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Monday, January 31, 2022

Validation of Revised International Creutzfeldt-Jakob Disease Surveillance Network Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease Singeltary Comment Submission

Validation of Revised International Creutzfeldt-Jakob Disease Surveillance Network Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease Singeltary Comment Submission

Validation of Revised International Creutzfeldt-Jakob Disease Surveillance Network Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease 

Neil Watson, MD; Peter Hermann, MD; Anna Ladogana, MD; Angeline Denouel, MSc; Simone Baiardi, MD, PhD; Elisa Colaizzo, MD; Giorgio Giaccone, MD; Markus Glatzel, MD; Alison J. E. Green, PhD; Stéphane Haïk, MD, PhD; Daniele Imperiale, MD; Janet MacKenzie, PG Cert Epid; Fabio Moda, PhD; Colin Smith, MD; David Summers, MD; Dorina Tiple, MD; Luana Vaianella, MD; Gianluigi Zanusso, MD, PhD; Maurizio Pocchiari, MD; Inga Zerr, MD; Piero Parchi, MD, PhD; Jean-Philippe Brandel, MD; Suvankar Pal, MD 

Abstract 

IMPORTANCE 

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly lethal disease. Rapid, accurate diagnosis is imperative for epidemiological surveillance and public health activities to exclude treatable differentials and facilitate supportive care. In 2017, the International CJD Surveillance Network diagnostic criteria were revised to incorporate cortical ribboning on magnetic resonance imaging and the real-time quaking-induced conversion (RT-QuIC) assay, developments that require multicenter evaluation. 

OBJECTIVE 

To evaluate the accuracy of revised diagnostic criteria through the retrospective diagnosis of autopsy-confirmed cases (referred to as in-life diagnosis). 

DESIGN, SETTING, AND PARTICIPANTS 

This diagnostic study used a 3-year clinicopathological series using all cases of autopsy-confirmed sCJD and a noncase group with alternative neuropathological diagnoses from national surveillance centers in the United Kingdom, France, Germany, and Italy. Data were collected from January 2017 to December 2019 and analyzed from January 2020 to November 2021. 

MAIN OUTCOMES AND MEASURES 

Sensitivity and specificity of revised diagnostic criteria and diagnostic investigations. Secondary analyses assessing sCJD subgroups by genotype, pathological classification, disease duration, and age. RESULTS A total of 501 sCJD cases and 146 noncases were included. Noncase diagnoses included neurodegenerative diseases, autoimmune encephalitis, and cerebral insults such as anoxia. Participants in the sCJD cases cohort were younger (mean [SD] age, 68.8 [9.8] years vs 72.8 [10.9] years; P < .001) and had longer median (IQR) disease duration (118 [74.8-222.3] days vs 85 [51.5- 205.5] days; P = .002); sex ratios were equivalent (253 [50.5%] male cases vs 74 [50.7%] male noncases). Sensitivity of revised criteria in in-life diagnosis (450 of 488 [92.2%] diagnoses; 95% CI, 89.5%-94.4%) was increased compared with prior criteria (378 of 488 [77.5%] diagnoses; 95% CI, 73.5%-81.1%; P < .001), while specificity (101 of 125 [80.8%] diagnoses; 95% CI, 72.8%-87.3%) was unchanged (102 of 125 [81.6%] diagnoses; 95% CI, 73.7%-88.0%; P > .99). Among 223 cases and 52 noncases with the full panel of investigations performed, sensitivity of revised criteria (97.8%; 95% CI, 94.9%-99.3%) was increased compared with prior criteria (76.2%; 95% CI, 70.1%-81.7%; P < .001) while specificity was unchanged (67.3%; 95% CI, 52.9%-79.7% vs 69.2%; 95% CI, 54.9%- 81.3%; P > .99). In 455 cases and 111 noncases, cortical ribboning was 67.9% sensitive (95% CI, 63.4%-72.2%) and 86.5% specific (95% CI, 78.7%-92.2%). In 274 cases and 77 noncases, RT-QuIC was 91.6% sensitive (95% CI, 87.7%-94.6%) and 100% specific (95% CI, 96.2%-100%). Investigation sensitivity varied with genetic and pathological features, disease duration, and age.

Conclusions and Relevance This diagnostic study demonstrated significantly improved sensitivity of revised sCJD diagnostic criteria with unaltered specificity. The revision has enhanced diagnostic accuracy for clinical care and surveillance.

Key Points

Question 

How sensitive and specific are the 2017 revised International Creutzfeldt-Jakob disease Surveillance Network diagnostic criteria for the diagnosis of sporadic Creutzfeldt Jakob disease?

Findings 

In this diagnostic study of 647 individuals conducted by a multinational team of surveillance experts, the revised diagnostic criteria, which incorporate cerebrospinal fluid real-time quaking induced conversion assay and cortical ribboning on brain magnetic resonance imaging, were significantly more sensitive than previous criteria with no loss of specificity.

Meaning 

These results suggest that the revised diagnostic criteria achieve superior diagnostic sensitivity and maintain a high degree of specificity compared with previous criteria, enhancing diagnostic accuracy for clinical care and surveillance.

snip...

Conclusions

In this study, we demonstrated the excellent performance of the revised CJD International Surveillance Network diagnostic criteria. Our results showed that the new criteria greatly enhanced in-life case classification, with improvements among cases with clinically limited sCJD and with prolonged survival. Rapid, accurate in-life diagnosis enables effective supportive care, public health interventions, and clinical trial recruitment.

Supplemental Content



WOW, so tell me where the vpspr tse prion cases are included? 

WHY do some countries count vpspr as sporadic cjd tse prion, and some countries don't?

THIS problem must be addressed immediately imo.

WE have the USA classifying Variably protease-sensitive prionopathy (VPSPr) (formerly known as Protease Sensitive Prionopathy) as sporadic Creutzfeldt Jakob Disease sCJD, and we have Canada not even mentioning in on there statistics links, like vpspr does not even exist, so this is a problem for any valid surveillance imo. IN fact, personal communication from Canada Surveillance et al;

QUOTE;

''Well Terry, we have the data. We simply do not report it separately because we do not believe it has any specific epidemiologic significance, including zoonotic transmission (this opinion is shared unanimously by the international CJD surveillance community, and was established very quickly after the discovery of VPSPr). The key reason in my mind why the US system reports it – in a footnote to their sporadic CJD data – is that they discovered it, and want to follow up on it publicly to validate the reality of their finding scientifically (which is distinct from its significance).''

''The simple answer to your question is that we do not track VPSPr separately, as we view is as a form of sporadic CJD with an unusual phenotype but no specific epidemiological significance. Even the USA surveillance figures do not report it separately.''

end

Hell of a way for a surveillance system for any country to look for any suspect unusual zoonosis zoonotic disease from any mutated TSE Prion strain from any species. 

OH, that's right, Canada is already investigating a mystery cjd (like) brain disease, that mimics CJD, from what the papers media are saying, but doctors are saying it's not CJD. MY POINT is, VPSPR, and how Canada is treating that vs USA. just smells fishy to me, what if vpspr was some how related to CWD TSE Prion, or an iatrogenic event there from? do we know with certainty that vpspr tse prion is not a zoonosis disease?


especially considering, with the diagnostic criteria still set up for the UKBSEnvCJD only theory, and all other human tse prion disease a sporadic spontaneous event, just appears to me that no one wants to find another zoonotic TSE Prion disease, even though the science is staring them in the face stating otherwise, with Chronic Wasting Disease CWD TSE PrP of Cervid being a highly likely source of some cases of the sporadic cjd's.

Having better diagnostic tools to diagnose human TSE Prion disease is a great thing, we must use them, but continuing to use the old UKBSEnvCJD only diagnostic criteria to differentiate between everything other than typical c-type BSE and nvCJD, when there is a world of science saying otherwise, will only continue to spread the TSE Prion agent, imo...terry

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.


Creutzfeldt Jakob Disease CJD TSE Prion Update December 25, 2021

Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined¹

Updated quarterly.

Last updated on: December 10th, 2021

Year Total Referrals² Prion Disease Sporadic Familial Iatrogenic vCJD

1999 & earlier 383 231 201 27 3 0

2000 145 102 90 12 0 0

2001 209 118 110 8 0 0

2002 241 144 124 18 2 0

2003 259 160 137 21 2 0

2004 315 180 163 16 0 1³

2005 328 179 157 21 1 0

2006 365 179 159 17 1 2⁴

2007 374 210 191 19 0 0

2008 384 221 205 16 0 0

2009 397 231 210 20 1 0

2010 401 246 218 28 0 0

2011 392 238 214 24 0 0

2012 413 244 221 23 0 0

2013 416 258 223 34 1 0

2014 355 208 185 21 1 1⁵

2015 401 263 243 20 0 0

2016 395 277 248 29 0 0

2017 375 266 247 19 0 0

2018 308 221 202 18 1 0

2019 432 280 259 21 0 0

2020 362 250 225 24 1 0

2021 282 183 157 15 0 0

TOTAL 79326 48897 43898 4609 14 4

1Listed based on the year of death or, if not available, on the year of referral; 

2Cases with suspected prion disease for which brain tissue was submitted; 

3Disease acquired in the United Kingdom; 

4Disease acquired in the United Kingdom in one case and in Saudi Arabia in the other; 

5Disease possibly acquired in a Middle Eastern or Eastern European country; 

6Includes 35 cases in which the diagnosis is pending (1 from 1999, 2 from 2020 and 32 from 2021), and 19 inconclusive cases; 

7Includes 11 (11 from 2021) cases with type determination pending in which the diagnosis of vCJD has been excluded. 

