Norway, Nordfjella VKM 2018 16 Factors that can contribute to spread of CWD TSE Prion UPDATE December 14, 2018
Report from the Norwegian Scientific Committee for Food and Environment (VKM) 2018: 16 Factors that can contribute to spread of CWD – an update on the situation in Nordfjella, Norway
Opinion of Panel on biological hazards of the Norwegian Scientific Committee for Food and Environment
13.12.2018
ISBN: 978-82-8259-316-8
ISSN: 2535-4019
Norwegian Scientific Committee for Food and Environment (VKM)
Po 222 Skøyen
0213 Oslo
Norway
Phone: +47 21 62 28 00
Email: vkm@vkm.no
vkm.no
vkm.no/English
Cover photo: Wild reindeer visiting a mineral lick in early spring. Aerial photo by Roy Andersen, NINA.
Suggested citation: VKM, Bjørnar Ytrehus, Danica Grahek-Ogden, Olav Strand, Michael Tranulis, Atle Mysterud, Marina Aspholm, Solveig Jore, Georg Kapperud, Trond Møretrø, Truls Nesbakken, Lucy Robertson, Kjetil Melby, Taran Skjerdal. (2018) Factors that can contribute to spread of CWD – an update on the situation in Nordfjella, Norway. Opinion of the Panel on biological hazards. ISBN: 978-82-8259-316-8. Norwegian Scientific Committee for Food and Environment (VKM), Oslo, Norway.
VKM Report 2018: 16
Factors that can contribute to spread of CWD – an update on the situation in Nordfjella, Norway
Preparation of the opinion
The Norwegian Scientific Committee for Food and Environment (Vitenskapskomiteen for mat og miljø, VKM) appointed a project group to answer the request from the Norwegian Food Safety Authority. The project group consisted of one VKM member of the Panel on Microbial Ecology, two external experts and a project leader from the VKM secretariat. An external referee commented on and reviewed the manuscript. The VKM Panel on biological hazards evaluated and approved the final opinion drafted by the project group.
Authors of the opinion
Members of the project group that contributed to the drafting of the opinion (in alphabetical order after chair of the project group):
Bjørnar Ytrehus – Chair of the project group and member of the Panel on Microbial Ecology.
Affiliation: 1) VKM; 2) Norwegian Institute for Nature Research (NINA)
Danica Grahek-Ogden – Project leader from the VKM secretariat. Affiliation: VKM Atle Mysterud - Member of the project group. Affiliation: 1) University of Oslo (UiO) Olav Strand - Member of the project group. Affiliation: 1) Norwegian Institute for Nature Research (NINA)
Michael Tranulis – Member of the project group. Affiliation: 1) Norwegian University of Life Sciences (NMBU)
Members of the Panel on biological hazards that contributed to the assessment and approval of the opinion (in alphabetical order):
Marina Elisabeth Aspholm - Affiliation: 1) VKM; 2) Norwegian University of Life Sciences (NMBU)
Solveig Jore – Affiliation: 1) VKM; 2) Norwegian Institute of Public Health (NIPH) Georg Kapperud – Affiliation: 1) VKM; 2) Norwegian Institute of Public Health (NIPH) Kjetil Klaveness Melby - Affiliation: 1) VKM; 2) Oslo University Hospital/ University of Oslo (UiO)
Trond Møretrø – Affiliation: 1) VKM; 2) NOFIMA
Truls Nesbakken – Affiliation: 1) VKM; 2) Norwegian University of Life Sciences VKM Report 2018: 16
Lucy Robertson – Affiliation: 1) VKM; 2) Norwegian University of Life Sciences Olaug Taran Skjerdal - Affiliation: 1) VKM; 2) Norwegian Veterinary Institute
Acknowledgment
VKM would like to thank Geir Rune Rauset (Norwegian Institute for Nature Research, NINA) for excellent help with map and GIS analysis and Michael Angeloff (Norwegian Institute for Bioeconomy, NIBIO) for kindly providing data on sheep grazing and farming. Erling Solberg (Norwegian Institute for Nature Research, NINA), Erling Meisingset (Norwegian Institute of Bioeconomy Research, NIBIO) and Christer Rolandsen (Norwegian Institute for Nature Research, NINA) are thanked for their contribution on moose, red deer and roe deer population development and movement patterns, and André Høva, Torodd Urnes and several other officers in Norwegian Food Safety Authority (NFSA) for sharing knowledge and data on the efforts performed to combat CWD. We are also in debt to Runar S. Bjøberg and Asgrim Opdal in Filefjell reinlag who shared knowledge about their reindeer herd, and Harald Skjerdal in Aurland fjellstyre who gave us information about his work to prevent contact between Zone 1 and 2. We are also thankful to Roar Gudding (VKM and Norwegian Veterinary Institute) for providing constructive criticism.
Competence of VKM experts
Persons working for VKM, either as appointed members of the Committee or as external experts, do this by virtue of their scientific expertise, not as representatives for their employers or third party interests. The Civil Services Act instructions on legal competence apply for all work prepared by VKM.
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Table of Contents
Summary................................................................................................................ 7
Sammendrag på norsk ......................................................................................... 11
Background and terms of reference as provided by the Norwegian Food Safety
Authority ...................................................................................................... 15
1 Introduction................................................................................................. 16
Definitions of areas described in this report............................................................17
Management actions already enforced...................................................................18
Eradication of affected herd .......................................................................19
Nation-wide surveillance for CWD...............................................................19
Efforts to eliminate “hotspots” for transmission............................................20
Efforts to minimize entry and transit of wild or semi-domesticated reindeer into Zone 1 24
Population reduction in neighbour areas......................................................25
Scientific projects initiated ....................................................................................25
Bioassay experiments in laboratory rodents .................................................25
Oral inoculation of newborn lambs with VRQ/VRQ PrP genotype....................26
Samples of rectal tissue and faeces from sheep that have grazed in Nordfjella Z1 26 PRNP-genetic analysis of cervids in Fennoscandia ........................................27
Supplementary salt licks as a potential transmission hot spot for CWD prions .27
2 Literature search.......................................................................................... 28
Relevance screening.............................................................................................28
3 Hazard identification and characterisation .................................................. 28
Environmental reservoirs ......................................................................................28
Transmission of prions and the transmission barrier................................................30
Carriers of disease ...............................................................................................33
“Preclinical carriers”: Animals shedding infectious prions during the incubation period 33
“Nonclinical carrier” ...................................................................................35
“Latent carriers”:.......................................................................................36
“Passive carrier”:.......................................................................................36
Non-biological mechanical transport of CWD prions ......................................38
Cervids in Nordfjella.............................................................................................38
Wild reindeer ............................................................................................38
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3.4.1.1 Large scale drivers and factors external to Nordfjella .................................38
3.4.1.2 Local drivers in Nordfjella ........................................................................40
3.4.1.3 Translocation of reindeer from Nordfjella to other areas.............................41
Semi-domesticated reindeer in Filefjell Reinlag.............................................42
Red deer ..................................................................................................46
Moose ......................................................................................................46
Roe deer ..................................................................................................47
Domestic animals grazing in Nordfjella...................................................................47
Use of mineral licks ..............................................................................................52
Mineral licks and animal movements ...........................................................54
The difficulty of restoring mineral licks...................................................................54
Human activities in Nordfjella................................................................................56
4 Exposure characterisation............................................................................ 58
Environmental contamination in Nordfjella .............................................................58
Transmission of CWD to reindeer ..........................................................................62
Transmission to other cervids (preclinical and/or nonclinical carriers) .......................63
Transmission by sheep and other livestock (nonclinical and/or passive carriers) ........64
Transmission with passive carriers.........................................................................65
Mechanical transport of CWD infectivity .................................................................67
Concluding remarks on exposure characterisation...................................................67
5 Conclusion with answers to the request ...................................................... 68
6 Data gaps ..................................................................................................... 71
7 References ................................................................................................... 73
8 Appendix I.................................................................................................... 83
Cervid populations in Nordfjella Management Area .................................................83
Distribution and population development ...............................................................84
Movements and migrations ........................................................................86
8.2.1.1 Reindeer................................................................................................87
8.2.1.2 Red deer................................................................................................88
8.2.1.3 Moose ...................................................................................................88
8.2.1.4 Roe deer................................................................................................88
The role of salt licks for cervid distribution...................................................88
9 Appendix II .................................................................................................. 91
Sheep farming in Norway .....................................................................................91
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Summary
In spring 2018 the last wild reindeer in Zone 1 in Nordfjella wildlife area was shot. In total 2024 wild reindeer were killed, mostly through culling organized by the Norwegian Nature Inspectorate. The background for this measure, unparalleled in Norwegian game management, was the detection of the contagious and lethal Chronic Wasting Disease (CWD) in the spring 2016.
CWD is well known from North America where experiences and research have shown that disease is very difficult to eradicate. This is, among other things, due to infected animals going through a long incubation period when they shed infectious agents but do not show signs of disease. They act as silent carriers.
Infected animals can shed prions, for example through saliva, urine and faeces infecting other animals directly or by contaminating the environment where prions can then be picked up by a susceptible animal.
Another important aspect is that the infectious agent, misfolded proteins called prions, are very resilient. They can withstand radiation, heat and chemicals better than most contaminants we know. This allows them to "survive", ie, to be infectious in the environment for many years. The prions have also the ability to bind to soil, and they can be taken up in plants.
On that background, the Norwegian Food Safety Authority asked for an update of important factors affecting the spread of CWD within and out of the Nordfjella area.
CWD, in the form known from North America, has so far only been found in the wild reindeer population in Nordfjella Zone 1. Due to the resilience of prions, we must expect that they still persist in the areas used by the eradicated wild reindeer herd. Also, we cannot exclude that infected cervids can be found in the populations surrounding Nordfjella Zone 1. The prevalence of infected animals were low and the herd roamed over large mountain areas. In theory, this reduces the likelihood that new animals will contract infection from the environment. However, environmental conditions that promote aggregation of many animals in small areas will significantly increase the likelihood of contracting infection from the environment. A large number of mineral licks are placed in Nordfjella. These are attractive also for reindeer and other cervids. Many of the mineral licks are placed in areas used by the now exterminated wild reindeer population. Mineral licks and their surroundings, surfaces of both rocks, soil, plants, lichen could have been contaminated by saliva, urine and faeces from infected animals. As the soil around a mineral lick will be rich in salt, cervids and sheep will not only visit the lick itself but also lick or eat soil from the surrounding area. Since it is known that prions bind to and can survive for long time in soil, this could lead to prolonged exposure to infectious agents left behind by the extinct population.
