Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission
Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats,
blood, and mother to offspring transmission
HD.13: CWD infection in the spleen of humanized transgenic mice
Liuting Qing and Qingzhong Kong
Case Western Reserve University; Cleveland, OH USA
Chronic wasting disease (CWD) is a widespread prion disease in free-ranging
and captive cervid species in North America, and there is evidence suggesting
the existence of multiple CWD strains. The susceptibility of human CNS and
peripheral organs to the various CWD prion strains remains largely unclear.
Current literature suggests that the classical CWD strain is unlikely to infect
human brain, but the potential for peripheral infection by CWD in humans is
unknown. We detected protease-resistant PrpSc in the spleens of a few humanized
transgenic mice that were intracerebrally inoculated with natural CWD isolates,
but PrpSc was not detected in the brains of any of the CWD-inoculated mice. Our
ongoing bioassays in humanized Tg mice indicate that intracerebral challenge
with such PrpSc-positive humanized mouse spleen already led to prion disease in
most animals. These results indicate that the CWD prion may have the potential
to infect human peripheral lymphoid tissues.
=====
HD.12: Comparative study of the distribution of the prion protein in the
squirrel monkey (Saimiri sciureus) following experimental challenge with variant
and sporadic CJD
Diane L. Ritchie,1 Paul Brown,2 Susan Gibson,3 Thomas R. Kreil,4 Christian
Abee3 and James W. Ironside1
1National CJD Surveillance Unit; Edinburgh, UK; 2Bethesda; Bethesda, MD
USA; 3Deparment of Comparative Medicine; University of South Alabama; Mobile, AL
USA; 4Baxter Bioscience; Vienna, Austria
Introduction, Reports suggest that the number of tissues and organs showing
the presence of the abnormal prion protein (PrPTSE) in variant CJD (vCJD)
patients may be greater than previously thought. A limited peripheral
involvement in some cases of sporadic CJD (sCJD) has also been reported. This
accumulation of PrPTSE outside the brain has raised concerns about the possible
iatrogenic transmission risk of vCJD. The squirrel monkey (Saimiri sciureus) has
been shown to be highly susceptible to experimental challenge with human prion
disease. Neuropathological and biochemical analyses of CNS tissue have shown
that sCJD and vCJD can be distinguished in the squirrel monkey and that many of
the strain characteristics that define these agents are conserved after
transmission. Following on from these initial studies, immunohistochemistry and
western blot analysis were performed on a wide range of peripheral tissues
including, lymphoreticular tissues and peripheral neural tissue to establish the
full-body distribution of PrPTSE in this primate animal model.
Materials and Methods. Brain homogenates from sCJD or vCJD patients were
inoculated into the frontal cortex of squirrel monkeys. Animals were kept under
constant clinical surveillance. At post-mortem, formalin fixed CNS tissue and a
wide range of peripheral tissues were taken for immunohistochemical analysis
together with frozen tissues taken for the biochemical detection of PrPTSE.
Results. Immunohistochemical analysis showed no evidence of PrPTSE
deposition in peripheral tissues in either variant or sporadic CJD-infected
animals. However, western blot assays detected PrPTSE in the spleen of a
proportion of the vCJD- infected animals. The PrPTSE isotype resembled that
detected in CNS tissue from the vCJD- infected animals and from human vCJD
cases. ***In addition, western blot analysis detected PrPTSE in the spleen of a
single animal following challenge with sporadic CJD. The PrPTSE type in this
animal resembled that found in CNS tissue from the same animal, with a PrPTSE
type similar to that found in human sCJD type 1 cases.
Conclusion. This study confirms the accumulation of PrPTSE in the CNS and
spleen of a proportion of squirrel monkeys infected intra-cerebrally with human
vCJD. Furthermore, this study extends the evidence that there may be a
peripheral involvement in some cases of sCJD. PrPTSE typing confirms the
conservation of PrPTSE type on transmission to the squirrel monkey and suggests
that there are no tissue-specific adaptations in the biochemical phenotype of
the agent strain following primate-to-primate transmission.
