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.
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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. ...
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