VARIANT CJD (vCJD) or nvCJD

New Variant Creutzfeldt Jakob Disease nvCJD, was linked to young people and BSE in the U.K., aka mad cow disease...

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My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS

Saturday, April 06, 2019

Variant Creutzfeldt-Jakob disease strain is identical in individuals of two PRNP codon 129 genotypes

Variant Creutzfeldt-Jakob disease strain is identical in individuals of two PRNP codon 129 genotypes

Abigail B. Diack,1 Aileen Boyle,1 Christopher Plinston,1 Emma Hunt,1 Matthew T. Bishop,2,† Robert G. Will2,* and Jean C. Manson3,4,* *These authors contributed equally to this work.

In 2004, a subclinical case of variant Creutzfeldt-Jakob disease in a PRNP 129 methionine/valine heterozygous individual infected via blood transfusion was reported, and we established that the spleen from this individual was infectious. Since host genetics is an important factor in strain modification, the identification of variant Creutzfeldt-Jakob disease infection in a PRNP 129 methionine/ valine heterozygous individual has raised the possibility that the properties of the variant Creutzfeldt-Jakob disease agent could change after transmission to this different genetic background and concerns that this could lead to a more virulent strain of variant Creutzfeldt-Jakob disease. The variant Creutzfeldt-Jakob disease strain has to date been characterized only in methionine homozygous individuals, therefore to establish whether the strain characteristics of variant Creutzfeldt-Jakob disease had been modified by the host genotype, spleen material with prion protein deposition from a PRNP 129 methionine/valine individual was inoculated into a panel of wild-type mice. Three passages in mice were undertaken to allow stabilization of the strain characteristics following its passage into mice. In each passage, a combination of clinical signs, neuropathology (transmissible spongiform encephalopathy vacuolation and prion protein deposition) were analysed and biochemical analysis carried out. While some differences were observed at primary and first subpassage, following the second subpassage, strain characteristics in the methionine/valine individual were totally consistent with those of variant Creutzfeldt-Jakob disease transmitted to 129 methionine/valine individuals thus demonstrated no alteration in strain properties were imposed by passage through the different host genotype. Thus we have demonstrated variant Creutzfeldt-Jakob disease strain properties are not affected by transmission through an individual with the PRNP methionine/valine codon 129 genotype and thus no alteration in virulence should be associated with the different host genotype.

1 The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, UK, EH25 9RG 2 National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK 3 Centre for Dementia Prevention, University of Edinburgh, Edinburgh, UK 4 Edinburgh Neuroscience, University of Edinburgh, Edinburgh, UK † Present address: Edinburgh Genomics, University of Edinburgh, Edinburgh, UK Correspondence to: Abigail Diack

The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, UK, EH25 9RG E-mail: abigail.diack@roslin.ed.ac.uk

Keywords: variant Creutzfeldt-Jakob disease; prion; PRNP; transmissible spongiform encephalopathy Abbreviations: BSE = bovine spongiform encephalopathy; PrP = prion protein; TSE = transmissible spongiform encephalopathy; vCJD = variant Creutzfeldt-Jakob disease

doi:10.1093/brain/awz076 BRAIN 2019: 0; 1–13 | 1

Received November 14, 2018. Revised January 17, 2019. Accepted January 31, 2019

 The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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Introduction

Variant Creutzfeldt-Jakob disease (vCJD) is an acquired prion disease linked to the consumption of food products contaminated with the bovine spongiform encephalopathy (BSE) agent (Bruce et al., 1997; Hill et al., 1997) and was first reported in the UK in 1996. A peak in deaths was recorded in 2000 and it has since declined with a total of 178 deaths between 1995 and 2018 in the UK (Will et al., 1996; National CJD Research and Surveillance Unit, 2019).