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Recent studies indicate that the prion isolated from the wild reindeer in Nordfjella is somewhat different from the strains found and investigated in North America. This may mean that the infectious potential and the development of disease in different species may deviate from what one would expect if it was similar prion type. However, we must assume that reindeer is easily susceptible to infection and has a disease development similar to that seen in North America. We must also assume that other cervids are susceptible, but we cannot tell how quickly the disease would develop. This, and the fact that cervids exposed to environmental contamination, may be exposed to low doses of contaminants, can cause the disease to develop slowly. In that case, the probability for silent carriers among cervids around Zone 1 would increase. Based on a combination of what we currently know about the degree of contact between populations and what we can say about susceptibility, we consider the probability for silent carriers within the Nordfjella area greatest for the wild reindeer population in Nordfjella Zone 2, the wild red deer in Lærdal and Aurland and the semi-domesticated reindeer in Filefjell. We assess the likelihood that there are such animals in the wild reindeer population in Lærdals-Årdalsfjella or red deer, moose or roe deer in other parts of the Nordfjella area to be lower.
Very high density of cervids in the areas around Zone 1 increases the likelihood of infection since the number of cervids visiting Zone 1 increases proportionally to population. We cannot say that mineral lick sites are important for attracting cervids into the area, but they represent points where the deer can still contract infection. A large population would also require more extensive testing to reach adequate level of certainty considering the absence of silent carriers. A significant reduction in cervid population would reduce the likelihood of new animals being infected and increase the likelihood of any contaminated animals being removed while increasing the knowledge of where the infection occurs.
Nordfjella has long been an important grazing area, not least for sheep. Every year there are several tens of thousands of sheep on summer pastures there. Most of the sheep belong in the area close to the Nordfjella, while others come from far away, on a so-called guest pasture. In recent decades, the use of man-made, permanent mineral licks has become common in sheep management. The licks help to supplement the sheep's salt needs and facilitate the observation and control of the animals on mountain pastures. However, in the areas previously occupied by the infected reindeer population, the mineral licks will increase the probability for the sheep to be exposed to CWD prions. We believe the likelihood that the sheep may become infected and develop disease is very small. However, a hypothetical and poorly investigated possibility is that the sheep can become silent carriers not developing the disease but still spreading small amounts of infectious agent. The probability of transmission of CWD from Nordfjella Zone 1 to other cervid populations by this mode is considered small, but cannot be excluded. In addition, sheep and other animals moving in Zone 1 can ingest prions which then are passed through the digestive tract, and wool and hooves can be contaminated with soil containing infectious material. However, a series of unfortunate circumstances must occur if CWD prions are to be transferred from Nordfjella to cervids in new locations in this way. This is very unlikely in a case of a single sheep, but as there are several tens of thousands of sheep on the pasture, this cannot be entirely disregarded. Sheep that has been on a guest pasture in Nordfjella, and then being transported home to a
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completely different area and released on a farm there, represents a special challenge in this context, as the preparedness for and monitoring of possible outbreak of CWD supposedly is lower there than in Nordfjella area.
Other animals (scavengers, carnivores, rodents, etc.) inhabiting Nordfjella can also be considered to carry infection. The number of those animals, the degree of contact and/or the degree of susceptibility is assumed to be low, hence the likelihood of the transmission of contamination within or out of the Nordfjella area is considered to be very low. It has been shown that canids and crows ingesting prion-containing material are capable of passing infectious prions in their faeces, and this confer a low risk of spread.
The same applies also to mechanical transport of infection by humans via, for example, excrements and soil on boots, vehicles or equipment. It is not very likely that such transmission of infection would cause outbreak of CWD in other cervid populations. However, humans can move far and unpredictably, so the infection may appear in completely unexpected locations where there is no monitoring and preparedness.
More than 200 mineral licks are registered in the area where CWD was detected. In addition, there are another 500 mineral licks placed in other parts of the Nordfjella area. Mineral licks in the Zone 1 represent the greatest known potential source for further spread of CWD, both to nearby cervid populations and via sheep. The likelihood of spreading would be significantly reduced by removing these possible sources of infection.
Presence of the remaining mineral licks in the area and the placement of new ones would represent a hazard if infected animals still live in the area or if new animals get infected from the environment. Mineral lick sites would then most likely represent effective points for spread of infection. Reduction of the number of mineral licks would therefore be an important preventive measurement for reducing this probability of spread of infection. An important issue in this context is that we do not yet have a simple, feasible method either for the detection of prions in the environment or for decontamination of mineral licks and surrounding areas. Therefore, the reduction of the numbers of those places would reduce the potential efforts related to a reoccurring outbreak.
Based on the current knowledge, but with considerable uncertainty, we have identified the following factors being able to contribute to the spread of CWD from and within the Nordfjella area:
1. Presence of undetected carriers of CWD in cervid populations around Zone 1; either animals that were infected before the wild reindeer population was eradicated or animals exposed to environmental contamination in Zone 1 after the eradication. The probability of this is considered to be greatest for the red deer in Lærdal and Aurland, the wild reindeer population in Zone 2 and semi-domesticated reindeer population in Filefjell.
2. Reindeer from Zone 2 or Filefjell that moves into Zone 1 and becomes infected.
3. Red deer, moose and roe deer from the nearby populations entering Zone 1 and becoming infected.
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4. Sheep grazing in Zone 1 and carrying infectious material to susceptible cervid populations.
5. Human activity in Zone 1, transporting infectious material to susceptible cervid populations.
6. Other animals present in Zone 1 carrying infectious material from there to susceptible cervid populations.
In each of these cases, the number of currently available mineral lick sites previously used by eradicated wild reindeer population in Zone 1, have a great importance for the likelihood of spread of infection. The likelihood of cervids entering Zone 1 becoming infected would be greatly reduced if these sites were not available. Equally, the likelihood of sheep transferring the infection will be significantly reduced.
The likelihood that any carriers outside Zone 1 would spread the infection to new areas and that the disease becomes established there can be reduced by continued intensive monitoring, high alertness and preparedness. General reduction in the number of mineral lick sites and other places where cervids gather, reduction in the density of the nearby cervid populations, measures minimizing animal movements between areas and continued information to humans using the area would also help to reduce the likelihood of infection spreading.
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Below, we summarize the main elements discussed in this report, regarding probabilities for dissemination of CWD prions within and beyond Nordfjella. The emphasis is on variables that can be adjusted through management:
• Continued use and/or inadequate closing/clean-up of mineral licks previously used by wild reindeer in Zone 1
o High probability of CWD transmission. Wild reindeer from Zone 2 or semidomestic reindeer from Filefjell reinlag entering Zone 1 and visiting mineral lick areas.
o Moderate to high probability of transmission. Entry of red deer and moose into Zone 1 with visit of mineral lick areas. We do not know the sensitivity of red deer or moose to the Nordfjella CWD strain, but high sensitivity is assumed. High-density populations of red deer and moose probably increase the number of animals entering Zone 1.
o Low to moderate probability for passive transmission. Sheep visiting mineral lick areas and subsequent passive spread to cervids
o Low/unknown probability for spread via nonclinical carriers among sheep
o Very low probability of transmission via sheep that are infected and develop clinical CWD
Taking into consideration that CWD-infected cervids might be present (undetected) in contact populations surrounding Zone 1 (i.e. Zone 2, Filefjell reinlag, red deer, roe deer and moose in the Management Area), the following scenarios are relevant:
• Continued spread from infected reindeer in Zone 2, Filefjell or any of the reindeer herds that have received animals translocated from Nordfjella to other animals in the same population and to neighbouring cervid populations. Enhanced surveillance, followed by adequate measures, will minimize this probability.
• Southward movement of CWD infected wild reindeer from Zone 2 to Hardangervidda and direct (unlikely) or indirect (more likely if mineral licks are present) spread of CWD to the main Hardangervidda population. If this occurred, it would escalate the challenges of CWD substantially. Enhanced surveillance and decreased population size, especially of reindeer males, will minimize this probability.
• Continued spread from infected red deer, moose or roe deer in the populations around Zone 1. The probability of presence of such cases in the large red deer populations in the western part of the area, having a very high density and documented space use and visits of mineral licks within Zone 1, both before and after the eradication, must be regarded to be relatively high in this context. If undetected spread of CWD within these populations occurs, further spread to new areas has to
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be expected due to extensive seasonal migrations. Enhanced surveillance combined with population reduction will minimize this probability.
• Since absence of CWD infected cervids in the periphery of Zone 1 cannot be completely confirmed, establishment of new mineral licks inside Zone 1 and continued use of mineral licks in Zones 2 and 0, might facilitate spread of the prion agents if carriers shedding infectious prions are present or reappear, with mineral licks being hotspots for disease transmission. Reduction in the number of mineral licks will decrease this probability.
• The combination of high numbers of sheep grazing in Nordfjella with access to mineral lick sites, particularly those in Zone 1, but also elsewhere, increase the probability of passive transmission via sheep both within Zone 1 and out of the zone to other areas of Nordfjella. The probability that this should cause transmission to cervids is regarded to be very low for each case, but the cumulative probability might be low to moderate, depending on (among other things) the number of sheep that are put on home pastures accessible for cervids. is not negligible.
• High numbers of “guest grazing” sheep in Nordfjella that are subsequently transported to their home range, increase the probability of long-distance spread of CWD.
• Inadequate cleaning and/or disinfection of equipment, vehicles or garment used in Nordfjella increase probability of mechanical CWD spread. The probability of this causing spread to susceptible cervids is regarded as low but cannot be neglected.
• Non-ruminant animals (and humans) visiting Nordfjella and transporting contaminated material either in gastrointestinal tract or as dirt in feathers or fur and/or on feet cannot be excluded but is not regarded to represent a high probability of transmission to susceptible cervids.
6 Data gaps
Hazard identification and characterization
• The level and distribution of environmental CWD contamination in Nordfjella is unknown.
• The environmental persistence of the CWD strain in Nordfjella is unknown, especially the interaction between the prions and the soil and rocks in Nordfjella and the impact of the variable and moist weather there.
• The range of species susceptible to the Nordfjella CWD strain is unknown. Precautionary measures suggest that all cervids should be regarded susceptible.
• The transmission rate of the current strain in different Norwegian species of cervids
• The disease’s course of infection with the strain in Nordfjella in different species of cervids and in eventual other species that prove to be susceptible.
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• The ability of sheep and other species to act as nonclinical carriers that shed (small amounts) of prions without developing disease.
• The persistence and infectivity of prions in plants.
• The true prevalence or absence of CWD in cervid populations that have had contact with wild reindeer from NF-Z1 or their excreta.
• The number of reindeer (wild or semi-domesticated) that enter Nordfjella Zone 1 is unknown (assumed to be very low).
• The numbers of red deer and moose that enter and/or cross into Nordfjella Zone 1 is unknown.
• Whether mineral licks in Nordfjella Zone 1 (or other areas) attract cervids and thereby increase the number of animals entering from surrounding populations is unknown.
• The susceptibility of non-cervid species, such as livestock and humans to the Nordfjella CWD strain is unknown. Epidemiological and experimental evidence form North-America and studies of similar CWD strains suggest that livestock and humans share a very low susceptibility towards CWD prions in general. However, with the advent of new strains, this must be carefully investigated in each case.
