Friday, August 11, 2017

Infectivity in bone marrow from sporadic CJD patients

Brief Definitive Report

Infectivity in bone marrow from sporadic CJD patients

Authors

Accepted manuscript online: 9 August 2017 DOI: 10.1002/path.4954 

Abstract 

Prion infectivity was recently identified in the blood of both sporadic and variant Creutzfeldt-Jakob disease (CJD) patients. In variant CJD (vCJD) the widespread distribution of prions in peripheral tissues of both asymptomatic and symptomatic patients is likely to explain the occurrence of the observed prionaemia. However, in sporadic CJD (sCJD) prion infectivity is described to be located principally in the central nervous system. In this study, we investigated the presence of prion infectivity in bone marrow collected after death in patients affected with different sCJD agents. Bioassays in transgenic mice expressing the human prion protein revealed the presence of unexpectedly high levels of infectivity in the bone marrow from seven out of eight sCJD cases. These findings may explain the presence of blood-borne infectivity in sCJD patients. They also suggest that the distribution of prion infectivity in peripheral tissues in sCJD patients could be wider than currently believed, with potential implications for the iatrogenic transmission risk of this disease.

snip...

 Results and discussion 

We first performed endpoint titrations of one MM1 and one VV2 reference sCJD brain homogenate (10% frontal cortex) in tgMet and tgVal (20 µL intracerebral inoculation) (Table 2). The MM1 and VV2 isolates transmitted in both mouse models. However, both the final end-point dilution and incubation periods indicated that the tgMet mice displayed a higher efficiency than tgVal for the propagation of prion in the MM1 sample. Conversely, the VV2 sample propagated with greater efficiency in tgVal than in tgMet. Based on these results, 10% w/v bone marrow and temporal cortex homogenates from eight different sCJD patients were inoculated (20 µl intracerebral) into tgMet or tgVal according to their PRNP genotype at codon 129 and PrPres type (Table 1). 

The inoculation of the brain homogenate from all eight sCJD cases resulted in a 100% transmission rate in the tgHu mice (Table 3). The incubation periods, PrPres western blot patterns (Figure 1) and the lesion profile (Figure 2) in tgMet inoculated with the MM1 sCJD samples were identical to those observed in tgMet inoculated with the MM1 reference sample. Similar observations were made in tgVal mice inoculated with MV/VV2 sCJD samples and the reference VV2 sample. These data strongly support the contention that the prion strains in the brains of MM1 (sCJD 1 to 4) and MV/VV2 (sCJD 5 to 8) patients were similar to those in the MM1 and VV2 reference isolates, respectively. 

The inoculation into tgHu mice of all but one (sCJD 8) of the bone marrow homogenates from the sCJD patients resulted in a clinical disease in tgHu mice (Table 3). Bone marrow from a control non-sCJD patient failed to transmit a clinical disease or to cause abnormal PrP accumulation in inoculated tgHu mice. 

On first passage, bone marrow-inoculated mice displayed a longer incubation period (and in some instances a lower attack rate) than mice inoculated with the corresponding brain homogenate. However, identical abnormal PrP western blot profiles were seen in brain tissue of mice inoculated with brain or bone marrow from the same single patient. On second passage, incubation periods in groups of tgHu mice inoculated with brain or bone marrow from the same patient mice were similar (Table 3). Moreover, the lesion profiles in the brains of animals that were inoculated with the bone marrow or the brain homogenate from the same patient were identical (Figure 2). These results are consistent with the presence of the same prion strain in the bone marrow and in the brain of the sCJD patients. 

Finally, the titres of infectivity in bone marrow and brain homogenates were estimated using the method developed by Arnold et al. [10]. The relationship between the titre of inoculum and the probability of infection and the length of the incubation period were derived from data corresponding to endpoint titration of the MM1 and VV2 reference isolates in tgMet and tgVal mice respectively (Table 2). A normal distribution for the relationship between dose and incubation period was assumed, and the probability of infection versus dose was assumed to follow a logistic regression curve (supplementary material, Figure S1). According to this model, the infectious titre in the positive bone marrow samples was estimated to range between 102.6 and 105.4 ID50 per gram of tissue in tgMet for MM1 patients and from 102.5 to 102.6 per gram in tgVal for the MV/VV2 patients (Table 3). 

Together, these results unequivocally demonstrate the presence of prion infectivity in the bone marrow of patients affected by different subtypes of sCJD. These findings contradict the view that in sCJD patients the distribution of prion infectivity in the peripheral tissues is quite limited, and indicate that tissues other than CNS can contain high amount of infectivity [14]. The brain to bone marrow infectivity ratios indicated that in some patients (sCJD 3 and 7) the prion load in one gram of bone marrow was equivalent to the infectivity in up to 10–20 mg of temporal cortex. These values are three to four orders of magnitude higher than those previously observed in the plasma of MM1 sCJD patients [6]. They were also greatly in excess of the level of infectivity measured in the blood of various animal models of transmissible spongiform encephalopathies [15,16]. It is therefore very unlikely that residual blood that might be in bone marrow could explain the levels of infectivity found. 

At what disease stage prions accumulate in bone marrow in sCJD is unknown, and the nature of the cells that accumulate or propagate infectivity in this tissue remains to be clarified. Primary cell cultures established from post-mortem bone marrow samples collected from two sCJD affected patients indicated that mesenchymal bone marrow cells could accumulate and replicate prions [17]. Moreover the expression of cellular PrP in haematopoietic stem cells, T and B lymphocyte, monocyte and granulocyte lineages indicates that most haematopoietic cells have the potential capacity to replicate prions [18-20]. Additional experiments are ongoing to determine the role that these different cell lineages could play in the pathobiology of prion diseases. ***Whatever the outcome of these new investigations, the presence of prions in bone marrow supports the view that this tissue might contribute to the prionaemia observed in some sCJD patients. 



PLEASE REMEMBER, ALL IATROGENIC CJD IS, IS SPORADIC CJD UNTIL THE ROUTE, SOURCE, THE IATROGENIC EVENT, IS TRACED BACK, THEN DOCUMENTED, THEN PUT INTO THE ACADEMIC DOMAIN, AND FINALLY THE PUBLIC DOMAIN, WHICH VERY SELDOM HAPPENS DO TO THE LONG INCUBATION PERIOD, SURVEILLANCE, AND LACK OF ANY TRACE BACK EFFORTS, thus 85%+ of all human TSE prion disease i.e. sporadic spontaneous CJD...

sporadic/spontaneous cjd is not a single strain, but many strains of cjd, this spontaneous/sporadic term is used as an excuse. all iatrogenic cjd is, is sporadic cjd, until sporadic/spontaneous cjd has now been linked to typical and atypical BSE, to typical and atypical scrapie, and to cwd.

