Research Article
Distribution of Peripheral PrPSc in Sheep with Naturally Acquired Scrapie
María Carmen Garza, Marta Monzón, Belén Marín, Juan José Badiola, Eva
Monleón mail
Published: May 14, 2014 •DOI: 10.1371/journal.pone.0097768
Abstract
Accumulation of prion protein (PrPSc) in the central nervous system is the
hallmark of transmissible spongiform encephalopathies. However, in some of these
diseases such as scrapie or chronic wasting disease, the PrPSc can also
accumulate in other tissues, particularly in the lymphoreticular system. In
recent years, PrPSc in organs other than nervous and lymphoid have been
described, suggesting that distribution of this protein in affected individuals
may be much larger than previously thought. In the present study, 11
non-nervous/non-lymphoid organs from 16 naturally scrapie infected sheep in
advanced stages of the disease were examined for the presence of PrPSc. Fourteen
infected sheep were of the ARQ/ARQ PRNP genotype and 2 of the VRQ/VRQ, where the
letters A, R, Q, and V represent the codes for amino-acids alanine, arginine,
glutamine and valine, respectively. Adrenal gland, pancreas, heart, skin,
urinary bladder and mammary gland were positive for PrPSc by
immunohistochemistry and IDEXX HerdChek scrapie/BSE Antigen EIA Test in at least
one animal. Lung, liver, kidney and skeletal muscle exhibited PrPSc deposits by
immunohistochemistry only. To our knowledge, this is the first report regarding
the presence of PrPSc in the heart, pancreas and urinary bladder in naturally
acquired scrapie infections. In some other organs examined, in which PrPSc had
been previously detected, PrPSc immunolabeling was observed to be associated
with new structures within those organs. The results of the present study
illustrate a wide dissemination of PrPSc in both ARQ/ARQ and VRQ/VRQ infected
sheep, even when the involvement of the lymphoreticular system is scarce or
absent, thus highlighting the role of the peripheral nervous system in the
spread of PrPSc.
Citation: Garza MC, Monzón M, Marín B, Badiola JJ, Monleón E (2014)
Distribution of Peripheral PrPSc in Sheep with Naturally Acquired Scrapie. PLoS
ONE 9(5): e97768. doi:10.1371/journal.pone.0097768
Editor: Anthony E. Kincaid, Creighton University, United States of
America
Received: January 30, 2014; Accepted: April 22, 2014; Published: May 14,
2014
Copyright: © 2014 Garza et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Funding: This study was supported by the Gobierno de Aragón (grant
218-315/3) and FEDER (CONCOTSA EFA205/11). Dr. Garza was supported by a FPU
doctoral grant from the Spanish Ministry of Education (grant AP2007-03842). The
funders had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
snip...
Overall, the results from the present study showed large variation in
peripheral spread of PrPSc among sheep. Although all of the infected animals
included in the study presented a widespread PrPSc accumulation in the CNS, they
did not show a similar PrPSc dissemination through the PNS. The heterogeneous
distribution of PrPSc-containing nerve fibres within the peripheral organs in
conjunction with the small amounts observed could explain the variation between
animals. This variation has also been observed in the skeletal muscle [6],
kidney [7], liver [10] and skin [9] of sheep infected with scrapie. It should be
highlighted that only 2 pieces of tissue were collected from fairly big organs,
one for IHC and one for EIA test. Sampling multiple sites within organs and
using more sensitive techniques would most likely result in a higher number of
peripheral positive organs in each animal, but the study is not intended to be
representative in nature. In addition, the results from the IHC and IDEXX EIA
analyses showed a poor correlation between both techniques, with a higher number
of positive samples observed via IHC in comparison with the IDEXX EIA. This
IDEXX EIA is a commercial immunoassay for PrPSc detection in nervous or lymphoid
tissues. In the present study, all samples were analysed and interpreted
according to the manufacturer’s cut-off criterion. In some previous studies that
have used commercial ELISA tests for PrPSc detection in non-nervous or
non-lymphoid tissues, the cut-off value has been recalculated as a function of
the type of tissue analysed (as 3 standard deviations above the mean of the
negative controls [10], [41]). The cut off values determined in these cases were
lower than those set by the manufacturers (i.e., 0.059 for liver samples [10]).
