VARIANT CJD (vCJD) or nvCJD

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Location: BACLIFF, Texas, United States

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

Monday, August 21, 2017

Similarities of Variant Creutzfeldt-Jakob Disease Strain in Mother and Son in Spain to UK Reference Case

Similarities of Variant Creutzfeldt-Jakob Disease Strain in Mother and Son in Spain to UK Reference Case


Abigail B. Diack, Aileen Boyle, Diane Ritchie, Chris Plinston, Dorothy Kisielewski, Jesús de Pedro-Cuesta, Alberto Rábano, Robert G. Will,1 Jean C. Manson1


We investigated transmission characteristics of variant Creutzfeldt-Jakob disease in a mother and son from Spain. Despite differences in patient age and disease manifestations, we found the same strain properties in these patients as in UK vCJD cases. A single strain of agent appears to be responsible for all vCJD cases to date.


I n 2008 in Spain, 2 cases of variant Creutzfeldt-Jakob disease (vCJD) in first-degree relatives were identified. After the death of a 41-year-old man (patient 1) from vCJD, his 64-year-old mother (patient 2) began showing symptoms of anxiety and depression and, 2 months later, a gait disorder and progressive dementia. Although the clinical duration was relatively short and the early symptoms uncommon in comparison to vCJD cases in the United Kingdom, the overall clinical phenotype and posterior thalamic hyperintensities as seen in an MRI brain scan led to a diagnosis of suspected vCJD. Neuropathological examination confirmed the diagnosis of vCJD. Both patients were 129MM homozygous, had never received a blood transfusion or tissue graft, and had lived in the same town within the Castilla-León region of Spain (Table 1) (1). The region is a farming area at high risk for bovine spongiform encephalopathy (BSE); 3 of the 5 cases of vCJD reported in Spain came from this region (1). The patients had similar eating habits, which included ingestion of bovine brain. We conducted a study to determine whether these 2 vCJD cases were caused by the BSE agent, whether the agent strain was similar to previously characterized human vCJD cases, and whether the age of the patients would influence the strain characteristics.


Conclusions


This transmission study of central nervous system tissue from 2 first-degree relatives with vCJD confirms that the same infectious transmissible spongiform encephalopathy (TSE) agent was responsible for both cases. Comparisons of incubation period, TSE neuropathology, and PrPres biochemistry indicate that this strain is consistent with that of a UK case of vCJD and with historical vCJD transmission data (6). The epidemiologic investigation of the 2 related patients indicated that they had shared a common residence and dietary habits, including cattle brain consumption, for >30 years. This finding suggests a common source of infection linked to the consumption of highrisk material in a known BSE area, and these transmission studies support the hypothesis that consumption of BSE-contaminated food products is a major risk factor for vCJD (7).


A feature of the UK vCJD epidemic was the relatively young age of the patients at onset. During 1995–2014, only 6 of 177 cases of vCJD identified in the United Kingdom were in persons >55 years of age at the onset of symptoms. Clinical phenotypes in these 6 patients were less consistent than those observed in younger patients (8). The evidence suggests that age is not a barrier to either infection or developing the disease; diagnosis of vCJD may become more important as exposed populations become older. Our study demonstrates that older persons harbor the vCJD agent in the central nervous system in a similar manner to younger persons. Small differences in incubation periods and the intensity of TSE vacuolation are apparent, which may be indicative of variation in the titer of the isolates. It is unknown when the 2 patients from Spain were infected, but if they were exposed at the same time, the 23-year difference in age at time of exposure may have influenced pathogenesis and the ability of the agent to replicate. A delay in neuroinvasion or slower rates of replication in the brain could explain why clinical symptoms are more variable in older patients. 

Although our study demonstrates that clinical presentation and infective titer may differ between patients, the overall strain characteristics remain similar. Thus, the vCJD strain can be identified using our strain typing panel regardless of these variable factors.

This study highlights the need for awareness of vCJD in older age groups, particularly in patients with clinical manifestations of atypical dementias. These findings add additional supporting evidence to the hypothesis that a single strain of TSE agent is responsible for vCJD cases, regardless of geographic origin or age at infection, and indirectly support the hypothesis of a dietary origin for primary cases of vCJD.




the UKBSEnvCJD of adolescents only theory falls further into the abyss, along with the notion that it was nvCJD only that was zoonosis zoonotic disease there from, imo...tss


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.
 
==============
 
 

 Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency 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.
 
 
 

Saturday, April 23, 2016
 
Scrapie ZOONOSIS PRION CONFERENCE TOKYO 2016
 
*** SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016 ***
 
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X
 
 


SUNDAY, AUGUST 09, 2009 

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




TUESDAY, AUGUST 18, 2009 

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




WEDNESDAY, OCTOBER 09, 2013 

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




THURSDAY, AUGUST 17, 2017 

JAVMA NEWS Atypical BSE found in Alabama cow September 01, 2017




THURSDAY, AUGUST 17, 2017 

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




MONDAY, JUNE 19, 2017 

PRION 2017 CONFERENCE ABSTRACT P61 vCJD strain properties in a Spanish mother and son replicate as those of a young UK case



FRIDAY, MARCH 10, 2017

OIE Spain Prion (Atypical BSE type L) Bovine Spongiform Encephalopathy Mad Cow Disease




wasted days and wasted nights...Freddy Fender


Terry S. Singeltary Sr.
Bacliff, Texas USA 
Galveston Bay, on the bottom

Monday, June 19, 2017

PRION 2017 CONFERENCE ABSTRACT P61 vCJD strain properties in a Spanish mother and son replicate as those of a young UK case

P61 vCJD strain properties in a Spanish mother and son replicate as those of a young UK case 

Dr Abigail Diack1, Mrs Aileen Boyle, Dr Diane Ritchie2, Jesus de Pedro-Cuesta3, Alberto Rabano4, Prof Robert WiLL2, Prof Jean Manson1
1The Roslin Institute, Easter Bush, United Kingdom, 2National CJD Research & Surveillance Centre, Edinburgh, United Kingdom, 3National Center of Epidemiology and CIBERNED, Madrid, Spain, 4CIEN Tissue Bank, ClEN Foundation, and ClBERNED, Madrid, Spain 

Aims 
Since the first report in 1996, there have been 228 cases of vCJD worldwide. Comparative studies of vCJD cases have demonstrated similar clinical symptoms, patterns of neuropathology and biochemical phenotype between cases originating from different countries. Here we have investigated transmission characteristics of the first cases of vCJD in first-degree relatives, a mother and son who resided in Spain. Both individuals are in the older age range of reported vCJD cases and had relatively atypical early clinical symptoms when compared to UK cases. 

