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Thursday, March 18, 2021

New Brunswick monitoring more than 40 cases of unknown neurological disease symptoms are similar to Creutzfeldt-Jakob disease?

New Brunswick monitoring more than 40 cases of unknown neurological disease symptoms are similar to Creutzfeldt-Jakob disease?

FIRST AND FOREMOST, LET US PRAY THIS IS NOT A TSE PRION DISEASE!

i wanted to wait and let this unfold before posting this, but felt it was too important not to post asking questions...terry

New Brunswick official comments on neurological disease detected in the province

New Brunswick’s chief medical officer of health Dr. Jennifer Russell commented Thursday on a rare neurological disease that has been detected in the province, saying “it most likely is a new disease” and that the symptoms are similar to Creutzfeldt-Jakob disease, a degenerative and fatal brain disorder.


New Brunswick

New Brunswick monitoring more than 40 cases of unknown neurological disease

Memo sent to health-care professionals in province says symptoms are similar to Creutzfeldt-Jakob disease 

CBC News · Posted: Mar 17, 2021 5:22 PM AT | Last Updated: 3 hours ago

Public Health is closely monitoring a cluster of more than 40 New Brunswick patients with symptoms similar to those of Creutzfeldt-Jakob disease, a rare and fatal brain disease.

In an internal memo obtained by Radio-Canada, sent on March 5 by the office of the chief medical officer of health to the New Brunswick Medical Society and to associations of doctors and nurses, the department notes the existence of a cluster of 42 cases of a progressive neurological syndrome of unknown origin.

A first case was diagnosed in 2015, according to the memo. Three years later, in 2019, 11 additional cases were discovered, with 24 more cases discovered in 2020 and another six cases in 2021. Five people have died.

Shepody woman dies after being diagnosed with Creutzfeldt-Jakob disease The disease affects all age groups and appears to be concentrated in the Acadian Peninsula in northeast New Brunswick and the Moncton region in the southeast. 

"We are collaborating with different national groups and experts; however, no clear cause has been identified at this time," the memo states.

According to preliminary data from a research group on the subject, headed by neurologist Alier Marrero of Moncton's Dr. Georges-L.-Dumont University Hospital Centre, the disease is not genetic and could be contracted from water, food or air. 

No other cases have been reported in Canada.

"For now it has only been found here," Marrero said. 

Possibly a new disease The symptoms of the cases detected since 2015 are similar to those of prion diseases, which include Creutzfeldt-Jakob disease and some of its variants, including mad cow disease, or bovine spongiform encephalopathy, or BSE.

However, despite many similarities, tests for Creutzfeldt-Jakob disease have so far ruled out known prion diseases, the Public Health memo states.

Scientists are currently looking into the possibility that this is a new variant of a prion disease — or a new disease entirely.

"These are patients who have clinical features that correspond to prion diseases, of which Creutzfeldt-Jakob disease is one," but show no evidence of having Creutzfeldt-Jakob disease or any other form of prion disease, Marrero said in an interview.

Frustration mounts over Horizon's response to deadly disease The identified cases were all reported to the Canadian Creutzfeldt-Jakob Disease Surveillance System. Public Health said the location of the cases — in the northeast and Moncton region — reflects where the patients lived at the time they were referred to the system, not before that. 

Marrero cautioned against rushing to assume the current cases are of a prion disease, an ultra-rare disease for which there is no effective treatment.

"Before coming out with a definition of a new condition, you need to have a lot of information to be sure that you are not diagnosing something else," such as a disease that is treatable, he said.

Symptoms progress over 18 to 36 months Chief Medical Officer of Health Dr. Jennifer Russell said the March 5 memo was intended to alert physicians to this diagnostic possibility when a patient presents certain symptoms.

In an email, New Brunswick Medical Society spokesperson Eric Lewis confirmed the society received the memo and distributed it to physicians on March 9. 

Symptoms health professionals will watch out for include changes in behaviour, sleep disturbances, unexplained pain, visual hallucinations, co-ordination problems and severe muscle and brain atrophy.

2 Alberta flocks quarantined after fatal disease related to mad cow found in sheep Symptoms progress over a period of 18 to 36 months, according to Marrero.

Russell said she is monitoring the situation closely, and that further research is needed to understand the "common links" that could be causing the disease.

