Friday, April 25, 2014

Accuracy of administrative diagnostic data for pathologically confirmed cases of Creutzfeldt-Jakob disease in Massachusetts, 2000-2008

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

 


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;

 

 


 

 

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


 

 

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


 

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 ***

 
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).

 

 

TSS

posted by Terry S. Singeltary Sr. at 1:28 PM

Thursday, April 17, 2014

Novant: Three more may have been exposed to disease CJD

Novant: Three more may have been exposed to disease

 

Related Stories Related: Woman wants answers from Forsyth Medical Center

 

Related: 18 patients exposed to deadly disease at Forsyth Medical Center

 

Posted: Thursday, April 17, 2014 9:02 am

 

Novant: Three more may have been exposed to disease

 

By Richard Craver Winston-Salem Journal news-record.com

 

WINSTON-SALEM — Novant Health Inc. said Wednesday three more brain or spinal surgical patients may have exposed to Creutzfeldt-Jakob disease at Forsyth Medical Center earlier this year.

 

The system also said three of the 18 patients initially identified and notified Feb. 10-11 are no longer considered at risk.

 

It is the first update by Novant since it disclosed publicly the exposure risk Feb. 10.

 

Jeff Lindsay, Forsyth’s president, and Dr. Jim Lederer, its top infectious-disease expert, said at that time the 18 patients may have been exposed to the rare but fatal degenerative brain disorder through surgical equipment used in procedures that occurred from Jan. 18 to Feb. 6.

 

A patient who had brain surgery Jan. 18 was later diagnosed with CJD through testing of tissue at Case Western University’s National Prion Center. Novant said the equipment used in those procedures was removed Feb. 6.

 

Novant spokeswoman Caryn Klebba said federal privacy laws prohibit the system from disclosing the gender of the patients.

 

“We made this new determination based upon an in-depth review of patient files, a review of the surgical instruments used, and an examination of when the instruments were sterilized,” Klebba said.

 

“We recognize this new information is disappointing to the three additional potentially exposed patients.

 

“However, we believe if anyone may have been potentially exposed to these surgical instruments, they have a right to know and we have a responsibility to tell them.”

 

When Novant announced its exposure risk, it was the latest of at least nine incidents at U.S. hospitals this century.

 

Lindsay has said that “any exposure is simply unacceptable” even as Lederer described the risk to the patients as “very low.” In 85 percent of CJD cases, it occurs spontaneously in the brain from a mutated gene – without warning or symptoms.

 

The disease is caused by a rare type of protein, or prion, that can adhere to surgical equipment and withstand standard sterilization treatments. The specialized surgical equipment used on the Forsyth patient with the disease did not receive the enhanced sterilization procedures recommended for CJD by The Joint Commission.

 

According to federal regulatory agencies, the last confirmed case of a CJD transmission though surgical instruments occurred in 1976. In the past 14 years, there have been about 4,900 patients nationwide who may have been potentially exposed to CJD in that manner.

 

Klebba said Novant brought in a national epidemiologist who is an expert in infection prevention and CJD.

 

“She conducted a significant review to validate our processes to ensure we were accurate in which patients were identified as potentially exposed,” Klebba said.

 

“Surgical instruments are used in a variety of surgeries and different operating room suites; therefore, in this second review we worked to match dates, times, types of surgeries and surgical instruments to each patient.”

 

Klebba said Novant’s standard procedures is to use disposable surgical instruments in cases where CJD is suspected where possible, and to apply enhanced cleaning processes to non-disposable surgical instruments to prevent possibly transmitting the disease to others.

 

“We have shared that although there were reasons to suspect CJD, it was determined that such a diagnosis based on clinical data was unlikely,” Klebba said. “We have also candidly shared that, in hindsight the enhanced sterilization should have occurred.

 

“We have changed our policy to now heighten awareness of CJD as a possible diagnosis and establish a reporting requirement to our infection prevention team in the case of potential CJD cases.

