Chronic Wasting Disease: Experts urge immediate action to contain the epidemic Chronic Wasting Disease CWD TSE Prion

EXPERTS URGE IMMEDIATE ACTION TO CONTAIN THE EPIDEMIC CHRONIC WASTING DISEASE CWD TSE PRION

June17, 2019

To the URGENT attention of:

Rt. Hon. Prime Minister Trudeau

Hon. Marie-Claude Bibeau

Hon. Ralph Goodale

Hon. Ginette Petitpas Taylor

Hon. Catherine McKenna

Hon. Carolyn Bennett

Hon. Seamus O’Reagan

Hon. Jim Carr

Hon. Bill Morneau

Government of Canada

House of Commons

Ottawa, Ontario

K1A 0A6

Dear Rt. Hon. Prime Minister Trudeau, and Honourable Ministers,

Protecting the health and wellbeing of current and future Canadians is entrusted as the highest priority of our governments. It requires comprehensive analysis of dynamic ecosystems, communities, and economies that scale from local to global. Carefully crafted, well-enforced laws, with monitoring and adaptation can prevent or contain crises, protect our wellbeing, and ensure a favourable and opportune future.

There has been no greater threat to health and wellbeing than infectious diseases—and risks are amplified by the intensity and speed of globalized economies. In 2003, even without infection of people, finding a single cow infected with bovine spongiform encephalopathy (BSE) or ‘mad cow’ in Alberta triggered devastating trade restrictions with multi-billion dollar consequences across Canada. Our governments learned from the UK’s official BSE Inquiry (2000), and enacted aggressive measures to contain the epidemic, protect consumers, and safeguard our economy. Today, we need a comparable response to a vastly larger epidemic of a sister prion disease called CWD, or “chronic wasting disease.” Like BSE, the epidemic of CWD is relatively new and largely manmade. Both are invariably fatal, with no adequate live animal tests, no preventive vaccines, and no treatments; but CWD is far more virulent because it is highly contagious between living animals.

CWD is currently afflicting members of the deer family, where it has repeatedly jumped species barriers and many strains have evolved. It was declared a “State of Emergency” by the U.S. Secretary of Agriculture in 2001. Transmission is facilitated via infective (misfolded) prions that are amplified, shed, and present in saliva, feces, urine, blood, lymphoid, and muscle tissue. CWD prions are extremely resilient, can persist in the environment indefinitely, and can spread animal to animal, or via soil, plants, agricultural products, and from contaminated surfaces or equipment. As such, CWD presents profound threats to wildlife and the environment, to agriculture and international trade, to Indigenous rights, traditions, treaties, food security, and, potentially, to human health. Evidence documenting the severity of the CWD crisis and the necessity of vital responses is clear, compelling, and uncontested. Consensus extends across disciplines, sectors, jurisdictions, departments, agencies, and among virtually all experts, vital interests, and stakeholders—as was reaffirmed at the 2018 One Health Congress, at an Assembly of First Nations meeting last December, at a February 2019 conference of agri-food representatives, and at a comprehensive conference on CWD convened by the Ontario Federation of Anglers and Hunters in March.

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The primary driver of all known prion disease epidemics has been intensive agriculture: as scrapie in domestic sheep, TME on mink farms, BSE from “ruminant feed” (feeding cows to cows), and CWD spread widely through schemes to privatize and exploit ‘captive wildlife’ (on game farms). As scientists had warned, CWD was imported to Canada in captive cervids from the U.S. and repeatedly spilled through fences to infect wildlife. Failure to contain the CWD epidemic has allowed continued growth and spread—now confirmed in 26 states and 3 Canadian provinces. Studies in wild deer populations confirm severe impacts and possible extinctions that present catastrophic threats to Canada’s biodiversity, our economy, cultural identity, and food security.

While no human cases of CWD have been confirmed, scientists note that while low, the risk is not zero—and it is evolving. Evidence suggests that CWD conversion is more adaptive than BSE, and following efficient transfer to a second species of non-human primates, Health Canada advised that “CWD has the potential to infect humans.” Thousands of CWD-infected animals are being consumed by hunters and their families across North America every year. Even a single transfer to a person—proving that humans are susceptible—would bring catastrophic consequences with limited options. The potential threat to our blood supply cannot be ignored, as demonstrated when BSE cost the UK access to their domestic plasma supply. All of this underscores the need for precautionary measures and preparation of an emergency plan.

It is vital to note, however, that threats to agricultural economies do not require human transfer. The capacity to spread CWD to susceptible species of deer all over the world via agricultural crops has already resulted in trade actions. On October 24th, 2018 Norway banned imports of hay or straw from any state or province with CWD. This could easily expand to other products and spread to other economic regions seeking, not just to avoid the threats, but to leverage tens of billions of dollars per year in competitive advantage. Economists describe the prospects for such outcomes as “probable” and the consequences as “severe and probably recessionary, with cascading effects and few immediate remedies.” As recent events have shown, these threats extend to investment markets. Despite the lessons of BSE and the dire threat posed by CWD, official policy still allows translocation of live animals, products, and equipment from cervid farms, movement of hunter carcasses, and continued human exposure—in violation of basic principles of science, public trust, and professional ethics.

We urge the federal government, in collaboration with provinces and territories to immediately mandate, fund, and undertake emergency directives to:

1. Contain the geographic spread of CWD. Enact and enforce an immediate ban on the movement of all live cervids, all potentially CWD-infected carcasses, animal parts, products, exposed equipment, or other sources of infectious materials. Enact measures to ensure proper disposal of infected carcasses. Eliminate cervid farms with a plan for compensation and/or transition of operations to acceptable alternatives. Contain, mitigate, and where possible, eradicate CWD in wild populations by developing and implementing rapid response plans.

2. Prevent human exposure. Prevent transfer and/or amplification of CWD via food and feed chains by mandating and implementing convenient, cost-free, rapid testing of all animals harvested from CWD-affected areas. Provide hunters and communities with guidance and means for risk reduction. Mandate that all food banks only accept venison following negative test results.

3. Maintain and strengthen the current federal program of human prion disease surveillance and develop a preparedness plan for the possible emergence of human CWD in Canada, including possible impacts to our blood supply.

4. Initiate and fund an independent, interdisciplinary approach dedicated to comprehensive, collaborative, international, nation to nation, science and evidence-based initiatives to:

• Prevent transfer and/or amplification of CWD via food and feed chains;

• Contain, mitigate, and where possible, eradicate CWD in wild populations;

• Ensure Canadians’ future wellness by protecting wildlife, ecosystems, communities, safe, nutritious, sustainable food, and economies; and

• Invest in research and innovation to support Canadian efforts to better understand and advance scientific, economic, and biomedical insights and opportunities, while reducing threats.

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We have assembled a multi-sector coalition of experts and vital stakeholders to support these measures, to inform prudent public policy, and engage in collaborative efforts going forward.

