Article in Press
Accuracy of administrative diagnostic data for pathologically confirmed
cases of Creutzfeldt-Jakob disease in Massachusetts, 2000-2008
Jed A. Barash, MD Affiliations Department of Medicine, Yale University
School of Medicine, Robert Wood Johnson Foundation Clinical Scholars Program,
New Haven, CT Department of Neurology, Veterans Affairs Medical Center, West
Haven, CT Corresponding Author InformationAddress correspondence to Jed A.
Barash, MD, Lahey Clinic, Department of Neurology, 41 Mall Rd, Burlington, MA
01805. email address, James K. West, PhD Affiliations Bureau of Infectious
Diseases, Massachusetts Department of Public Health, Boston, MA , Alfred DeMaria
Jr., MD Affiliations Bureau of Health Statistics, Research, and Evaluation,
Massachusetts Department of Public Health, Jamaica Plain, MA published online 10
April 2014. Corrected Proof
Abstract
Background Creutzfeldt-Jakob disease (CJD) is a transmissible disorder that
is monitored by public health authorities at the state and national levels in
the United States. Little is known about the current accuracy and concurrence of
CJD diagnoses across national and state sources of surveillance data.
Methods Using multiple sources, including the National Prion Disease
Pathology Surveillance Center (NPDPSC) registry, we sought to identify all
deceased Massachusetts patients with pathologically diagnosed CJD between 2000
and 2008. Pathologically verified CJD cases were then matched to their
respective records in the Massachusetts hospital discharge and death certificate
datasets. Using these data, we also aimed to estimate the sensitivity and
specificity of death certificate diagnoses.
Results Death certificate and hospital discharge dataset diagnoses of CJD
combined accounted for 80% (35 of 44) of pathologically confirmed cases. The
estimated sensitivity and specificity for death certificate diagnoses alone were
71% (27 of 38) and 75% (9 of 12), respectively.
Conclusions Death certificate diagnoses were less sensitive for
pathologically confirmed CJD than reported previously. Increasing reliance on
autopsy over biopsy and an expanding spectrum of health care delivery may be
responsible for this discrepancy. The findings reported here underscore the
value of using multiple mechanisms in national CJD surveillance.
Key Words: Prion diseases, Surveillance, Death certificate
J Neurol Neurosurg Psychiatry published online August 21, 2013
Genevieve M J A Klug, Handan Wand, Marion Simpson, et al.
Intensity of human prion disease surveillance predicts observed disease
incidence
ABSTRACT
Background Prospective national screening and surveillance programmes serve
a range of public health functions. Objectively determining their adequacy and
impact on disease may be problematic for rare disorders. We undertook to assess
whether objective measures of disease surveillance intensity could be developed
for the rare disorder sporadic Creutzfeldt–Jakob disease (CJD) and whether such
measures correlate with disease incidence.
Method From 10 countries with national human prion disease surveillance
centres, the annual number of suspected prion disease cases notified to each
national unit (n=17 610), referrals for cerebrospinal fluid (CSF) 14-3-3 protein
diagnostic testing (n=28 780) and the number of suspect cases undergoing
diagnostic neuropathological examination (n=4885) from 1993 to 2006 were
collected. Age and survey year adjusted incidence rate ratios with 95% CIs were
estimated using Poisson regression models to assess risk factors for sporadic,
non-sporadic and all prion disease cases. Results Age and survey year adjusted
analysis showed all three surveillance intensity measures (suspected human prion
disease notifications, 14-3-3 protein diagnostic test referrals and
neuropathological examinations of suspect cases) significantly predicted the
incidence of sporadic CJD, non-sporadic CJD and all prion disease.
Conclusions Routine national surveillance methods adjusted as population
rates allow objective determination of surveillance intensity, which correlates
positively with reported incidence for human prion disease, especially sporadic
CJD, largely independent of national context. The predictive relationship
between surveillance intensity and disease incidence should facilitate more
rapid delineation of aberrations in disease occurrence and assessment of the
adequacy of disease monitoring by national registries.
snip...
COMMENT
This is the first study to directly address and verify previous suggestive
findings17 and prevailing assumptions that greater scrutiny of a population may
lead to higher rates of human prion disease detection and thereby reported
disease incidence. Integral to the more objective assessment approach described
in our study is the adjustment of surveillance detection methods as population
interrogation rates. Employing this method, we have shown that relatively
simple, accessible measures (clinical case recognition with notification made to
a national surveillance centre combined with a routine diagnostic test like CSF
14-3-3 protein detection and neuropathological examination) can be adjusted to
generate metrics of surveillance intensity, which correlate sufficiently with
sporadic CJD incidence to be predictive. The broad multinational context, very
large number of cases included and the extended time period of the study all add
support for the robustness of the findings. As such, our observations provide
important insight into factors that contribute to variations in reported prion
disease incidence, particularly for sporadic CJD.9 Nevertheless, in the absence
of universal autopsy, some uncertainty inevitably persists regarding the
ascertainment of all human prion disease cases and the absolute incidence of
CJD.
