Dispatch
Horizontal
Transmission of Chronic Wasting Disease in Reindeer
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)
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.
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).
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)).
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.
We thank
Martha Church, Robyn Kokemuller, Joe Lesan, Virginia Montgomery, Dennis Orcutt,
and Trudy Tatum for excellent technical support.
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
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
Tables
Technical Appendix
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.
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.
>>>Another alternative would be an absolute prohibition
on the movement of deer within the state for any purpose. While this
alternative would significantly reduce the potential spread of CWD, it would
also have the simultaneous effect of preventing landowners and land managers
from implementing popular management strategies involving the movement of deer,
and would deprive deer breeders of the ability to engage in the business of
buying and selling breeder deer. Therefore, this alternative was rejected
because the department determined that it placed an avoidable burden on the regulated
community.<<<
Wednesday, December 16, 2015
Objects in contact with
classical scrapie sheep act as a reservoir for scrapie transmission
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.
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 CWD
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
Prion 2016 Purchase
options Price * Issue Purchase USD 198.00
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.
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 ***
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.
0 Comments:
Post a Comment
Subscribe to Post Comments [Atom]
<< Home