Friday, November 23, 2012

sporadic Creutzfeldt-Jakob Disease update As at 5th November 2012 UK, USA, AND CANADA


As at 5th November 2012

Summary of vCJD cases


Deaths from definite vCJD (confirmed): 122

Deaths from probable vCJD (without neuropathological confirmation): 54

Deaths from probable vCJD (neuropathological confirmation pending): 0

Number of deaths from definite or probable vCJD (as above): 176


Number of definite/probable vCJD cases still alive: 0

Total number of definite or probable vCJD (dead and alive): 176

1 excludes a total of 7 cases of Variably Protease-Sensitive Prionopathy (VPSPr) identified by NCJDRSU

2 includes all genetic prion disease, including Gerstmann Sträussler Scheinker syndrome (GSS

Twentieth Annual Report 2011


The recently described form of prion disease originally termed Protease Sensitive Prionopathy and renamed Variably Protease Sensitive Prionopathy, is of uncertain nosological significance but is presently considered a form of sporadic prion disease, alongside sporadic CJD. The NCJDRSU has so far identified at total of 5 such cases in the UK and is continuing to monitor this form of disease.


The identification of 3 cases of vCJD in the small cohort of known recipients of blood from persons incubating vCJD, together with the fact that 2 of the cases were associated with a common blood donor, establishes beyond reasonable doubt that blood transfusion is a transmission route for vCJD. (Collaborators on this project: Dr P.E. Hewitt, Dr C.A. Llewelyn, Ms M Malfroy).

As of 31st December 2011, after nearly 15 years of surveillance, 3187 patients with suspected PIND had been reported and the Expert Group had discussed 2157 of these. 1335 cases had a confirmed underlying cause other than vCJD, being categorised into over 150 known neurodegenerative diseases12. There have been six cases of vCJD; four definite and two probable. Three were reported in 1999, one in 2000 and 2 in mid-2001.

One girl was aged 12 at onset - the youngest UK case of vCJD identified to date.

(Collaborators on this project: Dr C. Verity, Prof A. Nicoll, Ms L. Stellitano, Ms AM Winstone)


A general population control group, recruited in 2002-2003, has been used in analyses comparing risk factors of the control group with cases of vCJD and sCJD, based on information provided by the families of cases and controls at interview (for details of the findings please see below). The methodology of the recruitment of this control group can be found in Ward et al, 2006, Annals of Neurology13

Results from the case-control study of reported risk factors for variant CJD are consistent with dietary exposure to contaminated beef products being the main route of infection of vCJD, but recall bias cannot be excluded as an explanation13.

For sporadic CJD, an analysis of reported medical risk factors, found that it was unlikely that a high proportion of UK sCJD cases are the result of transmission during surgery, but we cannot exclude the possibility that such transmission occurs occasionally14.

Although funding for the case-control study has now ceased, the Unit continues to collect risk factor information for all suspect cases of human prion diseases referred to the Unit as part of its core work. In addition, analysis continues to be undertaken on data gathered already, such as the ongoing examination of medical risk factor data obtained directly from primary care records. Ad hoc studies that may require extra funding (for example the dental study15, funded by Department of Health, UK) have been and will continue to be undertaken as necessary. If in the future it is thought necessary, funding will be sought to recruit further controls.


The number of cases of vCJD have declined in the UK, with 2 cases being examined in 2011. In contrast, we received more cases of sporadic CJD in 2011 than in the previous year, and there was also an increase in the number of cases referred in which sporadic CJD was suspected, but not confirmed on the results of the investigations performed in our laboratory. Fewer cases of CJD have been referred from outside the UK, reflecting the decline in suspect cases of vCJD overseas.


