World Organisation for Animal Health 90th General Session of the World Assembly of Delegates BSE TSE Prion 2023
What do I need to know about the official status procedures related to the new BSE standards?
This Q&A aims to clarify some procedural aspects concerning the new Bovine Spongiform Encephalopathy (BSE) standards and their implementation for the procedures of official recognition, annual reconfirmation, and maintenance of BSE risk status proposed for adoption at the May 2023 General Session.
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Q1. Which BSE standards should be referred to if my country is planning to submit an application to WOAH for the recognition of official BSE (controlled or negligible) risk status during the 2023-2024 evaluation cycle?
A. The BSE standards in Chapters 1.8 and 11.4 of the 2022 edition of the Terrestrial Animal Health Code (Terrestrial Code) should be used. As the 2023 edition of the Terrestrial Code will replace the 2022 version on WOAH’s website after the General Session of May 2023, Chapters 1.8 and 11.4 of the 2022 edition of the Terrestrial Code will remain available on the dedicated website for official status recognition (www.woah.org/official-status). Applications based on the new BSE standards will only be accepted from the 2024-2025 evaluation cycle.
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Q2. Why delay the use of the new BSE standards for official status procedures until May 2024?
A. The new BSE standards will enter into force the day after the General Session of May 2023. Nevertheless, WOAH acknowledges the challenges and time it takes for Members to modify and adapt their current BSE risk management measures and surveillance systems in accordance with the new BSE standards, hence the one-year delay for the application of procedures for official recognition and annual reconfirmation of BSE risk status.
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Q3. Could you further elaborate on the delay and specify how it relates to the new BSE standards (please refer to Annex 1 for further details)?
A.
New BSE standards related to: Applies from May 2023* Applies from May 2024*
Application for official recognition of BSE risk status X1 Annual reconfirmation of BSE risk status X1 Maintenance of BSE risk status after the occurrence of an indigenous case of classical BSE X Surveillance/risk management Transition period X Trade recommendations X
* After WOAH’s General Session
1 Members should follow the new application/reconfirmation form.
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Q4. How is the date from which the risk of the BSE agents being recycled within the cattle population has been negligible (starting date) estimated?
A. The Scientific Commission for Animal Diseases (hereafter the Scientific Commission) agreed that the year of official recognition of the BSE risk status by WOAH could be used by all Members to estimate the starting date:
• For countries and zones with negligible BSE risk status: at least eight years prior to the year of official recognition by WOAH.
2
• For countries and zones with a controlled BSE risk status: at least from the year of official recognition by WOAH.
For example, for a Member officially recognised as having a negligible BSE risk status in 2016, the starting date would be considered as 8 years prior, which would be 2008.
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Q5. Why did WOAH and the Scientific Commission decide not to undertake evaluations retrospectively to determine the exact starting date?
A. The Scientific Commission was of the opinion that, should there be a need, Members could determine the exact starting date on their own by using the provisions in the new BSE standards (Chapter 1.8.) as guidance and using their dossiers already submitted to WOAH (ref. February 2022 report). The reference to the year of official recognition (see Q4) would also provide a basis for all Members.
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Q6. When will the dates of official recognition of BSE risk status of countries and zones already having a BSE risk status be published on WOAH’s website?
A. By August 2023. After WOAH’s General Session of May 2023, WOAH will send a letter to all Delegates of Members with an official BSE risk status explaining the date proposed to be published on WOAH’s website. Upon confirmation by all Delegates, the dates will be published on the dedicated website.
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Q7. Will the adoption of the new BSE standards impact the already recognised official BSE risk status of Members?
A. Between September 2019 and 2022, the Scientific Commission assessed the potential impact of the revision of the BSE standards of the Terrestrial Code on existing statuses, focusing on Members whose risk status was previously recognised based on a negligible entry assessment (with a non-negligible exposure assessment) and concluded that the new BSE standards would not impact the already recognised BSE risk status of countries and zones.
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Q8. What happens if my country reports a classical BSE case on the day after the new BSE standards are adopted?
A. It will be treated according to the new BSE standards (Please refer to the table under Q3 and Annex 1). The official BSE risk status accorded to the country/zone will be maintained for up to 90 days, during which the relevant documentation on the epidemiological investigations carried out providing evidence that there was no breach in the BSE control or surveillance measures should be submitted to WOAH. The Scientific Commission will assess this information before a decision is made on the maintenance of the official BSE risk status. In the case that the documentation is submitted after the 90-days, the officially recognised BSE risk status of the country or zone will be suspended. Precise details for this process will become available on WOAH’s website shortly after the General Session of May 2023.
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Q9. What should my country do if an atypical BSE case is detected on the day after the new BSE standards are adopted?
A. The notification to WOAH of the occurrence of BSE cases would be limited to classical BSE. The information on atypical BSE cases should be provided as part of the annual reconfirmation (and when submitting a dossier for the official recognition of a BSE risk status) in substantiating the effectiveness of the BSE surveillance system.
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DRAFT RESOLUTION No. 20
Second addendum to Resolution No. 15 of 29 May 2020 on the “Procedures for Members for the official recognition and maintenance of animal health status of certain animal diseases or risk status of bovine spongiform encephalopathy and for the endorsement of official control programmes”
CONSIDERING THAT
1. During the Adapted Procedure 2020, the World Assembly of Delegates (the Assembly) adopted Resolution No. 15, which described the procedures that Members should follow to achieve the official recognition and maintenance of animal health status of certain animal diseases or risk status of bovine spongiform encephalopathy (BSE) and for the endorsement of official control programmes,
2. During the 90th General Session, the Assembly adopted Resolution No. 23, which included in the Terrestrial Animal Health Code the revised provisions on BSE and on the application for official recognition by WOAH of risk status for BSE,
THE ASSEMBLY DECIDES THAT
1. the evaluation of the applications for the official recognition and the annual reconfirmation of BSE risk status will be based on the revised provisions adopted during the 90th General Session, beginning from the annual cycle of May 2024 – May 2025;
2. the maintenance of the BSE risk status, should a case of BSE occur in a Member or zone recognised as posing a negligible or controlled risk for BSE, will be defined based on the revised provisions adopted during the 90th General Session, immediately after their entry into force as defined in the Resolution No. 23;
3. this Resolution No. 20 complements Resolution No. 15 adopted during the Adapted Procedure 2020 and Resolution No. 22 adopted at the 88th General Session, which remains in force.
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YOU CAN SEE THE MARKED UP BSe HERE;
World Organisation for Animal Health 90th General Session of the World Assembly of Delegates (BSE TSE Prion) From 21/05/2023 to 25/05/2023 Singeltary Concerns...
***> THIS PRETTY MUCH SAYS IT ALL!
Q9. What should my country do if an atypical BSE case is detected on the day after the new BSE standards are adopted?
A. The notification to WOAH of the occurrence of BSE cases would be limited to classical BSE. The information on atypical BSE cases should be provided as part of the annual reconfirmation (and when submitting a dossier for the official recognition of a BSE risk status) in substantiating the effectiveness of the BSE surveillance system.
THIS IS ABSOLUTELY INCREDIBLY STUPID imo, as with atypical sheep Scrapie, the watering down of said BSE regulations continues, imo, with atypical BSE TSE Prion, which has been shown to be more virulent than the so called typical C-Type BSE, and both Atypical L-type and H-type transmitting orally. Industry wins again over sound science. Let me be perfectly clear here, nobody wants to eradicate BSE, or any other TSE Prion disease in livestock now. it's just a mathematical formula to test as least as possible, to keep said TSE prion infected herds down to said desirable numbers, they simply don't want to know just HOW BAD it is. this was proven way back during the infamous USA ENHANCED BSE SURVEILLACE was put forth, BUT HALTED ABRUBPLY, when all the atypical BSE showed up. Plus, Science has shown that atypical BSE looks like sporadic CJD, plus, BSE can propagate as nvCJD or sporadic CJD, take your pick. well, once again, the World Organization for Animal Health WHO, OIE, et al, choosing industry over human and animal health, imo, with regards, to the Transmissible Spongiform Encephalopathy TSE Prion disease (especially with Chronic Wasting Disease and Camel Prion Disease now).
Atypical BSE should be designated the same as typical BSE, period! your only fooling yourselves$$$
YOU did the same with atypical Scrapie, when you all chose to make that a legal trading commodity with the same type junk science, imo! (see reference materials and history below)...
CHRONIC WASTING DISEASE TSE PRION CERVID apparently no problem in 2023...
5.2.1. Working Group on Wildlife
Due to time constraints, the Commission was unable to discuss the report of the Working Group on Wildlife. Nonetheless, the Commission acknowledged the report of the Working Group on 90 SG/1 – PARIS, MAY 2023 13 Wildlife and agreed to look into the recommendations on the definition of ‘emerging disease’ in further detail at its next meeting.
my plight with OIE et al on CWD;
Tuesday, May 31, 2022
89th General Session of the World Assembly of OIE Delegates for WOAH General Summit 2022 Chronic Wasting Disease CWD TSE Prion Discussions and Concerns 89th General Session of the World Assembly of OIE Delegates for WOAH General Summit 2022 Chronic Wasting Disease CWD TSE Prion Discussions and Concerns
89th General Session of the World Assembly of OIE Delegates for WOAH General Summit From 23/05/2022 to 26/05/2022 12:00pm - 4:30pm (GMT+1:00) Paris
Chronic Wasting Disease CWD Transmissible Spongiform Encephalopathy TSE Prion PrP Disease, NO DISCUSSIONS OR CONCERNS AT 89th General Session of the World Assembly of OIE Delegates for WOAH General Summit From 23/05/2022 to 26/05/2022...terry
From: Gregorio Torres <g.torres@oie.int>
Sent: 30 May 2022 14:15
To: scientific dept <scientific.dept@oie.int>; Sara Linnane <s.linnane@oie.int>
Subject: RE: OIE 89th Session: CWD
HI CWD was not discussed this year.
However it was discussed in several occasions by the Specialist commission. The last discussion was in September 2021 (page 5)
From: Terry Singeltary <flounder9@verizon.net>
Sent: 27 May 2022 19:37
To: scientific dept <scientific.dept@oie.int>
Subject: Re: OIE 89th Session
i can't seem to get a reply?
''i was wondering if chronic wasting disease cwd tse prion of cervid will be addressed at all at the OIE #89, and if so, what session? ''
kind regards, terry
***> However it was discussed in several occasions by the Specialist commission. The last discussion was in September 2021 (page 5)
snip...end...tss
REPORT OF THE MEETING OF THE OIE TERRESTRIAL ANIMAL HEALTH STANDARDS COMMISSION Virtual meeting, 7–16 & 23 September 2021
snip...
The Code Commission was provided with an update on the progress of the work to develop case definitions to support notification being conducted by the Scientific Commission. In response to this update, the Code Commission recognised the value of this work and reminded Members that in order to support notification, newly developed case definitions of listed diseases would be published on the OIE Website if they do not conflict with existing OIE Standards. These case definitions would then be considered for inclusion in the relevant disease-specific chapter of the Terrestrial Code according to the prioritisation of the Code Commission’s work programme and the standard-setting process.
The Code Commission acknowledged the rationale provided in the Scientific Commission’s February 2021 report that chronic wasting disease does not meet the criteria for listing, specifically for point 2 of Article 1.2.2. of Chapter 1.2. Criteria for the inclusion of diseases, infections and infestations in the OIE list. The Commission also noted that the Scientific Commission will consider the expert consultation reports and the opinion of the Laboratories Commission on assessments undertaken for paratuberculosis and West Nile virus in accordance with Chapter 1.2.
The Code Commission wished to thank the Scientific Commission for its collaborative work in providing opinions to support the consideration of relevant Member comments received. The Code Commission reminded Members that its consideration of the Scientific Commission contributions is noted under the relevant agenda items of this report and encouraged Members to read this report together with the September 2021 Scientific Commission report.
REPORT OF THE MEETING OF THE OIE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES Virtual, 1–11 February 2021
iv) Chronic wasting disease
The Commission considered the request by the Code Commission for clarification on the rationale for the Commission’s opinion that CWD did not fulfil the criteria for listing, specifically for point 2 of Article 1.2.26 of the Terrestrial Code. The Commission explained that the opinion was based on an extensive consultation process that took into account the opinions of the ad hoc Group on BSE, the Working Group on Wildlife and several subject-matter expert consultations. Based on this extensive consultation, the Commission indicated that the low disease prevalence, the impractical nature of currently available diagnostic tests, and the limited number of control measures make it difficult to eliminate the disease or scientifically provide evidence to demonstrate either freedom or impending freedom. The Commission considered also that despite the implementation of surveillance programmes by some Members, no country can currently demonstrate either freedom or impending freedom from disease.
Annex 19
WORK PROGRAMME OF THE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES (FEB 2021)
Define a procedure for the evaluation of diseases against the listing criteria of Chapter 1.2., and responding to requests for listing decisions
Evaluated proposals for (de)listing of:
• M. tuberculosis • Infestation of honey bees with Acarapis woodi • Infestation of honey bees with Tropilaelaps spp.
• Chronic wasting disease
• Atypical BSE
6.8. Bovine spongiform encephalopathy (Chapter 11.4.), Application for official recognition by the OIE of risk status for bovine spongiform encephalopathy (Chapter 1.8.) and Glossary definition for ‘protein meal’
Background
In February 2018, following preliminary work and scientific exchanges, the Code Commission and the Scientific Commission agreed to an in-depth review of Chapter 11.4. Bovine spongiform encephalopathy (BSE). The OIE convened three different ad hoc Groups between July 2018 and March 2019: i) an ad hoc Group on BSE risk assessment, which met twice, ii) an ad hoc Group on BSE surveillance, which met once, and iii) a joint ad hoc Group on BSE risk assessment and surveillance, which met once. The Code Commission, at its September 2019 meeting, reviewed the four ad hoc Group reports and the opinion of the Scientific Commission regarding the draft revised chapter and circulated a revised draft Chapter 11.4. for comments. In February 2020, the Code Commission considered comments received on the revised draft Chapter 11.4. and requested that the joint ad hoc Group on BSE risk assessment and surveillance be reconvened to address comments of a technical nature. In June 2020, the joint ad hoc Group was convened to address relevant comments and was also requested to review Chapter 1.8. Application for official recognition by the OIE of risk status for bovine spongiform encephalopathy to ensure alignment with the proposed changes in Chapter 11.4.
In September 2020, the Code Commission reviewed the joint ad hoc Group report and the revised draft Chapters 11.4. and 1.8. and made some additional amendments and circulated the revised chapters for comments in its September 2020 report. In February 2021, the Commission considered comments received and amended the chapters, as appropriate, and circulated the revised chapters for a third round of comments. In preparation for the September 2021 meetings, some members of the Code Commission and the Scientific Commission met to discuss key aspects of the revision of Chapters 11.4. and 1.8. to ensure a common understanding of the main concerns raised by Members, the decisions made on the revised chapters and their impact on the official status recognition, as well as on the adapted procedures that will be required. During this meeting, it was agreed that each Commission would address the issues relevant to its meeting and document discussions in their respective reports.
Discussion
SNIP...SEE FULL TEXT;
OIE Conclusions on transmissibility of atypical BSE among cattle
Given that cattle have been successfully infected by the oral route, at least for L-BSE, it is reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle are exposed to contaminated feed. In addition, based on reports of atypical BSE from several countries that have not had C-BSE, it appears likely that atypical BSE would arise as a spontaneous disease in any country, albeit at a very low incidence in old cattle. In the presence of livestock industry practices that would allow it to be recycled in the cattle feed chain, it is likely that some level of exposure and transmission may occur. As a result, since atypical BSE can be reasonably considered to pose a potential background level of risk for any country with cattle, the recycling of both classical and atypical strains in the cattle and broader ruminant populations should be avoided.
Annex 7 (contd) AHG on BSE risk assessment and surveillance/March 2019
34 Scientific Commission/September 2019
3. Atypical BSE
The Group discussed and endorsed with minor revisions an overview of relevant literature on the risk of atypical BSE being recycled in a cattle population and its zoonotic potential that had been prepared ahead of the meeting by one expert from the Group. This overview is provided as Appendix IV and its main conclusions are outlined below. With regard to the risk of recycling of atypical BSE, recently published research confirmed that the L-type BSE prion (a type of atypical BSE prion) may be orally transmitted to calves1 . In light of this evidence, and the likelihood that atypical BSE could arise as a spontaneous disease in any country, albeit at a very low incidence, the Group was of the opinion that it would be reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle were to be exposed to contaminated feed. Therefore, the recycling of atypical strains in cattle and broader ruminant populations should be avoided.
The Group acknowledged the challenges in demonstrating the zoonotic transmission of atypical strains of BSE in natural exposure scenarios. Overall, the Group was of the opinion that, at this stage, it would be premature to reach a conclusion other than that atypical BSE poses a potential zoonotic risk that may be different between atypical strains.
4. Definitions of meat-and-bone meal (MBM) and greaves
snip...
REFERENCES
SNIP...END SEE FULL TEXT;
ATYPICAL BSE
The L-type BSE prion is much more virulent in primates and in humanized mice than is the classical BSE prion, which suggests the possibility of zoonotic risk associated with the L-type BSE prion
Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
Thus, it is imperative to maintain measures that prevent the entry of tissues from cattle possibly infected with the agent of L-BSE into the food chain.
Atypical L-type bovine spongiform encephalopathy (L-BSE) transmission to cynomolgus macaques, a non-human primate
Fumiko Ono 1, Naomi Tase, Asuka Kurosawa, Akio Hiyaoka, Atsushi Ohyama, Yukio Tezuka, Naomi Wada, Yuko Sato, Minoru Tobiume, Ken'ichi Hagiwara, Yoshio Yamakawa, Keiji Terao, Tetsutaro Sata
Affiliations expand
PMID: 21266763
Abstract
A low molecular weight type of atypical bovine spongiform encephalopathy (L-BSE) was transmitted to two cynomolgus macaques by intracerebral inoculation of a brain homogenate of cattle with atypical BSE detected in Japan. They developed neurological signs and symptoms at 19 or 20 months post-inoculation and were euthanized 6 months after the onset of total paralysis. Both the incubation period and duration of the disease were shorter than those for experimental transmission of classical BSE (C-BSE) into macaques. Although the clinical manifestations, such as tremor, myoclonic jerking, and paralysis, were similar to those induced upon C-BSE transmission, no premonitory symptoms, such as hyperekplexia and depression, were evident. Most of the abnormal prion protein (PrP(Sc)) was confined to the tissues of the central nervous system, as determined by immunohistochemistry and Western blotting. The PrP(Sc) glycoform that accumulated in the monkey brain showed a similar profile to that of L-BSE and consistent with that in the cattle brain used as the inoculant. PrP(Sc) staining in the cerebral cortex showed a diffuse synaptic pattern by immunohistochemistry, whereas it accumulated as fine and coarse granules and/or small plaques in the cerebellar cortex and brain stem. Severe spongiosis spread widely in the cerebral cortex, whereas florid plaques, a hallmark of variant Creutzfeldt-Jakob disease in humans, were observed in macaques inoculated with C-BSE but not in those inoculated with L-BSE.
see full text;
''H-TYPE BSE AGENT IS TRANSMISSIBLE BY THE ORONASAL ROUTE''
This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
A Surprisingly High Number of the Plaque-Like VV sCJD Subtype Among the Polish sCJD-is There a Connection with BASE?
PPo4-15:
A Surprisingly High Number of the Plaque-Like VV sCJD Subtype Among the Polish sCJD—is There a Connection with BASE?
Beata Sikorska and Pawel P. Liberski Department of Molecular Pathology and Neuropathology; Medical University of Lodz; Lodz, Poland
Recently described bovine amyloidotic spongiform encephalopathy (BASE) or L type BSE—was is overrepresented in Poland (15% of all cases of BSE). Moreover, the number of BASE cases in Poland per million bovines is the highest in Europe. A potential human risk from BASE is evident from experimental transmission to “humanized” transgenic animals and primates. Taking into consideration that non-human primate inoculated with BASE had a shorter incubation period than monkeys infected with classical BSE, and that humanized Tg mice have been found to be highly susceptible to infection with atypical form of BSE, it seems probable that BASE may be more pathogenic for humans than BSE, but the transmitted disease may differ from BSE-derived vCJD. Among 47 cases which have been diagnosed as definite in our laboratory, in 19 cases complete histopathological examination and codon 129 status were available. On the basis of the histological pattern and codon 129 status the cases of sCJD were divided into subtypes according to the Parchi&Gambetti classification. The results are as follows: type 1 (MMorMV)- 42%, type 2 (VV)-32%, type 3 (MV)-10.5%, type 4c (MM)- 10.5% and type 5 (VV)-5 %. Although the number of cases is too low to conclude a significantly different distribution of sCJD subtypes in Polish population those data show surprisingly high number of the plaque-like VV sCJD subtype. Interestingly, it was shown before that Tg mice inoculated with BASE showed granular and plaque-like aggregates or PrPSc in brains resembling those observed in VV2 subtype of sCJD.
