Chronic Wasting Disease in Bank Voles: Characterisation of the Shortest Incubation Time Model for Prion Diseases
Research Article Chronic Wasting Disease in Bank Voles: Characterisation of
the Shortest Incubation Time Model for Prion Diseases
Michele Angelo Di Bari mail, * E-mail: michele.dibari@iss.it
Affiliation: Department of Veterinary Public Health and Food Safety,
Istituto Superiore di Sanità, Rome, Italy
X Romolo Nonno, Affiliation: Department of Veterinary Public Health and
Food Safety, Istituto Superiore di Sanità, Rome, Italy
X Joaquín Castilla, Affiliation: CIC bioGUNE and IKERBASQUE, Basque
Foundation for Science, Derio and Bilbao, Bizkaia, Spain
X Claudia D'Agostino, Affiliation: Department of Veterinary Public Health
and Food Safety, Istituto Superiore di Sanità, Rome, Italy
X Laura Pirisinu, Affiliation: Department of Veterinary Public Health and
Food Safety, Istituto Superiore di Sanità, Rome, Italy
X Geraldina Riccardi, Affiliation: Department of Veterinary Public Health
and Food Safety, Istituto Superiore di Sanità, Rome, Italy
X Michela Conte, Affiliation: Department of Veterinary Public Health and
Food Safety, Istituto Superiore di Sanità, Rome, Italy
X Juergen Richt, Affiliation: National Animal Disease Center, Agricultural
Research Service, United States Department of Agriculture, Ames, Iowa, United
States of America
Current address: Diagnostic Medicine/Pathobiology, College of Veterinary
Medicine, Kansas State University, Manhattan, Kansas, United States of America
X Robert Kunkle, Affiliation: National Animal Disease Center, Agricultural
Research Service, United States Department of Agriculture, Ames, Iowa, United
States of America
X Jan Langeveld, Affiliation: Department of Infection Biology, Central
Veterinary Institute of Wageningen UR, Lelystad, Netherlands
X Gabriele Vaccari, Affiliation: Department of Veterinary Public Health and
Food Safety, Istituto Superiore di Sanità, Rome, Italy
X Umberto Agrimi
Abstract
In order to assess the susceptibility of bank voles to chronic wasting
disease (CWD), we inoculated voles carrying isoleucine or methionine at codon
109 (Bv109I and Bv109M, respectively) with CWD isolates from elk, mule deer and
white-tailed deer. Efficient transmission rate (100%) was observed with mean
survival times ranging from 156 to 281 days post inoculation. Subsequent
passages in Bv109I allowed us to isolate from all CWD sources the same
vole-adapted CWD strain (Bv109ICWD), typified by unprecedented short incubation
times of 25–28 days and survival times of ~35 days. Neuropathological and
molecular characterisation of Bv109ICWD showed that the classical features of
mammalian prion diseases were all recapitulated in less than one month after
intracerebral inoculation. Bv109ICWD was characterised by a mild and discrete
distribution of spongiosis and relatively low levels of protease-resistant PrPSc
(PrPres) in the same brain regions. Despite the low PrPres levels and the short
time lapse available for its accumulation, end-point titration revealed that
brains from terminally-ill voles contained up to 108,4 i.c. ID50 infectious
units per gram. Bv109ICWD was efficiently replicated by protein misfolding
cyclic amplification (PMCA) and the infectivity faithfully generated in vitro,
as demonstrated by the preservation of the peculiar Bv109ICWD strain features on
re-isolation in Bv109I. Overall, we provide evidence that the same CWD strain
was isolated in Bv109I from the three-cervid species. Bv109ICWD showed unique
characteristics of “virulence”, low PrPres accumulation and high infectivity,
thus providing exceptional opportunities to improve basic knowledge of the
relationship between PrPSc, neurodegeneration and infectivity.
Author Summary Chronic wasting disease (CWD) is a prion disease that
affects free-ranging and captive cervids and is expanding increasingly in the
USA and Canada. Animal models are of key importance in the study of prion
diseases but their development for CWD has long been hampered by its very
inefficient transmission to wild-type mice. Significant progress was made
following the generation of transgenic mice over-expressing cervid PrP. Here we
show that the bank vole (Myodes glareolus), a wild rodent species that we
demonstrated to be susceptible to many animal and human prion diseases, is also
very susceptible to CWD from elk, mule deer and white-tailed deer. Adaptation of
CWD to bank vole led to the isolation of a prion strain with peculiar
characteristics: unprecedented short incubation and survival times, respectively
of 25–28 and ~35 days, low PrPSc levels compared with other vole-adapted prion
strains and high infectious titre. These features were all faithfully maintained
upon the generation of this strain in vitro by protein misfolding cyclic
amplification. The development of a model for prion diseases that led to disease
in less than one month accumulating high infectious titres but low PrPSc levels,
represents a significant tool for investigating the still unclear relationship
between PrPSc, neurodegeneration and infectivity in prion diseases.
Citation: Di Bari MA, Nonno R, Castilla J, D'Agostino C, Pirisinu L, et al.
(2013) Chronic Wasting Disease in Bank Voles: Characterisation of the Shortest
Incubation Time Model for Prion Diseases. PLoS Pathog 9(3): e1003219.
doi:10.1371/journal.ppat.1003219
Editor: David Westaway, University of Alberta, Canada
Received: August 31, 2012; Accepted: January 12, 2013; Published: March 7,
2013
This is an open-access article, free of all copyright, and may be freely
reproduced, distributed, transmitted, modified, built upon, or otherwise used by
anyone for any lawful purpose. The work is made available under the Creative
Commons CC0 public domain dedication.
Funding: This work was financially supported by the European Union
(Neuroprion Network of Excellence, CT-2004-506579), the Alliance Biosecure
Foundation (“Vole PMCA” research grant), the Italian Ministry of Health, a
national grant from Spain (AGL2009-11553-C02-01) and from the Basque Government
(PI2010-18). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests
exist.
snip...
Discussion
In the present study we investigated the susceptibility of Bv109I and
Bv109M to seven CWD isolates from three deer species and found that these animal
models are highly permissive to CWD, showing 100% attack rate and mean survival
times between 156 and 281 d.p.i.. A deepened transmission and characterization
study of CWD was carried out in Bv109I. The susceptibility of this model
appeared comparable to that of transgenic mice expressing cervid PrP [6], [7],
[9], [10], [11]. The reasons for such a high susceptibility are unclear but
apparently not related to a different expression of PrPC. As a matter of fact,
its expression level in Bv109I is comparable to that of mouse and hamster
(Figure S5). The dramatic drop in survival time with vole-to-vole sub-passages
suggests that CWD still encounters a high transmission barrier in Bv109I,
implying that Bv109I permissiveness to CWD was not due to the absence of
transmission barrier, as observed in transgenic mice expressing cervid PrP.
Using Bv109M voles we have previously shown that this species is permissive to a
variety of human and animal prion diseases. Studies aimed at investigating the
molecular basis of the susceptibility of bank voles to foreign prions and their
selective strain preferences suggested that two asparagine residues at positions
150 and 170, specific to vole PrP, might play a role [18], [22], [25].
Interestingly, cervid PrP also has asparagine at residue 170, suggesting that
sequence identity at codon 170 might facilitate the transmission of CWD to
Bv109I. This interpretation is supported by the relative ease of transmission of
CWD to meadow voles [14], which also have asparagine at positions 150 and 170,
as well as by studies in MoPrP170N, 174T transgenic mice [24], [26] and by in
vitro amplification of CWD by PMCA [27].
A striking feature of Bv109I-adapted CWD was the short incubation time of
less than one month. In an earlier work, we showed that bank voles and related
rodent species have peculiarly short survival times after infection with adapted
prions, and presumably support equally fast prion replication kinetics, possibly
due to the previously mentioned 150N–170N PrP residues [22]. This was also
observed in vitro using Bv109M brain homogenates as substrate for PMCA-driven
prion replication [28]. Notwithstanding this, our previous and on-going studies
with Bv109M have not shown evidence of ultra-fast strains such as Bv109ICWD, and
the fastest strains observed so far in voles show incubation times of ~2 months
[19, unpublished data). Transmission studies of CWD to Bv109M have not yet
completed but we have observed that also CWD adapts to Bv109M with survival
times longer than Bv109ICWD (60–100 d.p.i.) (unpublished data). The short
survival time of Bv109ICWD is also unprecedented when compared with those found
in transgenic mouse models, in which PrP overexpression greatly fosters prion
diseases [6], [7], [8], [9], [10], [11]. Indeed, the fastest rodent models
reported so far, i.e. Tga20 [29], Tg52NSE [30], Tg7 [31], Tg4053 [32] and Tg338
mice [33], express several-fold higher PrP levels compared with wild-type mice
and have incubation periods at least twice as long as Bv109ICWD. Interestingly,
it was recently shown that TgS3581 mice overexpressing vole PrP encoding for
Isoleucine at position 109, undergo spontaneous prion disease and that it adapts
to the same model with mean survival time of 35 days [34]. These findings
suggest that the presence of Isoleucine at position 109 of the vole PrP plays a
specific role in determining the short survival time of Bv109ICWD
In the present work we provide evidence that all the hallmarks of TSEs were
recapitulated within one month in bank vole CWD. The finding that
neurodegeneration and PrPSc deposition showed a discrete brain distribution,
involving specific neuronal populations such as those in the medulla and
thalamus, might suggest that Bv109ICWD replication primarily involves the so
called clinical target areas (CTAs) which, once colonised by prions, trigger the
clinical signs and death of the animals [35], [36]. A recent study showed that
shorter time periods were needed to initiate the clinical phase when the 127S
scrapie strain primarily targeted CTAs, as in intraperitoneally-inoculated Tg338
mice, compared with intracerebrally-inoculated mice [37]. This was accompanied
by comparatively low levels of PrPres and infectivity in the brain of
ip-inoculated mice. In Bv109ICWD we also observed unusually low levels of
PrPres, compared with those observed in most of the vole-adapted prion strains
(Figure 3). However, by endpoint titration we found unexpected high prion titres
in Bv109ICWD, 108,4 i.c. ID50 U g−1, similar to those usually observed in
standard hamster and mouse-adapted scrapie strains, whose incubation times are
3–10 times longer than Bv109ICWD. This implies that Bv109ICWD undergoes
extraordinarily fast replication kinetics in Bv109I brain.