• Whether sheep or other species can act as nonclinical carriers that might shed (small amounts) of prions without themselves developing CWD, is not known. Exposure characterization
• How many carcasses of animals that have died from or with CWD have there been in Nordfjella
• The amount of CWD prions in different areas and sites of Nordfjella
• How many wild red deer and moose are exposed to CWD prions and how often does this occur
• The infectious dose of CWD prions in various susceptible species
• The consequence of exposure to repeated small doses of CWD prions on disease progression
• The spatiotemporal movement patterns of reindeer males, red deer, moose and roe deer in the area
• The destiny of the semi-domesticated reindeer at Geitrygghytta
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7 References
NORWAY Skrantesjuke CHRONIC WASTING DISEASE CWD TSE PRION
(the following page is electronically google language translated, may be errors...terry)
Scratch Disease (CWD) - Changes in CWD Zone Regulations Published 30.11.2018 Last changed 30.11.2018 Print The Ministry of Agriculture and Food has established changes to the CWD zone regulation
The background for the changes in the CWD zone regulation is that there is a need to change the rules in line with known knowledge, the disease picture and the occurrence of the disease, in order to combat and prevent the spread of scarcity as best as possible.
The changes are as follows:
Changing the zone limit for the Nordfjella zone in Ulvik municipality. The ox peninsula is excluded because the zone boundary should be defined by natural geographical boundaries. The rest of Ulvik municipality will still be covered by the zone regulations and is therefore not affected by the changes. The introduction of a ban in the Nordfjella zone against catching deer animals from the zone to deer facilities in captivity in the zone. This is because we want to prevent infectious spread in and from the zones, and therefore it is already a ban on the removal of live and dead deer from the zones. However, it is currently permitted to move live and dead deer inside the zones of the regulation. When breeding facilities for deer and zoos collect wild deer to their plant, this can also be a risk of infection. Prescription of injunctions to indicate location or GPS coordinates for licking places for the Food Safety Authority for those who have or during the past five years have had the licking stall standing in the Nordfjella zone. This because the lung areas in Nordfjella constitute a risk of infection. It is necessary to classify how infectious the various licking sites are to provide a basis for proper management of these. For this reason, it is essential and necessary that the Norwegian Food Safety Authority has knowledge of the location of the licking sites, both active and previously used licking places. The introduction of a rule that the Norwegian Food Safety Authority may, without the consent of the landowner, take the necessary measures to reduce contagion risk from areas in the Nordfjella zone. This may include infestation and fencing of licking sites to make them inaccessible to beasts and deer. This applies to areas where it has stood or has been licking over the last five years. The regulatory changes were sent for consultation and the consultation deadline expired on 13.09.2018.
Link to the regulatory process: Proposed change in regulation on zones in detecting Chronic Wasting Disease
The regulatory changes came into force 28.11.2018.
Regulations for change in sonication regulation when detecting Chronic Wasting Disease (CWD zone)
Date FOR-2018-11-23-1768
Ministry Ministry of Agriculture and Food Commencement
23/11/2018
Changing FOR-2017-06-12-734
Applies to Norway Legal LOV-2003-12-19-124-§14 , LOV-2003-12-19-124-§19 , FOR-2003-12-19-1790 promulgated 28.11.2018 kl. 15.00 Corrected 29.11.2018 (Section 4, paragraph 1, letter a) Journalnr 2018-1060
short Title Change in CWD zone regulation Legal basis: Established by the Ministry of Agriculture and Food on November 23, 2018, pursuant to Act No. 19 of 19 December 2003 on food production and food safety, etc. (matloven) § 14 and section 19, cf. Delegation Decree December 19, 2003 No. 1790.
IN In Regulation 12 June 2017 No. 734 on zones for detection of Chronic Wasting Disease (CWD zone), the following changes are made:
Section 4 shall read:
§ 4. Zones This regulation applies to measures in the following zones:
1. Northern Mountains Zone:
a) the municipalities of Lærdal, Aurland and Hemsedal.
b) the municipalities of Eidfjord, Hol and Ål north of the national road 7.
c) municipality Ulvik northeast of the river Tysso to Stokkvatnet and to Espelandsvatnet.
2. Selbu zone:
a) the municipalities of Selbu, Klæbu, Trondheim, Tydal and Malvik
b) the municipalities Stjørdal and Meråker south of the river Tevla and Stjørdalselva
c) the municipality of Melhus east of the river Gaula
d) the municipality of central Gauldal north of the river Gaula
e) the municipality of Holtålen north and east of Gaula river from the municipal border to the center of Gauldal to the center of Ålen, further east of the national road 30 to the municipal border to Røros
f) Røros municipality east of national road 30 from municipal boundary towards Holtålen to Glåmos, further north of county road 561 to Brekken, further north of national road 31 to the national border in the east. § 5 third paragraph new fourth sentence shall read:
It is also prohibited to collect live deer from the zone of a deer in captivity facility in the Nordfjella zone.
Section 6, new fifth paragraph shall read:
Anyone who has an active luncheon placement in the Nordfjella zone or who has had the lick in the Nordfjella zone within the last five years must report GPS coordinates or information about the location of these licking spots to the Norwegian Food Safety Authority.
Section 7, new third paragraph, shall read:
The Norwegian Food Safety Authority may, without the consent of the landowner, take the necessary measures to reduce the risk of infection from areas in the Nordfjella zone. This may include infestation and fencing of licking sites to make them inaccessible to beasts and deer. The second sentence applies to both areas where there are lick stones and areas where lick sticks have been in the last five years.
II
Regulations come into force immediately.
Volume 24, Number 12—December 2018
Research
Novel Type of Chronic Wasting Disease Detected in Moose (Alces alces), Norway
Laura Pirisinu, Linh Tran, Barbara Chiappini, Ilaria Vanni, Michele A. Di Bari, Gabriele Vaccari, Turid Vikøren, Knut Ivar Madslien, Jørn Våge, Terry Spraker, Gordon Mitchell, Aru Balachandran, Thierry Baron, Cristina Casalone, Christer M. Rolandsen, Knut H. Røed, Umberto Agrimi, Romolo Nonno, and Sylvie L. BenestadComments to Author
Author affiliations: Istituto Superiore di Sanità, Rome, Italy (L. Pirisinu, B. Chiappini, I. Vanni, M.A. Di Bari, G. Vaccari, U. Agrimi, R. Nonno); Norwegian Veterinary Institute, Oslo, Norway (L. Tran, T. Vikøren, K. Madslien, J. Våge, S.L. Benestad); Colorado State University, Fort Collins, Colorado, USA (T. Spraker); Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell, A. Balachandran); Anses Lyon Unité “Maladies Neuro-Dégénératives”, Lyon, France (T. Baron); Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d’Aosta, Torino, Italy (C. Casalone); Norwegian Institute for Nature Research, Trondheim, Norway (C.M. Rolandsen); Norwegian University of Life Sciences, Faculty of Veterinary Science, Oslo (K.H. Røed) Suggested citation for this article
Abstract
Chronic wasting disease (CWD) persists in cervid populations of North America and in 2016 was detected for the first time in Europe in a wild reindeer in Norway. We report the detection of CWD in 3 moose (Alces alces) in Norway, identified through a largescale surveillance program. The cases occurred in 13–14-year-old female moose, and we detected an abnormal form of prion protein (PrPSc) in the brain but not in lymphoid tissues. Immunohistochemistry revealed that the moose shared the same neuropathologic phenotype, characterized by mostly intraneuronal deposition of PrPSc. This pattern differed from that observed in reindeer and has not been previously reported in CWD-infected cervids. Moreover, Western blot revealed a PrPSc type distinguishable from previous CWD cases and from known ruminant prion diseases in Europe, with the possible exception of sheep CH1641. These findings suggest that these cases in moose represent a novel type of CWD.
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Results
CWD was diagnosed in 2 moose in May 2016 in Norway’s Selbu municipality and in 1 moose in October 2017 in Lierne municipality. Selbu and Lierne are respectively located ≈300 and ≈450 km northeast of Nordfjella, where CWD in reindeer was detected in 2016. Norway is populated by several species of wild cervids with varying degrees of overlapping range. Seasonal migrations are common and distances might exceed 150 km (13–15). However, studies tracking global positioning satellite–collared moose have not documented regular seasonal migrations between Selbu and Lierne municipalities, suggesting that these can be considered different moose subpopulations.
We initially detected PrPSc in brain samples by using a rapid test and then confirmed by WB (data not shown) and IHC. Sequencing analysis of the entire PrP coding sequence revealed that the 3 moose had the wild type PrP genotype, homozygous for lysine at codon 109 and for methionine at codon 209 (KK109MM209) (GenBank accession no. MH230115).
Discriminatory PrPSc Immunohistochemistry Show Differences between Reindeer and Moose Thumbnail of Immunohistochemical detection of disease-associated prion protein in brain sections at the level of the obex in cervids with chronic wasting disease, Norway. A–E) Reindeer; F–J) moose. mAbs used were 12B2 (A, F), 9A2 (B, G), L42 (C, H), SAF 84 (D, I), and F99/97.6 (E, J). Staining obtained in the reindeer tissues are similar regardless of mAbs used (A–E). Conversely, for moose tissues, the staining was primarily observed intraneuronally with L42, SAF84, and F99/97.6 (H–J) but was no Figure 1. Immunohistochemical detection of disease-associated prion protein in brain sections at the level of the obex in cervids with chronic wasting disease, Norway. A–E) Reindeer; F–J) moose. mAbs used were 12B2 (A,...
The distribution of PrPSc staining was examined by IHC and compared in the tissues of the 3 moose and the reindeer by using 5 different antibodies (Figure 1). No staining was observed in CWD-negative reindeer and moose independently of the antibody used. The distribution of PrPSc in the reindeer was identical for each of the 5 antibodies and did not differ from the description of PrPSc distribution in North America cervids (16–18). The labeling was most consistent within the gray matter of the medulla oblongata, particularly in the dorsal motor of the vagus nerve (7). The thalamic and brain stem regions of the brain were most affected, with a minimal amount of PrPSc identified dorsal to the corpus callosum.
PrPSc labeling in the moose brains (Figure 1, panels F–J) was clearly different from that of the reindeer (Figure 1, panels A–E). In the moose, after staining with F99/97.6 and L42, PrPSc was almost exclusively observed as intraneuronal aggregates, although intraastrocytic type (multiple small granules scattered in the cytoplasm of astrocyte-resembling cells) and intramicroglial type (1 as single or a few large granules in close proximity to microglia-like nuclei) were also observed in the cerebral cortices and olfactory bulb (Technical Appendix Figure 1). The degree of PrPSc staining was more intensive and appeared more widespread in the neuropil using SAF84.
At the level of the obex, we found stained neurons in all nuclei, whereas the dorsal motor of the vagus nerve was not remarkably stained, as observed in reindeer. The intensity of labeling varied between the 3 moose; no. 2 displayed sparse labeling, no. 3 widespread and abundant labeling, and no. 1 intermediate labeling intensity. We observed PrPSc in all parts of the brain investigated except the cerebellums of moose nos. 1 and 2. A diffuse or discrete punctate staining was observed in the granular layer of the cerebellum of moose no. 3, with stronger staining in some Golgi neurons (Technical Appendix Figure 1, panel B). In all 3 moose, the cortical regions showed laminar staining of neurons in all the cell layers, especially in fusiform-shaped neurons. The neurons of the olfactory tubercle from all 3 also stained strongly, and some glia-associated staining could be observed.