 

“We continue to use disposable instruments where possible and will quarantine any non-disposable surgical instruments used in cases of suspected CJD and, if confirmed, to incinerate the instruments,” she said. “Cost of the surgical instruments is not a factor in making this safety determination.”

 

Klebba said of the 18 patients currently considered at exposure risk, some are from other states.

 

“We have made all reports required by North Carolina and federal law,” Klebba said. She said officials with the N.C. Department of Health Service Regulation conducted a three-day survey Feb. 18-20 “to determine if we had corrected any underlying issues.”

 

“They determined that we had taken the necessary steps to prevent this from happening in the future. The Joint Commission has asked for additional information and has shared with us that they do not believe an on-site review is necessary.

 

“As a result of self-disclosing and taking immediate action to fix the issues, we do not expect to and have not received any sanctions.”

 

Klebba said Novant is declining to discuss any potential financial obligation to the patients, including paying for the cost of their procedures and subsequent testing. “We cannot discuss legal matters,” she said.

 


 

North Carolina Hospital Potentially Exposes Patients To Deadly Disease

 


 

could not find this report on Novant public news feed yet...TSS

 

NOVANT HEALTH NOTIFIES PATIENTS OF POSSIBLE EXPOSURE TO CREUTZFELDT-JAKOB DISEASE

 

18 neurosurgical patients at Forsyth Medical Center may have been exposed to CJD during surgery

 

Winston-Salem, NC February 10, 2014 – Novant Health Forsyth Medical Center has learned that 18 neurosurgical patients within the last three weeks may have been exposed to a rare degenerative brain disease while undergoing surgery at the hospital.

 

The disease, sporadic Creutzfeldt-Jakob Disease (CJD), affects approximately one person per million worldwide, and has no known cause. The possibility of contracting CJD through surgical exposure is very remote. The last confirmed case of a patient acquiring CJD through the use of surgical instruments was in 1976.

 

Forsyth Medical Center staff have reached out to all 18 patients to inform them of the potential risk, and all surgical instruments used in the surgeries have been put through enhanced sterilization procedures, as recommended by the Centers for Disease Control and Prevention.

 

“On behalf of Forsyth Medical Center, I want to offer my sincerest apology to the neurosurgical patients who may have been exposed to CJD while undergoing surgery at our hospital,” said Jeff Lindsay, Forsyth president and CEO. “We recognize that the risk to these patients is very small. However, we take any potential exposure seriously, and are here to support these individuals and their families both now and in the future. We have taken appropriate steps to prevent any future occurrence. We value the trust our patients place in us, and we remain fully committed to the health and safety of everyone who comes through our doors.”

 

The potential exposure dates to Jan. 18, when a medical team at Forsyth Medical Center performed a procedure on a patient who later tested positive for sporadic CJD. The surgical instruments used during the patient’s surgery were sterilized using standard hospital procedures. However, they were not subjected to the enhanced sterilization procedures necessary on instruments used in confirmed or suspected cases of CJD.

 

Forsyth Medical Center is currently working with local and state health departments, as well as following guidelines from the Centers for Disease Control and Prevention, to ensure the facility is taking every necessary precaution to prevent a similar occurrence in the future. The hospital is also working with the patients and their families on an individual basis to provide support and care.

 

About Novant Health

 

Novant Health is a four-state integrated network of physician practices, outpatient centers and hospitals that deliver a seamless and convenient healthcare experience to our communities. The Novant Health network consists of more than 1,100 physicians and 24,000 employees who make healthcare remarkable at more than 450 locations including 14 medical centers and hundreds of outpatient facilities and physician clinics. Headquartered in Winston-Salem, NC, Novant Health is committed to making healthcare

 


 

Tuesday, February 11, 2014

 

Novant Health Forsyth Medical Center Information on potential CJD exposure

 


 

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

 


 

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

 


 

Friday, February 14, 2014

 

Creutzfeldt-Jakob disease (CJD) biannual update (February 2014), with briefing on novel human prion disease National CJD Research and Surveillance Unit NCJDRSU

 


 

 TSS

posted by Terry S. Singeltary Sr. at 2:53 PM

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

SPORADIC CJD and the potential for zoonotic transmission there from, either directly or indirectly via friendly fire iatrogenic mode, evidence to date

 

BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein

 

Variant Creutzfeldt–Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.