The following signatories implore you to recognize the dire nature of this epidemic, of your acknowledgement of the public trust, and the responsibilities of your office. We stand in support of your announcement of the government of Canada’s urgent undertaking of all necessary actions to meet these challenges and protect Canadian interests. Yours truly,

Dr. Neil Cashman, Professor, Department of Medicine, University of British Columbia (former) Scientific Director, PrioNet Canada

Dr. Hermann Schaetzl, M.D., Dr.med./PhD, Professor, Prion Biology and Immunology, University of Calgary

Dr. Sabine Gilch, Associate Professor, Canada Research Chair in Prion Diseases, University of Calgary

Dr. David Swann, FRCP, MLA (Retired)

Dr. Arthur W. Clark, Physician Professor Emeritus, Pathology & Laboratory Medicine and Clinical Neurosciences, University of Calgary

Alastair R. Lucas, QC, Professor of Law, Senior Research Associate, Canadian Institute of Resources Law

Dr. Paul Sockett, Director, Foodborne, Waterborne and Zoonotic Infections Division, Public Health Agency of Canada (1996 - 2008) Science Advisor, First Nations and Inuit Health Branch, Health Canada (2008 - 2012). (Retired)

Dr. Michael T. Osterholm, PhD, MPH, Regents Professor, McKnight Endowed Presidential Chair in Public Health Director, Center for Infectious Disease Research and Policy, Distinguished University Teaching Professor, Environmental Health Sciences, School of Public Health, Professor, Technological Leadership Institute, College of Science and Engineering Adjunct Professor, Medical School Kat Lanteigne, Executive Director, BloodWatch.org

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(Support confirmed via email)

Michèle Brill-Edwards MD, FRCPC Board Member, Canadian Health Coalition

Michael D. Samuel, Professor Emeritus,Forest and Wildlife Ecology University of Wisconsin-Madison

Dave Clausen, DVM, (former) Chair, Wisconsin Natural Resources Board

Jerry Potts, North Piikani Nation Elder, Thunder Medicine Pipe Keeper Chief Stanley Grier, Piikani Nation

Councillor Brian Jackson, Piikani Nation (Support confirmed via email)

Dr. Lana R. Potts BScN MD CCFP Indigenous Family Medicine

Norman Yakeleya, Dene National Chief AFN Regional Chief

Christine Laing, Acting Executive Director Public Interest Law Clinic, University of Calgary (Support confirmed via email)

Dr. Greg Douglas, (former) Chief Veterinary Officer Saskatchewan, (former) Chief Veterinarian, Ontario

Dr. Richard Gray, Professor and Grain Policy Chair, Agriculture & Resources Economics, University of Saskatchewan

Dr. Vince Crichton, (former) Co-Chair, Canada’s National Wildlife Disease Strategy

Dr. Val Geist, Professor (Emeritus), Environmental Science, University of Calgary Darrel Rowledge, Executive Director, Alliance for Public Wildlife

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Bill Bosch, President, BC Wildlife Federation

Brian Dingreville, President, Alberta Fish and Game Association

Clark Schultz, President, Saskatchewan Wildlife Federation

David Pezderic, Saskatchewan Wildlife Federation

Dr. Brian Kotak, Manitoba Wildlife Federation

Charles Shewen, President, Yukon Fish and Game Association

Kelli Miller Kickhom, President, PEI Wildlife Federation

Andrew Bouzan, President Newfoundland and Labrador Wildlife

Serge Lariviere, Director, Quebec Federation of Anglers and Hunters

Angelo Lombardo, Executive Director Ontario Federation of Anglers and Hunterds

Rick Bates, Canadian Wildlife Federation

https://mwf.mb.ca/wp-content/uploads/2019/06/CWD-Ltr-to-PM-Ministers-CWD-June-2019-1.pdf

The Threat of Chronic Wasting Disease (CWD) – At a glance

• CWD is a new type of threat

o CWD is a newly emerged, highly contagious, invariably fatal disease currently afflicting members of the deer family (white-tailed deer, mule deer, elk, and moose; caribou are susceptible and at risk).

o CWD is a sister disease of bovine spongiform encephalopathy (BSE), or ‘mad cow’ disease, but more virulent because it is highly contagious between living animals.

o Rating virulence of transmissible spongiform encephalopathies (TSEs), a leading expert with the Canadian Food Inspection Agency put BSE as the mildest, least virulent, and easiest to contain. At the opposite end she placed CWD as the most severe.

o First detected in Colorado in 1967, CWD has been spread widely across North America through commercial game farming initiatives. It is now confirmed in 26 states and 3 Canadian provinces, most recently Quebec.

o CWD has no adequate live animal tests, no preventative vaccine, and no cure for infected animals.

o CWD transmission occurs via prions (misfolded prions) that are amplified, shed, and present in saliva, feces, urine, blood, lymphoid, and muscle tissue.

o Prions are not living organisms and are extremely resilient, can persist in the environment indefinitely, and spread via soil, plants, agricultural products, and from contaminated surfaces or equipment.

• CWD threatens Canada’s wildlife and environment, and the Canadians who depend on them

o CWD is fatal to deer, moose, elk, and caribou and studies have shown it has led to severe population impacts including potential extinction models.

o CWD threatens biodiversity, species at risk such as caribou, and the income, cultural identity, and food security of many Canadians.

o Wildlife-based economies (hunting, tourism, photography, and viewing), depend on healthy deer species, and contribute greatly to the economic, social, and cultural well-being of many Canadians.

o Where CWD is detected, drastic measures, like the depopulation of wild herds, are needed to even attempt to eradicate it. In response to a 2016 detection in wild reindeer—consistent with recommendation from leading North American scientists—the Norwegian government culled an entire herd of over 2,000 animals.

o Containment is vital, as response measures are not always sufficient, yet significantly drain the already limited resources and budgets of fish and wildlife agencies. New York State spent over $1,000,000 in their successful 2005 CWD response to seven positive cases (and only 3.5 weeks of work). Chronic Wasting Disease (CWD)

The largest, most contagious, most persistent biomass of infectious prions in global history

Experts urge immediate action to contain the epidemic, fund independent, interdisciplinary task force to reduce impacts, prevent threats, and protect Canadian interests

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• CWD threatens Canada’s fiduciary obligation to Indigenous peoples

o The food security and cultural sustainability of Indigenous peoples is directly tied to deer, elk, moose, and caribou. In some cases, economic prosperity related to guiding and tourism is also at stake.

• CWD threatens Canada’s agricultural and agri-food economies:

o In 2003, even without infection of people, a single cow infected with BSE in Alberta triggered devastating trade restrictions with multi-billion dollar consequences in Canada.

o In 2018, Norway banned imports of hay or straw from any state or province with CWD. Economists fear this has the potential to expand to other agricultural products, and spread to other economic regions, seeking, not just to protect wildlife, ecosystems, economies, and public health, but to secure tens of billions of dollars in market share gains annually.

• CWD threatens Canada’s public health:

o No human cases of CWD have been confirmed, primate studies including macaques—the closest nonhuman primates allowed in research—confirm efficient transfer through the consumption of CWDpositive meat. This led Health Canada to advise that: “CWD has the potential to infect humans.”

o Global health officials and agencies—including Canada’s—recommend against consumption of any TSE material, including meat or other products from CWD-positive animals.

o There is no current field test, and existing hunter harvest testing programs take months (far too long) to receive results.

o Despite regulatory measures, products from CWD-positive game farm animals have repeatedly entered the human food and feed chains (including velvet antler, venison, and pet food). Urine-based scents are a substantial risk and should be banned.

o The Canadian blood system would be severely challenged if CWD presented in humans, as prions cannot be completely fractionated out or rendered benign; BSE cost the UK access to their domestic plasma supply.