Equally, we calculated the cut off for liver, pancreas and urinary bladder from
10 negative sheep (as 4 standard deviations above the mean) and obtained values
of 0.069, 0.040 and 0.063, respectively. If these cut off values were used, all
of the samples that were positive by IHC only, would be confirmed by IDEXX EIA;
however, we would also have 1 positive sample only by IDEXX EIA in the case of
liver tissue, 7 in the pancreas and 2 in the urinary bladder. Therefore,
although it is possible that by applying the manufacturer’s cut-off criterion we
would obtain a lower IDEXX EIA sensitivity, a more in-depth study is needed to
adapt the cut off value for each individual tissue.
Together with previous reports, the present study indicates that scrapie
infection may spread through the PNS to most, if not all, parts of the body. The
PrPSc presence in non-nervous organs does not appear to have any additional
pathological role but demonstrates that some of these organs are potentially
infectious (which has not been considered thus far [21]) and generates new
insights into horizontal transmission. In addition, our observations regarding
naturally acquired scrapie may provide indirect information about the spread of
the agent in related TSEs such as vCJD and CWD.
Supporting Information
snip...see full text ;
ONCE again, many many thanks to PLOS et al AND especially the authors,
scientist et al that participate in open access, thank you kindly for OPEN
ACCESS for dummies like me. ...tss
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep
and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were
exposed to the infectious agents only by their nonforced consumption of known
infectious tissues. The asymptomatic incubation period in the one monkey exposed
to the virus of kuru was 36 months; that in the two monkeys exposed to the virus
of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the
two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively.
Careful physical examination of the buccal cavities of all of the monkeys failed
to reveal signs or oral lesions. One additional monkey similarly exposed to kuru
has remained asymptomatic during the 39 months that it has been under
observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie
by natural feeding to squirrel monkeys that we have reported provides further
grounds for concern that scrapie-infected meat may occasionally give rise in
humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is
transmissible to man. This has followed reports that the disease has been
transmitted to primates. One particularly lurid speculation (Gajdusek 1977)
conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and
transmissible encephalopathy of mink are varieties of a single "virus". The U.S.
Department of Agriculture concluded that it could "no longer justify or permit
scrapie-blood line and scrapie-exposed sheep and goats to be processed for human
or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is
emphasised by the finding that some strains of scrapie produce lesions identical
to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be
transmissible to man raises two considerations. First, the safety of laboratory
personnel requires prompt attention. Second, action such as the "scorched meat"
policy of USDA makes the solution of the acrapie problem urgent if the sheep
industry is not to suffer grievously.
snip...
76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes
of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey
(Macaca fascicularis) with an incubation period of more than 5 yr from the time
of intracerebral inoculation of scrapie-infected mouse brain. The animal
developed a chronic central nervous system degeneration, with ataxia, tremor and
myoclonus with associated severe scrapie-like pathology of intensive astroglial
hypertrophy and proliferation, neuronal vacuolation and status spongiosus of
grey matter. The strain of scrapie virus used was the eighth passage in Swiss
mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral
passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton,
Berkshire).
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2
December 2010
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
Thursday, December 23, 2010
Molecular Typing of Protease-Resistant Prion Protein in Transmissible
Spongiform Encephalopathies of Small Ruminants, France, 2002-2009
Volume 17, Number 1 January 2011
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform
encephalopathy following passage in sheep
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
Thursday, March 29, 2012
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
Increased Atypical Scrapie Detections
Press reports indicate that increased surveillance is catching what
otherwise would have been unreported findings of atypical scrapie in sheep. In
2009, five new cases have been reported in Quebec, Ontario, Alberta, and
Saskatchewan. With the exception of Quebec, all cases have been diagnosed as
being the atypical form found in older animals. Canada encourages producers to
join its voluntary surveillance program in order to gain scrapie-free status.