8The sporadic cases include 4276 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 76 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 37 cases of sporadic Fatal Insomnia (sFI). 

9Total does not include 291 Familial cases diagnosed by blood test only.


***> 6Includes 35 cases in which the diagnosis is pending (1 from 1999, 2 from 2020 and 32 from 2021), and 19 inconclusive cases; 

***> 7Includes 11 (11 from 2021) cases with type determination pending in which the diagnosis of vCJD has been excluded. 

***> 8The sporadic cases include 4276 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 

***> 76 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 37 cases of sporadic Fatal Insomnia (sFI). 

***> CANADA NO VPSPR ???

CANADA CJD TSE PRION

Referrals of suspected CJD reported by CJDSS, 1998-2021 As of November 30, 2021

Year of reporting Number of referrals

1998 43

1999 63

2000 82

2001 101

2002 103

2003 75

2004 90

2005 97

2006 80

2007 101

2008 100

2009 104

2010 76

2011 102

2012 103

2013 99

2014 99

2015 98

2016 117

2017 116

2018 125

2019 142

2020 123

2021 119

Total 2358

Definite and probable CJD, 1998-2021 As of November 30, 2021

Year Sporadic Iatrogenic CJD Genetic vCJD Total

1998 22 1 1 0 24

1999 27 2 3 0 32

2000 32 0 3 0 35

2001 27 0 3 0 30

2002 31 0 2 1 36

2003 27 1 1 0 29

2004 42 0 4 0 44

2005 42 0 2 0 44

2006 39 0 5 0 44

2007 35 0 4 0 39

2008 48 0 1 0 49

2009 48 0 5 0 53

2010 35 0 3 0 38

2011 46 0 4 1 51

2012 62 0 1 0 63

2013 50 0 1 0 51

2014 51 0 5 0 56

2015 44 0 8 0 52

2016 57 1 6 0 64

2017 82 0 5 0 87

2018 75 1 5 0 81

2019 76 0 2 0 78

2020 61 0 4 0 65

2021 21 0 1 0 23

Total 1080 6 80 2 1168

CJD deaths in Canada

Year of death Total CJD cases Population of Canada Crude mortality rate

1998 24 30,244,982 0.79

1999 32 30,492,106 1.05

2000 35 30,783,969 1.14

2001 30 31,130,030 0.96

2002 36 31,450,443 1.14

2003 29 31,734,851 0.91

2004 44 32,037,434 1.37

2005 44 32,352,233 1.36

2006 44 32,678,986 1.35

2007 39 33,001,076 1.18

2008 49 33,371,810 1.47

2009 53 33,756,714 1.57

2010 38 34,131,451 1.11

2011 51 34,472,304 1.48

2012 63 34,880,248 1.81

2013 51 35,289,003 1.45

2014 56 35,675,834 1.57

2015 52 35,702,707 1.46

2016 64 36,286,400 1.76

2017 86 36,712,658 2.37

2018 80 37,589,262 2.15

2019 78 37,802,043 2.06

Cases with definite and probable diagnosis to date

Population estimates as of July each year (Statistics Canada population estimates, quarterly)




why has Canada not detected not one case of VPSPR TSE PRION ???

97. In vitro seeding activity of glycoform-deficient prions from variably protease-sensitive prionopathy and familial CJD associated with PrPV180I mutation 

Zerui Wanga,b, Jue Yuana, Pingping Shena,b, Romany Abskharonc, Yue Langa,b, Johnny Danga, Alise Adornatoa, Ling Xua, Jiafeng Chenb, Jiachun Fengb, Mohammed Moudjoud, Tetsuyuki Kitamotoe, Jan Langeveldf, Brian Applebya,g,h, Jiyan Mac, Qingzhong Konga,g,h, Robert B. Petersena,i, Li Cuib and Wen-Quan Zoua,b,g,h

aDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; bDepartment of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, the People’s Republic of China; cCenter for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA; dNRA, Université Paris-Saclay, UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France; eCenter for Prion Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan; fWageningen BioVeterinary Research, Lelystad, the Netherlands; gNational Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 8Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; iFoundation Sciences, Central Michigan University College of Medicine, Mount Pleasant, MI, USA

CONTACT Wen-Quan Zou WQZ wxz6@case.edu

ABSTRACT

Both sporadic variably protease-sensitive prionopathy (VPSPr) and familial Creutzfeldt-Jakob disease linked to the prion protein (PrP) V180I mutation (fCJDV180I) have been found to share a unique pathological prion protein (PrPSc) pattern that lacks the protease-resistant PrPSc glycosylated at residue 181, apparently because two of four cellular PrP (PrPC) glycoforms are not converted into PrPSc. To investigate the seeding activity of these unique PrPSc molecules, we conducted in vitro prion conversion experiments using serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC) assays with different PrPC substrates. Unexpectedly, we observed that the seeding of PrPSc from VPSPr or fCJDV180I in the sPMCA reaction with brain homogenates from normal human or humanized transgenic (Tg) mice generated PrPSc molecules that are dominated by the diglycosylated isoform, along with PrPSc monoglycosylated at residue 181. The efficiency of PrPSc amplification was significantly higher in MM than in VV human brain homogenate, whereas it was higher in TgVV than in TgMM mouse brain homogenate. PrPC from the brain homogenate mixture of TgMM and Tg mice expressing PrPV180I mutation (Tg180), but not that from TgV180I alone, was converted into PrPSc by seeding with the VPSPr or fCJDV180I. The RT-QuIC seeding activity of PrPSc from VPSPr and fCJDV180I was significantly lower than that of sCJD. Our results suggest that the formation of glycoform-selective prions may be associated with an unidentified factor in the affected brain and the glycoform-deficiency of PrPSc does not affect the glycoforms of in vitro newly-amplified PrPSc

Funding

Supported in part by the CJD Foundation and the National Institutes of Health (NIH) NS062787 and NS087588 to W.Q.Z., NS062787 and NS109532 to W.Q.Z., and Q.K., NS088604 to Q.K., the Centers for Disease Control and Prevention Contract UR8/CCU515004 to B.S.A., the National Natural Science Foundation of China (NNSFC) [No. 81,801,207] to PS, as well as NNSFC [No. 81,671,186] to LC.


Volume 25, Number 1—January 2019

Research

Variable Protease-Sensitive Prionopathy Transmission to Bank Voles

Romolo Nonno1, Silvio Notari1, Michele Angelo Di Bari, Ignazio Cali, Laura Pirisinu, Claudia d’Agostino, Laura Cracco, Diane Kofskey, Ilaria Vanni, Jody Lavrich, Piero Parchi, Umberto Agrimi, and Pierluigi GambettiComments to Author 

Author affiliations: Istituto Superiore di Sanità, Rome, Italy (R. Nonno, M.A. Di Bari, L. Pirisinu, C. d’Agostino, I. Vanni, U. Agrimi); Case Western Reserve University, Cleveland, Ohio, USA (S. Notari, I. Cali, L. Cracco, D. Kofskey, J. Lavrich, P. Gambetti); University of Bologna, Bologna, Italy (P. Parchi); Istituto delle Scienze Neurologiche di Bologna, Bologna (P. Parchi)

Abstract

Variably protease-sensitive prionopathy (VPSPr), a recently described human sporadic prion disease, features a protease-resistant, disease-related prion protein (resPrPD) displaying 5 fragments reminiscent of Gerstmann-Sträussler-Scheinker disease. Experimental VPSPr transmission to human PrP–expressing transgenic mice, although replication of the VPSPr resPrPD profile succeeded, has been incomplete because of second passage failure. We bioassayed VPSPr in bank voles, which are susceptible to human prion strains. Transmission was complete; first-passage attack rates were 5%–35%, and second-passage rates reached 100% and survival times were 50% shorter. We observed 3 distinct phenotypes and resPrPD profiles; 2 imitated sporadic Creutzfeldt-Jakob disease resPrPD, and 1 resembled Gerstmann-Sträussler-Scheinker disease resPrPD. The first 2 phenotypes may be related to the presence of minor PrPD components in VPSPr. Full VPSPr transmission confirms permissiveness of bank voles to human prions and suggests that bank vole PrP may efficiently reveal an underrepresented native strain but does not replicate the complex VPSPr PrPD profile.


Chapter 10 - Variably protease-sensitive prionopathy

Author links open overlay panel Silvio Notari1 Brian S.Appleby1234 Pierluigi Gambetti1

1 Department of Pathology, Case Western Reserve University, Cleveland, OH, United States

2 National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, United States

3 Department of Neurology, Case Western Reserve University, Cleveland, OH, United States

4 Department of Psychiatry, Case Western Reserve University, Cleveland, OH, United States

Available online 7 June 2018.


