PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS
THANK YOU PRION 2015 TAYLOR & FRANCIS, Professor Chernoff, and
Professor Aguzzi et al, for making these PRION 2015 Congressional Poster and
Oral Abstracts available freely to the public. ...Terry S. Singeltary Sr.
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, Val erie 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 longe 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...TSS
===============
O.08: H-type bovine spongiform encephalopathy associated with E211K prion
protein polymorphism: Clinical and pathologic features in wild-type and E211K
cattle following intracranial inoculation
S Jo Moore, M Heather West Greenlee, Jodi Smith, Eric Nicholson, Cathy
Vrentas, and Justin Greenlee United States Department of Agriculture; Ames, IA
USA
In 2006 an H-type bovine spongiform encephalopathy (BSE) case was reported
in an animal with an unusual polymorphism (E211K) in the prion protein gene.
Although the prevalence of this polymorphism is low, cattle carrying the K211
allele are predisposed to rapid onset of H-type BSE when exposed. The purpose of
this study was to investigate the phenotype of this BSE strain in wild-type
(E211E) and E211K heterozygous cattle. One calf carrying the wild-type allele
and one E211K calf were inoculated intracranially with H-type BSE brain
homogenate from the US 2006 case that also carried one K211 allelle. In
addition, one wild-type calf and one E211K calf were inoculated intracranially
with brain homogenate from a US 2003 classical BSE case. All animals succumbed
to clinical disease. Survival times for E211K H-type BSE inoculated catttle (10
and 18 months) were shorter than the classical BSE inoculated cattle (both 26
months). Significant changes in retinal function were observed in H-type BSE
challenged cattle only. Animals challenged with the same inoculum showed similar
severity and neuroanatomical distribution of vacuolation and disease-associated
prion protein deposition in the brain, though differences in neuropathology were
observed between E211K H-type BSE and classical BSE inoculated animals. Western
blot results for brain tissue from challenged animals were consistent with the
inoculum strains. ***This study demonstrates that the phenotype of E211K H-type
BSE remains stable when transmitted to cattle without the E211K polymorphism,
and exhibits a number of features that differ from classical BSE in both
wild-type and E211K cattle.
==============
***This study demonstrates that the phenotype of E211K H-type BSE remains
stable when transmitted to cattle without the E211K polymorphism, and exhibits a
number of features that differ from classical BSE in both wild-type and E211K
cattle.***
PLEASE SEE ;
Wednesday, May 27, 2015
BSE Case Associated with Prion Protein Gene Mutation
==============
P.108: Successful oral challenge of adult cattle with classical BSE
Sandor Dudas1,*, Kristina Santiago-Mateo1, Tammy Pickles1, Catherine
Graham2, and Stefanie Czub1 1Canadian Food Inspection Agency; NCAD Lethbridge;
Lethbridge, Alberta, Canada; 2Nova Scotia Department of Agriculture; Pathology
Laboratory; Truro, Nova Scotia, Canada
Classical Bovine spongiform encephalopathy (C-type BSE) is a feed- and
food-borne fatal neurological disease which can be orally transmitted to cattle
and humans. Due to the presence of contaminated milk replacer, it is generally
assumed that cattle become infected early in life as calves and then succumb to
disease as adults.
Here we challenged three 14 months old cattle per-orally with 100 grams of
C-type BSE brain to investigate age-related susceptibility or resistance. During
incubation, the animals were sampled monthly for blood and feces and subjected
to standardized testing to identify changes related to neurological
disease.
At 53 months post exposure, progressive signs of central nervous system
disease were observed in these 3 animals, and they were euthanized. Two of the
C-BSE animals tested strongly positive using standard BSE rapid tests, however
in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not
detected using rapid tests for BSE. Subsequent testing resulted in the detection
of pathologic lesion in unusual brain location and PrPsc detection by PMCA
only.
Our study demonstrates susceptibility of adult cattle to oral transmission
of classical BSE. We are further examining explanations for the unusual disease
presentation in the third challenged animal.
========================
***Our study demonstrates susceptibility of adult cattle to oral
transmission of classical BSE. ***
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA
and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, ***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.
================
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. ***
ALSO, PLEASE SEE ;
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
================
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
The propensity for trans-species prion transmission is related to the
structural characteristics of the enciphering and heterologous PrP, but the
exact mechanism remains mostly mysterious. Studies of the effects of primary or
tertiary prion protein structures on trans-species prion transmission have
relied primarily upon animal bioassays, making the influence of prion protein
structure vs. host co-factors (e.g. cellular constituents, trafficking, and
innate immune interactions) difficult to dissect. As an alternative strategy, we
used real-time quakinginduced conversion (RT-QuIC) to investigate trans-species
prion conversion.
To assess trans-species conversion in the RT-QuIC system, we compared
chronic wasting disease (CWD) and bovine spongiform encephalopathy (BSE) prions,
as well as feline CWD (fCWD) and feline spongiform encephalopathy (FSE). Each
prion was seeded into each host recombinant PrP (full-length rPrP of
white-tailed deer, bovine or feline). We demonstrated that fCWD is a more
efficient seed for feline rPrP than for white-tailed deer rPrP, which suggests
adaptation to the new host.
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 protein:protein interactions, the barrier preventing transmission of CWD to
humans is less robust than previously estimated.
================
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.***
================
Willingham, Erin McNulty, Kelly Anderson, Jeanette Hayes-Klug, Amy Nalls,
and Candace Mathiason Colorado State University; Fort Collins, CO USA
Chronic wasting disease (CWD) is the transmissible spongiform
encephalopathy (TSE), of free-ranging and captive cervids (deer, elk and moose).
The presence of infectious prions in the tissues, bodily fluids and
environments of clinical and preclinical CWD-infected animals is thought to
account for its high transmission efficiency. Recently it has been recognized
that mother to offspring transmission may contribute to the facile transmission
of some TSEs. Although the mechanism behind maternal transmission is not yet
known, the extended asymptomatic TSE carrier phase (lasting years to decades)
suggests that it may have implications in the spread of prions.
Placental trafficking and/or secretion in milk are 2 means by which
maternal prion transmission may occur. In these studies we explore these avenues
during early and late infection using a transgenic mouse model expressing cervid
prion protein. Na€ıve and CWD-infected dams were bred at both timepoints, and
were allowed to bear and raise their offspring. Milk was collected from the dams
for prion analysis, and the offspring were observed for TSE disease progression.
Terminal tissues harvested from both dams and offspring were analyzed for
prions.
We have demonstrated that
(1) CWDinfected TgCerPRP females successfully breed and bear offspring, and
(2) the presence of PrPCWD in reproductive and mammary tissue from
CWD-infected dams.
We are currently analyzing terminal tissue harvested from offspring born to
CWD-infected dams for the detection of PrPCWD and amplification competent
prions. These studies will provide insight into the potential mechanisms and
biological significance associated with mother to offspring transmission of
TSEs.
==============
P.157: Uptake of prions into plants
Christopher Johnson1, Christina Carlson1, Matthew Keating1,2, Nicole
Gibbs1, Haeyoon Chang1, Jamie Wiepz1, and Joel Pedersen1 1USGS National Wildlife
Health Center; Madison, WI USA; 2University of Wisconsin - Madison; Madison, WI
USA
Soil may preserve chronic wasting disease (CWD) and scrapie infectivity in
the environment, making consumption or inhalation of soil particles a plausible
mechanism whereby na€ıve animals can be exposed to prions. Plants are known to
absorb a variety of substances from soil, including whole proteins, yet the
potential for plants to take up abnormal prion protein (PrPTSE) and preserve
prion infectivity is not known. In this study, we assessed PrPTSE uptake into
roots using laser scanning confocal microscopy with fluorescently tagged PrPTSE
and we used serial protein misfolding cyclic amplification (sPMCA) and detect
and quantify PrPTSE levels in plant aerial tissues. Fluorescence was identified
in the root hairs of the model plant Arabidopsis thaliana, as well as the crop
plants alfalfa (Medicago sativa), barley (Hordeum vulgare) and tomato (Solanum
lycopersicum) upon exposure to tagged PrPTSE but not a tagged control
preparation. Using sPMCA, we found evidence of PrPTSE in aerial tissues of A.
thaliana, alfalfa and maize (Zea mays) grown in hydroponic cultures in which
only roots were exposed to PrPTSE. Levels of PrPTSE in plant aerial tissues
ranged from approximately 4 £ 10 ¡10 to 1 £ 10 ¡9 g PrPTSE g ¡1 plant dry weight
or 2 £ 105 to 7 £ 106 intracerebral ID50 units g ¡1 plant dry weight. Both stems
and leaves of A. thaliana grown in culture media containing prions are
infectious when intracerebrally-injected into mice. ***Our results suggest that
prions can be taken up by plants and that contaminated plants may represent a
previously unrecognized risk of human, domestic species and wildlife exposure to
prions.
===========
***Our results suggest that prions can be taken up by plants and that
contaminated plants may represent a previously unrecognized risk of human,
domestic species and wildlife exposure to prions.***
SEE ;
Friday, May 15, 2015 Grass Plants Bind, Retain, Uptake, and Transport
Infectious Prions
Report
============
P.19: Characterization of chronic wasting disease isolates from freeranging
deer (Odocoileus sp) in Alberta and Saskatchewan, Canada
Camilo Duque Velasquez1, Chiye Kim1, Nathalie Daude1, Jacques van der
Merwe1, Allen Herbst1, Trent Bollinger2, Judd Aiken1, and Debbie McKenzie1
1Centre for Prions and Protein Folding Diseases; University of Alberta;
Edmonton, Canada; 2Western College of Veterinary Medicine; University of
Saskatchewan; Saskatoon, Canada
Chronic wasting disease (CWD) is an emerging prion disease of free ranging
and captive species of Cervidae. In North America, CWD is enzootic in some wild
cervid populations and can circulate among different deer species. The
contagious nature of CWD prions and the variation of cervid PRNP alleles, which
influence host susceptibility, can result in the emergence and adaptation of
different CWD strains. These strains may impact transmission host range, disease
diagnosis, spread dynamics and efficacy of potential vaccines. We are
characterizing different CWD agents by biochemical analysis of the PrPCWD
conformers, propagation in vitro cell assays1 and by comparing transmission
properties and neuropathology in Tg33 (Q95G96) and Tg60 (Q95S96) mice.2 Although
Tg60 mice expressing S96- PrPC have been shown resistant to CWD infectivity from
various cervid species,2,3
***these transgenic mice are susceptible to H95 C CWD, a CWD strain derived
from experimental infection of deer expressing H95G96-PrPC. The diversity of
strains present in free-ranging mule deer (Odocoileus hemionus) and white-tailed
deer (Odocoileus virginianus) from Alberta and Saskatchewan is being determined
and will allow us to delineate the properties of CWD agents circulating in CWD
enzootic cervid populations of Canada.
References
1. van der Merwe J, Aiken J, Westaway D, McKenzie D. The standard scrapie
cell assay: Development, utility and prospects. Viruses 2015; 7(1):180–198;
PMID:25602372; http://dx.doi.org/10.3390/v7010180
2. Meade-White K, Race B, Trifilo M, Bossers A, Favara C, Lacasse R, Miller
M, Williams E, Oldstone M, Race R, Chesebro B. Resistance to chronic wasting
disease in transgenic mice expressing a naturally occurring allelic variant of
deer prion protein. J Virol 2007; 81(9):4533–4539; PMID: 17314157; http://dx. doi.org/10.1128/JVI.02762-06
3. Race B, Meade-White K, Miller MW, Fox KA, Chesebro B. In vivo comparison
of chronic wasting disease infectivity from deer with variation at prion protein
residue 96. J Virol 2011; 85(17):9235–9238; PMID: 21697479; http://dx.doi.org/10.1128/JVI.00790-11
=========
***these transgenic mice are susceptible to H95 C CWD, a CWD strain derived
from experimental infection of deer expressing H95G96-PrPC.
==========
P.136: Mother to offspring transmission of CWD—Detection in fawn tissues
using the QuIC assay
Amy Nalls, Erin McNulty, Clare Hoover, Jeanette Hayes-Klug, Kelly Anderson,
Edward Hoover, and Candace Mathiason Colorado State University; Fort Collins, CO
USA
To investigate the role mother to offspring transmission plays in chronic
wasting disease (CWD), we have employed a small, polyestrous breeding, indoor
maintainable cervid model, the Reeves’ muntjac deer. Muntjac doe were inoculated
with CWD and tested positive by lymphoid biopsy at 4 months post inoculation.
From these CWD-infected doe, we obtained 3 viable fawns. These fawns tested
IHC-positive for CWD by lymphoid biopsy as early as 40 d post birth, and all
have been euthanized due to clinical disease at 31, 34 and 59 months post birth.
The QuIC assay demonstrates sensitivity and specificity in the detection of
conversion competent prions in peripheral IHC-positive tissues including tonsil,
mandibular, partotid, retropharyngeal, and prescapular lymph nodes, adrenal
gland, spleen and liver. In summary, using the muntjac deer model, we have
demonstrated CWD clinical disease in offspring born to CWD-infected doe and
found that the QuIC assay is an effective tool in the detection of prions in
peripheral tissues. ***Our findings demonstrate that transmission of prions from
mother to offspring can occur, and may be underestimated for all prion
diseases.
===============
***Our findings demonstrate that transmission of prions from mother to
offspring can occur, and may be underestimated for all prion diseases.
SEE ;
Friday, April 24, 2015
The placenta shed from goats with classical scrapie is infectious to goat
kids and lambs
Tuesday, September 17, 2013
Mother to Offspring Transmission of Transmissible Spongiform Encephalopathy
TSE prion disease
================
P.139: Tissue distribution and in utero transmission of chronic-wasting
diseaseassociated prions in free-ranging Rocky Mountain elk
Anca Selariu1, Jenny G Powers2, Margaret A Wild2, Monica Brandhuber1, Amber
Mayfield1, Stephenie Fullaway1, Amy Nalls1, Edward A Hoover1, and Candace K
Mathiason1 1Prion Research Center; Department of Microbiology, Immunology, and
Pathology; College of Veterinary Medicine and Biomedical Sciences; Colorado
State University; Fort Collins, CO USA; 2National Park Service; Biological
Resources Division; Fort Collins, CO USA
The presence of disease-associated prions in tissues and bodily fluids of
chronic wasting disease (CWD)-infected cervid has received much investigation,
yet little is known about CWD mother to offspring transmission. Our previous
work demonstrated that mother to offspring transmission is efficient in an
experimental setting (34). To address the question of relevance in a
naturally-exposed free-range population, we have assessed maternal and fetal
tissues derived from 19 elk dam-calf pairs harvested from Rocky Mountain
National Park (RMNP), a known CWD endemic region. Conventional
immunohistochemistry (IHC) identified 3/19 CWD positive dams, whereas a more
sensitive assay – the serial protein misfolding cyclic amplification (sPMCA) –
detected cervid prions (PrPCWD) in 15/19 dams. PrPCWD tissue distribution, as
demonstrated by sPMCA, was widespread and included the central nervous system
(CNS), lymphoreticular system (LRS), reproductive, secretory, excretory and
adipose tissues. Interestingly, 5 of the 15 sPMCA positive dams showed no
evidence of PrPCWD in either CNS or LRS, sites typically assessed in diagnosing
CWD. Analysis of fetal tissues harvested from the 15 sPMCA positive dams
revealed PrPCWD in 80% of fetuses (12/15), regardless of gestational stage.
***These findings demonstrate that PrPCWD is more abundant in free-range elk
peripheral tissues than current diagnostic methods suggest, and that
transmission of prions from mother to offspring may contribute to the efficient
transmission of the CWD in native cervid populations.
===========
These findings demonstrate that PrPCWD is more abundant in free-range elk
peripheral tissues than current diagnostic methods suggest, and that
transmission of prions from mother to offspring may contribute to the efficient
transmission of the CWD in native cervid populations.
===========
P.142: Chronic wasting disease (CWD) transmission into hamsters
Elizabeth Triscott, Camilo Duque-Velasquez, Judd M Aiken, and Debbie
McKenzie Center for Prions and Protein Folding Diseases; University of Alberta;
Edmonton, Canada
KEYWORDS. chronic wasting disease, interspecies transmission, prion
strains
Chronic wasting disease (CWD) is a contagious prion disease of cervids. The
continued expansion of the disease in North America is resulting in the
increasing number of mammalian species exposed to this infectious agent. As CWD
is able to infect multiple cervid species, it is likely that variation of the
agent might occur, due to PrP polymorphisms within and between cervid species.
Using Syrian Golden hamsters as a model for interspecies transmission, we
infected the hamsters with genetically defined CWD isolates from white-tailed
deer as well as with hunter-harvested mule deer and white-tailed deer from
Saskatchewan. ***The majority of the CWD isolates resulted in successful
transmission to hamsters. Biochemical and neuropathological analyses suggests
differences between the CWD isolates.
===========
P.144: Transmission of CWD to nonhuman primates: Interim results of a 6
year risk assessment study on the transmissibility to humans
Bianka Mussil1, Dirk Motzkus1, Georgia Hesse1, Sabine Borchert1, Barbara
Schiller1, Christiane Stahl-Hennig1 , Walter Schulz-Schaeffer2, Michael Beekes3,
Martin Daus3, Hermann M Schatzl5, Sandor Dudas4, Jianmin Yang4, Jean-Philippe
Deslys6, and Stefanie Czub4,5 1German Primate Center; Goettingen, Germany;
2Faculty of Medicine; Department of Neuropathology; Goettingen, Germany; 3Robert
Koch Institute; Berlin, Germany; 4University of Calgary; Faculty of Veterinary
Medicine; Calgary, Canada; 5Canadian and OIE Reference Laboratories for BSE;
Canadian Food Inspection Agency Lethbridge Laboratory; Lethbridge, Alberta,
Canada; 6Commissariat a l’Energie Atomique; Fontenay-aux-Roses, France
Rapid spread and high prevalence of CWD in North American captive and
free-ranging cervids have raised concerns about a potential risk to human
health. Evidence exists that skeletal muscles might harbor significant amount of
prion infectivity which is of great importance to consumers of venison, velvet
and other cervid products. In order to assess the risk of primary
CWD-transmission, cynomolgus macaques (Macaca fascicularis) were inoculated with
high-titer brain homogenates of CWD-infected white-tailed deer material by
intracerebral, intragastric and dermal scarification routes. Another group
obtained a total amount of 5 kg CWD-positive muscle homogenate using a repeated
low-dose regimen (each received »125 applications of 40 g muscle homogenate over
a 3 y period). Risk of secondary CWD-transmission via blood or bloodderived
products is judged by blood transfusion of monkey-adapted CWD to naive
recipients. Based on the in vitro conversion of recombinant prion protein, a
real-time quaking-induced conversion (RT-QuiC) assay was optimized by using
lymph node tissues, cerebrospinal fluid samples and brain homogenate derived
from BSE-inoculated macaques. Results have shown robust, sensitive, specific
detection, high interand moderate intra-assay variances in samples derived from
BSE-infected macaques. ***So far, all analyzed samples from CWD-inoculated
macaques did not reveal any seeding activity. ***Future findings of our risk
assessment study will greatly contribute to policy decisions including
monitoring of human blood products, CWD surveillance and CWD control in captive
and free-ranging cervids. Here we will present an update on the current state of
the ongoing project.
===========
***So far, all analyzed samples from CWD-inoculated macaques did not reveal
any seeding activity.
***Future findings of our risk assessment study will greatly contribute to
policy decisions including monitoring of human blood products, CWD surveillance
and CWD control in captive and free-ranging cervids. Here we will present an
update on the current state of the ongoing project.