The World Animal Health will not classify Canada as scrapie-free until no new
cases are reported for seven years. The Canadian Sheep Federation is calling on
the government to fund a wider surveillance program in order to establish the
level of prevalence prior to setting an eradication date. Besides long-term
testing, industry is calling for a compensation program for farmers who report
unusual deaths in their flocks.
Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine
(reticular) deposits, see also ; All of the Heidenhain variants were of the
methionine/ methionine type 1 molecular subtype.
Tuesday, July 29, 2008
Heidenhain Variant Creutzfeldt Jakob Disease Case Report
snip...
Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'
DIVISION OF NEUROPATHOLOGY
University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas
77555-0785
FAX COVER SHEET DATE: 4-23-98
TO: Mr. Terry Singeltary @ -------
FROM: Gerald Campbell FAX: (409) 772-5315 PHONE: (409) 772-2881 Number of
Pages (including cover sheet):
Message: *CONFIDENTIALITY NOTICE*
This document accompanying this transmission contains confidential
information belonging to the sender that is legally privileged. This information
is intended only for the use of the individual or entry names above. If you are
not the intended recipient, you are hereby notified that any disclosure, copying
distribution, or the taking of any action in reliances on the contents of this
telefaxed information is strictly prohibited. If you received this telefax in
error, please notify us by telephone immediately to arrange for return of the
original documents.
--------------------------
Patient Account: 90000014-518 Med. Rec. No.: (0160)118511Q Patient Name:
POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C Attending
Dr.: Date / Time Admitted : 12/14/97 1228 Copies to: UTMB University of Texas
Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683
Pathology Report FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858 Autopsy
NO.: AU-97-00435 AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown
Residence: Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of
Autopsy: 12/15/97 15:00 Pathologist/Resident: Pencil/Fernandez Service: Private
Restriction: Brain only FINAL AUTOPSY DIAGNOSIS I. Brain: Creutzfeldt-Jakob
disease, Heidenhain variant.
snip...see full text ;
P.5.21 Parallels between different forms of sheep scrapie and types of
Creutzfeldt-Jakob disease (CJD)
Wiebke M. Wemheuer1, Sylvie L. Benestad2, Arne Wrede1, Wilhelm E.
Wemheuer3, Tatjana Pfander1, Bjørn Bratberg2, Bertram Brenig3,Walter J.
Schulz-Schaeffer1 1University Medical Center Goettingen, Germany; 2Institute of
Veterinary Medicine Oslo, Norway; 3Institute of Veterinary Medicine Goettingen,
Germany
Background: Scrapie in sheep and goats is often regarded as the archetype
of prion diseases. In 1998, a new form of scrapie - atypical/Nor98 scrapie - was
described that differed from classical scrapie in terms of epidemiology, Western
blot profile, the distribution of pathological prion protein (PrPSc) in the body
and its stability against proteinase K. In a similar way, distinct disease types
exist in sporadic Creutzfeldt-Jakob disease (CJD). They differ with regard to
their clinical outcome, Western blot profile and PrPSc deposition pattern in the
central nervous system (CNS). Objectives: The comparison of PrPSc deposits in
sheep scrapie and human sporadic CJD.
Methods: Tissues of the CNS of sheep with classical scrapie, sheep with
atypical/Nor98 scrapie and 20 patients with sporadic CJD were examined using the
sensitive Paraffin Embedded Tissue (PET) blot method. The results were compared
with those obtained by immunohistochemistry. With the objective of gaining
information on the protein conformation, the PrPSc of classical and
atypical/Nor98 sheep scrapie and sporadic CJD was tested for its stability
against denaturation with guanidine hydrochloride (GdnHCl) using a Membrane
Adsorption Assay.