Until 2016, all definite and probable cases of vCJD with genotype data had occurred in the 129 methionine homozygous (MM) genotype suggesting other genotypes may be more resistant to vCJD. In 2016 the first case of clinical vCJD in a 129 methionine/valine heterozygous (MV) individual was reported demonstrating that individuals with other genotypes were susceptible to vCJD and raising the possibility of a second wave of vCJD in individuals of this genotype (Mok et al., 2017). Transmission studies in transgenic mice expressing human prion protein (PrP, encoded by PRNP) had predicted that all three genotypes were susceptible to vCJD albeit with differences in susceptibility and incubation period. The 129MV and 129VV genotypes were predicted to have longer incubation periods than in the 129MM individuals and indeed 129MV and 129 valine homozygous (VV) individuals may not develop clinical signs of disease (Bishop et al., 2006). However, since vCJD infection can reside in peripheral tissues there is potential for onward transmission of infection from individuals of all three genotypes (Bruce et al., 2001; Ritchie et al., 2009).

Human to human transmission of vCJD has already been demonstrated and while the majority of vCJD cases are primary cases presumed to be acquired from BSE, three clinical cases of vCJD have been identified in 129MM individuals who had received non-leucoreduced red blood cell concentrates from asymptomatic UK donors (Llewelyn et al., 2004; Hewitt et al., 2006; Wroe et al., 2006). Evidence of misfolded PrP in peripheral tissues has been identified in two other individuals linked to blood and blood products, both of whom were of the 129MV genotype and remained asymptomatic until death from nonvCJD related causes (Peden et al., 2004, 2010). Studies on one of these individuals who had received a red blood cell transfusion from a 129MM donor showed no evidence of abnormal PrP in the brain but deposition in the spleen and a cervical lymph node was observed (Peden et al., 2004) and using protein misfolding cyclic amplification (PMCA), prion seeding potential was demonstrated in a range of tissues (Bougard et al., 2016). Bioassay of the spleen material from this individual also confirmed the presence of vCJD infectivity (Bishop et al., 2013). The other 129MV individual was an adult haemophilic patient who had received factor VIII concentrate prepared from plasma pools known to include a donation from a vCJD infected donor. In this case, spleen material tested positive for the presence of PrPres by western blot analysis (Peden et al., 2010).

Three retrospective studies of anonymized human appendix samples have been carried out in the UK to ascertain the prevalence of vCJD infection (Hilton et al., 2004; Ironside et al., 2006; Gill et al., 2013; Public Health England, 2016). The most recent study identified seven positives out of 15 939 giving a prevalence of 1:2000 individuals carrying abnormal PrP (Public Health England, 2016). In these three retrospective studies, misfolded PrP has been found in all three codon 129 genotypes.

The single nucleotide polymorphism at codon 129 of the prion protein gene, PRNP, encoding either M or V, is recognized as influencing host susceptibility and modifying strain characteristics for human prion diseases such as Creutzfeldt-Jakob disease, Kuru, Gerstmann-Stra¨usslerScheinker syndrome and fatal familial insomnia (Lee et al., 2001; Pocchiari et al., 2004; Kobayashi et al., 2015). It was thus recognized that vCJD in different host genotypes may display different strain characteristics.

We have reported previously the infectivity of spleen tissue from an asymptomatic MV blood recipient (MVR) and the spleen and brain tissue of the MM donor to that individual (MMD) in RIII and transgenic mice (Bishop et al., 2013). The transmission of MVR and spleen and brain homogenate of the MMD into RIII mice also demonstrated differences in incubation times and attack rates between the two inocula suggesting either differences in titre of infectivity or different strain properties between MMD and MVR (Bishop et al., 2013). It was therefore important to determine the underlying reason for these differences observed on the initial passage to mice, since strain differences could impact on the transmission potential of the strains.