PRNP Codon 129 distribution in sporadic CJD

The distribution of PRNP codon 129 genotypes in sporadic CJD has been analysed since the inception of the Unit in 1990. The overall distribution of PRNP codon 129 genotypes in sporadic CJD is 63% MM, 19% MV, 18% VV (see Table 6). There appears to be evidence (p=0.005) of a change in the PRNP codon 129 distribution in sporadic CJD between the periods 1990-1995 and 1996-2010. The explanation for this remains unclear and is being investigated further. It should be noted that not all cases are genotyped (data available on 62%) and, therefore, changes in PRNP codon 129 distribution may reflect changes in the way in which cases are selected for analysis.

Table 6 PRNP codon 129 genotypes of cases of sporadic CJD in the UK, 1990-2011



Many requests for CSF 14-3-3 and S-100b analysis are on patients where the clinical suspicion of CJD is low and the request is made to exclude the diagnosis. However, if a CSF 14-3-3 request is made for a patient where CJD is reasonably suspected the referring clinician is encouraged to formally refer the patient to the NCJDRSU.


The Lancet Infectious Diseases, Volume 12, Issue 12, Page 897, December 2012

doi:10.1016/S1473-3099(12)70302-XCite or Link Using DOI

Prion diseases remain a mystery

The Lancet Infectious Diseases

In the 1980s and 1990s, the UK outbreak of bovine spongiform encephalopathy (BSE) in cattle, and the subsequent human cases of a then novel variant of Cruetzfeldt-Jakob disease (vCJD) linked to the bovine disease, led to some of the defining political moments of the time and large-scale reassessment of agricultural practices and food safety. From the then Agriculture Minister, John Gummer, giving his daughter a hamburger to reassure the nation that British beef was safe in 1990, to the mass slaughter of over 4 million cattle to contain the BSE epidemic, images from the period still resonate in the country's consciousness. Given the lingering shadow of the BSE and vCJD outbreaks, the news, as reported by David Holmes in this month's Newsdesk, that so far in 2012 not a single case of the human disease has been reported in the UK is particularly welcome. 2012 looks like being the first year since 1995 without a reported case.

One could easily think that this news should be cause for celebration, a sign that the outbreak of this devastating, rapidly progressive, and invariably fatal disease is coming to an end. Indeed, since a peak in 2000 when 28 people died from vCJD, the number of deaths seemed to tail off, with no more than five deaths a year since 2005. But, as suggested several times since the start of the outbreak, serious concern exists that these early cases could be just the tip of the iceberg. All confirmed patients so far have had a particular prion-protein genotype (methionine homozygotes at codon 129), but people who are either homozygous for valine or heterozygous at this codon might have a longer incubation time, so a second wave of vCJD related to consumption of contaminated meat remains a possibility. Moreover, there is evidence that as many as one in 2000 people of all genotypes are asymptomatic carriers of the defective prions that cause the disease. Not only might these people go on to develop vCJD, but also they might pass on the infection to susceptible individuals through tissue donations and transplants.

These concerns highlight the real problem with vCJD and other prion diseases that affect human beings: the dearth of knowledge. So little is known about the role of normal prion proteins, how pathogenic prions replicate without genetic information, the pathogenic mechanisms, and why different prion diseases have different presentations. True of familial, sporadic, and iatrogenic CJD, fatal familial insomnia, and kuru, our limited understanding of these diseases prohibits attempts to develop sensitive diagnostic tests let alone effective treatments. As such, prion diseases remain a death sentence.

Thankfully, these diseases are rare. The total number of cases of vCJD in the UK in 1995—2011 was 176, with another 49 being recorded in 11 other countries. The UK has done detailed surveillance of CJD since the height of the BSE crisis in 1990. The latest report (published on Oct 8, 2012) from the National CJD Research and Surveillance Unit in Edinburgh shows that although the cases of vCJD have declined, the number of cases of sporadic CJD have remained fairly constant for the past 15 years, hovering around 70 per year, although in 2008, 2009, and 2011, the number of deaths was 85 or higher.

