Susceptibilities of Nonhuman Primates to Chronic Wasting Disease
November 2012
Research
Susceptibilities of Nonhuman Primates to Chronic Wasting Disease
Brent Race1 , Kimberly D. Meade-White1, Michael W. Miller, Kent D. Barbian,
Richard Rubenstein, Giuseppe LaFauci, Larisa Cervenakova, Cynthia Favara, Donald
Gardner, Dan Long, Michael Parnell, James Striebel, Suzette A. Priola, Anne
Ward, Elizabeth S. Williams2, Richard Race3, and Bruce Chesebro3
Author affiliations: Rocky Mountain Laboratories, Hamilton, Montana, USA
(B. Race, K.D. Meade-White, K.D. Barbian, C. Favara, D. Gardner, D. Long, M.
Parnell, J. Striebel, S.A. Priola, A. Ward, R. Race, B. Chesebro); Colorado
Division of Wildlife, Fort Collins, Colorado, USA (M.W. Miller); State
University of New York Downstate Medical Center, Brooklyn, New York, USA (R.
Rubenstein); New York State Institute for Basic Research in Developmental
Disabilities, Staten Island, New York, USA (G. LaFauci); American Red Cross,
Rockville, Maryland, USA (L. Cervenakova); University of Wyoming, Laramie,
Wyoming, USA (E.S. Williams)
Abstract
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy,
or prion disease, that affects deer, elk, and moose. Human susceptibility to CWD
remains unproven despite likely exposure to CWD-infected cervids. We used 2
nonhuman primate species, cynomolgus macaques and squirrel monkeys, as human
models for CWD susceptibility. CWD was inoculated into these 2 species by
intracerebral and oral routes. After intracerebral inoculation of squirrel
monkeys, 7 of 8 CWD isolates induced a clinical wasting syndrome within 33–53
months. The monkeys’ brains showed spongiform encephalopathy and
protease-resistant prion protein (PrPres) diagnostic of prion disease. After
oral exposure, 2 squirrel monkeys had PrPres in brain, spleen, and lymph nodes
at 69 months postinfection. In contrast, cynomolgus macaques have not shown
evidence of clinical disease as of 70 months postinfection. Thus, these 2
species differed in susceptibility to CWD. Because humans are evolutionarily
closer to macaques than to squirrel monkeys, they may also be resistant to CWD.
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are
neurodegenerative diseases that affect many mammalian species. Some examples
include bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and
goats, Creutzfeldt-Jakob disease (CJD) in humans, and chronic wasting disease
(CWD) in cervids. CWD was first found in captive deer in Colorado in 1967 (1)
and was later identified in several US states and Canadian provinces (2).
Epidemiologic evidence suggests that CWD continues to spread among cervid
populations in North America (3), creating concern that CWD may cross species
barriers to infect humans or domestic animals that may be eaten by humans. Thus,
the host range of CWD and the level of protection provided by species barriers
should be determined.
Substantial progress has been made in testing species barriers for CWD by
using transgenic mice expressing species-specific prion protein (PrP), by direct
infection into new species, or by in vitro conversion assays. The most sensitive
method for testing susceptibility to TSE agents is intracerebral injection.
Unfortunately, this route does not mimic most natural situations and only
enables assessment of whether the possibility of transmission exists. Hamir et
al. infected cattle and sheep with CWD by the intracerebral route and found
protease-resistant PrP (PrPres) in 5 of 13 cattle and 2 of 8 sheep, which
indicated that these ruminant species can propagate CWD (4,5). However, oral
exposure in these hosts apparently does not cause disease (2).
CWD cross-species transmission to nonagricultural and laboratory animals
has shown variable levels of susceptibility depending on the route of
transmission. For example, ferrets were 100% susceptible to CWD by intracerebral
infection but were not susceptible to oral infection (6,7). Mink were only 25%
susceptible to CWD by intracerebral infection and were not susceptible to oral
infection (8). CWD has been successfully transmitted and adapted to laboratory
rodents, including hamsters, transgenic mice expressing hamster PrP, and
transgenic mice overexpressing mouse PrP (9,10). In contrast, transgenic mice
expressing human PrP were not susceptible to CWD by intracerebral infection
(11,12), a finding that provided evidence for a human species barrier against
CWD infection. However, work started in 1980 and published in 2005 by Marsh et
al. showed that 2 squirrel monkeys (Saimiri sciureus) infected by the
intracerebral route with brain homogenate from a single CWD-affected mule deer
became clinically sick at 31 and 34 months postinfection, and both were positive
for PrPres (13). This evidence that at least 1 species of nonhuman primate was
susceptible to CWD weakened the conclusion that humans may be protected from CWD
by a species barrier.
We addressed 4 questions raised by the original observation that squirrel
monkeys are susceptible to CWD (13). First, we compared intracerebral and oral
routes of infection. This comparison was of interest because the oral route is
likely to be an important natural route of disease transmission, and
susceptibility is known to be lower by this route in most models. Second, we
compared 2 species of nonhuman primates, cynomolgus macaques (Macaca
fascicularis) and squirrel monkeys, each of which has previously shown
susceptibility to various human prion diseases (14–16). However, humans are
believed to be evolutionarily closer to cynomolgus macaques than to squirrel
monkeys (17), and cynomolgus macaques may be a more accurate model for a human
species barrier. Third, because only 1 CWD source was tested by Marsh et al.
(13), we studied 8 different pools of CWD representing wild and captive cervids,
including mule deer, white-tailed deer, and elk, from separate regions in the
United States. Fourth, we tested the species tropism of CWD agent passaged in
squirrel monkeys.
snip...
Discussion
As new CWD foci continue to emerge among cervid populations, the risk for
CWD transmission to humans needs to be assessed. We used 2 monkey species and 2
routes of inoculation to test the susceptibility of primates to 8 different
pools of CWD. To date, we have verified CWD in 11 of 13 intracerebrally
inoculated squirrel monkeys; average incubation period was 41 months (range
33–53 months). Using a single CWD pool, Marsh et al. noted infection in 2 of 2
squirrel monkeys 31–34 months after intracerebral inoculation (13).
Intracerebral inoculation of squirrel monkeys with other TSE agents, including
agents of kuru, variant CJD, sporadic CJD, and sheep scrapie, had incubation
periods of ≈24 months and attack rates of ≈100% (14,15,32). The extended
incubation periods and lower attack rates for our squirrel monkeys may result
from a partial species barrier to CWD.
The signs of wasting syndrome in CWD-infected monkeys were similar to those
of CWD infection in cervids, in which loss of body condition is nearly always a
major component of infection and neurologic deficits vary (2). The correlation
of clinical signs between CWD in cervids and squirrel monkeys suggests that CWD
might affect a common brain region in each species. We observed PrPres
deposition in squirrel monkeys primarily in the frontal lobe of the cerebral
cortex, claustrum, putamen, and thalamus. Cervids typically have the most
abundant and predictable PrPres in the dorsal motor vagus nucleus (obex),
olfactory cortex, and diencephalon (including thalamus, hypothalamus,
metathalamus, and epithalamus) (2,33). A plausible hypothesis could be that
disruption of regions within the hypothalamus and thalamus leads to a metabolic
imbalance, resulting in a severe wasting syndrome.
We did not observe a strong correlation between infectivity titer
inoculated and attack incidence or incubation period (Table 1). One potential
explanation is that the variation in speed of disease progression might not be
relevant given the low number of animals in each group. A second possibility is
that our squirrel monkeys varied at PrP alleles that may affect CWD
susceptibility. However, analysis of 23 squirrel monkeys showed no PrP sequence
differences correlating with susceptibility to CWD (Tables 1, 2, 4). A third
possibility is that genes other than the gene for PrP might influence CWD
susceptibility.
For humans, eating infected or contaminated tissue is a likely route of CWD
exposure. In other animal models, oral transmission of TSE is generally
1,000-fold less effective than direct intracerebral challenge and results in
longer incubation periods and lower efficiency of disease transmission. In our
oral transmission experiments, we found evidence of CWD infection in 3 monkeys;
2 at 69 mpi had abundant PrPres in brain and lower levels in spleen and lymph
nodes, and 1 euthanized at 39 mpi had PrPres in lymphatic tissues only. Thus,
transmission seems to be slower by the oral route than by the intracerebral
route, and other orally infected monkeys may be affected in the future.