The MV case demonstrates that there is the risk of transmission between asymptomatic individuals of the MV genotype through blood transfusion or blood products. With the possibility of strain modification and adaptation of the vCJD agent following transmission to a different genotype, it is thus important to assess whether vCJD is modified by the genetic background and whether there are alterations in virulence or pathogenesis. To address this we have carried out an extensive stain typing analysis on the strain of agent found within the spleen of an asymptomatic codon 129MV individual. We have established that the characteristics of this strain are consistent with that of vCJD from 129MM individuals. Thus we have demonstrated that strain properties of vCJD are not altered by the PRNP codon 129 genotype of an individual.

Materials and methods

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Results

In this study, we carried out a characterization study of the MVR and MMD (CNS and spleen) at primary passage in our strain typing panel of wild-type mice. This panel consists of RIII and C57BL6 mice, both of the Prnpa genotype and VM mice, Prnpb genotype. This combination of mouse lines gives highly reproducible and characteristic incubation periods (time between inoculation and death with clinical signs), incubation period rankings (order in which mouse lines succumb to disease) and neuropathology (TSE vacuolation and/or PrP deposition) when inoculated with the BSE or vCJD prion strain. These results were compared to a previously published transmission of brain homogenate from a MM blood donor (MMD2008) and the associated MM blood recipient (MMR2008) (Bishop et al., 2008). We then carried out a second passage of MVR, MMD (CNS and spleen), MMD2008 and MMR2008 and finally a third passage of the MVR, MMD (CNS) and MMD2008 to allow stabilization and full characterization of each strain.

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Discussion

This study provides the first evidence that codon 129 genotype of the host does not influence the strain characteristics of vCJD. In light of the identification of a clinical MV case of vCJD and abnormal PrP deposition in appendixes of all codon 129 genotypes, this finding is important for public health. Strain properties are often influenced by the PRNP genetic background of the host and modifications in the strain properties can result in different host ranges and clinical outcomes; until now, it was unknown whether a different genetic background could alter vCJD characteristics. The characterization of the infectious agent from spleen from this asymptomatic case of vCJD in a codon 129 heterozygous individual has provided answers to these key questions.

Our study finds no evidence of a novel vCJD strain after passage through an MV individual; however, this could be because of the methionine-carrying prion proteins acting as a dominant species. While other studies have demonstrated that replication of the infectious agent is possible in all three genotypes, the 129VV genotype was clearly less susceptible to disease (Bishop et al., 2006). Thus the presence of methionine in the 129MV genotype may dominate any replication process giving rise to strain characteristics identical to that in 129MM genotypes. At present, we cannot be sure of the effect of valine homozygosity on strain characteristics although mouse studies indicate there may be potential for different strain characteristics to emerge (Takeuchi et al., 2013; Fernandez-Borges et al., 2017).

Our initial study showed that the spleen of the MV recipient was infectious (Bishop et al., 2013) but on this primary passage there were inconsistencies in strain characteristics when compared with those of previously characterised vCJD cases from MM individuals. The BSE/ vCJD strain has consistently produced unique characteristics upon primary passage to mouse strain typing panels. Most notably these include high attack rates, a characteristic TSE vacuolation profile in RIII mice and a consistent incubation period ranking; RIII followed by C57BL6 100 days later than VM mice (Bruce et al., 1994, 1997; Ritchie et al., 2009; Diack et al., 2012, 2017). The majority of prion strains tend to show low attack rates with long incubation periods upon primary passage. Further mouse subpassages generally show a shortening in incubation periods and 100% susceptibility in terms of clinical and pathological signs of disease indicative of the removal of the species barrier. These properties then remain consistent throughout further subpassages (Bruce, 2003). As the studies in the MV recipient demonstrated inconsistences at primary passage, a full strain characterization study was required. However, the strain characteristics stabilized and were identical to that of previous vCJD and BSE transmissions with the second mouse subpassage resulting in either a 301C or 301V type TSE strain as determined by mouse line (Bruce et al., 2002; Ritchie et al., 2009).

