AGFC finds 28 new cases of CWD in north Arkansas
Date 11/21/2016
Description
LITTLE ROCK – Twenty-eight new cases of CWD have been identified from
voluntary sampling stations run by the Arkansas Game and Fish Commission during
opening weekend of modern gun season, Nov. 12-13. The samples were collected
from 25 sampling sites in the CWD Management Zone in north Arkansas.
The AGFC conducted voluntary sampling sites in 25 locations within the
10-county CWD Management Zone, and the following counties had deer test
positive for CWD:
Carroll – eight deer
Marion – two deer
Newton – 14 deer
Pope – two deer
Searcy – one deer
Yell – one deer
Marion and Yell counties were the only new counties to have a
CWD-positive case, and Searcy County was just added to the CWD-positive list a
week ago upon confirmation of the state’s lone CWD-positive elk sample for
2016.
“The Marion County cases were right across the border from Boone
County, which already had CWD-positive cases, but the Yell County one is a
little disheartening,” said Cory Gray, AGFC deer program coordinator. “It’s our
southernmost case yet, and was found on the south side of the Arkansas River.”
Hunters voluntarily submitted 535 samples during the two-day period,
about 10 percent of the checked harvest in the CWD Management Zone that
weekend.
Biologists did not receive as many samples as they were hoping to get
in the CWD Management Zone from hunters, but Gray says he hopes that means
hunters still consider deer hunting priority over any disease concern.
So far, license sales and overall harvest tend to reinforce that
thought.
“Many states with CWD have seen a drop in hunting license sales and
deer harvest immediately following the detection of the disease, but we
currently aren’t seeing a decrease,” Gray said. “Our hunting license sales are
on the same trend as before CWD was detected, and the harvest has actually
increased in many of the CWD-positive counties compared to the previous five
years.”
Gray says the increased harvest may be a result of liberalized seasons
in the CWD Management Zone to help control the spread of the disease.
“We didn’t get the number of samples in the management zone that we
wanted, but I would much rather hunters be there enjoying the resource and
killing those deer we need killed to keep the herd at healthy levels,” Gray
said. “We will adjust our strategy to get any extra samples and review our
methods for next season.”
Gray says the results also helped fill in some gaps left from roadkill
surveys throughout the year, particularly in Pope, Johnson and Newton counties,
which is mostly national forest with very few roads from which to collect
roadkills.
Gray says an additional 411 samples taken from roadkills and deer that
were reported sick throughout the state have been sent for testing, bringing
the total number of statewide samples taken since March well over 3,000.
Biologists will continue to sample deer and elk that are reported sick on a
statewide basis, and roadkill samples also will be collected, but Gray says the
effort will be diminished from the current round-the-clock response.
“Our staff has done a tremendous job in collecting samples statewide
since March 25,” Gray said. “They’ve been collecting samples 24 hours a day,
seven days a week. So we’re going to back down those efforts to be during
business hours.”
Gray says all staff have been instructed never to pass up a roadkill
without checking for a viable sampling opportunity, but responding to calls
about roadkills at all hours of the night will slow down.
“We can’t thank the public enough for helping us locate roadkills when
they saw them, and we still want people to report any sick deer they see to us
through our radio room (800-482-9262).”
UPDATE DECEMBER 15, 2016
PLEASE NOTE ;
Results from two cases of CWD reversed, disease not detected in Yell County | |
| Date |
12/14/2016
|
| Description |
LITTLE ROCK – Two white-tailed deer previously identified as CWD positive during the Arkansas modern gun deer season opener have tested negative for chronic wasting disease during confirmation tests performed earlier this week. The announcement was made during Wednesday’s regularly scheduled committee meetings of the Arkansas Game and Fish Commission.
One of Marion County’s two CWD-positive samples and the lone positive sample in Yell County from those taken during opening weekend of the 2016-17 deer season have been reversed, due to results from immunohistochemistry (IHC) tests sent to verify the initial findings. “We submit samples to a laboratory that conducts the ELISA (enzyme-linked immunosorbent assay) method as a screening test. This ELISA test has the ability to process a large number of samples at a quick rate, and can produce a specificity exceeding 99 percent,” said Cory Gray, deer program coordinator for the AGFC. “But, in some cases, the confidence level in a sample result can be low. In those situations, we follow up the ELISA test with the IHC test to ensure an accurate test result. In addition, anytime we receive a CWD-positive suspect in a new county, we send an additional sample collected from that animal to run the IHC test. The IHC is extremely accurate and reliable – the gold standard in regard to CWD testing – but the downside is that it may take weeks before sample results are received versus a few days with ELISA.” In two of the resubmitted samples, the IHC test came back clean. During the AGFC’s first detection of the disease in February, additional samples also were sent for confirmation testing to ensure accurate results before the AGFC’s first announcement to the public. The identification of these false positives will help the AGFC’s future detection of the disease, and any samples that indicate CWD at a low threshold in ELISA testing will be resubmitted for further analysis. Currently, the AGFC has one additional sample from Searcy County waiting for IHC testing as a follow-up from the initial ELISA results. The reversal of the Yell County sample results offers some relief from biologists’ fears that the disease had crossed the Arkansas River. “The river really doesn’t pose a huge barrier because deer can swim pretty well,” Gray said. “But anything that can slow the spread of the disease a little more is always welcome. Research in other states suggests that rivers, roads and ridges may serve as barriers, hindering the spread of the disease.” The AGFC has collected samples from 1,592 road-killed deer, 298 deer reported as sick by the public and 1,136 samples from hunter-harvested animals. To date, 150 white-tailed deer and six elk have been confirmed with CWD in Arkansas. “We do have 394 samples taken by cooperating taxidermists that we are still waiting on results from,” Gray said. “And the Missouri Department of Conservation has taken 47 samples from Arkansas deer that were transported across the state line by Missouri hunters.” |
Wednesday, November 16, 2016
Arkansas One elk from 2016 regular season tests positive for CWD
Wednesday, August 10, 2016
Arkansas Chronic Wasting Disease CWD TSE Prion Potentially Trucked in
from Missouri, what about Florida and ?
Wednesday, July 27, 2016
Arkansas CWD 101 positive cases documented to date, Biologists to take
additional samples in in southern Pope County, Aug. 1-5
Tuesday, May 03, 2016
*** Arkansas Chronic Wasting Disease CWD TSE Prion and Elk Restoration
Project and Hunkering Down in the BSE Situation Room USDA 1998
Horizontal Transmission of Chronic Wasting Disease in Reindeer CDC
Volume 22, Number 12—December 2016
Sunday, November 13, 2016
Horizontal Transmission of Chronic Wasting Disease in Reindeer CDC
Volume 22, Number 12—December 2016
Wednesday, November 09, 2016
Chronic Wasting Disease (CWD) Program Standards - Review and Comment
By Terry S Singeltary Sr. November 9, 2016
Friday, November 18, 2016
IMPORTANT: SAWCorp CWD Test is NOT APHIS Approved
Monday, May 02, 2016
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
Saturday, April 23, 2016
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases
in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN:
1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a.
Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ).
Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents
Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires,
Jouy-en-Josas. France
Dietary exposure to bovine
spongiform encephalopathy (BSE) contaminated bovine tissues is considered as
the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE
agent is the only recognized zoonotic prion. Despite the variety of
Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating
for centuries in farmed ruminants there is no apparent epidemiological link
between exposure to ruminant products and the occurrence of other form of TSE
in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic
potential of the diversity of circulating TSE agents has never been
systematically assessed. The major issue in experimental assessment of TSEs
zoonotic potential lies in the modeling of the ‘species barrier‘, the
biological phenomenon that limits TSE agents’ propagation from a species to
another. In the last decade, mice genetically engineered to express normal
forms of the human prion protein has proved essential in studying human prions
pathogenesis and modeling the capacity of TSEs to cross the human species
barrier.
To assess the zoonotic
potential of prions circulating in farmed ruminants, we study their
transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two
lines of mice expressing different forms of the human PrPC (129Met or 129Val)
are used to determine the role of the Met129Val dimorphism in
susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to
propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be
susceptible to BSE in sheep or goat to a greater degree than the BSE agent in
cattle and that these agents can convey molecular properties and neuropathological
indistinguishable from vCJD. However homozygous 129V mice are resistant to all
tested BSE derived prions independently of the originating species suggesting a
higher transmission barrier for 129V-PrP variant.
Transmission data also revealed
that several scrapie prions propagate in HuPrP-Tg mice with ef?ciency
comparable to that of cattle BSE. While the ef?ciency of transmission at
primary passage was low, subsequent passages resulted in a highly virulent
prion disease in both Met129 and Val129 mice. Transmission of the different
scrapie isolates in these mice leads to the emergence of prion strain
phenotypes that showed similar characteristics to those displayed by MM1 or VV2
sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential
and raise new questions about the possible link between animal and human
prions.
