A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation
From: Terry S. Singeltary Sr.
Sent: Monday, September 05, 2016 9:11 PM
To: Terry S. Singeltary Sr.
Subject: A comparison of classical and H-type bovine spongiform
encephalopathy associated with E211K prion protein polymorphism in wild type and
EK211 cattle following intracranial inoculation
Original Research ARTICLE Front. Vet. Sci. | doi: 10.3389/fvets.2016.00078
A comparison of classical and H-type bovine spongiform encephalopathy
associated with E211K prion protein polymorphism in wild type and EK211 cattle
following intracranial inoculation
Jo Moore1, M. Heather West Greenlee2, 3, Jodi D. Smith1, Catherine E.
Vrentas1, Eric M. Nicholson1 and Justin J. Greenlee1* 1Virus and Prion Research
Unit, US Dept of Agriculture, Agricultural Research Service, National Animal
Disease Center, USA 2Department of Biomedical Sciences, Iowa State University
College of Veterinary Medicine, USA 3Interdepartmental Toxicology Program, Iowa
State University, USA
In 2006, a case of H-type bovine spongiform encephalopathy (BSE-H) was
diagnosed in a cow that was associated with a heritable polymorphism in the
bovine prion protein gene (PRNP) resulting in a lysine for glutamine amino acid
substitution at codon 211 (called E211K) of the prion protein. Although the
prevalence of this polymorphism is low, cattle carrying the K211 allele may be
predisposed to rapid onset of BSE-H when exposed or to the potential development
of a genetic BSE. This study was conducted to better understand the relationship
between the K211 polymorphism and its effect on BSE phenotype. BSE-H from the US
2006 case was inoculated intracranially (IC) in one PRNP wild type (EE211) calf
and one EK211 calf. In addition, one wild type calf and one EK211 calf were
inoculated IC with brain homogenate from a US 2003 classical BSE case. All
cattle developed clinical disease. The survival times of the E211K BSE-H
inoculated EK211 calf (10 months) was shorter than the wild type calf (18
months). This genotype effect was not observed in classical BSE inoculated
cattle (both 26 months). Significant changes in retinal function were observed
in H-type BSE challenged cattle only. Cattle challenged with the same inoculum
showed similar severity and neuroanatomical distribution of vacuolation and
disease-associated prion protein deposition in the brain, though differences in
neuropathology were observed between E211K BSE-H and classical BSE inoculated
animals. Western blot results for brain tissue from challenged animals were
consistent with the inoculum strains. This study demonstrates that the phenotype
of E211K BSE-H remains stable when transmitted to cattle without the K211
polymorphism, and exhibits a number of features that differ from classical BSE
in both wild type and heterozygous EK211 animals.
Keywords: Bovine spongiform encephalopathy, Brain Diseases, Cattle, E211K,
prion protein, transmissible spongiform encephalopathy
Citation: Moore J, West Greenlee M, Smith JD, Vrentas CE, Nicholson EM and
Greenlee JJ (2016). A comparison of classical and H-type bovine spongiform
encephalopathy associated with E211K prion protein polymorphism in wild type and
EK211 cattle following intracranial inoculation. Front. Vet. Sci. 3:78. doi:
10.3389/fvets.2016.00078
Received: 12 Apr 2016; Accepted: 31 Aug 2016.
Edited by:
Mary M. Christopher, University of California, Davis, USA Reviewed by:
Torsten Seuberlich, University of Bern, Switzerland Andrew Miller, Cornell
University College of Veterinary Medicine, USA Copyright: © 2016 Moore, West
Greenlee, Smith, Vrentas, Nicholson and Greenlee. This is an open-access article
distributed under the terms of the Creative Commons Attribution License (CC BY).
The use, distribution or reproduction in other forums is permitted, provided the
original author(s) or licensor are credited and that the original publication in
this journal is cited, in accordance with accepted academic practice. No use,
distribution or reproduction is permitted which does not comply with these
terms.
* Correspondence: Dr. Justin J. Greenlee, US Dept of Agriculture,
Agricultural Research Service, National Animal Disease Center, Virus and Prion
Research Unit, Ames, USA, Justin.greenlee@ars.usda.gov
snip...
411
412 Discussion
413 In this study we investigated the role of the E211K polymorphism and
its interaction with disease
414 phenotype in animals inoculated with classical BSE or BSE-H from an
animal with the E211K
415 polymorphism (E211K BSE-H). The results presented here extend on
previous published results of
416 challenge of an EK211 calf with E211K BSE-H (10) by including data from
the challenge of wild type
417 cattle with E211K BSE-H, and challenge of EK211 and wild type (EE211)
cattle with BSE-C. Overall,
418 inoculum strain had a greater effect on disease phenotype than host
genotype, although some
419 differences were observed between cattle challenged with the same
inoculum, in particular amongst the
420 E211K BSE-H challenged cattle. However, due to the small number of
animals in this study biological
421 variation between individual animals may have contributed to the
observed differences.
422
423 The phenotype of BSE-C was similar in EK211 and wild type cattle with
regards to almost all
424 parameters tested. For example, the incubation periods (31, 32)
(Hawkins, unpublished data) and
425 vacuolation profiles (33, 34) of both BSE-C challenged animals were
similar to each other, and
426 consistent with previous studies of cattle challenged with classical
BSE via the intracranial route. These
427 results are consistent with the observation that BSE-C is caused by a
single prion strain with reliably
428 consistent biological characteristics (35, 36).
429
430 One point of difference was that the wild type, but not the EK211
animal, developed abnormal licking
431 and chewing behaviors in the clinical phase of disease. These behaviors
were similar to those observed
432 in the EK211 animal challenged with E211K BSE-H (10). The lack of any
clear inoculum or genotype
433 association with the abnormal licking and chewing behaviors suggests
that it is possible that they are
434 part of the spectrum of biological variation in the clinical
presentation of BSE. A second point of
435 difference was that the EE211 BSE-C challenged animal developed
statistically significant changes in
436 retinal function and thickness that were not as severe as in the EK211
BSE-C challenged animal.
437
438 In contrast to the relatively homogenous phenotype observed in BSE-C
challenged cattle, a number of
439 striking differences were observed between the EK211 and wild type
cattle challenged with E211K
440 BSE-H.
441
442 The incubation time for the wild type animal (18 MPI) was similar to
that reported for cattle challenged
443 intracranially with BSE-H isolates from France (16.5-21 MPI) (37, 38),
Canada (15-16 MPI) (34), or
444 Germany (14-16 MPI) (39). The clinical duration of the wild type animal
(3.3 months) falls within the
445 average clinical duration for BSE-H of 2-4.5 months reported in
previous studies (34, 37-39).
446 Interestingly, the incubation period for the EK211 animal (9.8 MPI) was
just 55% of that of the wild
447 type animal challenged with the same inoculum and the clinical duration
(2 weeks) was also very short.
448 This supports our hypothesis that cattle with the E211K polymorphism
are predisposed to a rapid onset
449 of BSE-H when exposed (10).
450
451 Prominent large aggregates and plaque-like accumulations of PrPSc were
observed in the wild type
452 animal which is consistent with previous reports for BSE-H challenged
cattle (34, 37). These
453 immunolabeling types were not observed in the E211K animal (or BSE-C
challenged cattle). Both
454 E211K BSE-H challenged cattle showed characteristic PrPSc accumulation
in retinal ganglion cells and
455 a significant increase in b-wave implicit time, significant retinal
thinning compared to age-matched
456 controls, as has been reported previously for E211K and wild type BSE-H
cases (10, 40).
457
458 The K211 allele did not affect the molecular profile of PrPSc in BSE-C
challenged cattle, and thus
Provisional
13
459 would not mask the presence of feedborne BSE-C. PrPSc from the
brainstem at the level of the obex
460 showed a similar western blot migration pattern in the two E211K BSE-H
challenged cattle. However,
461 the relative amounts of mono- versus diglycosylated PrPSc in these
samples were different, with values
462 for the EK211 animal lying midway between the wild type EK211 BSE-H
challenged animal and the
463 two BSE-C challenged animals. Furthermore, on western blot of
cerebellum, an additional band was
464 observed in the EK211 animal challenged with E211K BSE-H but not the
wild type animal. These
465 differences in the molecular characteristics appear to be genotype,
rather than inoculum, driven and
466 further work is needed to determine the molecular explanations for
these observations.
467
468 Previously, we demonstrated that BSE-C and BSE-H cattle brain
homogenates can be discriminated by
469 their resistance to denaturation in guanidine hydrochloride (GdnHCl) in
a whole-homogenate, ELISA470
based stability assay (30). Specifically, BSE-H PrPSc is more resistant to
denaturation in GdnHCl than
471 BSE-C PrPSc. Data from the present study support our previous findings.
In addition, stability curves
472 for cattle that received the same inoculum were similar to each other,
regardless of PRNP genotype,
473 and even in the case of heterologous inoculum-host genotype
combinations, the stability curve of the
474 recipient was similar to the inoculum isolate, rather than the
homologous genotype inoculum isolate.
475
476 The bovine E211K PRNP polymorphism is homologous to the human E200K
mutation that is
477 associated with familial Creutzfeldt-Jakob disease (fCJD) (41).
Therefore, we considered possible
478 similarities between the epidemiology and phenotypic expression of
prion disease in EK200 humans
479 and EK211 cattle.
480
481 The human E200K mutation accounts for >70% of cases of fCJD (42)
while the bovine E211K
482 polymorphism has only been detected in a single case (8) out of the
approximately 60 cases of atypical
483 BSE-H diagnosed to date (43). The E211K polymorphism is very rare in
cattle; it has not been detected
484 in cattle tested in the United States (n = 6062 cattle tested) (44),
China (n = 349) (45), Poland (46), or
485 Pakistan (n = 236 cattle and n = 281 buffalo) (47). We currently have
non-inoculated heterozygous and
486 homozygous K211 cattle under observation for the potential development
of genetic BSE-H.
487
488 On western blot, an additional fragment in PrPSc from cerebellum has
been reported in an E200K-129V
489 CJD case (48). This band migrates at 17 kDa in contrast to the 23 kDa
additional band observed in the
490 cerebellum from the E211K BSE-H challenged EK211 animal in this study
(10). With regards to
491 immunohistochemistry, the characteristic stripe-like immunolabeling in
the molecular layer of the
492 cerebellar cortex reported in E200K CJD cases (4) was not observed in
cattle in this study. Nor was
493 ‘type III’ intraneuronal immunoreactivity (small, globular, 1.5-4.0 μm
diameter, darkly
494 immunostained, intracytoplasmic PrPSc accumulations), which has been
significantly associated with a
495 subset of E200K fCJD cases (49).
496
497 Due to the rarity of the E211K polymorphism in cattle and the small
number of cases of prion disease
498 in E211K cattle available for examination at this time, further work is
needed to determine the
499 relationship between prion disease associated with the E211K bovine
polymorphism and the human
500 E200K mutation.
501
502 In this study we have demonstrated that, in EK211 and wild type cattle
challenged with BSE-C or
503 E211K BSE-H, inoculum strain has a greater effect on disease phenotype
than host genotype. The
504 phenotype of E211K BSE-H remains stable when transmitted to cattle
without the K211
505 polymorphism, although a number of differences were observed between
the EK211 compared to the
506 wild type animal. In addition, the phenotype of E211K BSE-H shows a
number of features that allow it
Provisional
14
507 to be differentiated from BSE-C in both wild type and heterozygous
animals.
508
509 Acknowledgements
510 The authors thank Martha
Eric Nicholson, Ph.D. Research Chemist National Animal Disease Center U.S.
Department of Agriculture Ames, IA
Abstract:
Thermodynamic insight into the basis of genetic prion disease in
cattle
Prion diseases or transmissible spongiform encephalopathies (TSEs), are an
unusual class of infectious disease. The causative agent of TSEs is a misfolded
form of a host-encoded protein. In humans and cattle, prion disease can
originate through infectious, spontaneous, and genetic processes. The most
common genetic prion disease in humans is caused by the substitution of a lysine
for a glutamic acid at position 200 (E200K) resulting in a heritable form of
CJD. Rodent models of E200K CJD have proven interesting but have significant
limitations including the need to use human-mouse chimeric protein constructs to
reproduce a disease phenotype. The analogous amino acid substitution in cattle
(E211K) was first identified in a case of BSE in the U.S. in 2006 and
subsequently found in the only living offspring of that animal. This EK211
heterozygous animal has been used to develop a herd of EE211, EK211, and KK211
cattle for research on genetic TSEs. To date, our results do not faithfully
replicate the observations from transgenic rodent models. These results led us
to pursue additional studies of the folding and stability of E211K prion
protein. Our studies implicate differences in the unfolded state of the
wild-type and E211K protein in genetic prion disease in cattle.
Monday, May 09, 2016
A comparison of classical and H-type bovine spongiform encephalopathy
associated with E211K prion protein polymorphism in wild type and EK211 cattle
following intracranial inoculation
Alabama BSE Investigation Final Epidemiology Report
May 2, 2006
Summary:
Despite a thorough investigation of two farms that were known to contain
the index cow, and 35 other farms that might have supplied the index cow to the
farms where the index case was known to have resided, the investigators were
unable to locate the herd of origin. The index case did not have unique or
permanent identification, plus, the size and color of the cow being traced is
very common in the Southern United States. Due to the unremarkable appearance of
solid red cows, it is not easy for owners to remember individual animals. In the
Southern United States, it is common business practice to buy breeding age cows
and keep them for several years while they produce calves. Most calves produced
are sold the year they are born, whereas breeding cows are sold when there is a
lapse in breeding, which can occur multiple times in cows’ lives. For all of
these reasons, USDA was unable to locate the herd of origin.
Wednesday, May 2, 2012
ALABAMA MAD COW g-h-BSEalabama In this study, we identified a novel
mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed
BSE positive cow from Alabama, United States of America. This mutation is
identical to the E200K pathogenic mutation found in humans with a genetic form
of CJD. This finding represents the first report of a confirmed case of BSE with
a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that
the bovine Prnp E211K mutation most likely has caused BSE in "the approximately
10-year-old cow" carrying the E221K mutation.
Saturday, August 14, 2010
Monday, August 9, 2010
However, a BSE expert said that consumption of infected material is the
only known way that cattle get the disease under natural conditons.
“In view of what we know about BSE after almost 20 years experience,
contaminated feed has been the source of the epidemic,” said Paul Brown, a
scientist retired from the National Institute of Neurological Diseases and
Stroke.
BSE is not caused by a microbe. It is caused by the misfolding of the
so-called “prion protein” that is a normal constituent of brain and other
tissues. If a diseased version of the protein enters the brain somehow, it can
slowly cause all the normal versions to become misfolded. It is possible the
disease could arise spontaneously, though such an event has never been recorded,
Brown said.
What irks many scientists is the USDA’s April 25 statement that the rare
disease is “not generally associated with an animal consuming infected
feed.”
The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown,
one of the world’s experts on this type of disease who retired recently from the
National Institutes of Health. "(The agency) has no foundation on which to base
that statement.”
