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Wednesday, December 14, 2016

Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples


Original Investigation



December 12, 2016



Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples





Author Affiliations Article Information

              

  • 1Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy
  • 2Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana
  • 3Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy
  • 4Struttura Complessa di Otorinolaringoiatria, Ospedale Santa Maria della Misericordia, Rovigo, Italy
  • 5Copan Italia SpA, Brescia, Italy
  • 6Biocrystallography Laboratory, Department of Biotechnology, University of Verona, Italy
  • 7Department of Neuroscience, University of Padova, Padova, Italy
  • 8Istituto di Ricovero e Cura a Carattere Scientifico San Camillo Hospital, Venice, Italy
  • 9Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
  • 10Neurology Unit, Ospedale Maria Vittoria, Torino, Italy
  • 11Neurology Unit, Ospedale Cattinara, Trieste, Italy



JAMA Neurol. Published online December 12, 2016. doi:10.1001/jamaneurol.2016.4614





Key Points

                          

Question  How can diagnosis of Creutzfeldt-Jakob disease be optimized using cerebrospinal fluid and nasal swabbing samples?



Findings  In this case-control laboratory analysis, a diagnostic algorithm had 100% sensitivity and 100% specificity for 61 cases of sporadic Creutzfeldt-Jakob disease relative to 71 non–prion disease cases using real-time quaking-induced conversion analysis of cerebrospinal fluid and/or olfactory mucosa samples. The sensitivity for genetic prion diseases was 75%, and gentler nasal swabs worked as well as cytobrushes for olfactory mucosa sampling.



Meaning  Real-time quaking-induced conversion testing can provide rapid and accurate intra vitam diagnosis of Creutzfeldt-Jakob disease.



Abstract



Importance  Early and accurate in vivo diagnosis of Creutzfeldt-Jakob disease (CJD) is necessary for quickly distinguishing treatable from untreatable rapidly progressive dementias and for future therapeutic trials. This early diagnosis is becoming possible using the real-time quaking-induced conversion (RT-QuIC) seeding assay, which detects minute amounts of the disease-specific pathologic prion protein in cerebrospinal fluid (CSF) or olfactory mucosa (OM) samples.



Objective  To develop an algorithm for accurate and early diagnosis of CJD by using the RT-QuIC assay on CSF samples, OM samples, or both.



Design, Setting, and Participants  In this case-control study, samples of CSF and OM were collected from 86 patients with a clinical diagnosis of probable (n = 51), possible (n = 24), or suspected (n = 11) CJD and 104 negative control samples (54 CSF and 50 OM). The CSF and OM samples were analyzed using conventional RT-QuIC. The CSF samples underwent further testing using improved RT-QuIC conditions. In addition, the diagnostic performance of a novel, easy-to-use, gentle flocked swab for sampling of OM was evaluated. Data were collected from January 1 to June 30, 2015.



Main Outcome and Measures  Correlations between RT-QuIC results and the final diagnosis of recruited patients.



Results  Among the 86 patients (37 men [43%] and 49 women [57%]; mean [SD] age, 65.7 [11.5] years) included for analysis, all 61 patients with sporadic CJD had positive RT-QuIC findings using OM or CSF samples or both for an overall RT-QuIC diagnostic sensitivity of 100% (95% CI, 93%-100%). All patients with a final diagnosis of non–prion disease (71 CSF and 67 OM samples) had negative RT-QuIC findings for 100% specificity (95% CI, 94%-100%). Of 8 symptomatic patients with various mutations causing CJD or Gerstmann-Sträussler-Scheinker syndrome, 6 had positive and 2 had negative RT-QuIC findings for a sensitivity of 75% (95% CI, 36%-96%).



Conclusions and Relevance  A proposed diagnostic algorithm for sporadic CJD combines CSF and OM RT-QuIC testing to provide virtually 100% diagnostic sensitivity and specificity in the clinical phase of the disease.










Today is my Mothers Anniversary date for her demise from the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD, DOD December 14, 1997, confirmed. This post is for Mom. RIP MOM! i'm still here...tss





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.

http://jama.jamanetwork.com/article.aspx?articleid=1031186





Saturday, April 23, 2016
 


PRION 2016 TOKYO



Saturday, April 23, 2016



 SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016



 Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online



Taylor & Francis



Prion 2016 Animal Prion Disease Workshop Abstracts



WS-01: Prion diseases in animals and zoonotic potential



Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a



"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France



 Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.