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.***


THURSDAY, AUGUST 10, 2017 

Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017


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.
==============
 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.
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. 

TUESDAY, AUGUST 8, 2017 

Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2016-0092]


SUNDAY, AUGUST 06, 2017 

USA Chronic Wasting Disease CWD TSE Prion Emergency Response Plan Singeltary et al 


MONDAY, JULY 17, 2017 

National Scrapie Eradication Program May 2017 Monthly Report Fiscal Year 2017 


SUNDAY, JULY 30, 2017 

Do we need to explain the occurrence of atypical scrapie?


TUESDAY, JULY 18, 2017 

USDA announces Alabama case of Bovine Spongiform Encephalopathy Alabama


THURSDAY, JULY 20, 2017 

USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200


SUNDAY, JULY 23, 2017

atypical L-type BASE Bovine Amyloidotic Spongiform Encephalopathy BSE TSE PRION


SUNDAY, JULY 23, 2017

Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy


Saturday, July 23, 2016

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


Tuesday, July 26, 2016

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016


Monday, June 20, 2016

Specified Risk Materials SRMs BSE TSE Prion Program


THURSDAY, JULY 13, 2017 

EFSA BSE Sixty cases of mad cow disease since 2001 breached feed ban likely the cause 

Scientists investigate origin of isolated BSE cases


SATURDAY, JULY 29, 2017

Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC


PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS 

 Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO

PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS

PRION 2017 CONFERENCE VIDEO



Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened?

TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress


TUESDAY, JULY 04, 2017

*** PRION 2017 CONFERENCE ABSTRACTS ON CHRONIC WASTING DISEASE CWD TSE PRION ***




Terry S. Singeltary Sr.

Thursday, August 10, 2017

Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017

Guidance 

Minimise transmission risk of CJD and vCJD in healthcare settings

PreventionMinimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017 of CJD and vCJD by Advisory Committee on Dangerous Pathogens' Transmissible Spongiform Encephalopathy (ACDP TSE) Subgroup.

SEE ALL UPDATES;



ANNEX J - PRE-SURGERY ASSESSMENT TO IDENTIFY PATIENTS WITH, OR AT RISK OF, CJD



Previous revision date: January 2013

Changes new to this edition:

Date Change Notes

*** August 2017 Addition of explanatory diagrams to

1. Describe patients who are considered at risk of CJD or vCJD and the types of surgery where infection prevention and control precautions should be taken (Figure J1)

2. Clarify actions needed if a patient reports a history of blood transfusion or treatment (Figure J2)

3. Clarify actions needed if a patient reports a history of CJD or other prion disease in their family (Figure J3)

These diagrams are found on pages 10-12 




Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex E

Published: 2 June 2003 Updated: August 2016

1

ANNEX E

Quarantining of surgical instruments

Previous revision date: January 2011

Changes new to this edition: Date August 2016

Change Clarification regarding the need to reprocess instruments prior to quarantining – Paragraph E5.

Notes None

E1. Part 4 and Annex L of this guidance allows for the quarantining of instruments that have been used for procedures involving tissues designated as high or medium infectivity, on patients either;

 with, or at increased risk of, CJD/vCJD, for reuse exclusively on the same patient; or

 with a possible CJD/vCJD diagnosis, pending a confirmed diagnosis. Although it is not expected that this facility will need to be used widely, this Annex provides guidance on the procedures which should be followed when quarantining surgical instruments may be considered.

E2. During a surgical procedure as defined in paragraph E1, instruments should be separated according to the principles set out in the NICE interventional procedures guidance 196. Instruments that come into contact with tissues designated as high or medium infectivity should be kept separate from those that only come into contact with tissues designated as low infectivity.

E3. After completion of a surgical procedure as defined in paragraph E1, single-use instruments should be separated and disposed of by incineration with normal clinical waste. Re-usable instruments that have only come into contact with tissues designated as low infectivity may be decontaminated and returned to routine use.

E4. Re-usable instruments that have come into contact with tissues designated as high or medium infectivity should be washed to remove gross soil. Care should be taken to avoid splashing and generating aerosols, by holding instruments below the surface of the water in a sink into which water is running and draining out 

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex E Published: 2 June 2003 Updated: August 2016

2

continuously, for example in a sink in the theatre sluice room. Instruments should not be held directly under a flowing tap as this is likely to generate splashes. Operatives should wear protective gloves and either a visor or goggles, and care must be taken to avoid penetrating injuries. The sink does not require high level decontamination afterwards – the dilution effect from the running water will be sufficient to remove contamination.

E5. After washing, instruments should be reprocessed through the Sterile Services Department in the usual manner before quarantining. No special precautions are necessary because of the high dilution factor involved in the washer/disinfection process. It is important to ensure that the set is tracked through the whole decontamination cycle. After reprocessing the instruments should be placed in an impervious rigid plastic container with a close-fitting lid. The lid should be sealed with heavy duty tape and labelled with the patient’s identification details (i.e. name, date of birth and hospital number). The label should also state the surgical procedure in which the instruments were used and the name of the responsible person (e.g. the Team or Unit Manager). The disposable instrument tray should be disposed of by incineration with normal clinical waste. The sealed box can be stored indefinitely in a suitable designated place until the outcome of any further investigations is known (see paragraph E6), or the instruments are required for another surgery on the same patient (see paragraphs E7 and E8).

E6. For patients with a possible CJD/vCJD diagnosis, if the patient is confirmed as suffering from CJD or vCJD, the box and its contents should be incinerated, or retained for use in research (see Part 4 for details), without any further examination. If an alternative diagnosis is confirmed, the instruments may be removed from the box by the responsible person (or a named deputy) and reprocessed according to best practice and returned to use. Additional decontamination procedures are not required.

E7. Rarely, it may be necessary to consider the re-use of a quarantined set of surgical instruments on the same patient. One such scenario would be the need to repeat a liver transplant on a patient who is at increased risk of vCJD. In these circumstances, the instrument set should be reprocessed according to best Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex E Published: 2 June 2003 Updated: August 2016

3

practice; again it is important to ensure that the set is tracked through the whole decontamination cycle as previously directed.