 


 

 

-------- Original Message --------

 

Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD

 

Date: Thu, 28 Nov 2002 10:23:43 -0000

 

From: "Asante, Emmanuel A" e.asante@ic.ac.uk

 

To: "'flounder@wt.net'" flounder@wt.net

 

Dear Terry,

 

I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention.

 

Thank you for your interest in the paper.

 

In respect of your first question, the simple answer is, yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.

 

I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.

 

Emmanuel Asante

 

<>

 

____________________________________

 

Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)

 

____________________________________

 


 

 

Rosa, then there is a substantial amount of mounting scientific evidence that indeed the nvCJD only theory was bogus from the start, and they knew it in 1985, and later in 1995, when science was changed with Vicky Rimmer, the farmers with BSE herds dying with sporadic CJD and their wives dying with sporadic CJD. on my mothers grave, 100 years from now, mad cow disease and deaths there from (all human and animal TSE prion disease), will go down as a big a cover up as was/is Tobacco and Asbestos, because they knew 100+ years ago that those to products were killing folks, but the governments and the industry chose to let it continue and kill, just because of the long incubation period and $$$...tss

 

 

Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate

 

Conclusion/Significance Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.

 


 

LAST MAD COW IN USA, IN CALIFORNIA, WAS ATYPICAL L-TYPE BASE BSE TSE PRION DISEASE Thursday, February 20, 2014

 

Unnecessary precautions BSE MAD COW DISEASE Dr. William James FSIS VS Dr. Linda Detwiler 2014

 


 

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)

 


 

*** What irks many scientists is the USDA’s April 25 statement that the rare disease is “not generally associated with an animal consuming infected feed.”

 

The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown, one of the world’s experts on this type of disease who retired recently from the National Institutes of Health. "(The agency) has no foundation on which to base that statement.”

 


 

Owens, Julie

 

From: Terry S. Singeltary Sr. [flounder9@verizon.net]

 

Sent: Monday, July 24, 2006 1:09 PM

 

To: FSIS RegulationsComments

 

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Page 1 of 98

 


 

FSIS, USDA, REPLY TO SINGELTARY

 


 

 Wednesday, January 01, 2014

 

Molecular Barriers to Zoonotic Transmission of Prions

 

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

 

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

 


 


 

Thursday, August 12, 2010

 

Seven main threats for the future linked to prions

 

First threat

 

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

 

***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...

 


 

EFSA Journal 2011 The European Response to BSE: A Success Story

 

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

 

Monday, October 10, 2011

 

EFSA Journal 2011 The European Response to BSE: A Success Story

 

snip...

 

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far ***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...

 


 


 

see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

 


 

*** 2010-2011 ***

 

When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. 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.

 

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

 


 

Monday, September 26, 2011 L-BSE BASE prion and atypical sporadic CJD

 

Risk.12:

 

Transmission of Atypical Italian sCJD Case to Humanized Mice Reveals a Novel Infectious Strain

 

Roberta Galeno,1,† Marco Sbriccoli,1 Loredana Ingrosso,1 Silvia Graziano,1 Angelina Valanzano,1 Anna Poleggi,1 Angela De Pascalis,1 Anna Ladogana,1 Franco Cardone,1 Maria Puopolo,1 Gianluigi Zanusso2 and Maurizio Pocchiari1

 

1Istituto Superiore di Sanità; Rome, Italy; 2University of Verona; Verona, Italy†Presenting author; Email: roberta.galeno@iss.it

 

Sporadic Creutzfeldt-Jakob disease (sCJD) is a neurodegenerative prion disorder with uncertain etiology characterized by a typical combination of clinical symptoms, neuropathological lesions, and by the deposition of the pathological protein PrPTSE in the brain.