• The California cow's BSE might have come from feed—and cows are still
being fed cow protein. Now, as noted above, the USDA reports that the California
case had "atypical" BSE, which, it says, is thought to derive spontaneously, not
from feed. "USDA confirmed the animal was positive for atypical BSE, a very rare
form of the disease not generally associated with an animal consuming infected
feed," the USDA wrote in a Wednesday statement. In a Friday morning email, a
USDA press officer confirmed to me that the atypical BSE in question is of the
L-type, which, as I showed in my last post, has been shown under lab conditions
to be far more virulent than what scientists call "classical" BSE, the kind that
wrought havoc in the UK in the 1990s.
The feed question is vital. If the cow indeed developed BSE through some
genetic mutation and not through feed, then this particular mad cow instance can
be viewed as a random and extremely rare event. But if feed was the pathway,
then we have to ask hard—and for the dairy and beef industries, extremely
uncomfortable—questions about just what we're feeding our nation's vast herd of
cows. And if that cow contracted BSE from what it ate, wouldn't other cows have
been exposed, too?
Paul Brown, a scientist retired from the National Institute of Neurological
Diseases and Stroke, questions the USDA's assertion that atypical BSE isn't
associated with feed. "The most likely explanation is that it arises from the
same source as typical BSE," he said, which is infected feed. He added that it's
a "theoretical possibility" that the California BSE case arose spontaneously,
but "there's no evidence for it."
Linda Detwiler, a clinical professor in the Department of Pathobiology and
Population Medicine at Mississippi State University, told me via phone that the
current scientific thinking is that "atypical" BSE types do probably arise
spontaneously, but "feed certainly can't be ruled out." Ermias Belay, associate
director for epidemiological science at the CDC's Division of High-Consequence
Pathogens and Pathology, echoed that assessment in a phone interview.
Now, back in 1997, in response to the UK mad cow crisis, the FDA banned the
longstanding practice of feeding rendered cow protein to cows, and in 2008
banned "the tissues that have the highest risk for carrying the agent thought to
cause BSE"—brains and spinal tissue from cows older than 30 months—from animal
feed altogether.
But there is still at least one pathway through which cow proteins move
into cow feed: the practice of feeding "poultry litter"—poultry feces mixed with
bedding, spilled feed, and chicken carcasses—to cows. How does that bring cow
protein into cow diets?
----- Original Message -----
From: "Terry S. Singeltary Sr." flounder9@VERIZON.NET
To:
Sent: Tuesday, June 20, 2006 9:30 AM
Subject: MAD COW FEED RECALL USA Albertville, AL -- June 16, 2006 -- H.J.
Baker & Bro.
##################### Bovine Spongiform Encephalopathy
#####################
Subject: MAD COW FEED RECALL USA Albertville, AL -- June 16, 2006 -- H.J.
Baker & Bro. Date: June 20, 2006 at 6:55 am PST MAD COW FEED RECALL USA
Albertville, AL -- June 16, 2006 -- H.J. Baker & Bro. Recall -- Firm Press
Release
FDA posts press releases and other notices of recalls and market
withdrawals from the firms involved as a service to consumers, the media, and
other interested parties. FDA does not endorse either the product or the
company. This listserv covers mainly Class I (life-threatening) recalls. A
complete listing of recalls can be found in the FDA Enforcement Report at:
HJ Baker and Bro., Inc. Announces National Recall of Three Animal Feed
Products Containing Prohibited Ingredients Contact: Mark Hohnbaum
501-664-4870
FOR IMMEDIATE RELEASE -- Albertville, AL -- June 16, 2006 -- H.J. Baker
& Bro. has announced today that in cooperation with the US Food & Drug
Administration (FDA) it has begun efforts to retrieve PRO-PAK WITH PORCINE MEAT
AND BONE, PRO-LAK, AND PRO-AMINO II produced at its Albertville, AL facility.
These products are used as an ingredient in the manufacturing of livestock feed,
including feed for dairy animals. This action is being taken to address
potential risk of unintentional contamination with ruminant derived protein that
may have occurred at this facility from August 2005 to June 2006.
Certain mammalian protein is prohibited for use in ruminant feed. These
products were distributed in bulk or bags to feed manufacturers and dairy farms
in Georgia, Kentucky, Michigan, Florida, Alabama, Tennessee, Mississippi,
California, and Louisiana.
If you have received any of these products, discontinue their use
immediately. Quarantine the product so that it cannot be inadvertently used in
the manufacture of feeds and contact the manufacturer at 501-664-4870 for
further instructions.
"All production and shipment of these products from the Albertville mill
have ceased and all of our customers are being notified of the potential
contamination. With the advice and support of the FDA, we were able to respond
rapidly to address this matter," said Christopher Smith, President &
CEO.
H.J. Baker & Bro., Inc., headquartered in Westport, CT, has served the
fertilizer and animal feed industries since the Company was founded in
1850.
####
FDA's Recalls, Market Withdrawals and Safety Alerts Page:
lets see here now, we have mad cows in Alabama, we have mad cow feed in
Alabama, however JUST another spontaneous event of more BSe. ...TSS
#################### https://lists.aegee.org/bse-l.html
####################
Subject: MAD COW PROTEIN IN COMMERCE USA 2006 RECALL UPDATE
From: "Terry S. Singeltary Sr." <[log in to unmask]>
Reply-To: SAFETY <[log in to unmask]>
Date: Mon, 9 Oct 2006 14:10:37 -0500 Content-Type: text/plain
Parts/Attachments: text/plain (558 lines)
Subject: MAD COW FEED RECALL USA SEPT 6, 2006 1961.72 TONS IN COMMERCE AL,
TN, AND WV
Date: September 6, 2006 at 7:58 am PST
PRODUCT a) EVSRC Custom dairy feed, Recall # V-130-6; b) Performance Chick
Starter, Recall # V-131-6; c) Performance Quail Grower, Recall # V-132-6; d)
Performance Pheasant Finisher, Recall # V-133-6. CODE None RECALLING
FIRM/MANUFACTURER Donaldson & Hasenbein/dba J&R Feed Service, Inc.,
Cullman, AL, by telephone on June 23, 2006 and by letter dated July 19, 2006.
Firm initiated recall is complete.
REASON Dairy and poultry feeds were possibly contaminated with ruminant
based protein.
VOLUME OF PRODUCT IN COMMERCE 477.72 tons DISTRIBUTION AL
______________________________
snip...
Subject: MAD COW FEED RECALLS ENFORCEMENT REPORT FOR AUGUST 9, 2006 KY,
LA, MS, AL, GA, AND TN 11,000+ TONS
Date: August 16, 2006 at 9:19 am PST RECALLS AND FIELD CORRECTIONS:
VETERINARY MEDICINE - CLASS II
______________________________
snip...
______________________________
PRODUCT Bulk custom dairy pre-mixes, Recall # V-120-6 CODE None RECALLING
FIRM/MANUFACTURER Ware Milling Inc., Houston, MS, by telephone on June 23, 2006.
Firm initiated recall is complete.
REASON Possible contamination of dairy animal feeds with ruminant derived
meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE 350 tons DISTRIBUTION AL and MS
______________________________
PRODUCT a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet, 50
lb. bags, Recall # V-121-6; b) Tucker Milling, LLC #31120, Game Bird Breeder
Pellet, 50 lb. bags, Recall # V-122-6; c) Tucker Milling, LLC #31232 Game Bird
Grower, 50 lb. bags, Recall # V-123-6; d) Tucker Milling, LLC 31227-Crumble,
Game Bird Starter, BMD Medicated, 50 lb bags, Recall # V-124-6; e) Tucker
Milling, LLC #31120, Game Bird Breeder, 50 lb bags, Recall # V-125-6; f) Tucker
Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags, Recall # V-126-6; g)
Tucker Milling, LLC #30116, TM Broiler Finisher, 50 lb bags, Recall # V-127-6
CODE All products manufactured from 02/01/2005 until 06/20/2006 RECALLING
FIRM/MANUFACTURER Recalling Firm: Tucker Milling LLC, Guntersville, AL, by
telephone and visit on June 20, 2006, and by letter on June 23, 2006.
Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated recall
is ongoing.
REASON Poultry and fish feeds which were possibly contaminated with
ruminant based protein were not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 7,541-50 lb bags
DISTRIBUTION AL, GA, MS, and TN
END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006
###
Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125
TONS
Products manufactured from 02/01/2005 until 06/06/2006 Date: August 6, 2006
at 6:16 pm PST PRODUCT a) CO-OP 32% Sinking Catfish, Recall # V-100-6; b)
Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6;
c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6; d) CO-OP 32% Sinking
Catfish Food Medicated, Recall # V-103-6; e) "Big Jim's" BBB Deer Ration, Big
Buck Blend, Recall # V-104-6; f) CO-OP 40% Hog Supplement Medicated Pelleted,
Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6; g) Pig Starter Pell II, 18%
W/MCDX Medicated 282020, Carbadox -- 0.0055%, Recall # V-106-6; h) CO-OP
STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to 20 Weeks,
Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6;
i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6; j)
CO-OP LAYING CRUMBLES, Recall # V-109-6; k) CO-OP QUAIL FLIGHT CONDITIONER
MEDICATED, net wt 50 Lbs, Recall # V-110-6; l) CO-OP QUAIL STARTER MEDICATED,
Net Wt. 50 Lbs, Recall # V-111-6; m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs,
Recall # V-112-6 CODE Product manufactured from 02/01/2005 until 06/06/2006
RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL, by
telephone, fax, email and visit on June 9, 2006. FDA initiated recall is
complete.
REASON Animal and fish feeds which were possibly contaminated with ruminant
based protein not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 125 tons DISTRIBUTION AL and FL
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE Sun Jul 16, 2006
09:22 71.248.128.67
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II
______________________________
PRODUCT a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy
Animals, Recall # V-079-6; b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net
weight 50lb (22.6 kg), Recall # V-080-6; c) PRO-PAK, MARINE & ANIMAL PROTEIN
CONCENTRATE FOR USE IN ANIMAL FEED, Recall # V-081-6; d) Feather Meal, Recall #
V-082-6 CODE a) Bulk b) None c) Bulk d) Bulk RECALLING FIRM/MANUFACTURER H. J.
Baker & Bro., Inc., Albertville, AL, by telephone on June 15, 2006 and by
press release on June 16, 2006. Firm initiated recall is ongoing.
REASON Possible contamination of animal feeds with ruminent derived meat
and bone meal.
VOLUME OF PRODUCT IN COMMERCE 10,878.06 tons
DISTRIBUTION Nationwide
END OF ENFORCEMENT REPORT FOR July 12, 2006
###
*** (see mad cow feed in COMMERCE IN ALABAMA...TSS)
BANNED MAD COW FEED IN COMMERCE IN ALABAMA
Date: September 6, 2006 at 7:58 am PST PRODUCT a) EVSRC Custom dairy feed,
Recall # V-130-6; b) Performance Chick Starter, Recall # V-131-6; c) Performance
Quail Grower, Recall # V-132-6; d) Performance Pheasant Finisher, Recall #
V-133-6.
CODE None RECALLING FIRM/MANUFACTURER Donaldson & Hasenbein/dba J&R
Feed Service, Inc., Cullman, AL, by telephone on June 23, 2006 and by letter
dated July 19, 2006. Firm initiated recall is complete.
REASON
Dairy and poultry feeds were possibly contaminated with ruminant based
protein.
VOLUME OF PRODUCT IN COMMERCE 477.72 tons
DISTRIBUTION AL
______________________________
PRODUCT Bulk custom dairy pre-mixes, Recall # V-120-6 CODE None RECALLING
FIRM/MANUFACTURER Ware Milling Inc., Houston, MS, by telephone on June 23, 2006.
Firm initiated recall is complete.
REASON Possible contamination of dairy animal feeds with ruminant derived
meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE 350 tons
DISTRIBUTION AL and MS
______________________________
PRODUCT a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet, 50
lb. bags, Recall # V-121-6; b) Tucker Milling, LLC #31120, Game Bird Breeder
Pellet, 50 lb. bags, Recall # V-122-6; c) Tucker Milling, LLC #31232 Game Bird
Grower, 50 lb. bags, Recall # V-123-6; d) Tucker Milling, LLC 31227-Crumble,
Game Bird Starter, BMD Medicated, 50 lb bags, Recall # V-124-6; e) Tucker
Milling, LLC #31120, Game Bird Breeder, 50 lb bags, Recall # V-125-6; f) Tucker
Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags, Recall # V-126-6; g)
Tucker Milling, LLC #30116, TM Broiler Finisher, 50 lb bags, Recall #
V-127-6
CODE All products manufactured from 02/01/2005 until 06/20/2006 RECALLING
FIRM/MANUFACTURER Recalling Firm: Tucker Milling LLC, Guntersville, AL, by
telephone and visit on June 20, 2006, and by letter on June 23, 2006.
Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated recall
is ongoing.
REASON Poultry and fish feeds which were possibly contaminated with
ruminant based protein were not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 7,541-50 lb bags
DISTRIBUTION AL, GA, MS, and TN
END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006
###
Subject: MAD COW FEED RECALL AL AND FL
VOLUME OF PRODUCT IN COMMERCE 125 TONS
Products manufactured from 02/01/2005 until 06/06/2006 Date: August 6, 2006
at 6:16 pm PST PRODUCT
a) CO-OP 32% Sinking Catfish, Recall # V-100-6; b) Performance Sheep Pell
W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6; c) Pro 40% Swine Conc
Meal -- 50 lb, Recall # V-102-6; d) CO-OP 32% Sinking Catfish Food Medicated,
Recall # V-103-6; e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall #
V-104-6; f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton,
50 lb. bag, Recall # V-105-6; g) Pig Starter Pell II, 18% W/MCDX Medicated
282020, Carbadox -- 0.0055%, Recall # V-106-6; h) CO-OP STARTER-GROWER CRUMBLES,
Complete Feed for Chickens from Hatch to 20 Weeks, Medicated, Bacitracin
Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6; i) CO-OP LAYING
PELLETS, Complete Feed for Laying Chickens, Recall # 108-6; j) CO-OP LAYING
CRUMBLES, Recall # V-109-6; k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt
50 Lbs, Recall # V-110-6; l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs,
Recall # V-111-6; m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 CODE
Product manufactured from 02/01/2005 until 06/06/2006
RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL,
by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is
complete.
REASON Animal and fish feeds which were possibly contaminated with ruminant
based protein not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 125 tons
DISTRIBUTION AL and FL
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE Sun Jul 16, 2006
09:22 71.248.128.67
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II
______________________________
PRODUCT a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy
Animals, Recall # V-079-6; b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net
weight 50lb (22.6 kg), Recall # V-080-6; c) PRO-PAK, MARINE & ANIMAL PROTEIN
CONCENTRATE FOR USE IN ANIMAL FEED, Recall # V-081-6; d) Feather Meal, Recall #
V-082-6 CODE a) Bulk b) None c) Bulk d) Bulk RECALLING FIRM/MANUFACTURER H. J.