SEE ;
Prion
Volume 7, Issue 3, 2013
Early detection of chronic wasting disease prions in urine of
pre-symptomatic deer by real-time quaking-induced conversion assay
Open access
DOI:10.4161/pri.24430Theodore R. Johna, Hermann M. Schätzlabc & Sabine
Gilchad*
pages 253-258
Publishing models and article dates explained
Received: 7 Feb 2013 Accepted: 24 Mar 2013 Published online: 10 Apr
2013
Article Views: 105
Abstract
Chronic wasting disease (CWD) is a prion disease of captive and
free-ranging deer (Odocoileus spp), elk (Cervus elaphus nelsonii) and moose
(Alces alces shirasi). Unlike in most other prion diseases, in CWD prions are
shed in urine and feces, which most likely contributes to the horizontal
transmission within and between cervid species. To date, CWD ante-mortem
diagnosis is only possible by immunohistochemical detection of protease
resistant prion protein (PrPSc) in tonsil or recto-anal mucosa-associated
lymphoid tissue (RAMALT) biopsies, which requires anesthesia of animals. We
report on detection of CWD prions in urine collected from pre-symptomatic deer
and in fecal extracts by using real time quaking-induced conversion (RT-QuIC).
This assay can be useful for non-invasive pre-symptomatic diagnosis and
surveillance of CWD.
snip...
Introduction
Chronic wasting disease (CWD) is to date the most contagious prion disease
and affects captive and free-ranging elk, deer and moose in North America.1 The
disease is caused by the accumulation of an abnormally folded isoform of the
cellular prion protein PrPc, denominated PrPSc.3 CWD is the cervid equivalent of
bovine spongiform encephalopathy (BSE), scrapie in sheep and goat5 or
Creutzfeldt-Jakob disease (CJD) in humans.6 Although transmission studies of CWD
prions to humanized transgenic mice or non-human primates suggest a strong
species barrier,7 recent in vitro studies have demonstrated that human PrP can
be converted by CWD prions into PrPSc upon adaptation.10 ***Therefore, a
potential for zoonotic transmission, as exemplified by BSE,11 cannot be
completely excluded.
A huge body of evidence suggests that CWD can be efficiently transmitted
horizontally within and between cervid species,12 which may be the reason for
geographical spread and increase in case numbers. Horizontal transmission is
explained by the rather unusual peripheral distribution of prions in CWD
affected animals and the high susceptibility to the disease by oral infection.13
Unlike in most other prion diseases, CWD prions can be found in a wide variety
of tissues, such as skeletal and cardiac muscle15 or kidney,17 in addition to
the lymphoreticular system and blood.18 Furthermore, they are shed in
significant amounts in saliva,18 ,19 urine19 or feces,20 which enables oral
infection of animals by foraging on contaminated pastures. In addition, it has
been demonstrated that prions can persist in soil21 and that water in endemic
areas can contain CWD-associated PrPSc 22.
***Therefore, a potential for zoonotic transmission, as exemplified by
BSE,11 cannot be completely excluded.
*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent
*** Here we report that a human prion strain that had adopted the cervid
prion protein (PrP) sequence through passage in cervidized transgenic mice
efficiently infected transgenic mice expressing human PrP,
*** indicating that the species barrier from cervid to humans is prion
strain-dependent and humans can be vulnerable to novel cervid prion strains.
PPo2-27:
Generation of a Novel form of Human PrPSc by Inter-species Transmission of
Cervid Prions
*** Our findings suggest that CWD prions have the capability to infect
humans, and that this ability depends on CWD strain adaptation, implying that
the risk for human health progressively increases with the spread of CWD among
cervids.
PPo2-7:
Biochemical and Biophysical Characterization of Different CWD Isolates
*** The data presented here substantiate and expand previous reports on
the existence of different CWD strains.
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.
>>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO
CONVERSION OF THE HUMAN PRION PROTEIN<<<
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
Wednesday, January 01, 2014
Molecular Barriers to Zoonotic Transmission of Prions
*** 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.
PRION2013 CONGRESSIONAL ABSTRACTS CWD
Sunday, August 25, 2013
HD.13: CWD infection in the spleen of humanized transgenic mice
***These results indicate that the CWD prion may have the potential to
infect human peripheral lymphoid tissues.
Oral.15: Molecular barriers to zoonotic prion transmission: Comparison of
the ability of sheep, cattle and deer prion disease isolates to convert normal
human prion protein to its pathological isoform in a cell-free system
***However, they also show that there is no absolute barrier to conversion of
human prion protein in the case of chronic wasting disease.
PRION2013 CONGRESSIONAL ABSTRACTS CWD
Sunday, August 25, 2013
***Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood,
and mother to offspring transmission
PPo3-7:
Prion Transmission from Cervids to Humans is Strain-dependent
Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi
Gambetti and Liuting Qing Department of Pathology; Case western Reserve
University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial
Sloan-Kettering Cancer Center; New York, NY USA
Key words: CWD, strain, human transmission
Chronic wasting disease (CWD) is a widespread prion disease in cervids
(deer and elk) in North America where significant human exposure to CWD is
likely and zoonotic transmission of CWD is a concern. Current evidence indicates
a strong barrier for transmission of the classical CWD strain to humans with the
PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD
strains. What remain unknown is whether individuals with the PrP-129VV/MV
genotypes are also resistant to the classical CWD strain and whether humans are
resistant to all natural or adapted cervid prion strains. Here we report that a
human prion strain that had adopted the cervid prion protein (PrP) sequence
through passage in cervidized transgenic mice efficiently infected transgenic
mice expressing human PrP, indicating that the species barrier from cervid to
humans is prion strain-dependent and humans can be vulnerable to novel cervid
prion strains. Preliminary results on CWD transmission in transgenic mice
expressing human PrP-129V will also be discussed.
Acknowledgement Supported by NINDS NS052319 and NIA AG14359.
PPo2-27:
Generation of a Novel form of Human PrPSc by Inter-species Transmission of
Cervid Prions
Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A.
Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer’s disease and
related Brain disorders; Dept of Neurology; University of Texas Houston Medical
School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular
Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky
Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve
University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago;
Chicago, IL USA
Prion diseases are infectious neurodegenerative disorders affecting humans
and animals that result from the conversion of normal prion protein (PrPC) into
the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of
cervids is a prion disorder of increasing prevalence within the United States
that affects a large population of wild and captive deer and elk. CWD is highly
contagious and its origin, mechanism of transmission and exact prevalence are
currently unclear. The risk of transmission of CWD to humans is unknown.
Defining that risk is of utmost importance, considering that people have been
infected by animal prions, resulting in new fatal diseases. To study the
possibility that human PrPC can be converted into the infectious form by CWD
PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification
(PMCA) technique, which mimic in vitro the process of prion replication. Our
results show that cervid PrPSc can induce the pathological conversion of human
PrPC, but only after the CWD prion strain has been stabilized by successive
passages in vitro or in vivo. Interestingly, this newly generated human PrPSc
exhibits a distinct biochemical pattern that differs from any of the currently
known forms of human PrPSc, indicating that it corresponds to a novel human
prion strain. Our findings suggest that CWD prions have the capability to infect
humans, and that this ability depends on CWD strain adaptation, implying that
the risk for human health progressively increases with the spread of CWD among
cervids.
PPo2-7:
Biochemical and Biophysical Characterization of Different CWD Isolates
Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin, Germany
Key words: CWD, strains, FT-IR, AFM
Chronic wasting disease (CWD) is one of three naturally occurring forms of
prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie
in sheep. CWD is contagious and affects captive as well as free ranging cervids.
As long as there is no definite answer of whether CWD can breach the species
barrier to humans precautionary measures especially for the protection of
consumers need to be considered. In principle, different strains of CWD may be
associated with different risks of transmission to humans. Sophisticated strain
differentiation as accomplished for other prion diseases has not yet been
established for CWD. However, several different findings indicate that there
exists more than one strain of CWD agent in cervids. We have analysed a set of
CWD isolates from white-tailed deer and could detect at least two biochemically
different forms of disease-associated prion protein PrPTSE. Limited proteolysis
with different concentrations of proteinase K and/or after exposure of PrPTSE to
different pH-values or concentrations of Guanidinium hydrochloride resulted in
distinct isolate-specific digestion patterns. Our CWD isolates were also
examined in protein misfolding cyclic amplification studies. This showed
different conversion activities for those isolates that had displayed
significantly different sensitivities to limited proteolysis by PK in the
biochemical experiments described above. We further applied Fourier transform
infrared spectroscopy in combination with atomic force microscopy. This
confirmed structural differences in the PrPTSE of at least two disinct CWD
isolates. The data presented here substantiate and expand previous reports on
the existence of different CWD strains.
2012
Envt.06:
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human
Primates
Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Aru Balachandran,2
Jürgen Richt,3 Vincent Beringue,4 Juan-Maria Torres,5 Paul Brown,1 Bob Hills6
and Jean-Philippe Deslys1
1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Canadian Food
Inspection Agency; Ottawa, ON Canada; 3Kansas State University; Manhattan, KS
USA; 4INRA; Jouy-en-Josas, France; 5INIA; Madrid, Spain; 6Health Canada; Ottawa,
ON Canada
†Presenting author; Email: emmanuel.comoy@cea.fr
The constant increase of chronic wasting disease (CWD) incidence in North
America raises a question about their zoonotic potential. A recent publication
showed their transmissibility to new-world monkeys, but no transmission to
old-world monkeys, which are phylogenetically closer to humans, has so far been
reported. Moreover, several studies have failed to transmit CWD to transgenic
mice overexpressing human PrP. Bovine spongiform encephalopathy (BSE) is the
only animal prion disease for which a zoonotic potential has been proven. We
described the transmission of the atypical BSE-L strain of BSE to cynomolgus
monkeys, suggesting a weak cattle-to-primate species barrier. We observed the
same phenomenon with a cattleadapted strain of TME (Transmissible Mink
Encephalopathy). Since cattle experimentally exposed to CWD strains have also
developed spongiform encephalopathies, we inoculated brain tissue from
CWD-infected cattle to three cynomolgus macaques as well as to transgenic mice
overexpressing bovine or human PrP. Since CWD prion strains are highly
lymphotropic, suggesting an adaptation of these agents after peripheral
exposure, a parallel set of four monkeys was inoculated with CWD-infected cervid
brains using the oral route. Nearly four years post-exposure, monkeys exposed to
CWD-related prion strains remain asymptomatic. In contrast, bovinized and
humanized transgenic mice showed signs of infection, suggesting that CWD-related
prion strains may be capable of crossing the cattle-to-primate species barrier.
Comparisons with transmission results and incubation periods obtained after
exposure to other cattle prion strains (c-BSE, BSE-L, BSE-H and cattle-adapted
TME) will also be presented, in order to evaluate the respective risks of each
strain.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2
Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch
Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and
Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany
†Presenting author; Email: dausm@rki.de
Chronic wasting disease (CWD) is a contagious, rapidly spreading
transmissible spongiform encephalopathy (TSE) occurring in cervids in North
America. Despite efficient horizontal transmission of CWD among cervids natural
transmission of the disease to other species has not yet been observed. Here, we
report a direct biochemical demonstration of pathological prion protein PrPTSE
and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected
cervids. The presence of PrPTSE was detected by Western- and postfixed frozen
tissue blotting, while the seeding activity of PrPTSE was revealed by protein
misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal
muscles of CWD-infected WTD was estimated to be approximately 2000- to
10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE
was located in muscle- associated nerve fascicles but not, in detectable
amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal
muscle from CWD-infected cervids suggests prevention of such tissue in the human
diet as a precautionary measure for food safety, pending on further
clarification of whether CWD may be transmissible to humans.
P.10.15
ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A
WISCONSIN STRAIN OF CWD
Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of
Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2
Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary
Research Institute, 4.Center for Prions and Protein Folding Diseases, 5
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
T6G 2P5
The identification and characterization of prion strains is increasingly
important for the diagnosis and biological definition of these infectious
pathogens. Although well-established in scrapie and, more recently, in BSE,
comparatively little is known about the possibility of prion strains in chronic
wasting disease (CWD), a disease affecting free ranging and captive cervids,
primarily in North America. We have identified prion protein variants in the
white-tailed deer population and demonstrated that Prnp genotype affects the
susceptibility/disease progression of white-tailed deer to CWD agent. The
existence of cervid prion protein variants raises the likelihood of distinct CWD
strains. Small rodent models are a useful means of identifying prion strains. We
intracerebrally inoculated hamsters with brain homogenates and phosphotungstate
concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD
endemic area) and experimentally infected deer of known Prnp genotypes. These
transmission studies resulted in clinical presentation in primary passage of
concentrated CWD prions. Subclinical infection was established with the other
primary passages based on the detection of PrPCWD in the brains of hamsters and
the successful disease transmission upon second passage. Second and third
passage data, when compared to transmission studies using different CWD inocula
(Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin
white-tailed deer population is different than the strain(s) present in elk,
mule-deer and white-tailed deer from the western United States endemic region.
CHRONIC WASTING DISEASE CWD
Transmissibility to humans.
The current state of epidemiological research suggests a rather robust
barrier for the transmission of CWD to humans. Particularly, the surveillance of
human prion diseases in areas with a long history of endemic CWD such as
Colorado and Wyoming did not reveal evidence for zoonotic transmissions of the
disease to cervid hunters or consumers of meat from elk and deer.66. Belay ED,
Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting
disease and potential transmission to humans. Emerg Infect Dis 2004; 10:977 -
984; PMID: 15207045 [CrossRef] View all references,1111. Belay ED, Abrams J,
Kenfield J, Weidenbach K, Maddox RA, Lawaczeck E, et al. Monitoring the
potential transmission of chronic wasting disease to humans (Abstract Oral.40,
Prion 2011 Oral Presentations). Prion 2011; 5:17 Supplemental Issue
April/May/June 2011 View all references
However, as discussed by Belay et al.66. Belay ED, Maddox RA, Williams ES,
Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential
transmission to humans. Emerg Infect Dis 2004; 10:977 - 984; PMID: 15207045
[CrossRef] View all references
the intensity of human exposure to CWD prions may increase due to a
further spread and rising prevalence of the disease in cervids. Therefore, and
with the generally long latency periods of human prion diseases in mind,
previous epidemiological findings cannot be readily extrapolated. Until
recently, experimental studies that pursued biochemical approaches or used
transgenic mice to ascertain the susceptibility of humans to CWD infections
consistently seemed to corroborate current epidemiological findings:
CWD-infected cervid brain tissue did not seed the conversion of PrPC into PrPres
in PMCA assays using brain homogenate from macaques or transgenic mice
expressing human PrPC as test substrate,1212. Kurt TD, Telling GC, Zabel MD,
Hoover EA. Trans-species amplification of PrP(CWD) and correlation with rigid
loop 170N. Virology 2009; 387:235 - 243; PMID: 19269662; http://dx.doi.org/10.1016/j.virol.2009.02.025
[CrossRef] View all references
and transgenic mice overexpressing human PrPC were resistant to infection
after intracerebral challenge with CWD prions from mule deer.1313. Sandberg MK,
Al-Doujaily H, Sigurdson CJ, Glatzel M, O'Malley C, Powell C, et al. Chronic
wasting disease prions are not transmissible to transgenic mice overexpressing
human prion protein. J Gen Virol 2010; 91:2651 - 2657; PMID: 20610667; http://dx.doi.org/10.1099/vir.0.024380-0
[CrossRef] View all references
However, a study published by Barria et al.1414. Barria MA, Telling GC,
Gambetti P, Mastrianni JA, Soto C. Generation of a new form of human PrPSc in
vitro by interspecies transmission from cervid prions. J Biol Chem 2011;
286:7490 - 7495; PMID: 21209079; http://dx.doi.org/10.1074/jbc.M110.198465
[CrossRef] View all references
in March 2011 found that cervid PrPTSE can seed the conversion of human
PrPC into PrPres by PMCA when the CWD agent has been previously passaged in
vitro or in vivo. Specifically, this was demonstrated for CWD prions from
naturally affected mule deer either passaged by serial PMCA using deer PrPC as
conversion substrate or in transgenic mice expressing cervid PrPC. The authors
of this study pointed out that CWD prions may undergo a gradual process of
change and adaptation via successive passages in the cervid population. They
concluded that the reported findings, if corroborated by infectivity assays, may
imply “that CWD prions have the potential to infect humans and that this ability
progressively increases with CWD spreading.” Cynomolgus macaques used as a
primate model for testing the susceptibility of humans to CWD as close to
reality as possible have not shown clinical signs of a prion disease at nearly 6
years after intracerebral or peroral inoculation of CWD agents from white-tailed
deer, Rocky Mountain elk or mule deer.1515. Race B, Meade-White KD, Miller MW,
Barbian KD, Rubenstein R, LaFauci G, et al. Susceptibilities of nonhuman
primates to chronic wasting disease. Emerg Infect Dis 2009; 15:1366 - 1376;
PMID: 19788803; http://dx.doi.org/10.3201/eid1509.090253
[CrossRef] View all references
In contrast to macaques, squirrel monkeys were susceptible to CWD
infection by the intracerebral route and showed even a low rate of disease
transmission after oral challenge.1515. Race B, Meade-White KD, Miller MW,
Barbian KD, Rubenstein R, LaFauci G, et al. Susceptibilities of nonhuman
primates to chronic wasting disease. Emerg Infect Dis 2009; 15:1366 - 1376;
PMID: 19788803; http://dx.doi.org/10.3201/eid1509.090253
[CrossRef] View all references,1616. Marsh RF, Kincaid AE, Bessen RA, Bartz JC.
Interspecies transmission of chronic wasting disease prions to squirrel monkeys
(Saimiri sciureus). J Virol 2005; 79:13794 - 13796; PMID: 16227298; http://dx.doi.org/10.1128/JVI.79.21.13794-6.2005
[CrossRef] View all references
Since humans are phylogenetically closer related to macaques than to
squirrel monkeys, macaques are regarded as the more relevant primate model for
assessing the zoonotic transmissibility of CWD.1515. Race B, Meade-White KD,
Miller MW, Barbian KD, Rubenstein R, LaFauci G, et al. Susceptibilities of
nonhuman primates to chronic wasting disease. Emerg Infect Dis 2009; 15:1366 -
1376; PMID: 19788803; http://dx.doi.org/10.3201/eid1509.090253
[CrossRef] View all references
Ongoing transmission studies in macaques. In addition to the primate study
by Race et al.1515. Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R,
LaFauci G, et al. Susceptibilities of nonhuman primates to chronic wasting
disease. Emerg Infect Dis 2009; 15:1366 - 1376; PMID: 19788803; http://dx.doi.org/10.3201/eid1509.090253
[CrossRef] View all references
two further studies in which macaques were challenged with tissue
homogenates from CWD-affected cervids by intracerebral inoculation or via the
oral route have been reported to be in progress.1717. Comoy E, Durand V, Correia
E, Balachandran A, Richt JA, Beringue V, et al. Zoonotic potential of CWD:
Experimental transmissions to non-human primates (Abstract Envt.06, Prion 2011
Poster Presentations). Prion 2011; 5:101 View all references,1818. Motzkus D,
Schulz-Schaeffer WJ, Beekes M, Schätzl HM, Jirik FR, Schmädicke AC, et al.
