>>>Recently transmission of prions from blood of patients with
sporadic CJD to humanized mice could be demonstrated.<<<
>>>Further-on, urine samples of a control population (normal and
neurological population) showed no signal in the study; *** however, in samples
from patients with sporadic CJD and vCJD, a signal was detected in both patient
populations.<<<
Meeting Report: 2015 PDA Virus & TSE Safety Forum
Hannelore Willkommena, Johannes Blümelb, Kurt Brorsonc,*, Dayue Chend, Qi
Chene, Albrecht Grönerf, Thomas R. Kreilg, Michel Ruffingh, Sol Ruizi, Dorothy
Scottj and Glenda Silvesterk + Author Affiliations
1. aRegulatory Affairs & Biological Safety Consulting, Erzhausen,
Germany 2. bPaul-Ehrlich Institut, Langen, Germany 3. cCDER/FDA, Silver Spring
MD, USA 4. dEli Lilly and Company, Indianapolis, IN, USA 5. eGenentech Inc.,
South San Francisco, CA, USA 6. fPathoGuard Consult, Seeheim-Jugenheim, Germany
7. gBaxalta, Vienna, Austria 8. hBoehringer Ingelheim Pharma GmbH&KG,
Bieberach an der Riss, Germany 9. iSpanish Medicines Agency (AEMPS), Madrid,
Spain 10. jCBER/FDA, Silver Spring MD, USA 11. kEuropean Medicines Agency,
London, UK ↵* Corresponding Author: Kurt Brorson, CDER/FDA, Silver Spring MD
20993, USA. E-mail: Kurt.Brorson@fda.hhs.gov
Abstract The report provides a summary of the presentations at the Virus
& TSE Safety Forum 2015 organized by the Parenteral Drug Association (PDA)
and held in Cascais, Portugal, from 9 to 11 June, 2015. As with previous
conferences of this series, the PDA Virus & TSE Safety Forum 2015 provided
an excellent forum for the exchange of information and opinions between the
industry, research organizations, and regulatory bodies. Regulatory updates on
virus and TSE safety aspects illustrating current topics of discussion at
regulatory agencies in Europe and the United States were provided; the
conference covered emerging viruses and new virus detection systems that may be
used for the investigation of human pathogenic viruses as well as the virus
safety of cell substrates and of raw material of ovine/caprine or human origin.
Progress of development and use of next-generation sequencing methods was shown
by several examples. Virus clearance data illustrating the effectiveness of
inactivation or removal methods were presented and data provided giving insight
into the mechanism of action of these technologies. In the transmissible
spongiform encephalopathy (TSE) part of the conference, the epidemiology of
variant Creutzfeldt-Jakob disease was reviewed and an overview about diagnostic
tests provided; current thinking about the spread and propagation of prions was
presented and the inactivation of prions by disinfection (equipment) and in
production of bovine-derived reagents (heparin) shown. The current report
provides an overview about the outcomes of the 2015 PDA Virus & TSE Safety
Forum, a unique event in this field.
Virus TSE Safety Biotechnology Plasma derivatives Regulatory affairs Virus
clearance
snip...
3. Tse Safety Forum
TSE Risk and Risks Mitigation
Existing and emerging TSEs still present potential concerns for safety of
biological products. This session provided an update on human and animal TSEs
including recent considerations of the FDA’s TSE Advisory Committee,
epidemiology of vCJD, blood testing, and recent findings related to pathogenesis
and dissemination of infectivity in the host. Safety measures to prevent TSE
contamination of products were presented—including TSE clearance studies for a
bovine- sourced product, and sanitisation of manufacturing equipment.
Luisa Gregori (Laboratory of Plasma Derivatives, US FDA-CBER) presented, on
behalf of Dorothy Scott, a summary of the TSE Advisory Committee meeting from 1
June 2015 re-considering the FDA’s geographically based donor deferral policy to
reduce the risk of transfusion-transmitted vCJD. The majority of the committee
agreed that current deferral policy should be changed, but the committee did not
agree with the FDA’s proposal to defer donors who traveled to the UK for at
least 3 cumulative months from 1980 through 1986 (unchanged from current policy)
and to defer donors who traveled to France and Ireland for cumulative 5 years
from 1980 through 2001. This change would relax the deferral for all other
European countries. Universal leukoreduction was recommended by the committee to
further mitigate the risk for transfusion-transmitted vCJD.
The second talk by L. Gregori was on heparin and the risk of bovine
spongiform encephalopathy (BSE). Heparin is a widely used anticoagulant produced
from porcine intestinal mucosa. Manufacturers discontinued production of heparin
from bovine intestinal mucosa in 1999 to 2001 due to concerns of transmission of
the BSE agent. L. Gregori has initiated validation studies to evaluate the
capacity of selected heparin manufacturing process steps (alkaline treatment at
50 °C, bleaching with H2O2, filtration with diatomaceous earth, methanol
precipitation) to reduce TSE agents. Crude heparin was spiked with
brain-homogenate from scrapie-infected hamsters (scrapie as surrogate for BSE)
and samples were analyzed by Western blot (WB) and bioassay. Preliminary WB data
indicated effective inactivation with NaOH treatment and further reduction with
filtration and bleaching steps. The ongoing bioassay indicates a log10 reduction
factor of 2.8 for the NaOH treatment. Prion reduction is further evaluated using
the very sensitive real-time quakinginduced conversion assay (RT-QuIC) where
recombinant PrP substrate is converted into fibrils in the presence of
Thioflavin T and PrPsc from test samples. The outcome of this assay was
consistent with the results from the ongoing bioassay.
L. Gregori further presented the current geographical BSE risk
classification and import regulation from the US Department of Agriculture for
bovine materials and reviewed FDA guidance for industry for viral vaccines and
somatic cell therapy. Robert Will (National CJD Surveillance Unit and University
of Edinburgh) reviewed the current epidemiology of vCJD. Although the incidence
vCJD has declined, uncertainty remains regarding possible future cases and
subclinical carriers with a risk for secondary transmission of the disease. Chen
and Wang (11) estimated more than 5 million living inhabitants in UK who have
been exposed via food to BSE agents while only 177 clinical cases have been
reported so far in UK. Considering the amount of consumed contaminated food, the
numbers seemed in line with an infectious threshold estimate of 12 bovine ID50
for hu- 186 PDA Journal of Pharmaceutical Science and Technology Downloaded from
journal.pda.org on May 9, 2016 mans. This would be equivalent to 1.2 g of a
BSEinfected brain. The recent study on prion proteins in human appendices showed
16 of 32,441 (1:2000) samples positive, and there could be about 32,000
asymptomatic carriers. Another study on appendices sampled before 1980 or after
1996 is under way.
Four cases of transmission of the vCJD agent via transfusion have been
detected, and there is enhanced surveillance of recipients of blood and plasma
products in the UK. However, the absence of a past history of transfusion in
most cases of vCJD excludes a large number of unrecognised
transfusion-transmitted cases. Infectious prions have been detected in the
spleen from a subclinical individual with Methionin/Valine genotype who received
prion infection via transfusion. The agent was successfully transmitted to
humanized mice. However the risk of serial transmissions appeared low as fewer
mice showed abnormal PrP with each serial passage. ***Recently transmission of
prions from blood of patients with sporadic CJD to humanized mice could be
demonstrated.
Graham S. Jackson (MRC Prion Unit, London, UK) discussed different assays
for the detection of prion infection and the challenge associated with
developing sensitive and specific diagnostic tests for vCJD. The use of
stainless steel powder, capturing and enriching disease-associated prion
material from whole blood, resulted in an assay with 71% sensitivity and 100%
specificity. In a further study, no repeat reactive falsepositive results (0 of
5000 US and 0 of 200 UK normal whole blood samples) were detected. Seventeen of
21 vCJD patient samples were positive (sensitivity 71%). In order to evaluate
the prevalence of vCJD in the UK, besides the analysis of archived appendix
tissues, he assessed the use of blood samples in the pre-clinical stage of
disease without convincing evidence of suitability of this approach when
studying infected mice. Further-on, urine samples of a control population
(normal and neurological population) showed no signal in the study; *** however,
in samples from patients with sporadic CJD and vCJD, a signal was detected in
both patient populations.
Peter Kloehn (MRC Prion Unit, London, UK) presented novel insights into the
spread and propagation of prions after infection from the periphery to,
ultimately, the brain. As a high proportion of prions are detected in natural
killer cells and dendritic cells isolated from the spleen of infected mice, it
is assumed that these prion-carrying immune cells will disseminate prions via
exosomes after mobilising these cells in the periphery. It is of interest that
shortly after inoculation the majority of the infectivity is not correlated with
the presence of proteinase K-resistant PrPSc, which lags behind the exponential
increase of infectivity. Transcriptome analysis of highly susceptible and
prion-resistant cell lines revealed that genes controlling cell differentiation
regulate the rate of prion replication at the extracellular matrix. Albrecht
Gröner (PathoGuard Consult, Germany) discussed sanitisation of equipment used in
the production of biologicals. The unique properties of PrP isoforms results in
sanitisation requirements that are distinctly different from those for
contamination by viruses and microorganisms and in distinct methods to quantify
the inactivation capacity for prions such as bioassays, prion amplification
techniques, conformation- dependent immunoassay, and, less suitable, Western
blot. Cleaning with NaOH at a concentration of at least 0.1 M, preferably in the
presence of detergent, removes and inactivates prion material from surfaces as
well as from resins to a very high degree. A risk estimation concluded that
standard cleaning/sanitisation procedures inherent in the production process of
biologicals due to current GMP will avoid a batch-tobatch contamination also in
the extremely rare event that a donation from a donor developing vCJD would be
pooled.
4. Conclusion
The 2015 PDA Virus & TSE Safety Forum provided again a much-needed
platform for debating the current knowledge, gaps, and developments related to
the virus and TSE safety of biopharmaceuticals. It provided an overview of the
landscape of challenges related to viruses and TSEs, experience of the industry
in risk mitigation strategies, progress in executing virus clearance studies and
interpreting the data, defining limitations, and working on such issues to
clarify mechanism of action and critical operational parameters. The conference
supported this process by aiding the dialog between industry, academic
researchers, and regulators.
Acknowledgements
We thank the PDA, especially Sylvia Becker and Georg Rössling, for the
initiative and continued support in organizing and conducting the conference. We
thank all speakers and all participants who contributed Vol. 70, No. 2,
March–April 2016 187 Downloaded from journal.pda.org on May 9, 2016 to the
discussion and finally to the success of the conference.
Conflict of Interest Declaration
The authors declare that they have no competing interests. References
snip...end
Sunday, February 08, 2015
*** FDA SCIENCE BOARD TO THE FOOD AND DRUG ADMINISTRATION BOVINE HEPARIN
BSE CJD TSE PRION Wednesday, June 4, 2014 ***
>>>Recently transmission of prions from blood of patients with
sporadic CJD to humanized mice could be demonstrated.<<<
>>>Further-on, urine samples of a control population (normal and
neurological population) showed no signal in the study; *** however, in samples
from patients with sporadic CJD and vCJD, a signal was detected in both patient
populations.<<<
see latest from the Baxter study ;
‘’These results, together with other laboratory studies in rodents and
non-human primates and epidemiological observations in humans, indicate that GSS
(and perhaps other familial forms of TSE) carries a greater transfusion risk
than sCJD, and that blood can be infectious during the incubation period of
vCJD, but the question of a decades-long asymptomatic carrier state in vCJD
remains unresolved.’’