=====
Oral.15: Molecular barriers to zoonotic prion transmission: Comparison of
the ability of sheep, cattle and deer prion disease isolates to convert normal
human prion protein to its pathological isoform in a cell-free system
Marcelo A.Barria,1 Aru Balachandran,2 Masanori Morita,3 Tetsuyuki
Kitamoto,4 Rona Barron,5 Jean Manson,5 Richard Kniqht,1 James W. lronside1 and
Mark W. Head1
1National CJD Research and Surveillance Unit; Centre for Clinical Brain
Sciences; School of Clinical Sciences; The University of Edinburgh; Edinburgh,
UK; 2National and OIE Reference Laboratory for Scrapie and CWD; Canadian Food
Inspection Agency; Ottawa Laboratory; Fallowfield. ON Canada; 3Infectious
Pathogen Research Section; Central Research Laboratory; Japan Blood Products
Organization; Kobe, Japan; 4Department of Neurological Science; Tohoku
University Graduate School of Medicine; Sendai. Japan; 5Neurobiology Division;
The Roslin Institute and R(D)SVS; University of Edinburgh; Easter Bush;
Midlothian; Edinburgh, UK
Background. Bovine spongiform encephalopathy (BSE) is a known zoonotic
prion disease, resulting in variant Creurzfeldt- Jakob disease (vCJD) in humans.
In contrast, classical scrapie in sheep is thought to offer little or no danger
to human health. However, a widening range of prion diseases have been
recognized in cattle, sheep and deer. The risks posed by individual animal prion
diseases to human health cannot be determined a priori and are difficult to
assess empirically. The fundamemal event in prion disease pathogenesis is
thought to be the seeded conversion of normal prion protein (PrPC) to its
pathological isoform (PrPSc). Here we report the use of a rapid molecular
conversion assay to test whether brain specimens from different animal prion
diseases are capable of seeding the conversion of human PrPC ro PrPSc.
Material and Methods. Classical BSE (C-type BSE), H-type BSE, L-type BSE,
classical scrapie, atypical scrapie, chronic wasting disease and vCJD brain
homogenates were tested for their ability to seed conversion of human PrPC to
PrPSc in protein misfolding cyclic amplification (PMCA) reactions. Newly formed
human PrPSc was detected by protease digestion and western blotting using the
antibody 3F4.
Results. C-type BSE and vCJD were found to efficiently convert PrPC to
PrPSc. Scrapie failed to convert human PrPC to PrPSc. Of the other animal prion
diseases tested only chronic wasting disease appeared to have the capability ro
convert human PrPC to PrPSc. The results were consistent whether the human PrPC
came from human brain, humanised transgenic mouse brain or from cultured human
cells and the effect was more pronounced for PrPC with methionine at codon 129
compared with that with valine.
Conclusion. Our results show that none of the tested animal prion disease
isolates are as efficient as C-type BSE and vCJD in converting human prion
protein in this in vitro assay. However, they also show that there is no
absolute barrier ro conversion of human prion protein in the case of chronic
wasting disease.
=====
Invited.16: Studies of chronic wasting disease transmission in cervid and
non-cervid species
Edward A, Hoover,1 Candace K. Mathiason,1 Davin M. Henderson,1 Nicholas J.
Haley,1 Davis M. Seelig,1 Nathaniel D. Denkers,1 Amy V. Nalls,1 Mark D. Zabe,1
Glenn C. Telling,1 Fernando Goni2 and Thomas Wisniewski,2
1Prion Research Center; Colorado State University; Fort Collins, CO USA;
2New York University School of Medicine; New York, NY USA
How and why some misfolded proteins become horizontally transmitted agents
and occasionally cross species barriers are issues fundamental to understanding
prion disease. Chronic wasting disease (CWD) of cervids is perhaps a prototype
of horizontal prion transmission, encompassing efficient mucosal uptake,
lymphoid amplification, neuroinvasion, peripheralization, and dissemination via
mucosal excretion. Efficient mucosal transmission of CWD in deer has been
demonstrated by oral, nasal, aerosol, and indirect contact exposure. In
addition, other studies (Mathiason CK, et al.) reported at the symposium support
a significant role for pre- and/or postnatal transmission of CWD from doe to
offspring. Accumulating, yet still incomplete, evidence also suggests that the
period of relatively covert CWD infection may be longer than originally thought.