Several observations suggest that prion infectivity and toxicity might be
uncoupled [38], [39], [40] and these observations are currently incorporated in
a general model of prion replication and toxicity [41]. According to this model,
neurotoxicity is mediated by a lethal PrP species, PrPL, which is distinct from
PrPSc, but its formation is catalysed during the autocatalytic replication of
PrPSc. Neurotoxicity may require a critical PrPL concentration to be reached,
which would depend on the kinetics of prion propagation. The relative levels of
toxicity and infectivity are governed by the ratio of the initial rate of PrPC
conversion (which leads to the production of PrPL) to the rate of its maturation
into PrPSc. Thus fast prion replication in Bv109ICWD might have triggered the
production of high levels of PrPL in short time periods, leading to rapid
disease onset and animal death. The low levels of PrPSc and the fast replication
kinetics observed in Bv109ICWD are consistent with this interpretation.
A recent work showed that in mice inoculated with the RML scrapie strain
the concentration of PrPC did not affect the overall level of prion infectious
titres at terminal disease, while it was directly related to the incubation
time, suggesting that the production of PrPL is directly proportional to PrPC
concentrations [42]. Our observations with Bv109ICWD, i.e. the unusually short
survival time and the high prion infectious titre in a model that does not
overexpress PrPC, suggest that the kinetics of prion propagation and toxicity
are governed by mechanisms that cannot be interpreted solely on the basis of the
amount of available substrate (PrPC).
The unique and easily distinguishable features of Bv109ICWD prompted us to
pursue its in vitro propagation by saPMCA. Bv109ICWD PrPSc was indeed easily
propagated in vitro, which allowed us to produce Bv109ICWDPMCA PrPSc,
theoretically devoid of any PrPSc formed in vivo. Bv109ICWDPMCA was highly
infectious and faithfully reproduced the peculiar phenotype of Bv109ICWD. These
findings confirm that CWD prions can be generated in vitro, as already
demonstrated by others using transgenic mice expressing cervid PrP [43], [44],
[45], [46] and prairie voles [47]. Furthermore, given the unique characteristics
of this strain, it is extremely unlikely that their faithful maintenance during
saPMCA could have occurred by chance and our results represent a convincing
confirmation of other studies that have already demonstrated the ability of PMCA
to replicate prion strains faithfully [44], [45], [47], [48], [49].
Elk, mule deer and white-tailed deer are the species most affected by CWD.
The homogeneous and peculiar phenotypes observed in Bv109I inoculated with CWD
isolates from these three cervid species indicate that the same CWD strain was
isolated from all species. Interestingly, Bv109ICWD was isolated not only from
natural cases of disease in elk (CWD1, 2 and 4) and mule deer (CWD3), but also
from white-tailed deer experimentally inoculated with CWD-affected white-tailed
deer, mule deer and elk (CWD5, 7 and 8, respectively). Along with previous
findings in transgenic mice expressing cervid PrP [6], [9], and in keeping with
the ease of indirect horizontal transmission of CWD [50], these data suggest
that the same CWD strain circulates among different cervid species and maintains
its characteristics following interspecies transmission. Recently, a large
transmission study with elk and mule deer isolates provided substantial evidence
for two prevalent CWD prion strains and suggested that individual CWD inocula
might contain mixtures of the two prion strains [11]. Interestingly, we found
similar evidence in at least two of the seven inocula investigated, derived from
elk and mule deer, although we were unable to stabilize two different
Bv109I-adapted CWD strains. Indeed, on primary transmission of CWD2, CWD3 and
CWD4 inocula we observed voles that developed clinical signs after unusually
long times, showing a slightly different neuropathological profile from that of
voles with shorter survival times. A sub-passage in Bv109I of two of these
outliers induced a survival time of 150–160 d.p.i. on second passage, compared
with 35–45 d.p.i. observed with all other sub-passages. Such a long survival
time might have depended on a low infectious titre in the brain from outlier
voles, although they showed levels of PrPres similar to the other voles of their
groups. However this hypothesis is excluded when these results are compared with
the survival times observed in the endpoint titration experiment, which showed
that even 10−5 dilution of Bv109ICWD had a mean survival time <80 2="" a="" according="" addition="" also="" and="" as="" be="" before="" both="" bv109icwd="" by="" conformers="" converged="" cwd="" d.p.i..="" deviant="" div="" elimination="" evanescent="" extremely="" fast="" findings="" fitting="" following="" for="" in="" interpreted="" interspecies="" lesion="" less="" might="" nature="" neuropathological="" observed="" occurred="" of="" our="" outcompeted="" outlier="" outliers="" overall="" presence="" preserved="" prions="" profile="" progressive="" progressively="" propagated="" proposed="" quasi="" rapid="" second="" slightly="" species="" strain.="" strain="" strongly="" sub-passages="" suggest="" survival="" that="" the="" time="" to="" transmission.="" vole="" voles="" was="" which="" with="">
Here we demonstrate the high susceptibility of Bv109I to CWD, which adds
Bv109I to the portfolio of animal models useful for the study of CWD strains.
The unique properties of Bv109ICWD provide exceptional opportunities to improve
basic knowledge of the relationship between PrPSc, neurodegeneration and
infectivity. The short survival time of Bv109ICWD, coupled with its high
infectious titre, offers useful advantages for titration studies, while its
unique clinico-pathological phenotype makes Bv109ICWD one of the best options
for studies aimed at investigating strain fidelity in experimental conditions.
J Gen Virol. 2012 January; 93(Pt 1): 212–221. doi: 10.1099/vir.0.035006-0
PMCID: PMC3352335
Evidence for distinct chronic wasting disease (CWD) strains in experimental
CWD in ferrets
Matthew R. Perrott,1 Christina J. Sigurdson,2 Gary L. Mason,3 and Edward
A. Hoover3
Abstract
Chronic wasting disease (CWD) is an evolving prion disease of cervids
(deer, elk and moose) that has been recognized in North America and Korea.
Infection of non-cervid reservoir or transport species in nature is not
reported. However, the ferret (Mustela putorius furo) is susceptible to CWD
after experimental inoculation. Here, we report that infection of ferrets with
either of two ferret CWD isolates by various routes of exposure has revealed
biologically distinct strain-like properties distinguished by different clinical
progression and survival period. The isolates of ferret CWD were also
differentiated by the distribution of the infectious prion protein (PrPCWD) in
the brain and periphery, and by the proteinase K sensitivity of PrPCWD. These
findings suggest that diversity in prion conformers exists in CWD-infected
cervids.
snip...
The results of these studies support the growing evidence for multiple
strains of CWD prions.
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET
AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF
THE STUDIES ON CWD TRANSMISSION TO CATTLE ;
CWD to cattle figures CORRECTION
Greetings,
I believe the statement and quote below is incorrect ;
"CWD has been transmitted to cattle after intracerebral inoculation,
although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This
finding raised concerns that CWD prions might be transmitted to cattle grazing
in contaminated pastures."
Please see ;
Within 26 months post inoculation, 12 inoculated animals had lost weight,
revealed abnormal clinical signs, and were euthanatized. Laboratory tests
revealed the presence of a unique pattern of the disease agent in tissues of
these animals. These findings demonstrate that when CWD is directly inoculated
into the brain of cattle, 86% of inoculated cattle develop clinical signs of the
disease.
" although the infection rate was low (4 of 13 animals [Hamir et al.
2001]). "
shouldn't this be corrected, 86% is NOT a low rate. ...
kindest regards,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Thank you!
Thanks so much for your updates/comments. We intend to publish as rapidly
as possible all updates/comments that contribute substantially to the topic
under discussion.
re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author
Affiliations
1Institute for Neurodegenerative Diseases, University of California, San
Francisco, San Francisco, California 94143 2Department of Neurology, University
of California, San Francisco, San Francisco, California 94143 Correspondence:
stanley@ind.ucsf.edu
Mule deer, white-tailed deer, and elk have been reported to develop CWD.
