Thursday, February 2, 2023

EFSA OIE WOHA UPDATES ON CHRONIC WASTING DISEASE CWD TSE PrP ZOONOSIS

EFSA OIE WOHA UPDATES ON CHRONIC WASTING DISEASE CWD TSE PRP ZOONOSIS

CHRONIC WASTING DISEASE CWD TSE PRION ZOONOSIS AND WHO MAKES THE CALL $$$

THE CODE COMMISSION ACKNOWLEDGED THE RATIONALE PROVIDED IN THE SCIENTIFIC COMMISSION’S FEBRUARY 2021 REPORT THAT CHRONIC WASTING DISEASE DOES NOT MEET THE CRITERIA FOR LISTING, SPECIFICALLY FOR POINT 2 OF ARTICLE 1.2.2. OF CHAPTER 1.2. CRITERIA FOR THE INCLUSION OF DISEASES, INFECTIONS AND INFESTATIONS IN THE OIE LIST


FROM: TERRY SINGELTARY <FLOUNDER9@VERIZON.NET>
SENT: 27 MAY 2022 19:37
TO: SCIENTIFIC DEPT <SCIENTIFIC.DEPT@OIE.INT>
SUBJECT: RE: OIE 89TH SESSION

 

I CAN'T SEEM TO GET A REPLY?

 

''I WAS WONDERING IF CHRONIC WASTING DISEASE CWD TSE PRION OF CERVID WILL BE ADDRESSED AT ALL AT THE OIE #89, AND IF SO, WHAT SESSION? ''

 

KIND REGARDS, TERRY

***> HOWEVER IT WAS DISCUSSED IN SEVERAL OCCASIONS BY THE SPECIALIST COMMISSION. THE LAST DISCUSSION WAS IN SEPTEMBER 2021 (PAGE 5)  


HTTPS://WWW.WOAH.ORG/APP/UPLOADS/2021/11/A-TAHSC-SEPT-2021-REPORT.PDF


SNIP...END...TSS


 REPORT OF THE MEETING OF THE OIE TERRESTRIAL ANIMAL HEALTH STANDARDS COMMISSION VIRTUAL MEETING, 7–16 & 23 SEPTEMBER 2021

SNIP...

THE CODE COMMISSION WAS PROVIDED WITH AN UPDATE ON THE PROGRESS OF THE WORK TO DEVELOP CASE DEFINITIONS TO SUPPORT NOTIFICATION BEING CONDUCTED BY THE SCIENTIFIC COMMISSION. IN RESPONSE TO THIS UPDATE, THE CODE COMMISSION RECOGNISED THE VALUE OF THIS WORK AND REMINDED MEMBERS THAT IN ORDER TO SUPPORT NOTIFICATION, NEWLY DEVELOPED CASE DEFINITIONS OF LISTED DISEASES WOULD BE PUBLISHED ON THE OIE WEBSITE IF THEY DO NOT CONFLICT WITH EXISTING OIE STANDARDS. THESE CASE DEFINITIONS WOULD THEN BE CONSIDERED FOR INCLUSION IN THE RELEVANT DISEASE-SPECIFIC CHAPTER OF THE TERRESTRIAL CODE ACCORDING TO THE PRIORITISATION OF THE CODE COMMISSION’S WORK PROGRAMME AND THE STANDARD-SETTING PROCESS.

THE CODE COMMISSION ACKNOWLEDGED THE RATIONALE PROVIDED IN THE SCIENTIFIC COMMISSION’S FEBRUARY 2021 REPORT THAT CHRONIC WASTING DISEASE DOES NOT MEET THE CRITERIA FOR LISTING, SPECIFICALLY FOR POINT 2 OF ARTICLE 1.2.2. OF CHAPTER 1.2. CRITERIA FOR THE INCLUSION OF DISEASES, INFECTIONS AND INFESTATIONS IN THE OIE LIST. THE COMMISSION ALSO NOTED THAT THE SCIENTIFIC COMMISSION WILL CONSIDER THE EXPERT CONSULTATION REPORTS AND THE OPINION OF THE LABORATORIES COMMISSION ON ASSESSMENTS UNDERTAKEN FOR PARATUBERCULOSIS AND WEST NILE VIRUS IN ACCORDANCE WITH CHAPTER 1.2.

THE CODE COMMISSION WISHED TO THANK THE SCIENTIFIC COMMISSION FOR ITS COLLABORATIVE WORK IN PROVIDING OPINIONS TO SUPPORT THE CONSIDERATION OF RELEVANT MEMBER COMMENTS RECEIVED. THE CODE COMMISSION REMINDED MEMBERS THAT ITS CONSIDERATION OF THE SCIENTIFIC COMMISSION CONTRIBUTIONS IS NOTED UNDER THE RELEVANT AGENDA ITEMS OF THIS REPORT AND ENCOURAGED MEMBERS TO READ THIS REPORT TOGETHER WITH THE SEPTEMBER 2021 SCIENTIFIC COMMISSION REPORT. 

HTTPS://WWW.WOAH.ORG/APP/UPLOADS/2021/11/A-TAHSC-SEPT-2021-REPORT.PDF

REPORT OF THE MEETING OF THE OIE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES VIRTUAL, 1–11 FEBRUARY 2021 

IV) CHRONIC WASTING DISEASE

THE COMMISSION CONSIDERED THE REQUEST BY THE CODE COMMISSION FOR CLARIFICATION ON THE RATIONALE FOR THE COMMISSION’S OPINION THAT CWD DID NOT FULFIL THE CRITERIA FOR LISTING, SPECIFICALLY FOR POINT 2 OF ARTICLE 1.2.26 OF THE TERRESTRIAL CODE. THE COMMISSION EXPLAINED THAT THE OPINION WAS BASED ON AN EXTENSIVE CONSULTATION PROCESS THAT TOOK INTO ACCOUNT THE OPINIONS OF THE AD HOC GROUP ON BSE, THE WORKING GROUP ON WILDLIFE AND SEVERAL SUBJECT-MATTER EXPERT CONSULTATIONS. BASED ON THIS EXTENSIVE CONSULTATION, THE COMMISSION INDICATED THAT THE LOW DISEASE PREVALENCE, THE IMPRACTICAL NATURE OF CURRENTLY AVAILABLE DIAGNOSTIC TESTS, AND THE LIMITED NUMBER OF CONTROL MEASURES MAKE IT DIFFICULT TO ELIMINATE THE DISEASE OR SCIENTIFICALLY PROVIDE EVIDENCE TO DEMONSTRATE EITHER FREEDOM OR IMPENDING FREEDOM. THE COMMISSION CONSIDERED ALSO THAT DESPITE THE IMPLEMENTATION OF SURVEILLANCE PROGRAMMES BY SOME MEMBERS, NO COUNTRY CAN CURRENTLY DEMONSTRATE EITHER FREEDOM OR IMPENDING FREEDOM FROM DISEASE. 


ANNEX 19

WORK PROGRAMME OF THE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES (FEB 2021)

DEFINE A PROCEDURE FOR THE EVALUATION OF DISEASES AGAINST THE LISTING CRITERIA OF CHAPTER 1.2., AND RESPONDING TO REQUESTS FOR LISTING DECISIONS

EVALUATED PROPOSALS FOR (DE)LISTING OF:

• M. TUBERCULOSIS • INFESTATION OF HONEY BEES WITH ACARAPIS WOODI • INFESTATION OF HONEY BEES WITH TROPILAELAPS SPP. 

• CHRONIC WASTING DISEASE 

• ATYPICAL BSE





ON MONDAY, MAY 30, 2022 AT 10:35:20 AM CDT, 

SCIENTIFIC DEPT <SCIENTIFIC.DEPT@OIE.INT> WROTE:

DEAR DR SINGELTARY,

THANK YOU FOR YOUR MESSAGE, AND APOLOGIES FOR OUR RATHER TARDY RESPONSE.

BELOW IS THE ANSWER TO YOUR QUERY.

WE ARE HAPPY TO HELP SHOULD YOU HAVE ADDITIONAL QUESTIONS.

CHEERS.

FROM: GREGORIO TORRES <G.TORRES@OIE.INT>
SENT: 30 MAY 2022 14:15
TO: SCIENTIFIC DEPT <SCIENTIFIC.DEPT@OIE.INT>; SARA LINNANE <S.LINNANE@OIE.INT>
SUBJECT: RE: OIE 89TH SESSION: CWD

HI CWD WAS NOT DISCUSSED THIS YEAR.

HOWEVER IT WAS DISCUSSED IN SEVERAL OCCASIONS BY THE SPECIALIST COMMISSION. THE LAST DISCUSSION WAS IN SEPTEMBER 2021 (PAGE 5)  HTTPS://WWW.WOAH.ORG/APP/UPLOADS/2021/11/A-TAHSC-SEPT-2021-REPORT.PDF

4.1. SCIENTIFIC COMMISSION FOR ANIMAL DISEASES 

THE OIE SECRETARIAT UPDATED THE CODE COMMISSION ON RELEVANT ONGOING ACTIVITIES OF THE SCIENTIFIC COMMISSION. THE SCIENTIFIC COMMISSION, AT ITS SEPTEMBER 2021 MEETING, WILL CONSIDER A NUMBER OF TOPICS RELEVANT TO THE CODE COMMISSION’S WORK PROGRAMME, AND WILL PROVIDE ITS OPINIONS ON A NUMBER OF POINTS REGARDING CHAPTER 8.14. INFECTION WITH RABIES VIRUS; CHAPTER 8.15. INFECTION WITH RIFT VALLEY FEVER VIRUS; CHAPTER 12.7. EQUINE PIROPLASMOSIS; AND CHAPTER 8.X. AND CHAPTER 12.3. ON SURRA AND DOURINE. THE CODE COMMISSION, AT ITS FEBRUARY 2022 MEETING, WILL CONSIDER THE OPINION OF THE SCIENTIFIC COMMISSION TOGETHER WITH OTHER PENDING ISSUES, IN ORDER TO PROGRESS WORK ON THE REVISION OF THESE CHAPTERS. 

OIE TERRESTRIAL ANIMAL HEALTH STANDARDS COMMISSION/SEPTEMBER 2021 

5 

THE CODE COMMISSION WAS PROVIDED WITH AN UPDATE ON THE PROGRESS OF THE WORK TO DEVELOP CASE DEFINITIONS TO SUPPORT NOTIFICATION BEING CONDUCTED BY THE SCIENTIFIC COMMISSION. IN RESPONSE TO THIS UPDATE, THE CODE COMMISSION RECOGNISED THE VALUE OF THIS WORK AND REMINDED MEMBERS THAT IN ORDER TO SUPPORT NOTIFICATION, NEWLY DEVELOPED CASE DEFINITIONS OF LISTED DISEASES WOULD BE PUBLISHED ON 
THE OIE WEBSITE IF THEY DO NOT CONFLICT WITH EXISTING OIE STANDARDS. THESE CASE DEFINITIONS WOULD THEN BE CONSIDERED FOR INCLUSION IN THE RELEVANT DISEASE-SPECIFIC CHAPTER OF THE TERRESTRIAL CODE ACCORDING TO THE PRIORITISATION OF THE CODE COMMISSION’S WORK PROGRAMME AND THE STANDARD-SETTING PROCESS. 

THE CODE COMMISSION ACKNOWLEDGED THE RATIONALE PROVIDED IN THE SCIENTIFIC COMMISSION’S FEBRUARY 2021 REPORT THAT CHRONIC WASTING DISEASE DOES NOT MEET THE CRITERIA FOR LISTING, SPECIFICALLY FOR POINT 2 OF ARTICLE 1.2.2. OF CHAPTER 1.2. CRITERIA FOR THE INCLUSION OF DISEASES, INFECTIONS AND INFESTATIONS IN THE OIE LIST. THE COMMISSION ALSO NOTED THAT THE SCIENTIFIC COMMISSION WILL CONSIDER THE EXPERT CONSULTATION REPORTS AND THE OPINION OF THE LABORATORIES COMMISSION ON ASSESSMENTS UNDERTAKEN FOR PARATUBERCULOSIS AND WEST NILE VIRUS IN ACCORDANCE WITH CHAPTER 1.2. 

THE CODE COMMISSION WISHED TO THANK THE SCIENTIFIC COMMISSION FOR ITS COLLABORATIVE WORK IN PROVIDING OPINIONS TO SUPPORT THE CONSIDERATION OF RELEVANT MEMBER COMMENTS RECEIVED. THE CODE COMMISSION REMINDED MEMBERS THAT ITS CONSIDERATION OF THE SCIENTIFIC COMMISSION CONTRIBUTIONS IS NOTED UNDER THE RELEVANT AGENDA ITEMS OF THIS REPORT AND ENCOURAGED MEMBERS TO READ THIS REPORT TOGETHER WITH THE SEPTEMBER 2021 SCIENTIFIC COMMISSION REPORT.