Abstract

Variably protease-sensitive prionopathy (VPSPr), originally identified in 2008, was further characterized and renamed in 2010. Thirty-seven cases of VPSPr have been reported to date, consistent with estimated prevalence of 0.7–1.7% of all sporadic prion diseases. The lack of gene mutations establishes VPSPr as a sporadic form of human prion diseases, along with sporadic Creutzfeldt–Jakob disease (sCJD) and sporadic fatal insomnia. Like sCJD, VPSPr affects patients harboring any of the three genotypes, MM, MV, and VV at the prion protein (PrP) gene polymorphic codon 129, with VPSPr VV accounting for 65% of all VPSPr cases. Distinguishing clinical features include a median 2-year duration and presentation with psychiatric signs, speech/language impairment, or cognitive decline. Neuropathology comprises moderate spongiform degeneration, PrP amyloid miniplaques, and a target-like or plaque-like PrP deposition. The abnormal PrP associated with VPSPr typically forms an electrophoretic profile of five to seven bands (according to the antibody) presenting variable protease resistance depending on the 129 genotype. The familial prion disease associated with the V180I PrP gene mutation which harbors an abnormal PrP with similar electrophoretic profile might serve as a model for VPSPr. Transmission to animals has definitively established VPSPr as a prion disease. Because of its recent identification, rarity, and the elusiveness of its abnormal PrP, VPSPr remains largely understudied.

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Keywords

sensitive transmissible sporadic anchorless internal fragment psychiatric abnormalities speech impairment cognitive declinenormal-pressure hydrocephalus atypical dementia


*** Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109. The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98. 

OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles 

Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1 Istituto Superiore di Sanità; Rome, Italy; 2 Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3 Case Western Reserve University; Cleveland, OH USA 

Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles. 

Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.

Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases. In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions. 

Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109. The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.


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.


Subject: CWD GSS TSE PRION SPINAL CORD, Confucius Ponders, What if?

Saturday, February 2, 2019 

CWD GSS TSE PRION SPINAL CORD, Confucius Ponders, What if?

snip... 

 ***> 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) <*** 

REVIEW 

***> 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) <***

Thursday, March 8, 2018 

Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein


Saturday, February 2, 2019 

CWD GSS TSE PRION SPINAL CORD, Confucius Ponders, What if?


WEDNESDAY, JANUARY 12, 2022 

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


Thursday, October 28, 2021 

Chronic Wasting Disease (CWD) TSE Prion Zoonosis, friendly fire, iatrogenic transmission, blood products, sporadic CJD, what if?


Thursday, July 29, 2021 

TSE PRION OCCUPATIONAL EXPOSURE VIA ANIMAL OR HUMAN, iatrogenic transmission, nvCJD or sCJD, what if? 


FRIDAY, JANUARY 10, 2014

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ???

Greetings Friends, Neighbors, and Colleagues,

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ???

Confucius is confused again.

I was just sitting and thinking about why there is no genetic link to some of these TSE prion sGSS, sFFi, and it’s really been working on my brain, and then it hit me today.

what if, vpspr, sgss, sffi, TSE prion disease, was a by-product from iatrogenic gss, ffi, familial type prion disease ???

it could explain the cases of no genetic link to the gss, ffi, familial type prion disease, to the family.

sporadic and familial is a red herring, in my opinion, and underestimation is spot on, due to the crude prehistoric diagnostic procedures and criteria and definition of a prion disease.

I say again, what if, iatrogenic, what if, with all these neurological disorders, with a common denominator that is increasingly showing up in the picture, called the prion.

I urge all scientist to come together here, with this as the utmost of importance about all these neurological disease that are increasingly showing up as a prion mechanism, to put on the front burners, the IATROGENIC aspect and the potential of transmission there from, with diseases/disease??? in question.

by definition, could they be a Transmissible Spongiform Encephalopathy TSE prion type disease, and if so, what are the iatrogenic chances of transmission?

this is very important, and should be at the forefront of research, and if proven, could be a monumental breakthrough in science and battle against the spreading of these disease/diseases.

the US National Library of Medicine National Institutes of Health pub-med site, a quick search of the word SPORADIC will give you a hit of 40,747. of those, there are a plethora of disease listed under sporadic. sporadic simply means (UNKNOWN).


the US National Library of Medicine National Institutes of Health pub-med site, a quick search of the word FAMILIAL will give you a hit of 921,815. of those, there are a plethora of disease listed under familial.


again, sporadic and familial is a red herring, in my opinion.

also, in my opinion, when you start have disease such as sporadic Fatal Familial Insomnia, (and or sporadic GSS, or the VPSPr type prion disease), and there is NO familial genetic linkage to the family of the diseased, I have serious questions there as to a familial type disease, and thus, being defined as such.

*UPDATE* NOVEMBER 16, 2014 vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ??? 

Friday, January 10, 2014


Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more Prionbaloney ?


Wednesday, March 28, 2012

VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $

OR-10 15:25 - 15:40 VARIABLY PROTEASE-SENSITIVE PRIONOPATHY IS TRANSMISSIBLE IN BANK VOLES Nonno




O.10.5

A novel human prion disease affecting subjects with the three prion protein codon 129 genotypes: could it be the sporadic form of Gerstmann-Straussler?

Pierluigi Gambetti Case Western Reserve University, USA

Background: We recently described a novel prion disease, named protease-sensitive prionopathy or PSPr, characterized by the presence of an abnormal prion protein (PrP) that was 60 fold less protease resistant than that of sporadic Creutzfeldt-Jakob disease (sCJD) and on immunoblot generated a distinct ladder-like profile. All affected subjects where homozygous for valine at codon 129 (VV) and had no mutation in the PrP gene.

Methods: We have characterized several new cases in our surveillance and received from Europe.

Results: 1) A disease overall similar to that reported in the 129VV subjects also affects subjects that are methionine/valine heterozygous (MV) and methionine homozygous (MM) at codon 129 and have no PrP gene mutation; 2) The clinical and histopathological features of the new MV and MM PSPr cases are similar but distinguishable from those of the original VV cases; 3) The electrophoretic profiles generated by the abnormal PrP isoforms associated with the MV and MM cases are similar to VV cases but show increasing levels of proteaseresistance; 3) abnormal tau is present in all three genotypic forms of PSPr with features apparently similar to those of primary tauopathies placing PSPr at the intersection of tauopathies and prion diseases.

Discussion: Will focus on: 1) the features of the abnormal PrP in the newly discovered 129MV and 129MM PSPr; 2) the effect of the 129 polymorphism on PSPr compared to that on sCJD; 3) the relationship of PSPr with tauopathies; 4) whether PSPr now with the three 129 genotypic forms is the long sought sporadic form of GSS.

(Supported by NIH AG-14359, NS052319, CDC UR8/CCU515004).


Ann Neurol. 2010 Aug;68(2):162-72.

Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein.

Zou WQ, Puoti G, Xiao X, Yuan J, Qing L, Cali I, Shimoji M, Langeveld JP, Castellani R, Notari S, Crain B, Schmidt RE, Geschwind M, Dearmond SJ, Cairns NJ, Dickson D, Honig L, Torres JM, Mastrianni J, Capellari S, Giaccone G, Belay ED, Schonberger LB, Cohen M, Perry G, Kong Q, Parchi P, Tagliavini F, Gambetti P.

Department of Pathology, National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH 44106, USA. wenquan.zou@case.edu

Abstract OBJECTIVE: The objective of the study is to report 2 new genotypic forms of protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV).

METHODS: Fifteen affected subjects with 129MM, 129MV, and 129VV underwent comparative evaluation at the National Prion Disease Pathology Surveillance Center for clinical, histopathologic, immunohistochemical, genotypical, and PrP characteristics.

RESULTS: Disease duration (between 22 and 45 months) was significantly different in the 129VV and 129MV subjects. Most other phenotypic features along with the PrP electrophoretic profile were similar but distinguishable in the 3 129 genotypes. A major difference laid in the sensitivity to protease digestion of the disease-associated PrP, which was high in 129VV but much lower, or altogether lacking, in 129MV and 129MM. This difference prompted the substitution of the original designation with "variably protease-sensitive prionopathy" (VPSPr). None of the subjects had mutations in the PrP gene coding region.

INTERPRETATION: Because all 3 129 genotypes are involved, and are associated with distinguishable phenotypes, VPSPr becomes the second sporadic prion protein disease with this feature after Creutzfeldt-Jakob disease, originally reported in 1920. However, the characteristics of the abnormal prion protein suggest that VPSPr is different from typical prion diseases, and perhaps more akin to subtypes of Gerstmann-Sträussler-Scheinker disease.

PMID: 20695009 [PubMed - indexed for MEDLINE]


None of the subjects had mutations in the PrP gene coding region....???...TSS 


iatrogenic, what if?

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

PLEASE NOTE;

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

Olivier Andreoletti, INRA Research Director, Institut National de la Recherche Agronomique (INRA) – École Nationale Vétérinaire de Toulouse (ENVT), invited speaker, presented the results of two recently published scientific articles of interest, of which he is co-author: ‘Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice’ (MarinMoreno et al., 2020) and ‘The emergence of classical BSE from atypical/Nor98 scrapie’ (Huor et al., 2019).

In the first experimental study, H-type and L-type BSE were inoculated into transgenic mice expressing all three genotypes of the human PRNP at codon 129 and into adapted into ARQ and VRQ transgenic sheep mice. The results showed the alterations of the capacities to cross the human barrier species (mouse model) and emergence of sporadic CJD agents in Hu PrP expressing mice: type 2 sCJD in homozygous TgVal129 VRQ-passaged L-BSE, and type 1 sCJD in homozygous TgVal 129 and TgMet129 VRQ-passaged H-BSE.

Tuesday, April 27, 2021 

Working Document on Camel Prion Disease (CPrD) 14/09/2020


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

Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease 

Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.



Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP 

Author item MOORE, S - Orise Fellow item Kokemuller, Robyn item WEST-GREENLEE, M - Iowa State University item BALKEMA-BUSCHMANN, ANNE - Friedrich-Loeffler-institut item GROSCHUP, MARTIN - Friedrich-Loeffler-institut item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 5/10/2018 Publication Date: 5/22/2018 Citation: Moore, S.J., Kokemuller, R.D., West-Greenlee, M.H., Balkema-Buschmann, A., Groschup, M.H., Greenlee, J.J. 2018. The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP. Prion 2018, Santiago de Compostela, Spain, May 22-25, 2018. Paper No. WA15, page 44.

Interpretive Summary:

 The successful transmission of pig-passaged CWD to Tg40 mice reported here suggests that passage of the CWD agent through pigs results in a change of the transmission characteristics which reduces the transmission barrier of Tg40 mice to the CWD agent. If this biological behavior is recapitulated in the original host species, passage of the CWD agent through pigs could potentially lead to increased pathogenicity of the CWD agent in humans.


cwd scrapie pigs oral routes 

***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <*** 

>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <*** 

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

***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains. 




Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.


CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

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.....


***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.

https://www.nature.com/articles/srep11573 

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). 

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. 

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. 

=============== 

***thus questioning the origin of human sporadic cases*** 

=============== 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 

============== 

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf 

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20 

PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

Title: Transmission of scrapie prions to primate after an extended silent incubation period) 

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. 

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

GAME FARM INDUSTRY WANTS TO COVER UP FINDINGS OF INCREASE RISK TO CJD FROM CERVID

BSE INQUIRY

CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane 

BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results regarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all. 

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf

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 emphasized by the finding that some strains of scrapie produce lesions identical to the once which characterize 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 scrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6

http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

reference...

RB3.20

TRANSMISSION TO CHIMPANZEES

1. Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.

2. We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, ilp and i/v) :

3. I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. Proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.

4. In view of Dr Gibbs' probable use of chimpazees Mr Wells' comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.

5. A positive result from a chimpanzee challenged severely would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

6. A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans' susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive. We may learn more about public reactions following next Monday' s meeting.

R. Bradley

23 September 1990

CVO (+Mr Wells' comments)

Dr T W A Little

Dr B J Shreeve

90/9.23/1.1.

http://web.archive.org/web/20090506041740/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

IN CONFIDENCE CHIMPANZEES

CODE 18-77 Reference RB3.46

Some further information that may assist in decision making has been gained by discussion with Dr Rosalind Ridley.

She says that careful study of Gajdusek's work shows no increased susceptibility of chimpanzees over New World Monkeys such as Squirrel Monkeys. She does not think it would tell you anything about the susceptibility to man. Also Gajdusek did not, she believes, challenge chimpanzees with scrapie as severely as we did pigs and we know little of that source of scrapie. Comparisons would be difficult. She also would not expect the Home Office to sanction such experiments here unless there was a very clear and important objective that would be important for human health protection. She doubted such a case could be made. If this is the case she thought it would be unethical to do an experiment abroad because we could not do it in our own country.

Retrospectively she feels they should have put up more marmosets than they did. They all remain healthy. They would normally regard the transmission as negative if no disease resulted in five years.

We are not being asked for a decision but I think that before we made one we should gain as much knowledge as we can. If we decided to proceed we would have to bear any criticisms for many years if there was an adverse view by scientists or ­media. This should not be undertaken lightly. There is already some adverse comment here, I gather, on the pig experiment though that will subside.

The Gibbs' (as' distinct from Schellekers') study is somewhat different. We are merely supplying material for comparative studies in a laboratory with the greatest experience of human SEs in the world and it has been sanctioned by USDA (though we do not know for certain yet if chimpanzees specifically will be used). This would keep it at a lower profile than if we conducted such an experiment in the UK or Europe.

I consider we must have very powerful and defendable objectives to go beyond Gibbs' proposed experiments and should not initiate others just because an offer has been made.

Scientists have a responsibility to seek other methods of investigative research other than animal experimentation. At present no objective has convinced me we need to do research using Chimpanzees - a species in need of protection. Resisting such proposals would enable us to communicate that information to the scientist and the public should the need arise. A line would have been drawn.

CVO cc Dr T Dr B W A Little Dr B J Shreeve

R Bradley

26 September 1990

90/9.26/3.2

http://web.archive.org/web/20090506041605/http://www.bseinquiry.gov.uk/files/yb/1990/09/26003001.pdf

this is tse prion political theater here, i.e. what i call TSE PRION POKER...tss

http://web.archive.org/web/20031028205208/www.bseinquiry.gov.uk/files/yb/1990/08/28002001.pdf

http://web.archive.org/web/20030822170317/www.bseinquiry.gov.uk/files/yb/1990/11/01005001.pdf

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs.

snip...

PAGE 26

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.

The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA viewed it as a wildlife problem and consequently not their province! ...page 26. 

snip...see;

IN CONFIDENCE

PERCEPTIONS OF UNCONVENTIONAL SLOW VIRUS DISEASE OF ANIMALS IN THE USA

GAH WELLS

REPORT OF A VISIT TO THE USA

APRIL-MAY 1989

http://web.archive.org/web/20090506002237/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

why do we not want to do TSE transmission studies on chimpanzees $

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. 

***> I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. 

***> Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

https://web.archive.org/web/20090506041740/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

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


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).


ARS RESEARCH Generation of human chronic wasting disease in transgenic mice 

Publication Acceptance Date: 9/8/2021

Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: Generation of human chronic wasting disease in transgenic mice

Author item WANG, ZERUI - Case Western Reserve University (CWRU) item QIN, KEFENG - University Of Chicago item CAMACHO, MANUEL - Case Western Reserve University (CWRU) item SHEN, PINGPING - Case Western Reserve University (CWRU) item YUAN, JUE - Case Western Reserve University (CWRU) item Greenlee, Justin item CUI, LI - Jilin University item KONG, QINGZHONG - Case Western Reserve University (CWRU) item MASTRIANNI, JAMES - University Of Chicago item ZOU, WEN-QUAN - Case Western Reserve University (CWRU)

Submitted to: Acta Neuropathologica Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/8/2021 Publication Date: N/A Citation: N/A

Interpretive Summary: Prion diseases are invariably fatal neurologic diseases for which there is no known prevention or cure. Chronic wasting disease (CWD) is the prion disease of deer and elk and is present in farmed and free ranging herds throughout North America. To date there is no clear evidence that the CWD agent could be transmitted to humans. This manuscript describes the use of an in vitro technique, cell-free serial protein misfolding cyclic amplification (sPMCA), to generate a CWD prion that is infectious to transgenic mice expressing the human prion protein. This study provides the first evidence that CWD prions may be able to cause misfolding in the human prion protein. This information will impact medical experts and those involved in making policy for farmed cervids and wildlife.

Technical Abstract: Chronic wasting disease (CWD) is a cervid spongiform encephalopathy or prion disease caused by the infectious prion or PrPSc, a misfolded conformer of cellular prion protein (PrPC). It has rapidly spread in North America and also has been found in Asia and Europe. In contrast to the zoonotic mad cow disease that is the first animal prion disease found transmissible to humans, the transmissibility of CWD to humans remains uncertain although most previous studies have suggested that humans may not be susceptible to CWD. Here we report the generation of an infectious human PrPSc by seeding CWD PrPSc in normal human brain PrPC through the in vitro cell-free serial protein misfolding cyclic amplification (sPMCA). Western blotting confirms that the sPMCA-induced proteinase K-resistant PrPSc is a human form, evidenced by a PrP-specific antibody that recognizes human but not cervid PrP. Remarkably, two lines of humanized transgenic (Tg) mice expressing human PrP-129Val/Val (VV) or -129Met/Met (MM) polymorphism develop prion disease at 233 ± 6 (mean ± SE) days post-inoculation (dpi) and 552 ± 27 dpi, respectively, upon intracerebral inoculation with the sPMCA-generated PrPSc. The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns. We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.


''The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns.'' 

''We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.''

Published: 26 September 2021

Generation of human chronic wasting disease in transgenic mice

Zerui Wang, Kefeng Qin, Manuel V. Camacho, Ignazio Cali, Jue Yuan, Pingping Shen, Justin Greenlee, Qingzhong Kong, James A. Mastrianni & Wen-Quan Zou

Acta Neuropathologica Communications volume 9, Article number: 158 (2021)

Abstract

Chronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with 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 PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.

Snip...

It is worth noting that the annual number of sporadic CJD (sCJD) cases in the USA has increased, with the total number of suspected and confirmed sCJD cases rising from 284 in 2003 to 511 in 2017 (https://www.cdc.gov/prions/cjd/occurrence-transmission.html). The greatly enhanced CJD surveillance and an aging population in the USA certainly contributed to the observed increase in annual sCJD case numbers in recent years, but the possibility cannot be excluded that some of the increased sCJD prevalence is linked to CWD exposure.

