sporadic Creutzfeldt-Jakob Disease update As at 5th November 2012 UK, USA, AND CANADA
UK
As at 5th November 2012
Summary of vCJD cases
Deaths
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
Alive
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
CREUTZFELDT-JAKOB DISEASE SURVEILLANCE IN THE UK
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.
snip...
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)
snip...
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.
snip...
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.
snip...
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
snip...
???
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.
LANCET INFECTIOUS DISEASE JOURNAL
Volume 3, Number 8 01 August 2003
Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem.
49-year-old Singeltary is one of a number of people who have remained
largely unsatisfied after being told that a close relative died from a rapidly
progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease
(CJD). So he decided to gather hundreds of documents on transmissible spongiform
encephalopathies (TSE) and realised that if Britons could get variant CJD from
bovine spongiform encephalopathy (BSE), Americans might get a similar disorder
from chronic wasting disease (CWD)the relative of mad cow disease seen among
deer and elk in the USA. Although his feverish search did not lead him to the
smoking gun linking CWD to a similar disease in North American people, it did
uncover a largely disappointing situation.
Singeltary was greatly demoralised at the few attempts to monitor the
occurrence of CJD and CWD in the USA. Only a few states have made CJD
reportable. Human and animal TSEs should be reportable nationwide and
internationally, he complained in a letter to the Journal of the American
Medical Association (JAMA 2003; 285: 733). I hope that the CDC does not continue
to expect us to still believe that the 85% plus of all CJD cases which are
sporadic are all spontaneous, without route or source.
Until recently, CWD was thought to be confined to the wild in a small
region in Colorado. But since early 2002, it has been reported in other areas,
including Wisconsin, South Dakota, and the Canadian province of Saskatchewan.
Indeed, the occurrence of CWD in states that were not endemic previously
increased concern about a widespread outbreak and possible transmission to
people and cattle.
To date, experimental studies have proven that the CWD agent can be
transmitted to cattle by intracerebral inoculation and that it can cross the
mucous membranes of the digestive tract to initiate infection in lymphoid tissue
before invasion of the central nervous system. Yet the plausibility of CWD
spreading to people has remained elusive.
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.
SNIP...FULL TEXT ;
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
USA
*** 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.
Canada
*** 3. Final classification of 48 cases from 2009, 2010, 2011 and 2012 is
pending.
MEXICO
clueless
AS OF AUGUST 2012 ;
CJD UPDATE USA
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 CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE
INVESTIGATION JULY 2012
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
CENSORSHIP IS A TERRIBLE THING $$$
Canada has had a COVER-UP policy of mad cow disease since about the 17th
case OR 18th case of mad cow disease. AFTER THAT, all FOIA request were ignored
$$$
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
REPORT ON THE INVESTIGATION OF THE SIXTEENTH CASE OF BOVINE SPONGIFORM
ENCEPHALOPATHY (BSE) IN CANADA
Thursday, August 19, 2010
REPORT ON THE INVESTIGATION OF THE SEVENTEENTH CASE OF BOVINE SPONGIFORM
ENCEPHALOPATHY (BSE) IN CANADA
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
MEXICO IS UNDER or MIS DIAGNOSING CREUTZFELDT JAKOB DISEASE AND OTHER PRION
DISEASE SOME WITH POSSIBLE nvCJD
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
31 USA SENATORS ASK PRESIDENT OBAMA TO HELP SPREAD MAD COW DISEASE 2012
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
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE
RISE IN NORTH AMERICA
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
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 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
Greetings,
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
UPDATE - CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO
BRAIN AND SPINAL CORD MATTER
Monday, March 29, 2010
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010
in Mesquite Texas
CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN
AND SPINAL CORD MATTER
Thursday, May 27, 2010
CDC - INQUIRY ABOUT vCJD DEATH OF SLAUGHTER HOUSE WORKER IRMA LINDA ANDABLO
Archive Number 20100405.1091 Published Date 05-APR-2010
Subject PRO/AH/EDR> Prion disease update 1010 (04)
snip...
[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)
U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?
(see video at bottom)
Sunday, September 6, 2009
MAD COW USA 1997
(SEE SECRET VIDEO)
Let's review some history ;
IDIOPATHIC BRAIN STEM NEURONAL CHROMATOLYSIS AND HIPPOCAMPAL
SCLEROSIS
(VET REC 1992, M Jeffrey, J W Wilesmith p359-362)
snip...
BRIEFING
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).
BD - THE LINE TO TAKE
2. Disease clinically similar to BSE but pathologically distinct. BD is NOT
a form of BSE.
snip...
R BRADLEY
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.
snip...
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.
W L GARDNER VHS
23 October 1992
92/10.23/2.2
''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$
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...
http://web.archive.org/web/20030327015011/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
Wednesday, October 08, 2008
Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein
related disorder of cattle?
''LINE TO TAKE"
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...
snip...
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
NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS
"All of the 15 cattle tested showed that the brains had abnormally
accumulated PrP"
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
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
2012 PRICE OF PRIONOPATHY POKER GOES UP $$$
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion
poker goes up again $
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until
now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
OR-10 15:25 - 15:40 VARIABLY PROTEASE-SENSITIVE PRIONOPATHY IS
TRANSMISSIBLE IN BANK VOLES Nonno
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
*** 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.
SEE USA PRION REPORTS HERE ;
Tuesday, November 6, 2012
Transmission of New Bovine Prion to Mice, Atypical Scrapie, BSE, and
Sporadic CJD, November-December 2012 update
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
*** 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.
2011
*** 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 Claudio.Soto@uth.tmc.edu The
latest version is at http://www.jbc.org/cgi/doi/10.1074/jbc.M110.198465
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 www.jbc.org 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: claudio.soto@uth.tmc.edu.
Abstract
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.
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010 CWD PRION CONGRESS SEPTEMBER 8-11 2010
CHRONIC WASTING DISEASE CWD RISK FACTORS FOR TRANSMISSION TO HUMANS
Envt.06:
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: emmanuel.comoy@cea.fr
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.
Envt.07:
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: dausm@rki.de
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)
Synopsis
Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting Disease
snip...
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...
snip...
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,...
snip...
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
COMMITTEE ON CAPTIVE WILDLIFE AND ALTERNATIVE LIVESTOCK and CWD 2009-2012 a
review
Wednesday, November 14, 2012
PENNSYLVANIA 2012 THE GREAT ESCAPE OF CWD INVESTIGATION MOVES INTO
LOUISIANA and INDIANA
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
MEXICO NOR98 ATYPICAL SCRAPIE
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 year.......it is a big fat sponge...the agent
continues to eat the brain ......you 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
action........it 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
chair........you 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 them.......like a
buzzard to the bone...you 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.)
END...TSS
IN CONFIDENCE
Perceptions of unconventional slow virus in the USA
GAH WELLS Report of a visit to the U.S.A. April-May 1989
snip...
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. ...page 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
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
RIP MOM 12/14/97 CONFIRMED HVCJD
layperson
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
1:10 PM