 To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.



These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.



 Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with ef?ciency comparable to that of cattle BSE. While the ef?ciency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 









 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


*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.



 *** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
 


 *** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.



O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
 


 Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
 


 Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.



 *** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,



 ***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),



 ***is the third potentially zoonotic PD (with BSE and L-type BSE),



 ***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.



 ===============
 


***thus questioning the origin of human sporadic cases***



 ***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 




SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016



Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online








*** WDA 2016 NEW YORK ***

 We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions.

 Student Presentations Session 2

 The species barriers and public health threat of CWD and BSE prions

 Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University

 Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD.

Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders

http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf




PRION 2016 TOKYO

Zoonotic Potential of CWD Prions: An Update

Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3, Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6, Pierluigi Gambetti1, Qingzhong Kong1,5,6 1Department of Pathology, 3National Prion Disease Pathology Surveillance Center, 5Department of Neurology, 6National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. 4Department of Biological Sciences and Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada, 2Encore Health Resources, 1331 Lamar St, Houston, TX 77010

Chronic wasting disease (CWD) is a widespread and highly transmissible prion disease in free-ranging and captive cervid species in North America. The zoonotic potential of CWD prions is a serious public health concern, but the susceptibility of human CNS and peripheral organs to CWD prions remains largely unresolved. We reported earlier that peripheral and CNS infections were detected in transgenic mice expressing human PrP129M or PrP129V. Here we will present an update on this project, including evidence for strain dependence and influence of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of experimental human CWD prions.

PRION 2016 TOKYO In Conjunction with Asia Pacific Prion Symposium 2016 PRION 2016 Tokyo Prion 2016

http://prion2016.org/dl/newsletter_03.pdf


Cervid to human prion transmission

Kong, Qingzhong

Case Western Reserve University, Cleveland, OH, United States

Abstract

Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans. We hypothesize that:

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;

(3) Reliable essays can be established to detect CWD infection in humans;and

(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.

Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of "humanized" Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental "human CWD" samples will also be generated for Aim 3.

Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1.

Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental "human CWD" samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.

Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.

Public Health Relevance There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.

Funding Agency Agency National Institute of Health (NIH)

Institute National Institute of Neurological Disorders and Stroke (NINDS)

Type Research Project (R01)

Project # 1R01NS088604-01A1

Application # 9037884

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May

Project Start 2015-09-30

Project End 2019-07-31

Budget Start 2015-09-30

Budget End 2016-07-31

Support Year 1

Fiscal Year 2015

Total Cost $337,507

Indirect Cost $118,756

Institution

Name Case Western Reserve University

Department Pathology

Type Schools of Medicine

DUNS # 077758407

City Cleveland

State OH

Country United States

Zip Code 44106

http://grantome.com/grant/NIH/R01-NS088604-01A1
 



Monday, May 02, 2016

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

 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

http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf


http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160


SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html





CDC EMERGING INFECTIOUS DISEASE JOURNAL DECEMBER 2016 CWD HORIZONTAL TRANSMISSION








Sunday, August 28, 2016





 CONFIDENTIAL





 Transmissible Spongiform Encephalopathy TSE Prion and how Politics and Greed by the Industry spread madcow type diseases from species to species and around the globe





 TSE PRIONS AKA MAD COW TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH MY!










 see more here ;





Tuesday, September 06, 2016




A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation











Tuesday, August 9, 2016



Concurrence with OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2015-0055]




BILLING CODE: 3410-34-P DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service










 Saturday, July 23, 2016





BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016










Tuesday, July 26, 2016





*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016 










 Saturday, July 16, 2016





Importation of Sheep, Goats, and Certain Other Ruminants [Docket No. APHIS-2009-0095]RIN 0579-AD10





WITH great disgust and concern, I report to you that the OIE, USDA, APHIS, are working to further legalize the trading of Transmissible Spongiform Encephalopathy TSE Pion disease around the globe.





THIS is absolutely insane. it’s USDA INC.