"At this point, we have more questions than answers," she said.

With files from Nicolas Steinbach/Radio-Canada

CBC's Journalistic Standards and Practices|About CBC News


UPDATED MARCH 20, 2021

"We are very, very worried about it," Godin said. "Residents are anxious, they're asking 'Is it moose meat? Is it deer? Is it contagious?' We need to know, as fast as possible, what is causing this disease."

Dr. Neil Cashman understands the concern.

Cashman, a professor in the University of British Columbia's faculty of medicine, is a neurologist with a special expertise in prion diseases — a group of neurodegenerative diseases caused by proteinaceous infectious particles, or prions — including Creutzfeldt-Jakob disease.

When Cashman first heard about the cases in New Brunswick, he says his first thought was, "We have a problem on our hands."

Clearly, he said, "this was a call to arms to identify the cause."

Those efforts are already underway.

Teams of researchers, scientists and epidemiologists began assembling about a year ago, both at the national level at Health Canada's Creutzfeldt-Jakob Disease Surveillance System, to which Cashman is acting as an adviser, and at the provincial level with a research team headed by Moncton neurologist Dr. Alier Marrero.

Having this news put under "the active scrutiny of the public" this week has been a good thing, Cashman said, because it has pulled in clinical and scientific expertise from across Canada.

"There are people offering to help, and these people would not be doing that unless they were aware of this cluster."

But their work is just beginning.

'This is something new'

Cashman has a pretty good idea what this mystery disease is not.

All the evidence, he said, points to this not being a prion disease such as Creutzfeldt-Jakob disease.

"There is no evidence, not a hint — even in the three autopsies that have been performed — of a human prion disease. That came as a surprise to me, frankly," he said. "So in essence, this is something new, and we need to get on the stick and figure out what this is."

Cashman said he's tapping into his expertise in neurology and environmental toxins to look for other explanations.

The fact that the cases are limited to certain regions "fits with the notion of an environmental toxin," he said.

A possible culprit might be B-methylamino-L-alanine (BMAA), an environmental toxin made by certain bacteria that can accumulate in fish and shellfish.

Domoic acid, another toxin produced by bacteria and that accumulates in shellfish, sardines and anchovies, is another possibility. So is lead, which can be responsible for clusters of neurodegeneration.

Dr. Neil Cashman, an expert in neurology, says an environmental toxin could be the cause. Dr. Neil Cashman, an expert in neurology, says an environmental toxin could be the cause.(Submitted by Neil Cashman) "All of these are speculation at this point," Cashman stressed. "A lot of scientific acumen will be required to pin it down to a cause."

That will take time, and no one can say for sure how long.

"It's possible ongoing investigations will give us the cause in a week, or it's possible it will give us the cause in a year," he said.

"There's no sensible timeline I can provide on when we'll have an answer. It's just something that has to be the focus of scientific attention, and as rapidly as possible."

In the meantime, he said, he'd advise residents to continue doing what they have been doing, try not to be consumed by anxiety and have faith that a solution will be found.

"I know it sounds like a tired statement, but I would say stay calm, carry on," he said. "We've got to figure it out and the Public Health Agency of Canada is in a good position to do that and come up with a cause ... and then of course it can be ameliorated."


2012

New Brunswick Health Indicators

Issue 4-March 2012

A population health bulletin published by the Office of the Chief Medical Officer of Health

Neurodegenerative diseases are chronic, progressive disorders of the central nervous system, characterized by the steady loss of neurons in the brain and spinal cord, affecting mental abilities or motor abilities. They represent one of the leading causes of disability in the Canadian population1 . The most prevalent neurodegenerative diseases are Alzheimer’s disease and Parkinson’s disease. Others include multiple sclerosis, motor neuron diseases (e.g., amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease), Huntington’s disease and a large number of rarer diseases.

Signs and symptoms of neurodegenerative disease may vary among individuals, and prognosis varies depending on the type of disease and the age of onset. As with other health conditions, the onset of mental or physical symptoms among individuals can result in help-seeking, diagnosis and treatment, including, in some cases, hospitalization. In 2008, 3,979 New Brunswickers (53 per 10,000 population) had been hospitalized with diagnosed Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, motor neuron disease or Huntington’s disease. The rate of persons hospitalized for Alzheimer’s disease was 29 per 10,000, and the rate for Parkinson’s disease was 11 per 10,000. Figure 1 shows the breakdown of these rates by health region. These numbers should be interpreted with caution, especially for regions with smaller populations.