Cynomolgus macaques are evolutionarily closer to humans than are squirrel
monkeys (17). At nearly 6 years postinoculation, no macaques have shown clinical
signs of CWD. Intracerebral inoculation of cynomolgus macaques with BSE causes
disease in 3 years; human variant CJD requires 2–3 years, and human sporadic CJD
requires 5 years (16,34). However, oral inoculation of cynomolgus macaques with
BSE agent required a minimum of 5 years before clinical disease was observed
(35). Therefore, we cannot rule out CWD transmission to cynomolgus macaques.
snip...
The PrP gene sequence can influence cross-species transmission of prion
disease. Therefore, we compared squirrel monkey and cynomolgus macaque PrP gene
sequences to look for differences that might account for different
susceptibilities of these monkeys to CWD. In the PrP gene excluding the signal
peptide, deer differed from squirrel monkeys at 17 residues and from cynomolgus
macaques at 16 residues, but 14 of these differing residues were identical in
squirrel monkeys and macaques (Figure 4). Therefore, there are only 2 residues
in cynomolgus macaques (100 and 108) and 3 residues in squirrel monkeys (56, 159
and 182) at which these monkeys differ from deer and also from each other. These
residues might play a role in susceptibility differences seen in our
study.
Human exposure to CWD-infected cervids in past decades is likely. The
highest levels of prion infectivity are present in the central nervous system
and lymphatic tissues of CWD-infected cervids; contamination of knives, saws,
and muscles with these tissues can easy occur when processing game. Despite the
likelihood of exposures, epidemiologic studies of humans living in CWD-endemic
areas of Colorado and Wyoming during 1979–2001 have not shown any increases in
human TSE cases (36,37). Ongoing studies by the Colorado Department of Public
Health and Environmental Human Prion Disease Surveillance Program, in
conjunction with the University of Colorado School of Medicine, have also
concluded that no convincing cases of CWD transmission to humans have been
detected in Colorado (38). However, if CWD in humans appears like a wasting
syndrome similar to that observed in the squirrel monkeys in our study, affected
persons might receive a diagnosis of a metabolic disorder and never be tested
for TSE. Fortunately, additional laboratory data are consistent with the
epidemiologic data, and these results support the conclusion that a species
barrier protects humans from CWD infection (11–13,20,36,37).
> Because humans are evolutionarily closer to macaques than to squirrel
monkeys, they may also be resistant to CWD.
> This evidence that at least 1 species of nonhuman primate was
susceptible to CWD weakened the conclusion that humans may be protected from CWD
by a species barrier.
> Therefore, we cannot rule out CWD transmission to cynomolgus macaques.
> However, if CWD in humans appears like a wasting syndrome similar to
that observed in the squirrel monkeys in our study, affected persons might
receive a diagnosis of a metabolic disorder and never be tested for TSE.
> Fortunately, additional laboratory data are consistent with the
epidemiologic data, and these results support the conclusion that a species
barrier protects humans from CWD infection
I can only quote what an old TSE prion scientist stated about this study
last night ;
=================================
this is a gross misrepresentation of the species barrier. evolutionary
distance is a very dangerous, unreliable proxy for transmission, as seen by the
situation in rodents.
i really oppose this stance of encouraging people to eat cwd deer and elk
and scrapie sheep. exact opposite of precautionary principle. very dangerous
experiment.
==================================
I could not agree more. ...TSS
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)
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
HOUND STUDY
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to
other species will invariably present pathology typical of a scrapie-like
disease.
snip...
OR-09: Canine spongiform encephalopathy—A new form of animal prion disease
Monique David, Mourad Tayebi UT Health; Houston, TX USA
It was also hypothesized that BSE might have originated from an
unrecognized sporadic or genetic case of bovine prion disease incorporated into
cattle feed or even cattle feed contaminated with prion-infected human remains.1
However, strong support for a genetic origin of BSE has recently been
demonstrated in an H-type BSE case exhibiting the novel mutation E211K.2
Furthermore, a specific prion protein strain causing BSE in cattle is believed
to be the etiological agent responsible for the novel human prion disease,
variant Creutzfeldt-Jakob disease (vCJD).3 Cases of vCJD have been identified in
a number countries, including France, Italy, Ireland, the Netherlands, Canada,
Japan, US and the UK with the largest number of cases. Naturally occurring
feline spongiform encephalopathy of domestic cats4 and spongiform
encephalopathies of a number of zoo animals so-called exotic ungulate
encephalopathies5,6 are also recognized as animal prion diseases, and are
thought to have resulted from the same BSE-contaminated food given to cattle and
humans, although and at least in some of these cases, a sporadic and/or genetic
etiology cannot be ruled out. The canine species seems to display resistance to
prion disease and no single case has so far been reported.7,8
Here, we describe a case of a 9 week old male Rottweiler puppy presenting
neurological deficits; and histological examination revealed spongiform
vacuolation characteristic of those associated with prion diseases.9 Initial
biochemical studies using anti-PrP antibodies revealed the presence of partially
proteinase K-resistant fragment by western blotting. Furthermore,
immunohistochemistry revealed spongiform degeneration consistent with those
found in prion disease and displayed staining for PrPSc in the cortex.
Of major importance, PrPSc isolated from the Rottweiler was able to cross
the species barrier transmitted to hamster in vitro with PMCA and in vivo (one
hamster out of 5). Futhermore, second in vivo passage to hamsters, led to 100%
attack rate (n = 4) and animals displayed untypical lesional profile and shorter
incubation period.
In this study, we show that the canine species might be sensitive to prion
disease and that PrPSc isolated from a dog can be transmitted to dogs and
hamsters in vitro using PMCA and in vivo to hamsters.
If our preliminary results are confirmed, the proposal will have a major
impact on animal and public health and would certainly lead to implementing new
control measures for ‘canine spongiform encephalopathy’ (CSE).
References
1. Colchester AC, Colchester NT. The origin of bovine spongiform
encephalopathy: the human prion disease hypothesis. Lancet 2005; 366:856-61;
PMID:16139661; http://
dx.doi.org/10.1016/S0140-6736(05)67218-2.
2. Richt JA, Hall SM. BSE case associated with prion protein gene mutation.
PLoS Pathog 2008; 4:e1000156; PMID:18787697; http://dx.doi.org/10.1371/journal.
ppat.1000156.
3. Collinge J. Human prion diseases and bovine spongiform encephalopathy
(BSE). Hum Mol Genet 1997; 6:1699-705; PMID:9300662; http://dx.doi.org/10.1093/ hmg/6.10.1699.
4. Wyatt JM, Pearson GR, Smerdon TN, Gruffydd-Jones TJ, Wells GA, Wilesmith
JW. Naturally occurring scrapie-like spongiform encephalopathy in five domestic
cats. Vet Rec 1991; 129:233-6; PMID:1957458; http://dx.doi.org/10.1136/vr.129.11.233.
5. Jeffrey M, Wells GA. Spongiform encephalopathy in a nyala (Tragelaphus
angasi). Vet Pathol 1988; 25:398-9; PMID:3232315; http://dx.doi.org/10.1177/030098588802500514.
6. Kirkwood JK, Wells GA, Wilesmith JW, Cunningham AA, Jackson SI.
Spongiform encephalopathy in an arabian oryx (Oryx leucoryx) and a greater kudu
(Tragelaphus strepsiceros). Vet Rec 1990; 127:418-20; PMID:2264242.
7. Bartz JC, McKenzie DI, Bessen RA, Marsh RF, Aiken JM. Transmissible mink
encephalopathy species barrier effect between ferret and mink: PrP gene and
protein analysis. J Gen Virol 1994; 75:2947-53; PMID:7964604; http://dx.doi.org/10.1099/0022-1317-
75-11-2947.
8. Lysek DA, Schorn C, Nivon LG, Esteve-Moya V, Christen B, Calzolai L, et
al. Prion protein NMR structures of cats, dogs, pigs, and sheep. Proc Natl Acad
Sci U S A 2005; 102:640-5; PMID:15647367; http://dx.doi.org/10.1073/pnas.0408937102.
9. Budka H. Neuropathology of prion diseases. Br Med Bull 2003; 66:121-30;
PMID:14522854; http://dx.doi.org/10.1093/bmb/66.1.121.
Monday, March 8, 2010
Canine Spongiform Encephalopathy aka MAD DOG DISEASE
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.
why do we not want to do TSE transmission studies on chimpanzees $
snip...
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
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.