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
*** In complement to the recent
demonstration that humanized mice are susceptible to scrapie, we report here
the first observation of direct transmission of a natural classical scrapie
isolate to a macaque after a 10-year incubation period. Neuropathologic
examination revealed all of the features of a prion disease: spongiform change,
neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation
strengthens the questioning of the harmlessness of scrapie to humans, at a time
when protective measures for human and animal health are being dismantled and
reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the
importance of precautionary and protective measures and the necessity for
long-term experimental transmission studies to assess the zoonotic potential of
other animal prion strains.
O.05: Transmission of prions to
primates after extended silent incubation periods: Implications for BSE and
scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline
Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra,
Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses,
France
Prion diseases (PD) are the
unique neurodegenerative proteinopathies reputed to be transmissible under
field conditions since decades. The transmission of Bovine Spongiform
Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic
under appropriate conditions. Contrarily, in the absence of obvious
(epidemiological or experimental) elements supporting a transmission or genetic
predispositions, PD, like the other proteinopathies, are reputed to occur
spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human
prion cases). Non-human primate models provided the first evidences supporting
the transmissibiity of human prion strains and the zoonotic potential of BSE.
Among them, cynomolgus macaques brought major information for BSE risk
assessment for human health (Chen, 2014), according to their phylogenetic
proximity to humans and extended lifetime. We used this model to assess the
zoonotic potential of other animal PD from bovine, ovine and cervid origins
even after very long silent incubation periods.
*** We recently observed the
direct transmission of a natural classical scrapie isolate to macaque after a
10-year silent incubation period,
***with features similar to
some reported for human cases of sporadic CJD, albeit requiring fourfold long
incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard,
2014),
***is the third potentially
zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin
of human sporadic cases. We will present an updated panorama of our different
transmission studies and discuss the implications of such extended incubation
periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
***our findings suggest that
possible transmission risk of H-type BSE to sheep and human. Bioassay will be
required to determine whether the PMCA products are infectious to these
animals.
SCRAPIE WS-01: Prion diseases
in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Volume 22, Number 12—December
2016
Dispatch
Horizontal Transmission of Chronic Wasting Disease in Reindeer
S. Jo Moore, Robert Kunkle, M.
Heather West Greenlee, Eric Nicholson, Jürgen Richt, Amir Hamir1, W. Ray
Waters, and Justin
Greenlee(http://wwwnc.cdc.gov/eid/article/22/12/16-0635_article#comment)
Author affiliations: US Department of Agriculture, Ames, Iowa, USA
(S.J. Moore, R. Kunkle, E. Nicholson, J. Richt, A. Hamir, W.R. Waters, J.
Greenlee):; Iowa State University, Ames (M.H. West Greenlee)
Suggested citation for this article
Abstract
We challenged reindeer by the intracranial route with the agent of
chronic wasting disease sourced from white-tailed deer, mule deer, or elk and
tested for horizontal transmission to naive reindeer. Reindeer were susceptible
to chronic wasting disease regardless of source species. Horizontal
transmission occurred through direct contact or indirectly through the
environment.
Reindeer are susceptible to
chronic wasting disease (CWD) after experimental oral challenge (1), and
recently, CWD was identified in a free-ranging reindeer in Norway (2,3).
Horizontal transmission is the primary mode of CWD transmission in deer. Direct
horizontal transmission occurs when naive animals are exposed to infectious
excreta (i.e., saliva, urine, feces) during close contact with CWD-affected
animals (reviewed in 4). Indirect horizontal transmission occurs through
exposure to environments contaminated with infectious material (e.g., excreta
or decomposed carcasses) (5,6).
The Eurasian reindeer (Rangifer
tarundus tarundus) is closely related to the North American caribou (R. t.
caribou, R. t. granti, R. t. groenlandicus). In North America, overlapping
geographic ranges of free-ranging populations of potentially CWD-infected
white-tailed deer (Odocoileus virginianus), mule deer (O. hemionus), or elk
(Cervus elaphus nelsoni) present a risk for horizontal transmission to caribou.
Exposure also could occur in farmed populations where contact occurs between
reindeer and captive and/or free-ranging CWD-affected cervids. We investigated
the transmission of CWD from white-tailed deer, mule deer, or elk to reindeer
through the intracranial route and assessed them for direct and indirect
horizontal transmission to uninoculated sentinels.
The Study
Figure 1
Figure
1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f1). Immunohistochemical
analysis for the prion protein showing scrapie prion protein (PrPSc) deposits
in brains (A–D) and retinas (E, F) from reindeer (Rangifer tarandus tarandus)
with chronic wasting disease. PrPSc immunodetection using...
In 2005, we challenged reindeer
fawns from a farm in Alaska, USA, where CWD had never been reported, by
intracranial inoculation (7) with pooled brain material from CWD-affected elk
from South Dakota (CWDelk), CWD-affected mule deer from Wyoming (CWDmd), or CWD
from white-tailed deer from Wisconsin combined with brain material from
experimentally challenged white-tailed deer (CWDwtd) (Table
1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t1); Technical Appendix[PDF -
251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)).
Additional uninoculated fawns served as negative controls, controls for
indirect transmission, and controls for direct transmission (Table
1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t1); online Technical
Appendix). We determined the prion protein gene (PRNP) genotype of each fawn
(Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)), and we
tried to ensure that each PRNP genotype was present in each group (Table
2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)). Control reindeer were
housed in the same barn as inoculated reindeer but in separate pens that
prevented direct physical contact (i.e., nose-to-nose) between control and
inoculated animals (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf) Figure 1).
Indirect and direct contact control groups were formed 25 months after
intracranially challenged reindeer were inoculated (Technical Appendix[PDF -
251 KB - 7 pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)
Figure 1, panel B).
Clinical signs consistent with CWD were first observed 20.9 months
after inoculation (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)).
Common clinical features included found dead without clinical signs noted, loss
of body condition, recumbency, and lethargy (Table
2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2); online Technical
Appendix).
At death, a full necropsy was
performed on all reindeer. Two sets of tissue samples were collected: 1 set was
fixed in 10% buffered formalin, embedded in paraffin wax, sectioned at 5 μm for
microscopy examination after hematoxylin and eosin staining or
immunohistochemical staining using primary antibody F99/96.7.1 (Technical
Appendix[PDF - 251 KB - 7 pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)).
A second set of tissues was frozen, and selected tissues were used for
immunodetection of scrapie prion protein (PrPSc) by Western blot (brain tissue
only) as described previously (7) but with some modifications, or an ELISA
(brainstem and/or retropharyngeal lymph node) using a commercial kit (IDEXX
HerdChek BSE-Scrapie Antigen ELISA; IDEXX, Westbrook, ME, USA) according to the
manufacturers’ instructions (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)).
In the intracranially
inoculated groups, when intercurrent deaths were excluded, reindeer with the
NN138 polymorphism (reindeer nos. 2, 6, and 12) had the shortest survival times
in each group (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)).
Different inocula did not produce significantly different survival times
(log-rank test, p = 0.0931), but we observed differences in the amount of
vacuolation and PrPSc in the brain at the clinical stages of disease in CWDwtd-
and CWDelk-inoculated reindeer, compared with CWDmd-inoculated reindeer (Table
2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2); Technical Appendix[PDF -
251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)). In the
indirect contact animals, PrPSc was present in the brain but restricted to the
dorsal motor nucleus of the vagus nerve and area postrema.
We observed different patterns
of PrPSc deposition in the brain (Figure 1, panels A–D; Technical Appendix[PDF
- 251 KB - 7 pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)),
the most striking of which was dominated by aggregated deposits of various
sizes, including plaque-like deposits (Figure 1, panels A,B). This pattern was
seen in reindeer with the NS138 NN176 (no. 8, CWDelk; no. 13, CWDmd) or SS138
DD176 (no. 4, CWDwtd) genotypes. With regard to immunoreactivity in the retina
(Figure 1, panels E, F; online Technical Appendix), in 2 of 3 reindeer with
aggregated deposits in the brain (nos. 8 and 13), aggregated immunoreactivity
also was observed in the inner plexiform layer of the retina (Figure 1, panel
f).
Figure 2
Figure 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f2). Western
blot characterization of the inocula used to inoculate reindeer and brainstem
samples from representative reindeer from each experimental group in study of
chronic wasting disease transmission. Scrapie prion protein (PrPSc)...
Reindeer that were negative by
immunohistochemical analysis in brain also were negative by Western blot and
ELISA. Different Western blot migration patterns were observed in
PrPSc-positive animals (Figure 2), but we found no clear association between
migration pattern and challenge group or PRNP genotype.