Given the above, minimally invasive sensitive assays based on body fluids from
live animals would aid substantially in understanding the biology of CWD. We
have been applying seeded realtirne quaking-induced amplification of recombinant
PrP substrates (i.e., RT-QuIC methodology) to: (1) investigate antemortem CWD
detection, and (2) model PrP-based species barriers and trans-species
adaptation-topics we previously explored using sPMCA and in vivo bioassays. At
this symposium, we report sensitive and specific detection CWD prions in saliva,
urine, blood (Mathiason lab), and rectal and pharyngeal lymph node samples
(Haley NJ, et al.) from pre-symptomatic and symptomatic experimentally and
naturally exposed deer. Other ongoing studies are employing RT-QuIC methodology
to model amplification barriers among CWD, FSE, BSE, and CJD prions using
cervine, feline, bovine, human, and promiscuous rPrP substrates and the above
species prion seeds, cellular co-factors, and transgenic mice. Finally, in
collaboration with the Wisniewski laboratory, we are conducting of experimental
CWD vaccination studies in deer employing oral administration of an attenuated
Salmonella vector expressing cervid PrP epitopes.
=====
AD.06: Detecting prions in the brain and blood of TSE-infected deer and
hamsters
Alan Elder,1 Davin Henderson,1 Anca Selariu,1 Amy Nalls,1 Byron Caughey,2
Richard Bessen,1 Jason Bartz3 and Candace Mathiason1
1Colorado State University; Fort Collins, CO USA; 2NIH Rocky Mountain
Laboratories; Hamilton, MT USA; 3Creighton University; Omaha, NE USA
While large quantities of protease resistant prion protein (PrPres) can be
demonstrated by western blot or IHC in lymphoid biopsies or post-mortem brain
tissues harvested from prion-infected animals, these conventional assays are
less reliable as means to detect the small quantities of prions thought to be
present in bodily fluids or associated with early and asymptomatic phases of TSE
disease. The Real Time-Quaking Induced Conversion (RT-QuIC) assay is capable of
detecting prions at concentrations below the level of sensitivity of
conventional assays and provides a real-time fluorescent readout negating the
use of proteases. We have made modifications to the RT-QuIC assay to utilize it
for the detection of PrPres in brain and blood harvested from various species
infected with prions. In this study, we analyzed CWD-infected deer and
CWD/TME-infected hamster whole blood to determine the effect of:
(1) various anticoagulants,
(2) freezing and
(3) NaPTA precipitation.
Brain tissue and blood collected from naive deer and hamsters served as
negative controls.
We were able to demonstrate amplifiable prions in
(1) brain and blood samples harvested from CWD/TME-infected animals,
(2) heparinized blood,
(3) frozen vs. fresh blood and
(4) NaPTA treated samples.
The RT-QuIC assay is able to detect PrPres in various species of animals
and shows promise as an antemortem diagnostic tool for blood-borne TSEs.
