Volume 26, Number 10—October 2020
Research Letter
Eliminating Spiked Bovine Spongiform Encephalopathy Agent Activity from Heparin
On This Page Research Letter Suggested Citation Tables Table Downloads RIS [TXT - 2 KB] Article Metrics Metric Details Cyrus BettComments to Author , Omozusi Andrews, David M. Asher, Teresa Pilant, David Keire, and Luisa Gregori Author affiliations: US Food and Drug Administration, Silver Spring, Maryland, USA (C. Bett, O. Andrews, D.M. Asher, T. Pilant, L. Gregori); US Food and Drug Administration, St. Louis, Missouri, USA (D. Keire) Suggested citation for this article
Abstract US manufacturers, concerned about bovine spongiform encephalopathy (BSE), ceased marketing bovine heparin in the 1990s. Recent short supplies of safe porcine heparin suggest that reintroducing bovine heparin might benefit public health. We purified heparin from crude bovine extract spiked with BSE agent, removing substantial infectivity and abnormal prion proteins (PrPTSE).
Heparin is a widely used injectable anticoagulant. In the 1990s, bovine-derived heparin was withdrawn from the US market because of concerns about possible contamination of bovine tissues with the agent of bovine spongiform encephalopathy (BSE), the causative agent of variant Creutzfeldt-Jakob disease (vCJD) in humans (1). Currently, only porcine heparin, mostly from China, is marketed in the United States. The US Food and Drug Administration has encouraged reintroduction of bovine-sourced heparin into the US market to improve the reliability of the heparin supply chain by diversifying sources (2,3). The risk that BSE agent might contaminate bovine tissues is now very small because of safeguards implemented during the BSE crisis (4).
We previously showed that a model 4-step bench-scale heparin manufacturing process cleared substantial amounts of spiked scrapie agent, a surrogate for BSE agent (5). Our protocol yielded heparin with physicochemical identity, purity, and potency similar to those of United States Pharmacopeia (USP) standard heparin. In this study, we spiked commercial crude bovine heparin with BSE agent itself and processed samples using the same manufacturing process we applied to scrapie agent. We tested each intermediate product for residual abnormal prion protein (PrPTSE, a biochemical marker of BSE) and infectivity. We assayed BSE infectivity using intracerebral inoculations of 30-μL volumes into BSE-susceptible transgenic mice (TgBo110) overexpressing the bovine prion-protein–encoding (PRNP) gene (6). To overcome heparin’s acute toxicity when administered intracerebrally into mice, we diluted the samples; 10−4 was the lowest dilution tolerated.
We ended the study 2 years after inoculations, testing brains of all mice for PrPTSE using the HerdCheck BSE-Scrapie Ag Test (IDEXX Laboratories, https://www.idexx.comExternal Link) (7), which was previously found to be more sensitive than Western blots (8), to assign final disease status (Table). We detected infectivity in samples up to the diatomaceous-earth (DE) filtration step. We estimated removals by DE filtration conservatively, assuming that a 10-fold lower dilution, not tested, would have infected all mice. Sodium hydroxide (NaOH) treatment removed 1.7 log10 of BSE infectivity and DE filtration removed >1.1 log10 of BSE infectivity. To increase sensitivity of the mouse bioassay, we removed heparin by centrifuging samples (20,000 × g, 1 hr, 4°C), washed the pellets, resuspended them in inoculation buffer, and inoculated mice as described. We tested brains of all mice for PrPTSE as reported previously (5). We detected residual infectivity in all aliquots, including the final product. NaOH treatment removed 1.5 log10 of BSE infectivity. We estimated removals by other steps. DE filtration removed ≥1.4 log10 of BSE infectivity. The hydrogen peroxide bleaching and methanol precipitation (final product) steps each removed <1 a="" considered="" cumulatively="" heparin="" infectivity="" log10="" negligible.="" of="" purification="" removed="" scaled-down="" thus="" total="">2.9 log10 of BSE infectivity; NaOH treatment and DE filtration were the only effective steps.