Transmission of CWD to non-human primates: Interim results of a comprehensive
study on the transmissibility to humans (Abstract Envt. 22, Prion 2011 Poster
Presentations). Prion 2011; 5:107 Supplemental Issue April/May/June 2011 View
all references
The purpose, research effort, financial investment and ethical aspects of
these studies demand an utmost experimental scrutiny, careful data analysis and
thorough exploitation of results. This has two immediate implications: (1) Since
the incubation period of CWD may be very long in case of primary (i.e.,
inter-species) transmission to macaques a sustained monitoring of the animals
appears mandatory for many years despite negative interim findings. (2)
Increasing evidence suggests the existence of different CWD agents (see below),
and theoretically, CWD prions may also change over time thereby possibly
altering their potential host range. Thus, CWD isolates used in individual or
pooled inocula for the challenge of macaques should be typed as precisely as
possible in terms of their strain characteristics and molecular identity. Other
field isolates could then be checked for their similarity or dissimilarity to
the macaque-tested CWD agents in order to ascertain whether or not they are
covered by the ongoing primate risk assessments. Evidence for Distinct CWD
Strains Jump to section Transmissible Spongiform... Exposure of Humans to CWD
Prions CWD Risk Assessments Evidence for Distinct CWD Strains Outlook Disclosure
of Potential Conflicts of Interest Funding Figures and Tables Biochemical
indications for isolate-dependent structural differences of PrPTSE. In 2002 it
was reported that glycoform patterns of PrPTSE showed differences among
individual CWD-affected cervids.1919. Race RE, Raines A, Baron TG, Miller MW,
Jenny A, Williams ES. Comparison of abnormal prion protein glycoform patterns
from transmissible spongiform encephalopathy agent-infected deer, elk, sheep and
cattle. J Virol 2002; 76:12365 - 12368; PMID: 12414979; http://dx.doi.org/10.1128/JVI.76.23.12365-8.2002
[CrossRef] View all references
In a variety of studies the glycosylation of PrPTSE had been previously
established as a biochemical feature that may differ between distinct TSE
agents.2020. Parchi P, Capellari S, Chen SG, Petersen RB, Gambetti P, Kopp N, et
al. Typing prion isoforms. Nature 1997; 386:232 - 234; PMID: 9069279; http://dx.doi.org/10.1038/386232a0
[CrossRef] View all references,2121. Aguzzi A, Heikenwalder M, Polymenidou M.
Insights into prion strains and neurotoxicity. Nat Rev Mol Cell Biol 2007; 8:552
- 561; PMID: 17585315; http://dx.doi.org/10.1038/nrm2204
[CrossRef] View all references
Accordingly, the finding by Race et al. possibly indicated CWD infections
with different or multiple strains of agent, although, alternatively, it could
also be explained by random selection from a heterogeneous population of
CWD-affected ruminants.1919. Race RE, Raines A, Baron TG, Miller MW, Jenny A,
Williams ES. Comparison of abnormal prion protein glycoform patterns from
transmissible spongiform encephalopathy agent-infected deer, elk, sheep and
cattle. J Virol 2002; 76:12365 - 12368; PMID: 12414979; http://dx.doi.org/10.1128/JVI.76.23.12365-8.2002
[CrossRef] View all references
Using a conformation-dependent immunoassay (CDI), Safar et al. found
evidence for different conformations of PrPTSE in elk CWD as compared with
white-tailed and mule deer CWD.2222. Safar JG, Scott M, Monaghan J, Deering C,
Didorenko S, Vergara J, et al. Measuring prions causing bovine spongiform
encephalopathy or chronic wasting disease by immunoassays and transgenic mice.
Nat Biotechnol 2002; 20:1147 - 1150; PMID: 12389035; http://dx.doi.org/10.1038/nbt748
[CrossRef] View all references
However, the amino acid sequences of elk and deer PrPC differ at residues
226 (glutamic acid in elk and glutamine in deer), and it remained to be
established whether the structural differences detected by CDI were related to
biologically distinct CWD strains. Isolation of CWD-associated agents causing
distinct phenotypes in laboratory rodents. Classically, prion strains are
differentiated based on their incubation periods in inbred mice with distinct
PrP genotypes and by lesion profiles of the vacuolation in selected brain areas
of reporter animals.2323. Bruce ME, Fraser H. Scrapie strain variation and its
implications. Curr Top Microbiol Immunol 1991; 172:125 - 138; PMID: 1810707
[CrossRef] View all references
When Raymond et al. serially passaged a CWD inoculum from mule deer either
in Syrian hamsters or first into transgenic mice expressing hamster PrPC, and
then further on in hamsters, they obtained two distinct isolates termed
SghaCWDmd-f and SghaCWDmd-s, respectively.2424. Raymond GJ, Raymond LD,
Meade-White KD, Hughson AG, Favara C, Gardner D, et al. Transmission and
adaptation of chronic wasting disease to hamsters and transgenic mice: evidence
for strains. J Virol 2007; 81:4305 - 4314; PMID: 17287284; http://dx.doi.org/10.1128/JVI.02474-06
[CrossRef] View all references
The first isolate showed an about 5-fold shorter incubation period in
Syrian hamsters than the latter, and the cerebral patterns of PrPTSE deposition
and gliosis in clinically affected hamsters were also different. Based on their
findings the authors concluded that the “cervid-derived inocula may have
contained or diverged into at least two distinct transmissible spongiform
encephalopathy strains.” Angers et al. transmitted CWD inocula from elk and deer
to transgenic mice expressing cervid PrP and found that these mice were affected
by one of two strains, referred to as CWD1 and CWD2, that caused different
incubation times and lesion profiles.2525. Angers RC, Kang HE, Napier D,
Browning S, Seward T, Mathiason C, et al. Prion strain mutation determined by
prion protein conformational compatibility and primary structure. Science 2010;
328:1154 - 1158; PMID: 20466881; http://dx.doi.org/10.1126/science.1187107
[CrossRef] View all references
The results of this study “appear to reflect strain constitutions in the
natural host, rather than adaptation and divergence of progenitor strains in
recipient mice,” according to the authors. Interestingly, CWD1 and CWD2 did not
show recognizably different biochemical properties of their PrPTSE. The
electrophoretic migration and glycosylation patterns as well as the stability
characteristics after treatment with guanidine hydrochloride were
indistinguishable for CWD1- and CWD2-associated PrPTSE. Consistent with these
findings it has been previously reported that biologically distinct prion
strains cannot always be differentiated by biochemical PrPTSE-typing or
characterization of the conformational stability of PrPTSE.2626. Thomzig A,
Spassov S, Friedrich M, Naumann D, Beekes M. Discriminating scrapie and bovine
spongiform encephalopathy isolates by infrared spectroscopy of pathological
prion protein. J Biol Chem 2004; 279:33847 - 33854; PMID: 15155741; http://dx.doi.org/10.1074/jbc.M403730200
[CrossRef] View all references,2727. Peretz D, Scott MR, Groth D, Williamson RA,
Burton DR, Cohen FE, et al. Strain-specified relative conformational stability
of the scrapie prion protein. Protein Sci 2001; 10:854 - 863; PMID: 11274476; http://dx.doi.org/10.1110/ps.39201
[CrossRef] View all references
UPDATED DATA ON 2ND CWD STRAIN Wednesday, September 08, 2010 CWD PRION
CONGRESS SEPTEMBER 8-11 2010
OR-12: Chronic wasting disease transmission and pathogenesis in cervid and
non-cervid Species
Edward A. Hoover, Candace K. Mathiason, Nicholas J. Haley, Timothy D.
Kurt, Davis M. Seelig, Nathaniel D. Denkers, Amy V. Nalls, Mark D. Zabel, and
Glenn C. Telling
Prion Research Program, Department of Microbiology, Immunology, and
Pathology; Colorado State University; Fort Collins, CO USA
Since its recognition as a TSE in the late 1970s, chronic wasting disease
(CWD) of cervids has been distinguished by its facile spread and is now
recognized in 18 states, 2 Canadian provinces, and South Korea. The efficient
horizontal spread of CWD reflects a prion/host relationship that facilitates
efficient mucosal uptake, peripheral lymphoid amplification, and dissemination
by exploiting excretory tissues and their products, helping to establish
indirect/environmental and well as direct (e.g., salivary) transmission. Recent
studies from our group also support the likelihood of early life mother to
offspring and aerosol CWD prion transmission. Studies of cervid CWD exposure by
natural routes indicate that incubation period for detection of overt infection,
while still uncertain, may be much longer than originally thought.
Several non-cervid species can be infected by CWD experimentally (e.g.,
ferrets, voles, cats) with consequent species-specific disease phenotypes. The
species-adapted prions so generated can be transmitted by mucosal, i.e., more
natural, routes. Whether non-cervid species sympatric with deer/elk can be
infected in nature, however, remains unknown. In vitro CWD prion amplification
studies, in particular sPMCA, can foreshadow in vivo susceptibility and suggest
the importance of the PrPC rigid loop region in species barrier permissiveness.
Trans-species CWD amplification appears to broaden the host range/strain
characteristics of the resultant prions. The origins of CWD remain unknown,
however, the existence of multiple CWD prion strains/ quasi-species, the
mechanisms of prion shedding/dissemination, and the relationship between sheep
scrapie and CWD merit further investigation.
Monday, May 23, 2011
CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning
Public release date: 23-May-2011
Contact: Francesca Costanzo adajmedia@elsevier.com 215-239-3249 Elsevier
Health Sciences
CDC assesses potential human exposure to prion diseases Study results
reported in the Journal of the American Dietetic Association Philadelphia, PA,
May 23, 2011 – Researchers from the Centers for Disease Control and Prevention
(CDC) have examined the potential for human exposure to prion diseases, looking
at hunting, venison consumption, and travel to areas in which prion diseases
have been reported in animals. Three prion diseases in particular – bovine
spongiform encephalopathy (BSE or “Mad Cow Disease”), variant Creutzfeldt-Jakob
disease (vCJD), and chronic wasting disease (CWD) – were specified in the
investigation. The results of this investigation are published in the June issue
of the Journal of the American Dietetic Association.
“While prion diseases are rare, they are generally fatal for anyone who
becomes infected. More than anything else, the results of this study support the
need for continued surveillance of prion diseases,” commented lead investigator
Joseph Y. Abrams, MPH, National Center for Emerging and Zoonotic Infectious
Diseases, CDC, Atlanta.”But it’s also important that people know the facts about
these diseases, especially since this study shows that a good number of people
have participated in activities that may expose them to infection-causing
agents.”
Although rare, human prion diseases such as CJD may be related to BSE.
Prion (proteinaceous infectious particles) diseases are a group of rare brain
diseases that affect humans and animals. When a person gets a prion disease,
brain function is impaired. This causes memory and personality changes,
dementia, and problems with movement. All of these worsen over time. These
diseases are invariably fatal. Since these diseases may take years to manifest,
knowing the extent of human exposure to possible prion diseases could become
important in the event of an outbreak.
CDC investigators evaluated the results of the 2006-2007 population survey
conducted by the Foodborne Diseases Active Surveillance Network (FoodNet). This
survey collects information on food consumption practices, health outcomes, and
demographic characteristics of residents of the participating Emerging
Infections Program sites. The survey was conducted in Connecticut, Georgia,
Maryland, Minnesota, New Mexico, Oregon, and Tennessee, as well as five counties
in the San Francisco Bay area, seven counties in the Greater Denver area, and 34
counties in western and northeastern New York.
Survey participants were asked about behaviors that could be associated
with exposure to the agents causing BSE and CWD, including travel to the nine
countries considered to be BSE-endemic (United Kingdom, Republic of Ireland,
France, Portugal, Switzerland, Italy, the Netherlands, Germany, Spain) and the
cumulative length of stay in each of those countries. Respondents were asked if
they ever had hunted for deer or elk, and if that hunting had taken place in
areas considered to be CWD-endemic (northeastern Colorado, southeastern Wyoming
or southwestern Nebraska). They were also asked if they had ever consumed
venison, the frequency of consumption, and whether the meat came from the wild.
The proportion of survey respondents who reported travel to at least one
of the nine BSE endemic countries since 1980 was 29.5%. Travel to the United
Kingdom was reported by 19.4% of respondents, higher than to any other
BSE-endemic country. Among those who traveled, the median duration of travel to
the United Kingdom (14 days) was longer than that of any other BSE-endemic
country. Travelers to the UK were more likely to have spent at least 30 days in
the country (24.9%) compared to travelers to any other BSE endemic country. The
prevalence and extent of travel to the UK indicate that health concerns in the
UK may also become issues for US residents.
The proportion of survey respondents reporting having hunted for deer or
elk was 18.5% and 1.2% reported having hunted for deer or elk in CWD-endemic
areas. Venison consumption was reported by 67.4% of FoodNet respondents, and
88.6% of those reporting venison consumption had obtained all of their meat from
the wild. These findings reinforce the importance of CWD surveillance and
control programs for wild deer and elk to reduce human exposure to the CWD
agent. Hunters in CWD-endemic areas are advised to take simple precautions such
as: avoiding consuming meat from sickly deer or elk, avoiding consuming brain or
spinal cord tissues, minimizing the handling of brain and spinal cord tissues,
and wearing gloves when field-dressing carcasses.
According to Abrams, “The 2006-2007 FoodNet population survey provides
useful information should foodborne prion infection become an increasing public
health concern in the future. The data presented describe the prevalence of
important behaviors and their associations with demographic characteristics.
Surveillance of BSE, CWD, and human prion diseases are critical aspects of
addressing the burden of these diseases in animal populations and how that may
relate to human health.”
###
The article is “Travel history, hunting, and venison consumption related
to prion disease exposure, 2006-2007 FoodNet population survey” by Joseph Y.
Abrams, MPH; Ryan A. Maddox, MPH; Alexis R Harvey, MPH; Lawrence B. Schonberger,
MD; and Ermias D. Belay, MD. It appears in the Journal of the American Dietetic
Association, Volume 111, Issue 6 (June 2011) published by Elsevier.
In an accompanying podcast CDC’s Joseph Y. Abrams discusses travel,
hunting, and eating venison in relation to prion diseases. It is available at http://adajournal.org/content/podcast.
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease
Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages
858-863, June 2011.
Travel History, Hunting, and Venison Consumption Related to Prion Disease
Exposure, 2006-2007 FoodNet Population Survey
Joseph Y. Abrams, MPH, Ryan A. Maddox, MPH , Alexis R. Harvey, MPH ,
Lawrence B. Schonberger, MD , Ermias D. Belay, MD
Accepted 15 November 2010. Abstract Full Text PDF References .
Abstract
The transmission of bovine spongiform encephalopathy (BSE) to human beings
and the spread of chronic wasting disease (CWD) among cervids have prompted
concerns about zoonotic transmission of prion diseases. Travel to the United
Kingdom and other European countries, hunting for deer or elk, and venison
consumption could result in the exposure of US residents to the agents that
cause BSE and CWD. The Foodborne Diseases Active Surveillance Network 2006-2007
population survey was used to assess the prevalence of these behaviors among
residents of 10 catchment areas across the United States. Of 17,372 survey
respondents, 19.4% reported travel to the United Kingdom since 1980, and 29.5%
reported travel to any of the nine European countries considered to be
BSE-endemic since 1980. The proportion of respondents who had ever hunted deer
or elk was 18.5%, and 1.2% had hunted deer or elk in a CWD–endemic area. More
than two thirds (67.4%) reported having ever eaten deer or elk meat. Respondents
who traveled spent more time in the United Kingdom (median 14 days) than in any
other BSE-endemic country. Of the 11,635 respondents who had consumed venison,
59.8% ate venison at most one to two times during their year of highest
consumption, and 88.6% had obtained all of their meat from the wild. The survey
results were useful in determining the prevalence and frequency of behaviors
that could be important factors for foodborne prion transmission.
CDC
Saturday, February 18, 2012
Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting
Disease
CDC Volume 18, Number 3—March 2012
SNIP…
Interspecies transmission of CWD to noncervids has not been observed under
natural conditions. CWD infection of carcass scavengers such as raccoons,
opossums, and coyotes was not observed in a recent study in Wisconsin (22). In
addition, natural transmission of CWD to cattle has not been observed in
experimentally controlled natural exposure studies or targeted surveillance (2).
However, CWD has been experimentally transmitted to cattle, sheep, goats, mink,
ferrets, voles, and mice by intracerebral inoculation (2,29,33).
CWD is likely transmitted among mule, white-tailed deer, and elk without a
major species barrier (1), and other members of the cervid family, including
reindeer, caribou, and other species of deer worldwide, may be vulnerable to CWD
infection. Black-tailed deer (a subspecies of mule deer) and European red deer
(Cervus elaphus) are susceptible to CWD by natural routes of infection (1,34).
Fallow deer (Dama dama) are susceptible to CWD by intracerebral inoculation
(35). Continued study of CWD susceptibility in other cervids is of considerable
interest.
Reasons for Caution There are several reasons for caution with respect to
zoonotic and interspecies CWD transmission. First, there is strong evidence that
distinct CWD strains exist (36). Prion strains are distinguished by varied
incubation periods, clinical symptoms, PrPSc conformations, and CNS PrPSc
depositions (3,32). Strains have been identified in other natural prion
diseases, including scrapie, BSE, and CJD (3). Intraspecies and interspecies
transmission of prions from CWD-positive deer and elk isolates resulted in
identification of >2 strains of CWD in rodent models (36), indicating that
CWD strains likely exist in cervids. However, nothing is currently known about
natural distribution and prevalence of CWD strains. Currently, host range and
pathogenicity vary with prion strain (28,37). Therefore, zoonotic potential of
CWD may also vary with CWD strain. In addition, diversity in host (cervid) and
target (e.g., human) genotypes further complicates definitive findings of
zoonotic and interspecies transmission potentials of CWD.
Intraspecies and interspecies passage of the CWD agent may also increase
the risk for zoonotic CWD transmission. The CWD prion agent is undergoing serial
passage naturally as the disease continues to emerge. In vitro and in vivo
intraspecies transmission of the CWD agent yields PrPSc with an increased
capacity to convert human PrPc to PrPSc (30). Interspecies prion transmission
can alter CWD host range (38) and yield multiple novel prion strains (3,28). The
potential for interspecies CWD transmission (by cohabitating mammals) will only
increase as the disease spreads and CWD prions continue to be shed into the
environment. This environmental passage itself may alter CWD prions or exert
selective pressures on CWD strain mixtures by interactions with soil, which are
known to vary with prion strain (25), or exposure to environmental or gut
degradation.
Given that prion disease in humans can be difficult to diagnose and the
asymptomatic incubation period can last decades, continued research,
epidemiologic surveillance, and caution in handling risky material remain
prudent as CWD continues to spread and the opportunity for interspecies
transmission increases. Otherwise, similar to what occurred in the United
Kingdom after detection of variant CJD and its subsequent link to BSE, years of
prevention could be lost if zoonotic transmission of CWD is subsequently
identified, CWD will likely continue to emerge in North America. …
SNIP…
Generation of a new form of human PrPSc in vitro by inter-species
transmission from cervids prions
Our results have far-reaching implications for human health, since they
indicate that cervid PrPSc can trigger the conversion of human PrPC into PrPSc,
suggesting that CWD might be infectious to humans. Interestingly our findings
suggest that unstable strains from CWD affected animals might not be a problem
for humans, but upon strain stabilization by successive passages in the wild,
this disease might become progressively more transmissible to man.
Our results also have profound implications for understanding the
mechanisms of the prion species barrier and indicate that the transmission
barrier is a dynamic process that depends on the strain and moreover the degree
of adaptation of the strain. If our findings are corroborated by infectivity
assays, they will imply that CWD prions have the potential to infect humans and
that this ability progressively increases with CWD spreading.
I thought your readers and hunters and those that consume the venison,
should have all the scientific facts, personally, I don’t care what you eat, but
if it effects me and my family down the road, it should then concern everyone,
and the potential of iatrogenic transmission of the TSE prion is real i.e.
‘friendly fire’, medical, surgical, dental, blood, tissue, and or products there
from...like deer antler velvet and TSE prions and nutritional supplements there
from, all a potential risk factor that should not be ignored or silenced. ...
the prion gods at the cdc state that there is ;
''no strong evidence''
but let's see exactly what the authors of this cwd to human at the cdc
state ;
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 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 ;
Thursday, October 10, 2013
*************CJD REPORT 1994 increased risk for consumption of veal and
venison and lamb**************
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
*** our results raise the possibility that CJD cases classified as VV1 may
include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne
infection by type 1 prions from animals, e.g., chronic wasting disease prions in
cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have
been reported (40, 41). The results of the present study emphasize the need for
traceback studies and careful re-examination of the biochemical properties of
sCJD-VV1 prions. ***
snip...see full text ;
Thursday, January 2, 2014
*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant
Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ??? ***
*** 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.
*** We hypothesize that both BSE prions and CWD prions passaged through
felines will seed human recPrP more efficiently than BSE or CWD from the
original hosts, evidence that the new host will dampen the species barrier
between humans and BSE or CWD. The new host effect is particularly relevant as
we investigate potential means of trans-species transmission of prion disease.