TUESDAY, MAY 31, 2022

89TH GENERAL SESSION OF THE WORLD ASSEMBLY OF OIE DELEGATES FOR WOAH GENERAL SUMMIT 2022 CHRONIC WASTING DISEASE CWD TSE PRION DISCUSSIONS AND CONCERNS

89TH GENERAL SESSION OF THE WORLD ASSEMBLY OF OIE DELEGATES FOR WOAH GENERAL SUMMIT 2022 CHRONIC WASTING DISEASE CWD TSE PRION DISCUSSIONS AND CONCERNS

89TH GENERAL SESSION OF THE WORLD ASSEMBLY OF OIE DELEGATES FOR WOAH GENERAL SUMMIT FROM 23/05/2022 TO 26/05/2022 12:00PM - 4:30PM (GMT+1:00) PARIS



CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION PRP DISEASE, NO DISCUSSIONS OR CONCERNS AT 89TH GENERAL SESSION OF THE WORLD ASSEMBLY OF OIE DELEGATES FOR WOAH GENERAL SUMMIT FROM 23/05/2022 TO 26/05/2022...TERRY

FROM: GREGORIO TORRES <G.TORRES@OIE.INT>
SENT: 30 MAY 2022 14:15
TO: SCIENTIFIC DEPT <SCIENTIFIC.DEPT@OIE.INT>; SARA LINNANE <S.LINNANE@OIE.INT>
SUBJECT: RE: OIE 89TH SESSION: CWD

 

HI CWD WAS NOT DISCUSSED THIS YEAR.


HOWEVER IT WAS DISCUSSED IN SEVERAL OCCASIONS BY THE SPECIALIST COMMISSION. THE LAST DISCUSSION WAS IN SEPTEMBER 2021 (PAGE 5)


 HTTPS://WWW.WOAH.ORG/APP/UPLOADS/2021/11/A-TAHSC-SEPT-2021-REPORT.PDF

 

FROM: TERRY SINGELTARY <FLOUNDER9@VERIZON.NET>
SENT: 27 MAY 2022 19:37
TO: SCIENTIFIC DEPT <SCIENTIFIC.DEPT@OIE.INT>
SUBJECT: RE: OIE 89TH SESSION

 

I CAN'T SEEM TO GET A REPLY?

HTTPS://WOAHOIE.BLOGSPOT.COM/2022/05/89TH-GENERAL-SESSION-OF-WORLD-ASSEMBLY.HTML


THURSDAY, MARCH 31, 2022

EFSA ONE Conference 2022 Chronic Wasting Disease CWD TSE PrP of Cervid and Zoonosis Zoonotic Transmission Singeltary Submission

EFSA ONE Conference 2022 Chronic Wasting Disease CWD TSE PrP of Cervid and Zoonosis Zoonotic Transmission Singeltary Submission

Greetings EFSA One Conference 2022 et al.



I would kinly like to submit the following.

I would kindly like to bring my concerns of Chronic Wasting Disease CWD TSE PrP and the very likely potential of Zoonosis Zoonotic transmission there from, if it has not already happened and is being masked as sporadic CJD.

I Have been hounding the OIE on this very topic for over 2 decades. have written and submitted much science on this very topic. 

I Have been very critical of the OIE et al handling of the BSE mad cow debacle since i lost my mother to hvCJD. 

MUCH science has come to pass since then. 

I kindly submit, once again, an updated overview of Chronic Wasting Disease CWD TSE PrP, and my fear of friendly fire i.e. IATROGENIC CJD THERE FROM, and someone needs to finally pull the trigger and make chronic wasting disease cwd tse prp a zoonotic zoonosis disease, and treat it as such.

I will list the latest science on this topic, and then the history of my submissions to the OIE...Thank YOU!

CHRONIC WASTING DISEASE CWD PrP CERVID ZOONOTIC ZOONOSIS TRANSMISSION, HAS IT ALREADY HAPPENED AND WHAT ABOUT FRIENDLY FIRE THERE FROM, IATROGENIC CJD?

OIE et al got lucky with typical C-type BSE TSE PrP in cattle, and zoonosis zoonotic transmission, TO DATE, however, science has shown that the atypical BSE, atypical Scrapie are capable of being a zoonotic disease, transmitting to humans as sporadic CJD, and we know that atypical BSE and atypical Scrapie are risk factors for transmission in feed. New OIE evidence shows this;

Given that cattle have been successfully infected by the oral route, at least for L-BSE, it is reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle are exposed to contaminated feed. In addition, based on reports of atypical BSE from several countries that have not had C-BSE, it appears likely that atypical BSE would arise as a spontaneous disease in any country, albeit at a very low incidence in old cattle. In the presence of livestock industry practices that would allow it to be recycled in the cattle feed chain, it is likely that some level of exposure and transmission may occur. As a result, since atypical BSE can be reasonably considered to pose a potential background level of risk for any country with cattle, the recycling of both classical and atypical strains in the cattle and broader ruminant populations should be avoided. 


***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.

ATYPICAL SCRAPIE ROUGHLY HAS 50 50 CHANCE ATYPICAL SCRAPIE IS CONTAGIOUS, AS NON-CONTAGIOUS, TAKE YOUR PICK, BUT I SAID IT LONG AGO WHEN USDA OIE ET AL MADE ATYPICAL SCRAPIE A LEGAL TRADING COMODITY, I SAID YOUR PUTTING THE CART BEFORE THE HORSE, AND THAT'S EXACTLY WHAT THEY DID, and it's called in Texas, TEXAS TSE PRION HOLDEM POKER, WHO'S ALL IN $$$
https://efsaopinionbseanimalprotein.blogspot.com/2022/03/efsa-one-conference-2022-chronic.html

EFSA UPDATES ON CHRONIC WASTING DISEASE (CWD)

Evidence and supporting documents for EFSA-Q-2022-00114

Evidence reports submitted in the dossier

Notified studies not submitted in the dossier

Other documents Title Author More details Download File

Request for a scientific opinion on the monitoring of Chronic Wasting Disease (CWD) EFSA 04/02/2022

Request for a scientific opinion on the monitoring of Chronic Wasting Disease (CWD) European Commission 21/02/2022

Completion

Date

See Details 2022_02_17_Acceptance letter CWD monitoring_pub.pdf

See Details Ares(2022)822733 CWD mndate-pub.pdf 



Saturday, April 9, 2022

EFSA EU Request for a scientific opinion on the monitoring of Chronic Wasting Disease (CWD) EFSA-Q-2022-00114 M-2022-00040 Singeltary Submission



Sent: Fri, Apr 8, 2022 3:42 pm

Subject: EFSA EU Request for a scientific opinion on the monitoring of Chronic Wasting Disease (CWD) EFSA-Q-2022-00114 M-2022-00040 Singeltary Submission


EFSA EU Request for a scientific opinion on the monitoring of Chronic Wasting Disease (CWD) EFSA-Q-2022-00114 M-2022-00040 Singeltary Submission

Greetings Honorable EU, EFSA, OIE, Officials, Scientist, Politicians et al, 

I write to you with great urgency on the Request for a scientific opinion on the monitoring of Chronic Wasting Disease (CWD) EFSA-Q-2022-00114 M-2022-00040. 

PLEASE, do not make the same mistakes with CWD, as were made with BSE.

CWD TSE Prion disease is spreading across the USA, Canada, Mexico? (nobody has a clue), and as you know, Norway, Sweden, Finland, and look at the most recent stats below from 

FRIDAY, MARCH 18, 2022 

TUESDAY, MARCH 29, 2022

OIE Agent causing chronic wasting disease (CWD) TSE Prion of Cervid

OIE Agent causing chronic wasting disease (CWD) Tue, Mar 29, 2022 4:12 pm

Terry Singeltary flounder9@verizon.net

To scientific.dept@oie.int scientific.dept@oie.int

Cc media@oie.int media@oie.int, FAO-Newsroom@FAO.org FAO-Newsroom@FAO.org, mediainquiries@who.int mediainquiries@who.int, m.eloit@oie.int m.eloit@oie.int, g.torres@oie.int g.torres@oie.int, s.messori@oie.int s.messori@oie.int, j.y.park@oie.int j.y.park@oie.int, n.mapitse@oie.int n.mapitse@oie.int, m.park@oie.int m.park@oie.int, am.baka@oie.int am.baka@oie.int, oie@oie.int oie@oie.int

OIE Agent causing chronic wasting disease (CWD) TSE Prion of Cervid

Agent causing chronic wasting disease (CWD)

Aetiology 

Epidemiology Diagnosis Prevention and Control

Potential Impacts of Disease Agent Beyond Clinical Illness References

AETIOLOGY

Classification of the causative agent

Chronic wasting disease (CWD) is a contagious prion disease of free-ranging and captive deer, elk, and moose. The cellular prion protein (PrPC ) serves as the normal host-encoded cellular prion protein.

It is when PrPC directly binds to the misfolded isoform PrPSc that PrPC adopts the diseaseassociated conformation. Normal prion proteins can be found most abundantly in the brain and spinal cord.

CWD is a member of the transmissible spongiform encephalopathy (TSE) family of prion diseases, and it is believed there are multiple strains within the United States as well as a strain unique to Norway.

Resistance to physical and chemical action

Temperature: Highly resistant to heat and radiation (UV, microwave, ionising); inactivation by autoclaving at 134°C (273°F) for 18 minutes at 30 lb/in2 is suitable, but parameters may vary pending type of sample contaminated.

pH: Bioavailability of the CWD prion in soil is greater when pH>6.6.

Chemicals/Disinfectants: Highly resistant to chemical inactivation and few disinfectants effectively inactivate them; primarily, 50% concentrated household bleach with a contact time of 30-60 minutes or sodium hydroxide for 60 minutes are recommended, but concentrations and contact times may vary pending the type of sample contaminated.

Survival: Remains viable for long periods in fluids, faeces and tissues; persists in soil; partially resistant to protease digestion and can accumulate within neurones, eventually causing neuronic death.

EPIDEMIOLOGY

Hosts

● It is known to affect multiple cervid species including but not limited to: elk ( Cervus canadensis), moose (Alces alces), mule deer ( Odocoileus hemionus), white-tailed deer ( Odocoileus virinianus), and reindeer (Rangifer tarandus).

Transmission

● Direct:

○ Contact of mucous membranes between affected and healthy animals

● Indirect:

○ Environmental contamination of soil, food, or water

○ Consumption of plants that have uptaken prion proteins from contaminated soil (currently experimentally proven in hamsters only)

Sources

● Blood, tissues, secretions and excretions of sick and dead animals

Occurrence

CWD is present in captive and/or free-ranging deer, elk, and moose. It has been reported in three provinces of Canada, at least 26 states of the continental United States, Norway, Finland, Sweden, and in imported animals in South Korea.

For up-to-date information about the distribution of CWD in North America, see the referenced “Distribution of Chronic Wasting Disease in North America” URL provided by the USGS National Wildlife Health Center. For up-to-date information about the distribution of CWD in Sweden, see the referenced ”Map of Chronic Wasting Disease” URL provided by the National Veterinary Institute.

DIAGNOSIS

The minimum incubation period is approximately 16 months, and the average incubation period is approximately 2 to 4 years.

Clinical diagnosis

● CWD is fatal

● Clinical diagnosis may be difficult to observe in free-ranging animals, particularly early in the course of the disease

● Animals may present asymptomatically and die suddenly.

● Cervids can develop progressive weight loss and behavioural changes (lethargy, hyperexcitability, low carriage of head with fixed gaze) over several weeks to months.