PPo2-26:
Transmission of Classical and Atypical (L-type) Bovine Spongiform Encephalopathy (BSE) Prions to Cynomolgus macaques
Fumiko Ono,1 Yoshio Yamakawa,2 Minoru Tobiume,3 Yuko Sato,3 Harutaka Katano,3 Kenichi Hagiwara,2 Iori Itagaki,1 Akio Hiyaoka,1 Katuhiko Komatuzaki,1 Yasunori Emoto,1 Hiroaki Shibata,4 Yuichi Murayama,5 Keiji Terao,4 Yasuhiro Yasutomi4 and Tetsutaro Sata3
1The Corporation for Production and Research of Laboratory Primates; Tsukuba City, Japan; 2Departments of Cell Biology and Biochemistry; and 3Pathology; National Institute of Infectious Diseases; Tokyo, Japan; 4Tsukuba Primate Research Center; National Institute of Biomedical Innovation; Tsukuba City, Japan; 5Prion Disease Research Team; National Institute of Animal Health; Tsukuba City, Japan
Key words: L-type BSE, cBSE, cynomolgus macaques, transmission
BSE prion derived from classical BSE (cBSE) or L-type BSE was characterized by inoculation into the brain of cynomolgus macaques. The neurologic manifestation was developed in all cynomolgus macaques at 27–43 months after intracerebral inoculation of brain homogenate from cBSE-affected cattle (BSE JP/6). Second transmission of cBSE from macaque to macaque shortened incubation period to 13–18 months. cBSE-affected macaques showed the similar clinical signs including hyperekplexia, tremor and paralysis in both primary and second transmission.
Two macaques were intracerebrally inoculated brain homogenate from the L-type BSE-affected cattle (BSE JP/24). The incubation periods were 19–20 months in primary transmission.
The clinical course of the L-type BSE-affected macaques differed from that in cBSE-affected macaques in the points of severe myoclonus without hyperekplexia. The glycoform profile of PrPSc detected in macaque CNS was consistent with original pattern of either cBSE or L-typeBSE PrPSc, respectively. Although severe spongiform change in the brain was remarkable in all BSE-affected macaques, severe spongiform spread widely in cerebral cortex in L-type BSE-affected macaques. Heavy accumulation of PrPSc surrounded by vacuola formed florid plaques in cerebral cortex of cBSE-affected macaques. Deposit of PrPSc in L-type BSE-affected macaque was weak and diffuse synaptic pattern in cerebrum, but large PrPSc plaques were evident at cerebellum. MRI analysis, T2, T1, DW and flair sequences, at the time of autopsy revealed that brain atrophy and dilatation of cerebral ventricles were significantly severe in L-type BSE-affected macaques. These results suggest that L-type BSE is more virulent strain to primates comparing to cBSE.
SP1-4:
Evidence from Molecular Strain Typing
Gianluigi Zanusso Department of Neurological and Visual Sciences; Section of Clinical Neurology; University of Verona; Verona, Italy
Key words: molecular analysis, strain typing, atypical BSE, CJD
In 2001, active surveillance for bovine spongiform encephalopathy (BSE) led to the discovery of atypical BSE phenotypes in aged cattle distinct from classical BSE (C-type). These atypical BSE cases had been classified as low L-type (BASE) or high H-type BSE based on the molecular mass and the degree of glycosylation of of the pathological prion protein (PrPSc). Transmission studies in TgBov mice showed that H-type BSE, C-type BSE and BASE behave as distinct prion strains with different incubation periods, PrPSc molecular patterns and pathological phenotypes. A still unclear issue concerns the potential transmissibility and phenotypes of atypical BSEs in humans. We previously indicated that BASE was similar to a distinct subgroup of sporadic form of Creutzfeldt-Jakob disease (sCJD) MV2, based on molecular similarities and on neuropathological pattern of PrP deposition. To investigate a possible link between BASE and sCJD, Kong et al. and Comoy et al. experimentally inoculated TgHu mice (129MM) and a non-human primate respectively, showing in both models that BASE was more virulent compare to BSE. Further, non-human primate reproduced a clinical phenotype resembling to that of sCJD subtype MM2. Here, we presented a comparative analysis of the biochemical fingerprints of PrPSc between the different sCJD subtypes and animal TSEs and after experimental transmission to animals.
PRION 2010
WEDNESDAY, SEPTEMBER 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
PRION 2010
International Prion Congress: From agent to disease September 8–11, 2010 Salzburg, Austria
Where has atypical BSE been found? ..
Although the greatest number of cases is in France(12), increasing numbers of cases have now been identified in other countries – Canada (1), Germany (2), Italy (2), Japan (2), Netherlands (4), Poland (7), Sweden (1), Switzerland (1), UK (1), and USA (2). In Sweden and the USA the atypical cases represent the only indigenous cases detected. In other words – typical BSE has not been detected in native cattle in these two countries (34). .. In France, Poland, Netherlands and Germany both H and L forms of atypical BSE have been reported(25).
http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_ATYPICAL_SCRAPIE_AND_%20ATYPICAL_BSE_070516.pdf
tafsforum.org
atypical BSE strains and sporadic CJD strains, is there a connection and why shouldn't there be $
Tuesday, August 19, 2008
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate
"the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine."
just another one of those sporadic CJD coincidences i suppose $$$
NOT to forget ;
Thursday, June 05, 2008
Review on the epidemiology and dynamics of BSE epidemics
Vet. Res. (2008) 39:15 www.vetres.org DOI: 10.1051/vetres:2007053 c INRA, EDP Sciences, 2008 Review article
snip...
And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17]. These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.
snip...
Cases of atypical BSE have only been found in countries having implemented large active surveillance programs. As of 1st September 2007, 36 cases (16 H, 20 L) have been described all over the world in cattle: Belgium (1 L) [23], Canada (1 H)15, Denmark (1 L)16, France (8 H, 6 L)17, Germany (1 H, 1 L) [13], Italy (3 L)18, Japan (1 L) [71], Netherlands (1 H, 2 L)19, Poland (1 H, 6 L)20, Sweden (1 H)21, United Kingdom (1 H)22, and USA (2 H)23. Another H-type case has been found in a 19 year old miniature zebu in a zoological park in Switzerland [56]. It is noteworthy that atypical cases have been found in countries that did not experience classical BSE so far, like Sweden, or in which only few cases of classical BSE have been found, like Canada or the USA.
And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17]. These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.
full text 18 pages ;
please see full text ;
P26
TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS
Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA
Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C. The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.
III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)
http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf
PRION CONFERENCE 2009
Prion special issue related to the III International Symposium on “The New Prion Biology
Research Project: GENETIC AND BIOLOGICAL DETERMINANTS OF RESPIRATORY DISEASE SUSCEPTIBILITY Location: Animal Health Systems Research
Title: Association of a bovine prion gene haplotype with atypical BSE
Author
Clawson, Michael
Submitted to: Meeting Abstract Publication Type: Abstract Publication Acceptance Date: December 2, 2008 Publication Date: January 1, 2009 Citation: Clawson, M.L. 2009. Association of a bovine prion gene haplotype with atypical BSE [abstract]. Plant and Animal Genomes XVII Conference. Abstract No. W091. Available: http://www.intl-pag.org/17/abstracts/
Technical Abstract: Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a class of fatal neurodegenerative disorders that occur in humans, ruminants, cats, and mink. Three distinct TSEs afflict cattle: classical bovine spongiform encephalopathy (BSE), atypical H-type BSE, and atypical L-type BSE. Classical BSE was identified in the 1980s and is acquired by cattle through the consumption of feed contaminated with the infectious prion agent. Atypical BSEs have only recently been recognized as distinct cattle prion diseases and are extremely rare. The full extent of genetic susceptibilities to atypical BSEs is unknown; however, one atypical H-type case identified in the United States (2006) was most likely caused by a genetic mutation in the prion gene, E211K. We have identified an association of a bovine prion DNA haplotype with atypical BSE that is independent of E211K. The haplotype spans a portion of the prion gene that includes part of intron 2, the entire coding region of exon 3, and part of the three prime untranslated region of exon 3 (13 kb). Despite the low frequency of this haplotype among general cattle populations, it was present in a majority of H- and L-type atypical BSE cases from Canada, France, and the United States. This result indicates that there is a genetic component to atypical BSE susceptibility in addition to E211K.
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''
Professor Kong reply ;
.....snip
''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''
Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA
END...TSS
I look forward to further transmission studies, and a true ENHANCED BSE/atypical BSE surveillance program put forth testing all cattle for human and animal consumption for 5 years. a surveillance program that uses the most sensitive TSE testing, and has the personnel that knows how to use them, and can be trusted. I look forward to a stringent mad cow feed ban being put forth, and then strictly enforced. we need a forced, not voluntary feed ban, an enhanced feed ban at that, especially excluding blood. we need some sort of animal traceability. no more excuses about privacy. if somebody is putting out a product that is killing folks and or has the potential to kill you, then everybody needs to know who they are, and where that product came from. same with hospitals, i think medical incidents in all states should be recorded, and made public, when it comes to something like a potential accidental transmission exposure event. so if someone is out there looking at a place to go have surgery done, if you have several hospitals having these type 'accidental exposure events', than you can go some place else. it only makes sense. somewhere along the road, the consumer lost control, and just had to take whatever they were given, and then charged these astronomical prices. some where along the line the consumer just lost interest, especially on a long incubating disease such as mad cow disease i.e. Transmissible Spongiform Encephalopathy. like i said before, there is much more to the mad cow story than bovines and eating a hamburger, we must start focusing on all TSE in all species. ...TSS
P02.35
Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK-resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
http://www.neuroprion.com/pdf_docs/conf ... t_book.pdf
Research Project: Study of Atypical Bse
Location: Virus and Prion Diseases of Livestock
Project Number: 3625-32000-086-05 Project Type: Specific Cooperative Agreement
Start Date: Sep 15, 2004 End Date: Sep 14, 2009
Objective: The objective of this cooperative research project with Dr. Maria Caramelli from the Italian BSE Reference Laboratory in Turin, Italy, is to conduct comparative studies with the U.S. bovine spongiform encephalopathy (BSE) isolate and the atypical BSE isolates identified in Italy. The studies will cover the following areas: 1. Evaluation of present diagnostics tools used in the U.S. for the detection of atypical BSE cases. 2. Molecular comparison of the U.S. BSE isolate and other typical BSE isolates with atypical BSE cases. 3. Studies on transmissibility and tissue distribution of atypical BSE isolates in cattle and other species.
Approach: This project will be done as a Specific Cooperative Agreement with the Italian BSE Reference Laboratory, Istituto Zooprofilattico Sperimentale del Piemonte, in Turin, Italy. It is essential for the U.S. BSE surveillance program to analyze the effectiveness of the U.S diagnostic tools for detection of atypical cases of BSE. Molecular comparisons of the U.S. BSE isolate with atypical BSE isolates will provide further characterization of the U.S. BSE isolate. Transmission studies are already underway using brain homogenates from atypical BSE cases into mice, cattle and sheep. It will be critical to see whether the atypical BSE isolates behave similarly to typical BSE isolates in terms of transmissibility and disease pathogenesis. If transmission occurs, tissue distribution comparisons will be made between cattle infected with the atypical BSE isolate and the U.S. BSE isolate. Differences in tissue distribution could require new regulations regarding specific risk material (SRM) removal.
Wednesday, February 11, 2009
Atypical BSE North America Update February 2009
Both of the BSE cases ascertained in the US native-born cattle were atypical cases (H-type), which contributed to the initial ambiguity of the diagnosis. 174, 185 In Canada, there have been 2 atypical BSE cases in addition to the 14 cases of the classic UK strain of BSE2: one was the H-type, and the other was of the L-type.198
snip...end
source :
Enhanced Abstract Journal of the American Veterinary Medical Association January 1, 2009, Vol. 234, No. 1, Pages 59-72
Bovine spongiform encephalopathy
Jane L. Harman, DVM, PhD; Christopher J. Silva, PhD
http://avmajournals.avma.org/doi/ref/10 ... a.234.1.59
Atypical BSE North America Update February 2009
Volume 12, Number 12—December 2006
On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy and Creutzfeldt-Jakob Disease
Paul Brown*Comments to Author , Lisa M. McShane†, Gianluigi Zanusso‡, and Linda Detwiler§ Author affiliations: *Bethesda, Maryland, USA; †National Institutes of Health, Bethesda, Maryland, USA; ‡University of Verona, Verona, Italy,; §Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA
Abstract Strategies to investigate the possible existence of sporadic bovine spongiform encephalopathy (BSE) require systematic testing programs to identify cases in countries considered to have little or no risk of orally acquired disease or to detect a stable occurrence of atypical cases in countries in which orally acquired disease is disappearing. To achieve 95% statistical confidence that the prevalence for sporadic BSE is no greater than 1 per million (i.e., the annual incidence of sporadic Creutzfeldt-Jakob disease [CJD] in humans) would require negative tests in 3 million randomly selected older cattle. A link between BSE and sporadic CJD has been suggested on the basis of laboratory studies but is unsupported by epidemiologic observation. Such a link might yet be established by the discovery of a specific molecular marker or of particular combinations of trends over time of typical and atypical BSE and various subtypes of sporadic CJD, as their numbers are influenced by a continuation of current public health measures that exclude high-risk bovine tissues from the animal and human food chains.
Snip…
Sporadic CJD The possibility that at least some cases of apparently sporadic CJD might be due to infection by sporadic cases of BSE cannot be dismissed outright. Screening programs needed to identify sporadic BSE have yet to be implemented, and we know from already extant testing programs that at least a proportion of infected animals have no symptoms and thus would never be identified in the absence of systematic testing. Thus, sporadic BSE (or for that matter, sporadic disease in any mammalian species) might be occurring on a regular basis at perhaps the same annual frequency as sporadic CJD in humans, that is, in the range of 1 case per million animals.
Whether humans might be more susceptible to atypical forms of BSE cannot be answered at this time. Experimentally transmitted BASE shows shorter incubation periods than BSE in at least 1 breed of cattle, bovinized transgenic mice, and Cynomolgus monkeys (12,13). In humanized transgenic mice, BASE transmitted, whereas typical BSE did not transmit (13). Paradoxically, the other major phenotype (H) showed an unusually long incubation period in bovinized transgenic mice (12).
The limited experimental evidence bearing on a possible relationship between BSE and sporadic CJD is difficult to interpret. The original atypical BASE strain of BSE had a molecular protein signature very similar to that of 1 subtype (type 2 M/V) of sporadic CJD in humans (5). In another study, a strain of typical BSE injected into humanized mice encoding valine at codon 129 showed a glycopattern indistinguishable from the same subtype of sporadic CJD (15). In a third study, the glycopatterns of both the H and L strains of atypical BSE evidently did not resemble any of the known sporadic CJD subtypes (12).
To these molecular biology observations can be added the epidemiologic data accumulated during the past 30 years. The hypothesis that at least some cases of apparently sporadic CJD are due to unrecognized BSE infections cannot be formally refuted, but if correct, we might expect by now to have some epidemiologic evidence linking BSE to at least 1 cluster of apparently sporadic cases of CJD. Although only a few clusters have been found (and still fewer published), every proposed cluster that has been investigated has failed to show any common exposure to bovines. For that matter, no common exposure has been shown to any environmental vehicles of infection, including the consumption of foodstuffs from bovine, ovine, and porcine sources, the 3 livestock species known to be susceptible to transmissible spongiform encephalopathies. Additional negative evidence comes from several large case-control studies in which no statistically significant dietary differences were observed between patients with sporadic CJD and controls (16,17).
On the other hand, the difficulty of establishing a link between BSE and CJD may be compounded by our ignorance of the infectious parameters of a sporadic form of BSE (e.g., host range, tissue distribution of infectivity, route of transmission, minimum infectious dose for humans, whether single or multiple). Presumably, these parameters would resemble those of variant CJD; that is, high infectivity central nervous system and lymphoreticular tissues of an infected cow find their way into products consumed by humans. Transmissions that might have occurred in the past would be difficult to detect because meat products are generally not distributed in a way that results in detectable geographic clusters.
Barring the discovery of a specific molecular signature (as in variant CJD), the most convincing clue to an association will come from the observation of trends over time of the incidence of typical and atypical BSE and of sporadic and variant CJD. With 4 diseases, each of which could have increasing, unchanging, or decreasing trends, there could be 81 (34) possible different combinations. However, it is highly likely that the trends for typical BSE and variant CJD will both decrease in parallel as feed bans continue to interrupt recycled contamination. The remaining combinations are thus reduced to 9 (32), and some of them could be highly informative.
For example, if the incidence of atypical BSE declines in parallel with that of typical BSE, its candidacy as a sporadic form of disease would be eliminated (because sporadic disease would not be influenced by current measures to prevent oral infection). If, on the other hand, atypical BSE continues to occur as typical BSE disappears, this would be a strong indication that it is indeed sporadic, and if in addition at least 1 form of what is presently considered as sporadic CJD (such as the type 2 M/V subtype shown to have a Western blot signature like BASE) were to increase, this would suggest (although not prove) a causal relationship (Figure 5).
Recognition of the different forms of BSE and CJD depends upon continuing systematic testing for both bovines and humans, but bovine testing will be vulnerable to heavy pressure from industry to dismantle the program as the commercial impact of declining BSE cases ceases to be an issue. Industry should be aware, however, of the implications of sporadic BSE. Its occurrence would necessitate the indefinite retention of all of the public health measures that exclude high-risk bovine tissues from the animal and human food chains, whereas its nonoccurrence would permit tissues that are now destroyed to be used as before, once orally acquired BSE has disappeared.
Dr Brown recently retired from the Laboratory of CNS Studies at the National Institutes of Health.
Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA?, what if?
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Sheep are susceptible to the agent of TME by intracranial inoculation and have evidence of infectivity in lymphoid tissues
Author item CASSMANN, ERIC - Oak Ridge Institute For Science And Education (ORISE) item MOORE, SARA - Oak Ridge Institute For Science And Education (ORISE) item SMITH, JODI - Iowa State University item Greenlee, Justin
Submitted to: Frontiers in Veterinary Science Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/14/2019 Publication Date: 11/29/2019 Citation: Cassmann, E.D., Moore, S.J., Smith, J.D., Greenlee, J.J. 2019.
Sheep are susceptible to the agent of TME by intracranial inoculation and have evidence of infectivity in lymphoid tissues.
Frontiers in Veterinary Science. 6:430. https://doi.org/10.3389/fvets.2019.00430. DOI: https://doi.org/10.3389/fvets.2019.00430
Interpretive Summary: Prion diseases are protein misfolding diseases that are transmissible between animals. The outcome of prion infection is irreversible brain damage and death. Transmission can occur between animals of the same or different species, however, transmission between different species is usually less efficient due to the species barrier, which results from differences in the amino acid sequence of the prion protein between the donor and recipient species. The present work evaluated whether transmissible mink encephalopathy (TME) can infect sheep. Our results demonstrate that sheep are susceptible to the TME agent and that the TME agent has similar properties to the agent of L-type atypical bovine spongiform encephalopathy (L-BSE). This work supports the ideas that L-BSE is a possible source for TME in mink and that the practice of feeding cattle with neurologic disease to mink should be avoided. This information is important to farmers who raise cattle, sheep, or mink.
Technical Abstract: Transmissible mink encephalopathy (TME) is a food borne prion disease. Epidemiological and experimental evidence suggests similarities between the agent of TME and L-BSE. This experiment demonstrates the susceptibility of four different genotypes of sheep to the agent of TME by intracranial inoculation. The four genotypes of sheep used in this experiment had polymorphisms corresponding to codons 136 and 171 of the prion gene: VV136QQ171, AV136QQ171, AA136QQ171, and AA136QR171. All intracranially inoculated sheep without comorbidities (15/15) developed clinical scrapie and had detectable PrPSc by immunohistochemistry, western blot, and enzyme immunoassay (EIA). The mean incubation periods in TME infected sheep correlated with their relative genotypic susceptibility. There was peripheral distribution of PrPSc in the trigeminal ganglion and neuromuscular spindles; however, unlike classical scrapie and C-BSE in sheep, ovine TME did not accumulate in the lymphoid tissue. To rule out the presence of infectious, but proteinase K susceptible PrPSc, the lymph nodes of two sheep genotypes, VV136QQ171 and AA136QQ171, were bioassayed in transgenic ovinized mice. None of the mice (0/32) inoculated by the intraperitoneal route had detectable PrPSc by EIA. Interestingly, mice intracranially inoculated with RPLN tissue from a VV136QQ171 sheep were EIA positive (3/17) indicating that sheep inoculated with TME harbor infectivity in their lymph nodes. Western blot analysis demonstrated similarities in the migration patterns between ovine TME and the bovine TME inoculum. Overall, these results demonstrate that sheep are susceptible to the agent of TME, and that the tissue distribution of PrPSc in TME infected sheep is distinct from classical scrapie.