Baker & Bro., Inc., Albertville, AL, by telephone on June 15, 2006 and by
press release on June 16, 2006. Firm initiated recall is ongoing.
REASON
Possible contamination of animal feeds with ruminent derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE 10,878.06 tons
DISTRIBUTION Nationwide
END OF ENFORCEMENT REPORT FOR July 12, 2006
###
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN
COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
___________________________________
PRODUCT Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash
Dried, Recall # V-024-2007 CODE Cattle feed delivered between 01/12/2007 and
01/26/2007 RECALLING FIRM/MANUFACTURER Pfeiffer, Arno, Inc, Greenbush, WI. by
conversation on February 5, 2007. Firm initiated recall is ongoing.
REASON
Blood meal used to make cattle feed was recalled because it was cross-
contaminated with prohibited bovine meat and bone meal that had been
manufactured on common equipment and labeling did not bear cautionary BSE
statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI ___________________________________
PRODUCT Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL
Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal,
TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY
Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST
POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY
Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC
MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR,
V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML
W/SMARTA, Recall # V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with
commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm
initiated recall is complete.
REASON Products manufactured from bulk feed containing blood meal that was
cross contaminated with prohibited meat and bone meal and the labeling did not
bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
Saturday, November 6, 2010
TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the
EU
Berne, 2010 TAFS INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND
FOOD SAFETY a non-profit Swiss Foundation
MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...
***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate
Model
***Infectivity in skeletal muscle of BASE-infected cattle
***feedstuffs- It also suggests a similar cause or source for atypical BSE
in these countries.
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim
McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre,
Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of
Calgary, Canada
Background: Three BSE types (classical and two atypical) have been
identified on the basis of molecular characteristics of the misfolded protein
associated with the disease. To date, each of these three types have been
detected in Canadian cattle. Objectives: This study was conducted to further
characterize the 16 Canadian BSE cases based on the biochemical properties of
there associated PrPres.
Methods: Immuno-reactivity, molecular weight, glycoform profiles and
relative proteinase K sensitivity of the PrPres from each of the 16 confirmed
Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type
and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and
changes in glycosylation similar to other atypical BSE cases. PK digestion under
mild and stringent conditions revealed a reduced protease resistance of the
atypical cases compared to the C-type cases. N terminal- specific antibodies
bound to PrPres from H type but not from C or L type. The C-terminal-specific
antibodies resulted in a shift in the glycoform profile and detected a fourth
band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular
characteristics similar to those described for classical and atypical BSE cases
from Europe and Japan. This supports the theory that the importation of BSE
contaminated feedstuff is the source of C-type BSE in Canada. It also suggests a
similar cause or source for atypical BSE in these countries.
***feedstuffs- It also suggests a similar cause or source for atypical BSE
in these countries.
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans.
full text ;
atypical L-type BASE BSE
Tuesday, May 1, 2012
BSE MAD COW LETTERS TO USDA (Tom Vilsack, Secretary of Agriculture) and FDA
(Magaret Hamburg, Commissioner of FDA) May 1, 2012
Wednesday, July 15, 2015
Additional BSE TSE prion testing detects pathologic lesion in unusual brain
location and PrPsc by PMCA only, how many cases have we missed?
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67
PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in
unusual brain location and PrPsc detection by PMCA only.
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Posted by flounder on 03 Jul 2015 at 16:53 GMT
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched.
However, in the PMCA with supplements (digitonin, synthetic polyA and
heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, our findings suggest that possible transmission risk of H-type
BSE to sheep and human. Bioassay will be required to determine whether the PMCA
products are infectious to these animals.
>>>Although these results were not compatible with the previous
reports describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, our findings suggest that possible transmission risk of H-type
BSE to sheep and human.<<<
Sunday, August 28, 2016
CONFIDENTIAL
Transmissible Spongiform Encephalopathy TSE Prion and how Politics and
Greed by the Industry spread madcow type diseases from species to species and
around the globe
TSE PRIONS AKA MAD COW TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH
MY!
P-088 Transmission of experimental CH1641-like scrapie to bovine PrP
overexpression mice
Kohtaro Miyazawa1, Kentaro Masujin1, Hiroyuki Okada1, Yuichi Matsuura1,
Takashi Yokoyama2
1Influenza and Prion Disease Research Center, National Institute of Animal
Health, NARO, Japan; 2Department of Planning and General Administration,
National Institute of Animal Health, NARO
Introduction: Scrapie is a prion disease in sheep and goats. CH1641-lke
scrapie is characterized by a lower molecular mass of the unglycosylated form of
abnormal prion protein (PrpSc) compared to that of classical scrapie. It is
worthy of attention because of the biochemical similarities of the Prpsc from
CH1641-like and BSE affected sheep. We have reported that experimental
CH1641-like scrapie is transmissible to bovine PrP overexpression (TgBoPrP) mice
(Yokoyama et al. 2010). We report here the further details of this transmission
study and compare the biological and biochemical properties to those of
classical scrapie affected TgBoPrP mice.
Methods: The details of sheep brain homogenates used in this study are
described in our previous report (Yokoyama et al. 2010). TgBoPrP mice were
intracerebrally inoculated with a 10% brain homogenate of each scrapie strain.
The brains of mice were subjected to histopathological and biochemical analyses.
Results: Prpsc banding pattern of CH1641-like scrapie affected TgBoPrP mice
was similar to that of classical scrapie affected mice. Mean survival period of
CH1641-like scrapie affected TgBoPrP mice was 170 days at the 3rd passage and it
was significantly shorter than that of classical scrapie affected mice (439
days). Lesion profiles and Prpsc distributions in the brains also differed
between CH1641-like and classical scrapie affected mice.
Conclusion: We succeeded in stable transmission of CH1641-like scrapie to
TgBoPrP mice. Our transmission study demonstrates that CH 1641-like scrapie is
likely to be more virulent than classical scrapie in cattle.
WS-02
Scrapie in swine: A diagnostic challenge
Justin J Greenlee1, Robert A Kunkle1, Jodi D Smith1, Heather W. Greenlee2
1National Animal Disease Center, US Dept. of Agriculture, Agricultural
Research Service, United States; 2Iowa State University College of Veterinary
Medicine
A naturally occurring prion disease has not been recognized in swine, but
the agent of bovine spongiform encephalopathy does transmit to swine by
experimental routes. Swine are thought to have a robust species barrier when
exposed to the naturally occurring prion diseases of other species, but the
susceptibility of swine to the agent of sheep scrapie has not been thoroughly
tested.
Since swine can be fed rations containing ruminant derived components in
the United States and many other countries, we conducted this experiment to test
the susceptibility of swine to U.S. scrapie isolates by intracranial and oral
inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the
brains of clinically ill sheep from the 4th passage of a serial passage study of
the U.S scrapie agent (No. 13-7) through susceptible sheep that were homozygous
ARQ at prion protein residues 136, 154, and 171, respectively. Pigs were
inoculated intracranially (n=19) with a single 0.75 ml dose or orally (n=24)
with 15 ml repeated on 4 consecutive days. Necropsies were done on a subset of
animals at approximately six months post inoculation (PI), at the time the pigs
were expected to reach market weight. Remaining pigs were maintained and
monitored for clinical signs of TSE until study termination at 80 months PI or
when removed due to intercurrent disease (primarily lameness). Brain samples
were examined by immunohistochemistry (IHC), western blot (WB), and
enzyme-linked immunosorbent assay (ELISA). Brain tissue from a subset of pigs in
each inoculation group was used for bioassay in mice expressing porcine PRNP.
At six-months PI, no evidence of scrapie infection was noted by any
diagnostic method. However, at 51 months of incubation or greater, 5 animals
were positive by one or more methods: IHC (n=4), WB (n=3), or ELISA (n=5).
Interestingly, positive bioassay results were obtained from all inoculated
groups (oral and intracranial; market weight and end of study).
Swine inoculated with the agent of scrapie by the intracranial and oral
routes do not accumulate abnormal prion protein (PrPSc) to a level detectable by
IHC or WB by the time they reach typical market age and weight. However, strong
support for the fact that swine are potential hosts for the agent of scrapie
comes from positive bioassay from both intracranially and orally inoculated pigs
and multiple diagnostic methods demonstrating abnormal prion protein in
intracranially inoculated pigs with long incubation times.
Curriculum Vitae
Dr. Greenlee is Research Veterinary Medical Officer in the Virus and Prion
Research Unit at the National Animal Disease Center, US Department of
Agriculture, Agricultural Research Service. He applies his specialty in
veterinary anatomic pathology to focused research on the intra- and interspecies
transmission of prion diseases in livestock and the development of antemortem
diagnostic assays for prion diseases. In addition, knockout and transgenic mouse
models are used to complement ongoing experiments in livestock species. Dr.
Greenlee has publications in a number of topic areas including prion agent
decontamination, effects of PRNP genotype on susceptibility to the agent of
sheep scrapie, characterization of US scrapie strains, transmission of chronic
wasting disease to cervids and cattle, features of H-BSE associated with the
E211 K polymorphism, and the development of retinal assessment for antemortem
screening for prion diseases in sheep and cattle. Dr. Greenlee obtained his DVM
degree and completed the PhD/residency program in Veterinary Pathology at Iowa
State University. He is a Diplomate of the American College of Veterinary
Pathologists.
and I am reminded of the ch1641 strain that is like BSE ;
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q
(AAQQ) and the disease phenotype is similar to that seen with experimental
strain CH1641.
RESEARCH ARTICLE
Phenotype Shift from Atypical Scrapie to CH1641 following Experimental
Transmission in Sheep
Marion M. Simmons*, S. Jo Moore¤a, Richard Lockey¤b, Melanie J. Chaplin,
Timm Konold, Christopher Vickery, John Spiropoulos
Animal and Plant Health Agency—Weybridge, Woodham Lane, Addlestone, Surrey,
KT15 3NB, United Kingdom
¤a Current address: School of Veterinary and Biomedical Sciences, Murdoch
University, South Street, Murdoch, Western Australia, 6150, Australia
¤b Current address: University of Southampton, Southampton, SO17 1BJ,
United Kingdom * marion.simmons@apha.gsi.gov.uk
Abstract
The interactions of host and infecting strain in ovine transmissible
spongiform encephalopathies are known to be complex, and have a profound effect
on the resulting phenotype of disease. In contrast to classical scrapie, the
pathology in naturally-occurring cases of atypical scrapie appears more
consistent, regardless of genotype, and is preserved on transmission within
sheep homologous for the prion protein (PRNP) gene. However, the stability of
transmissible spongiform encephalopathy phenotypes on passage across and within
species is not absolute, and there are reports in the literature where
experimental transmissions of particular isolates have resulted in a phenotype
consistent with a different strain. In this study, intracerebral inoculation of
atypical scrapie between two genotypes both associated with susceptibility to
atypical forms of disease resulted in one sheep displaying an altered phenotype
with clinical, pathological, biochemical and murine bioassay characteristics all
consistent with the classical scrapie strain CH1641, and distinct from the
atypical scrapie donor, while the second sheep did not succumb to challenge. One
of two sheep orally challenged with the same inoculum developed atypical scrapie
indistinguishable from the donor. This study adds to the range of transmissible
spongiform encephalopathy phenotype changes that have been reported following
various different experimental donor-recipient combinations. While these
circumstances may not arise through natural exposure to disease in the field,
there is the potential for iatrogenic exposure should current disease
surveillance and feed controls be relaxed. Future sheep to sheep transmission of
atypical scrapie might lead to instances of disease with an alternative
phenotype and onward transmission potential which may have adverse implications
for both public health and animal disease control policies.
snip...
Despite naturally-occurring atypical scrapie being observed in a range of
genotypes, successful experimental transmissions of clinical disease have so far
only been reported within a particular homologous donor-recipient genotype model
using sheep which are AHQ/AHQ homozygous [8,15,16]. These published
transmissions represent part of a large study at APHA which has been running
since 2004, investigating the potential transmissibility of atypical scrapie in
a range of both homologous and cross-genotype combinations. Here we describe an
unexpected and interesting finding from that study where one experimental
challenge in which atypical scrapie from an ARR/ARR donor was inoculated
intracerebrally into two AHQ/AHQ recipient sheep, and in one of them the
resulting disease had a phenotype that was indistinguishable from CH1641 [29], a
classical scrapie strain which has some BSE-like Western blot properties.
Subject: more on scrapie/BSE strain CH1641
From: tom
Reply-To: Bovine Spongiform Encephalopathy
Date: Sun, 10 Jan 1999 21:52:05 -0800
Content-Type: text/plain
Parts/Attachments: Parts/Attachments text/plain (37 lines) Reply Reply
Recall a forthcoming J Gen Virol Jan 1999 v80:1 - 4 says there are
similarities between BSE and an experimental isolate of natural scrapie, CH1641.
This might then be the long-sought missing scrapie strain that could have given
rise to the BSE epidemic. It would raise additional questions about the
harmlessness to humans of scrapie.
On the other hand, CH1641 happened to be one of the scrapie strains studied
very recently by Collinge's group, Neurosci Lett. 1998 Oct 23;255(3):159-62. It
did not have the prp-sc type identical to BSE passaged in sheep.
The CH1641 strain is mentioned only twice before in Medline abstracts
(though there could be many fulltext mentions), one of these being the original
naming of the strain in 1988:
The unusual properties of CH1641, a sheep-passaged isolate of
scrapie.
Foster JD, Dickinson AG Vet Rec 1988 Jul 2;123(1):5-8
An isolate of scrapie designated CH1641 was identified from a natural case
of scrapie in a Cheviot sheep by passage in sheep and goats. It has not been
possible to transmit scrapie to mice from this source. The Sip gene which
controls the incubation periods of experimental scrapie in Cheviot sheep has two
alleles; sA which shortens and pA which lengthens the incubation periods of most
strains of scrapie after the first experimental injection in sheep (the A group
of strains). The CH1641 isolate differs from them in that the alleles of Sip act
in the opposite way, with incubation being shorter in the pA homozygotes. There
is some evidence that one or more genes, in addition to Sip, may be implicated
in the control of scrapie incubation in sheep and the possibility of a carrier
infection with CH1641 is also discussed.
Novel polymorphisms in the caprine PrP gene: a codon 142 mutation
associated with scrapie incubation period.
J Gen Virol 1996 Nov;77 ( Pt 11):2885-91 Published erratum appears in J Gen
Virol 1997 Mar;78(Pt 3):697 Goldmann W, Martin T, Foster J, Hughes S, Smith G,
Hughes K, Dawson M, Hunter N
Age at disease onset and rate of progression of transmissible spongiform
encephalopathies in man, sheep and mice are modulated by the host genome, in
particular by the PrP gene and its allelic forms. Analysis of the caprine PrP
gene revealed several different alleles. Four PrP protein variants were found,
three of which were goat specific with single amino acid changes at codons 142,
143 and 240. The fourth was identical to the most common sheep PrP protein
variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile --> Met)
appeared to be associated with differing disease incubation periods in goats
experimentally infected with isolates of bovine spongiform encephalopathy, sheep
scrapie CH1641 or sheep-passaged ME7 scrapie.
