Friday, March 19, 2021

Could Sporadic Creutzfeldt-Jakob Disease Be Underdiagnosed in China? Experience From Four Cases

Could Sporadic Creutzfeldt-Jakob Disease Be Underdiagnosed in China? Experience From Four Cases

Yi-Liu Zhang1 , Xiao-Mei Wu1 , Yang Chen1 , Wen-Ping Gu2 * and Wei Lu1 * 1 Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China, 2 Department of Neurology, Xiangya Hospital, Central South University, Changsha, China

Background: Creutzfeldt-Jakob Disease (CJD) is a rapidly progressive neurodegenerative disease caused by the misfolded version of the cellular prion protein. Here we report four cases of sporadic CJD (sCJD) and describe the diagnostic methods available in order avoid missed or delayed recognition of CJD in China.

Case presentation: We report four patients diagnosed with sCJD between March 2018 and December 2019 at Xiangya Hospital and the Second Xiangya Hospital of Central South University. All patients were admitted to the hospital because of a progressive cognitive decline. Although their routine tests and biochemical indicators in the cerebrospinal fluid (CSF), as well as computed tomography (CT) imaging, did not reveal any apparent abnormalities, the presence of “cortical ribboning” was incidentally found on diffusion-weighted imaging (DWI). The patients were subsequently diagnosed with CJD based on positive testing for 14-3-3 protein in their CSF, and the presence of periodic sharp and slow wave complexes (PSWCs) on their electroencephalograms (EEG). Additionally, two of patients was confirmed pathological examination of cerebral biopsies demonstrating neuronal loss, gliosis, and spongiform changes.

Conclusions: CJD is a rare disease and is easily misdiagnosed by clinician in China due to a lack of recognition and awareness of CJD. Based on our experience described in this report, enhanced vigilance for CJD is required for patients with rapidly progressive dementia in China and other developing countries. DWI, EEG and detection of 14-3-3 protein in CSF should be performed in order to achieve a timely diagnosis of CJD.

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CONCLUSION

CJD is a rare disease, but the limited availability of more advance diagnostic methods combined with a lack of awareness about CJD in China and other developing countries may be leading to a missed diagnoses, misdiagnoses and low diagnostic rate. New, less invasive and more accessible diagnostic techniques as an alternative to brain biopsy, including EEG, DWI, RT-QuIC, 14-3-3 protein, and other biomarkers, could improve the accuracy of diagnosing prion diseases. We diagnosed four cases within a <2-year period, which alerts us to CJD being a public health concern that requires greater attention. In China, awareness should be generated for patients with rapidly progressive dementia in clinical practice, and patients should be examined by methods such as DWI, testing for 14-3-3 proteins in the CSF, RT-QuIC, and so on, in order to ensure a correct diagnosis.

Keywords: Creutzfeldt-Jakob disease, prion disease, neuroinfectious disease, PrPSC, rapidly progressive dementia


FRIDAY, OCTOBER 30, 2020 

Analysis of Chinese patients with sporadic Creutzfeldt-Jakob disease


Eur Neurol 2020;83:65–72

Sporadic Creutzfeldt-Jakob Disease: A Retrospective Analysis of 104 Cases

Chang Qia, b Jia-Tang Zhanga, b Wei Zhaoc Xiao-Wei Xingb Sheng-Yuan Yua, b a Medical School of Chinese PLA, Beijing, China; bDepartment of Neurology, Chinese PLA General Hospital, Beijing, China; c Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, China Received: November 3, 2019 Accepted: March 5, 2020 Published online: April 28, 2020 Dr. Jia-Tang Zhang Department of Neurology, Chinese PLA General Hospital Medical School of Chinese PLA No. 28, Fuxing Road, Beijing 100853 (China) zjt1128@aliyun.com © 2020 The Author(s) Published by S. Karger AG, Basel karger@karger.com www.karger.com/ene DOI: 10.1159/000507189

Abstract

Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is an extremely rare fatal and infectious neurodegenerative brain disorder characterized by rapidly progressive dementia, cerebellar ataxia, and visual disturbances. This article summarizes the retrospective analysis of 104 sCJD patients in the First Medical Center of Chinese PLA General Hospital from 2003 to 2019. 