As the only prion disease identified in free-ranging animals, CWD appears to be
far more communicable than other forms of prion disease. CWD was first described
in 1967 and was reported to be a spongiform encephalopathy in 1978 on the basis
of histopathology of the brain. Originally detected in the American West, CWD
has spread across much of North America and has been reported also in South
Korea. In captive populations, up to 90% of mule deer have been reported to be
positive for prions (Williams and Young 1980). The incidence of CWD in cervids
living in the wild has been estimated to be as high as 15% (Miller et al. 2000).
The development of transgenic (Tg) mice expressing cervid PrP, and thus
susceptible to CWD, has enhanced detection of CWD and the estimation of prion
titers (Browning et al. 2004; Tamgüney et al. 2006). Shedding of prions in the
feces, even in presymptomatic deer, has been identified as a likely source of
infection for these grazing animals (Williams and Miller 2002; Tamgüney et al.
2009b). CWD has been transmitted to cattle after intracerebral inoculation,
although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This
finding raised concerns that CWD prions might be transmitted to cattle grazing
in contaminated pastures.
snip...
----- Original Message -----
From: David Colby To: flounder9@verizon.net
Cc: stanley@XXXXXXXX
Sent: Tuesday, March 01, 2011 8:25 AM
Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 +
Author Affiliations
Dear Terry Singeltary,
Thank you for your correspondence regarding the review article Stanley
Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner
asked that I reply to your message due to his busy schedule. We agree that the
transmission of CWD prions to beef livestock would be a troubling development
and assessing that risk is important. In our article, we cite a peer-reviewed
publication reporting confirmed cases of laboratory transmission based on
stringent criteria. The less stringent criteria for transmission described in
the abstract you refer to lead to the discrepancy between your numbers and ours
and thus the interpretation of the transmission rate. We stand by our assessment
of the literature--namely that the transmission rate of CWD to bovines appears
relatively low, but we recognize that even a low transmission rate could have
important implications for public health and we thank you for bringing attention
to this matter.
Warm Regards, David Colby -- David Colby, PhD
Assistant Professor Department of Chemical Engineering University of
Delaware
===========END...TSS==============
SNIP...SEE FULL TEXT ;
Sunday, August 19, 2012
Susceptibility of cattle to the agent of chronic wasting disease from elk
after intracranial inoculation 2012
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Unit
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
Thursday, May 31, 2012
CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission,
Scrapie, cats, species barrier, burial, and more
CHRONIC WASTING DISEASE, CWD, AND THE DEER PENS AT THE FOOT HILLS CAMPUS
page 30,
*** Spraker suggested an interesting explanation for the occurrence of CWD.
The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr.
Bob Davis. At or about that time, allegedly, some scrapie work was conducted at
this site. When deer were introduced to the pens they occupied ground that had
previously been occupied by sheep.
(PLEASE NOTE SOME OF THESE OLD UK GOVERNMENT FILE URLS ARE SLOW TO OPEN,
AND SOMETIMES YOU MAY HAVE TO CLICK ON MULTIPLE TIMES, PLEASE BE PATIENT, ANY
PROBLEMS PLEASE WRITE ME PRIVATELY, AND I WILL TRY AND FIX OR SEND YOU OLD PDF
FILE...TSS)
IN CONFIDENCE
PERCEPTIONS OF UNCONVENTIONAL SLOW VIRUS DISEASES OF ANIMALS IN USA
GAH WELLS
REPORT OF A VISIT TO THE USA APRIL-MAY 1989
PAGE 25
Transmission Studies
Mule deer transmissions of CWD were by intracerebral inoculation and
compared with natural cases resulted in a more rapidly progressive clinical
disease with repeated episodes of synocopy ending in coma. One control animal
became affected, it is believed through contamination of inoculam (?saline).
Further CWD transmissions were carried out by Dick Marsh into ferret, mink
and squirrel monkey. Transmission occurred in all of these species with the
shortest incubation period in the ferret.
2011 Annual Report
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Unit
2011 Annual Report
In Objective 1, Assess cross-species transmissibility of transmissible
spongiform encephalopathies (TSEs) in livestock and wildlife, numerous
experiments assessing the susceptibility of various TSEs in different host
species were conducted. Most notable is deer inoculated with scrapie, which
exhibits similarities to chronic wasting disease (CWD) in deer suggestive of
sheep scrapie as an origin of CWD.
snip...
4.Accomplishments 1. Deer inoculated with domestic isolates of sheep
scrapie. Scrapie-affected deer exhibit 2 different patterns of disease
associated prion protein. In some regions of the brain the pattern is much like
that observed for scrapie, while in others it is more like chronic wasting
disease (CWD), the transmissible spongiform encephalopathy typically associated
with deer. This work conducted by ARS scientists at the National Animal Disease
Center, Ames, IA suggests that an interspecies transmission of sheep scrapie to
deer may have been the origin of CWD. This is important for husbandry practices
with both captive deer, elk and sheep for farmers and ranchers attempting to
keep their herds and flocks free of CWD and scrapie.
now, years later, see the latest studies here on scrapie and cwd ;
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed
deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture;
Agricultural Research Service, National Animal Disease Center; Ames, IA USA
Interspecies transmission studies afford the opportunity to better
understand the potential host range and origins of prion diseases. The purpose
of these experiments was to determine susceptibility of white-tailed deer (WTD)
to scrapie and to compare the resultant clinical signs, lesions, and molecular
profiles of PrPSc to those of chronic wasting disease (CWD). We inoculated WTD
intracranially (IC; n = 5) and by a natural route of exposure (concurrent oral
and intranasal (IN); n = 5) with a US scrapie isolate. All deer were inoculated
with a 10% (wt/vol) brain homogenate from sheep with scrapie (1ml IC, 1 ml IN,
30 ml oral). All deer inoculated by the intracranial route had evidence of PrPSc
accumulation. PrPSc was detected in lymphoid tissues as early as 7
months-post-inoculation (PI) and a single deer that was necropsied at 15.6
months had widespread distribution of PrPSc highlighting that PrPSc is widely
distributed in the CNS and lymphoid tissues prior to the onset of clinical
signs. IC inoculated deer necropsied after 20 months PI (3/5) had clinical
signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural
and lymphoid tissues. The results of this study suggest that there are many
similarities in the manifestation of CWD and scrapie in WTD after IC inoculation
including early and widespread presence of PrPSc in lymphoid tissues, clinical
signs of depression and weight loss progressing to wasting, and an incubation
time of 21-23 months. Moreover, western blots (WB) done on brain material from
the obex region have a molecular profile similar to CWD and distinct from
tissues of the cerebrum or the scrapie inoculum. However, results of microscopic
and IHC examination indicate that there are differences between the lesions
expected in CWD and those that occur in deer with scrapie: amyloid plaques were
not noted in any sections of brain examined from these deer and the pattern of
immunoreactivity by IHC was diffuse rather than plaque-like. After a natural
route of exposure, 100% of WTD were susceptible to scrapie. Deer developed
clinical signs of wasting and mental depression and were necropsied from 28 to
33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB.
Similar to IC inoculated deer, samples from these deer exhibited two different
molecular profiles: samples from obex resembled CWD whereas those from cerebrum
were similar to the original scrapie inoculum. On further examination by WB
using a panel of antibodies, the tissues from deer with scrapie exhibit
properties differing from tissues either from sheep with scrapie or WTD with
CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive
when probed with mAb P4, however, samples from WTD with scrapie are only weakly
immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from
sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from
WTD with scrapie are strongly positive. This work demonstrates that WTD are
highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is
differentiable from CWD.
White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection
Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion
Research Unit, National Animal Disease Center, USDA-ARS
Interspecies transmission studies afford the opportunity to better
understand the potential host range and origins of prion diseases. Previous
experiments demonstrated that white-tailed deer are susceptible to sheep-derived
scrapie by intracranial inoculation. The purpose of this study was to determine
susceptibility of white-tailed deer to scrapie after a natural route of
exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal
(1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep
clinically affected with scrapie. Non-inoculated deer were maintained as
negative controls. All deer were observed daily for clinical signs. Deer were
euthanized and necropsied when neurologic disease was evident, and tissues were
examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and
western blot (WB). One animal was euthanized 15 months post-inoculation (MPI)
due to an injury. At that time, examination of obex and lymphoid tissues by IHC
was positive, but WB of obex and colliculus were negative. Remaining deer
developed clinical signs of wasting and mental depression and were necropsied
from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and
WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal
and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work
demonstrates for the first time that white-tailed deer are susceptible to sheep
scrapie by potential natural routes of inoculation. In-depth analysis of tissues
will be done to determine similarities between scrapie in deer after
intracranial and oral/intranasal inoculation and chronic wasting disease
resulting from similar routes of inoculation.
see full text ;
Envt.11: Swine Are Susceptible to Chronic Wasting Disease by Intracerebral
Inoculation
Justin Greenlee,† Robert Kunkle and Jodi Smith National Animal Disease
Center, ARS, USDA; Ames, IA USA †Presenting author; Email:
justin.greenlee@ars.usda.gov
Transmissible spongiform encephalopathies (TSEs, prion diseases) are
chronic neurodegenerative diseases that occur in humans, cattle, sheep, goats,
cervids and a number of laboratory animal models. There is no evidence of the
natural occurrence of any form of TSE in the pig, but pigs have been shown to be
susceptible to Bovine Spongiform Encephalopathy (BSE) infection by
multiple-route parenteral challenge. However, pigs orally exposed at eight weeks
of age to large amounts of brain from cattle clinically affected with BSE did
not support infection after seven years of observation. In the US, feeding of
ruminant by-products to ruminants is prohibited, but feeding of ruminant
materials to swine, mink and poultry still occurs. Although unlikely, the
potential for swine to have access to TSE-contaminated feedstuffs exists. The
potential for swine to serve as a host for the agent of chronic wasting disease
(CWD) is unknown. The purpose of this study was to perform intracerebral
inoculation of the CWD agent to determine the potential of swine as a host for
the CWD agent and their clinical susceptibility. This study utilized 26 swine
randomly divided into controls (n = 6) and intracranial inoculates (n = 20). CWD
inoculum was a pooled 10% (w/v) homogenate derived from three white-tailed deer
clinically ill with CWD from three different sources (elk, white-tailed deer,
mule deer) and was given by a single intracranial injection of 0.75 ml.