TSE PRION UPDATE USA 2012
re-BSE in goats can be mistaken for scrapie
Wednesday, January 18, 2012
BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE
February 1, 2012
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural
Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology:
February 2012 - Volume 71 - Issue 2 - p 140–147
Monday, March 21, 2011
Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP
Transgenic Mice
snip...
On the other hand, this component would not be distinguishable from
bovine-passaged BSE prions due to the current limits of the standard biological
methods and/or the molecular tools employed here to characterize prion strains.
Whatever the mechanism, the notion that a passage through an intermediate
species can profoundly alter prion virulence for the human species has important
public-health issues, regarding emerging and/or expanding TSEs, like atypical
scrapie or CWD.
snip...
Taken all together, our results suggest that the possibility of a small
ruminant BSE prion as vCJD causal agent could not be ruled out, which has
important implications on public and animal health policies. On one hand,
although the exact magnitude and characteristic of the vCJD epidemic is still
unclear, its link with cattle BSE is supported by strong epidemiological ground
and several experimental data. On the other hand, the molecular typing performed
in our studies, indicates that the biochemical characteristics of the PrPres
detected in brains of our sheep and goat BSE-inoculated mice seem to be
indistinguishable from that observed in vCJD. Considering the similarity in
clinical manifestation of BSE- and scrapie-affected sheep [48], a masker effect
of scrapie over BSE, as well as a potential adaptation of the BSE agent through
subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have
been detected in many peripheral organs, small ruminant-passaged BSE prions
might be a more widespread source of BSE infectivity compared to cattle [19],
[49], [50]. This fact is even more worrying since our transmission studies
suggest that apparently Met129 human PrP favours a BSE agent with ovine rather
than a bovine sequence. Finally, it is evident that, although few natural cases
have been described and so far we cannot draw any definitive conclusion about
the origin of vCJD, we can not underestimate the risk of a potential goat and/or
sheep BSE agent.
snip...
Technical Abstract:
Prion strains may vary in their ability to transmit to humans and animals.
Few experimental studies have been done to provide evidence of differences
between U.S. strains of scrapie, which can be distinguished by incubation times
in inbred mice, microscopic lesions, immunoreactivity to various antibodies, or
molecular profile (electrophoretic mobility and glycoform ratio). Recent work on
two U.S. isolates of sheep scrapie supports that at least two distinct strains
exist based on differences in incubation time and genotype of sheep affected.
One isolate (No. 13-7) inoculated intracerebrally caused scrapie in sheep AA at
codon 136 (AA136) and QQ at codon 171 (QQ171) of the prion protein in an average
of 19 months post-inoculation (PI) whereas a second isolate (No. x124) caused
disease in less than 12 months after oral inoculation in AV136/QQ171 sheep.
Striking differences were evident when further strain analysis was done in R111,
VM, C57Bl6, and C57Bl6xVM (F1) mice. No. 13-7 did not induce disease in any
mouse strain at any time post-inoculation (PI) nor were brain tissues positive
by western blot (WB). Positive WB results were obtained from mice inoculated
with isolate No. x124 starting at day 380 PI. Incubation times averaged 508,
559, 601, and 633 days PI for RIII, C57Bl6, VM, and F1 mice, respectively.
Further passage will be required to characterize these scrapie strains in mice.
This work provides evidence that multiple scrapie strains exist in U.S.
sheep.
One of these isolates (TR316211) behaved like the CH1641 isolate, with
PrPres features in mice similar to those in the sheep brain. From two other
isolates (O100 and O104), two distinct PrPres phenotypes were identified in
mouse brains, with either high (h-type) or low (l-type) apparent molecular
masses of unglycosylated PrPres, the latter being similar to that observed with
CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions
in the brains of the individual mice. In contrast with BSE, l-type PrPres from
"CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of
these cases (O104), a second passage in mice was performed for two mice with
distinct PrPres profiles. This showed a partial selection of the l-type
phenotype in mice infected with a mouse brain with predominant l-type PrPres,
and it was accompanied by a significant increase in the proportions of the
diglycosylated band. These results are discussed in relation to the diversity of
scrapie and BSE strains.
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q
(AAQQ) and the disease phenotype is similar to that seen with experimental
strain CH1641.
snip...see ;
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical
Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
SHEEP AND BSE
PERSONAL AND CONFIDENTIAL
SHEEP AND BSE
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be
experimentally infected with BSE by intracerebral (ic) or oral challenge (the
latter being equivalent to 0.5 gram of a pool of four cow brains from animals
confirmed to have BSE).
RB264
BSE - TRANSMISSION STUDIES
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural
Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology:
February 2012 - Volume 71 - Issue 2 - p 140–147
4.2.9 A further hypothesis to explain the occurrence of BSE is the
emergence or selection of a strain or strains of the scrapie agent pathogenic
for cattle. Mutations of the scrapie agent. which can occur after a single
passage in mice. have been well documented (9). This phenomenon cannot be
dismissed for BSE. but given the form of the epidemic and the geographically
widespread occurrence of BSE, such a hypothesis" would require the emergence of
a mutant scrapie strain simultaneously in a large . number of sheep flocks, or
cattle. throughout the country. Also. if it resulted "from a localised chance
transmission of the scrapie strain from sheep to cattle giving rise , . to a
mutant. a different pattern of disease would have been expected: its range would
'. have increased with time. Thus the evidence from Britain is against the
disease being due to a new strain of the agent, but we note that in the United
States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to
have Increased markedly. now being nearly 3 times as high as during any previous
period (18).
If the scrapie agent is generated from ovine DNA and thence causes disease
in other species, then perhaps, bearing in mind the possible role of scrapie in
CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the
notifiable disease. ...
PRION 2016 CONFERENCE TOKYO
Saturday, April 23, 2016
*** SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
***
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X
ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION DISEASE
>>> Both of the atypical BSE subtypes are believed to occur
spontaneously,<<<
LMAO!
LOL!
this is a myth, never proven, based on the myth of sporadic cjd, which we
now know is either iatrogenic or zoonotic. it’s also why France wanted or did
stop testing for madcow disease, because France and Poland had an epidemic of
atypical BSE cases, thus proving imo, it was NOT spontaneous...we know now that
the zoonotic potential is very real for scrapie, bse, and cwd, and it may have
already happened, and is being masked as sporadic cjd cases...
SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY
***Moreover, sporadic disease has never been observed in breeding colonies
or primate research laboratories, most notably among hundreds of animals over
several decades of study at the National Institutes of Health25, and in nearly
twenty older animals continuously housed in our own facility.***
Discussion: The C, L and H type BSE cases in Canada exhibit molecular
characteristics similar to those described for classical and atypical BSE cases
from Europe and Japan. This supports the theory that the importation of BSE
contaminated feedstuff is the source of C-type BSE in Canada.
*** It also suggests a similar cause or source for atypical BSE in these
countries.
Maximizing profits is all that is going on now, thanks to the OIE BSE MRR
policy, the legal trading of all strains of TSE prion disease globally. ...Terry
S. Singeltary Sr.
atypical BSE spontaneous sporadic ???
Saturday, May 26, 2012
Are USDA assurances on mad cow case 'gross oversimplification'?
SNIP...
*** What irks many scientists is the USDA’s April 25 statement that the
rare disease is “not generally associated with an animal consuming infected
feed.”
*** The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul
Brown, one of the world’s experts on this type of disease who retired recently
from the National Institutes of Health.
*** "(The agency) has no foundation on which to base that statement.”
*** “We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an
official with the USDA during the Clinton Administration now at Mississippi
State.
*** In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows
the origins of atypical cases of BSE,” she said
*** The argument about feed is critical because if feed is the cause, not a
spontaneous mutation, the California cow could be part of a larger outbreak.
SNIP...
Atypical BSE...Spontaneous...LOL
BSE identified in France
Posted May 2, 2016
A cow in northern France has been confirmed to have bovine spongiform
encephalopathy, according to the World Organisation for Animal Health
(OIE).
The cow had developed partial paralysis and was euthanized March 1, a March
25 OIE report states.
BSE is a fatal neurologic prion disease with a typical incubation period of
four to five years. The cow in France was almost 5 years old.
The affected cow had the classic form of BSE, which is most often
associated with feed containing neurologic tissue from infected animals. It is
distinct from atypical BSE, which may develop spontaneously, according to
information from the U.S. Centers for Disease Control and Prevention.
Investigators were trying to identify the source of infection and other
animals at risk for BSE at the time the report was published.
The affected bovine, a Salers female born on April, 8th 2011, showed
paresis and was euthanized on March, 1st 2016. Samples made on March, 4th 2016
during rendering were analyzed at the Department Laboratory of La Somme. The
rapid test proved positive on March, 8th 2016 and the samples were then sent for
further analysis to the National Reference Laboratory, ANSES, which confirmed a
case of classical BSE on March, 21st 2016. The European Union Reference
Laboratory confirmed those results on the basis of documentation on March, 23rd
2016.
>>> It is distinct from atypical BSE, which may develop
spontaneously, according to information from the U.S. Centers for Disease
Control and Prevention.
THIS IS A MYTH $$$
***atypical spontaneous BSE in France LOL***
FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many
spontaneous events of mad cow disease $$$
***so 20 cases of atypical BSE in France, compared to the remaining 40
cases in the remaining 12 Countries, divided by the remaining 12 Countries,
about 3+ cases per country, besides Frances 20 cases. you cannot explain this
away with any spontaneous BSe. ...TSS
Sunday, October 5, 2014
France stops BSE testing for Mad Cow Disease
Thursday, March 24, 2016
FRANCE CONFIRMS BOVINE SPONGIFORM ENCEPHALOPATHY BSE MAD COW (ESB) chez une
vache dans les Ardennes
***atypical spontaneous BSE in France LOL***
FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many
spontaneous events of mad cow disease $$$
If you Compare France to other Countries with atypical BSE, in my opinion,
you cannot explain this with ‘spontaneous’.
Table 1: Number of Atypical BSE cases reported by EU Member States in the
period 2001–2014 by country and by type (L- and H-BSE) (extracted from EU BSE
databases on 1 July 2014). By 2015, these data might be more comprehensive
following a request from the European Commission to Member States for re-testing
and retrospective classification of all positive bovine isolates in the EU in
the years 2003–2009
BSE type
Country 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013(a)
2014(a) Total
H-BSE Austria 1 1
France(b) 1 2 3 1 2 2 2 2 15
Germany 1 1 2
Ireland 1 1 2 1 5
The Netherlands 1 1
Poland 1 1 2
Portugal 1 1
Spain 1 1 2
Sweden 1 1
United Kingdom 1 1 1 1 1 5
Total 2 3 3 1 1 2 2 2 4 4 5 1 4 1 35
L-BSE Austria 1 1 2
Denmark 1 1
France(b) 1 1 1 1 2 1 3 2 1 1 14
Germany 1 1 2
Italy 1 1 1 1 1 5
The Netherlands 1 1 1 3
Poland 1 2 2 1 2 1 2 1 12
Spain 2 2
United Kingdom 1 1 1 1 4
Total 0 5 3 4 3 3 6 3 3 4 3 6 1 1 45
Total Atypical cases (H + L)
2 8 6 5 4 5 8 5 7 8 8 7 5 2 80
(a): Data for 2013-2014 are incomplete and may not include all
cases/countries reported.
(b): France has performed extensive retrospective testing to classify BSE
cases, which is probably the explanation for the higher number of Atypical BSE
cases reported in this country.
The number of Atypical BSE cases detected in countries that have already
identified them seems to be similar from year to year. In France, a
retrospective study of all TSE-positive cattle identified through the compulsory
EU surveillance between 2001 and 2007 indicated that the prevalence of H-BSE and
L-BSE was 0.35 and 0.41 cases per million adult cattle tested, respectively,
which increased to 1.9 and 1.7 cases per million, respectively, in tested
animals over eight years old (Biacabe et al., 2008). No comprehensive study on
the prevalence of Atypical BSE cases has yet been carried out in other EU Member
States. All cases of Atypical BSE reported in the EU BSE databases have been
identified by active surveillance testing (59 % in fallen stock, 38 % in healthy
slaughtered cattle and 4 % in emergency slaughtered cattle). Cases were reported
in animals over eight years of age, with the exception of two cases (one H-BSE
and one L-BSE) detected in Spain in 2011/2012. One additional case of H-BSE was
detected in Switzerland in 2012 in a cow born in Germany in 2005 (Guldimann et
al., 2012).
Atypical BSE study protocol
EFSA Journal 2014;12(7):3798 8
Table 1: Number of Atypical BSE cases reported by EU Member States in the
period 2001–2014 by country and by type (L- and H-BSE) (extracted from EU BSE
databases on 1 July 2014). By 2015, these data might be more comprehensive
following a request from the European Commission to Member States for re-testing
and retrospective classification of all positive bovine isolates in the EU in
the years 2003–2009
BSE type Country 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
2012 2013(a) 2014(a) Total
H-BSE
Austria 1 1
France(b) 1 2 3 1 2 2 2 2 15
Germany 1 1 2 Ireland 1 1 2 1 5
The Netherlands 1 1
Poland 1 1 2
Portugal 1 1
Spain 1 1 2
Sweden 1 1
United Kingdom 1 1 1 1 1 5
Total 2 3 3 1 1 2 2 2 4 4 5 1 4 1 35
L-BSE
Austria 1 1 2
Denmark 1 1
France(b) 1 1 1 1 2 1 3 2 1 1 14
Germany 1 1 2 Italy 1 1 1 1 1 5
The Netherlands 1 1 1 3
Poland 1 2 2 1 2 1 2 1 12
Spain 2 2
United Kingdom 1 1 1 1 4
Total 0 5 3 4 3 3 6 3 3 4 3 6 1 1 45
Total Atypical cases (H + L) 2 8 6 5 4 5 8 5 7 8 8 7 5 2 80
(a): Data for 2013-2014 are incomplete and may not include all
cases/countries reported.
(b): France has performed extensive retrospective testing to classify BSE
cases, which is probably the explanation for the higher number of Atypical BSE
cases reported in this country.
snip...
> (b): France has performed extensive retrospective testing to classify
BSE cases, which is probably the explanation for the higher number of Atypical
BSE cases reported in this country.
LOL!!!
Thursday, July 24, 2014
*** Protocol for further laboratory investigations into the distribution of
infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical
BSE investigations
Sunday, October 5, 2014
*** France stops BSE testing for Mad Cow Disease
we have seen the spontaneous BSE epidemic in France, what about the other
HIGH INCIDENCE ATYPICAL BSE COUNTRY OF POLAND, another atypical spontaneous
event of high incidence. how can this be blamed on a happenstance of nothing,
i.e. old age? goes against all junk science to date on the spontaneous atypical
BSE i.e.
> In 2015, the OIE determined that atypical BSE occurred spontaneously
at a low rate in all cattle populations and would be excluded for BSE risk.
...
