Tuesday, October 31, 2017

Clinical findings of a probable case of MM2-cortical-type sporadic Creutzfeldt-Jakob disease with antibodies to anti-N-terminus of α-enolase

Case Report 

Clinical findings of a probable case of MM2-cortical-type sporadic Creutzfeldt-Jakob disease with antibodies to anti-N-terminus of α-enolase 

Yuichi Hayashi ORCID Icon, Megumi Yamada, Akio Kimura, Takahiko Asano, Katsuya Satoh, Tetsuyuki Kitamoto, show all Pages 1-11 | Received 02 Aug 2017, Accepted 05 Sep 2017, Accepted author version posted online: 02 Oct 2017, Published online: 02 Oct 2017 Download citation http://dx.doi.org/10.1080/19336896.2017.1377876 Select Language​▼ Translator disclaimer 

ABSTRACT 

We report the case of a 76-year-old woman presenting with 47-month history of progressive dementia and cortical blindness with no family history. Antibodies against thyroid glands and the N-terminus of α-enolase (NAE) were detected in her serum. Neurological examination revealed progressive dementia, frontal signs, visual disturbance, and exaggerated bilateral tendon reflexes in both legs. Diffusion MRI showed cortical hyper-intensities in the bilateral occipital and parietal, and the left frontal and temporal cortices. 99mTc-ethyl cysteinate dimer-single photon emission computed tomography indicated decreased regional cerebral blood flow throughout the bilateral parietal lobes and partially in the left frontal and temporal lobes. PRNP gene analysis showed no mutations with methionine homozygosity at codon 129 in peripheral blood. Cerebrospinal fluid examination, including 14-3-3 and total tau protein detection, revealed normal levels; however, prion proteins were amplified by the real-time quaking-induced conversion method. Hashimoto's encephalopathy was excluded on the basis of unresponsiveness to corticosteroids. The symptoms progressed slowly. Periodic sharp-wave complexes were observed on electroencephalogram 36 months after the onset of symptoms; the patient reached a state of akinetic mutism at 47 months. This was a probable case of MM2-cortical-type sCJD with anti-NAE antibodies based on the World Health Organization (WHO) diagnostic criteria for sCJD, genetic information, and the slowly progressive course. However, this case did not meet with the probable WHO diagnostic criteria until 3 years after symptom onset, highlighting the difficulty of diagnosing a living case of the MM2-type of sCJD. Therefore, establishment of clinical diagnostic criteria for MM2-type of sCJD is required.

KEYWORDS: anti-N-terminus of α-enolase antibody, corticosteroid, Hashimoto encephalopathy, MM2-cortical-type, MRI, real-time quaking-induced conversion assay, sporadic Creutzfeldt-Jakob disease

http://www.tandfonline.com/doi/full/10.1080/19336896.2017.1377876

MONDAY, OCTOBER 02, 2017 

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


THURSDAY, AUGUST 17, 2017 

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

Singeltary et al


FRIDAY, AUGUST 11, 2017 

Infectivity in bone marrow from sporadic CJD patients

Bioassays in transgenic mice expressing the human prion protein revealed the presence of unexpectedly high levels of infectivity in the bone marrow from seven out of eight sCJD cases. These findings may explain the presence of blood-borne infectivity in sCJD patients. They also suggest that the distribution of prion infectivity in peripheral tissues in sCJD patients could be wider than currently believed, with potential implications for the iatrogenic transmission risk of this disease. 


THURSDAY, AUGUST 10, 2017 

Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017


National Prion Center could lose all funding just as concern about CWD jumping to humans rises

SATURDAY, JULY 15, 2017 

*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises


SATURDAY, JULY 29, 2017 

Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC 


Transmission of scrapie prions to primate after an extended silent incubation period

Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports 5, Article number: 11573 (2015)

doi:10.1038/srep11573

Download Citation

EpidemiologyNeurological manifestationsPrion diseases

Received: 16 February 2015

Accepted: 28 May 2015

Published online: 30 June 2015

Abstract

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.

snip...

In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free. Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.

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.***


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 



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.


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

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

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





Terry S. Singeltary Sr.

Monday, October 02, 2017

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

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


National Prion Disease Pathology Surveillance Center Cases Examined(1) (May 18, 2017)

Year Total Referrals(2) Prion Disease Sporadic Familial Iatrogenic vCJD

1997 & earlier 170 104 90 13 1 0

1998 89 53 45 7 1 0

1999 121 73 65 7 1 0

2000 144 101 89 12 0 0

2001 209 118 110 8 0 0

2002 242 144 124 18 2 0

2003 258 160 137 21 2 0

2004 314 179 161 17 0 1(3)

2005 327 178 156 21 1 0

2006 367 181 161 17 1 2(4)

2007 372 208 189 19 0 0

2008 385 222 206 16 0 0

2009 399 233 212 20 1 0

2010 402 246 218 28 0 0

2011 394 240 216 24 0 0

2012 409 241 218 23 0 0

2013 415 257 222 34 1 0

2014 354 209 186 21 1 1(5)