The inconsistences noted at primary passage in attack rate and lack of TSE vacuolation, could have been a consequence of the interaction between human and mouse genetic backgrounds i.e. PRNP codon 129 genotype and Prnpa or Prnpb or could be due to a lower titre of infectivity in the spleen isolates causing longer incubation periods and decreased numbers of mice exhibiting signs of prion disease within their lifespan (Bruce et al., 2001; Bruce, 2003; Ritchie et al., 2009). Similar to earlier studies of extraneural tissue transmission, we find that the strain of agent is not altered by the tissue of origin (Bruce et al., 2001; Ritchie et al., 2009). In vivo transmission studies have suggested that different prion strains can be isolated from CNS and lymphoid tissue in the same host the mechanisms of which are not yet understood (Beringue et al., 2012). Beringue et al. (2012) also demonstrated that prions can exist in the periphery for nearly one-third of a host’s life before CNS detection. In vCJD a body of evidence including the transmission of vCJD through blood transfusion (Peden et al., 2004; Hewitt et al., 2006; Wroe et al., 2006; Gillies et al., 2009), detection of PrPTSE through PMCA (Bougard et al., 2016) and in vivo infectivity studies have shown that prion infectivity can be present without CNS involvement (Bishop et al., 2013). Three retrospective studies in anonymized UK appendix samples have revealed the presence of abnormal PrP in all three codon 129 genotypes (Ironside et al., 2000; Gill et al., 2013; Public Health England, 2016). This has given a prevalence estimate of 1 in 2000 individuals in the UK with abnormal PrP in their appendix that could be considered asymptomatic vCJD. It is currently not known exactly what the abnormal PrP present in these appendix samples represents. Possibilities include infection with vCJD, infection with another prion disease or artefact unrelated to prion disease. The results from this study of an asymptomatic individual may be important in deciphering the results from these retrospective appendix studies.

We have demonstrated that vCJD strain properties have not been impacted by host genotype, human-to-human transmission through blood transfusion, tissue of origin or point of infectivity in the disease course. However, with the identification of a primary case of clinical vCJD in a 129 heterozygous individual and abnormal PrP in appendixes of all codon 129 genotypes it is clear that continued human surveillance is required to identify new cases of vCJD and recognize any differences in disease phenotype that could be indicative of changes to the prion strain. Strain characterization studies of the clinical case of primary vCJD in a codon 129 heterozygous individual are currently being undertaken. Any changes in prion strain could lead to changes in infectious properties, which is an immediate concern for public health and it is essential that we do not become complacent in our approach to these fatal diseases.


SATURDAY, JUNE 23, 2018

CDC 

***> Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification 

Volume 24, Number 7—July 2018 Dispatch 




''It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people.''

Volume 2: Science 

4. The link between BSE and vCJD 

Summary 

4.29 The evidence discussed above that vCJD is caused by BSE seems overwhelming. Uncertainties exist about the cause of CJD in farmers, their wives and in several abattoir workers. It seems that farmers at least might be at higher risk than others in the general population. 1 Increased ascertainment (ie, increased identification of cases as a result of greater awareness of the condition) seems unlikely, as other groups exposed to risk, such as butchers and veterinarians, do not appear to have been affected. The CJD in farmers seems to be similar to other sporadic CJD in age of onset, in respect to glycosylation patterns, and in strain-typing in experimental mice. Some farmers are heterozygous for the methionine/valine variant at codon 129, and their lymphoreticular system (LRS) does not contain the high levels of PrPSc found in vCJD. It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people.

4.30 Estimates of the likely scale of a possible epidemic of vCJD are wide-ranging and the subject of much debate. To know the likely number of cases is very important, not least to enable preparations to be made for the care of victims, as well as to be able to draw up guidelines to reduce the risk of transmission from infected but asymptomatic people. Preliminary results of the study examining tonsil and appendix material for signs of infection were not informative in this regard and full results are awaited. A blood test that would allow the widespread screening of the population by a simple method is still being sought.