Methods 
A strain typing panel of wild-type mice was inoculated with brain homogenate prepared from both the Spanish mother (aged 64) and son (aged 41) and compared with a UK case of vCJD. Mice were assessed for clinical signs, neuropathology and PrPres glycoform profile. 

Results 
All three vCJD brain isolates transmitted successfully to the wild-type mouse panel with the appearance of clinical and pathological signs associated with TSE transmission to mice. Inocula from the Spanish mother and son showed the same temporal order of clinical endpoint in each mouse strain when compared with the UK case. The distribution of TSE vacuolation was consistent for each vCJD inocula however variability in the intensity of vacuolation distribution was apparent. This was most evident in the VM mice challenged with the Spanish mother and may be indicative of low titre. PrP deposition patterns were similar between inocula with variability in the intensity of PrP accumulation between mice observed both within and between groups. PrPres was detected in the brains of RIII and VM mice challenged with all three isolates with no differences detected. 

Conclusions This study of two first degree relatives with vCJD confirms that the same infectious TSE agent was responsible for both cases and is consistent with that of a UK case of vCJD and historical vCJD transmission data. This is the first strain characterisation study of an older individual with vCJD and highlights the need for awareness of vCJD in older age groups particularly in those presenting with atypical dementias. These findings add additional supporting evidence to the hypothesis that a single strain of TSE agent is responsible for vCJD cases regardless of geographical origin or age at infection and indirectly support the hypothesis of a dietary origin for primary cases of vCJD. 

PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS 


SEAC 102nd Meeting on Wednesday 4 March 2009 (SEE DH risk assessment on sourcing and pooling plasma) SEACAgenda 102nd Meeting on Wednesday 4 March 2009 Room 808, Nobel House, 17 Smith Square, Defra, London SW1P 3JR10.05 Approval of draft minutes from SEAC 101

snip...

ITEM 3 - CURRENT ISSUES 8. SEAC was informed about the following issues: . A mother and son in Spain had died of variant Creutzfeldt-Jakob Disease (vCJD). This is the first recorded instance of more than one case of vCJD within one family. As both the mother and son lived in a region of Spain with a history of BSE, had frequently shared meals of cattle brain, and as no other risk factor has been identified, it seems most likely that both infections were acquired from dietary exposure. Furthermore, the similar times of onset of disease of the cases did not suggest transmission had occurred from one to the other.

snip...

Thursday, February 26, 2009 

SEAC 102nd Meeting on Wednesday 4 March 2009 (SEE DH risk assessment on sourcing and pooling plasma) 



-----Original Message----- From: Terry Singeltary To: flounder9 Sent: Mon, Jun 19, 2017 11:25 am Subject: mother and son nvCJD

Published Date: 2008-11-03 19:00:43 Subject: PRO/AH/EDR> Prion disease update 2008 (12) Archive Number: 20081103.3458 PRION DISEASE UPDATE 2008 (12)

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A ProMED-mail post <http://www.promedmail.org> ProMED-mail is a program of the International Society for Infectious Diseases <http://www.isid.org>

[With the continuing decline in the number of cases in the human population of variant Creutzfeldt-Jakob disease -- abbreviated previously as vCJD or CJD (new var.) in ProMED-mail -- it has been decided to broaden the scope of the occasional ProMED-mail updates to include other prion-related diseases. Data on vCJD cases and other forms of CJD: sporadic, iatrogenic, familial, and GSS (Gerstmann-Straussler-Scheinker disease) are included also when they have some relevance to the incidence and etiology of vCJD. - Mod.CP]

In this update: [1] UK: National CJD Surveillance Unit - monthly statistics as of Mon 3 Nov 2008 [2] France: Institut de Veille Sanitaire - monthly report as of 30 Oct 2008 [3] US National Prion Disease Pathology Surveillance Center - cases examined through September 2008 [4] & [5] The Spanish cluster of vCJD [6] CJD incidence in China 2006/2007 [7] CJD in dura mater grafts - Japan, 1978-2008 [8] Blood products risk update (US) - vCJD

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[1] UK: National CJD Surveillance Unit - monthly statistics as of Mon 3 Nov 2008 Date: Mon 3 Nov 2008 Source: UK National CJD Surveillance Unit, monthly statistics [edited] <http://www.cjd.ed.ac.uk/figures.htm>

 The number of suspect cases of vCJD referred to the CJD surveillance unit in Edinburgh and the number of deaths of definite and probable variant Creutzfeldt-Jakob disease [abbreviated in ProMED-mail as CJD (new var.) or vCJD], the form of the disease thought to be linked to BSE (bovine spongiform encephalopathy), remain unchanged since the previous monthly report; that is, the number of definite or probable vCJD cases (dead and alive) remains 167.

This situation is consistent with the view that the vCJD outbreak in the UK is in decline. The 1st cases were observed in 1995, and the peak number of deaths was 28 in the year 2000, followed by 20 in 2001, 17 in 2002, 18 in 2003, 9 in 2004, 5 in 2005, 5 in 2006, 5 in 2007, and only one so far (up to the end of October) in 2008.

Totals for all types of CJD cases in the year 2008

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As of 3 Nov 2008 in the UK, so far there have been 114 referrals, 62 deaths from sporadic CJD, 4 deaths from iatrogenic CJD, 3 from GSS, 2 from familial CJD, and one from vCJD.