Methods: A retrospective analysis of the medical records of the 104 patients diagnosed with sCJD was performed from the aspects of demographic data, clinical manifestations, laboratory examinations, cerebrospinal fluid analysis, electroencephalograms (EEGs), diffusionweighted imaging (DWI) scans, positron emission tomography (PET) scans, and prion protein gene mutations. 

Results: In the 104 sCJD patients, pathological evidence of a spongiform change was found in 11 patients, while the remaining 93 patients were probable sCJD. The 104 patients included 57 males and 47 females, with the age of onset ranging from 29 to 82 (mean: 58, median: 60) years. The time from disease onset to death ranged from 1 to 36 months. Most of the patients died 7–12 months after the onset of sCJD. In most patients, rapidly progressive dementia appeared as the initial symptom, followed by cerebellar ataxia, visual disturbances, and neurobehavioral disorders. Most patients’ DWI images showed symmetric or asymmetric hyperintensity in the cortex. In terms of EEGs, 38.2% of the patients had periodic sharp wave complexes. The sensitivity of 14-3-3 protein detection was 34.1%. The brain PET scans of 50 patients with sCJD presented 96% sensitivity for the diagnosis of sCJD. 

Conclusions: This study indicated that sCJD occurred at an early age in patients in China. The sensitivity of 14-3-3 protein detection was significantly low, but brain PET was highly sensitive in the diagnosis of sCJD.

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. In conclusion, this study retrospectively analyzed 104 patients diagnosed with sCJD pathologically and clinically. The characteristics of sCJD were summarized from the perspectives of demographic data and auxiliary examinations, and the results were compared with those from sCJD patients in other reports. This study may represent the characteristics of sCJD patients in China or even in Asia. In addition, PET-CT and PET-MRI examinations were important for the early diagnosis of sCJD due to their high sensitivity.

© 2020 The Author(s) Published by S. Karger AG, Basel


Incidence of and Mortality Due to Human Prion Diseases in Taiwan: A Prospective 20-Year Nationwide Surveillance Study from 1998 to 2017

This article was published in the following Dove Press journal: Clinical Epidemiology

Yu Sun 1,2 Chih-Ching Liu3, * Ling-Yun Fan4, * Chung-Te Huang5 Ta-Fu Chen2 Chien-Jung Lu1,2 Wan-Yuo Guo 6,7 Yang-Chyuan Chang2,8 Ming-Jang Chiu 2,9 

Department of Neurology, En Chu Kong Hospital, New Taipei City, Taiwan; 2 Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; 3 Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan; 4 Queensland Brain Institute, University of Queensland, St. Lucia, Brisbane, QLD, Australia; 5 Center for Research, Diagnostics and Vaccine Development, Taiwan Centers for Disease Control, Taipei, Taiwan; 6 Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; 7 School of Medicine, National Yang-Ming University, Taipei, Taiwan; 8 Department of Neurology, Min-Sheng General Hospital, Taoyuan, Taiwan; 9 Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan; 10Graduate Institute of Psychology, College of Science, National Taiwan University, Taipei, Taiwan; 11Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan

*These authors contributed equally to this work 

Correspondence: Ming-Jang Chiu Tel +886-2-23123456 ext 65339 Fax +886-2-23418395 Email mjchiu@ntu.edu.tw

Introduction: Epidemiologic studies of Creutzfeldt-Jakob disease (CJD) have been undertaken worldwide since the new variant CJD outbreak in 1996 in the United Kingdom. A nationwide report system, the Creutzfeldt-Jakob Disease Surveillance Unit (CJDSU), directed by the Centers for Disease Control of Taiwan, was established in 1997 to identify human prion diseases.

