Sunday, October 09, 2016

Absence of evidence for a causal link between L-BSE and known forms of sporadic CJD in human PrP transgenic mice

Absence of evidence for a causal link between L-BSE and known forms of sporadic CJD in human PrP transgenic mice

Emilie Jaumain1, Isabelle Quadrio2,3, Laetitia Herzog1,Fabienne Reine1, Human Rezaei1, Olivier Andréoletti4, Hubert Laude1,Armand Perret-Liaudet2,3, Stéphane Haïk5,6 and Vincent Béringue1* +Author Affiliations
1VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Absence of evidence for a causal link between L-BSE and known forms of sporadic CJD in human PrP transgenic mice, France. 2Neurobiology Laboratory, Biochemistry and Molecular Biology Department, Hôpitaux de Lyon, Lyon, France. 3University of Lyon 1, CNRS UMR5292, INSERM U1028, BioRan, Lyon, France. 4IHAP, INRA, Ecole Nationale Vétérinaire de Toulouse, 31000, Toulouse, France. 5INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ. Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France. 6Centre National de Référence des Agents Transmissibles Non Conventionnels, F-75013 Paris, France.

ABSTRACT

Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between host cellular prion protein (PrPC) and the infecting pathological PrP assemblies (PrPSc) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrPC and in non-human primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrPSc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD.
IMPORTANCE Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population.
FOOTNOTES ↵*Correspondence: Vincent Béringue, vincent.beringue@inra.frsnip...
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Finally, we examined whether L-BSE prions ‘breed true’ in tg650 mice. tg650-derived L-BSE agents at the first to third passage were transmitted back into bovine PrP mice (25) via the intracerebral route. As shown in Table 2, tg650-derived L-BSE prions were as pathogenic as parental L-BSE prions in these mice. Based on the PrPres glycopattern in the brains of the diseased mice, the strain type re-isolated was fully consistent with L-BSE prions (Figure 1G). Together, these data indicate that L-BSE prions were propagated in human PrP mice without apparent transmission barrier.


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Discussion


We further demonstrated in this study that atypical L-BSE prions propagate with no significant barrier in human PrP transgenic mice (Met129), as shown by the full disease incidence, the absence of a drastic reduction in incubation time over 4 passages, the conservation of the L-type PrPres electrophoretic pattern and the immediate re-isolation of L220 prions in bovine PrP transgenic mice from the first back-passage onwards. Although gene-targeted transgenic mice expressing physiological levels of human PrP did not show any clinical disease on primary challenge with L-BSE prions (33), they were later found to harbor remnant or low levels of infectivity in their brains (34), thus suggesting the disease developed at a slow pace. Non-human primates, which can live longer, were found to succumb to L-BSE more rapidly than C-BSE (20, 21).


*** Together, these data indicate that L-BSE prions have a clear zoonotic potential. We found no evidence that L-BSE prions cause a known form of sporadic CJD. Although tg650-derived L-BSE prions share similar strain properties with cortical MM2-sCJD prions in terms of PrPres signature, resistance to guanidinium chloride treatment, lympho-incompetence and neuroanatomical PrPres deposition, the 2-fold difference in disease progression over at least four passages and the differential resistance to proteinase K digestion suggest no etiological link between L-BSE and cortical MM2-sCJD prions. This absence of an etiological link was further substantiated by the divergent transmission properties of the two agents in ovine PrP transgenic mice (17, 24). The extreme rareness of the cortical sCJD MM2 subtype precluded a comparison with a larger panel of cases to definitively exclude any etiological link.


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Our study confirmed the existence of diverse strains 239 of prions associated with sCJD. We identified 4 distinct groups, MM1/MV1, MM2-cortical, MV2/VV2 and VV1, as previously inferred from the transmission or absence of transmission of these subtypes in gene-targeted transgenic mice expressing human PrP (23, 35). The MV2 and VV2 subtypes, however, showed dissimilar neuroanatomical distributions of PrPres deposits. Further studies that include transmission to other human PrP genotypes are needed to confirm whether MV2 and VV2 prions are truly differentiable with regard to their biological properties.