Results: The PrPSc of atypical/Nor98 scrapie cases and of CJD prion type 1
patients exhibits a mainly reticular/synaptic deposition pattern in the brain
and is relatively sensitive to denaturation with GdnHCl. In contrast classical
scrapie cases and CJD prion type 2 patients have a more complex PrPSc deposition
pattern in common that consists of larger PrPSc aggregates and the PrPSc itself
is comparatively stable against denaturation.
Discussion: The similarity between CJD types and scrapie types indicates
that at least two comparable forms of the misfolded prion protein exist beyond
species barriers and can elicit prion diseases. It seems therefore reasonable to
classify classical and atypical/Nor98 scrapie - in analogy to the existing CJD
types - as different scrapie types.
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01
Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine
issue 2284. Subscribe and get 4 free issues. FOUR years ago, Terry Singeltary
watched his mother die horribly from a degenerative brain disease. Doctors told
him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit
her violent symptoms, and he demanded an autopsy. It showed she had died of
sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by
chance into a killer. But Singeltary thinks otherwise. He is one of a number of
campaigners who say that some sCJD, like the variant CJD related to BSE, is
caused by eating meat from infected animals. Their suspicions have focused on
sheep carrying scrapie, a BSE-like disease that is widespread in flocks across
Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no
evidence that it poses a risk to human health. But if the French finding means
that scrapie can cause sCJD in people, countries around the world may have
overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They
injected the brains of macaque monkeys with brain from BSE cattle, and from
French and British vCJD patients. The brain damage and clinical symptoms in the
monkeys were the same for all three. Mice injected with the original sets of
brain tissue or with infected monkey brain also developed the same
symptoms.
As a control experiment, the team also injected mice with brain tissue from
people and animals with other prion diseases: a French case of sCJD; a French
patient who caught sCJD from human-derived growth hormone; sheep with a French
strain of scrapie; and mice carrying a prion derived from an American scrapie
strain. As expected, they all affected the brain in a different way from BSE and
vCJD. But while the American strain of scrapie caused different damage from
sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been
epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute
for Animal Health in Edinburgh, who was a member of the same team as Deslys.
"You see about the same incidence of the disease everywhere, whether or not
there are many sheep, and in countries such as New Zealand with no scrapie." In
the only previous comparisons of sCJD and scrapie in mice, Bruce found they were
dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would
not necessarily see a relationship between the two with epidemiology if only
some strains affect only some people," says Deslys. Bruce is cautious about the
mouse results, but agrees they require further investigation. Other trials of
scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion
protein, and each type of protein can fold up two different ways. Kretschmar has
found that these six combinations correspond to six clinical types of sCJD: each
type of normal prion produces a particular pathology when it spontaneously
deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing
prion, the relationship between pathology and prion type should be different, as
it is in vCJD. "If we look at brain samples from sporadic CJD cases and find
some that do not fit the pattern," says Kretschmar, "that could mean they were
caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence
elsewhere. Singeltary and other US activists think that some of these people
died after eating contaminated meat or "nutritional" pills containing dried
animal brain. Governments will have a hard time facing activists like Singeltary
if it turns out that some sCJD isn't as spontaneous as doctors have
insisted.
Deslys's work on macaques also provides further proof that the human
disease vCJD is caused by BSE. And the experiments showed that vCJD is much more
virulent to primates than BSE, even when injected into the bloodstream rather
than the brain. This, says Deslys, means that there is an even bigger risk than
we thought that vCJD can be passed from one patient to another through
contaminated blood transfusions and surgical instruments.