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...
full text ;
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.
Sunday, January 22, 2012
Chronic Wasting Disease CWD cervids interspecies transmission
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 ????
CONCLUSIONS: Although the occurrence of 3 unusually young patients with CJD
who consumed venison suggested a possible relationship with CWD, our follow-up
investigation found no strong evidence for a causal link. Ongoing CJD
surveillance remains important for continuing to assess the risk, if any, of CWD
transmission to humans.
“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
Observation| March 2007
Colorado Surveillance Program for Chronic Wasting Disease Transmission to
HumansLessons From 2 Highly Suspicious but Negative CasesFREE
C. Alan Anderson, MD; Patrick Bosque, MD; Christopher M. Filley, MD; David
B. Arciniegas, MD; B. K. Kleinschmidt-DeMasters, MD; W. John Pape, BS; Kenneth
L. Tyler, MD
[+] Author Affiliations
Arch Neurol. 2007;64(3):439-441. doi:10.1001/archneur.64.3.439.
Objective To describe 2 patients with rapidly progressive dementia and risk
factors for exposure to chronic wasting disease (CWD) in whom extensive testing
negated the possible transmission of CWD.
Design/Methods We describe the evaluation of 2 young adults with initial
exposure histories and clinical presentations that suggested the possibility of
CWD transmission to humans.
Patients A 52-year-old woman with possible laboratory exposure to CWD and a
25-year-old man who had consumed meat from a CWD endemic area.
Interventions Clinical evaluation, neuropathological examination, and
genetic testing.
Results Neuropathological and genetic assessment in the 2 patients proved
the diagnoses of early-onset Alzheimer disease and a rare genetic prion
disease.
Conclusion No convincing cases of CWD transmission to humans have been
detected in our surveillance program.
snip...
CASE 1 .
A 52-year-old right-handed woman presented with a 1-year history of
progressive memory loss, language impairment, visuospatial disturbance, and
myoclonus. She related that she had been a histology technician in a laboratory
that processed tissue specimens from deer and elk with CWD and had handled
specimens without wearing gloves. Both she and her family expressed significant
concerns about the possibility of transdermal transmission of CWD. Her family
history was negative for dementia and other neurologic disorders. Brain magnetic
resonance imaging showed mild diffuse volume loss, and electroencephalography
demonstrated mild diffuse slowing. Other laboratory studies were unremarkable.
Cerebrospinal fluid findings were unremarkable except for a weakly
immunostaining 14-3-3 protein band, an indeterminate finding for the diagnosis
of prion disease. Genetic testing of the prion protein gene was normal,
revealing methionine homozygosity at codon 129. Brain biopsy results were
negative for the presence of protease-resistant prion protein but showed
definite Alzheimer disease with numerous neuritic plaques and tau-positive
neurofibrillary tangles (Figure). Further analysis of brain tissue at the
National Prion Disease Pathology Surveillance Center was negative for prion
disease by Western blot analysis. Subsequent investigation by the state
department of health revealed the patient had worked in an area of the
laboratory that conducted necropsies on domestic animals and had never been
assigned to the CWD testing laboratory. The Colorado Department of Public Health
and Environment could not confirm that the technician had ever worked with deer
and elk tissues.
CASE 2 .
This 25-year-old right-handed man had a 4-month history of progressive gait
disturbance, myoclonus, hallucinations, slowed cognition, impaired attention,
and memory loss. He had hunted deer and elk in a CWD endemic area of southern
Wyoming and cooked and ate the field-dressed meat. His family history was
significant in that his mother had died of a dementing disease at age 40 years,
although there was neither a clinical diagnosis nor an autopsy. Brain magnetic
resonance imaging findings were unremarkable, and electroencephalography
demonstrated 1-Hz high-amplitude periodic sharp wave complexes. Other laboratory
studies had negative results. Testing for the 14-3-3 protein had positive
results, but the cerebrospinal fluid was otherwise unremarkable. The diagnosis
of Gerstmann-Sträussler-Scheinker syndrome, a familial prion disease, was
confirmed with a detailed autopsy examination and referral of the brain to the
National Prion Disease Pathology Surveillance Center. Autopsy brain tissue
showed the presence of protease-resistant prion protein by Western blot
analysis. Genetic evaluation revealed the P102L mutation in the prion protein
gene with methionine/valine heterozygosity at codon 129.
Sunday, November 13, 2011
COLORADO CWD CJD TSE PRION REPORTING 2011
Saturday, August 01, 2009
Cases of Early-Onset Sporadic Creutzfeld-Jakob Disease in Michigan Chronic
Wasting Disease and Potential Transmission to Humans
Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,† Michael W.
Miller,‡ Pierluigi Gambetti,§ and Lawrence B. Schonberger*
snip...
In 2001, two additional CJD patients 26 and 28 years of age were reported
from a single state (Table 2) (34). The patients grew up in adjacent counties
and had illness onset within several months of each other. As a result of this
fact and their unusually young age, a possible environmental source of
infection, including exposure to CWD-infected venison, was considered. One of
the patients died after an illness lasting 5–6 months that was characterized by
progressive aphasia, memory loss, social withdrawal, vision disturbances, and
seizure activity leading to status epilepticus and induced coma.
Histopathologic, immunohistochemical, and Western blot testing of brain biopsy
and autopsy samples confirmed a CJD diagnosis. The patient’s disease phenotype
corresponded to the MM2 sporadic CJD subtype reported by Parchi et al. (35).
This patient did not hunt, and family members provided no history of regularly
eating venison. The patient may have occasionally eaten venison originating from
the Upper Peninsula of Michigan while away from home during his college years.
However, ongoing surveillance has not detected CWD in Michigan deer (36).
The second patient died from an illness lasting ˜16 months. The patient’s
illness began with behavioral changes, including unusual outbursts of anger and
depression. Confusion, memory loss, gait disturbances, incontinence, headaches,
and photophobia also developed. Western blot analysis of frozen brain biopsy
tissue confirmed a prion disease diagnosis. Immunohistochemical analysis of
brain tissue obtained after the patient’s death
showed prion deposition consistent with GSS. Aprion protein gene analysis
could not be performed because appropriate samples were lacking. However, prion
protein gene analysis of a blood sample from one of the patient’s parents
indicated a GSS P102L mutation. The patient did not hunt but may have eaten
venison from Michigan once when he was 1–2 years old. The GSS diagnosis greatly
reduced the likelihood that the two patients reported from adjacent counties had
disease with a common origin. Recently, rare neurologic disorders resulting in
the deaths of three men who participated in “wild game feasts” in a cabin owned
by one of the decedents created concern about the possible relationship of their
illnesses with CWD (Table 2) (37). Two of the patients reportedly died of CJD,
and the third died from Pick’s disease. More than 50 persons were identified as
possibly participating in these feasts; the three patients were the only
participants reported to have died of a degenerative neurologic disorder.
Reanalysis of autopsy brain tissues from the three patients at the National
Prion Disease Pathology Surveillance Center indicated that two of them had no
evidence of a prion disease by immunohistochemical analysis. CJD was confirmed
in the third patient, who had clinicopathologic, codon 129, and prion
characteristics similar to the most common sporadic CJD subtype (MM1/MV1) (35).
This patient participated in the feasts only once, perhaps in the mid-1980s. In
addition, the investigation found no evidence that the deer and elk meat served
during the feasts originated from the known CWD-endemic areas of Colorado and
Wyoming.
In 2003, CJD in two deer and elk hunters (54 and 66 years of age) was
reported (38). The report implied that the patients had striking neuropathologic
similarities and that their illness may represent a new entity in the spectrum
of prion diseases. A third patient (63 years of age), who was also purported to
have been a big game hunter, was subsequently reported from the same area.
However, none of the three patients were reported to have eaten venison from the
CWD-endemic areas of the western United States. The 66- year-old patient hunted
most of his life in Washington State. Although information about the 54-year-old
patient was limited, there was no evidence that he hunted in CWD-endemic areas.
The third patient was not a hunter but ate venison harvested from Pennsylvania
and Washington. The neuropathologic changes, Western blot profile, and genotype
at codon 129 of the three patients each fit the MM1, VV1, or VV2 sporadic CJD
subtype, indicating absence of phenotypic similarity among the cases or atypical
neuropathologic features (35). To date, only two nonfamilial CJD cases with a
positive history of exposure to venison obtained from the known CWD-endemic
areas have been reported. One of the patients was a 61-year-old woman who grew
up in an area where this disease is known to be endemic, and she ate venison
harvested locally. She died in 2000, and analysis of autopsy brain specimens
confirmed that the patient’s CJD phenotype fit the MM1 subtype, with no atypical
neuropathologic features. The second patient was a 66-yearold man who was
reported to have eaten venison from two deer harvested in a CWD-endemic area.