E8. Under no circumstances should quarantined instrument sets be reprocessed for use on other patients unless the diagnosis of CJD or vCJD has been positively excluded. The possibility of residual abnormal prion on the instruments is of far greater concern than the possibility of contamination of instruments in other sets processed in the washer/disinfector either concurrently or subsequently.

E9. Records must be kept of all decisions, and the Sterile Service Department must be informed about the decision before the instruments are sent for routine reprocessing.





Revised and updated: October 2015 

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex F 1 

Published: September 2004 Revised and updated: October 2015 Annex F ENDOSCOPY



This includes sporadic CJD, sporadic fatal insomnia, VPSPr, iatrogenic CJD (other than iatrogenically acquired variant CJD), and genetic CJD, FFI and GSS.

Symptomatic sCJD patients (definite, probable)

F5. Neurological endoscopes would not normally be used on pat ients whose diagnosis is definite or probable sCJD. However, should such use be necessary, the endoscope should be single use if possible. If this is not feasible or appropriate, the endoscope should be removed from use or destroyed.

F6. Endoscopes that come into contact with the nasal cavity may, on occasion, be used in patients with definite or probable sCJD. If there is a risk that the endoscope could become contaminated with olfactory epithelium (see paragraph F2 above), a single use endoscope should be used if possible. If this is inappropriate, the endoscope should be removed from use or destroyed (as above).

F7. For all other types of endoscopy, decontaminate according to CFPP 01-06 or equivalent national guidance and the BSG guidance with the additional precautions for flexible endoscopes as set out in paragraph F1 above. 




Terry S. Singeltary Sr.

FRIDAY, AUGUST 11, 2017 

Infectivity in bone marrow from sporadic CJD patients

Bioassays in transgenic mice expressing the human prion protein revealed the presence of unexpectedly high levels of infectivity in the bone marrow from seven out of eight sCJD cases. These findings may explain the presence of blood-borne infectivity in sCJD patients. They also suggest that the distribution of prion infectivity in peripheral tissues in sCJD patients could be wider than currently believed, with potential implications for the iatrogenic transmission risk of this disease. 





THIS pretty much sums it up for me, with regards to how indestructible this tse prion agent is ; 

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery. 

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them. 


*** Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 Singeltary et al

re-Singeltary to Bramble et al Evidence For CJD/TSE Transmission Via Endoscopes 


MONDAY, JUNE 19, 2017 

Transmissible Spongiform Encephalopathies Advisory Committee June 2017 CJD, BSE, Scrapie, CWD, TSE, Prion?


SATURDAY, MAY 20, 2017 

Sporadic Creutzfeldt-Jakob Disease in 2 Plasma Product Recipients, United Kingdom


Saturday, January 16, 2016 

Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Products Guidance for Industry 


Wednesday, January 06, 2016 

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE U.K. 23rd ANNUAL REPORT 2014 (published 18th November 2015) 


SATURDAY, FEBRUARY 13, 2016 

The Risk of Prion Infection through Bovine Grafting Materials in dentistry


Sunday, January 17, 2016 

*** Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease *** 


TUESDAY, MAY 26, 2015

Minimise transmission risk of CJD and vCJD in healthcare settings Last updated 15 May 2015


FRIDAY, DECEMBER 04, 2015 

Iatrogenic and sporadic Creutzfeldt-Jakob disease in two sisters without mutation in the prion protein gene


Tuesday, May 26, 2015 

Minimise transmission risk of CJD and vCJD in healthcare settings Last updated 15 May 2015 


Thursday, November 12, 2015

Evaluation of the protection of primates transfused with variant Creutzfeldt-Jakob disease–infected blood products filtered with prion removal devices: a 5-year update


Thursday, August 13, 2015 

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years 


Thursday, January 23, 2014 

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574] 


Wednesday, September 10, 2014 

Creutzfeldt-Jakob disease (CJD) biannual update (August 2014), with updated guidance on decontamination of gastrointestinal endoscopy equipment 

Research and analysis

Tuesday, August 26, 2014 

Blood reference materials from macaques infected with variant Creutzfeldt-Jakob disease agent

Wednesday, November 27, 2013 

NHS failed to sterilise surgical instruments contaminated with 'mad cow' disease


 Saturday, November 16, 2013 

Management of neurosurgical instruments and patients exposed to creutzfeldt-jakob disease 2013 December 

Infect Control Hosp Epidemiol. 


 Wednesday, December 11, 2013

*** Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease ***


THE BAXTER STUDY...SEE MORE HERE ;


Monday, April 15, 2013 

Dr. Stephen B. Thacker Director Centers for Disease Control and Prevention′s Office of Science, Epidemiology and Laboratory Services (OSELS) dies from Creutzfeldt Jakob Disease CJD 


Tuesday, September 24, 2013 

NORDION (US), INC., AND BIOAXONE BIOSCIENCES, INC., Settles $90M Mad Cow TSE prion Contamination Suit Cethrin(R) 

Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 1 of 15 


Thursday, November 14, 2013 

Prion diseases in humans: Oral and dental implications 


Thursday, April 12, 2012

Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to 2010 

Eurosurveillance, Volume 17, Issue 15, 12 April 2012 

Research articles


Saturday, February 12, 2011 

Another Pathologists dies from CJD, another potential occupational death ? 

another happenstance of bad luck, a spontaneous event from nothing, or friendly fire ??? 


Tuesday, March 29, 2011 

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE 


Monday, May 16, 2011 

Does Poor Dental Health Have a Role in the Emergence of Variant Creutzfeldt Jakob Disease in the United Kingdom? 


Sunday, October 23, 2011 

The oral secretion of infectious scrapie prions occurs in pre-clinical sheep with a range of PRNP genotypes JVI Accepts, published online ahead of print on 19 October 2011 


Wednesday, August 24, 2011 

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD 


Wednesday, August 24, 2011 

There Is No Safe Dose of Prions 


LET US look at some history of science and debate there from of the potential/likelihood of TSE prion transmission via the dental route, some of the SEAC links no longer work, and then towards the bottom, the latest on the BSE, CWD, Scrapie, TSE PRION risk factor to human updates from PRION2015 conference... 