Blood transmission studies of prion infections in the squirrel monkey
(Saimiri sciureus)
Susan V. Gibson1, Diane L. Ritchie2, Oksana Yakovleva3, Paula Saá3,
Christian R. Abee4 Thomas R. Kreil5, James W. Ironside2, Larisa Cervenakova3,
and Paul Brown6, 1 College of Medicine, University of South Alabama, Mobile, AL,
USA (deceased)
2National CJD Research & Surveillance Unit, School of Clinical
Sciences, University of Edinburgh, Western General Hospital, Edinburgh, EH46
7EA, Scotland
3Scientific Affairs, American Red Cross, Rockville, MD, USA
4University of Texas MD Anderson Cancer Center, Bastrop, TX, USA
5 Global Pathogen Safety, Baxter Bioscience, Vienna, Austria
6 National Institute of Neurological Diseases and Stroke, National
Institutes of Health, Bethesda, MD, USA (retired)
Five blood-related vCJD transmissions (3 symptomatic and 2
pre-symptomatic), and an estimated one ‘silent’ infection per 2000 apparently
healthy UK residents emphasize the continued need for information about disease
risk in humans. We here describe a 4-part study of infectivity in a non-human
primate model.
Study 1) Groups of 3-4 monkeys were inoculated ic with 10-1 and 10-3
dilutions of pooled brain tissue from UK cases of vCJD (3) or sCJD (2), or a
10-1 dilution of normal human brain: all CJD-inoculated animals became ill after
2-3 year incubation periods, and exosomes extracted from the blood of 5 of 7 of
the vCJD-infected animals tested positive by PMCA for PrPTSE (the normal animal
tested negative; the test is not yet optimized for sCJD infections).
Study 2) Individual ‘buddy’ monkeys were transfused every 3 months with
whole blood taken from each vCJD and sCJD monkey inoculated with 10-1 brain
tissue in the above study: none developed disease by clinical,
neuropathological, or immuno-histological criteria, but blood exosome studies
are still in progress.
Study 3) Groups of 2-4 monkeys were inoculated ic or ic/iv with either
plasma or buffy coat from UK cases of sCJD and vCJD: none developed symptoms
during a 6-8 year period of observation and at autopsy had no signs of disease
by either neuropathological or immuno-histological criteria.
Study 4) Pairs of monkeys were inoculated ic with various purified blood
components from chimp-passaged US cases of GSS (1 case) and sCJD (2 cases), and
observed for 5-6 years: only GSS leukocytes transmitted disease (both inoculated
animals).
These results, together with other laboratory studies in rodents and
non-human primates and epidemiological observations in humans, indicate that GSS
(and perhaps other familial forms of TSE) carries a greater transfusion risk
than sCJD, and that blood can be infectious during the incubation period of
vCJD, but the question of a decades-long asymptomatic carrier state in vCJD
remains unresolved.
This work was funded by Baxter Bioscience (Vienna, Austria) and the
Fondation Alliance Biosécure (Paris, France)
[[[old history of Baxter study...tss http://tseac.blogspot.com/2009/09/tseac-meeting-february-12-2004-baxter.html
]]]
==============================
Using patient-specific fibroblasts and iPSC-derived neurons to uncover
cellular phenotypes associated with prion diseases
Jue Yuan1, Leslie Cooperman1, Christina Orru2, Dongyun Han1, Hisashi
Fujioka1, Elizabeth Shick1, Yi-An Zhan1, Mark Rodgers1, Robert Wyza1, Brian
Appleby1, Miguel Quinones-Mateu1, Shulin Zhang1, Tingwei Mu1, Byron Caughey2,
Xin Qi1, Paul Tesar1, Wen-Quan Zou1
1Case Western Reserve University, Cleveland, OH, USA, 2NIH/NIAID Rocky
Mountain Laboratories, Hamilton, MT, USA
Cell biology of prion formation and spread remains incompletely understood,
largely because of lack of authentic cell models. We report isolation of
fibroblasts from skin tissues, derivation of induced pluripotent stem cells
(iPSCs), differentiation of iPSCs into mature neurons, and detection of
disease-related phenotypes in fibroblasts and
10
HUMAN PRIONS
iPSC-derived neurons. Fibroblasts were isolated from skin samples of 23
subjects including nine asymptomatic subjects carrying six different PrP
mutations, four patients with sporadic CJD (sCJD), and ten normal controls.
Surprisingly, not only protease-resistant PrP was detected with Western blotting
but also seeding activity was detected with RT-QuIC in fibroblasts of some PrP
mutation carriers or sCJD patients. After iPSCs were derived from fibroblasts of
mutation carriers (E200K or D178N) and normal controls, functional mature
iPSCderived neurons were further differentiated, as evidenced by immunostaining
with the neuronal marker Map2 and by patch-clamp recording of GABA-induced
current. While migration and glycosylation of PrP from fibroblasts were
different from those of brain PrP, iPSC-derived neurons exhibited the PrP
profile similar to the brain PrP. Notably, shortened neurites and
neuritic-beading, characteristics of neurodegeneration, were more readily
observed in iPSC-derived E200K neurons or in iPSC-derived neurons challenged
with sCJD brain homogenates compared to neurons derived from iPSCs of normal
subjects. Our study has generated patient-specific fibroblasts and iPSC-derived
neurons that exhibit cellular phenotypes and seem to be authentic cell models
for probing human prion diseases. [Supported by the CJD Foundation Award,
NIHNS087588, NIHNS062787, and bridge funding from University Hospitals Case
Medical Center.]
Oral Session14:45~15:00O-12 Wenquan Zou
*** PrPSc in the skin of CJD patients
Accessing transmissibility and diagnostic marker of skin prions.
Kong, Qingzhong Safar, Jiri G. Zou, Wen-Quan
Case Western Reserve University, Cleveland, OH, United States
Abstract The fatal, transmissible animal and human prion diseases are
characterized by the deposition in the brain of a proteinase K (PK)-resistant
infectious prion protein (PrPSc), an isoform derived from the cellular protein
(PrPC) through misfolding. A definitive antemortem diagnosis is virtually
impossible for most patients because of the difficulty in obtaining the brain
tissues by biopsy. Recently, PrPSc has been reported to be detected in the skin
of experimentally or naturally scrapie-infected animals (Thomzig et al., 2007).
Consistent with this finding, we have observed PK-resistant PrP in the skin of a
patient with variant Creutzfeldt-Jakob disease (vCJD), an acquired form of human
prion disease caused by bovine prion (Notari et al., 2010). Unexpectedly, our
latest preliminary study identified two types of PK-resistant PrP molecules
[with gel mobility similar to the PrPSc types 1 and 2 from the brain of sporadic
CJD (sCJD)] in the fibroblast cells extracted from the skin of clinical sCJD
patients and asymptomatic subjects carrying PrP mutations linked to familial CJD
(fCJD). We also detected PrPSc in the skin of humanized transgenic (Tg) mice
inoculated intracerebrally with a human prion. Moreover, prion infectivity has
been observed in the skin of infected greater kudu (Cunningham et al., 2004) and
a murine prion inoculated to mice via skin scarification can not only propagate
in the skin, but also spread to the brain to cause prion disease (Wathne et al.,
2012). We hypothesize that the skin of patients with prion disease harbors prion
infectivity and the presence of PK-resistant PrP in the skin is a novel
diagnostic marker for preclinical CJD patients. To test the hypotheses, we
propose to (1) determine prion infectivity of the skin- derived fibroblasts and
skin of sCJD patients and asymptomatic PrP-mutation carriers using humanized Tg
mouse bioassay, (2) to pinpoint the earliest stage at which PrPSc becomes
detectable in the skin of prion- infected Tg mice, and (3) to detect PrPSc in
the skin of various human prion diseases, using conventional as well as highly
sensitive RT-QuIC assays for both (2) and (3). If successful, our proposal may
not only help prevent potential transmission of human prion diseases but also
enable definitive and less intrusive antemortem diagnosis of prion diseases.
Finally, knowledge generated from this study may also enhance our understanding
of other neurodegenerative diseases such as Alzheimer's disease.
Public Health Relevance Currently it is unclear whether or not the skin of
patients with prion diseases is infectious and, moreover, there is no
alternative preclinical definitive testing or the brain biopsy in the prion
diseases. The aim of our proposal is to address the issues by detection of the
infectivity of patients' skin samples using animal bioassay and a new highly
sensitive RT-QuIC assay. We believe that our study will not only provide
insights into the pathogenesis and transmissibility of prion disease but also
will develop preclinical definitive testing for prion disease.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Neurological Disorders and Stroke
(NINDS)
Type Exploratory/Developmental Grants (R21)
Project # 1R21NS096626-01
Application # 9092119
Study Section Special Emphasis Panel (ZRG1)
Program Officer Wong, May Project Start 2016-02-01
Project End 2018-01-31
Budget Start 2016-02-01
Budget End 2017-01-31
Support Year 1
Fiscal Year 2016
Total Cost
Indirect Cost Institution Name Case Western Reserve University
Department Pathology
Type Schools of Medicine
DUNS # 077758407
City Cleveland
State OH
Country United States
Zip Code 44106
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a.
Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos,
Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT.
Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas.
France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated
bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD)
disease in human. To date, BSE agent is the only recognized zoonotic prion.
Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that
have been circulating for centuries in farmed ruminants there is no apparent
epidemiological link between exposure to ruminant products and the occurrence of
other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD).
However, the zoonotic potential of the diversity of circulating TSE agents has
never been systematically assessed. The major issue in experimental assessment
of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the
biological phenomenon that limits TSE agents’ propagation from a species to
another. In the last decade, mice genetically engineered to express normal forms
of the human prion protein has proved essential in studying human prions
pathogenesis and modeling the capacity of TSEs to cross the human species
barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants,
we study their transmission ability in transgenic mice expressing human PrPC
(HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC
(129Met or 129Val) are used to determine the role of the Met129Val dimorphism in
susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to
propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be
susceptible to BSE in sheep or goat to a greater degree than the BSE agent in
cattle and that these agents can convey molecular properties and
neuropathological indistinguishable from vCJD. However homozygous 129V mice are
resistant to all tested BSE derived prions independently of the originating
species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in
HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the
efficiency of transmission at primary passage was low, subsequent passages
resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the
emergence of prion strain phenotypes that showed similar characteristics to
those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie
prions have a zoonotic potential and raise new questions about the possible link
between animal and human prions.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of scrapie prions to primate after an extended silent
incubation period
Authors
item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire,
Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item
Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item
Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron,
Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item
Deslys, Jean-Philippe -
Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015
Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E.,
Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C.,
Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J.
2015. Transmission of scrapie prions to primate after an extended silent
incubation period. Scientific Reports. 5:11573.
Interpretive Summary: The transmissible spongiform encephalopathies (also
called prion diseases) are fatal neurodegenerative diseases that affect animals
and humans. The agent of prion diseases is a misfolded form of the prion protein
that is resistant to breakdown by the host cells. Since all mammals express
prion protein on the surface of various cells such as neurons, all mammals are,
in theory, capable of replicating prion diseases. One example of a prion
disease, bovine spongiform encephalopathy (BSE; also called mad cow disease),
has been shown to infect cattle, sheep, exotic undulates, cats, non-human
primates, and humans when the new host is exposed to feeds or foods contaminated
with the disease agent. The purpose of this study was to test whether non-human
primates (cynomologous macaque) are susceptible to the agent of sheep scrapie.
