Atypical Bovine Spongiform Encephalopathy BSE OIE, FDA 589.2001 FEED REGULATIONS, and Ingestion Therefrom
Atypical Bovine Spongiform Encephalopathy BSE OIE, FDA 589.2001 FEED REGULATIONS, and Ingestion Therefrom
Objective 1: Investigate the mechanisms of protein misfolding in prion disease, including the genetic determinants of misfolding of the prion protein, environmental influences on abnormal prion conversion, and environmental influences on protein misfolding as it relates to prion diseases. Objective 2: Investigate the pathobiology of prion strains in natural hosts, including the influence of prion source genotype on interspecies transmission and the pathobiology of atypical transmissible spongiform encephalopathies (TSEs) and the presence of CWD prion strains in natural hosts by processing field samples through a strain identification program. Subobjective 2.A: Investigate the pathobiology of atypical TSEs. Subobjective 2.B: Investigate the influence of prion source genotype on interspecies transmission. Objective 3: Investigate sampling methodologies for antemortem detection of prion disease, including the utility of blood sampling as a means to assess prion disease status of affected animals and the utility of environmental sampling for monitoring herd prion disease status. Subobjective 3.A: Investigate the utility of blood sampling as a means to assess prion disease status of affected animals. Subobjective 3.B: Investigate the utility of environmental sampling for monitoring herd prion disease status. Objective 4: Determine the association of disease susceptibility or resistance with naturally occurring prion protein genotypes not yet associated with positive cases on infected premises, including genotype associated differences in prion accumulation and excretion, and develop a logic-based decision tree for CWD strain determination. Objective 5: Develop improved live animal test for the detection of CWD-affected cervids, including a sensitive live animal test to detect CWD prions in individual animals, a sensitive live animal screening test for the purpose of determining a herd’s CWD status, and a sensitive deployable CWD test for use by State diagnostic labs.
The studies will focus on three animal transmissible spongiform encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease (CWD) of deer, elk, and moose. The research will address sites of protein folding and misfolding as it relates to prion disease, accumulation of misfolded protein in the host, routes of infection, and ante mortem diagnostics with an emphasis on controlled conditions and natural routes of infection. Techniques used will include spectroscopic monitoring of protein folding/misfolding, clinical exams, histopathology, immunohistochemistry, and biochemical analysis of proteins. The enhanced knowledge gained from this work will help understand the underlying mechanisms of prion disease and mitigate the potential for unrecognized epidemic expansions of these diseases in populations of animals that could either directly or indirectly affect food animals.
Five of the seven project plan milestones for FY20 were fully met with the remaining two substantially met. Research efforts directed toward meeting Objective 1 of our project plan originally centered around the production of recombinant prion protein from either bacteria or mammalian tissue culture systems and collection of data on the folding and misfolding of the recombinant prion protein produced. The amount of expressed protein from mammalian expression systems was inherently too low to fully accomplish all aspects of the proposed work. Due to this we have altered our research plan but are still able to accomplish the end goal of understanding the influence of metal ions on prion disease using a mutagenesis based approach altering the metal ion binding sites. Due to the long-term nature of Objective 2, the progress status of the objective has not changed. All studies have been initiated and animals are under observation for the development of clinical signs. The animal studies for this objective are long term and will continue until onset of clinical signs. In vitro studies planned in parallel to the animal's studies have similarly been initiated and are ongoing. Objective 3 of the project plan focuses on the detection of disease associated prion protein in body fluids and feces collected from a time course study of chronic wasting disease inoculated animals. At this time sample collection is complete and preliminary methods have been established. Optimization of those methods is nearing completion and the feasibility of using pooled samples to assess overall herd status is being investigated. Objectives 4 and 5 were recently added to the project and work on both is in the preliminary stages.
1. Differing genetic backgrounds of prion disease sources do not affect likelihood of disease progression. Prion diseases are fatal neurodegenerative diseases that affect a wide range of livestock and wildlife. The disease process occurs through the misfolding of a normally occurring protein. A recently developed approach for the detection of this misfolded protein uses a technique referred to as Real-time quaking induced conversion (RT-QulC). RT-QulC amplifies the amount of misfolded protein for detection and has been used to differentiate prion diseases through differences in the rate of misfolding. ARS scientists in Ames, Iowa, completed a study comparing the relative rates of misfolding in RT-QulC from different sources of chronic wasting disease using both human and bank vole prion protein as the substrate for amplification. Regardless of the chronic wasting disease source and genotype, the bank vole substrate was equivalently sensitive indicating the utility of this substrate for the detection of CWD regardless of host or genotype. Similarly, with human prion protein substrate no differences were found indicating that at the level of conversion of the human prion protein to the fibril form conformation all tested CWD isolates are equivalent. From a diagnostic perspective this further justifies the use of bank vole prion protein as a universal substrate and indicates that regardless of genotype of the CWD source the risk to humans is likely the same. Both results provide important information for knowledge based regulatory decisions by state and federal agencies.
https://www.nature.com/articles/srep11573
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.