 

The vast majority of patients affected by sCJD can be categorized according to the genotype at the polymorphic position www.landesbioscience.com Prion 127

 

129 of PrP (methionine or valine) and to the molecular mass of PrPTSE (type 1 or 2, corresponding to 21 or 19 kDa), yielding six possible combinations (MM1, MM2, VV1, VV2, MV1, and MV2) that associate with five clinico-pathological variants. Transmission studies of these sCJD subtypes into transgenic mice expressing the human prion protein allowed to identify four different infectious strains, which can partly explain the heterogeneity observed in sCJD patients.1

 

We recently described a novel molecular and pathological phenotype of sCJD (MV at position 129 of PrP), associated with an unprecedented electrophoretic pattern of PrPTSE characterized by the absence of the highly glycosylated isoform. In this work, we sought to characterize the prion strain associated with this atypical case by intracerebral inoculation into gene-targeted transgenic mice (HuTg) carrying the human PRNP gene with the three 129 genotype combinations. For comparison, three Italian sCJD cases heterozygous at position 129 of the prion protein, belonging to different subtypes (MV1, MV1/2, MV2), were transmitted to the same panel of transgenic mice. Survival times, attack rates, lesion profiles, and molecular analysis of the PrPTSE type recovered from mouse brains injected with the atypical case were compared with data from control animals. Mice inoculated with the atypical case displayed a restricted host tropism, with only a small number of VV animals that resulted PrPTSE-positive after an exceedingly long survival time. Interestingly, PrPTSE accumulated in brains from these mice lacks the diglycosylated band similar to that in sCJD inoculum, yet dissimilar to any other PrPTSE observed in HuTg mice by us and by other authors.1,2 Overall, *** these results strongly indicate that our atypical case associates with a new infectious strain of sCJD. Further investigations are needed to understand the possible connection with other human and animal prion diseases.

 

References

 

1. Bishop MT, Will RG, Manson JC. Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties. Proc Natl Acad Sci USA 2010; 107:12005-10.

 

2. Bishop MT, Hart P, Aitchison L, Baybutt HN, Plinston C, Thomson V, et al. Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 2006; 5:393-8.

 


 

Saturday, June 25, 2011

 

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

 

"BSE-L in North America may have existed for decades"

 


 

Sunday, June 26, 2011

 

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

 


 

2011 Monday, September 26, 2011

 

L-BSE BASE prion and atypical sporadic CJD

 


 

1: J Infect Dis 1980 Aug;142(2):205-8

 

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

 

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

 

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

 

snip...

 

*** The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

 

PMID: 6997404

 


 

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

 


 

Wednesday, March 28, 2012

 

VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion poker goes up again $

 


 

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)

 


 

UPDATE

 

 I ask Professor Kong ; Thursday, December 04, 2008 3:37 PM

 

Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment ''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....'' Professor Kong reply ;

 

.....snip

 

''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''

 

Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA END...TSS

 

Thursday, December 04, 2008 2:37 PM

 

"we have found that H-BSE can infect humans."

 

personal communication with Professor Kong. ...TSS

 

BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.

 

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.

 


 


 

 please see below from PRION2013 ;

 

*** This study imply the possibility that the novel BSE prions with high virulence in cattle will be emerged during intraspecies transmission.

 

AD.56: The emergence of novel BSE prions by serial passages of H-type BSE in bovinized mice

 

Kentaro Masujin, Naoko Tabeta, Ritsuko Miwa, Kohtaro Miyazawa, Hiroyuki Okada, Shirou Mohri and Takashi Yokoyama National Institute of Animal Health; Tsukuba, Japan

 