PrPSc was widespread in
lymphoid tissues from most reindeer (Table
2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2); online Technical
Appendix). Reindeer with the NS138 genotype had a significantly lower average
percentage of lymphoid follicles positive than did reindeer with NN138
(analysis of variance, p = 0.003) or SS138 (p = 0.003) deer. Excluding
intercurrent deaths, PrPSc was detected in all 4 CWDwtd-challenged reindeer,
all 5 CWDelk-challenged reindeer, all 4 CWDmd-challenged reindeer, both
indirect contact reindeer, and 2 of 4 direct contact reindeer (Table
2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)).
Conclusions
Potential sources of
infectivity for direct contact animals include urine, feces, and saliva from
their CWDwtd-challenged pen-mates, as has been shown for CWD-affected
white-tailed deer (6,8,9). Pinpointing the source of infectivity in the
indirect contact group is more difficult. Infectious prions can travel at least
30 m in airborne particulate (10), but because the negative control reindeer in
the pen adjacent to the indirect contact reindeer did not become positive, a
more direct route of transmission is likely in this case. Penning, feeding, and
watering protocols were designed to prevent exposure of negative control and
indirect contact reindeer to potential infectivity on feed and water buckets,
bedding, or fencing (6,11). However, reindeer might have had access to bedding
from adjacent pens that had spread into the central alleyway.
During the 5-year course of
this study, reindeer were moved between pens several times to maintain an
optimal number of animals per pen (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf) Figure 1).
Prolonged persistence of prion infectivity in the natural environment has been
documented for both CWD (2 years [5]) and scrapie (up to 16 years [12]). In
addition, thorough cleaning and disinfection might not be sufficient to remove
all infectivity from the environment, leading to persistence of infectivity
under experimental housing conditions (13).
In reindeer challenged orally
with the agent of CWD, the SS138 genotype (serine/serine at PRNP codon 138) has
been associated with susceptibility to disease and the NS138
(asparagine/serine) genotype with resistance (1). In the study we report,
disease developed in reindeer with the NS138 genotype after intracranial inoculation,
although the extent of lymphoreticular system involvement was significantly
lower than in NN138 and SS138 reindeer. The potential association of the NN138
polymorphism with shorter survival times is interesting. However, as with all
potential genotype versus phenotype interactions, care should be taken not to
over-interpret these results given the small group sizes and the large number
of PRNP genotype groups in this study.
Our results demonstrate that
reindeer are susceptible to the agent of CWD from white-tailed deer, mule deer,
and elk sources after intracranial inoculation. Furthermore, naive reindeer are
susceptible to the agent of CWD after direct and indirect exposure to
CWD-infected reindeer, suggesting a high potential for horizontal transmission
of CWD within and between farmed and free-ranging reindeer (and caribou)
populations.
Dr. Moore is a postdoctoral
research associate at the National Animal Disease Center, US Department of
Agriculture, Ames, Iowa. Her research interests include pathogenesis and
pathology of animal diseases with a special interest in neuropathology and
prion diseases.
On This Page
· The Study
· Conclusions
· Suggested Citation
Figures
· Figure 1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f1)
· Figure 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f2)
Tables
· Table 1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t1)
· Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)
Technical Appendices
· Technical
Appendix(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)
Downloads
· RIS[TXT - 2 KB] (http://wwwnc.cdc.gov/eid/article/22/12/16-0635.ris)
Acknowledgment
We thank Martha Church, Robyn Kokemuller, Joe Lesan, Virginia Montgomery,
Dennis Orcutt, and Trudy Tatum for excellent technical support.
References
1. Mitchell GB, Sigurdson CJ, O’Rourke KI, Algire J, Harrington NP,
Walther I, Experimental oral transmission of chronic wasting disease to
reindeer (Rangifer tarandus tarandus). PLoS One. 2012;7:e39055.DOIPubMed
2. Norwegian Veterinary Institute. The first detection of chronic
wasting disease (CWD) in Europe. 2016 April 4 [cited 2016 Apr 5].
http://www.vetinst.no/sykdom-og-agens/chronic-wasting-disease/the-first-detection-of-chronic-wasting-disease-cwd-in-europe
3. Becker R. Deadly animal prion disease appears in Europe. 2016
[cited 2016 Jun 16].
http://www.nature.com/news/deadly-animal-prion-disease-appears-in-europe-1.19759
4. Haley NJ, Hoover EA. Chronic wasting disease of cervids: current
knowledge and future perspectives. Annu Rev Anim Biosci.
2015;3:305–25.DOIPubMed
5. Miller MW, Williams ES, Hobbs NT, Wolfe LL. Environmental sources
of prion transmission in mule deer. Emerg Infect Dis. 2004;10:1003–6.DOIPubMed
6. Henderson DM, Denkers ND, Hoover CE, Garbino N, Mathiason CK,
Hoover EA. Longitudinal detection of prion shedding in saliva and urine by
CWD-infected deer by real-time quaking-induced conversion. J Virol. 2015;89:9338–47.DOIPubMed
7. Greenlee JJ, Smith JD, Kunkle RA. White-tailed deer are susceptible
to the agent of sheep scrapie by intracerebral inoculation. Vet Res.
2011;42:107.DOIPubMed
8. Mathiason CK, Hays SA, Powers J, Hayes-Klug J, Langenberg J, Dahmes
SJ, Infectious prions in pre-clinical deer and transmission of chronic wasting
disease solely by environmental exposure. PLoS One. 2009;4:e5916.DOIPubMed
9. Tamgüney G, Richt JA, Hamir AN, Greenlee JJ, Miller MW, Wolfe LL,
Salivary prions in sheep and deer. Prion. 2012;6:52–61.DOIPubMed
10. Gough KC, Baker CA, Simmons HA, Hawkins SA, Maddison BC.
Circulation of prions within dust on a scrapie affected farm. Vet Res.
2015;46:40.DOIPubMed
11. Maddison BC, Baker CA, Terry LA, Bellworthy SJ, Thorne L, Rees HC,
Environmental sources of scrapie prions. J Virol. 2010;84:11560–2.DOIPubMed
12. Georgsson G, Sigurdarson S, Brown P. Infectious agent of sheep
scrapie may persist in the environment for at least 16 years. J Gen Virol.
2006;87:3737–40.DOIPubMed
13. Hawkins SA, Simmons HA, Gough KC, Maddison BC. Persistence of
ovine scrapie infectivity in a farm environment following cleaning and
decontamination. Vet Rec. 2015;176:99.DOIPubMed
Figures
· Figure 1. Immunohistochemical analysis for the prion protein showing
scrapie prion protein (PrPSc) deposits in brains (A–D) and retinas (E, F) from
reindeer (Rangifer tarandus tarandus) with chronic wasting disease.
PrPSc...(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f1)
· Figure 2. Western blot characterization of the inocula used to
inoculate reindeer and brainstem samples from representative reindeer from each
experimental group in study of chronic wasting disease transmission. Scrapie
prion...(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f2)
Tables
· Table 1. Animal data for reindeer (Rangifer tarandus tarandus) in a
study of transmission of CWD
(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t1)
· Table 2. Resutls of tissue testing for chronic wasting disease in
reindeer based on immunohistochemical detection of PrPSc, assessment of
spongiform change in formalin-fixed tissues, or both
(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)
Technical Appendix
· Technical Appendix. Additional materials and methods and results
from a study of horizontal transmission of chronic wasting disease among
reindeer. 251 KB(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)
Suggested citation for this article: Moore SJ, Kunkle R, West Greenlee
MH, Nicholson E, Richt J, Hamir et al. Horizontal transmission of chronic
wasting disease in reindeer. Emerg Infect Dis. 2016 Dec [date cited].
http://dx.doi.org/10.3201/eid2212.160635
DOI: 10.3201/eid2212.160635
1Deceased.
Table of Contents – Volume 22, Number 12—December
2016(http://wwwnc.cdc.gov/eid/articles/issue/22/12/table-of-contents)
Wednesday, November 09, 2016
Norway and Finland Rule Changes
for importation and exportation of deer to limit the spread of skrantesjuke
(CWD)
Title: Pathological features of
chronic wasting disease in reindeer and demonstration of horizontal
transmission
Monday, September 05, 2016
Pathological features of chronic wasting disease in reindeer and
demonstration of horizontal transmission Major Findings for
Norway
Thursday, September 22, 2016
NORWAY DETECTS 5TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION
Skrantesjuke
SUNDAY, OCTOBER 02, 2016
*** What is the risk of a cervid TSE being introduced from Norway into
Great Britain? Qualitative Risk Assessment September 2016
Wednesday, September 7, 2016
*** An assessment of the long-term persistence of prion infectivity in
aquatic environments
Friday, September 02, 2016
*** Chronic Wasting Disease Drives Population Decline of White-Tailed
Deer
*** Infectious agent of sheep scrapie may persist in the environment
for at least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
Using in vitro prion replication for high sensitive detection of
prions and prionlike proteins and for understanding mechanisms of transmission.