=====
Oral.08: Mother to offspring transmission of chronic wasting disease in
Reeve's Muntjac deer
Amy Nalls,1 Erin McNulty,1 Jenny Powers,2 Davis Seelig,1 Clare Hoover,1
Nicholas Haley,1 Jeanette Hayes-Klug,1 Kelly Anderson,1 Paula Stewart,3 Wilfred
Goldmann,3 Edward A. Hoover1 and Candace K. Mathiason1
1Colorado State University; Fort Collins, CO USA; 2National Park Service;
Fort Collins, CO USA; 3The Roslin Institute and Royal School of Veterinary
Studies; Edinburgh, UK
To investigate the role mother to offspring transmission plays in chronic
wasting disease (CWD), we have developed a cervid model employing the Reeve's
muntjac deer (Muntiacus reevesi). Eight muntjac doe were orally inoculated with
CWD and tested PrPCWD lymphoid positive by 4 mo post infection. Fourteen fawns
were born to these eight CWD-infected doe-3 were born viable, 6 were born
non-viable and 5 were harvested as fetuses from early or end-stage CWD-infected
doe. All three viable fawns have demonstrated CWD IHC lymphoid biopsy positivity
between 43 d post birth and 11 mo post birth. Two of these three CWD positive
viable offspring have developed clinical signs consistent with TSE disease
(28-33 mo post birth). Moreover, CWD prions have been detected by sPMCA in 11 of
16 tissues harvested from 6 full-term non-viable fawns and in 7 of 11 fetal
tissues harvested in utero from the second and third trimester fetuses.
Additional tissues and pregnancy related fluids from doe and offspring are being
analyzed for CWD prions. In summary, using the muntjac deer model we have
demonstrated CWD clinical disease in offspring born to CWD-infected doe, and in
utero transmission of CWD from mother to offspring. These studies provide basis
to further investigate the mechanisms of maternal transfer of prions.
=====
AD.63: Susceptibility of domestic cats to chronic wasting disease
Amy V.Nalls,1 Candace Mathiason,1 Davis Seelig,2 Susan Kraft,1 Kevin
Carnes,1 Kelly Anderson,1 Jeanette Hayes-Klug1 and Edward A. Hoover1
1Colorado State University; Fort Collins, CO USA; 2University of Minnesota;
Saint Paul, MN USA
Domestic and nondomestic cats have been shown to be susceptible to feline
spongiform encephalopathy (FSE), almost certainly caused by consumption of
bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and
free-ranging nondomestic felids scavenge cervid carcasses, including those in
areas affected by chronic wasting disease (CWD), we evaluated the susceptibility
of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5
cats each were inoculated either intracerebrally (IC) or orally (PO) with
CWD-infected deer brain. At 40 and 42 mo post-inoculation, two IC-inoculated
cats developed signs consistent with prion disease, including a stilted gait,
weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail
tremors, and ataxia, and progressed to terminal disease within 5 mo. Brains from
these two cats were pooled and inoculated into cohorts of cats by IC, PO, and
intraperitoneal and subcutaneous (IP/SC) routes. Upon subpassage, feline-adapted
CWD (FelCWD) was transmitted to all IC-inoculated cats with a decreased
incubation period of 23 to 27 mo. FelCWD was detected in the brains of all the
symptomatic cats by western blotting and immunohistochemistry and abnormalities
were seen in magnetic resonance imaging, including multifocal T2 fluid
attenuated inversion recovery (FLAIR) signal hyper-intensities, ventricular size
increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4
IP/SQ and 2 of 4 PO inoculared cats have developed abnormal behavior patterns
consistent with the early stage of feline CWD. These results demonstrate that
CWD can be transmitted and adapted to the domestic cat, thus raising the issue
of potential cervid-to- feline transmission in nature.
Sunday, July 21, 2013
*** As Chronic Wasting Disease CWD rises in deer herd, what about risk for
humans?
> sCJDMM1-2 should be considered as a separate entity at this time.
> All of the Heidenhain variants were of the methionine/ methionine type
1 molecular subtype.
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
Thursday, May 31, 2012
CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission,
Scrapie, cats, species barrier, burial, and more
Monday, August 8, 2011
Susceptibility of Domestic Cats to CWD Infection
Enforcement Report - Week of February 20, 2013
Product Detail Product Description Regular Chicken 50#
Ingredients: Corn, Wheat, Oats, Oyster shells, Medium Grit, CCC, ADS, Plant
Protein Products, Animal Protein Products, Processed Grain By-Products, Roughage
Products, Animal Fat procession with DHA, etc
Recall Number V-137-2013 Classification Class III Code Info 8/6/2012
Product Distributed Qty 5400lbs (50lb bags)
Reason For Recall During an FDA sample collection, the firms 50# Regular
Chicken Feed was found to contain mammalian protein. The label does not contain
the warning statement.