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communicated by: ProMED-mail <promed@promedmail.org>

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[2] France: Institut de Veille Sanitaire - monthly report as of 30 Oct 2008 Date: Thu 30 Oct 2008 Source: IVS - Maladie de Creutzfeldt-Jakob et maladies apparentees [French, trans. & summ. Mod.CP, edited] <http://www.invs.sante.fr/display/?doc=publications/mcj/donnees_mcj.html>

 During the period 1992 to 2008, there were 23 cases of vCJD, all now deceased. They occurred between 1996 and 2007: one case in 1996, one in 2000, one in 2001, 3 in 2002, none in 2003, 2 in 2004, 6 in 2005, 6 in 2006, 3 in 2007, and none so far in 2008. There were 12 male and 11 female patients.

Their ages at time of death ranged from 19 to 58 years (mean 39); 6 of the patients resided in the Ile-de-France [Paris area] and 17 in the provinces. All the cases were met-met homozygotes for codon 129 of the prion protein gene. No special risk factors were evident, which distinguished these patients from those with other forms of CJD (sporadic, genetic, iatrogenic). However, one patient had visited the UK at regular intervals.

Totals for all types of CJD cases in the year 2008

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As of 30 Oct 2008 in France, so far in 2008 there have been 1230 referrals, 56 deaths from sporadic CJD, 3 deaths from iatrogenic CJD, 7 from familial CJD, none from GSS, and none from vCJD.

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communicated by: ProMED-mail <promed@promedmail.org>

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[3] US National Prion Disease Pathology Surveillance Center - cases examined through September 2008 Date: 30 Sep 2008 Source: US National Prion Disease Pathology Surveillance Center [edited] <http://www.cjdsurveillance.com/resources- casereport.html>

 Cases examined - as of September 2008

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During the period 1997 to 2008, 2 cases of vCJD were reported, both contracted overseas. The 1st case was recorded in 2004 (disease contracted in the UK), and the 2nd in 2006 (disease contracted in Saudi Arabia).

Totals for all types of CJD cases in the year 2008

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So far in 2008, there have been 273 referrals, 124 cases of prion disease, including 109 cases of sporadic CJD, 15 cases of familial CJD, no cases of iatrogenic CJD, and no indigenous cases of vCJD.

Overall during the period 1997 to 2008, there have been 2962 referrals, 1663 cases of prion disease, 1413 cases of sporadic CJD, 244 cases of familial CJD, 4 cases of iatrogenic CJD, and no indigenous cases of vCJD.

[During 2008 so far, the USA, with about 2.5 times the combined populations of the UK and France, has reported fewer cases of sporadic CJD (109 versus 117). Whether this is due to a difference in surveillance procedure or actual disease incidence is unclear at present. - Mod.CP]

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communicated by: ProMED-mail <promed@promedmail.org>

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[4] The Spanish cluster of vCJD Date: Wed 22 Oct 2008 Source: Scribd.com [edited] <http://www.scribd.com/doc/6224550/Memorandum-on-a-Variant-CJD-Family-Cluster>

 Statement on a variant CJD family cluster

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Three cases of pathologically confirmed variant CJD have been identified in Spain in recent years, including a man in his early 40s who died earlier this year [2008]. The clinical illness in this individual was typical of variant CJD, including the appearances on the MRI brain scan.

A few months ago, his mother, who was in her 60s, developed a rapidly progressive neurological illness and died about 5 months from the onset of this illness. An MRI brain scan showed appearances suggestive of variant CJD, and preliminary results from post-mortem examination suggest that the suspected diagnosis of variant CJD is correct. Further results, which may confirm this diagnosis, should be available within a few days.

Since 1994, there have been 167 cases of variant CJD in the UK, 23 cases in France and 15 cases in other countries, excluding Spain. The occurrence of variant CJD in more than one member of the same family has not been seen before, and it has been the general view that family members of variant CJD cases are not themselves at greater risk of developing this condition. This raises the question as to why 2 cases of variant CJD have now been found in a family in Spain.

There is no evidence of a genetic form of CJD in these Spanish cases, and preliminary investigation has not shown any risk of CJD through medical or surgical treatment. There is no evidence of any risk of transmission of CJD through direct personal contact. The mother and son lived in an area of Spain in which BSE has been found, and it is possible that direct consumption of material with high levels of BSE infection may have been the source of the infection. In the UK and other countries, it is believed that processed bovine tissues were the most likely source of BSE infection, and it is possible that different forms of exposure to BSE infection may explain the occurrence of variant CJD in 2 family members in Spain and not elsewhere.

This, however, is uncertain, and public health policies in relation to variant CJD may have to be reviewed in the light of these 2 cases in Spain.

[This statement is attributed to Professor Robert G Will, UK National CJD Surveillance Unit, Edinburgh. - Mod.CP]

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communicated by: Terry S Singeltary Sr <flounder9@verizon.net>

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[5] The Spanish cluster of vCJD

Date: 15 Oct 2008

Source: Spongiform Encephalopathy Advisory Committee (SEAC), 101st meeting report [edited] <http://www.seac.gov.uk/papers/101-summary.pdf>

 Current issues

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Regarding a mother and son in Spain who had died of variant Creutzfeldt-Jakob Disease (vCJD): this is the 1st recorded instance of more than one case of vCJD within one family. Both the mother and son lived in a region of Spain with a history of BSE and had frequently shared meals of cattle brain. As no other risk factor has been identified, it seems most likely that both infections were acquired from dietary exposure.

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communicated by: Terry S Singeltary Sr <flounder9@verizon.net>

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[6] CJD incidence in China 2006/2007 Date: Sat 18 Oct 20008 Source: BMC Public Health online [edited] <http://www.biomedcentral.com/1471-2458/8/360/abstract>

 Surveillance for Creutzfeldt-Jakob disease in China from 2006 to 2007

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[The following is the provisional abstract of a paper with the above title, by Qi Shi, Chen Gao, Wei Zhou, Baoyun Zhang, Jianming Chen, Chan Tian, et al; published in BMC Public Health 2008; 8: 360]

Background

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Human transmissible spongiform encephalopathies (HTSE), or Creutzfeldt-Jakob disease (CJD), is a group of rare and fatal diseases in the central nervous system. Since outbreak of bovine spongiform encephalopathy (BSE) and variant CJD, a worldwide CJD surveillance network has been established under the proposition of WHO. In China, a national CJD surveillance system has started since 2002. The data of CJD surveillance from 2006 to 2007 was analyzed.