Claudio Soto
Mitchell Center for Alzheimer's diseases and related Brain disorders,
Department of Neurology, University of Texas Medical School at Houston.
Prion and prion-like proteins are misfolded protein aggregates with
the ability to selfpropagate to spread disease between cells, organs and in
some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r
m encephalopathies (TSEs), prions are mostly composed by a misfolded form of
the prion protein (PrPSc), which propagates by transmitting its misfolding to
the normal prion protein (PrPC). The availability of a procedure to replicate
prions in the laboratory may be important to study the mechanism of prion and
prion-like spreading and to develop high sensitive detection of small
quantities of misfolded proteins in biological fluids, tissues and
environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a
simple, fast and efficient methodology to mimic prion replication in the test
tube. PMCA is a platform technology that may enable amplification of any
prion-like misfolded protein aggregating through a seeding/nucleation process.
In TSEs, PMCA is able to detect the equivalent of one single molecule of
infectious PrPSc and propagate prions that maintain high infectivity, strain
properties and species specificity. Using PMCA we have been able to detect
PrPSc in blood and urine of experimentally infected animals and humans affected
by vCJD with high sensitivity and specificity. Recently, we have expanded the
principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn)
aggregates implicated in Alzheimer's and Parkinson's diseases, respectively.
Experiments are ongoing to study the utility of this technology to detect Aβ
and α-syn aggregates in samples of CSF and blood from patients affected by
these diseases.
=========================
***Recently, we have been using PMCA to study the role of
environmental prion contamination on the horizontal spreading of TSEs. These
experiments have focused on the study of the interaction of prions with plants
and environmentally relevant surfaces. Our results show that plants (both
leaves and roots) bind tightly to prions present in brain extracts and excreta
(urine and feces) and retain even small quantities of PrPSc for long periods of
time. Strikingly, ingestion of prioncontaminated leaves and roots produced
disease with a 100% attack rate and an incubation period not substantially
longer than feeding animals directly with scrapie brain homogenate.
Furthermore, plants can uptake prions from contaminated soil and transport them
to different parts of the plant tissue (stem and leaves). Similarly, prions
bind tightly to a variety of environmentally relevant surfaces, including
stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces
efficiently transmit prion disease when these materials were directly injected
into the brain of animals and strikingly when the contaminated surfaces were
just placed in the animal cage. These findings demonstrate that environmental
materials can efficiently bind infectious prions and act as carriers of
infectivity, suggesting that they may play an important role in the horizontal
transmission of the disease.
========================
Since its invention 13 years ago, PMCA has helped to answer
fundamental questions of prion propagation and has broad applications in
research areas including the food industry, blood bank safety and human and
veterinary disease diagnosis.
see ;
with CWD TSE Prions, I am not sure there is any absolute yet, other
than what we know with transmission studies, and we know tse prion kill, and
tse prion are bad. science shows to date, that indeed soil, dirt, some better
than others, can act as a carrier. same with objects, farm furniture. take it
with how ever many grains of salt you wish, or not. if load factor plays a role
in the end formula, then everything should be on the table, in my opinion. see
; ***Recently, we have been using PMCA to study the role of environmental prion
contamination on the horizontal spreading of TSEs. These experiments have
focused on the study of the interaction of prions with plants and
environmentally relevant surfaces. Our results show that plants (both leaves
and roots) bind tightly to prions present in brain extracts and excreta (urine
and feces) and retain even small quantities of PrPSc for long periods of time.
Strikingly, ingestion of prioncontaminated leaves and roots produced disease
with a 100% attack rate and an incubation period not substantially longer than
feeding animals directly with scrapie brain homogenate. Furthermore, plants can
uptake prions from contaminated soil and transport them to different parts of
the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety
of environmentally relevant surfaces, including stones, wood, metals, plastic,
glass, cement, etc. Prion contaminated surfaces efficiently transmit prion
disease when these materials were directly injected into the brain of animals
and strikingly when the contaminated surfaces were just placed in the animal
cage. These findings demonstrate that environmental materials can efficiently
bind infectious prions and act as carriers of infectivity, suggesting that they
may play an important role in the horizontal transmission of the disease.
Since its invention 13 years ago, PMCA has helped to answer
fundamental questions of prion propagation and has broad applications in
research areas including the food industry, blood bank safety and human and
veterinary disease diagnosis.
see ;
Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil
Particles
Author Summary
Transmissible spongiform encephalopathies (TSEs) are a group of
incurable neurological diseases likely caused by a misfolded form of the prion
protein. TSEs include scrapie in sheep, bovine spongiform encephalopathy (‘‘mad
cow’’ disease) in cattle, chronic wasting disease in deer and elk, and
Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are
unique among TSEs because they can be transmitted between animals, and the
disease agents appear to persist in environments previously inhabited by
infected animals. Soil has been hypothesized to act as a reservoir of
infectivity and to bind the infectious agent. In the current study, we orally
dosed experimental animals with a common clay mineral, montmorillonite, or
whole soils laden with infectious prions, and compared the transmissibility to
unbound agent. We found that prions bound to montmorillonite and whole soils
remained orally infectious, and, in most cases, increased the oral transmission
of disease compared to the unbound agent. The results presented in this study
suggest that soil may contribute to environmental spread of TSEs by increasing
the transmissibility of small amounts of infectious agent in the environment.
tse prion soil
Wednesday, December 16, 2015
Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
The sources of dust borne prions are unknown but it seems reasonable
to assume that faecal, urine, skin, parturient material and saliva-derived
prions may contribute to this mobile environmental reservoir of infectivity.
This work highlights a possible transmission route for scrapie within the farm
environment, and this is likely to be paralleled in CWD which shows strong
similarities with scrapie in terms of prion dissemination and disease
transmission. The data indicate that the presence of scrapie prions in dust is
likely to make the control of these diseases a considerable challenge.
Particle-associated PrPTSE molecules may migrate from locations of
deposition via transport processes affecting soil particles, including
entrainment in and movement with air and overland flow.
Fate of Prions in Soil: A Review
Christen B. Smith, Clarissa J. Booth, and Joel A. Pedersen*
Several reports have shown that prions can persist in soil for several
years. Significant interest remains in developing methods that could be applied
to degrade PrPTSE in naturally contaminated soils. Preliminary research
suggests that serine proteases and the microbial consortia in stimulated soils
and compost may partially degrade PrPTSE. Transition metal oxides in soil (viz.
manganese oxide) may also mediate prion inactivation. Overall, the effect of
prion attachment to soil particles on its persistence in the environment is not
well understood, and additional study is needed to determine its implications
on the environmental transmission of scrapie and CWD.
P.161: Prion soil binding may explain efficient 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.
Wednesday, December 16, 2015
Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C.
Maddison4, Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1
1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge,
Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency
Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and
Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary
Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School
of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington,
UK Classical scrapie is an environmentally transmissible prion disease of sheep
and goats. Prions can persist and remain potentially infectious in the
environment for many years and thus pose a risk of infecting animals after
re-stocking. In vitro studies using serial protein misfolding cyclic
amplification (sPMCA) have suggested that objects on a scrapie affected sheep
farm could contribute to disease transmission. This in vivo study aimed to
determine the role of field furniture (water troughs, feeding troughs, fencing,
and other objects that sheep may rub against) used by a scrapie-infected sheep
flock as a vector for disease transmission to scrapie-free lambs with the prion
protein genotype VRQ/VRQ, which is associated with high susceptibility to
classical scrapie. When the field furniture was placed in clean accommodation,
sheep became infected when exposed to either a water trough (four out of five)
or to objects used for rubbing (four out of seven). This field furniture had
been used by the scrapie-infected flock 8 weeks earlier and had previously been
shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of
23) through exposure to contaminated field furniture placed within pasture not
used by scrapie-infected sheep for 40 months, even though swabs from this
furniture tested negative by PMCA. This infection rate decreased (1 out of 12)
on the same paddock after replacement with clean field furniture. Twelve
grazing sheep exposed to field furniture not in contact with scrapie-infected
sheep for 18 months remained scrapie free. The findings of this study highlight
the role of field furniture used by scrapie-infected sheep to act as a
reservoir for disease re-introduction although infectivity declines
considerably if the field furniture has not been in contact with
scrapie-infected sheep for several months. PMCA may not be as sensitive as
VRQ/VRQ sheep to test for environmental contamination.
snip...