In the present study, using serial protein misfolding cyclic amplification (sPMCA) assay we generate PrPSc by seeding CWD prions in normal human brain homogenates. Importantly, we reveal that two lines of humanized Tg mice expressing human PrP-129VV and 129MM develop prion diseases upon intracerebral inoculation of the abnormal PrP generated by sPMCA. We believe that our study provides the first opportunity to dissect the clinical, pathological and biochemical features of the CWD-derived human prion disease in two lines of humanized Tg mice expressing two major human PrP genotypes, respectively.


i thought i might share some news about cwd zoonosis that i got, that i cannot share or post to the public yet, i promised for various reasons, one that it will cause a shit storm for sure, but it was something i really already knew from previous studies, but, i was told that ;

==================

''As you can imagine, 2 and 5 (especially 5) may raise alarms.  The evidence we have for 4 are not as strong or tight as I would like to have.   At this point, please do not post any of the points publicly yet, but you can refer to points 1-3 in private discussions and all 5 points when discussing with relevant public officials to highlight the long-term risks of CWD zoonosis.''

====================

so, i figure your as about as official as it gets, and i think this science is extremely important for you to know and to converse about with your officials. it's about to burn a whole in my pocket. this is about as close as it will ever get for cwd zoonosis to be proven in my time, this and what Canada Czub et al found with the Macaques, plus an old study from cjd surveillance unit back that showed cjd and a 9% increase in risk from folks that eat venison, i will post all this below for your files Sir. i remember back in the BSE nvCJD days, from when the first BSE case in bovine was confirmed around 1984 maybe 83, i forget the good vets named that screwed it up first, Carol something, but from 83ish to 95 96 when nvCJD was linked to humans from BSE in cattle, so that took 10 to 15 years. hell, at that rate, especially with Texas and cwd zoonsis, hell, i'll be dead before it's official, if ever, so here ya go Sir. there was a grant study on cwd zoonosis that had been going on for some time, i followed it over the years, then the grant date for said study had expired, so, i thought i would write the good Professor about said study i.e. Professor Kong, CWRU et al. i will post the grant study abstract first, and then after that, what reply i got back, about said study that i was told not to post/publish...

CWD ZOONOSIS GRANT FIRST;

===============

Cervid to human prion transmission

Kong, Qingzhong 

Case Western Reserve University, Cleveland, OH, United States

 Abstract Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans. We hypothesize that: (1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues; (2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence; (3) Reliable essays can be established to detect CWD infection in humans; and (4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches. 

Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of humanized Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental human CWD samples will also be generated for Aim 3. 

Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1. 

Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental human CWD samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions. 

Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.

Public Health Relevance There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.

 Funding Agency Agency National Institute of Health (NIH) Institute National Institute of Neurological Disorders and Stroke (NINDS) Type Research Project (R01) Project # 1R01NS088604-01A1 Application # 9037884 Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND) Program Officer Wong, May Project Start 2015-09-30 Project End 2019-07-31 Budget Start 2015-09-30 Budget End 2016-07-31 Support Year 1 Fiscal Year 2015 Total Cost $337,507 Indirect Cost $118,756

snip... 


Professor Kongs reply to me just this month about above grant study that has NOT been published in peer reveiw yet...

=================================

Here is a brief summary of our findings:

snip...can't post, made a promise...tss

On Sat, Apr 3, 2021 at 12:19 PM Terry Singeltary <flounder9@verizon.net> wrote:

snip...

end...tss

==============

CWD ZOONOSIS THE FULL MONTY TO DATE

International Conference on Emerging Diseases, Outbreaks & Case Studies & 16th Annual Meeting on Influenza March 28-29, 2018 | Orlando, USA

Qingzhong Kong

Case Western Reserve University School of Medicine, USA

Zoonotic potential of chronic wasting disease prions from cervids

Chronic wasting disease (CWD) is the prion disease in cervids (mule deer, white-tailed deer, American elk, moose, and reindeer). It has become an epidemic in North America, and it has been detected in the Europe (Norway) since 2016. The widespread CWD and popular hunting and consumption of cervid meat and other products raise serious public health concerns, but questions remain on human susceptibility to CWD prions, especially on the potential difference in zoonotic potential among the various CWD prion strains. We have been working to address this critical question for well over a decade. We used CWD samples from various cervid species to inoculate transgenic mice expressing human or elk prion protein (PrP). We found infectious prions in the spleen or brain in a small fraction of CWD-inoculated transgenic mice expressing human PrP, indicating that humans are not completely resistant to CWD prions; this finding has significant ramifications on the public health impact of CWD prions. The influence of cervid PrP polymorphisms, the prion strain dependence of CWD-to-human transmission barrier, and the characterization of experimental human CWD prions will be discussed.

Speaker Biography Qingzhong Kong has completed his PhD from the University of Massachusetts at Amherst and Post-doctoral studies at Yale University. He is currently an Associate Professor of Pathology, Neurology and Regenerative Medicine. He has published over 50 original research papers in reputable journals (including Science Translational Medicine, JCI, PNAS and Cell Reports) and has been serving as an Editorial Board Member on seven scientific journals. He has multiple research interests, including public health risks of animal prions (CWD of cervids and atypical BSE of cattle), animal modeling of human prion diseases, mechanisms of prion replication and pathogenesis, etiology of sporadic Creutzfeldt-Jacob disease (CJD) in humans, normal cellular PrP in the biology and pathology of multiple brain and peripheral diseases, proteins responsible for the α-cleavage of cellular PrP, as well as gene therapy and DNA vaccination.






*** 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


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;



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: <3daf5023 .4080804="" wt.net="">

Dear Terry,

An excellent piece of review as this literature is desparately difficult to get back from Government sites.

What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!

Steve Dealler =============== 


''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 ;




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


TUESDAY, MAY 11, 2021 
 A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
''We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.''
FRIDAY, JANUARY 28, 2022 
Chronic Wasting Disease Transmission Risk Assessment for Farmed Cervids in Minnesota and Wisconsin 
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
03 Jul 2015 at 16:53 GMT

Terry S. Singeltary Sr.


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

Greetings APHIS et al, 

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

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

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

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

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

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

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



TAHC Chapter 40, Chronic Wasting Disease Terry Singeltary Comment Submission

***> 1st and foremost your biggest problem is 'VOLUNTARY'! AS with the BSE 589.2001 FEED REGULATIONS, especially since it is still voluntary with cervid, knowing full well that cwd and scrapie will transmit to pigs by oral route. VOLUNTARY DOES NOT WORK! all animal products should be banned and be made mandatory, and the herd certification program should be mandatory, or you don't move cervid. IF THE CWD HERD CERTIFICATION IS NOT MANDATORY, it will be another colossal tse prion failure from the start.

***> 2nd USA should declare a Declaration of Extraordinary Emergency due to CWD, and all exports of cervid and cervid products must be stopped internationally, and there should be a ban of interstate movement of cervid, until a live cwd test is available.

***> 3rd Captive Farmed cervid ESCAPEES should be made mandatory to report immediately, and strict regulations for those suspect cwd deer that just happen to disappear. IF a cervid escapes and is not found, that farm should be indefinitely shut down, all movement, until aid MIA cervid is found, and if not ever found, that farm shut down permanently.

***> 4th Captive Farmed Cervid, INDEMNITY, NO MORE Federal indemnity program, or what i call, ENTITLEMENT PROGRAM for game farm industry. NO MORE BAIL OUTS FROM TAX PAYERS. if the captive industry can't buy insurance to protect not only themselves, but also their customers, and especially the STATE, from Chronic Wasting Disease CWD TSE Prion or what some call mad deer disease and harm therefrom, IF they can't afford to buy that insurance that will cover all of it, then they DO NOT GET A PERMIT to have a game farm for anything. This CWD TSE Prion can/could/has caused property values to fall from some reports in some places. roll the dice, how much is a state willing to lose?

***> 5th QUARANTINE OF ALL FARMED CAPTIVE, BREEDERS, URINE, ANTLER, VELVET, SPERM, OR ANY FACILITY, AND THEIR PRODUCTS, that has been confirmed to have Chronic Wasting Disease CWD TSE Prion, the QUARANTINE should be for 21 years due to science showing what scrapie can do. 5 years is NOT near long enough. see; Infectious agent of sheep scrapie may persist in the environment for at least 16 to 21 years.

***> 6th America BSE 589.2001 FEED REGULATIONS CWD TSE Prion

***> 7TH TRUCKING TRANSPORTING CERVID CHRONIC WASTING DISEASE TSE PRION VIOLATING THE LACEY ACT

***> 8TH ALL CAPTIVE FARMING CERVID OPERATIONS MUST BE INSURED TO PAY FOR ANY CLEAN UP OF CWD AND QUARANTINE THERE FROM FOR THE STATE, NO MORE ENTITLEMENT PROGRAM FOR CERVID GAME FARMING PAY TO PLAY FOR CWD TSE PRION OFF THE TAX PAYERS BACK.

***> 9TH ANY STATE WITH DOCUMENTED CWD, INTERSTATE, NATIONAL, AND INTERNATIONAL MOVEMENT OF ALL CERVID, AND ALL CERVID PRODUCTS MUST BE HALTED!

