Sunday, August 25, 2013

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."
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
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 $$$
 Inspections conducted by State and FDA investigators are classified to reflect the compliance status at the time of the inspection, based upon whether objectionable conditions were documented. Based on the conditions found, inspection results are recorded in one of three classifications:
OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions.
VAI (Voluntary Action Indicated) when inspectors find objectionable conditions or practices that do not meet the threshold of regulatory significance, but warrant an advisory to inform the establishment that inspectors found conditions or practices that should be voluntarily corrected. VAI violations are typically technical violations of the 1997 BSE Feed Rule. These violations include minor recordkeeping lapses or conditions involving non-ruminant feeds.
NAI (No Action Indicated) when inspectors find no objectionable conditions or practices or, if they find objectionable conditions, those conditions are of a minor nature and do not justify further actions.
when sound science was bought off by junk science, in regards to the BSE TSE prion mad cow type disease, by the USDA, CFIA, WHO, OIE, et al. $$$
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
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
(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
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


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