Discussion
Classical scrapie is an environmentally transmissible disease because
it has been reported in naïve, supposedly previously unexposed sheep placed in
pastures formerly occupied by scrapie-infected sheep (4, 19, 20). Although the
vector for disease transmission is not known, soil is likely to be an important
reservoir for prions (2) where – based on studies in rodents – prions can
adhere to minerals as a biologically active form (21) and remain infectious for
more than 2 years (22). Similarly, chronic wasting disease (CWD) has
re-occurred in mule deer housed in paddocks used by infected deer 2 years
earlier, which was assumed to be through foraging and soil consumption (23).
Our study suggested that the risk of acquiring scrapie infection was
greater through exposure to contaminated wooden, plastic, and metal surfaces
via water or food troughs, fencing, and hurdles than through grazing. Drinking
from a water trough used by the scrapie flock was sufficient to cause infection
in sheep in a clean building. Exposure to fences and other objects used for
rubbing also led to infection, which supported the hypothesis that skin may be
a vector for disease transmission (9). The risk of these objects to cause
infection was further demonstrated when 87% of 23 sheep presented with PrPSc in
lymphoid tissue after grazing on one of the paddocks, which contained metal
hurdles, a metal lamb creep and a water trough in contact with the scrapie
flock up to 8 weeks earlier, whereas no infection had been demonstrated
previously in sheep grazing on this paddock, when equipped with new fencing and
field furniture. When the contaminated furniture and fencing were removed, the
infection rate dropped significantly to 8% of 12 sheep, with soil of the
paddock as the most likely source of infection caused by shedding of prions
from the scrapie-infected sheep in this paddock up to a week earlier.
This study also indicated that the level of contamination of field
furniture sufficient to cause infection was dependent on two factors: stage of
incubation period and time of last use by scrapie-infected sheep. Drinking from
a water trough that had been used by scrapie sheep in the predominantly
pre-clinical phase did not appear to cause infection, whereas infection was
shown in sheep drinking from the water trough used by scrapie sheep in the
later stage of the disease. It is possible that contamination occurred through
shedding of prions in saliva, which may have contaminated the surface of the
water trough and subsequently the water when it was refilled. Contamination
appeared to be sufficient to cause infection only if the trough was in contact
with sheep that included clinical cases. Indeed, there is an increased risk of
bodily fluid infectivity with disease progression in scrapie (24) and CWD (25)
based on PrPSc detection by sPMCA. Although ultraviolet light and heat under
natural conditions do not inactivate prions (26), furniture in contact with the
scrapie flock, which was assumed to be sufficiently contaminated to cause
infection, did not act as vector for disease if not used for 18 months, which
suggest that the weathering process alone was sufficient to inactivate prions.
PrPSc detection by sPMCA is increasingly used as a surrogate for
infectivity measurements by bioassay in sheep or mice. In this reported study,
however, the levels of PrPSc present in the environment were below the limit of
detection of the sPMCA method, yet were still sufficient to cause infection of
in-contact animals. In the present study, the outdoor objects were removed from
the infected flock 8 weeks prior to sampling and were positive by sPMCA at very
low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive
reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay
could not detect PrPSc on any of the objects above the background of the assay.
False positive reactions with sPMCA at a low frequency associated with de novo
formation of infectious prions have been reported (27, 28). This is in contrast
to our previous study where we demonstrated that outdoor objects that had been
in contact with the scrapie-infected flock up to 20 days prior to sampling
harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions
(12)] and was significantly more positive by the assay compared to analogous
samples from the scrapie-free farm. This discrepancy could be due to the use of
a different sPMCA substrate between the studies that may alter the efficiency
of amplification of the environmental PrPSc. In addition, the present study had
a longer timeframe between the objects being in contact with the infected flock
and sampling, which may affect the levels of extractable PrPSc. Alternatively,
there may be potentially patchy contamination of this furniture with PrPSc,
which may have been missed by swabbing. The failure of sPMCA to detect
CWD-associated PrP in saliva from clinically affected deer despite confirmation
of infectivity in saliva-inoculated transgenic mice was associated with as yet
unidentified inhibitors in saliva (29), and it is possible that the sensitivity
of sPMCA is affected by other substances in the tested material. In addition,
sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more
difficult from furniture exposed to weather, which is supported by the observation
that PrPSc was detected by sPMCA more frequently in indoor than outdoor
furniture (12). A recent experimental study has demonstrated that repeated
cycles of drying and wetting of prion-contaminated soil, equivalent to what is
expected under natural weathering conditions, could reduce PMCA amplification
efficiency and extend the incubation period in hamsters inoculated with soil
samples (30). This seems to apply also to this study even though the reduction
in infectivity was more dramatic in the sPMCA assays than in the sheep model.
Sheep were not kept until clinical end-point, which would have enabled us to
compare incubation periods, but the lack of infection in sheep exposed to
furniture that had not been in contact with scrapie sheep for a longer time
period supports the hypothesis that prion degradation and subsequent loss of
infectivity occurs even under natural conditions.
In conclusion, the results in the current study indicate that removal
of furniture that had been in contact with scrapie-infected animals should be
recommended, particularly since cleaning and decontamination may not
effectively remove scrapie infectivity (31), even though infectivity declines
considerably if the pasture and the field furniture have not been in contact
with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc
in furniture that was subjected to weathering, even though exposure led to
infection in sheep, this method may not always be reliable in predicting the
risk of scrapie infection through environmental contamination. These results
suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the
detection of environmentally associated scrapie, and suggest that extremely low
levels of scrapie contamination are able to cause infection in susceptible
sheep genotypes.
Keywords: classical scrapie, prion, transmissible spongiform
encephalopathy, sheep, field furniture, reservoir, serial protein misfolding
cyclic amplification
Wednesday, December 16, 2015
*** Objects in contact with classical scrapie sheep act as a reservoir
for scrapie transmission ***
*** Infectious agent of sheep scrapie may persist in the environment
for at least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
2016 Comment from Terry Singeltary Sr.
The is a Comment on the Food and Drug Administration (FDA) Notice: 158
Guidance for Industry Use of Material from Deer and Elk in Animal Feed
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 ;
*** 2001 Terry S. Singeltary Sr. comment submission ***
Circulation of prions within
dust on a scrapie affected farm
Kevin C Gough1, Claire A
Baker2, Hugh A Simmons3, Steve A Hawkins3 and Ben C Maddison2*
Abstract
Prion diseases are fatal neurological disorders that affect humans and
animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk
are contagious prion diseases where environmental reservoirs have a direct link
to the transmission of disease. Using protein misfolding cyclic amplification
we demonstrate that scrapie PrPSc can be detected within circulating dusts that
are present on a farm that is naturally contaminated with sheep scrapie. The
presence of infectious scrapie within airborne dusts may represent a possible
route of infection and illustrates the difficulties that may be associated with
the effective decontamination of such scrapie affected premises.
snip...
Discussion
We present biochemical data illustrating the airborne movement of
scrapie containing material within a contaminated farm environment. We were
able to detect scrapie PrPSc within extracts from dusts collected over a 70 day
period, in the absence of any sheep activity. We were also able to detect
scrapie PrPSc within dusts collected within pasture at 30 m but not at 60 m
distance away from the scrapie contaminated buildings, suggesting that the
chance of contamination of pasture by scrapie contaminated dusts decreases with
distance from contaminated farm buildings. PrPSc amplification by sPMCA has
been shown to correlate with infectivity and amplified products have been shown
to be infectious [14,15]. These experiments illustrate the potential for low
dose scrapie infectivity to be present within such samples. We estimate low ng
levels of scrapie positive brain equivalent were deposited per m2 over 70 days,
in a barn previously occupied by sheep affected with scrapie. This movement of
dusts and the accumulation of low levels of scrapie infectivity within this
environment may in part explain previous observations where despite stringent
pen decontamination regimens healthy lambs still became scrapie infected after
apparent exposure from their environment alone [16]. The presence of sPMCA
seeding activity and by inference, infectious prions within dusts, and their
potential for airborne dissemination is highly novel and may have implications
for the spread of scrapie within infected premises. The low level circulation
and accumulation of scrapie prion containing dust material within the farm
environment will likely impede the efficient decontamination of such scrapie
contaminated buildings unless all possible reservoirs of dust are removed.
Scrapie containing dusts could possibly infect animals during feeding and
drinking, and respiratory and conjunctival routes may also be involved. It has
been demonstrated that scrapie can be efficiently transmitted via the nasal
route in sheep [17], as is also the case for CWD in both murine models and in
white tailed deer [18-20].
The sources of dust borne prions are unknown but it seems reasonable
to assume that faecal, urine, skin, parturient material and saliva-derived
prions may contribute to this mobile environmental reservoir of infectivity.
This work highlights a possible transmission route for scrapie within the farm
environment, and this is likely to be paralleled in CWD which shows strong
similarities with scrapie in terms of prion dissemination and disease
transmission. The data indicate that the presence of scrapie prions in dust is
likely to make the control of these diseases a considerable challenge.