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
Thursday, December 20, 2012
OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED, WISHES TO
CONTINUE SPREADING IT AROUND THE GLOBE
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH
CODE, DOES NOT SURPRISE ME $
Wednesday, December 4, 2013
Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine
Products; Final Rule Federal Register / Vol. 78 , No. 233 / Wednesday, December
4, 2013 TO ALL IMPORTING COUNTRIES THAT IMPORTS FROM THE USA, BE WARNED, NEW MAD
COW BSE REGULATIONS USDA, AND OIE, not worth the paper the regulations were
wrote on, kind of like the mad cow feed ban of August 1997, nothing but ink on
paper $$$
full text ;
AND ATYPICAL NOR-98 SCRAPIE IS EVEN MORE OF A CONCERN FOR TRANSMISSION TO
HUMANS, AND THE ATYPICAL NOR-98 HAS SPREAD FROM COAST TO COAST HERE IN THE USA ;
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
AND WHAT HAVE THE PRION GODS SAID OF THE ATYPICAL NOR-98, AND IT'S
POTENTIAL FOR TRANSMISSION TO HUMANS ;
A newly identified type of scrapie agent can naturally infect sheep with
resistant PrP genotypes
Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne
Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?,
Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author
Affiliations
*Virologie Immunologie Moléculaires and ?Génétique Biochimique et
Cytogénétique, Institut National de la Recherche Agronomique, 78350
Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la
Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte
Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire
des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon,
France; **Pathologie Infectieuse et Immunologie, Institut National de la
Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology,
National Veterinary Institute, 0033 Oslo, Norway
***Edited by Stanley B. Prusiner, University of California, San Francisco,
CA (received for review March 21, 2005)
Abstract Scrapie in small ruminants belongs to transmissible spongiform
encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative
disorders that affect humans and animals and can transmit within and between
species by ingestion or inoculation. Conversion of the host-encoded prion
protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP
(PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified
surveillance of scrapie in the European Union, together with the improvement of
PrPSc detection techniques, has led to the discovery of a growing number of
so-called atypical scrapie cases. These include clinical Nor98 cases first
identified in Norwegian sheep on the basis of unusual pathological and PrPSc
molecular features and "cases" that produced discordant responses in the rapid
tests currently applied to the large-scale random screening of slaughtered or
fallen animals. Worryingly, a substantial proportion of such cases involved
sheep with PrP genotypes known until now to confer natural resistance to
conventional scrapie. Here we report that both Nor98 and discordant cases,
including three sheep homozygous for the resistant PrPARR allele (A136R154R171),
efficiently transmitted the disease to transgenic mice expressing ovine PrP, and
that they shared unique biological and biochemical features upon propagation in
mice.
*** These observations support the view that a truly infectious TSE agent,
unrecognized until recently, infects sheep and goat flocks and may have
important implications in terms of scrapie control and public health.
OR
***The pathology features of Nor98 in the cerebellum of the affected sheep
showed similarities with those of sporadic Creutzfeldt-Jakob disease in
humans.
OR
*** Intriguingly, these conclusions suggest that some pathological features
of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion
poker goes up again $
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until
now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in
BvI109.
The discovery of previously unrecognized prion diseases in both humans and
animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion
diseases might be wider than expected and raises crucial questions about the
epidemiology and strain properties of these new forms. We are investigating this
latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
IN A NUT SHELL ;
(Adopted by the International Committee of the OIE on 23 May 2006) 11.
Information published by the OIE is derived from appropriate declarations made
by the official Veterinary Services of Member Countries. The OIE is not
responsible for inaccurate publication of country disease status based on
inaccurate information or changes in epidemiological status or other significant
events that were not promptly reported to the Central Bureau,
Thursday, May 30, 2013
World Organization for Animal Health (OIE) has upgraded the United States'
risk classification for mad cow disease to "negligible" from "controlled", and
risk further exposing the globe to the TSE prion mad cow type disease U.S. gets
top mad-cow rating from international group and risk further exposing the globe
to the TSE prion mad cow type disease
Saturday, April 19, 2014
Exploring the zoonotic potential of animal prion diseases: In vivo and in
vitro approaches
*** These results would seem to suggest that CWD does indeed have zoonotic
potential, at least as judged by the compatibility of CWD prions and their human
PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests
that if zoonotic CWD occurred, it would most likely effect those of the PRNP
codon 129-MM genotype and that the PrPres type would be similar to that found in
the most common subtype of sCJD (MM1).
