Development of Dose-Response Models of Creutzfeldt-Jakob Disease Infection in Nonhuman Primates for Assessing the Risk of Transfusion-Transmitted variant Creutzfeldt-Jakob Disease
Development of Dose-Response Models of Creutzfeldt-Jakob Disease Infection
in Nonhuman Primates for Assessing the Risk of Transfusion-Transmitted variant
Creutzfeldt-Jakob Disease
Yin Huanga, Luisa Gregorib, Steven A. Andersona, David M. Asherb and Hong
Yanga# + Author Affiliations
Office of Biostatistics & Epidemiology, U.S. Food and Drug
Administration, Silver Spring, Maryland, USAa Office of Blood Research and
Review, U.S. Food and Drug Administration, Silver Spring, Maryland, USAb
ABSTRACT
Estimates for the risk of transmitting variant Creutzfeldt-Jakob
disease (vCJD) via blood transfusion have largely relied on data from rodent
experiments, but the relationship between dose (amount of infected blood) and
response (vCJD infection) has never been well quantified. The goal of this study
was to develop a dose-response model based on nonhuman primate data to better
estimate the likelihood of transfusion-transmitted vCJD (TTvCJD) in humans. Our
model used dose-response data from nonhuman primates inoculated intracerebrally
(IC) with brain tissues of patients with sporadic and familial CJD. We analyzed
the data statistically using a beta-Poisson dose-response model. We further
adjusted model parameters to account for the differences in infectivity between
blood and brain tissue and in transmission efficiency between intravenous (IV)
and IC routes to estimate dose-dependent TTvCJD infection.
*** The model estimates a
mean infection rate of 76% among recipients who receive one unit of whole blood
collected from an infected donor near the end of the incubation period. The
nonhuman primate model provides estimates that are more consistent with those
derived from a risk analysis of transfused non-leukoreduced red blood cells in
United Kingdom compared to prior estimates based on rodent models.
IMPORTANCE TTvCJD was recently identified as one of three emerging
infectious diseases posing the greatest immediate threat to the safety of the
blood supply. Cases of TTvCJD were reported in recipients of non-leukoreduced
red blood cells and coagulation Factor VIII manufactured from blood of UK
donors. As the quantity of abnormal prions (the causative agent of TTvCJD)
varies significantly in different blood components and products, it is necessary
to quantify the dose-response relationship for a wide range of doses for the
vCJD agent in transfused blood and plasma derivatives. In this paper we suggest
the first mechanistic dose-response model for TTvCJD infection based on data
from experiments with nonhuman primates. This new model may improve estimates of
the possible risk to humans.
FOOTNOTES ↵#Address correspondence to Hong Yang, Hong.Yang@fda.hhs.gov
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
can anyone say TSEAC meeting in 2014 ???
negative...tss
Tuesday, August 26, 2014
Blood reference materials from macaques infected with variant
Creutzfeldt-Jakob disease agent
Thursday, August 21, 2014
FDA Switzerland Reason For Recall Blood product, collected from a donor who
was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed
2014-05-16
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type
prion disease, what it ???
Monday, May 19, 2014
Variant CJD: 18 years of research and surveillance
Sunday, June 29, 2014
Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
Tuesday, August 12, 2014
*** MAD COW USDA TSE PRION COVER UP or JUST IGNORANCE, for the record
AUGUST 2014 ***
see history of record of either the biggest cover up of mad cow disease, or
one of the biggest blunders of the mad cow debacle, just my opinion of the
facts...tss
Monday, June 02, 2014
*** Confirmed Human BSE aka mad cow Variant CJD vCJD or nvCJD Case in Texas
***
WHAT IS THE BIG SECRET HERE ?
why no information on this case $
Sent: Wednesday, June 04, 2014 11:52 AM
Subject: RE: nvCJD Texas ???
Adult male from
Texas with extensive travel history. That’s the extent of the information I can
provide at this time.