Saturday, December 12, 2015
NOTICE: Environmental Impact Statement on Large Livestock Carcasses
TSE Prion REPORT December 14, 2015
Friday, August 14, 2015
Carcass Management During a Mass Animal Health Emergency Draft
Programmatic Environmental Impact Statement—August 2015
Wednesday, November 09, 2016
Chronic Wasting Disease (CWD)
Program Standards - Review and Comment By Terry S Singeltary Sr.
November 9, 2016
***Moreover, sporadic disease has never been observed in breeding
colonies or primate research laboratories, most notably among hundreds of
animals over several decades of study at the National Institutes of Health25,
and in nearly twenty older animals continuously housed in our own facility.***
***at present, no cervid PrP allele conferring absolute resistance to
prion infection has been identified.
P-145 Estimating chronic wasting disease resistance in cervids using
real time quaking- induced conversion
Nicholas J Haley1, Rachel Rielinqer2, Kristen A Davenport3, W. David
Walter4, Katherine I O'Rourke5, Gordon Mitchell6, Juergen A Richt2
1 Department of Microbiology and Immunology, Midwestern University,
United States; 2Department of Diagnostic Medicine and Pathobiology, Kansas
State University; 3Prion Research Center; Colorado State University; 4U.S.
Geological Survey, Pennsylvania Cooperative Fish and Wildlife Research Unit;
5Agricultural Research Service, United States Department of Agriculture; 6Canadian
Food Inspection Agency, National and OlE Reference Laboratory for Scrapie and
CWO In mammalian species, the susceptibility to prion diseases is affected, in
part, by the sequence of the host's prion protein (PrP). In sheep, a gradation
from scrapie susceptible to resistant has been established both in vivo and in
vitro based on the amino acids present at PrP positions 136, 154, and 171,
which has led to global breeding programs to reduce the prevalence of scrapie
in domestic sheep. In cervids, resistance is commonly characterized as a
delayed progression of chronic wasting disease (CWD); at present, no cervid PrP
allele conferring absolute resistance to prion infection has been identified.
To model the susceptibility of various naturally-occurring and hypothetical
cervid PrP alleles in vitro, we compared the amplification rates and efficiency
of various CWD isolates in recombinant PrPC using real time quaking-induced
conversion. We hypothesized that amplification metrics of these isolates in
cervid PrP substrates would correlate to in vivo susceptibility - allowing
susceptibility prediction for alleles found at 10 frequency in nature, and that
there would be an additive effect of multiple resistant codons in hypothetical
alleles. Our studies demonstrate that in vitro amplification metrics predict in
vivo susceptibility, and that alleles with multiple codons, each influencing
resistance independently, do not necessarily contribute additively to
resistance. Importantly, we found that the white-tailed deer 226K substrate
exhibited the slowest amplification rate among those evaluated, suggesting that
further investigation of this allele and its resistance in vivo are warranted
to determine if absolute resistance to CWD is possible.
***at present, no cervid PrP allele conferring absolute resistance to
prion infection has been identified.
PRION 2016 CONFERENCE TOKYO
PRION 2016 TOKYO
Zoonotic Potential of CWD Prions: An Update
Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane
Kofskey1,3, Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan
Zou1,3,5,6, Pierluigi Gambetti1, Qingzhong Kong1,5,6 1Department of Pathology,
3National Prion Disease Pathology Surveillance Center, 5Department of
Neurology, 6National Center for Regenerative Medicine, Case Western Reserve
University, Cleveland, OH 44106, USA. 4Department of Biological Sciences and
Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton,
Alberta, Canada, 2Encore Health Resources, 1331 Lamar St, Houston, TX 77010
Chronic wasting disease (CWD) is a widespread and highly transmissible
prion disease in free-ranging and captive cervid species in North America. The
zoonotic potential of CWD prions is a serious public health concern, but the
susceptibility of human CNS and peripheral organs to CWD prions remains largely
unresolved. We reported earlier that peripheral and CNS infections were
detected in transgenic mice expressing human PrP129M or PrP129V. Here we will
present an update on this project, including evidence for strain dependence and
influence of cervid PrP polymorphisms on CWD zoonosis as well as the
characteristics of experimental human CWD prions.
PRION 2016 TOKYO In Conjunction with Asia Pacific Prion Symposium 2016
PRION 2016 Tokyo Prion 2016
Cervid to human prion transmission
Kong, Qingzhong
Case Western Reserve University, Cleveland, OH, United States
Abstract
Prion disease is transmissible and invariably fatal. Chronic wasting
disease (CWD) is the prion disease affecting deer, elk and moose, and it is a
widespread and expanding epidemic affecting 22 US States and 2 Canadian
provinces so far. CWD poses the most serious zoonotic prion transmission risks
in North America because of huge venison consumption (>6 million
deer/elk hunted and consumed annually in the USA alone), significant prion
infectivity in muscles and other tissues/fluids from CWD-affected cervids, and
usually high levels of individual exposure to CWD resulting from consumption of
the affected animal among often just family and friends. However, we still do
not know whether CWD prions can infect humans in the brain or peripheral
tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and
we have no essays to reliably detect CWD infection in humans. We hypothesize
that:
(1) The classic CWD prion strain can infect humans at low levels in
the brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the
cervid prion strain and influenced by the host (human) prion protein (PrP)
primary sequence;
(3) Reliable essays can be established to detect CWD infection in
humans;and
(4) CWD transmission to humans has already occurred. We will test
these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary
in vitro approaches.
Aim 1 will prove that the classical CWD strain may infect humans in
brain or peripheral lymphoid tissues at low levels by conducting systemic
bioassays in a set of "humanized" Tg mouse lines expressing common
human PrP variants using a number of CWD isolates at varying doses and routes.
Experimental "human CWD" samples will also be generated for Aim 3.
Aim 2 will test the hypothesis that the cervid-to-human prion
transmission barrier is dependent on prion strain and influenced by the host
(human) PrP sequence by examining and comparing the transmission efficiency and
phenotypes of several atypical/unusual CWD isolates/strains as well as a few
prion strains from other species that have adapted to cervid PrP sequence,
utilizing the same panel of humanized Tg mouse lines as in Aim 1.
Aim 3 will establish reliable essays for detection and surveillance of
CWD infection in humans by examining in details the clinical, pathological,
biochemical and in vitro seeding properties of existing and future experimental
"human CWD" samples generated from Aims 1-2 and compare them with
those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.
Aim 4 will attempt to detect clinical CWD-affected human cases by
examining a significant number of brain samples from prion-affected human
subjects in the USA and Canada who have consumed venison from CWD-endemic areas
utilizing the criteria and essays established in Aim 3. The findings from this
proposal will greatly advance our understandings on the potential and characteristics
of cervid prion transmission in humans, establish reliable essays for CWD
zoonosis and potentially discover the first case(s) of CWD infection in humans.
Public Health Relevance There are significant and increasing human
exposure to cervid prions because chronic wasting disease (CWD, a widespread
and highly infectious prion disease among deer and elk in North America)
continues spreading and consumption of venison remains popular, but our
understanding on cervid-to-human prion transmission is still very limited,
raising public health concerns. This proposal aims to define the zoonotic risks
of cervid prions and set up and apply essays to detect CWD zoonosis using mouse
models and in vitro methods. The findings will greatly expand our knowledge on
the potentials and characteristics of cervid prion transmission in humans,
establish reliable essays for such infections and may discover the first
case(s) of CWD infection in humans.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Neurological Disorders and Stroke
(NINDS)
Type Research Project (R01)
Project # 1R01NS088604-01A1
Application # 9037884
Study Section Cellular and Molecular Biology of Neurodegeneration
Study Section (CMND)
Program Officer Wong, May
Project Start 2015-09-30
Project End 2019-07-31
Budget Start 2015-09-30
Budget End 2016-07-31
Support Year 1
Fiscal Year 2015
Total Cost $337,507
Indirect Cost $118,756
Institution
Name Case Western Reserve University
Department Pathology
Type Schools of Medicine
DUNS # 077758407
City Cleveland
State OH
Country United States
Zip Code 44106
===========================================================
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in
the brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the
cervid prion strain and influenced by the host (human) prion protein (PrP) primary
sequence;
(3) Reliable essays can be established to detect CWD infection in
humans;and
(4) *** CWD transmission to humans has already occurred. *** We will
test these hypotheses in 4 Aims using transgenic (Tg) mouse models and
complementary in vitro approaches.
============================================================
Key Molecular Mechanisms of TSEs
Zabel, Mark D.