Methods: From 1998 to 2017, 647 cases were referred to the committee for confirmation. The report to CJDSU included a structured questionnaire recording the clinical, demographic data, and potential iatrogenic exposure, and the results of the clinical and laboratory examination, including tests of blood and cerebrospinal fluid, electroencephalography, and brain magnetic resonance imaging.

Results: In total, 356 cases (women, n=178) were ascertained to be human prion diseases, and 97.4% (n=347) were sporadic CJD, including three definite, 314 probable, and 30 possible cases; one probable variant CJD and 8 cases of the genetic form human prion diseases. The age- and gender-specific average annual incidence were also significantly higher in the second decade (0.95/1,000,000) than in the first decade (0.63/1,000,000), with an incidence rate ratio of 1.51. The incidences increased with increasing age, reaching a peak at the age of 70–79 years. The 10-year survival curve for sCJD patients showed that the 1-, 5-, and 10-year cumulative survival rate were 52%, 5%, and 1%, respectively. PRNP polymorphisms in 170 patients showed that 98.8% were M129M and 97.6% E219E.

Discussion: The significant increase in incidence after 2008 suggests the increase in the awareness of this rare disease among physicians. The longer disease duration in patients with sCJD in Taiwan than in other countries indicates that the comprehensive support of the health care system, as well as the end-of-life care culture in Taiwan, may prolong survival time in patients with such a progressive and fatal disease.

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Discussion

Our previous epidemiological research of CJD from 1998 to 2007 has been reported 10 years ago.3 In current analysis, we rechecked the information of all the ascertained cases of the first decade in the registry and found that 9 cases before 2005 should be excluded because they could not meet the diagnostic criteria with some missing data. Moreover, 2 cases that were identified in 2008 actually had their disease onset in 2007 by tracing their history again.

The overall incidence rate of CJD from 1998 to 2017 in Taiwan was 0.79 per million persons. The incidence significantly increased after 2008 to approximately 1 case per million persons per year, comparable to the worldwide incidence, typically reported to be approximately 1–2 per million person-years based on surveillance from 2005 onward.2,20 The increase in incidence for the second decade could be explained by the enhanced awareness of clinical physicians, the improved diagnostic tests, and the increase in the aging population in Taiwan, as the incidence of CJD cases, peaked in the 70- to 79-year-old age group similar distribution to the USA study. 21 The incidence of CJD onset after 80 years of age was still high, without a sharp decline, which was different from other reports.6,22 Since the start of the CJDSU in 1997, several national or international symposiums focused on human transmissible spongiform encephalopathy have been held by the Taiwan Neurological Society to educate neurologists and general physicians about the updated diagnostic criteria and management of CJD patients. The Taiwan CDC has regularly revised the workbook.23 In 2008, an imported case of vCJD was reported to CJDSU.19 This first acquired case of CJD in Taiwan was a critical public health concern and might have helped raise awareness of the disease among neurologists, leading to an increase in the number of reported cases afterward. In 2009, an updated set of criteria, including MRI findings, were proposed and soon adopted by the CJDSU.17 The pattern of high signal intensity had high sensitivity and specificity for the differential diagnosis, assisting in distinguishing sCJD from other neurological diseases and helping clinicians detect suspected cases early; this, in part, resulted in the increase in the number of referrals in subsequent years.

The polymorphism at codon 129 (M129V) of PRNP is a recognized genetic marker for susceptibility to CJD in Caucasians.24 In Europe, 51% of the general population has methionine/valine (MV) heterozygosity, while 37% has methionine homozygosity (MM).25,26 In East Asia, the MM genotype was found in 94% of Koreans27 and 92% of Japanese individuals.26 Ethnic Han Chinese, who account for over 95% of the Taiwanese population, has a remarkably high frequency (98%) of methionine homozygosity in the general population.28 Methionine homozygosity is high in both healthy individuals and diseased patients, with 98.8% of CJD patients in our study having the MM genotype and less than 2% carrying the MV genotype. Prion susceptibility and protective alleles can exhibit marked geographic differences, with the effects being different in the Asian and Caucasian populations.26