We also quantified residual PrPTSE in each sample using the real-time quaking-induced conversion (RT-QuIC) assay with hamster–sheep chimeric prion protein (9) as substrate, expressing results as log10 50% seeding doses (SD50), as reported previously (5). We detected PrPTSE in unspun BSE spike and NaOH-treated samples but only inconsistent signals in aliquots from successive steps (data not shown). To increase sensitivity and remove heparin interfering with RT-QuIC at low concentrations of PrPTSE, we centrifuged all samples as we did previously. To quantify PrPTSE, we resuspended pellets and serially diluted each sample in phosphate-buffered saline 0.05% sodium dodecyl sulfate, adding 2 µL of each dilution to seed RT-QuIC, each dilution into quadruplicate wells (see log10 SD50 values in Table). NaOH treatment removed 2.4 log10 of PrPTSE and DE filtration steps removed 1.3 log10 of PrPTSE. Hydrogen peroxide bleaching and methanol precipitation reduced PrPTSE by only negligible amounts. Thus, processing from crude heparin to final pharmaceutical heparin cumulatively removed 3.7 log10 of spiked PrPTSE.
We showed previously, using a rodent-adapted scrapie agent, that heparin processing removed 3.6 log10 of scrapie infectivity and 3.4 log10 of PrPTSE (5). Here, we report studies with the more relevant BSE agent itself, showing similar reduction by 3.7 log10 of PrPTSE. We could demonstrate only >2.9 log10 reduction in infectivity, because the starting titer of the BSE-infected brain homogenate was low. However, we detected both residual BSE infectivity and PrPTSE seeding activity after final steps of processing, so our model process did not yield sterile heparin. We found NaOH treatment and DE filtration to be the most effective steps for removing both BSE infectivity and PrPTSE seeding activity, consistent with previous results using scrapie agent.
Overall, our data suggest that typical heparin manufacturing is likely to remove substantial amounts of BSE agent. Furthermore, a probabilistic model assessing the vCJD risk for bovine heparin sourced from cattle in the United States and Canada estimated the risk to be very low (10). The demonstrated ability of a typical heparin purification process to remove substantial amounts of contaminating BSE agent, taken together with careful selection of low-risk bovine material to manufacture heparin, provides additional assurance of safety, supporting eventual reintroduction of bovine heparin to the US market.
Dr. Bett is a chemist at the US Food and Drug Administration, Silver Spring, Maryland, USA. His research focuses on protecting biological products from contamination with TSE agents to advance public health.
Top
Acknowledgments We thank the staff in the Food and Drug Administration (FDA) Division of Veterinary Services for the outstanding care of animals. We owe special thanks to the staff in the laboratory of Byron Caughey at Rocky Mountain Laboratory, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, for giving us the recombinant constructs.
The FDA Animal Care and Use Committee approved all animal studies (ASP #2015-07). Intramural grants from the FDA supported the work.
''Here, we report studies with the more relevant BSE agent itself, showing similar reduction by 3.7 log10 of PrPTSE.''
''We could demonstrate only >2.9 log10 reduction in infectivity, because the starting titer of the BSE-infected brain homogenate was low.''
''However, we detected both residual BSE infectivity and PrPTSE seeding activity after final steps of processing, so our model process did not yield sterile heparin.''
WEDNESDAY, JULY 31, 2019
Congress seeks briefing on potential threat to U.S. heparin supply, what about mad pig disease and cwd ?
Congress seeks briefing on potential threat to U.S. heparin supply
SUNDAY, MAY 26, 2019
Validation studies of bovine heparin manufacturing process spiked with BSE agent
Sunday, February 08, 2015
FDA SCIENCE BOARD TO THE FOOD AND DRUG ADMINISTRATION BOVINE HEPARIN BSE CJD TSE PRION Wednesday, June 4, 2014
speaking of mad pig disease ;
Wednesday, January 28, 2015
BOVINE HEPARIN POSITION STATEMENT ON THE REINTRODUCTION and POTENTIAL BSE TSE PRION RISK FACTORS THEREFROM
MONDAY, OCTOBER 31, 2011
Getting the Farm Out of Pharma for Heparin Production
2019
="">
cwd scrapie pigs oral routes
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> 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 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" 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.
May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...
3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...
But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...
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...
It was not until . . . August 1990, that the result from the pig persuaded both SEAC and us to change our view and to take out of pig rations any residual infectivity that might have arisen from the SBOs.