Methods

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A total of 12 provinces are included in the CJD surveillance system. The surveillance unit in each province consists of one or 2 sentinel hospitals and the provincial CDC. All suspected CJD cases reported from CJD surveillance were diagnosed and subtyped based on the diagnostic criteria for CJD issued by WHO.

Results

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A total of 192 suspected CJD cases were reported and 5 genetic CJD, 51 probable and 30 possible sporadic CJD (sCJD) cases were diagnosed. The collected sCJD cases distribute sporadically without geographical clustering and seasonal relativity, and the highest incidences in both probable and possible sCJD cases appeared in the group of 60-69 years old.

The most common 3 foremost symptoms were progressive dementia, cerebellum and mental-related symptoms. The probable sCJD patients having both typical EEG alteration and being CSF protein 14-3-3 positive have more characteristic clinical syndromes than the ones having only one positive. The polymorphisms of codon 129 of all tested reported cases show typical patterns of Han Chinese, as in previous reports that M129M is predominant, whereas M129V is rare.

Conclusion

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Chinese CJD patients possessed similar epidemiological and clinical characteristics as the population worldwide.

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communicated by: Terry S Singeltary Sr <flounder9@verizon.net>

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[7] CJD in dura mater grafts - Japan, 1978-2008 Date Fri 24 Oct 2008 Source: MMWR Weekly 57(42);1152-1154 [edited] <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5742a3.htm>

 Update: Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts, Japan, 1978-2008

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Creutzfeldt-Jakob disease (CJD) is the most common of the human prion diseases (also known as transmissible spongiform encephalopathies), which, according to the leading hypothesis, are caused by an abnormal protein (that is, prion) that is able to induce abnormal folding of normal cellular prion proteins. Annual worldwide incidence of these always fatal neurodegenerative diseases is estimated at 0.5-2.0 cases per million population. CJD can occur sporadically, or as a genetic disease, or can be transmitted iatrogenically. In 1996, a new human prion disease, variant CJD (vCJD), was 1st described in the United Kingdom. This disease was believed to have resulted from human consumption of cattle products contaminated with the prions responsible for bovine spongiform encephalopathy (BSE, commonly known as mad cow disease). That year, in part to check for possible vCJD cases, a national survey was conducted in Japan; 821 CJD cases were identified, including 43 cases associated with receipt of cadaveric dura mater grafts (1). A single brand of dural graft (Lyodura) produced by a German manufacturer before May 1987 was identified as the most likely vehicle of transmission in all but one case (2,3). By 2003, continued surveillance in Japan had identified a total of 97 such cases (2). Since then, an additional 35 cases have been identified. This report updates previous reports and summarizes the investigation of all 132 cases to date linked to dural grafts. The results suggest that, because of the long incubation period between graft receipt and symptom onset (possibly greater than 24.8 years), continued surveillance in Japan might identify additional CJD cases associated with dural grafts. Since 1996 in Japan, a nongovernmental CJD surveillance group supported by the Ministry of Health and Welfare (later renamed the Ministry of Health, Labour, and Welfare) has conducted a national survey seeking cases of human prion disease. The survey is mailed to neurologic, psychiatric, and neuropathologic departments of hospitals with a minimum bed capacity of 100 (overall response rate: 74 per cent) (1,2). A case of CJD associated with a dura mater graft is defined as physician-diagnosed CJD in the recipient of a cadaveric dura mater graft whose disease was reviewed and accepted as CJD by the surveillance system's panel of neurologists.

During 1996-2008, as clinicians reported additional CJD cases to the surveillance system sponsored by the Ministry of Health and Welfare, the number of persons identified with CJD associated with cadaveric dura mater grafts increased from 43 initially to 132. All 132 patients had received dura mater grafts during 1978-1993. Three patients received more than one dural graft during this period, including one patient reported previously. For purposes of analysis, the 1st graft was assumed to be the source of infection in all 3 patients. Of the 132 patients, the most common medical conditions leading to the use of dural grafts were tumor (60 patients, 45 per cent), brain hemorrhage (21, 16 per cent), Jannetta procedure for facial palsy (18, 14 per cent) and for trigeminal neuralgia (7, 5 per cent), and intracranial aneurysm (9, 7 per cent). The other conditions were unspecified anomalies (6 patients), hematoma (6), injury (4), and ossification of the spinal posterior longitudinal ligament (one).

Illness onset for the 132 CJD patients ranged from September 1985 to October 2006. The mean age of the 132 patients at onset was 55 years (range: 15-80 years); the median age was 57 years. A total of 79 (60 per cent) patients were female. Neuropathologic confirmation of CJD diagnosis was obtained from 31 (23 per cent) patients; 81 (80 per cent) of the other 101 patients with physician-diagnosed CJD had an electroencephalogram with a periodic synchronous discharge pattern characteristic of CJD.

Incubation periods ranged from 1.2 years (receipt in 1987 and onset in 1989) to 24.8 years (receipt in 1981 and onset in 2006). The median and mean incubation periods were 12.4 years and 11.8 years, respectively.

A total of 120 of the 132 patients (91 per cent) were documented to have received Lyodura dural grafts; investigators were unable to identify the lot numbers of the grafts used. For the 12 other patients, the brand name of the dural graft was unknown. A total of 109 (83 per cent) patients received their dural grafts during 1983-1987, when an estimated 100 000 persons received Lyodura grafts in Japan (2,4).

[Reported by: Y Nakamura, MD, R Uehara, MD, PhD, M Watanabe, MD, PhD, A Sadakane, MD, Dept of Public Health, Jichi Medical Univ, Shimotsuke; M Yamada, MD, Dept of Neurology, Kanazawa Univ Graduate School of Medical Science, Kanazawa; H Mizusawa, MD, Dept of Neurology, Tokyo Medical and Dental Univ School of Medicine, Tokyo, Japan. R Maddox, MPH, J Sejvar, MD, E Belay, MD, L Schonberger, MD, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, CDC]

MMWR editorial note:

--------------------

New cases of CJD associated with dural grafts continue to be reported in Japan, and Lyodura grafts remain the most likely vehicle for transmission. Similar to other allogeneic dura mater grafts, Lyodura grafts were derived from cadaveric dura mater and used by surgeons for soft-tissue reconstruction of damaged, missing, or impaired tissues (primarily dura mater). According to the manufacturer, the grafts were gradually absorbed in situ, colonized by fibroblasts and stem cells, and eventually replaced by endogenous connective tissue.