SEAC Spongiform Encephalopathy Advisory Committee 


Thursday, December 22, 2011 

Risk of Prion Disease Transmission through Bovine-Derived Bone Substitutes: A Systematic Review 

Clin Implant Dent Relat Res. 2011 Dec 15. doi: 10.1111/j.1708-8208.2011.00407.x. [Epub ahead of print] 


SEAC REVIEW ; 

Saturday, February 27, 2010 

SEAC Agenda 104th meeting on Friday 5th March 2010 


Thursday, August 12, 2010 

SEAC August 2010 Drayton Farm report update and more 


Tuesday, March 16, 2010 

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Part 4 REVISED FEB. 2010 


Tuesday, May 11, 2010 

Current risk of iatrogenic Creutzfeld-Jakob disease in the UK: efficacy of available cleaning chemistries and reusability of neurosurgical instruments 


 Published Date: 2010-03-04 16:00:03 

Subject: PRO/AH/EDR> Prion disease update (03) Archive Number: 20100304.0709 


*** Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 Singeltary et al

re-Singeltary to Bramble et al Evidence For CJD/TSE Transmission Via Endoscopes 


Saturday, December 12, 2009 

103RD MEETING OF THE SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE 


Thursday, February 26, 2009 

SEAC 102nd Meeting on Wednesday 4 March 2009 (SEE DH risk assessment on sourcing and pooling plasma) 


 Monday, August 17, 2009 

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex J,K, AND D Published: 2009 


Friday, July 17, 2009 

Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery 

units Volume 3 No 28; 17 July 2009 


Thursday, January 31, 2008 

SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 99th meeting held on 14th December 2007 

snip... 

ITEM 8 – PUBLIC QUESTION AND ANSWER SESSION 40. 

The Chair explained that the purpose of the question and answer session was to give members of the public an opportunity to ask questions related to the work of SEAC. 

Mr Terry Singeltary (Texas, USA) had submitted a question prior to the meeting, asking: 

“With the Nor-98 now documented in five different states so far in the USA in 2007, and with the two atypical BSE H-base 

13 © SEAC 2007 

cases in Texas and Alabama, with both scrapie and chronic wasting disease (CWD) running rampant in the USA, is there any concern from SEAC with the rise of sporadic CJD in the USA from ''unknown phenotype'', and what concerns if any, in relations to blood donations, surgery, optical, and dental treatment, do you have with these unknown atypical phenotypes in both humans and animals in the USA? 

Does it concern SEAC, or is it of no concern to SEAC? 

Should it concern USA animal and human health officials?” 

41. A member considered that this question ............ 



Thursday, October 23, 2008 

ONE HUNDRED AND FIRST MEETING OF THE SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE 



Tuesday, August 12, 2008 

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases) 


Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al

Evidence For CJD/TSE Transmission Via Endoscopes

From Terry S. Singletary, Sr flounder@wt.net 1-24-3

Bacliff, Texas 77518 USA


Professor Michael Farthing wrote:

Louise Send this to Bramble (author) for a comment before we post. Michael

snip...

Evidence For CJD/TSE Transmission Via Endoscopes

From Terry S. Singletary, Sr flounder@wt.net 1-24-3

I have researched human/animal TSEs now for over 5 years due to the death of my Mother from the Heidenhain Variant Creutzfeldt Jakob disease, one of six - known - variants of the infamous 'sporadic' CJD.

I did a little survey several years ago about CJD and ENDOSCOPY in 2001, and then went there again when another article was released recently. However, they seemed to only be concerned with the vCJD strain and risk from endoscopy equipment.

My concerns are if vCJD can be transmitted by blood, and there are now 6 variants of the infamous sporadic CJDs that they are documenting to date, how do they know that none of these 6 variants will not transmit the agent (prion) via blood?...especially since the sporadic CJDs are the only ones documented to date to transmit via the surgical arena and now that the CWD is spreading more and more, who knows about the cattle?

I would always read this study and it would bring me back to reality as to how serious/dangerous this agent is in the surgical/medical arena. You might want to read this short abstract from the late, great Dr. Gibbs twice, and let it really sink in. And please remember while reading some of these transmission studies, that most all, if not ALL these agents transmit freely to primates. Humans, of course, are primates.

Regarding claims that:

'Well, it has never been documented to transmit to humans."

There are two critical factors to think about:

A. CJD/TSEs in the USA are NOT reportable in most states and there is NO CJD/TSE questionnaire for most victims and their families, and the one they are now issuing asks absolutely nothing about route and source of the (prion) agent, only how the disease was diagnosed. Furthermore, the elderly are only very rarely autopsied, ie looking for Alzheimer's or 'FAST Alzheimer's' OR prion disease-related factors and phenomena, such as heart failure caused by disease.

B. It is unethical and against the law to do transmission studies of TSEs to humans, they are 100% FATAL.

I suggest you read these case studies about medical arena CJD transmission very carefully:

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.


Tissue Infectivity and TSEs (brain = high / rectum = medium)

snip...see full text ;

Evidence For CJD TSE Transmission Via Endoscopes 1-24-3

re-Singeltary to Bramble et al

Evidence For CJD/TSE Transmission Via Endoscopes

From Terry S. Singletary, Sr flounder@wt.net 1-24-3


Friday, December 04, 2009 

*** New guidance on decontamination of trial contact lenses and other contact devices has been revealed for CJD AND vCJD 


Thursday, January 29, 2009 

***Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999–2008 (WARNING TO Neurosurgeons and Ophthalmologists) 


Wednesday, August 20, 2008 

***Tonometer disinfection practice in the United Kingdom: A national survey 


Home / Science News 

***Eye procedure raises CJD concerns*** 

By STEVE MITCHELL, Medical Correspondent | 

Nov. 18, 2004 at 4:01 PM WASHINGTON, Nov. 18 (UPI) -- A New York man who died from a rare brain disorder similar to mad cow disease in May underwent an eye procedure prior to his death that raises concerns about the possibility of transmitting the fatal disease to others, United Press International has learned. 

The development comes on the heels of the announcement Thursday by U.S. Department of Agriculture officials of a possible second case of mad cow disease in U.S. herds. Richard Da Silva, 58, of Orange County, N.Y., died from Creutzfeldt Jakob disease, an incurable brain-wasting illness that strikes about one person per million. 

Richard's wife Ann Marie Da Silva told UPI he underwent a check for the eye disease glaucoma in 2003, approximately a year before his death. 

The procedure involves the use of a tonometer, which contacts the cornea -- an eye tissue that can contain prions, the infectious agent thought to cause CJD. 

Ann Marie's concern is that others who had the tonometer used on them could have gotten infected. 

A 2003 study by British researchers suggests her concerns may be justified. A team led by J.W. Ironside from the National Creutzfeldt-Jakob Disease Surveillance Unit at the University of Edinburgh examined tonometer heads and found they can retain cornea tissue that could infect other people -- even after cleaning and decontaminating the instrument. 