The tg650 mouse model allows the gauging of prion ability to replicate in the lymphoid tissue (6, 16, 36). We showed here that MV2, VV2 and VV1 sCJD prions replicated in tg650 mouse spleens, albeit at lower rate than vCJD, as determined by PrPres accumulation levels in this tissue. This result suggests that the commonly shared view that sCJD prion replication is primarily confined to the central nervous system (37-39) is subtype dependent. Refined analysis of spleen tissue from sCJD-affected patients demonstrated the presence of PrPres in all subtypes (40). The presence of PrPres appeared to correlate with longer duration of disease, as we found here. Systematic analysis of clinical sCJD subtypes for the presence of infectivity or seeding activity (41-43) in central and extraneural tissues (44, 45) is needed to assess the risk of sCJD iatrogenic spread after surgical procedures in preclinical patients.


Careful extrapolation of our data raises the possibility that an unrecognized human prion strain type may emerge from the accidental transfer of L-BSE prions to humans. Together with the risk that L-BSE prions will propagate with better efficacy in humans than C-BSE prions (19-21, 32), these data highlight the need for continued long-term utilization of precautionary measures to diagnose (46) and prevent these agents from entering the human food chain and the maintenance of an active surveillance of prion strains 263 within the CJD population.


265


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266 Acknowledgments



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Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...




In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

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. .
..

”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 it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” ...page 26.


*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.



SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY

***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.***


Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
"BSE-L in North America may have existed for decades"


Tuesday, July 26, 2016

*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016 ***


Saturday, July 23, 2016

BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016


Wednesday, September 28, 2016

Norway sides with OIE, decides to expose millions of consumers to the ATYPICAL BSE SRM TSE Prion aka mad cow type disease


***Transmission studies to transgenic mice overexpressing bovine PrP (Tgbov mice) showed that the BASE strain is more aggressive than the BSE strain [10]. Furthermore, Tg mice overexpressing human PrP as well as non-human primates are more susceptible to infection with BASE than with BSE [11]–[14].

Overall these data raise concern about the potential risk of transmission of BASE to humans and it is urgent to determine the presence and distribution of infectivity in peripheral tissues of BASE-affected cattle. To investigate this issue, we inoculated Tgbov mice with different peripheral tissues from experimentally and naturally BASE-affected cattle and found that various skeletal muscles contained infectivity and PrP-immunoreactive deposits within individual fibers.

snip...

The present data offer novel information on the tropism of the BASE agent and highlight relevant public health issues. While the transmission barrier for classical BSE is high in most species, BASE prions are readily transmissible to a variety of mammals including non-human primates [11]–[13], [35]. Accordingly, the possibility of spreading of BASE prions through skeletal muscle to other species should be taken into account and evaluated in risk analysis studies.




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

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
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.


Tuesday, December 16, 2014

Evidence for zoonotic potential of ovine scrapie prions

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics

Abstract

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

snip...

Do our transmission results in tgHu imply that sheep scrapie is the cause of sCJD cases in humans? This question challenges well-established dogma that sCJD is a spontaneous disorder unrelated to animal prion disease. In our opinion, our data on their own do not unequivocally establish a causative link between natural exposure to sheep scrapie and the subsequent appearance of sCJD in humans. However, our studies clearly point out the need to re-consider this possibility. Clarification on this topic will be aided by informed and modern epidemiological studies to up-date previous analysis that was performed at the end of the last century3, 4. The value of such an approach is highlighted by the implementation in the year 2000 of large-scale active animal TSE surveillance programs around the world that provided an informed epidemiological-based view of the occurrence and geographical spread of prion disease in small ruminant populations51. The fact that both Australia and New-Zealand, two countries that had been considered for more than 50 years as TSE-free territories, were finally identified positive for atypical scrapie in their sheep flocks provides an example of how prion dogma can be reversed52. However, the incubation period for prion disease in humans after exposure to prions via the peripheral route, such as in iatrogenic CJD transmission and Kuru, can exceed several decades53, 54. In this context, it will be a challenge to combine epidemiological data collected contemporarily in animal populations and humans to investigate the existence of a causative link between prion disease occurrence in these different hosts. Furthermore, it is crucial to bear in mind that sporadic sCJD in humans is a rare disease (1–2 individuals per million of the population per year) and that scrapie has been circulating in small ruminants populations used for food purposes for centuries. Consequently, it is our opinion that even if a causative link was established between sheep scrapie exposure and the occurrence of certain sCJD cases, it would be wrong to consider small ruminant TSE agents as a new major threat for public health. Despite this, it remains clear that our data provide a new impetus to establish the true zoonotic potential of sheep scrapie prions.

