Preclinical Detection of Variant CJD and BSE Prions in Blood
Published: June 12, 2014 DOI: 10.1371/journal.ppat.1004202 Article About
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Introduction Methods Results Discussion Supporting Information Acknowledgments
Author Contributions References Reader Comments (0) Media Coverage (3) Figures
Abstract
The emergence of variant Creutzfeldt Jakob Disease (vCJD) is considered a
likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy
(BSE) agent. More recently, secondary vCJD cases were identified in patients
transfused with blood products prepared from apparently healthy donors who later
went on to develop the disease. As there is no validated assay for detection of
vCJD/BSE infected individuals the prevalence of the disease in the population
remains uncertain. In that context, the risk of vCJD blood borne transmission is
considered as a serious concern by health authorities. In this study,
appropriate conditions and substrates for highly efficient and specific in vitro
amplification of vCJD/BSE agent using Protein Misfolding Cyclic Amplification
(PMCA) were first identified. This showed that whatever the origin (species) of
the vCJD/BSE agent, the ovine Q171 PrP substrates provided the best
amplification performances. These results indicate that the homology of PrP
amino-acid sequence between the seed and the substrate is not the crucial
determinant of the vCJD agent propagation in vitro. The ability of this method
to detect endogenous vCJD/BSE agent in the blood was then defined. In both sheep
and primate models of the disease, the assay enabled the identification of
infected individuals in the early preclinical stage of the incubation period.
Finally, sample panels that included buffy coat from vCJD affected patients and
healthy controls were tested blind. The assay identified three out of the four
tested vCJD affected patients and no false positive was observed in 141 healthy
controls. The negative results observed in one of the tested vCJD cases concurs
with results reported by others using a different vCJD agent blood detection
assay and raises the question of the potential absence of prionemia in certain
patients.
Author Summary Variant Creutzfeldt Jakob Disease (vCJD) cases were
identified in patients who received blood products that had been prepared from
donors who later developed the disease. The blood borne transmission of vCJD is
a major concern for blood transfusion banks, plasma derived products
manufacturers and public health authorities. A vCJD blood screening test would
represent an ideal solution for identifying donors/blood donations that might be
at risk. In this study, we describe a blood assay which is based on the in vitro
amplification of vCJD agent by Protein Misfolding Cyclic Amplification (PMCA).
In vCJD animal models (sheep and primate), the assay enabled the identification
of infected individuals in a very early stage of the asymptomatic incubation
phase. We also provide evidence of the high specificity and the high analytical
sensitivity of this assay using blood samples from vCJD affected and healthy
patients.
snip...
Despite all the remaining difficulties, the results obtained so far by two
different methodologies (PMCA as presented here and the abnormal PrP capture),
and the rapid progress of QuIC derived technologies, allow potential new
possibilities for vCJD screening and the prevention of its iatrogenic
transmission.
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 ***
Monday, May 19, 2014
Variant CJD: 18 years of research and surveillance
Saturday, June 14, 2014
Rep. Rosa DeLauro (D-CT) Calls for Briefing on Beef Recalled for Mad Cow
Potential Rep. Rosa DeLauro (D-CT)
Monday, June 9, 2014
TEXAS MAD COW COVER UP (human BSE) AGAIN IN TEXAS, Mr. President Sir, we
need your help please
Governor Rick Perry has done everything he can to cover up mad cow disease
and human TSE prion disease there from in Texas over the last 15 years or so. We
have another nvCJD case here in Texas i.e. human BSE, still no information there
from, another lame excuse, typical though, and more junk science, we need help
Mr. President...
Thursday, June 12, 2014
*** Missouri Firm Recalls Ribeye and Carcass Products That May Contain
Specified Risk Materials 4,012 pounds of fresh beef products because the dorsal
root ganglia may not have been completely removed
Seven main threats for the future linked to prions
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases
constitute an unforeseen first threat that could sharply modify the European
approach to prion diseases.
Second threat
snip...
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
*** but the possibility that a small proportion of human cases so far
classified as "sporadic" CJD are of zoonotic origin could not be excluded.
Moreover, transmission experiments to non-human primates suggest that some TSE
agents in addition to Classical BSE prions in cattle (namely L-type Atypical
BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic
wasting disease (CWD) agents) might have zoonotic potential.
snip...
***In addition, non-human primates are specifically susceptible for
atypical BSE as demonstrated by an approximately 50% shortened incubation time
for L-type BSE as compared to C-type. Considering the current scientific
information available, it cannot be assumed that these different BSE types pose
the same human health risks as C-type BSE or that these risks are mitigated by
the same protective measures.
***Infectivity in skeletal muscle of BASE-infected cattle
***feedstuffs- It also suggests a similar cause or source for atypical BSE
in these countries.
Saturday, August 4, 2012
Final Feed Investigation Summary – California ATYPICAL L-TYPE BASE BSE Case
- July 2012
PO-028: Oral transmission of L-type bovine spongiform encephalopathy
(L-BSE) in primate model Microcebus murinus
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans.
*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada
seeing an extreme increase of 48% between 2008 and 2010 ***
Sunday, October 13, 2013
*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012
Tuesday, April 01, 2014
*** Questions linger in U.S. CJD cases 2005, and still do in 2014
Monday, June 9, 2014
*** TEXAS MAD COW COVER UP (human BSE) AGAIN IN TEXAS, Mr. President Sir,
we need your help please
Governor Rick Perry has done everything he can to cover up mad cow disease
and human TSE prion disease there from in Texas over the last 15 years or so. We
have another nvCJD case here in Texas i.e. human BSE, still no information there
from, another lame excuse, typical though, and more junk science, we need help
Mr. President...
what’s the big secret about the age and history of this poor gentleman ???
MAD COW COVER UP USA, THE EVIDENCE MOUNTS $$$
Monday, June 02, 2014
*** Confirmed Human BSE aka mad cow Variant CJD vCJD or nvCJD Case in Texas
Friday, April 25, 2014
Accuracy of administrative diagnostic data for pathologically confirmed
cases of Creutzfeldt-Jakob disease
Article in Press
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