After an incubation period of approximately 10 years a macaque developed
progressive clinical signs suggestive of neurologic disease. Upon postmortem
examination and microscopic examination of tissues, there was a widespread
distribution of lesions consistent with a transmissible spongiform
encephalopathy. This information will have a scientific impact since it is the
first study that demonstrates the transmission of scrapie to a non-human primate
with a close genetic relationship to humans. This information is especially
useful to regulatory officials and those involved with risk assessment of the
potential transmission of animal prion diseases to humans. Technical Abstract:
Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease
that also causes variant Creutzfeldt-Jakob disease in humans. Over the past
decades, c-BSE's zoonotic potential has been the driving force in establishing
extensive protective measures for animal and human health.
*** In complement to the recent demonstration that humanized mice are
susceptible to scrapie, we report here the first observation of direct
transmission of a natural classical scrapie isolate to a macaque after a 10-year
incubation period. Neuropathologic examination revealed all of the features of a
prion disease: spongiform change, neuronal loss, and accumulation of PrPres
throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of
scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated.
*** Our results underscore the importance of precautionary and protective
measures and the necessity for long-term experimental transmission studies to
assess the zoonotic potential of other animal prion strains.
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
PRION 2016 TOKYO
Zoonotic Potential of CWD Prions: An Update
Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3,
Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6,
Pierluigi Gambetti1, Qingzhong Kong1,5,6
1Department of Pathology, 3National Prion Disease Pathology Surveillance
Center, 5Department of Neurology, 6National Center for Regenerative Medicine,
Case Western Reserve University, Cleveland, OH 44106, USA.
4Department of Biological Sciences and Center for Prions and Protein
Folding Diseases, University of Alberta, Edmonton, Alberta, Canada,
2Encore Health Resources, 1331 Lamar St, Houston, TX 77010
Chronic wasting disease (CWD) is a widespread and highly transmissible
prion disease in free-ranging and captive cervid species in North America. The
zoonotic potential of CWD prions is a serious public health concern, but the
susceptibility of human CNS and peripheral organs to CWD prions remains largely
unresolved. We reported earlier that peripheral and CNS infections were detected
in transgenic mice expressing human PrP129M or PrP129V. Here we will present an
update on this project, including evidence for strain dependence and influence
of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of
experimental human CWD prions.
PRION 2016 TOKYO
In Conjunction with Asia Pacific Prion Symposium 2016
PRION 2016 Tokyo
Prion 2016
LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL
THE WRONG PLACES $$$
*** 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).***
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
O18
Zoonotic Potential of CWD Prions
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1,
Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1
1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University
of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA
*** These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.
==================
***These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.***
==================
P.105: RT-QuIC models trans-species prion transmission
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover
Prion Research Center; Colorado State University; Fort Collins, CO USA
Conversely, FSE maintained sufficient BSE characteristics to more
efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was
competent for conversion by CWD and fCWD.
***This insinuates that, at the level of proteinrotein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.
================
***This insinuates that, at the level of proteinrotein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.***
================
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
*** chronic wasting disease, there was no absolute barrier to conversion of
the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay
when seeded with CWD, resembles that found in the most common human prion
disease, namely sCJD of the MM1 subtype.
*** 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).***
*** 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).***
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
Chronic Wasting Disease and Potential Transmission to Humans
Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,† Michael W.
Miller,‡ Pierluigi Gambetti,§ and Lawrence B. Schonberger*
Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner
area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected
in other parts of the United States. Although detection in some areas may be
related to increased surveillance, introduction of CWD due to translocation or
natural migration of animals may account for some new foci of infection.
Increasing spread of CWD has raised concerns about the potential for increasing
human exposure to the CWD agent. The foodborne transmission of bovine spongiform
encephalopathy to humans indicates that the species barrier may not completely
protect humans from animal prion diseases. Conversion of human prion protein by
CWDassociated prions has been demonstrated in an in vitro cellfree experiment,
but limited investigations have not identified strong evidence for CWD
transmission to humans. More epidemiologic and laboratory studies are needed to
monitor the possibility of such transmissions.
Conclusions
The lack of evidence of a link between CWD transmission and unusual cases
of CJD, despite several epidemiologic investigations, and the absence of an
increase in CJD incidence in Colorado and Wyoming suggest that the risk, if any,
of transmission of CWD to humans is low. Although the in vitro studies
indicating inefficient conversion of human prion protein by CWD-associated
prions raise the possibility of low-level transmission of CWD to humans, no
human cases of prion disease with strong evidence of a link with CWD have been
identified. However, the transmission of BSE to humans and the resulting vCJD
indicate that, provided sufficient exposure, the species barrier may not
completely protect humans from animal prion diseases. Because CWD has occurred
in a limited geographic area for decades, an adequate number of people may not
have been exposed to the CWD agent to result in a clinically recognizable human
disease. The level and frequency of human exposure to the CWD agent may increase
with the spread of CWD in the United States. Because the number of studies
seeking evidence for CWD transmission to humans is limited, more epidemiologic
and laboratory studies should be conducted to monitor the possibility of such
transmissions. Studies involving transgenic mice expressing human and cervid
prion protein are in progress to further assess the potential for the CWD agent
to cause human disease. Epidemiologic studies have also been initiated to
identify human cases of prion disease among persons with an increased risk for
exposure to potentially CWD-infected deer or elk meat (47). If such cases are
identified, laboratory data showing similarities of the etiologic agent to that
of the CWD agent would strengthen the conclusion for a causal link. Surveillance
for human prion diseases, particularly in areas where CWD has been detected,
remains important to effectively monitor the possible transmission of CWD to
humans. Because of the long incubation period associated with prion diseases,
convincing negative results from epidemiologic and experimental laboratory
studies would likely require years of follow-up. In the meantime, to minimize
the risk for exposure to the CWD agent, hunters should consult with their state
wildlife agencies to identify areas where CWD occurs and continue to follow
advice provided by public health and wildlife agencies. Hunters should avoid
eating meat from deer and elk that look sick or test positive for CWD. They
should wear gloves when field-dressing carcasses, boneout the meat from the
animal, and minimize handling of brain and spinal cord tissues. As a precaution,
hunters should avoid eating deer and elk tissues known to harbor the CWD agent
(e.g., brain, spinal cord, eyes, spleen, tonsils, lymph nodes) from areas where
CWD has been identified.
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 ;
CJD is so rare in people under age 30, one case in a billion (leaving out
medical mishaps), that four cases under 30 is "very high," says Colorado
neurologist Bosque. "Then, if you add these other two from Wisconsin [cases in
the newspaper], six cases of CJD in people associated with venison is very, very
high." Only now, with Mary Riley, there are at least seven, and possibly eight,
with Steve, her dining companion. "It's not critical mass that matters,"
however, Belay says. "One case would do it for me." The chance that two people
who know each other would both contact CJD, like the two Wisconsin sportsmen, is
so unlikely, experts say, it would happen only once in 140 years.
Given the incubation period for TSEs in humans, it may require another
generation to write the final chapter on CWD in Wisconsin. "Does chronic wasting
disease pass into humans? We'll be able to answer that in 2022," says Race.
Meanwhile, the state has become part of an immense experiment.
I urge everyone to watch this video closely...terry
*** you can see video here and interview with Jeff's Mom, and scientist
telling you to test everything and potential risk factors for humans ***
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
***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.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Rachel C. Angers1,*, Shawn R. Browning1,*,†, Tanya S. Seward2, Christina J.
Sigurdson4,‡, Michael W. Miller5, Edward A. Hoover4, Glenn C. Telling1,2,3,§
snip...
Abstract The emergence of chronic wasting disease (CWD) in deer and elk in
an increasingly wide geographic area, as well as the interspecies transmission
of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt
Jakob disease, have raised concerns about the zoonotic potential of CWD. Because
meat consumption is the most likely means of exposure, it is important to
determine whether skeletal muscle of diseased cervids contains prion
infectivity. Here bioassays in transgenic mice expressing cervid prion protein
revealed the presence of infectious prions in skeletal muscles of CWD-infected
deer, demonstrating that humans consuming or handling meat from CWD-infected
deer are at risk to prion exposure.
***********CJD REPORT 1994 increased risk for consumption of veal and
venison and lamb***********
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL
REPORT AUGUST 1994
Consumption of venison and veal was much less widespread among both cases
and controls. For both of these meats there was evidence of a trend with
increasing frequency of consumption being associated with increasing risk of
CJD. (not nvCJD, but sporadic CJD...tss)
These associations were largely unchanged when attention was restricted to
pairs with data obtained from relatives. ...
Table 9 presents the results of an analysis of these data.
There is STRONG evidence of an association between ‘’regular’’ veal eating
and risk of CJD (p = .0.01).
Individuals reported to eat veal on average at least once a year appear to
be at 13 TIMES THE RISK of individuals who have never eaten veal.
There is, however, a very wide confidence interval around this estimate.
There is no strong evidence that eating veal less than once per year is
associated with increased risk of CJD (p = 0.51).
The association between venison eating and risk of CJD shows similar
pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK
OF CJD (p = 0.04).
There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY
OF LAMB EATING (p = 0.02).
The evidence for such an association between beef eating and CJD is weaker
(p = 0.14). When only controls for whom a relative was interviewed are included,
this evidence becomes a little STRONGER (p = 0.08).
snip...
It was found that when veal was included in the model with another
exposure, the association between veal and CJD remained statistically
significant (p = < 0.05 for all exposures), while the other exposures
ceased to be statistically significant (p = > 0.05).
snip...
In conclusion, an analysis of dietary histories revealed statistical
associations between various meats/animal products and INCREASED RISK OF CJD.
When some account was taken of possible confounding, the association between
VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS
STATISTICALLY. ...
snip...
In the study in the USA, a range of foodstuffs were associated with an
increased risk of CJD, including liver consumption which was associated with an
apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3
studies in relation to this particular dietary factor, the risk of liver
consumption became non-significant with an odds ratio of 1.2 (PERSONAL
COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
snip...see full report ;
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge
Spencers Lane BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third
annual report from the CJD Surveillance Unit. I am sorry that you are
dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the
Department of Health is committed to publishing their reports as soon as they
become available. In the circumstances it is not the practice to circulate the
report for comment since the findings of the report would not be amended. In
future we can ensure that the British Deer Farmers Association receives a copy
of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed
of the results of any research in respect of CJD. This report was entirely the
work of the unit and was produced completely independantly of the the
Department.
The statistical results reqarding the consumption of venison was put into
perspective in the body of the report and was not mentioned at all in the press
release. Media attention regarding this report was low key but gave a realistic
presentation of the statistical findings of the Unit. This approach to
publication was successful in that consumption of venison was highlighted only
once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed statistical
links between CJD and consumption of venison, would increase, and quite possibly
give damaging credence, to the whole issue. From the low key media reports of
which I am aware it seems unlikely that venison consumption will suffer
adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
*** 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).***
O.05: Transmission of prions to primates after extended silent incubation
periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni,
Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys
Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies
reputed to be transmissible under field conditions since decades. The
transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that
an animal PD might be zoonotic under appropriate conditions. Contrarily, in the
absence of obvious (epidemiological or experimental) elements supporting a
transmission or genetic predispositions, PD, like the other proteinopathies, are
reputed to occur spontaneously (atpical animal prion strains, sporadic CJD
summing 80% of human prion cases). Non-human primate models provided the first
evidences supporting the transmissibiity of human prion strains and the zoonotic
potential of BSE. Among them, cynomolgus macaques brought major information for
BSE risk assessment for human health (Chen, 2014), according to their
phylogenetic proximity to humans and extended lifetime. We used this model to
assess the zoonotic potential of other animal PD from bovine, ovine and cervid
origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical
scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD,
albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked
in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases. We will present an
updated panorama of our different transmission studies and discuss the
implications of such extended incubation periods on risk assessment of animal PD
for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. Bioassay will be required to determine whether the PMCA
products are infectious to these animals.