In contrast to the reindeer, the downstream flexible tail mAbs 12B2 and 9A2 did not stain in the moose (Figure 1, panels F and G), suggesting that the moose PrPSc was truncated by endogenous proteases further upstream in the N terminus than was reindeer PrPSc. Contrary to previous findings in reindeer, PrPSc was not detected in the Ln from moose no. 1 or in the Ln and tonsils from moose no. 3 (lymphoid tissues were not available in moose no. 2) by either IHC or ELISA.
PrPSc from Norway Moose Compared with Other CWD Isolates from Canada and Norway Thumbnail of Western blot analysis of PrPres in brains of chronic wasting disease-affected cervids from Norway and Canada. A) Western blot analysis PrPres in brains of moose and reindeer from Norway. Membrane was probed with L42 monoclonal antibodies. Molecular weights (kDa) are indicated on the right. Tissue equivalent loaded per lane was 1 mg. B) Western blot analysis of PrPres from moose isolates from Norway (lanes 6–7) compared with PrPres from chronic wasting disease–affected elk or wapiti Figure 2. Western blot analysis of PrPres in brains of chronic wasting disease-affected cervids from Norway and Canada. A) Western blot analysis PrPres in brains of moose and reindeer from Norway. Membrane was...
We compared the PrPSc features in moose from Norway with those of other CWD isolates from Norway and Canada by discriminatory WB, which enabled comparison of PrPres by epitope mapping with different antibodies. Norway moose PrPres had a lower apparent molecular weight (MW) than PrPres from Norway reindeer (Figure 2, panel A) or from Canada isolates (Figure 2, panel B). This lower MW was explained by the occurrence of more C-terminal cleavage of PrPSc by protease K, as confirmed by the partial loss of the 12B2 epitope (Figure 2, panel B).
Thumbnail of Characterization of PrPres fragments from moose (Alces alces) in Europe by epitope mapping. Mapping with mAbs spanning the whole prion protein enabled the analysis of PrPres in moose samples before (PNGase F–) and after deglycosylation (PNGase F+), based on presence or absence of the epitopes and apparent molecular weight. Solid arrowheads indicate C-terminal fragment of ≈13 kDa fragment (present in both samples and detected with SAF84 mAbs). Open arrowheads indicate C-terminal frag Figure 3. Characterization of PrPres fragments from moose (Alces alces) in Europe by epitope mapping. Mapping with mAbs spanning the whole prion protein enabled the analysis of PrPres in moose samples before (PNGase...
Given the unusual pattern observed in moose isolates from Norway, we further investigated their biochemical characteristics with additional mAbs and by enzymatic deglycosylation (Figure 3). Moose samples showed a main C-terminal fragment of ≈17 kDa, detected with SAF84, L42, and 9A2, and an additional glycosylated C-terminal fragment of ≈13 kDa (CTF13) detected only with SAF84. The N terminal 12B2 epitope was mainly lost, although a small amount of PrPres was still detectable in moose no. 1 (Figure 3) and no. 3 (Technical Appendix Figure 2) with this antibody.
In moose nos. 2 and 3, an additional glycosylated C-terminal fragment of ≈16 kDa (CTF16) was detected by SAF84 and L42 mAbs (Figure 3; Technical Appendix Figure 2). We cannot exclude that a small amount of CTF16 was also present in moose no. 1, given that a weak PrPres fragment of ≈16 kDa was detectable upon deglycosylation and long exposure of blots (Figure 3; Technical Appendix Figure 3). Moose nos. 1 and 3 also had a nonglycosylated internal fragment of ≈10 kDa, cleaved at both N and C termini of PrPSc, which was recognized by using mAbs 9A2 (Figure 3). Moreover, the analysis of PrPres from different neuroanatomic regions showed that the slight differences observed among the 3 moose were not dependent on the area analyzed (Technical Appendix Figure 2).
Comparison of the PrPSc Features of the Norway Moose with Sheep and Cattle Prion Strains from Europe Thumbnail of Bar graph of antibody-signal ratios (y-axis) showing discrimination of the ovine, bovine, moose and reindeer samples (x-axis) analyzed in a study characterizing chronic wasting disease in moose (Alces alces), Norway. The antibody ratio is the L42/12B2 ratio of the chemiluminescence signal relative to the L42/12B2 ratio of the control scrapie loaded in each blot. Bars represent median values of >3 independent determinations; error bars represent the range of observed values. Bars Figure 4. Bar graph of antibody-signal ratios (y-axis) showing discrimination of the ovine, bovine, moose and reindeer samples (x-axis) analyzed in a study characterizing chronic wasting disease in moose (Alces alces), Norway. The...
Thumbnail of Comparison of protease-resistant PrPres from moose (Alces alces) with chronic wasting disease and from sheep with scrapie, Europe. Representative blots show epitope mapping analysis ofPrPres (lane 4, CH1641; lane 5, moose no. 1; lane 6, moose no. 2) in comparison with different ovine transmissible spongiform encephalopathy isolates (lane 1, atypical/Nor98; lane 2, classical scrapie; and lane 3, CH1641). A chronic wasting disease isolate from Canada was loaded as control (lane 7). Th Figure 5. Comparison of protease-resistant PrPres from moose (Alces alces) with chronic wasting disease and from sheep with scrapie, Europe. Representative blots show epitope mapping analysis ofPrPres (lane 4, CH1641; lane 5, moose...
Comparison with ovine and bovine prions was performed to determine the N terminal cleavage of the main PrPres fragment by analyzing the different PrPres fragments in each sample, the MW of these fragments, and the L42/12B2 antibody ratio (Figure 4; Technical Appendix Table). Among ovine prions, classical scrapie and atypical/Nor98 were easily discriminated from moose isolates (Figure 5). Classical scrapie PrPres had a higher MW than moose PrPres, as confirmed by the preservation of 12B2 epitope. As previously observed (19), Nor98 PrPres was cleaved at both the N and C termini, and the characteristic 11–12 kDa band was detected by L42, 9A2, and 12B2 mAbs (Figure 5). In contrast, CH1641 samples showed molecular features partially overlapping with the moose (Figure 5). CH1641 samples showed a PrPres of ≈17 kDa and were accompanied by an additional C-terminal fragment of 13–14 kDa detected by using SAF84 mAbs (20). However, CTF16 and the internal PrPres fragment of 10 kDa could not be detected in CH1641 samples.
Thumbnail of Comparison of protease-resistant core of abnormal form of prion protein from moose (Alces alces) in Europe with chronic wasting disease and from cattle with BSE. Representative blots show epitope mapping analysis of protease-resistant core of abnormal form of prion protein in moose (lane 5, moose no. 1; lane 6, moose no. 2) in comparison with different BSE isolates (lane 2, classical BSE; lane 3, H-type BSE; and lane 4, L-type BSE). A sheep scrapie isolate was loaded as control (lan Figure 6. Comparison of protease-resistant core of abnormal form of prion protein from moose (Alces alces) in Europe with chronic wasting disease and from cattle with BSE. Representative blots show epitope mapping analysis...
Moose PrPSc did not overlap with any type of bovine PrPSc. The lack of the 12B2 epitope in moose PrPres was similar to C-type and L-type atypical BSE, but the 2 bovine prions had neither CTF13, CTF16, nor the internal fragment (Figure 6). H-type atypical BSE showed the CTF13 and the internal fragment similar to moose PrPres, but the main PrPres fragment showed a higher MW and preserved the 12B2 epitope (Figure 6).
The ratio of reactivity obtained with L42 and 12B2 antibodies reflected the N terminal cleavage of the main fragment of PrPSc, enabling confirmation that the differences observed in MW of PrPres actually depend on different N terminal proteinase K cleavage, irrespective of the host species (Figure 4). Values >2 are indicative of BSE-like cleavage, whereas values <1 12b2="" a="" behavior="" better="" bse-like="" compared="" epitope="" in="" indicate="" moose="" of="" preservation="" prpres="" ratio="" respect="" scrapie.="" the="" this="" was="" with="">2). However, moose no. 1 had a ratio lower than moose nos. 2 and 3. The CH1641-like field sample was similar to moose no. 1 in this respect, whereas CH1641 was similar to moose nos. 2 and 3. Finally, the value <1 and="" appendix="" atypical="" bse="" canada="" classical="" compared="" cwd="" div="" for="" from="" h-type="" higher="" in="" isolates="" mw="" observed="" online="" prpres="" reflected="" reindeer="" scrapie="" table="" technical="" their="" with="">
Discussion
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https://www.ars.usda.gov/research/publications/publication/?seqNo115=353091
The phenotype variant found in moose from Norway could be hypothetically attributed to host species factors. To address this issue, we directly compared PrPSc characteristics in the Norway moose with those in a Canada moose with CWD. In agreement with the available evidence, we found that the Canada moose PrPSc had features different from Norway moose PrPSc and were indistinguishable from other cervids with classical CWD. This finding suggests that the variant PrPSc type observed in Norway moose could not simply reflect a host species factor. Notably, in both natural and experimental conditions, CWD-affected moose in North America have been reported to display disease features indistinguishable from CWD in other cervids and had detectable PrPSc in lymphoid tissues (21,27).
Species-specific amino acid polymorphisms in the cervid PrP are associated with CWD susceptibility, incubation time, and pathology (28–30). In transmission experiments, atypical features were reported in elk or wapiti and mule deer with genotypes associated with a relative resistance to disease, extension of the incubation period, or both (31,32). Moose PrP is polymorphic at codon 109 (K/Q) and 209 (M/I), combined in 3 alleles: K109M209 (observed in Europe and North America), Q109M209 (observed in Europe), and K109I209 (observed in North America) (33,34). The 3 moose with CWD from Norway had the KK109MM209 genotype, whereas the moose case from Canada used for comparison had KK109II209 genotype. Thus, we cannot exclude that the differences observed between Norway and Canada moose in our study are dependent on differences in PrP genotype. However, a classical CWD phenotype has been reported in naturally (21) and experimentally infected (27) moose with the KK109MM209 genotype, suggesting that a difference at PrP codon 209 is probably not the cause of the variant phenotype observed in moose in Norway. All of these findings suggest that neither the species nor the individual PrP genotypes are likely to have caused the variant phenotypes observed and imply that this variant phenotype could represent a novel CWD strain.
CWD is known to be a highly contagious disease in North America; however, data relating to the disease in moose is sparse and insufficient to understand the epidemiology and the implications of CWD in this species. The apparent low CWD prevalence reported for moose in North America compared with other cervid species might be attributable to the individual social behavior of moose and the minimal habitat overlap between moose and other cervids in areas with CWD. Additionally, surveillance program design, disease variability, and host genetics might influence the prevalence of the disease. Based on the epizootic dynamics in North America, CWD plausibly could have become established in reindeer in Norway more than a decade ago (35). In this scenario, the disease in moose could possibly be linked to the disease observed in reindeer, with strain mutation or phenotype shift putatively caused by interspecific transmission. However, a main cause of strain mutation after interspecies transmission (i.e., PrP amino acid differences between the donor and host species) is not relevant in this case because reindeer and moose share the same PrP primary sequence. An alternative hypothesis could be that moose have a prion disease which is independent of the reindeer epidemic, being either specific to the Norwegian moose or acquired by species other than the reindeer.