• We know what to do. We just need to do it. These actions include:

o Containing the geographic spread

§ Phasing out so-called ‘captive wildlife’ industry

§ Stopping the movement of live animals, potentially infected tissues, and carcasses

§ Being ready for a fast and aggressive response wherever CWD is detected

o Preventing human exposure

§ Taking steps to keep CWD-tainted meat out of the human food chain

§ Strengthen human prion disease surveillance, and preparedness for human CWD

• Inaction is not an option

o Successive governments have failed to take simple actions to protect Canadians from the threat of CWD.

o Evidence documenting the severity of CWD and necessity of vital responses is clear, compelling, and uncontested.

o Consensus extends across disciplines, sectors, jurisdictions, agencies, and virtually all vital stakeholders.

o Our most effective and least costly option is to halt the spread of CWD and keep it out of areas that don’t have it.

o If it turns out that humans can be infected, then inaction by successive government will be responsible.

For more information on Chronic Wasting Disease, please visit: www.ofah.org/cwd

https://mwf.mb.ca/wp-content/uploads/2019/06/CWD-Briefing-Note.pdf

2019

2019 CHRONIC WASTING DISEASE CWD TSE PRION, THE KILLER AMONG US, REVISITED

PRION 2019 ABSTRACTS

1. Interspecies transmission of the chronic wasting disease agent

Justin Greenlee

Virus and Prion Research Unit, National Animal Disease Center, USDA Agriculture Research Service

ABSTRACT

The presentation will summarize the results of various studies conducted at our research center that assess the transmissibility of the chronic wasting disease (CWD) agent to cattle, pigs, raccoons, goats, and sheep. This will include specifics of the relative attack rates, clinical signs, and microscopic lesions with emphasis on how to differentiate cross-species transmission of the CWD agent from the prion diseases that naturally occur in hosts such as cattle or sheep. Briefly, the relative difficulty of transmitting the CWD agent to sheep and goats will be contrasted with the relative ease of transmitting the scrapie agent to white-tailed deer.

53. Evaluation of the inter-species transmission potential of different CWD isolates

Rodrigo Moralesa, Carlos Kramma,b, Paulina Sotoa, Adam Lyona, Sandra Pritzkowa, Claudio Sotoa

aMitchell Center for Alzheimer’s disease and Related Brain Disorders, Dept. of Neurology, McGovern School of Medicine University of Texas Health Science Center at Houston, TX, USA; bFacultad de Medicina, Universidad de los Andes, Santiago, Chile

ABSTRACT

Chronic Wasting Disease (CWD) has reached epidemic proportions in North America and has been identified in South Korea and Northern Europe. CWD-susceptible cervid species are known to share habitats with humans and other animals entering the human food chain. At present, the potential of CWD to infect humans and other animal species is not completely clear. The exploration of this issue acquires further complexity considering the differences in the prion protein sequence due to species-specific variations and polymorphic changes within species. While several species of cervids are naturally affected by CWD, white-tailed deer (WTD) is perhaps the most relevant due to its extensive use in hunting and as a source of food. Evaluation of inter-species prion infections using animals or mouse models is costly and time consuming. We and others have shown that the Protein Misfolding Cyclic Amplification (PMCA) technology reproduces, in an accelerated and inexpensive manner, the inter-species transmission of prions while preserving the strain features of the input PrPSc. In this work, we tested the potential of different WTD-derived CWD isolates to transmit to humans and other animal species relevant for human consumption using PMCA. For these experiments, CWD isolates homozygous for the most common WTD-PrP polymorphic changes (G96S) were used (96SS variant obtained from a pre-symptomatic prion infected WTD). Briefly, 96GG and 96SS CWD prions were adapted in homologous or heterologous substrate by PMCA through several (15) rounds. End products, as well as intermediates across the process, were tested for their inter-species transmission potentials. A similar process was followed to assess seed-templated misfolding of ovine, porcine, and bovine PrPC. Our results show differences on the inter-species transmission potentials of the four adapted materials generated (PrPC/PrPSc polymorphic combinations), being the homologous combinations of seed/substrate the ones with the greater apparent zoonotic potential. Surprisingly, 96SS prions adapted in homologous substrate were the ones showing the easiest potential to template PrPC misfolding from other animal species. In summary, our results show that a plethora of different CWD isolates, each comprising different potentials for inter-species transmission, may exist in the environment. These experiments may help to clarify an uncertain and potentially worrisome public health issue. Additional research in this area may be useful to advise on the design of regulations intended to stop the spread of CWD and predict unwanted zoonotic events.

56. Understanding chronic wasting disease spread potential for at-risk species

Catherine I. Cullingham, Anh Dao, Debbie McKenzie and David W. Coltman

Department of Biological Sciences, University of Alberta, Edmonton AB, Canada

CONTACT Catherine I. Cullingham cathy.cullingham@ualberta.ca

ABSTRACT

Genetic variation can be linked to susceptibility or resistance to a disease, and this information can help to better understand spread-risk in a population. Wildlife disease incidence is increasing, and this is resulting in negative impacts on the economy, biodiversity, and in some instances, human health. If we can find genetic variation that helps to inform which individuals are susceptible, then we can use this information on at-risk populations to better manage negative consequences. Chronic wasting disease, a fatal, transmissible spongiform encephalopathy of cervids (both wild and captive), continues to spread geographically, which has resulted in an increasing host-range. The disease agent (PrPCWD) is a misfolded conformer of native cellular protein (PrPC). In Canada, the disease is endemic in Alberta and Saskatchewan, infecting primarily mule deer and white-tail deer, with a smaller impact on elk and moose populations. As the extent of the endemic area continues to expand, additional species will be exposed to this disease, including bison, bighorn sheep, mountain goat, and pronghorn antelope. To better understand the potential spread-risk among these species, we reviewed the current literature on species that have been orally exposed to CWD to identify susceptible and resistant species. We then compared the amino acid polymorphisms of PrPC among these species to determine whether any sites were linked to susceptibility or resistance to CWD infection. We sequenced the entire PrP coding region in 578 individuals across at-risk populations to evaluate their potential susceptibility. Three amino acid sites (97, 170, and 174; human numbering) were significantly associated with susceptibility, but these were not fully discriminating. All but one species among the resistant group shared the same haplotype, and the same for the susceptible species. For the at-risk species, bison had the resistant haplotype, while bighorn sheep and mountain goats were closely associated with the resistant type. Pronghorn antelope and a newly identified haplotype in moose differed from the susceptible haplotype, but were still closely associated with it. These data suggest pronghorn antelope will be susceptible to CWD while bison are likely to be resistant. Based on this data, recommendations can be made regarding species to be monitored for possible CWD infection.

KEYWORDS: Chronic wasting disease; Prnp; wildlife disease; population genetics; ungulates

75. Mortality surveillance of individuals potentially exposed to chronic wasting disease

Ryan A. Maddoxa, Rachel F. Klosb, Suzanne N. Gibbons-Burgenerb, Bobbi L. Bryanta, Joseph Y. Abramsa, Brian S. Applebyc, Lawrence B. Schonbergera and Ermias D. Belaya

aNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA; bWisconsin Department of Health Services, Division of Public Health, Madison, WI, USA; cNational Prion Disease Pathology Surveillance Center (NPDPSC), Case Western Reserve University, Cleveland, OH, USA

CONTACT Ryan A. Maddox rmaddox@cdc.gov

ABSTRACT

Introduction: Chronic wasting disease (CWD) is a prion disease of cervids. It is unknown whether CWD prions can infect people; if so, transmission would most likely occur through consumption of meat from infected animals. Since 2003, Wisconsin Department of Health Services, Division of Public Health (WDHS) personnel have maintained a database consisting of information collected from hunters who reported eating, or an intention to eat, venison from cervids positive for CWD. This data source makes it possible to evaluate causes of mortality in individuals potentially exposed to CWD.