Both deer tested negative for CWD, and the patient’s illness was consistent with
the MM1 CJD phenotype.
September 29, 2004
Grand Forks man dies from rare disease
State health officials say lab results are not expected for several weeks
on a Grand Forks man who is believed to have died from Creutzfeldt-jakob
(croitz-feld juh-COHB') disease, or C-J-D.
It's a rare neurological disease with symptoms similar to mad cow
disease.
State Epidemiologist Larry Shireley says North Dakota has seen only a
couple of cases of CJD in recent years. Scientists say about 250 people are
diagnosed with it in the United States each year.
Shireley says a Cleveland lab that specializes in CJD wants to test tissue
samples to make sure 48-old Michael Jose did not have new variant CJD, also
known as mad cow disease. Both diseases have some similar symptoms, but no human
mad cow cases have been reported in this country.
The testing will be done at the National Prion Disease Pathology
Surveillance Center at Case Western Reserve University.
Family members said Jose was never hospitalized and lived at home until the
time of his death last Saturday.
Doctor James Hargreaves is an infectious disease specialist at Altru
Hospital in Grand Forks. He says it's difficult to know how long Jose had the
disease.
February 21, 2003 / 52(07);125-127
Fatal Degenerative Neurologic Illnesses in Men Who Participated in Wild
Game Feasts --- Wisconsin, 2002
Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans.
CJD is one of a group of conditions known as transmissible spongiform
encephalopathies (TSEs), or prion diseases, that are believed to be caused by
abnormally configured, host-encoded prion proteins that accumulate in the
central nervous tissue (1). CJD has an annual incidence of approximately 1 case
per million population in the United States (1) and occurs in three forms:
sporadic, genetically determined, and acquired by infection. In the latter form,
the incubation period is measured typically in years. Recent evidence that prion
infection can cross the species barrier between humans and cattle has raised
increasing public health concerns about the possible transmission to humans of a
TSE among deer and elk known as chronic wasting disease (CWD) (2). During
1993--1999, three men who participated in wild game feasts in northern Wisconsin
died of degenerative neurologic illnesses. This report documents the
investigation of these deaths, which was initiated in August 2002 and which
confirmed the death of only one person from CJD. Although no association between
CWD and CJD was found, continued surveillance of both diseases remains important
to assess the possible risk for CWD transmission to humans.
Case Reports
Case 1. In December 1992, a Wisconsin man aged 66 years with a history of
seizures since 1969 sought treatment for recurring seizures, increasing
forgetfulness, and worsening hand tremors. Electroencephalographic (EEG)
examination demonstrated focal epileptiform activity and nonspecific diffuse
abnormalities, but no specific diagnosis was made. In February 1993, he was
hospitalized for increasing confusion, ataxia, and movement tremors of his
extremities. A magnetic resonance image (MRI) demonstrated mild, nonspecific
enhancement along the inferior parasagittal occipital lobe. A repeat EEG showed
bifrontal intermittent, short-interval, periodic sharp waves, suggesting a
progressive encephalopathy; a diagnosis of CJD was suspected. The man died later
that month; neuropathologic examination of brain tissue during autopsy indicated
subacute spongiform encephalopathy, compatible with CJD.
The man was a lifelong hunter who ate venison frequently. He hunted
primarily in northern Wisconsin but also at least once in Montana. He hosted
wild game feasts at his cabin in northern Wisconsin from 1976 until shortly
before his death. Fixed brain tissue obtained during the autopsy was sent for
analysis to the National Prion Disease Pathology Surveillance Center (NPDPSC)
and reexamined at the institution where the autopsy was conducted.
Histopathologic examination did not substantiate the diagnosis of prion disease.
In addition, 27 brain tissue sections were negative for prions by immunostaining
despite positive antibody reactions against other proteins (controls), which
indicated that other epitopes in the tissue samples were preserved.
Case 2. In May 1999, a Minnesota man aged 55 years with no previous history
of a neurologic disease sought evaluation and treatment following a 3-month
history of progressive difficulty in writing and unsteadiness of gait. A
computerized tomography (CT) scan and MRI examination of his head did not
indicate any abnormality. In June 1999, he was hospitalized following onset of
dementia, speech abnormalities, and myoclonic jerking. An EEG indicated
left-hemispheric periodic sharp waves and moderate generalized background
slowing; CJD was diagnosed clinically. In July 1999, following worsening
symptoms and development of right upper extremity dystonia, the patient died.
Neuropathologic evaluation of brain tissue during autopsy demonstrated
widespread subcortical spongiform lesions, consistent with CJD.
The man was not a hunter but had a history of eating venison. He made an
estimated 12 visits to the cabin where the wild game feasts were held, but he
participated in only one feast during the mid-1980s. Sections of fixed and
frozen brain tissue obtained during autopsy were analyzed at NPDPSC, and prion
disease was confirmed by immunohistochemical and Western blot testing. The
Western blot characteristics and prion disease phenotype in this patient were
consistent with the most common form of sporadic CJD, classified as M/M (M/V) 1
(3). Subsequent genetic typing confirmed the presence of methionine homozygosity
(M/M) at codon 129 of the patient's prion protein gene.
Case 3. In June 1992, a Wisconsin man aged 65 years sought treatment for
progressive slowing of speech, worsening memory, and personality changes. By
January 1993, his speech was reduced to one-word utterances. Neurologic
examination showed a flat affect, decreased reflexes, and apraxia. A CT head
scan showed mild atrophy, and an EEG was normal. Pick's disease was diagnosed.
By May, he was unable to perform any daily living activities; he died in August
1993. Neuropathologic evaluation of brain tissue during autopsy showed
symmetrical frontal lobe cerebral cortical atrophy and mild temporal lobe
atrophy. No Pick's bodies or spongiform lesions were observed.
The man had a history of eating venison and participated regularly in wild
game feasts held at the cabin owned by patient 1. He was a lifelong hunter and
hunted mostly in Wisconsin but also in Wyoming and British Columbia. No game was
brought to the wild game feasts from his hunting trips outside of Wisconsin.
Examination of fixed brain tissue sent to NPDPSC demonstrated no lesions
indicative of CJD, and immunohistochemical testing with antibody to the prion
protein did not demonstrate the granular deposits seen in prion diseases.
Epidemiologic Investigation
Wild game feasts consisting of elk, deer, antelope, and other game that
occurred at a cabin in northern Wisconsin owned by patient 1 began in 1976 and
continued through 2002. These feasts typically involved 10--15 participants and
usually occurred on weekends before or during hunting seasons in the fall and
occasionally in the spring. Wild game brought to these feasts usually were
harvested in Wisconsin, but three men who attended these feasts reported hunting
in the western United States and bringing game back to Wisconsin. These
activities took place in Colorado (near the towns of Cortez, Trinidad, Collbran,
Durango, and Meeker), Wyoming (near the towns of Gilette and Cody), and Montana
(near the town of Malta). CWD was not known to be endemic in these areas at the
time that these hunting activities took place.
Information was obtained for 45 (85%) of 53 persons who were identified as
possibly participating in the wild game feasts; all were male. Information was
obtained by direct interview or from family members of decedents. Of the 45
persons, for whom information was obtained, 34 were reported to have attended
wild game feasts. Seven of the 34 feast attendees were deceased, including the
three patients. None of the four other decedents had a cause of death attributed
to or associated with a degenerative neurologic disorder. None of the living
participants had any signs or symptoms consistent with a degenerative neurologic
disorder.
Reported by: JP Davis, MD, J Kazmierczak, DVM, M Wegner, MD, R Wierzba, Div
of Public Health, State of Wisconsin Dept of Health and Family Svcs. P Gambetti,
National Prion Disease Pathology Surveillance Center, Case Western Reserve
University, Cleveland, Ohio. L Schonberger, MD, R Maddox, MPH, E Belay, MD, Div
of Viral and Rickettsial Diseases, National Center for Infectious Diseases; V
Hsu, MD, EIS Officer, CDC.