Previous work has shown that the Stetsonville, WI outbreak of TME could have been precipitated by feeding mink a downer cow with atypical BSE; therefore, it very well may have originated from a cow with L-BSE. The agent of TME appears to remain stable, and it has a high transmission efficiency after a sequence of interspecies transmission events. Although C-BSE is the archetypal foodborne TSE, our findings indicate that L-BSE and bTME have greater transmission efficiencies in bovinized mice. Previous work has demonstrated that L-BSE also is more virulent than C-BSE in mice expressing the human prion protein [46, 55]. Although the documented incidence of L-BSE is low, the propensity of L-BSE and the TME agent to cross species barriers support the continued monitoring for atypical BSE.
***>This work supports the ideas that L-BSE is a possible source for TME in mink and that the practice of feeding cattle with neurologic disease to mink should be avoided. This information is important to farmers who raise cattle, sheep, or mink.<***
1985
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...
RECENT MAD COW CASES
WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification
United States of America - Bovine spongiform encephalopathy - Immediate notification
GENERAL INFORMATION
COUNTRY/TERRITORY OR ZONE
COUNTRY/TERRITORY
ANIMAL TYPE
TERRESTRIAL
DISEASE CATEGORY
Listed disease
EVENT ID 5067
DISEASE Bovine spongiform encephalopathy
CAUSAL AGENT Bovine spongiform encephalopathy prion, atypical strain, L-type
GENOTYPE / SEROTYPE / SUBTYPE
Wednesday, May 24, 2023
WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification
Singeltary full report and some history on mad cow in the usa.
May 2, 2023 Singeltary Submission to APHIS et al on BSE;
Docket No. APHIS–2023–0027 Notice of Request for Revision to and Extension of Approval of an Information Collection; National Veterinary Services Laboratories; Bovine Spongiform Encephalopathy Surveillance Program Singeltary Submission
Document APHIS-2023-0027-0001 BSE Singeltary Comment Submission
Greetings again APHIS et al,
I would kindly like to again, post my concern or urgency, on why said information is so critical, and why the 3 year extension is so critical, especially today, with the recent mad cow cases in the UK, Switzerland, Brazil, Spain, and The Netherlands all atypical BSE cases, and the fact the OIE is so concerned with the recent science about atypical L-type BSE and atypical H-type BSE, both of which can transmit orally, (see OIE BSE atypical in my reference materials), new outbreak of a new Prion disease in a new livestock species, i.e. the camel. The fact Chronic Wasted Disease CWD TSE Prion of Cervid, is spreading across the USA, with no stopping it in the near future, now with 10 different strains, a spillover into cattle or sheep would be devastating, and the ramifications of human zoonosis there from, has great concern throughout the scientific community. The fact that the USA BSE feed ban was and is a joke today (see why, with the fact that CWD positive deer could enter the food/feed chain for other ruminants and what the DEFRA says), how the BSE surveillance and testing has failed us so terribly bad to date, by testing only 25k bovines a year for BSE, you will not find BSE until it's too late, again. THIS is all why INFORMATION COLLECTION is so vital for BSE and all human and animal Transmissible Spongiform Encephalopathy TSE Prion disease.
''The purpose of this notice is to solicit comments from the public (as well as affected agencies) concerning our information collection. These comments will help us:''
(1) Evaluate whether the collection of information is necessary for the proper performance of the functions of the Agency, including whether the information will have practical utility;
(2) Evaluate the accuracy of our estimate of the burden of the collection of information, including the validity of the methodology and assumptions used;
(3) Enhance the quality, utility, and clarity of the information to be collected; and
(4) Minimize the burden of the collection of information on those who are to respond, through use, as appropriate, of automated, electronic, mechanical, and other collection technologies; ...end
The question should be, what will the burden be, if WE DON'T COLLECT SAID INFORMATIONS ON BSE, and we find ourselves again facing a BSE epidemic?
I want to bring your attention too, and emphasize;
(3) Enhance the quality, utility, and clarity of the information to be collected; and...
I remember that infamous TEXAS MAD COW that instead of a 48 turnaround at Weybridge, said suspect positive, was declared NEGATIVE, until an Act of Congress and the Honorable Phyllis Fong overrode Texas negative test, sent that BSE sample to Weybridge, and 6 MONTHS LATER ON A 48 HOUR TURNAROUND (BSE REDBOOKS), that BSE sample was CONFIRMED POSITIVE (see history in my references).
Let's not kid ourselves, the BSE ENHANCED BSE SURVEILLANE efforts way back was a total failure, that's why it was shut down, too many atypical BSE cases were showing up.
ONLY by the Grace of God, have we not had a documented BSE outbreak, that and the fact the USDA et al are only testing 25K cattle for BSE, a number too low to find mad cow disease from some 28.9 million beef cows in the United States as of Jan. 1, 2023, down 4% from last year. The number of milk cows in the United States increased to 9.40 million. U.S. calf crop was estimated at 34.5 million head, down 2% from 2021. Jan 31, 2023.
ALL it would take is one BSE positive, yet alone a handful of BSE cases, this is why the Enhanced BSE was shut down, and the BSE testing shut down to 25k, and the BSE GBRs were replaced with BSE MRRs, after the 2003 Christmas Mad cow, the cow that stole Christmas, making it legal to trade BSE, imo.
THE world was set back to square one with the BSE Minimal Risk Regions, from the BSE GBRs.
WE must enhance our BSE Surveillance and BSE Testing, and the FDA PART 589 TSE PRION FEED BAN must be revised to include Cervid by-products and SRM, and it should be made MANDATORY, AND THIS SHOULD BE WELL DOCUMENTED with information collection.
said 'burden' cost, will be a heavy burden to bear, if we fail with Bovine Spongiform Encephalopathy BSE TSE Prion disease, that is why this information collection is so critical...
Singeltary References
see full submission;
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. ...
Monday, March 20, 2023
WAHIS, WOAH, OIE, REPORT United Kingdom Bovine Spongiform Encephalopathy Atypical H-Type
WAHIS, WOAH, OIE, REPORT Switzerland Bovine Spongiform Encephalopathy Atypical L-Type
Switzerland Bovine Spongiform Encephalopathy Atypical L-Type
Switzerland - Bovine spongiform encephalopathy - Immediate notification
BRAZIL BSE START DATE 2023/01/18
BRAZIL BSE CONFIRMATION DATE 2023/02/22
BRAZIL BSE END DATE 2023/03/03
SPAIN BSE START DATE 2023/01/21
SPAIN BSE CONFIRMATION DATE 2023/02/03
SPAIN BSE END DATE 2023/02/06
NETHERLANDS BSE START DATE 2023/02/01
NETHERLANDS BSE CONFIRMATION DATE 2023/02/01
NETHERLANDS BSE END DATE 2023/03/13
The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSE) in 2021
Published:
30 November 2022
Approved: 3 November 2022
Metadata
EFSA Journal 2022;20(11):7655
Keywords: TSE, BSE, CWD, scrapie, classical, atypical, surveillance
On request from: European Commission Question Number: EFSA‐Q‐2021‐00765
Contact: zoonoses@efsa.europa.eu
Abstract
This report presents the results of surveillance on transmissible spongiform encephalopathies (TSE) in cattle, sheep, goats, cervids and other species, and genotyping in sheep and goats, carried out in 2021 by 27 Member States (MS, EU27), the United Kingdom (in respect of Northern Ireland) (XI), and eight other non‐EU reporting countries: Bosnia and Herzegovina, Iceland, Montenegro, North Macedonia, Norway, Serbia, Switzerland and Turkey.
In total, 1,021,252 cattle were tested by EU27 and XI (−9%, compared with 2020 when data from the United Kingdom were not restricted to Northern Ireland), and 66,121 cattle by eight non‐EU reporting countries,
with two cases of H‐BSE in France and Spain, and four L‐BSE in France (2), Germany and Spain.
In total, 311,174 sheep and 118,457 goats were tested in the EU27 and XI (−6.4% and −1.8%, respectively, compared to 2020 when data from the whole United Kingdom were considered).
In sheep, 551 cases of scrapie were reported by 17 MS and XI: 448 classical scrapie (CS) by six MS [80 index cases (IC) with genotypes of susceptible groups in 97% of the cases], 103 atypical scrapie (AS) (96 IC) by 13 MS and XI.
In the other non‐EU reporting countries, 27,594 sheep were tested with 55 CS and 1 AS in Iceland and 8 AS in Norway.
Ovine random genotyping was reported by nine MS and genotypes of susceptible groups accounted for 7.9%.
In goats, 224 cases of scrapie were reported by six EU MS: 219 CS (30 IC) by six MS, and five AS (5 IC) by three MS.
In total, 5,854 cervids were tested for chronic wasting disease by eight MS; all resulted negative. Norway tested 21,670 cervids with two moose and one red deer positive. In total, 149 animals from four other species tested negative in Finland and Turkey.
© European Food Safety Authority
see full text;
I remember writing about all the spontaneous atypical BSE in France...
***atypical spontaneous BSE in France LOL***
FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many spontaneous events of mad cow disease $$$
***so 20 cases of atypical BSE in France, compared to the remaining 40 cases in the remaining 12 Countries, divided by the remaining 12 Countries, about 3+ cases per country, besides Frances 20 cases. you cannot explain this away with any spontaneous BSe. ...TSS
Sunday, October 5, 2014
France stops BSE testing for Mad Cow Disease
Thursday, March 24, 2016
FRANCE CONFIRMS BOVINE SPONGIFORM ENCEPHALOPATHY BSE MAD COW (ESB) chez une vache dans les Ardennes
***atypical spontaneous BSE in France LOL***
FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many spontaneous events of mad cow disease $$$
If you Compare France to other Countries with atypical BSE, in my opinion, you cannot explain this with ‘spontaneous’.
Table 1: Number of Atypical BSE cases reported by EU Member States in the period 2001–2014 by country and by type (L- and H-BSE) (extracted from EU BSE databases on 1 July 2014). By 2015, these data might be more comprehensive following a request from the European Commission to Member States for re-testing and retrospective classification of all positive bovine isolates in the EU in the years 2003–2009
BSE type
Country 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013(a) 2014(a) Total
H-BSE Austria 1 1
France(b) 1 2 3 1 2 2 2 2 15
Germany 1 1 2
Ireland 1 1 2 1 5
The Netherlands 1 1
Poland 1 1 2
Portugal 1 1
Spain 1 1 2
Sweden 1 1
United Kingdom 1 1 1 1 1 5
Total 2 3 3 1 1 2 2 2 4 4 5 1 4 1 35
L-BSE Austria 1 1 2
Denmark 1 1
France(b) 1 1 1 1 2 1 3 2 1 1 14
Germany 1 1 2
Italy 1 1 1 1 1 5
The Netherlands 1 1 1 3
Poland 1 2 2 1 2 1 2 1 12
Spain 2 2
United Kingdom 1 1 1 1 4
Total 0 5 3 4 3 3 6 3 3 4 3 6 1 1 45
Total Atypical cases (H + L)
2 8 6 5 4 5 8 5 7 8 8 7 5 2 80
(a): Data for 2013-2014 are incomplete and may not include all cases/countries reported.
(b): France has performed extensive retrospective testing to classify BSE cases, which is probably the explanation for the higher number of Atypical BSE cases reported in this country.
The number of Atypical BSE cases detected in countries that have already identified them seems to be similar from year to year. In France, a retrospective study of all TSE-positive cattle identified through the compulsory EU surveillance between 2001 and 2007 indicated that the prevalence of H-BSE and L-BSE was 0.35 and 0.41 cases per million adult cattle tested, respectively, which increased to 1.9 and 1.7 cases per million, respectively, in tested animals over eight years old (Biacabe et al., 2008). No comprehensive study on the prevalence of Atypical BSE cases has yet been carried out in other EU Member States. All cases of Atypical BSE reported in the EU BSE databases have been identified by active surveillance testing (59 % in fallen stock, 38 % in healthy slaughtered cattle and 4 % in emergency slaughtered cattle). Cases were reported in animals over eight years of age, with the exception of two cases (one H-BSE and one L-BSE) detected in Spain in 2011/2012. One additional case of H-BSE was detected in Switzerland in 2012 in a cow born in Germany in 2005 (Guldimann et al., 2012).
see;
https://animalhealthreportpriontse.blogspot.com/2018/08/usda-finds-bse-infection-in-florida-cow.html
CAMEL PRION DISEASE
no word of concerns about that either i could find either.
***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.
ATYPICAL SCRAPIE ROUGHLY HAS 50 50 CHANCE ATYPICAL SCRAPIE IS CONTAGIOUS, AS NON-CONTAGIOUS, TAKE YOUR PICK, BUT I SAID IT LONG AGO WHEN USDA OIE ET AL MADE ATYPICAL SCRAPIE A LEGAL TRADING COMODITY, I SAID YOUR PUTTING THE CART BEFORE THE HORSE, AND THAT'S EXACTLY WHAT THEY DID, and it's called in Texas, TEXAS TSE PRION HOLDEM POKER, WHO'S ALL IN $$$
THURSDAY, JULY 8, 2021
EFSA Scientific report on the analysis of the 2‐year compulsory intensified monitoring of atypical scrapie
Volume 26, Number 6—June 2020
Research
Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
Snip…
Atypical BSE Transmission into Human-PrP Transgenic Mouse Models after Adaptation to the Sheep-PrP Sequence
We inoculated prions obtained after 2 passages of L-BSE and H-BSE isolates in ovine PrP expressing mice into TgMet129 and TgVal129. TgMet129 mice inoculated with L-BSE passaged into TgVRQ showed neither clinical signs nor PrPres accumulation in their brain (Figure 1, panels A, B). By contrast, TgVal129 inoculated with the same isolates had disease characterized by 100% attack rates and short incubation times in the second passage (Figure 1, panel A). The obtained PrPresresembles a sporadic Creutzfeldt-Jakob disease (sCJD) Val/Val129 type 2 (sCJD VV2) profile (Figure 1, panel B). PET blotting showed a deposition pattern similar to that of sCJD VV2 in the same mice (Figure 1, panel A). Lesion profiles of both strains also were coincident (Figure 1, panel C). Furthermore, the prion generated in the TgVal129 transgenic mouse line is not able to infect back in TgBo (Table 3). By contrast, ARQ-adapted L-BSE loses its ability to infect human-PrP TgMet129transgenic mouse lines (Figure 1, panel A).
VRQ-adapted H-BSE can now infect both human-PrP TgMet129 and TgVal129 mouse lines, showing 100% attack rates and short incubation times in the second passage (Figure 1, panel A). The obtained PrPres in both cases is similar to that of sCJD Met/Met129 type 1 (sCJD MM1) (Figure 1, panel B). PET blotting showed similarities with the deposition patterns typical of sCJD MM1 in TgMet129 and TgVal129 (Figure 1, panel A). Lesion profiles of both strains also were coincident (Figure 1, panel C). Both generated prions can infect back in TgBo (Table 3; Figure 3).
VRQ-adapted L-BSE reduces its zoonotic potential toward human-PrP TgMet129 mice, as shown by a total abolishment of prion replication in TgMet129 (Figure 1, panel A). Strikingly, intermediate passage of L-BSE into TgVRQ increased its zoonotic potential toward TgVal129 mice (Figure 1, panel A).
Snip…
The transmission of atypical BSEs into sheep resulted in the emergence of prions similar to types 1 and 2 sCJD in terms of mean survival times, attack rates, PrPres profile, and PrPres deposition pattern in the brain of human-PrP transgenic mice. The similarities between the sheep-adapted atypical BSE prions propagated into our human-PrP transgenic mouse lines and sCJD prions could suggest a link between them. The well-established dogma that sCJD is a spontaneous disorder unrelated to animal prion disease has been questioned in a previous study given the resemblance of scrapie prions transmitted into human transgenic mouse models to sCJD strains (26); however, the data from that study do not unequivocally establish a causative link between exposure to sheep scrapie and the subsequent appearance of sCJD in humans, and the same could apply to our findings. An alternative explanation that cannot be ruled out is that, although being different strains, only a limited number of phenotypes could be generated for the human-PrP, indicating phenotypic convergence. Updates to old epidemiologic research is needed to reconsider all these results involving a possible infectious origin of sCJD. In any case, continuing the characterization of this newly emerged prion strain would be useful to finally discarding or refuting a link with sCJD prions.
Extrapolation of results from prion transmission studies based on transgenic mice should be done with caution, especially when human susceptibility to prions is analyzed. However, 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. The supposed sporadic nature of atypical BSE makes its transmission to sheep and later to humans unlikely. 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.
Ms. Marín-Moreno is a PhD student in the Prion Group at Centro de Investigación en Sanidad Animal–Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain. Her primary research interests are the characterization of prion strains and the pathogenesis of prion diseases and their effects on animal and human health.
https://wwwnc.cdc.gov/eid/article/26/6/18-1790_article
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.
***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.
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
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.
2. Determined that pigs naturally exposed to chronic wasting disease (CWD) may act as a reservoir of CWD infectivity. Chronic wasting disease is a naturally occurring, fatal, neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of CWD disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Pigs were assigned to 1 of 3 groups: intracranially inoculated; orally inoculated; or non-inoculated. At market weight age, half of the pigs in each group were tested ('market weight' groups). The remaining pigs ('aged' groups) were allowed to incubate for up to 73 months post inoculation (MPI). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by multiple diagnostic methods. Brain samples from selected pigs were bioassayed in mice expressing porcine prion protein. Some pigs from each inoculated group were positive by one or more tests. Bioassay was positive in 4 out of 5 pigs assayed. Although only small amounts of PrPSc were detected using sensitive methods, this study demonstrates that pigs can serve as hosts for CWD. Detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds. These results indicating the susceptibility of pigs to CWD, 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.
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
LINE TO TAKE
3. If questions on pharmaceuticals are raised at the Press conference, the suggested line to take is as follows:-
"There are no medicinal products licensed for use on the market which make use of UK-derived porcine tissues with which any hypothetical “high risk" ‘might be associated. The results of the recent experimental work at the CSM will be carefully examined by the CSM‘s Working Group on spongiform encephalopathy at its next meeting.
DO Hagger RM 1533 MT Ext 3201
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.....
SO, what about that mad cow feed ban in the USA since 1997???
here's a few, i stopped tracking them after all the FOIA got just too burdensome...see;
scroll to bottom and see USA repeating our same failures, over and over again...8. 21 CFR Part 589.2000
8. 21 CFR Part 589.2000 Failed Mad Cow Feed Ban in USA (these are just a few examples of 100s i have filed...terry)
BANNED MAD COW FEED IN COMMERCE IN ALABAMA
Date: September 6, 2006 at 7:58 am PST PRODUCT
a) EVSRC Custom dairy feed, Recall # V-130-6;
b) Performance Chick Starter, Recall # V-131-6;
c) Performance Quail Grower, Recall # V-132-6;
d) Performance Pheasant Finisher, Recall # V-133-6.
CODE None RECALLING FIRM/MANUFACTURER Donaldson & Hasenbein/dba J&R Feed Service, Inc., Cullman, AL, by telephone on June 23, 2006 and by letter dated July 19, 2006. Firm initiated recall is complete.
REASON
Dairy and poultry feeds were possibly contaminated with ruminant based protein.