Data from multiple sources (e.g., health-care utilization records, death records, population-based surveys and records from community support groups) show that neurodegenerative diseases are a significant public health problem, but there are still important gaps in understanding many issues about their nature, incidence, prevalence, treatment and impacts. The causes are generally not well known; depending on the type of disease, genetic, environmental, toxic, viral or personal risk factors may be implicated2,3. Most of these diseases have no known cure or treatment available to reverse the deterioration, although some treatments may help improve symptoms or keep them from getting worse for a limited time.

Depending on the condition, life expectancy for persons affected by neurodegenerative disease may remain essentially the same compared to the general population or it may be severely reduced. Based on Vital Statistics data, 214 New Brunswickers (or 2.9 per 10,000 population) died from Alzheimer’s disease or Parkinson’s disease in 2008, out of a provincial total of 6,450 deaths among residents (or 86.4 per 10,000 population)4.

Increasing numbers of cases of neurodegenerative diseases are often found in aging populations. Observations of greater incidences of certain neurodegenerative diseases in recent decades may be partly due to improvements in diagnostic methods and case ascertainment5 . Some diseases with neuropsychiatric sequelae (notably, dementia) may now be diagnosed with fair certainty through medical history, neuropsychological tests, brain imaging and other clinical tests. Post-mortem examination of the brain is required for a definitive diagnosis, however.

The Public Health Agency of Canada routinely investigates 80 to 100 suspected cases of Creutzfeldt-Jakob disease (CJD) and a few suspected cases of variant CJD annually, with an average of about 35 of these cases being confirmed as CJD by pathology and other comprehensive medical reviews6.

According to the Canadian Institute for Health Information, the annual direct health-care costs, including hospital care, physician care and drug expenditures, for four neurodegenerative diseases − Alzheimer’s, Parkinson’s, multiple sclerosis and ALS – were estimated at $786 million in Canada, with an additional $2.227 billion in annual indirect morbidity and mortality costs3 . The World Health Organization reports that,“a large body of evidence shows that policymakers and health-care providers may be unprepared to cope with the predicted rise in the prevalence of neurological and other chronic disorders and the disability resulting from the extension of life expectancy and aging of populations globally.”7

Alzheimer’s disease

Alzheimer’s disease, the most common cause of dementia, is characterized by slow, progressive loss of brain functions3 . In 2008, 2,186 New Brunswickers (29 per 10,000 population) had been hospitalized with Alzheimer’s disease. Most persons hospitalized at least once for the disease between 2004 and 2008 were 75 or older (86 per cent) and females (65 per cent). Figure 2 shows the age distribution of persons admitted to hospital with a diagnosis of Alzheimer’s disease.

The 2008 crude mortality rate for Alzheimer’s disease in New Brunswick was 2.3 per 10,000 population, higher than the Canadian average of 2.04. The observed difference may be explained in part by differences in age structure; census data from 2006 reveal that the median age among the New Brunswick population (41.5 years) was older than the national median (39.5 years)8. The age-standardized mortality rates, used to control for the effect of age on mortality, were similar in both jurisdictions, with 1.3 deaths per 10,000 population in 20084.

The age-standardized mortality rate for Alzheimer’s disease was higher among female New Brunswickers than males (1.4 versus 1.2 in 2008)4, linked to the higher risk among women of developing the disease, partly because they live longer than men3. More data on mortality rates for Alzheimer’s disease by gender and across Canada are in the annex. 


Surveillance for Progressive Intellectual and Neurological Deterioration in the Canadian Paediatric Population 

Daniel L. Keene, Terry Sutcliffe, Pat Harman, and Danielle Grenier on behalf of the Canadian Paediatric Surveillance Program

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/31125AB68F3C12B990472F294279DDBA/S0317167100053865a.pdf/surveillance-for-progressive-intellectual-and-neurological-deterioration-in-the-canadian-paediatric-population.pdf



TUESDAY, DECEMBER 01, 2020

Sporadic Creutzfeldt Jakob Disease sCJD and Human TSE Prion Annual Report December 14, 2020

snip...