Subject terms: Biological sciences• Medical research At a glance


Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

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

Authors

item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -

Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.

Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans. Technical Abstract: Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health.

*** 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.



 2015

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.

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


Tuesday, December 16, 2014

*** Evidence for zoonotic potential of ovine scrapie prions

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics

Abstract

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE.
***The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans.

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

Subject terms: Biological sciences• Medical research At a glance


see more here ;


Monday, May 02, 2016

*** Zoonotic Potential of CWD Prions: An Update 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



MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT JAKOB DISEASE 1978

THE SCRAPIE FILES

CONFIDENTIAL

IN CONFIDENCE

SCJD

Subject: 1978 SCRAPIE IN CONFIDENCE SCJD 1978 SCRAPIE IN CONFIDENCE SCJD

Annex: MEDICAL RESEARCH COUNCIL

IN CONFIDENCE

Circulation Participants MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT-JAKOB DISEASE

Minutes of meeting held on Thursday 9 March 1978 at 20 Park Crescent London WIN 4AL Present: Professor J N Walton (Chairman), Dr A M Adelstein, Professor J R Batchelor, Mr K N Burns (ARC), Professor J A N Corsellis, Dr T J Crow, Dr R Levy, Professor W B Matthews, Dr J T Stamp, Professor B E Tomlinson, Professor M P Vessey, Professor P Wildy, Dr A Smithies (Health Department Observer). Headquarters staff: Dr Katherine levy, Dr Victoria Harrison, Miss Roberta Withnall. Amlogies for absence: Professor A N Davison, Dr R H Kimberlin, Dr W A Lishman, Professor C A Mims- 1.

Introduction and background The Chairman opened the meeting by explaining that its purpose was to advise the Neurosciences Board on the value and feasibility of carrying out epidemiological studies on Creutzfeldt—Jakob (C—J) disease; suggestions for work on other aspects of the disease were not, however, precluded.

***The meeting had been called following the Agricultural Research Council's (ARC) report of their Advisory Committee on Scrapie, a document which should be regarded as confidential. One of the main issues which merited discussion was whether those whose occupation suggested they might be in contact with scrapie had a higher risk of developing C—J disease. While fully appreciating that the problem of infectivity was one of great concern the present meeting was not constituted to discuss this problem per se. The recently set up ARC Advisory Group on Scrapie would be taking up this question; it was also of concern to the Health Departments who wished to be kept informed of developments. Mr Burns reported that the ARC had already had preliminary discussions on the safety aspects which would be necessary in the event of C—J work being carried out in their Institute at Compton. Dr Levy agreed to act as liaison officer between the two Councils and the Health Departments.

The meeting considered the mortality data provided by OPCS (CJD 78/2) and that provided by Professor Matthews (paper tabled). The interpretation of these data was complicated by possibilities of both under and over reporting. Under-reporting was likely in that G—J disease might:

(a) be undiagnosed, particularly in large mental hospitals; and

(b) not appear on death certificates either because the actual cause of death was eg. bronchial pneumonia, or because reference to dementia (in any form) was excluded to spare the feelings of the family. Over-reporting might occur because, although the rapidly progressive form of the disease was readily diagnosed in life, the less dramatic forms were more difficult. to recognise clinically and could be diagnosed in error (see below). It was notes: that the OPCS data showed an apparently higher incidence of the disease in social class I: a possible explanation was that this group was investigated more carefully. An added difficulty, common to all occupational data obtained from death certificates alone, was that it was based solely on information provided by the person registering the death. Professor Vessey drew attention to the temporal differences between the OPCS data and those provided by Professor Matthews.

S 803/10 78/3.9/1.1

The meeting then considered the implication of:

a) incompleteness; and

b) inaccuracy of the data. Incompleteness would matter if it was associated with the factor under study, eg. if only those cases occurring in certain occupational groups were missing: if accurate incidence, prevalence or mortality rates were required; and in examining space/time clustering (see below). Inaccuracy would matter less since the dilution of the mortality data with diseases other than C—J would merely tend to weaken any association present.