Colorado State University-Fort Collins, Fort Collins, CO, United
States Abstract Prion diseases, or transmissible spongiform encephalopathies
(TSEs), are fatal neurodegenerative diseases affecting humans, cervids, bovids,
and ovids. The absolute requirement of PrPC expression to generate prion
diseases and the lack of instructional nucleic acid define prions as unique
infectious agents. Prions exhibit species-specific tropism, inferring that
unique prion strains exist that preferentially infct certain host species and
confront transmission barriers to heterologous host species. However,
transmission barriers are not absolute. Scientific consensus agrees that the
sheep TSE scrapie probably breached the transmission barrier to cattle causing
bovine spongiform encephalopathy that subsequently breached the human
transmission barrier and likely caused several hundred deaths by a new-variant form
of the human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to
human health, emotion and economies can still be felt in areas like farming,
blood and organ donations and the threat of a latent TSE epidemic. This
precedent raises the real possibility of other TSEs, like chronic wasting
disease of cervids, overcoming similar human transmission barriers. A
groundbreaking discovery made last year revealed that mice infected with
heterologous prion strains facing significant transmission barriers replicated
prions far more readily in spleens than brains6. Furthermore, these splenic
prions exhibited weakened transmission barriers and expanded host ranges
compared to neurogenic prions. These data question conventional wisdom of
avoiding neural tissue to avoid prion xenotransmission, when more promiscuous
prions may lurk in extraneural tissues. Data derived from work previously
funded by NIH demonstrate that Complement receptors CD21/35 bind prions and
high density PrPC and differentially impact prion disease depending on the
prion isolate or strain used. Recent advances in live animal and whole organ
imaging have led us to generate preliminary data to support novel, innovative
approaches to assessing prion capture and transport. We plan to test our
unifying hypothesis for this proposal that CD21/35 control the processes of
peripheral prion capture, transport, strain selection and xenotransmission in
the following specific aims. 1. Assess the role of CD21/35 in splenic prion
strain selection and host range expansion. 2. Determine whether CD21/35 and C1q
differentially bind distinct prion strains 3. Monitor the effects of CD21/35 on
prion trafficking in real time and space 4. Assess the role of CD21/35 in
incunabular prion trafficking
Public Health Relevance Transmissible spongiform encephalopathies, or
prion diseases, are devastating illnesses that greatly impact public health,
agriculture and wildlife in North America and around the world. The impact to
human health, emotion and economies can still be felt in areas like farming,
blood and organ donations and the threat of a latent TSE epidemic. This
precedent raises the real possibility of other TSEs, like chronic wasting
disease (CWD) of cervids, overcoming similar human transmission barriers. Early
this year Canada reported its first case of BSE in over a decade audits first
case of CWD in farmed elk in three years, underscoring the need for continued
vigilance and research. Identifying mechanisms of transmission and zoonoses
remains an extremely important and intense area of research that will benefit
human and other animal populations.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Allergy and Infectious Diseases
(NIAID)
Type High Priority, Short Term Project Award (R56)
Project # 1R56AI122273-01A1
Application # 9211114
Study Section Cellular and Molecular Biology of Neurodegeneration
Study Section (CMND)
Program Officer Beisel, Christopher E
Project Start 2016-02-16
Project End 2017-01-31
Budget Start 2016-02-16
Budget End 2017-01-31
Support Year 1
Fiscal Year 2016
Total Cost
Indirect Cost Institution Name Colorado State University-Fort Collins
Department Microbiology/Immun/Virology
Type Schools of Veterinary Medicine
DUNS # 785979618 City Fort Collins
State CO
Country United States
Zip Code 80523
PMCA Detection of CWD Infection in Cervid and Non-Cervid Species
Hoover, Edward Arthur
Colorado State University-Fort Collins, Fort Collins, CO, United
States
Abstract Chronic wasting disease (CWD) of deer and elk is an emerging
highly transmissible prion disease now recognized in 18 States, 2 Canadian
provinces, and Korea. We have shown that Infected deer harbor and shed high
levels of infectious prions in saliva, blood, urine, and feces, and in the
tissues generating those body fluids and excreta, thereby leading to facile
transmission by direct contact and environmental contamination. We have also
shown that CWD can infect some non-cervid species, thus the potential risk CWD
represents to domestic animal species and to humans remains unknown. Whether
prions borne in blood, saliva, nasal fluids, milk, or excreta are generated or
modified in the proximate peripheral tissue sites, may differ in subtle ways
from those generated in brain, or may be adapted for mucosal infection remain
open questions. The increasing parallels in the pathogenesis between prion
diseases and human neurodegenerative conditions, such as Alzheimer's and
Parkinson's diseases, add relevance to CWD as a transmissible protein
misfolding disease. The overall goal of this work is to elucidate the process
of CWD prion transmission from mucosal secretory and excretory tissue sites by
addressing these questions: (a) What are the kinetics and magnitude of CWD
prion shedding post-exposure? (b) Are excreted prions biochemically distinct,
or not, from those in the CNS? (c) Are peripheral epithelial or CNS tissues, or
both, the source of excreted prions? and (d) Are excreted prions adapted for
horizontal transmission via natural/trans-mucosal routes? The specific aims of
this proposal are: (1) To determine the onset and consistency of CWD prion
shedding in deer and cervidized mice; (2); To compare the biochemical and
biophysical properties of excretory vs. CNS prions; (3) To determine the
capacity of peripheral tissues to support replication of CWD prions; (4) To
determine the protease- sensitive infectious fraction of excreted vs. CNS
prions; and (5) To compare the mucosal infectivity of excretory vs. CNS prions.
Understanding the mechanisms that enable efficient prion dissemination and
shedding will help elucidate how horizontally transmissible prions evolve and
succeed, and is the basis of this proposal. Understanding how infectious
misfolded proteins (prions) are generated, trafficked, shed, and transmitted
will aid in preventing, treating, and managing the risks associated with these
agents and the diseases they cause.
Public Health Relevance Chronic wasting disease (CWD) of deer and elk
is an emergent highly transmissible prion disease now recognized throughout the
USA as well as in Canada and Korea. We have shown that infected deer harbor and
shed high levels of infectious prions in saliva, blood, urine, and feces
thereby leading to transmission by direct contact and environmental
contamination. In that our studies have also shown that CWD can infect some
non-cervid species, the potential risk CWD may represents to domestic animal
species and humans remains unknown. The increasing parallels in the development
of major human neurodegenerative conditions, such as Alzheimer's and
Parkinson's diseases, and prion diseases add relevance to CWD as a model of a
transmissible protein misfolding disease. Understanding how infectious
misfolded proteins (prions) are generated and transmitted will aid in
interrupting, treating, and managing the risks associated with these agents and
the diseases they cause.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Neurological Disorders and Stroke
(NINDS)
Type Research Project (R01)
Project # 4R01NS061902-07
Application # 9010980
Study Section Cellular and Molecular Biology of Neurodegeneration
Study Section (CMND)
Program Officer Wong, May Project Start 2009-09-30
Project End 2018-02-28
Budget Start 2016-03-01
Budget End 2017-02-28
Support Year 7
Fiscal Year 2016
Total Cost $409,868
Indirect Cost $134,234 Institution Name Colorado State University-Fort
Collins
Department Microbiology/Immun/Virology
Type Schools of Veterinary Medicine
DUNS # 785979618 City Fort Collins
State CO
Country United States
Zip Code 80523
LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN
ALL THE WRONG PLACES $$$
*** These results would seem to suggest that CWD does indeed have
zoonotic potential, at least as judged by the compatibility of CWD prions and
their human PrPC target. Furthermore, extrapolation from this simple in vitro
assay suggests that if zoonotic CWD occurred, it would most likely effect those
of the PRNP codon 129-MM genotype and that the PrPres type would be similar to
that found in the most common subtype of sCJD (MM1).***
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
O18
Zoonotic Potential of CWD Prions
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane
Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western
Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples,
Italy, 3Encore Health Resources, Houston, Texas, USA
*** These results indicate that the CWD prion has the potential to
infect human CNS and peripheral lymphoid tissues and that there might be
asymptomatic human carriers of CWD infection.
==================
***These results indicate that the CWD prion has the potential to
infect human CNS and peripheral lymphoid tissues and that there might be
asymptomatic human carriers of CWD infection.***
==================
P.105: RT-QuIC models trans-species prion transmission
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward
Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA
Conversely, FSE maintained sufficient BSE characteristics to more
efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was
competent for conversion by CWD and fCWD.
***This insinuates that, at the level of 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.***
================
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2,
2014
*** chronic wasting disease, there was no absolute barrier to
conversion of the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro
assay when seeded with CWD, resembles that found in the most common human prion
disease, namely sCJD of the MM1 subtype.