Because of the short disease duration in most cases, the increase in mortality with time parallels the temporal trend in incidence, as the mortality rate was significantly higher in the second decade than in the first decade. There was no difference in the incidence and mortality rates between men and women in our study. Some countries reported a higher incidence in women than men because of the larger number of women among older populations.21 The disease duration varied based on CJD types, with a relatively chronic course in some genetic forms. The mean survival time was 56.4 (range, 35.1–67.4) months in four GSS patients (P102L), 15.4 (9.0, 21.7) months in two E196A patients, and 11.9 months in an R148H patient, while a substantially shorter disease duration of 2.4 months was noted in a patient with a 72-base pair insertion. Because of the small number of gCJD patients in our study, it is challenging to compare Taiwan with other countries regarding these patients’ survival time.

Among the patients with sCJD, women and those with younger ages at onset had longer disease durations. This finding is comparable with the results from a collaborative multi-national CJD surveillance program (EUROCJD) conducted by the European Union and allied countries. The precise mechanisms underlying the effects of age and gender effects on survival time are not known. Agerelated variations in care or resistance to terminal infections have been proposed as possible explanations.29 Whether gender-specific factors influence the disease duration needs to be studied. In this national cohort, we found some long-term survivors of sCJD, with 3-, 5- and 10-year survival rates of 13%, 5%, and 1%, respectively. The median survival time was 13.5 months (mean: 19.1 months), and 48% died within one year of onset. Our data were similar to those in the report from Japan, in which the mean survival time of sCJD patients was 15.7 (range: 1–126) months, and 46.0% of all patients with prion disease died within one year. 29 However, reports from other counties revealed a much shorter survival time. The study by the EUROCJD involving 2,451 sCJD patients showed that the median survival time was five months (range: 1–81), and 85.8% died within one year of onset.11 The median duration in a study involving 150 definite or probable sCJD cases in Argentina was 4.6 (range: 1–70) months,30 while a Swedish study involving 123 patients with prion disease found that 74.6% of patients died within one year. 31 A study from China also showed a short survival time, with a median duration of 7.1 months (range: 1.0–23.3), and 78.5% of patients died within one year of onset.10

within one year of onset.10 The survival times of patients with sCJD in Taiwan and Japan were relatively longer than those reported in most of the other countries in the world. Japanese researchers explained the prolonged survival as the effects of their robust public medical insurance system and a culture allowing patients with end-stage neurological disease to receive intensive life-sustaining treatments such as tube feeding and intravenous high-calorie infusion.9,32 Taiwan adopted a single-payer National Health Insurance (NHI) system in 1995 that also provides comprehensive healthcare support.33 Patients with human prion disease do not need to pay any co-payment for outpatient or inpatient care. In addition, Taiwanese also share this end-of-life care culture.

There are several limitations to the current study. First, the percentage of definite cases of human spongiform encephalopathies was relatively small. Because of the traditional ethical values among the general population in Taiwanese society, the very low autopsy rate has long been acknowledged as an unfortunate and unavoidable reality. In recent years, using the real-time quaking-induced conversion assay to detect the pathological prion protein in the CSF or other tissues has been developed and has high diagnostic accuracy. 34 However, this technique was not used by the CJDSU in Taiwan during our study period. Without obtaining tissue specimens or testing for the pathological prion protein, we are not only unable to make a definite diagnosis but also are unable to assess the various molecular subtypes of sCJD, which is useful for phenotypic classification. Second, underreporting and underestimation of CJD are inevitable. Because of the older age at onset, patients with CJD may be misdiagnosed with other diseases with the rapid progression of neurological symptoms such as stroke,35 encephalitides,36 degenerative dementia,37 and epilepsy. 38 A retrospective archival survey published in 1995 showed that only approximately 60% of prion disease patients with pathologically spongiform encephalopathy were diagnosed clinically while alive. In recent decades, diagnostic accuracy has been improved by the use of CSF biomarkers and brain MRI.17 Not infrequently, the committee recommended that the primary care physician follow-up during the clinical course and perform MRI/EEG in case of uncertainty. They were obliged to report back at the next relevant meeting.