3. Accuracy of clinical diagnosis: neuropathology

The neuropathologists present explained that it was now generally considered that there were 3 categories of the disease:

(i) a rapidly progressive form of subacute spongiform encephalopathy (the Nevin—Jones Syndrome) usually leading to death within 6—9 months; this is the only form which has been transmitted to animals;

(ii) a variant in which the cerebellum appears to bear the brunt of the pathology and

(iii) "classical" C—J disease which follows a more protracted course. Diagnosis is based on the typical EEG picture - which in the slower forms of the disease may not arise until late in the course of the illness — and on the characteristic spongiform features seen on neuropathological examination. The less rapidly progressive forms could be confused with other forms of dementia or arteriosclerotic disease, Alzheimer's disease with myoclonus, myoclonic epilepsy, corticostrionigral degeneration, Pick's disease or motor neurone disease.

While there could be doubt about a diagnosis made on a biopsy specimen it would be very rare for a neuropathologist to make a mistake at autopsy. However, in less specialised hands there was a very significant chance that cases could be missed.

Dr Stamp pointed out that in scrapie no spongiform encephalopathy was detected and that in many cases confirmed by transmission experiments no neuropathological abnormality could be found.

4. Specialist care of C—J patients

The question of whether C—J patients Were in the main looked after by neurologists or by psychiatrists was discussed. The View of the meeting was that most patients were seen by neurologists, but that there might be an unknown, even considerable number of cases (presumably of the more chronic form) in major mental hospitals.

5. Frequency of biopsies and post mortems

Until a few years ago a biopsy was carried out in the majority of suspected case. referred to major centres: the situation had now changed and biopsies were performed less often, partly because diagnosis could be based on the clinical and EEG picture .

Dr Adelstein pointed out that 50% of C-J deaths recorded in the OPCS figures had come to post mortem, during the six year period up to 1976. The figures may be dropping for both biopsies and post mortems not only because they are thought unnecessary in view of the improvement in other methods of diagnosis but also because of both the shortage of neuropathologists and their awareness of the possible infectivity of the agent.*
*‘There is no evidence to suggest that there is only one agent; there may well be several. But for the purposes of this record the term 'agent‘ is used throughout

-2-

78/3.9/1.2

6. Gajdusek's evidence

The Chairman invited Professor Wildy to speak to his paper (CJD 78/3) on the hazards of the C—J agent and other possible agents to hospital staff and pathologists. Professor Wildy emphasised that in general Gajdusek's evidence should be treated with great caution since his hypothesis was based on the presumed analogy with the scrapie agent (or agents). Hard data were not available about the C—J agent itself. It was resistant to many physical and chemical treatments: there was a need to establish a reliable means of sterilisation, as Gajdusek's published data on autoclaving was open to criticism. It is likely that, as with scrapie, some C—J strains would prove to be much more resistant than others.

7. Risk of infection

The two reports of iatrogenic man—to—man transmission of C—J disease have involved corneal grafting and neurosurgery respectively. While the implications for sterilisation of instruments etc. had been widely discussed in the literature the additional point was made that corneae for grafts were often obtained from old peoples' homes: caution should therefore be exercised in using tissue from this source.

Overall there was no indication either from OPCS data or from anecdotal evidence that pathologists, mortuary attendants or research workers had ever developed C—J disease. On available evidence it was, however, clear that contact between C—J infected material and lacerated skin must be avoided. Nor was there evidence that anyone working with scrapie diseased animals (veterinary surgeons, slaughter house workers, butchers, shepherds and shepherdesses or research workers) have developed the disease. It was nonetheless worth undertaking retrospective epidemiological studies if only to provide reassurance that there was no excess mortality from C—J disease in these and other professional groups — including neurosurgeons, neurologists, undertakers and embalmers. It should however be borne in mind that some of the latter categories may be under—represented, occupation euphemisms having been used on the death certificates.

8. Prevalence and mode of infectivity of C—J agent

While the prevalence and mode of infectivity of the C—J agent are unknown it would be difficult to account for the world wide distribution of the disease unless the agent were common. If prevalence were low it would be difficult to postulate how the agent would replicate. This suggested that one might be dealing with a transferred ubiquitous and relatively banal agent — the analogy being measles and SSPE. It was agreed that while this was pure speculation, the possibility could not be ruled out. Dr Crow pointed out that the age incidence of C—J disease would not suggest that it was due to an infective agent. In this connection Dr Stamp reported that both lateral and vertical transmission occur in scrapie: genetic factors determine the incubation period and so—called "resistant" sheep may die before there was time for them to show clinical signs of the disease. It was not known how scrapie was transmitted, though it can exist outside its host for an indefinite period. However the usefulness of the scrapie analogy is uncertain. Dr Stamp emphasised that in scrapie the innoculated and natural disease are two very different conditions.