*** also see ;
REPORT OF THE MEETING OF THE OIE TERRESTRIAL ANIMAL HEALTH STANDARDS
COMMISSION Paris, 19–28 February 2013
In response to a Member Country’s detailed justification for listing of
chronic wasting disease of cervids (CWD) against the criteria of Article 1.2.2.,
the Code Commission recommended this disease be reconsidered for listing.
REPORT OF THE MEETING OF THE OIE TERRESTRIAL ANIMAL HEALTH STANDARDS
COMMISSION Paris, 17–26 September 2013
Item 5 Criteria for listing diseases (Chapter 1.2.)
Comments were received from Australia, EU, Japan, New Zealand, Switzerland,
Thailand and AU-IBAR The Code Commission noted a Member Country’s comment
suggesting that greater clarity was needed for the term ‘significant morbidity
and mortality’. As noted in the February 2013 report, the Code Commission
considered that the structured process of listing diseases, first by an expert
group whose conclusions are documented and circulated for Member Countries’
review and comment, then consideration by the World Assembly of Delegates before
final adoption, is sufficiently rigorous and transparent.
link updated ;
Monday, May 05, 2014
*** Member Country details for listing OIE CWD 2013 against the criteria of
Article 1.2.2., the Code Commission recommends consideration for listing
Wednesday, February 26, 2014
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION 2004 THROUGHT PRION 2013
CONFERENCE ABSTRACT BOOKS
Friday, April 25, 2014
Accuracy of administrative diagnostic data for pathologically confirmed
cases of Creutzfeldt-Jakob disease
Article in Press
WHAT about the sporadic CJD TSE proteins ?
WE now know that some cases of sporadic CJD are linked to atypical BSE and
atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all
it’s sub-types $$$
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada
seeing an extreme increase of 48% between 2008 and 2010 ***
Sunday, October 13, 2013
*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012
Sunday, March 09, 2014
A Creutzfeldt-Jakob Disease (CJD) Lookback Study: Assessing the Risk of
Blood Borne Transmission of Classic Forms of Creutzfeldt-Jakob Disease
FDA TSEAC CIRCUS AND TRAVELING ROAD SHOW FOR THE TSE PRION DISEASES
Sunday, April 06, 2014
SPORADIC CJD and the potential for zoonotic transmission there from, either
directly or indirectly via friendly fire iatrogenic mode, evidence to date
***Singeltary reply to Plos ;
Molecular, Biochemical and Genetic Characteristics of BSE in Canada
Singeltary reply ;
***Singeltary submission to PLOS ;
No competing interests declared.
see full text ;
Re: vCJD in the USA * BSE in U.S. 15 November 1999 Terry S Singeltary, NA
CWD is just a small piece of a very big puzzle. I have seen while deer
hunting, deer, squirrels and birds, eating from cattle feed troughs where they
feed cattle, the high protein cattle by products, at least up until Aug. 4,
1997. So why would it be so hard to believe that this is how they might become
infected with a TSE. Or, even by potentially infected land. It's been well
documented that it could be possible, from scrapie.
It was proven in Oprah Winfrey's trial, that Cactus Cattle feeders, sent
neurologically ill cattle, some with encephalopathy stamped on the dead slips,
were picked up and sent to the renders, along with sheep carcasses.
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as
well...
2 January 2000 Terry S Singeltary
The exact same recipe for B.S.E. existed in the U.S. for years and years.