***> CANADA, I find it very odd that Canada has NO recorded or documented cases of Variably Protease-Sensitive Prionopathy (VPSPr)?

CANADA Creutzfeldt-Jakob disease surveillance system (CJDSS) report

Definite and probable CJD, 1998-2020

As of 31 October, 2020

Year Sporadic Iatrogenic Familial GSS FFI vCJD Total

1998 22 1 0 1 0 0 24

1999 27 2 2 1 0 0 32

2000 32 0 0 3 0 0 35

2001 27 0 2 1 0 0 30

2002 31 0 2 2 0 1 36

2003 27 1 1 0 0 0 29

2004 42 0 1 1 0 0 44

2005 42 0 1 1 0 0 44

2006 39 0 1 3 1 0 44

2007 35 0 0 4 0 0 39

2008 48 0 1 0 0 0 49

2009 48 0 3 2 0 0 53

2010 35 0 3 0 0 0 38

2011 46 0 3 1 0 1 51

2012 62 0 1 0 0 0 63

2013 50 0 0 0 1 0 51

2014 51 0 4 0 1 0 56

2015 44 0 5 1 2 0 52

2016 57 1 5 1 0 0 64

2017 82 0 2 1 1 0 86

2018 74 1 4 0 1 0 80

2019 76 0 2 0 0 0 78

2020 30 0 2 0 0 0 32

Total 1027 6 45 23 7 2 1110

Cases with definite and probable diagnosis to date.

Gerstmann-Sträussler-Scheinker disease (GSS)

Fatal familial insomnia (FFI)

Variant CJD (vCJD)


snip...see full report;


odd, USA HUMAN TSE REPORTS 71 cases of Variably Protease-Sensitive Prionopathy (VPSPr), UK reports 1 There are in addition a total of 17 cases of vPSPr (death in 1997(1 case), 2004(1), 2006(1), 2008(3), 2010(1), 2012(4), 2013(1), 2016(3), 2017(1), 2018(1)) not included in the above figures, WHILE CANADA HAS REPORTED NONE, ZERO, NO CASES OF VPSPR, WHATS UP WITH THAT? 

how were these cases diagnosed? 

what testing type were used that confirmed the negative tse prion testing, is/was it post-mortem, or was it typical ante-mortem clinical tests?

is it a new TSE Prion disease?

what would cervid cwd in humans look like?

we have a new tse prion disease in camels, CPD i.e. camel prion disease? 

is it iatrogenic tse Prion? history of surgeries, etc., ?


Japan also just had it's first case of VPSPr;

Sunday, December 27, 2020 

First autopsy proven case of VPSPr: Variably protease‐sensitive prionopathy in Japan


FRIDAY, JANUARY 10, 2014 

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ???


SATURDAY, MARCH 13, 2021 

Canada's application for negligible risk status for BSE passes an important milestone?


CANADA CHRONIC WASTING DISEASE CWD TSE PRION CERVID

SUNDAY, NOVEMBER 22, 2020 

Canada October 2020 CWD TSE Prion Confirmed in Five Herds


CWD AND SCRAPIE TRANSMITS BY ORAL ROUTES TO PIGS, PRICE OF TSE PRION POKER GOES UP!

2021 Transmissible Spongiform Encephalopathy TSE Prion End of Year Report 2020

CJD FOUNDATION VIRTUAL CONFERENCE CJD Foundation Research Grant Recipient Reports Panel 2 Nov 3, 2020

zoonotic potential of PMCA-adapted CWD PrP 96SS inoculum


4 different CWD strains, and these 4 strains have different potential to induce any folding of the human prion protein. 


***> PIGS, WILD BOAR, CWD <***

***> POPULATIONS OF WILD BOARS IN THE UNITED STATES INCREASING SUPSTANTUALLY AND IN MANY AREAS WE CAN SEE  A HIGH DENSITY OF WILD BOARS AND HIGH INCIDENT OF CHRONIC WASTING DISEASE

HYPOTHOSIS AND SPECIFIC AIMS

HYPOTHOSIS 

BSE, SCRAPIE, AND CWD, EXPOSED DOMESTIC PIGS ACCUMULATE DIFFERENT QUANTITIES AND STRAINS OF PRIONS IN PERIPHERAL TISSUES, EACH ONE OF THEM WITH PARTICULAR ZOONOTIC POTENTIALS


Final Report – CJD Foundation Grant Program A. 