Editorial Note:
CWD was first described in the United States in the 1960s and classified as
a TSE in 1978. Previously localized to a contiguous endemic area in northeastern
Colorado and southeast Wyoming, since 2000, CWD has been found in free-ranging
deer or elk in Illinois, Nebraska, New Mexico, South Dakota, Wisconsin, and
outside the previously known endemic areas of Colorado and Wyoming. CWD has been
identified also in captive deer or elk in Colorado, Kansas, Minnesota, Montana,
Nebraska, Oklahoma, South Dakota, and Wisconsin (4). Because a variant form of
CJD, with specific neuropathologic and molecular characteristics that
distinguish it from sporadic CJD, has been associated with eating cattle
products infected with a prion that causes bovine spongiform encephalopathy (5),
concern has been raised about the possibility that the prion associated with CWD
might be transmitted to humans in a similar way.
In this investigation, because only one of the three cases in Wisconsin had
neuropathologic confirmation of a prion disease, no association could be made
between case participation in the wild game feasts and the development of CJD.
Although patient 2 had confirmed CJD, he was unlikely to have eaten CWD-infected
venison at these feasts because venison and other game from outside Wisconsin
that was served at these feasts did not originate from known CWD-endemic areas,
and the man participated in the feasts only once. In addition, the prion disease
in this case was consistent with the most common form of sporadic CJD, without
apparent unusual neuropathologic or molecular characteristics that might occur
if the prion related to CWD had been responsible for the disease.
The findings in this report are subject to at least two limitations. First,
not all members participating in wild game feasts could be identified, and not
all persons listed as participating could be contacted for interviews. Second,
interviews that were conducted required recall of events that occurred up to 25
years ago, limiting the detail or accuracy of events. However, the similar
responses obtained from different sources support the accuracy of the
investigation findings.
A previous investigation of unusually young CJD patients in whom the
transmission of CWD was suspected also did not provide convincing evidence for a
causal relationship between CWD and CJD (2). However, limited epidemiologic
investigations cannot rule out the possibility that CWD might play a role in
causing human illness. Ongoing surveillance of CJD, particularly in states with
CWD, is important to assess the risk, if any, for CWD transmission to humans.
Because the confirmation of CJD and the detection of a new prion disease require
neuropathologic study of brain tissue, physicians are encouraged to contact
NPDPSC (http://www.cjdsurveillance.com;
telephone, 216-368-0587) to confirm diagnoses of CJD and to distinguish its
various subtypes. Because of the known severity of TSEs in humans and the
possibility that the CWD prion can affect humans, animals with evidence of CWD
should be excluded from the human food or animal feed chains. Hunters and wild
venison consumers should follow precautionary guidelines available from the
Wisconsin Department of Agriculture, Trade, and Consumer Protection (http://datcp.state.wi.us/core/consumerinfo)
to prevent potential exposures to the CWD agent.
References
Belay E. Transmissible spongiform encephalopathies in humans. Annu Rev
Microbiol 1999;53:283--314. Belay E, Gambetti P, Schonberger L, et al.
Creutzfeldt-Jakob disease in unusually young patients who consumed venison. Arch
Neurol 2001;58:1673--8. Parchi P, Giese A, Capellari S, et al. Classification of
sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of
300 subjects. Ann Neurol 1999;46:224--33. U.S. Department of Agriculture.
Positive CWD cases: cumulative through Dec 2002 (including farm herds already
depopulated). Available at http://aphisweb.aphis.usda.gov/vs/nahps//cwd/USAMapOfInfectedHerds.jpg.
Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob
disease in the UK. Lancet 1996;347:921--5.
CMAJ. 2003 September 2; 169(5): 443.
PMCID: PMC183301
Public Health
Wild game feasts and fatal degenerative neurologic illness
John Hoey
Author information ► Copyright and License information ►
This article has been cited by other articles in PMC.
Background and epidemiology: Creutzfeldt–Jakob disease (CJD) is one of a
group of conditions known as prion diseases that are caused by abnormally
configured host-encoded prion proteins that accumulate in central nervous system
tissue. There are 3 forms: sporadic, genetically determined and, more recently,
variant CJD, acquired by infection when the disease crosses the species barrier
between humans and cattle.1 A similar prion disease in deer and elk known as
chronic wasting disease (CWD) has raised concerns that this prion could also
cross species barriers in people who eat wild game.
A report was recently published describing 3 cases of CWD in men who had
attended wild game feasts.2 In the first case, a 66-year-old man who had been a
lifelong hunter and who ate venison frequently had hosted wild game feasts at
his cabin in Montana for 26 years before he died in 1992 of an autopsy-confirmed
subacute spongiform encephalopathy compatible with CJD. He had a history of
seizures since the age of 43 and had sought treatment for recurring seizures,
increasing forgetfulness and worsening hand tremors about a month before he
died.
The 2 other cases involved men aged 55 and 65 who died of neurologic
illness. These men had histories of eating venison and participating in 1 or
more of the first patient's wild game feasts. The younger man presented in 1999
with a 3-month history of difficulty in writing and unsteadiness of gait,
followed by dementia, speech abnormalities and myoclonic jerking. Pathologic
examination of the brain at autopsy 3 months later revealed widespread
subcortical spongiform lesions consistent with CJD. He had visited the first
patient's cabin 12 times and had participated in 1 wild game feast.
The older man sought treatment in 1992 for progressive slowing of speech,
worsening memory and personality changes. His speech became reduced to
single-word utterances, and he died 10 months after initial presentation. He had
been a lifelong hunter and had hunted mostly in Wisconsin but also in Wyoming
and British Columbia. He had participated regularly in the first patient's wild
game feasts. No game had been brought to the wild game feasts from his hunting
trips outside of Wisconsin.
Testing of fixed brain tissue from all 3 men revealed no evidence on
immunostaining for prions using antibodies to the prion protein in the first and
third patients. In the second patient prion disease was confirmed by means of
immunohistochemical and Western blot testing. The blot characteristics and prion
disease phenotype were consistent with the common form of sporadic CJD,
classified as M/M (M/V) 1. Subsequent genetic typing revealed methionine
homozygosity (M/M) at codon 129 of the patient's prion protein gene, making it
likely that the patient had the most common form of sporadic CJD.
Information obtained for 45 people of 53 identified as possibly
participating in the wild game feasts revealed that only 34 had actually
attended them. Of the 34, 7 were dead, including the 3 described here; none of
the other 4 had died of a degenerative neurologic disorder. None of the living
participants had any signs or symptoms consistent with a degenerative neurologic
disorder.
Clinical management: Because of the continuing possibility that CWD in deer
and elk might be transmissible to humans, physicians should attempt to confirm
cases of illness compatible with a transmissible spongiform encephalopathy
through pathological examination of brain tissue and by alerting the Canadian
CJD surveillance unit (www.hc-sc.gc.ca/pphb-dgspsp/hcai-iamss/cjd-mcj; tel 888
489-2999) or the US National Prion Disease Pathology Surveillance Center
(www.cjdsurveillance.com). There is no known treatment for the condition.
Prevention: CWD was first identified in the United States in 1967. In
Canada, only 8 cases of CWD have been reported in wild deer, all in
Saskatchewan. In the United States, CWD has been found in free-ranging deer and
elk in Illinois, Nebraska, New Mexico, South Dakota, Wisconsin, Colorado and
Wyoming. Limited epidemiologic investigations to date cannot exclude the
possibility that CWD may cause human disease. Because of the severity of the
spongiform encephalopathies in humans and the absence of treatment, animals with
evidence of CWD should be excluded from human and animal food chains.
John Hoey CMAJ
Doctors study brain tissue of elk hunter / Montana man had symptoms similar
to mad cow disease David Perlman
Chronicle Science Editor Published 4:00 a.m., Saturday, September 7, 2002
snip...
Researchers at UC San Francisco are analyzing the brain tissue of a Montana
elk hunter who died last month with symptoms of a rare human disorder similar to
mad cow disease in cattle and the chronic wasting disease that has felled elk
and deer in the Midwest and Rocky mountains.
Last October, 50-year-old Gary Padgham of Bozeman first showed the
stumbling gait, the dementia and the impaired vision and memory loss that are
typical of Creutzfeldt-Jacob disease, known also as CJD. He was taken to a
hospital in Seattle where doctors first diagnosed his illness as Huntington's
disease, and then as CJD.
Padgham was later moved to Monterey where his family lives, and after he
died in August his body was taken to UCSF for a specialized autopsy.