Necropsies were done on ten animals at six months post inoculation (PI), at
approximately the time the pigs were expected to reach market weight. Additional
pigs have been necropsied due to intercurrent disease (primarily lameness) over
the course of the study (29–64 months). Samples collected at necropsy were
examined for spongiform change after routine staining (hematoxylin and eosin)
and for immunoreactivity to prion protein (PrPSc) by immunohistochemistry.
Further, brain samples from at least two regions were tested by western blot. No
results suggestive of spongiform encephalopathy were obtained from animals
necropsied at six months PI, but positive results after an incubation period of
only six months would be uncharacteristic. A single animal was positive for CWD
by IHC and WB at 64 months PI. Two inoculated pigs and one control pig remain
alive, so it is not possible to determine the attack rate of CWD in swine at
this time. However, lack of positive results in pigs necropsied at 29–56 months
PI and the long incubation of the single positive case suggest that swine are
unlikely to be affected by CWD if inoculated by a natural route.
PO-041: Susceptibility of domestic cats to CWD infection
Amy Nalls, Jeanette Hayes-Klug, Kelly Anderson, Davis Seelig, Kevin Carnes,
Susan Kraft, Edward Hoover, Candace Mathiason
Colorado State University; Fort Collins, CO USA
Domestic and non-domestic cats have been shown to be susceptible to feline
spongiform encephalopathy (FSE); very likely due to consumption of bovine
spongiform encephalopathy (BSE) contaminated meat. Because domestic and
free-ranging nondomestic felids scavenge cervid carcasses, including those in
areas affected by chronic wasting disease (CWD), we evaluated the susceptibility
of domestic cats to CWD infection experimentally. Groups of n = 5 cats each were
inoculated either intracerebrally (IC) or orally (PO) with CWD-infected deer
brain homogenate.
Between 40 and 43 months two IC-inoculated cats developed slowly
progressive symptoms including weight loss, anorexia, polydipsia, patterned
motor behaviors, and ataxia”’ultimately mandating euthanasia. PrPCWD was
detected in the brains of these animals by western blot, immunohistochemistry
(IHC), and quaking-induced conversion (RT-QuIC) assays. No clinical signs of TSE
were detected in the remaining primary passage cats at 86 months pi.
Feline-adapted CWD (FelCWD) was sub-passaged into groups (n = 4 or 5) of cats by
IC, PO, and IP/SQ routes.
All 5 IC inoculated cats developed symptoms of disease 20–24 months pi
(approximately half the incubation period of primary passage). Additional
symptoms in these animals included increasing aggressiveness and hyper
responsiveness. FelCWD was demonstrated in the brains of all the affected cats
by western blot and IHC. Currently, 3 of 4 IP/SQ, and 1 of 4 PO inoculated cats
have developed abnormal behavior patterns consistent with the early stage of
feline CWD. Magnetic resonance imaging (MRI) has been performed on 11 cats (6
clinically ill, 2 asymptomatic, and 3 age-matched negative controls).
Abnormalities were detected in 4 of 6 clinically ill cats and included
multifocal signal changes consistent with inflammation, ventricular size
increases, more prominent sulci, and white matter tract cavitation.
These results demonstrate that CWD can be transmitted and adapted to the
domestic cat, and raise the potential for cervid-to-feline transmission in
nature.
PO-055: Transgenetic modeling of the CWD species barrier to humans
Eri Saijo,1 Sehun Kim,2 Claudio Soto,3 Glenn Telling2 1University of
Kentucky College of Medicine; Fort Collins, CO USA; 2Department of Microbiology,
Immunology and Pathology; Colorado State University; Fort Collins, CO USA ;
3Department of Neurology; University of Texas Houston Medical School; Houston,
TX USA
Our recent studies raise significant concerns about the zoonotic potential
of CWD. First, we showed that tissues consumed by humans derived from deer or
elk with CWD, including skeletal muscle and antler velvet, harbor infectious
prions. In other studies, cervid PrPSc converted human PrPC after CWD prions
were stabilized by successive passages in vitro or in vivo.
We also identified at least two distinct strains of CWD, referred to as
CWD1 and CWD2, the host-range properties of which are currently undefined. Other
studies showed that codon 129, and the corresponding 132 residue in elk,
significantly influenced the transmission of BSE and CWD prions respectively in
transgenic (Tg) mouse models.
We inoculated Tg mice expressing human PrP encoding either methionine (M)
or valine (V) at codon 129 with deer or elk CWD prions that previously produced
disease in Tg mice expressing deer PrP with characteristics typical of CWD1 and
CWD2 strains, as well as CWD prions that had been passaged multiple times in Tg
mice expressing deer PrP.
While most Tg mice remained free of signs of prion disease for >260
days, small numbers of inoculated mice developed multiple, progressive
neurological signs, that were consistent with prion disease. However,
examination of brain materials from diseased mice failed to confirm the presence
of protease-resistant human PrP. These preliminary results are consistent with a
significant species barrier in humans to these CWD strains, and indicate that
the 129 polymorphism does not modulate susceptibility.
PO-056: PrPCWD profiling of white-tailed deer (Odocoileus virginianus) with
different Prnp genotypes following experimental oral infection
Camilo Duque Velasquez,1 Allen Herbst,1 Chad Johnson,2 Judd Aiken,1 Debbie
McKenzie1 1Centre for Prions and Protein Folding Diseases; University of
Alberta; Edmonton, AB Canada; 2Department of Soil Science; University of
Wisconsin; Madison, WI USA
Chronic wasting disease (CWD) affects captive and free-ranging cervid
populations in North America and farmed cervids of South Korea. CWD and scrapie
are the only prion diseases in which the transmission occurs horizontally. The
cervid Prnp gene is polymorphic at various positions. The effect of these
changes on infection is influenced by the sequence and structure compatibility
between the host and the infectious source. Prion strains have been described
virtually in every prion disease and strongly impact disease characteristics
(clinical symptoms, neuropathological profiles, incubation periods, species
tropism as well as biochemical and biophysical properties of the abnormally
folded prion protein). Prion protein sequence differences can result, upon
subsequent infection, in the generation of novel strains as documented in sheep
scrapie. We have previously shown that Prnp polymorphisms influence
susceptibility to CWD in free-ranging white-tailed deer. In CWD-positive deer
populations, alleles Q95G96 (wt) were over-represented compared to the H95G96
and Q95S96 alleles. Experimental oral infection of white-tailed deer with known
Prnp genotypes (with inoculum from CWDpositive wt/wt deer) confirmed the link
between prion protein primary sequence and the progression of disease.
Heterozygous interference occurred in varying degrees as evidenced by the
difference in the extension of the incubation period as an effect of alleles
Q95S96 and H95G96. Interestingly, the biochemical profiles of the wt/Q95S96 and
wt/H95G96 isolates resemble the wt/wt, differing only in the amount of protease
resistant PrPCWD present suggesting that the wt allele is preferentially
converted. PrPCWD profiling revealed differences between deer with at least one
wt allele and the H95G96/Q95S96 deer suggesting that this PrPCWD is unique
compared to the PrPCWD from wt/wt animals.
PO-057: Host factors influence prion strain adaptation
Crystal Meyerett Reid, Mark Zabel Colorado State University; Fort Collins,
CO USA
Background. Chronic Wasting disease (CWD) is one of many prion-mediated
diseases known as transmissible spongiform encephalopathies (TSEs). There is
ever-increasing biological and biochemical evidence that prion pathogenesis is
caused by the conversion of the normal host protein (PrPC) into an abnormal
disease causing conformation (PrPRES). How prions encipher heritable strain
properties without nucleic acid remains unclear. Previously we have shown that
host factors have contributed to the adaptation of an original deer CWD prion
strain to transgenic mice.
Materials and Methods. We assessed strain differences using biological and
biochemical assays and found that amplified cervid prions and serial-passaged
cervid prions were significantly different than that of the original cervid
strain. It is possible that prion mutation and adaptation can broaden the host
range. Previous reports, however, indicate that there is a strict species
barrier preventing CWD infection in wildtype mice.
Results. Here we show the generation of a mouse-adapted strain of CWD upon
serial passage into transgenic cervidized mice and then subsequent passage into
wildtype mice. All wildtype mice remained non-clinical upon first passage but
became completely susceptible after second passage with similar incubation times
to those of mice terminally ill from a mouse adapted scrapie strain. Inoculation
of our mouse adapted CWD strain back into cervidized mice delayed progression to
terminal disease.