The observed predictive relationship between surveillance intensity and
sporadic CJD incidence was present despite the recognised clinical profile
variations across the sporadic CJD subtypes,11 18 suggesting that national
surveillance can be achieved for a disease through primarily relying on clinical
detection even when there is a somewhat diverse phenotypic spectrum. It is also
of interest that advanced age, well beyond that more typically associated with
sporadic CJD, does not appear to impede clinical recognition, with previous
studies suggesting that increased incidence appears to correlate with increased
referrals of suspect cases in the very elderly.17 19
The epidemiological history of human prion diseases, especially acquired
forms such as those related to the therapeutic use of cadaveric dura mater
explants and pituitary hormones20 as well as variant CJD21 and ongoing concerns
regarding transmission risks posed by routine surgery, including
nonneurosurgery, 22 23 should serve as a sobering precaution against any public
health complacency in relation to this group of diseases. The key objectives of
prospective national surveillance programmes are to ensure adequate detection of
the disease and accurate depiction of the epidemiological profile so that
significant departures in disease incidence or demographic characteristics can
be recognised.24 Our findings should subserve both of these objectives. As
described for variant CJD,21 an altered phenotype can indicate important
epidemiological changes with respect to disease aetiology. Notwithstanding this
influence, a more accurately defined and predictive relationship between
population surveillance intensity and disease recognition rates (with 95% CIs)
should facilitate more rapid and confident delineation of significant deviations
in national disease incidence for a given surveillance intensity and serve to
prompt more detailed evaluation of why this change has occurred, possibly
leading to more expeditious deployment of public health responses.
Our study revealed major variations, approximately two orders of magnitude,
in annual crude notification rates of persons with suspected prion disease
across the study period in the countries assessed. Although some of this
variation may be a natural finding based on variable population sizes, it
demonstrates the likely underappreciation of true differences when only drawing
comparisons of unadjusted, average disease incidence rates from countries with
varied population sizes. Over the study timeframe, CJD awareness and recognition
increased markedly both nationally and globally due to factors including the
bovine spongiform encephalopathy (BSE) epidemic, improved surveillance systems
and advances in diagnostic capabilities, in particular the CSF 14-3-3 diagnostic
test. These influences have contributed to improved notification and diagnostic
assessment of suspected cases, a feature reflected in the positive temporal
trends observed for suspect case and 14-3-3 CSF test referrals and, to a lesser
degree, with neuropathological examination in the participant countries.
Although temporal variation in predictor and outcome variables was significant
between the countries over the study period, the analysis of pooled data,
adjusted for time and age, demonstrated that time was independent of the
association between surveillance intensity measurements and incidence, further
underscoring the strength of this study.
Referrals for 14-3-3 CSF analysis in France and Germany were noticeably
higher than in other countries. We surmise this may be due to subsidisation of
the costs of testing and/or the strong tradition of employing CSF surrogate
biomarker detection in the evaluation of dementias, including CJD. In Hungary
and the Czech Republic, the lower number of referrals for 14-3-3 testing is due
to the later point at which 14-3-3 testing was introduced and adopted into the
criteria in comparison with France and Germany. However, despite the higher
levels of CSF testing in Germany and France, incidence was not increased in
comparison with other countries, suggesting that the correlation with sporadic
CJD incidence also relies on referral of suspect cases to a national reference
centre, as well as neuropathological examination. Furthermore, this finding
argues against a potential misconception from this study that widespread 14-3-3
CSF testing is required for optimal case ascertainment. The negative association
observed between CSF referrals and non-sporadic CJD cases may relate in part to
modest increases in prion protein gene (PRNP) testing observed over the study
timeframe, translating into a reduced likelihood of non-sporadic CJD cases
(mainly genetic) undergoing 14-3-3 CSF testing. This is a plausible explanation,
however, unverified in this study, with the negative association also possibly
related to the fact that CSF 14-3-3 protein detection was primarily developed
for sporadic CJD detection.
The multi-national context of the present study was an intended and
important design feature by which it was ensured relatively minor but ‘real
life’ variations in specific mechanisms of national prion disease surveillance
were encompassed. Despite this, the findings clearly demonstrate overall support
for a positive and predictive correlation between surveillance intensity and
sporadic CJD incidence; however, we note that this predictive association was
not observed in two of the nine countries. The reason for this is uncertain but
may relate to unapparent variations in surveillance methods employed within
these countries or a potential saturation point where no new cases are
identified despite increasing surveillance intensity.
Although the public health and epidemiological context of each disease
undergoing national screening or surveillance is relatively unique, and
therefore of limited direct comparability, the finding that observed population
diagnosis rates can be influenced by testing and resourcing issues is not unique
to CJD. HIV infection diagnosis in the UK is estimated at 74% of all infections,
while in Australia, the estimate is 85%–90%.25 26 The Australian epidemic
remains largely transmitted through male homosexual contact, a well-informed
group with a high rate of HIV testing.27 In contrast, the epidemic in the UK is
more heterogenous and often associated with migration to the UK from high
prevalence countries.28
So, in conclusion, our study has confirmed that routine national
surveillance methods adjusted as population rates allow objective determination
of surveillance intensity, which correlates positively with reported incidence
for human prion disease, especially sporadic CJD, largely independent of
national context. The predictive relationship between surveillance intensity and
disease incidence should facilitate more rapid delineation of aberrations in
disease occurrence and permit objective assessment of the adequacy of disease
monitoring by national registries. Further, the approach outlined in our study
could extend to other rare disorders, and should allow more objective assessment
of the adequacy of population scrutiny by extant or potential members of
surveillance consortia.
-------- Original Message --------
Subject: Challenging the Clinical Utility of the 14-3-3 Protein for the
Diagnosis of Sporadic Creutzfeldt-Jakob Disease
Date: Mon, 16 Jun 2003 16:38:34 –0500
From: "Terry S. Singeltary Sr."