***> 10TH BAN THE SALE OF STRAW BRED BUCKS AND ALL CERVID SEMEN AND URINE PRODUCTS

***> 11th ALL CAPTIVE FARMED CERVID AND THEIR PRODUCTS MUST BE CWD TSE PRION TESTED ANNUALLY AND BEFORE SALE FOR CWD TSE PRION

SEE FULL SCIENCE REFERENCES AND REASONINGS ;

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


Saturday, December 18, 2021 

Direct neural transmission of vCJD/BSE in macaque after finger incision 


TUESDAY, DECEMBER 14, 2021

Transmissible Spongiform Encephalopathy TSE Prion end of year report December 14, 2021


TUESDAY, SEPTEMBER 07, 2021

Atypical Bovine Spongiform Encephalopathy BSE OIE, FDA 589.2001 FEED REGULATIONS, and Ingestion Therefrom



Sporadic Creutzfeldt-Jakob Disease in a Very Young Person Singeltary Reply 2021

October 26, 2021; 97 (17) CLINICAL/SCIENTIFIC NOTES

Sporadic Creutzfeldt-Jakob Disease in a Very Young Person

Brian Stephen Appleby, Ryan Maddox, Lawrence B. Schonberger, Ignazio Cali, Teresa Hammett, Mark Cohen, View ORCID Profile Ermias Belay

First published September 8, 2021, DOI: http:// https://doi.org/10.1212/WNL.0000000000012737

Abstract Background and Objectives Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease and typically occurs in middle to late life. sCJD in early adulthood is extremely uncommon. The purpose of this report is to raise awareness of cases of sCJD in young patients that are not associated with a genetic mutation or acquired prion disease risk factors.

Methods We describe the clinical presentation, diagnostic workup, and postmortem examination of a 22-year-old man with sCJD.

Results The patient presented with a rapidly progressive neurocognitive disorder consisting of early and prominent psychiatric symptoms. CSF real-time quaking-induced conversion (RT-QuIC) was indeterminate, and brain MRI was suggestive of prion disease. Neuropathologic examination and the absence of a genetic mutation and acquired prion disease risk factors resulted in a final diagnosis of sCJD.

Conclusion Although extremely rare, sCJD can occur in young people and should be considered in the setting of rapidly progressive neuropsychiatric conditions. Postmortem examination is required to diagnose the type of prion disease and remains important to surveil for known and potentially novel acquired prion diseases.

Glossary CJD=Creutzfeldt-Jakob disease; NPDPSC=National Prion Disease Pathology Surveillance Center; RT-QuIC=real-time quaking-induced conversion; sCJD=sporadic Creutzfeldt-Jakob disease Footnotes Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Editorial, page 801

Received April 30, 2021. Accepted in final form August 23, 2021. © 2021 American Academy of Neurology


October 26, 2021; 97 (17) EDITORIAL

The Intractable Puzzle of Sporadic Creutzfeldt-Jakob Disease in Very Young People

 View ORCID Profile Simon Mead

First published September 8, 2021, DOI: https://doi.org/10.1212/WNL.0000000000012739

In the era of randomized controlled trials and multicenter observational studies, it is easy for academic neurology to overlook the compelling questions posed by individual patient cases. Sporadic Creutzfeldt-Jakob disease (sCJD) in a 21-year-old patient was the right diagnosis, but hardly a satisfactory explanation for either the doctor or patient and his family in the Clinical/Scientific Note by Appleby et al.1 in this week's issue of Neurology®. How can a typically late-onset disorder occur in someone so young?

Footnotes Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the author, if any, are provided at the end of the editorial.

See page 813

© 2021 American Academy of Neurology View Full Text


Greetings Journal Neurology, Good Doctors, Authors, et al CDC, 

i must comment with reply about this very very important health threat TSE Prion spontaneous sporadic CJD.

Something about pay-per-view, when it comes to peer review, especially when you have donated loved ones brain tissues for science, something about pay-per-view just still makes me mad. it would cost me $78.00 just to study this. i would kindly like to comment on this bizarre phenomenon of spontaneous/sporadic CJD, and just what this consists of. furthermore, Professor Mead is absolutely correct;

''Sporadic Creutzfeldt-Jakob disease (sCJD) in a 21-year-old patient was the right diagnosis, but hardly a satisfactory explanation for either the doctor or patient and his family in the Clinical/Scientific Note by Appleby et al.1 in this week's issue of Neurology®. How can a typically late-onset disorder occur in someone so young?''

Exactly, absolutely, Yes Sir, and here is why it is not acceptable, imo, the science has been there, but political, legislative, junk science, does not allow sound science to make this call yet, i.e. the industries involved, and they are many. you just had to have been there to see it over the last 23 years. so please let me plead my case of urgency, it's long, it's 23 years, daily, as i know it, but the science is there, but nobody seems to care about the truth, they would rather stick their heads in the sand and call it spontaneous or sporadic $$$

FIRST OFF, spontaneous/sporadic CJD and a brief history of spontaneous sporadic cjd science put forth to date, history there from.

let's compare apple to oranges first I.E. spontaneous sporadic TSE Prion Primates Research Laboratories

***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.

https://www.nature.com/articles/srep11573 

NEXT, just what does spontaneous/sporadic, mean?

sporadic, spontaneous CJD, 85%+ of all human TSE, just 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 = 68,704 results for definition of various diseases https://www.ncbi.nlm.nih.gov/pubmed/?term=sporadic

spontaneous = 444,312 results for definition of various diseases https://www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous 

SO PLEASE, the least we could do is define what spontaneous and sporadic, in terms of Transmissible Spongiform Encephalopathy TSE Prion disease are, define exactly what that means, for those that still think 85%+ of all human TSE Prion disease i.e. and this is a very broad term including vpspr, sffi, sgss, and SPORADIC CJD, for those that still believe all sCJD is just a happening of a spontaneous even of a protein flipping out on it's own, with no cause, just happens, in 85%+ of all human TSE Prion, without a shread of documented evidence to prove this. the UKBSEnvCJD only theory is, was, and will be, not scientific, and we must move away from that. With the science at hand, animal transmission studies, molecular studies, there is enough evidence to date, (as much today, as there was back in 1995 linking nvCJD to c-BSE), to declare that there is evidence that if not all, some of the sporadic CJD strains are indeed a zoonosis disease, or, are a iatrogenic event from either a zoonotic source by friendly fire, pass it forward, from a subclinical host from said sporadic CJD cases, from either CWD in cervid, BSE in cattle, or Scrapie in sheep and goats, both typical and atypical, and all of the above have now been linked by science to the infamous spontaneous/sporadic CJDs. we have wasted too much effort on the UKBSEnvCJD only theory imo. for the announcement for science to link nvcjd to humans from UK c-BSE in 1984 or 1985, it took an additional 10 years to finally make the call that nvcjd was infecting humans in 1995. i think BSE started actually before Carol Richardson and the case there (see source references below) , but we can't wait for another 10 years for a call to be made for zoonosis of CWD, BSE, and Scrapie, for some of the cases, if not all, of the sporadic CJDs as zoonosis disease. to continue this thinking, will only allow the TSE Prion disease to continue to be spread via iatrogenic events. we cannot wash our hands of these events, with a spontaneous or sporadic ideology. WE MUST MOVE FORWARD WITH THE ZOONOISIS science of sporadic CJD as zoonosis, and work ourselves down from there, trying to prove it's not, instead of spreading to hell and back around the globe for 5 decades or so, saying it is not, without proof. i think science has been screaming for over a decade that indeed, sporadic CJD, is zoonosis, and govern from there. THIS CHARADE MUST END!

CJD is not reportable in all states, but no evidence of increase in the number of cases has been observed in the U.S. However, the NPDPSC examines about 64% of the approximately 300 cases expected to occur in the U.S. per year...

expected to occur in the U.S. per year???

oxymoron

you must have _all_ key components of a math formula to correctly solve a math problem, or in this case, figuring statistics. yet we don't have all the key components. 

not all states report cjd tse prion, and some that do, only report in 55 and older, yet some do make in reportable of all ages. plus, you figure in misdiagnosis, that's another key element/component, it happens. 

for example;

CJD is not a reportable disease in West Virginia. Because the disease is 100% fatal the occurrence of CJD is tracked through death certificates.


I would kindly like to add to my initial concerns, something I brought up years ago, and I believe that still hold true today, more so even than when I first stated these concerns in 2003 ; 

 routine passive mortality CJD surveillance USA ? 

THIS has been proven not to be very useful in the U.K.; 

THE EPIDEMIOLOGY OF CJD RG WILL 1984 (182 PAGES)

snip...

One reason for this was the _inaccuracy_ in coding of cases correctly certified as CJD Coding is carried out by staff who are not medically qualified and it is not surprising that coding errors occur in the processing of large numbers of certificates. In 1982, 12,000 certificates per week were processed at the office of population censuses and surveys by 15 coders and 6 checkers (Alderson et al., 1983). The occurrence of both inter- and intra-observer coding errors has been described (Curb et al., 1983) and the _inaccuracies_ of BOTH certification and coding discovered in this study _support_ the introduction of a more accurate system of death certificates and a more detailed and specific coding system...

snip...



Draft Proposal For The Monitoring of Creutzfeldt-Jakob Disease 1989 Dr. R. Will

snip...

IDENTIFICATION OF CASES

Cases of CJD may be identified from death certificates, but this alone is unlikely to provide adequate monitoring. ERRORS are made in certification and diagnosis; in the Oxford study death certificates were obtained on a series of known confirmed cases and CJD was mentioned in only 66% of certificates. In another series of 175 certified cases, 42 patients were judged not to have suffered from CJD after examination of case notes (7)...

full text;



Confucius is confused again? how in 1996 and earlier can the 28 sporadic CJD victims and the one-in-a-million there from, how can it still be one in a million in 2008, with the sporadic CJD count rising to 205, still be one-in-a-million? and the years in-between, steady rise just about every year, and it still be only one-in-a-million, year after year after years? I suppose just more of that fuzzy math, which you can see here;


Please see my complete comment to this synopsis here ;

Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010

see full text;

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 ; 

snip...