==============
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of scrapie prions to primate after an extended silent
incubation period
Authors
item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire,
Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item
Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item
Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron,
Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item
Deslys, Jean-Philippe -
Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015
Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E.,
Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C.,
Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J.
2015. Transmission of scrapie prions to primate after an extended silent
incubation period. Scientific Reports. 5:11573.
Interpretive Summary: The transmissible spongiform encephalopathies (also
called prion diseases) are fatal neurodegenerative diseases that affect animals
and humans. The agent of prion diseases is a misfolded form of the prion protein
that is resistant to breakdown by the host cells. Since all mammals express
prion protein on the surface of various cells such as neurons, all mammals are,
in theory, capable of replicating prion diseases. One example of a prion
disease, bovine spongiform encephalopathy (BSE; also called mad cow disease),
has been shown to infect cattle, sheep, exotic undulates, cats, non-human
primates, and humans when the new host is exposed to feeds or foods contaminated
with the disease agent. The purpose of this study was to test whether non-human
primates (cynomologous macaque) are susceptible to the agent of sheep scrapie.
After an incubation period of approximately 10 years a macaque developed
progressive clinical signs suggestive of neurologic disease. Upon postmortem
examination and microscopic examination of tissues, there was a widespread
distribution of lesions consistent with a transmissible spongiform
encephalopathy. This information will have a scientific impact since it is the
first study that demonstrates the transmission of scrapie to a non-human primate
with a close genetic relationship to humans. This information is especially
useful to regulatory officials and those involved with risk assessment of the
potential transmission of animal prion diseases to humans. Technical Abstract:
Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease
that also causes variant Creutzfeldt-Jakob disease in humans. Over the past
decades, c-BSE's zoonotic potential has been the driving force in establishing
extensive protective measures for animal and human health.
*** In complement to the recent demonstration that humanized mice are
susceptible to scrapie, we report here the first observation of direct
transmission of a natural classical scrapie isolate to a macaque after a 10-year
incubation period. Neuropathologic examination revealed all of the features of a
prion disease: spongiform change, neuronal loss, and accumulation of PrPres
throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of
scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated.
*** Our results underscore the importance of precautionary and protective
measures and the necessity for long-term experimental transmission studies to
assess the zoonotic potential of other animal prion strains.
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
”The occurrence of CWD must be viewed against the contest of the locations
in which it occurred. It was an incidental and unwelcome complication of the
respective wildlife research programmes. Despite it’s subsequent recognition as
a new disease of cervids, therefore justifying direct investigation, no specific
research funding was forthcoming. The USDA veiwed it as a wildlife problem and
consequently not their province!” page 26.
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to
accord it a very low profile indeed. Dr. A Thiermann showed the picture in the
''Independent'' with cattle being incinerated and thought this was a fanatical
incident to be avoided in the US at all costs. ...
Evidence That Transmissible Mink Encephalopathy Results from Feeding
Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult
mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer
or dead dairy cattle...
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES
Pennsylvania AND California
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive
Prionopathy and Gerstmann-Sträussler-Scheinker Disease
Monday, May 09, 2016
*** A comparison of classical and H-type bovine spongiform encephalopathy
associated with E211K prion protein polymorphism in wild type and EK211 cattle
following intracranial inoculation ***
LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL
THE WRONG PLACES $$$
*** 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).***
Saturday, May 30, 2015
PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS
Wednesday, June 10, 2015
Zoonotic Potential of CWD Prions LATE-BREAKING ABSTRACTS
Friday, April 22, 2016
*** COLORADO CHRONIC WASTING DISEASE CWD TSE PRION SURVEILLANCE AND TESTING
PROGRAM IS MINIMAL AND LIMITED ***
snip...
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
22
Visits to Colorado State University, College of Veterinary Medicine and the
Wyoming Game and Fish Department, Sybille Wildlife Research and Conservation
Education Unit.
The main objective here was to obtain some understanding of CWD. A visit
was made to the University of wyoming Game and Fish Department, Sybille wildlife
Research and Conservation Education Unit where most of the cases of CWD have
occurred. The Sybille Wildlife facility is situated some 50 miles northeast of
Laramie, Wyoming through the Laramie Mountains. Here most of the hoofed big game
species of North America; Hule Deer (odocoileus hemionus), Whitetail Deer
(Odocoileus virginianus), Elk (Cervis canadensis) Mountain Goat (Oreamnos
americana), Bighorn Sheep (0vis canadensis** and Pronghorn (Antilocapra
americana) and some other wildlife species are kept in small numbers for
experimental use in the investigation of wildlife diseases.
A colony of the blackfooted ferret (Hustela nigripes) has been established
because of its imminent extinction. At present there are only 35 but it is
proposed to breed up to 200 and then, probably in 1991, re-introduce them into
the wild in a nation wide operation. Blackfooted ferret diet is mainly Prairie
Dog (Cynoms spp.) and it is thought that the elimination of this species from
large areas by poisoning campaigns in the past has been responsible for the
precipitous ferret decline.
The buildings and pens at the facility are entirely of wooden/log
construction with heavy duty wire mesh fences. Pen floors are bare earth. A long
race connecting many different areas within the facility enables movement of
deer and antelope between pens when necessary. There is provision for holding
deer of different sizes in a custom built crush for bleeding and
treatments.
23
The educational role of the unit includes school visits to provide
instruction in the work of the department and to promote conservation. I was
accompanied on this visit by Stuart Young and Beth Williams. on arrival I was
introduced to Hughie Dawson who has managed the facility for some 20
years.
CWD occurred principally in two locations, this one at Sybille and in a
similar facility at Fort Collins, Colorado, some 120 miles southwest. It was
estimated that in total probably 60-10 cases of CWD have occurred.
It was difficult to gain a clear account of incidence and temporal sequence
of events ( - this presumably is data awaiting publication - see below) but
during the period 1981-84, 10-15 cases occurred at the Sybille facility.
Recollections as to the relative total numbers of cases at each facility were
confusing. Beth Williams recalled that more cases had occurred in the Colorado
facility.
The morbidity amongst mule deer in the facilities ie. those of the natural
potentially exposed group has been about 90% with 100% mortality. the age
distribution of affected deer was very similar to that in ESE. The clinical
duration of cases was 6-8 weeks. Mortality in CWD cases was greatest in winter
months which can be very cold.
When the problem was fully appreciated both the Sybille and the Colorado
facilities were depopulated. All cervids were culled but Pronghorn, Bighorn
Sheep and Mountain goat, where present simultaneously in the facility, were
retained. There have been no cases of CWD in these non cervid species.
A few cases continue to occur at Sybille, the last was 4 months ago.
24
An account of the occurrence of CWD at the Colorado facility was obtained
from Terry spraker, Diagnostic Laboratory, CSU College of Veterinary Medicine,
Fort Collins. He examined tissues from cases of CWD at the Colorado facility
some time prior to Beth Williams's involvement and examination of brains which
resulted in the initial diagnosis. The deer holding facilities in Colorado
comprise the Colorado Division of Wildlife Research Pen, established 10 years
ago and some older deer pens at the Foot Hills Campus of CSU, close to Fort
Collins. Originally there were just 1-2 cases CWD/year and a total of 24 over
several years. In contrast to Beth Williams recollection Terry Spraker thought
more cases had‘ occurred at Sybille than in Colorado. The cull at the Colorado
facility involved 20-30 clinically normal deer. Early lesions in dorsal nucleus
of the vagus and olfactory cortex were found in (some) of these deer. At the
time of the cull here Pronghorn was the only other hoofed species present.
Bighorn sheep and Mountain Goat were introduced only one year after the cull and
occupied ground where CWD had occurred. Immediately after depopulation the
ground was ploughed and disinfection was carried out using ?1% NaOH. The
buildings/pens were not changed. There has been no recurrence of disease at the
Colorado facility since the cull.
25
Transmission Studies
Mule deer transmissions of CWD were by intracerebral inoculation and
compared with natural cases (‘’first passage by this route’’ MARKED OUT...TSS)
resulted in a more rapidly progressive clinical disease with repeated episodes
of synocopy ending in coma. one control animal became affected, it is J believed
through contamination of inoculum (?saline). Further CWD transmissions were
carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission
occurred in all of these species with the shortest incubation period in the
ferret.
Mouse and hamster transmissions were attempted at Wyoming State Diagnostic
Laboratory, Laramie and at CSU Fort Collins but were unsuccessful.
Also at the Wyoming State Diagnostic Laboratory, Laramie, transmission to
goats was attempted. In 1984 three goats were inoculated intracerebrally with a
10% CWD brain suspension. one goat, untreated, was placed in contact with the
CWD inoculated goats and three controls, housed separately, received saline
intracerebrally. To date these animals remain healthy.
Epidemiology of CWD
Descriptive epidemiological data has been collected from the two wildlife
facilities and a publication is in preparation.
The occurrence of CWD must be viewed against the context of the locations
in which it occurred. It was an incidental and unwelcome complication of the
respective wildlife research programmes. Despite its subsequent recognition as a
new disease of cervids, therefore justifying direct investigation, no specific
research funding was forthcoming. The USDA viewed it as a wildlife problem and
consequently not their province! Thus
26
there have been no specific epidemiological studies, other than information
gained from noting the occurrence of cases. Because of the relatively short term
nature of the programmed research at the facilities it has not been possible to
keep Mule Deer under the appropriate experimental circumstances or for
sufficient periods to establish horizontal or maternal transmission. Beth
Williams is of the view that the occurrence of CWD at Sybille is entirely
related to propagative spread by contagion. Investigations have failed to
identify any common source of infection and the incident has presented a
protracted time course with sporadic cases throughout. There is no evidence that
wild born deer were responsible for introduction of the disease to the
facility.
I asked Hughie Dawson about the nutritional aspects of the deer kept at
Sybille. Mule Deer calves are reared on condensed milk and homogenised or
pasteurised domestic cow's milk from birth to 1 month or to 6 months. some would
be given "Lamb milk replacer" which has a higher butter fat content than either
of the former products, but is derived also from domestic cow's milk. It was
thought that at the Colorado facility calves would receive only "evaporated
milk". Calves are weaned on to a pelletted feed containing corn, wheat bran and
linseed meal with no crude mineral suppliment. Salt licks ("sulphur blocks")
which have a specific mineral composition are supplied.
CWD has occurred or is suspected to have occurred in establishments
supplied with Mule Deer from the Colorado facility. In some cases evidence for
this is tenuous. For example, it is understood that Denver zoo state that "they
have not had cases of CWD" and yet they have had cases of Mule Deer succumbing
to a chronic wasting disorder which was not diagnosed. A case of CWD occurred in
a Mule Deer in Toronto zoo in 1976. The animal in
27
question came from Denver zoo but was originally from the Colorado wildlife
facility.