"Retained corneal epithelial cells, following the standard decontamination routine of tonometer prisms, may represent potential prion infectivity," the researchers wrote in the British Journal of Ophthalmology last year. "Once the infectious agent is on the cornea, it could theoretically infect the brain." 

Prions, misfolded proteins thought to be the cause of mad cow, CJD and similar diseases, are notoriously difficult to destroy and are capable of withstanding most sterilization procedures. 

Laura Manuelidis, an expert on these diseases and section chief of surgery in the neuropathology department at Yale University, agreed with the British researchers that tonometers represent a potential risk of passing CJD to other people. Manuelidis told UPI she has been voicing her concern about the risks of corneas since 1977 when her own study, published in the New England Journal of Medicine, showed the eye tissue, if infected, could transmit CJD. 

At the time the procedure was done on Richard Da Silva, about a year before he died, she said it was "absolutely" possible he was infectious. 

The CJD Incidents Panel, a body of experts set up by the U.K. Department of Health, noted in a 2001 report that procedures involving the cornea are considered medium risk for transmitting CJD. 

The first two patients who have a contaminated eye instrument used on them have the highest risk of contracting the disease, the panel said. 

In 1999, the U.K. Department of Health banned opticians from reusing equipment that came in contact with patients' eyes out of concern it could result in the transmission of variant CJD, the form of the disease humans can contract from consuming infected beef products. Richard Da Silva was associated with a cluster of five other cases of CJD in southern New York that raised concerns about vCJD. 

None of the cases have been determined to stem from mad cow disease, but concerns about the cattle illness in the United States could increase in light of the USDA announcement Thursday that a cow tested positive on initial tests for the disease. If confirmed, this would be the second U.S. case of the illness; the first was detected in a Washington cow last December. 

The USDA said the suspect animal disclosed Thursday did not enter the food chain. The USDA did not release further details about the cow, but said results from further lab tests to confirm the initial tests were expected within seven days. 

Ann Marie Da Silva said she informed the New York Health Department and later the eye doctor who performed the procedure about her husband's illness and her concerns about the risk of transmitting CJD via the tonometer. 

The optometrist -- whom she declined to name because she did not want to jeopardize his career -- "didn't even know what this disease was," she said. 

"He said the health department never called him and I called them (the health department) back and they didn't seem concerned about it," she added. 

"I just kept getting angrier and angrier when I felt I was being dismissed." She said the state health department "seems to have an attitude of don't ask, don't tell" about CJD. 

"There's a stigma attached to it," she said. "Is it because they're so afraid the public will panic? I don't know, but I don't think that the answer is to push things under the rug." 

New York State Department of Health spokeswoman Claire Pospisil told UPI she would look into whether the agency was concerned about the possibility of transmitting CJD via tonometers, but she had not called back prior to story publication. 

Disposable tonometers are readily available and could avoid the risk of transmitting the disease, Ironside and colleagues noted in their study. 

Ann Marie Da Silva said she asked the optometrist whether he used disposable tonometers and "he said 'No, it's a reusable one.'" 

Ironside's team also noted other ophthalmic instruments come into contact with the cornea and could represent a source of infection as they are either difficult to decontaminate or cannot withstand the harsh procedures necessary to inactivate prions. 

These include corneal burrs, diagnostic and therapeutic contact lenses and other coated lenses. 

Terry Singletary, whose mother died from a type of CJD called Heidenhain Variant, told UPI health officials were not doing enough to prevent people from being infected by contaminated medical equipment. 

"They've got to start taking this disease seriously and they simply aren't doing it," said Singletary, who is a member of CJD Watch and CJD Voice -- advocacy groups for CJD patients and their families. 

U.S. Centers for Disease Control and Prevention spokeswoman Christine Pearson did not return a phone call from UPI seeking comment. 

The agency's Web site states the eye is one of three tissues, along with the brain and spinal cord, that are considered to have "high infectivity." 

The Web site said more than 250 people worldwide have contracted CJD through contaminated surgical instruments and tissue transplants. 

This includes as many as four who were infected by corneal grafts. The agency noted no such cases have been reported since 1976, when sterilization procedures were instituted in healthcare facilities. 

Ironside and colleagues noted in their study, however, many disinfection procedures used on optical instruments, such as tonometers, fail. 

They wrote their finding of cornea tissue on tonometers indicates that "no current cleaning and disinfection strategy is fully effective." 

Singletary said CDC's assertion that no CJD cases from infected equipment or tissues have been detected since 1976 is misleading. 

"They have absolutely no idea" whether any cases have occurred in this manner, he said, because CJD cases often aren't investigated and the agency has not required physicians nationwide report all cases of CJD. 

"There's no national surveillance unit for CJD in the United States; people are dying who aren't autopsied, the CDC has no way of knowing" whether people have been infected via infected equipment or tissues, he said. 

Ann Marie Da Silva said she has contacted several members of her state's congressional delegation about her concerns, including Rep. Sue Kelly, R-N.Y., and Sen. Charles Schumer, D-N.Y. "Basically, what I want is to be a positive force in this, but I also want more of a dialogue going on with the public and the health department," she said. 


Cadaver corneal transplants -- without family permission Houston, Texas channel 11 news 28 Nov 99 

Reported by Terry S. Singeltary Sr.son of CJD victim 




2017 PRION CONFERENCE 2017 TSE PRION UPDATE

MONDAY, APRIL 03, 2017 

Accessing transmissibility and diagnostic marker of skin prions


Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿ 

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations

Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, Montana 59840 Next Section ABSTRACT

Chronic wasting disease (CWD) is a neurodegenerative prion disease of cervids. Some animal prion diseases, such as bovine spongiform encephalopathy, can infect humans; however, human susceptibility to CWD is unknown. In ruminants, prion infectivity is found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle. In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.


Prions in Skeletal Muscles of Deer with Chronic Wasting Disease 

Rachel C. Angers1,*, Shawn R. Browning1,*,†, Tanya S. Seward2, Christina J. Sigurdson4,‡, Michael W. Miller5, Edward A. Hoover4, Glenn C. Telling1,2,3,§ ↵* These authors contributed equally to this work. ↵† Present address: Department of Infectology, Scripps Research Institute, 5353 Parkside Drive, RF-2, Jupiter, FL 33458, USA. ↵‡ Present address: Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland. + See all authors and affiliations Science 24 Feb 2006: Vol. 311, Issue 5764, pp. 1117 DOI: 10.1126/science.1122864 Article Figures & Data Info & Metrics eLetters PDF You are currently viewing the abstract.