● Neurological signs may be subtle but can include: ataxia, head tremors, teeth grinding, and pacing of an enclosure’s perimeter

● Animals may develop aspiration pneumonia secondary to oesophageal dilation and/or regurgitation, leading to death

● Polyuria (excessive urination) and polydipsia (excessive drinking) are common signs in the terminal stages

Lesions ● Post-mortem lesions:

○ Nonspecific; often emaciated but some carcases may be in good condition with few or no gross lesions (particularly in the early stages of disease)

○ Megaesophagus and aspiration bronchopneumonia can be seen

○ In summer, patchy retention of winter coat

○ Abomasal or omasal ulcers

Differential diagnoses

● Meningitis, encephalitis, brain abscess

● Fading elk syndrome

● Chronic malignant catarrhal fever

● Chronic epizootic haemorrhagic disease (EHD)

● Starvation, dental attrition

● Nutritional deficiencies, e.g., polioencephalomalacia, copper deficiency

● Toxicities, e.g., ryegrass staggers

● Stress

● Arthritis

● Traumatic Injuries

● Pneumonia

Laboratory diagnosis

Samples

For isolation of agent

● Antemortem:

○ Deer - palatine tonsil

○ Deer, elk - rectal lymphoid tissue

● Post-mortem:

○ Brain (obex), retropharyngeal lymph nodes, tonsils

Serologic Samples

● Serology is not used to make CWD diagnoses

Procedures

Identification of the agent

● Immunohistochemistry is the gold standard for diagnosing CWD

● Histopathology of lymphoid tissues and/or CNS

● Immunoblotting (Western blotting), enzyme-linked immunosorbent assays (ELISA), and rapid antigen-detection strip tests can also be used to screen cervids

Serological tests

● Serology is not feasible for antemortem testing; antibodies are not made against PRPSc

● Protein misfolding cyclic amplification (PMCA) and real-time quaking-induced conversion assay (RT-QUiC) are newly developed assays that can detect CWD prions at preclinical stages from noninvasive, antemortem samples, but are currently still under development for diagnostic use

PREVENTION AND CONTROL

Sanitary prophylaxis & Control

Captive Herds

● Minimize introduction of outside individuals; maintain a closed herd if possible

○ Replacement animals should be from certified CWD-negative herds

● Utilize strategic fencing to reduce or eliminate contact between captive and wild cervids

● In the United States, mandatory CWD reporting varies by state

Wild Herds

● Control is difficult in free-ranging cervids

● Discouraging congregation of cervids in focal areas can decrease the rate of transmission between animals

○ Behaviors such as feeding or baiting are banned in many areas for this reason

● Many states and provinces restrict transportation of tissues from hunter-killed cervids in endemic areas

● Some areas have culled wild populations of cervids, but efficacy appears to be variable

Medical prophylaxis

● There is no vaccine available for CWD

POTENTIAL IMPACTS OF DISEASE AGENT BEYOND CLINICAL ILLNESS

Risks to public health

● There is currently no evidence that CWD poses a threat to humans, but zoonotic potential is not well understood

● Hunters can have carcasses tested for CWD and should avoid eating meat from animals that are of ill-thrift; gloves should be worn when field-dressing carcasses

Risks to agriculture

● There is currently no evidence that CWD prions have infected any animals other than cervids in endemic areas.

○ Experimentally infected species include: voles, mice, cats, raccoons, squirrel-monkeys

● Decontaminating soil is currently proven to be impractical; soil microorganisms may degrade prions in buried carcasses, and plants are capable of uptaking prion protein and transporting it to aerial tissues (leaves, stems), both of which are currently under investigation for better characterisation.

REFERENCES AND OTHER INFORMATION

● Centers for Disease Control and Prevention (CDC) (2007). - Chronic wasting disease. Website accessed in 2019. http://www.cdc.gov/ncidod/dvrd/cwd/.

● Department for Environment, Food, and Rural Affairs: Animal & Plant Health Agency: Veterinary & Science Policy Advice Team - International Disease Monitoring. (2018) Update on Chronic Wasting Disease in Europe. Website accessed in 2019.


● Dorak, SJ., Green, M.L., Wander, M.M., Ruiz, M.O., Buhnerkempe, M.G., Tian, T., Novakofski, J.E., Mateus-Pinilla, N.E. (2017). - Clay content and pH: soil characteristic associations with the persistent presence of chronic wasting disease in northern Illinois. Sci Rep.

● EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards), Ricci, A., Allende, A., Bolton, D., Chemaly, M., Davies, R., Fernandez Escamez, P.S., Girones, R., Herman, L., Koutsoumanis, K., Lindqvist, R., Nørrung, B., Robertson, L., Sanaa, M., Skandamis, P., Snary, E., Speybroeck, N., Kuile, B.T., Threlfall, J., Wahlstrom, H., Benestad, S., Gavier-Widen, D., Miller, M.W., Ru, G., Telling, G.C., Tryland, M., Ortiz Pelaez, A. Simmons, M. (2017). - Scientific opinion on chronic wasting disease (CWD) in cervids. EFSA Journal;15(1): 4667, 62.

● Gilch, S. (2013). - Overview of chronic wasting disease. The Merck Veterinary Manual. Website accessed in 2019: http://www.merckvetmanual.com/mvm/nervous_system/chron ic_wasting_disease/overview_of_chronic_wasting_disease.html

● National Veterinary Institute (2019). Map of Chronic Wasting Disease. Website accessed in 2019. https://www.sva.se/en/animal-health/wildlife/map-of-chronic-wasting-disease-cwd

● Pritzkow, S., Morales, R., Moda, F., Khan, U., Telling, G.C., Hoover, E., Soto, C. (2015). - Grass plants bind, retain, uptake, and transport infectious prions. Cell Rep. 11, 1168–75.

● USGS National Wildlife Health Center (2019). Distribution of Chronic Wasting Disease in North America. Website accessed in 2019. https://www.usgs.gov/centers/nwhc/science/expanding-distribution-chronic-wasting-disease?qt-sc ience_center_objects=0#qt-science_center_objects.

● Zabel, M., Ortega, A. (2017). The ecology of prions. Microbiol Mol Biol Rev 81:e00001-17.

* * * The OIE will periodically update the OIE Technical Disease Cards. Please send relevant new references and proposed modifications to the OIE Science Department (scientific.dept@oie.int). Last updated 2019. Written by Marie Bucko and Samantha Gieger with assistance from the USGS National Wildlife Health Center.


***> Please send relevant new references and proposed modifications to the OIE Science Department (scientific.dept@oie.int). <***

New international expert panel to address the emergence and spread of zoonotic diseases Joint Press Release 

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The page link has been copied to your clipboard View more 20 May 2021

Geneva/Paris/Rome, 20 May 2021 – International organisations have come together to launch a new One Health High-Level Expert Panel to improve understanding of how diseases with the potential to trigger pandemics, emerge and spread.

The panel will advise four international organisations – the Food and Agriculture Organization of the United Nations (FAO); the World Organisation for Animal Health (OIE); the United Nations Environment Programme (UNEP); and the World Health Organization (WHO) – on the development of a long-term global plan of action to avert outbreaks of diseases like H5N1 avian influenza; MERS; Ebola; Zika, and, possibly, COVID-19. Three quarters of all emerging infectious diseases originate in animals.

It will operate under the One Health Approach, which recognizes the links between the health of people, animals, and the environment and highlights the need for specialists in multiple sectors to address any health threats and prevent disruption to agri-food systems.

Key first steps will include systematic analyses of scientific knowledge about the factors that lead to transmission of a disease from animal to human and vice versa; development of risk assessment and surveillance frameworks; identification of capacity gaps as well as agreement on good practices to prevent and prepare for zoonotic outbreaks.

The panel will consider the impact of human activity on the environment and wildlife habitats. Critical areas will include food production and distribution; urbanization and infrastructure development; international travel and trade; activities that lead to biodiversity loss and climate change; and those that put increased pressure on the natural resource base – all of which can lead to the emergence of zoonotic diseases.

The panel will guide development of a dynamic new research agenda and draw up evidence-based recommendations for global, regional, national and local action.

Dr Tedros Adhanom Ghebreyesus, WHO Director-General said: “Human health does not exist in a vacuum, and nor can our efforts to protect and promote it. The close links between human, animal and environmental health demand close collaboration, communication and coordination between the relevant sectors. The High-Level Expert Panel is a much-needed initiative to transform One Health from a concept to concrete policies that safeguard the health of the world’s people.”

Dr QU Dongyu, FAO Director General, told the panel: “This panel will contribute to advancing the One Health agenda, by helping to better understand the root causes of disease emergence and spread, and informing decision-makers to prevent long-term public health risks. I encourage it to be a shining example of silo-breaking, systems thinking and open dialogue. Expectations for collective action and the need for effective collaboration have never been higher.”

Dr Monique Éloit, Director General of the World Organisation for Animal Health noted: “The COVID-19 pandemic is a stark reminder that collaboration across sectors is absolutely critical for global health. The newly established One Health High-Level Expert Panel will contribute to bringing together diverse scientific expertise. United, we will better anticipate global health threats and work to control risks at the animal source. Our Organisation is proud to provide high-level expertise, along with our partners, to develop science-based ‘One Health’ strategies and programmes.“

Inger Andersen, Executive Director of UNEP observed: “To end the triple planetary crisis of climate change, biodiversity loss and pollution that threaten our peace and prosperity, we have to understand that human, animal and planetary health go hand in hand. We must do more to promote transformative actions that target the root causes of nature’s destruction. The One Health High-Level Expert Panel is an important step in recognizing the complex, multidisciplinary issues at the interface of human, animal, and environmental health.“

The Ministers for Foreign Affairs of France and Germany also joined the public launch of the One Health High-Level Expert Panel:

Mr Jean-Yves Le Drian, Minister for Europe and Foreign Affairs, France commented: “The COVID-19 pandemic, whose zoonotic origin is strongly suspected, underlines how closely human, animal and environmental health are linked. It demonstrates the importance of the ‘One Health’ approach. It is in this context that France, together with Germany, proposed the creation of such a Panel at the meeting of the Alliance for Multilateralism organized on the occasion of the Paris Peace Forum on 12 November 2020.”

Mr Heiko Maas, Minister for Foreign Affairs, Germany, said: “COVID-19 has painfully reminded us that the health of humans, animals and the environment around the world is closely connected: Nobody is safe until everybody is safe. This is what we have to bear in mind to prevent future pandemics. The establishment of the One Health High-Level Expert Panel thus marks an important step in the right direction. Germany and France will continue to support the panel’s work.”

Media contacts:




***> Please send relevant new references and proposed modifications to the OIE Science Department (scientific.dept@oie.int). <***

Greetings OIE and New international expert panel to address the emergence and spread of zoonotic diseases et al. 

I would kindly like to bring my concerns of Chronic Wasting Disease CWD TSE PrP and the very likely potential of Zoonosis Zoonotic transmission there from, if it has not already happened and is being masked as sporadic CJD.

I Have been hounding the OIE on this very topic for over 2 decades. have written and submitted much science on this very topic. 

I Have been very critical of the OIE et al handling of the BSE mad cow debacle since i lost my mother to hvCJD. 

MUCH science has come to pass since then. 

I kindly submit, once again, an updated overview of Chronic Wasting Disease CWD TSE PrP, and my fear of friendly fire i.e. IATROGENIC CJD THERE FROM, and someone needs to finally pull the trigger and make chronic wasting disease cwd tse prp a zoonotic zoonosis disease, and treat it as such.

I will list the latest science on this topic, and then the history of my submissions to the OIE...Thank YOU!

Update on chronic wasting disease (CWD) III 

Published: 11 November 2019 Adopted: 26 September 2019

Metadata EFSA Journal 2019;17(11):5863 DOI: https://doi.org/10.2903/j.efsa.2019.5863 

Keywords: chronic, wasting, cervids, strain, risk, zoonotic 

On request from: European Commission Question Number: EFSA-Q-2018-00763 Biological Hazards Contact: biohaz@efsa.europa.eu Panel members at the time of adoption Kostas Koutsoumanis, Ana Allende, Avelino Alvarez‐Ordoñez, Declan Bolton, Sara Bover‐Cid, Marianne Chemaly, Robert Davies, Alessandra De Cesare, Lieve Herman, Friederike Hilbert, Roland Lindqvist, Maarten Nauta, Luisa Peixe, Giuseppe Ru, Marion M. Simmons, Panagiotis Skandamis and Elisabetta Suffredini. 

Abstract 

The European Commission asked EFSA for a Scientific Opinion: to revise the state of knowledge about the differences between the chronic wasting disease (CWD) strains found in North America (NA) and Europe and within Europe; to review new scientific evidence on the zoonotic potential of CWD and to provide recommendations to address the potential risks and to identify risk factors for the spread of CWD in the European Union. Full characterisation of European isolates is being pursued, whereas most NA CWD isolates have not been characterised in this way. The differing surveillance programmes in these continents result in biases in the types of cases that can be detected. Preliminary data support the contention that the CWD strains identified in Europe and NA are different and suggest the presence of strain diversity in European cervids. Current data do not allow any conclusion on the implications of strain diversity on transmissibility, pathogenesis or prevalence. Available data do not allow any conclusion on the zoonotic potential of NA or European CWD isolates. The risk of CWD to humans through consumption of meat cannot be directly assessed. At individual level, consumers of meat, meat products and offal derived from CWD‐infected cervids will be exposed to the CWD agent(s). Measures to reduce human dietary exposure could be applied, but exclusion from the food chain of whole carcasses of infected animals would be required to eliminate exposure. Based on NA experiences, all the risk factors identified for the spread of CWD may be associated with animals accumulating infectivity in both the peripheral tissues and the central nervous system. A subset of risk factors is relevant for infected animals without involvement of peripheral tissues. All the risk factors should be taken into account due to the potential co‐localisation of animals presenting with different disease phenotypes.

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3.6.3. Concluding remarks

•The identification of risk factors associated with the spread of the disease can only be based on the epidemiological and biological understanding of NA CWD outbreaks, although the biological characterisation of the European isolates indicates that they differ from the known NA strains.

•The presence/absence of detectable PrPSc in the peripheral tissues as well as the CNS of affected animals can be used as an indicator of the probability of natural spread and animals assigned to different categories based on their pathogenesis. Both infected carriers and passive carriers are thought to be involved in the dissemination of the agent.