VOLUME OF PRODUCT IN COMMERCE 477.72 tons
DISTRIBUTION AL
______________________________
http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html
PRODUCT Bulk custom dairy pre-mixes,
Recall # V-120-6 CODE None RECALLING FIRM/MANUFACTURER Ware Milling Inc., Houston, MS, by telephone on June 23, 2006. Firm initiated recall is complete. REASON Possible contamination of dairy animal feeds with ruminant derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE 350 tons
DISTRIBUTION AL and MS
______________________________
PRODUCT
a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet, 50 lb. bags, Recall # V-121-6;
b) Tucker Milling, LLC #31120, Game Bird Breeder Pellet, 50 lb. bags, Recall # V-122-6;
c) Tucker Milling, LLC #31232 Game Bird Grower, 50 lb. bags, Recall # V-123-6;
d) Tucker Milling, LLC 31227-Crumble, Game Bird Starter, BMD Medicated, 50 lb bags, Recall # V-124-6;
e) Tucker Milling, LLC #31120, Game Bird Breeder, 50 lb bags, Recall # V-125-6;
f) Tucker Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags, Recall # V-126-6;
g) Tucker Milling, LLC #30116, TM Broiler Finisher, 50 lb bags, Recall # V-127-6
CODE All products manufactured from 02/01/2005 until 06/20/2006 RECALLING FIRM/MANUFACTURER Recalling Firm: Tucker Milling LLC, Guntersville, AL, by telephone and visit on June 20, 2006, and by letter on June 23, 2006. Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated recall is ongoing.
REASON Poultry and fish feeds which were possibly contaminated with ruminant based protein were not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 7,541-50 lb bags
DISTRIBUTION AL, GA, MS, and TN
END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006
###
http://www.fda.gov/bbs/topics/ENFORCE/2006/ENF00964.html
Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125 TONS Products manufactured from 02/01/2005 until 06/06/2006
Date: August 6, 2006 at 6:16 pm PST PRODUCT
a) CO-OP 32% Sinking Catfish, Recall # V-100-6;
b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6;
c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;
d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6;
e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6;
f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6;
g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%, Recall # V-106-6;
h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to 20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6;
i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6;
j) CO-OP LAYING CRUMBLES, Recall # V-109-6;
k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall # V-110-6;
l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6;
m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 CODE
Product manufactured from 02/01/2005 until 06/06/2006
RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is complete.
REASON Animal and fish feeds which were possibly contaminated with ruminant based protein not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 125 tons
DISTRIBUTION AL and FL
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html
MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE Sun Jul 16, 2006 09:22 71.248.128.67
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II
______________________________
PRODUCT
a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy Animals, Recall # V-079-6;
b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net weight 50lb (22.6 kg), Recall # V-080-6;
c) PRO-PAK, MARINE & ANIMAL PROTEIN CONCENTRATE FOR USE IN ANIMAL FEED, Recall # V-081-6;
d) Feather Meal, Recall # V-082-6 CODE
a) Bulk
b) None
c) Bulk
d) Bulk
RECALLING FIRM/MANUFACTURER H. J. Baker & Bro., Inc., Albertville, AL, by telephone on June 15, 2006 and by press release on June 16, 2006. Firm initiated recall is ongoing.
REASON
Possible contamination of animal feeds with ruminent derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE 10,878.06 tons
DISTRIBUTION Nationwide
END OF ENFORCEMENT REPORT FOR July 12, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
___________________________________
PRODUCT
Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
Firm initiated recall is ongoing.
REASON
Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI
___________________________________
PRODUCT
Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.
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.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm
WEDNESDAY, MARCH 29, 2023
The use of animal by-products in a circular bioeconomy: Time for a TSE road map 3?
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
August 5, 2001
Mad cow disease: Could it be here?
Man's stubborn crusade attracts experts' notice
Photo of Carol Christian
Carol Christian
Chron.com / Houston Chronicle
Monday, May 22, 2023
BSE TSE Prion MAD COW TESTING IN THE USA COMPARED TO OTHER COUNTRIES?
This is where STUPID meets the road imo, where you have politicians trying to take chocolate milk from THE SCHOOL LUNCH PROGRAM, claims it's bad for our baby's.
BUT IT'S PERFECTLY OK TO FEED OUR CHILDREN, FOR FOUR FUCKING YEARS, THE MOST HIGH RISK CATTLE FOR BSE MAD COW DISEASE, VIA THE SAME SCHOOL LUNCH PROGRAM...i don't make this stuff up people!
Saturday, September 21, 2013
Westland/Hallmark: 2008 Beef Recall A Case Study by The Food Industry Center January 2010 THE FLIM-FLAM REPORT
SUNDAY, MARCH 19, 2023
Abandoned factory ‘undoubtedly’ contains dormant Mad Cow Disease that could threaten humans, Thruxted Mill, Queniborough CJD
DEFRA
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip.....
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law. Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip.....
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. snip..... The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip.....
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion. snip..... In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip.....
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip.....
*** PLEASE SEE THIS URGENT UPDATE ON CWD AND FEED ANIMAL PROTEIN ***
Sunday, March 20, 2016
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed ***UPDATED MARCH 2016*** Singeltary Submission
PLoS One. 2020; 15(8): e0237410. Published online 2020 Aug 20. doi: 10.1371/journal.pone.0237410 PMCID: PMC7446902 PMID: 32817706
Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease
Nathaniel D. Denkers, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – review & editing,#1 Clare E. Hoover, Conceptualization, Data curation, Investigation, Writing – original draft, Writing – review & editing,#2 Kristen A. Davenport, Conceptualization, Data curation, Investigation, Writing – review & editing,3 Davin M. Henderson, Conceptualization, Data curation, Investigation, Methodology,1 Erin E. McNulty, Data curation, Investigation, Methodology, Writing – review & editing,1 Amy V. Nalls, Conceptualization, Investigation, Methodology, Writing – review & editing,1 Candace K. Mathiason, Conceptualization, Funding acquisition, Investigation, Supervision, Writing – review & editing,1 and Edward A. Hoover, Conceptualization, Data curation, Funding acquisition, Supervision, Writing – review & editing1,* Byron Caughey, Editor Author information Article notes Copyright and License information Disclaimer This article has been corrected.
See PLoS One. 2021 June 10; 16(6): e0253356. Associated Data Data Availability Statement
Abstract
The minimum infectious dose required to induce CWD infection in cervids remains unknown, as does whether peripherally shed prions and/or multiple low dose exposures are important factors in CWD transmission. With the goal of better understand CWD infection in nature, we studied oral exposures of deer to very low doses of CWD prions and also examined whether the frequency of exposure or prion source may influence infection and pathogenesis. We orally inoculated white-tailed deer with either single or multiple divided doses of prions of brain or saliva origin and monitored infection by serial longitudinal tissue biopsies spanning over two years. 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.
snip...
In conclusion, we have attempted to model and better understand CWD infection relative to natural exposure. The results demonstrate: (a) that the minimum CWD oral infectious dose is vastly lower than historical studies used to establish infection; (b) that a direct relationship exists between dose and incubation time to first prion replication detection in tonsils, irrespective of genotype; (c) that a difference was not discernible between brain vs. saliva source prions in ability to establish infection or in resultant disease course; and (d) that the CWD infection process appears to conform more to a threshold dose than an accumulative dose dynamic.
Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle
G. A. H. Wells,1 T. Konold,1 M. E. Arnold,1 A. R. Austin,1 3 S. A. C. Hawkins,1 M. Stack,1 M. M. Simmons,1 Y. H. Lee,2 D. Gavier-Wide´n,3 M. Dawson1 4 and J. W. Wilesmith1 1 Correspondence G. A. H. Wells
g.a.h.wells@vla.defra.gsi.gov.uk
1 Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK
2 National Veterinary Research and Quarantine Service, Anyang, Republic of Korea
3 National Veterinary Institute (SVA), SE-75189 Uppsala, Sweden
Received 27 July 2006
Accepted 18 November 2006
The dose–response of cattle exposed to the bovine spongiform encephalopathy (BSE) agent is an important component of modelling exposure risks for animals and humans and thereby, the modulation of surveillance and control strategies for BSE. In two experiments calves were dosed orally with a range of amounts of a pool of brainstems from BSE-affected cattle. Infectivity in the pool was determined by end-point titration in mice. Recipient cattle were monitored for clinical disease and, from the incidence of pathologically confirmed cases and their incubation periods (IPs), the attack rate and IP distribution according to dose were estimated. The dose at which 50 % of cattle would be clinically affected was estimated at 0.20 g brain material used in the experiment, with 95 % confidence intervals of 0.04–1.00 g. The IP was highly variable across all dose groups and followed a log-normal distribution, with decreasing mean as dose increased. There was no evidence of a threshold dose at which the probability of infection became vanishingly small, with 1/15 (7 %) of animals affected at the lowest dose (1 mg).
snip...
DISCUSSION
The study has demonstrated that disease in cattle can be produced by oral exposure to as little as 1 mg brain homogenate (¡100.4 RIII mouse i.c./i.p. ID50 units) from clinically affected field cases of BSE and that the limiting dose for infection of calves is lower than this exposure...
snip...end
P04.27
Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route
Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmzas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Lwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat Energie Atomique, France; 3Instituto Superiore di Sanit, Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August University, Germany; 6German Primate Center, Germany
Background:
In 2001, a study was initiated in primates to assess the risk for humans to contract BSE through contaminated food. For this purpose, BSE brain was titrated in cynomolgus monkeys.
Aims:
The primary objective is the determination of the minimal infectious dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for humans. Secondly, we aimed at examining the course of the disease to identify possible biomarkers.
Methods:
Groups with six monkeys each were orally dosed with lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).
Results:
In an ongoing study, a considerable number of high-dosed macaques already developed simian vCJD upon oral or intracerebral exposure or are at the onset of the clinical phase. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of biomarkers.
Conclusions:
Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate. The difference in the incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However, there are rapid progressors among orally dosed monkeys that develop simian vCJD as fast as intracerebrally inoculated animals.
The work referenced was performed in partial fulfilment of the study 'BSE in primates' supported by the EU (QLK1-2002-01096).
1.3. Determination of the Minimal Infectious BSE Dose in Non-human Primates
In a concerted European effort involving 5 laboratories including ours, the BSE-macaque model was then used to evaluate the minimal amount of BSE-infected material necessary to induce vCJD in primates. Results so far show that 5g of infectious BSE cattle brain is sufficient to induce the disease in all recipient animals by the oral route, with 500 mg yielding an incomplete attack rate10,11). The ID50 of BSE cattle brain is 200 mg for cattle12). These results suggest a low species barrier between cattle and non-human primates.
look at the table and you'll see that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE;
Risk of oral infection with bovine spongiform encephalopathy agent in primates
Corinne Ida Lasmzas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frdric Auvr, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Sals, Gerald Wells, Paul Brown, Jean-Philippe Deslys
Summary The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is compounded by incomplete knowledge about the efficiency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these findings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man.
snip...
BSE bovine brain inoculum
100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 01 mg 001 mg
Primate (oral route)* 1/2 (50%)
Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%)
RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)
PrPres biochemical detection
The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was
inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the first positive animal (%). The accuracy of
bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and int****ritoneal.
Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula
Published online January 27, 2005
It is clear that the designing scientists must
also have shared Mr Bradley's surprise at the results because all the dose
levels right down to 1 gram triggered infection.
6. It also appears to me that Mr Bradley's answer (that it would take less than say 100 grams) was probably given with the benefit of hindsight; particularly if one considers that later in the same answer Mr Bradley expresses his surprise that it could take as little of 1 gram of brain to cause BSE by the oral route within the same species. This information did not become available until the "attack rate" experiment had been completed in 1995/96. This was a titration experiment designed to ascertain the infective dose. A range of dosages was used to ensure that the actual result was within both a lower and an upper limit within the study and the designing scientists would not have expected all the dose levels to trigger infection.
The dose ranges chosen by the most informed scientists at that time ranged from 1 gram to three times one hundred grams.
It is clear that the designing scientists must have also shared Mr Bradley's surprise at the results because all the dose levels right down to 1 gram triggered infection.
Notice of Request To Renew an Approved Information Collection: Specified Risk Materials DOCKET NUMBER Docket No. FSIS-2022-0027 Singeltary Submission
Greetings FSIS, USDA, et al,
Thank you kindly for allowing the public to comment on ;
(a) whether the proposed collection of information is necessary for the proper performance of FSIS’ functions, including whether the information will have practical utility;
(b) the accuracy of FSIS’ estimate of the burden of the proposed collection of information, including the validity of the method and assumptions used;
(c) ways to enhance the quality, utility, and clarity of the information to be collected; and
(d) ways to minimize the burden of the collection of information, including through the use of appropriate automated, electronic, mechanical, or other technological collection techniques, or other forms of information technology.
I will be commenting mostly on a, b, and c, because d, is wanting to minimize the burden of collection, and i do not think that is possible if ''These statutes mandate that FSIS protect the public by verifying that meat, poultry, and egg products are safe, wholesome, and properly labeled and packaged.'', is truly the intent of these statutes, and i would kindly like to explain why, and why it is so critical that these Specified Risk Materials SRM TSE Prion Statues are so important for public health, and WHY there is an urgent need to enhance them, considering the risk factors of Chronic Wasting Disease CWD TSE Prion in Cervid.
THIS collection of SRM materials information should be done all the time, year after year, and ending it EVER would be foolish, imo, not scientific, and will lead to future risk to public health, if you consider just how bad USDA/FSIS/APHIS/FDA failed so badly with the FDA PART 589 TSE PRION FEED BAN, the SRM REMOVAL, THE BSE SURVEILLANCE AND TESTING PROGRAMS, THEY FAILED ALL OF THEM TERRIBLY IMO, AND BY CONTINUING TO INSIST ON TESTING 25K CATTLE FOR BSE IS A DISASTER WATING TO HAPPEND IMO!
SPECIFIED RISK MATERS
Specified Risk Materials SRMs, are the most high risk infectious materials, organs, of a cow that is infected with Bovine Spongiform Encephalopathy, Transmissible Spongiform Encephalopathy, BSE TSE Prion. the atypical BSE strains are, like atypical L-type BSE are more infectious that the typical C-type BSE. Also, Science of the BSE TSE has evolved to show that there are more infectious tissues and organs than previously thought. I wish to kindly post all this evidence, as to show you why this information collection of SRMs are so vital to public safety, and why they should be enhanced for cattle, cervid, sheep, and goats, oh, and not to forget the new livestock prion disease in camel, the Camel Prion Disease CPD.
ONE other thing, you must remember, SCIENCE AND TRANSMISSION STUDIES have now shown that CWD and Scrapie can transmit to PIGS by Oral route. This should be included in any enhancement of the SRM or FDA PART 589 TSE PRION FEED ban.
NOT to forget Zoonosis of all of the above, i will post the latest science to date at the bottom of the attached files.
Thank You, terry
Singeltary further comments in attachment;
Specified Risk Materials DOCKET NUMBER Docket No. FSIS-2022-0027 Singeltary Submission Attachment https://downloads.regulations.gov/FSIS-2022-0027-0002/attachment_1.pdf Monday, December 5, 2022 Notice of Request To Renew an Approved Information Collection: Specified Risk Materials DOCKET NUMBER Docket No. FSIS-2022-0027 Singeltary Submission
SEE MAD COW FEED VIOLATIONS AFER MAD COW FEED VIOLATIONS ;
Docket No. APHIS–2023–0027 Notice of Request for Revision to and Extension of Approval of an Information Collection; National Veterinary Services Laboratories; Bovine Spongiform Encephalopathy Surveillance Program Singeltary Submission Document APHIS-2023-0027-0001 BSE Singeltary Comment Submission
see full submission;
Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission
Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification
APHIS Indemnity Regulations [Docket No. APHIS-2021-0010] RIN 0579-AE65 Singeltary Comment Submission Singeltary Sr., Terry
Sep 8, 2022
Monday, May 22, 2023
BSE TSE Prion MAD COW TESTING IN THE USA COMPARED TO OTHER COUNTRIES?
DID YOUR CHILD CONSUME SOME OF THESE DEAD STOCK DOWNER COWS, THE MOST HIGH RISK FOR MAD COW DISEASE ??? this recall was not for the welfare of the animals. ...tss
you can check and see here ; (link now dead, does not work...tss)
http://www.fns.usda.gov/fns/safety/pdf/Hallmark-Westland_byState.pdf
try this link ;
or here;
Sunday, November 13, 2011
California BSE mad cow beef recall, QFC, CJD, and dead stock downer livestock
some history about the OIE coming from the inside
bse-tester Well-known member JoinedJul 1, 2005 Messages517 Reaction score0 LocationEdmonton, Alberta, Canada Dec 19, 2007 #41 Question wrote:
Maybe familiarize yourself with the OIE. The primary concern is animal health of the world they are the animal version of the WHO. It is a long way down from that ivory tower but here we go, until pressured by the USA representatives a country could not export animals for 6 years after finding a BSE/BASE positive animal so under the old rules the US would not be able to export anywhere in the world for another 4 1/2 years. Who got the risk levels system put in to allow some trade - your US representatives. You guys want to change rules - OK , but you do not get special rules that only apply to the US. As i have told you before Sand h I market all my own slaughter animals and you know that, so don't do the whole holier than thow act.
With all due respect, it is obvious that you know little about the OIE and how it actually works. Having been to their offices in Paris and talked personally with the Head of the Animal Test Section, you would choke if you knew how many lobby groups attend that office daily. There is a steady stream of paid lobby groups that have one goal in life and that is to sway the Section Heads of each department within the OIE to suit the needs of different juristictions around the world, which curiously enough, also includes the USA and Canada. Anyone can go there and chat with them - providing they can provide valid cause to be let in. To say that the only goal of the OIE is animal health is actually only part of their function. They are more than that and my discussions with Dr. Diaz there has showed me that. But to blindly make a statement regarding what they do when you have no idea what they actually do is like eating the skin of the orange and not knowing what is actually under.
Interestingly you state that the US Government applied pressure (to the OIE) I assume and that is a great example of the lobby groups doing their job. So, at the end of the day, one can safely assume that it is the pressure applied by certain influential lobby groups that will determine a likely aoutcome to an apparent OIE directive. Man alive, isn't it great to live in a democracy wherein the people get to make the choices and not just some "other" interested party or group - say like........Cargyll or Tyson for example?
So, one last question, question?
Who wags the tail of that dog?? And for what reason other than one that is purely associated with trade and international agreements and greed?
And you think it is so simply explainable.
bse-tester Well-known member Joined Jul 1, 2005 Messages517 Reaction score0 Location Edmonton, Alberta, Canada Dec 20, 2007
#47
Actually QUESTION, the guy in charge is Dr. Francois Diaz. He runs the BSE Section for the OIE and has done so for many years. As far as I know, there are no extremists there but there are some in Canada apparently.
You state:
These guys have their own agenda and it has nothing to do with consumer safety or eliminating BSE.
You obviously know nothing about the OIE and what it is really all about. But it is convenient for you to simply label them as extremists with their own agenda and that is how you view the world. You talk of being sure that you keep your cattle free of BSE. How do you do that? Do you simply go over to them and one at a time, look into their eyes and make a wish?? How the hell do you know what is living inside them on a day to day basis. Last year alone in the UK there were over 200 cases of BSE/Scrapie found prior to slaughter. These animals were not generally reported in the media because the UK Government has decided to simply do discreet surveillance and take them out of the loop wherever possible but they still admit that there is a significant risk that some animals are going through the system.
Also, in the USA, I have been advised that there are a Typical (classic PrPsc) and an A-Typical brain from animals born and raised in the USA. Do you honestly think that there are no conspiracies within the Canadian, UK and US Governments that prevent us and the rest of the world from knowing the depths to which BSE goes in their respective National herds - you can bank on it!!! The folks I have met at the OIE take their jobs extremely seriously and have shown repeatedly that they are dedicated to the ellimination of BSE, Scrapie and all known TSE's. :D :D
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bse-tester Well-known member Joined Jul 1, 2005 Messages 517 Reaction score0 Location Edmonton, Alberta, Canada Dec 21, 2007
#83
SRM removal is a smoke screen brought about by the packer lobbys who fought to have this angle introduced and by government officials who thought it a good idea to have something to tell the public at large when their credibility was failing at the height of the BSE crisis.
SRM removal was put forward as a means to provide a so-called scientific excuse to the general public to alleviate their fear that BSE was going to be brought into the human food chain. Removing only certain tissues from an animal is a farce when one can find PrPsc throughout the entire carcass. Just think about those poor smucks who competed on that TV show "Fear Factor" and ate cattle eye-balls and raw bovine liver and guts to make a few bucks. Mmmmmmmmm, where will they be in a few decades I wonder?
So who the hell is fooling whom??? Come on Timmy, I know you are going to wail in on this one - don't bother pal, stick to what you know and not what you think you know.
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Chronic Wasting Disease CWD TSE Prion
Published: 06 September 2021
***> Chronic wasting disease: a cervid prion infection looming to spillover
Alicia Otero, Camilo Duque Velásquez, Judd Aiken & Debbie McKenzie
Veterinary Research volume 52, Article number: 115 (2021)
PRION CONFERENCE 2022 ABSTRACTS CWD TSE PrP ZOONOSIS
Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.