To: Bovine Spongiform Encephalopathy
CC: CJDvoice , bloodcjd@yahoogroups.com
Challenging the Clinical Utility of the 14-3-3 Protein for the Diagnosis of
Sporadic Creutzfeldt-Jakob Disease
Michael D. Geschwind, MD, PhD; Jennifer Martindale, BS; Deborah Miller, MD;
Stephen J. DeArmond, MD, PhD; Jane Uyehara-Lock, MD; David Gaskin, MD; Joel H.
Kramer, PhD; Nicholas M. Barbaro, MD; Bruce L. Miller, MD
Arch Neurol. 2003;60:813-816.
Background Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and
fatal neurodegenerative disorder for which there is no noninvasive and
disease-specific test for premortem diagnosis. Previous studies have suggested
that, in the proper clinical context, the 14-3-3 protein in cerebrospinal fluid
is a reliable marker for sporadic CJD.
Objective To assess the sensitivity of the cerebrospinal fluid 14-3-3
protein test among patients with definite sporadic CJD.
Design and Setting We reviewed cases of sporadic CJD referred to our
institution that were ultimately proved by pathological examination and on which
cerebrospinal fluid 14-3-3 testing had been performed.
Participants Patients with CJD referred to our institution for clinical
and/or pathological evaluation (biopsy- or autopsy-confirmed diagnosis) from
January 1, 1998, through July 15, 2002, and on whom 14-3-3 testing had been
performed. Thirty-two such patients with definite sporadic CJD were
identified.
Main Outcome Measure The 14-3-3 test results, from various laboratories, in
these 32 patients.
Results Seventeen of the 32 patients had a positive result for the 14-3-3
test, yielding a sensitivity of only 53%. A positive 14-3-3 result was
significantly correlated with a shorter time between disease onset and the
lumbar puncture for the 14-3-3 test.
Conclusions Testing for the 14-3-3 protein is only modestly sensitive to
sporadic CJD, and we caution against ruling out a diagnosis of the disease on
the basis of a negative 14-3-3 result.
From the Departments of Neurology (Drs Geschwind, D. Miller, Kramer, and B.
L. Miller and Ms Martindale), Pathology (Drs DeArmond, Uyehara-Lock, and
Gaskin), and Neurosurgery (Dr Barbaro), University of California, San Francisco
Medical Center, San Francisco.
> Conclusions Testing for the 14-3-3 protein is only modestly sensitive
to sporadic CJD,
> and we caution against ruling out a diagnosis of the disease on the
basis of a negative > 14-3-3 result.
but how many were ruled out as having CJD with 14-3-3 ?
kinda makes the one-in-a-million myth, just that, a myth...TSS
Asante/Collinge et al, that BSE transmission to the 129-methionine genotype
can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc,
the commonest _sporadic_ CJD;
Original Contribution | June 2003
Challenging the Clinical Utility of the 14-3-3 Protein for the Diagnosis of
Sporadic Creutzfeldt-Jakob Disease
FREE Michael D. Geschwind, MD, PhD; Jennifer Martindale, BS; Deborah
Miller, MD; Stephen J. DeArmond, MD, PhD; Jane Uyehara-Lock, MD; David Gaskin,
MD; Joel H. Kramer, PhD; Nicholas M. Barbaro, MD; Bruce L. Miller, MD [+-]
Author Affiliations From the Departments of Neurology (Drs Geschwind, D. Miller,
Kramer, and B. L. Miller and Ms Martindale), Pathology (Drs DeArmond,
Uyehara-Lock, and Gaskin), and Neurosurgery (Dr Barbaro), University of
California, San Francisco Medical Center, San Francisco.
Arch Neurol. 2003;60(6):813-816. doi:10.1001/archneur.60.6.813. Text Size:
A A A Published online Article Tables References Comments ABSTRACT ABSTRACT |
METHODS | RESULTS | COMMENT | ARTICLE INFORMATION | REFERENCES Background
Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal
neurodegenerative disorder for which there is no noninvasive and
disease-specific test for premortem diagnosis. Previous studies have suggested
that, in the proper clinical context, the 14-3-3 protein in cerebrospinal fluid
is a reliable marker for sporadic CJD.
Objective To assess the sensitivity of the cerebrospinal fluid 14-3-3
protein test among patients with definite sporadic CJD.
Design and Setting We reviewed cases of sporadic CJD referred to our
institution that were ultimately proved by pathological examination and on which
cerebrospinal fluid 14-3-3 testing had been performed.
Participants Patients with CJD referred to our institution for clinical
and/or pathological evaluation (biopsy- or autopsy-confirmed diagnosis) from
January 1, 1998, through July 15, 2002, and on whom 14-3-3 testing had been
performed. Thirty-two such patients with definite sporadic CJD were
identified.
Main Outcome Measure The 14-3-3 test results, from various laboratories, in
these 32 patients.
Results Seventeen of the 32 patients had a positive result for the 14-3-3
test, yielding a sensitivity of only 53%. A positive 14-3-3 result was
significantly correlated with a shorter time between disease onset and the
lumbar puncture for the 14-3-3 test.
Conclusions Testing for the 14-3-3 protein is only modestly sensitive to
sporadic CJD, and we caution against ruling out a diagnosis of the disease on
the basis of a negative 14-3-3 result.