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 the National Prion Disease Pathology Surveillance Center (NPDPSC) neuropathology database. Vital status of individuals with date of birth available will be tracked through the identification of possible matches in the National Death Index (NDI) and the evaluation of corresponding cause of death codes.

Results: The database consists of 1561 records for hunt years 2003–2017. Of these, 613 records had accompanying date of birth; 14 entries were removed as duplicates, 1 of whom had consumed venison from a CWD-positive deer during three different hunt years, leaving 599 unique individuals for pending submission to NDI. Of these individuals, 265 of 399 (66%) who ate venison from a CWD-positive deer and provided processing information reported self-processing. No matches were found among persons in the database cross-checked with NPDPSC data.

Conclusion: Because of the robust data link between person and CWD-positive animal, reviewing the cause of mortality in potentially exposed persons is possible; those individuals who self-processed and consumed the meat are likely the best source of information about the potential for zoonotic transmission. The expected long incubation period, should transmission to humans occur, necessitates many years of vital status tracking.

77. Assessing chronic wasting disease strain differences in free-ranging cervids across the United States

Kaitlyn M. Wagnera, Caitlin Ott-Connb, Kelly Strakab, Bob Dittmarc, Jasmine Battend, Robyn Piercea, Mercedes Hennessya, Elizabeth Gordona, Brett Israela, Jenn Ballarde and Mark D Zabela

aPrion Research Center at Colorado State University; bMichigan Department of Natural Resources; cTexas Parks and Wildlife Department; dMissouri Department of Conservation, 5. Arkansas Game and Fish Commission

CONTACT Kaitlyn M. Wagner miedkait@rams.colostate.edu

ABSTRACT

Background/Introduction: Chronic wasting disease (CWD) is an invariably fatal prion disease affecting captive and free-ranging cervids, including white-tailed deer, mule deer, moose, elk, and reindeer. Since the initial description of the disease in the 1960’s, CWD has spread to 23 states, 3 Canadian Provinces, South Korea, Norway and, most recently, Finland. While some outbreaks of CWD were caused by transport of infected animals from endemic regions, the origin of CWD in other epizootics is unclear and has not been characterized. Previous studies have shown that there are two distinct strains of CWD. However, the continuous spread and the unclear origin of several outbreaks warrant continued surveillance and further characterization of strain diversity.

Materials and Methods: To address these knowledge gaps, we used biochemical tests to assess strain differences between CWD outbreaks in Michigan, Texas, Missouri, and Colorado, USA. Brain or lymph node samples were homogenized and digested in 50 µg/mL proteinase K (PK). These samples were then run on a Western blot to assess glycoform ratio and electrophoretic mobility. Texas samples were digested in 100 µg/mL PK. To assess conformational stability, brain or lymph node homogenates were incubated in increasing concentrations of guanidine hydrochloride from 0 M to 4 M in 0.5 M increments. Samples were then precipitated in methanol overnight, washed and PK digested in 50 µg/mL PK before slot blotting.

Results: Our results have found significant differences in glycoform ratio between CWD from Michigan and Colorado, but no differences were observed in conformational stability assays. Interestingly, when testing our CWD isolates from Texas to analyse electrophoretic mobility and glycoform ratio, we found that these samples did not exhibit the characteristic band shift when treated with PK, but PK resistant material remained. Additionally, results from our conformational stability assay demonstrate a unique profile of these Texas isolates. Testing of samples from Missouri is currently underway.

Conclusions: Thus far, our data indicate that there are strain differences between CWD circulating in Michigan and CWD in Colorado and provide important insight into CWD strain differences between two non-contiguous outbreaks. We have also identified a unique strain of CWD in Texas with biochemical strain properties not seen in any of our other CWD isolates. These results highlight the importance of continued surveillance to better understand this devastating disease. These results have important implications for CWD emergence, evolution and our understanding of prion strain heterogeneity on the landscape.

Thursday, May 23, 2019

Prion 2019 Emerging Concepts CWD, BSE, SCRAPIE, CJD, SCIENTIFIC PROGRAM Schedule and Abstracts

https://prionconference.blogspot.com/2019/05/prion-2019-emerging-concepts-cwd-bse.html

see full Prion 2019 Conference Abstracts

https://www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197

Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis

We hypothesize that:

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;

(3) Reliable essays can be established to detect CWD infection in humans; and

(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.

http://grantome.com/grant/NIH/R01-NS088604-04

ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

here is the latest;

PRION 2018 CONFERENCE

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

Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).

To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.

After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.

Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.

The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.

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

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

https://prion2018.org/

READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;

P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States

Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..

SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD
states.

AND ANOTHER STUDY;

P172 Peripheral Neuropathy in Patients with Prion Disease

Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..

IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,

AND

included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),

AND

THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.

snip...

see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below...terry

https://prion2018.org/wp-content/uploads/2018/05/program.pdf

https://prion2018.org/

Thursday, May 23, 2019

Prion 2019 Emerging Concepts CWD, BSE, SCRAPIE, CJD, SCIENTIFIC PROGRAM Schedule and Abstracts

https://prionconference.blogspot.com/2019/05/prion-2019-emerging-concepts-cwd-bse.html

see full Prion 2019 Conference Abstracts

https://www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197

FRIDAY, MAY 24, 2019

Assessing chronic wasting disease strain differences in free-ranging cervids across the United States

https://chronic-wasting-disease.blogspot.com/2019/05/assessing-chronic-wasting-disease.html

SATURDAY, JUNE 01, 2019

***> Primary structural differences at residue 226 of deer and elk PrP dictate selection of distinct CWD prion strains in gene-targeted mice

https://chronic-wasting-disease.blogspot.com/2019/06/primary-structural-differences-at.html

> 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).***

http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys

http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true

https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article

the British disease...NOT, the UKBSEnvCJD only theory was/is bogus $$$

https://histodb11.usz.ch/Images/videos/video-009/video-009.html

*** USA sporadic CJD MAD COW DISEASE HAS HUGE PROBLEM Video

*** sporadic CJD linked to mad cow disease

*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***

https://histodb11.usz.ch/Images/videos/video-004/video-004.html

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

BSE INQUIRY EVIDENCE

Why did the appearance of new TSEs in animals matter so much? It has always been known that TSEs will transfer across species boundaries. The reason for this was never known until the genetic nature of the prion gene was fully investigated and found to be involved. The gene is found to have well preserved sites and as such there is a similar gene throughout the animal kingdom...and indeed a similar gene is found in insects! It is NOT clear that the precise close nature of the PrP gene structure is essention for low species barriers. Indeed it is probably easier to infect cats with BSE than it is to infect sheep. As such it is not clear that simply because it is possible to infect BSE from cattle into certain monkeys then other apes will necessarily be infectable with the disease. One factor has stood out, however, and that is that BSE, when inoculated into mice would retain its apparent nature of disease strain, and hence when it was inoculated back into cattle, then the same disease was produced. Similarly if the TSE from kudu was inoculated into mice then a similar distribution of disease in the brain of the mouse is seen as if BSE had been inoculated into the mouse. This phenomenon was not true with scrapie, in which the transmission across a species barrier was known to lose many of the scrapie strain phenomena in terms of incubation period or disease histopathology. This also suggested that BSE was not derived from scrapie originally but we probably will never know.