In reading over the Qualitative Analysis of BSE Risk Factors-1, this is a 25
page report by the USDA:APHIS:VS. It could have been done in one page. The first
page, fourth paragraph says it all;
"Similarities exist in the two countries usage of continuous rendering
technology and the lack of usage of solvents, however, large differences still
remain with other risk factors which greatly reduce the potential risk at the
national level."
Then, the next 24 pages tries to down-play the high risks of B.S.E. in the
U.S., with nothing more than the cattle to sheep ratio count, and the
geographical locations of herds and flocks. That's all the evidence they can
come up with, in the next 24 pages.
Something else I find odd, page 16;
"In the United Kingdom there is much concern for a specific continuous
rendering technology which uses lower temperatures and accounts for 25 percent
of total output. This technology was _originally_ designed and imported from the
United States. However, the specific application in the production process is
_believed_ to be different in the two countries."
A few more factors to consider, page 15;
"Figure 26 compares animal protein production for the two countries. The
calculations are based on slaughter numbers, fallen stock estimates, and product
yield coefficients. This approach is used due to variation of up to 80 percent
from different reported sources. At 3.6 million tons, the United States produces
8 times more animal rendered product than the United Kingdom."
"The risk of introducing the BSE agent through sheep meat and bone meal is
more acute in both relative and absolute terms in the United Kingdom (Figures 27
and 28). Note that sheep meat and bone meal accounts for 14 percent, or 61
thousand tons, in the United Kingdom versus 0.6 percent or 22 thousand tons in
the United States. For sheep greater than 1 year, this is less than one-tenth of
one percent of the United States supply."
"The potential risk of amplification of the BSE agent through cattle meat
and bone meal is much greater in the United States where it accounts for 59
percent of total product or almost 5 times more than the total amount of
rendered product in the United Kingdom."
Considering, it would only take _one_ scrapie infected sheep to contaminate
the feed. Considering Scrapie has run rampant in the U.S. for years, as of Aug.
1999, 950 scrapie infected flocks. Also, Considering only one quarter spoonful
of scrapie infected material is lethal to a cow. Considering all this, the sheep
to cow ration is meaningless. As I said, it's 24 pages of B.S.e.
To be continued...
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA
Competing interests: None declared
Letters
JAMA. 2001;285(6):733-734. doi: 10.1001/jama.285.6.733
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr Bacliff, Tex
Since this article does not have an abstract, we have provided the first
150 words of the full text.
KEYWORDS: creutzfeldt-jakob disease, diagnosis. 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.
References 1. Gibbons RV, Holman RC, Belay ED, Schonberger LB.
Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA.
2000;284:2322-2323.
Published March 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease
in the United States
Terry S. Singeltary, retired (medically)
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?
Published March 26, 2003
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.
The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003
doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Original
Xavier Bosch
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is
one of a number of people who have remained largely unsatisfied after being told
that a close relative died from a rapidly progressive dementia compatible with
spontaneous Creutzfeldt—Jakob ...
SEE FULL TEXT ;
-------- Original Message --------
Subject: Tracking spongiform encephalopathies in North America LANCET
INFECTIOUS DISEASE Volume 3, Number 8 01 August 2003
Date: Tue, 29 Jul 2003 17:35:30 –0500
From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
Volume 3, Number 8 01 August 2003
Previous
Next
Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem.
49-year-old Singeltary is one of a number of people who have remained
largely unsatisfied after being told that a close relative died from a rapidly
progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease
(CJD). So he decided to gather hundreds of documents on transmissible spongiform
encephalopathies (TSE) and realised that if Britons could get variant CJD from
bovine spongiform encephalopathy (BSE), Americans might get a similar disorder
from chronic wasting disease (CWD)the relative of mad cow disease seen among
deer and elk in the USA. Although his feverish search did not lead him to the
smoking gun linking CWD to a similar disease in North American people, it did
uncover a largely disappointing situation.
