Tuesday, September 13, 2022

BSE pathogenesis in the ileal Peyer’s patches and the central and peripheral nervous system of young cattle 8 months post oral BSE challenge

BSE pathogenesis in the ileal Peyer’s patches and the central and peripheral nervous system of young cattle 8 months post oral BSE challenge

Ivett Ackermanna, Reiner Ulrichb, Kerstin Tauscherc, Olanrewaju I. Fatolaa, Christine Fasta, Markus Kellera, James C. Shawulua,d, Mark Arnolde, Stefanie Czubf, Martin H. Groschupa, and Anne Balkema-Buschmanna

aFriedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany; bInstitute of Veterinary Pathology, Faculty of Veterinary Medicine, Leipzig University, Germany; cFriedrich-Loeffler-Institut, Department of Experimental Animal Facilities and Biorisk Management, Greifswald-Insel Riems, Germany; dDepartment of Veterinary Anatomy, University of Abuja, Nigeria; eAnimal and Plant Health Agency Sutton Bonington, Sutton Bonington, Loughborough, England; fCanadian Food Inspection Agency, Lethbridge Laboratory, Lethbridge, Alberta, Canada

Aims: After oral exposure of cattle with classical bovine spongiform encephalopathy (C-BSE), the infectious agent ascends from the gut to the central nervous system (CNS) primarily via the autonomic nervous as the first entry port to system. However, the early timeline of the progression from the gut to the brain has so far remained widely undetermined. To shed light on the early BSE pathogenesis in unweaned calves, we orally infected calves at six to eight weeks of age with a high dose of classical BSE, and followed the pathogenesis within the first eight months post infection.

Material and Methods: 18 unweaned Simmental calves aged 4 to 6 weeks were orally challenged with 100 g each of a classical BSE brainstem pool, while two calves served as negative controls. The animals were euthanized and necropsied at predetermined time points of 1 week as well as 2, 4, 6 and 8 months post infection (mpi). Two infected cattle were kept until the development of clinical symptoms of BSE and served as positive controls. For each of the 18 infected and two negative control calves, samples of the ileal Peyer’s patches as well as the CNS and peripheral nervous system (PNS) were examined by immunohistochemistry (IHC), protein misfolding cyclic amplification (PMCA) and by transgenic Tgbov XV mouse bioassay.

Results: In the ileal Peyer’s patches, BSE prions were detectable as early as two mpi by PMCA and transgenic mouse bioassay. From four mpi, PrPScaccumulation was detectable by IHC in tingible body macrophages (TBMs) of the IPP follicles and already in follicular dendritic cells (FDCs). We were also able to show that as early as 8 mpi, the thoracic spinal cord as well as the parasympathetic nodal ganglion of these animals may contain PrPBSEand BSE infectivity. The positive control animals developed clinical signs of BSE after incubation periods of 32 mpi and 36 mpi, respectively.

Conclusions: Our study demonstrates for the first time PrPBSE(by PMCA) and prion infectivity (by mouse bioassay) in the ileal Peyer’s patch (IPP) of young calves as early as 2 months after infection. From 4 mpi nearly all calves showed PrPBSEpositive IPP follicles by IHC. We could also show that the centripetal prion spread starts early after challenge at least in this age group, which represents an essential piece of information for the risk assessments for food, feed and pharmaceutical products produced from young calves.

Funded by: This research was funded by WALA Heilmittel GmbH. The sponsors had no role in the design, execution, interpretation, or writing of the study.

Acknowledgement: We thank the Scientific Advisory Group (SAG), namely Thierry Baron (ANSES Lyon), Michael Beekes (RKI Berlin), Jim Hope, Marion Simmons, John Spiropoulos (all APHA Weybridge) and Paul Brown (NINDS Bethesda, USA) for their advice and input regarding the design and interpretation of this study. Julia Neumeister, Daniel Balkema and Bärbel Hammerschmidt are acknowledged for their skillful technical assistance. We are thankful to Lukas Steinke, Nicole Sinkwitz, Kerstin Kerstel and Doreen Fiedler for their excellent care of the bioassay mice. We are grateful to Stefanie Marzahl, Ben Schiller and Volker Netz for the great care and handling of the experimental cattle.

PRION 2022 ABSTRACTS, AND A BIG THANK YOU TO 

On behalf of the Prion2020/2022 Congress Organizing Committee and the NeuroPrion Association, we heartily invite you to join us for the International Conference Prion2020/2022 from 13.-16. September 2022 in Göttingen.

Prion 2022 Conference abstracts: pushing the boundaries


Sunday, January 10, 2021 
APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission June 17, 2019

APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission

Greetings APHIS et al, 

I would kindly like to comment on APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], and my comments are as follows, with the latest peer review and transmission studies as references of evidence.

THE OIE/USDA BSE Minimal Risk Region MRR is nothing more than free pass to import and export the Transmissible Spongiform Encephalopathy TSE Prion disease. December 2003, when the USDA et al lost it's supposedly 'GOLD CARD' ie BSE FREE STATUS (that was based on nothing more than not looking and not finding BSE), once the USA lost it's gold card BSE Free status, the USDA OIE et al worked hard and fast to change the BSE Geographical Risk Statuses i.e. the BSE GBR's, and replaced it with the BSE MRR policy, the legal tool to trade mad cow type disease TSE Prion Globally. The USA is doing just what the UK did, when they shipped mad cow disease around the world, except with the BSE MRR policy, it's now legal. 