*** We hypothesize that both BSE prions and CWD prions passaged through
felines will seed human recPrP more efficiently than BSE or CWD from the
original hosts, evidence that the new host will dampen the species barrier
between humans and BSE or CWD. The new host effect is particularly relevant as
we investigate potential means of trans-species transmission of prion disease.
Monday, August 8, 2011
*** Susceptibility of Domestic Cats to CWD Infection ***
Oral.29: Susceptibility of Domestic Cats to CWD Infection
Amy Nalls, Nicholas J. Haley, Jeanette Hayes-Klug, Kelly Anderson, Davis
M. Seelig, Dan S. Bucy, Susan L. Kraft, Edward A. Hoover and Candace K.
Mathiason†
Colorado State University; Fort Collins, CO USA†Presenting author; Email:
ckm@lamar.colostate.edu
Domestic and non-domestic cats have been shown to be susceptible to one
prion disease, feline spongiform encephalopathy (FSE), thought to be transmitted
through consumption of bovine spongiform encephalopathy (BSE) contaminated meat.
Because domestic and free ranging felids scavenge cervid carcasses, including
those in CWD affected areas, we evaluated the susceptibility of domestic cats to
CWD infection experimentally. Groups of n = 5 cats each were inoculated either
intracerebrally (IC) or orally (PO) with CWD deer brain homogenate. Between
40–43 months following IC inoculation, two cats developed mild but progressive
symptoms including weight loss, anorexia, polydipsia, patterned motor behaviors
and ataxia—ultimately mandating euthanasia. Magnetic resonance imaging (MRI) on
the brain of one of these animals (vs. two age-matched controls) performed just
before euthanasia revealed increased ventricular system volume, more prominent
sulci, and T2 hyperintensity deep in the white matter of the frontal hemisphere
and in cortical grey distributed through the brain, likely representing
inflammation or gliosis. PrPRES and widely distributed peri-neuronal vacuoles
were demonstrated in the brains of both animals by immunodetection assays. No
clinical signs of TSE have been detected in the remaining primary passage cats
after 80 months pi. Feline-adapted CWD was sub-passaged into groups (n=4 or 5)
of cats by IC, PO, and IP/SQ routes. Currently, at 22 months pi, all five IC
inoculated cats are demonstrating abnormal behavior including increasing
aggressiveness, pacing, and hyper responsiveness.
*** Two of these cats have developed rear limb ataxia. Although the
limited data from this ongoing study must be considered preliminary, they raise
the potential for cervid-to-feline transmission in nature.
AD.63:
Susceptibility of domestic cats to chronic wasting disease
Amy V.Nalls,1 Candace Mathiason,1 Davis Seelig,2 Susan Kraft,1 Kevin
Carnes,1 Kelly Anderson,1 Jeanette Hayes-Klug1 and Edward A. Hoover1 1Colorado
State University; Fort Collins, CO USA; 2University of Minnesota; Saint Paul, MN
USA
Domestic and nondomestic cats have been shown to be susceptible to feline
spongiform encephalopathy (FSE), almost certainly caused by consumption of
bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and
free-ranging nondomestic felids scavenge cervid carcasses, including those in
areas affected by chronic wasting disease (CWD), we evaluated the susceptibility
of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5
cats each were inoculated either intracerebrally (IC) or orally (PO) with
CWD-infected deer brain. At 40 and 42 mo post-inoculation, two IC-inoculated
cats developed signs consistent with prion disease, including a stilted gait,
weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail
tremors, and ataxia, and progressed to terminal disease within 5 mo. Brains from
these two cats were pooled and inoculated into cohorts of cats by IC, PO, and
intraperitoneal and subcutaneous (IP/SC) routes. Upon subpassage, feline-adapted
CWD (FelCWD) was transmitted to all IC-inoculated cats with a decreased
incubation period of 23 to 27 mo. FelCWD was detected in the brains of all the
symptomatic cats by western blotting and immunohistochemistry and abnormalities
were seen in magnetic resonance imaging, including multifocal T2 fluid
attenuated inversion recovery (FLAIR) signal hyper-intensities, ventricular size
increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4
IP/SQ and 2 of 4 PO inoculared cats have developed abnormal behavior patterns
consistent with the early stage of feline CWD.
*** These results demonstrate that CWD can be transmitted and adapted to
the domestic cat, thus raising the issue of potential cervid-to- feline
transmission in nature.
Tuesday, November 04, 2014
*** Six-year follow-up of a point-source exposure to CWD contaminated
venison in an Upstate New York community: risk behaviours and health outcomes
2005–2011
www.landesbioscience.com
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
FELINE SPONGIFORM ENCEPHALOPATHY FSE
Thursday, July 03, 2014
*** How Chronic Wasting Disease is affecting deer population and what’s
the risk to humans and pets?
Saturday, January 31, 2015
European red deer (Cervus elaphus elaphus) are susceptible to Bovine
Spongiform Encephalopathy BSE by Oral Alimentary route
*** Singeltary reply ;
ruminant feed ban for cervids in the United States ?
31 Jan 2015 at 20:14 GMT
Friday, January 30, 2015
*** Scrapie: a particularly persistent pathogen ***
===========
P.153: An independent and blinded confirmation of real-time quakinginduced
conversion (RT-QuIC) analysis of cervid rectal biopsies for detection of chronic
wasting disease
Sireesha Manne1,*, Naveen Kondru1, Nicholas Haley2, Tracy Nichols3, Bruce
Thomsen4, Roger Main5, Patrick Halbur5, Arthi Kanthasamy1, and Anumantha
Kanthasamy1 1Biomedical Sciences; Iowa State University; Ames, IA USA; 2Kansas
State University; Manhattan, KS USA; 3United States Department of Agriculture;
Fort Collins, CO USA; 4National Veterinary Service Laboratories; Ames, IA USA;
5VDPAM; Iowa State University; Ames, IA USA
Prion diseases are transmissible spongiform encephalopathies (TSEs)
characterized by an always fatal, progressive neuronal degeneration in the brain
due to infectious misfolded prion proteins whose prolonged incubation periods
often make ante-mortem diagnosis difficult. Chronic wasting disease (CWD) is a
TSE affecting both wild and captive populations of mule deer, whitetailed deer,
elk and moose. CWD in cervids was first identified in Rocky Mountain States and
has recently spread to several other states including Iowa. In this current
study, we attempted to independently confirm the results of a Real-Time
Quaking-Induced Conversion (RT-QuIC) assay to diagnose CWD using rectal biopsy
sections from farmed white-tailed deer. First, we generated recombinant prion
protein substrate and then validated the quality of protein for RT-QuIC using a
reference prion protein kindly provided by Dr. Caughey’s lab. After validating
the assay, we blindly evaluated approximately 350 rectal biopsy samples analyzed
previously by another institution. All assay plates included positive and
negative controls and were analyzed in triplicate. Samples were analyzed using
the Biotek Cytation-3 multimode plate reader for 24-hrs duration. Our RT-QuIC
assays showed 55% positivity for 356 rectal samples analyzed. Comparison of
RT-QuIC results with the immunohistochemical results of obex revealed 93%
sensitivity (95% confidence limits: 88.05–95.78%) and 96% specificity (95% CL:
91–99%), confirming that the RT-QuIC assay may be one of the most promising
rapid assays for detecting CWD prions. We are currently working on applying the
RT-QuIC assay to other test samples (ISU Presidential Wildlife initiative,
ISU-CVM Diagnostic lab and ES10586).
==========
P.154: Brain derived lipids inhibit prion amyloid formation in vitro
Clare Hoover, Davin Henderson, Mark Zabel, and Edward Hoover Colorado State
University; Fort Collins, CO USA
The normal cellular prion protein (PrPC) resides in cellular outer membrane
lipid rafts and conversion from PrPC to the pathogenic misfolded isoform is
believed to occur at the lipid membrane. In vitro assays have demonstrated the
intimate association between prion conversion and lipids, specifically
phosphatidylethanolamine, which is a critical cofactor in the formation of
synthetic infectious prions. In the current work, we demonstrate an opposing
property of lipids, the ability to inhibit amyloid formation in vitro. The
real-time quakinginduced conversion assay (RT-QuIC) was used to investigate
whole brain lipid effects on prion amyloid formation. An alcohol based
extraction technique was used to remove the lipid content from terminal chronic
wasting disease (CWD)- infected white tailed deer brain homogenates. Eliminating
lipids increased the sensitivity of RT-QuIC detection of CWD in brain samples
one hundred-fold. Addition of brain-derived lipid extracts to CWD prion samples
inhibited amyloid formation in a dose-dependent manner. Brain-derived lipids
also inhibited prion amyloid formation in RT-QuIC reaction seeds derived from
lymphoid tissues. This is the first demonstration of brain derived lipids
directly inhibiting prion amyloid formation in vitro and highlights the diverse
roles lipids play in the conversion process. Further experiments will identify
the individual lipid species or groups of lipids responsible for this inhibitory
activity.
============
P.160: Detecting the temporal status of prionemia in transmissible
spongiform encephalopathy-infected hosts
Alan Elder1, Davin Henderson1, Amy Nalls1, Kristen Davenport1, Anthony
Kincaid2, Edward Hoover1, Jason Bartz2, and Candace Mathiason1 1Colorado State
University; Fort Collins, CO USA; 2Creighton University; Omaha, NE USA
Infectious prions can traverse epithelial barriers and gain access to the
circulatory system early in infection. The details of prion entry, temporal
status, and persistence in the blood remain unknown. Furthermore, it is unknown
if the route of inoculation plays a role in the development of prionemia. We
previously demonstrated PrPC amyloid conversion activity in the blood
(prionemia) of deer and hamsters infected with transmissible spongiform
encephalopathies (TSEs) using whole blood real-time quaking-induced conversion
(wbRT-QuIC). In this study we analyzed the temporal status of prionemia,
spanning 0–100% of the disease course, in hosts exposed to TSEs via blood
transfusion or other peripheral means (i.e. oral, aerosol, extranasal, and
subcutaneous). Our results demonstrate the presence of PrPC amyolid conversion
activity in the blood of all TSE-inoculated hosts as early as 15 minutes post
inoculation likely-representing the point source inoculum–which was cleared from
the circulatory system by 72 hours post exposure. De novo host generated
hematogenous PrPC amyloid conversion activity, or prionemia, was identified at
4–5% of the TSE disease course and persisted throughout disease. ***Our results
indicate that hematogenous prions can traverse mucosal surfaces and enter the
circulatory system with the same speed and efficiency as those entering the
blood directly by blood transfusion, and that an asymptomatic carrier state is
established within minutes of TSE exposure.
==========
***Our results indicate that hematogenous prions can traverse mucosal
surfaces and enter the circulatory system with the same speed and efficiency as
those entering the blood directly by blood transfusion, and that an asymptomatic
carrier state is established within minutes of TSE exposure.***
===========
P.161: Prion soil binding may explain efficient horizontal CWD
transmission
Nathaniel Denkers1, Davin Henderson1, Shannon Bartelt-Hunt2, Jason Bartz3,
and Edward Hoover1 1Colorado State University; Fort Collins, Colorado USA;
2University of Nebraska-Lincoln; Omaha, Nebraska USA; 3Creighton University;
Omaha, Nebraska USA
Background. Chronic wasting disease (CWD) is unique due to the facile
spread in nature. The interaction of excreted CWD prions and soil is a
hypothesized contributor in environmental transmission. The present study
examines whether and to what degree CWD prions bind to silty clay loam (SCL)
using an adapted version of real-time quaking-induced conversion (RT-QuIC)
methodology.
Materials and Methods. Varying amounts (50–3.12 mg) of SCL were incubated
with 1 mL-serial dilutions of CWD (C), CWD (¡), or no brain homogenate (BH).
Samples were centrifuged, washed, diluted 1:10 in 0.1% SDS, and 2.5 uL seeded in
RT-QuIC assays employing recombinant Syrian hamster prion PrP substrate.
Multiple well replicates of sample and supernatant fractions were assayed for
positive seeding activity (recorded as thioflavin T fluorescence emission; 480
nm). Samples were considered positive if they crossed a threshold of 25,000.
Reaction rates (RR) were calculated, averaged, and expressed as 1/RR.
Results. Positive seeding activity was detected for most SCL samples
incubated with CWD (C) BH dilutions. Higher SCL concentrations (50 mg) produced
low fluorescent readings due to optical interference. Lower SCL concentrations
(6.25 mg) produced minimal optical interference and removed the vast majority of
seeding activity from CWDC BH in a concentration-dependent manner; determined by
seeding activity in residual BH supernatants. Control SCL and supernatants
produced minimal falsepositive reactions (8 of 240 replicates; 3.3%). We
estimated the prion binding capacity of SCL to be 0.16 ng/mg.
***Conclusion. Silty clay loam exhibits highly efficient prion binding,
inferring a durable environmental reservoir, and an efficient mechanism for
indirect horizontal CWD transmission.
==============
***Conclusion. Silty clay loam exhibits highly efficient prion binding,
inferring a durable environmental reservoir, and an efficient mechanism for
indirect horizontal CWD transmission.
=============
P.66: Transport of CWD prions in Alberta soils
Alsu Kuznetsova1, Debbie McKenzie2, Tariq Siddique1, and Judd Aiken2
1University of Alberta; Department of Renewable Resources; Edmonton, Canada;
2University of Alberta; Centre for Prions and Protein Folding Diseases;
Edmonton, Canada
The transmission of chronic wasting disease (CWD) includes environmental
pathways, particularly soils as disease reservoirs. Soils differ dramatically in
their capacity to adsorb PrPCWD due to differences in mineral composition, humus
content and particle surface area. Mineral and organic compounds have the
ability to bind PrPCWD impacting infectious properties. The extreme variability
of these soil constituents suggests that the PrPCWD fate and behavior will
depend on specific soil properties. The soil moisture regime also has the
potential to affect transportation of compounds through a soil profile. PrPCWD
can be bound to soil particles with Prion 2015 Poster Abstracts S45 3
hypothetical scenarios for prion fate: (i) prions stay in the surface soil
horizon and remain bioavailable for grazing animals; (ii) prions can be
transported into lower soil horizons and become unavailable for consumption; or
(iii) prions can migrate through the soil profile and end up in ground water. We
performed bench-scale experiments with soil columns to evaluate the potential
for transportation of PrPCWD using soils from different regions of Alberta,
Canada. The Luvisols found in northern Alberta have an ustic/udic moisture
regime and illite as a predominant clay mineral. The prion binding capacity of
illite is poor suggesting it cannot contribute to prion binding and PrPCWD can
migrate through the soil profile. Chernozems are found in the CWD-endemic region
in southern Alberta and have an aridic soil moisture regime, high amount of
humus content and contain montmorillonite. In the Chernozem soil columns PrPCWD
remains on the soil surface and does not migrate in lower horizons.
===========
PLEASE SEE;
Friday, May 22, 2015
Chronic Wasting Disease and Program Updates - 2014 NEUSAHA Annual Meeting
12-14 May 2014
============
P.70: Experimental transmission of chronic wasting disease to sheep and
goats
Gordon Mitchell, Nishandan Yogasingam, Ines Walther, and Aru Balachandran
National and OIE Reference Laboratory for Scrapie and CWD; Canadian Food
Inspection Agency; Ottawa, ON, Canada
The persistence of chronic wasting disease (CWD) in North American cervids,
coupled with efforts to eradicate scrapie in sheep and goats, necessitates an
understanding of the transmission, clinical and diagnostic characteristics of
CWD in small ruminants. Oral and intracerebral transmission studies were
conducted in sheep and goats using tissues from CWD-infected elk. Four lambs and
4 goats were orally inoculated with a pooled brain and lymph node homogenate
from a group of farmed elk with clinical CWD. At study endpoint, there was no
evidence of primary CWD transmission in the sheep or goat tissues examined by
ELISA, western blot and immunohistochemistry (IHC). Two lambs which were
challenged intracerebrally with the same pooled elk inoculate displayed
neurological signs beginning at 27 months postinoculation (mpi) and were
euthanized within 10 d of each other at 28 mpi. Testing of tissues by ELISA and
IHC confirmed disease transmission and revealed differences in the distribution
and intensity of PrPd deposition between animals. Western immunoblot analysis
identified characteristics permitting the differentiation of CWD in sheep from
other prion diseases in small ruminants. CWD-infected tissue from the
intracerabrally-inoculated sheep has undergone secondary passage into sheep and
goats and currently shows no evidence of oral transmission in rectal mucosa
biopsies at 20 mpi. These findings corroborate evidence of a significant species
barrier preventing the oral transmission of CWD to sheep and goats, and identify
diagnostic characteristics to enable the differentiation of prion diseases
affecting small ruminants.
===========
P.97: Scrapie transmits to white-tailed deer by the oral route and has a
molecular profile similar to chronic wasting disease and distinct from the
scrapie inoculum
Justin Greenlee1, S Jo Moore1, Jodi Smith1, M Heather West Greenlee2, and
Robert Kunkle1 1National Animal Disease Center; Ames, IA USA; 2Iowa State
University; Ames, IA USA
The purpose of this work was to determine susceptibility of white-tailed
deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to
that of the original inoculum and chronic wasting disease (CWD). We inoculated
WTD by a natural route of exposure (concurrent oral and intranasal (IN); n D 5)
with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc
accumulation. PrPSc was detected in lymphoid tissues at preclinical time points,
and deer necropsied after 28 months post-inoculation had clinical signs,
spongiform encephalopathy, and widespread distribution of PrPSc in neural and
lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular
profiles. WB on cerebral cortex had a profile similar to the original scrapie
inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc
with a higher profile resembling CWD. Homogenates with the 2 distinct profiles
from WTD with clinical scrapie were further passaged to mice expressing cervid
prion protein and intranasally to sheep and WTD. In cervidized mice, the 2
inocula have distinct incubation times. Sheep inoculated intranasally with WTD
derived scrapie developed disease, but only after inoculation with the inoculum
that had a scrapie-like profile. The WTD study is ongoing, but deer in both
inoculation groups are positive for PrPSc by rectal mucosal biopsy.*** In
summary, this work demonstrates that WTD are susceptible to the agent of
scrapie, 2 distinct molecular profiles of PrPSc are present in the tissues of
affected deer, and inoculum of either profile readily passes to deer.
=================
*** In summary, this work demonstrates that WTD are susceptible to the
agent of scrapie, 2 distinct molecular profiles of PrPSc are present in the
tissues of affected deer, and inoculum of either profile readily passes to deer.
***
================
P.128: Bioassay using ovine and cervid PrP transgenic mice for
discrimination of scrapie and CWD origins in sheep and goats
Sally Madsen-Bouterse1,*, Dongyue Zhuang2, David Schneider2, Rohana
Dassanayake1, Aru Balachandran3, Gordon Mitchell3, and Katherine O’Rourke1
1Department of Veterinary Microbiology and Pathology; College of Veterinary
Medicine; Washington State University; Pullman, WA USA; 2Animal Disease Research
Unit; Agricultural Research Service; US. Department of Agriculture; Pullman, WA
USA; 3National and OIE Reference Laboratory for Scrapie and CWD; Canadian Food
Inspection Agency; Ottawa Laboratory– Fallowfield; Ottawa, ON Canada
As the United States works toward the eradication of scrapie, identifying
TSE reservoirs that could lead to disease re-emergence is imperative.
Development of transgenic mice expressing either the ovine or cervid prion
protein has aided characterization of scrapie and CWD, respectively. We
hypothesize that transgenic mouse models will discern whether new incidents of
scrapie in sheep and goats with clinical disease originated from CWD exposure.