The 3 moose were 13, 14, and 13 years of age. Although moose can reach ages beyond 20 years, we consider these moose as old because female moose >10–12 years of age start to show signs of senescence and declining survival and reproduction rates (36,37). The old age of the moose, the absence of lymphoid tissue involvement, and the low disease prevalence observed so far (3 of 10,531 moose tested) could suggest that CWD in moose is less contagious than classical CWD or could represent a spontaneous TSE. The finding that the affected moose were from the same geographic area does not seem to support a spontaneous origin of the disease; however, the actual evidence for geographic clustering could have been biased by oversampling in Trøndelag County, where the first positive moose was detected. Lack of detailed data on the ages of the moose tested so far in different geographic areas prevents any definitive conclusion. Still, the recent detection of a positive moose in Finland, several hundred kilometers from Trøndelag County, might indicate that the disease is not restricted to Norway (38). The ongoing intensive surveillance in Norway and several European Union countries with large moose populations will help to better clarify the actual geographic distribution and prevalence and will be critical for understanding the contagious or spontaneous nature of the disease.
The 3 moose analyzed shared a distinctive IHC pattern, mainly characterized by intraneuronal accumulation of PrPSc, and common PrPSc features, such as the proteinase K N-terminal cleavage and the presence of an additional CTF13 fragment. However, we also observed unexpected differences among the 3 moose. By WB, the CTF16 fragment was observed in moose nos. 2 and 3 but not in moose no. 1, whereas the nonglycosylated internal fragment of 10 kDa was evident in moose nos. 1 and 3 but could not be detected in moose no. 2. Furthermore, we also showed that these differences did not depend on the brain area investigated. We cannot rule out that these slight differences might depend on technical issues rather than represent actual PrPSc variations. The outcome of the ongoing bioassay experiments will help to clarify the meaning of the observed variations.
By comparing the moose PrPSc features with other animal TSEs circulating in Europe, we found no evidence of similarities with bovine and ovine prions. Minimal similarities were observed with CH1641 samples; however, CH1641 cases have not yet been detected in Norway. Bioassay in a large spectrum of rodent models will assist in determining whether these molecular similarities imply biologic association between the atypical CWD in moose and small ruminant CH1641. Transmission studies in several rodent models are underway and will help to clarify whether the different phenotype observed (designated Nor16CWD) could reflect the presence of a new cervid prion strain in moose from Norway.
Dr. Pirisinu is a researcher at the Istituto Superiore di Sanità in Rome, Italy. Her primary research interests include the prion strain characterization and zoonotic potential of animal prion diseases.
Acknowledgments
THURSDAY, OCTOBER 25, 2018
***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion
TUESDAY, JULY 03, 2018
Chronic Wasting Disease CWD TSE Prion Global Report Update, USA, CANADA, KOREA, NORWAY, FINLAND, Game Farms and Fake news
MONDAY, AUGUST 14, 2017
NORWAY CWD, SHEEP GRAZING, and Scrapie, What If? Scrapie/reindeer investigation
TUESDAY, JUNE 13, 2017
PRION 2017 CONFERENCE
ABSTRACT
Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD
P178 Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD
Dr Laura Pirisinu1, Dr Linh Tran2, Dr Gordon Mitchell3, Dr Aru Balachandran3, Dr Thierry Baron4, Dr Cristina Casalone5, Dr Michele Di Bari1, Dr Umberto Agrimi1. Dr Romolo Nonno1, Dr Sylvie Benestad2
1Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanita, Rome, Italy, 2Norwegian Veterinary Institute, Oslo, Norway, 3Canadian Food Inspection Agency, National and OlE Reference Laboratory for Scrapie and CWD, Ottawa Laboratory Fallowfield, Ottawa, Canada, 4Neurodeqenerative Diseases Unit, ANSES - French Agency for Food, Environmental and Occupational Health & Safety, Lyon, France, 5Istituto Zooprofilattico Sperimentale del Pietnonte, Liguria e Valle d'Aosta, Turin, Italy
Aims: In 2016, Chronic Wasting Disease (CWD) was detected for the first time in Europe in three wild Norwegian reindeer (Rangifer tarandus tarandus) and in two moose (Alces alces). The biochemical analysis and the immunohistochemical distribution of PrPSc from Norwegian reindeer revealed a pattern similar to North American (NA) isolates1. In this study, we studied the biochemical features of PrPSc from the two CWD cases in Norwegian moose.
Methods: Western blot (WB) analysis of PK-treated PrPSc (PrPres) from Norwegian moose and reindeer isolates was performed according to the ISS discriminatory WB protocol (used in BSE and scrapie Italian surveillance). PrPres fragments were determined by epitope mapping (SAF84, L42, 9A2, 12B2 mAbs), before and after deglycosylation. CWD isolates from Canadian cervids (wapiti, moose and white tailed deer) and a panel of small ruminant and bovine prion strains circulating in Europe were also analysed.
Results: WB analysis with different mAbs showed that PrPres from both Norwegian moose samples was different from that usually associated with CWD in cervids. Indeed, their main C-terminal fragment had a MW lower than the other CWD isolates, and could be discriminated by the absence of the 12B2 epitope. Furthermore, while NA CWD PrPSc is composed of a single PrPres fragment, Norwegian moose samples had an additional C-terminal PrPres fragment of ~13 kDa (CTF13). Among ovine TSEs, classical scrapie and Nor98 were discriminated from both Norwegian moose isolates, while CH1641 samples had molecular features partially overlapping with the moose, i.e. a low MW PrPres and the presence of CTF13. In contrast, moose PrPSc did not overlap with any bovine PrPSc. Indeed, the MW of moose PrPres was lower than H-BSE and similar to C-BSE and L-BSE PrPres, but the two bovine prions lacked additional PrPres fragments.
Conclusions: Unexpectedly, PrPSc from Norwegian moose revealed features substantially different from all other CWD isolates. The PrPSc pattern of Norwegian moose was also different from Canadian moose, suggesting that the variant PrPSc type observed does not simply reflect a host factor and could represent a new CWD strain. Furthermore, PrPSc of Norwegian moose can be easily discriminated from all BSE types, classical scrapie and Nor98, while showing significant overlapping only with CH1641. Bioassay in voles will help to clarify whether the different PrPSc types observed reflect the presence of a new CWD strain in Norwegian moose, and its relationships with known animal TSEs.
References: 1Benestad et al, Vet Res (2016}47:88
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS
please see;
***Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
***Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.
P-088 Transmission of experimental CH1641-like scrapie to bovine PrP overexpression mice
Kohtaro Miyazawa1, Kentaro Masujin1, Hiroyuki Okada1, Yuichi Matsuura1, Takashi Yokoyama2
1Influenza and Prion Disease Research Center, National Institute of Animal Health, NARO, Japan; 2Department of Planning and General Administration, National Institute of Animal Health, NARO
Introduction: Scrapie is a prion disease in sheep and goats. CH1641-lke scrapie is characterized by a lower molecular mass of the unglycosylated form of abnormal prion protein (PrpSc) compared to that of classical scrapie. It is worthy of attention because of the biochemical similarities of the Prpsc from CH1641-like and BSE affected sheep. We have reported that experimental CH1641-like scrapie is transmissible to bovine PrP overexpression (TgBoPrP) mice (Yokoyama et al. 2010). We report here the further details of this transmission study and compare the biological and biochemical properties to those of classical scrapie affected TgBoPrP mice.
Methods: The details of sheep brain homogenates used in this study are described in our previous report (Yokoyama et al. 2010). TgBoPrP mice were intracerebrally inoculated with a 10% brain homogenate of each scrapie strain. The brains of mice were subjected to histopathological and biochemical analyses.
Results: Prpsc banding pattern of CH1641-like scrapie affected TgBoPrP mice was similar to that of classical scrapie affected mice. Mean survival period of CH1641-like scrapie affected TgBoPrP mice was 170 days at the 3rd passage and it was significantly shorter than that of classical scrapie affected mice (439 days). Lesion profiles and Prpsc distributions in the brains also differed between CH1641-like and classical scrapie affected mice.
Conclusion: We succeeded in stable transmission of CH1641-like scrapie to TgBoPrP mice. Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.
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RESEARCH ARTICLE
Phenotype Shift from Atypical Scrapie to CH1641 following Experimental Transmission in Sheep
Marion M. Simmons*, S. Jo Moore¤a, Richard Lockey¤b, Melanie J. Chaplin, Timm Konold, Christopher Vickery, John Spiropoulos
Animal and Plant Health Agency—Weybridge, Woodham Lane, Addlestone, Surrey, KT15 3NB, United Kingdom
¤a Current address: School of Veterinary and Biomedical Sciences, Murdoch University, South Street, Murdoch, Western Australia, 6150, Australia
¤b Current address: University of Southampton, Southampton, SO17 1BJ, United Kingdom * marion.simmons@apha.gsi.gov.uk
Abstract
The interactions of host and infecting strain in ovine transmissible spongiform encephalopathies are known to be complex, and have a profound effect on the resulting phenotype of disease. In contrast to classical scrapie, the pathology in naturally-occurring cases of atypical scrapie appears more consistent, regardless of genotype, and is preserved on transmission within sheep homologous for the prion protein (PRNP) gene. However, the stability of transmissible spongiform encephalopathy phenotypes on passage across and within species is not absolute, and there are reports in the literature where experimental transmissions of particular isolates have resulted in a phenotype consistent with a different strain. In this study, intracerebral inoculation of atypical scrapie between two genotypes both associated with susceptibility to atypical forms of disease resulted in one sheep displaying an altered phenotype with clinical, pathological, biochemical and murine bioassay characteristics all consistent with the classical scrapie strain CH1641, and distinct from the atypical scrapie donor, while the second sheep did not succumb to challenge. One of two sheep orally challenged with the same inoculum developed atypical scrapie indistinguishable from the donor. This study adds to the range of transmissible spongiform encephalopathy phenotype changes that have been reported following various different experimental donor-recipient combinations. While these circumstances may not arise through natural exposure to disease in the field, there is the potential for iatrogenic exposure should current disease surveillance and feed controls be relaxed. Future sheep to sheep transmission of atypical scrapie might lead to instances of disease with an alternative phenotype and onward transmission potential which may have adverse implications for both public health and animal disease control policies.