Samia Hannaouia, Ginny Chenga, Wiebke Wemheuerb, Walter J. Schulz-Schaefferb, Sabine Gilcha, and Hermann M. Schätzla aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine & Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bInstitute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany
Aims: Chronic wasting disease (CWD) is a prion disease of cervids. Its rapid geographic expansion, shedding of infectivity and persistence in the environment for many years are of concern for humans. Here, we provide the first evidence by transmission experiments to different transgenic mouse models and bank voles that Cynomolgus macaques inoculated via different routes with CWD-positive cervid tissues harbor infectious prions that elicit clinical disease in rodents.
Material and Methods: We used tissue materials from macaques inoculated with CWD to inoculate transgenic mice overexpressing cervid PrPCfollowed by transmission into bank voles. We used RT-QuIC, immunoblot and PET blot analysis to assess brains, spinal cords, and tissues of the gastrointestinal tract (GIT) for the presence of prions.
Results: Our results show that of the macaque materials that induced clinical disease in transgenic mice,73% were from the CNS (46% spinal cord and 27% brain), and 27% were from the spleen, although attack rates were low around 20%. Clinical mice did not display PK-resistant PrPSc(PrPres) in immunoblot, but showed low-levels of prion seeding activity. Transmission into bank voles from clinical transgenic mice led to a 100% attack rate with typical PrPressignature in immunoblot, which was different from that of voles inoculated directly with CWD or scrapie prions. High-level prion seeding activity in brain and spinal cord and PrPresdeposition in the brain were present. Remarkably, we also found prion seeding activity in GIT tissues of inoculated voles. Second passage in bank voles led to a 100% attack rate in voles inoculated with brain, spinal cord and small intestine material from first round animals, with PrPresin immunoblot, prion seeding activity, and PrPresdeposition in the brain. Shortened survival times indicate adaptation in the new host. This also shows that prions detected in GIT tissues are infectious and transmissible. Transmission of brain material from sick voles back to cervidized mice revealed transmission in these mice with a 100% attack rate, and interestingly, with different biochemical signature and distribution in the brain.
Conclusions: Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including oral one. The disease manifested as atypical in macaques and transgenic mice, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.
Funded by: The National Institutes of Health, USA, and the Alberta Prion Research Institute/Alberta Innovates Canada. Grant number: 1R01NS121016-01; 201,600,023
Acknowledgement: We thank Umberto Agrimi, Istituto Superiore di Sanità, Rome, Italy, and Michael Beekes, Robert-Koch Institute Berlin, Germany, for providing the bank vole model. We thank the University of Calgary animal facility staff and Dr. Stephanie Anderson for animal care.
Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD
Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha
aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine; Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bUniversité Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France; cDepartment of Biological Sciences, Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada
Aims: Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we aimed to determine the zoonotic potential of CWD using a mouse model for human prion diseases.
Material and Methods: Transgenic mice overexpressing human PrPChomozygous for methionine at codon 129 (tg650) were inoculated intracerebrally with brain homogenates of white-tailed deer infected with Wisc-1/CWD1 or 116AG CWD strains. Mice were monitored for clinical signs and were euthanized at terminal disease. Brains were tested by RT-QuIC, western blot upon PK digestion, and immunohistochemistry; fecal homogenates were analyzed by RT-QuIC. Brain/spinal cord and fecal homogenates of CWD-inoculated tg650 mice were inoculated into tg650 mice or bank voles. Brain homogenates of bank voles inoculated with fecal homogenates of CWD-infected tg650 mice were used for second passage in bank voles.
Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650 brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.
Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.
Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.
Funded by: We are grateful for financial support from the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, Genome Canada, and the Alberta Prion Research Institute. SG is supported by the Canada Research Chairs program.
Acknowledgement: We thank Dr. Trent Bollinger, WCVM, University of Saskatchewan, Saskatoon, Canada, for providing brain tissue from the WTD-116AG isolate, Dr. Stéphane Haïk, ICM, Paris, France, for providing brain tissue from vCJD and sCJD cases, and Dr. Umberto Agrimi, Istituto Superiore di Sanità, Italy, for the bank vole model. We thank animal facility staff for animal care, Dr. Stephanie Anderson for veterinary oversight, and Yo-Ching Cheng for preparing recombinant PrP substrates. Thank you to Dr. Stephanie Booth and Jennifer Myskiw, Public Health Agency of Canada, Canada.
The chronic wasting disease agent from white-tailed deer is infectious to humanized mice after passage through raccoons
Eric Cassmanna, Xu Qib, Qingzhong Kongb, and Justin Greenleea
aNational Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA, USA bDepartments of Pathology, Neurology, National Center for Regenerative Medicine, and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA
Aims: Evaluate the zoonotic potential of the raccoon passaged chronic wasting disease (CWD) agent in humanized transgenic mice in comparison with the North American CWD agent from the original white-tailed deer host.
Material and Methods: Pooled brain material (GG96) from a CWD positive herd was used to oronasally inoculate two white-tailed deer with wild-type prion protein genotype and intracranially inoculate a raccoon. Brain homogenates (10% w/v) from the raccoon and the two white-tailed deer were used to intracranially inoculate separate groups of transgenic mice that express human prion protein with methionine (M) at codon 129 (Tg40h). Brains and spleens were collected from mice at experimental endpoints of clinical disease or approximately 700 days post-inoculation. Tissues were divided and homogenized or fixed in 10% buffered neutral formalin. Immunohistochemistry, enzyme immunoassay, and western blot were used to detect misfolded prion protein (PrPSc) in tissue.
Results: Humanized transgenic mice inoculated with the raccoon passaged CWD agent from white-tailed deer exhibited a 100% (12/12) attack rate with an average incubation period of 605 days. PrPScwas detected in brain tissue by enzyme immunoassay with an average optical density of 3.6/4.0 for positive brains. PrPScalso was detected in brain tissue by western blot and immunohistochemistry. No PrPScwas detected in the spleens of mice inoculated with the raccoon passaged CWD agent. Humanized mice inoculated with the CWD agent from white-tailed deer did not have detectable PrPScusing conventional immunoassay techniques.
Conclusions: The host range of the CWD agent from white-tailed deer was expanded in our experimental model after one passage through raccoons.
Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Acknowledgement: We thank Quazetta Brown, Lexi Frese, Rylie Frese, Kevin Hassall, Leisa Mandell, and Trudy Tatum for providing excellent technical support to this project.
Stable and highly zoonotic cervid prion strain is possible
Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, and Qingzhong Kong Department of Pathology, Case Western Reserve University, Cleveland, USA
Aims: Whether CWD prions can infect humans remains unclear despite the very substantial scale and long history of human exposure of CWD in some areas. Multiple in vitro conversion experiments and in vivo animal studies suggest that the CWD-to-human transmission barrier is not unbreakable. A major public health concern on CWD zoonosis is the emergence of highly zoonotic CWD strains. We aim to address the question of whether highly zoonotic CWD strains are possible.
Material and Methods: We inoculated a few sCJD brain samples into cervidized transgenic mice, which were intended as negative controls for bioassays of brain tissues from sCJD cases who had hunted or consumed vension from CWD-endemic states. Some of these mice became infected and their brain tissues were further examined by serial passages in humanized or cervidized mice.
Results: Passage of sCJDMM1 in transgenic mice expressing elk PrP (Tg12) resulted in a ‘cervidized’ CJD strain that we termed CJDElkPrP. We observed 100% transmission of CJDElkPrPin transgenic mice expressing human PrP (Tg40h). We passaged CJDElkPrPtwo more times in the Tg12 mice. We found that such second and third passage CJDElkPrPprions also led to 100% infection in the Tg40h mice. In contrast, we and others found zero or poor transmission of natural elk CWD isolates in humanized mice, despite that natural elk CWD isolates and CJDElkPrPshare the same elk PrP sequence.
Conclusions: Our data demonstrate that highly zoonotic cervid prion strains are not only possible but also can be stably maintained in cervids and that CWD zoonosis is prion strain-dependent.
Funded by: NIH
Grant number: R01NS052319, R01NS088604, R01NS109532
Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O’Rourke for providing the sCJD samples and the CWD samples, respectively.
Adaptation of chronic wasting disease (CWD) prion strains in hosts with different PRNP genotypes
Camilo Duque Velasqueza,c, Elizabeth Triscotta,c, Chiye Kima,c, Diana Morenoa,c, Judd Aikenb,c, and Debbie McKenziea,c
aDepartment of Biological Science, University of Alberta, Edmonton, AB T6G 2G8, Canada; bDepartment of Agriculture, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G 2G8, Canada; cCentre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada
Aims: The contagious nature of CWD epizootics and the PrPCamino acid variation of cervids (and susceptible sympatric species) guarantee the expansion of prion conformational diversity and selective landscapes where new strains can arise. CWD strains can have novel transmission properties including altered host range that may increase zoonotic risk as circulating strains diversify and evolve. We are characterizing the host adaptability of characterized CWD strains as well as CWD isolates from different cervid species in various enzootic regions.
Material and Methods: Characterized CWD strains as well as a number of isolates from hunter-harvested deer were bioassayed in our rodent panel (transgenic mice expressing cervid alleles G96, S96 and H95-PrPC, elk PrPC, bovine PrPC, and both hamsters and non-transgenic laboratory mice). Strain characteristics were compared using computer based scoring of brain pathology (e.g. PrPCWDbrain distribution), western blot and protein misfolding cyclic amplification (PMCA).
Results: Transmission of various isolates resulted in the selection of strain mixtures in hosts expressing similar PrPC, particularly for polymorphic white-tailed deer and for Norwegian reindeer. As of the second passage, transmission of P153 moose prions from Norway has not resulted in emergence of strains with properties similar to any North American CWD strains in our taxonomic collection (Wisc-1, CWD2, H95+and 116AG).
Conclusions: Our data indicates polymorphic white-tailed deer can favor infection with more than one strain. Similar to transmission studies of Colorado CWD isolates from cervids expressing a single PrPCprimary structure, the isolate from Norway reindeer (V214) represents a strain mixture, suggesting intrinsic strain diversity in the Nordfjella epizootic. The diversity of CWD strains with distinct transmission characteristics represents a threat to wildlife, sympatric domestic animals and public health.
Funded by: Genome Canada and Genome Alberta (Alberta Prion Research Institute and Alberta Agriculture & Forestry); NSERC Grant number: #LSARP 10205; NSERC RGPIN-2017-05539
Acknowledgement: We would like to thank Margo Pybus (Alberta Environment and Parks) Trent Bollinger (University of Saskatchewan) for providing us with tissue samples from hunter-harvested deer and Sylvie Benestad for providing moose and reindeer samples.
Application of PMCA to understand CWD prion strains, species barrier and zoonotic potential
Sandra Pritzkowa, Damian Gorskia, Frank Ramireza, Fei Wanga, Glenn C. Tellingb, Justin J. Greenleec, Sylvie L. Benestadd, and Claudio Sotoa aDepartment of Neurology, University of Texas Medical School at Houston, Houston, Texas, USA; bDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA; cVirus and Prion Research Unit, United States Department of Agriculture, Ames, Iowa, USA; dNorwegian Veterinary Institute, OIE Reference Laboratory for CWD, Ås, Norway
Aims: Chronic wasting disease (CWD) is a prion disease affecting various species of cervids that continues to spread uncontrollably across North America and has recently been detected in Scandinavia (Norway, Sweden and Finland). The mechanisms responsible for the natural transmission of CWD are largely unknown. Furthermore, the risk of CWD transmission to other species, including humans, is also unknown and remains a dangerous enigma. In this study, we investigated the potential of CWD prions to infect several other animal species (sheep, cattle, pig, hamster, and mouse) including humans, by examining their capacity to convert the normal prion protein of distinct species in a PMCA reaction. Moreover, we also investigated whether the in vivo passage of CWD through intermediate species alters their capacity for zoonotic transmission, which may represent a major hazard to human health.
Material and Methods: For these studies, we used brain material from CWD-infected white-tailed deer (Odocoileus virginianus), elk (Cervus canadensis), and mule deer (Odocoileus hemionus) as species native to North America. We also used CWD-infected Moose (Alces alces), reindeer (Rangifer tarandus) and red deer (Cervus elaphus) as Norwegian cervids. We also used brains from cattle, sheep and pigs experimentally infected by CWD. To study interspecies-transmission and zoonotic potential, samples were tested via PMCA for the conversion of PrPCinto PrPScusing different combinations of inoculum and host species. Based on these analyses we estimated the spillover and zoonotic potential for different CWD isolates. We define and quantify spillover and zoonotic potential indices as the efficiency by which CWD prions sustain prion generation in vitro at the expense of normal prion proteins from various mammals and human, respectively.
Results: Our results show that prions from some cervid species, especially those found in Northern Europe, have a higher potential to transmit disease characteristics to other animals. Conversely, CWD-infected cervids originated in North America appear to have a greater potential to generate human PrPSc. We also found that in vivo transmission of CWD to cattle, but not to sheep or pigs substantially increases the ability of these prions to convert human PrPCby PMCA.
Conclusions: Our findings support the existence of different CWD prion strains with distinct spillover and zoonotic potentials. We also conclude that transmission of CWD to other animal species may increase the risk for CWD transmission to humans. Our studies may provide a tool to predict the array of animal species that a given CWD prion could affect and may contribute to understanding the risk of CWD for human health.
Funded by: National Institute of Health Grant number: P01 AI077774
Generation of human chronic wasting disease in transgenic mice
Zerui Wanga, Kefeng Qinb, Manuel V. Camachoa, Ignazio Cali a,c, Jue Yuana, Pingping Shena, Tricia Gillilanda, Syed Zahid Ali Shaha, Maria Gerasimenkoa, Michelle Tanga, Sarada Rajamanickama, Anika Yadatia, Lawrence B. Schonbergerd, Justin Greenleee, Qingzhong Konga,c, James A. Mastriannib, and Wen-Quan Zoua,c
aDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; bDepartment of Neurology and Center for Comprehensive Care and Research on Memory Disorders, the University of Chicago Pritzker School of Medicine, Chicago, USA; cNational Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; dDivision of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USA; eVirus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Avenue, Ames, IA, USA
Aims: Chronic wasting disease (CWD) results from the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC) in the brains of deer and elk. It has been spreading rapidly throughout many regions of North America, exported inadvertently to South Korea, and more recently identified in Europe. Mad cow disease has caused variant Creutzfeldt-Jakob disease (vCJD) in humans and is currently the only known zoonotic prion disease. Whether CWD is transmissible to humans remains uncertain. The aims of our study were not only to confirm whether CWD prion isolates can convert human brain PrPCinto PrPScin vitro by serial protein misfolding cyclic amplification (sPMCA) but also to determine whether the sPMCA-induced CWD-derived human PrPScis infectious.
Material and Methods: Eight CWD prion isolates from 7 elks and 1 deer were used as the seeds while normal human brain homogenates containing either PrP-129 MM (n = 2) or PrP-129 VV (n = 1) were used as the substrates for sPMCA assay. A normal elk brain tissue sample was used as a negative control seed. Two lines of humanized transgenic (Tg) mice expressing either human PrP-129VV or −129 MM polymorphism were included for transmission studies to determine the infectivity of PMCA-amplified PrPSc. Wester blotting and immunohistochemistry and hematoxylin & eosin staining were used for determining PrPScand neuropathological changes of inoculated animals.
Results: We report here the generation of the first CWD-derived infectious human PrPScusing elk CWD PrPScto initiate conversion of human PrPCfrom normal human brain homogenates with PMCA in vitro. Western blotting with a human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPScwas derived from the human brain PrPCsubstrate. Two lines of humanized transgenic mice expressing human PrPCwith either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPScpatterns and neuropathological changes in the brain.
Conclusions: Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSchas the potential to overcome the species barrier and directly convert human PrPCinto infectious PrPScthat can produce bona fide prion disease when inoculated into humanized transgenic mice.
Funded by: CJD Foundation and NIH
Mortality surveillance of persons potentially exposed to chronic wasting disease
R.A. Maddoxa, R.F. Klosb, L.R. Willb, S.N. Gibbons-Burgenerb, A. Mvilongoa, J.Y. Abramsa, B.S. Applebyc, L.B. Schonbergera, and E.D. Belaya aNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, USA; bWisconsin Department of Health Services (WDHS), Division of Public Health, Madison, USA; cNational Prion Disease Pathology Surveillance Center (NPDPSC), Case Western Reserve University, Cleveland, USA
Aims: It is unknown whether chronic wasting disease (CWD), a prion disease of cervids, can infect people, but consumption of meat from infected animals would be the most likely route of transmission. Wisconsin Department of Health Services, Division of Public Health (WDHS) personnel maintain a database consisting of information collected from hunters who reported eating, or an intention to eat, venison from CWD-positive cervids. These data, collected since 2003, allow for the evaluation of causes of mortality in individuals potentially exposed to CWD.
Material and Methods: The WDHS database contains the name, date of birth, when available, year of CWD-positive deer harvest, and city and state of residence for each potentially exposed individual. The database also includes information on how the deer was processed (self-processed or by a commercial operator) and when applicable, names of others with whom the venison was shared. Duplicate entries (i.e., those who consumed venison from CWD-positive deer in multiple hunt years) are determined by first name, last name, and date of birth. All names in the database are cross-checked with reported cases of human prion disease in Wisconsin and cases in the National Prion Disease Pathology Surveillance Center (NPDPSC) diagnostic testing database. Persons with date of birth available are also cross-checked with prion disease decedents identified through restricted-use national multiple cause-of-death data via a data use agreement with the National Center for Health Statistics (NCHS).
Results: The database currently consists of 1561 records for hunt years 2003–2017 and 87 additional records for 2018–2019. Of these, 657 records have accompanying date of birth; 15 entries were removed as duplicates leaving 642 unique individuals. Of these individuals, 278 of 426 (66%) who ate venison from a CWD-positive deer and provided processing information reported self-processing. No matches were found among any persons in the database cross-checked with WDHS human prion disease surveillance data, NPDPSC data (February 2022 update), and NCHS data through 2020.
Conclusions: Because of the linkage of person and CWD-positive animal in the WDHS database, reviewing the cause of mortality in potentially exposed persons is possible. The number of individuals cross-checked so far is likely only a small percentage of those potentially exposed to CWD in Wisconsin, and many more years of vital status tracking are needed given an expected long incubation period should transmission to humans occur. Nevertheless, the findings of this ongoing review are thus far reassuring.
Prion disease incidence, United States, 2003–2020
R.A. Maddoxa, M.K. Persona, K. Kotobellib, A. Mvilongoa, B.S. Applebyb, L.B. Schonbergera, T.A. Hammetta, J.Y. Abramsa, and E.D. Belaya aNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, USA; bNational Prion Disease Pathology Surveillance Center (NPDPSC), Case Western Reserve University, Cleveland, USA
Aims: Mortality data, in conjunction with neuropathological and genetic testing results, are used to estimate prion disease incidence in the United States.
Material and Methods: Prion disease decedents for 2003–2020 were identified from restricted-use U.S. national multiple cause-of-death data, via a data use agreement with the National Center for Health Statistics, and from the National Prion Disease Pathology Surveillance Center (NPDPSC) database. NPDPSC decedents with neuropathological or genetic test results positive for prion disease for whom no likely match was found in the NCHS multiple cause-of-death data were added as cases for incidence calculations, while those with negative neuropathology results but with cause-of-death data indicating prion disease were removed. Unmatched cases in the NPDPSC database lacking neuropathological testing but with a positive real-time quaking-induced conversion (RT-QuIC) test result were additionally assessed. Age-specific and age-adjusted average annual incidence rates were calculated from the combined data; the year 2000 as the standard population and the direct method were used for age-adjustment.
Results: A total of 7,921 decedents were identified as having prion disease during 2003–2020 for an age-adjusted average annual incidence of 1.2 per million population. The age-adjusted incidence between males and females (1.3 and 1.1 per million, respectively) differed significantly (p < 0.0001). The age-specific average annual incidence among those <55 and ≥55 years of age was 0.2 and 4.8 per million, respectively; incidence among those ≥65 was 6.1 per million. Eighteen cases were <30 years of age for an age-specific incidence of 8.0 per billion; only 6 of these very young cases were sporadic (3 sporadic CJD, 3 sporadic fatal insomnia), with the rest being familial (9), variant (2), or iatrogenic (1). The age-adjusted annual incidence for the most recent year of data, 2020, was 1.3 per million. However, assessment of RT-QuIC positive cases lacking neuropathology in the NPDPSC database suggested that approximately 20% more cases may have occurred in that year; the addition of a subset of these cases that had date of death information available (n = 44) increased the 2020 rate to 1.4 per million.