In 1987, the 1st identified case of CJD associated with a Lyodura graft was reported in the United States (5). During the US investigation of that case, the manufacturer reported revising collection and processing procedures for Lyodura to reduce the risk for CJD transmission (6). Only 6 of the 132 patients in Japan received their dural grafts after 1987, and only one of these 6 patients is known to have received a Lyodura graft that was most likely produced after 1987. This patient had received 2 dura mater grafts in 1991 at a hospital that reported using only Lyodura or another brand of dural grafts, Tutoplast (3). No cases have been reported in Japan among patients who received their 1st dural graft after 1993.

The substantial number of CJD cases associated with dural grafts in Japan likely reflects the widespread use in that country of Lyodura grafts produced before May 1987. During 1983-1987, an estimated 20 000 persons in Japan received Lyodura grafts each year, about 50 times higher than the estimated number of recipients in the US (2,4). Although Lyodura was then available to US hospitals through the mail, the German manufacturer produced Lyodura for distribution in Japan and other countries but not for distribution in the US (7). In June 1987, after the company learned of the 1st CJD case associated with a Lyodura graft, the manufacturer reported revising procedures for the collection and processing of its dura mater grafts after 1 May 1987, to reduce the risk for CJD transmission (6). The key reported processing changes included conversion from batch to individual processing of dura mater and treatment of each dura mater graft with 1.0 normal sodium hydroxide (NaOH); no practical final screening test of the product for prion contamination is available. However, the change to individual processing of dura mater greatly limited the number of grafts that could be contaminated by a single infected donor. In addition, 1.0 normal NaOH is known to be highly effective for inactivating prions (3).

In the US, after report of the 1st Lyodura-associated CJD case, the Food and Drug Administration (FDA) issued a recall in late April 1987 of Lyodura that was packaged in 1982, the year the graft used in the initial US case had been packaged. In addition, after receiving report of a 2nd Lyodura-associated CJD case in a patient in New Zealand, CDC advised avoiding Lyodura grafts produced before May 1987 (6). However, no international recall of Lyodura produced before May 1987 occurred. Therefore, the implicated Lyodura with its potential contaminant might have remained in use at Japanese hospitals for several years.

Cases of dural graft-associated CJD in Japan have occurred since 1985, peaking during 1995-1999, when 51 of the 132 patients became ill. As this outbreak has continued, the median incubation period has increased to 12.4 years, and the longest period between graft surgery and onset of illness is now 24.8 years. In the US, 2 more patients with Lyodura-associated CJD have been identified since the 1st reported case in 1987. Most recently, a patient aged 26 years died in 2006 from autopsy-confirmed CJD (7). The incubation period in this case was 18.7 years.

The long incubation period and always fatal outcome of CJD and other transmissible spongiform encephalopathies underscore the importance of efforts to minimize potential exposures of persons to prions. However, implementing timely preventive measures against these diseases can be difficult because the public health significance of certain actions might not become apparent for years, if at all. For example, in 1987, the producer of Lyodura revised collection and production measures without knowing at the time that these actions likely would prevent many future deaths from Lyodura-associated CJD. Similarly, in 1997, a feed ban was instituted to prevent BSE in the United States, even though no endemic BSE had been recognized in North America. In addition, to prevent potential cases of vCJD in the United States, prospective blood donors who might have been exposed to BSE in the United Kingdom were deferred, even before transmission of the vCJD agent via blood transfusion had been documented in that country (8).

In 1997, the FDA's Transmissible Spongiform Encephalopathy Advisory Committee recognized that use of human dura mater carries an inherent risk for transmitting CJD. However, the committee recommended that the use of such grafts be left to the discretion of the treating neurosurgeon, provided that the human dura mater is procured and processed according to additional safety measures outlined by the committee (9). After the committee's recommendations were issued, the number of dural grafts distributed for use in the US declined from an estimated 4500 in 1997 to an estimated 900 in 2002, to a documented 389 in 2006, and 368 in 2007 (2) (BE Buck, MD, Miami Tissue Bank, personal communication, August 2008).

CDC continues to conduct surveillance for cases of CJD in the US through various mechanisms, including 1) receipt and investigation, in collaboration with local and state health departments, of case reports from physicians and patient support groups; 2) analysis of national multiple cause-of-death data; and 3) review of prion disease cases confirmed by the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University (Cleveland, Ohio). During 1996-1997, CDC established NPDPSC in collaboration with the American Association of Neuropathologists to help maintain and enhance US human prion disease surveillance. NPDPSC provides, free of charge, advanced neuropathologic and biochemical prion disease diagnostic services to US physicians and other appropriate health personnel, including local and state health officials. Patients with a rapidly progressive dementia consistent with CJD and a history of dural graft implantation should be reported through local or state health departments to CDC, telephone 404-639-3091.

References

---------

1. Nakamura Y, Yanagawa H, Hoshi K, Yoshino H, Urata J, Sato T. Incidence rate of Creutzfeldt-Jakob disease in Japan. Int J Epidemiol 1999; 28: 130-4. 2. CDC. Update: Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts--Japan, 1979-2003. MMWR 2003; 52: 1179-81. 3. CDC. Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts---Japan, January 1979--May 1996. MMWR 1997; 46: 1066-9. 4. Brown P, Preece M, Brandel JP, et al. Iatrogenic Creutzfeldt- Jakob disease at the millennium. Neurology 2000; 55: 1075-81. 5. CDC. Epidemiologic notes and reports update: Creutzfeldt-Jakob disease in a patient receiving a cadaveric dura mater graft. MMWR 1987; 36: 324-5. 6. Janssen RS, Schonberger LB. Creutzfeldt-Jakob disease from allogeneic dura: a review of risks and safety [Discussion]. J Oral Maxillofac Surg 1991; 49: 274-5. 7. Blossom DB, Maddox RA, Beavers SF, et al. A case of Creutzfeldt- Jakob disease associated with a dura mater graft in the United States. Infect Control Hosp Epidemiol 2007; 28: 1396-7. 8. Zou S, Fang CT, Schonberger LB. Transfusion transmission of human prion diseases. Transfus Med Rev 2008; 22: 58-69. 9. Food and Drug Administration. Class II special controls guidance document: human dura mater. Guidance for industry and FDA. Rockville, MD: Food and Drug Administration; 2002. Available at <http://www.fda.gov/cdrh/ode/guidance/054.html>.