>Atypical BSE occurs in older cattle, usually 8 years of age or greater,
and does not appear to be associated with contaminated feed. Like classic or
sporadic CJD in humans, it seems to arise rarely and spontaneously.
and if you believe that lie, myth, junk science, then you will believe this
i.e.
> Regulations from the Food and Drug Administration (FDA) have
prohibited the inclusion of mammalian protein in feed for cattle and other
ruminants since 1997 and have also prohibited high risk tissue materials in all
animal feed since 2009.
LAUGH OUT LOUD ! LOL!
POLAND ATYPICAL BSE AND SPORADIC CJD
Issue 2 Journal for Veterinary Medicine, Biotechnology and Biosafety
Volume 1, Issue 2, June 2015, Pages 12–14
ISSN 2411-3174 (print version) ISSN 2411-0388 (online version)
EPIDEmIOLOGY Of BOVINE SPONGIfORm ENCEPHALOPATHY IN CATTLE IN POLAND
Polak M. P., Zmudzinski J. F.
National Veterinary Research Institute, Pulawy, Poland e-mail:
ppolak@piwet.pulawy.pl
Download PDF (print version)
Citation for print version: Polak M. P. and Zmudzinski J. F. (2015)
‘Epidemiology of bovine spongiform encephalopathy in cattle in Poland’, Journal
for Veterinary Medicine, Biotechnology and Biosafety, 1(2), pp. 12–14.
Download PDF (online version)
Citation for online version: Polak M. P. and Zmudzinski J. F. (2015)
‘Epidemiology of bovine spongiform encephalopathy in cattle in Poland’, Journal
for Veterinary Medicine, Biotechnology and Biosafety. [Online] 1(2), pp. 12–14.
Available at:
Summary. The aim of the paper was to present the epidemiological situation
regarding BSE epidemic in Poland with respect to cattle population, active
surveillance and the control measures. Epidemiological data from the archives of
the national reference laboratory for animal TSEs at the National Veterinary
Research Institute and from the archives of the General Veterinary Inspectorate
in Warsaw were used in the study. Between 2001 and the end of April 2015 BSE was
diagnosed in 75 animals. Sixty one cases were classical BSE and 14 were atypical
BSE (12 of L-type and 2 of H-type). Almost 6 million animals were tested using
rapid tests. Dynamics of C-type BSE shows constant rise until 2005 when the
highest number of cases (20) was recorded with sharp drop in the following
years. Prevalence of atypical BSE shows stable trend with slight fluctuations.
Traditional feeding was used in 65 and 90% of classical and atypical BSE cases,
respectively. On the other hand, traditional feed was supplemented with MBM and
milk replacers in 46 and 10% of classical and atypical BSE cases, respectively.
Despite the high infectious load introduced into Poland especially with MBM, the
number of cases was relatively low. In Poland, relatively high number of
atypical BSE cases was recorded, comprising 19% of all BSE-positive animals.
Mean age of classical BSE cases diagnosed annually does not show a decreasing
trend which may reflect the late introduction of feed ban in Poland.
Keywords: bovine spongiform encephalopathy, Poland, prevalence, prion
protein, control measures
Saturday, July 23, 2016
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND
SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
O.08: H-type bovine spongiform encephalopathy associated with E211K prion
protein polymorphism: Clinical and pathologic features in wild-type and E211K
cattle following intracranial inoculation
S Jo Moore, M Heather West Greenlee, Jodi Smith, Eric Nicholson, Cathy
Vrentas, and Justin Greenlee
United States Department of Agriculture; Ames, IA USA
In 2006 an H-type bovine spongiform encephalopathy (BSE) case was reported
in an animal with an unusual polymorphism (E211K) in the prion protein gene.
Although the prevalence of this polymorphism is low, cattle carrying the K211
allele are predisposed to rapid onset of H-type BSE when exposed. The purpose of
this study was to investigate the phenotype of this BSE strain in wild-type
(E211E) and E211K heterozygous cattle.
One calf carrying the wild-type allele and one E211K calf were inoculated
intracranially with H-type BSE brain homogenate from the US 2006 case that also
carried one K211 allelle. In addition, one wild-type calf and one E211K calf
were inoculated intracranially with brain homogenate from a US 2003 classical
BSE case. All animals succumbed to clinical disease. Survival times for E211K
H-type BSE inoculated catttle (10 and 18 months) were shorter than the classical
BSE inoculated cattle (both 26 months). Significant changes in retinal function
were observed in H-type BSE challenged cattle only. Animals challenged with the
same inoculum showed similar severity and neuroanatomical distribution of
vacuolation and disease-associated prion protein deposition in the brain, though
differences in neuropathology were observed between E211K H-type BSE and
classical BSE inoculated animals. Western blot results for brain tissue from
challenged animals were consistent with the inoculum strains.
This study demonstrates that the phenotype of E211K H-type BSE remains
stable when transmitted to cattle without the E211K polymorphism, and exhibits a
number of features that differ from classical BSE in both wild-type and E211K
cattle.
===================
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi
Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA
and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, our findings suggest that possible transmission risk of H-type
BSE to sheep and human. Bioassay will be required to determine whether the PMCA
products are infectious to these animals.
==============
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. Bioassay will be required to determine whether the PMCA
products are infectious to these animals.
==============
Monday, May 09, 2016
A comparison of classical and H-type bovine spongiform encephalopathy
associated with E211K prion protein polymorphism in wild type and EK211 cattle
following intracranial inoculation
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease
(CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk
Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE,
or less virulent than cBSE? just curious.....''
Professor Kong reply ;
.....snip
''As to the H-BSE, we do not have sufficient data to say one way or
another, but we have found that H-BSE can infect humans. I hope we could publish
these data once the study is complete. Thanks for your interest.''
Best regards, Qingzhong Kong, PhD Associate Professor Department of
Pathology Case Western Reserve University Cleveland, OH 44106 USA
END...TSS
Thursday, December 04, 2008 2:37 PM
"we have found that H-BSE can infect humans."
personal communication with Professor Kong. ...TSS
BSE-H is also transmissible in our humanized Tg mice.
The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
Monday, March 19, 2012
Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform
Encephalopathy PLoS One. 2012; 7(2): e31449.
Tuesday, August 9, 2016
*** Concurrence with OIE Risk Designations for Bovine Spongiform
Encephalopathy [Docket No. APHIS-2015-0055]
Saturday, July 23, 2016
*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING,
AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
Tuesday, July 26, 2016
*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY
2016
Saturday, July 16, 2016
*** Importation of Sheep, Goats, and Certain Other Ruminants [Docket No.
APHIS-2009-0095]RIN 0579-AD10
WITH great disgust and concern, I report to you that the OIE, USDA, APHIS,
are working to further legalize the trading of Transmissible Spongiform
Encephalopathy TSE Pion disease around the globe.
THIS is absolutely insane. it’s USDA INC.
Thursday, October 22, 2015
*** Former Ag Secretary Ann Veneman talks women in agriculture and we talk
mad cow disease USDA and what really happened those mad cows in Texas ***
Monday, June 20, 2016
*** Specified Risk Materials SRMs BSE TSE Prion Program ***
2016 PIGS TSE PRION UPDATE
WS-02
Scrapie in swine: A diagnostic challenge
Justin J Greenlee1, Robert A Kunkle1, Jodi D Smith1, Heather W. Greenlee2
1National Animal Disease Center, US Dept. of Agriculture, Agricultural
Research Service, United States; 2Iowa State University College of Veterinary
Medicine
A naturally occurring prion disease has not been recognized in swine, but
the agent of bovine spongiform encephalopathy does transmit to swine by
experimental routes. Swine are thought to have a robust species barrier when
exposed to the naturally occurring prion diseases of other species, but the
susceptibility of swine to the agent of sheep scrapie has not been thoroughly
tested.
Since swine can be fed rations containing ruminant derived components in
the United States and many other countries, we conducted this experiment to test
the susceptibility of swine to U.S. scrapie isolates by intracranial and oral
inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the
brains of clinically ill sheep from the 4th passage of a serial passage study of
the U.S scrapie agent (No. 13-7) through susceptible sheep that were homozygous
ARQ at prion protein residues 136, 154, and 171, respectively. Pigs were
inoculated intracranially (n=19) with a single 0.75 ml dose or orally (n=24)
with 15 ml repeated on 4 consecutive days. Necropsies were done on a subset of
animals at approximately six months post inoculation (PI), at the time the pigs
were expected to reach market weight. Remaining pigs were maintained and
monitored for clinical signs of TSE until study termination at 80 months PI or
when removed due to intercurrent disease (primarily lameness). Brain samples
were examined by immunohistochemistry (IHC), western blot (WB), and
enzyme-linked immunosorbent assay (ELISA). Brain tissue from a subset of pigs in
each inoculation group was used for bioassay in mice expressing porcine PRNP.
At six-months PI, no evidence of scrapie infection was noted by any
diagnostic method. However, at 51 months of incubation or greater, 5 animals
were positive by one or more methods: IHC (n=4), WB (n=3), or ELISA (n=5).
Interestingly, positive bioassay results were obtained from all inoculated
groups (oral and intracranial; market weight and end of study).
Swine inoculated with the agent of scrapie by the intracranial and oral
routes do not accumulate abnormal prion protein (PrPSc) to a level detectable by
IHC or WB by the time they reach typical market age and weight. However, strong
support for the fact that swine are potential hosts for the agent of scrapie
comes from positive bioassay from both intracranially and orally inoculated pigs
and multiple diagnostic methods demonstrating abnormal prion protein in
intracranially inoculated pigs with long incubation times.
Curriculum Vitae
Dr. Greenlee is Research Veterinary Medical Officer in the Virus and Prion
Research Unit at the National Animal Disease Center, US Department of
Agriculture, Agricultural Research Service. He applies his specialty in
veterinary anatomic pathology to focused research on the intra- and interspecies
transmission of prion diseases in livestock and the development of antemortem
diagnostic assays for prion diseases. In addition, knockout and transgenic mouse
models are used to complement ongoing experiments in livestock species. Dr.
Greenlee has publications in a number of topic areas including prion agent
decontamination, effects of PRNP genotype on susceptibility to the agent of
sheep scrapie, characterization of US scrapie strains, transmission of chronic
wasting disease to cervids and cattle, features of H-BSE associated with the
E211 K polymorphism, and the development of retinal assessment for antemortem
screening for prion diseases in sheep and cattle. Dr. Greenlee obtained his DVM
degree and completed the PhD/residency program in Veterinary Pathology at Iowa
State University. He is a Diplomate of the American College of Veterinary
Pathologists.
Prion
Volume 9, Issue 4, 2015
Porcine prion protein amyloid
DOI:10.1080/19336896.2015.1065373Per Hammarströma & Sofie Nyströma*
pages 266-277
Received: 1 Jun 2015 Accepted: 17 Jun 2015 Accepted author version posted
online: 28 Jul 2015
© 2015 The Author(s). Published with license by Taylor & Francis Group,
LLC Additional license information
ABSTRACT
Mammalian prions are composed of misfolded aggregated prion protein (PrP)
with amyloid-like features. Prions are zoonotic disease agents that infect a
wide variety of mammalian species including humans. Mammals and by-products
thereof which are frequently encountered in daily life are most important for
human health. It is established that bovine prions (BSE) can infect humans while
there is no such evidence for any other prion susceptible species in the human
food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or
susceptible and resistant pets (cat and dogs, respectively). PrPs from these
species have been characterized using biochemistry, biophysics and neurobiology.
Recently we studied PrPs from several mammals in vitro and found evidence for
generic amyloidogenicity as well as cross-seeding fibril formation activity of
all PrPs on the human PrP sequence regardless if the original species was
resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was
among the studied. Experimentally inoculated pigs as well as transgenic mouse
lines overexpressing porcine PrP have, in the past, been used to investigate the
possibility of prion transmission in pigs. The pig is a species with
extraordinarily wide use within human daily life with over a billion pigs
harvested for human consumption each year. Here we discuss the possibility that
the largely prion disease resistant pig can be a clinically silent carrier of
replicating prions.
SNIP...
CONCLUDING REMARKS Should the topic of porcine PrP amyloid be more of a
worry than of mere academic interest? Well perhaps. Prions are particularly
insidious pathogens. A recent outbreak of peripheral neuropathy in human,
suggests that exposure to aerosolized porcine brain is deleterious for human
health.43,44 Aerosolization is a known vector for prions at least under
experimental conditions.45-47 where a mere single exposure was enough for
transmission in transgenic mice. HuPrP is seedable with BoPrP seeds and even
more so with PoPrP seed (Fig. 1), indicating that humans could be infected by
porcine APrP prions while neurotoxicity associated with spongiform
encephalopathy if such a disease existed is even less clear. Importantly
transgenic mice over-expressing PoPrP are susceptible to BSE and BSE passaged
through domestic pigs implicating that efficient downstream neurotoxicity
pathways in the mouse, a susceptible host for prion disease neurotoxicity is
augmenting the TSE phenotype.25,26 Prions in silent carrier hosts can be
infectious to a third species. Data from Collinge and coworkers.21 propose that
species considered to be prion free may be carriers of replicating prions.
Especially this may be of concern for promiscuous prion strains such as
BSE.19,48 It is rather established that prions can exist in both replicating and
neurotoxic conformations.49,50 and this can alter the way in which new host
organisms can react upon cross-species transmission.51 The na€ıve host can
either be totally resistant to prion infection as well as remain non-infectious,
become a silent non-symptomatic but infectious carrier of disease or be
afflicted by disease with short or long incubation time. The host can harbor
and/or propagate the donor strain or convert the strain conformation to adapt it
to the na€ıve host species. The latter would facilitate infection and shorten
the incubation time in a consecutive event of intra-species transmission. It may
be advisable to avoid procedures and exposure without proper biosafety
precautions as the knowledge of silence carrier species is poor. One case of
iatrogenic CJD in recipient of porcine dura mater graft has been reported in the
literature.52 The significance of this finding is still unknown. The low public
awareness in this matter is exemplified by the practice of using proteolytic
peptide mixtures prepared from porcine brains (Cerebrolysin) as a nootropic
drug. While Cerebrolysin may be beneficial for treatment of severe diseases such
as vascular dementia,53 a long term follow-up of such a product for recreational
use is recommended.
Friday, August 21, 2015
Porcine prion protein amyloid or mad pig disease PSE Porcine Spongiform
Encephalopathy ?
Tuesday, December 16, 2014
Evidence for zoonotic potential of ovine scrapie prions
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves
Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle
Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia
Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier
Andréoletti1, Affiliations Contributions Corresponding author Journal name:
Nature Communications Volume: 5, Article number: 5821 DOI:
doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014
Published 16 December 2014 Article tools Citation Reprints Rights &
permissions Article metrics
Abstract
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant
Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie
prions remains unknown. Mice genetically engineered to overexpress the human
prion protein (tgHu) have emerged as highly relevant models for gauging the
capacity of prions to transmit to humans. These models can propagate human
prions without any apparent transmission barrier and have been used used to
confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie
prions transmit to several tgHu mice models with an efficiency comparable to
that of cattle BSE. The serial transmission of different scrapie isolates in
these mice led to the propagation of prions that are phenotypically identical to
those causing sporadic CJD (sCJD) in humans. These results demonstrate that
scrapie prions have a zoonotic potential and raise new questions about the
possible link between animal and human prions.