H-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE, and has been detected in several European countries, and North America. Transmission studies of H-type BSE led to the emergence of the classical BSE (C-BSE) phenotypes during passages in inbred wild type and bovinized PrP-overexpressing transgenic mice. In this study, we conducted serial passages of Canadian H-type BSE isolate in bovinized PrP-overexpressing transgenic mice (TgBoPrP). H-type BSE isolate was transmitted to TgBoPrP with incubation periods of 320 ± 12.2 d at primary passage. The incubation period of 2nd and 3rd passage were constant (~= 220 d), no clear differences were observed in their biological and biochemical properties. However, at the forth passage, 2 different BSE phenotypes were confirmed; one is shorter survival times (109 ± 4 d) and the other is longer survival times. TgBoPrP mice with longer incubation period showed the H-type phenotype of PrPsc profile and pathology. However, those of shorter incubation period were different phenotypes from previously existed BSE prions (C-BSE, L-type BSE, and H-type BSE).

 

*** This study imply the possibility that the novel BSE prions with high virulence in cattle will be emerged during intraspecies transmission.

 


 

 www.landesbioscience.com

 

 please see ;

 

Thursday, August 15, 2013

 

The emergence of novel BSE prions by serial passages of H-type BSE in bovinized mice

 


 

 Sunday, September 1, 2013

 

*** Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy

 

We previously described the biochemical similarities between PrPres derived from L-BSE infected macaque and cortical MM2 sporadic CJD: those observations suggest a link between these two uncommon prion phenotypes in a primate model (it is to note that such a link has not been observed in other models less relevant from the human situation as hamsters or transgenic mice overexpressing ovine PrP [28]). We speculate that a group of related animal prion strains (L-BSE, c-BSE and TME) would have a zoonotic potential and lead to prion diseases in humans with a type 2 PrPres molecular signature (and more specifically type 2B for vCJD)

 

snip...

 

Together with previous experiments performed in ovinized and bovinized transgenic mice and hamsters [8,9] indicating similarities between TME and L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME outbreaks in North America and Europe during the mid-1900s.

 


 

 

TEXAS ATYPICAL H-BSE MAD COW CASE

 

On June 24, 2005, the USDA announced receipt of final results from The Veterinary Laboratories Agency in Weybridge, England, confirming BSE in a cow that had conflicting test results in 2004. This cow was from Texas, died at approximately 12 years of age, and represented the first endemic case of BSE in the United States. (see Texas BSE Investigation, Final Epidemiology Report, August 2005 External Web Site Policy PDF Document Icon (PDF – 83 KB))

 

ALABAMA ATYPICAL H-TYPE GENETIC BSE

 

On March 15, 2006, the USDA announced the confirmation of BSE in a cow in Alabama. The case was identified in a non-ambulatory (downer) cow on a farm in Alabama. The animal was euthanized by a local veterinarian and buried on the farm. The age of the cow was estimated by examination of the dentition as 10-years-old. It had no ear tags or distinctive marks; the herd of origin could not be identified despite an intense investigation (see second featured item above and Alabama BSE Investigation, Final Epidemiology Report, May 2006 External Web Site PolicyPDF Document Icon (PDF – 104 KB)).

 

In August 2008, several ARS investigators reported that a rare, genetic abnormality that may persist within the cattle population "is considered to have caused" BSE in this atypical (H-type) BSE animal from Alabama. (See Identification of a Heritable Polymorphism in Bovine PRNP Associated with Genetic Transmissible Spongiform Encephalopathy: Evidence of Heritable BSE External Web Site Policy. Also see BSE Case Associated with Prion Protein Gene Mutation External Web Site Policy.)

 

On December 23, 2003, the U.S. Department of Agriculture (USDA) announced a presumptive diagnosis of the first known case of BSE in the United States. It was in an adult Holstein cow from Washington State. This diagnosis was confirmed by an international reference laboratory in Weybridge, England, on December 25. Trace-back based on an ear-tag identification number and subsequent genetic testing confirmed that the BSE-infected cow was imported into the United States from Canada in August 2001. Because the animal was non-ambulatory (a "downer cow") at slaughter, brain tissue samples were taken by USDA's Animal and Plant Health Inspection Service as part of its targeted surveillance for BSE. However the animal's condition was attributed to complications from calving. After the animal was examined by a USDA Food Safety and Inspection Service (FSIS) veterinary medical officer both before and after slaughter, the carcass was released for use as food for human consumption. During slaughter, the tissues considered to be at high risk for the transmission of the BSE agent were removed. On December 24, 2003, FSIS recalled beef from cattle slaughtered in the same plant on the same day as the BSE positive cow. (see Bovine Spongiform Encephalopathy in a Dairy Cow - Washington State, 2003.)