4.303 The minutes of the meeting record that:
It was very difficult to draw conclusions from one experimental result for what may happen in the field. However it would be prudent to exclude specified bovine offals from the pig diet. Although any relationship between BSE and the finding of a spongiform encephalopathy in cats had yet to be demonstrated, the fact that this had occurred suggested that a cautious view should be taken of those species which might be susceptible. The 'specified offals' of bovines should therefore be excluded from the feed of all species. 17
IN CONFIENCE
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
1. CMO should be aware that a pig inoculated experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months developed an illness, now confirmed as a spongiform encephalopathy. This is the first ever description of such a disease in a pig, although it seems there ar no previous attempts at experimental inoculation with animal material. The Southwood group had thought igs would not be susceptible. Most pigs are slaughtered when a few weeks old but there have been no reports of relevant neurological illness in breeding sows or other elderly pigs. ...see full text ;
IN CONFIDENCE
So it is plausible pigs could be preclinically affected with BSE but since so few are allowed to reach adulthood this has not been recognised through clinical disease. ...
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.
May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...
3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...
But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...
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.....
BSE TO PIGS NEWS RELEASE
CONFIDENTIAL
BSE: PRESS PRESENTATION
INDUSTRY RESPONSE TYPICAL
DEFENSIVE BRIEFING
CONFIDENTIAL
pigs & pharmaceuticals
COMMERCIAL IN CONFIDENCE COMMITTEE ON SAFETY OF MEDICINE NOT FOR PUBLICATION BOVINE SPONGIFORM ENCEPHALOPATHY WORKING GROUP
There are only two products using porcine brain and these use corticotrophin BP, made from porcine pituitary, source from outside the UK.............
snip...
7 OF 10 LITTLE PIGGIES WENT ON TO DEVELOP BSE;
1: J Comp Pathol. 2000 Feb-Apr; 122(2-3): 131-43. Related Articles,
The neuropathology of experimental bovine spongiform encephalopathy in the pig.
Ryder SJ, Hawkins SA, Dawson M, Wells GA.
Veterinary Laboratories Agency Weybridge, Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, UK.
In an experimental study of the transmissibility of BSE to the pig, seven of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral inoculation with a homogenate of bovine brain from natural BSE cases developed lesions typical of spongiform encephalopathy. The lesions consisted principally of severe neuropil vacuolation affecting most areas of the brain, but mainly the forebrain. In addition, some vacuolar change was identified in the rostral colliculi and hypothalamic areas of normal control pigs. PrP accumulations were detected immunocytochemically in the brains of BSE-infected animals. PrP accumulation was sparse in many areas and its density was not obviously related to the degree of vacuolation. The patterns of PrP immunolabelling in control pigs differed strikingly from those in the infected animals.
PMID: 10684682 [PubMed - indexed for MEDLINE]
snip...
In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility.
see full text and more transmission studies here ;
Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie.
Emerg Infect Dis. 2009 Aug; [Epub ahead of print]
***> NEW TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE (MAD CAMEL DISEASE) IN A NEW SPECIES <***NEW OUTBREAK OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE IN A NEW SPECIESSubject: Prion Disease in Dromedary Camels, AlgeriaOur identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.Wednesday, May 30, 2018Dromedary camels in northern Africa have a neurodegenerative prion disease that may have originated decades ago***> IMPORTS AND EXPORTS <***SEE MASSIVE AMOUNTS OF BANNED ANIMAL PROTEIN AKA MAD COW FEED IN COMMERCE USA DECADES AFTER POST BANWEDNESDAY, JULY 11, 2018CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000TUESDAY, JULY 10, 2018CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS*** ''but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.''CONFIDENTIAL SPONGIFORM ENCEPHALOPATHY OF PIGS
MONDAY, FEBRUARY 25, 2019
MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
FRIDAY, JULY 26, 2019
Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species
TUESDAY, JULY 30, 2019
Guidelines for reporting surveillance data on Transmissible Spongiform Encephalopathies (TSE) in the EU within the framework of Regulation (EC) No 999/2001 APPROVED: 9 July 2019
TUESDAY, JULY 23, 2019
APHIS USDA Administrator Announces Several Senior Leadership Changes As Trump Prepares Apparently To Fire 100's of Scientists That Don't Agree With Him, what about mad cow type disease tse prion?
THURSDAY, AUGUST 17, 2017
*** Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States revisited 2017
Singeltary et al
FRIDAY, JUNE 21, 2019
CJD TSE Prion cases update USA, Texas, Canada, and UK
Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Fri, 18 Oct 2002 23:12:22 +0100
From: Steve Dealler
Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member
To: BSE-L@ References: <3daf5023 .4080804="" a="" fg_rewritten="1" fg_scanned="1" href="http://wt.net/" nbsp="" rel="nofollow" style="background-color: rgb(200, 26, 0) !important; color: blue; cursor: pointer; padding-bottom: 3px; padding-left: 3px; padding-right: 3px;" target="_blank">wt.net
Dear Terry,
An excellent piece of review as this literature is desparately difficult to get back from Government sites.