Alongside the detailed surveillance from the National Surveillance Unit, research done at the Medical Research Council Prion Unit (University College London Institute of Neurology, UK) has begun to elucidate possible mechanisms for human prion diseases and last year reported the first reliable blood assay to detect vCJD prions. This ongoing research and surveillance will be essential to further our understanding of these diseases in the hope of better assessing future risks and developing approaches to disease management.

In a research Article published online in The Lancet Infectious Diseases, Michael Head (University College London) and colleagues have estimated UK investments in global infectious diseases research from 1997 to 2010; they found that more than £30 million had been spent on research into prion disease, around £20 million of which came from the Department of Health. When compared with research investments in HIV (£461 million), hepatitis B (£12 million), hepatits C (£60 million), and malaria (£346 million), the spending may seem disproportionate to the burden of disease. However, given the incurable nature of these diseases, the potential for prions to cross the species barrier, and the potential for future outbreaks among asymptomatic carriers of pathogenic prions, continued surveillance and research is essential to fill in the many gaps in our knowledge.


Volume 3, Number 8 01 August 2003


Tracking spongiform encephalopathies in North America

Xavier Bosch

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

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

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

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

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

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.


Greetings BSE-L members et al, and others,

Confucius is confused again on the infamous ‘classification pending sporadic creutzfeldt jakob disease’ cpsCJD, (because nvCJD has been ruled out).

Confucius is confused about why the increase of these cpsCJD cases in the USA and Canada which we have been seeing, but I saw no reports in the UK surveillance reports of the infamous North American Classification Pending Sporadic Creutzfeldt Jakob disease cases.

if truly a supposedly sporadic spontaneous disease, would you not see these cpsCJD cases popping up all over the world in random ???

or, could these cpsCJD cases be of a North American zoonotic or iatrogenic from North American zoonoses sub-clinical source ???

or both ???

with so many documented Transmissible Spongiform Encephalopathy TSE prion disease in so many different species here in North America, and consumption there from, I believe that this should be at the forefront of research. ...

Confused Confucius...flounder


*** 5 Includes 8 cases in which the diagnosis is pending, and 18 inconclusive cases;

*** 6 Includes 10 (9 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded.


*** 3. Final classification of 48 cases from 2009, 2010, 2011 and 2012 is pending.





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

2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;

3 Disease acquired in the United Kingdom;

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

*** 5 Includes 8 cases in which the diagnosis is pending, and 18 inconclusive cases; *** 6 Includes 10 (9 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded.

*** The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2224 cases of sporadic Creutzfeldt-Jakob disease (sCJD).

CJD Deaths Reported by CJDSS1, 1994-20122

As of Oct 31, 2012

Deaths of Definite and Probable CJD

Year Sporadic Iatrogenic Familial GSS FFI vCJD Total

1994 2 0 0 1 0 0 3

1995 3 0 0 0 0 0 3

1996 13 0 0 0 0 0 13

1997 16 0 1 1 0 0 18

1998 22 1 0 1 0 0 24

1999 27 2 2 1 0 0 32

2000 32 0 0 3 0 0 35

2001 27 0 2 1 0 0 30

2002 31 0 2 2 0 1 36

2003 27 1 1 0 0 0 29

2004 42 0 1 1 0 0 44

2005 41 0 1 1 0 0 43

2006 39 0 1 3 1 0 44

2007 35 0 0 4 0 0 39

2008 48 0 1 0 0 0 49

2009 48 0 3 2 0 0 53

2010 35 0 3 0 0 0 38

2011 41 0 2 1 0 1 45

2012 20 0 0 0 0 0 20

Total 549 4 20 22 1 2 598

1. CJDSS began in 1998

2. Data before 1998 are retrospective and partial, data from 1998 to 2008 are complete, and data for 2009 - 2012 are provisional

3. Final classification of 48 cases from 2009, 2010, 2011 and 2012 is pending.

Tuesday, November 6, 2012

Transmission of New Bovine Prion to Mice, Atypical Scrapie, BSE, and Sporadic CJD, November-December 2012 update