 


 

Tuesday, August 22, 2006

 

BSE ATYPICAL TEXAS AND ALABAMA UPDATE JANUARY 20, 2007

 


 

Monday, June 27, 2011

 

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

 


 

 

BSE: TIME TO TAKE H.B. PARRY SERIOUSLY

 

If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...

 


 

Suspect symptoms

 

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

 

28 Mar 01

 

Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284. Subscribe and get 4 free issues. FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

 

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD. "This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

 

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

 

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

 

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

 

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

 

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

 

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

 

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

 

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

 

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

 


 

why do we not want to do TSE transmission studies on chimpanzees $

 

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

 

snip...

 

R. BRADLEY

 


 

1: J Infect Dis 1980 Aug;142(2):205-8

 

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

 

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

 

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

 

snip...

 

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

 

PMID: 6997404

 


 

 

Sunday, December 12, 2010

 

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

 


 

 Wednesday, January 18, 2012

 

BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE

 

February 1, 2012

 


 

Thursday, December 23, 2010

 

Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002-2009

 

Volume 17, Number 1 January 2011

 


 

Thursday, November 18, 2010

 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

 


 

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

 


 

Tuesday, August 18, 2009

 

* BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009

 


 

 CANADA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic CJD’s). ...tss

 

PLEASE NOTE, type determination pending Creutzfeldt Jakob Disease (tdpCJD) in Canada is also on a steady increase.

 

please see ;

 

> 3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is pending.

 

CJD Deaths Reported by CJDSS1, 1994-20122

 

CJD Deaths Reported by CJDSS1, 1994-20122

 

As of May 31, 2012

 


 


 

SEE DECEMBER 2012 CANADA

 


 

USA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic CJD’s). ...tss

 

National Prion Disease Pathology Surveillance Center

 

Cases Examined1

 

(May 18, 2012)

 

 5 Includes 14 cases in which the diagnosis is pending, and 18 inconclusive cases;

 

6 Includes 17 (16 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 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).

 

Rev 5/18/2012

 


 

> 6 Includes

 

> 17 (16 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 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).

 

WELL, it seems the USA mad cow strains in humans classified as type determination pending tdpCJD, VPSPr, sFFI, and sCJD) have steadily increased over the years, and the same old song and dance continues with sporadic CJD cases $$$

 


 

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 ***

 


 

Sunday, October 13, 2013

 

*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012

 


 

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

 


 

 

 *** 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.

 

Results and Conclusions. Comparative analysis of the electrophoretic mobilities revealed that the relative molecular weight of the Nor98 PrPres internal fragment is greater than those of the matching fragment associated with VPSPr and GSSA117V, whereas it is similar to those of GSSF198S and GSSP102L. However, epitope mapping suggests that the PrPres internal fragments have different N- and C- terminal cleavage sites in each disease. Finally, preliminary results by CSSA indicate that the PrP conformational stability of human and sheep TSEs characterized by internal PrPres fragments is also different, with VPSPr showing a higher conformational stability than Nor98. Overall, our results show an unexpected heterogeneity of the molecular features among human and sheep TSEs associated with internal PrPres fragments, which is consistent with strain diversity despite the presence of similar PrPres fragments.

 

 Supported by the Italian Ministry of Health, the National Institutes of Health (NIH) NS062787, NIH AG-08012, AG-14359, Alliance BioSecure, as well as CDC Contract UR8/CCU515004.

 

 


 

 

Monday, June 27, 2011

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html


 

Increased Atypical Scrapie Detections

 

Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.