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


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. 


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?


Reply to Singletary 26 March 2003

Ryan A. Maddox, MPH

Mr. Singletary raises several issues related to current Creutzfeldt- Jakob disease (CJD) surveillance activities. Although CJD is not a notifiable disease in most states, its unique characteristics, particularly its invariably fatal outcome within usually a year of onset, make routine mortality surveillance a useful surrogate for ongoing CJD surveillance.[1] In addition, because CJD is least accurately diagnosed early in the course of illness, notifiable-disease surveillance could be less accurate than, if not duplicative of, current mortality surveillance.[1] However, in states where making CJD officially notifiable would meaningfully facilitate the collection of data to monitor for variant CJD (vCJD) or other emerging prion diseases, CDC encourages the designation of CJD as a notifiable disease.[1] Moreover, CDC encourages physicians to report any diagnosed or suspected CJD cases that may be of special public health importance (e.g., vCJD, iatrogenic CJD, unusual CJD clusters).

As noted in our article, strong evidence is lacking for a causal link between chronic wasting disease (CWD) of deer and elk and human disease,[2] but only limited data seeking such evidence exist. Overall, the previously published case-control studies that have evaluated environmental sources of infection for sporadic CJD have not consistently identified strong evidence for a common risk factor.[3] However, the power of a case-control study to detect a rare cause of CJD is limited, particularly given the relatively small number of subjects generally involved and its long incubation period, which may last for decades. Because only a very small proportion of the US population has been exposed to CWD, a targeted surveillance and investigation of unusual cases or case clusters of prion diseases among persons at increased risk of exposure to CWD is a more efficient approach to detecting the possible transmission of CWD to humans. In collaboration with appropriate local and state health departments and the National Prion Disease Pathology Surveillance Center, CDC is facilitating or conducting such surveillance and case- investigations, including related laboratory studies to characterize CJD and CWD prions.

Mr. Singletary also expresses concern over a recent publication by Asante and colleagues indicating the possibility that some sporadic CJD cases may be attributable to bovine spongiform encephalopathy (BSE).[4] The authors reported that transgenic mice expressing human prion protein homozygous for methionine at codon 129, when inoculated with BSE prions, developed a molecular phenotype consistent with a subtype of sporadic CJD. Although the authors implied that BSE might cause a sporadic CJD-like illness among persons homozygous for methionine, the results of their research with mice do not necessarily directly apply to the transmission of BSE to humans. If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic CJD cases would be expected to first occur in the United Kingdom, where the vast majority of vCJD cases have been reported. In the United Kingdom during 1997 through 2002, however, the overall average annual mortality rate for sporadic CJD was not elevated; it was about 1 case per million population per year. In addition, during this most recent 6-year period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of UK sporadic CJD deaths.[3, 5] Furthermore, surveillance in the UK has shown no increase in the proportion of sporadic CJD cases that are homozygous for methionine (Will RG, National CJD Surveillance Unit, United Kingdom, 2003; personal communication).

References

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Diagnosis and reporting of Creutzfeldt-Jakob disease. JAMA 2001;285:733-734.

2. Belay ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States. Neurology 2003;60:176-181.

3. Belay ED. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol 1999;53:283-314.

4. Asante EA, Linehan JM, Desbruslais M, et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 2002;21:6358-6366.

5. The UK Creutzfeldt-Jakob Disease Surveillance Unit. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm. Accessed February 18, 2003.



SPORADIC CJD LAYING ODDS


In brief

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

Rapid Response:

02 January 2000

Terry S Singeltary

retired

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


Rapid response to:

US scientists develop a possible test for BSE

15 November 1999

Terry S Singeltary

NA

BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7220.1312b (Published 13 November 1999)

Cite this as: BMJ 1999;319:1312

Article Related content Article metrics 

Rapid responses 

Response 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 clerical 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 digestional 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 endoscopes 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


Competing interests: No competing interests


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 

“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..” 



Scientific Advisors and Consultants Staff 2001 Advisory Committee TSE PRION Singeltary Submission 

Freas Monday, January 08,2001 3:03 PM 

FDA Singeltary submission 2001 

Greetings again Dr. Freas and Committee Members, 

I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version). I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, or on 2 or 3 pages, but will attempt here: 

snip...see full text ; 


Subject: Prion Scientific Advisors and Consultants Staff Meeting Singeltary Submission Freas Monday, January 08,2001 3:03 PM

PLEASE be aware, my submission here has now been removed from the www, or changed to a different url that no one knows now, and does not come up in search engines anymore, after 17 years...wonder why that could be, i guess the truth just hurt to much$$$ 

Freas, William

From: Terry S. Singeltary Sr. [flounder@wt.net]

Sent: Monday, January 08,2001 3:03 PM


Subject: CJD/BSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)

CJD/BSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)

Greetings again Dr. Freas and Committee Members,

I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version).

I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, or on 2 or 3 pages, but will attempt here:

remember AIDS/HIV, 'no problem to heterosexuals in the U.S.? no need to go into that, you know of this blunder:

DO NOT make these same stupid mistakes again with human/animal TSE's aka MADCOW DISEASE. I lost my Mom to hvCJD, and my neighbor lost his Mother to sCJD as well (both cases confirmed). I have seen many deaths, from many diseases. I have never seen anything as CJD, I still see my Mom laying helpless, jerking tremendously, and screaming "God, what's wrong with me, why can't I stop this". I still see this, and will never forget. Approximately 10 weeks from 1st of symptoms to death. This is what drives me. I have learned more in 3 years about not only human/animal TSE's but the cattle/rendering/feeding industry/government than i ever wished to.

I think you are all aware of CJD vs vCJD, but i don't think you all know the facts of human/animal TSE's as a whole, they are all very very similar, and are all tied to the same thing, GREED and MAN.

I am beginning to think that the endless attempt to track down and ban, potential victims from known BSE Countries from giving blood will be futile. You would have to ban everyone on the Globe eventually? AS well, I think we MUST ACT SWIFTLY to find blood test for TSE's, whether it be blood test, urine test, .eyelid test, anything at whatever cost, we need a test FAST.

DO NOT let the incubation time period of these TSEs fool you.

To think of Scrapie as the prime agent to compare CJD, but yet overlook the Louping-ill vaccine event in 1930's of which 1000's of sheep where infected by scrapie from a vaccine made of scrapie infected sheep brains, would be foolish. I acquired this full text version of the event which was recorded in the Annual Congress of 1946 National Vet. Med. Ass. of Great Britain and Ireland. from the BVA and the URL is posted in my (long version).

U.S.A. should make all human/animal TSE's notifiable at all ages, with requirements for a thorough surveillance and post-mortem examinations free of charge, if you are serious about eradicating this horrible disease in man and animal.

There is histopathology reports describing o florid plaques" in CJD victims in the USA and some of these victims are getting younger. I have copies of such autopsies, there has to be more. PLUS, sub-clinical human TSE's will most definitely be a problem.

THEN think of vaccineCJD in children and the bovine tissues used in the manufacturing process, think of the FACT that this agent surviving 6OO*C. PNAS -- Brown et al. 97 (7): 3418 scrapie agent live at 600*C

Then think of the CONFIDENTIAL documents of what was known of human/animal TSE and vaccines in the mid to late 80s, it was all about depletion of stock, to hell with the kids, BUT yet they knew. To think of the recall and worry of TSE's from the polio vaccine, (one taken orally i think?), but yet neglect to act on the other potential TSE vaccines (inoculations, the most effective mode to transmit TSEs) of which thousands of doses were kept and used, to deplete stockpile, again would be foolish.

--Oral polio; up to 1988, foetal calf serum was used from UK and New Zealand (pooled); since 1988 foetal calf serum only from New Zealand. Large stocks are held.

--Rubella; bulk was made before 1979 from foetal calf serum from UK and New Zealand. None has been made as there are some 15 years stock.

--Diphtheria; UK bovine beef muscle and ox heart is used but since the end of 1988 this has been sourced from Eire. There are 1,250 litres of stock.

--Tetanus; this involves bovine material from the UK mainly Scottish. There are 21,000 litres of stock.

--Pertussis; uses bovine material from the UK. There are 63,000 litres of stock. --They consider that to switch to a non-UK source will take a minimum of 6-18 months and to switch to a non-bovine source will take a minimum of five years.

3. XXXXXXXXXXX have measles, mumps, MMR, rubella vaccines. These are sourced from the USA and the company believes that US material only is used.

89/2.14/2.1

============

BSE3/1 0251

4. XXXXXXXXXXX have a measles vaccine using bovine serum from the UK. there are 440,000 units of stock. They have also got MMR using bovine serum from the UK.

5. XXXXXXXXXXX have influenza, rubella, measles,' MMR vaccines likely to be used in children. Of those they think that only MMR contains bovine material which is probably a French origin.

6. XXXXXXXXXXX have diphtheria/tetanus and potasses on clinical trial. hese use veal material, some of which has come from the UK and has been ade by XXXXXXXXXXX (see above).

I have documents of imports from known BSE Countries, of ferments, whole blood, antiallergenic preparations,

2 

human blood plasma, normal human blood sera, human immune blood sera, fetal bovine serum, and other blood fractions not elsewhere specified or included, imported glands, catgut, vaccines for both human/animal, as late as 1998. Let us not forget about PITUITARY EXTRACT. This was used to help COWS super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease.