......................................................
Carrie
Williams
Director of Media
Relations
512-776-7119
From: Terry S.
Singeltary Sr. [mailto:flounder9@verizon.net]
Sent: Wednesday, June 04, 2014 11:51 AM
To: Williams,Carrie C (DSHS)
Subject: Re: nvCJD Texas ???
Sent: Wednesday, June 04, 2014 11:51 AM
To: Williams,Carrie C (DSHS)
Subject: Re: nvCJD Texas ???
Thank you for your kind reply. can you please
tell me anything else? age? sex? length of stay here in USA, diet, surgeries,
blood, etc., anything???
kind regards, terry
Greetings Carrie,I am wondering if there is any validity to this news report, and if so, is there a statement from DSHS or anyone else in Texas ?Published On: Mon, Jun 2nd, 2014Outbreak News / US News | By Robert HerrimanTexas: Variant Creutzfeldt-Jakob Disease death confirmed, infection likely occurred overseas
http://www.theglobaldispatch.com/texas-variant-creutzfeldt-jakob-disease-death-confirmed-infection-likely-occurred-overseas-94391/
kind regards,terry
*** Confirmed Human BSE aka mad cow Variant CJD vCJD or nvCJD Case in Texas
***
Tuesday, April 01, 2014
*** Questions linger in U.S. CJD cases 2005, and still do in 2014 ***
Monday, August 18, 2014
*** Barriers to Creutzfeldt-Jakob Disease Autopsies, California and the
USA
Saturday, July 07, 2012
Class II, Blood products, collected from a donor who was at risk for
variant Creutzfeldt-Jakob disease ( vCJD) USA
Enforcement Report
Monday, June 11, 2012
Guidance for Industry Draft Guidance for Industry: Amendment to “Guidance
for Industry: Revised Preventive Measures to Reduce the Possible Risk of
Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease
by Blood and Blood Products”
IN SHORT ;
“However, based on animal studies, as well as on FDA risk assessments, the
possibility of vCJD transmission by a U.S.-licensed plasma derivative, while
extremely small, cannot be absolutely ruled out. For these reasons, the
recommendations for labeling for plasma derivatives will include mention of vCJD
for the first time, and the potential risk for its transmission. The recommended
elements of the warning label for CJD are unchanged and continue to describe its
transmission as a theoretical risk, given that there is no confirmed evidence
that CJD is transmitted by blood (Refs. 4-7).“
IN FULL, as follows ;
Monday, June 11, 2012
Guidance for Industry Draft Guidance for Industry: Amendment to “Guidance
for Industry: Revised Preventive Measures to Reduce the Possible Risk of
Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease
by Blood and Blood Products”
Friday, June 29, 2012
Highly Efficient Prion Transmission by Blood Transfusion
Sunday, June 3, 2012
A new neurological disease in primates inoculated with prion-infected blood
or blood components
Sunday, March 09, 2014
A Creutzfeldt-Jakob Disease (CJD) Lookback Study: Assessing the Risk of
Blood Borne Transmission of Classic Forms of Creutzfeldt-Jakob Disease
FDA TSEAC CIRCUS AND TRAVELING ROAD SHOW FOR THE TSE PRION DISEASES
Sunday, April 06, 2014
SPORADIC CJD and the potential for zoonotic transmission there from, either
directly or indirectly via friendly fire iatrogenic mode, evidence to date
Wednesday, December 11, 2013
*** Detection of Infectivity in Blood of Persons with Variant and Sporadic
Creutzfeldt-Jakob Disease ***
what is the BIG SECRET about this recent case of nvCJD in Texas ???