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

TSE in wild UK deer? The first case of BSE (as we now realise) was in a nyala in London zoo and the further zoo cases in ungulates were simply thought of as being interesting transmissions of scrapie initially. The big problem started to appear with animals in 1993-5 when it became clear that there was an increase in the CJD cases in people that had eaten deer although the statistics involved must have been questionable. The reason for this was that the CJD Surveillance was well funded to look into the diet of people dying of CJD. This effect is not clear with vCJD...if only because the numbers involved are much smaller and hence it is difficult to gain enough statistics. They found that many other foods did not appear to have much association at all but that deer certainly did and as years went by the association actually became clearer. The appearance of vCJD in 1996 made all this much more difficult in that it was suddenly clearer that the cases of sporadic CJD that they had been checking up until then probably had nothing to do with beef...and the study decreased. During the period there was an increasing worry that deer were involved with CJD..

see references:

DEER BRAIN SURVEY

https://web.archive.org/web/20090506025229/http://www.bseinquiry.gov.uk/files/yb/1991/11/20004001.pdf

https://www.facebook.com/groups/1557515941145821/permalink/2299600233604051/?hc_location=ufi

i have not updated my blogspot url with all this data archived, but i will work on it...but until then, i have updated this on the above links with live urls to the actual BSE Inquiry documents...

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: <3daf5023 .4080804="" a="" href="http://wt.net/" nbsp="" rel="noopener noreferrer" style="color: blue; cursor: pointer;" target="_blank">wt.net

="">

Dear Terry,

An excellent piece of review as this literature is desparately 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 ===============

https://caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html

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

https://web.archive.org/web/20090506043910/http://www.bseinquiry.gov.uk/files/yb/1993/12/08003001.pdf

reports of sheep and calf carcasses dumped...

https://web.archive.org/web/20090505232801/http://www.bseinquiry.gov.uk/files/yb/1993/12/07002001.pdf

re-scrapie to cattle GAH Wells BSE Inquiry

https://web.archive.org/web/20090506043931/http://www.bseinquiry.gov.uk/files/yb/1993/12/09001001.pdf

Dr. Dealler goes rogue to confirm BSE

https://web.archive.org/web/20090506043930/http://www.bseinquiry.gov.uk/files/yb/1993/12/14003001.pdf

https://web.archive.org/web/20090505231533/http://www.bseinquiry.gov.uk/files/yb/1993/12/17003001.pdf

Confirmation BSE Dealler's mad cow

https://web.archive.org/web/20090505231342/http://www.bseinquiry.gov.uk/files/yb/1993/12/16006001.pdf

BSE vertical transmission

https://web.archive.org/web/20090506043834/http://www.bseinquiry.gov.uk/files/yb/1993/12/13003001.pdf

1993 cjd report finds relationship with eat venison and cjd increases 9 fold, let the cover up begin...tss

https://web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf

FINDINGS

*** 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 ;

https://web.archive.org/web/2 0170126073306/http://collections..europarchive..org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf

GAME FARM INDUSTRY WANTS TO COVER UP FINDINGS OF INCREASE RISK TO CJD FROM CERVID

BSE INQUIRY

CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane

BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf

The BSE Inquiry / Statement No 324

Dr James Kirkwood (not scheduled to give oral evidence)

Statement to the BSE Inquiry

James K Kirkwood BVSc PhD FIBiol MRCVS

[This witness has not been asked to give oral evidence in Phase 1 of the Inquiry]

1. I became involved in the field of TSEs through my work as Head of the Veterinary Science Group at the Zoological Society of London’s Institute of Zoology. I held this post from November 1984 until June 1996, when I took up my present post at UFAW. During this time, concurrent with the BSE epidemic, cases of scrapie-like spongiform encephalopathies occurred in animals at the Zoological Society of London’s collections at Regent’s Park and Whipsnade and in other zoos. It was appropriate to investigate the epidemiology of these cases in order to try to determine the possible impact on zoo animals and breeding programmes, and to consider how the disease in zoo animals might be controlled.

2. Throughout the period from 1985 to March 1996, I worked at the Institute of Zoology (IoZ). I was Head of the Veterinary Science Group of the IoZ and Senior Veterinary Officer of the Zoological Society of London (ZSL). I was responsible for the provision of the veterinary service for the ZSL collections.

3. During the period from 1985 to March 1996, scrapie-like spongiform encephalopathies were diagnosed in the following animals which died, or were euthanased, at London Zoo and Whipsnade:

Animal Sex Date of Death Age (mos)

Arabian Oryx Oryx leucoryx F 24.3.89 38

Greater kudu Tragelaphus strepsiceros (Linda) F 18.8.89 30

Greater kudu (Karla) F 13.11.90 19 Greater kudu (Kaz) M 6.6.91 37

Greater kudu (Bambi) M 24.10.91 36

Greater kudu (346/90) M 26.2.92 18

Greater kudu (324/90) F 22.11.92 38

Cheetah Acinonyx jubatus (Michelle) F 22.12.93 91

All these cases were described in papers published in the scientific literature (as cited below).

https://web.archive.org/web/20090506004016/http://www.bseinquiry.gov.uk/files/ws/s324.pdf

EYES, RETINA, SHOULD NOT BE USED IN SCHOOLS, BAB, SOB, MRM,

https://web.archive.org/web/20090506065716/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf

BSE, PET FOOD, CRUSHED HEADS

https://web.archive.org/web/20090505225022/http://www.bseinquiry.gov.uk/files/yb/1989/03/17004001.pdf

IN PARTICULAR CRUSHED HEADS

https://web.archive.org/web/20090505233039/http://www.bseinquiry.gov.uk/files/yb/1989/04/14001001.pdf

YOU explained that imported crushed heads were extensively used in the petfood industry...

https://web.archive.org/web/20090505233039/http://www.bseinquiry.gov.uk/files/yb/1989/04/14001001.pdf

https://web.archive.org/web/20090506054223/http://www.bseinquiry.gov.uk/files/yb/1989/04/14005001.pdf

In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed.

https://web.archive.org/web/20090505233046/http://www.bseinquiry.gov.uk/files/yb/1989/04/24003001.pdf

BSE IN PETFOOD

1. The Secretary asked on 19 April whether I was content with the advice in para 3 of the record of the meeting on 17 March with the Parliamentary Secretary (Mr Thompson). The simple answer is ''not entirely''.

2. On occasions, material obtained from slaughterhouses will be derived from sheep affected with scrapie or cattle that may be incubating BSE for use in petfood manufacture. Some of this material must be classified as high risk since it contains brain, spinal cord, spleen or lymphatic glands.

https://web.archive.org/web/20090505233052/http://www.bseinquiry.gov.uk/files/yb/1989/05/03007001.pdf

Meldrum's notes on pet foods and materials used

https://web.archive.org/web/20090505233041/http://www.bseinquiry.gov.uk/files/yb/1989/05/16001001.pdf

https://web.archive.org/web/20090506015917/http://www.bseinquiry.gov.uk/files/yb/1989/05/16002001.pdf

IN CONFIDENCE CJD TO CATS...