THE 14-3-3 protein is a normal neuronal protein that is released into
cerebrospinal fluid (CSF) in association with acute neuronal injury.1 It has
been suggested that the presence of 14-3-3 protein in CSF is a reliable marker
for Creutzfeldt-Jakob disease (CJD), with sensitivity and specificity for this
protein reported as high as 96% and 93% to 100%, respectively.2- 4 These reports
have recently led the World Health Organization to revise its diagnostic
criteria for probable sporadic CJD (sCJD) to allow substitution of a positive
14-3-3 test for a positive electroencephalogram, provided the disease has less
than a 2-year duration.5 Yet, a series of studies has suggested that both
sensitivity and specificity for sCJD are lacking with this test.1,6,7
Previous studies that have examined the sensitivity of the 14-3-3 protein
for CJD were performed in a single laboratory and did not restrict themselves to
pathology-proved cases.4,8,9 In this study, to assess the true sensitivity of
the 14-3-3 test, we included only cases that were pathology-proved for sCJD. In
addition, because 14-3-3 tests were sent by referring physicians to one or more
of several possible laboratories, this study may better reflect typical clinical
experience with 14-3-3 in the United States.
Ann Neurol. Author manuscript; available in PMC Aug 1, 2013. Published in
final edited form as: Ann Neurol. Aug 2012; 72(2): 278–285. doi:
10.1002/ana.23589 PMCID: PMC3458796 NIHMSID: NIHMS365401
Copyright notice and Disclaimer
RT-QuIC analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob
disease
Lynne I. McGuire, PhD,1 Alexander H. Peden, PhD,1 Christina D. Orrú, PhD,3
Jason M. Wilham, PhD,3 Nigel E. Appleford, Cbiol,2 Gary Mallinson, PhD,2 Mary
Andrews, BSc,1 Mark W. Head, PhD,1 Byron Caughey, PhD,3 Robert G. Will, FRCP,1
Richard S.G. Knight, FRCP,1 and Alison J.E. Green, PhD1 1The National CJD
Research & Surveillance Unit, University of Edinburgh, Edinburgh, Scotland,
UK 2Bristol Institute for Transfusion Sciences, NHS Blood and Transplant,
Bristol, UK 3Laboratory of Persistent Viral Disease, NIAID Rocky Mountain
Laboratories, National Institutes of Health, Montana, USA Corresponding author:
Dr Alison J.E. Green, The National CJD Research & Surveillance Unit,
University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom EH4
2XU, Tel no: + 44 (0)131 537 3075, Fax no: + 44 (0) 131 343 1404, Email:
Alison.Green@ed.ac.uk Small right arrow pointing to: The publisher's final
edited version of this article is available at Ann Neurol Small right arrow
pointing to: See other articles in PMC that cite the published article. Other
Sections▼
Abstract
INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION Supplementary
Material References
Abstract
Objective Current cerebrospinal fluid (CSF) tests for sporadic
Creutzfeldt-Jakob disease (sCJD) are based on the detection of surrogate markers
of neuronal damage such as CSF 14-3-3 which are not specific for sCJD. A number
of prion protein conversion assays have been developed, including real-time
quaking induced conversion (RT-QuIC). The objective of this study is to
investigate whether CSF RT-QuIC analysis could be used as a diagnostic test in
sCJD.
Methods An exploratory study was undertaken which analysed 108 CSF samples
from patients with neuropathologically confirmed sCJD or from control patients.
Of the 108 CSF samples 56 were from sCJD patients (30 female, 26 male, aged
31–84 years; 62.3 ± 13.5 years) and 52 were from control patients (26 female, 26
male, aged 43–84 years; 67.8 ± 10.4 years). A confirmatory group of 118 patients
were subsequently examined which consisted of 67 cases of neuropathologically
confirmed sCJD (33 female, 34 male, aged 39–82 years; 67.5 ± 9.0 years) and 51
control cases (26 female, 25 male, aged 36–87 years; 63.5 ± 11.6 years).
Results The exploratory study showed that RT-QuIC analysis had a
sensitivity of 91% and a specificity of 98% for the diagnosis of sCJD. These
results were confirmed in the confirmatory study which showed that CSF RT-QuIC
analysis had a sensitivity and specificity of 87% and 100% respectively.
Interpretation This study shows that CSF RT-QuIC analysis has the potential to
be a more specific diagnostic test for sCJD than current CSF tests.
Evidence-based guideline: Diagnostic accuracy of CSF 14-3-3 protein in
sporadic Creutzfeldt-Jakob disease
Report of the Guideline Development Subcommittee of the American Academy of
Neurology Taim Muayqil, MBBS, FRCPC Gary Gronseth, MD, FAAN Richard Camicioli,
MD, FRCPC
ABSTRACT
Objective: To assess the available evidence for the diagnostic accuracy of
CSF testing for protein 14-3-3 in patients with suspected sporadic
Creutzfeldt-Jakob disease (sCJD).
Methods: The authors performed a systematic review of the available
literature from 1995 to January 1, 2011, to identify articles involving patients
who were suspected of having sCJD and who had CSF analysis for protein 14-3-3.
Studies were rated according to the American Academy of Neurology classification
of evidence scheme for diagnostic studies, and recommendations were linked to
the strength of the evidence. A pooled estimate of sensitivity and specificity
was obtained for all studies rated Class II or higher. The question asked is
“Does CSF 14-3-3 protein accurately identify Creutzfeldt-Jakob disease (CJD) in
patients with sCJD?”