Pathology of CWD
A paper (Williams et al) is in preparation on the distribution of brain
lesions in CWD. Vacuolar changes occur predominantly in the dorsal nucleus of
the vagus nerve (this nucleus is invariably affected), the hypothalamus and the
olfactory cortex with occasional vacuolation of the olfactory tract white
matter.
Cerebellar lesions are sometimes present but there are very few changes in
the spinal cord which probably accounts for the rarity of ataxia clinically. As
in sheep scrapie the hypothalamic lesions correlate with the common clinical
occurrence of polydipsia. Beth Williams is aware of occasional neuronal vacuoles
occurring in the red nucleus of clinically normal deer! Spraker has added that
he has experienced vacuoles in neurons of Gasserian ganglia and at the level of
the obex in normal deer.
It has never been reported but Pat Merz carried out SAF detection on CWD
brain material. Work may be undertaken with NIH on the immunohistological
demonstration of PrP in sections but to date there has been no PrP work.
Does CWD occur in free-living cervids?
There is some, mostly circumstantial, evidence that CWD occurs in
free-living cervids but to what extent, if at all, this represents an
established reservoir of infection in the wild is not known.
At Sybille two Mule Deer orphans (wild caught) and a White—tail Deer
(Odocoileus virginianus) hybrid developed clinical signs when only 2 1/2 years
of age.
28
An Elk (Cervus canadensis) wild caught as an adult, presumed 2 years old,
developed signs when 3-4 years old.
Another group of elk, wild caught 400 miles from the facility, with an age
range 2-8 years, old subsequently developed the disease in the facility (?period
of captivity). The location of capture relative to the facility did not
apparently rule out that they may have at some time had fence-line nose contact
with animals in the facility!
Cases have also occurred in Mule Deer that were obtained from the wild
within one hour of birth but these were never kept completely isolated through
to maturity.
Also at Sybille there has been one case of CWD diagnosed in a free ranging
Elk. It was killed in Sybille Canyon 3 miles from the facility. It could have
had fence-line contact with captive Mule Deer in the facility.
Similar incidents had occurred in Colorado. In 1985 a free-ranging affected
Elk was caught in the Rocky Mountain National Park within a 2 mile radius of the
Colorado Division of Wildlife Research Pen. In 1986 and again in 1987 a single
affected Mule Deer on each occasion was caught within a 5 mile radius of the
Pen. These latter cases occurred within 2 years of the -cervid cull at the Pen
(?1985). Brain tissue from the free—ranging Elk brain was inoculated into mice
but for some reason these were kept for only 6 months and then the experiment
was abandoned.
A specific exercise has been carried out by Beth Williams with the Wyoming
State Diagnostic Laboratory and Fish Department to sample the brains of healthy
wild Mule Deer for histological examination. On two separate occasions the first
in 1985 and again in 1987 a total of 150 Mule Deer
29
brains were collected from areas of, and ajacent to, Sybille Canyon. These
deer would have been shot under a game permit by local hunters. As they were
brought down from the hills to the Game station for the mandatory registration
of the kill the heads were removed and ages estimated. Most were 2-5 year old
with a few 6 year old. For obvious reasons hunters were reluctant to give up
stag heads. Thus, but for 15-20 brains from stags, examinations were on brains
from females. No evidence of CWD lesions was found in any of these brains.
However, it was considered that sporadic cases of CWD, should they occur in the
wild population, would soon become separated from the herd and fall prey to
coyotes (Canis latrans).
The possibility of any reservoir of infection in wild cervids originating
from scrapie in domestic sheep flocks seems remote. Scrapie has been recorded in
only three flocks in Wyoming since 1947 and Beth Williams could recall only one
previous occurrence in 1966. This had involved a Suffolk flock close to the
border with Nebraska. However, there has been one new confirmed and a suspected
affected flock this year in Wyoming. In the latter a ewe bought—in from an
Illinois flock is incriminated.
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. Whether they were scrapie infected sheep or
not is unclear. There were domestic sheep and goats present in the facility also
in the 1960's but there is no evidence that these animals developed scrapie.
During the 60's hybridization studies between the Bighorn and domestic sheep
were carried
30
out, again, without evidence of scrapie. Domestic goats were also kept at
Sybille in the 1960's.
Spraker considers that the nasal route is responsible for transmission of
CWD through nose to nose contact, which may well occur also between captive and
free—living individuals.
In domestic cattle of which about 15-20 adults were necropsied per year at
the Diagnostic Laboratory, CSU., Spraker had not encountered any lesions
suggesting BSE. Polioencephalomalacia (PEM) and Encephalic Listeriosis were the
most common morphologic neuropathological diagnoses. No bovine rabies was
seen.
31
Appendix I
VISIT TO USA - OR A E WRATHALL — INFO ON BSE AND SCRAPIE
Dr Clark lately of the Scrapie Research Unit, Mission Texas has I
successfully transmitted ovine and caprine Scrapie to cattle. The experimental
results have not been published but there are plans to do this. This work was
initiated in 1978. A summary of it is:-
Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with a
2nd Suffolk scrapie passage:- i/c 1ml; i/m, 5ml; s/c 5ml; oral 30ml.
1/6 went down after 48 months with a scrapie/BS2-like disease.
Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat virus
2/6 went down similarly after 36 months.
Expt C Mice inoculated from brains of calves/cattle in expts A & B were
resistant, only 1/20 going down with scrapie and this was the reason given for
not publishing.
Diagnosis in A, B, C was by histopath. No reports on SAF were given.
2. Dr Warren Foote indicated success so far in eliminating scrapie in
offspring from experimentally— (and naturally) infected sheep by ET. He had
found difficulty in obtaining embryos from naturally infected sheep (cf
SPA).
3. Prof. A Robertson gave a brief accout of BSE. The us approach was
to
32
accord it a very low profile indeed. Dr A Thiermann showed the picture in
the "Independent" with cattle being incinerated and thought this was a fanatical
incident to be avoided in the US at all costs. BSE was not reported in
USA.
4. Scrapie incidents (ie affected flocks) have shown a dramatic increase
since 1978. In 1953 when the National Control scheme was started there were
10-14 incidents, in 1978 - 1 and in 1988 so far 60.
5. Scrapie agent was reported to have been isolated from a solitary fetus.
6. A western blotting diagnostic technique (? on PrP) shows some
promise.
7. Results of a questionnaire sent to 33 states on" the subject of the
national sheep scrapie programme survey indicated
17/33 wished to drop it
6/33 wished to develop it
8/33 had few sheep and were neutral
Information obtained from Dr Wrathall‘s notes of a meeting of the U.S.
Animal Health Association at Little Rock, Arkansas Nov. 1988.
33
snip...see full text ;
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to
accord it a very low profile indeed. Dr. A Thiermann showed the picture in the
''Independent'' with cattle being incinerated and thought this was a fanatical
incident to be avoided in the US at all costs. ...
snip...see full text ;
SEE CWD HIGH INFECTION RATE MAPS FOR COLORADO !
Sunday, May 08, 2016
*** WISCONSIN CHRONIC WASTING DISEASE CWD TSE PRION SPIRALING FURTHER INTO
THE ABYSS UPDATE
Tuesday, May 03, 2016
*** Arkansas Chronic Wasting Disease CWD TSE Prion and Elk Restoration
Project and Hunkering Down in the BSE Situation Room USDA 1998
Monday, April 25, 2016
Arkansas AGFC Phase 2 sampling reveals CWD positive deer in Madison and
Pope counties
Tuesday, April 19, 2016
Arkansas First Phase of CWD sampling reveals 23 percent prevalence rate in
focal area With 82 Confirmed to Date
Wednesday, May 04, 2016
TPWD proposes the repeal of §§65.90 -65.94 and new §§65.90 -65.99
Concerning Chronic Wasting Disease - Movement of Deer Singeltary Comment
Submission
Saturday, April 02, 2016
TEXAS TAHC BREAKS IT'S SILENCE WITH TWO MORE CASES CWD CAPTIVE DEER
BRINGING TOTAL TO 10 CAPTIVES REPORTED TO DATE
Friday, February 26, 2016
TEXAS Hartley County Mule Deer Tests Positive for Chronic Wasting Disease
CWD TSE Prion
Friday, February 05, 2016
TEXAS NEW CHRONIC WASTING DISEASE CWD CASE DISCOVERD AT CAPTIVE DEER
RELEASE SITE
Wednesday, April 27, 2016
WYOMING GAME AND FISH DEPARTMENT CHRONIC WASTING DISEASE MANAGEMENT PLAN
APRIL 22, 2016
Friday, April 22, 2016
Missouri MDC finds seven new cases of ChronicWasting Disease CWD during
past‐season testing
Wednesday, April 20, 2016
UTAH CHRONIC WASTING DISEASE CWD TSE PRION SURVEILLANCE AND TESTING PROGRAM
70 mule deer and two elk have tested positive
KANSAS CWD CASES ALARMING
Wednesday, March 02, 2016 Kansas Chronic Wasting Disease CWD TSE Prion 52
cases 2015 updated report 'ALARMING'
Tuesday, February 02, 2016
Illinois six out of 19 deer samples tested positive for CWD in the Oswego
zone of Kendall County
Thursday, March 31, 2016
*** Chronic Wasting Disease CWD TSE Prion Roundup USA 2016 ***
Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in
a Mule Deer
Thursday, April 07, 2016
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
Sheep and cattle may be exposed to CWD via common grazing areas with
affected deer but so far, appear to be poorly susceptible to mule deer CWD
(Sigurdson, 2008).
***In contrast, cattle are highly susceptible to white-tailed deer CWD and
mule deer CWD in experimental conditions but no natural CWD infections in cattle
have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how
susceptible humans are to CWD but given that the prion can be present in muscle,
it is likely that humans have been exposed to the agent via consumption of
venison (Sigurdson, 2008). Initial experimental research, however, suggests that
human susceptibility to CWD is low and there may be a robust species barrier for
CWD transmission to humans (Sigurdson, 2008). It is apparent, though, that CWD
is affecting wild and farmed cervid populations in endemic areas with some deer
populations decreasing as a result.
snip...
For the purpose of the qualitative risk assessment developed here it is
necessary to estimate the probability that a 30-ml bottle of lure contains urine
from an infected deer. This requires an estimate of the proportion of deer herds
in the USA which are infected with CWD together with the within herd
prevalence.
The distribution map of CWD in US shows it is present mainly in central
states (Figure 1). However, Virginia in the east of the country has recorded
seven recent cases of CWD (Anon 2015a). Some US manufacturers claim to take
steps to prevent urine being taken from infected animals eg by sourcing from
farms where the deer are randomly tested for CWD (Anon 2015a). However, if
disease is already present and testing is not carried out regularly, captive
populations are not necessarily disease free (Strausser 2014). Urine-based deer
lures have been known to be collected from domestic white-tailed deer herds and
therefore there is a recognised risk. This is reflected by 6 US States which
have
14
banned the use of natural deer urine for lures, as the deer urine may be
sourced from CWD-endemic areas in the USA as well as from areas free of CWD. For
example, the US State of Virginia is banning the use of urine-based deer lures
on July 2015 and Vermont from 2016 due to the risk of spread of CWD. Alaska
banned their use in 2012 (Anon 2015a). Pennsylvania Game Commission has banned
urine-based deer lures and acknowledged that there is no way to detect their use
(Strausser 2014). On the basis of unpublished data (J. Manson, Pers. Comm.) it
appears that up to 50% of deer herds can be infected with 80-90% of animals
infected within some herds.