Subject terms: Biological sciences• Medical research At a glance
*** In complement to the recent demonstration that humanized mice are
susceptible to scrapie, we report here the first observation of direct
transmission of a natural classical scrapie isolate to a macaque after a 10-year
incubation period. Neuropathologic examination revealed all of the features of a
prion disease: spongiform change, neuronal loss, and accumulation of PrPres
throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of
scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated.
*** Our results underscore the importance of precautionary and protective
measures and the necessity for long-term experimental transmission studies to
assess the zoonotic potential of other animal prion strains.
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a.
Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos,
Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT.
Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas.
France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated
bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD)
disease in human. To date, BSE agent is the only recognized zoonotic prion.
Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that
have been circulating for centuries in farmed ruminants there is no apparent
epidemiological link between exposure to ruminant products and the occurrence of
other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD).
However, the zoonotic potential of the diversity of circulating TSE agents has
never been systematically assessed. The major issue in experimental assessment
of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the
biological phenomenon that limits TSE agents’ propagation from a species to
another. In the last decade, mice genetically engineered to express normal forms
of the human prion protein has proved essential in studying human prions
pathogenesis and modeling the capacity of TSEs to cross the human species
barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants,
we study their transmission ability in transgenic mice expressing human PrPC
(HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC
(129Met or 129Val) are used to determine the role of the Met129Val dimorphism in
susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to
propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be
susceptible to BSE in sheep or goat to a greater degree than the BSE agent in
cattle and that these agents can convey molecular properties and
neuropathological indistinguishable from vCJD. However homozygous 129V mice are
resistant to all tested BSE derived prions independently of the originating
species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in
HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the
efficiency of transmission at primary passage was low, subsequent passages
resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the
emergence of prion strain phenotypes that showed similar characteristics to
those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie
prions have a zoonotic potential and raise new questions about the possible link
between animal and human prions.
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
1978 SCRAPIE IN CONFIDENCE SCJD
1979
SILENCE ON CJD AND SCRAPIE
1980
SILENCE ON CJD AND SCRAPIE
*** 1981 NOVEMBER
Thursday, August 04, 2016
*** MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON
CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL
SCJD
2016
SCRAPIE AND CWD ZOONOSIS
PRION 2016 CONFERENCE TOKYO
Saturday, April 23, 2016
*** SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
***
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X
Transmission of scrapie prions to primate after an extended silent
incubation period
***Moreover, sporadic disease has never been observed in breeding colonies
or primate research laboratories, most notably among hundreds of animals over
several decades of study at the National Institutes of Health25, and in nearly
twenty older animals continuously housed in our own facility.***
Transmission of scrapie prions to primate after an extended silent
incubation period
Emmanuel E. Comoy , Jacqueline Mikol , Sophie Luccantoni-Freire , Evelyne
Correia , Nathalie Lescoutra-Etchegaray , Valérie Durand , Capucine Dehen ,
Olivier Andreoletti , Cristina Casalone , Juergen A. Richt , Justin J. Greenlee
, Thierry Baron , Sylvie L. Benestad , Paul Brown & Jean-Philippe Deslys
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion
disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD)
in humans and having guided protective measures for animal and human health
against animal prion diseases. Recently, partial transmissions to humanized mice
showed that the zoonotic potential of scrapie might be similar to c-BSE. We here
report the direct transmission of a natural classical scrapie isolate to
cynomolgus macaque, a highly relevant model for human prion diseases, after a
10-year silent incubation period, with features similar to those reported for
human cases of sporadic CJD. Scrapie is thus actually transmissible to primates
with incubation periods compatible with their life expectancy, although fourfold
longer than BSE. Long-term experimental transmission studies are necessary to
better assess the zoonotic potential of other prion diseases with high
prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98
scrapie.
snip...
In addition to previous studies on scrapie transmission to primate1,8,9 and
the recently published study on transgenic humanized mice13, our results
constitute new evidence for recommending that the potential risk of scrapie for
human health should not be dismissed. Indeed, human PrP transgenic mice and
primates are the most relevant models for investigating the human transmission
barrier. To what extent such models are informative for measuring the zoonotic
potential of an animal TSE under field exposure conditions is unknown. During
the past decades, many protective measures have been successfully implemented to
protect cattle from the spread of c-BSE, and some of these measures have been
extended to sheep and goats to protect from scrapie according to the principle
of precaution. Since cases of c-BSE have greatly reduced in number, those
protective measures are currently being challenged and relaxed in the absence of
other known zoonotic animal prion disease. We recommend that risk managers
should be aware of the long term potential risk to human health of at least
certain scrapie isolates, notably for lymphotropic strains like the classical
scrapie strain used in the current study. Relatively high amounts of infectivity
in peripheral lymphoid organs in animals infected with these strains could lead
to contamination of food products produced for human consumption. Efforts should
also be maintained to further assess the zoonotic potential of other animal
prion strains in long-term studies, notably lymphotropic strains with high
prevalence like CWD, which is spreading across North America, and atypical/Nor98
scrapie (Nor98)50 that was first detected in the past two decades and now
represents approximately half of all reported cases of prion diseases in small
ruminants worldwide, including territories previously considered as scrapie
free. Even if the prevailing view is that sporadic CJD is due to the spontaneous
formation of CJD prions, it remains possible that its apparent sporadic nature
may, at least in part, result from our limited capacity to identify an
environmental origin.
***Moreover, sporadic disease has never been observed in breeding colonies
or primate research laboratories, most notably among hundreds of animals over
several decades of study at the National Institutes of Health25, and in nearly
twenty older animals continuously housed in our own facility.***
2015
O.05: Transmission of prions to primates after extended silent incubation
periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni,
Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys
Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies
reputed to be transmissible under field conditions since decades. The
transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that
an animal PD might be zoonotic under appropriate conditions. Contrarily, in the
absence of obvious (epidemiological or experimental) elements supporting a
transmission or genetic predispositions, PD, like the other proteinopathies, are
reputed to occur spontaneously (atpical animal prion strains, sporadic CJD
summing 80% of human prion cases). Non-human primate models provided the first
evidences supporting the transmissibiity of human prion strains and the zoonotic
potential of BSE. Among them, cynomolgus macaques brought major information for
BSE risk assessment for human health (Chen, 2014), according to their
phylogenetic proximity to humans and extended lifetime. We used this model to
assess the zoonotic potential of other animal PD from bovine, ovine and cervid
origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical
scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD,
albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked
in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases. We will present an
updated panorama of our different transmission studies and discuss the
implications of such extended incubation periods on risk assessment of animal PD
for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. Bioassay will be required to determine whether the PMCA
products are infectious to these animals.
==============
CWD TSE PRION HUMAN ZOONOSIS POTENTIAL, has it already happened, and being
masked as sporadic CJD? and what about iatrogenic, or the pass if forward,
friendly fire mode of transmission of cwd to humans, same thing, sporadic cjd
?
*** WDA 2016 NEW YORK ***
We found that CWD adapts to a new host more readily than BSE and that human
PrP was unexpectedly prone to misfolding by CWD prions. In addition, we
investigated the role of specific regions of the bovine, deer and human PrP
protein in resistance to conversion by prions from another species. We have
concluded that the human protein has a region that confers unusual
susceptibility to conversion by CWD prions.
Student Presentations Session 2
The species barriers and public health threat of CWD and BSE prions
Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr.
Edward Hoover1 1Colorado State University
Chronic wasting disease (CWD) is spreading rapidly through cervid
populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease)
arose in the 1980s because cattle were fed recycled animal protein. These and
other prion diseases are caused by abnormal folding of the normal prion protein
(PrP) into a disease causing form (PrPd), which is pathogenic to nervous system
cells and can cause subsequent PrP to misfold. CWD spreads among cervids very
efficiently, but it has not yet infected humans. On the other hand, BSE was
spread only when cattle consumed infected bovine or ovine tissue, but did infect
humans and other species. The objective of this research is to understand the
role of PrP structure in cross-species infection by CWD and BSE. To study the
propensity of each species’ PrP to be induced to misfold by the presence of PrPd
from verious species, we have used an in vitro system that permits detection of
PrPd in real-time. We measured the conversion efficiency of various combinations
of PrPd seeds and PrP substrate combinations. We observed the cross-species
behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found
that CWD adapts to a new host more readily than BSE and that human PrP was
unexpectedly prone to misfolding by CWD prions. In addition, we investigated the
role of specific regions of the bovine, deer and human PrP protein in resistance
to conversion by prions from another species. We have concluded that the human
protein has a region that confers unusual susceptibility to conversion by CWD
prions. CWD is unique among prion diseases in its rapid spread in natural
populations. BSE prions are essentially unaltered upon passage to a new species,
while CWD adapts to the new species. This adaptation has consequences for
surveillance of humans exposed to CWD.
Wildlife Disease Risk Communication Research Contributes to Wildlife Trust
Administration Exploring perceptions about chronic wasting disease risks among
wildlife and agriculture professionals and stakeholders
Ms. Alyssa Wetterau1, Dr. Krysten Schuler1, Dr. Elizabeth Bunting1, Dr.
Hussni Mohammed1 1Cornell University
Chronic wasting disease (CWD) is a fatal disease of North American
Cervidae. New York State (NYS, USA) successfully managed an outbreak of CWD in
2005 in both captive and wild white-tailed deer (Odocoileus virginianus) with no
reoccurrence of the disease as of 2015. To attain maximum compliance and
efficacy of management actions for prevention of CWD entry, understanding the
varied risk perceptions will allow for targeted, proactive communication efforts
to address divergences between expert-derived risk assessments and stakeholder
risk perceptions. We examined perceived risks associated with CWD introduction
and exposure among agricultural and wildlife agency professionals within and
outside of NYS, as well as stakeholder groups (e.g., hunters and captive cervid
owners). We measured perceived risk using a risk assessment questionnaire online
via Qualtrics survey software and evaluated similarities within, as well as
differences in, perception among participant groups. New York State biologists
employed by the Department of Environmental Conservation and independent non-NYS
wildlife and agricultural professionals thought CWD risks associated with
captive cervids were high; captive cervid owners thought risks for wild and
captive cervids were low. Agriculture and wildlife professional groups agreed on
general risk perceptions. We ranked 15 individual risk hazards into high and low
medium categories based on all responses. Differences between groups were most
evident in hypothetical disease pathways. Any pathway involving inter-state
import of live cervids received high ranking for all groups except captive
cervid owners. Comparatively low risk perceptions by captive cervid operators
may stem from misinformation, lack of understanding of testing programs, and
indemnity payments for animal depopulation. Communication and education directed
at areas of disagreement may facilitate effective disease prevention and
management.
* No evaluation of determination of CWD risk is required for alternative
livestock or captive wildlife shipped directly to slaughter or to a biosecure
facility approved by the Division and the Dept. of Agriculture.
*** We found that CWD adapts to a new host more readily than BSE and that
human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we
investigated the role of specific regions of the bovine, deer and human PrP
protein in resistance to conversion by prions from another species. We have
concluded that the human protein has a region that confers unusual
susceptibility to conversion by CWD prions. CWD is unique among prion diseases
in its rapid spread in natural populations. BSE prions are essentially unaltered
upon passage to a new species, while CWD adapts to the new species. This
adaptation has consequences for surveillance of humans exposed to CWD. ***
PRION 2016 TOKYO
Zoonotic Potential of CWD Prions: An Update
Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3,
Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6,
Pierluigi Gambetti1, Qingzhong Kong1,5,6
1Department of Pathology, 3National Prion Disease Pathology Surveillance
Center, 5Department of Neurology, 6National Center for Regenerative Medicine,
Case Western Reserve University, Cleveland, OH 44106, USA.
4Department of Biological Sciences and Center for Prions and Protein
Folding Diseases, University of Alberta, Edmonton, Alberta, Canada,
2Encore Health Resources, 1331 Lamar St, Houston, TX 77010
Chronic wasting disease (CWD) is a widespread and highly transmissible
prion disease in free-ranging and captive cervid species in North America. The
zoonotic potential of CWD prions is a serious public health concern, but the
susceptibility of human CNS and peripheral organs to CWD prions remains largely
unresolved. We reported earlier that peripheral and CNS infections were detected
in transgenic mice expressing human PrP129M or PrP129V. Here we will present an
update on this project, including evidence for strain dependence and influence
of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of
experimental human CWD prions.
PRION 2016 TOKYO
In Conjunction with Asia Pacific Prion Symposium 2016
PRION 2016 Tokyo
Prion 2016
Prion 2016
Purchase options Price * Issue Purchase USD 198.00
Cervid to human prion transmission
Kong, Qingzhong
Case Western Reserve University, Cleveland, OH, United States
Abstract
Prion disease is transmissible and invariably fatal. Chronic wasting
disease (CWD) is the prion disease affecting deer, elk and moose, and it is a
widespread and expanding epidemic affecting 22 US States and 2 Canadian
provinces so far. CWD poses the most serious zoonotic prion transmission risks
in North America because of huge venison consumption (>6 million deer/elk
hunted and consumed annually in the USA alone), significant prion infectivity in
muscles and other tissues/fluids from CWD-affected cervids, and usually high
levels of individual exposure to CWD resulting from consumption of the affected
animal among often just family and friends. However, we still do not know
whether CWD prions can infect humans in the brain or peripheral tissues or
whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no
essays to reliably detect CWD infection in humans. We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the
brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid
prion strain and influenced by the host (human) prion protein (PrP) primary
sequence;
(3) Reliable essays can be established to detect CWD infection in
humans;and
(4) CWD transmission to humans has already occurred. We will test these
hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in
vitro approaches.
Aim 1 will prove that the classical CWD strain may infect humans in brain
or peripheral lymphoid tissues at low levels by conducting systemic bioassays in
a set of "humanized" Tg mouse lines expressing common human PrP variants using a
number of CWD isolates at varying doses and routes. Experimental "human CWD"
samples will also be generated for Aim 3.
Aim 2 will test the hypothesis that the cervid-to-human prion transmission
barrier is dependent on prion strain and influenced by the host (human) PrP
sequence by examining and comparing the transmission efficiency and phenotypes
of several atypical/unusual CWD isolates/strains as well as a few prion strains
from other species that have adapted to cervid PrP sequence, utilizing the same
panel of humanized Tg mouse lines as in Aim 1.
Aim 3 will establish reliable essays for detection and surveillance of CWD
infection in humans by examining in details the clinical, pathological,
biochemical and in vitro seeding properties of existing and future experimental
"human CWD" samples generated from Aims 1-2 and compare them with those of
common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.