It should be noted that under experimental conditions cats succumb to an encephalopathy after intracerebral inoculation of material derived from patients affected with Creutzfeldt-Jakob Disease.

https://web.archive.org/web/20090506055329/http://www.bseinquiry.gov.uk/files/yb/1989/05/18002001.pdf

Confidential BSE and __________________

3. I have thought very hard about whether the Branch should carry out a similar exercise with meat and meat products for human foods. On balance I do NOT think we should undertake it, but a final decision has not been taken and you may wish to discuss this further. ...

https://web.archive.org/web/20090505220118/http://www.bseinquiry.gov.uk/files/yb/1989/05/22012001.pdf

1st case natural FSE

NATURAL SPONGIFORM ENCEPHALOPATHY IN A DOMESTIC CAT

1. We have heard from MAFF that a domestic Siamese cat from the Bristol area has had spongiform encephalopathy confirmed. Although there are previous instances of experimental infection in cats, there have been no previous natural infections reported. The assumption must be the cat became infected by scrapie/BSE agent in it's food. ...

https://web.archive.org/web/20090506015733/http://www.bseinquiry.gov.uk/files/yb/1990/05/09002001.pdf

FSE and pharmaceuticals

1. An analysis by MCA Professional staff of the results to the questionnaire sent out to industry to obtain additional data about the use of animal materials of any origin in the manufacture of pharmaceutical products for human use, reveals that material of feline or canine origin is used in only two licensed products. In both instances the material is sourced from outside the U.K. and from areas currently believed to be free from B.S.E.

https://web.archive.org/web/20090506041332/http://www.bseinquiry.gov.uk/files/yb/1990/05/10005001.pdf

CONFIDENTIAL

Confidential cats/dogs and unsatisfactory posture MAFFs failure to assure key research

3. First, I am very uneasy about the relative lack of urgency and interest that MAFF appear to hold for getting the necessary research programme on BSE and related encephalopathies started, and getting it going fast. FOR EXAMPLE, MR BRADLEY of CVL said that there were difficulties in organizing transmission experiments from the brain of the cat which died of an encephalopathy in Bristol. There were arguments going on about who should pay for this work. Should it be MAFF, the Bristol Veterinary School or someone else? Dr. Tyrrell was clearly exasperated.

snip...

11. The Committee were even LESS FORTHCOMING on what their reaction might be if an encephalopathy is found in another species, perhaps in DOGS. Their first reaction was that, as with the cats, the first step could be to investigate whether this was really a new disease, or simply one that had not previously been recognized and to see whether it has any links to BSE, scrapie or other transmissible encephalopathies. Indeed, some members of the Committee seem to regard the whole question of another species as a hypothetical question to be addressed only when it happened. A rather UNSATISFACTORY POSTURE.

12. In advance of your meeting with Dr Tyrrell on Monday morning, I have not voiced my ANXIETIES about the support the Committee is receiving from MAFF to anyone OTHER THAN DR PICKLES. ...

https://web.archive.org/web/20090506040545/http://www.bseinquiry.gov.uk/files/yb/1990/06/14006001.pdf

SPONGIFORM ENCEPHALOPATHY IN A CAPTIVE PUMA

an article in yesterday's Times (attached) which suggested that the puma concerned had never ''eaten any part of a cow or sheep which, in the opinion of Government Scientists, could transmit the species to a different species''.

3. You explained to me that this was INCORRECT. The position was as set out in the briefing for Prime Minister's questions attached to Mr Taylor's note. The puma had probably been fed low quality beef meat in the form of split carcasses. ...

https://web.archive.org/web/20090506032628/http://www.bseinquiry.gov.uk/files/yb/1992/11/13001001.pdf

Subject: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY Date: Thu, 17 Oct 2002 17:04:51 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L

Greetings BSE-L,

is there any other CWD surveys/testing in the UK on their deer? what sort of testing has been done to date on UK/EU deer? any input would be helpful... thank you

DEER SPONGIFORM ENCEPHALOPATHY SURVEY

3. This will be a low key study with no publicity to avoid unnecessary media interest. It will be carried out in two stages ;

(I) A small scale examination of around 30 deer brains to establish the normal histology of the healthy brain; and

(II) A larger scale random examination of 300 or more adult deer brains drawn from both deer farms and parks to establish whether there is any evidence of a cervine spongiform encephalopathy. ...

https://web.archive.org/web/20090506025229/http://www.bseinquiry.gov.uk/files/yb/1991/11/20004001.pdf

Ministry of Agriculture Fisheries and Food Veterinary Investigation Centre West House. Station Road. Thirsk Y07 IPZ Telephone: 0845·522065 Fax: 0845·525224

Your reference

Our reference RJH/ASB

Date 4 November 1992

DEER SPONGIFORM ENCEPHALOPATHY SURVEY

Dear Paul

I have now found time to review the 10 deer- brains collected from Mr Walker farm··via Winchester Via Winchester VIC. In answer to your specific question was there sufficient difference in preservation of brain tissue to warrant the extra effort involved in rapid brain removal on the farm, the answer is definitely "Yes." The original five brains (Winchester ref M487/11) showed varying degrees of autolytic vacuolation affecting both white and grey matter throughout the brain. vacuolation and separation of Purkinje cells and marked perivascular spaces. These artifacts made interpretation of subtle, specific pathological vacuolation more difficult. By contrast the second submission (Winchester reference N736/2) showed excellent preservation of white and grey matter. Any vacuolar Change present could be confidently interpreted as pathological albeit of unknown pathogenesis.

I can only reiterate the comments made by Gerald Wells and myself at the preliminary discussion at Weybridge in Autumn 1991. If the survey's purpose is an accurate histopathological interpretation of brain tissue. the material must be collected in a pristine state. This is particularly valid when looking for ar unrecognised and undefined spongiform encephalopathy in a new species. Deer brains are very large structures which take a lot of fixation and therefore must be handled sympathetically from the start. We have already seen the problems encountered in comparatively smaller hound brains where delayed fixation was a major limitation on interpretation of true pathological change.

The bottom line must be that if a pathologist's expertise is to be used, it is critical to collect artefact free brain material. If the politics or economics do not allow this, then I would suggest that an electron microscopy survey involving detection of scrapie associated fibrils would be much more appropriate.

Best wishes Yours sincerely

R J HIGGINS VIO 92/11.4/2.1

https://web.archive.org/web/20090506032702/http://www.bseinquiry.gov.uk/files/yb/1992/11/04002001.pdf

HOUND SURVEY

I am sorry, but I really could have been a co-signatory of Gerald's minute.

I do NOT think that we can justify devoting any resources to this study, especially as larger and more important projects such as the pathogenesis study will be quite demanding.

If there is a POLITICAL need to continue with the examination of hound brains then it should be passed entirely to the VI Service.

J W WILESMITH Epidemiology Unit 18 October 1991

Mr. R Bradley

cc: Mr. G A H Wells

https://web.archive.org/web/20090506031345/http://www.bseinquiry.gov.uk/files/yb/1991/10/18001001.pdf

***> 3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would by the end of the year, identify the three brains that were from the ''POSITIVE'' end of the lesion spectrum.

https://web.archive.org/web/20090506043913/http://www.bseinquiry.gov.uk/files/yb/1993/12/06001001.pdf

HOUND SURVEY PATHOLOGICAL REPORT (see positive results) and MAD DOGS AND ENGLISHMAN...

ya'll thought i was making this stuff up didn't ya...i don't make this stuff up!

https://web.archive.org/web/20090506035936/http://www.bseinquiry.gov.uk/files/yb/1990/11/28001001.pdf

It is clear that the designing scientists must also have shared Mr Bradley's surprise at the results because all the dose levels right down to 1 gram triggered infection.

https://web.archive.org/web/20090506002904/http://www.bseinquiry.gov.uk/files/ws/s145d.pdf

second supplementary

https://web.archive.org/web/20090506004507/http://www.bseinquiry.gov.uk/files/ws/s147f.pdf

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

see references:

DEER BRAIN SURVEY

https://web.archive.org/web/20090506025229/http://www.bseinquiry.gov.uk/files/yb/1991/11/20004001.pdf

1993 cjd report finds relationship with eat venison and cjd increases 9 fold, let the cover up begin...tss

https://webarchive.nationalarchives.gov.uk/.../00001001.pdf

FINDINGS

*** 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)..

snip...

snip...see full report ;

https://web.archive.org/web/20170126073306/http://collections..europarchive..org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf

GAME FARM INDUSTRY WANTS TO COVER UP FINDINGS OF INCREASE RISK TO CJD FROM CERVID

BSE INQUIRY

CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane

BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf

Management In Confidence

BSE: Private Submission of Bovine Brain Dealler

https://web.archive.org/web/20090506043910/http://www.bseinquiry.gov.uk/files/yb/1993/12/08003001.pdf

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: <3daf5023 .4080804="" a="" href="http://wt.net/" nbsp="" rel="noopener noreferrer" style="color: blue; cursor: pointer;" target="_blank">wt.net

="">

Dear Terry,

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

Steve Dealler

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

===============

https://caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html

*** DEFRA TO SINGELTARY ON HOUND STUDY AND BSE 2001 ***

DEFRA Department for Environment, Food & Rural Affairs Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk GTN: FAX: Mr T S Singeltary P.O. Box Bacliff Texas USA 77518 21 November 2001

Dear Mr Singeltary

TSE IN HOUNDS Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding. As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.

Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.

Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to peer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less critical.

For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf

new url;

https://web.archive.org/web/20040513023227/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf

As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address. Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK

You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any su

https://caninespongiformencephalopathy.blogspot.com/

===============

U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001

Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001

Date: Tue, 9 Jan 2001 16:49:00 -0800

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de

snip...

[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.

[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?

[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]

[host Richard] could you repeat the question?

[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?

[not sure whom ask this] what group are you with?

[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.

[not sure who is speaking] could you please disconnect Mr. Singeltary

[TSS] you are not going to answer my question?

[not sure whom speaking] NO

snip...see full archive and more of this;

http://tseac.blogspot.com/2011/02/usa-50-state-bse-mad-cow-conference.html

===============

2019

cwd scrapie pigs oral routes

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

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

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

***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period.

This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.

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

https://www.ars.usda.gov/research/publications/publication/?seqNo115=353091

https://www.ars.usda.gov/research/project/?accnNo=432011&fy=2017

https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105

Scrapie Transmits To Pigs By Oral Route, what about the terribly flawed USA tse prion feed ban?

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

2017 Annual Report

1a. Objectives (from AD-416):

Objective 1: Investigate the mechanisms of protein misfolding in prion disease, including the genetic determinants of misfolding of the prion protein and the environmental influences on protein misfolding as it relates to prion diseases. Subobjective 1.A: Investigate the differences in the unfolded state of wild-type and disease associated prion proteins to better understand the mechanism of misfolding in genetic prion disease. Subobjective 1.B: Investigate the influence of metal ions on the misfolding of the prion protein in vitro to determine if environmental exposure to metal ions may alter disease progression. Objective 2: Investigate the pathobiology of prion strains in natural hosts, including the influence of prion source genotype on interspecies transmission and the pathobiology of atypical transmissible spongiform encephalopathies (TSEs). Subobjective 2.A: Investigate the pathobiology of atypical TSEs. Subobjective 2.B: Investigate the influence of prion source genotype on interspecies transmission. Objective 3: Investigate sampling methodologies for antemortem detection of prion disease, including the utility of blood sampling as a means to assess prion disease status of affected animals and the utility of environmental sampling for monitoring herd prion disease status. Subobjective 3.A: Investigate the utility of blood sampling as a means to assess prion disease status of affected animals. Subobjective 3.B: Investigate the utility of environmental sampling for monitoring herd prion disease status.

1b. Approach (from AD-416):

The studies will focus on three animal transmissible spongiform encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease (CWD) of deer, elk, and moose. The research will address sites of protein folding and misfolding as it relates to prion disease, accumulation of misfolded protein in the host, routes of infection, and ante mortem diagnostics with an emphasis on controlled conditions and natural routes of infection. Techniques used will include spectroscopic monitoring of protein folding/misfolding, clinical exams, histopathology, immunohistochemistry, and biochemical analysis of proteins. The enhanced knowledge gained from this work will help understand the underlying mechanisms of prion disease and mitigate the potential for unrecognized epidemic expansions of these diseases in populations of animals that could either directly or indirectly affect food animals.

3. Progress Report:

All 8 project plan milestones for FY17 were fully met. Research efforts directed toward meeting objective 1 of our project plan center around the production of recombinant prion protein from either bacteria or mammalian tissue culture systems and collection of thermodynamic data on the folding of the recombinant prion protein produced. Both bacterial and mammalian expression systems have been established. Thermodynamic data addressing the denatured state of wild-type and a disease associated variant of bovine prion protein has been collected and a manuscript is in preparation. In research pertaining to objective 2, all studies have been initiated and animals are under observation for the development of clinical signs. The animal studies for this objective are long term and will continue until onset of clinical signs. In vitro studies planned in parallel to the animals studies have similarly been initiated and are ongoing. Objective 3 of the project plan focuses on the detection of disease associated prion protein in body fluids and feces collected from a time course study of chronic wasting disease inoculated animals. At this time samples are being collected as planned and methods for analysis are under development.

4. Accomplishments

1. Showed that swine are potential hosts for the scrapie agent. A naturally occurring prion disease has not been recognized in swine, but the agent of bovine spongiform encephalopathy does transmit to swine by experimental routes. Swine are thought to have a robust species barrier when exposed to the naturally occurring prion diseases of other species, but the susceptibility of swine to the agent of sheep scrapie has not been thoroughly tested. ARS researchers at Ames, Iowa conducted this experiment to test the susceptibility of swine to U.S. scrapie isolates by intracranial and oral inoculation. Necropsies were done on a subset of animals at approximately 6 months post inoculation (PI): the time the pigs were expected to reach market weight. Remaining pigs were maintained and monitored for clinical signs of transmissible spongiform encephalopathies (TSE) until study termination at 80 months PI or when removed due to intercurrent disease. Brain samples were examined by multiple diagnostic approaches, and for a subset of pigs in each inoculation group, bioassay in mice expressing porcine prion protein. At 6 months PI, no evidence of scrapie infection was noted by any diagnostic method. However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.

2. Determined that pigs naturally exposed to chronic wasting disease (CWD) may act as a reservoir of CWD infectivity. Chronic wasting disease is a naturally occurring, fatal, neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of CWD disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Pigs were assigned to 1 of 3 groups: intracranially inoculated; orally inoculated; or non-inoculated. At market weight age, half of the pigs in each group were tested ('market weight' groups). The remaining pigs ('aged' groups) were allowed to incubate for up to 73 months post inoculation (MPI). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by multiple diagnostic methods. Brain samples from selected pigs were bioassayed in mice expressing porcine prion protein. Some pigs from each inoculated group were positive by one or more tests. Bioassay was positive in 4 out of 5 pigs assayed. Although only small amounts of PrPSc were detected using sensitive methods, this study demonstrates that pigs can serve as hosts for CWD. Detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds. These results indicating the susceptibility of pigs to CWD, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.