Conclusion. We conclude that prion strain adaptation and mutation is highly
dependent upon host factors and host encoded PrPC primary sequence. Upon serial
passage the adapted prion strain shares more characteristics with prion strains
from the new host rather than the original species.
OR-12: Chronic wasting disease transmission and pathogenesis in cervid and
non-cervid Species
Edward A. Hoover, Candace K. Mathiason, Nicholas J. Haley, Timothy D. Kurt,
Davis M. Seelig, Nathaniel D. Denkers, Amy V. Nalls, Mark D. Zabel, and Glenn C.
Telling
Prion Research Program, Department of Microbiology, Immunology, and
Pathology; Colorado State University; Fort Collins, CO USA
Since its recognition as a TSE in the late 1970s, chronic wasting disease
(CWD) of cervids has been distinguished by its facile spread and is now
recognized in 18 states, 2 Canadian provinces, and South Korea. The efficient
horizontal spread of CWD reflects a prion/host relationship that facilitates
efficient mucosal uptake, peripheral lymphoid amplification, and dissemination
by exploiting excretory tissues and their products, helping to establish
indirect/environmental and well as direct (e.g., salivary) transmission. Recent
studies from our group also support the likelihood of early life mother to
offspring and aerosol CWD prion transmission. Studies of cervid CWD exposure by
natural routes indicate that incubation period for detection of overt infection,
while still uncertain, may be much longer than originally thought.
Several non-cervid species can be infected by CWD experimentally (e.g.,
ferrets, voles, cats) with consequent species-specific disease phenotypes. The
species-adapted prions so generated can be transmitted by mucosal, i.e., more
natural, routes. Whether non-cervid species sympatric with deer/elk can be
infected in nature, however, remains unknown. In vitro CWD prion amplification
studies, in particular sPMCA, can foreshadow in vivo susceptibility and suggest
the importance of the PrPC rigid loop region in species barrier permissiveness.
Trans-species CWD amplification appears to broaden the host range/strain
characteristics of the resultant prions. The origins of CWD remain unknown,
however, the existence of multiple CWD prion strains/ quasi-species, the
mechanisms of prion shedding/dissemination, and the relationship between sheep
scrapie and CWD merit further investigation.
PO-060: Transmission of chronic wasting disease from mother to offspring
Candace Mathiason, Amy Nalls, Stephenie Fullaway, Kelly Anderson, Jeanette
Hayes-Klug, Nicholas Haley, Edward Hoover
Colorado State University; Fort Collins, CO USA
To investigate the role mother to offspring transmission plays in chronic
wasting disease (CWD) we have developed a cervid model employing the Reeve’s
muntjac deer (Muntiacus reevesi). Eight muntjac doe were orally inoculated with
CWD and tested PrPCWD lymphoid positive by 4 mo post infection. Twelve fawns
were born to these eight CWD-infected doe, 3 were born viable, 6 were born
non-viable, and 3 were harvested as fetuses (1 each from first, second or third
trimester of pregnancy) from CWDinfected doe euthanized at end-stage disease.
The viable fawns have been monitored for CWD infection by immunohistochemistry
(IHC) performed on serial tonsil and rectal lymphoid tissue biopsies. One fawn
that was IHC PrPCWD positive at 40 d of age is now, at 28 mo of age, showing
early clinical signs associated with CWD infection. Moreover, CWD prions have
been detected by sPMCA in placenta, brain, spleen and mesenteric lymphoid tissue
harvested from 5 full-term non-viable fawns, and in fetal placenta and brain
tissue harvested in utero from the second and third trimester fetuses.
Additional tissues and pregnancy related fluids from doe and offspring are being
analyzed for CWD prions. In summary, using the muntjac deer model we have
demonstrated CWD clinical disease in an offspring born to a CWD-infected doe,
and in utero transmission of CWD from mother to offspring. These studies provide
basis to further investigate the mechanisms of maternal transfer of prions.
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
Davis Seelig, Amy Nalls, Maryanne Flasik, Victoria Frank, Candace
Mathiason, Edward Hoover Colorado State University; Fort Collins, CO USA
Background and Introduction. Chronic wasting disease (CWD) is an
efficiently transmitted prion disease of cervids with an as yet to be fully
defined host range. Moreover, the risk that CWD poses to feline predators and
scavangers, through crossspecies consumption and subsequent transmission, is
unknown. Previous and ongoing studies in our laboratory evaluating the
susceptibility of domestic cats (Felis catus) to CWD (Mathiason et. al.,
NeuroPrion 2011, Nalls et. al., NeuroPrion 2012) have documented the
susceptibility of domestic cats to CWD following intracerebral (IC) inoculation.
However, many of the pathologic features of feline-adapted CWD, including the
neural and systemic patterns of PrPCWD accumulation and neuropathology, remain
unknown.
The chief objectives of this work were:
(1) to design a sensitive, enhanced immunohistochemical (E-IHC) protocol
for the detection of CWD prions (PrPCWD) in feline tissues;
(2) to document the systemic distribution of PrPCWD in CWD-infected cats
through E-IHC;
(3) to utilize single and multiple-label immunostaining and laser scanning
confocal microscopy (LSCM) to provide insights into the subcellular patterns of
PrPCWD accumulation and neuropathologic features of CWD-infected cats; and
(4) to compare feline CWD to the other known feline TSE Materials and
Methods. Periodate-lysine-paraformaldehyde (PLP)-fixed, paraffin-embedded
(PLP-PE) from terminal, IC-inoculated (n = 9) and sham-inoculated (n = 2), 1st
and 2nd passage, CWD-infected cats were examined by E-IHC for the presence of
PrPCWD and its association with markers of cell phenotype and organelles.
Results. The most sensitive E-IHC technique for the detection of PrPCWD in
feline tissues incorporated a combination of slide pretreatment with
proteinase-K (PK) in concert with tyramide signal amplification (TSA). With this
protocol, we identified PrPCWD deposits throughout the CNS, which, in the 1st
passage cats was primarily restricted to the obex, but increased in distribution
and severity upon 2nd passage to include a number of midbrain nuclei, cortical
gray matter, the thalamus and hypothalamus, and the hippocampus. Peripheral
PrPCWD deposits were detected only in the 2nd passage cats, and included the
enteric nervous system, the Peyer’s patches, and the retropharyngeal and
mesenteric lymph nodes. PrPCWD was not detected in the sham-inoculated cats.
Moreover, using multi-label analysis, intracellular PrPCWD aggregates were
seen in association with neurofilament heavy chain (NFH)-positive neurons and
GFAP-positive astrocytes. In addition, large aggregates of intracellular PrPCWD
were identified within LAMP1-positive lysosomes.
Conclusions. Feline PrPCWD is present in CNS neurons, astrocytes and
LAMP-1-positive lysosomes. The morphologic overlap between the PrPCWD deposits
in feline CWD and BSE-origin feline spongiform encephalopathy (FSE), implicates
the importance of the host as a key determinant in the development of prion
neuropathology and suggest a signature for detection of potential spontaneous
feline prion disease.
PO-099: Estimating the risk of CWD transmission to humans—An interim
report of a comprehensive study in non-human primates
Ann-Christin Schmaedicke DPZ; Goettingen, Germany
Chronic Wasting Disease (CWD) is a transmissible prion disease that occurs
primarily among North American cervid species. CWD has emerged as a prion
disease in captive as well as freeranging cervids with rising incidence.
Continuous consumption of cervid-derived products in conjunction with increasing
CWD prevalence suggests a risk for human exposure to CWD prions.
Although surveillance data collected in the North American population did
not provide epidemiological evidence for CWD transmissions to humans it remains
unclear whether a biological risk for such transmissions exists or can be
excluded. In order to gauge the potential transmissibility of CWD to humans, a
comprehensive CWD risk assessment in cynomolgus macaques has been initiated. To
test for the CWD interspecies transmission to humans, we used a primate species
previously shown to mimic the BSE susceptibility of humans. In addition, this
species is phylogenetically close to humans with a homologous amino acid
sequence of the prion protein. When we assessed the genotype of macaque PrP, the
homozygosity for methionine at codon 129 was confirmed in all animals.
The zoonotic potential of CWD is evaluated by challenging groups of animals
via different inoculation routes. General transmissibility of CWD to macaques is
tested by intracerebral (i.c.) inoculation of brain homogenate from CWD-infected
white-tailed deer (WTD) and elk. This was either done by direct injection of 10
mg CWDWTD to two animals (> 880 dpi) or by surgical implantation of CWD-WTD
or CWD-elk contaminated steel wires in two animals (> 750 dpi) or three
animals (> 400 dpi), respectively.
To address the risk of hunters while field dressing carcasses, we
inoculated two animals with CWD-WTD by dermal scarification (> 920 dpi). To
simulate human consumption of CWDinfected food products, we orally challenged
three animals with 10 g CWD-WTD brain (> 820 dpi) and three animals with 3 kg
CWD muscle tissue from different cervid species (> 950 dpi) by repeated
feeding. Mock-inoculated macaques are co-housed in the same cage allowing
exposure to saliva and faeces of CWDinoculated macaques.