 


 

 

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

 


 

Monday, December 14, 2009

 

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

 

(hmmm, this is getting interesting now...TSS)

 

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

 

see also ;

 

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

 


 

see full text ;

 

Monday, December 14, 2009

 

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

 


 

Friday, March 09, 2012

 

Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

 

Research article

 


 

Thursday, June 23, 2011

 

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

 


 

P03.141

 

Aspects of the Cerebellar Neuropathology in Nor98

 

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

 

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

 

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

 


 

PR-26

 

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

 

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

 

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.

 

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

 

119

 


 

A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

 

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations

 

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

 

***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

 

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice.

 

*** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

 


 

Monday, December 1, 2008

 

When Atypical Scrapie cross species barriers

 

Authors

 

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

 

Content

 

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

 

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

 

*** Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model.

 

*** Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

 

*** Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

 

*** (i) the unsuspected potential abilities of atypical scrapie to cross species barriers

 

*** (ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

 

*** These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.

 


 

Friday, February 11, 2011

 

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

 


 


 

THE COVER UP OF MAD COW DISEASE IN FARMERS, FARMERS WIVES, AND VICKY RIMMER, THE DAY MAD COW SCIENCE CHANGED $$$

 

Monday, May 19, 2008

 

*** SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND ABATTOIRS ***

 


 

Wednesday, October 09, 2013

 

*** WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281 in compensation ***

 


 

Thursday, November 18, 2010

 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

 


 

Monday, November 30, 2009

 

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

 


 

Thursday, December 20, 2012

 

OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED AND SAME OLD BSe WITH BOVINE MAD COW DISEASE

 


 

Thursday, May 30, 2013

 

World Organization for Animal Health (OIE) has upgraded the United States' risk classification for mad cow disease to "negligible" from "controlled", and risk further exposing the globe to the TSE prion mad cow type disease

 

U.S. gets top mad-cow rating from international group and risk further exposing the globe to the TSE prion mad cow type disease

 


 

Wednesday, February 12, 2014

 

USDA/APHIS NOTICE: Final Rule Regarding Imports and BSE Effective March 4, 2014

 


 
Sunday, March 30, 2014

*** Chronic Wasting Disease Agents in Nonhuman Primates ***
http://chronic-wasting-disease.blogspot.com/2014/03/chronic-wasting-disease-agents-in.html

 

 

Subject: PRICE OF CWD TSE PRION POKER GOES UP IN 2014

 

Greetings PRION2014, Professor Prusiner, et al,

 

*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***

 

Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014

 

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

 

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

 

Wednesday, January 01, 2014

 

Molecular Barriers to Zoonotic Transmission of Prions

 

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

 

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

 


 


 

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

 


 

Thursday, January 2, 2014

 

*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ??? ***

 

SNIP...

 

Subtype 1: (sCJDMM1 and sCJDMV1)

 

This subtype is observed in patients who are MM homozygous or MV heterozygous at codon 129 of the PrP gene (PRNP) and carry PrPSc Type 1. Clinical duration is short, 3‑4 months.32 The most common presentation in sCJDMM1 patients is cognitive impairment leading to frank dementia, gait or limb ataxia, myoclonic jerks and visual signs leading to cortical blindness (Heidenhain’s syndrome)...

 


 

Animals injected with iatrogenic Creutzfeldt–Jakob disease MM1 and genetic Creutzfeldt–Jakob disease MM1 linked to the E200K mutation showed the same phenotypic features as those infected with sporadic Creutzfeldt–Jakob disease MM1 prions...