•Two distinct, hypothetical working scenarios have been built on these categories: a contagious form (Scenario 1) affecting animals which can spread infectivity through direct contacts with other animals and/or contamination of the environment and a non-contagious form (Scenario2) that is transmitted through environmental contamination from infected carcasses or via human activity, scavengers or via the feed chain.

•Thirteen main groups of risk factors have been identified based on their biological plausibility to spread CWD. Some of them are supported by epidemiological evidence from NA CWD.

•The only risk factors for the spread of CWD affecting exclusively Scenario 1 refer to animal to animal contact which will increase through the aggregation of live animals, promoted, or not, by human activities.

•All other risk factors refer to natural or man-mediated movement or translocation of wild or farmed/free ranging animals and to environmental contamination and the subsequent exposure of animals to contaminated soil or vegetation. This can occur at the point of contamination (close to a fallen animal) or following translocation of contaminated materials by humans or scavengers. These risks will also vary depending on the social structures of different species and by habitat and the geography of specific regions. In wild populations, the co-existence of different species makes it important to consider all the identified risk factors in both scenarios.

•Risk reduction through intervention would be possible for some man-mediated risk factors, namely activities leading to the translocation or aggregation of both wild and farmed live animals, as well as fallen stock management and appropriate disposal of carcasses and slaughter by-products. 

Figure 1:Conceptual map summarising the relationship among risk factors within risk pathways and potential targets for preventive measures Chronic Wasting Disease (CWD) III http://www.efsa.europa.eu/efsajournal46EFSA Journal 2019;17(11):5863

3.7. Uncertainty analysis The sources of uncertainty associated with the available data have been summarised in tabular format (Table10), describing the nature or cause of the uncertainty. The factors contributing to the list of uncertainties are mostly missing or incomplete data on disease prevalence, pathogenesis and isolate characterisation, affecting the entire Opinion and the answers to all of the ToRs.

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SEE FULL TEXT;



Scientific opinion on chronic wasting disease (II) 

EFSA Panel on Biological Hazards (BIOHAZ), Antonia Ricci, Ana Allende, Declan Bolton, Marianne Chemaly, Robert Davies, Pablo Salvador Fernández Escámez … See all authors 

First published: 17 January 2018 https://doi.org/10.2903/j.efsa.2018.5132

Citations: 9

Correspondence: biohaz@efsa.europa.eu

Requestor: European Commission

Question number: EFSA-Q-2016-00411

Panel members: Antonia Ricci, Ana Allende, Declan Bolton, Marianne Chemaly, Robert Davies, Pablo Salvador Fernández Escámez, Rosina Gironés, Lieve Herman, Kostas Koutsoumanis, Roland Lindqvist, Birgit Nørrung, Lucy Robertson, Moez Sanaa, Panagiotis Skandamis, Emma Snary, Niko Speybroeck, Benno Ter Kuile, Giuseppe Ru, Marion Simmons, John Threlfall and Helene Wahlström.

Adopted: 6 December 2017

Reproduction of the images listed below is prohibited and permission must be sought directly from the copyright holder: Figure 3: © USGS; Table B.1; Figure B.1: © OIE 

Abstract The European Commission asked EFSA for a scientific opinion on chronic wasting disease in two parts. Part one, on surveillance, animal health risk-based measures and public health risks, was published in January 2017. This opinion (part two) addresses the remaining Terms of Reference, namely, ‘are the conclusions and recommendations in the EFSA opinion of June 2004 on diagnostic methods for chronic wasting disease still valid? If not, an update should be provided’, and ‘update the conclusions of the 2010 EFSA opinion on the results of the European Union survey on chronic wasting disease in cervids, as regards its occurrence in the cervid population in the European Union’. Data on the performance of authorised rapid tests in North America are not comprehensive, and are more limited than those available for the tests approved for statutory transmissible spongiform encephalopathies surveillance applications in cattle and sheep. There are no data directly comparing available rapid test performances in cervids. The experience in Norway shows that the Bio-Rad TeSeE™ SAP test, immunohistochemistry and western blotting have detected reindeer, moose and red deer cases. It was shown that testing both brainstem and lymphoid tissue from each animal increases the surveillance sensitivity. Shortcomings in the previous EU survey limited the reliability of inferences that could be made about the potential disease occurrence in Europe. Subsequently, testing activity in Europe was low, until the detection of the disease in Norway, triggering substantial testing efforts in that country. Available data neither support nor refute the conclusion that chronic wasting disease does not occur widely in the EU and do not preclude the possibility that the disease was present in Europe before the survey was conducted. It appears plausible that chronic wasting disease could have become established in Norway more than a decade ago. Summary In 2016, the European Food Safety Authority (EFSA) was asked by the European Commission to deliver a scientific opinion on three Terms of Reference (ToRs): (1) surveillance, (2) public health and (3) (animal health risk-based measures) by 31 December 2016. On 18 January 2017, EFSA published a scientific opinion on chronic wasting disease (CWD) in cervids addressing these three ToRs (EFSA BIOHAZ Panel, 2017a). Within the same mandate, EFSA was asked to deliver by 31 December 2017 a scientific opinion on the following ToR: (4) are the conclusions and recommendations in the EFSA opinion of June 2004 on diagnostic methods for CWD still valid? If not, an update should be provided, and (5) update the conclusions of the 2010 EFSA opinion on the results of the European Union (EU) survey on CWD in cervids, as regards the occurrence of CWD in the cervid population in the EU.

No formal validation of test performance equivalent to the existing EU requirements for tests used for statutory surveillance in cattle and sheep has been undertaken for cervid material. A qualitative evaluation of the suitability of the Bio-Rad and the IDEXX rapid tests (RT) commercially available for the diagnosis of CWD was carried out by means of literature review (both an ad hoc literature review on the diagnosis of CWD and the references retrieved by the search conducted for the 2017 Opinion (EFSA BIOHAZ Panel, 2017a)), the data provided by the manufacturers, and the knowledge and expertise of the Working Group (WG) members.

A review of the available approaches to the diagnosis of CWD including the considerations underpinning the selection of animals, tissues and diagnostic tests has been conducted, as well as a review of the different diagnostic methods applied for the detection of CWD, both in the context of large-scale surveillance and for research purposes. Screening tests and confirmatory diagnostic methods have been reviewed along with methods for classification of isolates based on data from confirmatory testing, bioassay in potential natural host species and bioassay in rodent models. Requirements for the validation of new diagnostic tests, in particular, the steps and different pathways as defined by the International Organization of Animal Health (OIE) for validation of tests for wild populations, were considered. A review of all the validation exercises of RT for the detection of bovine spongiform encephalopathy (BSE) and for the diagnosis of transmissible spongiform encephalopathies (TSE) in small ruminants conducted in the EU has been included for comparison with the data current available for the rapid tests presently used for the detection of CWD in North America.

Sensitive amplification methods, such as protein misfolding cyclic amplification (PMCA) and real-time quaking-induced conversion (rtQuiC) that are currently under development for in vivo screening, or for the detection of environmental contamination, are also considered, but they are not yet at a point in their development where they could be applied in a statutory surveillance context.

To demonstrate how the potential for patchy CWD distribution could complicate surveillance in a heterogeneous geographic area the size of Europe, historical and contemporary maps of CWD distribution in the 28 contiguous US states east of the Mississippi River, spanning ~ 2.5 M km2, were used. This area approximates the EU (28 Member States (MS): > 4.4 M km2) with respect to several ecological, epidemiological and jurisdictional features relevant to CWD surveillance in the context of ToR 5.

Data on surveillance in Europe in 2015, 2016 and 2017 were extracted from annual reports submitted by the MS, and from the background information provided by the European Commission, and included in the mandate and the European Commission database. Surveillance data from Norway for the period 1 January 2017–27 November 2017 have been provided by the Norwegian Veterinary Institute, upon request. These data were used together with historical surveillance data from five Colorado mule deer herds collected over 15–21 years to provide a temporal reference of the estimated prevalence in new incursions of CWD and potential time lags in ‘epidemic’ emergence. Data from North America were used to generate a composite epidemic curve, and data from a published model were graphed for comparison with the observed data. The point estimate of comparable survey data from Norwegian reindeer (Nordfjella 1 region) was also calculated.

The experience in Norway so far shows that the Bio-Rad RT (TeSeE™ SAP) has detected cases of CWD in reindeer, moose and red deer. It has also been shown that antibodies raised against the core or C-terminal parts of the prion protein used for immunohistochemistry (IHC) and western blot (WB) were able to detect these cases.

Developments in immunoblotting techniques have resulted in the ability to discriminate experimental BSE from CWD in red deer. However, there is only limited information on the biological and molecular characteristics that define different strains in the North American cervid population against which the EU isolates could be compared and classified.

The conclusions (1, 2, 3, 4) and recommendations (3, 5, 6, 7) of the 2004 EFSA opinion on diagnostic methods for CWD remain valid. The available formal data on the performance of authorised RT for the detection of CWD in cervids in North America are not comprehensive and are much more limited than those available for the detection of BSE in cattle and scrapie in sheep. The lack of sufficient positive reference samples Europe, and a current lack of information on the strain(s) that might be circulating, make the estimation of the diagnostic sensitivity (DSe) of any test unfeasible for cervid samples, and preclude the development of alternative tests for use in European TSE surveillance in cervids. No direct comparison of test performance (i.e. parallel testing on the same panel of samples) can be made from the data available so there is no possibility to identify any differences between the two RT available on the market.

The generation of positive control material for European CWD strain/s, as recommended in both the 2004 and 2010 EFSA opinions (EFSA, 2004a,b; EFSA BIOHAZ Panel, 2010), for example, by experimental inoculation of a range of cervid species would be useful but is very difficult to perform, and would raise a number of practical and welfare issues. It would require the maintenance of experimentally infected individuals from non-domesticated species in high biosafety facilities for a long period of time. In the absence of the specific pathogenesis data that such studies would provide and in the light of the results from the Norwegian surveillance, both brainstem and lymphoid tissue should be tested from each animal to improve sensitivity possible from collected material. The added sensitivity conferred by the testing of lymphoid tissues in addition to the brainstem is further corroborated by the experience from the testing conducted in Norway; three out of the eight positive reindeer were positive on lymphoid tissue only and five were positive in both brainstem and lymphoid tissue. Similarly, the Norwegian experience indicates that there was no detectable lymphoid involvement in the moose and red deer cases.

The tissue distribution of infectivity in some CWD-infected cervids is now known to extend beyond the central nervous system and lymphoid tissues. While the removal of these specific tissues from the food chain, as recommended in the 2004 Opinion, would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure.

The conclusions (1, 2, 4, 5, 6) and all recommendations (1, 2, 3, 4) of the 2010 EFSA opinion remain valid. Shortcomings in the 2006–2010 EU CWD survey design and subsequent implementation limited the reliability of inferences that could be made about the potential occurrence of CWD in Europe. Despite the lack of substantial surveillance in the EU since that time, cases of CWD have now been detected in wild Norwegian reindeer, moose and red deer, confirming the long-held suspicion that at least some European cervid species are susceptible. Since the implementation of the 2006–2010 EU survey, testing activity has been low in Europe until the detection of CWD in Norway triggered a substantial testing effort in this country in 2016 and 2017. The surveillance programme proposed in the 2017 EFSA opinion supersedes the specifications of the EU-wide survey that was implemented following the recommendations of the 2004 EFSA opinion.

Current available data do not preclude the possibility that CWD was present in Norway and perhaps elsewhere in Europe before the 2006–2010 EU CWD survey was conducted, whether in epidemic form or not. Comparing the point estimates of CWD prevalence among ‘adult’ (> 1 year old) reindeer harvested in Nordfjella 1 in 2016 (0.97%, 95% C.I.: 0.2–2.8%) and for the period 1 January–27 November 2017 (0.68%, 95% CI: 0.22–1.6%) to the epidemic curve for mule deer in investigated herds in the US, it appears plausible that CWD could have become established in Norway more than a decade ago.

Adhering to contemporary surveillance recommendations (EFSA BIOHAZ Panel, 2017a), especially with respect to focusing sampling on high-risk individuals and developing a biologically meaningful spatial sampling framework relevant to the populations being monitored, with the aim of achieving set target sample sizes at the primary sampling unit level, should improve the reliability and value of data arising from renewed CWD surveillance efforts by some MS in coming years. The finding of the first case of CWD in red deer in Norway means that the surveillance scheme as in Reg. 999/2001, as amended, does not cover geographically all the MS in which red deer are present.

Further recommendations have been made, among them, the incorporation of sampling and testing for CWD into any wildlife health surveillance programmes, and the increase of awareness and dissemination of information about CWD in appropriate forums in the EU in order to improve the reporting of suspect cases. In addition, it is recommended to use only trained personnel for sample collection, and to avoid any test or detection method that uses antibodies for which the epitope is known to be polymorphic in cervids, unless successful binding in positive animals with those polymorphisms can be demonstrated. Residual samples, including relevant metadata, should be retained from all positive animals, and from as many tissues as possible, for isolate classification, future test evaluation, epidemiology or research purposes. Complementary studies should be conducted to identify any relevant differences influencing the epidemiology of the disease and to investigate the presence and frequency of potentially resistant alleles in the European cervid population. Finally, it is recommended to keep the performance of all currently applied tests, including those still being developed, under review and revise and update statutory testing protocols as new data become available.