Monday, June 02, 2014
*** Confirmed Human BSE aka mad cow Variant CJD vCJD or nvCJD Case in Texas
Tuesday, April 01, 2014
*** Questions linger in U.S. CJD cases 2005, and still do in 2014 ***
Sunday, March 09, 2014
A Creutzfeldt-Jakob Disease (CJD) Lookback Study: Assessing the Risk of
Blood Borne Transmission of Classic Forms of Creutzfeldt-Jakob Disease
FDA TSEAC CIRCUS AND TRAVELING ROAD SHOW FOR THE TSE PRION DISEASES
Sunday, April 06, 2014
SPORADIC CJD and the potential for zoonotic transmission there from, either
directly or indirectly via friendly fire iatrogenic mode, evidence to date
Wednesday, September 10, 2014
Creutzfeldt-Jakob disease (CJD) biannual update (August 2014), with updated
guidance on decontamination of gastrointestinal endoscopy equipment Research and
analysis
Tuesday, September 16, 2014
mad cow scaremongers consumerfreedom.com December 20, 2003 article and a
2014 review
Wednesday, September 17, 2014
*** Cost benefit analysis of the development and use of ante-mortem tests
for transmissible spongiform encephalopathies ***
snip... In summary, none of the respondents indicated that a live test for
BSE was likely to be available in the immediate future. Nevertheless, it is
known that at least three commercial companies that were not amongst the
respondents are still interested in marketing a test for CJD in humans, and can
legitimately be considered to have a real interest in the testing of bovines.
This is no longer a priority for them however, and will probably not be
progressed if they fail to gain approval for the testing of human blood.
snip...see full text ;
Wednesday, September 17, 2014
*** Cost benefit analysis of the development and use of ante-mortem tests for
transmissible spongiform encephalopathies ***
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
Transmissible Spongiform Encephalopathy TSE Prion Disease have now been
discovered in a wide verity of species across North America. typical C-BSE,
atypical L-type BASE BSE, atypical H-type BSE, atypical H-G BSE, of the bovine,
typical and atypical Scrapie strains, in sheep and goats, with atypical Nor-98
Scrapie spreading coast to coast in about 5 years. Chronic Wasting Disease CWD
in cervid is slowly spreading without any stopping it in Canada and the USA and
now has mutated into many different strains. Transmissible Mink Encephalopathy
TME outbreaks. These Transmissible Spongiform Encephalopathy TSE Prion Disease
have been silently mutating and spreading in different species in North America
for decades.
The USDA, FDA, et al have assured us of a robust Triple BSE TSE prion
Firewall, of which we now know without a doubt, that it was nothing but ink on
paper. Since the 1997 mad cow feed ban in the USA, literally tons and tons of
banned mad cow feed has been put out into commerce, never to return, as late as
December of 2013, serious, serious breaches in the FDA mad cow feed ban have
been documented. The 2004 enhanced BSE surveillance program was so flawed, that
one of the top TSE prion Scientist for the CDC, Dr. Paul Brown stated ; Brown,
who is preparing a scientific paper based on the latest two mad cow cases to
estimate the maximum number of infected cows that occurred in the United States,
said he has "absolutely no confidence in USDA tests before one year ago" because
of the agency's reluctance to retest the Texas cow that initially tested
positive.
see ;
The BSE surveillance and testing have also been proven to be flawed, and
the GAO and OIG have both raised serious question as to just how flawed it has
been (see GAO and OIG reports). North America has more documented TSE prion
disease, in different documented species (excluding the Zoo BSE animals in the
EU), then any other place on the Globe. This does not include the very
likelihood that TSE prion disease in the domestic feline and canine have been
exposed to high doses of the TSE prion disease vid pet food. To date, it’s still
legal to include deer from cwd zone into pet food or deer food. Specified Risk
Material i.e. SRM bans still being breach, as recently as just last month.
nvCJD or what they now call vCJD, another case documented in Texas last
month, with very little information being released to the public on about this
case? with still the same line of thought from federal officials, ‘it can’t
happen here’, so another vCJD blamed on travel of a foreign animal disease from
another country, while ignoring all the BSE TSE Prion risk factors we have here
in the USA and Canada, and the time that this victim and others, do spend in the
USA, and exposed to these risk factors, apparently do not count in any way with
regard to risk factor. a flawed process of risk assessment.