Project Title: Systematic evaluation of the zoonotic potential of different CWD isolates. Principal Investigator: Rodrigo Morales, PhD.


Systematic evaluation of the zoonotic potential of different CWD isolates. Rodrigo Morales, PhD Assistant Professor Protein Misfolding Disorders lab Mitchell Center for Alzheimer’s disease and Related Brain Disorders Department of Neurology University of Texas Health Science Center at Houston Washington DC. July 14th, 2018

Conclusions and Future Directions • We have developed a highly sensitive and specific CWD-PMCA platform to be used as a diagnostic tool. • Current PMCA set up allow us to mimic relevant prion inter-species transmission events. • Polymorphic changes at position 96 of the prion protein apparently alter strain properties and, consequently, the zoonotic potential of CWD isolates. • Inter-species and inter-polymorphic PrPC → PrPSc conversions further increase the spectrum of CWD isolates possibly present in nature. • CWD prions generated in 96SS PrPC substrate apparently have greater inter-species transmission potentials. • Future experiments will explore the zoonotic potential of CWD prions along different adaptation scenarios, including inter-species and inter-polymorphic.



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 - Orise Fellow item Kunkle, Robert item KONDRU, NAVEEN - Iowa State University item MANNE, SIREESHA - Iowa State University item SMITH, JODI - Iowa State University item KANTHASAMY, ANUMANTHA - Iowa State University item WEST GREENLEE, M - Iowa State University 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 month challenge groups). The remaining pigs (>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 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 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.



Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP 

Author item MOORE, S - Orise Fellow item Kokemuller, Robyn item WEST-GREENLEE, M - Iowa State University item BALKEMA-BUSCHMANN, ANNE - Friedrich-Loeffler-institut item GROSCHUP, MARTIN - Friedrich-Loeffler-institut item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 5/10/2018 Publication Date: 5/22/2018 Citation: Moore, S.J., Kokemuller, R.D., West-Greenlee, M.H., Balkema-Buschmann, A., Groschup, M.H., Greenlee, J.J. 2018. The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP. Prion 2018, Santiago de Compostela, Spain, May 22-25, 2018. Paper No. WA15, page 44.

Interpretive Summary:

Technical Abstract: We have previously shown that the chronic wasting disease (CWD) agent from white-tailed deer can be transmitted to domestic pigs via intracranial or oral inoculation although with low attack rates and restricted PrPSc accumulation. The objective of this study was to assess the potential for cross-species transmission of pig-passaged CWD using bioassay in transgenic mice. Transgenic mice expressing human (Tg40), bovine (TgBovXV) or porcine (Tg002) PRNP were inoculated intracranially with 1% brain homogenate from a pig that had been intracranially inoculated with a pool of CWD from white-tailed deer. This pig developed neurological clinical signs, was euthanized at 64 months post-inoculation, and PrPSc was detected in the brain. Mice were monitored daily for clinical signs of disease until the end of the study. Mice were considered positive if PrPSc was detected in the brain using an enzyme immunoassay (EIA). In transgenic mice expressing porcine prion protein the average incubation period was 167 days post-inoculation (dpi) and 3/27 mice were EIA positive (attack rate = 11%). All 3 mice were found dead and clinical signs were not noted prior to death. One transgenic mouse expressing bovine prion protein was euthanized due to excessive scratching at 617 dpi and 2 mice culled at the end of the study at 700 dpi were EIA positive resulting in an overall attack rate of 3/16 (19%). None of the transgenic mice expressing human prion protein that died or were euthanized up to 769 dpi were EIA positive and at study end point at 800 dpi 2 mice had positive EIA results (overall attack rate = 2/20 = 10%). The EIA optical density (OD) readings for all positive mice were at the lower end of the reference range (positive mice range, OD = 0.266-0.438; test positive reference range, OD = 0.250-4.000). To the authors’ knowledge, cervid-derived CWD isolates have not been successfully transmitted to transgenic mice expressing human prion protein. The successful transmission of pig-passaged CWD to Tg40 mice reported here suggests that passage of the CWD agent through pigs results in a change of the transmission characteristics which reduces the transmission barrier of Tg40 mice to the CWD agent. If this biological behavior is recapitulated in the original host species, passage of the CWD agent through pigs could potentially lead to increased pathogenicity of the CWD agent in humans.


cwd scrapie pigs oral routes 

***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <*** 

>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <*** 

***> 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 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 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. 




Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research

Title: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease

Author 

 item Greenlee, Justin item Moore, S - Orise Fellow item Smith, Jodi - Iowa State University item Kunkle, Robert item West Greenlee, M - Iowa State University Submitted to: American College of Veterinary Pathologists Meeting Publication Type: Abstract Only Publication Acceptance Date: 8/12/2015 Publication Date: N/A Citation: N/A

Interpretive Summary:

Technical Abstract: The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy. In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.


223. Scrapie in white-tailed deer: a strain of the CWD agent that efficiently transmits to sheep?

Justin J. Greenleea, Robyn D. Kokemullera, S. Jo Moorea and Heather West Greenleeb

aVirus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, USA; bDepartment of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, USA

CONTACT Justin J. Greenlee Justin.Greenlee@ars.usda.gov

ABSTRACT

Scrapie is a transmissible spongiform encephalopathy of sheep and goats that is associated with widespread accumulation of abnormal prion protein (PrPSc) in the central nervous and lymphoid tissues. Chronic wasting disease (CWD) is the natural prion disease of cervid species, and the tissue distribution of PrPSc in affected cervids is similar to scrapie in sheep. There are several lines of evidence that suggest that multiple strains of CWD exist, which may affect the agent’s potential to transmit to hosts of the same or different species. We inoculated white-tailed deer with the scrapie agent from ARQ/ARQ sheep, which resulted in 100% attack rates by either the intracranial or oronasal route of inoculation. When examining tissues from the brainstems or lymphoid tissues by traditional diagnostic methods such as immunohistochemistry or western blots, it is difficult to differentiate tissues from deer infected with scrapie from those infected with CWD. However, there are several important differences between tissues from scrapie-infected white-tailed deer (WTD scrapie) and those infected with CWD (WTD CWD). First, there are different patterns of PrPSc deposition in the brains of infected deer: brain tissues from deer with WTD scrapie had predominantly particulate and stellate immunoreactivity whereas those from deer with WTD-CWD had large aggregates and plaque-like deposits. Secondly, the incubation periods of WTD scrapie isolates are longer than CWD isolates in mice expressing cervid prion protein. Most notably, the transmission potential of these two isolates back to sheep is distinctly different. Attempts to transmit various CWD isolates to sheep by the oral or oronasal routes have been unsuccessful despite observation periods of up to 7 years. However, WTD scrapie efficiently transmitted back to sheep by the oronasal route. Upon transmission back to sheep, the WTD scrapie isolate exhibited different phenotypic properties when compared to the sheep receiving the original sheep scrapie inoculum including different genotype susceptibilities, distinct PrPSc deposition patterns, and much more rapid incubation periods in transgenic mice expressing the ovine prion protein. The scrapie agent readily transmits between sheep and deer after oronasal exposure. This could confound the identification of CWD strains in deer and the eradication of scrapie from sheep.


2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

PLEASE NOTE;

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strainsNo

Olivier Andreoletti, INRA Research Director, Institut National de la Recherche Agronomique (INRA) – École Nationale Vétérinaire de Toulouse (ENVT), invited speaker, presented the results of two recently published scientific articles of interest, of which he is co-author: ‘Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice’ (MarinMoreno et al., 2020) and ‘The emergence of classical BSE from atypical/Nor98 scrapie’ (Huor et al., 2019).

In the first experimental study, H-type and L-type BSE were inoculated into transgenic mice expressing all three genotypes of the human PRNP at codon 129 and into adapted into ARQ and VRQ transgenic sheep mice. The results showed the alterations of the capacities to cross the human barrier species (mouse model) and emergence of sporadic CJD agents in Hu PrP expressing mice: type 2 sCJD in homozygous TgVal129 VRQ-passaged L-BSE, and type 1 sCJD in homozygous TgVal 129 and TgMet129 VRQ-passaged H-BSE. 