2015 400 262 242 20 0 0

2016 394 275 246 29 0 0

2017 118 84 51 3 0 0

TOTAL 6283(6) 3768(7) 3344(8) 378(9) 12 4 

1 Listed based on the year of death or, if not available, on year of referral; 

2 Cases with suspected prion disease for which brain tissue was submitted; 

3 Disease acquired in the United Kingdom; 

4 Disease acquired in the United Kingdom in one case and in Saudi Arabia in the other;

5 Disease possibly acquired in a Middle Eastern or Eastern European country; 

6 Includes 11 cases in which the diagnosis is pending, and 20 inconclusive cases; 

7 Includes 30 (30 from 2017) cases with type determination pending in which the diagnosis of vCJD has been excluded. 

8 The sporadic cases include 3257 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 57 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 30 cases of sporadic Fatal Insomnia (sFI).

9 Total does not include 225 Familial cases diagnosed by blood test only.

https://case.edu/medicine/pathology/media/school-of-medicine/pathology/images/npdpsc/Web-Table-2017_5_18.pdf



THURSDAY, JUNE 22, 2017 

National Prion Disease Pathology Surveillance Center Cases Examined(1) (May 18, 2017)



SATURDAY, MARCH 21, 2015 

Canada and United States Creutzfeldt Jakob TSE Prion Disease Incidence Rates Increasing



Creutzfeldt Jakob Disease Steadily Increasing in the United Kingdom U.K.


i am sure that the officials will ascertain the steady increase in CJD to be from better surveillance and better reporting, same thing that has been said from day one, year, after year, after year...$$$

also, please note;

1 There are in addition a total of 14 cases of VPSPr (death in 1997(1 case), 2004(1), 2006(1), 2008(3), 2010(1), 2012(4), 2013(1), 2016(1), 2017(1)) not included in the above figures. 


Creutzfeldt Jakob Disease Steadily Increasing in the United Kingdom U.K.


CREUTZFELDT-JAKOB DISEASE IN THE UK (By Calendar Year) 

REFERRALS OF SUSPECT CJD DEATHS OF DEFINITE AND PROBABLE CJD 

Year Referrals Year Sporadic1 Iatrogenic Genetic2 vCJD Total Deaths 

1990 [53]† 1990 28 5 0 - 33 

1991 75 1991 31 1 4 - 36 

1992 96 1992 45 2 6 - 53 

1993 79 1993 36 4 7 - 47 

1994 119 1994 53 1 9 - 63 

1995 87 1995 35 4 5 3 47 

1996 132 1996 40 4 6 10 60 

1997 163 1997 59 6 6 10 81 

1998 155 1998 64 3 5 18 90 

1999 170 1999 62 6 2 15 85 

2000 178 2000 48 1 3 28 80 

2001 179 2001 58 4 6 20 88 

2002 164 2002 73 0 5 17 95 

2003 162 2003 79 5 6 18 108 

2004 114 2004 50 2 6 9 67 

2005 124 2005 67 4 13 5 89 

2006 112 2006 68 1 9 5 83 

2007 119 2007 64 2 10 5 81 

2008 150 2008 84 5 6 2 97 

2009 153 2009 78 2 8 3 91 

2010 150 2010 84 3 6 3 96 

2011 158 2011 91 4 14 5 114 

2012 127 2012 93 5 11 0 109 

2013 152 2013 106 2 8 1 117 

2014 130 2014 99 3 11 0 113 

2015 140 2015 104 0 4 0 108 

2016 149 2016 119 1 6 1 127 

2017 117 2017 75 0 6 0 81 

Total Referrals 3707 Total Deaths 1893 80 188 178 2339 

† Referral figure for 1990 is from 1 May onwards * As at 2 nd October 2017 

Summary of vCJD cases 

Deaths 

Deaths from definite vCJD (confirmed): 123 

Deaths from probable vCJD (without neuropathological confirmation): 55 

Deaths from probable vCJD (neuropathological confirmation pending): 0 

Number of deaths from definite or probable vCJD (as above): 178 

Alive 

Number of definite/probable vCJD cases still alive: 0 

Total number of definite or probable vCJD (dead and alive): 178 

1 There are in addition a total of 14 cases of VPSPr (death in 1997(1 case), 2004(1), 2006(1), 2008(3), 2010(1), 2012(4), 2013(1), 2016(1), 2017(1)) not included in the above figures. 

2 includes all genetic prion disease, including GSS.