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

EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors 

First published: 17 January 2018 https://doi.org/10.2903/j.efsa.2018.5132

also, see; 

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. 

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The tissue distribution of infectivity in CWD‐infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure. 



EFSA Chronic wasting disease (CWD) in cervids Published: 18 January 2017 Adopted: 2 December 2016

EFSA Journal 2017;15(1):4667 DOI: https://doi.org/10.2903/j.efsa.2017.4667

Keywords: chronic, wasting, cervids, surveillance, risk, introduction, spread 

On request from: European Commission Question Number: EFSA-Q-2016-00387 

Biological Hazards Contact: biohaz@efsa.europa.eu 

Panel members at the time of adoption Antonia Ricci, Ana Allende, Declan Bolton, Marianne Chemaly, Robert Davies, Pablo Salvador Fernández Escámez, Rosina Gironés, Lieve Herman, Kostas Koutsoumanis, Roland Lindqvist, Birgit Nørrung, Lucy Robertson, Moez Sanaa, Panagiotis Skandamis, Emma Snary, Niko Speybroeck, Benno Ter Kuile, Giuseppe Ru, Marion Simmons, John Threlfall and Helene Wahlström. 

Abstract 

In April and May of 2016, Norway confirmed two cases of chronic wasting disease (CWD) in a wild reindeer and a wild moose, respectively. In the light of this emerging issue, the European Commission requested EFSA to recommend surveillance activities and, if necessary, additional animal health risk-based measures to prevent the introduction of the disease and the spread into/within the EU, specifically Estonia, Finland, Iceland, Latvia, Lithuania, Norway, Poland and Sweden, and considering seven wild, semidomesticated and farmed cervid species (Eurasian tundra reindeer, Finnish (Eurasian) forest reindeer, moose, roe deer, white-tailed deer, red deer and fallow deer). It was also asked to assess any new evidence on possible public health risks related to CWD. A 3-year surveillance system is proposed, differing for farmed and wild or semidomesticated cervids, with a two-stage sampling programme at the farm/geographically based population unit level (random sampling) and individual level (convenience sampling targeting high-risk animals). The current derogations of Commission Implementing Decision (EU) 2016/1918 present a risk of introduction of CWD into the EU. Measures to prevent the spread of CWD within the EU are dependent upon the assumption that the disease is already present; this is currently unknown. The measures listed are intended to contain (limit the geographic extent of a focus) and/or to control (actively stabilise/reduce infection rates in an affected herd or population) the disease where it occurs. With regard to the zoonotic potential, the human species barrier for CWD prions does not appear to be absolute. These prions are present in the skeletal muscle and other edible tissues, so humans may consume infected material in enzootic areas. Epidemiological investigations carried out to date make no association between the occurrence of sporadic Creutzfeldt–Jakob disease in humans and exposure to CWD prions.

© European Food Safety Authority, 2017

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DEFRA 

What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016

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In the USA, under the Food and Drug Administration’s BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. 

With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. 

However, this recommendation is guidance and not a requirement by law. 

Animals considered at high risk for CWD include: 

1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and 

2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal. 

Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants. 

The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB cannot be determined, however, as it is not specified in TRACES. 

It may constitute a small percentage of the very low tonnage of non-fish origin processed animal proteins that were imported from US into GB. 

Overall, therefore, it is considered there is a greater than negligible risk that (non ruminant) animal feed and pet food containing deer and/or elk protein is imported into GB. 

There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products. 

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From: Terry S. Singeltary Sr.

Sent: Thursday, April 07, 2016 1:02 PM

To: psi@nationalarchives.gsi.gov.uk

Cc: helen.roberts@apha.gsi.gov.uk ; jan.opgenoorth@efsa.europa.eu ; Press@efsa.europa.eu ; SCER.PublicConsult.55@efsa.europa.eu ; scer@efsa.europa.eu ; publicmeetings@efsa.europa.eu ; Gemma.Smith@wales.gsi.gov.uk

BCC: ...

Subject: What is the risk of chronic wasting disease being introduced into Great Britain? 6 April 2016

Greetings DEFRA MAFF, EFSA, Welsh Government et al,

I kindly wish to again the urgent need to address CWD in the USA and risk factors to the world there from.

I see ‘What is the risk of chronic wasting disease being introduced into Great Britain?’ was published recently 6 April 2016 and would kindly like to send this additional information.

What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016


Since my last correspondence with you, CWD has exploded in new states, with Arkansas topping them all. Texas is reluctant to report in a timely manner, just how bad CWD is in the captive industry, but of course, Texas did the same thing with mad cow disease, covering up the last case for 7 months before it took an act of Congress to finally have that sample retested, which did confirm the mad cow, all this documented on the internet. with that said, I do not have any hope that CWD surveillance and timely reporting to the public will be any different. In two months Arkansas went from a few cases to a total of 56 cases in just two months, from a very small sample survey. also, I have pleaded with the FDA et al to please close the damn mad cow feed loop hole for cervids. FDA has finally readdressed the old Docket, updated it in March 2016, HOWEVER IT’S NON-BINDING, STILL NOTHING BUT INK ON PAPER. things don’t look good here at all. cwd is out of control, and corporate America is and will continue to let cwd spread further. as you all well know, our politicians are too worried about who’s ‘richard’ is bigger than the others, while Rome burns. I am embarrassed about our country and it’s politicians, so I shall apologize to the world for the sheer stupidity of it all. ...


What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016


Saturday, July 16, 2016

Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The British Deer Society 07/04/2016



Tuesday, March 15, 2016

*** Docket No. FDA-2016-N-0321 Risk Assessment of Foodborne Illness Associated with Pathogens from Produce Grown in Fields Amended with Untreated Biological Soil Amendments of Animal Origin; Request for Comments, Scientific Data, and Information Singeltary Submission ***


Friday, November 22, 2013 Wasting disease is threat to the entire UK deer population CWD TSE PRION DISEASE Singeltary submission to Scottish Parliament

From: Terry S. Singeltary Sr. [mailto:flounder9@verizon.net]

Sent: 23 November 2013 03:39

To: Official Report

Cc: Public Information

Subject: Wasting disease is threat to the entire UK deer population

The Scottish Parliament

Description: Description: Description: Description: Description: Description: Description: Description: Description: Description: Corp ID for Signatures

Dear Mr Singeltary,

Thank you for your email, which was received by Public Information at the Scottish Parliament. We provide impartial information about the Scottish Parliament, its membership, business and procedures.

The Scottish Parliament’s Rural Affairs, Climate Change and Environment Committee has been looking into deer management, as you can see from the following press release, ***and your email has been forwarded to the committee for information:

You may be interested in following the committee’s work. Papers for committee meetings and transcripts of past meetings (called Official Reports) appear on the following webpage:



I hope this information is of use to you. Please contact us again if you have any questions about the Scottish Parliament.

Yours sincerely,

George Clark Public Information and Publications The Scottish Parliament Our contact details Please note that any links to external websites are suggestions only. The Scottish Parliament is not responsible for the content of external websites...snip...end...tss

From: Terry S. Singeltary Sr. [mailto:flounder9@verizon.net] Sent: 23 November 2013 03:39 To: Official Report Cc: Public Information Subject: Fw: Wasting disease is threat to the entire UK deer population

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Guidance

Chronic wasting disease: how to spot and report the disease

How to spot chronic wasting disease (CWD), what to do if you suspect it and measures to prevent its spread.

From: Animal and Plant Health Agency and Department for Environment, Food & Rural Affairs

Published 2 June 2015

Last updated 18 October 2018 — See all updates


Sunday, July 21, 2013

Welsh Government and Food Standards Agency Wales Joint Public Consultation on the Proposed Transmissible Spongiform Encephalopathies (Wales) Regulations 2013

*** Singeltary Submission WG18417


Friday, December 14, 2012

DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012

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In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law.

Animals considered at high risk for CWD include:

1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and

2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.

Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.

The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.

Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.

There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.

snip...

36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011).

The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE).

Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison.

snip...

The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).

snip...

In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.

snip...

In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible. For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.

snip...

Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.

snip...


OIE Global Conference on Wildlife Animal Health and Biodiversity - Preparing for the Future (TSE AND PRIONS) Paris (France), 23-25 February 2011



CERVIDS & CHRONIC WASTING DISEASE MONITORING - MONITORING DATA

Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.

Samia Hannaouia, Ginny Chenga, Wiebke Wemheuerb, Walter J. Schulz-Schaefferb, Sabine Gilcha, and Hermann M. Schätzla

aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine & Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bInstitute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany

Aims: Chronic wasting disease (CWD) is a prion disease of cervids. Its rapid geographic expansion, shedding of infectivity and persistence in the environment for many years are of concern for humans. Here, we provide the first evidence by transmission experiments to different transgenic mouse models and bank voles that Cynomolgus macaques inoculated via different routes with CWD-positive cervid tissues harbor infectious prions that elicit clinical disease in rodents.

Material and Methods: We used tissue materials from macaques inoculated with CWD to inoculate transgenic mice overexpressing cervid PrPC followed by transmission into bank voles. We used RT-QuIC, immunoblot and PET blot analysis to assess brains, spinal cords, and tissues of the gastrointestinal tract (GIT) for the presence of prions.

Results: Our results show that of the macaque materials that induced clinical disease in transgenic mice,73% were from the CNS (46% spinal cord and 27% brain), and 27% were from the spleen, although attack rates were low around 20%. Clinical mice did not display PK-resistant PrPSc (PrPres) in immunoblot, but showed low-levels of prion seeding activity. Transmission into bank voles from clinical transgenic mice led to a 100% attack rate with typical PrPres signature in immunoblot, which was different from that of voles inoculated directly with CWD or scrapie prions. High-level prion seeding activity in brain and spinal cord and PrPres deposition in the brain were present. Remarkably, we also found prion seeding activity in GIT tissues of inoculated voles. Second passage in bank voles led to a 100% attack rate in voles inoculated with brain, spinal cord and small intestine material from first round animals, with PrPres in immunoblot, prion seeding activity, and PrPres deposition in the brain. Shortened survival times indicate adaptation in the new host. This also shows that prions detected in GIT tissues are infectious and transmissible. Transmission of brain material from sick voles back to cervidized mice revealed transmission in these mice with a 100% attack rate, and interestingly, with different biochemical signature and distribution in the brain.

Conclusions: Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including oral one. The disease manifested as atypical in macaques and transgenic mice, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.

Funded by: The National Institutes of Health, USA, and the Alberta Prion Research Institute/Alberta Innovates Canada.

Grant number: 1R01NS121016-01; 201,600,023

Acknowledgement: We thank Umberto Agrimi, Istituto Superiore di Sanità, Rome, Italy, and Michael Beekes, Robert-Koch Institute Berlin, Germany, for providing the bank vole model. We thank the University of Calgary animal facility staff and Dr. Stephanie Anderson for animal care.

Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD

Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha

aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine; Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bUniversité Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France; cDepartment of Biological Sciences, Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada

Aims: Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we aimed to determine the zoonotic potential of CWD using a mouse model for human prion diseases.

Material and Methods: Transgenic mice overexpressing human PrPC homozygous for methionine at codon 129 (tg650) were inoculated intracerebrally with brain homogenates of white-tailed deer infected with Wisc-1/CWD1 or 116AG CWD strains. Mice were monitored for clinical signs and were euthanized at terminal disease. Brains were tested by RT-QuIC, western blot upon PK digestion, and immunohistochemistry; fecal homogenates were analyzed by RT-QuIC. Brain/spinal cord and fecal homogenates of CWD-inoculated tg650 mice were inoculated into tg650 mice or bank voles. Brain homogenates of bank voles inoculated with fecal homogenates of CWD-infected tg650 mice were used for second passage in bank voles.

Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPC with deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650 brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.

Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.

Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.

Funded by: We are grateful for financial support from the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, Genome Canada, and the Alberta Prion Research Institute. SG is supported by the Canada Research Chairs program.

Acknowledgement: We thank Dr. Trent Bollinger, WCVM, University of Saskatchewan, Saskatoon, Canada, for providing brain tissue from the WTD-116AG isolate, Dr. Stéphane Haïk, ICM, Paris, France, for providing brain tissue from vCJD and sCJD cases, and Dr. Umberto Agrimi, Istituto Superiore di Sanità, Italy, for the bank vole model. We thank animal facility staff for animal care, Dr. Stephanie Anderson for veterinary oversight, and Yo-Ching Cheng for preparing recombinant PrP substrates. Thank you to Dr. Stephanie Booth and Jennifer Myskiw, Public Health Agency of Canada, Canada.


PRION CONFERENCE 2022 ABSTRACTS CWD TSE PrP ZOONOSIS 

Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.