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Abstract

The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.


First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 

Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 

University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 

This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 

Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 

At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 

PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS 

 Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO

PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS

PRION 2017 CONFERENCE VIDEO



Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened? 

SATURDAY, JULY 29, 2017

Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD


TUESDAY, JULY 04, 2017

*** PRION 2017 CONFERENCE ABSTRACTS ON CHRONIC WASTING DISEASE CWD TSE PRION ***


URINE

SUNDAY, JULY 16, 2017

*** Temporal patterns of chronic wasting disease prion excretion in three cervid species ***


PAGE 25 

Transmission Studies 

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases 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 inoculam (?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. 


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).***



Molecular Barriers to Zoonotic Transmission of Prions

 *** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

 *** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.



*** 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). ***

*** 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). ***

*** 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 ;


you can see more evidence here ;


*** WDA 2016 NEW YORK *** 

We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. 

Student Presentations Session 2 

The species barriers and public health threat of CWD and BSE prions 

Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University 

Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. 

On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. 

BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. 

This adaptation has consequences for surveillance of humans exposed to CWD. 

Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders 


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. 

============== 


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.


Saturday, April 23, 2016 

Scrapie ZOONOSIS PRION CONFERENCE TOKYO 2016 

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

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


Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. 

*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

*** It also suggests a similar cause or source for atypical BSE in these countries. ***

P.9.21

Molecular characterization of BSE in Canada

Jianmin Yang 1 , Sandor Dudas 2 , Catherine Graham 2 , Markus Czub 3 , Tim McAllister 1 , Stefanie Czub 1 1 Agriculture and Agri-Food Canada Research Centre, Canada; 2 National and OIE BSE Reference Laboratory, Canada; 3 University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle. Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres.

Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.

Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal-specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. It also suggests a similar cause or source for atypical BSE in these countries.

see page 176 of 201 pages...tss


*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply;


***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.

***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***

Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT


TUESDAY, AUGUST 1, 2017 

Could diabetes spread like mad cow disease?


i remember reading a lot about diabetes and tse prion during the BSE Inquiry days. i may have to go back and study that a bit closer.

also, interestingly, in the recent study with cwd and macaque, i also remember reading, In four animals wasting was observed, two of those had confirmed diabetes.


THURSDAY, AUGUST 3, 2017 

BSE INQUIRY DFA 18 COSMETICS FDA OVERSIGHT WARNING The Honorable Frank Pallone, Jr.


TUESDAY, AUGUST 1, 2017 

BSE INQUIRY DFA 17 Medicines and medical devices


TUESDAY, APRIL 18, 2017 

*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***


*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.

TUESDAY, MARCH 28, 2017 

*** Passage of scrapie to deer results in a new phenotype upon return passage to sheep ***

*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.


***2017***

TUESDAY, JULY 18, 2017 

*** USDA announces Alabama case of Bovine Spongiform Encephalopathy Alabama


SUNDAY, JULY 30, 2017 

*** PRION2017 Low levels of classical BSE infectivity in rendered fat tissue


THURSDAY, JULY 20, 2017 

USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200


SUNDAY, JULY 23, 2017

atypical L-type BASE Bovine Amyloidotic Spongiform Encephalopathy BSE TSE PRION


SUNDAY, JULY 23, 2017

Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy


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.***


P169 Low levels of classical BSE infectivity in rendered fat tissue

Dr. Christine Fast1, Dr. Markus Keller2, Dr. Ute Ziegler3, Prof. Dr. Martin Groschup4 1Friedrich-Loeffler-Institut, Greifswald, Germany, 2Friedrich-Loeffler-Institut, Greifswald, Germany, 3Friedrich-Loeffler-Institut, Greifswald, Germany, 4Friedrich-Loeffler-Institut, Greifswald, Germany

Aims: Specified Risk Materials (SRM) are the animal tissues potentially containing the highest levels of Bovine Spongiform Encephalopathy (BSE) prions; and their removal is the most important consumer protection measure against BSE. BSE infectivity in the mesentery fat is most likely associated with embedded nervous tissue. To date, it is unclear if contamination of the rendered fat could have occurred during tallow production at a slaughterhouse.

Methods: Samples were taken from five cattle originating from the German BSE pathogenesis study. Two animals were at preclinical, one at late preclinical and one animal at clinical stage of disease; one control animal was included. For all cattle, mouse bioassay results for the celiac and mesenteric ganglion complex (CMGC) were generated previously, showing either no, mild, moderate or substantial infectivity loads. Fat was rendered from CMGC samples embedded in mesentery fat by incubating for 20 minutes at 95°C, according to standard tallow production methods. Subsequently, the melted fat was 1:5 diluted in physiological saline and thoroughly vortexed. The liquid fat was cleaned by a short centrifugation at 10.000 rpm. Finally, 7-12 bovine prion protein overexpressing transgenic mice (Tgbov XV) were i.c. inoculated with 25-30 μl of the supernatant. Mice were sacrificed after 730 days or when showing clinical symptoms and mouse brains were subsequently examined by biochemical and immunohistochemical methods.

Results: Neither the control and the preclinical nor the late preclinical animals showed signs of infectivity in mouse bioassay of the fat samples after up to 730 days p.i. In contrast, low levels of infectivity were detected in the fat of the clinical animal as one mouse displayed a clear accumulation of pathological prion protein in the brain after an incubation period of 598 days p.i.

Conclusions: Our results clearly indicate the potential contamination of melted mesenteric fat by embedded nervous structures during standard tallow production. However, the BSE infectivity level was weak and detectable only in the fat rendered from one sample with documented high infectivity load in the ganglion itself (Kaatz et al. 2012). Albeit, this study is not representative as only one clinical animal was included, it provides a proof of principle. A broader examination would allow a better insight into temporal and spatial distribution pattern of BSE infectivity in rendered fat tissues of different origins.Such estimates have a critical role in qualitative and quantitative risk assessments and in providing advice on the designation and removal of certain SRM tissues.