Results: The analysis was conducted on the basis of samples of 1,849
patients with suspected sCJD from 9 Class II studies. Assays for CSF 14-3-3
protein are probably moderately accurate in diagnosing sCJD: sensitivity 92%
(95% confidence interval [CI] 89.8–93.6), specificity 80% (95% CI 77.4–83.0),
likelihood ratio of 4.7, and negative likelihood ratio of 0.10. Recommendation:
For patients who have rapidly progressive dementia and are strongly suspected of
having sCJD and for whom diagnosis remains uncertain (pretest probability 20%–
90%), clinicians should order CSF 14-3-3 assays to reduce the uncertainty of the
diagnosis (Level B). Neurology® 2012;79:1499–1506
Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of
variant Creutzfeldt-Jakob disease
A Green, E Thompson, G Stewart, M Zeidler, J McKenzie, M MacLeod, J
Ironside, R Will, and R Knight The National Creutzfeldt-Jakob Disease
Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
Email: Alison.Green@ed.ac.uk Author information ► Copyright and License
information ► Copyright notice This article has been cited by other articles in
PMC.
Abstract
OBJECTIVES—The detection of the protein 14-3-3 in the CSF has been shown to
be a reliable and sensitive marker for sporadic Creutzfeldt-Jakob disease (CJD).
Other brain-specific proteins such as neuron specific enolase (NSE), S-100b, and
tau protein have also been reported to be increased in the CSF of patients with
sporadic CJD. In 1996a variant of CJD (vCJD) was described which is likely to be
causally linked to the bovine spongiform encephalopathy agent. This study
reports and compares the findings of CSF brain specific protein analysis in 45
patients with vCJD and in 34 control patients.
METHODS—The CSF from 45 patients with vCJD and 34 controls were
investigated for the presence of 14-3-3 by SDS-polyacrylamide gel
electrophoresis (SDS-PAGE) and western blotting with chemiluminescent detection.
Tau protein, S-100b, and NSE concentrations in CSF were measured using enzyme
immunoassays.
RESULTS—Protein 14-3-3 was detected in the CSF of 22/45 patients with vCJD
and in 3/34 controls. The mean concentrations of NSE, S-100b, and tau protein in
CSF were significantly raised in patients with vCJD compared with controls. The
positive predictive value of CSF 14-3-3 was 86% and the negative predictive
value was 63%. These values are lower than those reported for sporadic CJD. An
increased CSF tau had a positive predictive value of 93% and a negative
predictive value of 81%. The combination of CSF 14-3-3 and/or increased CSF tau
had a positive predictive value of 91% and a negative predictive value of 84%.
CONCLUSIONS—CSF protein 14-3-3 is not as useful a marker for vCJD as it is
for sporadic CJD. Increased concentration of CSF tau was found to be a sensitive
marker of vCJD but as concentrations may be increased in many forms of non-CJD
dementia, this may limit its usefulness as a diagnostic test.
Published online 30 January 2011 | Nature | doi:10.1038/news.2011.59
News
CJD diagnosis just got easier Test for Creutzfeldt–Jakob disease raises
hopes of speedier diagnosis.
Tiffany O'Callaghan
human prionIn prion diseases such as CJD, an isomer of a prion protein
takes on an abnormal shape.AP Photo/Professors Stanley Prusiner/Fred Cohen,
University of California San Francisco Medical School Invasive biopsy is
currently the only sure way to diagnose the degenerative neurological condition
Creutzfeldt–Jakob Disease (CJD). But a highly sensitive assay could change that,
providing a fast, accurate alternative for early diagnosis of this rare but
deadly condition.
snip...
So Atarashi and his colleagues used a new assay known as a real-time
quaking-induced conversion (RT-QUIC) assay. 'Quaking-induced' refers to in vitro
shaking, which researchers believe helps to accelerate the reactions, enabling
the assay to produce results more quickly.
The team tested cerebrospinal fluid samples from 18 people with CJD and 35
people with other neurodegenerative diseases. This pilot group produced no false
positives, and CJD was correctly diagnosed more than 83% of the time.
The researchers compared these results with those obtained using an
existing assay that tests for levels of a protein known as 14-3-3, which is a
marker for sporadic CJD. When tested on patient samples, the accuracy of 14-3-3
was 72.2%, whereas the specificity was 85.7%.
In a subsequent blind trial on 30 cerebrospinal fluid samples from
Australia, RT-QUIC showed 100% specificity, resulting in no false positives
among the 14 control samples, and correct diagnoses of 87.5%. 14-3-3 was equally
accurate, but the rate of false positives was much higher.
"This technique allows definitive ante-mortem confirmation of CJD," says
Atarashi, adding that this is currently difficult because it demands the
detection of PrPSc in patients' biopsy specimens.
Tuesday, November 08, 2011
Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob
Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011
Original Paper
Conclusions:These findings raise doubt about the possibility of a reliable
CJD surveillance only based on mortality data.
Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health
Crisis
full text with source references ;
re-Human Prion Diseases in the United States
Posted by flounder on 01 Jan 2010 at 18:11 GMT
I kindly disagree with your synopsis for the following reasons ;
snip...
I would kindly like to add to my initial
concerns, something I brought up years ago, and I believe that still hold true
today, more so even than when I first stated these concerns in 2003
;
routine passive mortality CJD surveillance USA ?
THIS has been proven not to be very useful in the U.K.;
THE EPIDEMIOLOGY OF CJD RG WILL 1984 (182 PAGES)
snip...