Summary Report BSE 2012

Executive Summary

Saturday, August 4, 2012

Final Feed Investigation Summary - California BSE Case - July 2012

Saturday, August 4, 2012

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


Canada has had a COVER-UP policy of mad cow disease since about the 17th case OR 18th case of mad cow disease. AFTER THAT, all FOIA request were ignored $$$

THIS proves there is indeed an epidemic of mad cow disease in North America, and it has been covered up for years and years, if not for decades, and it’s getting worse $$$

Thursday, February 10, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011 and how to hide mad cow disease in Canada Current as of: 2011-01-31

Wednesday, August 11, 2010


Thursday, August 19, 2010


Friday, March 4, 2011

Alberta dairy cow found with mad cow disease

Tuesday, June 26, 2012

Creutzfeldt Jakob Disease Human TSE report update North America, Canada, Mexico, and USDA PRION UNIT as of May 18, 2012

type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the rise in Canada and the USA

Wednesday, June 13, 2012


Wednesday, April 4, 2012

Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products APHIS-2008-0010-0008 RIN:0579-AC68

Thursday, February 16, 2012

Bovine Spongiform Encephalopathy BSE


Sunday, February 12, 2012

National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas

National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas

Friday, February 10, 2012

Creutzfeldt-Jakob disease (CJD) biannual update (2012/1) potential iatrogenic (healthcare-acquired) exposure to CJD, and on the National Anonymous Tonsil Archive

Saturday, March 5, 2011


Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY

(see mad cow feed in COMMERCE IN ALABAMA...TSS)

Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)

(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)

Sunday, July 11, 2010

CJD or prion disease 2 CASES McLennan County Texas population 230,213 both cases in their 40s

Thursday, July 08, 2010


Tuesday, June 1, 2010

USA cases of dpCJD rising with 24 cases so far in 2010 USA cases of dpCJD rising with 24 cases so far in 2010


please be aware, i have termed this strange strain of 'diagnosis pending creutzfeldt jakob disease' as 'dpCJD', what ever that is suppose to mean. how many more years, decades, are we going to have to flounder for them to establish another name for the same disease ?

5 Includes 28 cases in which the diagnosis is pending, and 17 inconclusive cases;

6 Includes 28 (24 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded

Monday, April 5, 2010


Monday, March 29, 2010

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas


Thursday, May 27, 2010


Archive Number 20100405.1091 Published Date 05-APR-2010

Subject PRO/AH/EDR> Prion disease update 1010 (04)


[Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.

The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

see full text ;

Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease

(see video here)


(see video at bottom)

Sunday, September 6, 2009



Let's review some history ;


(VET REC 1992, M Jeffrey, J W Wilesmith p359-362)



1. The disease title is comlex and invites the press to coin a new one (such as BSE II, MAD COW II, or Son of BSE). It is suggested for now that it is called a brain disorder or brain dgeneration (BD).


2. Disease clinically similar to BSE but pathologically distinct. BD is NOT a form of BSE.



20 October 1992

Martin Jeffrey observes that there is a strong similarity between the histopathological picture in BBD and that produced by ME7 strain of Scrapie in mice.


7. There have to date been 42 cases of BBD out of a total of 2,598 brains submitted for BSE diagnosis in Scotland. The incidence of the condition appears to be 1 in 10,000 of beef suckler cows.


23 October 1992


''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$


page 9 of 14 ;30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...

snip... see full text

this information had been proved to be incorrect for a number of reasons...

Wednesday, October 08, 2008

Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?


6. Trouble has been brewing for some time. Dr Collinge is lobbying hard, and threatening to go to the media, claiming Dr Will is blocking his research...


9. ...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 Alzheimers and (3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest. ...

Saturday, February 28, 2009


"All of the 15 cattle tested showed that the brains had abnormally accumulated PrP"


Thursday, November 05, 2009

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

Thursday, July 10, 2008

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008

Thursday, July 10, 2008

A New Prionopathy update July 10, 2008

Sunday, August 10, 2008

A New Prionopathy OR more of the same old BSe and sporadic CJD



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

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

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

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

Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.