Event Detail Event Id 63743 Product Type Veterinary Status Terminated
Recalling Firm Cohoons Elevator Inc. City Midland State MI Country US Voluntary
/ Mandated Voluntary: Firm Initiated Recall Initiation Date 2012-11-21 Initial
Firm Notification of Consignee or Public Other Distribution Pattern Midland MI
area only.
Subject: DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material
From Deer and Elk in Animal Feed; Availability
Date: Fri, 16 May 2003 11:47:37 –0500
From: "Terry S. Singeltary Sr."
To: fdadockets@oc.fda.gov
Tuesday, June 11, 2013
Weld County Bi-Products dba Fort Morgan Pet Foods 6/1/12 significant
deviations from requirements in FDA regulations that are intended to reduce the
risk of bovine spongiform encephalopathy (BSE) within the United States
Thursday, June 6, 2013
BSE TSE PRION USDA FDA MAD COW FEED COMPLIANCE REPORT and NAI, OAI, and VAI
ratings as at June 5, 2013
Greetings,
since our fine federal friends have decided not to give out any more
reports on the USA breaches of the feed ban and surveillance etc. for the BSE
TSE prion mad cow type disease in the USDA livestock, I thought I might attempt
it. I swear, I just don’t understand the logic of the SSS policy, and that
includes all of it. I assure you, it would be much easier, and probably better
for the FDA and the USDA INC., if they would simply put some kind of report out
for Pete’s sake, instead of me doing it after I get mad, because I am going to
put it all out there. the truth.
PLEASE BE ADVISED, any breach of any of the above classifications OAI, VAI,
RTS, CAN lead to breaches into the feed BSE TSE prion protocols, and CAN lead to
the eventual suspect tainted feed reaching livestock. please, if any USDA
official out there disputes this, please explain then how they could not.
paperwork errors can eventually lead to breaches of the BSE TSE prion mad cow
feed ban reaching livestock, or contamination and exposure there from, as well.
I would sure like to see the full reports of just these ;
4018 CHI-DO 3007091297 Rancho Cantera 2866 N Sunnyside Rd Kent IL
61044-9605 OPR FR, OF HP 11/26/2012 OAI Y
9367 3008575486 Rocky Ford Pet Foods 21693 Highway 50 East Rocky Ford CO
81067 OPR RE, TH HP 2/27/2013 OAI N
9446 DEN-DO 1713202 Weld County Bi Products, Inc. 1138 N 11th Ave Greeley
CO 80631-9501 OPR RE, TH HP 10/12/2012 OAI N
9447 DEN-DO 3002857110 Weld County Bi-Products dba Fort Morgan Pet Foods
13553 County Road 19 Fort Morgan CO 80701-7506 OPR RE HP 12/7/2011 OAI N
see full list of the fda mad cow bse feed follies, toward the bottom, after
a short brief update on the mad cow bse follies, and our good friend Lester
Crawford that was at the FDA.
ALSO, I would kindly like to comment on this FDA BSE/Ruminant Feed
Inspections Firms Inventory (excel format)4 format, for reporting these breaches
of BSE TSE prion protocols, from the extensive mad cow feed ban warning letters
the fda use to put out for each violations. simply put, this excel format sucks,
and the FDA et al intentionally made it this difficult to follow the usda fda
mad cow follies. this is an intentional format to make it as difficult as
possible to follow these breaches of the mad cow TSE prion safety feed
protocols. to have absolutely no chronological or numerical order, and to format
such violations in a way that they are almost impossible to find, says a lot
about just how far the FDA and our fine federal friends will go through to hide
these continued violations of the BSE TSE prion mad cow feed ban, and any
breaches of protocols there from. once again, the wolf guarding the henhouse $$$
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
Inspections conducted by State and FDA investigators are classified to
reflect the compliance status at the time of the inspection, based upon whether
objectionable conditions were documented. Based on the conditions found,
inspection results are recorded in one of three classifications:
OAI (Official Action Indicated) when inspectors find significant
objectionable conditions or practices and believe that regulatory sanctions are
warranted to address the establishment’s lack of compliance with the regulation.