One reason for this was the _inaccuracy_ in coding of cases correctly certified as CJD Coding is carried out by staff who are not medically qualified and it is not surprising that coding errors occur in the processing of large numbers of certificates. In 1982, 12,000 certificates per week were processed at the office of population censuses and surveys by 15 coders and 6 checkers (Alderson et al., 1983). The occurrence of both inter- and intra-observer coding errors has been described (Curb et al., 1983) and the _inaccuracies_ of BOTH certification and coding discovered in this study _support_ the introduction of a more accurate system of death certificates and a more detailed and specific coding system...
snip...
http://web.archive.org/web/20040521215716/http://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf
routine passive mortality CJD surveillance USA ?
THIS has been proven not to be very useful in the U.K.;
THE EPIDEMIOLOGY OF CJD RG WILL 1984 (182 PAGES)
snip...
One reason for this was the _inaccuracy_ in coding of cases correctly certified as CJD Coding is carried out by staff who are not medically qualified and it is not surprising that coding errors occur in the processing of large numbers of certificates. In 1982, 12,000 certificates per week were processed at the office of population censuses and surveys by 15 coders and 6 checkers (Alderson et al., 1983). The occurrence of both inter- and intra-observer coding errors has been described (Curb et al., 1983) and the _inaccuracies_ of BOTH certification and coding discovered in this study _support_ the introduction of a more accurate system of death certificates and a more detailed and specific coding system...
snip...
http://web.archive.org/web/20040521215716/http://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf
Draft Proposal For The Monitoring of Creutzfeldt-Kakob Disease 1989 Dr. R. Will
snip...
IDENTIFICATION OF CASES
Cases of CJD may be identified from death certificates, but this alone is unlikely to provide adequate monitoring. ERRORS are made in certification and diagnosis; in the Oxford study death certificates were obtained on a series of known confirmed cases and CJD was mentioned in only 66% of certificates. In another series of 175 certified cases, 42 patients were judged not to have suffered from CJD after examination of case notes (7)...
full text;
http://web.archive.org/web/20050526035006/http://www.bseinquiry.gov.uk/files/yb/1989/05/00005001.pdf
snip...see my full text submission here ;
re-Human Prion Diseases in the United States
Posted by flounder on 01 Jan 2010 at 18:11 GMT
Views & Reviews
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in
the United States
Ermias D. Belay, MD, Ryan A. Maddox, MPH, Pierluigi Gambetti, MD and
Lawrence B. Schonberger, MD
+ Author Affiliations
From the Division of Viral and Rickettsial Diseases (Drs. Belay and
Schonberger and R.A. Maddox), National Center for Infectious Diseases, Centers
for Disease Control and Prevention, Atlanta, GA; and National Prion Disease
Pathology Surveillance Center (Dr. Gambetti), Division of Neuropathology,
Institute of Pathology, Case Western Reserve University, Cleveland, OH.
Address correspondence and reprint requests to Dr. Ermias D. Belay, 1600
Clifton Road, Mailstop A-39, Atlanta, GA 30333.
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment
on the CDC's attempts to monitor the occurrence of emerging forms of CJD.
Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al.
JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL
TEXT
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as
well
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North
America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember,
the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been
documented in North America, along with the typical scrapie's, and atypical
Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these
TSE in different species have been rendered and fed to food producing animals
for humans and animals in North America (TSE in cats and dogs ?), and that the
trading of these TSEs via animals and products via the USA and Canada has been
immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances
and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD
only theory in 2009. With all the science to date refuting it, to continue to
validate this old myth, will only spread this TSE agent through a multitude of
potential routes and sources i.e. consumption, medical i.e., surgical, blood,
dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and
the urgent need to make all human TSE in the USA a reportable disease, in every
state, of every age group, and to make this mandatory immediately without
further delay. The ramifications of not doing so will only allow this agent to
spread further in the medical, dental, surgical arena's. Restricting the
reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO
age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge,
Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al
and many more, that the world of TSE Transmissible Spongiform Encephalopathy is
far from an exact science, but there is enough proven science to date that this
myth should be put to rest once and for all, and that we move forward with a new
classification for human and animal TSE that would properly identify the
infected species, the source species, and then the route.
re-Diagnosis and treatment of rapidly progressive dementias
Greetings Dr. Geschwind, UCSF, Neurology et al,
Thank You for putting out this study to bring forth the challenges with all
the dementias, and diagnosis there from. Not having access to your full text
study, not knowing if the TSE prion disease was mentioned further into your
article, I wish to send the following information and submissions of this very
concern you bring forward.
My Mom died from the hvCJD ‘confirmed’, my Mema (her Mom) died with
moderate dementia or Alzheimer’s, and just got a call that my uncle Bo (my Moms
brother from Mema), was admitted again to the mental ward for aggression toward
his wife, he has severe dementia or Alzheimer’s, and my half brother from my Mom
died with severe mental retardation. he had been institutionalized for decades.
so, I am very much aware of the challenges that exist when trying to properly
diagnose an individual with rapid progressive dementia or Alzheimer’s or a
Transmissible Spongiform Encephalopathy TSE prion disease, like with my Mom i.e.
the Heidenhain Variant of Creutzfeldt Jakob disease, which was very, very rapid
from onset of first clinical symptoms to death, of about 3 months. we just never
could catch up with it.
What is Alzheimer’s anyway?
Alzheimer’s disease, Iatrogenic TSE, what if ???
snip...