Furthermore, due to our NHI system’s comprehensive coverage, patients with spongiform encephalopathy received complete financial support covering all necessary MRI or EEG follow-up. There is nearly a consensus in clinical practice among neurologists in Taiwan that for those patients with rapid cognitive decline, in addition to CSF studies, MRI and EEG examination, tests to exclude autoimmune encephalitis or paraneoplastic encephalopathy should usually be performed. Third, the finding of 2% (8/356) of gCJD among all CJD forms was far lower than the corresponding figures elsewhere in the world, which range from 10–14%.25,39 Although the incidence of gCJD varies considerably among countries, we speculate that the lower proportion of gCJD in our study is likely because the PRNP gene sequencing test was not routinely performed before 2009, only 170 of the 356 CJD cases tested. Approximately 60% of genetic CJD cases were reported in patients with no family history, suggesting that they could have been misclassified in the absence of the PRNP genetic analysis.39

In conclusion, this study reports the 20-year epidemiologic features of CJD in Taiwan. The second decade’s incidence rate was comparable with the corresponding figures in most other countries in the world. The significant increase in incidence after 2008 suggests the increase in awareness of this rare disease among clinical physicians and the increase in Taiwan’s aging population. The longer disease duration in patients with sCJD in Taiwan than in Western countries indicates that the healthcare system and end-of-life care culture in Taiwan may prolong survival time in patients with such a rapidly progressive and fatal disease. 

Keywords: human prion diseases, spongiform encephalopathy, incidence, mortality, disease duration



Sunday, November 1, 2020 

Taiwan Incidence of and Mortality Due to Human TSE Prion Diseases Sees Significant Increase In Incidence After 2008 

Sunday, November 1, 2020 

Taiwan Incidence of and Mortality Due to Human TSE Prion Diseases Sees Significant Increase In Incidence After 2008 


SATURDAY, SEPTEMBER 26, 2020 

A nationwide trend analysis in the incidence and mortality of Creutzfeldt–Jakob disease in Japan between 2005 and 2014 with increasing trends of incidence and mortality

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Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4–5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7–8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia.

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Sunday, December 27, 2020 

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


Tuesday, December 15, 2020

Risk of Transmissibility From Neurodegenerative Disease-Associated Proteins: Experimental Knowns and Unknowns


THURSDAY, JULY 02, 2020 

Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure


SATURDAY, AUGUST 01, 2020 

Sporadic Creutzfeldt-Jakob Disease among Physicians, Germany, 1993–2018 high proportion of physicians with sCJD were surgeons


SATURDAY, FEBRUARY 20, 2021 
Abnormal prion protein deposits with high seeding activities in the skeletal muscle, femoral nerve, and scalp of an autopsied case of sporadic Creutzfeldt–Jakob disease
TUESDAY, DECEMBER 01, 2020 

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

| VOLUME 20, ISSUE 3, P235-246, MARCH 01, 2021

Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease

Peter Hermann, MD Prof Brian Appleby, MD Jean-Philippe Brandel, MD Byron Caughey, PhD Prof Steven Collins, MD Prof Michael D Geschwind, PhD et al. Show all authors


Summary

Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrPSc). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG. Supportive biomarkers, such as high CSF total tau, could aid the diagnostic process. However, discordant studies have led to controversies about the clinical value of some established surrogate biomarkers. Development and clinical application of disease-specific protein aggregation and amplification assays, such as real-time quaking induced conversion (RT-QuIC), have constituted major breakthroughs for the confident pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Updated criteria for the diagnosis of sporadic Creutzfeldt-Jakob disease, including application of RT-QuIC, should improve early clinical confirmation, surveillance, assessment of PrPSc seeding activity in different tissues, and trial monitoring. Moreover, emerging blood-based, prognostic, and potentially pre-symptomatic biomarker candidates are under investigation.