An example of an OAI classification would be findings of manufacturing
procedures insufficient to ensure that ruminant feed is not contaminated with
prohibited material. Inspectors will promptly re-inspect facilities classified
OAI after regulatory sanctions have been applied to determine whether the
corrective actions are adequate to address the objectionable conditions.
VAI (Voluntary Action Indicated) when inspectors find objectionable
conditions or practices that do not meet the threshold of regulatory
significance, but warrant an advisory to inform the establishment that
inspectors found conditions or practices that should be voluntarily corrected.
VAI violations are typically technical violations of the 1997 BSE Feed Rule.
These violations include minor recordkeeping lapses or conditions involving
non-ruminant feeds.
NAI (No Action Indicated) when inspectors find no objectionable conditions
or practices or, if they find objectionable conditions, those conditions are of
a minor nature and do not justify further actions.
when sound science was bought off by junk science, in regards to the BSE
TSE prion mad cow type disease, by the USDA, CFIA, WHO, OIE, et al. $$$
when the infamous, and fraudulently USDA, FSIS, APHIS, FDA, gold card was
taken away that infamous day in December of 2003, all cards were off the table,
it was time to change the science, and change they did. ...tss
snip. ...please see full text ;
Thursday, June 6, 2013
BSE TSE PRION USDA FDA MAD COW FEED COMPLIANCE REPORT and NAI, OAI, and VAI
ratings as at June 5, 2013
Friday, July 19, 2013
PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED Revised
as of April 1, 2013 50# Regular Chicken Feed was found to contain mammalian
protein label does not contain the warning statement
IN A NUT SHELL ;
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate
declarations made by the official Veterinary Services of Member Countries. The
OIE is not responsible for inaccurate publication of country disease status
based on inaccurate information or changes in epidemiological status or other
significant events that were not promptly reported to the Central Bureau,
Thursday, May 30, 2013
World Organization for Animal Health (OIE) has upgraded the United States'
risk classification for mad cow disease to "negligible" from "controlled", and
risk further exposing the globe to the TSE prion mad cow type disease
U.S. gets top mad-cow rating from international group and risk further
exposing the globe to the TSE prion mad cow type disease
Tuesday, July 2, 2013
APHIS USDA Administrator Message to Stakeholders: Agency Vision and Goals
Eliminating ALL remaining BSE barriers to export market
Saturday, July 6, 2013
Small Ruminant Nor98 Prions Share Biochemical Features with Human
Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive
Prionopathy
Research Article
Sunday, August 11, 2013
Development of an oral vaccine for chronic wasting disease
Thursday, August 08, 2013
Characterization of the first case of naturally occurring chronic wasting
disease in a captive red deer (Cervus elaphus) in North America
Friday, August 09, 2013
CWD TSE prion, plants, vegetables, and the potential for environmental
contamination
Sunday, June 09, 2013
Missouri House forms 13-member Interim Committee on the Cause and Spread of
Chronic Wasting Disease CWD
Wednesday, August 21, 2013
IOWA DNR EMERGENCY CONSENT ORDER IN THE MATTER OF TOM & LINDA BRAKKE
D/B/A PINE RIDGE HUNTING LODGE UPDATE AUGUST 21, 2013
Friday, August 16, 2013
Creutzfeldt-Jakob disease (CJD) biannual update August 2013 U.K. and
Contaminated blood products induce a highly atypical prion disease devoid of
PrPres in primates
Sunday, August 11, 2013
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing
an extreme increase of 48% between 2008 and 2010
kind regards, terry
posted by Terry S. Singeltary Sr. at
12:03 PM
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