The institution is the nation's primary center for research in the varied
brain diseases of humans and animals that are all believed to be caused and
transmitted by malformed brain proteins called prions.
CJD is known to be one of the prion diseases, and researchers at UCSF study
as many as 20 cases of suspected prion brain diseases a year in an effort to
learn more about the invariably fatal malady.
The prions were discovered 20 years ago by Dr. Stanley B. Prusiner, a UCSF
neurologist and virologist at UCSF who had been studying several strange brain
diseases for a decade and won the 1997 Nobel prize in physiology and medicine
for his prion work. Prusiner coined the term prion from the words "proteinaceous
infectious particles."
Officials at the UCSF medical center would not discuss Padgham's case
specifically Friday because of privacy rules, but a spokeswoman did note that
although the disease-causing prions can be transmitted, there has never been a
known case of humans contracting CJD from infected elk or deer.
Specialists at the California state health department said the chances are
"slim to none" that Padgham could have contracted his disease from eating the
meat of the elk he hunted in Montana.
According to the Federal Centers for Disease Control and Prevention,
chronic wasting disease has hit captive deer and elk herds in several Midwestern
and mountain states, and some wild deer in Wisconsin -- a development that has
caused widespread fears among hunters.
In California, the Department of Fish and Game has asked hunters to stop
bringing deer and elk parts back from states where the wasting disease has been
found, and will seek a regulation banning the import of all high-risk parts,
such as brains.
The CDC and other state agencies are also investigating the deaths of
Padgham and three other hunters in Montana and Wisconsin. Two of the three died
of Creutzfeldt-Jacob disease and one of a different brain disorder called Pick's
Disease, where prions are not known to be involved.
Observation| October 2001
Creutzfeldt-Jakob Disease in Unusually Young Patients Who Consumed
VenisonFREE
Ermias D. Belay, MD; Pierluigi Gambetti, MD; Lawrence B. Schonberger, MD;
Piero Parchi, MD; Douglas R. Lyon, MD; Sabina Capellari, MD; Jennifer H.
McQuiston, DVM; Kristy Bradley, DVM; Gerrie Dowdle, MSPH; J. Michael Crutcher,
MD; Craig R. Nichols, MPA
[+] Author Affiliations
Arch Neurol. 2001;58(10):1673-1678. doi:10-1001/pubs.Arch
Neurol.-ISSN-0003-9942-58-10-nob10126.
PATIENT 1 .
In early 1997, a 28-year-old woman was examined several times in an
emergency department for abnormal mental status, weakness, and unsteady gait.
She also developed ataxia, dyskinesia, and marked dysarthria. The patient's
condition gradually deteriorated, and she was admitted to a community hospital
in March 1997. On admission, the patient had lethargia, athetoid and choreoform
movements, constant lip smacking, possible hallucination, and increased muscle
tone. After hospital admission, she developed primitive frontal release signs
and episodic focal seizures. The electroencephalogram showed a severely abnormal
tracing with diffuse, slow triphasic waves. The computed tomographic scan and
magnetic resonance image of the brain did not reveal any abnormality. A brain
biopsy performed to evaluate a suspected CJD diagnosis showed only gliosis. The
patient died in June 1997, almost 4 months after the onset of illness. .
Histologic examination of brain tissue samples obtained at autopsy showed
widespread spongiform degeneration involving the cerebral cortex. The spongiosis
was associated with astrogliosis and moderate loss of neurons. The lesions
seemed to be more prominent in the frontal lobe and in the entorhinal cortex.
The basal ganglia; the thalamus, especially the mediodorsal nucleus; the tectum
of the midbrain and pons; the substantia nigra; and the molecular layer of the
cerebellar cortex all showed spongiosis and astrogliosis. Immunohistochemical
examination for prion protein residues demonstrated a strong and consistent
"synaptic" or "punctate" pattern of immunostaining in the cerebral cortex.
Rarely, the immunostaining showed a preferential perineuronal distribution that
involved both cell body and processes. Analysis of the PRNP indicated a Met/Met
homozygosity at the polymorphic codon 129 and absence of genetic mutations. .
The patient's mother indicated that the patient had worked as a cashier at
different department stores and a fast food restaurant. She had undergone
tonsillar surgery at age 5 years. Her regular diet included consumption of beef,
pork, and chicken several times a week. She might have consumed lamb or mutton
once every several years. In addition, the patient consumed deer meat between
ages 1 and 6 years. The deer were harvested mostly from Maine by the patient's
father but occasionally from New Jersey by other family members. The deer
carcasses were usually prepared by a custom processor. The patient primarily
consumed the deer meat as steaks and ground meat mixed into sauce. At about 6
years of age, the patient had also consumed elk meat provided by a family friend
as a gift on 2 different occasions. Although the origin of the elk could not be
clearly ascertained, a family member reported that it was likely harvested in
Wyoming. The patient was also reported to have occasionally consumed meat from
squirrel, bear, and rabbits. No consumption of brain or organ meat from
domesticated or game animals was reported. .
PATIENT 2 .
In September 1998, a 29-year-old man was examined at a university hospital
for progressive cognitive difficulties. His illness began in May 1998, when he
experienced difficulty completing his travel expenses after a routine business
trip. The patient became increasingly forgetful, with inability to recall his
wife's name, his own home telephone number, and names of long-time family
friends. In August 1998 the patient resigned from his job because of the
cognitive problems. Subsequently, he developed behavioral problems and
difficulties with speech, writing, naming objects, and dressing without
assistance. The patient was ambulatory without imbalance but had dysmetria,
tremors, and occasional myoclonus. Findings from the initial 2
electroencephalograms, the computed tomographic scan, and cerebral angiographic
studies were normal. The magnetic resonance image showed cerebral atrophy
without any other abnormalities. Single-photon emission computed tomographic
imaging of the brain revealed a nonspecific, asymmetric, diminished perfusion
over the left parietal lobe. Results of initial cerebrospinal fluid analysis for
14-3-3 protein were negative in November 1998. A brain biopsy performed in
November 1998 showed diffuse spongiform encephalopathy consistent with CJD. The
patient died at age 30 years in March 1999, almost 10 months after the onset of
illness. .
Histologic examination of the brain tissue samples obtained at autopsy
showed prominent spongiform degeneration and gliosis with possible neuronal loss
in the cerebral cortex and basal ganglia. In contrast, the cerebellum showed
virtually no pathologic changes. The spongiosis often displayed a laminar
distribution that affected the deep cortical regions. Neurons that were
moderately ballooned were occasionally seen in the cerebral cortex. The pattern
of prion protein immunostaining was exclusively "synaptic" in the cerebral
cortex and basal ganglia, whereas the cerebellum was virtually unstained.
Analysis of the PRNP indicated that the patient was homozygous for valine at the
polymorphic codon 129. No PRNP mutation was detected. Immunoblot analysis showed
that the PrP-res fragment migrated to 21 kd, corresponding to the prion protein
type 1. .
His past occupations included working as a stock boy in a grocery store and
recently as a salesperson. The patient had undergone a hernia repair during
infancy and tonsillar surgery at approximately 10 years of age. His regular diet
included consumption of beef many times a week and pork several times a week. He
occasionally ate mutton and cow brain, approximately once every several years.
The patient was described as a regular hunter, hunting almost every year since
1985. He was reported to have hunted deer and elk in many areas, almost always
in Utah. He did, however, hunt an elk in the southwestern part of Wyoming in
1995 and was part of a team that hunted deer around Williams Lake, British
Columbia, in 1989. The patient usually field dressed the carcasses himself and
took them to a particular plant for custom processing. In addition, the family
has many times received gifts of deer and elk meat from the patient's brother,
who regularly hunted in Utah. The family usually ate the deer and elk meat as
steak, ground meat, and jerky almost once a month. Moreover, the patient
regularly ate liver from deer and elk but not other organ meat, including brain,
from any game animals. .
PATIENT 3 .
In December 1998, a 27-year-old man began experiencing difficulty finding
his hometown and lapses in memory while performing his duties as a truck driver.