 


 

*** our results raise the possibility that CJD cases classified as VV1 may include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne infection by type 1 prions from animals, e.g., chronic wasting disease prions in cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have been reported (40, 41). The results of the present study emphasize the need for traceback studies and careful re-examination of the biochemical properties of sCJD-VV1 prions. ***

 


 


 

SNIP...SEE FULL TEXT ;

 

Thursday, January 2, 2014

 

*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ??? ***

 


 

 

IATROGENIC TSE PRION

 

all iatrogenic cjd is, is sporadic CJD, until route and source of the iatrogenic event that took place, is detected, documented, placed in the academic domain as fact, and recorded, which happens very seldom due to a lot of factors, besides the incubation period, and that be mainly industry. kind of like asbestos and tobacco and the industry there from, they knew in the early 1900’s that they both were killing, and they both had long incubation, and somebody chose not to do anything about if for decades and decades. kind of like what we have here with the TSE prion disease. $$$

 

> In 12 of 15 hospitals with neurosurgical incidents, a decision was made to notify patients of their potential exposure.

 

SO, X number of patients, from 3 hospitals, where

 

''exposure to potentially CJD-contaminated instruments ''

 

took place on these patients, the final decision NOT to tell those folks about the potential exposure to the CJD TSE prion

 

insane, thus, the TSE prion agent continues to spread. ...please see further comments here ;

 


 

 

Tuesday, February 11, 2014

 

Novant Health Forsyth Medical Center Information on potential CJD exposure

 


 

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

 


 

 

Tuesday, March 11, 2014

 

Science and Technology Committee Oral evidence: Blood, tissue and organ screening, HC 990 Wednesday 5 March 2014 SPORADIC CJD

 

Actually, it is nearer 2 per million per year of the population will develop sporadic CJD, but your lifetime risk of developing sporadic CJD is about 1 in 30,000. So that has not really changed. When people talk about 1 per million, often they interpret that as thinking it is incredibly rare. They think they have a 1-in-a-million chance of developing this disease. You haven’t. You’ve got about a 1-in-30,000 chance of developing it.

 


 

 

Wednesday, April 02, 2014

 

Distinct origins of dura mater graft-associated Creutzfeldt-Jakob disease: past and future problems

 


 

 

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

 


 

 

Wednesday, April 2, 2014

 

Do prions cause Parkinson disease?: The evidence accumulates (pages 331–333)

 


 

 

Seems none of the officials remember, that went through the mad cow debacle, or mad cow follies as I have termed them, and they are ongoing, for anyone who thinks mad cow disease is gone, they are only fooling themselves, and at the same time, making fools out of everyone that goes along with this TSE prion mad cow junk science that the OIE has brought to every country around the globe, and we will ALL pay the price in the years and decades to come. ...

 

IT is of my opinion, that the OIE and the USDA et al, are the soul reason, and responsible parties, for Transmissible Spongiform Encephalopathy TSE prion diseases, including typical and atypical BSE, typical and atypical Scrapie, and all strains of CWD, and human TSE there from, spreading around the globe.

 

I have lost all confidence of this organization as a regulatory authority on animal disease, and consider it nothing more than a National Trading Brokerage for all strains of animal TSE, just to satisfy there commodity. AS i said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization.

 

JUST because of low documented human body count with nvCJD and the long incubation periods, the lack of sound science being replaced by political and corporate science in relations with the fact that science has now linked some sporadic CJD with atypical BSE and atypical scrapie, and the very real threat of CWD being zoonosis, I believed the O.I.E. has failed terribly and again, I call for this organization to be dissolved. ...

 

IN A NUT SHELL ;

 

(Adopted by the International Committee of the OIE on 23 May 2006)

 

11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,

 


 

Thursday, May 30, 2013

 

World Organization for Animal Health (OIE) has upgraded the United States' risk classification for mad cow disease to "negligible" from "controlled", and risk further exposing the globe to the TSE prion mad cow type disease

 

U.S. gets top mad-cow rating from international group and risk further exposing the globe to the TSE prion mad cow type disease

 


 




Wednesday, February 26, 2014

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION 2004 THROUGHT PRION 2013 CONFERENCE ABSTRACT BOOKS
http://transmissiblespongiformencephalopathy.blogspot.com/2014/02/transmissible-spongiform-encephalopathy.html

 

 

kindest regards,

terry

posted by Terry S. Singeltary Sr. at 12:42 PM