-3-

78/3.9/1.3

9. Clusters, familial incidence and conjugal C—J disease

Geographical and temporal clustering have been reported; these however had been small and difficult to evaluate statistically. In Professor Tomlinson's experience all cases of C—J were referrals from the better known neurological or psychiatric centres, implying that clustering could be an artefact. Professor Vessey offered with colleagues to examine the data provided by OPCS and Professor Matthews to see if these revealed any evidence of clustering. Different incubation periods could be built in and contact between cases could be looked for - the complex statistics had been worked out for Hodgkin's disease. The technique involved was nevertheless a crude one. Familial cases had been reported but the numbers involved were too low to be significant. Occurrence of the disease in cousins (2 in the UK, and 2 in the USA) and two cases of conjugal C—J disease were briefly mentioned.

10. Genetic screening, including HLA status

Professor Batchelor confirmed that the HLA status of C—J patients had not been investigated. Dr Stamp reported that there was no association with mouse histocompatibility antigens in scrapie; this had not been investigated in sheep. Professor Batchelor said that typing would not be difficult: 30—60 patients would be required depending on the rarity of the antigen. General genetic screening might also be worthwhile; he suggested that the Galton laboratories might be approached with a view to studying various isoenzymes in such cases. Samples of serum should be stored for future study of antibody profiles.

11 . General conclusions

(i) The meeting could only confirm that the epidemiology of C—J disease is poorly understood.

(ii) The existing mortality data were likely to be inaccurate; so far as they went no occupational association with the disease could be demonstrated. The prevalence and mode of infectivity of the agent were unknown and clusters reported had been small and difficult to evaluate statistically.

(iii) Gajdusek‘s evidence was open to criticism: however, while his assertions are unsupported by hard data, his claims might nonetheless have substance.

(iv) While the-analogy with scrapie was interesting and the scrapie and C—J agents displayed similarities in behaviour and character, there was no proof that the scrapie agent was in any way associated with C-J disease.

12. Possible action

The following suggestions were made about action which might be taken:

(1) OPCS might be asked to provide data on the occupations listed for all deaths due to dementia and the other diseases with which C—J might be confused recorded within, say, the last 3 years.

(ii) OPCS might be asked to collect prospectively notifications of all deaths from C—J disease, the dementias and other diseases with which it might be confused.

(iii) The data provided by OPCS might be correlated with that obtained by Professor Matthews (confirming diagnoses from case notes etc. in at least a sample of these cases) to see how many of the same C—J patients were involved. These data should be analysed for evidence of clustering.

-4- 78/3.9/1.4

(iv) Data provided by the Doll/Hill study of 34,000 doctors on the medical register in 1953 might (with the authors' agreement) be utilised to see if any excess death rates from C—J-disease, the dementias or other diseases with which it may be confused, could be identified among certain specialist groups.

(v) HLA status of C—J patients should be determined.

(vi) General genetic screening might be undertaken of patients with C—J disease.

(vii) Samples of serum from C—J patients should be stored for future study of antibody profiles.

(viii) Although technically outside their remit the meeting recommended that good work should be encouraged on the isolation, characterisation, distribution in the body, routes of infection and methods of destruction of the C—J agent.

The Chairman closed the meeting by thanking the participants for attending and for their help in reaching these conclusions.

78/3.9/1.5




BE SURE TO SEE THIS NEXT ONE WITH FIGURES...TSS

STUDIES ON CREUTZFELDT-JAKOB DISEASE 

i enclose a list of ICD categories showing the numbers of deaths attributed to each (as underlying cause) in England and Hales in 1975. ICD NO...Number of Certificates examined xxxxx...18...15 mentioned C-J xxxxx...122...1 mentioned C-J with dimentia, 24 mentioned Alzheimer’s disease, 1 mentioned Pick’s disease. xxxxx...22...4 mentioned Myoclonic epilepsy xxxxx...384...none mentioned Corticostrionigral degeneration xxxxx...2...none mentioned Corticostrionigral degeneration

snip...