To date, all inoculated animals remain asymptomatic. Cerebrospinal fluid
and blood from all animals were and are going to be collected bimonthly,
processed and stored in a repository. Analysis of these samples using
ultrasensitive prion detection methods has been initiated. Oral challenge of 50
mg BSE to cynomolgus macaques can lead to fatal disease only after more than 5 y
of incubation time (1952 dpi).
Thus, to estimate whether CWD could be transmitted to macaques or not, we
assume that observation of challenged animals would be necessary for at least
8–10 y.
PO-248: TSE infectivity survives burial for five years with little
reduction in titer
Allister Smith, Robert Somerville, Karen Fernie The Roslin Institute and
R(D)SVS; University of Edinburgh; Edinburgh, UK
BSE infected animals, BSE-contaminated materials and other sources of TSE
(prion) infection, such as carcasses from scrapie infected sheep, CWD infected
deer and cadavers of individuals infected with CJD may all end up in the
environment through burial or other methods of disposal. They may continue to
act as a reservoir of TSE infectivity if cattle or other susceptible animals
were to be exposed to these sources in the future. In order to address these
concerns, we performed two large scale demonstration experiments under field
conditions which were designed to mimic some of the ways by which TSE infected
materials may have been disposed of. The project examined the fate of TSE
infectivity over a period of five years in two scenarios; when the infectivity
was contained within bovine heads and when the infectivity was buried without
any containment. Two soil types were compared: a sandy loam and a clay loam. We
used the 301V TSE strain which was derived by serial passage of BSE in VM mice.
TSE infectivity was recovered from all the heads exhumed annually for five
years from both types of soil, with little reduction in the amount of
infectivity throughout the period of the experiment. Small amounts of
infectivity were found in the soil immediately surrounding the heads, but not in
samples remote from them. Similarly there was no evidence of significant lateral
movement of infectivity from the buried bolus. However large amounts of TSE
infectivity were recovered at the site of burial of both boluses. There was
limited vertical upward movement of infectivity from the bolus buried in clay
soil and downward movement from the bolus buried in sandy soil.
Now that these experiments are completed we conclude that TSE infectivity
is likely to survive burial for long periods of time with minimal loss of
infectivity and restricted movement from the site of burial. These experiments
emphasize that the environment is a viable reservoir for retaining large
quantities of TSE infectivity, and reinforce the importance of risk assessment
when disposing of this type of infectious material.
Chronic Wasting Disease Susceptibility of Four North American Rodents
Chad J. Johnson1*, Jay R. Schneider2, Christopher J. Johnson2, Natalie A.
Mickelsen2, Julia A. Langenberg3, Philip N. Bochsler4, Delwyn P. Keane4, Daniel
J. Barr4, and Dennis M. Heisey2 1University of Wisconsin School of Veterinary
Medicine, Department of Comparative Biosciences, 1656 Linden Drive, Madison WI
53706, USA 2US Geological Survey, National Wildlife Health Center, 6006
Schroeder Road, Madison WI 53711, USA 3Wisconsin Department of Natural
Resources, 101 South Webster Street, Madison WI 53703, USA 4Wisconsin Veterinary
Diagnostic Lab, 445 Easterday Lane, Madison WI 53706, USA *Corresponding author
email: cjohnson@svm.vetmed.wisc.edu
We intracerebrally challenged four species of native North American rodents
that inhabit locations undergoing cervid chronic wasting disease (CWD)
epidemics. The species were: deer mice (Peromyscus maniculatus), white-footed
mice (P. leucopus), meadow voles (Microtus pennsylvanicus), and red-backed voles
(Myodes gapperi). The inocula were prepared from the brains of hunter-harvested
white-tailed deer from Wisconsin that tested positive for CWD. Meadow voles
proved to be most susceptible, with a median incubation period of 272 days.
Immunoblotting and immunohistochemistry confirmed the presence of PrPd in the
brains of all challenged meadow voles. Subsequent passages in meadow voles lead
to a significant reduction in incubation period. The disease progression in
red-backed voles, which are very closely related to the European bank vole (M.
glareolus) which have been demonstrated to be sensitive to a number of TSEs, was
slower than in meadow voles with a median incubation period of 351 days. We
sequenced the meadow vole and red-backed vole Prnp genes and found three amino
acid (AA) differences outside of the signal and GPI anchor sequences. Of these
differences (T56-, G90S, S170N; read-backed vole:meadow vole), S170N is
particularly intriguing due its postulated involvement in "rigid loop" structure
and CWD susceptibility. Deer mice did not exhibit disease signs until nearly 1.5
years post-inoculation, but appear to be exhibiting a high degree of disease
penetrance. White-footed mice have an even longer incubation period but are also
showing high penetrance. Second passage experiments show significant shortening
of incubation periods. Meadow voles in particular appear to be interesting lab
models for CWD. These rodents scavenge carrion, and are an important food source
for many predator species. Furthermore, these rodents enter human and domestic
livestock food chains by accidental inclusion in grain and forage. Further
investigation of these species as potential hosts, bridge species, and
reservoirs of CWD is required.
please see ;
Title: Transmission of chronic wasting disease of mule deer to Suffolk
sheep following intracerebral inoculation
Authors
Hamir, Amirali Kunkle, Robert Cutlip, Randall - ARS RETIRED Miller, Janice
- ARS RETIRED Williams, Elizabeth - UNIV OF WYOMING, LARAMIE Richt, Juergen
Submitted to: Journal of Veterinary Diagnostic Investigation Publication
Type: Peer Reviewed Journal Publication Acceptance Date: June 20, 2006
Publication Date: November 1, 2006 Citation: Hamir, A.N., Kunkle, R.A., Cutlip,
R.C., Miller, J.M., Williams, E.S., Richt, J.A. 2006. Transmission of chronic
wasting disease of mule deer to Suffolk sheep following intracerebral
inoculation. Journal of Veterinary Diagnostic Investigation. 18(6):558-565.
Interpretive Summary: Chronic wasting disease (CWD) has been identified in
captive and free ranging deer and elk since 1967. To determine the
transmissibility of CWD to sheep and to provide information about the disease
and tests for detection of CWD in sheep, 8 lambs were inoculated with brain
suspension from mule deer naturally affected with CWD. Two other lambs were kept
as controls. Only 1 sheep developed clinical disease at 35 months after
inoculation. The study was terminated at 72 months after the inoculation. At
that time one other sheep was found to be positive for the disease. It is
proposed that the host's genetic makeup may play a role in transmission of the
disease to domestic sheep. Impact. This is the first study which shows that it
is possible to transmit CWD to a small number of sheep. Technical Abstract:
Chronic wasting disease (CWD) has been identified in captive and free-ranging
cervids since 1967. To determine the transmissibility of CWD to sheep and to
provide information about clinical course, lesions, and suitability of currently
used diagnostic procedures for detection of CWD in sheep, 8 Suffolk lambs (4 QQ
and 4 QR at codon 171 of prion protein (PRNP) gene) were inoculated
intracerebrally with brain suspension from mule deer naturally affected with CWD
(CWD**md). Two other lambs (1 QQ and 1 QR at codon 171 of PRNP gene) were kept
as non-inoculated controls. Within 36 months post inoculation (MPI), 2 animals
became recumbent and were euthanized. However, only 1 sheep (euthanized at 35
MPI) had shown clinical signs that were consistent with those of scrapie.
Microscopic lesions of spongiform encephalopathy (SE) were seen in this sheep
and its tissues were positive for the abnormal prion protein (PrPres) by
immunohistochemistry and Western blot. Retrospective examination of the PRNP
genotype of this animal revealed that it was heterozygous (AV) at codon 136. In
the next 24 months, 3 other sheep were euthanized because of conditions
unrelated to TSE. The remaining 3 sheep remained non-clinical at the termination
of the study (72 MPI) and were euthanized at that time. One of these 3 revealed
SE and its tissues were positive for PrPres. These findings demonstrate that it
is possible to transmit CWD**md agent to sheep via the intracerebral route.
However, the host genotype may play a significant part in successful
transmission and incubation period of this agent.
Chronic wasting disease: Fingerprinting the culprit in risk assessments
Volume 6, Issue 1 January/February/March 2012 Pages 17 - 22 http://dx.doi.org/10.4161/pri.6.1.17776
Keywords: Fourier transform-infrared (FT-IR) spectroscopy, chronic wasting
disease (CWD), prion, prion protein (PrP), prion typing, protein misfolding
cyclic amplification (PMCA), risk assessment, seeding activity, strains,
transmissible spongiform encephalopathies (TSE)
Authors: Martin L. Daus and Michael Beekes View affiliations Hide
affiliations Martin L. Daus
P24 -Transmissible Spongiform Encephalopathies;
Robert Koch-Institut; Berlin, Germany Michael Beekes Corresponding author:
BeekesM@rki.de P24 -Transmissible Spongiform Encephalopathies; Robert
Koch-Institut; Berlin, Germany
Abstract: Transmissible spongiform encephalopathies (prion diseases) in
animals may be associated with a zoonotic risk potential for humans as shown by
the occurrence of variant Creutzfeldt-Jakob disease in the wake of the bovine
spongiform encephalopathy epidemic. Thus, the increasing exposure of humans in
North America to cervid prions of chronic wasting disease (CWD) in elk and deer
has prompted comprehensive risk assessments. The susceptibility of humans to CWD
infections is currently under investigation in different studies using macaques
as primate models. The necessity for such studies was recently reinforced when
disease-associated prion protein and its seeding activity were detected in
muscles of clinically inconspicuous CWD-infected white-tailed deer (WTD).