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
Proposal ID: 29403
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease
have both been around a long time, and was discovered in or around the same time
frame, early 1900’s. Both disease, and it’s variants, in many cases are merely
names of the people that first discovered them. Both diseases are incurable and
debilitating brain disease, that are in the end, 100% fatal, with the
incubation/clinical period of the Alzheimer’s disease being longer than the TSE
prion disease. Symptoms are very similar, and pathology is very similar. I
propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation
disease, and that Alzheimer’s is Transmissible, and is a threat to the public
via the many Iatrogenic routes and sources. It was said long ago that the only
thing that disputes this, is Alzheimer’s disease transmissibility, or the lack
of. today, there is enough documented science (some confidential), that shows
that indeed Alzheimer’s is transmissible. The risk factor for friendly fire, and
or the pass-it-forward mode i.e. Iatrogenic transmission is a real threat, and
one that needs to be addressed immediately.
Methods
Through years of research, as a layperson, of peer review journals,
transmission studies, and observations of loved ones and friends that have died
from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant
Creutzfelt Jakob Disease CJD.
Results
The likelihood of many victims of Alzheimer’s disease from the many
different Iatrogenic routes and modes of transmission as with the TSE prion
disease. TSE prion disease survives ashing to 600 degrees celsius, that’s around
1112 degrees farenheit. you cannot cook the TSE prion disease out of meat. you
can take the ash and mix it with saline and inject that ash into a mouse, and
the mouse will go down with TSE. Prion Infected Meat-and-Bone Meal Is Still
Infectious after Biodiesel Production as well. the TSE prion agent also survives
Simulated Wastewater Treatment Processes. IN fact, you should also know that the
TSE Prion agent will survive in the environment for years, if not decades. you
can bury it and it will not go away. TSE prion agent is capable of infected your
water table i.e. Detection of protease-resistant cervid prion protein in water
from a CWD-endemic area. it’s not your ordinary pathogen you can just cook it
out and be done with. that’s what’s so worrisome about Iatrogenic mode of
transmission, a simple autoclave will not kill this TSE prion agent.
Conclusions
There should be a Global Congressional Science round table event (one of
scientist and doctors et al only, NO CORPORATE, POLITICIANS ALLOWED) set up
immediately to address these concerns from the many potential routes and sources
of the TSE prion disease, including Alzheimer’s disease, and a emergency global
doctrine put into effect to help combat the spread of Alzheimer’s disease via
the medical, surgical, dental, tissue, and blood arena’s. All human and animal
TSE prion disease, including Alzheimer’s should be made reportable in every
state, and Internationally, WITH NO age restrictions. Until a proven method of
decontamination and autoclaving is proven, and put forth in use universally, in
all hospitals and medical, surgical arena’s, or the TSE prion agent will
continue to spread. IF we wait until science and corporate politicians wait
until politics let science _prove_ this once and for all, and set forth
regulations there from, we will all be exposed to the TSE Prion agents, if that
has not happened already. what’s the use of science progressing human life to
the century mark, if your brain does not work?
combined cannot exceed 350 Words
shortened to proper word count ;
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease
have both been around a long time, and was discovered in or around the same time
frame, early 1900’s. Both diseases are incurable and debilitating brain disease,
that are in the end, 100% fatal, with the incubation/clinical period of the
Alzheimer’s disease being longer (most of the time) than the TSE prion disease.
Symptoms are very similar, and pathology is very similar.
Methods
Through years of research, as a layperson, of peer review journals,
transmission studies, and observations of loved ones and friends that have died
from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant
Creutzfelt Jakob Disease CJD.
Results
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long
incubation disease, and that Alzheimer’s is Transmissible, and is a threat to
the public via the many Iatrogenic routes and sources. It was said long ago that
the only thing that disputes this, is Alzheimer’s disease transmissibility, or
the lack of. The likelihood of many victims of Alzheimer’s disease from the many
different Iatrogenic routes and modes of transmission as with the TSE prion
disease.
Conclusions
There should be a Global Congressional Science round table event set up
immediately to address these concerns from the many potential routes and sources
of the TSE prion disease, including Alzheimer’s disease, and a emergency global
doctrine put into effect to help combat the spread of Alzheimer’s disease via
the medical, surgical, dental, tissue, and blood arena’s. All human and animal
TSE prion disease, including Alzheimer’s should be made reportable in every
state, and Internationally, WITH NO age restrictions. Until a proven method of
decontamination and autoclaving is proven, and put forth in use universally, in
all hospitals and medical, surgical arena’s, or the TSE prion agent will
continue to spread. IF we wait until science and corporate politicians wait
until politics lets science _prove_ this once and for all, and set forth
regulations there from, we will all be exposed to the TSE Prion agents, if that
has not happened already.
end...tss
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
source references
snip...
snip...end
Thank You for accepting my submission
# 29403, Alzheimer’s disease and Transmissible Spongiform Encephalopathy
prion disease, Iatrogenic, what if ? and the opportunity to present it, at the
Alzheimer’s Association International Conference 2012 (AAIC), as a poster
presentation. However, with great sadness, I must regretfully decline the
invitation due to a medical reasons, and traveling to Canada, of which is not
possible. ...
Thank You,
With Kindest Regards,
I am sincerely,
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
flounder9@verizon.net
From:
Sent: Saturday, April 07, 2012 8:20 PM
To: Terry S. Singeltary Sr.
Subject: RE: re-submission
Dear Terry,
Yes, your proposal was accepted as a poster presentation. Please decline
the invitation if appropriate.