In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.

Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.

*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.


Wednesday, March 28, 2012


*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.


Tuesday, November 6, 2012

Transmission of New Bovine Prion to Mice, Atypical Scrapie, BSE, and Sporadic CJD, November-December 2012 update


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


*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie.

Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions

Marcelo A. Barria1, Glenn C. Telling2, Pierluigi Gambetti3, James A. Mastrianni4 and Claudio Soto1,* 1Mitchell Center for Alzheimer’s disease and related Brain disorders, Dept of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA 2Dept of Microbiology, Immunology & Molecular Genetics, and Neurology, Sanders Brown Center on Aging, University of Kentucky Medical Center, Lexington, KY, USA 3Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA 4Dept of Neurology, University of Chicago, Chicago, IL, USA. Running Title: Conversion of human PrPC by cervid PrPSc Keywords: Prion / transmissible spongiform encephalopathy / infectivity / misfolded prion protein / prion strains * To whom correspondence should be addressed. University of Texas Houston Medical School, 6431 Fannin St, Houston, TX 77030. Tel 713-5007086; Fax 713-5000667; E-mail The latest version is at JBC Papers in Press.

Published on January 4, 2011 as Manuscript M110.198465 Copyright 2011 by The American Society for Biochemistry and Molecular Biology, Inc. 5, Downloaded from by guest, on November 11, 2012 2

Prion diseases are infectious neurodegenerative disorders affecting humans and animals that result from the conversion of normal prion protein (PrPC) into the misfolded prion protein (PrPSc). Chronic wasting disease (CWD) is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. Determining the risk of transmission of CWD to humans is of utmost importance, considering that people can be infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the misfolded form by CWD PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique, which mimic in vitro the process of prion replication. Our results show that cervid PrPSc can induce the conversion of human PrPC, but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, the newly generated human PrPSc exhibits a distinct biochemical pattern that differs from any of the currently known forms of human PrPSc. Our results also have profound implications for understanding the mechanisms of prion species barrier and indicate that the transmission barrier is a dynamic process that depend on the strain and moreover the degree of adaptation of the strain. If our findings are corroborated by infectivity assays, they will imply that CWD prions have the potential to infect humans, and that this ability depends on CWD strain adaptation.

Various studies aimed to analyze the transmission of CWD to transgenic mice expressing human PrP have consistently given negative results (9-11), indicating a strong species barrier. This conclusion is consistent with our many failed experiments to attempt converting human PrPC with natural CWD, even after pushing the PMCA conditions (see figure 1). We found successful conversion only after adaptation of the CWD prion strain by successive passages in vitro or in cervid transgenic mice. We are not aware that in any of the transgenic mice studies the inoculum used was a previously stabilized CWD strain. Although, it has been shown that strain stabilization in vitro by PMCA (17;26) and in vivo using experimental rodents (36) has similarities with the strain adaptation process occurring in natural hosts, we cannot rule out that the type of CWD strain adaptation that is required to produce strains transmissible to humans may take much longer time in cervids or not occur at all. An important experiment will be to study transmissibility to humanized transgenic mice of CWD passed experimentally in deer several times. Besides the importance of our results for public health in relation to the putative transmissibility of CWD to humans, our data also illustrate a very important and novel scientific concept related to the mechanism of prion transmission across species barriers. Today the view is that species barrier is mostly controlled by the degree of similarity on the sequence of the prion protein between the host and the infectious material (4). In our study we show that the strain and moreover the stabilization of the strain plays a major role in the inter-species transmission. In our system there is no change on the protein sequence, but yet strain adaptation results in a complete change on prion transmissibility with potentially dramatic consequences. Therefore, our findings lead to a new view of the species barrier that should not be seen as a static process, but rather a dynamic biological phenomenon that can change over time when prion strains mature and evolve. It remains to be investigated if other species barriers also change upon progressive strain adaptation of other prion forms (e.g. the sheep/human barrier).