3. Developed a method for amplification and discrimination of the 3 forms of BSE in cattle. The prion protein (PrP) is a protein that is the causative agent of transmissible spongiform encephalopathies (TSEs). The disease process involves conversion of the normal cellular PrP to a pathogenic misfolded conformation. This conversion process can be recreated in the lab using a misfolding amplification process known as real-time quaking induced conversion (RT-QuIC). RT-QuIC allows the detection of minute amounts of the abnormal infectious form of the prion protein by inducing misfolding in a supplied substrate. Although RT-QuIC has been successfully used to detect pathogenic PrP with substrates from a variety of host species, prior to this work bovine prion protein had not been proven for its practical uses for RT-QuIC. We demonstrated that prions from transmissible mink encephalopathy (TME) and BSE-infected cattle can be detected with using bovine prion proteins with RT-QuIC, and developed an RT-QuIC based approach to discriminate different forms of BSE. This rapid and robust method, both to detect and discriminate BSE types, is of importance as the economic implications for different types of BSE vary greatly.

Review Publications

Hwang, S., Greenlee, J.J., Nicholson, E.M. 2017. Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect cattle transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-type bovine spongiform encephalopathy. PLoS One. 12(2):e0172391.

Moore, S., Kunkle, R., Greenlee, M., Nicholson, E., Richt, J., Hamir, A., Waters, W., Greenlee, J. 2016. Horizontal transmission of chronic wasting disease in reindeer. Emerging Infectious Diseases. 22(12):2142-2145. doi:10.3201/eid2212.160635.

Moore, S.J., West Greenlee, M.H., Smith, J.D., Vrentas, C.E., Nicholson, E.M., Greenlee, J.J. 2016. A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation. Frontiers in Veterinary Science. 3:78.

Greenlee, J.J., Kunkle, R.A., Smith, J.D., West Greenlee, M.H. 2016. Scrapie in swine: a diagnostic challenge. Food Safety. 4(4):110-114. Kondru, N., Manne, S., Greenlee, J., West Greenlee, H., Anantharam, V., Halbur, P., Kanthasamy, A., Kanthasamy, A. 2017. Integrated organotypic slice cultures and RT-QuIC (OSCAR) assay: implications for translational discovery in protein misfolding diseases. Scientific Reports. 7:43155. doi:10.1038/srep43155.

Mammadova, N., Ghaisas, S., Zenitsky, G., Sakaguchi, D.S., Kanthasamy, A.G., Greenlee, J.J., West Greenlee, M.H. 2017. Lasting retinal injury in a mouse model of blast-induced trauma. American Journal of Pathology. 187(7):1459-1472. doi:10.1016/j.ajpath.2017.03.005.

https://www.ars.usda.gov/research/project/?accnNo=432011&fy=2017

FRIDAY, APRIL 20, 2018

*** Scrapie Transmits To Pigs By Oral Route, what about the terribly flawed USA tse prion feed ban?

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

http://scrapie-usa.blogspot.com/2018/04/scrapie-transmits-to-pigs-by-oral-route.html

back in time...

why do we not want to do TSE transmission studies on chimpanzees $

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man.

***> I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough.

***> Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

https://web.archive.org/web/20090506041740/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

*** ''but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.''

CONFIDENTIAL SPONGIFORM ENCEPHALOPATHY OF PIGS

CONFIDENTIAL

Ref: Pigs10i

IN CONFIDENCE

Dr. Metters

From Dr. H Pickles Med ISD/3

Date 10 September 1990

Copy: Dr G Jones Mr D Hagger Mr T Murray (o/r) Dr D Harper Dr Richardson Mrs Shersby

SPONGIFORM ENCEPHALOPATHY OF PIGS

1. There has been a preliminary meeting of the Tyrrell committee today to discuss the significance of the pig experiment in the light of other evidence, for example on feline spongiform encephalopathy.

2. The preliminary conclusions were:

we now know pigs are capable of expressing spongiform encephalopathy. Previously this had been doubted.

the clinical picture in pigs exposed to agent by these doses/routes is fairly distinctive and unlikely to have gone unrecognised.

even so improved monitoring/surveillance of neurological disease in older pigs should be considered.

feeding of the "specified offal" (ie nervous/lymphoid tissue from cattle) should no longer be permitted, to pigs or to any other species.

*** but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.

if one natural field case of spongiform encephalopathy were described in a pig, we would need a ban on offal from for human consumption.

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

90/9.10/7.1

whilst any such action on pharmaceuticals/devices is for others to decide, this group (which includes 4 key members of the CSM group) suggests non-UK sources should now be used, at least for "high risk" pharmaceuticals and devices (ie for those from nervous or RE System)

3. The full committee will meet on the 19th to confirm these conclusions, to review experimental protocols of transmission experiments, to reconsider the cat position in the light of additional cases and to consider scrapie in sheep and goats. In view of Mr Gummer's earlier commitments, we assume he willI want to go public on the pig soon after, so the Tyrrell committee will also prepare a brief written statement.

4. You may want to consider with the MCA and the Medical Device Agency what preparatory action is appropriate in anticipation of the formal advice from the Tyrrell group. The CSM subgroup not due to meet until the 31 October.

Hilary Pickles Room 414 Eileen House Ext: 22832

http://web.archive.org/web/20030822031154/www.bseinquiry.gov.uk/files/yb/1990/09/10007001.pdf

CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

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

http://web.archive.org/web/20031026000118/www.bseinquiry.gov.uk/files/yb/1990/08/23004001.pdf

http://web.archive.org/web/20030822031154/www.bseinquiry.gov.uk/files/yb/1990/09/10007001.pdf

May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...

http://web.archive.org/web/20030822052332/www.bseinquiry.gov.uk/files/yb/1990/09/11005001.pdf

3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...

http://web.archive.org/web/20030822052438/www.bseinquiry.gov.uk/files/yb/1990/09/12002001.pdf

But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...

http://web.archive.org/web/20030518170213/www.bseinquiry.gov.uk/files/yb/1990/09/13004001.pdf

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

http://web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf

snip...

It was not until . . . August 1990, that the result from the pig persuaded both SEAC and us to change our view and to take out of pig rations any residual infectivity that might have arisen from the SBOs.

http://web.archive.org/web/20071014143511/http://www.bseinquiry.gov.uk/files/tr/tab69.pdf

4.303 The minutes of the meeting record that:

It was very difficult to draw conclusions from one experimental result for what may happen in the field. However it would be prudent to exclude specified bovine offals from the pig diet. Although any relationship between BSE and the finding of a spongiform encephalopathy in cats had yet to be demonstrated, the fact that this had occurred suggested that a cautious view should be taken of those species which might be susceptible. The 'specified offals' of bovines should therefore be excluded from the feed of all species. 17

http://web.archive.org/web/20031026084516/http://www.bseinquiry.gov.uk/files/yb/1990/09/07001001.pdf

IN CONFIENCE

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

1. CMO should be aware that a pig inoculated experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months developed an illness, now confirmed as a spongiform encephalopathy. This is the first ever description of such a disease in a pig, although it seems there ar no previous attempts at experimental inoculation with animal material. The Southwood group had thought igs would not be susceptible. Most pigs are slaughtered when a few weeks old but there have been no reports of relevant neurological illness in breeding sows or other elderly pigs. ...see full text ;

http://web.archive.org/web/20040302031004/www.bseinquiry.gov.uk/files/yb/1990/08/23001001.pdf

IN CONFIDENCE

So it is plausible pigs could be preclinically affected with BSE but since so few are allowed to reach adulthood this has not been recognised through clinical disease. ...

http://web.archive.org/web/20040904150118/www.bseinquiry.gov.uk/files/yb/1990/08/23002001.pdf