Conclusions: Mortality data supplemented with the results of neuropathological, CSF RT-QuIC, and genetic testing can be used to estimate prion disease incidence. However, the identification in the NPDPSC database of RT-QuIC-positive cases lacking date of death information suggests that this strategy may exclude a number of probable prion disease cases. Prion disease cases <30 years of age, especially those lacking a pathogenic mutation, continue to be very rare.
Shedding of Chronic Wasting Disease Prions in Multiple Excreta Throughout Disease Course in White-tailed Deer
Nathaniel D. Denkersa, Erin E. McNultya, Caitlyn N. Krafta, Amy V. Nallsa, Joseph A. Westricha, Wilfred Goldmannb, Candace K. Mathiasona, and Edward A. Hoovera
aPrion Research Center, College of Veterinary Medicine and Biological Sciences, Department of Microbiology, Immunology, and Pathology; Colorado State University, Fort Collins, CO, USA; bDivision of Infection and Immunity, The Roslin Institute and the Royal Dick School of Veterinary Studies, University of Edinburgh, Midlothian, UK
Aims: Chronic wasting disease (CWD) now infects cervids in South Korea, North America, and Scandinavia. CWD is unique in its efficient transmission and shedding of prions in body fluids throughout long course infections. Questions remain as to the magnitude of shedding and the route of prion acquisition. As CWD continues to expand, the need to better understand these facets of disease becomes more pertinent. The purpose of the studies described was to define the longitudinal shedding profile of CWD prions in urine, saliva, and feces throughout the course of infection in white-tailed deer.
Material and Methods: Twelve (12) white-tailed deer were inoculated with either 1 mg or 300ng of CWD. Urine, saliva, and feces were collected every 3-month post-inoculation (MPI) throughout the study duration. Cohorts were established based on PNRP genotype: codon 96 GG (n = 6) and alternate codons 96 GS (n = 5) & 103NT (n = 1). Urine and saliva were analyzed using iron-oxide magnetic extraction (IOME) and real-time quaking induced conversion (RT-QuIC)(IQ). Feces were subjected to IOME, followed by 4 rounds protein misfolding cyclic amplification (PMCA) with products analyzed by RT-QuIC (IPQ). To determine whether IPQ may be superior to IQ, a subset of urine and saliva were also tested by IPQ. Results were compared with clinical disease status.
Results: Within the 96 GG cohort, positive seeding activity was detected in feces from all deer (100%), in saliva from 5 of 6 (83%), and in urine from 4 of 6 (66%). Shedding in all excreta occurred at, or just after, the first positive tonsil biopsy result. In the 96 GS/103NT cohort, positive seeding activity could be detected in feces from 3 of 6 (50%) deer, saliva in 2 of 6 (33%), and urine in 1 of 6 (16%). Shedding in excreta was detected >5 months after the first tonsil positive result. Four of six 96 GG deer developed clinical signs of CWD, whereas only 2 of the 96 GS/103NT did. Shedding was more frequently detected in deer with clinical disease. The IPQ protocol did not significantly improve detection in saliva or urine samples, however, it significantly augmented detection in feces by eliminating non-specific background commonly experienced with IQ. Negative control samples remained negative in samples tested.
Conclusions: These studies demonstrate: (a) CWD prion excretion occurs throughout infection; (2) PRNP genotype (GG≫GS/NT) influences the excreta shedding; and (3) detection sensitivity in excreta can vary with different RT-QuIC protocols. These results provide a more complete perspective of prion shedding in deer during the course of CWD infection.
Funded by: National Institutes of Health (NIH)
Grant number: RO1-NS061902-09 R to EAH, PO1-AI077774 to EAH, and R01-AI112956-06 to CKM
Acknowledgement: We abundantly thank Sallie Dahmes at WASCO and David Osborn and Gino D’Angelo at the University of Georgia Warnell School of Forestry and Natural Resources for their long-standing support of this work through provision of the hand-raised, CWD-free, white-tailed deer used in these studies
Large-scale PMCA screening of retropharyngeal lymph nodes and in white-tailed deer and comparisons with ELISA and IHC: the Texas CWD study
Rebeca Benaventea, Paulina Sotoa, Mitch Lockwoodb, and Rodrigo Moralesa
aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bTexas Park and Wildlife Department, Texas, USA
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that affects various species of cervids, and both free-ranging and captive animals. Until now, CWD has been detected in 3 continents: North America, Europe, and Asia. CWD prevalence in some states may reach 30% of total animals. In Texas, the first case of CWD was reported in a free-range mule deer in Hudspeth and now it has been detected in additional 14 counties. Currently, the gold standard techniques used for CWD screening and detection are ELISA and immunohistochemistry (IHC) of obex and retropharyngeal lymph nodes (RPLN). Unfortunately, these methods are known for having a low diagnostic sensitivity. Hence, many CWD-infected animals at pre-symptomatic stages may be misdiagnosed. Two promising in vitro prion amplification techniques, including the real-time quaking-induced conversion (RT-QuIC) and the protein misfolding cyclic amplification (PMCA) have been used to diagnose CWD and other prion diseases in several tissues and bodily fluids. Considering the low cost and speed of RT-QuIC, two recent studies have communicated the potential of this technique to diagnose CWD prions in RPLN samples. Unfortunately, the data presented in these articles suggest that identification of CWD positive samples is comparable to the currently used ELISA and IHC protocols. Similar studies using the PMCA technique have not been reported.
Aims: Compare the CWD diagnostic potential of PMCA with ELISA and IHC in RPLN samples from captive and free-range white-tailed deer. Material and Methods: In this study we analyzed 1,003 RPLN from both free-ranging and captive white-tailed deer collected in Texas. Samples were interrogated with the PMCA technique for their content of CWD prions. PMCA data was compared with the results obtained through currently approved techniques.
Results: Our results show a 15-fold increase in CWD detection in free-range deer compared with ELISA. Our results unveil the presence of prion infected animals in Texas counties with no previous history of CWD. In the case of captive deer, we detected a 16% more CWD positive animals when compared with IHC. Interestingly, some of these positive samples displayed differences in their electroforetic mobilities, suggesting the presence of different prion strains within the State of Texas.
Conclusions: PMCA sensitivity is significantly higher than the current gold standards techniques IHC and ELISA and would be a good tool for rapid CWD screening.
Funded by: USDA
Grant number: AP20VSSPRS00C143
ATYPRION project: assessing the zoonotic potential of interspecies transmission of CWD isolates to livestock (preliminary results).
Enric Vidala,b, Juan Carlos Espinosac, Samanta Gilera,b, Montserrat Ordóñeza,b, Guillermo Canteroa,b, Vincent Béringued, Justin J. Greenleee, and Juan Maria Torresc
aUnitat mixta d’Investigació IRTA-UAB en Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia; bIRTA. Programa de Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia; cCentro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Valdeolmos, Madrid, Spain; dMolecular Virology and Immunology, French National Research Institute for Agriculture, Food and Environment (INRAE), Université Paris-Saclay, Jouy-en-Josas, France; eVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA
Aims: Since variant Creutzfeldt-Jackob disease was linked to the consumption of bovine spongiform encephalopathy prions, the study of the pathobiological features of animal prions, particularly their zoonotic potential, is of great concern to the scientific community and public health authorities. Furthermore, interspecies transmission of prions has been demonstrated as a putative evolutionary mechanism for prions, that can lead to the emergence of new features including the ability to infect humans. For instance, small ruminants’ atypical scrapie prions, when propagated in a bovine or porcine host, can shift to a classical BSE phenotype thus posing a potential risk in case of human exposure. So far, no hard evidence of zoonotic transmission of cervids’ chronic wasting disease (CWD) to humans has been published, however experimental transmission to bovine, ovine and caprine hosts has been achieved. Our goal is to investigate if, once passaged through these domestic species, CWD prions might become infectious to humans.
Material and Methods: Different CWD isolates experimentally adapted to cattle, sheep and goat (Hamir et al, 2005, 2006, 2007, Greenlee et al 2012) have been intracerebrally inoculated to transgenic mouse models expressing the human cellular prion protein either homozygous for methionine or valine at codon 129 (Tg340-Met129 and Tg362-Val129). Additionally, inocula obtained from experimental transmission of elk CWD to ovinized (Tg501) and bovinized (BoTg110) transgenic mice, as well as white-tailed deer CWD to BoTg110 mice, are currently being bioassayed in both human PrPCtransgenic models.
Results and conclusions: No evidence of transmission has been found on first passage for bovine adapted elk and mule deer CWD to none of the humanized models. The remaining bioassays are ongoing without showing clinical signs yet, as well as second passages for the negative 1stpassages.
Funded by: La Marató de TV3 foundation. Grant number: ATYPRION (201,821–30-31-32)
Prion Conference 2018 Abstracts
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in freeranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.
Methods
Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).
Results
Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).
Conclusions
While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.
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P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2)
(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.
We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.
Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.
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P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission
Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.
Methods
We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.
Results
We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.
Conclusions
PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.
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P180 Clinico-pathological analysis of human prion diseases in a brain bank series
Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)
(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Background and objective:
The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.
Methods:
We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.
Results:
176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to GerstmannSträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.
Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.
Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.
Discussion:
A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:
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P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures
Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)
(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Aims:
Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.
Methods:
Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.
Results:
The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.
Conclusions:
Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.
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WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)
(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
See also poster P103
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
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WA16 Monitoring Potential CWD Transmission to Humans
Belay ED
Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.
The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.
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P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan
Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)
(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.
Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.
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Source Prion Conference 2018 Abstracts
Volume 24, Number 8—August 2018 Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
snip...
Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).
A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.
The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.
In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).
The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.
Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.
Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.
This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.
Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.
Prion 2017 Conference Abstracts
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.
At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS ABSTRACTS REFERENCE
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011 Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.
snip....
Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿
Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE. see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”
From: TSS Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091).
Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message----- From:
Sent: Sunday, September 29, 2002 10:15 AM To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
snip... *** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip... full text ;
> However, to date, no CWD infections have been reported in people.
sporadic, spontaneous CJD, 85%+ of all human TSE, did not just happen. never in scientific literature has this been proven. if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;
sporadic = 54,983 hits
spontaneous = 325,650 hits
key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD.
SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
> However, to date, no CWD infections have been reported in people.
key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL
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:
Dear Terry,
An excellent piece of review as this literature is desperately 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 ===============
''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994
Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss) These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...
Table 9 presents the results of an analysis of these data.
There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).
Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.
There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).
The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).
There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).
The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).
snip...
It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).
snip...
In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...
snip...
In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
snip...see full report ;
http://web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
http://web.archive.org/web/20090506050007/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
http://web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf
Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk
BSE Inquiry Steve Dealler
Management In Confidence
BSE: Private Submission of Bovine Brain Dealler
snip...see full text;
MONDAY, FEBRUARY 25, 2019
***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
***> ''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
FRIDAY, JANUARY 20, 2023
EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES
WEDNESDAY, FEBRUARY 03, 2021
Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al
WEDNESDAY, MARCH 16, 2022
SHEEP BY-PRODUCTS AND WHAT ABOUT Scrapie TSE PrP and Potential Zoonosis?
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
FRIDAY, DECEMBER 10, 2021
USDA APHIS National Scrapie Eradication Program October 2021 Monthly Report Fiscal Year 2022
WOAH Designated ADAFSA’s Veterinary Labs as First Collaborating Centre for Camel Diseases in Middle East
Subject: OIE Camel Prion Disease
OIE Bulletin
Camel prion disease: a possible emerging disease in dromedary camel populations?
The identification of a new prion disease in dromedary camels in Algeria and Tunisia, called camel prion disease (CPD), extends the spectrum of animal species naturally susceptible to prion diseases and opens up new research areas for investigation.
Camel prion disease was identified in 2018 in adult camels showing clinical signs at the ante mortem inspection at slaughterhouses in the region of Ouargla (Algeria), and in 2019 in the region of Tataouine (Tunisia). It adds to the group of existing animal prion diseases, including scrapie in sheep and goats, chronic wasting disease (CWD) in cervids and BSE (mainly in bovines). The detection of a new prion disease in the dromedary population requires attention and investigation needs to be carried out to assess the risks of this disease to animal and public health. As of today, very limited epidemiological information is available to assess the prevalence, geographical distribution and dynamic of the transmission of the disease.
Based on the clinical signs suggesting prion disease, CPD seems to have occurred in 3.1% of the dromedaries brought to the abattoir in Ouargla. Pathognomonic neurodegeneration and disease specific prion protein (PrPSc) were detected in brain tissue from three symptomatic animals (source:
In May 2019, the OIE received a report from Tunisia on a single case of a 12-year-old slaughtered dromedary camel showing neurological signs confirmed as CPD by the Istituto Superiore di Sanità (ISS) based in Italy.
©B. Babelhadj/University Kasdi Merbah, Algeria
www.oiebulletin.com
2
Is camel prion disease transmissible in natural conditions?
The involvement of lymphoid tissue in prion replication, observed both in the Algeria and Tunisia cases, is suggestive of a peripheral pathogenesis, which is thought to be a prerequisite for prion shedding into the environment. As with other animal prion diseases, such as scrapie and CWD, in which lymphoid tissues are extensively involved and horizontal transmission occurs efficiently under natural conditions, the detection of prion proteins in lymph nodes is suggestive of the infectious nature of CPD and concurs to hypothesise the potential impact of CPD on animal health. No evidence is currently available with which to argue for the relevance of CPD for human health. However, no absolute species barrier exists in prion diseases and minimising the exposure of humans to prion-infected animal products is an essential aspect of public health protection. As for the relationship between CPD and other animal prion diseases, preliminary analyses suggest that CPD prions have a different molecular signature from scrapie and BSE.
Actions on the follow up of CPD
Since the first description of CPD, the OIE promoted discussions on the impact of this new disease through the OIE Scientific Commission for Animal Diseases (Scientific Commission). The Scientific Commission consulted two OIE ad hoc Groups, one on BSE risk status evaluation of Members and the other on camelids. It analysed the information available from the Algeria and Tunisia cases to evaluate if CPD should be considered an ‘emerging disease’ based on the criteria listed in the Terrestrial Animal Health Code1 .
The OIE Scientific Commission noted that limited surveillance data were available on the prevalence of CPD and that the evidence was not sufficient to measure, at that time, the impact of the disease on animal or public health. Therefore, it was concluded that, with the current knowledge, CPD did not currently meet the criteria to be considered an emerging disease. Nonetheless, it was emphasised that CPD should be considered as a new disease not to be overlooked and called for the collection of further scientific evidence through research and surveillance in the affected countries and in countries with dromedary camel populations to measure the impact of the disease. As new scientific evidence becomes available, the OIE Scientific Commission will reassess whether this disease should be considered as an emerging disease.
The worldwide camel population is ~35 million head (FAO, 2019), 88% of which is found in Africa. The camel farming system is evolving rapidly, and these animals represent vital sources of meat, milk and transportation for millions of people living in the most arid regions of the world. This makes it necessary to assess the risk for animal and human health and to develop evidence-based policies to control and limit the spread of the disease in animals, and to minimise human exposure. As a first step, the awareness of Veterinary Services about CPD and its diagnostic capacity needs to be improved in all countries where dromedaries are part of the domestic livestock.
At the regional level, CPD was first discussed in the 18th Joint Permanent Committee of the Mediterranean Animal Health Network (REMESA) held in Cairo, Egypt, in June 2019 where an expert 1 a new occurrence in an animal of a disease, infection or infestation, causing a significant impact on animal or public health resulting from a) a change of a known pathogenic agent or its spread to a new geographic area or species, or b) a previously unrecognised pathogenic agent or disease diagnosed for the first time www.oiebulletin.com
3
from ISS, Italy, shared the knowledge available on the new disease with the 15 REMESA Member Countries. The discussion highlighted the need to strengthen surveillance systems in order to collect epidemiological data to inform the risk assessments. The results of these risk assessments will support the implementation of evidence-based policies to manage the risks in both animals and humans.
CPD was recently discussed atthe 15thConference of the OIE Regional Commission for the Middle East in November. During this conference, the CAMENET (Camel Middle East Network) launched a wide ranging proposal for training, coordinated surveillance and research on CPD. In addition, the ERFAN (Enhancing Research for Africa Network), a platform aimed at enhancing scientific cooperation between Africa and Italy, during its 2nd ERFAN meeting for North Africa, presented a project on CPD with the objective of increasing CPD coordinated surveillance in North Africa.
The OIE, through its Reference Laboratories for prion diseases, and by involving the above scientific initiatives, is keeping a close watch on the evolution of the disease to gather scientific evidence and to allow a proper and more thorough assessment of the risk associated with this novel disease.
◼ December 2019
Monday, November 14, 2022
Prion Diseases in Dromedary Camels (CPD) 2022 Review
Thursday, April 6, 2023
WOAH OIE CHAPTER 11.4 . BOVINE SPONGIFORM ENCEPHALOPATHY Article 11.4.1.
FRIDAY, APRIL 07, 2023
Case report: Two clusters of Creutzfeldt-Jakob disease cases within 1 year in West Michigan
SEAC SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Minutes of the 99th meeting held on 14th December 2007 Singeltary Submission
sporadic CJD and BSE ?
December 2002
BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein
Emmanuel A. Asante Jacqueline M. Linehan Melanie Desbruslais Susan Joiner Ian Gowland Andrew L. Wood Julie Welch Andrew F. Hill Sarah E. Lloyd Jonathan D.F. Wadsworth John Collinge
The EMBO Journal (2002)21:6358-6366 https://doi.org/10.1093/emboj/cdf653
Variant Creutzfeldt–Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.
Snip…
These studies further strengthen the evidence that vCJD is caused by a BSE-like prion strain. Also, remarkably, the key neuropathological hallmark of vCJD, the presence of abundant florid PrP plaques, can be recapitulated on BSE or vCJD transmission to these mice. However, the most surprising aspect of the studies was the finding that an alternate pattern of disease can be induced in 129MM Tg35 mice from primary transmission of BSE, with a molecular phenotype indistinguishable from that of a sub-type of sporadic CJD. This finding has important potential implications as it raises the possibility that some humans infected with BSE prions may develop a clinical disease indistinguishable from classical CJD associated with type 2 PrPSc. This is, in our experience, the commonest molecular sub-type of sporadic CJD. In this regard, it is of interest that the reported incidence of sporadic CJD has risen in the UK since the 1970s (Cousens et al., 1997). This has been attributed to improved case ascertainment, particularly as much of the rise is reported from elderly patients and similar rises in incidence were noted in other European countries without reported BSE (Will et al., 1998). However, it is now clear that BSE is present in many European countries, albeit at a much lower incidence than was seen in the UK. While improved ascertainment is likely to be a major factor in this rise, that some of these additional cases may be related to BSE exposure cannot be ruled out. It is of interest in this regard that a 2-fold increase in the reported incidence of sporadic CJD in 2001 has recently been reported for Switzerland, a country that had the highest incidence of cattle BSE in continental Europe between 1990 and 2002 (Glatzel et al., 2002). No epidemiological case–control studies with stratification of CJD cases by molecular sub-type have yet been reported. It will be important to review the incidence of sporadic CJD associated with PrPSc type 2 and other molecular sub-types in both BSE-affected and unaffected countries in the light of these findings. If human BSE prion infection can result in propagation of type 2 PrPSc, it would be expected that such cases would be indistinguishable on clinical, pathological and molecular criteria from classical CJD. It may also be expected that such prions would behave biologically like those isolated from humans with sporadic CJD with type 2 PrPSc. The transmission properties of prions associated with type 2 PrPSc from BSE-inoculated 129MM Tg35 mice are being investigated by serial passage.
Snip…
We consider these data inconsistent with contamination of some of the 129MM Tg35 mice with sporadic CJD prions. These transmission studies were performed according to rigorous biosafety protocols for preparation of inocula and both the inoculation and care of mice, which are all uniquely identified by sub-cutaneous transponders. However, crucially, the same BSE inocula have been used on 129VV Tg152 and 129MM Tg45 mice, which are highly sensitive to sporadic CJD but in which such transmissions producing type 2 PrPSc were not observed. Furthermore, in an independent experiment, separate inbred lines of wild-type mice, which are highly resistant to sporadic CJD prions, also propagated two distinctive PrPSc types on challenge with either BSE or vCJD. No evidence of spontaneous prion disease or PrPSc has been seen in groups of uninoculated or mock-inoculated aged 129MM Tg35 mice.