*** It is therefore assumed that probability that a 30-ml bottle of deer
urine lure imported from the USA is sources from an infected deer is
medium.
SNIP...
In the USA, under the Food and Drug Administration’s BSE Feed Regulation
(21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin)
from deer and elk is prohibited for use in feed for ruminant animals. With
regards to feed for non-ruminant animals, under FDA law, CWD positive deer may
not be used for any animal feed or feed ingredients. ***For elk and deer
considered at high risk for CWD, the FDA recommends that these animals do not
enter the animal feed system. ***However, this recommendation is guidance and
not a requirement by law.
***Animals considered at high risk for CWD include:
***1) animals from areas declared to be endemic for CWD and/or to be CWD
eradication zones and
***2) deer and elk that at some time during the 60-month period prior to
slaughter were in a captive herd that contained a CWD-positive animal.
***Therefore, in the USA, materials from cervids other than CWD positive
animals may be used in animal feed and feed ingredients for non-ruminants. The
amount of animal PAP that is of deer and/or elk origin imported from the USA to
GB cannot be determined, however, as it is not specified in TRACES. It may
constitute a small percentage of the very low tonnage of non-fish origin
processed animal proteins that were imported from US into GB.
*** Overall, therefore, it is considered there is a greater than negligible
risk that (non-ruminant) animal feed and pet food containing deer and/or elk
protein is imported into GB. There is uncertainty associated with this estimate
given the lack of data on the amount of deer and/or elk protein possibly being
imported in these products.
SNIP...
Summary and MORE HERE ;
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
Tuesday, April 12, 2016
*** The first detection of Chronic Wasting Disease (CWD) in Europe
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
Greetings again FDA and Mr. Pritchett et al, I would kindly like to comment
on ; Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
#158
Guidance for Industry
Use of Material from Deer and Elk in Animal Feed
This version of the guidance replaces the version made available
September15, 2003.
This document has been revised to update the docket number, contact
information, and standard disclosures. Submit comments on this guidance at any
time.
Submit electronic comments to http://www.regulations.gov. Submit written
comments to the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments
should be identified with the Docket No. FDA-2003-D-0432 (formerly 03D-0186).
For further information regarding this guidance, contact Burt Pritchett,
Center for Veterinary Medicine (HFV-222), Food and Drug Administration, 7519
Standish Place, Rockville, MD 20855, 240-402-6276, E-mail:
burt.pritchett@fda.hhs.gov.
Additional copies of this guidance document may be requested from the
Policy and Regulations Staff (HFV-6), Center for Veterinary Medicine, Food and
Drug Administration, 7519 Standish Place, Rockville, MD 20855, and may be viewed
on the Internet at either http://www.fda.gov/AnimalVeterinary/default.htm
or http://www.regulations.gov.
U.S. Department of Health and Human Services Food and Drug Administration
Center for Veterinary Medicine March 2016
Contains Nonbinding Recommendations
2
Guidance for Industry Use of Material from Deer and Elk in Animal Feed
This guidance represents the current thinking of the Food and Drug
Administration (FDA or Agency) on this topic. It does not establish any rights
for any person and is not binding on FDA or the public. You can use an
alternative approach if it satisfies the requirements of the applicable statutes
and regulations. To discuss an alternative approach, contact the FDA office
responsible for this guidance as listed on the title page.
I. Introduction
Under FDA’s BSE feed regulation (21 CFR 589.2000) most material from deer
and elk is prohibited for use in feed for ruminant animals. This guidance
document describes FDA’s recommendations regarding the use in all animal feed of
all material from deer and elk that are positive for Chronic Wasting Disease
(CWD) or are considered at high risk for CWD. The potential risks from CWD to
humans or non-cervid animals such as poultry and swine are not well understood.
However, because of recent recognition that CWD is spreading rapidly in
white-tailed deer, and because CWD’s route of transmission is poorly understood,
FDA is making recommendations regarding the use in animal feed of rendered
materials from deer and elk that are CWD-positive or that are at high risk for
CWD.
In general, FDA’s guidance documents do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency’s current thinking on a
topic and should be viewed only as recommendations, unless specific regulatory
or statutory requirements are cited. The use of the word should in Agency
guidances means that something is suggested or recommended, but not required.
II. Background
CWD is a neurological (brain) disease of farmed and wild deer and elk that
belong in the animal family cervidae (cervids). Only deer and elk are known to
be susceptible to CWD by natural transmission. The disease has been found in
farmed and wild mule deer, white-tailed deer, North American elk, and in farmed
black-tailed deer. CWD belongs to a family of animal and human diseases called
transmissible spongiform encephalopathies (TSEs). These include bovine
spongiform encephalopathy (BSE or “mad cow” disease) in cattle; scrapie in sheep
and goats; and classical and variant Creutzfeldt-Jakob diseases (CJD and vCJD)
in humans. There is no known treatment for these diseases, and there is no
vaccine to prevent them. In addition, although validated postmortem diagnostic
tests are available, there are no validated diagnostic tests for CWD that can be
used to test for the disease in live animals.
Contains Nonbinding Recommendations
III. Use in animal feed of material from CWD-positive deer and elk
Material from CWD-positive animals may not be used in any animal feed or
feed ingredients. Pursuant to Sec. 402(a)(5) of the Federal Food, Drug, and
Cosmetic Act, animal feed and feed ingredients containing material from a
CWD-positive animal would be considered adulterated. FDA recommends that any
such adulterated feed or feed ingredients be recalled or otherwise removed from
the marketplace.
IV. Use in animal feed of material from deer and elk considered at high
risk for CWD Deer and elk considered at high risk for CWD include:
(1) animals from areas declared by State officials to be endemic for CWD
and/or to be CWD eradication zones; and
(2) deer and elk that at some time during the 60-month period immediately
before the time of slaughter were in a captive herd that contained a
CWD-positive animal.
FDA recommends that materials from deer and elk considered at high risk for
CWD no longer be entered into the animal feed system. Under present
circumstances, FDA is not recommending that feed made from deer and elk from a
non-endemic area be recalled if a State later declares the area endemic for CWD
or a CWD eradication zone. In addition, at this time, FDA is not recommending
that feed made from deer and elk believed to be from a captive herd that
contained no CWD-positive animals be recalled if that herd is subsequently found
to contain a CWD-positive animal.
V. Use in animal feed of material from deer and elk NOT considered at high
risk for CWD FDA continues to consider materials from deer and elk NOT
considered at high risk for CWD to be acceptable for use in NON-RUMINANT animal
feeds in accordance with current agency regulations, 21 CFR 589.2000. Deer and
elk not considered at high risk include:
(1) deer and elk from areas not declared by State officials to be endemic
for CWD and/or to be CWD eradication zones; and
(2) deer and elk that were not at some time during the 60-month period
immediately before the time of slaughter in a captive herd that contained a
CWD-positive animal.
3
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
Greetings again FDA and Mr. Pritchett et al,
MY comments and source reference of sound science on this very important
issue are as follows ;
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
I kindly wish to once again submit to Docket No. FDA-2003-D-0432 (formerly
03D-0186) Use of Material from Deer and Elk in Animal Feed.
Thank you kindly for allowing me to comment again, ...and again...and
again, on a topic so important, why it is ‘NON-BINDING’ is beyond me. this
should have been finalized and made ‘BINDING’ or MANDATORY OVER A DECADE AGO.
but here lay the problem, once made ‘BINDING’ or ‘MANDATORY’, it is still
nothing but ink on paper. we have had a mad cow feed ban in place since August
1997, and since then, literally 100s of millions of pounds BANNED MAD COW FEED
has been sent out to commerce and fed out (see reference materials). ENFORCEMENT
OF SAID BINDING REGULATIONS HAS FAILED US TOO MANY TIMES.
so, in my opinion, any non-binding or voluntary regulations will not work,
and to state further, ‘BINDING’ or MANDATORY regulations will not work unless
enforced. with that said, we know that Chronic Wasting Disease CWD TSE Prion
easily transmits to other cervid through the oral route. the old transmission
studies of BSE TSE floored scientist once they figured out what they had, and
please don’t forget about those mink that were fed 95%+ dead stock downer cow,
that all came down with TME.
please see ; It is clear that the designing scientists must also have
shared Mr Bradleys surprise at the results because all the dose levels right
down to 1 gram triggered infection.
it is clear that the designing scientists must have also shared Mr Bradleys
surprise at the results because all the dose levels right down to 1 gram
triggered infection.
Evidence That Transmissible Mink Encephalopathy Results from Feeding
Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult
mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or
dead dairy cattle...
*** PLEASE SEE THIS URGENT UPDATE ON CWD AND FEED ANIMAL PROTEIN ***
Sunday, March 20, 2016 Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use
of Material from Deer and Elk in Animal Feed ***UPDATED MARCH 2016*** Singeltary
Submission
Sunday, March 20, 2016
UPDATED MARCH 2016 URGENT Docket No. FDA-2003-D-0432 (formerly 03D-0186)
Use of Material from Deer and Elk in Animal Feed Singeltary Submission
Tuesday, April 19, 2016
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards
Singeltary Comment Submission
I strenuously once again urge the FDA and its industry constituents, to
make it MANDATORY that all ruminant feed be banned to all ruminants, and this
should include all cervids as soon as possible for the following
reasons...
======
In the USA, under the Food and Drug Administrations BSE Feed Regulation (21
CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from
deer and elk is prohibited for use in feed for ruminant animals. With regards to
feed for non-ruminant animals, under FDA law, CWD positive deer may not be used
for any animal feed or feed ingredients. For elk and deer considered at high
risk for CWD, the FDA recommends that these animals do not enter the animal feed
system.