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Despite naturally-occurring atypical scrapie being observed in a range of genotypes, successful experimental transmissions of clinical disease have so far only been reported within a particular homologous donor-recipient genotype model using sheep which are AHQ/AHQ homozygous [8,15,16]. These published transmissions represent part of a large study at APHA which has been running since 2004, investigating the potential transmissibility of atypical scrapie in a range of both homologous and cross-genotype combinations. Here we describe an unexpected and interesting finding from that study where one experimental challenge in which atypical scrapie from an ARR/ARR donor was inoculated intracerebrally into two AHQ/AHQ recipient sheep, and in one of them the resulting disease had a phenotype that was indistinguishable from CH1641 [29], a classical scrapie strain which has some BSE-like Western blot properties.
*** One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.
Subject: more on scrapie/BSE strain CH1641
From: tom
Reply-To: Bovine Spongiform Encephalopathy
Date: Sun, 10 Jan 1999 21:52:05 -0800
Content-Type: text/plain
Parts/Attachments: Parts/Attachments text/plain (37 lines) Reply Reply
Recall a forthcoming J Gen Virol Jan 1999 v80:1 - 4 says there are similarities between BSE and an experimental isolate of natural scrapie, CH1641. This might then be the long-sought missing scrapie strain that could have given rise to the BSE epidemic. It would raise additional questions about the harmlessness to humans of scrapie.
On the other hand, CH1641 happened to be one of the scrapie strains studied very recently by Collinge's group, Neurosci Lett. 1998 Oct 23;255(3):159-62. It did not have the prp-sc type identical to BSE passaged in sheep.
The CH1641 strain is mentioned only twice before in Medline abstracts (though there could be many fulltext mentions), one of these being the original naming of the strain in 1988:
The unusual properties of CH1641, a sheep-passaged isolate of scrapie.
Foster JD, Dickinson AG Vet Rec 1988 Jul 2;123(1):5-8
An isolate of scrapie designated CH1641 was identified from a natural case of scrapie in a Cheviot sheep by passage in sheep and goats. It has not been possible to transmit scrapie to mice from this source. The Sip gene which controls the incubation periods of experimental scrapie in Cheviot sheep has two alleles; sA which shortens and pA which lengthens the incubation periods of most strains of scrapie after the first experimental injection in sheep (the A group of strains). The CH1641 isolate differs from them in that the alleles of Sip act in the opposite way, with incubation being shorter in the pA homozygotes. There is some evidence that one or more genes, in addition to Sip, may be implicated in the control of scrapie incubation in sheep and the possibility of a carrier infection with CH1641 is also discussed.
Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period.
J Gen Virol 1996 Nov;77 ( Pt 11):2885-91 Published erratum appears in J Gen Virol 1997 Mar;78(Pt 3):697 Goldmann W, Martin T, Foster J, Hughes S, Smith G, Hughes K, Dawson M, Hunter N
Age at disease onset and rate of progression of transmissible spongiform encephalopathies in man, sheep and mice are modulated by the host genome, in particular by the PrP gene and its allelic forms. Analysis of the caprine PrP gene revealed several different alleles. Four PrP protein variants were found, three of which were goat specific with single amino acid changes at codons 142, 143 and 240. The fourth was identical to the most common sheep PrP protein variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile --> Met) appeared to be associated with differing disease incubation periods in goats experimentally infected with isolates of bovine spongiform encephalopathy, sheep scrapie CH1641 or sheep-passaged ME7 scrapie.
BSE List Serve...tss
TSE PRION UPDATE USA 2012
re-BSE in goats can be mistaken for scrapie
Wednesday, January 18, 2012
BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE
February 1, 2012
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology:
February 2012 - Volume 71 - Issue 2 - p 140–147
Monday, March 21, 2011
Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice
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On the other hand, this component would not be distinguishable from bovine-passaged BSE prions due to the current limits of the standard biological methods and/or the molecular tools employed here to characterize prion strains. Whatever the mechanism, the notion that a passage through an intermediate species can profoundly alter prion virulence for the human species has important public-health issues, regarding emerging and/or expanding TSEs, like atypical scrapie or CWD.
snip...
Taken all together, our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, which has important implications on public and animal health policies. On one hand, although the exact magnitude and characteristic of the vCJD epidemic is still unclear, its link with cattle BSE is supported by strong epidemiological ground and several experimental data. On the other hand, the molecular typing performed in our studies, indicates that the biochemical characteristics of the PrPres detected in brains of our sheep and goat BSE-inoculated mice seem to be indistinguishable from that observed in vCJD. Considering the similarity in clinical manifestation of BSE- and scrapie-affected sheep [48], a masker effect of scrapie over BSE, as well as a potential adaptation of the BSE agent through subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have been detected in many peripheral organs, small ruminant-passaged BSE prions might be a more widespread source of BSE infectivity compared to cattle [19], [49], [50].
*** This fact is even more worrying since our transmission studies suggest that apparently Met129 human PrP favours a BSE agent with ovine rather than a bovine sequence. Finally, it is evident that, although few natural cases have been described and so far we cannot draw any definitive conclusion about the origin of vCJD, we can not underestimate the risk of a potential goat and/or sheep BSE agent.
snip...
Technical Abstract:
Prion strains may vary in their ability to transmit to humans and animals. Few experimental studies have been done to provide evidence of differences between U.S. strains of scrapie, which can be distinguished by incubation times in inbred mice, microscopic lesions, immunoreactivity to various antibodies, or molecular profile (electrophoretic mobility and glycoform ratio). Recent work on two U.S. isolates of sheep scrapie supports that at least two distinct strains exist based on differences in incubation time and genotype of sheep affected. One isolate (No. 13-7) inoculated intracerebrally caused scrapie in sheep AA at codon 136 (AA136) and QQ at codon 171 (QQ171) of the prion protein in an average of 19 months post-inoculation (PI) whereas a second isolate (No. x124) caused disease in less than 12 months after oral inoculation in AV136/QQ171 sheep. Striking differences were evident when further strain analysis was done in R111, VM, C57Bl6, and C57Bl6xVM (F1) mice. No. 13-7 did not induce disease in any mouse strain at any time post-inoculation (PI) nor were brain tissues positive by western blot (WB). Positive WB results were obtained from mice inoculated with isolate No. x124 starting at day 380 PI. Incubation times averaged 508, 559, 601, and 633 days PI for RIII, C57Bl6, VM, and F1 mice, respectively. Further passage will be required to characterize these scrapie strains in mice. This work provides evidence that multiple scrapie strains exist in U.S. sheep.
One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
snip...see ;
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
SHEEP AND BSE
PERSONAL AND CONFIDENTIAL
SHEEP AND BSE
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).
RB264
BSE - TRANSMISSION STUDIES
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology:
February 2012 - Volume 71 - Issue 2 - p 140–147
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts
S67 PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***
Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada
Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle. Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres.
Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. *** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *** It also suggests a similar cause or source for atypical BSE in these countries. ***
see page 176 of 201 pages...tss
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.
*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.
*** It also suggests a similar cause or source for atypical BSE in these countries. ***
see page 176 of 201 pages...tss
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply;
Interspecies transmission to bovinized transgenic mice uncovers new features of a CH1641-like scrapie isolate
Kohtaro MiyazawaEmail authorView ORCID ID profile,Kentaro Masujin,Yuichi Matsuura,Yoshifumi Iwamaru,Takashi Yokoyama andHiroyuki Okada Veterinary Research201849:116
© The Author(s) 2018 Received: 2 July 2018Accepted: 7 November 2018Published: 28 November 2018
Abstract
In animal prion diseases, including bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease in cervids, and scrapie in sheep and goats, a disease-associated isoform of prion protein (PrPd) accumulates in the brains of affected animals. Although the CH1641 scrapie isolate was experimentally established in the UK, a few natural CH1641-like scrapie cases have been reported in France and the UK. The molecular mass of the unglycosylated protease-resistant core of PrPd (PrPres) is known to be similar between CH1641-like scrapie and experimental BSE in sheep. We previously established an experimental CH1641-like scrapie isolate (Sh294) from a natural classical scrapie case. Here, we demonstrated that the Sh294 isolate was independent of both classical and atypical BSEs by cross-species transmission to bovine PrP overexpressing (TgBoPrP) mice and wild-type mice. Interestingly, we found that the Sh294 isolate altered its host range by the transmission to TgBoPrP mice, and we succeeded in the first stable reproduction of CH1641-like scrapie specific PrPres banding patterns with the ~12-kDa small C-terminal fragment in wild-type mice. This study provides new insight into the relationship between CH1641-like scrapie isolates and BSEs. In addition, interspecies transmission models such as we have demonstrated here could be a great help to investigate the origin and host range of animal prions.
SNIP...
DISCUSSION
The biological and biochemical properties of the experimental CH1641-like scrapie isolate (Sh294) in TgBoPrP mice were different from those of H- and C-BSE [25]. In contrast, TgBoPrP mice infected with Sh294 exhibited clinical signs and the triplet band pattern of PrPres similar to those of mice infected with L-BSE. However, the ~12-kDa small C-terminal fragment of PrPres could only be detected in TgBoPrP mice infected with Sh294. Moreover, the mean survival periods, lesion profiles, and PrPd distribution patterns in the brain were distinctly different between the mice infected with Sh294 and those infected with L-BSE. Interspecies transmission of TgBo-passaged Sh294 to wild-type (ICR) mice also demonstrated the biological differences between Sh294 and L-BSE passaged in TgBoPrP mice. It is known that L-BSE from cattle or TgBoPrP mice is unable to transmit to ICR mice [20, 27]. In contrast, TgBo-passaged Sh294 can transmit to ICR mice even though inefficiently. Since we previously reported that L-BSE could transmit to ICR mice after cross-species transmission to sheep [20], we can now compare the characteristics of the CH1641-like scrapie isolate and L-BSE in wild-type mice. The mean survival period of ICR mice infected with sheep-passaged L-BSE was significantly extended in comparison with that of ICR mice infected with TgBo-passaged Sh294 (Table 4). Although the glycoform profiles were similar between ICR mice infected with TgBo-passaged Sh294 and those infected with sheep-passaged L-BSE, the molecular mass of PrPres was distinctly different between them. In the histopathological analysis, florid plaques were detected in the brains of ICR mice infected with sheep-passaged L-BSE [20], but not in the brains of mice infected with TgBo-passaged Sh294. Thus, all our data demonstrate that the Sh294 isolate is independent of all three BSE strains, suggesting that CH1641-like scrapie isolates could not be candidates for the origin of BSEs. Indeed, several studies have suggested that spontaneously occurring atypical BSEs in cattle may have been the origin of C-BSE [28, 29, 30, 31, 32].