Two transgenic mouse lines (Tg338 and TgElk; minimum 5 mice/strain) were
inoculated with brain homogenate from clinically affected animals including
sheep or goats with naturally acquired classical scrapie, white-tailed deer with
naturally acquired CWD (WTD-CWD), or sheep experimentally inoculated with
elk-CWD (sheepelk- CWD). Transmission was assessed via survival analysis and
western blot characterization of brain PrPres. WTD-CWD transmitted efficiently
to TgElk with all mice culled due to clinical disease, whereas all Tg338
remained asymptomatic at endpoint with no PrPres detected in the brain. Ovine
and caprine scrapie transmitted poorly to TgElk with all mice asymptomatic at
endpoint and 6.8% brain-positive for PrPres, whereas all Tg338 were culled due
to clinical disease. Sheep elk-CWD yielded Tg338 that were all asymptomatic at
endpoint and were all brainpositive for PrPres. However, sheepelk-CWD yielded
TgElk with 5/22 displaying clinical disease near endpoint but 16/22
brain-positive for PrPres. Furthermore, TgElk-PrPres molecular mass appeared
lower when inoculated with caprine scrapie versus WTD-CWD and both molecular
masses were yielded when inoculated with sheepelk-CWD. ***These findings suggest
primary passage in Tg338 and TgElk could discern whether scrapie in sheep and
goats originated from CWD exposure.
===========
P.73: Oral challenge of goats with atypical scrapie
Silvia Colussi1, Maria Mazza1, Francesca Martucci1, Simone Peletto1,
Cristiano Corona1, Marina Gallo1, Cristina Bona1, Romolo Nonno2, Michele Di
Bari2, Claudia D’Agostino2, Nicola Martinelli3, Guerino Lombardi3, and Pier
Luigi Acutis1 1Istituto Zooprofilattico Sperimentale del Piemonte; Liguria e
Valle d’Aosta; Turin, Italy; 2Istituto Superiore di Sanit a; Rome, Italy;
3Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna;
Brescia, Italy
Atypical scrapie transmission has been demonstrated in sheep by
intracerebral and oral route (Simmons et al., Andreoletti et al., 2011) but data
about goats are not available yet. In 2006 we orally challenged four goats, five
months old, with genotype R/H and R/R at codon 154. Animals died starting from
24 to 77 months p.i. without clinical signs. They all resulted negative for
scrapie in CNS and peripheral tissues using Western blot and
immunohistochemistry. Nevertheless these goats could still represent carriers.
This hypothesis was investigated through bioassay in tg338 mice, a sensitive
animal model for atypical scrapie infectivity. By end-point dilution titration,
the starting inoculum contained 106.8 ID50/g. In contrast, all tissues from
challenged goats were negative by bioassay. These negative results could be
explained with the low infectivity of the starting inoculum, which could have
been unable to induce disease or infectivity within our period of observation.
However the challenge conditions could have been a bias too: as the matter of
the fact, while the oral challenge of classical scrapie is still effective in
sheep 6–10 months old (Andreoletti et al., 2011), Simmons et al. (2011)
demonstrated a very short efficacy period for atypical scrapie (24 hours after
birth), hypothesizing that natural transmission could occur mainly via milk.
***Our work suggests that this could be true also for goats and it should be
taken into account in oral challenges. However a low susceptibility of goats to
atypical scrapie transmission via oral route cannot be excluded.
=============
P.74: Transmission of experimental CH1641 scrapie to wild-type mice
Lucien van Keulen1,*, Jan Langeveld1, Corry Dolstra1, Jorg Jacobs1, Alex
Bossers1, and Fred van Zijderveld2 1Department of Infection Biology; Central
Veterinary Institute of Wageningen UR, Lelystad, The Netherlands; 2Department of
Bacteriology and TSEs; Central Veterinary Institute of Wageningen UR, Lelystad,
The Netherlands
Introduction. CH1641 was isolated in the UK in 1970 from a natural case of
scrapie in a Cheviot sheep and was further passaged intracerebrally in sheep.
CH1641 has been the subject of extensive research because of the biochemical
similarities of PrPres from CH1641- and BSE-affected sheep brains. Previous
attempts to transmit CH1641 to wild type mice have been unsuccessful. We report
here for the first time, the positive transmission of experimental CH1641 to
RIII mice and compare the incubation period, PrPSc profile and PrPres Western
blot properties to those of known scrapie and BSE reference strains.
Methods. The CH1641 brain homogenate used in this study came from a pool a
5 sheep brains which had been challenged intracerebrally with brain material
from the third passage of CH1641 in sheep. Groups of 15–20 RIII mice were
inoculated intracerebrally with a 10% brain homogenate of CH1641. The brains of
the mice were examined by PrPSc profiling and triplex Western blot as reported
previously.
Results. Surprisingly CH1641 transmitted to RIII mice with a 100% attack
rate although with a long incubation period (794 § 149 d). The resulting PrPSc
profile was unlike any of the profiles of the scrapie and BSE reference strains
reported previously. Triplex Western blot pointed after first passage to a very
low PrPres level. We observed a reduction of molecular mass of the non-glycosyl
PrPres moiety and concomittant N-terminal 12B2 epitope signal. In comparison to
the original CH1641 inoculum there was a lack of a dual population of
PrPres.
===========
***The serial transmission of different scrapie isolates in these mice led
to the propagation of prions that are phenotypically identical to those causing
sporadic CJD (sCJD) in humans.
***These results demonstrate that scrapie prions have a zoonotic potential
and raise new questions about the possible link between animal and human
prions.
Subject terms: Biological sciences• Medical research At a glance
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural
Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology: February 2012 -
Volume 71 - Issue 2 - p 140–147
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical
Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
===========
P.164: Blood transmission of prion infectivity in the squirrel monkey: The
Baxter study
Paul Brown1, Diane Ritchie2, James Ironside2, Christian Abee3, Thomas
Kreil4, and Susan Gibson5 1NIH (retired); Bethesda, MD USA; 2University of
Edinburgh; Edinburgh, UK; 3University of Texas; Bastrop, TX USA; 4Baxter
Bioscience; Vienna, Austria; 5University of South Alabama; Mobile, AL USA
Five vCJD disease transmissions and an estimated 1 in 2000 ‘silent’
infections in UK residents emphasize the continued need for information about
disease risk in humans. A large study of blood component infectivity in a
non-human primate model has now been completed and analyzed. Among 1 GSS, 4
sCJD, and 3 vCJD cases, only GSS leukocytes transmitted disease within a 5–6
year surveillance period. A transmission study in recipients of multiple whole
blood transfusions during the incubation and clinical stages of sCJD and vCJD in
ic-infected donor animals was uniformly negative. These results, together with
other laboratory studies in rodents and nonhuman primates and epidemiological
observations in humans, ***suggest that blood donations from cases of GSS (and
perhaps other familial forms of TSE) carry more risk than from vCJD cases, and
that little or no risk is associated with sCJD. The issue of decades-long
incubation periods in ‘silent’ vCJD carriers remains open.
=============
***suggest that blood donations from cases of GSS (and perhaps other
familial forms of TSE) carry more risk than from vCJD cases, and that little or
no risk is associated with sCJD...see;
Wednesday, December 11, 2013
*** Detection of Infectivity in Blood of Persons with Variant and Sporadic
Creutzfeldt-Jakob Disease ***
THE BAXTER STUDY...SEE MORE HERE ;
==============
P.23: An improved test for the detection of Creutzfeldt-Jakob Disease from
human CSF using new RT-QuIC conditions
Bradley R Groveman1, Christina D Orr u1, Andrew G Hughson1, Gianluigi
Zanusso2, Maurizio Pocchiari3, Michael B Coulthart4, and Byron Caughey1
1Laboratory of Persistent Viral Diseases; Rocky Mountain Laboratories; NIAID;
NIH; Hamilton, MT USA; 2Department of Neurological and Movement Sciences;
University of Verona; Verona, Italy; 3Department of Cell Biology and
Neurosciences; Istituto Superiore di Sanit a; Rome, Italy; 4Canadian CJD
Surveillance System; Public Health Agency of Canada; Ottawa, ON Canada
Neurodegenerative protein misfolding diseases are difficult to diagnose
early and accurately. This is particularly worrisome with human prion diseases,
such as Creutzfeldt- Jakob disease (CJD), because prions are transmissible,
deadly, and unusually resistant to decontamination. Real-time quaking-induced
conversion (RT-QuIC) assays allow highly sensitive and specific testing for CJD
using human cerebrospinal fluid (CSF) or nasal brushings and are being widely
implemented as important diagnostic tools. However, such laboratory analyses
have required 2.5 to 5 d to complete. Furthermore, CSF testing using previously
evaluated RT-QuIC conditions still yields false negative results in 11 to 23% of
CJD cases. We have now developed an improved RT-QuIC assay which can identify
positive CSF samples within 4 to 14 h with better analytical and diagnostic
sensitivity. Analysis of CSF samples from 11 CJD patients demonstrated that
while 7 were RT-QuIC positive using previous conditions, an additional 3 samples
were positive using the new assay. In these and subsequent analyses, a total of
46 of 48 CSF samples from sporadic CJD patients gave positive RT-QuIC responses,
while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity
and 100% specificity. This diagnostic sensitivity was significantly better than
that obtained using the previous conditions. We continue to expand the testing
of CJD-positive and -negative CSF samples to further establish the diagnostic
utility of this new assay for various human prion diseases. So far, our improved
RT-QuIC assay appears to allow for much faster, more accurate and practical
antemortem testing for CJD using CSF samples.
===========
P.159: Improvements of nasal brushing procedure for Creutzfeldt-Jakob
disease diagnosis
Matilde Bongianni1, Christina Orr u2, Giovanni Tonoli3, Bradley Groveman2,
Giorgo Triva4, Santina Castriciano4, Luca Sacchetto1, Andrew Hughson2,
Annachiara Cagnin5, Stefano Capaldi1, Sergio Ferrari1, Michele Fiorini1,
Salvatore Monaco1, Maurizio Pocchiari6, Byron Caughey2, and Gianluigi Zanusso1
1University of Verona; Verona, Italy; 2Rocky Montain Laboratories; Hamilton, MT
USA; 3Ospedale “Santa Maria della Misericordia”; Rovigo, Italy; 4Copan Italia
S.P.A.; Brescia, Italy; 5University of Padua; Padua, Italy; 6Istituto Superiore
di Sanit a; Rome, Italy
Introduction. We previously identified prion seeding activity in olfactory
mucosa (OM) of CJD patients using nasal brushings coupled with Real Time Quaking
induced Conversion (RT-QuIC) with 100% specificity and >97% sensitivity. OM
samples were collected using a sterile disposable Cyto-brush (Kito-Brush,
Kaltek) which might provoke a mild discomfort for patients. Therefore, we aimed
to use a more gentle tool for OM samplings such as short nylon fiber Flocked
swabs (Copan technologies).
Materials and Methods. We collected OM and CSF samples in 43 CJD patients.
To ensure efficient OM sample collection, each patient underwent to two OM
samplings using flocked swabs one in each nostril and a final with Cytobrush. OM
samples were processed and analyzed by RT-QuIC, as previously described.
Results. Using Cyto-brushes 32 out of 35 OM samples were positive by
RT-QuIC analysis, while flocked swabs in 40 out of 43 OM samples. In contrast,
CSF samples were positive in 33 out of 43. Two OM samples resulted negative for
both Cyto-brush and Flocked swab. Neither OM sampling technique or CSF produced
false positives.
***Conclusion. This study demonstrates that OM brushing following RT-QuIC
ssay is 95% sensitive and 100% specific in CJD diagnosis while CSF resulted 77%
sensitive. OM collection using flocked swabs is preferred and provides same
sensitivity as cyto-brush. These data recommend four separate samplings possibly
from both nostrils to maximize the sensitivity, using three Flocked swabs and
lastly a brush.
============
P.24: A comparative study of dura mater graft-associated Creutzfeldt-Jakob
disease between Japan and other countries
Tsuyoshi Hamaguchi1, Kenji Sakai1, Moeko Noguchi-Shinohara1, Ichiro
Nozaki1, Ichiro Takumi2, Nobuo Sanjo3, Yosikazu Nakamura4, Tetsuyuki Kitamoto5,
Nobuhito Saito6, Hidehiro Mizusawa7, and Masahito Yamada1 1Department of
Neurology and Neurobiology of Aging; Kanazawa University Graduate School of
Medical Science; Kanazawa, Japan; 2Department of Neurosurgery; Nippon Medical
School Musashi Kosugi Hospital; Kawasaki, Japan; 3Department of Neurology and
Neurological Science; Graduate School; Tokyo Medical and Dental University;
Tokyo, Japan; 4Department of Public Health; Jichi Medical University;
Shimotsuke, Japan; 5Departments of Prion Protein Research; Division of CJD
Science and Technology; Tohoku University Graduate School of Medicine; Sendai,
Japan; 6Department of Neurosurgery; Faculty of Medicine; The University of
Tokyo; Tokyo, Japan; 7National Center Hospital; National Center of Neurology and
Psychiatry; Tokyo, Japan
Objective. More than 60% of patients worldwide diagnosed with
Creutzfeldt-Jakob disease
(CJD) associated with dura mater graft (dCJD) have been identified in
Japan. The remarkable frequency of dura mater graft use in Japan might
contribute to the elevated incidence of dCJD, but the possible reasons for the
disproportionate use of this procedure in Japan remain unclear. We investigated
the differences between dCJD patients in Japan and those elsewhere to help
uncover an explanation for the unusually more frequent use of cadaveric dura
mater and high incidence of dCJD in Japan.
Methods. We obtained data of dCJD patients in Japan from the nationwide
surveillance of CJD in Japan and of those in other countries from extant
literature. We compared demographic, clinical, and pathological features of dCJD
patients between Japan and elsewhere.
Results. Data from 142 dCJD patients in Japan and 53 in other countries
were obtained. The medical conditions precipitating dura mater graft were
significantly different between Japan and other countries (P < 0.001); in
Japan, there were more cases of cerebrovascular disease and hemifacial spasm or
trigeminal neuralgia. Patients with dCJD in Japan received dura mater graft more
often for non-life-threatening conditions, such as meningioma, hemifacial spasm
and trigeminal neuralgia, than those in other countries.
Conclusion. Differences in the medical conditions precipitating dura mater
graft may contribute to the frequent use of cadaveric dura mater and the higher
incidence of dCJD in Japan.
===============
P.34: Preliminary study of Alzheimer’s disease transmission to bank
vole
Guido Di Donato1, Geraldina Riccardi1, Claudia D’Agostino1, Flavio
Torriani1, Maurizio Pocchiari2, Romolo Nonno1, Umberto Agrimi1, and Michele
Angelo Di Bari1 1Department of Food Safety and Veterinary Public Health Istituto
Superiore di Sanit a, Rome, Italy; 2Department of Cellular Biology and
Neuroscience; Istituto Superiore di Sanit a, Rome, Italy
Extensive experimental findings indicate that prion-like mechanisms underly
the pathogenesis of Alzheimer disease (AD). Transgenic mice have been pivotal
for investigating prionlike mechanisms in AD, still these models have not been
able so far to recapitulate the complex clinical-pathological features of AD.
Here we aimed at investigating the potential of bank vole, a wild-type rodent
highly susceptible to prions, in reproducing AD pathology upon experimental
inoculation.
Voles were intracerebrally inoculated with brain homogenate from a familial
AD patient. Animals were examined for the appearance of neurological signs until
the end of experiment (800 d post-inoculation, d.p.i.). Brains were studied by
immunohistochemistry for pTau Prion 2015 Poster Abstracts S29 (with AT180 and
PHF-1 antibodies) and b-amyloid (4G8).
Voles didn’t show an overt clinical signs, still most of them (11/16) were
found pTau positive when culled for intercurrent disease or at the end of
experiment. Interestingly, voles culled as early as 125 d.p.i. already showed
pTau aggregates. Deposition of pTau was similar in all voles and was
characterized by neuropil threads and coiled bodies in the alveus, and by rare
neurofibrillary tangles in gray matter. Conversely, b-amyloid deposition was
rather rare (2/16). Nonetheless, a single vole showed the contemporaneous
presence of pTau in the alveus and a few Ab plaque-like deposits in the
subiculum. Uninfected age-matched voles were negative for pTau and Ab.
These findings corroborate and extend previous evidences on the
transmissibility of pTau and Ab aggregation. Furthermore, the observation of a
vole with contemporaneous propagation of pTau and Ab is intriguing and deserves
further studies.
=================
PLEASE SEE ;
Self-Propagative Replication of Ab Oligomers Suggests Potential
Transmissibility in Alzheimer Disease
Received July 24, 2014; Accepted September 16, 2014; Published November 3,
2014
Singeltary comment ;
===============
P.36: Spontaneous in vitro conversion of full length recombinant human
prion protein in unseeded RT-QuIC reactions
Marcelo Barria Matus, Alexander Peden, Richard Knight, James Ironside, and
Mark Head National CJD Research & Surveillance Unit; The University of
Edinburgh, Edinburgh, UK
Sporadic Creutzfeldt–Jakob disease (sCJD) is the most common human prion
disease, affecting approximately 1–2 persons per one million of the population
per year. It is thought to arise as a result of spontaneous conversion of PrPC
to PrPSc, which becomes self-propagating. The prion protein polymorphism at
codon 129 encodes either methionine (M) or valine (V). Comparison of the codon
129 genotype distribution in sCJD cohorts with that of the normal Caucasian
population suggests that heterozygosity (MV) protects against sCJD and the
comparison has also been widely interpreted to mean that methionine homozygosity
predisposes to CJD.
We have used real-time quaking induced conversion (RT-QuIC) to model the
S30 Prion 2015 Poster Abstracts spontaneous formation of the abnormal form of
human PrP and to determine whether methionine or valine at the position 129 of
PrPC confers a greater susceptibility to spontaneous conversion to PrP
amyloid.
Unseeded RT-QuIC reactions using fulllength recombinant human prion protein
with either methionine or valine at position 129 both resulted in spontaneous
amyloid formation. The process appeared to have a pronounced stochastic element,
but when a sufficient number of replicates were performed a clear and
reproducible effect of codon 129 genotype was also evident, in which PrPC with
valine at codon 129 showed a greater predisposition to form amyloid than its
allelic counterpart containing methionine.
***These results question whether methionine at position 129 in PrPC can be
considered an intrinsic susceptibility factor for conversion to PrPSc, at least
in terms of the initiation of spontaneous, as opposed to seeded PrP amyloid
formation.
==========
P.69: Distinct pathological phenotypes of Creutzfeldt-Jakob disease in
recipients of prion-contaminated growth hormone
Ignazio Cali1,2, Cathleen Miller3, Tetsuyuky Kitamoto4, Joseph Parisi5,
Michael Geschwind6, Pierluigi Gambetti1, and Lawrence Schonberger7 1National
Prion Disease Pathology Surveillance Center (NPDPSC); Department of Pathology;
Case Western Reserve University; School of Medicine; Cleveland, OH USA;
2Department of Clinical and Experimental Medicine; Second University of Naples;
Naples, Italy; 3Kaiser Permanente Vancouver Medical Center; Vancouver, WA USA;
4Graduate School of Medicine; Tohoku University; Sendai, Japan; 5Departments of
Laboratory Medicine & Pathology and Neurology; Mayo Clinic; Rochester, MN
USA; 6Department of Neurology; Memory and Aging Center; University of
California; San Francisco, CA USA; 7National Center for Emerging and Zoonotic
Infectious Diseases; Centers for Disease Control and Prevention; Atlanta, GA
USA
The peripheral administration of growth hormone (GH) from
prion-contaminated cadaveric pituitary glands is believed to be causative of
iatrogenic Creutzfeldt-Jakob disease (iCJD) in more than 225 subjects worldwide.
The present study describes the neuropathology and molecular features of 3 of
the 30 identified iCJD cases among the approximately 7,700 recipients of
cadaveric pituitary hormone in the US National Hormone and Pituitary Program
(NHPP). All three cases were methionine (M) homozygous at codon 129 of the prion
protein (PrP) gene (GH-CJDMM) and all received NHPP hormone produced before 1977
when a new hormone purification protocol was introduced that reduced the risk of
prion contamination. Neuropathological examination revealed divergent
phenotypes. The first phenotype, observed in the most recent US NHPP GH-CJD
case, was characterized by the presence of amyloid plaques and reminiscent of
sCJDMV2-K and, to some extent, variant CJD (vCJD). The second phenotype showed
no plaques and shared several, but not all, characteristics with the sCJDMM(MV)1
subtype. However, PKresistant PrPSc (resPrPSc) from GH-CJDMM co-migrated with
resPrPSc type 1 (GHCJDMM1) of sCJDMM1, but not with type 2 of sCJDMV2-K.