While distinctive prion isolates have been derived from BSE passage in mice previously (designated 301C and 301V), these, in contrast to the data presented here, are propagated in mice expressing different prion proteins (Bruce et al., 1994). It is unclear whether our findings indicate the existence of more than one prion strain in individual cattle with BSE, with selection and preferential replication of distinct strains by different hosts, or that ‘mutation’ of a unitary BSE strain occurs in some types of host. Western blot analysis of single BSE isolates has not shown evidence of the presence of a proportion of monoglycosylated dominant PrPSc type in addition to the diglycosylated dominant pattern (data not shown). Extensive strain typing of large numbers of individual BSE-infected cattle either by biological or molecular methods has not been reported.
Snip…see;
-------- Original Message --------
Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD
Date: Thu, 28 Nov 2002 10:23:43 -0000
From: "Asante, Emmanuel A" e.asante@ic.ac.uk
To: "'flounder@wt.net'" flounder@wt.net
Dear Terry,
I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention.
Thank you for your interest in the paper.
In respect of your first question, the simple answer is, ***yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.
I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.
Emmanuel Asante
<<Asante et al 2002.pdf>>
____________________________________
Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)
____________________________________end
Deaths from sporadic CJD reported in Britain in the 1990s peaked at around 89 a year in 1998 and the number has stayed around the 80 mark ever since - far more than the 28 variant CJD cases in 2000, the worst year so far for variant CJD.
The number of people in the North-East officially confirmed to have died of vCJD is 13.
The number thought to have died of classical CJD is believed to number at least 200.
A spokesman for the Department of Health said: "These are interesting and potentially important findings, which we will need to consider in detail."
The £55m in compensation given by the Department of Health is not available for sporadic CJD victims or relatives, and there is no way yet scientists can distinguish between cases that arose from spontaneous changing in the form of the prion protein linked to both diseases, and those that might be diet-related.
Newcastle scientist Dr Harash Narang, who has spent many years researching CJD, said: "What Professor Collinge's research shows is that many of those who have been classified as dying from sporadic CJD in the past may in fact have died from BSE."
Page 2: Differences between classical CJD and vCJD....
BSE is 'linked' to CJD deaths
Differences between classical CJD and vCJD
Age when obvious symptoms occur after many years of incubation:
Identified in 1920s. Disease mainly of middle-aged and elderly. Incidence roughly one in a million, but steadily rising from 33 to 89 a year.
Identified in 1996. Average age late 20s. Found mainly in Britain: 130 cases with 122 deaths so far. Six in France, one each in Italy, Ireland, Canada, and United States.
Until now assumed a normal prion protein in the brain spontaneously changed into abnormal dangerous form. Recently suggested some cases possibly caused by surgical contamination during operations. BSE or similar diseases could now be factor.
Largely blamed on consumption of cheap cattle meat and offals during 1980s. Tough food controls meant to have significantly reduced risk. Concern remains over whether sheep might also have become infected with BSE and entered food chain.
Page 3: Duration of illness and symptoms...
BSE is 'linked' to CJD deaths
Duration of illness and symptoms
Time between obvious symptoms and death typically a few months. Loss of balance, sense of direction, and control over limbs and bodily functions. Fear, anxiety.
First symptoms often indicate psychological problems. Duration often well over a year. Several physical symptoms similar to sporadic CJD.
More questions, more victims
This weekend marked the seventh anniversary of the death of Peter Hall, of Chester-le-Street, from vCJD.
He was 20 years old and one of the first in the UK to be diagnosed with the new disease.
His parents, Frances and Derek, have been campaigning ever since and 18 months ago won a victory when the Government agreed to compensate the families of victims of vCJD.
Last night Frances, who is now secretary of the Human BSE Foundation, said: "When Peter died in 1996 I never thought that seven years later we still would not understand the disease that killed him.
"And yet here we are with yet more questions and more victims.
"This new study could have major implications for those who have died of CJD since BSE - particularly the young ones who until now were diagnosed with sporadic CJD.
"But it will take time and I suspect it will be years rather than months before we understand what is happening."
Page 4: Hospital report due out soon...
BSE is 'linked' to CJD deaths
Hospital report due out soon
An investigation into how North-East patients were potentially exposed to the deadly brain disease CJD is due to be published soon, health officials have confirmed.
A draft report into the incident at Middlesbrough General Hospital last year has been completed by Dr Bill Kirkup, regional director of public health in the North-East.
Dr Kirkup was asked by Chief Medical Officer Sir Liam Donaldson to investigate the incident, where 24 people were operated on with instruments used on someone who was later found to have CJD.
The hospital denies any procedural lapse as there was nothing to suggest the original patient had the disease prior to surgery. But the Department of Health said the instruments should have been quarantined to avoid contamination.
A DoH spokesman said: "There's a draft report that has been completed and we're hoping to be able to publish the findings shortly."
BMJ. 2002 Nov 9; 325(7372): 1055. doi: 10.1136/bmj.325.7372.1055/a PMCID: PMC1124571PMID: 12424157
Inquiry into handling of CJD alert welcomed Mark Hunter
Author information Copyright and License information Disclaimer
The chief executive of Middlesbrough General Hospital welcomed the launch of an independent inquiry into the hospital's handling of an alert involving Creutzfeldt-Jakob disease (CJD).
The alert arose when staff realised that instruments used on a patient who was later found to have the disease had been reused on 24 other patients.
Chief medical officer Liam Donaldson announced the inquiry last week as the Department of Health began frantically backtracking on its initial criticism of the hospital.
Having originally described the possible exposure of 24 patients to a risk of CJD infection as “an appalling incident” that reinforced the need to adhere to its “crystal clear guidance” on decontamination, the department later adopted a more conciliatory tone.
“This is a difficult and distressing situation for all the patients and families concerned, as well as for the dedicated staff at Middlesbrough General Hospital,” said Professor Donaldson. “I have asked the regional director of public health, Dr Bill Kirkup, to fully assess the facts and report to me shortly. His report will ensure that any measures necessary to improve local procedures or strengthen national policy are taken.”
Meanwhile, the medical director for South Tees Hospitals NHS Trust, Dr Paul Lawler, had made it clear to the press that the hospital had followed the Department of Health's guidance to the letter throughout the incident.
He said that the potential for contamination stemmed from a brain biopsy undertaken in July on an elderly woman who was later found to have the sporadic form of CJD.
“CJD was not suspected in this patient at the time of the operation,” stressed Dr Lawler. It was only when a “diligent” pathologist sent a sample of tissue to the CJD surveillance unit “to rule CJD out rather than confirm it” that the diagnosis was made.
In the intervening three weeks the instruments from the original biopsy were used on a further 24 patients.
“Once sporadic CJD was diagnosed we followed the procedure set down by the CJD incidents panel,” said Dr Lawler. This meant the immediate withdrawal of £90000 ($140000; €141000) worth of drills, craniotomy sets, and surgical instruments.
However, the 24 patients were not told that they were at potential risk of contamination until the story broke in the media last week, 12 weeks after the instruments were withdrawn.
The hospital's managers say that this was because they were waiting for a decision from the government's CJD panel on when and how to contact the patients.
The hospital has now contacted all the patients and will be allocating them “a named person at the trust who will fully support them for as long as they feel they need it.”
The trust's chief executive, Bill Murray, said: “We are deeply sorry for any distress caused to the patients and their families and will do everything we possibly can to help them through this difficult time.
“We welcome this independent inquiry.”
Sporadic CJD in Farmers, Farmers Wife, with BSE herd…
NEW URL LINK 2022
This was not simply another farmer but the third farmer......
NEW URL LINK 2022
http://web.archive.org/web/20090505233408/http://www.bseinquiry.gov.uk/files/yb/1995/06/21002001.pdf
suspect case of CJD in a farmer who has had a case of BSE in his beef suckler herd.
http://web.archive.org/web/20030331213802/http://www.bseinquiry.gov.uk/files/yb/1995/10/23006001.pdf
NEW URL LINK 2022
http://web.archive.org/web/20090506063655/http://www.bseinquiry.gov.uk/files/yb/1995/10/23006001.pdf
cover-up of 4th farm worker ???
http://web.archive.org/web/20030516083454/http://www.bseinquiry.gov.uk/files/yb/1995/10/23006001.pdf
NEW URL LINK 2022
http://web.archive.org/web/20090506063655/http://www.bseinquiry.gov.uk/files/yb/1995/10/23006001.pdf
MONDAY, MAY 19, 2008
SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND ABATTOIRS
The risk of CJD increases with age; the 2016–2020 average annual rate in the United States was about 5 cases per million in persons 55 years of age or older.
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor:
In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally..
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
WEDNESDAY, FEBRUARY 8, 2023
NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER SURVEILLANCE TABLES OF CASES EXAMINED January 11th, 2023
MONDAY, APRIL 24, 2023 2023
CDC REPORTS CJD TSE Prion 5 cases per million in persons 55 years of age or older
Singeltary 1999
US scientists develop a possible test for BSE
BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7220.1312b (Published 13 November 1999)
Cite this as: BMJ 1999;319:1312
15 November 1999
Terry S Singeltary
NA
medically retired
Rapid Response:
Re: vCJD in the USA * BSE in U.S.
In reading the recent article in the BMJ about the potential BSE tests being developed in the U.S. and Bart Van Everbroeck reply. It does not surprize me, that the U.S. has been concealing vCJD. There have been people dying from CJD, with all the symptoms and pathological findings that resemble U.K. vCJD for some time. It just seems that when there is one found, they seem to change the clarical classification of the disease, to fit their agenda. I have several autopsies, stating kuru type amyloid plaques, one of the victims was 41 years of age. Also, my Mom died a most hideous death, Heidenhain Variant Creutzfeldt Jakob disease.
Her symptoms resemble that of all the U.K. vCJD victims. She would jerk so bad at times, it would take 3 of us to hold her down, while she screamed "God, what's wrong with me, why can't I stop this." 1st of symptoms to death, 10 weeks, she went blind in the first few weeks. But, then they told me that this was just another strain of sporadic CJD. They can call it what ever they want, but I know what I saw, and what she went through. Sporadic, simply means, they do not know.
My neighbors Mom also died from CJD. She had been taking a nutritional supplement which contained the following;
vacuum dried bovine BRAIN, bone meal, bovine EYE, veal bone, bovine liver powder, bovine adrenal, vacuum dried bovine kidney, and vacuum dried porcine stomach. As I said, this woman taking these nutritional supplements, died from CJD.
The particular batch of pills that was located, in which she was taking, was tested. From what I have heard, they came up negative, for the prion protein. But, in the same breath, they said their testing, may not have been strong enough to pick up the infectivity. Plus, she had been taking these type pills for years, so, could it have come from another batch?
CWD is just a small piece of a very big puzzle. I have seen while deer hunting, deer, squirrels and birds, eating from cattle feed troughs where they feed cattle, the high protein cattle by products, at least up until Aug. 4, 1997.
So why would it be so hard to believe that this is how they might become infected with a TSE. Or, even by potentially infected land. It's been well documented that it could be possible, from scrapie. Cats becoming infected with a TSE. Have you ever read the ingredients on the labels of cat and dog food? But, they do not put these tissues from these animals in pharmaceuticals, cosmetics, nutritional supplements, hGH, hPG, blood products, heart valves, and the many more products that come from bovine, ovine, or porcine tissues and organs. So, as I said, this CWD would be a small piece of a very big puzzle. But, it is here, and it most likely has killed. You see, greed is what caused this catastrophe, rendering and feeding practices. But, once Pandora's box was opened, the potential routes of infection became endless.
No BSE in the U.S.A.? I would not be so sure of that considering that since 1990;
Since 1990 the U.S. has raised 1,250,880,700 cattle;
Since 1990 the U.S. has ONLY checked 8,881 cattle brains for BSE, as of Oct. 4, 1999;
There are apprx. 100,000 DOWNER cattle annually in the U.S., that up until Aug. 4, 1997 went to the renders for feed;
Scrapie running rampant for years in the U.S., 950 infected FLOCKS, as of Aug. 1999;
Our feeding and rendering practices have mirrored that of the U.K. for years, some say it was worse. Everything from the downer cattle, to those scrapie infected sheep, to any roadkill, including the city police horse and the circus elephant went to the renders for feed and other products for consumption. Then they only implemented a partial feed ban on Aug. 4, 1997, but pigs, chickens, dogs, and cats, and humans were exempt from that ban. So they can still feed pigs and chickens those potentially TSE tainted by-products, and then they can still feed those by-products back to the cows. I believe it was Dr. Joe Gibbs, that said, the prion protein, can survive the digestinal track. So you have stopped nothing. It was proven in Oprah Winfrey's trial, that Cactus Cattle feeders, sent neurologically ill cattle, some with encephalopathy stamped on the dead slips, were picked up and sent to the renders, along with sheep carcasses. Speaking of autopsies, I have a stack of them, from CJD victims. You would be surprised of the number of them, who ate cow brains, elk brains, deer brains, or hog brains.
I believe all these TSE's are going to be related, and originally caused by the same greedy Industries, and they will be many. Not just the Renders, but you now see, that they are re-using medical devices that were meant for disposal. Some medical institutions do not follow proper auto- claving procedures (even Olympus has put out a medical warning on their endescopes about CJD, and the fact you cannot properly clean these instruments from TSE's), and this is just one product. Another route of infection.
Regardless what the Federal Government in the U.S. says. It's here, I have seen it, and the longer they keep sweeping it under the rug and denying the fact that we have a serious problem, one that could surpass aids (not now, but in the years to come, due to the incubation period), they will be responsible for the continued spreading of this deadly disease.
It's their move, it's CHECK, but once CHECKMATE has been called, how many thousands or millions, will be at risk or infected or even dead. You can't play around with these TSE's. I cannot stress that enough. They are only looking at body bags, and the fact the count is so low. But, then you have to look at the fact it is not a reportable disease in most states, mis-diagnosis, no autopsies performed. The fact that their one-in-a- million theory is a crude survey done about 5 years ago, that's a joke, under the above circumstances. A bad joke indeed........
The truth will come, but how many more have to die such a hideous death. It's the Government's call, and they need to make a serious move, soon. This problem, potential epidemic, is not going away, by itself.
Terry S. Singeltary Sr.
Bacliff, Texas 77518 USA
flounder@wt.net
Competing interests: No competing interests
Singeltary 2000
BMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7226.8/b (Published 01 January 2000) Cite this as: BMJ 2000;320:8
02 January 2000 Terry S Singeltary retired
Rapid Response:
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well...
In reading your short article about 'Scientist warn of CJD epidemic' news in brief Jan. 1, 2000. I find the findings in the PNAS old news, made famous again. Why is the U.S. still sitting on their butts, ignoring the facts? We have the beginning of a CJD epidemic in the U.S., and the U.S. Gov. is doing everything in it's power to conceal it.
The exact same recipe for B.S.E. existed in the U.S. for years and years. In reading over the Qualitative Analysis of BSE Risk Factors-1, this is a 25 page report by the USDA:APHIS:VS. It could have been done in one page. The first page, fourth paragraph says it all;
"Similarities exist in the two countries usage of continuous rendering technology and the lack of usage of solvents, however, large differences still remain with other risk factors which greatly reduce the potential risk at the national level."
Then, the next 24 pages tries to down-play the high risks of B.S.E. in the U.S., with nothing more than the cattle to sheep ratio count, and the geographical locations of herds and flocks. That's all the evidence they can come up with, in the next 24 pages.
Something else I find odd, page 16;
"In the United Kingdom there is much concern for a specific continuous rendering technology which uses lower temperatures and accounts for 25 percent of total output. This technology was _originally_ designed and imported from the United States. However, the specific application in the production process is _believed_ to be different in the two countries."
A few more factors to consider, page 15;
"Figure 26 compares animal protein production for the two countries. The calculations are based on slaughter numbers, fallen stock estimates, and product yield coefficients. This approach is used due to variation of up to 80 percent from different reported sources. At 3.6 million tons, the United States produces 8 times more animal rendered product than the United Kingdom."
"The risk of introducing the BSE agent through sheep meat and bone meal is more acute in both relative and absolute terms in the United Kingdom (Figures 27 and 28). Note that sheep meat and bone meal accounts for 14 percent, or 61 thousand tons, in the United Kingdom versus 0.6 percent or 22 thousand tons in the United States. For sheep greater than 1 year, this is less than one-tenth of one percent of the United States supply."
"The potential risk of amplification of the BSE agent through cattle meat and bone meal is much greater in the United States where it accounts for 59 percent of total product or almost 5 times more than the total amount of rendered product in the United Kingdom."
Considering, it would only take _one_ scrapie infected sheep to contaminate the feed. Considering Scrapie has run rampant in the U.S. for years, as of Aug. 1999, 950 scrapie infected flocks. Also, Considering only one quarter spoonful of scrapie infected material is lethal to a cow.
Considering all this, the sheep to cow ration is meaningless. As I said, it's 24 pages of B.S.e.
To be continued...
Terry S. Singeltary Sr. Bacliff, Texas USA
Competing interests: No competing interests
Singeltary 2001
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor:
In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally..
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
Singeltary 2003
doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003.
Volume 3, Issue 8, August 2003, Page 463
Volume 3, Number 8 01 August 2003
Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.
49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD) the relative of mad cow disease seen among deer and elk in the USA. Although his feverish search did not lead him to the smoking gun linking CWD to a similar disease in North American people, it did uncover a largely disappointing situation.
Singeltary was greatly demoralised at the few attempts to monitor the occurrence of CJD and CWD in the USA. Only a few states have made CJD reportable. Human and animal TSEs should be reportable nationwide and internationally, he complained in a letter to the Journal of the American Medical Association (JAMA 2003; 285: 733). I hope that the CDC does not continue to expect us to still believe that the 85% plus of all CJD cases which are sporadic are all spontaneous, without route or source.
Until recently, CWD was thought to be confined to the wild in a small region in Colorado. But since early 2002, it has been reported in other areas, including Wisconsin, South Dakota, and the Canadian province of Saskatchewan. Indeed, the occurrence of CWD in states that were not endemic previously increased concern about a widespread outbreak and possible transmission to people and cattle.
To date, experimental studies have proven that the CWD agent can be transmitted to cattle by intracerebral inoculation and that it can cross the mucous membranes of the digestive tract to initiate infection in lymphoid tissue before invasion of the central nervous system. Yet the plausibility of CWD spreading to people has remained elusive.
Part of the problem seems to stem from the US surveillance system. CJD is only reported in those areas known to be endemic foci of CWD. Moreover, US authorities have been criticised for not having performed enough prionic tests in farm deer and elk.
Although in November last year the US Food and Drug Administration issued a directive to state public-health and agriculture officials prohibiting material from CWD-positive animals from being used as an ingredient in feed for any animal species, epidemiological control and research in the USA has been quite different from the situation in the UK and Europe regarding BSE.
Getting data on TSEs in the USA from the government is like pulling teeth, Singeltary argues. You get it when they want you to have it, and only what they want you to have.
Norman Foster, director of the Cognitive Disorders Clinic at the University of Michigan (Ann Arbor, MI, USA), says that current surveillance of prion disease in people in the USA is inadequate to detect whether CWD is occurring in human beings; adding that, the cases that we know about are reassuring, because they do not suggest the appearance of a new variant of CJD in the USA or atypical features in patients that might be exposed to CWD. However, until we establish a system that identifies and analyses a high proportion of suspected prion disease cases we will not know for sure. The USA should develop a system modelled on that established in the UK, he points out.
Ali Samii, a neurologist at Seattle VA Medical Center who recently reported the cases of three hunters two of whom were friends who died from pathologically confirmed CJD, says that at present there are insufficient data to claim transmission of CWD into humans; adding that [only] by asking [the questions of venison consumption and deer/elk hunting] in every case can we collect suspect cases and look into the plausibility of transmission further. Samii argues that by making both doctors and hunters more aware of the possibility of prions spreading through eating venison, doctors treating hunters with dementia can consider a possible prion disease, and doctors treating CJD patients will know to ask whether they ate venison.
CDC spokesman Ermias Belay says that the CDC will not be investigating the [Samii] cases because there is no evidence that the men ate CWD-infected meat. He notes that although the likelihood of CWD jumping the species barrier to infect humans cannot be ruled out 100% and that [we] cannot be 100% sure that CWD does not exist in humans& the data seeking evidence of CWD transmission to humans have been very limited.
Singeltary 2003
January 28, 2003; 60 (2) VIEWS & REVIEWS
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States Terry S. Singeltary, retired (medically)
Published March 26, 2003
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
Singeltary 2007
The Pathological Protein: Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
by Philip Yam
''Answering critics like Terry Singeltary, who feels that the US undercounts CJD, Schonberger _conceded_ that the current surveillance system has errors but stated that most of the errors will be confined to the older population''...