Increasing evidence points to the existence of different CWD strains, and CWD
prions may also change or newly emerge over time. Therefore, CWD isolates
examined in macaques should be characterized as precisely as possible for their
molecular identity. On this basis other CWD field samples collected in the past,
present or future could be systematically compared with macaque-tested inocula
in order to assess whether they are covered by the ongoing risk assessments in
primates. CWD typing by Fourier transform-infrared spectroscopy of pathological
prion protein may provide a method of choice for this purpose.
snip...
Exposure of humans to CWD prions
Chronic wasting disease is a TSE in white-tailed deer, mule deer, Rocky
Mountain elk and moose. Over the past years this disease has shown a sustained
spread in captive as well as free-ranging cervids in North America.6,7 The
increasingly frequent and widespread 5 occurrence of affected animals is likely
to augment the exposure of humans to the CWD agent. Prion infectivity or
TSE-associated prion protein have been detected in the central and peripheral
nervous system, in a variety of lymphoid tissues as well as in heart muscle,
blood, saliva, feces and urine of CWD-infected cervids7. Also, infectious CWD
agent was found in antler velvet of elk and in skeletal muscles of mule deer
with chronic wasting disease.8,9 Thus, particularly persons processing cervid
carcasses, users of medicinal products made from antler velvet and consumers of
venison may be exposed to an elevated risk for contamination with CWD prions.
Recently, PrPTSE and its proteinaceous seeding activity could be directly
demonstrated, for the first time, in skeletal muscles of CWD-infected cervids.10
The animals examined in this study were farmed and free-ranging WTD for which no
clinical signs of CWD had been recognized. However, they had been officially
confirmed positive for CWD based on the detection of PrPTSE in brain tissue or
lymph nodes and were thus apparently in a state of pre or subclinical infection.
Muscles from such clinically inconspicuous carrier animals appear more likely to
enter the human food chain than meat from cervids that show symptoms of CWD.
Whether this may provide a relevant mode for the inadvertent foodborne
transmission of CWD prions is still unclear. Yet, the presence and seeding
activity of PrPTSE in skeletal muscles of pre- or subclinically infected WTD
reinforced the need to comprehensively assess whether humans are susceptible to
zoonotic CWD infections.
snip...
Transmissibility to humans
The current state of epidemiological research suggests a rather robust
barrier for the transmission of CWD to humans. Particularly, the surveillance of
human prion diseases in areas with a long history of endemic CWD such as
Colorado and Wyoming did not reveal evidence for zoonotic transmissions of the
disease to cervid hunters or consumers of meat from elk and deer.6,11 However,
as discussed by Belay et al.,6 the intensity of human exposure to CWD prions may
increase due to a further spread and rising prevalence of the disease in
cervids. Therefore, and with the generally long latency periods of human prion
diseases in mind, previous epidemiological findings cannot be readily
extrapolated. Until recently, experimental studies that pursued biochemical
approaches or used transgenic mice to ascertain the susceptibility of humans to
CWD infections consistently seemed to corroborate current epidemiological
findings: CWD-infected cervid brain tissue did not seed the conversion of PrPC
133 into PrPres in PMCA assays using brain homogenate from macaques or
transgenic mice expressing human PrPC as test substrate12 , and transgenic mice
overexpressing human PrPC were resistant to infection after intracerebral
challenge with CWD prions from mule deer.13 However, a study published by Barria
et al.14 in March 2011 found that cervid PrPTSE can seed the conversion of human
PrPC into PrPres by PMCA when the CWD agent has been previously passaged in
vitro or in vivo. Specifically, this was demonstrated for CWD prions from
naturally affected mule deer either passaged by serial PMCA using deer PrPC as
conversion substrate or in transgenic mice expressing cervid PrPC. The authors
of this study pointed out that CWD prions may undergo a gradual process of
change and adaptation via successive passages in the cervid population. They
concluded that the reported findings, if corroborated by infectivity assays, may
imply “that CWD prions have the potential to infect humans and that this ability
progressively increases with CWD spreading”.
snip...
Volume 18, Number 3—March 2012
Samuel E. Saunders1, Shannon L. Bartelt-Hunt, and Jason C. Bartz
Author affiliations: University of Nebraska-Lincoln, Omaha, Nebraska, USA
(S.E. Saunders, S.L. Bartelt-Hunt); Creighton University, Omaha (J.C. Bartz)
Synopsis
Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting
Disease
snip...
Most epidemiologic studies and experimental work have suggested that the
potential for CWD transmission to humans is low, and such transmission has not
been documented through ongoing surveillance (2,3). In vitro prion replication
assays report a relatively low efficiency of CWD PrPSc-directed conversion of
human PrPc to PrPSc (30), and transgenic mice overexpressing human PrPc are
resistant to CWD infection (31); these findings indicate low zoonotic potential.
However, squirrel monkeys are susceptible to CWD by intracerebral and oral
inoculation (32). Cynomolgus macaques, which are evolutionarily closer to humans
than squirrel monkeys, are resistant to CWD infection (32). Regardless, the
finding that a primate is orally susceptible to CWD is of concern.
snip...
Intraspecies and interspecies passage of the CWD agent may also increase
the risk for zoonotic CWD transmission. The CWD prion agent is undergoing serial
passage naturally as the disease continues to emerge. In vitro and in vivo
intraspecies transmission of the CWD agent yields PrPSc with an increased
capacity to convert human PrPc to PrPSc (30). Interspecies prion transmission
can alter CWD host range (38) and yield multiple novel prion strains (3,28). The
potential for interspecies CWD transmission (by cohabitating mammals) will only
increase as the disease spreads and CWD prions continue to be shed into the
environment. This environmental passage itself may alter CWD prions or exert
selective pressures on CWD strain mixtures by interactions with soil, which are
known to vary with prion strain (25), or exposure to environmental or gut
degradation.
Given that prion disease in humans can be difficult to diagnose and the
asymptomatic incubation period can last decades, continued research,
epidemiologic surveillance, and caution in handling risky material remain
prudent as CWD continues to spread and the opportunity for interspecies
transmission increases. Otherwise, similar to what occurred in the United
Kingdom after detection of variant CJD and its subsequent link to BSE, years of
prevention could be lost if zoonotic transmission of CWD is subsequently
identified,...
snip...
2012 CDC REPORT ON CWD
Volume 18, Number 3—March 2012 Synopsis Occurrence, Transmission, and
Zoonotic Potential of Chronic Wasting Disease
snip...
Prevalence and Surveillance
Originally recognized only in southeastern Wyoming and northeastern
Colorado, USA, CWD was reported in Canada in 1996 and Wisconsin in 2001 and
continues to be identified in new geographic locations (Figure 1, panel A). CWD
has been identified in free-ranging cervids in 15 US states and 2 Canadian
provinces and in ≈100 captive herds in 15 states and provinces and in South
Korea (Figure 1, panel B).
snip...
CWD surveillance programs are now in place in almost all US states and
Canadian provinces (Figure 2, panel A). More than 1,060,000 free-ranging cervids
have reportedly been tested for CWD (Figure 2, panel B) and ≈6,000 cases have
been identified (Figure 2, panel C) according to data from state and provincial
wildlife agencies.
snip...
Testing of captive cervids is routine in most states and provinces, but
varies considerably in scope from mandatory testing of all dead animals to
voluntary herd certification programs or mandatory testing of only animals
suspected of dying of CWD.
snip...
Long-term effects of CWD on cervid populations and ecosystems remain
unclear as the disease continues to spread and prevalence increases. In captive
herds, CWD might persist at high levels and lead to complete herd destruction in
the absence of human culling. Epidemiologic modeling suggests the disease could
have severe effects on free-ranging deer populations, depending on hunting
policies and environmental persistence (8,9). CWD has been associated with large
decreases in free-ranging mule deer populations in an area of high CWD
prevalence (Boulder, Colorado, USA) (5). In addition, CWD-infected deer are
selectively preyed upon by mountain lions (5), and may also be more vulnerable
to vehicle collisions (10). Long-term effects of the disease may vary
considerably geographically, not only because of local hunting policies,
predator populations, and human density (e.g., vehicular collisions) but also
because of local environmental factors such as soil type (11) and local cervid
population factors, such as genetics and movement patterns (S.E. Saunders,
unpub. data).
snip...