Histopathological phenotypes with or without plaques also have been described in
2 groups of Japanese dura mater (d) graft-associated CJD (dCJD) with the same
129MM genotype but apparently different gel mobility of resPrPSc type 1. ***Our
study suggests that phenotypic diversity in these iatrogenic diseases reflects
adaptation of different exogenous prion strains to the 129MM host and/or to
different locations of the initial PrPC to PrPSc conversion.
===========
P.75: Development of pre-mortem diagnosis for suspected Creutzfeldt- Jakob
diseases’ patients
SuYeon Kim, JaeWook Hyeon, YeongRan Ju, JiYeon Lee, WonCheol Lee, and
YeongSeon Lee Korea NIH (KCDC); Cheonju, Chungcheongbukdo, Republic of
Korea
Creutzfeldt-Jakob disease (CJD) is the most representative human prion
disease caused by abnormal accumulation of misfolding prion protein. The
diagnosis is performed with features of magnetic resonance imaging,
electroencephalogram and elevated the 14-3-3 protein findings, prion protein
gene polymorphisms. In laboratory, the protein detection and analysis of the
gene polymorphisms have been monitored, and then clinicians determined as CJD
patient or not CJD case combining specific clinical opinions in Korea. We aimed
evaluate the epidemiological tendency, and the possibility of early diagnosis
through the application of clinical features included the protein tests and
genetic analysis. We detected 14-3-3 protein, and analyzed PRNP genotypes for
suspected cases (2010–2014). The results were combined with progressive
dementia, myoclonus, and memory decline, and their relationships were analyzed.
They were almost within the age range of 60–80 years, and the numbers of male
and female were similar. Approximately 49% showed positive for 14-3-3 protein,
and the polymorphisms reported to genetic pathogenic factor inherited CJD showed
in 11 patients. Three definite and 14 possible sCJD patients defined except for
one were positive for 14-3-3, and several probable sporadic cases had pathogenic
genetic factors like P102L, E200K and V180I. The clinical presentations showed
progressive dementia, visual illusion, myoclonus, ataxia, akinetic mutism, and
memory decline. Some MRI and EEG findings showed high signal abnormalities in
the fronto-temporal cortex and typical periodic sharp wave complexes. We
consider that the active following surveillance for patients would be added to
improve the specificity of early CJD diagnosis.
===============
==============
P.13: Detection of sCJD prions in human saliva by RT-QuIC
Matteo Manca1, Gianluigi Zanusso2, and Byron Caughey1 1Laboratory of
Persistent Viral Diseases; Rocky Mountain Laboratories (RML); National Institute
of Allergy and Infectious Disease (NIAID); National Institutes of Health (NIH);
Hamilton, MT USA; 2Department of Neurological and Movement Sciences; University
of Verona; Verona, Verona, Italy
Sporadic Creutzfeldt-Jakob Disease (sCJD) is the most common form of human
prion disease. A recent study showed that prion seeding activity is
RT-QuIC-detectable in the olfactory neuroepithelium of sCJD patients. Relatively
rapid turnover of the olfactory neuroepithelium and nasal mucus clearance
systems might lead to the transportation of prion seeds into the oral cavity and
shedding through saliva. Pooled human saliva was spiked with sCJD prions and
subjected to different treatments to investigate the suitability of such a
sample as a new and non-invasive diagnostic specimen. Our findings highlighted
the presence of yet unidentified factor( s) that could lead to spontaneous
conversion in the RT-QuIC assay. We will show our ongoing results on the attempt
to identify the factor (s) and eliminate it/them.
=================
P.85: Improving Creutzfeldt-Jakob disease incidence estimates by
incorporating results of neuropathological analyses, United States,
2003–2011
Ryan Maddox1, Marissa Person1, Arialdi Minino2, Janis Blevins3, Lawrence
Schonberger1, and Ermias Belay1 1National Center for Emerging and Zoonotic
Infectious Diseases; Centers for Disease Control and Prevention, Atlanta GA USA;
2National Center for Health Statistics; Centers for Disease Control and
Prevention; Hyattsville, MD USA; 3National Prion Disease Pathology Surveillance
Center; Case Western Reserve University; Cleveland, OH USA
Introduction. The incidence of invariably fatal prion diseases such as
Creutzfeldt-Jakob disease (CJD) can be estimated by analyzing death certificate
data, but there are limitations.
Methods. Prion disease decedents were identified from the US national
multiple cause-ofdeath data and the National Prion Disease Pathology
Surveillance Center (NPDPSC) database for 2003–2011. Due to limited personal
identifying information, an algorithm was constructed to determine likely
decedent matches between the 2 databases. NPDPSC decedents with a positive prion
disease autopsy or biopsy result or genetic mutation for whom no match was found
in the multiple cause-of-death data were added as cases for incidence
calculations; those with negative neuropathology results but
Prion 2015 Poster Abstracts S55
with a death certificate indicating prion disease were removed. The
resulting average annual age-adjusted incidence was then calculated. Results. A
total of 2986 decedents were identified as having prion disease indicated as a
cause of death in the multiple cause-of-death data; 469 additional NPDPSC
decedents were identified with positive neuropathology and/or genetic findings,
while 140 decedents with death certificates indicating prion disease had
negative neuropathology results. Incorporating the matched data, the average
annual age adjusted incidence of CJD in the United States was 1.2 per
million.
Conclusion. Analysis of multiple cause-ofdeath data is an efficient means
of conducting CJD surveillance. However, not all decedents are captured as the
death certificate may not list the diagnosis; conversely, a CJD diagnosis on the
certificate may be contradicted by neuropathology results. Incorporating
findings from NPDPSC neuropathological and genetic analyses produces an estimate
closer to the true incidence of the disease.
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
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
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 ...
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01 Most doctors believe that sCJD is caused by a prion protein
deforming by chance into a killer. But Singeltary thinks otherwise. He is one of
a number of campaigners who say that some sCJD, like the variant CJD related to
BSE, is caused by eating meat from infected animals. Their suspicions have
focused on sheep carrying scrapie, a BSE-like disease that is widespread in
flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds
weight to the campaigners' fears. To their complete surprise, the researchers
found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb...
Tuesday, December 16, 2014
Evidence for zoonotic potential of ovine scrapie prions
Scrapie from sheep could infect humans with 'mad cow disease', study finds
The Pathological Protein:
Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
Philip Yam
''Answering critics like Terry Singeltary, who feels that the US
undercounts CJD, Schonberger _conceded_ that the current surveillance system has
errors but stated that most of the errors will be confined to the older
population''....end
snip...
His combative, blunt, opinion- ated style sometimes borders on obsessive
ranting that earns praise from some officials and researchers but infuriates
others especially when he repeats his conviction that "the government has lied
to us, the feed industry has lied to us all over a buck." As evidence,
Singeltary cites the USDA's testing approach, which targets downer cows and
examined 19,900 of them in 2002. To him, the USDA should test 1 mil- lion
cattle, because the incidence of BSE may be as low as one in a mil- lion, as it
was in some European countries. That the U.S. does not, he thinks, is a sign
that the government is really not interested in finding mad cows because of
fears of an economic disaster.
Singeltary got into the field of transmissible spongiform encepha- lopathy
in 1997, just after his mother died of sporadic CJD. She had an especially
aggressive version the Heidenhain variant that first causes the patient to go
blind and then to deteriorate rapidly She died just ten weeks after her symptoms
began. Singeltary, who said he had watched his grandparents die of cancer,
considered her death by CJD to be much, much worse: "It's something you never
forget." Her uncon- trollable muscle twitching became so bad "that it took three
of us to hold her one time," Singeltary recalled. "She did everything but
levitate in bed and spin her head."
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in
North America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember,
the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been
documented in North America, along with the typical scrapie's, and atypical
Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these
TSE in different species have been rendered and fed to food producing animals
for humans and animals in North America (TSE in cats and dogs ?), and that the
trading of these TSEs via animals and products via the USA and Canada has been
immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only
enhances and helps the spreading of human TSE from the continued belief of the
UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to
continue to validate this old myth, will only spread this TSE agent through a
multitude of potential routes and sources i.e. consumption, medical i.e.,
surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics
etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and
the urgent need to make all human TSE in the USA a reportable disease, in every
state, of every age group, and to make this mandatory immediately without
further delay. The ramifications of not doing so will only allow this agent to
spread further in the medical, dental, surgical arena's. Restricting the
reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO
age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge,
Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al
and many more, that the world of TSE Transmissible Spongiform Encephalopathy is
far from an exact science, but there is enough proven science to date that this
myth should be put to rest once and for all, and that we move forward with a new
classification for human and animal TSE that would properly identify the
infected species, the source species, and then the route.
re-Self-Propagative Replication of Ab Oligomers Suggests Potential
Transmissibility in Alzheimer Disease
Received July 24, 2014; Accepted September 16, 2014; Published November 3,
2014
Singeltary comment ;
RE: re-Human Prion Diseases in the United States
part 2 flounder replied to flounder on 02 Jan 2010 at 21:26 GMT
No competing interests declared.
No competing interests declared.
see full text ;
*** PLOS Singeltary reply ;
Molecular, Biochemical and Genetic Characteristics of BSE in Canada
Singeltary reply ;
PLOS Singeltary reply ;
ruminant feed ban for cervids in the United States ?
Singeltary T. S.
31 Jan 2015 at 20:14 GMT
"Löcher wie in einem Schweizer Käse" hat auch Terry Singeltary im
Regelwerk der FDA ausgemacht. Der Texaner kam auf einem tragischen Umweg zu dem
Thema: Nachdem seine Mutter 1997 binnen weniger Wochen an der
Creutzfeldt-Jakob-Krankheit gestorben war, versuchte er, die Ursachen der
Infektion aufzuspüren. Er klagte auf die Herausgabe von Regierungsdokumenten und
arbeitete sich durch Fachliteratur; heute ist er überzeugt, dass seine Mutter
durch die stetige Einnahme von angeblich kräftigenden Mitteln erkrankte, in
denen - völlig legal - Anteile aus Rinderprodukten enthalten sind.
Von der Fachwelt wurde Singeltary lange als versponnener Außenseiter
belächelt. Doch mittlerweile sorgen sich auch Experten, dass ausgerechnet diese
verschreibungsfreien Wundercocktails zur Stärkung von Intelligenz, Immunsystem
oder Libido von den Importbeschränkungen ausgenommen sind. Dabei enthalten die
Pillen und Ampullen, die in Supermärkten verkauft werden, exotische Mixturen aus
Rinderaugen; dazu Extrakte von Hypophyse oder Kälberföten, Prostata, Lymphknoten
und gefriergetrocknetem Schweinemagen. In die USA hereingelassen werden auch
Blut, Fett, Gelatine und Samen. Diese Stoffe tauchen noch immer in US-Produkten
auf, inklusive Medizin und Kosmetika. Selbst in Impfstoffen waren möglicherweise
gefährliche Rinderprodukte enthalten. Zwar fordert die FDA schon seit acht
Jahren die US-Pharmaindustrie auf, keine Stoffe aus Ländern zu benutzen, in
denen die Gefahr einer BSE-Infizierung besteht. Aber erst kürzlich
verpflichteten sich fünf Unternehmen, darunter Branchenführer wie
GlaxoSmithKline, Aventis und American Home Products, ihre Seren nur noch aus
unverdächtigem Material herzustellen.
"Its as full of holes as Swiss Cheese" says Terry Singeltary of the FDA
regulations. ...
New York Times Magazine The Case of the Cherry Hill Cluster By D.T. MAX
Published: March 28, 2004
snip...
Skarbek did not know how to surmount this objection. But she was a
go-getter. She wasn't about to give up on her cluster so easily. Fortunately,
she was in contact with Terry Singeltary. She had seen his name quoted often on
the Web in articles on C.J.D. and mad cow. Singeltary lost his mother to an
extremely rare strain of sporadic C.J.D. in 1997. Soon after, he learned that a
year earlier to the day, the mother of his next-door neighbor died of the
disease. Since that time, he has become convinced that these sporadic cases are
not sporadic at all, that mad cow is now a disease of humans in America. He said
he believes that his mother was accidentally infected during surgery and the
mother of his neighbor from taking nutritional supplements made from high-risk
bovine tissue, which he calls ''mad cow in a pill.''
Singeltary has a sloping face and slicked-back hair. He is nearsighted,
with small blue eyes. He looks like Lewis Carroll's White Rabbit. From his
living room in Bacliff, Tex., he dominates the listservs and message boards of
an online debate over sporadic C.J.D. -- the scientists who say it exists; the
heartbroken family members who doubt it. Early, deep in his grief, he would sign
his e-mail messages to scientists, ''I am the madson of a deadmom who died of
madcow.'' Singeltary turned out to be helpful for Skarbek. He pointed her to a
paper that was published in 2002 in the journal of the European Molecular
Biology Organization by John Collinge, the premier prion researcher in England.
Collinge argued that experiments conducted in mice suggest that infections with
mad cow can sometimes look like sporadic C.J.D. Collinge accepted the
implications: he recommended that ''serious consideration should be given'' to
the idea that some of the more recent sporadic C.J.D. cases in Europe were in
fact related to mad cow disease.
2014
***Moreover, L-BSE has been transmitted more easily to transgenic mice
overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.
***It has been suggested that some sporadic CJD subtypes in humans may
result from an exposure to the L-BSE agent.
*** Lending support to this hypothesis, pathological and biochemical
similarities have been observed between L-BSE and an sCJD subtype (MV genotype
at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and
another sCJD subtype (MM genotype) [15].
snip...
BSE prions propagate as either variant CJD-like or sporadic CJD-like prion
strains in transgenic mice expressing human prion protein
*** Surprisingly, however, BSE transmission to these transgenic mice, in
addition to producing a vCJD-like phenotype, can also result in a distinct
molecular phenotype that is indistinguishable from that of sporadic CJD with
PrPSc type 2.
These data suggest that more than one BSEderived prion strain might infect
humans;
***it is therefore possible that some patients with a phenotype consistent
with sporadic CJD may have a disease arising from BSE exposure.
snip...
These studies further strengthen the evidence that vCJD is caused by a
BSE-like prion strain.
Also, remarkably, the key neuropathological hallmark of vCJD, the presence
of abundant florid PrP plaques, can be recapitulated on BSE or vCJD transmission
to these mice.
***However, the most surprising aspect of the studies was the finding that
an alternate pattern of disease can be induced in 129MM Tg35 mice from primary
transmission of BSE, with a molecular phenotype indistinguishable from that of a
subtype of sporadic CJD. This finding has important potential implications as it
raises the possibility that some humans infected with BSE prions may develop a
clinical disease indistinguishable from classical CJD associated with type 2
PrPSc. This is, in our experience, the commonest molecular sub-type of sporadic
CJD. In this regard, it is of interest that the reported incidence of sporadic
CJD has risen in the UK since the 1970s (Cousens et al., 1997)...
To date the OIE/WAHO assumes that the human and animal health standards
set out in the BSE chapter for classical BSE (C-Type) applies to all forms of
BSE which include the H-type and L-type atypical forms. This assumption is
scientifically not completely justified and accumulating evidence suggests that
this may in fact not be the case. Molecular characterization and the spatial
distribution pattern of histopathologic lesions and immunohistochemistry (IHC)
signals are used to identify and characterize atypical BSE. Both the L-type and
H-type atypical cases display significant differences in the conformation and
spatial accumulation of the disease associated prion protein (PrPSc) in brains
of afflicted cattle. Transmission studies in bovine transgenic and wild type
mouse models support that the atypical BSE types might be unique strains because
they have different incubation times and lesion profiles when compared to C-type
BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian
hamster the resulting molecular fingerprint had changed, either in the first or
a subsequent passage, from L-type into C-type BSE.
***In addition, non-human primates are specifically susceptible for
atypical BSE as demonstrated by an approximately 50% shortened incubation time
for L-type BSE as compared to C-type. Considering the current scientific
information available, it cannot be assumed that these different BSE types pose
the same human health risks as C-type BSE or that these risks are mitigated by
the same protective measures.
-------- Original Message --------
Subject: re-BSE prions propagate as either variant CJD-like or sporadic
CJD
Date: Thu, 28 Nov 2002 10:23:43 -0000
From: "Asante, Emmanuel A" e.asante@ic.ac.uk
To: "'flounder@wt.net'" flounder@wt.net
Dear Terry,
I have been asked by Professor Collinge to respond to your request. I am a
Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have
attached a pdf copy of the paper for your attention.
Thank you for your interest in the paper.
In respect of your first question, the simple answer is, ***yes. As you
will find in the paper, we have managed to associate the alternate phenotype to
type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim
any further sub-classification in respect of Heidenhain variant CJD or Vicky
Rimmer's version. It will take further studies, which are on-going, to establish
if there are sub-types to our initial finding which we are now reporting. The
main point of the paper is that, as well as leading to the expected new variant
CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an
alternate phenotype which is indistinguishable from type 2 PrPSc.
I hope reading the paper will enlighten you more on the subject. If I can
be of any further assistance please to not hesitate to ask. Best wishes.
Emmanuel Asante
<>
____________________________________
Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial
College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44
(0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until
9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)
____________________________________ END
Aug. 5, 2001, 12:25AM
Mad cow disease: Could it be here?
Man's stubborn crusade attracts experts' notice
By CAROL CHRISTIAN Copyright 2001 Houston Chronicle
Like Paul Revere with e-mail, Terry Singeltary Sr. is on a mission to
sound an alarm: Beware of mad cow disease.
As is true of many crusaders, however, his pleas often fall on deaf ears.
Health officials here and abroad insist that bovine spongiform encephalopathy --
popularly known as mad cow disease, a fatal brain disorder that can make cows
shake uncontrollably -- has been kept out of this country through surveillance
of the cattle industry.
But since his mother's death in December 1997, the Galveston County man
has been obsessed with possible connections between her deadly brain disorder,
sporadic Creutzfeldt-Jakob Disease, and mad cow disease.
And after much persistence on his part, people are taking notice of this
former machinist and high school dropout who jokes that he has a Ph.D. -- a Pool
Hall Degree.
"They called me Chicken Little for four years," he said. "Now they're
calling back, asking for more information."
For the past year he has been U.S. co-coordinator of an international
monitoring group called CJD Watch. He regularly gets e-mail from scientists and
journalists around the world.
Debora MacKenzie, a reporter for the British magazine New Scientist,
described Singeltary, 47, as a "dogged unearther and tabulator of government
documents." Singeltary monitors "every word written about CJD/BSE," said Anita
Manning of USA Today, also by e-mail.
"He's passionate, opinionated and not always tactful, although I like him
because he's such a character and he is so transparent," Manning said. "He is
what he appears to be."
Science and environment writer Jonathan Leake of the Sunday Times in
London said Singeltary has helped him track down families of people with CJD
along with academic research papers.
"I strongly suspect he is right in thinking the USA has had BSE cases,"
Leake said by e-mail.
"The American government is making the same mistake as the British in
putting the short-term commercial interests of its farmers before health
considerations," he added.
"It should start formal and widespread testing of cattle plus compulsory
autopsies for all human CJD victims at the state's expense. If there is BSE,
then leaving it to spread will kill people -- and that would eventually destroy
the industry, too."
Texas Department of Health epidemiologist Julie Rawlings said Singeltary's
careful monitoring of the disease had proven useful.
"Terry has been helpful in providing contact information regarding suspect
CJD cases so that the Health Department can initiate case investigations and
learn more about CJD in Texas," she said.
Noting that the department cannot release records on individual patients,
she added, "I think we learn more from him than he does from us."
Mad cow disease surfaced in England in 1986 and quickly became an
epidemic. It since has been reported in 15 European countries, most recently
Greece on July 2, and the Czech Republic on June 14. Two German-born cows tested
positive for BSE in November.