ANNEX 6

MEETING HELD ON 8 JUNE 1988 TO DISCUSS THE IMPLICATIONS OF BSE TO BIOLOGICAL PRODUCTS CONTAINING BOVINE - EXTRACTED MATERIAL

How much of this was used in the U.S.?

Please do not keep making the same mistakes; 'Absence of evidence is not evidence of absence'.

What are the U.S. rules for importing and manufacturing vaccines, medicines and medical devices?

Does the U.S.A. allow sourcing of raw material of ruminants from the U.S.A.?

U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds? The U.S. rendering system would easily amplify T.S.E.'s:

Have we increased the stability of the system (improved heat treatments) since the EU SSC report on the U.S.A. was published in july 2000?

What is done to avoid cross-contaminations in the U.S.A.?

How can the U.S. control absence of cross-contaminations of animal TSE's when pig and horse MBM and even deer and elk are allowed in ruminant feed, as well as bovine blood? I sadly think of the rendering and feeding policy before the Aug. 4, 1997 'partial' feed ban, where anything went, from the city police horse, to the circus elephant, i will not mention all the scrapie infected sheep. I am surprised that we have not included man 'aka soyent green'. It is a disgusting industry and nothing more than greed fuels it.

When will the U.S.. start real surveillance of the U.S. bovine population (not passive, this will not work)?

When will U.S. start removing SRMs?

Have they stopped the use of pneumatic stunners in the U.S.?

If so, will we stop it in all U.S. abattoirs or only in those abattoirs exporting to Europe?

If not, WHY NOT?

same questions for removal of SRM in the U.S.A., or just for export?

If not, WHY NOT?

How do we now sterilize surgical/dental instruments in the U.S.A.?

Where have we been sourcing surgical catgut?

(i have copies of imports to U.S., and it would floor you) hen will re-usable surgical instruments be banned?

'Unregulated "foods" such as 'nutritional supplements' containing various extracts from ruminants, whether imported or derived from

3 

US cattle/sheep/cervids ("antler velvet" extracts!) should be forbidden or at least very seriously regulated. (neighbors Mom, whom also died from CJD, had been taking bovine based supplement, which contained brain, eye, and many other bovine/ovine tissues for years, 'IPLEX').

What is the use of banning blood or tissue donors from Germany, France, etc... when the U.S.A. continues exposing cattle, sheep and people to SRM, refuses to have a serious feed ban, refuses to do systematic BSE-surveillance?

The FDA should feel responsible for the safety of what people eat, prohibit the most dangerous foods, not only prohibit a few more donors - the FDA should be responsible for the safe sourcing of medical devices, not only rely on banning donors "from Europe", The 'real' risks are here in the U.S. as well, and nave been for some time.

We must not forget the studies that have proven infectivity in blood from TSE's.

The Lancet, November 9, 1985

Sir, --Professor Manuelidis and his colleagues (Oct 19, p896) report transmission to animals of Creutzfeldt-Jakob disease (CJD) from the buffy coat from two patients. We also transmitted the disease from, whole blood samples of a patient (and of mice) infected with CJD.l Brain, Cornea, and urine from this patient were also infectious, and the clinicopathological findings2 are summarised as follows.

snip...

Samples,were taken aseptically at necropsy. 10% crude homogenates of brain and cornea in saline, whole blood (after crushing a clot), and untreated CSF and urine were innoculated intracerebrally into CFl strain mice (20 ul per animal). Some mice showed emaciation, bradykinesia, rigidity of the body and tail, and sometimes tremor after long incubation periods. Tissues obtained after the animal died (or was killed) were studied histologically (table). Animals infected by various inocula showed common pathological changes, consisting of severe spongiform changes, glial proliferation, and a moderate loss of nerve cells. A few mice inoculated with brain tissue or urine had the same amyloid plaques found in patients and animals with CJD.3

snip...

Department of Neuropathology,. Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka812, Japan JUN TATEISHI

(full text-long version)

and

CWD and transmission to man will be no different than other TSE's.

"Clearly, it is premature to draw firm conclusions about CWD passing naturally into humans, cattle and sheep, but the present results suggest that CWD transmissions to humans would be as limited by PrP incompatibility as transmissions of BSE or sheep scrapie to humans. Although there is no evidence that sheep scrapie has affected humans, it is likely that BSE has

4

caused variant CJD in 74 people (definite and probable variant CJD cases to date according to the UK CJD Surveillance Unit). Given the presumably large number of people exposed to BSE infectivity, the susceptibility of humans may still be very low compared with cattle, which would be consistent with the relatively inefficient conversion of human PrP-sen by PrPBSE. Nonetheless, since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure of humans (as well as sheep and cattle) to CWD infectivity as has been recommended for other animal TSEs,"

G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O'Rourke3, L.E. McHolland4, P.K. Bryant III4, M.W. Miller5, E.S. Williams6, M. Smits2 and B. Caughey1,7

or more recently transmission of BSE to sheep via whole blood Research letters Volume 356, Number 9234 16 September 2000

Transmission of BSE by blood transfusion in sheep

Lancet 2000; 356: 999 – 1000

F Houston, J D Foster, Angela Chong, N Hunter, C J Bostock

See Commentary

"We have shown that it is possible to transmit bovine spongiform encephalopathy (BSE) to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection. BSE and variant Creutzfeldt-Jakob disease (vCJD) in human beings are caused by the same infectious agent, and the sheep-BSE experimental model has a similar pathogenesis to that of human vCJD. Although UK blood transfusions are leucodepleted--a possible protective measure against any risk from blood transmission-- this report suggests that blood donated by symptom-free vCJD-infected human beings may represent a risk of spread of vCJD infection among the human population of the UK."

"The demonstration that the new variant of Creutzfeldt-Jakob disease (vCJD) is caused by the same agent that causes bovine spongiform encephalopathy (BSE) in cattle1 has raised concerns that blood from human beings in the symptom-free stages of vCJD could transmit infection to recipients of blood transfusions (full text long version)"

and...

"The large number of cases (1040), temporal clustering of the outbreaks (15 in the first 6 months of 1997), the high in-flock incidence, and the exceptional involvement of goats (390 cases), suggested an accidental infection. The source of the epidemic might have been TSE-contaminated meat and bonemeal, but eight flocks had never been fed any commercial feedstuff. Infection might have risen from the use of a formol-inactivated vaccine against contagious agalactia prepared by a single laboratory with brain and mammary gland homogenates of sheep infected with Mycoplasma agalactiae. Although clinical signs of TSE in the donor sheep have not been found, it is possible that one or more of them were harbouring the

5

infectious agent. Between 1995 and 1996, this vaccine was given subcutaneously to 15 of the affected flocks (to one flock in 1994) ; in these animals the disease appeared between 23 and 35 months after vaccination. No information is available for herd 13 because it was made up of stolen animals. Sheep from the remaining three flocks (1-3, figure) did not receive the vaccine, thus suggesting a naturally occurring disease.’’ (again, full text long version).

IN SHORT, please do under estimate this data and or human/animal TSE's including CWD in the U.S.A.

A few last words, please.

The cattle industry would love to have us turn our focus to CWD and forget about our own home grown TSE in Bovines. This would be easy to do. Marsh's work was from downer cattle feed, NOT downer deer/elk feed. This has been proven.

DO NOT MAKE THAT MISTAKE.

There should be NO LESS THAN 1,000,000 tests for BSE/TSE ' in 2001 for U.S.A. French are testing 20,000 a week. The tests are available. Why wait until we stumble across a case from passive surveillance, by then it is to late. IF we want the truth, this is a must???

United States Total ,Bovine Brain Submissions by State,

May 10 ,1990 thru October 31, 2000

Total 11,700

FROM 1.5 BILLION HEAD OF CATTLE since 1990 ???

with same feeding and rendering practices as that of U.K. for years and years, same scrapie infected sheep used in feed, for years and years, 950 scrapie infect FLOCKS in the U.S. and over 20 different strains of scrapie known to date. (hmmm, i am thinking why there is not a variant scrapie, that is totally different than all the rest)? just being sarcastic.

with only PARTIAL FEED BAN implemented on Aug. 4, 1997??? (you really need to reconsider that blood meal etc. 'TOTAL BAN')


AND PLEASE FOR GODS SAKE, STOP saying vCJD victims are the only ones tied to this environmental death sentence. "PROVE IT". It's just not true. The 'CHOSEN ONES' are not the only ones dying because of this man-made death sentence. When making regulations for human health from human/animal TSEs, you had better include ALL human TSE's, not just vCJD. Do NOT underestimate sporadic CJD with the 'prehistoric' testing available to date. This could be a deadly mistake. Remember, sCJD kills much faster from 1st onset of symptoms to death, and hvCJD is the fastest. Could it just be a higher titre of infectivity, or route or source, or all three?

Last, but not least. The illegal/legal harvesting of body parts and tissues will come back to haunt you. Maybe not morally, but due to NO background checks and human TSEs, again it will continue to spread.

Stupidity, Ignorance and Greed is what fuels this disease. You must stop all of this, and ACT AT ONCE...

Sent: Monday, January 08,2001 3:03 PM


FDA CJD BSE TSE Prion Scientific Advisors and Consultants Staff January 2001 Meeting Singeltary Submission

2001 FDA CJD TSE Prion Singeltary Submission


MONDAY, JULY 27, 2020 

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https://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html




Terry S. Singeltary Sr.
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