Source: NCJDRSU website www.cjd.ed.ac.uk - updated 02/10/2017


Variant Creutzfeldt-Jakob disease

Fact sheet N°180 Revised February 2012

Key facts

Variant Creutzfeldt-Jakob disease (vCJD) is a rare and fatal human neurodegenerative condition. The consumption of food of bovine origin contaminated with the agent of Bovine Spongiform Encephalopathy (BSE), a disease of cattle, has been strongly linked to the occurrence of vCJD in humans. 175 cases of vCJD were reported in the United Kingdom of Great Britain and Northern Ireland (United Kingdom), and 49 cases in other countries from October 1996 to March 2011. Following the successful containment of the BSE epidemic in cattle, the number of cases of vCJD in the United Kingdom has declined since 2000. Variant Creutzfeldt-Jakob disease (vCJD) is a rare and fatal human neurodegenerative condition which is classified as a Transmissible Spongiform Encephalopathy (TSE) because of its ability to be transmitted and the characteristic spongy degeneration of the brain that it causes.

vCJD was first described in the United Kingdom in March 1996 and has been linked with exposure to a TSE of cattle called Bovine Spongiform Encephalopathy (BSE), also known as Classical BSE1, which was first reported in the United Kingdom in 1986.

Total cases

From October 1996 to March 2011, 175 cases of vCJD have been reported in the United Kingdom, 25 in France, 5 in Spain, 4 in Ireland, 3 each in the Netherlands and the United States of America (USA), 2 each in Canada, Italy and Portugal, and one each in Japan, Saudi Arabia and Taiwan. The number of cases of vCJD in the United Kingdom peaked in 2000 with 28 deaths. It has since declined to about 2 diagnosed cases and 2 deaths per year in 2008.

Epidemiology

Before the identification of vCJD, Creutzfeldt-Jakob disease (CJD), the most common of the known human TSEs, was thought to exist in only three forms:

sporadic CJD, which occurs throughout the world at the rate of about one per million people, and accounts for about 85% of CJD cases; familial CJD, which is associated with a gene mutation and makes up 5–15% of CJD cases; and iatrogenic CJD, which results from accidental transmission via contaminated surgical equipment or as a result of corneal or meningeal (dura mater) transplants or the administration of human-derived pituitary growth hormones; this accounts for less than 5% of CJD cases. In contrast to the traditional forms of CJD, vCJD has affected younger patients (median age at death of 28 years, as opposed to 68 years) and has a relatively longer duration of illness (median of 14 months as opposed to 4.5 months).

The first person to develop symptoms of what turned out to be vCJD became ill in 1994. Most people who have developed vCJD lived in the United Kingdom. Some cases that were diagnosed in countries other than the United Kingdom occurred in people who were probably exposed to the BSE while residing in the United Kingdom.

As of early May 2011, the CJD surveillance unit for the United Kingdom reported 172 primary cases of vCJD, and three secondary cases of vCJD related to blood transfusion. Among primary cases, there are four additional cases in the United Kingdom and one in Canada where vCJD is strongly suspected, but the diagnosis has not yet been definitively confirmed by post mortem analysis.

Clinical features

Early in the illness, patients usually experience psychiatric or sensory symptoms, which most commonly take the form of depression, apathy or anxiety, and occasionally (in a third of the cases) unusual persistent and painful sensory symptoms. Neurological signs, including unsteadiness, difficulty walking and involuntary movements, develop as the illness progresses and, by the time of death, patients become completely immobile and mute.

Diagnosis

The clinical presentation, progressive nature of the disease and failure to find any other diagnosis are characteristic of vCJD. There are no completely reliable tests to use before the onset of clinical symptoms. However, magnetic resonance scans and tonsillar biopsy are useful diagnostic tests. The brainwave pattern observed during an electroencephalogram is abnormal in most vCJD patients. Currently, the diagnosis of vCJD can only be confirmed following pathological examination of the brain post mortem. Characteristically, multiple microscopic and abnormal aggregates encircled by holes are seen in the brain tissue, resulting in a daisy-like appearance described by the term "florid plaques". Probable cause

The nature of the vCJD agent is being investigated and is still a matter of debate. One prevalent theory is that the agent is composed largely, if not entirely, of a self-replicating misfolded protein, referred to as a prion.

There is strong scientific evidence that vCJD is linked with exposure to a TSE of cattle called BSE. The link between vCJD and BSE was first hypothesized because of the association of these two TSEs in time and place. In addition, laboratory evidence indicates that vCJD is linked causally with BSE.

Intensive surveillance in European countries has confirmed the high incidence of vCJD in the United Kingdom, the country with the largest potential exposure to BSE. Several cases in other countries were likely exposed to the BSE agent while residing in the United Kingdom.

The most likely cause of vCJD is exposure to the BSE agent through consumption of food from bovine origin most plausibly contaminated by infected bovine brain or other central nervous system tissue.

Only four cases of vCJD infection have been associated with blood transfusion: three of these cases developed symptoms of vCJD several years after transfusion, and one died from unrelated causes before developing symptoms of vCJD, but was shown to be infected with vCJD.