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. 
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

APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission

June 17, 2019

APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission

Greetings APHIS et al, 

I would kindly like to comment on APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], and my comments are as follows, with the latest peer review and transmission studies as references of evidence.

THE OIE/USDA BSE Minimal Risk Region MRR is nothing more than free pass to import and export the Transmissible Spongiform Encephalopathy TSE Prion disease. December 2003, when the USDA et al lost it's supposedly 'GOLD CARD' ie BSE FREE STATUS (that was based on nothing more than not looking and not finding BSE), once the USA lost it's gold card BSE Free status, the USDA OIE et al worked hard and fast to change the BSE Geographical Risk Statuses i.e. the BSE GBR's, and replaced it with the BSE MRR policy, the legal tool to trade mad cow type disease TSE Prion Globally. The USA is doing just what the UK did, when they shipped mad cow disease around the world, except with the BSE MRR policy, it's now legal. 

Also, the whole concept of the BSE MRR policy is based on a false pretense, that atypical BSE is not transmissible, and that only typical c-BSE is transmissible via feed. This notion that atypical BSE TSE Prion is an old age cow disease that is not infectious is absolutely false, there is NO science to show this, and on the contrary, we now know that atypical BSE will transmit by ORAL ROUTES, but even much more concerning now, recent science has shown that Chronic Wasting Disease CWD TSE Prion in deer and elk which is rampant with no stopping is sight in the USA, and Scrapie TSE Prion in sheep and goat, will transmit to PIGS by oral routes, this is our worst nightmare, showing even more risk factors for the USA FDA PART 589 TSE PRION FEED ban. 

The FDA PART 589 TSE PRION FEED ban has failed terribly bad, and is still failing, since August 1997. there is tonnage and tonnage of banned potential mad cow feed that went into commerce, and still is, with one decade, 10 YEARS, post August 1997 FDA PART 589 TSE PRION FEED ban, 2007, with 10,000,000 POUNDS, with REASON, Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. you can see all these feed ban warning letters and tonnage of mad cow feed in commerce, year after year, that is not accessible on the internet anymore like it use to be, you can see history of the FDA failure August 1997 FDA PART 589 TSE PRION FEED ban here, but remember this, we have a new outbreak of TSE Prion disease in a new livestock species, the camel, and this too is very worrisome.

WITH the OIE and the USDA et al weakening the global TSE prion surveillance, by not classifying the atypical Scrapie as TSE Prion disease, and the notion that they want to do the same thing with typical scrapie and atypical BSE, it's just not scientific.

WE MUST abolish the BSE MRR policy, go back to the BSE GBR risk assessments by country, and enhance them to include all strains of TSE Prion disease in all species. With Chronic Wasting CWD TSE Prion disease spreading in Europe, now including, Norway, Finland, Sweden, also in Korea, Canada and the USA, and the TSE Prion in Camels, the fact the the USA is feeding potentially CWD, Scrapie, BSE, typical and atypical, to other animals, and shipping both this feed and or live animals or even grains around the globe, potentially exposed or infected with the TSE Prion. this APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], under it's present definition, does NOT show the true risk of the TSE Prion in any country. as i said, it's nothing more than a legal tool to trade the TSE Prion around the globe, nothing but ink on paper.

AS long as the BSE MRR policy stays in effect, TSE Prion disease will continued to be bought and sold as food for both humans and animals around the globe, and the future ramifications from friendly fire there from, i.e. iatrogenic exposure and transmission there from from all of the above, should not be underestimated. ... 




Comment from Terry Singeltary Posted by the Animal and Plant Health Inspection Service on Jun 19, 2019

WEDNESDAY, JANUARY 1, 2020 USDA OIE BSE TSE PRION FDA PART 589 BSE TSE PRION aka MAD COW FEED BAN Failure 2020 UPDATE 


Terry S. Singeltary Sr.

posted by Terry S. Singeltary Sr. at 4:31 PM

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.




posted by Terry S. Singeltary Sr. at 4:39 PM