--

communicated by: ProMED-mail <promed@promedmail.org>

******

[8] Blood products risk update (US) - vCJD

Date: Fri 24 Oct 2008

Source: CBER 2007 Annual report assessing the potential risk of variant Creutzfeldt-Jakob disease from blood products, updated October 2008 [edited] <http://www.fda.gov/cber/inside/annrpt.htm#biological>

 Assessing the potential risk of variant Creutzfeldt-Jakob disease from blood products

---------------------------------------------

A rare but fatal brain infection called variant Creutzfeldt-Jakob Disease (vCJD) has emerged in recent years as a potential threat to recipients of plasma-derived clotting factors and other plasma-derived products, such as immune globulin and albumin. CBER developed a computer-assisted model for estimating this risk to recipients of plasma-derived clotting factors in order to ensure that both patients and physicians understand this issue. This model was developed to assess the risk of US-licensed, plasma-derived Factor VIII products and a plasma-derived Factor XI manufactured in the United Kingdom and used under IND in a small number of patients in the US between 1989 and 2000. The results of the risk assessments and communication strategies were presented to FDA's Transmissible Spongiform Encephalopathies (TSE) Advisory Committee in September and December 2006.

Based on the risk assessments, the Public Health Service (PHS) believes the risk of vCJD to patients who receive US-licensed, plasma-derived Factor VIII products is extremely small, although PHS does not know the risk with certainty. vCJD risk from other US-licensed, plasma-derived products, including Factor IX, is likely to be as small or smaller. In addition, the PHS believes the potential risk of vCJD infection from plasma-derived Factor XI, although not known for certain, is likely to be small.

Furthermore, CBER developed and implemented a risk communication plan in order to ensure the findings of the risk assessments reached the appropriate stakeholders. CBER partnered with patient advocates and risk communication experts to develop educational materials and arranged for hemophilia treatment centers and professional and advocacy organizations to publicize the findings through newsletters and other media. Finally, CBER launched a web page <http://www.fda.gov/cber/blood/vcjdrisk.htm> that provides the risk assessments and risk communication materials. Additional links are provided to FDA's current guidance documents on deferral of blood and plasma donors who may be at increased risk of vCJD and to other sources of information on vCJD.

--

communicated by: Terry S Singeltary Sr <flounder9@verizon.net> See Also

http://www.promedmail.org/post/20081103.3458


FRIDAY, MARCH 06, 2009 

Spain reports fifth human death from mad cow disease


see also ;


****** [3] CJD cluster (Spain) Date: Mon 21 May 2012 From: Terry Singeltary Creutzfeldt-Jakob disease cluster in the health area of Meixoeiro Hospital ——————————————– (M J Moreno, et al. Acta Neurologica Scandinavica, early view (online version) )

Objective ——— Galicia is the Spanish region in which most bovine spongiform encephalopathy cases have been registered. Meixoeiro Hospital is included in the Galician Health Service (SERGAS). The aim of the study was to analyze the clinical and epidemiological characteristics of Creutzfeldt-Jakob disease (CJD) in the health area of Meixoeiro Hospital and to identify possible specific risk factors to the general public.

Methods ——- All incident cases of CJD were identified in the health area of Meixoeiro Hospital (187 877 inhabitants) over a 14 year period, 1997-2010, and classified according to WHO diagnostic criteria. We obtained clinical details and epidemiological information on all cases. Crude and age-specific incidence rates were calculated. A review of surgical or invasive medical procedures was undertaken.

Results ——- We diagnosed 12 patients with CJD, 10 sporadic CJD (sCJD), and 2 genetic CJD (gCJD). No iatrogenic or variant CJD was detected. According to Poisson distribution, 3.9 CJD cases would be expected for our area over the 14 years researched. The average yearly mortality rate from CJD was 4.6 cases per million (3.8 from sCJD and 0.8 from gCJD). Eight patients (67 per cent) underwent at least one surgical or invasive medical procedure. 16 of 27 (59 per cent) of these procedures were undertaken in Meixoeiro Hospital.

Conclusions ———– The incidence of CJD in the health area of Meixoeiro Hospital is 3 times higher than expected. The hypothesis that at least some cases of sCJD are apparently because of covert transmission or zoonosis events should not be formally refuted and might explain the high rate found.

— Terry S Singeltary Sr


Eurosurveillance, Volume 17, Issue 15, 12 April 2012 

Research articles 

HEALTH PROFESSIONS AND RISK OF SPORADIC CREUTZFELDT–JAKOB DISEASE, 1965 TO 2010 

E Alcalde-Cabero1, J Almazán-Isla1, J P Brandel2, M Breithaupt3, J Catarino4, S Collins5, J Haybäck6, R Höftberger7, E Kahana8, G G Kovacs7,9, A Ladogana10, E Mitrova11, A Molesworth12, Y Nakamura13, M Pocchiari10, M Popovic14, M Ruiz-Tovar1, A L Taratuto15, C van Duijn16, M Yamada17, R G Will12, I Zerr3, J de Pedro Cuesta ()1

snip...


 In March 2009, a CJD case was reported to the Spanish CJD registry, who was classified as having sporadic CJD. As the patient was an experienced general pathologist and neuropathologist, it was speculated that the disease might have been a result of the person’s professional activities. The event was commented on in medical, scientific and mass media in Spain and elsewhere, e.g. [15]. The patient died after a four-month disease course, characterised mainly by cognitive decline, ataxia and myoclonus. The disease prion protein subtype, i.e. strain, was confirmed histochemically and biochemically as MM1, the most common subtype [2]. Risk factors for developing CJD, including blood transfusion, iatrogenic exposure (e.g. to dura mater, cadaveric pituitary-derived growth hormone) and mutations in the PRNP gene, were not identified. Assessment of the patient’s routine hospital work indicated that the patient had had a history of minor injuries during post-mortem examinations (personal communication, E. García-Albea, April 2009).