Wednesday, December 21, 2016 

TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2016 ANNUAL REPORT ARS RESEARCH 


Tuesday, September 06, 2016

A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation


Saturday, July 23, 2016

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


TUESDAY, JULY 18, 2017 

MINK FARMING USA TRANSMISSIBLE MINK ENCEPHALOPATHY TSE PRION DISEASE SURVEILLANCE AND TESTING



Sunday, March 20, 2016

Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed ***UPDATED MARCH 2016*** Singeltary Submission


SEE MAD COW FEED VIOLATIONS AFER MAD COW FEED VIOLATIONS ;


Tuesday, April 19, 2016

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


16 years post mad cow feed ban August 1997 2013 

Sunday, December 15, 2013 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE 


Tuesday, December 23, 2014 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION 


17 years post mad cow feed ban August 1997 

Monday, October 26, 2015 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE October 2015 


TUESDAY, JANUARY 17, 2017 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION


cwd to pig, orally ;

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

Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin

Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:

Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.

Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 challenge="" groups="" month="" pigs="" remaining="" the="">6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.

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

This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge.

CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.

Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.


CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...


we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.


 Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....


 snip...see much more here ;

WEDNESDAY, APRIL 05, 2017

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


EUROPE CWD TSE PRION

In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible. For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.

snip...

Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.

snip...

What is the risk of chronic wasting disease being introduced into Great Britain? A Qualitative Risk Assessment October 2012


Thursday, April 07, 2016

What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016


Subject: DEFRA What is the risk of a cervid TSE being introduced from Norway into Great Britain? Qualitative Risk Assessment September 2016

Friday, September 30, 2016

DEFRA What is the risk of a cervid TSE being introduced from Norway into Great Britain? Qualitative Risk Assessment September 2016



Scientific Opinion

Chronic wasting disease (CWD) in cervids

Authors

EFSA Panel on Biological Hazards (BIOHAZ),

First published: 18 January 2017Full publication history DOI: 10.2903/j.efsa.2017.4667View/save citation



TUESDAY, JUNE 20, 2017 

Norway Confirms 6th Case of Skrantesjuke CWD TSE Prion Disease


Tuesday, December 13, 2016

Norway Chronic Wasting Disease CWD TSE Prion disease Skrantesjuke December 2016 Update


Thursday, September 22, 2016

NORWAY DETECTS 5TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION Skrantesjuke


Saturday, September 03, 2016

NORWAY Regulation concerning temporary measures to reduce the spread of Chronic Wasting Disease (CWD) as 4th case of skrantesjuke confirmed in Sogn og Fjordane


Wednesday, August 31, 2016

*** NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOU


Wednesday, August 31, 2016

NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOU


Tuesday, August 02, 2016

Chronic wasting disease of deer – is the battle to keep Europe free already lost?


Tuesday, June 14, 2016

*** Chronic Wasting Disease (CWD) in a moose from Selbu in Sør-Trøndelag Norway ***


Thursday, July 07, 2016

Norway reports a third case Chronic Wasting Disease CWD TSE Prion in 2nd Norwegian moose

14/06/2016 - Norway reports a third case


Tuesday, April 12, 2016

The first detection of Chronic Wasting Disease (CWD) in Europe free-ranging reindeer from the Nordfjella population in South-Norway.



Saturday, April 9, 2016

The Norwegian Veterinary Institute (NVI, 2016) has reported a case of prion disease Cervid Spongiform Encephalopathy detected in free ranging wild reindeer (Rangifer tarandus tarandus)

Department for Environment, Food and Rural Affairs


Saturday, July 16, 2016

Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The British Deer Society 07/04/2016

Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?

could this have been cwd in the UK back in 1970’S ???





SEE FULL TEXT ;


THURSDAY, AUGUST 10, 2017

NORWAY MAKES CHANGES TO NATIONAL CHRONIC WASTING DISEASE CWD TSE PRION RULES


WEDNESDAY, JULY 26, 2017 

APHIS USDA Emerging Animal Disease Preparedness and Response Plan July 2017


THURSDAY, JUNE 22, 2017 

World Organisation for Animal Health (OIE) to establish liaison office in College Station, Texas


MONDAY, JANUARY 4, 2016 

Long live the OIE, or time to close the doors on a failed entity?


WEDNESDAY, MARCH 11, 2015 

OIE and Centers for Disease Control and Prevention Reinforce Collaboration


MONDAY, MAY 05, 2014

Member Country details for listing OIE CWD 2013 against the criteria of Article 1.2.2., the Code Commission recommends consideration for listing

OIE STILL FLOUNDERING WITH TSE PRION DISEASE, letting it spread around the globe with the bse mrr policy, and still ignoring cwd, and making atypical scrapie a legal trading commodity.


THURSDAY, MAY 30, 2013 

World Organization for Animal Health (OIE) has upgraded the United States' risk classification for mad cow disease to "negligible" from "controlled", and risk further exposing the globe to the TSE prion mad cow type disease


TUESDAY, JULY 17, 2012 

O.I.E. BSE, CWD, SCRAPIE, TSE PRION DISEASE Final Report of the 80th General Session, 20 - 25 May 2012


BSE TSE PRION USDA OIE NEEDLESS CONFLICT


2015 PRION CONFERENCE

*** RE-P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study

***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. ***

P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study

Paul Brown1, Diane Ritchie2, James Ironside2, Christian Abee3, Thomas Kreil4, and Susan Gibson5 1NIH (retired); Bethesda, MD USA; 2University of Edinburgh; Edinburgh, UK; 3University of Texas; Bastrop, TX USA; 4Baxter Bioscience; Vienna, Austria; 5University of South Alabama; Mobile, AL USA

Five vCJD disease transmissions and an estimated 1 in 2000 ‘silent’ infections in UK residents emphasize the continued need for information about disease risk in humans. A large study of blood component infectivity in a non-human primate model has now been completed and analyzed. Among 1 GSS, 4 sCJD, and 3 vCJD cases, only GSS leukocytes transmitted disease within a 5–6 year surveillance period. A transmission study in recipients of multiple whole blood transfusions during the incubation and clinical stages of sCJD and vCJD in ic-infected donor animals was uniformly negative. These results, together with other laboratory studies in rodents and nonhuman primates and epidemiological observations in humans, suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. The issue of decades-long incubation periods in ‘silent’ vCJD carriers remains open.


ran across an old paper from 1984 ;

***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent. ***


snip...see full text ;



VPSPr Variably protease-sensitive prionopathy TSE Prion

Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker disease (GSS). However, contrary to exclusively inherited GSS, no prion protein (PrP) gene variations have been detected in VPSPr, suggesting that VPSPr might be the long-sought sporadic form of GSS.

snip...

In conclusion, we propose that VPSPr is transmissible and, therefore, is an authentic prion disease. However, transmissibility cannot be sustained through serial passages presumably because human PrPC (or the mouse brain environment) cannot efficiently convert and propagate the VPSPr PrPSc species. If this is the case, uncovering the properties of human PrP that are required to replicate more efficiently the prion strains associated with VPSPr may help clarify the PrPSc mode of formation in this intriguing disease. 