During the next month, the patient became increasingly forgetful, constantly
asking for directions and instructions on how to operate the truck. He started
to exhibit impulsive and impatient behavior, the inability to dress properly,
difficulty finding words, and confusion. He also developed myoclonus and sleep
disturbances. The electroencephalographic tracing was abnormal but
nondiagnostic. The magnetic resonance image of the brain showed diffuse cortical
hyperintensity with an unusual but nonspecific pattern. Findings from the
cerebrospinal fluid 14-3-3 immunoassay were positive. Histopathologic
examination of the cerebral cortical tissue samples obtained at biopsy revealed
widespread spongiform degeneration associated with astrogliosis and a possible
loss of neurons. Analysis of the PRNP indicated a Met/Val heterozygosity at
codon 129 and absence of PRNP mutations. Immunoblot analysis showed that the
PrP-res fragment migrated to 21 kd, in the polyacrylamide gel corresponding to
the prion protein type 1. The patient died in April 2000 at age 28 years, almost
15 months after the onset of illness. No autopsy was performed. .
His occupations included driving a truck locally and spreading fertilizers.
Since 1993 he had also been assisting his father-in-law in raising beef cattle.
The patient had no history of surgical procedures. His regular diet included
consumption of beef, pork, and chicken several times a week. No consumption of
lamb or mutton was reported. The patient was described as an "avid hunter,"
hunting deer regularly since age 13 years, and frequently harvested at least 1
deer annually. Almost all his deer hunting took place exclusively in 2 very
localized areas within 2 counties close to his hometown. The patient usually
field dressed the deer carcasses himself and took them to a particular plant for
custom processing. During the previous 6 years, the patient and his family had
reportedly consumed only ground venison almost once a month. During his
childhood, the patient also consumed deer meat harvested by his father. The
patient's wife reported no consumption of deer or elk meat originating from
either Colorado or Wyoming. However, the custom processing plant where the
patient regularly took the deer carcasses for processing also processed
approximately 20 elk from Colorado every year. The exact geographic origin in
Colorado of these elk could not be ascertained. No consumption of brain or other
organs from domesticated or game animals was reported. On the basis of hunter
survey data obtained from the local Department of Wildlife Conservation, the
patient's hunting practices were typical of other game animal hunters in the
area. Analysis of the 1998 hunter licensing data estimated that approximately
24% of families and approximately 17% of households in the state might include a
licensed hunter.
Tuesday, 1 May, 2001, 12:28 GMT 13:28 UK
Mad deer disease in Colorado
snip...
John Pape from Colorado's Health Department said: "At this point, the
answers to these questions are unknown. Because of the BSE experience, it is
theoretically possible, and based on that there are some precautions that
hunters may want to take."
A farm in the mountains of Nevada may hold a key to the puzzle of Mad Deer
disease.
The farm's owner, a cowboy called Jim Koepke, died suddenly from
Creutzfeldt Jakob Disease (CJD), an illness very similar to both BSE and the Mad
Deer variant.
Brenda, Jim's widow, admits that he loved to hunt. It is possible that he
may have died from eating infected deer meat. "I couldn't comprehend that a
cowboy in the middle of farming Nevada could get such a horrendous disease," she
said. "So I dragged the poor man to many other doctors looking for something
that made an ounce of sense."
Just coincidence?
Jim Koepke was the third deer hunter to die in the last two years from CJD.
So far the evidence suggests that it is just coincidence.
But in Colorado, where as many as one in five deer and elk now has the
disease, the authorities are urging caution.
Family fears another blood-borne disaster Saturday 27 March 1999 Mark
Kennedy The Ottawa Citizen
Doug McEwen is dying of Creutzfeldt-Jakob disease, but plasma products from
his blood have been cleared for distribution. Mark Kennedy reports. SALT LAKE
CITY - Tracie McEwen reaches over to the dying man in the hospital bed that
crowds her small living room. His eyes are closed and he has rarely opened them
in recent days. As he moans softly, she strokes his arm and kisses his forehead.
"It's OK. Doug, it's OK."
Tracie married Doug exactly four years ago on this date in late March. She
marked their anniversary by pouring sparkling cider into cups, making a toast,
and lovingly dropping some into Doug's mouth. It is celebration enough that he
has survived this long, but it is a bittersweet experience. For he is just a
shell of the man he was a few short months ago.
Mr. McEwen is dying of Creutzfeldt-Jakob Disease (CJD), a rare and always
fatal neurological disorder that has many different forms. The horrifying
condition creeps up on its victims, eating away at the brain, giving it the
appearance of a sponge.
Experts say only one in a million people gets the most common strain, known
as "classical" CJD, which causes death within a year of symptoms first
appearing. The World Health Organization is so concerned about the potential
growth of CJD that it is holding an international meeting to discuss how to deal
with it.
Doug McEwen's case has spawned an international debate over whether a new,
more virulent strain -- dubbed "mad deer disease" -- has appeared in North
America.
Governments say Mr. McEwen, 30, has the classical strain, but some
scientists question that diagnosis. They say it's possible the Utah man, who was
an occasional hunter, is the first known victim of a newer strain contracted by
eating deer and elk -- much the same way some in Britain contracted "mad cow
disease" from eating infected beef in the 1980s.
In the nearby states of Colorado and Wyoming, there are herds of deer and
elk suffering from chronic wasting disease (CWD), a neurological disease in
animals associated with CJD. Consumer groups say governments are ignoring what
could be the beginning of a worldwide epidemic, but other scientists say there
is no basis for such a prediction, which they view as irresponsible and
alarmist.
Complicating the situation is the fact that Mr. McEwen has been a blood
plasma donor for nearly two years, starting in late 1996. His plasma was sent to
the pharmaceutical company Bayer, which fractionated it into various blood
products at its plant in Clayton, North Carolina. The products were then shipped
to 46 countries around the world, including Canada.
When Mr. McEwen was diagnosed with CJD late last year, Health Canada
ordered a temporary quarantine on products containing his plasma. Regulators
were alarmed by his age -- classical CJD victims usually get the disease in
their 50s and 60s. Only one per cent of them fall into Mr. McEwen's age bracket.
Could this be like mad cow disease, regulators asked. After consulting outside
experts, the U.S. Food and Drug Administration and Centers for Disease Control,
it was determined that Mr. McEwen has the classical form. On Christmas Eve,
blood products created with his plasma were cleared for redistribution.
At her apartment in the small town of Kaysville, 50 kilometres north of
Salt Lake City, Tracie McEwen has been swamped with calls and visits from U.S.
regulators and government scientists.
She believes governments in the U.S. and Canada have made a terrible error
by underestimating the potential seriousness of her husband's disease and by
prematurely lifting the ban on blood products linked to his plasma.
"I'm not a scientist but I think it's a serious threat," says the
28-year-old, who teaches geography to Grade 9 students. "It's a horrible disease
and until they know exactly how it's spread, I think that all the governments
are fools to ignore it the way they have. They're fools because they still can't
tell me how he got it."
She says her husband, a devout Mormon, was "devastated" at the thought that
somehow his disease might be spread through his plasma donations. "Of course, he
never would have donated, had we had known," says Tracie, tears welling up in
her eyes. "It made me sick when I found out they had put it back on the market.
They had it. They had it. They didn't have to use it. That would have been how
many less people getting it? And they still put it out. And they still don't
know. It's wrong."
Last summer, Doug was a big, strapping man who lived life to its fullest.
He fished and hiked, and rode his bicycle in the stunning Utah mountains. He
devoted himself to Tracie and their daughters, Sharon, 8, and Rilee, 3. Since
then, his weight has dropped from 230 pounds to 130 pounds. He has been trapped
in a body that has steadily given up on him.
It started slowly. First, there was the memory loss and the inability to do
simple math, then the light tremors. Eventually, came violent seizures as well
as the unexplainable outbursts of emotion -- hysterical laughter, sometimes
followed by uncontrollable crying. By late January, he could no longer speak in
sentences. Three weeks ago, he stopped walking.
Now, he is near death. Tracie, who has cared for all his needs and slept
next to him every night on a floor mattress, can only wait for the inevitable.
"This is the worst thing I have seen," she says. "I wouldn't wish it on my
worst enemy."
Cowboy Jim Koepke died of CJD
"We encourage hunters to wear gloves when they field-dress carcasses, and
at the very least to avoid consuming some of the tissues that we know harbour
the chronic wasting disease - things like brain and spinal cord," said Michael
Miller, a Colorado vet. What is eerie is how similar the comments of American
experts are to those of British government officials during the early years of
the Mad Cow crisis. There may be no evidence yet of a threat to humans, but no
one is even sure how this disease is transmitted from deer to deer, and the
British experience should show us that nothing can be taken for granted.