Samia Hannaouia, Ginny Chenga, Wiebke Wemheuerb, Walter J. Schulz-Schaefferb, Sabine Gilcha, and Hermann M. Schätzla aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine & Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bInstitute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany

Aims: Chronic wasting disease (CWD) is a prion disease of cervids. Its rapid geographic expansion, shedding of infectivity and persistence in the environment for many years are of concern for humans. Here, we provide the first evidence by transmission experiments to different transgenic mouse models and bank voles that Cynomolgus macaques inoculated via different routes with CWD-positive cervid tissues harbor infectious prions that elicit clinical disease in rodents.

Material and Methods: We used tissue materials from macaques inoculated with CWD to inoculate transgenic mice overexpressing cervid PrPC followed by transmission into bank voles. We used RT-QuIC, immunoblot and PET blot analysis to assess brains, spinal cords, and tissues of the gastrointestinal tract (GIT) for the presence of prions.

Results: Our results show that of the macaque materials that induced clinical disease in transgenic mice,73% were from the CNS (46% spinal cord and 27% brain), and 27% were from the spleen, although attack rates were low around 20%. Clinical mice did not display PK-resistant PrPSc(PrPres) in immunoblot, but showed low-levels of prion seeding activity. Transmission into bank voles from clinical transgenic mice led to a 100% attack rate with typical PrPres signature in immunoblot, which was different from that of voles inoculated directly with CWD or scrapie prions. High-level prion seeding activity in brain and spinal cord and PrPres deposition in the brain were present. Remarkably, we also found prion seeding activity in GIT tissues of inoculated voles. Second passage in bank voles led to a 100% attack rate in voles inoculated with brain, spinal cord and small intestine material from first round animals, with PrPres in immunoblot, prion seeding activity, and PrPres deposition in the brain. Shortened survival times indicate adaptation in the new host. This also shows that prions detected in GIT tissues are infectious and transmissible. Transmission of brain material from sick voles back to cervidized mice revealed transmission in these mice with a 100% attack rate, and interestingly, with different biochemical signature and distribution in the brain.

Conclusions: Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including oral one. The disease manifested as atypical in macaques and transgenic mice, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.

Funded by: The National Institutes of Health, USA, and the Alberta Prion Research Institute/Alberta Innovates Canada. Grant number: 1R01NS121016-01; 201,600,023

Acknowledgement: We thank Umberto Agrimi, Istituto Superiore di Sanità, Rome, Italy, and Michael Beekes, Robert-Koch Institute Berlin, Germany, for providing the bank vole model. We thank the University of Calgary animal facility staff and Dr. Stephanie Anderson for animal care.

Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD

Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha

aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine; Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bUniversité Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France; cDepartment of Biological Sciences, Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada

Aims: Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we aimed to determine the zoonotic potential of CWD using a mouse model for human prion diseases.

Material and Methods: Transgenic mice overexpressing human PrPC homozygous for methionine at codon 129 (tg650) were inoculated intracerebrally with brain homogenates of white-tailed deer infected with Wisc-1/CWD1 or 116AG CWD strains. Mice were monitored for clinical signs and were euthanized at terminal disease. Brains were tested by RT-QuIC, western blot upon PK digestion, and immunohistochemistry; fecal homogenates were analyzed by RT-QuIC. Brain/spinal cord and fecal homogenates of CWD-inoculated tg650 mice were inoculated into tg650 mice or bank voles. Brain homogenates of bank voles inoculated with fecal homogenates of CWD-infected tg650 mice were used for second passage in bank voles.

Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPC with deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650 brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.

Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.

Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.

Funded by: We are grateful for financial support from the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, Genome Canada, and the Alberta Prion Research Institute. SG is supported by the Canada Research Chairs program.

Acknowledgement: We thank Dr. Trent Bollinger, WCVM, University of Saskatchewan, Saskatoon, Canada, for providing brain tissue from the WTD-116AG isolate, Dr. Stéphane Haïk, ICM, Paris, France, for providing brain tissue from vCJD and sCJD cases, and Dr. Umberto Agrimi, Istituto Superiore di Sanità, Italy, for the bank vole model. We thank animal facility staff for animal care, Dr. Stephanie Anderson for veterinary oversight, and Yo-Ching Cheng for preparing recombinant PrP substrates. Thank you to Dr. Stephanie Booth and Jennifer Myskiw, Public Health Agency of Canada, Canada.

The chronic wasting disease agent from white-tailed deer is infectious to humanized mice after passage through raccoons

Eric Cassmanna, Xu Qib, Qingzhong Kongb, and Justin Greenleea

aNational Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA, USA bDepartments of Pathology, Neurology, National Center for Regenerative Medicine, and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA

Aims: Evaluate the zoonotic potential of the raccoon passaged chronic wasting disease (CWD) agent in humanized transgenic mice in comparison with the North American CWD agent from the original white-tailed deer host.

Material and Methods: Pooled brain material (GG96) from a CWD positive herd was used to oronasally inoculate two white-tailed deer with wild-type prion protein genotype and intracranially inoculate a raccoon. Brain homogenates (10% w/v) from the raccoon and the two white-tailed deer were used to intracranially inoculate separate groups of transgenic mice that express human prion protein with methionine (M) at codon 129 (Tg40h). Brains and spleens were collected from mice at experimental endpoints of clinical disease or approximately 700 days post-inoculation. Tissues were divided and homogenized or fixed in 10% buffered neutral formalin. Immunohistochemistry, enzyme immunoassay, and western blot were used to detect misfolded prion protein (PrPSc) in tissue.

Results: Humanized transgenic mice inoculated with the raccoon passaged CWD agent from white-tailed deer exhibited a 100% (12/12) attack rate with an average incubation period of 605 days. PrPSc was detected in brain tissue by enzyme immunoassay with an average optical density of 3.6/4.0 for positive brains. PrPSc also was detected in brain tissue by western blot and immunohistochemistry. No PrPSc was detected in the spleens of mice inoculated with the raccoon passaged CWD agent. Humanized mice inoculated with the CWD agent from white-tailed deer did not have detectable PrPSc using conventional immunoassay techniques.

Conclusions: The host range of the CWD agent from white-tailed deer was expanded in our experimental model after one passage through raccoons.

Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Acknowledgement: We thank Quazetta Brown, Lexi Frese, Rylie Frese, Kevin Hassall, Leisa Mandell, and Trudy Tatum for providing excellent technical support to this project.

Stable and highly zoonotic cervid prion strain is possible

Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, and Qingzhong Kong Department of Pathology, Case Western Reserve University, Cleveland, USA

Aims: Whether CWD prions can infect humans remains unclear despite the very substantial scale and long history of human exposure of CWD in some areas. Multiple in vitro conversion experiments and in vivo animal studies suggest that the CWD-to-human transmission barrier is not unbreakable. A major public health concern on CWD zoonosis is the emergence of highly zoonotic CWD strains. We aim to address the question of whether highly zoonotic CWD strains are possible.

Material and Methods: We inoculated a few sCJD brain samples into cervidized transgenic mice, which were intended as negative controls for bioassays of brain tissues from sCJD cases who had hunted or consumed vension from CWD-endemic states. Some of these mice became infected and their brain tissues were further examined by serial passages in humanized or cervidized mice.

Results: Passage of sCJDMM1 in transgenic mice expressing elk PrP (Tg12) resulted in a ‘cervidized’ CJD strain that we termed CJDElkPrP. We observed 100% transmission of CJDElkPrP in transgenic mice expressing human PrP (Tg40h). We passaged CJDElkPrPtwo more times in the Tg12 mice. We found that such second and third passage CJDElkPrP prions also led to 100% infection in the Tg40h mice. In contrast, we and others found zero or poor transmission of natural elk CWD isolates in humanized mice, despite that natural elk CWD isolates and CJDElkPrP share the same elk PrP sequence.

Conclusions: Our data demonstrate that highly zoonotic cervid prion strains are not only possible but also can be stably maintained in cervids and that CWD zoonosis is prion strain-dependent.

Funded by: NIH

Grant number: R01NS052319, R01NS088604, R01NS109532

Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O’Rourke for providing the sCJD samples and the CWD samples, respectively.

Adaptation of chronic wasting disease (CWD) prion strains in hosts with different PRNP genotypes

Camilo Duque Velasqueza,c, Elizabeth Triscotta,c, Chiye Kima,c, Diana Morenoa,c, Judd Aikenb,c, and Debbie McKenziea,c

aDepartment of Biological Science, University of Alberta, Edmonton, AB T6G 2G8, Canada; bDepartment of Agriculture, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G 2G8, Canada; cCentre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada

Aims: The contagious nature of CWD epizootics and the PrPC amino acid variation of cervids (and susceptible sympatric species) guarantee the expansion of prion conformational diversity and selective landscapes where new strains can arise. CWD strains can have novel transmission properties including altered host range that may increase zoonotic risk as circulating strains diversify and evolve. We are characterizing the host adaptability of characterized CWD strains as well as CWD isolates from different cervid species in various enzootic regions.

Material and Methods: Characterized CWD strains as well as a number of isolates from hunter-harvested deer were bioassayed in our rodent panel (transgenic mice expressing cervid alleles G96, S96 and H95-PrPC, elk PrPC, bovine PrPC, and both hamsters and non-transgenic laboratory mice). Strain characteristics were compared using computer based scoring of brain pathology (e.g. PrPCWD brain distribution), western blot and protein misfolding cyclic amplification (PMCA).

Results: Transmission of various isolates resulted in the selection of strain mixtures in hosts expressing similar PrPC, particularly for polymorphic white-tailed deer and for Norwegian reindeer. As of the second passage, transmission of P153 moose prions from Norway has not resulted in emergence of strains with properties similar to any North American CWD strains in our taxonomic collection (Wisc-1, CWD2, H95+and 116AG).

Conclusions: Our data indicates polymorphic white-tailed deer can favor infection with more than one strain. Similar to transmission studies of Colorado CWD isolates from cervids expressing a single PrPC primary structure, the isolate from Norway reindeer (V214) represents a strain mixture, suggesting intrinsic strain diversity in the Nordfjella epizootic. The diversity of CWD strains with distinct transmission characteristics represents a threat to wildlife, sympatric domestic animals and public health.

Funded by: Genome Canada and Genome Alberta (Alberta Prion Research Institute and Alberta Agriculture & Forestry); NSERC Grant number: #LSARP 10205; NSERC RGPIN-2017-05539

Acknowledgement: We would like to thank Margo Pybus (Alberta Environment and Parks) Trent Bollinger (University of Saskatchewan) for providing us with tissue samples from hunter-harvested deer and Sylvie Benestad for providing moose and reindeer samples.

Application of PMCA to understand CWD prion strains, species barrier and zoonotic potential

Sandra Pritzkowa, Damian Gorskia, Frank Ramireza, Fei Wanga, Glenn C. Tellingb, Justin J. Greenleec, Sylvie L. Benestadd, and Claudio Sotoa aDepartment of Neurology, University of Texas Medical School at Houston, Houston, Texas, USA; bDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA; cVirus and Prion Research Unit, United States Department of Agriculture, Ames, Iowa, USA; dNorwegian Veterinary Institute, OIE Reference Laboratory for CWD, Ås, Norway

Aims: Chronic wasting disease (CWD) is a prion disease affecting various species of cervids that continues to spread uncontrollably across North America and has recently been detected in Scandinavia (Norway, Sweden and Finland). The mechanisms responsible for the natural transmission of CWD are largely unknown. Furthermore, the risk of CWD transmission to other species, including humans, is also unknown and remains a dangerous enigma. In this study, we investigated the potential of CWD prions to infect several other animal species (sheep, cattle, pig, hamster, and mouse) including humans, by examining their capacity to convert the normal prion protein of distinct species in a PMCA reaction. Moreover, we also investigated whether the in vivo passage of CWD through intermediate species alters their capacity for zoonotic transmission, which may represent a major hazard to human health.

Material and Methods: For these studies, we used brain material from CWD-infected white-tailed deer (Odocoileus virginianus), elk (Cervus canadensis), and mule deer (Odocoileus hemionus) as species native to North America. We also used CWD-infected Moose (Alces alces), reindeer (Rangifer tarandus) and red deer (Cervus elaphus) as Norwegian cervids. We also used brains from cattle, sheep and pigs experimentally infected by CWD. To study interspecies-transmission and zoonotic potential, samples were tested via PMCA for the conversion of PrPC into PrPSc using different combinations of inoculum and host species. Based on these analyses we estimated the spillover and zoonotic potential for different CWD isolates. We define and quantify spillover and zoonotic potential indices as the efficiency by which CWD prions sustain prion generation in vitro at the expense of normal prion proteins from various mammals and human, respectively.

Results: Our results show that prions from some cervid species, especially those found in Northern Europe, have a higher potential to transmit disease characteristics to other animals. Conversely, CWD-infected cervids originated in North America appear to have a greater potential to generate human PrPSc. We also found that in vivo transmission of CWD to cattle, but not to sheep or pigs substantially increases the ability of these prions to convert human PrPC by PMCA.

