-tailed deer, and elk have been reported to develop CWD. As
the only prion disease identified in free-ranging animals, CWD appears to be far
more communicable than other forms of prion disease. CWD was first described in
1967 and was reported to be a spongiform encephalopathy in 1978 on the basis of
histopathology of the brain. Originally detected in the American West, CWD has
spread across much of North America and has been reported also in South Korea.
In captive populations, up to 90% of mule deer have been reported to be positive
for prions (Williams and Young 1980). The incidence of CWD in cervids living in
the wild has been estimated to be as high as 15% (Miller et al. 2000). The
development of transgenic (Tg) mice expressing cervid PrP, and thus susceptible
to CWD, has enhanced detection of CWD and the estimation of prion titers
(Browning et al. 2004; Tamgüney et al. 2006). Shedding of prions in the feces,
even in presymptomatic deer, has been identified as a likely source of infection
for these grazing animals (Williams and Miller 2002; Tamgüney et al. 2009b). CWD
has been transmitted to cattle after intracerebral inoculation, although the
infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding
raised concerns that CWD prions might be transmitted to cattle grazing in
contaminated pastures.
snip...
----- Original Message -----
From: David Colby To: flounder9@verizon.net
Cc: stanley@XXXXXXXX
Sent: Tuesday, March 01, 2011 8:25 AM
Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 +
Author Affiliations
Dear Terry Singeltary,
Thank you for your correspondence regarding the review article Stanley
Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner
asked that I reply to your message due to his busy schedule. We agree that the
transmission of CWD prions to beef livestock would be a troubling development
and assessing that risk is important. In our article, we cite a peer-reviewed
publication reporting confirmed cases of laboratory transmission based on
stringent criteria. The less stringent criteria for transmission described in
the abstract you refer to lead to the discrepancy between your numbers and ours
and thus the interpretation of the transmission rate. We stand by our assessment
of the literature--namely that the transmission rate of CWD to bovines appears
relatively low, but we recognize that even a low transmission rate could have
important implications for public health and we thank you for bringing attention
to this matter. Warm Regards, David Colby -- David Colby, PhDAssistant Professor
Department of Chemical Engineering University of Delaware
===========END...TSS==============
SNIP...SEE FULL TEXT ;
UPDATED DATA ON 2ND CWD STRAIN Wednesday, September 08, 2010 CWD PRION
CONGRESS SEPTEMBER 8-11 2010
Sunday, August 19, 2012
Susceptibility of cattle to the agent of chronic wasting disease from elk
after intracranial inoculation 2012
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Unit
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
Thursday, May 31, 2012
CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission,
Scrapie, cats, species barrier, burial, and more
PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER
AND ELK ;
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease
Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages
858-863, June 2011.
NOR IS THE FDA recalling this CWD positive elk meat for the well being of
the dead elk ;
Wednesday, March 18, 2009
Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat
derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS
AND FIELD CORRECTIONS: FOODS CLASS II
now, let’s see what the authors said about this casual link, personal
communications years ago. see where it is stated NO STRONG evidence. so, does
this mean there IS casual evidence ????
“Our conclusion stating that we found no strong evidence of CWD
transmission to humans”
From: TSS (216-119-163-189.ipset45.wt.net)
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To:
Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam,
In the Archives of Neurology you quoted (the abstract of which was attached
to your email), we did not say CWD in humans will present like variant CJD.
That assumption would be wrong. I encourage you to read the whole article
and call me if you have questions or need more clarification (phone:
404-639-3091). Also, we do not claim that "no-one has ever been infected with
prion disease from eating venison." Our conclusion stating that we found no
strong evidence of CWD transmission to humans in the article you quoted or in
any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message-----
From:
Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease
2008 1: Vet Res. 2008 Apr 3;39(4):41
A prion disease of cervids: Chronic wasting disease
Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported
to the Surveillance Center***,
snip...
full text ;
CWD ongoing experiment on humans, long term $$$
Monday, November 14, 2011
WYOMING Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011
Wednesday, November 16, 2011
Wisconsin Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011
Sunday, November 13, 2011
COLORADO CWD CJD TSE PRION REPORTING 2011
Thursday, March 29, 2012
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH
CODE
Wednesday, February 16, 2011
IN CONFIDENCE SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
reference...
RB3.20
TRANSMISSION TO CHIMPANZEES
1. Kuru and CJD have been successfully transmitted to chimpanzees but
scrapie and TME have not.
2. We cannot say that scrapie will not transmit to chimpanzees. There are
several scrapie strains and I am not aware that all have been tried (that would
have to be from mouse passaged material). Nor has a wide enough range of field
isolates subsequently strain typed in mice been inoculated by the appropriate
routes (i/c, ilp and i/v) :
3. I believe the proposed experiment to determine transmissibility, if
conducted, would only show the susceptibility or resistance of the chimpanzee to
infection/disease by the routes used and the result could not be interpreted for
the predictability of the susceptibility for man. Proposals for prolonged oral
exposure of chimpanzees to milk from cattle were suggested a long while ago and
rejected.
4. In view of Dr Gibbs' probable use of chimpazees Mr Wells' comments
(enclosed) are pertinent. I have yet to receive a direct communication from Dr
Schellekers but before any collaboration or provision of material we should
identify the Gibbs' proposals and objectives.