Aim 4 will attempt to detect clinical CWD-affected human cases by examining
a significant number of brain samples from prion-affected human subjects in the
USA and Canada who have consumed venison from CWD-endemic areas utilizing the
criteria and essays established in Aim 3. The findings from this proposal will
greatly advance our understandings on the potential and characteristics of
cervid prion transmission in humans, establish reliable essays for CWD zoonosis
and potentially discover the first case(s) of CWD infection in humans.
Public Health Relevance There are significant and increasing human exposure
to cervid prions because chronic wasting disease (CWD, a widespread and highly
infectious prion disease among deer and elk in North America) continues
spreading and consumption of venison remains popular, but our understanding on
cervid-to-human prion transmission is still very limited, raising public health
concerns. This proposal aims to define the zoonotic risks of cervid prions and
set up and apply essays to detect CWD zoonosis using mouse models and in vitro
methods. The findings will greatly expand our knowledge on the potentials and
characteristics of cervid prion transmission in humans, establish reliable
essays for such infections and may discover the first case(s) of CWD infection
in humans.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Neurological Disorders and Stroke (NINDS)
Type Research Project (R01)
Project # 1R01NS088604-01A1
Application # 9037884
Study Section Cellular and Molecular Biology of Neurodegeneration Study
Section (CMND)
Program Officer Wong, May
Project Start 2015-09-30
Project End 2019-07-31
Budget Start 2015-09-30
Budget End 2016-07-31
Support Year 1
Fiscal Year 2015
Total Cost $337,507
Indirect Cost $118,756
Institution
Name Case Western Reserve University
Department Pathology
Type Schools of Medicine
DUNS # 077758407
City Cleveland
State OH
Country United States
Zip Code 44106
===========================================================
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the
brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid
prion strain and influenced by the host (human) prion protein (PrP) primary
sequence;
(3) Reliable essays can be established to detect CWD infection in
humans;and
(4) *** CWD transmission to humans has already occurred. *** We will test
these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary
in vitro approaches.
============================================================
Key Molecular Mechanisms of TSEs
Zabel, Mark D.
Colorado State University-Fort Collins, Fort Collins, CO, United States
Abstract Prion diseases, or transmissible spongiform encephalopathies (TSEs),
are fatal neurodegenerative diseases affecting humans, cervids, bovids, and
ovids. The absolute requirement of PrPC expression to generate prion diseases
and the lack of instructional nucleic acid define prions as unique infectious
agents. Prions exhibit species-specific tropism, inferring that unique prion
strains exist that preferentially infct certain host species and confront
transmission barriers to heterologous host species. However, transmission
barriers are not absolute. Scientific consensus agrees that the sheep TSE
scrapie probably breached the transmission barrier to cattle causing bovine
spongiform encephalopathy that subsequently breached the human transmission
barrier and likely caused several hundred deaths by a new-variant form of the
human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to human
health, emotion and economies can still be felt in areas like farming, blood and
organ donations and the threat of a latent TSE epidemic. This precedent raises
the real possibility of other TSEs, like chronic wasting disease of cervids,
overcoming similar human transmission barriers. A groundbreaking discovery made
last year revealed that mice infected with heterologous prion strains facing
significant transmission barriers replicated prions far more readily in spleens
than brains6. Furthermore, these splenic prions exhibited weakened transmission
barriers and expanded host ranges compared to neurogenic prions. These data
question conventional wisdom of avoiding neural tissue to avoid prion
xenotransmission, when more promiscuous prions may lurk in extraneural tissues.
Data derived from work previously funded by NIH demonstrate that Complement
receptors CD21/35 bind prions and high density PrPC and differentially impact
prion disease depending on the prion isolate or strain used. Recent advances in
live animal and whole organ imaging have led us to generate preliminary data to
support novel, innovative approaches to assessing prion capture and transport.
We plan to test our unifying hypothesis for this proposal that CD21/35 control
the processes of peripheral prion capture, transport, strain selection and
xenotransmission in the following specific aims. 1. Assess the role of CD21/35
in splenic prion strain selection and host range expansion. 2. Determine whether
CD21/35 and C1q differentially bind distinct prion strains 3. Monitor the
effects of CD21/35 on prion trafficking in real time and space 4. Assess the
role of CD21/35 in incunabular prion trafficking
Public Health Relevance Transmissible spongiform encephalopathies, or prion
diseases, are devastating illnesses that greatly impact public health,
agriculture and wildlife in North America and around the world. The impact to
human health, emotion and economies can still be felt in areas like farming,
blood and organ donations and the threat of a latent TSE epidemic. This
precedent raises the real possibility of other TSEs, like chronic wasting
disease (CWD) of cervids, overcoming similar human transmission barriers. Early
this year Canada reported its first case of BSE in over a decade audits first
case of CWD in farmed elk in three years, underscoring the need for continued
vigilance and research. Identifying mechanisms of transmission and zoonoses
remains an extremely important and intense area of research that will benefit
human and other animal populations.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Allergy and Infectious Diseases (NIAID)
Type High Priority, Short Term Project Award (R56)
Project # 1R56AI122273-01A1
Application # 9211114
Study Section Cellular and Molecular Biology of Neurodegeneration Study
Section (CMND)
Program Officer Beisel, Christopher E
Project Start 2016-02-16
Project End 2017-01-31
Budget Start 2016-02-16
Budget End 2017-01-31
Support Year 1
Fiscal Year 2016
Total Cost
Indirect Cost Institution Name Colorado State University-Fort Collins
Department Microbiology/Immun/Virology
Type Schools of Veterinary Medicine
DUNS # 785979618 City Fort Collins
State CO
Country United States
Zip Code 80523
PMCA Detection of CWD Infection in Cervid and Non-Cervid Species
Hoover, Edward Arthur
Colorado State University-Fort Collins, Fort Collins, CO, United States
Abstract Chronic wasting disease (CWD) of deer and elk is an emerging highly
transmissible prion disease now recognized in 18 States, 2 Canadian provinces,
and Korea. We have shown that Infected deer harbor and shed high levels of
infectious prions in saliva, blood, urine, and feces, and in the tissues
generating those body fluids and excreta, thereby leading to facile transmission
by direct contact and environmental contamination. We have also shown that CWD
can infect some non-cervid species, thus the potential risk CWD represents to
domestic animal species and to humans remains unknown. Whether prions borne in
blood, saliva, nasal fluids, milk, or excreta are generated or modified in the
proximate peripheral tissue sites, may differ in subtle ways from those
generated in brain, or may be adapted for mucosal infection remain open
questions. The increasing parallels in the pathogenesis between prion diseases
and human neurodegenerative conditions, such as Alzheimer's and Parkinson's
diseases, add relevance to CWD as a transmissible protein misfolding disease.
The overall goal of this work is to elucidate the process of CWD prion
transmission from mucosal secretory and excretory tissue sites by addressing
these questions: (a) What are the kinetics and magnitude of CWD prion shedding
post-exposure? (b) Are excreted prions biochemically distinct, or not, from
those in the CNS? (c) Are peripheral epithelial or CNS tissues, or both, the
source of excreted prions? and (d) Are excreted prions adapted for horizontal
transmission via natural/trans-mucosal routes? The specific aims of this
proposal are: (1) To determine the onset and consistency of CWD prion shedding
in deer and cervidized mice; (2); To compare the biochemical and biophysical
properties of excretory vs. CNS prions; (3) To determine the capacity of
peripheral tissues to support replication of CWD prions; (4) To determine the
protease- sensitive infectious fraction of excreted vs. CNS prions; and (5) To
compare the mucosal infectivity of excretory vs. CNS prions. Understanding the
mechanisms that enable efficient prion dissemination and shedding will help
elucidate how horizontally transmissible prions evolve and succeed, and is the
basis of this proposal. Understanding how infectious misfolded proteins (prions)
are generated, trafficked, shed, and transmitted will aid in preventing,
treating, and managing the risks associated with these agents and the diseases
they cause.
Public Health Relevance Chronic wasting disease (CWD) of deer and elk is an
emergent highly transmissible prion disease now recognized throughout the USA as
well as in Canada and Korea. We have shown that infected deer harbor and shed
high levels of infectious prions in saliva, blood, urine, and feces thereby
leading to transmission by direct contact and environmental contamination. In
that our studies have also shown that CWD can infect some non-cervid species,
the potential risk CWD may represents to domestic animal species and humans
remains unknown. The increasing parallels in the development of major human
neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, and
prion diseases add relevance to CWD as a model of a transmissible protein
misfolding disease. Understanding how infectious misfolded proteins (prions) are
generated and transmitted will aid in interrupting, treating, and managing the
risks associated with these agents and the diseases they cause.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Neurological Disorders and Stroke (NINDS)
Type Research Project (R01)
Project # 4R01NS061902-07
Application # 9010980
Study Section Cellular and Molecular Biology of Neurodegeneration Study
Section (CMND)
Program Officer Wong, May Project Start 2009-09-30
Project End 2018-02-28
Budget Start 2016-03-01
Budget End 2017-02-28
Support Year 7
Fiscal Year 2016
Total Cost $409,868
Indirect Cost $134,234 Institution Name Colorado State University-Fort
Collins
Department Microbiology/Immun/Virology
Type Schools of Veterinary Medicine
DUNS # 785979618 City Fort Collins
State CO
Country United States
Zip Code 80523
LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL
THE WRONG PLACES $$$
*** These results would seem to suggest that CWD does indeed have zoonotic
potential, at least as judged by the compatibility of CWD prions and their human
PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests
that if zoonotic CWD occurred, it would most likely effect those of the PRNP
codon 129-MM genotype and that the PrPres type would be similar to that found in
the most common subtype of sCJD (MM1).***
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
O18
Zoonotic Potential of CWD Prions
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1,
Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve
University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy,
3Encore Health Resources, Houston, Texas, USA
*** These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.
==================
***These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.***
==================
P.105: RT-QuIC models trans-species prion transmission
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover
Prion Research Center; Colorado State University; Fort Collins, CO USA
Conversely, FSE maintained sufficient BSE characteristics to more
efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was
competent for conversion by CWD and fCWD.
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.
================
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.***
================
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
*** chronic wasting disease, there was no absolute barrier to conversion of
the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay
when seeded with CWD, resembles that found in the most common human prion
disease, namely sCJD of the MM1 subtype.
*** These results would seem to suggest that CWD does indeed have zoonotic
potential, at least as judged by the compatibility of CWD prions and their human
PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests
that if zoonotic CWD occurred, it would most likely effect those of the PRNP
codon 129-MM genotype and that the PrPres type would be similar to that found in
the most common subtype of sCJD (MM1).***
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
***********CJD REPORT 1994 increased risk for consumption of veal and
venison and lamb***********
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL
REPORT AUGUST 1994
Consumption of venison and veal was much less widespread among both cases
and controls. For both of these meats there was evidence of a trend with
increasing frequency of consumption being associated with increasing risk of
CJD. (not nvCJD, but sporadic CJD...tss)
These associations were largely unchanged when attention was restricted to
pairs with data obtained from relatives. ...
Table 9 presents the results of an analysis of these data.
There is STRONG evidence of an association between ‘’regular’’ veal eating
and risk of CJD (p = .0.01).
Individuals reported to eat veal on average at least once a year appear to
be at 13 TIMES THE RISK of individuals who have never eaten veal.
There is, however, a very wide confidence interval around this estimate.
There is no strong evidence that eating veal less than once per year is
associated with increased risk of CJD (p = 0.51).
The association between venison eating and risk of CJD shows similar
pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK
OF CJD (p = 0.04).
There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY
OF LAMB EATING (p = 0.02).
The evidence for such an association between beef eating and CJD is weaker
(p = 0.14). When only controls for whom a relative was interviewed are included,
this evidence becomes a little STRONGER (p = 0.08).
snip...
It was found that when veal was included in the model with another
exposure, the association between veal and CJD remained statistically
significant (p = < 0.05 for all exposures), while the other exposures ceased
to be statistically significant (p = > 0.05).
snip...
In conclusion, an analysis of dietary histories revealed statistical
associations between various meats/animal products and INCREASED RISK OF CJD.
When some account was taken of possible confounding, the association between
VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS
STATISTICALLY. ...
snip...
In the study in the USA, a range of foodstuffs were associated with an
increased risk of CJD, including liver consumption which was associated with an
apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3
studies in relation to this particular dietary factor, the risk of liver
consumption became non-significant with an odds ratio of 1.2 (PERSONAL
COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
snip...see full report ;
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge
Spencers Lane BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third
annual report from the CJD Surveillance Unit. I am sorry that you are
dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the
Department of Health is committed to publishing their reports as soon as they
become available. In the circumstances it is not the practice to circulate the
report for comment since the findings of the report would not be amended. In
future we can ensure that the British Deer Farmers Association receives a copy
of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed
of the results of any research in respect of CJD. This report was entirely the
work of the unit and was produced completely independantly of the the
Department.
The statistical results reqarding the consumption of venison was put into
perspective in the body of the report and was not mentioned at all in the press
release. Media attention regarding this report was low key but gave a realistic
presentation of the statistical findings of the Unit. This approach to
publication was successful in that consumption of venison was highlighted only
once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed statistical
links between CJD and consumption of venison, would increase, and quite possibly
give damaging credence, to the whole issue. From the low key media reports of
which I am aware it seems unlikely that venison consumption will suffer
adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
Monday, May 02, 2016
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD
*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent
*** Here we report that a human prion strain that had adopted the cervid
prion protein (PrP) sequence through passage in cervidized transgenic mice
efficiently infected transgenic mice expressing human PrP,
*** indicating that the species barrier from cervid to humans is prion
strain-dependent and humans can be vulnerable to novel cervid prion strains.
PPo2-27:
Generation of a Novel form of Human PrPSc by Inter-species Transmission of
Cervid Prions
*** Our findings suggest that CWD prions have the capability to infect
humans, and that this ability depends on CWD strain adaptation, implying that
the risk for human health progressively increases with the spread of CWD among
cervids.
PPo2-7:
Biochemical and Biophysical Characterization of Different CWD Isolates
*** The data presented here substantiate and expand previous reports on the
existence of different CWD strains.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
***The presence and seeding activity of PrPTSE in skeletal muscle from
CWD-infected cervids suggests prevention of such tissue in the human diet as a
precautionary measure for food safety, pending on further clarification of
whether CWD may be transmissible to humans.
>>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO
CONVERSION OF THE HUMAN PRION PROTEIN<<<
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
Wednesday, January 01, 2014
Molecular Barriers to Zoonotic Transmission of Prions
*** chronic wasting disease, there was no absolute barrier to conversion of
the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay
when seeded with CWD, resembles that found in the most common human prion
disease, namely sCJD of the MM1 subtype.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
***The presence and seeding activity of PrPTSE in skeletal muscle from
CWD-infected cervids suggests prevention of such tissue in the human diet as a
precautionary measure for food safety, pending on further clarification of
whether CWD may be transmissible to humans.