What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!
Steve Dealler ===============
snip...see full text;
MONDAY, FEBRUARY 25, 2019
MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
MONDAY, JULY 27, 2020
BSE Inquiry DFA's a review
2019
49. The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L
E. D. Cassmanna,b, S. J. Moorea,b, R. D. Kokemullera, A. Balkema-Buschmannc, M. H. Groschupcand J. J. Greenleea
aVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA (EDC, SJM, RDK, JJG); bOak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Department of Agriculture (USDA). ORISE is managed by ORAU under DOE contract number DE-SC0014664. (EDC, SJM), Department of Veterinary Pathology, Iowa State University, Ames, IA, USA (JDS); cInstitute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald – Isle of Riems, Germany (ABB, MHG)
CONTACT E. D. Cassmann eric.cassmann@usda.gov
ABSTRACT
Introduction: Transmissible mink encephalopathy (TME) is a fatal neurologic prion disease of farmed mink. Epidemiologic and experimental evidence following a Wisconsin outbreak in 1985 has linked TME to low-type bovine spongiform encephalopathy (BSE-L). Evidence suggests that farmed mink were likely exposed through feeding of BSE-L infected downer cattle. The interspecies transmission of TME to cattle has been documented. Recently, we demonstrated the susceptibility of sheep to cattle passaged TME by intracranial inoculation. The aim of the present study was to compare ovine passaged cattle TME to other prion diseases of food-producing animals. Using a bovine transgenic mouse model, we compared the disease phenotype of sheep TME to BSE-C and BSE-L.
Materials and Methods: Separate inoculants of sheep passaged TME were derived from animals with the VRQ/VRQ (VV136) and ARQ/VRQ (AV136) prion protein genotype. Transgenic bovinized mice (TgBovXV) were intracranially inoculated with 20 µl of 1% w/v brain homogenate. The disease phenotypes were characterized by comparing the attack rates, incubation periods, and vacuolation profiles in TgBovXV mice.
Results: The attack rate for BSE-C (13/13), BSE-L (18/18), and TMEVV (21/21) was 100%; whereas, the TMEAV group (15/19) had an incomplete attack rate. The average incubation periods were 299, 280, 310, and 541 days, respectively. The vacuolation profiles of BSE-L and TMEVV were most similar with mild differences observed in the thalamus and medulla. Vacuolation profiles from the BSE-C and TMEAV experimental groups were different than TMEVVand BSE-L.
Conclusion: Overall the phenotype of disease in TME inoculated transgenic mice was dependent on the sheep donor genotype (VV vs AV). The results of the present study indicate that TME isolated from VRQ/VRQ sheep is similar to BSE-L with regards to incubation period, attack rate, and vacuolation profile. Our findings are in agreement with previous research that found phenotypic similarities between BSE-L and cattle passaged TME in an ovine transgenic rodent model. In this study, the similarities between ovine TME and BSE-L are maintained after multiple interspecies passages.
Prion2019 Conference
2007
August 1988
Evidence That Transmissible Mink Encephalopathy Results From Feeding Infected Cattle
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. snip... The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
MONDAY, MAY 20, 2019
Tracking and clarifying differential traits of classical- and atypical L-type bovine spongiform encephalopathy prions after transmission from cattle to cynomolgus monkeys
SUNDAY, APRIL 14, 2019
Estimation of prion infectivity in tissues of cattle infected with atypical BSE by real time-quaking induced conversion assay
WEDNESDAY, APRIL 24, 2019
***> USDA Announces Atypical Bovine Spongiform Encephalopathy Detection Aug 29, 2018 A Review of Science 2019 <***
TUESDAY, MARCH 26, 2019
Joint Statement from President Donald J. Trump USA and President Jair Bolsonaro Brazil FOREIGN POLICY BSE TSE Prion aka mad cow disease
SATURDAY, JUNE 01, 2019
Brazil reports another cases of mad cow disease atypical BSE TSE Prion
PLEASE BE ADVISED THERE IS NO SCIENTIFIC PROOF THAT ANY ATYPICAL BSE TSE PRION IS OF A SPONTANEOUS OLD AGE DISEASE, NOT CAUSED BY FEED, THIS IS FALSE AND UNPROVEN, IN FACT, ATYPICAL BSE OF THE L AND H TYPE ARE TRANSMISSIBLE BY ORAL ROUTE. THIS STATEMENT THAT ATYPICAL BSE IS A SPONTANEOUS EVENT CAUSED BY OLD AGE, CAUSED BY NOTHING, IS ABSOLUTELY A LIE, AND THE GOVERNMENT OF BRAZIL, AND OTHER GOVERNMENTS THAT PRODUCE SUCH STATEMENTS, KNOWS THIS IS AN UNPROVEN STATEMENT...TERRY SINGELTARY SR.