It is of interest to us that TgBo-passaged Sh294 is transmitted to ICR mice with the CH1641-like scrapie-specific PrPres banding patterns because this scrapie isolate cannot transmit directly from sheep to wild-type mice [19]. The biological and biochemical features of TgBo-passaged Sh294 in ICR mice were evidently different from those of sheep-passaged L-BSE. Moreover, these features were also different from all other tested laboratory scrapie strains (22L, ME7, and Chandler), mouse-adapted Japanese scrapie isolates, and the mBSE strain, which were available in our laboratory (Figures 4A, B, D, and Additional file 2) [33, 34]. To the best of our knowledge, only a group reported the transmission of French natural CH1641-like scrapie isolates from sheep to wild-type (C57BL/6) mice [35]. In contrast to our results, these isolates easily transmitted to C57BL/6 mice. However, the PrPres banding patterns and the histopathological properties observed in diseased mice exhibited a classical scrapie phenotype. This discrepancy could be explained by the co-existence of two different scrapie prions in French natural CH1641-like scrapie isolates, i.e., a classical scrapie prion and a CH1641 scrapie prion. This notion could be supported by the previous finding that some of TgOvPrP4 mice, overexpressing ovine PrPARQ, exhibited the classical scrapie PrPres banding patterns after inoculation with the French natural CH1641-like scrapie isolates [36, 37]. It has also been reported that TgOvPrP4 mice inoculated with French natural CH1641-like scrapie isolates accumulate PrPres in both the brain and spleen [38]. Although TgOvPrP4 and TgOvPrP59 transgenic mouse lines were derived from different founders, they overexpressed approximately three times as much PrPARQ in the brain under the control of the neuron-specific enolase promoter as that in sheep brains [21]. Since the previous report failed to detect the expression of ovine PrP mRNA in non-nervous tissues of TgOvPrP4 mice by RT-PCR [39], the precise mechanisms by which PrPd accumulates in the spleen of this transgenic mouse line infected with classical scrapie isolates remain unknown. However, considering the ovine PrPC expression level and similar response to the classical scrapie isolate, TgOvPrP59 mice may be a useful model to examine the similarity of the Sh294 isolate to French natural CH1641-like isolates. We demonstrated that none of the Sh294 inoculated mice exhibited the PrPres banding patterns of classical scrapie, even after the third passage in TgOvPrP59 mice. Moreover, splenic PrPres was detected in five out of seven TgOvPrP59 mice inoculated with the classical scrapie isolate, but not in any TgOvPrP59 mice inoculated with Sh294 (Additional file 1 and Table 2). Likewise, TgOvPrP4 mice inoculated with the British CH1641 scrapie isolate have been reported not to accumulate PrPres in their spleens [38]. These data strongly support that the experimental Sh294 isolate consisted of a single scrapie prion, similar to the CH1641 scrapie prion found in the UK. Unlike natural CH1641-like scrapie isolates, selection of a particular scrapie prion might occur through the experimental intraspecies transmission in sheep. Further transmission study of the British CH1641 scrapie isolate to TgOvPrP59 mice is needed to elucidate the similarity between the British CH1641 scrapie isolate and the Sh294 isolate.
The CH1641 scrapie prion remains poorly understood. In this study, we first demonstrated that the CH1641-like scrapie isolate was independent of BSEs, including atypical BSE. Then, we showed that the range of host species susceptible to the CH1641-like scrapie isolate changed via an interspecies transmission route. Finally, we demonstrated the successful transmission of the CH1641-like scrapie isolate (Sh294) to wild-type mice with its specific PrPres banding patterns. Our findings improve the current understanding of the relationship between CH1641-like scrapie isolates and BSEs, including atypical BSE.
FINLAND MOOSE FOUND DEAD IN FOREST WITH CHRONIC WASTING DISEASE 8.3.2018 12:56
The chronic wasting disease (CWD) has been found in a moose or European elk (Alces alces) for the first time ever in Finland. The disease was diagnosed in Kuhmo in a 15-year old moose that had died naturally. The results of the analyses carried out by Finnish Food Safety Authority Evira have been verified by a EU reference laboratory. Species of the deer family, known as “cervids”, can suffer from the chronic wasting disease, and it is always fatal. The disease is not known to have been contracted by people.
Norway was before this case the only European country where CWD has been diagnosed. The monitoring of the occurrence of the disease was intensified from the beginning of 2018 in Finland and five other EU Member States.
In Finland, the occurrence of the disease has been studied already since 2003. None of the ca. 2 500 samples analysed so far had tested positive for the disease. The monitoring of the disease will now be further intensified in the Kuhmo and Kainuu region. Hunters are going to be provided with more instructions before the start of the next hunting season, if appropriate.
The chronic wasting disease is not known to have been contracted by people. Moose meat is safe to eat and no restrictions are imposed on the sales and exportation of meat of animals of the deer family. As a precautionary measure the export of live animals of the deer family to other countries will be discontinued for now.
CWD is a slowly progressing disease of deer, elk, reindeer, and moose which always leads to death. The chronic wasting disease is a prion disease and related to the BSE (bovine spongiform encephalopathy) and other TSE diseases (transmissible spongiform encephalopathy). The disease is common in North America. The moose found in Kuhmo did not suffer from the North American, highly contagious form of the chronic wasting disease. The disease seems to resemble most the form of cervid TSE diagnosed in Norway, which appears to be found incidentally in individual animals of the deer family.
For more information, please contact:
Leena Räsänen, Director, tel. +358 50 388 6518 (Food Safety)
Terhi Laaksonen, Head of Unit, tel. +358 40 159 5812 (Control of Animal Diseases)
Sirkka-Liisa Korpenfelt, Senior Resarcher, tel. + 358 50 351 0308 (Laboratory Analyses)
Antti Oksanen, Research Professor, tel. +358 44 561 6491 (Wild Animal Diseases)
Kajsa Hakulin, Ministerial Advisor, Ministry of Agriculture and Forestry, tel. +358 295 162361 (National and EU Legislation)
SATURDAY, MARCH 10, 2018
Chronic Wasting Disease CWD TSE Prion Goes Global Finland Falls, Behind Norway and S. Korea
FINLAND REPORTS FIRST CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN A moose or European elk (Alces alces)
FRIDAY, NOVEMBER 16, 2018
Norway atypical TSE Prion found in Fourth Moose
NORWAY CWD TSE HISTORY
OIE CWD TSE PRION NORWAY
International reference laboratory for Chronic Wasting Disease
Publisert 04.04.2018
The World Organization for Animal Health (OIE) has designated the Norwegian Veterinary Institute as the third reference laboratory for Chronic Wasting Disease (CWD) in the world, and the first one in Europe. Senior researcher Sylvie Benestad has been designated as the expert, responsible for the new reference laboratory. OIE has previously appointed laboratories in Canada and South Korea.
-Being designated as a reference laboratory for OIE is a major professional recognition. This is the result of 20 years of work on prion diseases, says senior researcher Sylvie Benestad who will be responsible for the new reference laboratory. Photo: Agnete Brun. The Norwegian Veterinary Institute is a national reference laboratory for the Norwegian Food Safety Authority regarding several diseases and infectious agents. As a reference laboratory worldwide, the institute will collaborate with other countries to confirm diagnoses and exchange knowledge within diagnostics, disease and epidemiology. Sharing of material for diagnostics is also an important task. An international reference function will also create opportunities for academic cooperation worldwide.
- Being designated as a reference laboratory for OIE is first and foremost a major professional recognition. This is the result of 20 years of work on prion diseases and shows that Norway has been central in this field, such as in connection to the Nor98 scrapie disease in sheep and goats. I hope that with this we can increase the cooperation with the North America and South Korea and facilitate exchange of material and experience. We will also be able to assist other countries in the world that will detect CWD, such as Finland recently did, says Sylvie Benestad.
As of today, the Norwegian Veterinary Institute has analyzed more than 40 500 CWD samples from cervids. 18 cases of CWD have been detected in wild reindeer, 3 in moose and 1 in red deer.
Del artikkel - See more at: http:// https://wwweng.vetinst.no/news/international-reference-laboratory-for-chronic-wasting-disease#sthash.A0SV52iq.dpuf
Department for Environment, Food and Rural Affairs Animal and Plant Health Agency Veterinary & Science Policy Advice Team - International Disease Monitoring 1
Preliminary Outbreak Assessment Cervid Spongiform Encephalopathy in Norway
7 th April 2016 Ref: VITT/1200
Cervid disease in Norway
WEDNESDAY, MARCH 28, 2018
The executioner in Nordfjella and Chronic Wasting Disease CWD TSE Prion Skrantesjuke
TUESDAY, FEBRUARY 27, 2018
NORWAY CWD TSE PRION Skrantesjuke Nordfjella zone 1 Complete Eradication Complete
TUESDAY, DECEMBER 05, 2017
Norway 30,000 deer animals have so far been tested for Skrantesyke chronic wasting disease CWD TSE PRION DISEASE
THURSDAY, NOVEMBER 30, 2017
Norway Animal welfare surveillance at Nordfjella Skrantesjuke CWD TSE Prion Update
WEDNESDAY, NOVEMBER 29, 2017
Norway another case of Skrantesjuke CWD TSE Prion Adult Reindeer pitcher field in Nordfjella (preliminary testing) 13th case if confirmed
FRIDAY, NOVEMBER 24, 2017
Norwegian Food Safety Authority makes changes to measures to limit the spread of disease Skrantesjuke (CWD) in deer wildlife
SATURDAY, NOVEMBER 18, 2017
Norway detects more Chronic Wasting Disease CWD TSE Prion Skrantesjuke
This is the eighth case of the lethal deer disease in the area since the survey started in 2016.
The reindeer cub was shot by a flock from the Norwegian National Guard, and the infectious agent was detected in the animal's lymph nodes.
WEDNESDAY, NOVEMBER 01, 2017
Norway detects CWD Skrantesjuke Deer possibly atypical Nor-98-type TSE?
Greetings TSE prion world,
i am seeing more and more references to the atypical Nor-98-type CWD TSE Prion in Norway as being of the non-infectious or non-infective variant. with science documented to date, i do not believe that any CWD Skrantesjuke TSE Prion typical or atypical in Norway or anywhere else can be classified as ''non-infective variant''. IF, Norway takes the USDA OIE views and makes atypical Nor-98 type CWD in Deer a International trading commodity fueled by junk science, as they did with sheep, i.e. no trade restrictions for Nor-98 in sheep, the world should then weep...terry
Nor-98 atypical Scrapie Transmission Studies Review
snip...see full text;
FRIDAY, OCTOBER 13, 2017
Norway, Two More New Cases of Chronic Wasting Disease CWD TSE Prion Skrantesjuke
TUESDAY, OCTOBER 10, 2017
Norway detects another case of CWD TSE PRION Skrantesjuke
SATURDAY, SEPTEMBER 30, 2017
Norway, CWD TSE Prion, Humans, Zoonosis, Fortsatt lite sannsynlig at mennesker kan smittes av skrantesyke?
MONDAY, AUGUST 14, 2017
NORWAY CWD, SHEEP GRAZING, and Scrapie, What If?
TUESDAY, JUNE 20, 2017
Norway Confirms 6th Case of Skrantesjuke CWD TSE Prion Disease
Tuesday, December 13, 2016
Norway Chronic Wasting Disease CWD TSE Prion disease Skrantesjuke December 2016 Update
Thursday, September 22, 2016
NORWAY DETECTS 5TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION Skrantesjuke
Saturday, September 03, 2016
NORWAY Regulation concerning temporary measures to reduce the spread of Chronic Wasting Disease (CWD) as 4th case of skrantesjuke confirmed in Sogn og Fjordane
Wednesday, August 31, 2016
*** NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOU
Wednesday, August 31, 2016
NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND CARIBOU
Tuesday, August 02, 2016
Chronic wasting disease of deer – is the battle to keep Europe free already lost?