Measures taken to protect public health

Due to the strong evidence of a link between vCJD and BSE, the UK government made BSE a notifiable disease in 1988. Since 1994, the European Union has progressively implemented control measures that have contained BSE. The main measures are detailed in the information sheet on Bovine Spongiform Encephalopathy. Since 1999, the United Kingdom has no longer sourced plasma from its inhabitants, and as a further precautionary measure against the occurrence of vCJD, has instituted leukocyte depletion (removal of white blood cells) from blood transfusions. Some countries have prohibited donations of blood from persons who have resided in countries with higher risk of BSE. WHO response

WHO has worked on:

convening scientific consultations on issues related to animal and human TSEs (these meetings have made recommendations aimed at protecting human and animal health); assisting with global surveillance of CJD and its variants, by holding training courses worldwide, particularly in developing countries, to help countries establish national surveillance of CJD and its variants; convening the Technical Consultation on BSE: Public Health, Animal Health and Trade, publishing the WHO manual for surveillance of human transmissible spongiform encephalopathies, including variant Creutzfeldt-Jakob disease. WHO recommendations To protect human health, WHO has several recommendations.

No tissue that is likely to contain the BSE agent, nor part or product of any animal which has shown signs of a TSE should enter the (human or animal) food chain. All countries should ban the use of ruminant tissues in ruminant feed. The pharmaceutical industry should avoid the use of bovine materials and materials from other animal species in which TSEs naturally occur. If their use is absolutely necessary, these materials should be obtained from countries which have a surveillance system for BSE in place and which reports zero cases of BSE. The Guidelines on tissue infectivity distribution in transmissible spongiform encephalopathies in 2006 provide information and assist national regulatory authorities in conducting risk assessments of vCJD transmission. In 2010, WHO updated the Tables on tissue infectivity distribution in transmissible spongiform encephalopathies. The Tables reflect the current status of knowledge about infectivity in body tissues, secretions, and excretions of humans and animals, and thus provide information about potential transmission of vCJD through human blood and blood products, as well as through medicinal products prepared with animal-derived materials.

1 The term "Classical BSE" has been introduced to differentiate the disease from Atypical BSE cases, which occur rarely in the cattle population.



Variant Creutzfeldt-Jakob disease (vCJD) is a prion disease that was first described in 1996 in the United Kingdom. There is now strong scientific evidence that the agent responsible for the outbreak of prion disease in cows, bovine spongiform encephalopathy (BSE or 'mad cow' disease), is the same agent responsible for the outbreak of vCJD in humans.
Variant CJD (vCJD) is not the same disease as classic CJD (often simply called CJD). It has different clinical and pathologic characteristics from classic CJD. Each disease also has a particular genetic profile of the prion protein gene. Both disorders are invariably fatal brain diseases with unusually long incubation periods measured in years, and are caused by an unconventional transmissible agent called a prion.
Classic CJD versus Variant CJD Recommend on FacebookTweetShare The variant form of CJD should not be confused with the classic form of CJD that is endemic throughout the world, including the United States. There are several important differences between these two forms of the disease. The median age at death of patients with classic CJD in the United States, for example, is 68 years, and very few cases occur in persons under 30 years of age. In contrast, the median age at death of patients with vCJD in the United Kingdom is 28 years.
vCJD can be confirmed only through examination of brain tissue obtained by biopsy or at autopsy, but a "probable case" of vCJD can be diagnosed on the basis of clinical criteria developed in the United Kingdom. The incubation period for vCJD is unknown because it is a new disease. However, it is likely that ultimately this incubation period will be measured in terms of many years or decades. In other words, whenever a person develops vCJD from consuming a BSE-contaminated product, he or she likely would have consumed that product many years or a decade or more earlier.
In contrast to classic CJD, vCJD in the United Kingdom predominantly affects younger people, has atypical clinical features, with prominent psychiatric or sensory symptoms at the time of clinical presentation and delayed onset of neurologic abnormalities, including ataxia within weeks or months, dementia and myoclonus late in the illness, a duration of illness of at least 6 months, and a diffusely abnormal non-diagnostic electroencephalogram.
The characteristic neuropathologic profile of variant CJD includes, in both the cerebellum and cerebrum, numerous kuru-type amyloid plaques surrounded by vacuoles and prion protein (PrP) accumulation at high concentration indicated by immunohistochemical analysis.
Recently published data indicate that the epidemic of variant CJD in the United Kingdom may have already reached a peak. A listing of monthly updated numbers of CJD and variant CJD cases in the United Kingdom. 
Int J Clin Pract. 1999 Sep;53(6):456-9. 
New variant Creutzfeldt-Jakob disease. 
Gordon N. 
Abstract It is now recognised that new variant Creutzfeldt-Jakob disease (CJD) can present during adolescence, so it may be within the experience of any paediatrician. Some observations on prion proteins are made, and some of the features of classical CJD are reviewed. Reports of patients with new variant CJD are given. The possible links between this condition and bovine spongiform encephalopathy (BSE) are considered, especially the finding that certain people who are homozygous for methionine at codon 129 of the prion protein may be particularly susceptible to this infection. The diagnosis of new variant CJD can be difficult. Early sensory and psychiatric symptoms can be suggestive, so can the initial signs of ataxia and involuntary movements. The EEG does not help in this variety. Although not specific some serum and CSF tests may give diagnostic support. It has been claimed that tonsillar biopsy may confirm the diagnosis, but this often necessitates brain biopsy; or the diagnosis may only be made at autopsy. Beliefs about the way infections spread will have to be modified, and more must be learnt about the nature of prions, how they enter the body, and how they spread in the brain.
PMID: 10622074 [Indexed for MEDLINE]
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

UPDATE* NOVEMBER 16, 2014
 
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???
 