Best Regards,
______________________________________
Alzheimer’s Association – National Office
225 North Michigan Avenue – Floor 17
Chicago, Illinois 60601
=============snip...end...source reference...# 29403==========
snip...full submission with references ;
Wednesday, May 16, 2012
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Proposal ID: 29403
Wednesday, December 11, 2013
*** Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease ***
http://creutzfeldt-jakob-disease.blogspot.com/2013/12/detection-of-infectivity-in-blood-of.html
Creutzfeldt-Jakob Disease CJD cases rising North America updated report August 2013
*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing an extreme increase of 48% between 2008 and 2010 ***
http://creutzfeldt-jakob-disease.blogspot.com/2013/08/creutzfeldt-jakob-disease-cjd-cases.html
Sunday, October 13, 2013
*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012
http://creutzfeldt-jakob-disease.blogspot.com/2013/10/cjd-tse-prion-disease-cases-in-texas-by.html
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
http://creutzfeldt-jakob-disease.blogspot.com/2014/03/a-creutzfeldt-jakob-disease-cjd.html
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
Tuesday, April 01, 2014
Questions linger in U.S. CJD cases 2005, and still do in 2014
Monday, March 10, 2014
Investigators study silent variant of mad cow disease Galveston Daily News
March 4, 2014
Thursday, February 27, 2014
BEEF, CANCER, PRIONS, AND OTHER DANGEROUS AND DEADLY PATHOGENS, APPARENTLY,
IT'S WHAT'S FOR DINNER
Thursday, March 6, 2014
TEXAS RECALL LIST MASSIVE FROM DEAD STOCK DOWNER CANCER COWS OFFAL from
Class I Recall 002-2014 and 013-2014 Health Risk: High Jan 13, 2014 and Feb 8,
2014 shipped to Texas, Florida, and Illinois UPDATE FEBRUARY 14, 2014
Thursday, March 20, 2014
JACK IN THE BOX NOW CAUGHT UP IN MASSIVE RANCHO DEAD STOCK DOWNER CANCER
COW RECALL
Friday, March 21, 2014
Rancho Dead Stock Cancer Downers Recall Explained FSIS March 20 2014
?
“As of March 20, 2014, FSIS has completed all checks (effectiveness checks
and disposition verification checks) for recalls 002-2014 and 013-2014 regarding
Rancho Feeding Corporation. FSIS has determined that based on the number of
successful checks (see Directive 8080.1, Attachment 1, Table 3) where businesses
were notified of the recall and removed affected products from commerce that the
recall activities were effective.”
Monday, March 10, 2014
Investigators study silent variant of mad cow disease Galveston Daily News
March 4, 2014
Thursday, February 20, 2014
Unnecessary precautions BSE MAD COW DISEASE Dr. William James FSIS VS Dr.
Linda Detwiler 2014
Saturday, November 2, 2013
APHIS Finalizes Bovine Import Regulations in Line with International Animal
Health Standards while enhancing the spread of BSE TSE prion mad cow type
disease around the Globe
Friday, April 4, 2014
China, Australia, Argentina, Brazil, Uruguay, Morocco, Israel, South Africa
and Saudi Arabia still retain BSE-related closures
Monday, March 3, 2014
*** Gov. C.L. "Butch" Otter of Idaho signs bill that will force consumers
to eat dead stock downers and whatever else the industry decides
see updated Rancho CLASS 1 HIGH RISK dead stock cancer downer recall for
IDAHO
*** Because typical clinical signs of BSE cannot always be observed in
nonambulatory disabled cattle, and because evidence has indicated these cattle
are more likely to have BSE than apparently healthy cattle, FDA is designating
material from nonambulatory disabled cattle as prohibited cattle materials.
Saturday, April 19, 2014
Human prion diseases and the risk of their transmission during anatomical
dissection
Saturday, April 19, 2014
Estimation of the Exposure of the UK Population to the Bovine Spongiform
Encephalopathy Agent through Dietary Intake During the Period 1980 to 1996
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
Thursday, April 17, 2014
Novant: Three more may have been exposed to disease CJD
http://creutzfeldt-jakob-disease.blogspot.com/2014/04/novant-three-more-may-have-been-exposed.html
Sunday, August 09, 2009
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html
http://prionopathy.blogspot.com/2011/05/variably-protease-sensitive-prionopathy.html
http://cjdusa.blogspot.com/
Subject: Re: Hello Dr. Gibbs...........
Date: Wed, 29 Nov 2000 14:14:18 –0500
From: "Clarence J. Gibbs, Jr., Ph.D."
To: "Terry S. Singeltary Sr." References:
<3a254430 .9fb97284="" wt.net="">
Hi Terry:
326 E Stret N.E., Washington, D. C. 20002.
Better shrimp and oysters than cards!!!!
Have a happy holiday and thanks for all the information you bring to the
screen.
Joe Gibbs ==========
Tuesday, August 18, 2009
* BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009
http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html
* BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009
http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html
CJD QUESTIONNAIRE USA
http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html
http://cjdquestionnaire.blogspot.com/
CJD and Baby foods (the great debate 1999)
Subject: Re: Girl, 13, shows CJD symptoms.
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
Date: Wed, 24 Nov 1999 11:35:44 -0600 Content-Type: text/plain
Parts/Attachments: text/plain (67 lines)
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
Sunday, May 18, 2008
BSE Inquiry DRAFT FACTUAL ACCOUNTS DFAs
Monday, May 19, 2008
*** SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND
ABATTOIRS ***
Saturday, April 19, 2014
*** Exploring the zoonotic potential of animal prion diseases: In vivo and
in vitro approaches ***
TSS