Conclusions: Our findings support the existence of different CWD prion strains with distinct spillover and zoonotic potentials. We also conclude that transmission of CWD to other animal species may increase the risk for CWD transmission to humans. Our studies may provide a tool to predict the array of animal species that a given CWD prion could affect and may contribute to understanding the risk of CWD for human health.

Funded by: National Institute of Health Grant number: P01 AI077774

Generation of human chronic wasting disease in transgenic mice

Zerui Wanga, Kefeng Qinb, Manuel V. Camachoa, Ignazio Cali a,c, Jue Yuana, Pingping Shena, Tricia Gillilanda, Syed Zahid Ali Shaha, Maria Gerasimenkoa, Michelle Tanga, Sarada Rajamanickama, Anika Yadatia, Lawrence B. Schonbergerd, Justin Greenleee, Qingzhong Konga,c, James A. Mastriannib, and Wen-Quan Zoua,c

aDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; bDepartment of Neurology and Center for Comprehensive Care and Research on Memory Disorders, the University of Chicago Pritzker School of Medicine, Chicago, USA; cNational Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; dDivision of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USA; eVirus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Avenue, Ames, IA, USA

Aims: Chronic wasting disease (CWD) results from the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC) in the brains of deer and elk. It has been spreading rapidly throughout many regions of North America, exported inadvertently to South Korea, and more recently identified in Europe. Mad cow disease has caused variant Creutzfeldt-Jakob disease (vCJD) in humans and is currently the only known zoonotic prion disease. Whether CWD is transmissible to humans remains uncertain. The aims of our study were not only to confirm whether CWD prion isolates can convert human brain PrPC into PrPSc in vitro by serial protein misfolding cyclic amplification (sPMCA) but also to determine whether the sPMCA-induced CWD-derived human PrPSc is infectious.

Material and Methods: Eight CWD prion isolates from 7 elks and 1 deer were used as the seeds while normal human brain homogenates containing either PrP-129 MM (n = 2) or PrP-129 VV (n = 1) were used as the substrates for sPMCA assay. A normal elk brain tissue sample was used as a negative control seed. Two lines of humanized transgenic (Tg) mice expressing either human PrP-129VV or −129 MM polymorphism were included for transmission studies to determine the infectivity of PMCA-amplified PrPSc. Wester blotting and immunohistochemistry and hematoxylin & eosin staining were used for determining PrPSc and neuropathological changes of inoculated animals.

Results: We report here the generation of the first CWD-derived infectious human PrPSc using elk CWD PrPSc to initiate conversion of human PrPC from normal human brain homogenates with PMCA in vitro. Western blotting with a human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human brain PrPC substrate. Two lines of humanized transgenic mice expressing human PrPC with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain.

Conclusions: Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc has the potential to overcome the species barrier and directly convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.

Funded by: CJD Foundation and NIH

Mortality surveillance of persons potentially exposed to chronic wasting disease

R.A. Maddoxa, R.F. Klosb, L.R. Willb, S.N. Gibbons-Burgenerb, A. Mvilongoa, J.Y. Abramsa, B.S. Applebyc, L.B. Schonbergera, and E.D. Belaya aNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, USA; bWisconsin Department of Health Services (WDHS), Division of Public Health, Madison, USA; cNational Prion Disease Pathology Surveillance Center (NPDPSC), Case Western Reserve University, Cleveland, USA

Aims: It is unknown whether chronic wasting disease (CWD), a prion disease of cervids, can infect people, but consumption of meat from infected animals would be the most likely route of transmission. Wisconsin Department of Health Services, Division of Public Health (WDHS) personnel maintain a database consisting of information collected from hunters who reported eating, or an intention to eat, venison from CWD-positive cervids. These data, collected since 2003, allow for the evaluation of causes of mortality in individuals potentially exposed to CWD.

Material and Methods: The WDHS database contains the name, date of birth, when available, year of CWD-positive deer harvest, and city and state of residence for each potentially exposed individual. The database also includes information on how the deer was processed (self-processed or by a commercial operator) and when applicable, names of others with whom the venison was shared. Duplicate entries (i.e., those who consumed venison from CWD-positive deer in multiple hunt years) are determined by first name, last name, and date of birth. All names in the database are cross-checked with reported cases of human prion disease in Wisconsin and cases in the National Prion Disease Pathology Surveillance Center (NPDPSC) diagnostic testing database. Persons with date of birth available are also cross-checked with prion disease decedents identified through restricted-use national multiple cause-of-death data via a data use agreement with the National Center for Health Statistics (NCHS).

Results: The database currently consists of 1561 records for hunt years 2003–2017 and 87 additional records for 2018–2019. Of these, 657 records have accompanying date of birth; 15 entries were removed as duplicates leaving 642 unique individuals. Of these individuals, 278 of 426 (66%) who ate venison from a CWD-positive deer and provided processing information reported self-processing. No matches were found among any persons in the database cross-checked with WDHS human prion disease surveillance data, NPDPSC data (February 2022 update), and NCHS data through 2020.

Conclusions: Because of the linkage of person and CWD-positive animal in the WDHS database, reviewing the cause of mortality in potentially exposed persons is possible. The number of individuals cross-checked so far is likely only a small percentage of those potentially exposed to CWD in Wisconsin, and many more years of vital status tracking are needed given an expected long incubation period should transmission to humans occur. Nevertheless, the findings of this ongoing review are thus far reassuring.

Prion disease incidence, United States, 2003–2020

R.A. Maddoxa, M.K. Persona, K. Kotobellib, A. Mvilongoa, B.S. Applebyb, L.B. Schonbergera, T.A. Hammetta, J.Y. Abramsa, and E.D. Belaya aNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, USA; bNational Prion Disease Pathology Surveillance Center (NPDPSC), Case Western Reserve University, Cleveland, USA

Aims: Mortality data, in conjunction with neuropathological and genetic testing results, are used to estimate prion disease incidence in the United States.

Material and Methods: Prion disease decedents for 2003–2020 were identified from restricted-use U.S. national multiple cause-of-death data, via a data use agreement with the National Center for Health Statistics, and from the National Prion Disease Pathology Surveillance Center (NPDPSC) database. NPDPSC decedents with neuropathological or genetic test results positive for prion disease for whom no likely match was found in the NCHS multiple cause-of-death data were added as cases for incidence calculations, while those with negative neuropathology results but with cause-of-death data indicating prion disease were removed. Unmatched cases in the NPDPSC database lacking neuropathological testing but with a positive real-time quaking-induced conversion (RT-QuIC) test result were additionally assessed. Age-specific and age-adjusted average annual incidence rates were calculated from the combined data; the year 2000 as the standard population and the direct method were used for age-adjustment.

Results: A total of 7,921 decedents were identified as having prion disease during 2003–2020 for an age-adjusted average annual incidence of 1.2 per million population. The age-adjusted incidence between males and females (1.3 and 1.1 per million, respectively) differed significantly (p < 0.0001). The age-specific average annual incidence among those <55 and ≥55 years of age was 0.2 and 4.8 per million, respectively; incidence among those ≥65 was 6.1 per million. Eighteen cases were <30 years of age for an age-specific incidence of 8.0 per billion; only 6 of these very young cases were sporadic (3 sporadic CJD, 3 sporadic fatal insomnia), with the rest being familial (9), variant (2), or iatrogenic (1). The age-adjusted annual incidence for the most recent year of data, 2020, was 1.3 per million. However, assessment of RT-QuIC positive cases lacking neuropathology in the NPDPSC database suggested that approximately 20% more cases may have occurred in that year; the addition of a subset of these cases that had date of death information available (n = 44) increased the 2020 rate to 1.4 per million.

Conclusions: Mortality data supplemented with the results of neuropathological, CSF RT-QuIC, and genetic testing can be used to estimate prion disease incidence. However, the identification in the NPDPSC database of RT-QuIC-positive cases lacking date of death information suggests that this strategy may exclude a number of probable prion disease cases. Prion disease cases <30 years of age, especially those lacking a pathogenic mutation, continue to be very rare.

Shedding of Chronic Wasting Disease Prions in Multiple Excreta Throughout Disease Course in White-tailed Deer

Nathaniel D. Denkersa, Erin E. McNultya, Caitlyn N. Krafta, Amy V. Nallsa, Joseph A. Westricha, Wilfred Goldmannb, Candace K. Mathiasona, and Edward A. Hoovera

aPrion Research Center, College of Veterinary Medicine and Biological Sciences, Department of Microbiology, Immunology, and Pathology; Colorado State University, Fort Collins, CO, USA; bDivision of Infection and Immunity, The Roslin Institute and the Royal Dick School of Veterinary Studies, University of Edinburgh, Midlothian, UK

Aims: Chronic wasting disease (CWD) now infects cervids in South Korea, North America, and Scandinavia. CWD is unique in its efficient transmission and shedding of prions in body fluids throughout long course infections. Questions remain as to the magnitude of shedding and the route of prion acquisition. As CWD continues to expand, the need to better understand these facets of disease becomes more pertinent. The purpose of the studies described was to define the longitudinal shedding profile of CWD prions in urine, saliva, and feces throughout the course of infection in white-tailed deer.

Material and Methods: Twelve (12) white-tailed deer were inoculated with either 1 mg or 300ng of CWD. Urine, saliva, and feces were collected every 3-month post-inoculation (MPI) throughout the study duration. Cohorts were established based on PNRP genotype: codon 96 GG (n = 6) and alternate codons 96 GS (n = 5) & 103NT (n = 1). Urine and saliva were analyzed using iron-oxide magnetic extraction (IOME) and real-time quaking induced conversion (RT-QuIC)(IQ). Feces were subjected to IOME, followed by 4 rounds protein misfolding cyclic amplification (PMCA) with products analyzed by RT-QuIC (IPQ). To determine whether IPQ may be superior to IQ, a subset of urine and saliva were also tested by IPQ. Results were compared with clinical disease status.

Results: Within the 96 GG cohort, positive seeding activity was detected in feces from all deer (100%), in saliva from 5 of 6 (83%), and in urine from 4 of 6 (66%). Shedding in all excreta occurred at, or just after, the first positive tonsil biopsy result. In the 96 GS/103NT cohort, positive seeding activity could be detected in feces from 3 of 6 (50%) deer, saliva in 2 of 6 (33%), and urine in 1 of 6 (16%). Shedding in excreta was detected >5 months after the first tonsil positive result. Four of six 96 GG deer developed clinical signs of CWD, whereas only 2 of the 96 GS/103NT did. Shedding was more frequently detected in deer with clinical disease. The IPQ protocol did not significantly improve detection in saliva or urine samples, however, it significantly augmented detection in feces by eliminating non-specific background commonly experienced with IQ. Negative control samples remained negative in samples tested.

Conclusions: These studies demonstrate: (a) CWD prion excretion occurs throughout infection; (2) PRNP genotype (GG≫GS/NT) influences the excreta shedding; and (3) detection sensitivity in excreta can vary with different RT-QuIC protocols. These results provide a more complete perspective of prion shedding in deer during the course of CWD infection.

Funded by: National Institutes of Health (NIH)

Grant number: RO1-NS061902-09 R to EAH, PO1-AI077774 to EAH, and R01-AI112956-06 to CKM

Acknowledgement: We abundantly thank Sallie Dahmes at WASCO and David Osborn and Gino D’Angelo at the University of Georgia Warnell School of Forestry and Natural Resources for their long-standing support of this work through provision of the hand-raised, CWD-free, white-tailed deer used in these studies

Large-scale PMCA screening of retropharyngeal lymph nodes and in white-tailed deer and comparisons with ELISA and IHC: the Texas CWD study

Rebeca Benaventea, Paulina Sotoa, Mitch Lockwoodb, and Rodrigo Moralesa

aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bTexas Park and Wildlife Department, Texas, USA

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that affects various species of cervids, and both free-ranging and captive animals. Until now, CWD has been detected in 3 continents: North America, Europe, and Asia. CWD prevalence in some states may reach 30% of total animals. In Texas, the first case of CWD was reported in a free-range mule deer in Hudspeth and now it has been detected in additional 14 counties. Currently, the gold standard techniques used for CWD screening and detection are ELISA and immunohistochemistry (IHC) of obex and retropharyngeal lymph nodes (RPLN). Unfortunately, these methods are known for having a low diagnostic sensitivity. Hence, many CWD-infected animals at pre-symptomatic stages may be misdiagnosed. Two promising in vitro prion amplification techniques, including the real-time quaking-induced conversion (RT-QuIC) and the protein misfolding cyclic amplification (PMCA) have been used to diagnose CWD and other prion diseases in several tissues and bodily fluids. Considering the low cost and speed of RT-QuIC, two recent studies have communicated the potential of this technique to diagnose CWD prions in RPLN samples. Unfortunately, the data presented in these articles suggest that identification of CWD positive samples is comparable to the currently used ELISA and IHC protocols. Similar studies using the PMCA technique have not been reported.