''It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people.''

Variant Creutzfeldt-Jakob disease in an elderly patient JW Lorains, FRCP C Henry, MRCPI DA Agbamu, MRCPath M Rossi, FRCPath M Bishop, BSC RG Will, FRCP et al. Show all authors Published:April 28, 2001DOI:https://doi.org/10.1016/S0140-6736(00)04504-9

Summary We report a case of variant Creutzfeldt-Jakob disease (vCJD) in a 74-year old man in whom diagnosis was made at necropsy. The occurrence of vCJD in an individual in this age group is unlikely to be an isolated event. Doctors need to be aware that vCJD can arise in elderly patients so that appropriate investigations (including magnetic resonance imaging) can be done, and permission for neuropathological necropsy requested, in suspected cases. This case could also have important implications for public health policy decisions and surveillance programmes that target the younger age range of vCJD cases.


Monday, May 19, 2008 

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


WEDNESDAY, MARCH 13, 2019 

CWD, TSE, PRION, MATERNAL mother to offspring, testes, epididymis, seminal fluid, and blood


SATURDAY, MARCH 16, 2019 

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) Guidance for Industry and Food and Drug Administration Staff Document issued on March 15, 2019 Singeltary Submission


TUESDAY, MARCH 12, 2019 

Early preclinical detection of prions in the skin of prion-infected animals


SUNDAY, MARCH 10, 2019 

National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated Feb 1, 2019 Variably protease-sensitive prionopathy VPSPr


Tuesday, March 20, 2018 

Variably protease-sensitive prionopathy (VPSPr), sporadic creutzfeldt jakob disease sCJD, the same disease, what if?


SUNDAY, APRIL 8, 2018 

Transmissible Spongiform Encephalopathy TSE Prion Disease Global Pandemic Urgent Update April 9, 2018


SATURDAY, OCTOBER 06, 2018 

Evaluation of iatrogenic risk of CJD transmission associated with corneal transplantation


SATURDAY, SEPTEMBER 22, 2018 

Emerging Diseases, Infection Control & California Dental Practice Act


WEDNESDAY, SEPTEMBER 26, 2018 

A new variant of Creutzfeldt-Jakob disease in the UK 1995 revisited 2018 a review of science


TUESDAY, DECEMBER 12, 2017 

Creutzfeldt Jakob Disease CJD National Prion Disease Pathology Surveillance Center Cases Examined to December 14, 2017

http://creutzfeldt-jakob-disease.blogspot.com/2017/12/creutzfeldt-jakob-disease-cjd-national.html

Tuesday, December 12, 2017 

Neuropathology of iatrogenic Creutzfeldt–Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology

http://tauopathies.blogspot.com/2017/12/neuropathology-of-iatrogenic.html

MONDAY, OCTOBER 02, 2017 

Creutzfeldt Jakob Disease United States of America USA and United Kingdom UK Increasing and Zoonotic Pontential From Different Species

http://creutzfeldt-jakob-disease.blogspot.com/2017/10/creutzfeldt-jakob-disease-united-states.html

THURSDAY, AUGUST 17, 2017 

*** Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States revisited 2017

Singeltary et al

http://creutzfeldt-jakob-disease.blogspot.com/2017/08/monitoring-occurrence-of-emerging-forms.html

SUNDAY, OCTOBER 21, 2018 

Surveillance for variant CJD: should more children with neurodegenerative diseases have autopsies? Singeltary Review


vCJD Appendix III study UPDATE

A further study was designed

– Appendix III – looking at two further population groups: appendices removed from individuals during surgery performed before 1980 and appendices removed from individuals born after 1996. These two groups being unexposed to dietary BSE risk, as discussed above. The expectation was, therefore, that no positive results would be found in either group. 

***> However, positive results were found in both and the numerical analysis found no statistically significant difference in the rate of abnormal appendices in the three time groups: pre1980, 1980-1996 and post-1996.