Singeltary said he became convinced that BSE is here as he watched his
mother, Barbara Poulter of Crystal Beach, dying of sporadic Creutzfeldt-Jakob
Disease. The rare, fatal brain disease is sometimes accompanied by severe
jerking.
"She would jerk so bad at times, it would take three of us to hold her
down," Singeltary said. "They can call it whatever they want, but I know what I
saw, and what she went through. `Sporadic' simply means they don't know."
Poulter, a retired telephone-company field worker, had a form of sporadic
CJD -- Haidenhain variant -- that is even less common than the typical sporadic
case. One of its first symptoms is loss of vision.
She started seeing brown spots in September 1997 and was virtually blind
within two weeks. By the eighth week of the illness Poulter was bedridden, and
in the 10th week she died. Before that she had been in good health.
In many countries and most U.S. states, physicians are not required to
report CJD cases to health officials. Texas made the disease reportable in 1998.
Through 2000, there were 17 probable or confirmed cases, according to the Texas
Department of Health.
In mid-June, a case of sporadic CJD was confirmed through brain biopsy at
Christus Spohn Hospital Shoreline in Corpus Christi, said Jane Bakos, hospital
vice president. The patient has since died, the hospital reported.
CJD and mad cow disease leave their victims' brains full of holes like a
sponge.
Although not contagious, the illnesses are thought to be transmissible
through prions, or nearly indestructible abnormal proteins.
Because the prion protein is not killed by standard sterilization,
sporadic CJD can be spread by contaminated surgical instruments.
In March 1996, the British government announced the discovery of a new
variant of CJD, most likely explained by exposure to bovine spongiform
encephalopathy.
Through June, 101 cases of new-variant CJD have been reported in the
United Kingdom, three in France and one in Ireland. In contrast to sporadic CJD,
the new variant usually affects younger patients and lasts longer.
No cases of new-variant CJD or BSE have been reported in the United
States. No relationship has been shown between sporadic CJD and mad cow disease.
There is no indication that new-variant CJD can be spread through blood
transfusions, but a U.S. Food and Drug Administration advisory committee voted
in June to broaden the categories for excluding potential donors. The
recommendations have not yet been approved by the FDA.
The American Red Cross has announced that on Sept. 17 it will begin
rejecting potential blood donors who, since 1980, have spent at least three
months in the United Kingdom or at least six months in any European country or
combination of countries. Those who have received a blood transfusion in Britain
since 1980 also will be rejected.
The primary collector of local blood donations is the Gulf Coast Regional
Blood Center, which will follow the FDA's guidelines, said Bill Teague,
president and chief executive officer.
Singeltary said it's naive to think that U.S. prevention efforts have kept
mad cow and new-variant CJD out of the United States.
"They haven't found it," he said, "because they haven't looked."
For one thing, he said, too few cows are tested for the disease. In the
first six months of this year, the European Union tested more than 3.2 million
cows, David Byrne of the European Commission said in a speech last month.
By contrast, it took the U.S. Department of Agriculture nearly 10 years to
analyze about 13,000 cow brains, according to the department's Web site.
With more than 68 million cattle slaughtered since 1990 in the United
States, according to the USDA, checking about 13,000 falls far short, Singeltary
said.
Though not a scholar, Singeltary has collected voluminous material on mad
cow and CJD. Disabled from a neck injury, Singeltary never used a computer until
1998.
He now spends hours each day on the Internet while his wife, Bonnie
Singeltary, runs a flower shop in their home in Bacliff, in north Galveston
County.
His challenge to the CJD/BSE establishment is courageous and refreshing,
said Dr. Lynette Dumble, former visiting professor of surgery at University of
Texas Medical School at Houston and a former senior research fellow in the
history and philosophy of science at the University of Melbourne in Australia.
"I certainly have no problem with Terry's ideas on BSE/CJD," said Dumble,
who coordinates the Global Sisterhood Network, a computer service that posts
media reports on developments affecting women. "His research skills are
excellent, and he is abreast of each and every development in the field."
Among Singeltary's worries now, he said, are widespread violations of an
August 1997 ban on feeding animal products to U.S. cattle. The FDA reported in
January that hundreds of feed manufacturers were not complying with regulations
designed to keep BSE out of this country.
(That same month, a Purina Mills feedlot near San Antonio told the FDA
that a "very low level" of cow parts had been found in cattle feed. The company
voluntarily removed 1,222 animals who had been fed the prohibited materials.)
He obtained copies of FDA letters to various feed mills that had been
found in violation of the regulations and immediately sent them by e-mail to
hundreds of people around the world.
Singeltary might not be so zealous in getting the word out if he weren't
convinced that someone is covering up the truth.
"They used to say BSE would never transmit to humans," he said, "and it
has. They lied about the feed ban being in place.
"I've lost faith in the whole process. I've discovered too many things."
Tuesday, March 16, 2010
COMMONWEALTH OF AUSTRALIA Hansard Import restrictions on beef FRIDAY, 5
FEBRUARY 2010 AUSTRALIA
COMMONWEALTH OF AUSTRALIA
Proof Committee Hansard
RRA&T 2 Senate Friday, 5 February 2010
RURAL AND REGIONAL AFFAIRS AND TRANSPORT
[9.03 am]
BELLINGER, Mr Brad, Chairman, Australian Beef Association CARTER, Mr John
Edward, Director, Australian Beef Association CHAIR—Welcome. Would you like to
make an opening statement? Mr Bellinger—Thank you. The ABA stands by its
submission, which we made on 14 December last year, that the decision made by
the government to allow the importation of beef from BSE affected countries is
politically based, not science based. During this hearing we will bring forward
compelling new evidence to back up this statement. When I returned to my
property after the December hearing I received a note from an American citizen.
I will read a small excerpt from the mail he sent me in order to reinforce the
dangers of allowing the importation of beef from BSE affected countries. I have
done a number of press releases on this topic, and this fellow has obviously
picked my details up from the internet. His name is Terry Singeltary and he is
from Bacliff, Texas. He states, and rightfully so: You should be worried. Please
let me explain. I’ve kept up with the mad cow saga for 12 years today, on
December 14th 1997, some four months post voluntary and partial mad cow feed ban
in the USA, I lost my mother to the Heinemann variant Creutzfeldt-Jakob disease
(CJD). I know this is just another phenotype of the infamous sporadic CJDs. Here
in the USA, when USA sheep scrapie was transmitted to USA bovine, the agent was
not UK BSE—it was a different strain. So why then would human TSE from USA
cattle look like UK CJD from UK BSE? It would not. So this accentuates that the
science is inconclusive still on this devastating disease. He goes on to state:
snip...see full text 110 pages ;
for those interested, please see much more here ;
This document provides itemized replies to the public comments received on
the 2005 updated Harvard BSE risk assessment. Please bear the following points
in mind:
Owens, Julie From: Terry S. Singeltary Sr. [flounder9@verizon.net]
Sent: Monday, July 24, 2006 1:09 PM To: FSIS RegulationsComments
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of
Bovine Spongiform Encephalopathy (BSE) Page 1 of 98 8/3/2006
Greetings FSIS, I would kindly like to comment on the following ;
Nature | Editorial
Needless conflict Nature 485, 279–280 (17 May 2012) doi:10.1038/485279b
Published online 16 May 2012
Tuesday, December 2, 2014
UK EXPORTS OF MBM TO WORLD Bovine Spongiform Encephalopathy BSE TSE Prion
aka Mad Cow Disease
USA, NORTH AMERICA, MBM (or any potential TSE prion disease) EXPORTS TO
THE WORLD (?) [protected by the BSE MRR policy] $$$
*** Qualitative Analysis of BSE Risk Factors in the United States
February 13, 2000 at 3:37 pm PST (BSE red book)
Tuesday, July 14, 2009 U.S.
*** Emergency Bovine Spongiform Encephalopathy Response Plan Summary and
BSE Red Book
Date: February 14, 2000 at 8:56 am PST
WHERE did we go wrong $$$
Friday, November 22, 2013
Wasting disease is threat to the entire UK deer population CWD TSE PRION
disease in cervids
***SINGELTARY SUBMISSION
The Scottish Parliament’s Rural Affairs, Climate Change and Environment
Committee has been looking into deer management, as you can see from the
following press release,
***and your email has been forwarded to the committee for information:
Sunday, July 21, 2013
Welsh Government and Food Standards Agency Wales Joint Public Consultation
on the Proposed Transmissible Spongiform Encephalopathies (Wales) Regulations
2013
*** Singeltary Submission WG18417
*** 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.
Subject: OIE cuts six European countries' mad cow risk level, while
increasing risk factors for humans to the BSE TSE PRION DISEASE around the
globe
Published May 27, 2015, 03:42 PM
OIE cuts six European countries' mad cow risk level
The World Organization for Animal Health said on Wednesday it had lowered
to the safest level the official risk of six countries for mad cow disease, a
move expected to open international market access for their beef exports. By:
Reuters ,
PARIS -- The World Organization for Animal Health said on Wednesday it had
lowered to the safest level the official risk of six countries for mad cow
disease, a move expected to open international market access for their beef
exports.
These countries are France, Ireland, Switzerland, the Czech Republic,
Cyprus and the Lichtenstein.
OIE members in Paris eased their status on bovine spongiform encephalopathy
(BSE), commonly known as mad cow disease, to "negligible risk" from "controlled
risk".
One of the OIE criteria to be categorized as a negligible BSE risk country
is to demonstrate that the last infected native animal was born more than 11
years ago, it said.
"The main advantage will be at international trade level because many
countries insist on limiting trade exchange to countries that have the same risk
status," Karin Schwabenbauer, head the OIE Council and World Assembly, told
reporters.
France welcomed the decision, noting that the BSE epidemic that spread from
Britain to mainland Europe in the 1980s because of contaminated meal had
prompted consumer distrust and trade restrictions.
"I appeal to countries that still have an embargo on exports of this sector
to lift it very quickly," French Agriculture Minister Stephane Le Foll said in a
statement.
Thirteen countries ban French beef and beef products because of BSE -
Brazil, China, Argentina, Saudi Arabia, Taiwan, South Africa, Botswana, Mali,
Uganda, South Korea, Iraq, Syria and Qatar - a Farm Ministry spokesman said.
Japan, Vietnam and Singapore ban meat from cattle older than 30 months.
Ireland earlier this year signed export deals with China and the United
States, making it the only European country to be allowed to export beef to both
countries.
Tags: mad cow, livestock, agribusiness, updates, cattle - See more at: http://www.agweek.com/event/article/id/26479/#sthash.2opRk32H.dpuf
it’s all about trade now, nothing else matters $$$
>>>PARIS -- The World Organization for Animal Health said on
Wednesday it had lowered to the safest level the official risk of six countries
for mad cow disease, a move expected to open international market access for
their beef exports. These countries are France, Ireland, Switzerland, the Czech
Republic, Cyprus and the Lichtenstein.<<<
THIS move is _not_ based on science, but on corporate profits and big ag.
to say now that France is a "negligible risk", would be like saying North
America is a "negligible risk", which is preposterous. not based on sound
science, but on greed and special interest. the only _move_ this ‘’BSE mad cow
negligible risk’’ assessment makes, is a move to increase global Transmissible
Spongiform Encephalopathy prion mad cow type disease, via the legal trading of
the TSE prion aka mad cow type disease via the BSE MRR i.e. Minimal Risk Region
policy, a policy set up to fail from the start. please, for whatever God you
pray to sake, please be warned.
‘’AS i said before, OIE should hang up there jock strap now, since it
appears they will buckle every time a country makes some political hay about
trade protocol, commodities and futures. IF they are not going to be science
based, they should do everyone a favor and dissolve there organization.’’
IN A NUT SHELL ;
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate
declarations made by the official Veterinary Services of Member Countries. The
OIE is not responsible for inaccurate publication of country disease status
based on inaccurate information or changes in epidemiological status or other
significant events that were not promptly reported to the Central Bureau,
Wednesday, March 11, 2015
OIE and Centers for Disease Control and Prevention Reinforce Collaboration
Friday, April 4, 2014
China, Australia, Argentina, Brazil, Uruguay, Morocco, Israel, South Africa
and Saudi Arabia still retain BSE-related closures
Thursday, May 30, 2013
World Organization for Animal Health (OIE) has upgraded the United States'
risk classification for mad cow disease to "negligible" from "controlled", and
risk further exposing the globe to the TSE prion mad cow type disease
U.S. gets top mad-cow rating from international group and risk further
exposing the globe to the TSE prion mad cow type disease
The OIE is nothing more than a trading brokerage for the Transmissible
Spongiform Encephalopathy TSE prion disease aka mad cow type disease. Frances is
still in the midst of a mad cow disease outbreak with atypical BSE cases still
growing. mad cow disease is so bad in France, as with the USA, they stopped
testing for mad cow disease (France altogether and the USA to figures so low,
you would only detect a case of mad cow disease, only by chance).
from the inside looking out ;
Quote: Maybe familirise yourself with the OIE. The primary concern is
animal health of the world they are the animal version of the WHO. It is a long
way down from that ivory tower but here we go, until pressured by the USA
repesentatives a country could not export animals for 6 years after finding a
BSE/BASE positive animal so under the old rules the US would not be able to
export anywhere in the world for another 4 1/2 years. Who got the risk levels
system put in to allow some trade - your US representatives. You guys want to
change rules - OK , but you do not get special rules that only apply to the US.
As i have told you before Sand h I market all my own slaughter animals and you
know that, so don't do the whole holier than thow act.
With all due respect, it is obvious that you know little about the OIE and
how it actually works. Having been to their offices in Paris and talked
personally with the Head of the Animal Test Section, you would choke if you knew
how many lobby groups attend that office daily. There is a steady stream of paid
lobby groups that have one goal in life and that is to sway the Section Heads of
each department within the OIE to suit the needs of different juristictions
around the world, which curiously enough, also includes the USA and Canada.
Anyone can go there and chat with them - providing they can privide valid cause
to be let in. To say that the only goal of the OIE is animal health is actually
only part of their function. They are more than that and my discussions with Dr.
Diaz there has showed me that. But to blindly make a statement regarding what
they do when you have no idea what they actually do is like eating the skin of
the orange and not knowing what is actually under.
Interstingly you state that the US Government applied pressure (to the OIE)
I assume and that is a great example of the lobby groups doing their job. So, at
the end of the day, one can safely assume that it is the pressure applied by
certain influential lobby groups that will determine a likely aoutcome to an
apparent OIE directive. Man alive, isn't it great to live in a democracy wherein
the people get to make the choices and not just some "other" interested party or
group - say like........Cargyll or Tyson for example?
So, one last question, question?
Who wags the tail of that dog?? And for what reason other than one that is
purely associated with trade and international agreements and greed?
And you think it is so simply explainable.
end...tss
please see ;
spontaneous atypical BSE ???
don’t let anyone fool you. spontaneous TSE prion disease is a hoax in
natural cases, never proven.
all one has to do is look at France. France is having one hell of an
epidemic of atypical BSE, probably why they stopped testing for BSE, problem
solved $$$ same as the USA, that’s why they stopped testing for BSE mad cow
disease in numbers they could find any with, after those atypical BSE cases
started showing up. shut down the testing to numbers set up by OIE that are so
low, you could only by accident find a case of BSE aka mad cow disease. and this
brilliant idea by the WHO et al, to change the name of mad cow disease, thinking
that might change things is preposterous. it’s all about money now folks, when
the OIE, USDA and everyone else went along and made the TSE prion disease aka
mad cow type disease a legal trading commodity by the BSE MRR policy, I would
say everyone bit off more then they can chew, and they will just have to digest
those TSE Prions coming from North America, and like it, and just prey you don’t
get a mad cow type disease i.e. Transmissible Spongiform Encephalopathy TSE
prion disease in the decades to come, and or pass it to some other poor soul via
the iatrogenic medical surgical tissue friendly fire mode of transmission i.e.
second hand transmission. it’s real folks, just not documented much, due to lack
of trace back efforts. all iatrogenic cjd is, is sporadic cjd, until the
iatrogenic event is tracked down and documented, and put into the academic and
public domain, which very seldom happens. ...
As of December 2011, around 60 atypical BSE cases have currently been
reported in 13 countries, *** with over one third in France.
FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many
spontaneous events of mad cow disease $$$
so 20 cases of atypical BSE in France, compared to the remaining 40 cases
in the remaining 12 Countries, divided by the remaining 12 Countries, about 3+
cases per country, besides Frances 20 cases. you cannot explain this away with
any spontaneous BSe. ...TSS
Sunday, October 5, 2014
France stops BSE testing for Mad Cow Disease
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
Saturday, May 09, 2015
Expression of genes involved in the T cell signalling pathway in
circulating immune cells of cattle 24 months following oral challenge with
Bovine Amyloidotic Spongiform Encephalopathy (BASE)
(c) The commonest form of CJD occurs as a sporadic disease, the cause of
which is unknown, although genetic factors (particularly the codon 129
polymorphism in the prion protein gene (PRNP)) influence disease susceptibility.
The familial forms of human TSEs (see Box 1) appear to have a solely genetic
origin and are closely associated with mutations or insertions in the PRNP gene.
Most, but not all, of the familial forms of human TSEs have been transmitted
experimentally to animals. There are no known familial or genetic TSEs of
animals, although polymorphisms in the PRNP gene of some species (sheep for
example) may influence the length of the incubation period and occurrence of
disease. (
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
Wednesday, May 27, 2015
*** BSE Case Associated with Prion Protein Gene Mutation ***
Saturday, May 09, 2015
Expression of genes involved in the T cell signalling pathway in
circulating immune cells of cattle 24 months following oral challenge with
Bovine Amyloidotic Spongiform Encephalopathy (BASE)
Tuesday, May 19, 2015
COUNTRY OF ORIGIN LABELING COOL H.R. 2393 Agriculture Chairman K. Michael
Conaway (R-TX) Fears of US imports infected with mad cow disease is emerging as
an issue in trans-Pacific trade talks
Tuesday, December 16, 2014
Evidence for zoonotic potential of ovine scrapie prions
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves
Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle
Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia
Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier
Andréoletti1, Affiliations Contributions Corresponding author Journal name:
Nature Communications Volume: 5, Article number: 5821 DOI:
doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014
Published 16 December 2014 Article tools Citation Reprints Rights &
permissions Article metrics
Abstract
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant
Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie
prions remains unknown. Mice genetically engineered to overexpress the human
prion protein (tgHu) have emerged as highly relevant models for gauging the
capacity of prions to transmit to humans. These models can propagate human
prions without any apparent transmission barrier and have been used used to
confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie
prions transmit to several tgHu mice models with an efficiency comparable to
that of cattle BSE. The serial transmission of different scrapie isolates in
these mice led to the propagation of prions that are phenotypically identical to
those causing sporadic CJD (sCJD) in humans. These results demonstrate that
scrapie prions have a zoonotic potential and raise new questions about the
possible link between animal and human prions.
Subject terms: Biological sciences• Medical research At a glance
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
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01 Most doctors believe that sCJD is caused by a prion protein
deforming by chance into a killer. But Singeltary thinks otherwise. He is one of
a number of campaigners who say that some sCJD, like the variant CJD related to
BSE, is caused by eating meat from infected animals. Their suspicions have
focused on sheep carrying scrapie, a BSE-like disease that is widespread in
flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb...
2001
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01
Like lambs to the slaughter
31 March 2001
by Debora MacKenzie Magazine issue 2284.
FOUR years ago, Terry Singeltary watched his mother die horribly from a
degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary
was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded
an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by
chance into a killer. But Singeltary thinks otherwise. He is one of a number of
campaigners who say that some sCJD, like the variant CJD related to BSE, is
caused by eating meat from infected animals. Their suspicions have focused on
sheep carrying scrapie, a BSE-like disease that is widespread in flocks across
Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no
evidence that it poses a risk to human health. But if the French finding means
that scrapie can cause sCJD in people, countries around the world may have
overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They
injected the brains of macaque monkeys with brain from BSE cattle, and from
French and British vCJD patients. The brain damage and clinical symptoms in the
monkeys were the same for all three. Mice injected with the original sets of
brain tissue or with infected monkey brain also developed the same symptoms.