Friday, January 10, 2014
 
Greetings again Friends, Neighbors, and Colleagues,
 
I would kindly like to follow up on ‘vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???’ ran across an old paper from 1984, that some might find interest in, and I will update the link with this old science paper from 1984, a 2010 paper from Japan, and some information on scrapie transmission. The paper from Japan first, then the 1984 paper, and then the scrapie transmission studies.
 
***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent.
 
 

Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more Prionbaloney ?



Wednesday, March 28, 2012

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

OR-10 15:25 - 15:40 VARIABLY PROTEASE-SENSITIVE PRIONOPATHY IS TRANSMISSIBLE IN BANK VOLES Nonno



SEE VPSPr, GSS, and atypical scrapie NOR-98



85%+ of all human TSE prion, i.e. sporadic CJD, does NOT happen spontaneously, as some would wish you to think. never say never with the TSE Prion disease. ...terry
 
***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.***
 


BSE INQUIRY
''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. 

BSE INQUIRY


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

Emmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth, and John Collinge1 

Abstract

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



BSE, Scrapie, and CWD, Zoonosis, Zoonotic Disease


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.
 
 


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. 



Transmission of scrapie prions to primate after an extended silent incubation period 

Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys

Scientific Reports 5, Article number: 11573 (2015) doi:10.1038/srep11573

Download Citation EpidemiologyNeurological manifestationsPrion diseases Received: 16 February 2015 Accepted: 28 May 2015 Published online: 30 June 2015

Abstract

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie. 

snip... 

Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. 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.

The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.

We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.

Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.

The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.

Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.

Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.

Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.

Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.

In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free. 

***Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.***

 
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
 

Subject: Prion 2017 Conference Abstracts CWD

 2017 PRION CONFERENCE 

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 

Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO 

PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS 

*** PRION 2017 CONFERENCE VIDEO 



 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


TUESDAY, JULY 04, 2017

*** PRION 2017 CONFERENCE ABSTRACTS ON CHRONIC WASTING DISEASE CWD TSE PRION ***


TUESDAY, JUNE 13, 2017

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


Wednesday, May 24, 2017 

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


SATURDAY, JULY 29, 2017 

Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC 


2017

Subject: ***CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 

Chronic Wasting Disease (CWD) 

Prevention 

If CWD could spread to people, it would most likely be through eating of infected deer and elk. In a 2006-2007 CDC survey of U.S. residents, nearly 20 percent of those surveyed said they had hunted deer or elk and more than two-thirds said they had eaten venison or elk meat. However, to date, no CWD infections have been reported in people. 

Hunters must consider many factors when determining whether to eat meat from deer and elk harvested from areas with CWD, including the level of risk they are willing to accept. Hunters harvesting wild deer and elk from areas with reported CWD should check state wildlife and public health guidance to see whether testing of animals is recommended or required in a given state or region. In areas where CWD is known to be present, CDC recommends that hunters strongly consider having those animals tested before eating the meat. 

Tests for CWD are monitoring tools that some state wildlife officials use to look at the rates of CWD in certain animal populations. Testing may not be available in every state, and states may use these tests in different ways. A negative test result does not guarantee that an individual animal is not infected with CWD, but it does make it considerably less likely and may reduce your risk of exposure to CWD. 

To be as safe as possible and decrease their potential risk of exposure to CWD, hunters should take the following steps when hunting in areas with CWD: 

Do not shoot, handle or eat meat from deer and elk that look sick or are acting strangely or are found dead (road-kill). When field-dressing a deer: Wear latex or rubber gloves when dressing the animal or handling the meat. Minimize how much you handle the organs of the animal, particularly the brain or spinal cord tissues. Do not use household knives or other kitchen utensils for field dressing. Check state wildlife and public health guidance to see whether testing of animals is recommended or required. Recommendations vary by state, but information about testing is available from many state wildlife agencies. Strongly consider having the deer or elk tested for CWD before you eat the meat. If you have your deer or elk commercially processed, consider asking that your animal be processed individually to avoid mixing meat from multiple animals. If your animal tests positive for CWD, do not eat meat from that animal. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service regulates commercially farmed deer and elk. The agency operates a national CWD herd certification program. As part of the voluntary program, states and individual herd owners agree to meet requirements meant to decrease the risk of CWD in their herds. Privately owned herds that do not participate in the herd certification program may be at increased risk for CWD. 