There are two broad explanations for this unexpected finding:

1.That abnormal prion protein in the appendix is not always an indication of BSE infection. However, if this is so, it is not clear as to what it would indicate.

2.That the dietary exposure period in the UK was more extensive than supposed – beginning before 1980 and extending after 1996. However, from what is known about the BSE epidemic, it is not straightforwardly obvious as to how this could be.

The full details of the Appendix III study are not yet published. Discussions are ongoing as to how to interpret the results as they stand and further research is planned to see if the questions raised can be answered. However, at the moment, uncertainty surrounds some of the assumptions that have been made about BSE and vCJD in the UK.


The Appendix III study looked at samples outside of the presumed BSE exposure period: those removed before 1980, and from young people born after 1996.

The results of the Appendix III study have not yet been reported in detail, but a preliminary report [67] revealed that positive samples were found in both groups examined, but not in any appendix removed before 1976 or in any individual born after 2000. It could be that there is a low background prevalence of abnormal prion protein in appendices, unrelated to the intensity of exposure to BSE, or that it is related to BSE exposure and that human exposure began in the late 1970s and continued until the mid-1990s, although at a lower rate than in the central years in the mid-1980s. 


Infection report

Volume 10 Number 26 Published on: 12 August 2016

Summary results of the third national survey of abnormal prion prevalence in archived appendix specimens

In July 2012, the Transmissible Spongiform Encephalopathies (TSE) Risk Assessment SubGroup of the Advisory Committee on Dangerous Pathogens (the successor national advisory committee to the Spongiform Encephalopathy Advisory Committee (SEAC)), considered the results of the second unlinked anonymous national survey of the prevalence of abnormal prion protein in human appendix samples (Appendix-II [1]), and concluded that a further similar survey should be conducted on tissues from population groups considered unexposed to BSE [2]. This third national survey (Appendix-III) of appendix specimens removed at operations prior to the BSE epizootic and appendix specimens from those born in 1996 or later, by which time measures had been put in place to protect the food chain, has now been concluded. This report provides a summary of the results of the Appendix-III survey prior to publication in due course of the complete data.

The Appendix-III survey examined by immunohistochemistry (IHC) appendices removed at operation and collected from 44 hospitals throughout England. Abnormal prion accumulation was detected within the follicular dendritic cells of seven appendices out of 29,516 suitable samples examined. Indirect comparison of available data showed that none of the positive appendices could have come from the 178 known vCJD cases in the UK.

Two of the seven positive samples were from the 14,692 appendices removed at operations conducted in 1962 through 1979: both these positive samples were from the 5,865 appendices removed in 1977 through 1979. The other five positive samples were found in the 14,824 appendices from subjects born in 1996 or later and removed at operation in 2000 through 2014: all five were in the sub-group of 10,074 born in 1996 through 2000. Therefore, none of the seven positive appendices were in specimens removed before 1977 or in patients born in 2001 or later.

The planned statistical analysis found no difference between the prevalence observed in the Appendix-II survey of 493 per million (95% Confidence Interval (CI): 282 to 801 per million) and the Appendix-III prevalence in appendices removed between 1962 through 1979 of 136 per 

Health Protection Report Vol. 10 No. 26 – 12 August 2016

million (95%CI: 16 to 492 per million; exact p=0.08), nor with the Appendix-III prevalence in appendices from those born in 1996 through 2000 of 337 per million (95%CI: 110 to 787 per million; exact p=0.64). Test accuracy calculations using the Appendix-III data suggest the IHC technique specificity is in the range of 99.975% to over 99.99%. Although specificity of this magnitude (99.99%) implies few false positives, if the true prevalence is very low, then the positive predictive value of the IHC technique will diminish. At the one in 7,000 prevalence observed in the Appendix-III survey of specimens removed in 1979 or earlier, the positive predictive value (PPV) will be 56%, for a specificity of 99.99% and a sensitivity of 90%, compared to a PPV of 82% at the one in 2,000 prevalence observed in the Appendix-II survey. The Appendix-II and -III surveys were conducted by a collaboration of PHE, the Department of Neurodegenerative Diseases at the UCL Institute of Neurology, the Animal and Plant Health Agency, the National Creutzfeldt-Jakob Disease Research and Surveillance Unit, the Histopathology Department of Derriford Hospital in Plymouth, and the MRC Prion Unit.