TUESDAY, JULY 16, 2019
Spain Bovine Spongiform Encephalopathy BSE TSE Prion July 5 2019
WEDNESDAY, AUGUST 15, 2018
The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge
WEDNESDAY, APRIL 17, 2019
Estimating the impact on food and edible materials of changing scrapie control measures: The scrapie control model
TUESDAY, MARCH 26, 2019 USDA ARS 2018
USAHA RESOLUTIONS TWO PRONGED APPROACH NEEDED FOR ADVANCING CATTLE TRACEABILITY
THURSDAY, MARCH 14, 2019
USDA APHIS CDC FDA BSE TSE PRION UPDATE 2019
THURSDAY, FEBRUARY 28, 2019
BSE infectivity survives burial for five years with only limited spread
MONDAY, JUNE 24, 2019
APHIS, FSIS, USDA, FDA, Transmissible Spongiform Encephalopathy TSE, BSE, CWD, Scrapie, Camel TSE Prion Disease, CJD Humans
TUESDAY, JULY 30, 2019
Guidelines for reporting surveillance data on Transmissible Spongiform Encephalopathies (TSE) in the EU within the framework of Regulation (EC) No 999/2001 APPROVED: 9 July 2019
2019
friendly fire, pass it forward, they call it iatrogenic cjd, or what i call 'tse prion poker', are you all in $$$
SATURDAY, MARCH 16, 2019
Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) Guidance for Industry and Food and Drug Administration Staff Document issued on March 15, 2019 Singeltary Submission
TUESDAY, APRIL 09, 2019
Horizon Health Network Moncton Hospital notified more than 700 patients after two cases of CJD were diagnosed both patients had undergone cataracts surgery before being diagnosed
SUNDAY, MAY 24, 2020
Cosmetics, Intestines, FDA, BSE, TSE, Prion, and Improving Biosecurity Procedures to Minimize the Risk of Spreading Pathogenic Infections Agents After Carcass Recycling
THURSDAY, JULY 02, 2020
Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure
THURSDAY, JUNE 25, 2020
First Report of the Potential Bovine Spongiform Encephalopathy (BSE)-Related Somatic Mutation E211K of the Prion Protein Gene (PRNP) in Cattle
WEDNESDAY, JUNE 10, 2020
Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.
our results clearly indicate that atypical BSE adaptation to an ovine-PrP sequence could modify the prion agent to potentially infect humans, showing strain features indistinguishable from those of classic sCJD prions, even though they might or might not be different agents.
However, the expanding range of TSE agents displaying the capacity to transmit in human-PrP–expressing hosts warrants the continuation of the ban on meat and bone meal recycling and underscores the ongoing need for active surveillance
A REVIEW of facts and science on scrapie zoonosis potential/likelihood and the USA incredible failure of the BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)
1st up BSE 589.2001 FEED REGULATIONS
Monday, April 20, 2020
PRION2020 POSTPONED TO 2021 – DUE TO CORONAVIRUS (COVID-19)
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
Greetings List Members,
I was lucky enough to sit in on this BSE conference call today and even managed to ask a question. that is when the trouble started.
I submitted a version of my notes to Sandra Blakeslee of the New York Times, whom seemed very upset, and rightly so.
"They tell me it is a closed meeting and they will release whatever information they deem fit. Rather infuriating."
and i would have been doing just fine, until i asked my question. i was surprised my time to ask a question so quick.
(understand, these are taken from my notes for now. the spelling of names and such could be off.)
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
snip...see full history of the infamous USDA 50 state emergency bse conference call 2001
wasted days and wasted nights...Freddy Fender
Terry S. Singeltary Sr.