Page last reviewed: August 17, 2017 Page last updated: August 17, 2017 Content source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of High-Consequence Pathogens and Pathology (DHCPP) 


 > However, to date, no CWD infections have been reported in people. 

key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry 

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. 


TUESDAY, SEPTEMBER 12, 2017 

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 


MONDAY, SEPTEMBER 25, 2017

Colorado Chronic Wasting Disease CWD TSE Prion Mandatory Submission of test samples in some areas and zoonosis

(see origin of cwd in Colorado debate and evidence there from...tss)


*** 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. 

2017


MONDAY, MAY 29, 2017 

Canada CCA optimistic over potential for revisions to OIE criteria for BSE negligible risk



THURSDAY, AUGUST 17, 2017 

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



THURSDAY, JULY 20, 2017 

USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200



SUNDAY, JULY 23, 2017

atypical L-type BASE Bovine Amyloidotic Spongiform Encephalopathy BSE TSE PRION



SUNDAY, JULY 23, 2017

Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy



Needless Conflict...



Saturday, July 23, 2016

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



Tuesday, July 26, 2016

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016



Monday, June 20, 2016

Specified Risk Materials SRMs BSE TSE Prion Program



THURSDAY, JULY 13, 2017 

*** EFSA BSE Sixty cases of mad cow disease since 2001 breached feed ban likely the cause 

Scientists investigate origin of isolated BSE cases



Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. 

*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

*** It also suggests a similar cause or source for atypical BSE in these countries. ***

P.9.21

Molecular characterization of BSE in Canada

Jianmin Yang 1 , Sandor Dudas 2 , Catherine Graham 2 , Markus Czub 3 , Tim McAllister 1 , Stefanie Czub 1 1 Agriculture and Agri-Food Canada Research Centre, Canada; 2 National and OIE BSE Reference Laboratory, Canada; 3 University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle. Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres.

Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.

Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal-specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. It also suggests a similar cause or source for atypical BSE in these countries.

see page 176 of 201 pages...tss



*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply;



***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.

***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***

Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT



*** PLEASE SEE THIS URGENT UPDATE ON CWD AND FEED ANIMAL PROTEIN ***

Sunday, March 20, 2016

Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed ***UPDATED MARCH 2016*** Singeltary Submission



SEE MAD COW FEED VIOLATIONS AFER MAD COW FEED VIOLATIONS ;



Tuesday, April 19, 2016

Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission



TUESDAY, JANUARY 17, 2017 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION



***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.***
 


MONDAY, JULY 17, 2017 

National Scrapie Eradication Program May 2017 Monthly Report Fiscal Year 2017



TUESDAY, JULY 18, 2017 

MINK FARMING USA TRANSMISSIBLE MINK ENCEPHALOPATHY TSE PRION DISEASE SURVEILLANCE AND TESTING




IN the USA, the failed ruminant mad cow feed ban is even much worse then the UK and EU. 

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Location: Virus and Prion Research

Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease

Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin

Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:

Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.

Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 challenge="" groups="" month="" pigs="" remaining="" the="">6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.

Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" oral="">6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). Conclusions:

This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge.

CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.

Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.



CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...



we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.


 
Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....


 
snip...see much more here ;


WEDNESDAY, APRIL 05, 2017

Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease



WEDNESDAY, APRIL 05, 2017

*** Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease ***



Chronic wasting disease continues to spread Disease of cervids causing local population declines



TUESDAY, SEPTEMBER 19, 2017 

USDA APHIS Notice: Animal Disease Traceability (ADT) Summary of Feedback on the ADT Program



TUESDAY, AUGUST 8, 2017 

Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2016-0092]



WEDNESDAY, JULY 26, 2017 

***APHIS USDA Emerging Animal Disease Preparedness and Response Plan July 2017



THURSDAY, JUNE 22, 2017 

World Organisation for Animal Health (OIE) to establish liaison office in College Station, Texas



THURSDAY, AUGUST 17, 2017 

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

Singeltary et al



FRIDAY, AUGUST 11, 2017 

Infectivity in bone marrow from sporadic CJD patients

Bioassays in transgenic mice expressing the human prion protein revealed the presence of unexpectedly high levels of infectivity in the bone marrow from seven out of eight sCJD cases. These findings may explain the presence of blood-borne infectivity in sCJD patients. They also suggest that the distribution of prion infectivity in peripheral tissues in sCJD patients could be wider than currently believed, with potential implications for the iatrogenic transmission risk of this disease. 



THURSDAY, AUGUST 10, 2017 

Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017



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

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

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



National Prion Center could lose all funding just as concern about CWD jumping to humans rises

SATURDAY, JULY 15, 2017 

*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises



CBCnews
 
*** USA sporadic CJD MAD COW DISEASE HAS HUGE PROBLEM Video
 
*** sporadic CJD linked to mad cow disease
 
*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***
 


1997 MAD COW VIDEO USA, the cover up begins $$$

1997-11-10: Panorama - The british disease
 
 *** Human Mad Cow Video
 



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. ...