Our results have far-reaching implications for human health, since they indicate that cervid PrPSc can trigger the conversion of human PrPC into PrPSc, suggesting that CWD might be infectious to humans. Interestingly our findings suggest that unstable strains from CWD affected animals might not be a problem for humans, but upon strain stabilization by successive passages in the wild, this disease might become progressively more transmissible to man.

Generation of a New Form of Human PrPScin Vitro by Interspecies Transmission from Cervid Prions*

Marcelo A. Barria‡, Glenn C. Telling§, Pierluigi Gambetti¶, James A. Mastrianni‖ and Claudio Soto‡,1 + Author Affiliations

From the ‡Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, Houston, Texas 77030, the §Departments of Microbiology, Immunology, and Molecular Genetics and Neurology, Sanders Brown Center on Aging, University of Kentucky Medical Center, Lexington, Kentucky 40506, the ¶Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, and the ‖Department of Neurology, The University of Chicago, Chicago, Illinois 60637 1 To whom correspondence should be addressed: University of Texas Medical School at Houston, 6431 Fannin St., Houston, TX 77030. Tel.: 713-500-7086; Fax: 713-500-0667; E-mail:


Prion diseases are infectious neurodegenerative disorders that affect humans and animals and that result from the conversion of normal prion protein (PrPC) into the misfolded prion protein (PrPSc). Chronic wasting disease (CWD) is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. Determining the risk of transmission of CWD to humans is of utmost importance, considering that people can be infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the misfolded form by CWD PrPSc, we performed experiments using the protein misfolding cyclic amplification technique, which mimics in vitro the process of prion replication. Our results show that cervid PrPSc can induce the conversion of human PrPC but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, the newly generated human PrPSc exhibits a distinct biochemical pattern that differs from that of any of the currently known forms of human PrPSc. Our results also have profound implications for understanding the mechanisms of the prion species barrier and indicate that the transmission barrier is a dynamic process that depends on the strain and moreover the degree of adaptation of the strain. If our findings are corroborated by infectivity assays, they will imply that CWD prions have the potential to infect humans and that this ability progressively increases with CWD spreading.


Wednesday, September 08, 2010 CWD PRION CONGRESS SEPTEMBER 8-11 2010



Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates

Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Aru Balachandran,2 Jürgen Richt,3 Vincent Beringue,4 Juan-Maria Torres,5 Paul Brown,1 Bob Hills6 and Jean-Philippe Deslys1

1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Canadian Food Inspection Agency; Ottawa, ON Canada; 3Kansas State University; Manhattan, KS USA; 4INRA; Jouy-en-Josas, France; 5INIA; Madrid, Spain; 6Health Canada; Ottawa, ON Canada

†Presenting author; Email:

The constant increase of chronic wasting disease (CWD) incidence in North America raises a question about their zoonotic potential. A recent publication showed their transmissibility to new-world monkeys, but no transmission to old-world monkeys, which are phylogenetically closer to humans, has so far been reported. Moreover, several studies have failed to transmit CWD to transgenic mice overexpressing human PrP. Bovine spongiform encephalopathy (BSE) is the only animal prion disease for which a zoonotic potential has been proven. We described the transmission of the atypical BSE-L strain of BSE to cynomolgus monkeys, suggesting a weak cattle-to-primate species barrier. We observed the same phenomenon with a cattleadapted strain of TME (Transmissible Mink Encephalopathy). Since cattle experimentally exposed to CWD strains have also developed spongiform encephalopathies, we inoculated brain tissue from CWD-infected cattle to three cynomolgus macaques as well as to transgenic mice overexpressing bovine or human PrP. Since CWD prion strains are highly lymphotropic, suggesting an adaptation of these agents after peripheral exposure, a parallel set of four monkeys was inoculated with CWD-infected cervid brains using the oral route. Nearly four years post-exposure, monkeys exposed to CWD-related prion strains remain asymptomatic. In contrast, bovinized and humanized transgenic mice showed signs of infection, suggesting that CWD-related prion strains may be capable of crossing the cattle-to-primate species barrier. Comparisons with transmission results and incubation periods obtained after exposure to other cattle prion strains (c-BSE, BSE-L, BSE-H and cattle-adapted TME) will also be presented, in order to evaluate the respective risks of each strain.


Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease

Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2 Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany

†Presenting author; Email:

Chronic wasting disease (CWD) is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE) occurring in cervids in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report a direct biochemical demonstration of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected cervids. The presence of PrPTSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrPTSE was revealed by protein misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal muscles of CWD-infected WTD was estimated to be approximately 2000- to 10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE was located in muscle- associated nerve fascicles but not, in detectable amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.

Volume 18, Number 3—March 2012

Samuel E. Saunders1, Shannon L. Bartelt-Hunt, and Jason C. Bartz

Author affiliations: University of Nebraska-Lincoln, Omaha, Nebraska, USA (S.E. Saunders, S.L. Bartelt-Hunt); Creighton University, Omaha (J.C. Bartz)


Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting Disease


Most epidemiologic studies and experimental work have suggested that the potential for CWD transmission to humans is low, and such transmission has not been documented through ongoing surveillance (2,3). In vitro prion replication assays report a relatively low efficiency of CWD PrPSc-directed conversion of human PrPc to PrPSc (30), and transgenic mice overexpressing human PrPc are resistant to CWD infection (31); these findings indicate low zoonotic potential. However, squirrel monkeys are susceptible to CWD by intracerebral and oral inoculation (32). Cynomolgus macaques, which are evolutionarily closer to humans than squirrel monkeys, are resistant to CWD infection (32). Regardless, the finding that a primate is orally susceptible to CWD is of concern...


Reasons for Caution There are several reasons for caution with respect to zoonotic and interspecies CWD transmission. First, there is strong evidence that distinct CWD strains exist (36). Prion strains are distinguished by varied incubation periods, clinical symptoms, PrPSc conformations, and CNS PrPSc depositions (3,32). Strains have been identified in other natural prion diseases, including scrapie, BSE, and CJD (3). Intraspecies and interspecies transmission of prions from CWD-positive deer and elk isolates resulted in identification of >2 strains of CWD in rodent models (36), indicating that CWD strains likely exist in cervids. However, nothing is currently known about natural distribution and prevalence of CWD strains. Currently, host range and pathogenicity vary with prion strain (28,37). Therefore, zoonotic potential of CWD may also vary with CWD strain. In addition, diversity in host (cervid) and target (e.g., human) genotypes further complicates definitive findings of zoonotic and interspecies transmission potentials of CWD.

Intraspecies and interspecies passage of the CWD agent may also increase the risk for zoonotic CWD transmission. The CWD prion agent is undergoing serial passage naturally as the disease continues to emerge. In vitro and in vivo intraspecies transmission of the CWD agent yields PrPSc with an increased capacity to convert human PrPc to PrPSc (30). Interspecies prion transmission can alter CWD host range (38) and yield multiple novel prion strains (3,28). The potential for interspecies CWD transmission (by cohabitating mammals) will only increase as the disease spreads and CWD prions continue to be shed into the environment. This environmental passage itself may alter CWD prions or exert selective pressures on CWD strain mixtures by interactions with soil, which are known to vary with prion strain (25), or exposure to environmental or gut degradation.

Given that prion disease in humans can be difficult to diagnose and the asymptomatic incubation period can last decades, continued research, epidemiologic surveillance, and caution in handling risky material remain prudent as CWD continues to spread and the opportunity for interspecies transmission increases. Otherwise, similar to what occurred in the United Kingdom after detection of variant CJD and its subsequent link to BSE, years of prevention could be lost if zoonotic transmission of CWD is subsequently identified,...