In summary, the Appendix-III survey data have not produced a clear answer to the question of whether abnormal prions detected by IHC in the British population is limited to those exposed to the BSE epizootic, and various interpretations are possible. The survey results have been considered by the ACDP TSE Sub-Group and a position paper detailing the conclusions of the committee has been published online, simultaneously with this summary report [3]. 

References

1. Gill ON, Spencer Y, Richard-Loendt, A, Kelly C, Dabaghian R, Boyes L, et al (2013). Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ 347: f5675, http://www.bmj.com/content/347/bmj.f5675.

2. Advisory Committee on Dangerous Pathogens TSE Risk Assessment Subgroup (July 2012). Position Statement on occurrence of vCJD and prevalence of infection in the UK population. Available from: ACDP TSE subgroup minutes, agendas and papers, https://app.box.com/s/hhhhg857fjpu2bnxhv6e.

3. Advisory Committee on Dangerous Pathogens TSE Risk Assessment Subgroup (August 2016). “Appendix-III” position statement. Available from: ACDP TSE subgroup minutes, agendas and papers, https://app.box.com/s/hhhhg857fjpu2bnxhv6e


some history...TSS

snip...see full text ;


SUNDAY, MARCH 10, 2019 

National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated Feb 1, 2019 Variably protease-sensitive prionopathy VPSPr


PRION CONFERENCE 2018

O3 Experimental studies on prion transmission barrier and TSE pathogenesis in large animals 

Rosa Bolea(1), Acín C(1)Marín B(1), Hedman C(1), Raksa H(1), Barrio T(1), Otero A(1), LópezPérez O(1), Monleón E(1),Martín-Burriel(1), Monzón M(1), Garza MC(1), Filali H(1),Pitarch JL(1), Garcés M(1), Betancor M(1), GuijarroIM(1), GarcíaM(1), Moreno B(1),Vargas A(1), Vidal E(2), Pumarola M(2), Castilla J(3), Andréoletti O(4), Espinosa JC(5), Torres JM(5), Badiola JJ(1). 

1Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, VeterinaryFaculty, Universidad de Zaragoza; Zaragoza,Spain.2 RTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB) 3 4 INRA, ÉcoleVétérinaire, Toulouse, France.5CIC bioGUNE, Prion researchlab, Derio, Spain CISA- INIA, Valdeolmos, Madrid 28130, Spain. 

Experimental transmission of Transmissible Spongiform Encephalopathies (TSE) has been understood and related with several factors that could modify the natural development of these diseases. In fact, the behaviour of the natural disease does not match exactly in each animal, being modified by parameters such as the age at infection, the genotype, the breed or the causative strain. Moreover, different TSE strains can target different animal species or tissues, what complicate the prediction of its transmissibility when is tested in a different species of the origin source. The aim of the experimental studies in large animals is to homogenize all those factors, trying to minimize as much as possible variations between individuals. These effects can be flattened by experimental transmission in mice, in which a specific strain can be selected after several passages. With this objective, several experimental studies in large animals have been developed by the presenter research team. 

Classical scrapie agent has been inoculated in cow, with the aim of demonstrate the resistance or susceptibility of this species to the first well known TSE; Atypical scrapie has been inoculated in sheep (using several routes of infection), cow and pig, with the objective of evaluating the potential pathogenicity of this strain; Classical Bovine Spongiform Encephalopathy (BSE) has been inoculated in goats aiming to demonstrate if the genetic background of this species could protect against this strain; goat BSE and sheep BSE have been inoculated in goats and pigs respectively to evaluate the effect of species barrier; and finally atypical BSE has been inoculated in cattle to assess the transmissibility properties of this newly introduced strain. 