sporadic CJD, along with new TSE prion disease in humans, of which the
young are dying, of which long duration of illness from onset of symptoms to
death have been documented, only to have a new name added to the pot of prion
disease i.e. sporadic GSS, sporadic FFI, and or VPSPR. I only ponder how a
familial type disease could be sporadic with no genetic link to any family
member? when the USA is the only documented Country in the world to have
documented two different cases of atypical H-type BSE, with one case being
called atypical H-G BSE with the G meaning Genetic, with new science now showing
that indeed atypical H-type BSE is very possible transmitted to cattle via oral
transmission (Prion2014). sporadic CJD and VPSPR have been rising in Canada,
USA, and the UK, with the same old excuse, better surveillance. You can only use
that excuse for so many years, for so many decades, until one must conclude that
CJD TSE prion cases are rising. a 48% incease in CJD in Canada is not just a
blip or a reason of better surveillance, it is a mathematical rise in numbers.
More and more we are seeing more humans exposed in various circumstance in the
Hospital, Medical, Surgical arenas to the TSE Prion disease, and at the same
time in North America, more and more humans are becoming exposed to the TSE
prion disease via consumption of the TSE prion via deer and elk, cattle, sheep
and goats, and for those that are exposed via or consumption, go on to further
expose many others via the iatrogenic modes of transmission of the TSE prion
disease i.e. friendly fire. I pondered this mode of transmission via the victims
of sporadic FFI, sporadic GSS, could this be a iatrogenic event from someone
sub-clinical with sFFI or sGSS ? what if?
Two decades have passed since Dr. Ironside first confirmed his first ten
nvCJD victims in 1995. Ten years later, 2005, we had Dr. Gambetti and his first
ten i.e. VPSPR in younger victims. now we know that indeed VPSPR is
transmissible. yet all these TSE prion disease and victims in the USA and Canada
are being pawned off as a spontaneous event, yet science has shown, the
spontaneous theory has never been proven in any natural case of TSE prion
disease, and scientist have warned, that they have now linked some sporadic CJD
cases to atypical BSE, to atypical Scrapie, and to CWD, yet we don’t here about
this in the public domain. We must make all human and animal TSE prion disease
reportable in every age group, in ever state and internationally, we must have a
serious re-evaluation and testing of the USA cattle herds, and we must ban
interstate movement of all cervids. Any voluntary effort to do any of this will
fail. Folks, we have let the industry run science far too long with regards to
the TSE prion disease. While the industry and their lobbyist continues to funnel
junk science to our decision policy makers, Rome burns. ...end
REFERENCES
Sunday, June 29, 2014
Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
Tuesday, August 12, 2014
MAD COW USDA TSE PRION COVER UP or JUST IGNORANCE, for the record AUGUST
2014
Monday, July 28, 2014
Mitigating the Risk of Transmission and Environmental Contamination of
Transmissible Spongiform Encephalopathies 2013 Annual Report
Wednesday, September 10, 2014
Creutzfeldt-Jakob disease (CJD) biannual update (August 2014), with updated
guidance on decontamination of gastrointestinal endoscopy equipment
Research and analysis
PLEASE REMEMBER ;
The Akron, Ohio-based CJD Foundation said the Center for Disease Control
revised that number in October of 2004 to about one in 9,000 CJD cases per year
in the population group age 55 and older.
HAVE YOU GOT YOUR CJD QUESTIONNAIRE ASKING REAL QUESTIONS PERTAINING TO
ROUTE AND SOURCE OF THE TSE AGENT THAT KILLED YOUR LOVED ONE ???
if not, why not...
Friday, November 30, 2007
CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION
TSS
posted by Terry S. Singeltary Sr. | 2:30 PM
|
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