As a control experiment, the team also injected mice with brain tissue from
people and animals with other prion diseases: a French case of sCJD; a French
patient who caught sCJD from human-derived growth hormone; sheep with a French
strain of scrapie; and mice carrying a prion derived from an American scrapie
strain. As expected, they all affected the brain in a different way from BSE and
vCJD. But while the American strain of scrapie caused different damage from
sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been
epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute
for Animal Health in Edinburgh, who was a member of the same team as Deslys.
"You see about the same incidence of the disease everywhere, whether or not
there are many sheep, and in countries such as New Zealand with no scrapie." In
the only previous comparisons of sCJD and scrapie in mice, Bruce found they were
dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would
not necessarily see a relationship between the two with epidemiology if only
some strains affect only some people," says Deslys. Bruce is cautious about the
mouse results, but agrees they require further investigation. Other trials of
scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion
protein, and each type of protein can fold up two different ways. Kretschmar has
found that these six combinations correspond to six clinical types of sCJD: each
type of normal prion produces a particular pathology when it spontaneously
deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing
prion, the relationship between pathology and prion type should be different, as
it is in vCJD. "If we look at brain samples from sporadic CJD cases and find
some that do not fit the pattern," says Kretschmar, "that could mean they were
caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence
elsewhere. Singeltary and other US activists think that some of these people
died after eating contaminated meat or "nutritional" pills containing dried
animal brain. Governments will have a hard time facing activists like Singeltary
if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
Deslys's work on macaques also provides further proof that the human
disease vCJD is caused by BSE. And the experiments showed that vCJD is much more
virulent to primates than BSE, even when injected into the bloodstream rather
than the brain. This, says Deslys, means that there is an even bigger risk than
we thought that vCJD can be passed from one patient to another through
contaminated blood transfusions and surgical instruments.
Friday, January 30, 2015
*** Scrapie: a particularly persistent pathogen ***
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH
CODE
I strenuously urge the USDA and the OIE et al to revoke the exemption of
the legal global trading of atypical Nor-98 scrapie TSE. ...TSS
Sunday, April 12, 2015
*** Research Project: Transmission, Differentiation, and Pathobiology of
Transmissible Spongiform Encephalopathies 2014 Annual Report ***
http://transmissiblespongiformencephalopathy.blogspot.com/2015/04/research-project-transmission.html
Friday, May 22, 2015
Chronic Wasting Disease and Program Updates - 2014 NEUSAHA Annual Meeting
12-14 May 2014
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
--------------------------------------------------------------------------------
Show agency attachment(s) Attachments View All (0)
--------------------------------------------------------------------------------
Comment View document:
WI
REASON
Products manufactured from bulk feed containing blood meal that was cross
contaminated with prohibited meat and bone meal and the labeling did not bear
cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
Terry S. Singeltary Sr.
*** See attached file(s) No documents available. Attachments View All (1)
Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm
Terry Singeltary Comment View Attachment:
Sunday, April 5, 2015
*** Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed
On-Farm Draft Guidance FDA-2014-D-1180 ***
Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed
On-Farm Draft Guidance FDA-2014-D-1180 Singeltary Comment
Greetings FDA et al,
I wish to comment on Guidance for Industry Ensuring Safety of Animal Feed
Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180.
Once again, I wish to kindly bring up the failed attempt of the FDA and the
ruminant to ruminant mad cow feed ban of August 4, 1997. This feed ban is still
failing today, as we speak. Even more worrisome, is the fact it is still legal
to feed cervids to cervids in the USA, in fact, the FDA only _recommends_ that
deer and elk considered to be of _high_ risk for CWD do not enter the animal
food chain, but there is NO law, its only voluntary, a recipe for a TSE prion
disaster, as we have seen with the ruminant to ruminant feed ban for cattle,
where in 2007, one decade post August 1997 mad cow feed ban, where in 2007
10,000,000 POUNDS OF BANNED BLOOD LACED MEAT AND BONE MEAL WHEN OUT INTO
COMMERCE, TO BE FED OUT. Since 2007, these BSE feed ban rules have been breached
time and time again. tons and tons of mad cow feed went out in Alabama as well,
where one of the mad cows were documented, just the year before in 2006, and in
2013 and 2014, breaches so bad (OAI) Official Action Indicated were issued.
those are like the one issued where 10 million pounds of banned blood laced meat
and bone meal were fed out.
What is the use of having a Guidance for Industry Ensuring Safety of Animal
Feed Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180, if it cannot be
enforced, as we have seen with a mandatory ruminant to ruminant feed ban?
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
19 May 2010 at 21:21 GMT
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
Tuesday, December 23, 2014
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION
2013
Sunday, December 15, 2013
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2013 UPDATE
DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From Deer
and Elk in Animal Feed; Availability Date: Fri, 16 May 2003 11:47:37 0500 EMC 1
Terry S. Singeltary Sr. Vol #: 1
PLEASE SEE FULL TEXT SUBMISSION ;
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN
COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
REASON
Blood meal used to make cattle feed was recalled because it was cross-
contaminated with prohibited bovine meat and bone meal that had been
manufactured on common equipment and labeling did not bear cautionary BSE
statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI
REASON
Products manufactured from bulk feed containing blood meal that was cross
contaminated with prohibited meat and bone meal and the labeling did not bear
cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
Terry S. Singeltary Sr.
*** See attached file(s) No documents available. Attachments View All (1)
Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm
Terry Singeltary Comment View Attachment:
Sunday, April 5, 2015
*** Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed
On-Farm Draft Guidance FDA-2014-D-1180 ***
Sunday, January 11, 2015
Docket No. APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of
Animals and Animal Products Singeltary Submission
This is a Comment on the Animal and Plant Health Inspection Service (APHIS)
Notice: Agency Information Collection Activities; Proposals, Submissions, and
Approvals: Bovine Spongiform Encephalopathy; Importation of Animals and Animal
Products
For related information, Open Docket Folder Docket folder icon
--------------------------------------------------------------------------------
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Comment View document:Docket No. APHIS-2014-0107 Bovine Spongiform
Encephalopathy; Importation of Animals and Animal Products Singeltary Submission
;
I believe that there is more risk to the world from Transmissible
Spongiform Encephalopathy TSE prion aka mad cow type disease now, coming from
the United States and all of North America, than there is risk coming to the USA
and North America, from other Countries. I am NOT saying I dont think there is
any risk for the BSE type TSE prion coming from other Countries, I am just
saying that in 2015, why is the APHIS/USDA/FSIS/FDA still ignoring these present
mad cow risk factors in North America like they are not here?
North America has more strains of TSE prion disease, in more species
(excluding zoo animals in the early BSE days, and excluding the Feline TSE and
or Canine TSE, because they dont look, and yes, there has been documented
evidence and scientific studies, and DEFRA Hound study, that shows the canine
spongiform encephalopathy is very possible, if it has not already happened, just
not documented), then any other Country in the world. Mink TME, Deer Elk cervid
CWD (multiple strains), cBSE cattle, atypical L-type BSE cattle, atypical H-type
BSE cattle, atyical HG type BSE cow (the only cow documented in the world to
date with this strain), typical sheep goat Scrapie (multiple strains), and the
atypical Nor-98 Scrapie, which has been linked to sporadic CJD, Nor-98 atypical
Scrapie has spread from coast to coast. sporadic CJD on the rise, with different
strains mounting, victims becoming younger, with the latest nvCJD human mad cow
case being documented in Texas again, this case, NOT LINKED TO EUROPEAN TRAVEL
CDC.
typical BSE can propagate as nvCJD and or sporadic CJD (Collinge et al),
and sporadic CJD has now been linked to atypical BSE, Scrapie and atypical
Scrapie, and scientist are very concerned with CWD TSE prion in the Cervid
populations. in my opinion, the BSE MRR policy, which overtook the BSE GBR risk
assessments for each country, and then made BSE confirmed countries legal to
trade mad cow disease, which was all brought forth AFTER that fateful day
December 23, 2003, when the USA lost its gold card i.e. BSE FREE status, thats
the day it all started. once the BSE MRR policy was shoved down every countries
throat by USDA inc and the OIE, then the legal trading of Scrapie was validated
to be a legal trading commodity, also shoved through by the USDA inc and the
OIE, the world then lost 30 years of attempted eradication of the BSE TSE prion
disease typical and atypical strains, and the BSE TSE Prion aka mad cow type
disease was thus made a legal trading commodity, like it or not. its all about
money now folks, trade, to hell with human health with a slow incubating
disease, that is 100% fatal once clinical, and forget the fact of exposure,
sub-clinical infection, and friendly fire there from i.e. iatrogenic TSE prion
disease, the pass it forward mode of the TSE PRION aka mad cow type disease. its
all going to be sporadic CJD or sporadic ffi, or sporadic gss, or now the
infamous VPSPr. ...problem solved $$$
the USDA/APHIS/FSIS/FDA triple mad cow BSE firewall, well, that was nothing
but ink on paper.
for this very reason I believe the BSE MRR policy is a total failure, and
that this policy should be immediately withdrawn, and set back in place the BSE
GBR Risk Assessments, with the BSE GBR risk assessments set up to monitor all
TSE PRION disease in all species of animals, and that the BSE GBR risk
assessments be made stronger than before.
lets start with the recent notice that beef from Ireland will be coming to
America.
Ireland confirmed around 1655 cases of mad cow disease. with the highest
year confirming about 333 cases in 2002, with numbers of BSE confirmed cases
dropping from that point on, to a documentation of 1 confirmed case in 2013, to
date. a drastic decrease in the feeding of cows to cows i.e. the ruminant mad
cow feed ban, and the enforcement of that ban, has drastically reduced the
number of BSE cases in Europe, minus a few BABs or BARBs. a far cry from the
USDA FDA triple BSE firewall, which was nothing more than ink on paper, where in
2007, in one week recall alone, some 10 MILLION POUNDS OF BANNED POTENTIAL MAD
COW FEED WENT OUT INTO COMMERCE IN THE USA. this is 10 years post feed ban. in
my honest opinion, due to the blatant cover up of BSE TSE prion aka mad cow
disease in the USA, we still have no clue as to the true number of cases of BSE
mad cow disease in the USA or North America as a whole. ...just saying.
Number of reported cases of bovine spongiform encephalopathy (BSE) in
farmed cattle worldwide* (excluding the United Kingdom)
Country/Year
snip...please see attached pdf file, with references of breaches in the USA
triple BSE mad cow firewalls, and recent science on the TSE prion disease.
...TSS
No documents available. AttachmentsView All (1) Empty Docket No.
APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of Animals and
Animal Products Singeltary Submission View Attachment:
Sunday, January 11, 2015
Docket No. APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of
Animals and Animal Products Singeltary Submission
Tuesday, February 17, 2015
*** Could we spot the next BSE?, asks BVA President ***
UK EXPORTS OF MBM TO WORLD
OTHERS BEEF AND VEAL
LIVE CATTLE http://web.archive.org/web/20060517075059/http://www.bseinquiry.gov.uk/files/mb/m11f/tab11.pdf
EMBRYOS http://web.archive.org/web/20060517075116/http://www.bseinquiry.gov.uk/files/mb/m11g/tab03.pdf
GELATIN ETC http://web.archive.org/web/20060517075315/http://www.bseinquiry.gov.uk/files/mb/m11g/tab02.pdf
SEMEN http://web.archive.org/web/20060517075135/http://www.bseinquiry.gov.uk/files/mb/m11g/tab04.pdf
Tuesday, September 2, 2014
COOL UPDATE September 2, 2014
Monday, February 23, 2015
20th BSE Case Raises New Concerns about Canada's Feeding Practices and
Voluntary Testing Program; Highlights Importance of COOL
Friday, February 20, 2015
A BSE CANADIAN COW MAD COW UPDATE Transcript - Briefing (February 18, 2015)
EDMONTON - Some of former Alberta premier Ralph Klein's most colourful
quotes — and the reactions they elicited:
SNIP...
"This all came about through the discovery of a single, isolated case of
mad cow disease in one Alberta cow on May 20th. The farmer — I think he was a
Louisiana fish farmer who knew nothing about cattle ranching. I guess any
self-respecting rancher would have shot, shovelled and shut up, but he didn't do
that." — Klein recalls how the mad cow crisis started and rancher Marwyn
Peaster's role. The premier was speaking at the Western Governors Association
meeting in Big Sky, Mont. September 2004.
"The premier meant that in an ironic or almost a sarcastic way." — Klein
spokesman Gordon Turtle.
---
"You would have to eat 10 billion meals of brains, spinal cords, ganglia,
eyeballs and tonsils." — Klein speaking in Montreal in January 2005 on the risk
of humans contracting mad cow disease.
---
"I would offer $5 billion to have a Japanese person to come over here and
eat nothing but Alberta beef for a year. And if he gets mad cow disease, I would
be glad to give him $5 billion — make it $10 billion — Canadian." — Klein
speaking after Japan closed its borders to Canadian beef.
---
Thursday, February 10, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011
and how to hide mad cow disease in Canada Current as of: 2011-01-31
Wednesday, August 11, 2010
REPORT ON THE INVESTIGATION OF THE SIXTEENTH CASE OF BOVINE SPONGIFORM
ENCEPHALOPATHY (BSE) IN CANADA
Thursday, August 19, 2010
REPORT ON THE INVESTIGATION OF THE SEVENTEENTH CASE OF BOVINE SPONGIFORM
ENCEPHALOPATHY (BSE) IN CANADA
Friday, March 4, 2011
Alberta dairy cow found with mad cow disease
Tuesday, May 21, 2013
Canada, USA, Bad feed, mad cows: Why we know three BSE cases had a common
origin and why the SSS policy is in full force $$$
Increased Atypical Scrapie Detections
Press reports indicate that increased surveillance is catching what
otherwise would have been unreported findings of atypical scrapie in sheep. In
2009, five new cases have been reported in Quebec, Ontario, Alberta, and
Saskatchewan. With the exception of Quebec, all cases have been diagnosed as
being the atypical form found in older animals. Canada encourages producers to
join its voluntary surveillance program in order to gain scrapie-free status.
The World Animal Health will not classify Canada as scrapie-free until no new
cases are reported for seven years. The Canadian Sheep Federation is calling on
the government to fund a wider surveillance program in order to establish the
level of prevalence prior to setting an eradication date. Besides long-term
testing, industry is calling for a compensation program for farmers who report
unusual deaths in their flocks.
Current as of: 2015-01-31
Sheep flocks and/or goat herds confirmed to be infected with classical
scrapie in Canada in 2015 Date confirmed Location Animal type infected January 5
Ontario Goat
Tuesday, February 10, 2015
Alberta Canada First case of chronic wasting disease found in farm elk
since 2002
Saturday, March 21, 2015
***Canada and United States Creutzfeldt Jakob TSE Prion Disease Incidence
Rates Increasing
Tuesday, May 26, 2015
*** Minimise transmission risk of CJD and vCJD in healthcare settings Last
updated 15 May 2015 ***
Tuesday, April 21, 2015
Transmissible Spongiform Encephalopathy Advisory Committee TSEAC MEETING
SCHEDULED FOR June 1, 2015
Saturday, April 18, 2015
*** vCJD TEXAS CDC Emerging Infectious Diseases May 2015 Baylor College of
Medicine Neuroscience 2014 case of human form of “mad cow disease” highlights
need for continued surveillance
Saturday, May 09, 2015
*** Psychiatric Symptoms in Patients With Sporadic Creutzfeldt-Jakob
Disease ***
Sunday, May 3, 2015
PRION2015 FORT COLLINS
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
2014
***Moreover, L-BSE has been transmitted more easily to transgenic mice
overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.
***It has been suggested that some sporadic CJD subtypes in humans may
result from an exposure to the L-BSE agent.
*** Lending support to this hypothesis, pathological and biochemical
similarities have been observed between L-BSE and an sCJD subtype (MV genotype
at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and
another sCJD subtype (MM genotype) [15].
snip...
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC)
recently delivered a scientific opinion on any possible epidemiological or
molecular association between TSEs in animals and humans (EFSA Panel on
Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical
BSE prions as the only TSE agents demonstrated to be zoonotic so far
*** but the possibility that a small proportion of human cases so far
classified as "sporadic" CJD are of zoonotic origin could not be excluded.
*** Moreover, transmission experiments to non-human primates suggest that
some TSE agents in addition to Classical BSE prions in cattle (namely L-type
Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME)
and chronic wasting disease (CWD) agents) might have zoonotic potential.
snip...
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection
against prion diseases is based on a certain numbers of hypotheses some of which
may turn out to be erroneous. In particular, a form of BSE (called atypical
Bovine Spongiform Encephalopathy), recently identified by systematic testing in
aged cattle without clinical signs, may be the origin of classical BSE and thus
potentially constitute a reservoir, which may be impossible to eradicate if a
sporadic origin is confirmed.
*** Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans.
*** These atypical BSE cases constitute an unforeseen first threat that
could sharply modify the European approach to prion diseases.
Second threat
snip...
Sunday, November 23, 2014
*** Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas
in June 2014 confirmed as USA case NOT European ***
Monday, November 3, 2014
USA CJD TSE PRION UNIT, TEXAS, SURVEILLANCE UPDATE NOVEMBER 2014
National Prion Disease Pathology Surveillance Center Cases Examined1
(October 7, 2014)
***6 Includes 11 cases in which the diagnosis is pending, and 19
inconclusive cases;
***7 Includes 12 (11 from 2014) cases with type determination pending in
which the diagnosis of vCJD has been excluded.
***The sporadic cases include 2660 cases of sporadic Creutzfeldt-Jakob
disease (sCJD),
***50 cases of Variably Protease-Sensitive Prionopathy (VPSPr)
***and 21 cases of sporadic Fatal Insomnia (sFI).
Thursday, January 15, 2015
41-year-old Navy Commander with sporadic Creutzfeldt–Jakob disease CJD TSE
Prion: Case Report
Subject: *** Becky Lockhart 46, Utah’s first female House speaker, dies
diagnosed with the extremely rare Creutzfeldt-Jakob disease aka mad cow type
disease
what is CJD ? just ask USDA inc., and the OIE, they are still feeding the
public and the media industry fed junk science that is 30 years old.
why doesn’t some of you try reading the facts, instead of rubber stamping
everything the USDA inc says.
sporadic CJD has now been linked to BSE aka mad cow disease, Scrapie, and
there is much concern now for CWD and risk factor for humans.
My sincere condolences to the family and friends of the House Speaker Becky
Lockhart. I am deeply saddened hear this.
with that said, with great respect, I must ask each and every one of you
Politicians that are so deeply saddened to hear of this needless death of the
Honorable House Speaker Becky Lockhart, really, cry me a friggen river. I am
seriously going to ask you all this...I have been diplomatic for about 17 years
and it has got no where. people are still dying. so, are you all stupid or
what??? how many more need to die ??? how much is global trade of beef and other
meat products that are not tested for the TSE prion disease, how much and how
many bodies is this market worth?
Saturday, January 17, 2015
*** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed
with the extremely rare Creutzfeldt-Jakob disease
*** ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD
strains, TSE prion aka Mad Cow Disease United States of America Update December
14, 2014 Report ***
*** Creutzfeldt-Jakob Disease Public Health Crisis VIDEO
Saturday, December 13, 2014
Terry S. Singeltary Sr. Publications TSE prion disease
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14,
2001 JAMA
snip...
lost my mom to the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD
12/14/97 confirmed. I just made a promise to mom, never forget (I could never
ever forget what I saw), and never let them forget...
layperson
Terry S. Singeltary Sr., Bacliff, Texas USA 77518 flounder9@verizon.net
Thursday, May 28, 2015
OIE cuts six European countries' mad cow risk level, while increasing risk
factors for humans to the BSE TSE PRION DISEASE around the globe
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