***However, this recommendation is guidance and not a requirement by law.
======
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
see Singeltary comment ;
Thursday, March 31, 2016
*** Chronic Wasting Disease CWD TSE Prion Roundup USA 2016 ***
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
*** It also suggests a similar cause or source for atypical BSE in these
countries. ***
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. ***
see page 176 of 201 pages...tss
Thursday, April 14, 2016
*** Arizona 22 year old diagnosed with Creutzfeldt Jakob Disease CJD
Saturday, April 23, 2016
*** v-CJD prion distribution in the tissues of patients at preclinical and
clinical stage of the disease
Saturday, April 16, 2016
*** APHIS [Docket No. APHIS-2016-0029] Secretary's Advisory Committee on
Animal Health; Meeting May 2, 2016, and June 16, 2016 Singeltary Submission
***
Sunday, May 1, 2016
*** Center for Biologics Evaluation and Research 25th Meeting of: The
Transmissible Spongiform Encephalopathies Advisory Committee June 1, 2015
Transcript ***
FOOD AND DRUG ADMINISTRATION
Sunday, February 08, 2015
*** FDA SCIENCE BOARD TO THE FOOD AND DRUG ADMINISTRATION BOVINE HEPARIN
BSE CJD TSE PRION Wednesday, June 4, 2014 ***
Saturday, January 16, 2016
*** Revised Preventive Measures to Reduce the Possible Risk of Transmission
of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and
Blood Products Guidance for Industry
Thursday, November 12, 2015
Evaluation of the protection of primates transfused with variant
Creutzfeldt-Jakob disease–infected blood products filtered with prion removal
devices: a 5-year update
Tuesday, August 4, 2015
*** FDA U.S. Measures to Protect Against BSE ***
Thursday, August 13, 2015
Iatrogenic CJD due to pituitary-derived growth hormone with genetically
determined incubation times of up to 40 years
Thursday, January 23, 2014
Medical Devices Containing Materials Derived from Animal Sources (Except
for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]
Comment
Subject: BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM
BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01
Date: January 9, 2007 at 9:08 am PST
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
Comment from Terry S Singletary
This is a Comment on the Animal and Plant Health Inspection Service (APHIS)
Proposed Rule: Bovine Spongiform Encephalopathy; Minimal-Risk Regions,
Identification of Ruminants and Processing and Importation of Commodities
For related information, Open Docket Folder Docket folder icon
Comment
I IMPLORE, that due to the lack of surveillance and proper BSE/TSE
protocols for testing and surveillance, the fact that sporadic CJD in the USA
has tripled over the last few years or so, the new findings of BASE, the fact
that CWD and Scrapie are out of control in the USA, I IMPLORE that the BSE MRR
policy be repealed and the BSE GBR risk assessments revised to address all TSEs
i.e. TSE GBR, for the following reasons ;
----- Original Message -----
From: "Terry S. Singeltary Sr." flounder9@verizon.net
To: "EFSA Press" Press@efsa.europa.eu
Sent: Tuesday, November 21, 2006 12:21 PM
Subject: Re: re-Geographical BSE Risk: EFSA consults on revision of
assessment methodology
Greetings EFSA,
a sad day. i think any weakening of the BSE GBR risk assessments,
especially for USA, is a huge mistake. i think the BSE GBR should be revised to
include all TSE i.e. TSE GBR. The USA has the most documented TSE in all the
world, BSE/BASE?/Scrapie/CWD/TME, all of which has been rendered and fed back to
animals for human and animal consumption for decades, and still are. The USA is
still feeding cows to cows as lates as Oct. 2006;
besides the other tons and tons of recall of potential BSE/BASE/TSE feed in
the USA in 2006;
see full text ;
FSIS, USDA, REPLY TO SINGELTARY
Comment from Terry Singeltary
This is a Comment on the Food and Drug Administration (FDA) Notice: Draft
Guidance for Industry on Ensuring Safety of Animal Feed Maintained and Fed
On-Farm; Availability
For related information, Open Docket Folder Docket folder icon
Comment from Terry Singeltary
This is a Comment on the Animal and Plant Health Inspection Service (APHIS)
Notice: Environmental Impact Statements; Availability, etc.: Animal Carcass
Management
Comment from Terry Singeltary This is a Comment on the Animal and Plant
Health Inspection Service (APHIS) Proposed Rule: Scrapie in Sheep and
Goats
For related information, Open Docket Folder Docket folder icon
Show agency attachment(s) AttachmentsView All (0)
Comment View document:
Indeed, much science has changed about the Scrapie TSE prion, including
more science linking Scrapie to humans. sadly, politics, industry, and trade,
have not changed, and those usually trump sound science, as is the case with all
Transmissible Spongiform Encephalopathy TSE Prion disease in livestock producing
animals and the OIE. we can look no further at the legal trading of the Scrapie
TSE prion both typical and atypical of all strains, and CWD all stains. With as
much science of old, and now more new science to back this up, Scrapie of all
types i.e. atypical and typical, BSE all strains, and CWD all strains, should be
regulated in trade as BSE TSE PRION. In fact, I urge APHIS et al and the OIE,
and all trading partners to take heed to the latest science on the TSE prion
disease, all of them, and seriously reconsider the blatant disregards for human
and animal health, all in the name of trade, with the continued relaxing of TSE
Prion trade regulations through the 'NEGLIGIBLE BSE RISK' PROGRAM, which was set
up to fail in the first place. If the world does not go back to the 'BSE RISK
ASSESSMENTS', enhance, and or change that assessment process to include all TSE
prion disease, i.e. 'TSE RISK ASSESSMENT', if we do not do this and if we
continue this farce with OIE and the USDA et al, and the 'NEGLIGIBLE BSE RISK'
PROGRAM, we will never eradicate the TSE prion aka mad cow type disease, they
will continue to mutate and spread among species of human and animal origin, and
they will continue to kill. ...
please see ;
AttachmentsView All (1) scrapie-usa-blogspot-com View Attachment:
Comment from Terry S. Singeltary Sr. Return to Docket Folder Summary This
is a Comment on the Food and Drug Administration (FDA) Notice:
Risk Assessment of Foodborne Illness Associated With Pathogens From Produce
Grown in Fields Amended With Untreated Biological Soil Amendments of Animal
Origin; Request for Scientific Data, Information, and Comments
Show agency attachment(s) AttachmentsView All (0)
Comment View document:Greetings FDA et al, I kindly would like to make
comment submission to ;
Docket No. FDA-2016-N-0321 Risk Assessment of Foodborne Illness Associated
with Pathogens from Produce Grown in Fields Amended with Untreated Biological
Soil Amendments of Animal Origin; Request for Comments, Scientific Data, and
Information
A Notice by the Food and Drug Administration on 03/04/2016
MY comment as follows,
There has been proven documented risk for Untreated Biological Soil
Amendments of Animal Origin and risk of transmitting Transmissible Spongiform
Encephalopathy TSE Prion disease aka mad cow type disease such as the typical
and atypical Bovine Spongiform Encephalopathy strains, typical and atypical
Scrapie strains, typical and atypical Chronic Wasting Disease CWD strains, and
even the Transmissible Mink Encephalopathy TME Prion disease.
Science has shown that infected deer harbor and shed high levels of
infectious prions in saliva, blood, urine, and feces thereby leading to
transmission by direct contact and environmental contamination.
Ingestion of prion contaminated leaves and roots produced disease with a
100% attack rate and an incubation period not substantially longer than feeding
animals directly with scrapie brain homogenate.
Plants can uptake prions from contaminated soil and transport them to
different parts of the plant tissue (stem and leaves) [please see data from Soto
et al Prion2015 Conference below in Science reference data].
Also, Detection of protease-resistant cervid prion protein in water from a
CWD-endemic area is very concerning.
Science has shown that soil plays a role in the spreading and transmission
of the CWD and Scrapie TSE prion agent.
For these reason and more (see reference materials) I urge the FDA to stop
this practice of Untreated Biological Soil Amendments of Animal Origin,
including blood, for use on our produce grown in fields, for the following
reasons,
please see attachments and updated TSE Prion science on these very
important matters here (I do not advertise or make money the science is there
for educational use for Transmissible Spongiform Encephalopathy TSE Prion
disease.
just made a promise to mom dod 12/14/97 confirmed Heidenhain Variant
Creutzfeldt Jakob Disease, hvCJD. ...
AttachmentsView All (1)
Comment from Terry S Singeltary Sr View Attachment: https://www.regulations.gov/#!documentDetail;D=FDA-2016-N-0321-0005
Tuesday, March 15, 2016 Docket No. FDA-2016-N-0321
Risk Assessment of Foodborne Illness Associated with Pathogens from Produce
Grown in Fields Amended with Untreated Biological Soil Amendments of Animal
Origin; Request for Comments, Scientific Data, and Information
Singeltary Submission
Thursday, February 25, 2016
U.S. Food & Drug Administration (FDA) FDA/CFSAN Cosmetics Update:
Cosmetics Program; Import and Domestic and Transmissible Spongiform
Encephalopathy TSE Prion Disease Risk Factors
***WARNING TO ALL CONSUMERS AND COUNTRIES AROUND THE WORLD***
***Note: FDA labs do not conduct BSE analysis and thus no sampling guidance
is issued for BSE. ***
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
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
Wednesday, December 11, 2013
*** Detection of Infectivity in Blood of Persons with Variant and Sporadic
Creutzfeldt-Jakob Disease ***
Saturday, December 12, 2015
CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015
BSE INQUIRY DFAs
Sunday, May 18, 2008
BSE Inquiry DRAFT FACTUAL ACCOUNTS DFA's
Sunday, May 18, 2008
BSE, CJD, and Baby foods (the great debate 1999 to 2005)
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
http://web.archive.org/web/20060517075135/http://www.bseinquiry.gov.uk/files/mb/m11g/tab04.pdf
http://bseinquiry.blogspot.com/2008/05/mad-cow-disease-bse-cjd-children.html
with reference to vaccine blunders, some might find interest here ;
8. The Secretary of State has a number of licences. We understand that the
inactivated polio vaccine is no longer being used. There is a stock of smallpox
vaccine. We have not been able to determine the source material. (Made in sheep
very unlikely to contain bovine ingredients).
CONFIDENTIAL
5.3.3 The greatest risk, in theory, would be from parenteral injection of
material derived from bovine brain or lymphoid tissue. Medicinal products for
injection or surgical implantation which are prepared from bovine tissues, or
which utilise bovine serum albumin or similar agents in their manufacture, might
also be capable of transmitting infectious agents. All medicinal products are
licensed under the Medicines Act by the Licensing Authority following guidance,
for example from the Committee on Safety of Medicines (CSM), the Committee on
Dental and Surgical Materials (CDSM) and their subcommittees. The Licensing
Authority have been alerted to potential concern about BSE in medicinal products
and will ensure that scrutiny of source materials and manufacturing processes
now takes account of BSE agent.
see all 76 pages ;
8. The Secretary of State has a number of licences. We understand that the
inactivated polio vaccine is no longer being used. There is a stock of smallpox
vaccine. We have not been able to determine the source material. (Made in sheep
very unlikely to contain bovine ingredients).
3. _________ have measles, mumps, MMR, rubella vaccines. These are sourced
from the USA and the company believes that US material only used.
CONFIDENTIAL
Scrapie Louping-ill vaccine blunder
MANAGEMENT IN CONFIDENCE
CERTIFIED BSE-FREE HERDS FOR SOURCE OF MATERIAL FOR BIOLOGICAL
PRODUCTS
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
Greetings List Members,
I was lucky enough to sit in on this BSE conference call today and even
managed to ask a question. that is when the trouble started.
I submitted a version of my notes to Sandra Blakeslee of the New York
Times, whom seemed very upset, and rightly so.
"They tell me it is a closed meeting and they will release whatever
information they deem fit. Rather infuriating."
and i would have been doing just fine, until i asked my question. i was
surprised my time to ask a question so quick.
(understand, these are taken from my notes for now. the spelling of names
and such could be off.)
[host Richard Barns] and now a question from Terry S. Singeltary of CJD
Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for
serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have
him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue
donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD
world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
snip...see full text ;
The documents below were provided by Terry S. Singeltary Sr on 8 May 2000.
They are optically character read (scanned into computer) and so may contain
typos and unreadable parts.
TIP740203/l 0424 CONFIDENTIAL
Mr Cunningham CMP3 From: D O Hagger MBI Dr Salisbury MED/IMCD3 Mr Burton
PD/STB/PG1B B/17/2 Date: 15.02.1989 Mr Dudley PD/AD4
BOVINE SPONGIFORM ENCEPHALOPATHY
1. The purpose of this minute is to alert you to recent developments on BSE
as they affect medicines and to invite representatives to a meeting in Market
Towers on 22 February 1989.
40,000 human heart valves a year from BSE herds Sun, 3 Sep 2000.
Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary
Sr. of Bacliff, Texas
‘’I shall not forget the profound effect on my emotions when I visited
these farms and was warmly welcomed because of the great benefits resulting from
the application of louping-ill vaccine, wheras the chief purpose of my visit was
to determine if scrapie was appearing in the inoculated sheep. The enquiry made
the position clear. Scrapie was developing in the sheep vaccinated in 1935 and
it was only in a few instances that the owner was associating the occurrence
with louping-ill vaccination. The disease was affecting all breeds and it was
confined to the animals vaccinated with batch 2.’’
KURU Transmissible Spongiform Encephalopthy TSE Prion Disease
*** Kuru Video ***
Kuru: The Science and The Sorcery
*** Scrapie Video
*** Human Mad Cow Video
*** USA sporadic CJD MAD COW DISEASE HAS HUGE PROBLEM Video
2001 FDA CJD TSE Prion Singeltary Submission TSEAC
1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes
contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a
middle aged woman with progressive dementia were previously implicated in the
accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger
patients. The diagnoses of CJD have been confirmed for all three cases. More
than two years after their last use in humans, after three cleanings and
repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were
implanted in the cortex of a chimpanzee. Eighteen months later the animal became
ill with CJD. This finding serves to re-emphasise the potential danger posed by
reuse of instruments contaminated with the agents of spongiform
encephalopathies, even after scrupulous attempts to clean them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
PLEASE REMEMBER, IN 55 YEARS AND OLDER, THE RATE OF DOCUMENTED CJD JUMPS TO
ONE IN 9,000. but officials don’t tell you that either. carry on...
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.
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?
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
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 ...
no need to print this, you will be laughed at like I have been for almost
two decades...terry
Terry S. Singeltary Sr.
Evidence for human transmission of amyloid-β pathology and cerebral amyloid
angiopathy
07 02:27 AM
Terry S. Singeltary Sr. said:
re-Evidence for human transmission of amyloid-β pathology and cerebral
amyloid angiopathy
2015-12-07 02:27 AM
Terry S. Singeltary Sr. said: re-Evidence for human transmission of
amyloid-β pathology and cerebral amyloid angiopathy
Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26
April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated
online 11 September 2015 Erratum (October, 2015)
I would kindly like to comment on the Nature Paper, the Lancet reply, and
the newspaper articles.
First, I applaud Nature, the Scientist and Authors of the Nature paper, for
bringing this important finding to the attention of the public domain, and the
media for printing said findings.
Secondly, it seems once again, politics is getting in the way possibly of
more important Transmissible Spongiform Encephalopathy TSE Prion scientific
findings. findings that could have great implications for human health, and
great implications for the medical surgical arena. but apparently, the
government peer review process, of the peer review science, tries to intervene
again to water down said disturbing findings.
where have we all heard this before? it’s been well documented via the BSE
Inquiry. have they not learned a lesson from the last time?
we have seen this time and time again in England (and other Country’s) with
the BSE mad cow TSE Prion debacle.
That ‘anonymous' Lancet editorial was disgraceful. The editor, Dick Horton
is not a scientist.
The pituitary cadavers were very likely elderly and among them some were on
their way to CJD or Alzheimer's. Not a bit unusual. Then the recipients who got
pooled extracts injected from thousands of cadavers were 100% certain to have
been injected with both seeds. No surprise that they got both diseases going
after thirty year incubations.
That the UK has a "system in place to assist science journalists" to squash
embargoed science reports they find ‘alarming’ is pathetic.
Sounds like the journalists had it right in the first place: ‘Alzheimer’s
may be a transmissible infection’ in The Independent to ’You can catch
Alzheimer’s’ in The Daily Mirror or ‘Alzheimer’s bombshell" in The Daily
Express.
if not for the journalist, the layperson would not know about these
important findings.
where would we be today with sound science, from where we were 30 years
ago, if not for the cloak of secrecy and save the industry at all cost
mentality?
when you have a peer review system for science, from which a government
constantly circumvents, then you have a problem with science, and humans die.
to date, as far as documented body bag count, with all TSE prion named to
date, that count is still relatively low (one was too many in my case, Mom
hvCJD), however that changes drastically once the TSE Prion link is made with
Alzheimer’s, the price of poker goes up drastically.
so, who makes that final decision, and how many more decades do we have to
wait?
the iatrogenic mode of transmission of TSE prion, the many routes there
from, load factor, threshold from said load factor to sub-clinical disease, to
clinical disease, to death, much time is there to spread a TSE Prion to
anywhere, but whom, by whom, and when, do we make that final decision to do
something about it globally? how many documented body bags does it take? how
many more decades do we wait? how many names can we make up for one disease, TSE
prion?
Professor Collinge et al, and others, have had troubles in the past with
the Government meddling in scientific findings, that might in some way involve
industry, never mind human and or animal health.
FOR any government to continue to circumvent science for monetary gain,
fear factor, or any reason, shame, shame on you.
in my opinion, it’s one of the reasons we are at where we are at to date,
with regards to the TSE Prion disease science i.e. money, industry, politics,
then comes science, in that order.
greed, corporate, lobbyist there from, and government, must be removed from
the peer review process of sound science, it’s bad enough having them in the
pharmaceutical aspect of healthcare policy making, in my opinion.
my mother died from confirmed hvCJD, and her brother (my uncle) Alzheimer’s
of some type (no autopsy?). just made a promise, never forget, and never let
them forget, before I do.
I kindly wish to remind the public of the past, and a possible future we
all hopes never happens again. ...
[9. Whilst this matter is not at the moment directly concerned with the
iatrogenic CJD cases from hgH, there remains a possibility of litigation here,
and this presents an added complication. There are also results to be made
available shortly (1) concerning a farmer with CJD who had BSE animals, (2) on
the possible transmissibility of Alzheimer’s and (3) a CMO letter on prevention
of iatrogenic CJD transmission in neurosurgery, all of which will serve to
increase media interest.]
snip...see full Singeltary Nature comment here;
see Singeltary comments to Plos ;
Subject: 1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO
PRIMATES POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN
BSE101/1 0136
IN CONFIDENCE
CMO
From: . Dr J S Metiers DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have
recognised the public sensitivity of these findings and intend to report them in
their proper context. 'This hopefully will avoid misunderstanding and possible
distortion by the media to portray the results as having more greater
significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection)
the researchers have demonstrated the transmission of a pathological process
from two cases one of severe Alzheimer's disease the other of
Gerstmann-Straussler disease to marmosets. However they have not demonstrated
the transmission of either clinical condition as the "animals were behaving
normally when killed". As the report emphasises the unanswered question is
whether the disease condition would have revealed itself if the marmosets had
lived longer. They are planning further research to see if the conditions, as
opposed to the partial pathological process, is transmissible.
what are the implications for public health?
3. The route 'of transmission is very specific and in the natural state of
things highly unusual. However it could be argued that the results reveal a
potential risk, in that brain tissue from these two patients has been shown to
transmit a pathological process. Should therefore brain tissue from such cases
be regarded as potentially infective? Pathologists, morticians, neuro surgeons
and those assisting at neuro surgical procedures and others coming into contact
with "raw" human brain tissue could in theory be at risk. However, on a priori
grounds given the highly specific route of transmission in these experiments
that risk must be negligible if the usual precautions for handling brain tissue
are observed.
1
92/11.4/1.1
BSE101/1 0137
4. The other dimension to consider is the public reaction. To some extent
the GSS case demonstrates little more than the transmission of BSE to a pig by
intra-cerebral injection. If other prion diseases can be transmitted in this way
it is little surprise that some pathological findings observed in GSS were also
transmissible to a marmoset. But the transmission of features of Alzheimer's
pathology is a different matter, given the much greater frequency of this
disease and raises the unanswered question whether some cases are the result of
a transmissible prion. The only tenable public line will be that "more research
is required’’ before that hypothesis could be evaluated. The possibility on a
transmissible prion remains open. In the meantime MRC needs carefully to
consider the range and sequence of studies needed to follow through from the
preliminary observations in these two cases. Not a particularly comfortable
message, but until we know more about the causation of Alzheimer's disease the
total reassurance is not practical.
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH
832 llllYc!eS 2 92/11.4/1.2
>>> The only tenable public line will be that "more research is
required’’ <<<
>>> possibility on a transmissible prion remains
open<<<
O.K., so it’s about 23 years later, so somebody please tell me, when is
"more research is required’’ enough time for evaluation ?
Self-Propagative Replication of Ab Oligomers Suggests Potential
Transmissibility in Alzheimer Disease
*** Singeltary comment PLoS ***
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
Sunday, November 22, 2015
*** Effect of heating on the stability of amyloid A (AA) fibrils and the
intra- and cross-species transmission of AA amyloidosis Abstract
Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by
extracellular deposition of AA fibrils. AA fibrils are found in several tissues
from food animals with AA amyloidosis. For hygienic purposes, heating is widely
used to inactivate microbes in food, but it is uncertain whether heating is
sufficient to inactivate AA fibrils and prevent intra- or cross-species
transmission. We examined the effect of heating (at 60 °C or 100 °C) and
autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western
blot analysis, transmission electron microscopy (TEM), and mouse model
transmission experiments. TEM revealed that a mixture of AA fibrils and
amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at
135 °C produced large amorphous aggregates. AA fibrils retained antigen
specificity in Western blot analysis when heated at 100 °C or autoclaved at 121
°C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and
bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly
stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA
fibrils at 121 °C or 135 °C significantly decreased amyloid deposition.
Moreover, amyloid deposition in mice injected with murine AA fibrils was more
severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils
autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These
results suggest that AA fibrils are relatively heat stable and that similar to
prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA
fibrils. These findings may contribute to the prevention of AA fibril
transmission through food materials to different animals and especially to
humans.
Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD
54.00
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes
contaminated during neurosurgery ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a
middle aged woman with progressive dementia were previously implicated in the
accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger
patients. The diagnoses of CJD have been confirmed for all three cases. More
than two years after their last use in humans, after three cleanings and
repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were
implanted in the cortex of a chimpanzee. Eighteen months later the animal became
ill with CJD. This finding serves to re-emphasise the potential danger posed by
reuse of instruments contaminated with the agents of spongiform
encephalopathies, even after scrupulous attempts to clean them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
the warning shots fired over the bow of the boat that were never heard ;
PITUITARY EXTRACT
This was used to help cows super ovulate. This tissue was considered to be
of greatest risk of containing BSE and consequently transmitting the disease...
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
snip...
I was quite prepared to believe in unofficial pituitary hormones, also in
the 1970's, whether as described by Dr. Little, or in other circumstances, for
animal use.
snip...
The fact that there were jars of pituitaries (or extract) around on shelves
is attested by the still potent 1943 pituitaries, described in Stockell Hartree
et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the
trouble to collect them, they were not lightly thrown out...
3. The extraction is from a pool of pituitary glands collected from
abbatoirs and the process used is unlikely to have any effect on the BSE agent.
Hormones extracted from human pituitary glands have been responsible for a small
number of Creutzfeldt Jacob disease in man.
SEE LOOPHOLE ;
SEE LOOPHOLE SHOULD BE CLOSED ;
Singeltary Submissions to Plos and Nature...
26/01/2016
Alzheimer-type brain pathology may be transmitted by grafts of dura mater
26/01/2016
Sunday, January 17, 2016
Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease
2001 FDA CJD TSE Prion Singeltary Submission
Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net
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