1979 SILENCE ON CJD AND SCRAPIE 1980 SILENCE ON CJD AND SCRAPIE *** 1981 NOVEMBER



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


why do we not want to do TSE transmission studies on chimpanzees $ IN CONFIDENCE TRANSMISSION TO CHIMPANZEES snip... 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. snip... R. BRADLEY


full text ;

RB3.20 IN CONFIDENCE TRANSMISSION TO CHIMPANZEE


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, i/p 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.
*** 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. CVO (+ Mr. Wells’ comments) Dr. T W A Little Dr. B J Shreeve R Bradley September 1990 90/9.23/1/1


Tuesday, May 31, 2016

Priority Interim Position Paper PROTECTING THE FOOD CHAIN FROM PRIONS Perspectives


TUESDAY, AUGUST 9, 2016

Concurrence with OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2015-0055]
BILLING CODE: 3410-34-P DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service


Monday, June 20, 2016

Specified Risk Materials SRMs BSE TSE Prion Program


Tuesday, April 19, 2016

Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission




Wednesday, April 25, 2012

4th MAD COW DISEASE U.S.A. CALIFORNIA ATYPICAL L-TYPE BSE 2012


Saturday, August 4, 2012

Final Feed Investigation Summary - California BSE Case - July 2012


SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE INVESTIGATION JULY 2012

Summary Report BSE 2012

Executive Summary


Saturday, August 4, 2012

Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation


Qualitative Analysis of BSE Risk Factors in the United States February 13, 2000 at 3:37 pm PST (BSE red book)


Tuesday, June 07, 2016

Comparison of two US sheep scrapie isolates supports identification as separate strains

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES


Thursday, June 09, 2016

Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base Scrapie TSE Prion Experiment 1964
How Did CWD Get Way Down In Medina County, Texas?



2016 PRION CONFERENCE TOKYO

*** NIH awards $11 million to UTHealth researchers to study deadly CWD prion diseases Claudio Soto, Ph.D. *** Public Release: 29-Jun-2016


I urge everyone to watch this video closely...terry *** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***


Sunday, July 24, 2016

Chronic Wasting Disease Prions in Elk Antler Velvet and Marketing of this Product in Nutritional Supplements for Humans? Research Project: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: THE ROLE OF GENETICS, STRAIN VARIATION, AND ENVIRONMENTAL CONTAMINATION IN DISEASE CONTROL


Saturday, December 12, 2015

CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015


Thursday, April 14, 2016

Arizona 22 year old diagnosed with Creutzfeldt Jakob Disease CJD


Tuesday, July 12, 2016

Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE, TSE, Prion Zoonosis Science History see history of NIH may destroy human brain collection


Friday, January 10, 2014

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


Monday, November 3, 2014

*** The prion protein protease sensitivity, stability and seeding activity in variably protease sensitive prionopathy brain tissue suggests molecular overlaps with sporadic Creutzfeldt-Jakob disease






*** 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.

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

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 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case 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.


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


Monday, February 24, 2014

Sporadic Fatal Insomnia in an Adolescent




To the best of our knowledge, this is the first case of CJD combined with Lewy body disease and argirophilic grain disease. Furthermore, we believe this case is an extremely rare combination of MM2-cortical-type and MM2-thalamic-type sporadic CJD (sCJD), which explains the broad spectrum of MM2-type sCJD findings and symptoms. Moreover, histological features of possible Alzheimer's disease were also reported.


Wednesday, September 03, 2014

Coexistence of mixed phenotype Creutzfeldt-Jakob disease, Lewy body disease and argyrophilic grain disease plus histological features of possible Alzheimer's disease: A multi-protein disorder in an autopsy case


Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009


Tuesday, August 18, 2009

BSE-The Untold Story - joe gibbs and singeltary 1999 – 2009


RE: re-Human Prion Diseases in the United States Singeltary PLoS part 2 flounder replied to flounder on 02 Jan 2010 at 21:26 GMT No competing interests declared. 

see full text ;


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.


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?


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


2 January 2000 British Medical Journal U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well


15 November 1999 British Medical Journal vCJD in the USA * BSE in U.S.



Terry S. Singeltary Sr.