5. A positive result from a chimpanzee challenged severely would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
6. A negative result would take a lifetime to determine but that would be a
shorter period than might be available for human exposure and it would still not
answer the question regarding mans' susceptibility. In the meantime no doubt the
negativity would be used defensively. It would however be counterproductive if
the experiment finally became positive. We may learn more about public reactions
following next Monday' s meeting.
R. Bradley
23 September 1990
CVO (+Mr Wells' comments)
Dr T W A Little
Dr B J Shreeve
90/9.23/1.1.
see full text ;
Thursday, March 29, 2012
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH
CODE
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...
EFSA Journal 2011 The European Response to BSE: A Success Story
This is an interesting editorial about the Mad Cow Disease debacle, and
it's ramifications that will continue to play out for decades to come ;
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 ;
2011 Monday, September 26, 2011
L-BSE BASE prion and atypical sporadic CJD
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE
RISE IN NORTH AMERICA
Wednesday, August 01, 2012
Behavioural and Psychiatric Features of the Human Prion Diseases:
Experience in 368 Prospectively Studied Patients
Monday, August 06, 2012
Atypical neuropathological sCJD-MM phenotype with abundant white matter
Kuru-type plaques sparing the cerebellar cortex
Tuesday, June 26, 2012
Creutzfeldt Jakob Disease Human TSE report update North America, Canada,
Mexico, and USDA PRION UNIT as of May 18, 2012
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the
rise in Canada and the USA
Friday, August 24, 2012
Iatrogenic prion diseases in humans: an update
Monday, July 23, 2012
The National Prion Disease Pathology Surveillance Center July 2012
2011 Monday, September 26, 2011
L-BSE BASE prion and atypical sporadic CJD
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE
RISE IN NORTH AMERICA
Wednesday, August 01, 2012
Behavioural and Psychiatric Features of the Human Prion Diseases:
Experience in 368 Prospectively Studied Patients
Monday, August 06, 2012
Atypical neuropathological sCJD-MM phenotype with abundant white matter
Kuru-type plaques sparing the cerebellar cortex
Tuesday, June 26, 2012
Creutzfeldt Jakob Disease Human TSE report update North America, Canada,
Mexico, and USDA PRION UNIT as of May 18, 2012
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the
rise in Canada and the USA
Friday, August 24, 2012
Iatrogenic prion diseases in humans: an update
Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health
Crisis
full text with source references ;
re-Human Prion Diseases in the United States Posted by flounder on 01 Jan
2010 at 18:11 GMT I kindly disagree with your synopsis for the following reasons
;
Tuesday, November 08, 2011
Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob
Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011
Original Paper
Conclusions:These findings raise doubt about the possibility of a reliable
CJD surveillance only based on mortality data.
Views & Reviews
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in
the United States
Ermias D. Belay, MD, Ryan A. Maddox, MPH, Pierluigi Gambetti, MD and
Lawrence B. Schonberger, MD
+ Author Affiliations
From the Division of Viral and Rickettsial Diseases (Drs. Belay and
Schonberger and R.A. Maddox), National Center for Infectious Diseases, Centers
for Disease Control and Prevention, Atlanta, GA; and National Prion Disease
Pathology Surveillance Center (Dr. Gambetti), Division of Neuropathology,
Institute of Pathology, Case Western Reserve University, Cleveland, OH.
Address correspondence and reprint requests to Dr. Ermias D. Belay, 1600
Clifton Road, Mailstop A-39, Atlanta, GA 30333.
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment
on the CDC's attempts to monitor the occurrence of emerging forms of CJD.
Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al.
JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL
TEXT
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as
well
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North
America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember,
the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been
documented in North America, along with the typical scrapie's, and atypical
Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these
TSE in different species have been rendered and fed to food producing animals
for humans and animals in North America (TSE in cats and dogs ?), and that the
trading of these TSEs via animals and products via the USA and Canada has been
immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances
and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD
only theory in 2009. With all the science to date refuting it, to continue to
validate this old myth, will only spread this TSE agent through a multitude of
potential routes and sources i.e. consumption, medical i.e., surgical, blood,
dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and
the urgent need to make all human TSE in the USA a reportable disease, in every
state, of every age group, and to make this mandatory immediately without
further delay. The ramifications of not doing so will only allow this agent to
spread further in the medical, dental, surgical arena's. Restricting the
reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO
age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge,
Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al
and many more, that the world of TSE Transmissible Spongiform Encephalopathy is
far from an exact science, but there is enough proven science to date that this
myth should be put to rest once and for all, and that we move forward with a new
classification for human and animal TSE that would properly identify the
infected species, the source species, and then the route.
re-Human Prion Diseases in the United States Posted by flounder on 01 Jan
2010 at 18:11 GMT I kindly disagree with your synopsis for the following reasons
;
Wednesday, May 16, 2012
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Proposal ID: 29403
Monday, August 20, 2012
CASE REPORTS CREUTZFELDT-JAKOB DISEASE: AN UNDER-RECOGNIZED CAUSE OF
DEMENTIA
Friday, October 05, 2012
Differential Diagnosis of Jakob-Creutzfeldt Disease
see the Duke, Pa, Yale, and Mexican study here, showing the misdiagnosis of
CJD TSE prion disease as Alzheimers ;
Monday, July 23, 2012
The National Prion Disease Pathology Surveillance Center July 2012
TSS