Friday, November 09, 2012

Chronic Wasting Disease CWD in cervidae and transmission to other species

Tuesday, June 05, 2012

Captive Deer Breeding Legislation Overwhelmingly Defeated During 2012 Legislative Session

Friday, August 31, 2012


Wednesday, November 14, 2012


Thursday, March 29, 2012

atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012

NIAA Annual Conference April 11-14, 2011San Antonio, Texas

Thursday, February 23, 2012

Atypical Scrapie NOR-98 confirmed Alberta Canada sheep January 2012


not a clue


DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever many grains of salt you wish. ...tss)

The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people...Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie.....why????than the UK...then would the same mechanisms that make different strains of scrapie here make different strains of BSE...if the patterns are different in sheep and mice for scrapie.....could not the BSE be different in the cattle, in the mink, in the humans.......I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........bse.....scrapie Scrape the damn slide and put it into mice.....wait.....chop up the mouse brain and and spinal cord........put into some more mice.....dammit amplify the thing and start the damned research.....This is NOT rocket science...we need to use what we know and get off our butts and move....the whining about how long everything takes.....well it takes a whole lot longer if you whine for a year and then start the research!!! Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde.....for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a is a big fat sponge...the agent continues to eat the brain can't make slides anymore because the agent has never stopped........and the old slides that are stained with Hemolysin and Eosin......they get holier and holier and degenerate and continue...what you looked at 6 months ago is not there........Gambetti better be photographing every damned thing he is looking at.....

Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........if you want to move this thing along and shake the earth....then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any is ALL gonna be sporadic!!!

And, if there is a case.......there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats....and this may be their biggest downfall...

Thanks as always for your help. (Recently had a very startling revelation from a rather senior person in government here..........knocked me out of my must keep pushing. If I was a power person....I would be demanding that there be a least a million bovine tested as soon as possible and agressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the burden to bare if there is any coverup!"

again it was said years ago and it should be taken seriously....BSE will NEVER be found in the US! As for the BSE conference call...I think you did a great service to freedom of information and making some people feign integrity...I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture! I hope there is a confidential panel organized by the new government to really investigate this thing.

You need to watch your back........but keep picking at a buzzard to the just may get to the truth!!! (You probably have more support than you know. Too many people are afraid to show you or let anyone else know. I have heard a few things myself... you ask the questions that everyone else is too afraid to ask.)



Perceptions of unconventional slow virus in the USA

GAH WELLS Report of a visit to the U.S.A. April-May 1989


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

and they meant it $$$

Friday, January 29, 2010

14th International Congress on Infectious Diseases H-type and L-type Atypical BSE January 2010 (special pre-congress edition)

see page 114 ;


The familial mutations, Gajdusek proposed, lowered the barrier to such accidental conversion. "Thus," he wrote in 1996, "with these mutations, this ordinarily rare event becomes a ... dominant inherited trait." But Weissmann's qualification still remained to be refuted: the mutations might simply allow easier entry to a lurking virus. 202 Deadly Feast


something to think about for sure.

but i interpret this as (1st not the gold standard, just my opinion;-), as because of certain gene mutations, one or a family, would be more susceptible to the many different strains of TSE, and the many different proven routes and sources, (which will cause different symptoms, different incubation periods from onset of clinical symptoms to death, different parts of the brain infected, etc.). in other words, it's NOT the gene mutation that CAUSES the disease, but the fact that it makes you more SUSCEPTIBLE, to the TSEs from the surrounding environment, and PLUS accumulation, i think this plays a critical role. maybe there is a one dose scenario, but i think there is more of the 'accumulators' that go clinical, than the 'one dose'. and what is the threshold to sub-clinical to clinical ?

anyway, just pondering out loud here.

also, for anyone interested, there are some studies with links to follow here ;

Wednesday, March 28, 2012




Terry S. Singeltary Sr.

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