Also, the whole concept of the BSE MRR policy is based on a false pretense, that atypical BSE is not transmissible, and that only typical c-BSE is transmissible via feed. This notion that atypical BSE TSE Prion is an old age cow disease that is not infectious is absolutely false, there is NO science to show this, and on the contrary, we now know that atypical BSE will transmit by ORAL ROUTES, but even much more concerning now, recent science has shown that Chronic Wasting Disease CWD TSE Prion in deer and elk which is rampant with no stopping is sight in the USA, and Scrapie TSE Prion in sheep and goat, will transmit to PIGS by oral routes, this is our worst nightmare, showing even more risk factors for the USA FDA PART 589 TSE PRION FEED ban. 

The FDA PART 589 TSE PRION FEED ban has failed terribly bad, and is still failing, since August 1997. there is tonnage and tonnage of banned potential mad cow feed that went into commerce, and still is, with one decade, 10 YEARS, post August 1997 FDA PART 589 TSE PRION FEED ban, 2007, with 10,000,000 POUNDS, with 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. you can see all these feed ban warning letters and tonnage of mad cow feed in commerce, year after year, that is not accessible on the internet anymore like it use to be, you can see history of the FDA failure August 1997 FDA PART 589 TSE PRION FEED ban here, but remember this, we have a new outbreak of TSE Prion disease in a new livestock species, the camel, and this too is very worrisome.

WITH the OIE and the USDA et al weakening the global TSE prion surveillance, by not classifying the atypical Scrapie as TSE Prion disease, and the notion that they want to do the same thing with typical scrapie and atypical BSE, it's just not scientific.

WE MUST abolish the BSE MRR policy, go back to the BSE GBR risk assessments by country, and enhance them to include all strains of TSE Prion disease in all species. With Chronic Wasting CWD TSE Prion disease spreading in Europe, now including, Norway, Finland, Sweden, also in Korea, Canada and the USA, and the TSE Prion in Camels, the fact the the USA is feeding potentially CWD, Scrapie, BSE, typical and atypical, to other animals, and shipping both this feed and or live animals or even grains around the globe, potentially exposed or infected with the TSE Prion. this APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], under it's present definition, does NOT show the true risk of the TSE Prion in any country. as i said, it's nothing more than a legal tool to trade the TSE Prion around the globe, nothing but ink on paper.

AS long as the BSE MRR policy stays in effect, TSE Prion disease will continued to be bought and sold as food for both humans and animals around the globe, and the future ramifications from friendly fire there from, i.e. iatrogenic exposure and transmission there from from all of the above, should not be underestimated. ... 






RE: Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9
TERRY S. SINGELTARY SR. 
  • retired
  •  
  • Mr.
seems that the USA feed ban for ruminant protein is still a serious problem, so there seems to still be a risk factor for pigs and Transmissible Spongiform Encephalopathy TSE prion disease. now with the updated science showing that pigs are susceptible to the Chronic Wasting Disease TSE Prion ORALLY, and cwd running rampant in the USA, any use of porcine organs should be tested for the CWD TSE Prion...

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research

Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin

Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:
Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.

Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 month challenge groups). The remaining pigs (>6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.

Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). Conclusions:

This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge.

CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.

Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.


CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...


we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.


Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....


snip...see much more here ;

Terry S. Singeltary Sr.


Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease

Nathaniel D. Denkers ,Clare E. Hoover ,Kristen A. Davenport,Davin M. Henderson,Erin E. McNulty,Amy V. Nalls,Candace K. Mathiason,Edward A. Hoover 

Published: August 20, 2020


We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.


TUESDAY, SEPTEMBER 07, 2021
Atypical Bovine Spongiform Encephalopathy BSE OIE, FDA 589.2001 FEED REGULATIONS, and Ingestion Therefrom



Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA?


WEDNESDAY, JANUARY 12, 2022 

Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA, what if?


PLOS ONE Journal 

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;


IBNC Tauopathy or TSE Prion disease, it appears, no one is sure 

Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT

***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 ***


MONDAY, NOVEMBER 30, 2020 

***> REPORT OF THE MEETING OF THE OIE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES Paris, 9–13 September 2019 BSE, TSE, PRION

see updated concerns with atypical BSE from feed and zoonosis...terry


WEDNESDAY, DECEMBER 8, 2021 

Importation of Sheep, Goats, and Certain Other Ruminants AGENCY: Animal APHIA, USDA, FINAL RULE [Docket No. APHIS–2009–0095] RIN 0579–AD10 


WEDNESDAY, MARCH 24, 2021 

USDA Animal and Plant Health Inspection Service 2020 IMPACT REPORT BSE TSE Prion Testing and Surveillance MIA 


THURSDAY, AUGUST 20, 2020 

Why is USDA "only" BSE TSE Prion testing 25,000 samples a year? 


SUNDAY, MARCH 21, 2021 

Investigation Results of Texas Cow That Tested Positive for Bovine Spongiform Encephalopathy (BSE) Aug. 30, 2005 Singeltary's Regiew 2021 


***> The U.S. cases were animals born and raised in the U.S. (Texas, Alabama).

SEE HISTORY AT THE BOTTOM...TSS

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006 


Saturday, August 14, 2010 

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY 

(see mad cow feed in COMMERCE IN ALABAMA...TSS) 


FRIDAY, APRIL 1, 2022 
USDA TAKES THE C OUT OF COOL, what's up with that?
Terry S. Singeltary Sr.

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