Friday, January 10, 2014

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


National Prion Center could lose all funding just as concern about CWD jumping to humans rises

THURSDAY, JULY 13, 2017 

TEXAS CREUTZFELDT JAKOB DISEASE CJD TSE PRION


National Prion Center could lose all funding just as concern about CWD jumping to humans rises

SATURDAY, JULY 15, 2017 

*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises


*** I URGE YOU ALL TO WATCH THESE VIDEOS ***



2001 FDA CJD TSE Prion Singeltary Submission


*** U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001 


Tracking spongiform encephalopathies in North America

Xavier Bosch

Published: August 2003


Summary;

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.”

49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD) the relative of mad cow disease seen among deer and elk in the USA. Although his feverish search did not lead him to the smoking gun linking CWD to a similar disease in North American people, it did uncover a largely disappointing situation.

Singeltary was greatly demoralised at the few attempts to monitor the occurrence of CJD and CWD in the USA. Only a few states have made CJD reportable. Human and animal TSEs should be reportable nationwide and internationally, he complained in a letter to the Journal of the American Medical Association (JAMA 2003; 285: 733). "I hope that the CDC does not continue to expect us to still believe that the 85% plus of all CJD cases which are sporadic are all spontaneous, without route or source."

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.


Until recently, CWD was thought to be confined to the wild in a small region in Colorado. But since early 2002, it has been reported in other areas, including Wisconsin, South Dakota, and the Canadian province of Saskatchewan. Indeed, the occurrence of CWD in states that were not endemic previously increased concern about a widespread outbreak and possible transmission to people and cattle.

To date, experimental studies have proven that the CWD agent can be transmitted to cattle by intracerebral inoculation and that it can cross the mucous membranes of the digestive tract to initiate infection in lymphoid tissue before invasion of the central nervous system. Yet the plausibility of CWD spreading to people has remained elusive.

Part of the problem seems to stem from the US surveillance system. CJD is only reported in those areas known to be endemic foci of CWD. Moreover, US authorities have been criticised for not having performed enough prionic tests in farm deer and elk.

Although in November last year the US Food and Drug Administration issued a directive to state public-health and agriculture officials prohibiting material from CWD-positive animals from being used as an ingredient in feed for any animal species, epidemiological control and research in the USA has been quite different from the situation in the UK and Europe regarding BSE.

"Getting data on TSEs in the USA from the government is like pulling teeth", Singeltary argues. "You get it when they want you to have it, and only what they want you to have."

Norman Foster, director of the Cognitive Disorders Clinic at the University of Michigan (Ann Arbor, MI, USA), says that "current surveillance of prion disease in people in the USA is inadequate to detect whether CWD is occurring in human beings"; adding that, "the cases that we know about are reassuring, because they do not suggest the appearance of a new variant of CJD in the USA or atypical features in patients that might be exposed to CWD. However, until we establish a system that identifies and analyses a high proportion of suspected prion disease cases we will not know for sure". The USA should develop a system modelled on that established in the UK, he points out.

Ali Samii, a neurologist at Seattle VA Medical Center who recently reported the cases of three hunters "two of whom were friends" who died from pathologically confirmed CJD, says that "at present there are insufficient data to claim transmission of CWD into humans"; adding that "[only] by asking [the questions of venison consumption and deer/elk hunting] in every case can we collect suspect cases and look into the plausibility of transmission further". Samii argues that by making both doctors and hunters more aware of the possibility of prions spreading through eating venison, doctors treating hunters with dementia can consider a possible prion disease, and doctors treating CJD patients will know to ask whether they ate venison.

CDC spokesman Ermias Belay says that the CDC "will not be investigating the [Samii] cases because there is no evidence that the men ate CWD-infected meat". He notes that although "the likelihood of CWD jumping the species barrier to infect humans cannot be ruled out 100%" and that "[we] cannot be 100% sure that CWD does not exist in humans& the data seeking evidence of CWD transmission to humans have been very limited". 



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? 


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 hvCJD in the USA * BSE in U.S. 


TUESDAY, AUGUST 8, 2017 

Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2016-0092]


Alzheimer’s disease, iatrogenic, and Transmissible Spongiform Encephalopathy TSE Prion disease, that is the question ??? 

>>> The only tenable public line will be that "more research is required’’ <<< 

>>> possibility on a transmissible prion remains open<<< 

O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?

[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. There are also results to be made available shortly (1) concerning a farmer with CJD who had BSE animals, (2) on the possible transmissibility of Alzheimer’s and (3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]





snip...see full Singeltary Nature comment here; 


see Singeltary comments to Plos ; 

Subject: 1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN BSE101/1 0136 IN CONFIDENCE CMO 

From: . Dr J S Metiers DCMO 4 November 1992 TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES 

1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. 'This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify. 

2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed". As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible. what are the implications for public health? 

3. The route 'of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed. 


92/11.4/1.1 

BSE101/1 0137 4. 

The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. 

But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. 

The only tenable public line will be that "more research is required’’ before that hypothesis could be evaluated. 

The possibility on a transmissible prion remains open. 

In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. 

Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical. 

J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832 llllYc!eS 2 92/11.4/1.2 


>>> The only tenable public line will be that "more research is required’’ <<< 

>>> possibility on a transmissible prion remains open<<< 

O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ? Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015) 

snip...see full Singeltary Nature comment here; 


Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease 

*** Singeltary comment PLoS 

*** Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ? 

Posted by flounder on 05 Nov 2014 at 21:27 GMT 



Ann N Y Acad Sci. 1982;396:131-43. 

Alzheimer's disease and transmissible virus dementia (Creutzfeldt-Jakob disease). 

Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC. 

Abstract 

Ample justification exists on clinical, pathologic, and biologic grounds for considering a similar pathogenesis for AD and the spongiform virus encephalopathies. However, the crux of the comparison rests squarely on results of attempts to transmit AD to experimental animals, and these results have not as yet validated a common etiology. Investigations of the biologic similarities between AD and the spongiform virus encephalopathies proceed in several laboratories, and our own observation of inoculated animals will be continued in the hope that incubation periods for AD may be even longer than those of CJD. 


Sunday, November 22, 2015 

*** Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis 

Abstract 

Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans. 

Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD 54.00 



*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery *** 

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them. 


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. 


Terry S. Singeltary Sr.