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. 



IN CONFIDENCE TRANSMISSION OF ALZHIMER TYPE PLAQUES TO PRIMATE



Alzheimer’s disease, iatrogenic, and Transmissible Spongiform Encephalopathy TSE Prion disease, that is the question ???
 
>>> The only tenable public line will be that "more research is required’’ <<<
 
>>> possibility on a transmissible prion remains open<<<
 
O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?

[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. There are also results to be made available shortly (1) concerning a farmer with CJD who had BSE animals, (2) on the possible transmissibility of Alzheimer’s and (3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]



snip...see full Singeltary Nature comment here;
 
 

see Singeltary comments to Plos ;

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease
 
*** Singeltary comment PLoS ***
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
 
Posted by flounder on 05 Nov 2014 at 21:27 GMT
 


Ann N Y Acad Sci. 1982;396:131-43. 

Alzheimer's disease and transmissible virus dementia (Creutzfeldt-Jakob disease). 

Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC. 

Abstract 

Ample justification exists on clinical, pathologic, and biologic grounds for considering a similar pathogenesis for AD and the spongiform virus encephalopathies. However, the crux of the comparison rests squarely on results of attempts to transmit AD to experimental animals, and these results have not as yet validated a common etiology. Investigations of the biologic similarities between AD and the spongiform virus encephalopathies proceed in several laboratories, and our own observation of inoculated animals will be continued in the hope that incubation periods for AD may be even longer than those of CJD. 

 

Sunday, November 22, 2015
 
*** Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis Abstract
 
Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.
 
Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD 54.00
 
 
 

*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***
 
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
 
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
 
 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease
 
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
 
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
 
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
 
Terry S. Singeltary, Sr Bacliff, Tex
 
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
 


BSE TSE PRION USDA OIE NEEDLESS CONFLICT



Tracking spongiform encephalopathies in North America

Xavier Bosch

Published: August 2003


Summary;

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.”

49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD) the relative of mad cow disease seen among deer and elk in the USA. Although his feverish search did not lead him to the smoking gun linking CWD to a similar disease in North American people, it did uncover a largely disappointing situation.

Singeltary was greatly demoralised at the few attempts to monitor the occurrence of CJD and CWD in the USA. Only a few states have made CJD reportable. Human and animal TSEs should be reportable nationwide and internationally, he complained in a letter to the Journal of the American Medical Association (JAMA 2003; 285: 733). "I hope that the CDC does not continue to expect us to still believe that the 85% plus of all CJD cases which are sporadic are all spontaneous, without route or source."

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.


Until recently, CWD was thought to be confined to the wild in a small region in Colorado. But since early 2002, it has been reported in other areas, including Wisconsin, South Dakota, and the Canadian province of Saskatchewan. Indeed, the occurrence of CWD in states that were not endemic previously increased concern about a widespread outbreak and possible transmission to people and cattle.

To date, experimental studies have proven that the CWD agent can be transmitted to cattle by intracerebral inoculation and that it can cross the mucous membranes of the digestive tract to initiate infection in lymphoid tissue before invasion of the central nervous system. Yet the plausibility of CWD spreading to people has remained elusive.

Part of the problem seems to stem from the US surveillance system. CJD is only reported in those areas known to be endemic foci of CWD. Moreover, US authorities have been criticised for not having performed enough prionic tests in farm deer and elk.

Although in November last year the US Food and Drug Administration issued a directive to state public-health and agriculture officials prohibiting material from CWD-positive animals from being used as an ingredient in feed for any animal species, epidemiological control and research in the USA has been quite different from the situation in the UK and Europe regarding BSE.

"Getting data on TSEs in the USA from the government is like pulling teeth", Singeltary argues. "You get it when they want you to have it, and only what they want you to have."

Norman Foster, director of the Cognitive Disorders Clinic at the University of Michigan (Ann Arbor, MI, USA), says that "current surveillance of prion disease in people in the USA is inadequate to detect whether CWD is occurring in human beings"; adding that, "the cases that we know about are reassuring, because they do not suggest the appearance of a new variant of CJD in the USA or atypical features in patients that might be exposed to CWD. However, until we establish a system that identifies and analyses a high proportion of suspected prion disease cases we will not know for sure". The USA should develop a system modelled on that established in the UK, he points out.

Ali Samii, a neurologist at Seattle VA Medical Center who recently reported the cases of three hunters "two of whom were friends" who died from pathologically confirmed CJD, says that "at present there are insufficient data to claim transmission of CWD into humans"; adding that "[only] by asking [the questions of venison consumption and deer/elk hunting] in every case can we collect suspect cases and look into the plausibility of transmission further". Samii argues that by making both doctors and hunters more aware of the possibility of prions spreading through eating venison, doctors treating hunters with dementia can consider a possible prion disease, and doctors treating CJD patients will know to ask whether they ate venison.