Generation of a new form of human PrPSc in vitro by inter-species
transmission from cervids prions
Marcelo A. Barria1, Glenn C. Telling2, Pierluigi Gambetti3, James A.
Mastrianni4 and Claudio Soto1,* 1Mitchell Center for Alzheimer’s disease and
related Brain disorders, Dept of Neurology, University of Texas Houston Medical
School, Houston, TX 77030, USA 2Dept of Microbiology, Immunology & Molecular
Genetics, and Neurology, Sanders Brown Center on Aging, University of Kentucky
Medical Center, Lexington, KY, USA 3Institute of Pathology, Case Western Reserve
University, Cleveland, OH, USA 4Dept of Neurology, University of Chicago,
Chicago, IL, USA. Running Title: Conversion of human PrPC by cervid PrPSc
Keywords: Prion / transmissible spongiform encephalopathy / infectivity /
misfolded prion protein / prion strains * To whom correspondence should be
addressed. University of Texas Houston Medical School, 6431 Fannin St, Houston,
TX 77030. Tel 713-5007086; Fax 713-5000667; E-mail Claudio.Soto@uth.tmc.edu The
latest version is at http://www.jbc.org/cgi/doi/10.1074/jbc.M110.198465
JBC Papers in Press.
Published on January 4, 2011 as Manuscript M110.198465 Copyright 2011 by
The American Society for Biochemistry and Molecular Biology, Inc. 5, Downloaded
from www.jbc.org by guest, on November 11, 2012 2
Prion diseases are infectious neurodegenerative disorders affecting humans
and animals that result from the conversion of normal prion protein (PrPC) into
the misfolded prion protein (PrPSc). Chronic wasting disease (CWD) is a prion
disorder of increasing prevalence within the United States that affects a large
population of wild and captive deer and elk. Determining the risk of
transmission of CWD to humans is of utmost importance, considering that people
can be infected by animal prions, resulting in new fatal diseases. To study the
possibility that human PrPC can be converted into the misfolded form by CWD
PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification
(PMCA) technique, which mimic in vitro the process of prion replication. Our
results show that cervid PrPSc can induce the conversion of human PrPC, but only
after the CWD prion strain has been stabilized by successive passages in vitro
or in vivo. Interestingly, the newly generated human PrPSc exhibits a distinct
biochemical pattern that differs from any of the currently known forms of human
PrPSc. Our results also have profound implications for understanding the
mechanisms of prion species barrier and indicate that the transmission barrier
is a dynamic process that depend on the strain and moreover the degree of
adaptation of the strain. If our findings are corroborated by infectivity
assays, they will imply that CWD prions have the potential to infect humans, and
that this ability depends on CWD strain adaptation.
Various studies aimed to analyze the transmission of CWD to transgenic mice
expressing human PrP have consistently given negative results (9-11), indicating
a strong species barrier. This conclusion is consistent with our many failed
experiments to attempt converting human PrPC with natural CWD, even after
pushing the PMCA conditions (see figure 1). We found successful conversion only
after adaptation of the CWD prion strain by successive passages in vitro or in
cervid transgenic mice. We are not aware that in any of the transgenic mice
studies the inoculum used was a previously stabilized CWD strain. Although, it
has been shown that strain stabilization in vitro by PMCA (17;26) and in vivo
using experimental rodents (36) has similarities with the strain adaptation
process occurring in natural hosts, we cannot rule out that the type of CWD
strain adaptation that is required to produce strains transmissible to humans
may take much longer time in cervids or not occur at all. An important
experiment will be to study transmissibility to humanized transgenic mice of CWD
passed experimentally in deer several times. Besides the importance of our
results for public health in relation to the putative transmissibility of CWD to
humans, our data also illustrate a very important and novel scientific concept
related to the mechanism of prion transmission across species barriers. Today
the view is that species barrier is mostly controlled by the degree of
similarity on the sequence of the prion protein between the host and the
infectious material (4). In our study we show that the strain and moreover the
stabilization of the strain plays a major role in the inter-species
transmission. In our system there is no change on the protein sequence, but yet
strain adaptation results in a complete change on prion transmissibility with
potentially dramatic consequences. Therefore, our findings lead to a new view of
the species barrier that should not be seen as a static process, but rather a
dynamic biological phenomenon that can change over time when prion strains
mature and evolve. It remains to be investigated if other species barriers also
change upon progressive strain adaptation of other prion forms (e.g. the
sheep/human barrier).
Our results have far-reaching implications for human health, since they
indicate that cervid PrPSc can trigger the conversion of human PrPC into PrPSc,
suggesting that CWD might be infectious to humans. Interestingly our findings
suggest that unstable strains from CWD affected animals might not be a problem
for humans, but upon strain stabilization by successive passages in the wild,
this disease might become progressively more transmissible to man.
Generation of a New Form of Human PrPScin Vitro by Interspecies
Transmission from Cervid Prions*
Marcelo A. Barria‡, Glenn C. Telling§, Pierluigi Gambetti¶, James A.
Mastrianni‖ and Claudio Soto‡,1 + Author Affiliations
From the ‡Mitchell Center for Alzheimer's Disease and Related Brain
Disorders, Department of Neurology, University of Texas Medical School at
Houston, Houston, Texas 77030, the §Departments of Microbiology, Immunology, and
Molecular Genetics and Neurology, Sanders Brown Center on Aging, University of
Kentucky Medical Center, Lexington, Kentucky 40506, the ¶Institute of Pathology,
Case Western Reserve University, Cleveland, Ohio 44106, and the ‖Department of
Neurology, The University of Chicago, Chicago, Illinois 60637 1 To whom
correspondence should be addressed: University of Texas Medical School at
Houston, 6431 Fannin St., Houston, TX 77030. Tel.: 713-500-7086; Fax:
713-500-0667; E-mail: claudio.soto@uth.tmc.edu.
Abstract
Prion diseases are infectious neurodegenerative disorders that affect
humans and animals and that result from the conversion of normal prion protein
(PrPC) into the misfolded prion protein (PrPSc). Chronic wasting disease (CWD)
is a prion disorder of increasing prevalence within the United States that
affects a large population of wild and captive deer and elk. Determining the
risk of transmission of CWD to humans is of utmost importance, considering that
people can be infected by animal prions, resulting in new fatal diseases. To
study the possibility that human PrPC can be converted into the misfolded form
by CWD PrPSc, we performed experiments using the protein misfolding cyclic
amplification technique, which mimics in vitro the process of prion replication.
Our results show that cervid PrPSc can induce the conversion of human PrPC but
only after the CWD prion strain has been stabilized by successive passages in
vitro or in vivo. Interestingly, the newly generated human PrPSc exhibits a
distinct biochemical pattern that differs from that of any of the currently
known forms of human PrPSc. Our results also have profound implications for
understanding the mechanisms of the prion species barrier and indicate that the
transmission barrier is a dynamic process that depends on the strain and
moreover the degree of adaptation of the strain. If our findings are
corroborated by infectivity assays, they will imply that CWD prions have the
potential to infect humans and that this ability progressively increases with
CWD spreading.
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010 CWD PRION CONGRESS SEPTEMBER 8-11 2010
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
Friday, November 09, 2012
Chronic Wasting Disease CWD in cervidae and transmission to other species
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until
now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in
BvI109.
The discovery of previously unrecognized prion diseases in both humans and
animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion
diseases might be wider than expected and raises crucial questions about the
epidemiology and strain properties of these new forms. We are investigating this
latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
AS OF AUGUST 2012 ;
CJD UPDATE USA
1 Listed based on the year of death or, if not available, on year of
referral; 2 Cases with suspected prion disease for which brain tissue and/or
blood (in familial cases) were submitted; 3 Disease acquired in the United
Kingdom; 4 Disease was acquired in the United Kingdom in one case and in Saudi
Arabia in the other case; *** 5 Includes 8 cases in which the diagnosis is
pending, and 18 inconclusive cases; *** 6 Includes 10 (9 from 2012) cases with
type determination pending in which the diagnosis of vCJD has been excluded. ***
The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42
cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2224 cases of
sporadic Creutzfeldt-Jakob disease (sCJD).
Tuesday, November 6, 2012
Transmission of New Bovine Prion to Mice, Atypical Scrapie, BSE, and
Sporadic CJD, November-December 2012 update
TSS
posted by Terry S. Singeltary Sr. at
1:27 PM
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