Revisiting Sporadic CJD
It’s not hard to get Terry Singeltary going. “I have my conspiracy theories,” admitted the 49-year-old Texan.1 Singeltary is probably the nation’s most relentless consumer advocate when it comes to issues in prion diseases. He has helped families learn about the sickness and coordinated efforts with support groups such as CJD Voice and the CJD Foundation. He has also connected with others who are critical of the American way of handling the threat of prion diseases. Such critics include Consumers Union’s Michael Hansen, journalist John Stauber, and Thomas Pringle, who used to run the voluminous www.madcow.org Web site. These three lend their expertise to newspaper and magazine stories about prion diseases, and they usually argue that
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prions represent more of a threat than people realize, and that the government has responded poorly to the dangers because it is more concerned about protecting the beef industry than people’s health.
Singeltary has similar inclinations, but unlike these men, he doesn’t have the professional credentials behind him. He is an 11th-grade dropout, a machinist who retired because of a neck injury sustained at work. But you might not know that from the vast stores of information in his mind and on his hard drive. Over the years, he has provided unacknowledged help to reporters around the globe, passing on files to such big-time players as The New York Times, Newsweek, and USA Today. His networking with journalists, activists, and concerned citizens has helped medical authorities make contact with suspected CJD victims. He has kept scientists informed with his almost daily posting of news items and research abstracts on electronic newsgroups, including the bulletin board on www.vegsource.com and the BSE-listserv run out of the University of Karlsruhe, Germany. His combative, blunt, opinionated style sometimes borders on obsessive ranting that earns praise from some officials and researchers but infuriates others—especially when he repeats his conviction that “the government has lied to us, the feed industry has lied to us—all over a buck.” As evidence, Singeltary cites the USDA’s testing approach, which targets downer cows and examined 19,900 of them in 2002. To him, the USDA should test 1 million cattle, because the incidence of BSE may be as low as one in a million, as it was in some European countries. That the U.S. does not, he thinks, is a sign that the government is really not interested in finding mad cows because of fears of an economic disaster.
Singeltary got into the field of transmissible spongiform encephalopathy in 1997, just after his mother died of sporadic CJD. She had an especially aggressive version—the Heidenhain variant—that first causes the patient to go blind and then to deteriorate rapidly. She died just ten weeks after her symptoms began. Singeltary, who said he had watched his grandparents die of cancer, considered her death by CJD to be much, much worse: “It’s something you never forget.” Her uncontrollable muscle twitching became so bad “that it took three of us to hold her one time,” Singeltary recalled. “She did everything but levitate in bed and spin her head.” Doctors originally diagnosed Alzheimer’s disease, but a postmortem neuropathological exam demanded by Singeltary revealed the true nature of her death.
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Classifying a disease as “sporadic” is another way for doctors to say they don’t know the cause. Normal prion proteins just turn rogue in the brain for no apparent reason. The term “sporadic” is often particularly hard for the victims’ families to accept, especially when the patient was previously in robust health. Maybe it was something in the water, they wonder, or in the air, or something they ate—the same questions CJD researchers tried to answer decades ago. The names “sporadic CJD” and “variant CJD” also confuse the public and raise suspicions that U.S. authorities are hiding something when they say there have been no native variant CJD cases in the country.
Singeltary suspected an environmental cause in his mother’s demise—a feeling reinforced a year later when a neighbor died of sporadic CJD. For years, the neighbor had been taking nutritional supplements that contained cow brain extracts. Researchers from the National Institutes of Health collected samples of the supplement, Singeltary recounted, and inoculated suspensions into mice. The mice remained healthy—which only means that those supplement samples tested were prion-free.
Scientists have made several attempts during the past few decades to find a connection between sporadic CJD and the environment. Often, these studies take the form of asking family members about CJD victims—their diet, occupation, medical history, hobbies, pets, and so forth—and comparing them with non-CJD subjects. Such case-control CJD studies have produced some intriguing—and sometimes contradictory—results. In 1985, Carleton Gajdusek and his NIH colleagues reported a correlation between CJD and eating a lot of roast pork, ham, hot dogs, and lamb, as well as rare meats and raw oysters.2 Yet they also recognized that the findings were preliminary and that more studies were needed.
Following up, Robert Will of the U.K. National CJD Surveillance Unit and others pooled this data with those from two other case-control studies on CJD (one from Japan and one from the U.K.). In particular, they figured the so-called odds ratio—calculated by dividing the frequency of a possible factor in the patient group by the frequency of the factor in the control group. An odds ratio greater than 1 means that the factor may be significant. In their study, Will and his collaborators found an increase of CJD in people who have worked as health professionals (odds ratio of 1.5) and people who have had contact with cows
Laying Odds 225
(1.7) and sheep (1.6). Unfortunately, those connections were not statistically significant: The numbers of pooled patients (117) and control subjects (333) were so small that the researchers felt the odds ratios needed to reach 2.5 to 8 (depending on the assumptions) before they could be deemed statistically significant. The only statistically significant correlations they found were between CJD and a family history of either CJD (19.1) or other psychotic disease (9.9), although the latter might simply be correlated because psychotic disease may be an early symptom of undiagnosed CJD.3 In contrast with earlier findings, the team concluded that there was no association between sporadic CJD and the consumption of organ meats, including brains (0.6).
Although these case-control studies shed a certain amount of light on potential risk factors for CJD, it’s impossible to draw firm conclusions. Obtaining data that produces statistically meaningful results can be difficult because of the rarity of CJD and hence the shortage of subjects. Human memory is quite fragile, too, so patients’ families may not accurately recall the lifestyle and dietary habits of their loved ones over the course of a decade or more. Consequently, researchers must cope with data that probably contain significant biases. In a review paper on CJD, Joe Gibbs of the NIH and Richard T. Johnson of Johns Hopkins University concluded that “the absence of geographic differences in incidence is more convincing evidence against major dietary factors, since large populations eschew pork and some consume no meat or meat products.” A CJD study of lifelong vegetarians, they proposed, could produce some interesting data.4
The inconclusive results of case-control studies do not completely rule out the environment as a possible cause of CJD. “Dr. Prusiner’s theory does fit much of the data of spontaneous generation of [malformed] PrP somewhere in the brain,” Will remarked—that is, the idea that sporadic CJD just happens by itself falls within the realm of the prion theory. Still, “it’s very odd, if you look at all the forms of human prion diseases there are, all of them are transmissible in the laboratory and could be due to some sort of infectious agent.”5 One of the great difficulties, he explained, is that “given that this is a disease of an extraordinarily long incubation period, are we really confident that we can exclude childhood exposure that is transmitted from person to person, as people move around? It’s difficult to be sure about that.” There might a “carrier state” that leaves people healthy yet still able to
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infect others. If so, “you would never be able to identify what’s causing the spread of the disease,” concluded Will, who hasn’t stopped looking for a possible environmental link. He has some preliminary data based on studies that trace CJD victims’ lives well before the time symptoms began—up to 70 years; they suggest some degree of geographic clustering, but no obvious candidates for a source of infection.
A Case for Undercounting
The difficulty in establishing causal links in sporadic prion diseases—if there are any in the first place—underlines the importance of thorough surveillance. The U.K. has an active program, and when a victim of CJD is reported, one of Robert Will’s colleagues visits and questions the victim’s family. “No one has looked for CJD systematically in the U.S.,” the NIH’s Paul Brown noted. “Ever.”6 The U.S., through the Centers for Disease Control and Prevention, has generally maintained a more passive system, collecting information from death certificates from the National Center for Health Statistics. Because CJD is invariably fatal, mortality data is considered to be an effective means of tabulating cases. The CDC assessed the accuracy of such data by comparing the numbers with figures garnered through an active search in 1996: Teams covering five regions of the U.S. contacted the specialists involved and reviewed medical records for CJD cases between 1991 and 1995. Comparing the actively garnered data with the death certificate information showed that “we miss about 14 percent,” said CDC epidemiologist Lawrence Schonberger. “That’s improving. Doctors are becoming more knowledgeable,” thanks to increased scientific and media attention given to prion diseases.7
The active surveillance study of 1996, however, only looked at cases in which physicians attributed the deaths to CJD. Misdiagnosed patients or patients who never saw a neurologist were not tabulated— thus CJD may be grossly underreported. Many neurological ailments share symptoms, especially early on. According to various studies, autopsies have found that CJD is misdiagnosed as other ills, such as dementia or Alzheimer’s disease, 5 to 13 percent of the time. The CDC finds that around 50,000Americans die from Alzheimer’s each year
Laying Odds 227
(about 4 million have the disease, according to the Alzheimer’s Association). Therefore, one could argue that thousands of CJD cases are being missed. (On the flip side, CJD could be mistakenly diagnosed as Alzheimer’s disease or dementia, but the number of CJD patients is so small that they wouldn’t dramatically skew the statistics for other neurological ills.)
In part to address the issue of misdiagnosis, CJD families have asked the CDC to place the disease on the national list of officially notifiable illnesses, which tends to include more contagious conditions such as AIDS, tuberculosis, hepatitis, and viral forms of encephalitis. Currently, only some states impose this requirement. CDC officials have discounted the utility of such an approach, arguing that it would duplicate the mortality data, which is more accurate than early diagnoses of CJD, anyway. Moreover, mandatory reporting of CJD cases does not necessarily guarantee the end to missed cases.8
One clue suggests that the passive system is undercounting CJD in the U.S.: racial difference. The number of black CJD victims is about 38 percent that of white victims. Rather than sporadic CJD being a onein-a-million lottery, it’s more like one-in-2.5-million for AfricanAmericans. Access to medical care might be one reason. Schonberger recounted that the CDC had asked other countries with substantial black populations to submit CJD figures for comparison but found that the surveillance in those countries was inadequate. “We haven’t been able to find any comparable literature on this issue, so it’s still up in the air,” Schonberger said. On the other hand, Alzheimer’s disease is more common among black people than whites, with an estimated higher prevalence ranging from 14 percent to almost 100 percent, according to a February 2002 report by the Alzheimer’s Association. Are some black CJD cases being misdiagnosed as Alzheimer’s?
Answering critics like Terry Singeltary, who feels that the U.S. undercounts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population. As Schonberger pointed out, no doctor would misdiagnose a 30-year-old CJD patient as having Alzheimer’s. The average age of the first 100 variant CJD victims was 29; should the epidemiology of vCJD change—if older people start coming down with it—then there would be problems. “The adequacy of our overall CJD surveillance would be greatly reduced should the proportion of older individuals affected by variant CJD substantially increase,” Schonberger explained.9
SNIP...SEE FULL TEXT;
''The average age of the first 100 variant CJD victims was 29; should the epidemiology of vCJD change—if older people start coming down with it—then there would be problems. “The adequacy of our overall CJD surveillance would be greatly reduced should the proportion of older individuals affected by variant CJD substantially increase,” Schonberger explained.9''
THE PATHOLOGICAL PROTEIN by Philip Yam
Singeltary Submission SEAC 2007
SEAC SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Minutes of the 99th meeting held on 14th December 2007 Singeltary Submission
This was 22 years to the day Mom died from the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. hvCJD, when i made this submission to SEAC and this was their reply to my questions of concern about cjd in the USA, my how things have changed...terry
SEAC SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Minutes of the 99th meeting held on 14th December 2007
ITEM 8 – PUBLIC QUESTION AND ANSWER SESSION 40. The Chair explained that the purpose of the question and answer session was to give members of the public an opportunity to ask questions related to the work of SEAC. Mr Terry Singeltary (Texas, USA) had submitted a question prior to the meeting, asking: “With the Nor-98 now documented in five different states so far in the USA in 2007, and with the two atypical BSE H-base cases in Texas and Alabama, with both scrapie and chronic wasting disease (CWD) running rampant in the USA, is there any concern from SEAC with the rise of sporadic CJD in the USA from ''unknown phenotype'', and what concerns if any, in relations to blood donations, surgery, optical, and dental treatment, do you have with these unknown atypical phenotypes in both humans and animals in the USA? Does it concern SEAC, or is it of no concern to SEAC? Should it concern USA animal and human health officials?”
41. A member considered that this question appeared to be primarily related to possible links between animal and human TSEs in the USA. There is no evidence that sCJD is increasing in the USA and no evidence of any direct link between TSEs and CJD in the USA. Current evidence does not suggest that CWD is a significant risk to human health. There are unpublished data from a case of human TSE in the USA that are suggestive of an apparently novel form of prion disease with distinct molecular characteristics. However, it is unclear whether the case had been further characterised, if it could be linked to animal TSEs or if other similar cases had been found in the USA or elsewhere. In relation to the possible public health implications of atypical scrapie, H-type BSE and CWD, research was being conducted to investigate possible links and surveillance was in place to detect any changes in human TSEs. Although possible links between these diseases and human TSEs are of concern and require research, there is no evidence to suggest immediate public health action is warranted. The possible human health risks from classical scrapie had been discussed earlier in the meeting. Members noted that there are effective channels of discussion and collaboration on research between USA and European groups. Members agreed it is important to keep a watching brief on new developments on TSEs.
Singeltary 2009
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009
August 10, 2009
Greetings,
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. North America seems to have the most species with documented Transmissible Spongiform Encephalopathy's, most all of which have been rendered and fed back to food producing animals and to humans for years. If you look at the statistics, sporadic CJD seems to be rising in the USA, and has been, with atypical cases of the sCJD. I find deeply disturbing in the year of 2009, that Human Transmissible Spongiform Encephalopathy of any strain and or phenotype, of all age groups, and I stress all age groups, because human TSE's do not know age, and they do not know borders. someone 56 years old, that has a human TSE, that has surgery, can pass this TSE agent on i.e. friendly fire, and or passing it forward, and there have been documented nvCJD in a 74 year old. Remembering also that only sporadic CJD has been documented to transmit via iatrogenic routes, until recently with the 4 cases of blood related transmission, of which the origin is thought to be nvCJD donors. However most Iatrogenic CJD cases are nothing more than sporadic CJD, until the source is proven, then it becomes Iatrogenic. An oxymoron of sorts, because all sporadic CJD is, are multiple forms, or strains, or phenotypes of Creutzfeldt Jakob Disease, that the route and source and species have not been confirmed and or documented. When will the myth of the UKBSEnvCJD only theory be put to bed for good. This theory in my opinion, and the following there from, as the GOLD STANDARD, has done nothing more than help spread this agent around the globe. Politics and money have caused the terrible consequences to date, and the fact that TSEs are a slow incubating death, but a death that is 100% certain for those that are exposed and live long enough to go clinical. once clinical, there is no recourse, to date. But, while sub-clinical, how many can one exposed human infect? Can humans exposed to CWD and scrapie strains pass it forward as some form of sporadic CJD in the surgical and medical arenas? why must we wait decades and decades to prove this point, only to expose millions needlessly, only for the sake of the industries involved? would it not have been prudent from the beginning to just include all TSE's, and rule them out from there with transmission studies and change policies there from, as opposed to doing just the opposite? The science of TSE's have been nothing more than a political circus since the beginning, and for anyone to still believe in this one strain, one group of bovines, in one geographical location, with only one age group of human TSE i.e. nvCJD myth, for anyone to believe this today only enhances to spreading of these human and animal TSE's. This is exactly why we have been in this quagmire.
The ones that believe that there is a spontaneous CJD in 85%+ of all cases of human TSE, and the ones that do not believe that cattle can have this same phenomenon, are two of the same, the industry, and so goes the political science aspect of this tobacco and or asbestos scenario i.e. follow the money. I could go into all angles of this man made nightmare, the real facts and science, for instance, the continuing rendering technology and slow cooking with low temps that brewed this stew up, and the fact that THE USA HAD THIS TECHNOLOGY FIRST AND SHIPPED IT TO THE U.K. SOME 5 YEARS BEFORE THE U.S. STARTED USING THE SAME TECHNOLOGY, to save on fuel cost. This is what supposedly amplified the TSE agent via sheep scrapie, and spread via feed in the U.K. bovine, and other countries exporting the tainted product. BUT most everyone ignores this fact, and the fact that the U.S. has been recycling more TSE, from more species with TSEs, than any other country documented, but yet, it's all spontaneous, and the rise in sporadic CJD in the U.S. is a happenstance of bad luck ??? I respectfully disagree. To top that all off, the infamous BSE-FIREWALL that the USDA always brags about was nothing more than ink on paper, and I can prove this. YOU can ignore it, but this is FACT (see source, as late as 2007, in one recall alone, some 10,000,000 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE TO BE FED OUT, and most was never recovered. This was banned blood laced, meat and bone meal. 2006 was a banner year for banned mad cow protein going into commerce in the U.S. (see source of FDA feed ban warning letter below). I stress that the August 4, 1997 USA mad cow feed ban and this infamous BSE firewall, was nothing more than ink on paper, it was never enforceable.
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route. This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down. Accumulation and Transmission are key to the threshold from sub- clinical to clinical disease, and key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain. In my opinion, to continue with this myth that the U.K. strain of BSE one strain TSE in cows, and the nv/v CJD one strain TSE humans, and the one geographical location source i.e. U.K., and that all the rest of human TSE are just one single strain i.e. sporadic CJD, a happenstance of bad luck that just happens due to a twisted protein that just twisted the wrong way, IN 85%+ OF ALL HUMAN TSEs, when to date there are 6 different phenotypes of sCJD, and growing per Gambetti et al, and that no other animal TSE transmits to humans ??? With all due respect to all Scientist that believe this, I beg to differ. To continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come. ONE was enough for me, My Mom, hvCJD i.e. Heidenhain Variant CJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human. WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE? Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...
please see history, and the ever evolving TSE science to date ;
Saturday, June 13, 2009
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009
Singeltary 2010
Human Prion Diseases in the United States
Robert C. Holman ,Ermias D. Belay,Krista Y. Christensen,Ryan A. Maddox,Arialdi M. Minino,Arianne M. Folkema,Dana L. Haberling,Teresa A. Hammett,Kenneth D. Kochanek,James J. Sejvar,Lawrence B. Schonberger
Published: January 1, 2010
https://doi.org/10.1371/journal.pone.0008521
re-Human Prion Diseases in the United States
Posted by flounder on 01 Jan 2010 at 18:11 GMT
I kindly disagree with your synopsis for the following reasons ;
Singeltary 2014
Alzheimer's disease, iatrogenic transmission, what if?
let's not forget the elephant in the room. curing Alzheimer's would be a great and wonderful thing, but for starters, why not start with the obvious, lets prove the cause or causes, and then start to stop that. think iatrogenic, friendly fire, or the pass it forward mode of transmission. think medical, surgical, dental, tissue, blood, related transmission. think transmissible spongiform encephalopathy aka tse prion disease aka mad cow type disease...
Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
*** Singeltary comment PLoS ***
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease have both been around a long time, and was discovered in or around the same time frame, early 1900’s. Both diseases are incurable and debilitating brain disease, that are in the end, 100% fatal, with the incubation/clinical period of the Alzheimer’s disease being longer (most of the time) than the TSE prion disease. Symptoms are very similar, and pathology is very similar.
Methods
Through years of research, as a layperson, of peer review journals, transmission studies, and observations of loved ones and friends that have died from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant Creutzfelt Jakob Disease CJD.
Results
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation disease, and that Alzheimer’s is Transmissible, and is a threat to the public via the many Iatrogenic routes and sources. It was said long ago that the only thing that disputes this, is Alzheimer’s disease transmissibility, or the lack of. The likelihood of many victims of Alzheimer’s disease from the many different Iatrogenic routes and modes of transmission as with the TSE prion disease.
Conclusions
There should be a Global Congressional Science round table event set up immediately to address these concerns from the many potential routes and sources of the TSE prion disease, including Alzheimer’s disease, and a emergency global doctrine put into effect to help combat the spread of Alzheimer’s disease via the medical, surgical, dental, tissue, and blood arena’s. All human and animal TSE prion disease, including Alzheimer’s should be made reportable in every state, and Internationally, WITH NO age restrictions. Until a proven method of decontamination and autoclaving is proven, and put forth in use universally, in all hospitals and medical, surgical arena’s, or the TSE prion agent will continue to spread. IF we wait until science and corporate politicians wait until politics lets science _prove_ this once and for all, and set forth regulations there from, we will all be exposed to the TSE Prion agents, if that has not happened already.
MONDAY, APRIL 24, 2023
Prion Disease on the Rise in the U.S., Now the question is, why?
''5 cases per million in persons 55 years of age or older.''
Terry S. Singeltary Sr.