Following notification of this patient, the Spanish registry circulated a request for information to each national surveillance team participating in the European Creutzfeldt Jakob Disease Surveillance Network (EuroCJD), which dates back to 1993 and currently encompasses 25 collaborating centres in EU Member States and European Free Trade Association (EFTA) countries and a further eight in countries around the world, including Australia, Canada and Japan [16]. These centres provide data from national registries either through the EuroCJD website or, as with Japanese data, at regular network meetings. The request asked for the following: (i) information on the diagnosis (year of birth and death, sex and place of residence) of reported cases of sporadic CJD among active or retired pathologists from 1996 onwards; and (ii) comments based on personal experience of occupational risk and CJD among health professionals, including technicians working at pathology laboratories. 

There has been limited systematic research targeted at identifying occupational risk factors for sCJD in healthcare settings. This paper reports on the data supplied to the Spanish CJD registry in response to the request, and on the results of two literature reviews of sCJD – one on case reports involving health professionals and the other on epidemiologically assessed healthcare-related occupational risk of sCJD.

snip...

REFERENCES

Terry S. Singeltary Sr. Doctor Antonio Ruiz Villaespesa, pathologist and CJD researcher deceased because of Creutzfeldt-Jakob Disease SPAIN. 21 Apr 2009. [Accessed 11 Apr 2012]. In: Monitoring the occurrence of emerging forms of CJD [blog]. Available from: 

snip...see full text ;


MONDAY, SEPTEMBER 01, 2008 

Two cases of variant Creutzfeldt-Jakob disease reported in Spain in 2007 and 2008


SUNDAY, MARCH 28, 2010 

SPAIN BSE, Nor-98 atypical scrapie, SPORADIC CJD HIGH INCIDENT RATE >2 PER MILLION 


FRIDAY, JANUARY 09, 2009 

Mad cow disease detected on Madrid farm Friday, January 9, 2009 



Eurosurveillance, Volume 10, Issue 31, 04 August 2005

Articles

Citation style for this article: Centro Nacional de Epidemiología, Instituto de Salud Carlos III. First case of vCJD reported in Spain. Euro Surveill. 2005;10(31):pii=2764. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=2764 

First case of vCJD reported in Spain 

Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain (http://cne.isciii.es/) 

The Spanish Ministry of Health has reported the detection of a case of variant Creutzfeldt-Jakob disease (vCJD) in Spain [1]. 

The patient was a 26 year old woman in Madrid who died on 10 July 2005. She had no specific risk factors for vCJD (no prior blood transfusions or visits to the United Kingdom). 

The patient’s symptoms began in November 2004, with rapid progression to dementia, normal MRI and EEG, and 14-3-3 protein found in cerebral spinal fluid. Other neurological manifestations including ataxia, dysarthria, apraxia and myoclonus appeared in early 2005. The first abnormal MRI was observed in April 2005. The patient was methionine homozygous at codon 129 of the prion protein gene (PRPN). There were no identified PRPN mutations or family history of CJD. 

The case was notified to the Spanish CJD state registry in May 2005 and initially fitted the criteria for both probable sporadic CJD (sCJD) and possible vCJD; it was registered as probable sCJD. Brain neuropathology results of tests conducted at Fundación Hospital de Alcorcón at Madrid subsequently confirmed vCJD. Materials have been sent to the European reference centre at the United Kingdom’s National CJD Surveillance Unit in Edinburgh for further study, and results are expected later in August. 

References: 

Ministerio de Sanidad y Consumo. La Comunidad de Madrid comunica al Ministerio de Sanidad la probable detección del primer caso de la variante de la enfermedad de Creutzfeldt-Jakob en España. Press release 29 July 2005. (http://www.msc.es/gabinetePrensa/notaPrensa/desarrolloNotaPrensa.jsp?id=385)


FRIDAY, MAY 12, 2017 

SPAIN OIE Bovine Spongiform Encephalopathy atypical L-type Camargo, CANTABRIA



Subject: PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress

First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 

University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 

This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 

Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. 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. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 

At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 

PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress


MONDAY, JUNE 19, 2017 

PRION 2017 P20 Descriptive epidemiology of human prion diseases in Japan: a prospective 16-year surveillance study

Japan Prion Disease Increasing Annually to 2.3 patients per 1 million populations in 2014

http://creutzfeldt-jakob-disease.blogspot.com/2017/06/prion-2017-p20-descriptive-epidemiology.html

FRIDAY, JUNE 16, 2017

PRION 2017 P55 Susceptibility of human prion protein to in vitro conversion by chronic wasting disease prions


FRIDAY, JUNE 16, 2017

P55 Susceptibility of human prion protein to in vitro conversion by chronic wasting disease prions


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD


Saturday, June 17, 2017

PRION 2017 P115 α- Synuclein prions from MSA patients exhibit similar transmission properties as PrPSc prions


SATURDAY, JUNE 10, 2017

Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened?



SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

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 efficiency comparable to that of cattle BSE. While the efficiency 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.


Title: Transmission of scrapie prions to primate after an extended silent incubation period) *** 

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. 


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

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



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. 


LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ 

*** 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).*** 




*** 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. 


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

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




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 


Subject: PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress

First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 

University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 

This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 

Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. 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. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 

At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 

PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS

 Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened?

IF human transmission studies are unethical and will never take place, how much evidence is enough, and how much exposure do we allow, before a call is made. 

HOW many humans do we expose before enough is enough?

How many body bags now are enough, for a very long incubating disease that the body bags will for sure mount later, if something is NOT finally done NOW.

the public must know.