 Thursday, August 4, 2016





Secretary's Advisory Committee on Animal Health [Docket No. APHIS-2016-0046] TSE PRION DISEASE










Tuesday, December 13, 2016



Norway Chronic Wasting Disease CWD TSE Prion disease Skrantesjuke December 2016 Update








Title: Pathological features of chronic wasting disease in reindeer and demonstration of horizontal transmission








Monday, September 05, 2016



Pathological features of chronic wasting disease in reindeer and demonstration of horizontal transmission Major Findings for Norway








Thursday, September 22, 2016



NORWAY DETECTS 5TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION Skrantesjuke








SUNDAY, OCTOBER 02, 2016



*** What is the risk of a cervid TSE being introduced from Norway into Great Britain? Qualitative Risk Assessment September 2016








Wednesday, September 7, 2016



*** An assessment of the long-term persistence of prion infectivity in aquatic environments








Friday, September 02, 2016



*** Chronic Wasting Disease Drives Population Decline of White-Tailed Deer








*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***

Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3






 


Thursday, December 08, 2016




TEXAS TAHC confirmed Chronic Wasting Disease (CWD) in a free-ranging elk Dallam County






 


Saturday, December 03, 2016




TEXAS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE 35 CASES TO DATE









Friday, November 18, 2016



IMPORTANT: SAWCorp CWD Test is NOT APHIS Approved










Wednesday, December 07, 2016



Student Assistant (Temporary) – Chronic Wasting Disease: Texas A&M Veterinary Medical Diagnostic Laboratory









Tuesday, November 22, 2016



AGFC finds 28 new cases of CWD in north Arkansas






 


Tuesday, November 29, 2016


 


Wyoming CWD Report monitoring efforts increase with focus on improving herd health









Tuesday, November 22, 2016



Minnesota Tests confirm 2 CWD-positive deer near Lanesboro






 


Tuesday, November 22, 2016




Michigan Suspect CWD deer harvested in Eagle Township, Clinton County






 


Saturday, November 12, 2016




Maine Medical Center received confirmation patient treated at the hospital has Creutzfeldt-Jakob disease



http://creutzfeldt-jakob-disease.blogspot.com/2016/11/maine-medical-center-received.html






Wednesday, November 09, 2016



Chronic Wasting Disease (CWD) Program Standards - Review and Comment By Terry S Singeltary Sr. November 9, 2016








Monday, August 29, 2016



*** NWHC USGS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE











Sunday, December 11, 2016



Clay Components in Soil Dictate Environmental Stability and Bioavailability of Cervid Prions in Mice













Friday, November 11, 2016




Canada Transmissible Spongiform Encephalopathy TSE Prion Report Update









Tuesday, November 29, 2016



Transmissibility of Gerstmann–Sträussler–Scheinker syndrome in rodent models: new insights into the molecular underpinnings of prion infectivity






 


Sunday, December 04, 2016




Heidenhain variant of Creutzfeldt–Jakob disease in a patient who had bovine bioprosthetic valve implantation


 


Year : 2016 | Volume : 64 | Issue : 10 | Page : 767-769








Sunday, November 06, 2016



UK Iatrogenic Creutzfeldt–Jakob disease: investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches








this must be on the forefront of research i.e. THE VERY REAL POTENTIAL FOR ‘iatrogenic’ transmission.



why has Alzheimer’s exploded over the past few decades ???



Alzheimer’s disease, iatrogenic, and Transmissible Spongiform Encephalopathy TSE Prion disease, that is the question ???



>>> The only tenable public line will be that "more research is required’’ <<<



>>> possibility on a transmissible prion remains open<<<



O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?











SWISS MEDICAL WEEKLY



Alzheimer-type brain pathology may be transmitted by grafts of dura mater 26/01/2016 Singeltary comment ;








re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy



Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)



snip...see full Singeltary Nature comment here;








Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease



*** Singeltary comment PLoS ***



Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?



Posted by flounder on 05 Nov 2014 at 21:27 GMT








Sunday, November 22, 2015



*** Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis Abstract



Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.



Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD 54.00











*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***



Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.



Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.








Monday, December 5, 2016



Prion Institute protein folding and misfolding; pathobiology of TSEs; surveillance, control; and TSEs








Thursday, December 1, 2016



PRION2017 DECIPHERING NEURODEGENERATIVE DISORDERS 23 – 26 May 2017 Edinburgh








Thursday, August 04, 2016



MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL SCJD








Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY








Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle



Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.



snip...



The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...














In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells



3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...








”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” ...page 26.








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.








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?








The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI



Tracking spongiform encephalopathies in North America



Original



Xavier Bosch



“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt—Jakob ...








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.








Suspect symptoms



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



28 Mar 01



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...








2001 FDA CJD TSE Prion Singeltary Submission










Terry S. Singeltary Sr. Bacliff, Texas USA flounder9@verizon.net


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