Singeltary was greatly demoralised at the few attempts to monitor the
occurrence of CJD and CWD in the USA. Only a few states have made CJD
reportable. Human and animal TSEs should be reportable nationwide and
internationally, he complained in a letter to the Journal of the American
Medical Association (JAMA 2003; 285: 733). I hope that the CDC does not continue
to expect us to still believe that the 85% plus of all CJD cases which are
sporadic are all spontaneous, without route or source.
Until recently, CWD was thought to be confined to the wild in a small
region in Colorado. But since early 2002, it has been reported in other areas,
including Wisconsin, South Dakota, and the Canadian province of Saskatchewan.
Indeed, the occurrence of CWD in states that were not endemic previously
increased concern about a widespread outbreak and possible transmission to
people and cattle.
To date, experimental studies have proven that the CWD agent can be
transmitted to cattle by intracerebral inoculation and that it can cross the
mucous membranes of the digestive tract to initiate infection in lymphoid tissue
before invasion of the central nervous system. Yet the plausibility of CWD
spreading to people has remained elusive.
Part of the problem seems to stem from the US surveillance system. CJD is
only reported in those areas known to be endemic foci of CWD. Moreover, US
authorities have been criticised for not having performed enough prionic tests
in farm deer and elk.
Although in November last year the US Food and Drug Administration issued a
directive to state public-health and agriculture officials prohibiting material
from CWD-positive animals from being used as an ingredient in feed for any
animal species, epidemiological control and research in the USA has been quite
different from the situation in the UK and Europe regarding BSE.
Getting data on TSEs in the USA from the government is like pulling teeth,
Singeltary argues. You get it when they want you to have it, and only what they
want you to have.
Norman Foster, director of the Cognitive Disorders Clinic at the University
of Michigan (Ann Arbor, MI, USA), says that current surveillance of prion
disease in people in the USA is inadequate to detect whether CWD is occurring in
human beings; adding that, the cases that we know about are reassuring, because
they do not suggest the appearance of a new variant of CJD in the USA or
atypical features in patients that might be exposed to CWD. However, until we
establish a system that identifies and analyses a high proportion of suspected
prion disease cases we will not know for sure. The USA should develop a system
modelled on that established in the UK, he points out.
Ali Samii, a neurologist at Seattle VA Medical Center who recently reported
the cases of three hunterstwo of whom were friendswho died from pathologically
confirmed CJD, says that at present there are insufficient data to claim
transmission of CWD into humans; adding that [only] by asking [the questions of
venison consumption and deer/elk hunting] in every case can we collect suspect
cases and look into the plausibility of transmission further. Samii argues that
by making both doctors and hunters more aware of the possibility of prions
spreading through eating venison, doctors treating hunters with dementia can
consider a possible prion disease, and doctors treating CJD patients will know
to ask whether they ate venison.
CDC spokesman Ermias Belay says that the CDC will not be investigating the
[Samii] cases because there is no evidence that the men ate CWD-infected meat.
He notes that although the likelihood of CWD jumping the species barrier to
infect humans cannot be ruled out 100% and that [we] cannot be 100% sure that
CWD does not exist in humans& the data seeking evidence of CWD transmission
to humans have been very limited.
Owens, Julie
From: Terry S. Singeltary Sr. [flounder9@verizon.net]
Sent: Monday, July 24, 2006 1:09 PM
To: FSIS RegulationsComments
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine
Spongiform Encephalopathy (BSE) Page 1 of 98
FSIS, USDA, REPLY TO SINGELTARY
Sunday, December 15, 2013
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE
Saturday, December 21, 2013
Complementary studies detecting classical bovine spongiform encephalopathy
infectivity in jejunum, ileum and ileocaecal junction in incubating cattle
Sunday, December 22, 2013
10 years after mad cow cover up started, and 16 years after Moms demise to
hvCJD, were still feeding cows to cows
layperson
mom dod 12/14/97 confirmed hvCJD...just made a promise to mom, never
forget, and never let them forget...tss
Terry S. Singeltary Sr.
Bacliff, Texas USA 77518