Yet, it has to be noted that our assessments of PrPTSE levels in skeletal
muscles were based on findings in presumably pre- or subclinically infected
animals. Therefore, the concentration of PrPTSE in skeletal muscles of WTD with
clinically manifest CWD may possibly exceed our estimate which refers to
clinically inconspicuous animals that are more likely to enter the human food
chain. Our tissue blot findings in skeletal muscles from CWD-infected WTD would
be consistent with an anterograde spread of CWD prions via motor nerve fibres to
muscle tissue (figure 4A). Similar neural spreading pathways of muscle infection
were previously found in hamsters orally challenged with scrapie [28] and
suggested by the detection of PrPTSE in muscle fibres and muscle-associated
nerve fascicles of clinically-ill non-human primates challenged with BSE prions
[29]. Whether the absence of detectable PrPTSE in myofibers observed in our
study is a specific feature of CWD in WTD, or was due to a pre- or subclinical
stage of infection in the examined animals, remains to be established. In any
case, our observations support previous findings suggesting the precautionary
prevention of muscle tissue from CWD-infected WTD in the human diet, and
highlight the need to comprehensively elucidate of whether CWD may be
transmissible to humans. While the understanding of TSEs in cervids has made
substantial progress during the past few years, the assessment and management of
risks possibly emanating from prions in skeletal muscles of CWD-infected cervids
requires further research.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Rachel C.
Angers1,*, Shawn R. Browning1,*,†, Tanya S. Seward2, Christina J. Sigurdson4,‡,
Michael W. Miller5, Edward A. Hoover4, Glenn C. Telling1,2,3,§ + Author
Affiliations
1 Department of Microbiology, Immunology and Molecular Genetics, University
of Kentucky, Lexington, KY 40536, USA. 2 Sanders Brown Center on Aging,
University of Kentucky, Lexington, KY 40536, USA. 3 Department of Neurology,
University of Kentucky, Lexington, KY 40536, USA. 4 Department of Microbiology,
Immunology and Pathology, Colorado State University, Fort Collins, CO 80523,
USA. 5 Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO
80526, USA. ↵§ To whom correspondence should be addressed. E-mail:
gtell2@uky.edu ↵* These authors contributed equally to this work.
↵† Present address: Department of Infectology, Scripps Research Institute,
5353 Parkside Drive, RF-2, Jupiter, FL 33458, USA.
↵‡ Present address: Institute of Neuropathology, University of Zurich,
Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
Abstract The emergence of chronic wasting disease (CWD) in deer and elk in
an increasingly wide geographic area, as well as the interspecies transmission
of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt
Jakob disease, have raised concerns about the zoonotic potential of CWD. Because
meat consumption is the most likely means of exposure, it is important to
determine whether skeletal muscle of diseased cervids contains prion
infectivity. Here bioassays in transgenic mice expressing cervid prion protein
revealed the presence of infectious prions in skeletal muscles of CWD-infected
deer, demonstrating that humans consuming or handling meat from CWD-infected
deer are at risk to prion exposure.
Exotic Meats USA Announces Urgent Statewide Recall of Elk Tenderloin
Because It May Contain Meat Derived From An Elk Confirmed To Have Chronic
Wasting Disease
Contact: Exotic Meats USA 1-800-680-4375
FOR IMMEDIATE RELEASE -- February 9, 2009 -- Exotic Meats USA of San
Antonio, TX is initiating a voluntary recall of Elk Tenderloin because it may
contain meat derived from an elk confirmed to have Chronic Wasting Disease
(CWD). The meat with production dates of December 29, 30 and 31, 2008 was
purchased from Sierra Meat Company in Reno, NV. The infected elk came from Elk
Farm LLC in Pine Island, MN and was among animals slaughtered and processed at
USDA facility Noah’s Ark Processors LLC.
Chronic Wasting Disease (CWD) is a fatal brain and nervous system disease
found in elk and deer. The disease is caused by an abnormally shaped protein
called a prion, which can damage the brain and nerves of animals in the deer
family. Currently, it is believed that the prion responsible for causing CWD in
deer and elk is not capable of infecting humans who eat deer or elk contaminated
with the prion, but the observation of animal-to-human transmission of other
prion-mediated diseases, such as bovine spongiform encephalopathy (BSE), has
raised a theoretical concern regarding the transmission of CWD from deer or elk
to humans. At the present time, FDA believes the risk of becoming ill from
eating CWD-positive elk or deer meat is remote. However, FDA strongly advises
consumers to return the product to the place of purchase, rather than disposing
of it themselves, due to environmental concerns.
Exotic Meats USA purchased 1 case of Elk Tenderloins weighing 16.9 lbs. The
Elk Tenderloin was sold from January 16 – 27, 2009. The Elk Tenderloins was
packaged in individual vacuum packs weighing approximately 3 pounds each. A
total of six packs of the Elk Tenderloins were sold to the public at the Exotic
Meats USA retail store. Consumers who still have the Elk Tenderloins should
return the product to Exotic Meats USA at 1003 NE Loop 410, San Antonio, TX
78209. Customers with concerns or questions about the Voluntary Elk Recall can
call 1-800-680-4375. The safety of our customer has always been and always will
be our number one priority.
Exotic Meats USA requests that for those customers who have products with
the production dates in question, do not consume or sell them and return them to
the point of purchase. Customers should return the product to the vendor. The
vendor should return it to the distributor and the distributor should work with
the state to decide upon how best to dispose. If the consumer is disposing of
the product he/she should consult with the local state EPA office.
#
COLORADO: Farmer's market meat recalled after testing positive for
CWD
24.dec.08 9News.com Jeffrey Wolf
Elk meat that was sold at a farmer's market is being recalled because tests
show it was infected with chronic wasting disease. The Boulder County Health
Department and Colorado Department of Public Health and Environment issued the
recall Wednesday after the meat was sold at the Boulder County Fairgrounds on
Dec. 13. Although there isn't any human health risk connected with CWD, the
recalled was issued as a precaution. About 15 elk were bought from a commercial
ranch in Colorado in early December and processed at a licensed plant. All 15
were tested for CWD and one came up positive. The labeling on the product would
have the following information: *Seller: High Wire Ranch *The type of cut:
"chuck roast," "arm roast," "flat iron," "ribeye steak," "New York steak,"
"tenderloin," "sirloin tip roast," "medallions" or "ground meat." *Processor:
Cedaredge Processing *The USDA triangle containing the number "34645" People
with questions about this meat can contact John Pape, epidemiologist at the
Colorado Department of Public Health and Environment at 303-692-2628.
COULD NOT FIND any warning or recalls on these two sites confirming their
recall of CWD infected meat. ...TSS
Wednesday, April 06, 2011
Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in
Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease
Prion Infectivity in Fat of Deer with Chronic Wasting Disease
Brent Race,# Kimberly Meade-White,# Richard Race, and Bruce Chesebro* Rocky
Mountain Laboratories, 903 South 4th Street, Hamilton, Montana 59840
Received 2 June 2009/ Accepted 24 June 2009
ABSTRACT Top ABSTRACT TEXT REFERENCES
Chronic wasting disease (CWD) is a neurodegenerative prion disease of
cervids. Some animal prion diseases, such as bovine spongiform encephalopathy,
can infect humans; however, human susceptibility to CWD is unknown. In
ruminants, prion infectivity is found in central nervous system and lymphoid
tissues, with smaller amounts in intestine and muscle. In mice, prion
infectivity was recently detected in fat. Since ruminant fat is consumed by
humans and fed to animals, we determined infectivity titers in fat from two
CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD
infectivity and might be a risk factor for prion infection of other
species.
snip...
The highest risk of human contact with CWD might be through exposure to
high-titer CNS tissue through accidental skin cuts or corneal contact at the
time of harvest and butchering. However, the likelihood of a human consuming fat
infected with a low titer of the CWD agent is much higher. It is impossible to
remove all the fat present within muscle tissue, and fat consumption is
inevitable when eating meat. Of additional concern is the fact that meat from an
individual deer harvested by a hunter is typically consumed over multiple meals
by the same group of people. These individuals would thus have multiple
exposures to the CWD agent over time, which might increase the chance for
transfer of infection.
In the Rocky Mountain region of North America, wild deer are subject to
predation by wolves, coyotes, bears, and mountain lions. Although canines such
as wolves and coyotes are not known to be susceptible to prion diseases, felines
definitely are susceptible to BSE (9) and might also be infected by the CWD
agent. Deer infected with the CWD agent are more likely to be killed by
predators such as mountain lions (11). Peripheral tissues, including lymph
nodes, muscle, and fat, which harbor prion infectivity are more accessible for
consumption than CNS tissue, which has the highest level of infectivity late in
disease. Therefore, infectivity in these peripheral tissues may be important in
potential cross-species CWD transmissions in the wild.
The present finding of CWD infectivity in deer fat tissue raises the
possibility that prion infectivity might also be found in fat tissue of other
infected ruminants, such as sheep and cattle, whose fat and muscle tissues are
more widely distributed in both the human and domestic-animal food chains.
Although the infectivity in fat tissues is low compared to that in the CNS,
there may be significant differences among species and between prion strains.
Two fat samples from BSE agent-infected cattle were reported to be negative by
bioassay in nontransgenic RIII mice (3, 6). However, RIII mice are
10,000-fold-less sensitive to BSE agent infection than transgenic mice
expressing bovine PrP (4). It would be prudent to carry out additional
infectivity assays on fat from BSE agent-infected cattle and scrapie
agent-infected sheep using appropriate transgenic mice or homologous species to
determine the risk from these sources.
0C7.04
North American Cervids Harbor Two Distinct CWD Strains
Authors
Angers, R. Seward, T, Napier, D., Browning, S., Miller, M., Balachandran
A., McKenzie, D., Hoover, E., Telling, G. 'University of Kentucky; Colorado
Division of Wildlife, Canadian Food Inspection Agency; University Of Wisconsin;
Colorado State University.
Content
Despite the increasing geographic distribution and host range of CWD,
little is known about the prion strain(s) responsible for distinct outbreaks of
the disease. To address this we inoculated CWD-susceptible Tg(CerPrP)1536+/·
mice with 29 individual prion samples from various geographic locations in North
America. Upon serial passage, intrastudy incubation periods consistently
diverged and clustered into two main groups with means around 210 and 290 days,
with corresponding differences in neuropathology. Prion strain designations were
utilized to distinguish between the two groups: Type I CWD mice succumbed to
disease in the 200 day range and displayed a symmetrical pattern of vacuolation
and PrPSc deposition, whereas Type II CWD mice succumbed to disease near 300
days and displayed a strikingly different pattern characterized by large local
accumulations of florid plaques distributed asymmetrically. Type II CWD bears a
striking resemblance to unstable parental scrapie strains such as 87A which give
rise to stable, short incubation period strains such as ME7 under certain
passage conditions. In agreement, the only groups of CWD-inoculated mice with
unwavering incubation periods were those with Type I CWD. Additionally,
following endpoint titration of a CWD sample, Type I CWD could be recovered only
at the lowest dilution tested (10-1), whereas Type II CWD was detected in mice
inoculated with all dilutions resulting in disease. Although strain properties
are believed to be encoded in the tertiary structure of the infectious prion
protein, we found no biochemical differences between Type I and Type II CWD. Our
data confirm the co·existence of two distinct prion strains in CWD-infected
cervids and suggest that Type II CWD is the parent strain of Type I CWD.
see page 29, and see other CWD studies ;
Sunday, November 23, 2008
PRION October 8th - 10th 2008 Book of Abstracts
ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A
WISCONSIN STRAIN OF CWD
Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of
Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2
Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary
Research Institute, 4.Center for Prions and Protein Folding Diseases, 5
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
T6G 2P5
The identification and characterization of prion strains is increasingly
important for the diagnosis and biological definition of these infectious
pathogens. Although well-established in scrapie and, more recently, in BSE,
comparatively little is known about the possibility of prion strains in chronic
wasting disease (CWD), a disease affecting free ranging and captive cervids,
primarily in North America. We have identified prion protein variants in the
white-tailed deer population and demonstrated that Prnp genotype affects the
susceptibility/disease progression of white-tailed deer to CWD agent. The
existence of cervid prion protein variants raises the likelihood of distinct CWD
strains. Small rodent models are a useful means of identifying prion strains. We
intracerebrally inoculated hamsters with brain homogenates and phosphotungstate
concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD
endemic area) and experimentally infected deer of known Prnp genotypes. These
transmission studies resulted in clinical presentation in primary passage of
concentrated CWD prions. Subclinical infection was established with the other
primary passages based on the detection of PrPCWD in the brains of hamsters and
the successful disease transmission upon second passage. Second and third
passage data, when compared to transmission studies using different CWD inocula
(Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin
white-tailed deer population is different than the strain(s) present in elk,
mule-deer and white-tailed deer from the western United States endemic
region.
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
Friday, August 14, 2015
*** Susceptibility of cattle to the agent of chronic wasting disease from
elk after intracranial inoculation ***
Saturday, May 28, 2016
*** Infection and detection of PrPCWD in soil from CWD infected farm in
Korea Prion 2016 Tokyo ***
SNIP...SEE FULL TEXT ;
*** Calling Canadian beef unsafe is like calling your twin sister ugly,"
Dopp said.
Thursday, August 25, 2016
*** FSIS Green Bay Dressed Beef Recalls Beef Products Due To Possible
Specified Risk Materials Contamination the most high risk materials for BSE TSE
PRION AKA MAD COW TYPE DISEASE ***
Friday, August 26, 2016
*** Journal Journal of Toxicology and Environmental Health, Part A Volume
79, 2016 - Issue 16-17 Prion Research in Perspective IV CANADA BSE CWD SCRAPIE
CJD TSE Prion Disease
Thursday, April 14, 2016
Arizona 22 year old diagnosed with Creutzfeldt Jakob Disease CJD
Thursday, January 15, 2015
41-year-old Navy Commander with sporadic Creutzfeldt–Jakob disease CJD TSE
Prion: Case Report
Saturday, January 17, 2015
*** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed
with the extremely rare Creutzfeldt-Jakob disease
Saturday, December 12, 2015
CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015
Sunday, August 21, 2016
Kay Ellen Roedl Schwister Deceased August 7, 2016 at the age of 53 with
Creutzfeldt-Jakob disease CJD TSE Prion spontaneous sporadic, zoonosis, or
iatrogenic?
Monday, August 22, 2016
CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES
HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES
*** Evidence That Transmissible Mink Encephalopathy Results from Feeding
Infected Cattle ***
Over the next 8-10 weeks, approximately 40% of all the adult mink on the
farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or
dead dairy cattle...
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to
accord it a very low profile indeed. Dr. A Thiermann showed the picture in the
''Independent'' with cattle being incinerated and thought this was a fanatical
incident to be avoided in the US at all costs. ...
”The occurrence of CWD must be viewed against the contest of the locations
in which it occurred. It was an incidental and unwelcome complication of the
respective wildlife research programmes. Despite it’s subsequent recognition as
a new disease of cervids, therefore justifying direct investigation, no specific
research funding was forthcoming. The USDA veiwed it as a wildlife problem and
consequently not their province!” ...page 26.
Monday, August 22, 2016
CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES
HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES
Terry S. Singeltary Sr.
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