CDC spokesman Ermias Belay says that the CDC "will not be investigating the [Samii] cases because there is no evidence that the men ate CWD-infected meat". He notes that although "the likelihood of CWD jumping the species barrier to infect humans cannot be ruled out 100%" and that "[we] cannot be 100% sure that CWD does not exist in humans& the data seeking evidence of CWD transmission to humans have been very limited". 




26 March 2003 

Terry S. Singeltary, retired (medically) CJD WATCH 

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc? 



2 January 2000 British Medical Journal U.S. 

Scientist should be concerned with a CJD epidemic in the U.S., as well 



15 November 1999 British Medical Journal hvCJD in the USA * BSE in U.S. 



2001 FDA CJD TSE Prion Singeltary Submission
 
*** U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001 
 


WEDNESDAY, OCTOBER 09, 2013 

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



SPORADIC CJD IN FARMERS AND THEIR WIVES WITH DOCUMENTED BSE HERDS



THURSDAY, SEPTEMBER 28, 2017

Pennsylvania GAME COMMISSION OFFERS FREE CWD TESTS FOR DMA-HARVESTED DEER



THURSDAY, SEPTEMBER 21, 2017

Pennsylvania Game Commission has scheduled a series of public meetings to ensure Pennsylvanians remain informed about chronic wasting disease CWD TSE Prion



SATURDAY, AUGUST 12, 2017

Pennsylvania 27 deer from Bedford County farm test positive for chronic wasting disease



WEDNESDAY, JULY 12, 2017

PENNSYLVANIA CWD FOUND IN THE WILD IN CLEARFIELD COUNTY



THURSDAY, SEPTEMBER 21, 2017

TEXAS TPWD CWD mandatory check stations for Chronic Wasting Disease in the South Central, Panhandle, and Trans-Pecos areas



WEDNESDAY, SEPTEMBER 27, 2017

TEXAS, TPWD, WIN CWD COURT CASE AGAINST DEER BREEDERS CAUSE NO. D-1-GN-15-004391



MONDAY, AUGUST 14, 2017

Texas Chronic Wasting Disease CWD TSE Prion History



THURSDAY, SEPTEMBER 21, 2017

Arkansas AGFC Video Public CWD Meeting in Clinton



WEDNESDAY, AUGUST 16, 2017
ARKANSAS CWD TSE PRION 214 CASES CONFIRMED TO DATE AS OF AUGUST 9, 2017

WEDNESDAY, AUGUST 16, 2017

OHIO Chronic Wasting Disease CWD TSE Prion UPDATE?


MONDAY, SEPTEMBER 25, 2017

Colorado Chronic Wasting Disease CWD TSE Prion Mandatory Submission of test samples in some areas and zoonosis



MONDAY, OCTOBER 02, 2017

Michigan 3 ½-year-old female deer likely to be the 10th free-ranging deer Chronic Wasting Disease CWD TSE Prion



Iowa Supreme Court rules law allows quarantine of CWD deer, not land

This is very, very concerning imo. 

IF this ruling is upheld as such ;

''The Iowa Supreme Court upheld the district court ruling — saying the law gives the DNR only the authority to quarantine the deer — not the land. The ruling says if the Iowa Legislature wants to expand the quarantine powers as suggested by the DNR, then it is free to do so.''

IF a 'precedent' is set as such, by the Legislature not intervening to expand quarantine powers to the DNR for CWD TSE Prion, and the precedent is set as such that the cervid industry and land there from, once contaminated with the CWD TSE Prion, are free to repopulate, sell the land, etc, imo, this will blow the lid off any containment efforts of this damn disease CWD TSE Prion. The Iowa Supreme Court did not just pass the cwd buck down the road, the Supreme Court of Iowa just threw the whole state of Iowa under the bus at 100 MPH. what about the exposure to the other species that come across that land, and then off to some other land? this makes no sense to me, if this is set in stone and the Legislation does not stop it, and stop if fast, any containment of the cwd tse prion will be futile, imo...terry

FRIDAY, JUNE 16, 2017

Iowa Supreme Court rules law allows quarantine of CWD deer, not land



THURSDAY, AUGUST 03, 2017

Wisconsin CWD Showing Up in Northern Wisconsin Deer Farms



Wednesday, February 10, 2016

SUNDAY, AUGUST 06, 2017 

USA Chronic Wasting Disease CWD TSE Prion Emergency Response Plan Singeltary et al 



TUESDAY, MARCH 28, 2017 

*** Passage of scrapie to deer results in a new phenotype upon return passage to sheep ***



THURSDAY, AUGUST 10, 2017

***NORWAY MAKES CHANGES TO NATIONAL CHRONIC WASTING DISEASE CWD TSE PRION RULES







Terry S. Singeltary Sr.
Bacliff, Texas 77518