Now, i will tell you all how this will be interpreted by our fine federal friends, and their lobbyist et al from corporate America, and Doctors there from, here is how this will still read, rubber stamped ;

''There is no direct evidence that CWD can transmit to humans, and CWD has never been identified in humans anywhere in the world, including in areas where CWD has been present in animal populations for decades.''

this is absurd, and fake news at it's finest.

what is 'direct evidence', if human transmission is not possible?

there is more than enough evidence to make that call now. 

with that, who will finally make that judgement call, knowing that if cwd transmits to humans, it will look like the most common human tse prion i.e. sporadic cjd?

who makes that final call, when, and how many more humans must die before that decision is made and put in the public domain so we can go on with this and try to implement rules and regulations that might finally turn the tide, or do just let corporate science run rampant? 

or, will they continue to run with the infamous UKBSEnvCJD only theory$

with cwd now being documented to transmit macaque, AND TO PIGS orally (lot of human medicine made from pigs), the price of continuing to play TSE Prion Poker with humans goes up drastically. 

This is criminal negligence now, imo...terry

*** Subject: CWD TRANSMITS TO MACAQUE ORALLY MUSCLE INTAKE ***

Notice to Members Regarding Chronic Wasting Disease (CWD)

Posted on: May 31st, 2017 

To: MNA Members From: Métis Nation of Alberta 

Date: Wednesday, May 31, 2017 

*** Métis Nation of Alberta (MNA) was made aware of a recent Canadian research study examining the transmission of Chronic Wasting Disease. The initial results of the study indicate that macaque monkeys (genetically similar to humans) can be infected with Chronic Wasting Disease (CWD) after eating deer that is infected with CWD. CWD is a prion disease, which are fatal, transmissible diseases characterized by abnormal proteins in the brain and nervous system. To date no research has shown that CWD can be passed on to humans, and no human cases of CWD have ever been identified. However, this new research indicates that it is a possibility. The Deputy Chief Medical Officer of Health has reached out to us to share with our Métis harvesters this important information. For more information you can visit:


Chronic Wasting Disease: CFIA Research Summary 

 Embargoed until May 23, 2017 

(OCR of a scanned original) 

Research Findings 

Chronic Wasting Disease (CWD) is a progressive, fatal disease of the nervous system of cervids including deer, elk, moose, and reindeer that is caused by abnormal proteins called prions. It is known as a transmissible spongiform encephalopathy (TSE). Other TSEs include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeldt-Jakob disease (CJD) in humans.

A limited number of experimental studies have demonstrated that non-human primates, specifically squirrel monkeys, are susceptible to CWD prions. An ongoing research study has now shown that CWD can also be transmitted to macaques, which are genetically closer to humans. 

The study led by Dr. Stefanie Czub, a scientist at the Canadian Food Inspection Agency (CFIA), and funded by the Alberta Prion Research institute has demonstrated that by orally administering material under experimental conditions from cervids (deer and elk) naturally infected with CWD, the disease can be transmitted to macaques. 

in this project, which began in 2009, 18 macaques were exposed to CWD in a variety of ways: by injecting into the brain, through contact with skin, oral administration, and intravenously (into the bloodstream through veins). So far, results are available from 5 animals. At this point, two animals that were exposed to CWD by direct introduction into the brain, one that was administered infected brain material by oral administration and two that were given infected muscle by oral administration have become infected with CWD. The study is ongoing and testing continues in the remaining animals. The early results will be presented at PRlON 2017, the annual international conference on prion diseases, in Edinburgh, Scotland, May 23 to 26, 2017. 

Potential impacts of the new finding

Since 2003 Canada has a policy that recommends that animals and materials known to be infected with prions be removed from the food chain and from health products. Although no direct evidence of CWD prion transmission to humans has ever been recorded, the policy advocates a precautionary approach to managing CWD and potential human exposure to prions. These initial findings do not change Health Canada’s Health Products and Food Branch (HPFB) position on food and health products. A precautionary approach is still recommended to manage the potential risks of exposure to prions through food and health products. Measures are in place at federal, provincial and territorial levels to reduce human exposure to products potentially contaminated by CWD by preventing known infected animals from entering the marketplace. 

While Federal and P/T government’s animal disease control policies continue to divert known CWD-infected animals away from entering the food and feed supply, research and development of sensitive detection methods including live-animal sampling techniques remain crucial for ensuring an accurate diagnosis. In addition, consistent federal, provincial and territorial communications of appropriate precautionary measures for hunters and indigenous communities are required. 

Next Steps

The CFlA will continue to collaborate with national and international partners to develop and validate new diagnostic techniques. The CFlA will also continue to offer confirmatory testing services and reference laboratory expertise to provincial and territorial partners on demand. 

Currently, CFlA laboratories are leading or collaborating on several research projects to understand the potential for CWD to infect humans. These projects use non‐human primates, genetically modified mice, and cell-free amplification approaches. Given the present findings, CFiA encourages continued research into TSEs. 

The results of this study reinforce the need to redesign the federal program to foster greater adoption of risk mitigation measures for farmed cervids. Federal and provincial government collaboration will continue as new program options are assessed. 

The results of Dr. Czub’s research into CWD will be of interest to scientists, governments, industry and people who consume cervid products. After the presentation at PRION 2017, the research will follow the normal steps of completion, peer review and publication. The Government of Canada will monitor the response to this research and determine whether further review of the science is required. Other studies underway by other researchers may also become public as a result of the presentation of Dr. Czub’s research. 

The Public Health Agency of Canada, Health Canada, CFlA and other Federal partners are working together to assess what policies or programs need further review as well as preparing other communications about the research and health policy and advice to Canadian. 2017/04/28 

===end...UNOFFICIAL...NO URL LINK...TSS===UPDATE, THE ABOVE INTERNAL DOCUMENT HAS NOW BEEN CONFIRMED, but still no link...TSS===

0:30 First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 

Dr Stefanie Czub University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency Canada 


see science to date that the call should be made NOW, that cwd to humans is possible, and all precautions there fore, should be take will great urgency.

WEDNESDAY, MAY 03, 2017

*** First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques


LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$

*** 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).***


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 association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

snip...see full report ;

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf

you can see more evidence here ;

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

Wednesday, May 24, 2017 

PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh UPDATE 1


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. ...


snip...see full text ;


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 its 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. 


*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep. 


Wednesday, May 24, 2017 

PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh UPDATE 1 

Subject: PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh

*see archives of previous Prion Conferences, the ones that are still available, scroll down towards bottom in this link.



Terry S. Singeltary Sr.