WEDNESDAY, OCTOBER 28, 2020 

***> EFSA Annual report of the Scientific Network on BSE-TSE 2020 Singeltary Submission


 ***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.***

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.

https://www.nature.com/articles/srep11573 

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. 

============== 

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf 

***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. 

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

PRION 2016 TOKYO

Saturday, April 23, 2016

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

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. 

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

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. 

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

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

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

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

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

snip...

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

PMID: 6997404


Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6


Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).

Gibbs CJ Jr, Gajdusek DC.

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).



Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE


Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission


APHIS-2021-0004-0002

https://www.regulations.gov/comment/APHIS-2021-0004-0002

https://downloads.regulations.gov/APHIS-2021-0004-0002/attachment_1.pdf

> 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).***
Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;
(3) Reliable essays can be established to detect CWD infection in humans; and
(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
Prion 2017 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 
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.
After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.
The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD..
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD
states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,
AND
included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),
AND
THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
snip…
see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below…terry
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
156. Screening and characterization of unusual sCJD cases in a CWD endemic state in the USA
Yihui Liua, Manuel Camachoa, Wenquan Zoua,b,c, Qingzhong Konga,b,c
aDepartment of Pathology, Case Western Reserve University (CWRU), Cleveland, USA; bDepartment of Neurology, CWRU, Cleveland, OH, USA; cNational Center for Regenerative Medicine, CWRU, Cleveland, USA
CONTACT Qingzhong Kong qxk2@case.edu
ABSTRACT
Background: Chronic wasting disease (CWD) has spread to 26 states in the USA and three provinces in Canada, and it has been detected recently in Norway and Finland. Potential CWD zoonosis is a serious public health concern. It is unclear whether CWD transmission to humans has already occurred. We aim to start to address this question by examining all available sCJD cases from a CWD endemic state in the USA.
Methods: Frozen brain tissues from all available sCJD cases archived in the National Prion Disease Pathology Surveillance Center from a US state that has been significantly impacted by CWD were sampled at five brain regions. These brain samples were subjected to detailed biochemical analysis to look for unusual patterns, characteristics, and/or distribution of PrPSc in comparison with sCJD samples from states that have not detected CWD. Unusual cases are further scrutinized for their clinical presentations, histopathological features, and history of cervid hunting and venison consumption.
Results and Conclusions: We have found some unusual sCJD cases in this CWD endemic state. We will report our preliminary findings on their features. Currently there is no convincing evidence to support a direct link to CWD for any of these unusual sCJD cases.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the position of the National Prion Disease Pathology Surveillance Center.
International Conference on Emerging Diseases, Outbreaks & Case Studies & 16th Annual Meeting on Influenza March 28-29, 2018 | Orlando, USA
Qingzhong Kong
Case Western Reserve University School of Medicine, USA
Zoonotic potential of chronic wasting disease prions from cervids
Chronic wasting disease (CWD) is the prion disease in cervids (mule deer, white-tailed deer, American elk, moose, and reindeer). It has become an epidemic in North America, and it has been detected in the Europe (Norway) since 2016. The widespread CWD and popular hunting and consumption of cervid meat and other products raise serious public health concerns, but questions remain on human susceptibility to CWD prions, especially on the potential difference in zoonotic potential among the various CWD prion strains. We have been working to address this critical question for well over a decade. We used CWD samples from various cervid species to inoculate transgenic mice expressing human or elk prion protein (PrP). We found infectious prions in the spleen or brain in a small fraction of CWD-inoculated transgenic mice expressing human PrP, indicating that humans are not completely resistant to CWD prions; this finding has significant ramifications on the public health impact of CWD prions. The influence of cervid PrP polymorphisms, the prion strain dependence of CWD-to-human transmission barrier, and the characterization of experimental human CWD prions will be discussed.
Speaker Biography Qingzhong Kong has completed his PhD from the University of Massachusetts at Amherst and Post-doctoral studies at Yale University. He is currently an Associate Professor of Pathology, Neurology and Regenerative Medicine. He has published over 50 original research papers in reputable journals (including Science Translational Medicine, JCI, PNAS and Cell Reports) and has been serving as an Editorial Board Member on seven scientific journals. He has multiple research interests, including public health risks of animal prions (CWD of cervids and atypical BSE of cattle), animal modeling of human prion diseases, mechanisms of prion replication and pathogenesis, etiology of sporadic Creutzfeldt-Jacob disease (CJD) in humans, normal cellular PrP in the biology and pathology of multiple brain and peripheral diseases, proteins responsible for the α-cleavage of cellular PrP, as well as gene therapy and DNA vaccination.
SATURDAY, FEBRUARY 23, 2019 

Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019


TUESDAY, NOVEMBER 04, 2014 

Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011

Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "


Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS

resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.

snip.... 


Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿ 

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations

In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species. 


Prions in Skeletal Muscles of Deer with Chronic Wasting Disease 

Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure. 


*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.

see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”

From: TSS 

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"

To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

Sent: Monday, September 30, 2002 9:22 AM

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam,

In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention

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

From: Sent: Sunday, September 29, 2002 10:15 AM


Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS

Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.

snip...

*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,

snip... full text ; 


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

sporadic, spontaneous CJD, 85%+ of all human TSE, just not just happen. never in scientific literature has this been proven.

if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;



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).*** 




*** IF CWD is not a risk factor for humans, then I guess the FDA et al recalled all this CWD tainted elk tenderloin (2009 Exotic Meats USA of San Antonio, TX) for the welfare and safety of the dead elk. ...tss
Exotic Meats USA Announces Urgent Statewide Recall of Elk Tenderloin Because It May Contain Meat Derived From An Elk Confirmed To Have Chronic Wasting Disease 
Contact: Exotic Meats USA 1-800-680-4375
FOR IMMEDIATE RELEASE -- February 9, 2009 -- Exotic Meats USA of San Antonio, TX is initiating a voluntary recall of Elk Tenderloin because it may contain meat derived from an elk confirmed to have Chronic Wasting Disease (CWD). The meat with production dates of December 29, 30 and 31, 2008 was purchased from Sierra Meat Company in Reno, NV. The infected elk came from Elk Farm LLC in Pine Island, MN and was among animals slaughtered and processed at USDA facility Noah’s Ark Processors LLC.
Chronic Wasting Disease (CWD) is a fatal brain and nervous system disease found in elk and deer. The disease is caused by an abnormally shaped protein called a prion, which can damage the brain and nerves of animals in the deer family. Currently, it is believed that the prion responsible for causing CWD in deer and elk is not capable of infecting humans who eat deer or elk contaminated with the prion, but the observation of animal-to-human transmission of other prion-mediated diseases, such as bovine spongiform encephalopathy (BSE), has raised a theoretical concern regarding the transmission of CWD from deer or elk to humans. At the present time, FDA believes the risk of becoming ill from eating CWD-positive elk or deer meat is remote. However, FDA strongly advises consumers to return the product to the place of purchase, rather than disposing of it themselves, due to environmental concerns.
Exotic Meats USA purchased 1 case of Elk Tenderloins weighing 16.9 lbs. The Elk Tenderloin was sold from January 16 – 27, 2009. The Elk Tenderloins was packaged in individual vacuum packs weighing approximately 3 pounds each. A total of six packs of the Elk Tenderloins were sold to the public at the Exotic Meats USA retail store. Consumers who still have the Elk Tenderloins should return the product to Exotic Meats USA at 1003 NE Loop 410, San Antonio, TX 78209. Customers with concerns or questions about the Voluntary Elk Recall can call 1-800-680-4375. The safety of our customer has always been and always will be our number one priority.
Exotic Meats USA requests that for those customers who have products with the production dates in question, do not consume or sell them and return them to the point of purchase. Customers should return the product to the vendor. The vendor should return it to the distributor and the distributor should work with the state to decide upon how best to dispose. If the consumer is disposing of the product he/she should consult with the local state EPA office.
#
RSS Feed for FDA Recalls Information11 [what's this?12]

FRIDAY, JULY 26, 2019 

Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species
MONDAY, NOVEMBER 30, 2020 

REPORT OF THE MEETING OF THE OIE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES Paris, 9–13 September 2019 BSE, TSE, PRION


WEDNESDAY, DECEMBER 23, 2020 

BSE research project final report 2005 to 2008 SE1796 SID5


Terry S. Singeltary Sr.




at