*** These results would seem to suggest that CWD does indeed have
zoonotic potential, at least as judged by the compatibility of CWD prions and
their human PrPC target. Furthermore, extrapolation from this simple in vitro
assay suggests that if zoonotic CWD occurred, it would most likely effect those
of the PRNP codon 129-MM genotype and that the PrPres type would be similar to
that found in the most common subtype of sCJD (MM1).***
*** 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.
***********CJD REPORT 1994 increased risk for consumption of veal and
venison and lamb***********
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD
ANNUAL REPORT AUGUST 1994
Consumption of venison and veal was much less widespread among both
cases and controls. For both of these meats there was evidence of a trend with
increasing frequency of consumption being associated with increasing risk of
CJD. (not nvCJD, but sporadic CJD...tss)
These associations were largely unchanged when attention was
restricted to pairs with data obtained from relatives. ...
Table 9 presents the results of an analysis of these data.
There is STRONG evidence of an association between ‘’regular’’ veal
eating and risk of CJD (p = .0.01).
Individuals reported to eat veal on average at least once a year
appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.
There is, however, a very wide confidence interval around this
estimate. There is no strong evidence that eating veal less than once per year
is associated with increased risk of CJD (p = 0.51).
The association between venison eating and risk of CJD shows similar
pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF
CJD (p = 0.04).
There is some evidence that risk of CJD INCREASES WITH INCREASING
FREQUENCY OF LAMB EATING (p = 0.02).
The evidence for such an association between beef eating and CJD is
weaker (p = 0.14). When only controls for whom a relative was interviewed are
included, this evidence becomes a little STRONGER (p = 0.08).
snip...
It was found that when veal was included in the model with another
exposure, the association between veal and CJD remained statistically
significant (p = < 0.05 for all exposures), while the other exposures
ceased to be statistically significant (p = > 0.05).
snip...
In conclusion, an analysis of dietary histories revealed statistical
associations between various meats/animal products and INCREASED RISK OF CJD.
When some account was taken of possible confounding, the association between
VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS
STATISTICALLY. ...
snip...
In the study in the USA, a range of foodstuffs were associated with an
increased risk of CJD, including liver consumption which was associated with an
apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3
studies in relation to this particular dietary factor, the risk of liver
consumption became non-significant with an odds ratio of 1.2 (PERSONAL
COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
snip...see full report ;
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge
Spencers Lane BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the
third annual report from the CJD Surveillance Unit. I am sorry that you are
dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the
Department of Health is committed to publishing their reports as soon as they
become available. In the circumstances it is not the practice to circulate the
report for comment since the findings of the report would not be amended. In
future we can ensure that the British Deer Farmers Association receives a copy
of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully
informed of the results of any research in respect of CJD. This report was
entirely the work of the unit and was produced completely independantly of the
the Department.
The statistical results reqarding the consumption of venison was put
into perspective in the body of the report and was not mentioned at all in the
press release. Media attention regarding this report was low key but gave a
realistic presentation of the statistical findings of the Unit. This approach
to publication was successful in that consumption of venison was highlighted
only once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed
statistical links between CJD and consumption of venison, would increase, and
quite possibly give damaging credence, to the whole issue. From the low key
media reports of which I am aware it seems unlikely that venison consumption
will suffer adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
Monday, May 02, 2016
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD
Monday, May 02, 2016
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
*** WDA 2016 NEW YORK ***
We found that CWD adapts to a
new host more readily than BSE and that human PrP was unexpectedly prone to
misfolding by CWD prions. In addition, we investigated the role of specific
regions of the bovine, deer and human PrP protein in resistance to conversion
by prions from another species. We have concluded that the human protein has a
region that confers unusual susceptibility to conversion by CWD prions.
Student Presentations Session 2
The species barriers and public
health threat of CWD and BSE prions
Ms. Kristen Davenport1, Dr.
Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State
University
Chronic wasting disease (CWD)
is spreading rapidly through cervid populations in the USA. Bovine spongiform
encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were
fed recycled animal protein. These and other prion diseases are caused by
abnormal folding of the normal prion protein (PrP) into a disease causing form
(PrPd), which is pathogenic to nervous system cells and can cause subsequent
PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet
infected humans. On the other hand, BSE was spread only when cattle consumed
infected bovine or ovine tissue, but did infect humans and other species. The
objective of this research is to understand the role of PrP structure in
cross-species infection by CWD and BSE. To study the propensity of each
species’ PrP to be induced to misfold by the presence of PrPd from verious
species, we have used an in vitro system that permits detection of PrPd in
real-time. We measured the conversion efficiency of various combinations of
PrPd seeds and PrP substrate combinations. We observed the cross-species
behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found
that CWD adapts to a new host more readily than BSE and that human PrP was
unexpectedly prone to misfolding by CWD prions. In addition, we investigated
the role of specific regions of the bovine, deer and human PrP protein in
resistance to conversion by prions from another species. We have concluded that
the human protein has a region that confers unusual susceptibility to
conversion by CWD prions. CWD is unique among prion diseases in its rapid
spread in natural populations. BSE prions are essentially unaltered upon
passage to a new species, while CWD adapts to the new species. This adaptation
has consequences for surveillance of humans exposed to CWD.
Wildlife Disease Risk Communication Research Contributes to Wildlife
Trust Administration Exploring perceptions about chronic wasting disease risks
among wildlife and agriculture professionals and stakeholders
Saturday, April 23, 2016
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a.
Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ).
Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents
Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie
MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE)
contaminated bovine tissues is considered as the origin of variant Creutzfeldt
Jakob (vCJD) disease in human. To date, BSE agent is the only recognized
zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy
(TSE) agents that have been circulating for centuries in farmed ruminants there
is no apparent epidemiological link between exposure to ruminant products and
the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob
Disease (sCJD). However, the zoonotic potential of the diversity of circulating
TSE agents has never been systematically assessed. The major issue in
experimental assessment of TSEs zoonotic potential lies in the modeling of the
‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation
from a species to another. In the last decade, mice genetically engineered to
express normal forms of the human prion protein has proved essential in
studying human prions pathogenesis and modeling the capacity of TSEs to cross
the human species barrier.
To assess the zoonotic potential of prions circulating in farmed
ruminants, we study their transmission ability in transgenic mice expressing
human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the
human PrPC (129Met or 129Val) are used to determine the role of the Met129Val
dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to
propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be
susceptible to BSE in sheep or goat to a greater degree than the BSE agent in
cattle and that these agents can convey molecular properties and
neuropathological indistinguishable from vCJD. However homozygous 129V mice are
resistant to all tested BSE derived prions independently of the originating
species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate
in HuPrP-Tg mice with ef?ciency comparable to that of cattle BSE. While the
ef?ciency of transmission at primary passage was low, subsequent passages
resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the
emergence of prion strain phenotypes that showed similar characteristics to
those displayed by MM1 or VV2 sCJD prion. These results demonstrate that
scrapie prions have a zoonotic potential and raise new questions about the
possible link between animal and human prions.
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
*** In complement to the recent demonstration that humanized mice are
susceptible to scrapie, we report here the first observation of direct
transmission of a natural classical scrapie isolate to a macaque after a
10-year incubation period. Neuropathologic examination revealed all of the
features of a prion disease: spongiform change, neuronal loss, and accumulation
of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness
of scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated.
*** Our results underscore the importance of precautionary and
protective measures and the necessity for long-term experimental transmission
studies to assess the zoonotic potential of other animal prion strains.
O.05: Transmission of prions to primates after extended silent
incubation periods: Implications for BSE and scrapie risk assessment in human
populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni,
Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys
Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies
reputed to be transmissible under field conditions since decades. The
transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that
an animal PD might be zoonotic under appropriate conditions. Contrarily, in the
absence of obvious (epidemiological or experimental) elements supporting a
transmission or genetic predispositions, PD, like the other proteinopathies,
are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD
summing 80% of human prion cases). Non-human primate models provided the first
evidences supporting the transmissibiity of human prion strains and the
zoonotic potential of BSE. Among them, cynomolgus macaques brought major
information for BSE risk assessment for human health (Chen, 2014), according to
their phylogenetic proximity to humans and extended lifetime. We used this
model to assess the zoonotic potential of other animal PD from bovine, ovine
and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural
classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic
CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently
evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases. We will present
an updated panorama of our different transmission studies and discuss the
implications of such extended incubation periods on risk assessment of animal
PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE
to sheep and human. Bioassay will be required to determine whether the PMCA
products are infectious to these animals.
==============
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
***This observation strengthens the questioning of the harmlessness of
scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated. Our results underscore the importance of precautionary and
protective measures and the necessity for long-term experimental transmission
studies to assess the zoonotic potential of other animal prion strains.
please see file attachment for full submission and recent science and
my deep concerns on the TSE Prion disease... No documents available.
AttachmentsView All (1) scrapie-usa-blogspot-com View Attachment:
Saturday, November 12, 2016
Maine Medical Center received
confirmation patient treated at the hospital has Creutzfeldt-Jakob disease
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
12:57 PM
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