Aims: Compare the CWD diagnostic potential of PMCA with ELISA and IHC in RPLN samples from captive and free-range white-tailed deer. Material and Methods: In this study we analyzed 1,003 RPLN from both free-ranging and captive white-tailed deer collected in Texas. Samples were interrogated with the PMCA technique for their content of CWD prions. PMCA data was compared with the results obtained through currently approved techniques.

Results: Our results show a 15-fold increase in CWD detection in free-range deer compared with ELISA. Our results unveil the presence of prion infected animals in Texas counties with no previous history of CWD. In the case of captive deer, we detected a 16% more CWD positive animals when compared with IHC. Interestingly, some of these positive samples displayed differences in their electroforetic mobilities, suggesting the presence of different prion strains within the State of Texas.

Conclusions: PMCA sensitivity is significantly higher than the current gold standards techniques IHC and ELISA and would be a good tool for rapid CWD screening.

Funded by: USDA

Grant number: AP20VSSPRS00C143

ATYPRION project: assessing the zoonotic potential of interspecies transmission of CWD isolates to livestock (preliminary results).

Enric Vidala,b, Juan Carlos Espinosac, Samanta Gilera,b, Montserrat Ordóñeza,b, Guillermo Canteroa,b, Vincent Béringued, Justin J. Greenleee, and Juan Maria Torresc

aUnitat mixta d’Investigació IRTA-UAB en Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia; bIRTA. Programa de Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia; cCentro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Valdeolmos, Madrid, Spain; dMolecular Virology and Immunology, French National Research Institute for Agriculture, Food and Environment (INRAE), Université Paris-Saclay, Jouy-en-Josas, France; eVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA

Aims: Since variant Creutzfeldt-Jackob disease was linked to the consumption of bovine spongiform encephalopathy prions, the study of the pathobiological features of animal prions, particularly their zoonotic potential, is of great concern to the scientific community and public health authorities. Furthermore, interspecies transmission of prions has been demonstrated as a putative evolutionary mechanism for prions, that can lead to the emergence of new features including the ability to infect humans. For instance, small ruminants’ atypical scrapie prions, when propagated in a bovine or porcine host, can shift to a classical BSE phenotype thus posing a potential risk in case of human exposure. So far, no hard evidence of zoonotic transmission of cervids’ chronic wasting disease (CWD) to humans has been published, however experimental transmission to bovine, ovine and caprine hosts has been achieved. Our goal is to investigate if, once passaged through these domestic species, CWD prions might become infectious to humans.

Material and Methods: Different CWD isolates experimentally adapted to cattle, sheep and goat (Hamir et al, 2005, 2006, 2007, Greenlee et al 2012) have been intracerebrally inoculated to transgenic mouse models expressing the human cellular prion protein either homozygous for methionine or valine at codon 129 (Tg340-Met129 and Tg362-Val129). Additionally, inocula obtained from experimental transmission of elk CWD to ovinized (Tg501) and bovinized (BoTg110) transgenic mice, as well as white-tailed deer CWD to BoTg110 mice, are currently being bioassayed in both human PrPC transgenic models.

Results and conclusions: No evidence of transmission has been found on first passage for bovine adapted elk and mule deer CWD to none of the humanized models. The remaining bioassays are ongoing without showing clinical signs yet, as well as second passages for the negative 1stpassages.

Funded by: La Marató de TV3 foundation. Grant number: ATYPRION (201,821–30-31-32)


Prion Conference 2018 Abstracts

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.

Background

Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in freeranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.

Methods

Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).

Results

Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).

Conclusions

While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.

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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.

Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein can also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.

We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases were male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.

Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.

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P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission

Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)

(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.

Background

Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.

Methods

We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.

Results

We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.

Conclusions

PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.

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P180 Clinico-pathological analysis of human prion diseases in a brain bank series

Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)

(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.

Background and objective:

The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.

Methods:

We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.

Results:

176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to Gerstmann Sträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.

Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.

Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.

Discussion:

A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:


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P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures

Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)

(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.

Aims:

Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.

Methods:

Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.

Results:

The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.

Conclusions:

Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.

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WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice

Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)

(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.

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 found in spinal cord and brain of 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 preclinical 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.

See also poster P103

***> 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.

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WA16 Monitoring Potential CWD Transmission to Humans

Belay ED

Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.

The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.

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P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan

Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)

(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.

Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.

=====

Source Prion Conference 2018 Abstracts




Volume 24, Number 8—August 2018 Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions

Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)

Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.

snip...

Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).

A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.

The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.

In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).

The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.

Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.

Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.

This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.

Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.



Prion 2017 Conference Abstracts
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 ABSTRACTS REFERENCE
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.


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, did 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 $$$ ***

> 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).***
CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL

Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY 

Date: Fri, 18 Oct 2002 23:12:22 +0100 

From: Steve Dealler 

Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member 

To: BSE-L@ References: 

Dear Terry,

An excellent piece of review as this literature is desperately difficult to get back from Government sites.

What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!

Steve Dealler =============== 


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

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994

Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss) These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...

Table 9 presents the results of an analysis of these data.

There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).

Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.

There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).

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

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

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

snip...

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

snip...

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

snip...

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

snip...see full report ;




Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk 

BSE Inquiry Steve Dealler

Management In Confidence

BSE: Private Submission of Bovine Brain Dealler

snip...see full text;

MONDAY, FEBRUARY 25, 2019

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


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

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

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

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

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

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


***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.


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 transmissibility 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. 

============== 

PRION 2015 CONFERENCE


***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. 


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. 


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. 




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



Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification



APHIS Indemnity Regulations [Docket No. APHIS-2021-0010] RIN 0579-AE65 Singeltary Comment Submission Singeltary Sr., Terry

Sep 8, 2022



Date: Fri, 16 May 2003 11:47:37 0500 EMC 1 Terry S. Singeltary Sr. Vol #: 1

2003D-0186 Guidance for Industry: Use of Material From Deer and Elk In Animal Feed 

EMC 1 Terry S. Singeltary Sr. Vol #: 1 


Notice of Request To Renew an Approved Information Collection: Specified Risk Materials DOCKET NUMBER Docket No. FSIS-2022-0027 Singeltary Submission

Singeltary further comments in attachment;

Specified Risk Materials DOCKET NUMBER Docket No. FSIS-2022-0027 Singeltary Submission Attachment

https://downloads.regulations.gov/FSIS-2022-0027-0002/attachment_1.pdf

Sunday, January 10, 2021 
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. ...


APHIS Indemnity Regulations [Docket No. APHIS-2021-0010] RIN 0579-AE65 Singeltary Comment Submission

Comment from Singeltary Sr., Terry

Posted by the Animal and Plant Health Inspection Service on Sep 8, 2022

https://www.regulations.gov/comment/APHIS-2021-0010-0003

https://downloads.regulations.gov/APHIS-2021-0010-0003/attachment_1.pdf

Comments on technical aspects of the risk assessment were then submitted to FSIS.

Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary.

This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:



Owens, Julie From: Terry S. Singeltary Sr. [flounder9@verizon.net]

Sent: Monday, July 24, 2006 1:09 PM To: FSIS RegulationsComments

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Page 1 of 98 8/3/2006

Greetings FSIS, I would kindly like to comment on the following ;



Suppressed peer review of Harvard study October 31, 2002.

October 31, 2002 Review of the Evaluation of the Potential for Bovine Spongiform Encephalopathy in the United States Conducted by the Harvard Center for Risk Analysis, Harvard School of Public Health and Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Final Report Prepared for U.S. Department of Agriculture Food Safety and Inspection Service Office of Public Health and Science Prepared by RTI Health, Social, and Economics Research Research Triangle Park, NC 27709 RTI Project Number 07182.024



FULL TEXT OF GOA REPORT BELOW (takes a while to load)

2. Mad Cow Disease: Improvements in the Animal Feed Ban and Other Regulatory Areas Would Strengthen U.S. Prevention Efforts. GAO-02-183, January 25.


SATURDAY, AUGUST 16, 2008 

Qualitative Analysis of BSE Risk Factors in the United States February 13, 2000 at 3:37 pm PST (BSE red book) 


FULL TEXT OF GOA REPORT BELOW (takes a while to load)

2. Mad Cow Disease: Improvements in the Animal Feed Ban and Other Regulatory Areas Would Strengthen U.S. Prevention Efforts. GAO-02-183, January 25.


8 hr BSE confirmation turnaround took 7+ months to confirm this case, so the BSE MRR policy could be put into place. ...TSS

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

Subject: re-USDA's surveillance plan for BSE aka mad cow disease

Date: Mon, 02 May 2005 16:59:07 -0500

From: "Terry S. Singeltary Sr."


Greetings Honorable Paul Feeney, Keith Arnold, and William Busbyet al at OIG, ...............

snip...

There will be several more emails of my research to follow. I respectfully request a full inquiry into the cover-up of TSEs in the United States of America over the past 30 years. I would be happy to testify...

Thank you, I am sincerely, Terry S. Singeltary Sr. P.O. Box , Bacliff, Texas USA 77518 xxx xxx xxxx

Date: June 14, 2005 at 1:46 pm PST

In Reply to:

Re: Transcript Ag. Secretary Mike Johanns and Dr. John Clifford, Regarding further analysis of BSE Inconclusive Test Results

posted by TSS on June 13, 2005 at 7:33 pm:

Secretary of Agriculture Ann M. Veneman resigns Nov 15 2004, three days later inclusive Mad Cow is announced. June 7th 2005 Bill Hawks Under Secretary for Marketing and Regulatory Programs resigns. Three days later same mad cow found in November turns out to be positive. Both resignation are unexpected. just pondering... TSS

*** 2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006 ***


Suppressed peer review of Harvard study October 31, 2002
October 31, 2002

Review of the Evaluation of the Potential for Bovine Spongiform Encephalopathy in the United States Conducted by the Harvard Center for Risk Analysis, Harvard School of Public Health and Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University

Final Report 

Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Update; Notice of Availability and Technical Meeting 

Owens, Julie

From: Terry S. Singeltary Sr. [flounder9@verizon.net]

Sent: Monday, July 24, 2006 1:09 PM

To: FSIS RegulationsComments

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)


Response to Public Comments on the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update,

October 31, 2005

INTRODUCTION

The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website: http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp). Comments on technical aspects of the risk assessment were then submitted to FSIS. Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, RCALF USA, Linda A Detwiler, and Terry S. Singeltary. This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind: 


03-025IFA

03-025IFA-2

Terry S. Singeltary

From: Terry S. Singeltary Sr. [flounder9@verizon.net]

Sent: Thursday, September 08, 2005 6:17 PM

To: fsis.regulationscomments@fsis.usda.gov

Subject: [Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle


ONE final comment tonight, i just cannot take anymore. well, ill just let the facts speak for themselves, no need to even comment ;

Section 2. Testing Protocols and Quality Assurance Controls

In November 2004, USDA announced that its rapid screening test, Bio-Rad Enzyme Linked Immunosorbent Assay (ELISA), produced an inconclusive BSE test result as part of its enhanced BSE surveillance program. The ELISA rapid screening test performed at a BSE contract laboratory produced three high positive reactive results.40 As required,41 the contract laboratory forwarded the inconclusive sample to the APHIS National Veterinary Services Laboratories (NVSL) for confirmatory testing. NVSL repeated the ELISA testing and again produced three high positive reactive results.42 In accordance with its established protocol, NVSL ran its confirmatory test, an immunohistochemistry (IHC) test, which was interpreted as negative for BSE. In addition, NVSL performed a histological43 examination of the tissue and did not detect lesions44 consistent with BSE.

Faced with conflicting results, NVSL scientists recommended additional testing to resolve the discrepancy but APHIS headquarters officials concluded no further testing was necessary because testing protocols were followed. In our discussions with APHIS officials, they justified their decision not to do additional testing because the IHC is internationally recognized as the "gold standard." Also, they believed that conducting additional tests would undermine confidence in USDA’s established testing protocols.

full text 130 pages ;


PDF]Freas, William TSS SUBMISSION
File Format: PDF/Adobe Acrobat -

Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary

Sr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ...

http://web.archive.org/web/20170301223601/https://www.fda.gov/OHRMS/DOCKETS/AC/01/slides/3681s2_09.pdf
WEDNESDAY, NOVEMBER 30, 2022 

USDA Bovine Spongiform Encephalopathy BSE, Scrapie, CWD, Testing and Surveillance 2022 A Review of History 


WEDNESDAY, JANUARY 11, 2023 

4th International Chronic Wasting Disease Symposium: Overcoming Barriers to Control CWD 


FRIDAY, DECEMBER 23, 2022 
House and Senate Send Important Chronic Wasting Disease Legislation to President’s Desk
https://chronic-wasting-disease.blogspot.com/2022/12/house-and-senate-send-important-chronic.html

Terry S. Singeltary Sr.

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another atypical bovine spongiform encephalopathy (BSE) in Ireland

another atypical bovine spongiform encephalopathy (BSE) in Ireland PLEASE NOTE, OIE ET AL, made it official, countries DO NOT have to report...