Once the experiments have been carried out on large animal species, a collection of samples from animals studied were inoculated in different types of tg mice overexpressing PrPcin order to study the infectivity of the tissues, and also were studied using PMCA. 

In summary, the parameters that have been controlled are the species, the strain, the route of inoculation, the time at infection, the genotype, the age, and the environmental conditions. 

To date, 

***> eleven of the atypical scrapie intracerebrally inoculated sheep have succumbed to atypical scrapie disease; 

***> six pigs to sheep BSE; 

***> one cow to classical scrapie; 

***> nine goats to goat BSE and 

***> five goats to classical BSE. 

***> PrPSC has been demonstrated in all cases by immunohistochemistry and western blot. 

=====> PRION CONFERENCE 2018 


Saturday, December 15, 2018 

***> ADRD Summit RFI Singeltary COMMENT SUBMISSION BSE, SCRAPIE, CWD, AND HUMAN TSE PRION DISEASE December 14, 2018


TUESDAY, NOVEMBER 20, 2018 

CDC Eyes of CJD patients show evidence of prions concerns for iatrogenic transmission 


WEDNESDAY, OCTOBER 17, 2018 

PRICE OF TSE PRION POKER GOES UP spectrum of human prion diseases may extend the current field and may notably include spinal cord diseases


REVIEW 

***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***

***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<*** 

***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***

***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<*** 

***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***

Saturday, February 2, 2019 

CWD GSS TSE PRION SPINAL CORD, Confucius Ponders, What if?


TUESDAY, MARCH 26, 2019 

USDA ARS 2018 USAHA RESOLUTIONS TWO PRONGED APPROACH NEEDED FOR ADVANCING CATTLE TRACEABILITY


THURSDAY, MARCH 14, 2019 

USDA APHIS CDC FDA BSE TSE PRION UPDATE 2019


THURSDAY, MARCH 14, 2019

USDA APHIS CDC Cervids: Chronic Wasting Disease Specifics Updated 2019


SATURDAY, MARCH 16, 2019

Chronic Wasting Disease CWD TSE Prion United States of America Update March 16, 2019


FRIDAY, MARCH 15, 2019

Saskatchewan Chronic Wasting Disease TSE Prion 349 Cases Positive for 2018


TUESDAY, MARCH 26, 2019

USDA ARS 2018 USAHA RESOLUTIONS Investigation of the Role of the Prion Protein Gene in CWD Resistance and Transmission of Disease


FRIDAY, MARCH 29, 2019

First Detection of Chronic Wasting Disease in a Wild Red Deer (Cervus elaphus) in Europe


WEDNESDAY, APRIL 03, 2019 

Estimating the amount of Chronic Wasting Disease infectivity passing through abattoirs and field slaughter


FRIDAY, MARCH 15, 2019 

USDA APHIS SCRAPIE TSE PRION Sheep and Goat Health Update 2019


MONDAY, FEBRUARY 25, 2019

MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019


Cows, Cash and Cover-ups? Investigating Variant CJD





TUESDAY, MARCH 26, 2019 

Joint Statement from President Donald J. Trump USA and President Jair Bolsonaro Brazil FOREIGN POLICY BSE TSE Prion aka mad cow disease


THURSDAY, OCTOBER 04, 2018

Cervid to human prion transmission 5R01NS088604-04 Update


MONDAY, APRIL 01, 2019 

PUBLIC HEALTH U of M launches Chronic Wasting Disease Program to address potential health crisis


prepare for the storm...

Terry S. Singeltary Sr.


posted by Terry S. Singeltary Sr. | 11:11 AM

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