Controlling the spread of CWD, especially by human action, is a more
attainable goal than eradication. Human movement of cervids has likely led to
spread of CWD in facilities for captive animals, which has most likely
contributed to establishment of new disease foci in free-ranging populations
(Figure 1, panel A). Thus, restrictions on human movement of cervids from
disease-endemic areas or herds continue to be warranted. Anthropogenic factors
that increase cervid congregation such as baiting and feeding should also be
restricted to reduce CWD transmission. Appropriate disposal of carcasses of
animals with suspected CWD is necessary to limit environmental contamination
(20), and attractive onsite disposal options such as composting and burial
require further investigation to determine contamination risks. The best options
for lowering the risk for recurrence in facilities for captive animals with
outbreaks are complete depopulation, stringent exclusion of free-ranging
cervids, and disinfection of all exposed surfaces. However, even the most
extensive decontamination measures may not be sufficient to eliminate the risk
for disease recurrence (20; S.E. Saunders et al. unpub. data)
full text ;
SEE CWD MAP MINUS TEXAS ;
SEE TEXAS CWD UPDATE AT BOTTOM OF THIS SUBMISSION...TSS
Envt.06:
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human
Primates
Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Aru Balachandran,2
Jürgen Richt,3 Vincent Beringue,4 Juan-Maria Torres,5 Paul Brown,1 Bob Hills6
and Jean-Philippe Deslys1
1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Canadian Food
Inspection Agency; Ottawa, ON Canada; 3Kansas State University; Manhattan, KS
USA; 4INRA; Jouy-en-Josas, France; 5INIA; Madrid, Spain; 6Health Canada; Ottawa,
ON Canada
†Presenting author; Email: emmanuel.comoy@cea.fr
The constant increase of chronic wasting disease (CWD) incidence in North
America raises a question about their zoonotic potential. A recent publication
showed their transmissibility to new-world monkeys, but no transmission to
old-world monkeys, which are phylogenetically closer to humans, has so far been
reported. Moreover, several studies have failed to transmit CWD to transgenic
mice overexpressing human PrP. Bovine spongiform encephalopathy (BSE) is the
only animal prion disease for which a zoonotic potential has been proven. We
described the transmission of the atypical BSE-L strain of BSE to cynomolgus
monkeys, suggesting a weak cattle-to-primate species barrier. We observed the
same phenomenon with a cattleadapted strain of TME (Transmissible Mink
Encephalopathy). Since cattle experimentally exposed to CWD strains have also
developed spongiform encephalopathies, we inoculated brain tissue from
CWD-infected cattle to three cynomolgus macaques as well as to transgenic mice
overexpressing bovine or human PrP. Since CWD prion strains are highly
lymphotropic, suggesting an adaptation of these agents after peripheral
exposure, a parallel set of four monkeys was inoculated with CWD-infected cervid
brains using the oral route. Nearly four years post-exposure, monkeys exposed to
CWD-related prion strains remain asymptomatic. In contrast, bovinized and
humanized transgenic mice showed signs of infection, suggesting that CWD-related
prion strains may be capable of crossing the cattle-to-primate species barrier.
Comparisons with transmission results and incubation periods obtained after
exposure to other cattle prion strains (c-BSE, BSE-L, BSE-H and cattle-adapted
TME) will also be presented, in order to evaluate the respective risks of each
strain.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2
Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch
Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and
Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany
†Presenting author; Email: dausm@rki.de
Chronic wasting disease (CWD) is a contagious, rapidly spreading
transmissible spongiform encephalopathy (TSE) occurring in cervids in North
America. Despite efficient horizontal transmission of CWD among cervids natural
transmission of the disease to other species has not yet been observed. Here, we
report a direct biochemical demonstration of pathological prion protein PrPTSE
and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected
cervids. The presence of PrPTSE was detected by Western- and postfixed frozen
tissue blotting, while the seeding activity of PrPTSE was revealed by protein
misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal
muscles of CWD-infected WTD was estimated to be approximately 2000- to
10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE
was located in muscle- associated nerve fascicles but not, in detectable
amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal
muscle from CWD-infected cervids suggests prevention of such tissue in the human
diet as a precautionary measure for food safety, pending on further
clarification of whether CWD may be transmissible to humans.
now, let’s see what the authors said about this casual link, personal
communications years ago. see where it is stated NO STRONG evidence. so, does
this mean there IS casual evidence ????
“Our conclusion stating that we found no strong evidence of CWD
transmission to humans”
From: TSS (216-119-163-189.ipset45.wt.net)
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To:
Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam,
In the Archives of Neurology you quoted (the abstract of which was attached
to your email), we did not say CWD in humans will present like variant CJD.
That assumption would be wrong. I encourage you to read the whole article
and call me if you have questions or need more clarification (phone:
404-639-3091). Also, we do not claim that "no-one has ever been infected with
prion disease from eating venison." Our conclusion stating that we found no
strong evidence of CWD transmission to humans in the article you quoted or in
any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message-----
From:
Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease
2008 1: Vet Res. 2008 Apr 3;39(4):41
A prion disease of cervids: Chronic wasting disease
Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported
to the Surveillance Center***,
snip...
full text ;
CWD ongoing experiment on humans, long term $$$
Monday, November 14, 2011
WYOMING Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011
Wednesday, November 16, 2011
Wisconsin Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011
Sunday, November 13, 2011
COLORADO CWD CJD TSE PRION REPORTING 2011
PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER
AND ELK ;
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease
Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages
858-863, June 2011.
NOR IS THE FDA recalling this CWD positive elk meat for the well being of
the dead elk ;
Wednesday, March 18, 2009
Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat
derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS
AND FIELD CORRECTIONS: FOODS CLASS II
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
please see ;
Wednesday, May 30, 2012
PO-248: TSE infectivity survives burial for five years with little
reduction in titer
Friday, February 08, 2013
*** Behavior of Prions in the Environment: Implications for Prion Biology
Friday, November 09, 2012
*** Chronic Wasting Disease CWD in cervidae and transmission to other
species
Sunday, November 11, 2012
*** Susceptibilities of Nonhuman Primates to Chronic Wasting Disease
November 2012
Friday, December 14, 2012
Susceptibility Chronic Wasting Disease (CWD) in wild cervids to Humans 2005
- December 14, 2012
LANCET INFECTIOUS DISEASE JOURNAL
Volume 3, Number 8 01 August 2003
Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem. 49-year-old Singeltary is
one of a number of people who have remained largely unsatisfied after being told
that a close relative died from a rapidly progressive dementia compatible with
spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of
documents on transmissible spongiform encephalopathies (TSE) and realised that
if Britons could get variant CJD from bovine spongiform encephalopathy (BSE),
Americans might get a similar disorder from chronic wasting disease (CWD)the
relative of mad cow disease seen among deer and elk in the USA. Although his
feverish search did not lead him to the smoking gun linking CWD to a similar
disease in North American people, it did uncover a largely disappointing
situation. Singeltary was greatly demoralised at the few attempts to monitor the
occurrence of CJD and CWD in the USA. Only a few states have made CJD
reportable. Human and animal TSEs should be reportable nationwide and
internationally, he complained in a letter to the Journal of the American
Medical Association (JAMA 2003; 285: 733). I hope that the CDC does not continue
to expect us to still believe that the 85% plus of all CJD cases which are
sporadic are all spontaneous, without route or source. Until recently, CWD was
thought to be confined to the wild in a small region in Colorado. But since
early 2002, it has been reported in other areas, including Wisconsin, South
Dakota, and the Canadian province of Saskatchewan. Indeed, the occurrence of CWD
in states that were not endemic previously increased concern about a widespread
outbreak and possible transmission to people and cattle. To date, experimental
studies have proven that the CWD agent can be transmitted to cattle by
intracerebral inoculation and that it can cross the mucous membranes of the
digestive tract to initiate infection in lymphoid tissue before invasion of the
central nervous system. Yet the plausibility of CWD spreading to people has
remained elusive. Getting data on TSEs in the USA from the government is like
pulling teeth, Singeltary argues. You get it when they want you to have it, and
only what they want you to have.
SNIP...FULL TEXT ;
-----Original Message-----
From: SANCO-INFO@ec.europa.eu
Sent: Wednesday, March 06, 2013 8:19 AM
Subject: RE: USA BSE GBR ASSESSMENT FRAUD
Dear Mr. Singeltary
Thank you for your message and comments. Please be informed that I have
forwarded your suggestions to the responsible unit.
With kind regards Joanna Kniaz-Hawrot
--------------------------
Unit 04 - Communication Health & Consumers Directorate-General European
Commission
-----Original Message-----
From: sanco-mailbox@ec.europa.eu [mailto:sanco-mailbox@ec.europa.eu]
Sent: Friday, February 22, 2013 5:55 PM
To: SANCO INFO
Subject: USA BSE GBR ASSESSMENT FRAUD
Title: Mr.
First name : Terry Last name : Singeltary
E-mail : flounder9@verizon.net
Country of residence: USA Category :
Citizen Address: p.o. box 42
Postcode : 77518
City : Bacliff Country: Texas
Theme : Animal Health Subject : USA BSE GBR ASSESSMENT FRAUD Question (max
2000chars) :
I urge you to NOT to list the USA as BSE GBR II, and to immediately list
the USA BSE GBR risk assessment to BSE GBR IV, for the following reasons, but
for one, the USA has more documented TSE prion disease in wild animals and
livestock animals than any other country in the world, excluding zoo animals,
cats, and dogs, because the USA is NOT looking, all of which at one time have
been fed back to food producing livestock animals, and to humans. ...the clock
is ticking.
thank you,
with kindest regards, terry
please see why, and full text source refererence here ;
Wednesday, February 20, 2013
World Organization for Animal Health Recommends United States' BSE Risk
Status Be Upgraded
Statement from Agriculture Secretary Tom Vilsack:
Thursday, February 14, 2013
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and
TSE prion disease
Thursday, February 21, 2013
National Prion Disease Pathology Surveillance Center Cases Examined January
16, 2013
Reply language : English
LAYPERSON
kind regards,
terry
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
posted by Terry S. Singeltary Sr. at
11:56 AM
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