==============
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
***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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
PRION 2016 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 online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** 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.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
Subject: MICHIGAN FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE BREACH APRIL 4, 2017
MICHIGAN FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE BREACH APRIL 4, 2017
FDA BSE/Ruminant Feed Inspections Firms Inventory
11998 DET-DO MI 48846-847 OPR 4/4/2017 OAI
http://www.accessdata.fda.gov/scripts/BSEInspect/bseinspections.csv
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
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...end...TSS
***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 ***
http://www.plosone.org/annotation/listThread.action?root=86610
Fri, Sep 3, 2021 5:02 pm
comments comments@tahc.texas.govHide
To Terry Singeltary flounder9@verizon.net
Cc comments comments@tahc.texas.gov
Mr. Singeltary,
This email is to acknowledge receipt of your proposed rule comments. Thank you for your interest and participation in the Texas Animal Health Commission’s rulemaking process.
Sincerely,
Amanda
Amanda Bernhard
Assistant to the Executive Director
Texas Animal Health Commission
512-719-0704
www.tahc.texas.gov
***> 2nd USA should declare a Declaration of Extraordinary Emergency due to CWD, and all exports of cervid and cervid products must be stopped internationally, and there should be a ban of interstate movement of cervid, until a live cwd test is available.
***> 3rd Captive Farmed cervid ESCAPEES should be made mandatory to report immediately, and strict regulations for those suspect cwd deer that just happen to disappear. IF a cervid escapes and is not found, that farm should be indefinitely shut down, all movement, until aid MIA cervid is found, and if not ever found, that farm shut down permanently.
***> 4th Captive Farmed Cervid, INDEMNITY, NO MORE Federal indemnity program, or what i call, ENTITLEMENT PROGRAM for game farm industry. NO MORE BAIL OUTS FROM TAX PAYERS. if the captive industry can't buy insurance to protect not only themselves, but also their customers, and especially the STATE, from Chronic Wasting Disease CWD TSE Prion or what some call mad deer disease and harm therefrom, IF they can't afford to buy that insurance that will cover all of it, then they DO NOT GET A PERMIT to have a game farm for anything. This CWD TSE Prion can/could/has caused property values to fall from some reports in some places. roll the dice, how much is a state willing to lose?
***> 5th QUARANTINE OF ALL FARMED CAPTIVE, BREEDERS, URINE, ANTLER, VELVET, SPERM, OR ANY FACILITY, AND THEIR PRODUCTS, that has been confirmed to have Chronic Wasting Disease CWD TSE Prion, the QUARANTINE should be for 21 years due to science showing what scrapie can do. 5 years is NOT near long enough. see; Infectious agent of sheep scrapie may persist in the environment for at least 16 to 21 years.
***> 6th America BSE 589.2001 FEED REGULATIONS CWD TSE Prion
***> 7TH TRUCKING TRANSPORTING CERVID CHRONIC WASTING DISEASE TSE PRION VIOLATING THE LACEY ACT
***> 8TH ALL CAPTIVE FARMING CERVID OPERATIONS MUST BE INSURED TO PAY FOR ANY CLEAN UP OF CWD AND QUARANTINE THERE FROM FOR THE STATE, NO MORE ENTITLEMENT PROGRAM FOR CERVID GAME FARMING PAY TO PLAY FOR CWD TSE PRION OFF THE TAX PAYERS BACK.
***> 9TH ANY STATE WITH DOCUMENTED CWD, INTERSTATE, NATIONAL, AND INTERNATIONAL MOVEMENT OF ALL CERVID, AND ALL CERVID PRODUCTS MUST BE HALTED!
***> 10TH BAN THE SALE OF STRAW BRED BUCKS AND ALL CERVID SEMEN AND URINE PRODUCTS
***> 11th ALL CAPTIVE FARMED CERVID AND THEIR PRODUCTS MUST BE CWD TSE PRION TESTED ANNUALLY AND BEFORE SALE FOR CWD TSE PRION
SEE FULL SCIENCE REFERENCES AND REASONINGS ;
WEDNESDAY, AUGUST 11, 2021
TAHC Chapter 40, Chronic Wasting Disease Terry Singeltary Comment Submission
https://chronic-wasting-disease.blogspot.com/2021/08/tahc-chapter-40-chronic-wasting-disease.html
Subject: Chronic Wasting Disease from pigs is infectious in transgenic mice expressing human PRNP
TUESDAY, MAY 11, 2021
A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
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