Tuesday, June 14, 2016
*** Chronic Wasting Disease (CWD) in a moose from Selbu in Sør-Trøndelag Norway ***
Thursday, July 07, 2016
Norway reports a third case Chronic Wasting Disease CWD TSE Prion in 2nd Norwegian moose
14/06/2016 - Norway reports a third case
Tuesday, April 12, 2016
The first detection of Chronic Wasting Disease (CWD) in Europe free-ranging reindeer from the Nordfjella population in South-Norway.
Saturday, April 9, 2016
The Norwegian Veterinary Institute (NVI, 2016) has reported a case of prion disease Cervid Spongiform Encephalopathy detected in free ranging wild reindeer (Rangifer tarandus tarandus)
Department for Environment, Food and Rural Affairs
Saturday, July 16, 2016
Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The British Deer Society 07/04/2016
Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?
could this have been cwd in the UK back in 1970’S ???
Clinical Communication Enzootic ataxia in Red deer
P.R. Wilson , Marjorie B. Orr & E.L. Key Pages 252-254 | Published online: 23 Feb 2011
SEE FULL TEXT ;
Sunday, February 25, 2018
PRION ROUND TABLE CONFERENCE 2018 MAY, 22-25 A REVIEW
Singeltary Submissions to EU on CWD TSE Prion
Friday, November 22, 2013
Wasting disease is threat to the entire UK deer population CWD TSE PRION disease in cervids
***SINGELTARY SUBMISSION
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:
Friday, November 22, 2013
Wasting disease is threat to the entire UK deer population
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
Sunday, June 23, 2013
National Animal Health Laboratory Network Reorganization Concept Paper (Document ID APHIS-2012-0105-0001)
***Terry S. Singeltary Sr. submission
CWD Positive Year Confirmed CWD Positive Confirmation Date Free Range/Captive County Source Species Sex Age
2018 11/30/2018 Breeder Release Site Medina Facility #4 white-tailed deer M 3.5
Showing 1 to 65 of 133 entries
Mon, Nov 26, 2018 11:08 pm
Texas TPWD Reports 2 more cases of Chronic Wasting Disease CWD TSE Prion in Breeder Deer, Release site total jumps to 132 Confirmed to date
Texas TPWD Reports 2 more cases of Chronic Wasting Disease CWD TSE Prion in Breeder Deer, Release site total jumps to 132 Confirmed to date
TUESDAY, DECEMBER 11, 2018
Montana Nine more deer found suspect for CWD: 3 south of Billings, 6 on the Hi-Line
TUESDAY, DECEMBER 04, 2018
Ohio Changes in CWD Sample Submission for IHC Testing, Ohio is considered free of CWD? LOL!
SATURDAY, DECEMBER 01, 2018
Missouri Detects 11 New CWD TSE Prion Disease Cases So Far This Season Total 86 to date
SUNDAY, DECEMBER 02, 2018
CWD TSE PRION, REGULATORY LEGISLATION, PAY TO PLAY, and The SPREAD of Chronic Wasting Disease
TUESDAY, DECEMBER 11, 2018
Michigan CWD TSE Prion Climbs To 105 Cases To Date
FRIDAY, MARCH 30, 2018
Michigan Mecosta County man sentenced following DNR investigation Game ranch owner falsified information related to chronic wasting disease testing
what is Michigan feeding their cervid ???
2017 Section 21 C.F.R. 589.2000, Animal Proteins Prohibited in Ruminant Feed
Subject: MICHIGAN FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE BREACH APRIL 4, 2017
MICHIGAN FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE BREACH APRIL 4, 2017
FDA BSE/Ruminant Feed Inspections Firms Inventory
11998 DET-DO MI 48846-847 OPR 4/4/2017 OAI
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation... An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions....end...TSS
WEDNESDAY, JULY 11, 2018
CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000
Wisconsin CWD TSE Prion
LISTEN TO THIS NICE LITTLE CWD BLUES DIDDY BY TAMI ABOUT WISCONSIN CWD TSE PRION. WOW, ANNUAL UPDATES NOW, FROM HERE ON OUT, ABOUT CWD...200,000 CWD TESTS, WITH OVER 3500 CWD POSITIVE CASES, SEEING INCREASING TRENDS IN PREVALENCE AND DISTRIBUTION...CARCASS DISPOSAL SIGNIFICANT CHALLENGE...CWD SAMPLING EFFORTS GONE DONE, WHILE CWD POSITIVES HAVE GONE UP...ALSO, 40 SELF SERVING KIOSKS ACROSS STATE AND FREE HUNTER SERVICE CWD TESTING AND SICK DEER POLICY REPORTING AND TESTING ACROSS STATE!
CWD, Wisconsin, Texas, and Dr. James Kroll
OPINION BLOG
These are just two insights into the man who has been asked to provide analysis and recommended changes to Wisconsin’s deer management program.
Kroll’s insights are from an article entitled “Which Side of the Fence Are You On?”
by Joe Nick Patoski for a past edition of Texas Monthly.
If nothing more, the article gives an unabashed look into the mind-set that will be providing the Wisconsin DNR with recommendations on how to change their deer management practices.
James Kroll (also known as “Deer Dr.”) was appointed to the Wisconsin “deer czar” position last fall.
He was hired by the Department of Administration and instructed to complete a review of the state’s deer management program.
Here’s a sample of the article:
“Game Management,” says James Kroll, driving to his high-fenced, two-hundred-acre spread near Nacogdoches, “is the last bastion of communism.”
Kroll, also known as Dr. Deer, is the director of the Forestry Resources Institute of Texas at Stephen F. Austin State University, and the “management” he is referring to is the sort practiced by the State of Texas.
The 55-year-old Kroll is the leading light in the field of private deer management as a means to add value to the land.
His belief is so absolute that some detractors refer to him as Dr. Dough, implying that his eye is on the bottom line more than on the natural world.
Kroll, who has been the foremost proponent of deer ranching in Texas for more than thirty years, doesn’t mind the controversy and certainly doesn’t fade in the heat.
People who call for more public lands are “cocktail conservationists,” he says, who are really pining for socialism.
He calls national parks “wildlife ghettos” and flatly accuses the government of gross mismanagement.
He argues that his relatively tiny acreage, marked by eight-foot fences and posted signs warning off would-be poachers, is a better model for keeping what’s natural natural while making money off the land.
snip...
It is interesting to note that, in 2001, the State of Texas shifted its deer management strategies toward the same leanings that Kroll has suggested for Wisconsin.
In Texas, the change was brought about via heavy lobbying from the high-fence deer ranching industry. This pressure helped convince the Texas Parks and Wildlife to change their regulations and allow private landowners to select the own deer biologists.
FRIDAY, JUNE 01, 2012
TEXAS DEER CZAR TO WISCONSIN ASK TO EXPLAIN COMMENTS
THURSDAY, MARCH 29, 2012
TEXAS DEER CZAR SAYS WISCONSIN DNR NOT DOING ENOUGH ABOUT CWD LIKE POT CALLING KETTLE BLACK
WEDNESDAY, OCTOBER 03, 2018
WISCONSIN CAVES TO GAME FARM INDUSTRY AGAIN WHILE STATE FALLS FURTHER INTO THE ABYSS OF MAD DEER DISEASE CWD TSE PRION
TUESDAY, NOVEMBER 20, 2018
WISCONSIN Captive CWD TSE Prion Lotto Entitlement Program Pays Out Again Indemnity From Taxpayers $330,000 To Farmers So Far This Year
TUESDAY, SEPTEMBER 25, 2018
Wisconsin CWD TSE PRION PLAN preferred option disposal in a landfill OR public land is acceptable to leave the carcass in the spot of the kill
stupid is, as stupid does, sometimes you can't fix stupid...tss
WEDNESDAY, JUNE 13, 2018
Wisconsin DATCP NVSL confirmed 21 WTD from a deer farm Iowa County tested positive for chronic wasting disease (CWD)
FRIDAY, FEBRUARY 16, 2018
Wisconsin Deer from Now-Quarantined PA Lancaster County Farm Tests Positive for Chronic Wasting Disease CWD TSE Prion
FRIDAY, FEBRUARY 16, 2018
Wisconsin Stop private deer industry from trucking CWD across state Durkin: Stop private deer industry from trucking CWD across state
MONDAY, MARCH 05, 2018
TRUCKING AROUND AND SPREADING CHRONIC WASTING DISEASE CWD TSE PRION VIA MOVEMENT OF CERVID AND TRANSPORTATION VEHICLES
MONDAY, MARCH 20, 2017
Wisconsin CWD TSE Prion Annual Roundup 441 positive
Sunday, May 08, 2016
*** WISCONSIN CHRONIC WASTING DISEASE CWD TSE PRION SPIRALING FURTHER INTO THE ABYSS UPDATE ***
Wisconsin Chronic Wasting Disease CWD TSE Prion
Wednesday, February 10, 2016
*** Wisconsin Two deer that escaped farm had chronic wasting disease CWD ***
Sunday, January 17, 2016
*** Wisconsin Captive CWD Lotto Pays Out Again indemnity payment of $298,770 for 228 white-tailed deer killed on farm ***
MONDAY, NOVEMBER 26, 2018
Wisconsin CWD spreads on deer and elk farms as control efforts stumble
Mon, Nov 26, 2018 11:08 pm
Texas TPWD Reports 2 more cases of Chronic Wasting Disease CWD TSE Prion in Breeder Deer, Release site total jumps to 132 Confirmed to date
Texas TPWD Reports 2 more cases of Chronic Wasting Disease CWD TSE Prion in Breeder Deer, Release site total jumps to 132 Confirmed to date
WEDNESDAY, OCTOBER 03, 2018
Texas Reports 13 more cases of Chronic Wasting Disease CWD TSE Prion in Breeder Deer state total jumps to 130 Confirmed to date
MONDAY, AUGUST 14, 2017
***> Singeltary on Texas Chronic Wasting Disease CWD TSE Prion History
MONDAY, DECEMBER 10, 2018
Wisconsin DATCP Confirms 11 additional animals from a deer farm in Washington County tested positive for CWD TSE Prion
MONDAY, DECEMBER 10, 2018
BOONE AND CROCKETT CLUB POSITION STATEMENT CHRONIC WASTING DISEASE AND THE TRANSPORTATION OF LIVE CERVIDS
SUNDAY, DECEMBER 02, 2018
CWD TSE PRION, REGULATORY LEGISLATION, PAY TO PLAY, and The SPREAD of Chronic Wasting Disease
COLORADO THE ORIGIN OF CHRONIC WASTING DISEASE CWD TSE PRION?
*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.
IN CONFIDENCE, REPORT OF AN UNCONVENTIONAL SLOW VIRUS DISEASE IN ANIMALS IN THE USA 1989
ALSO, one of the most, if not the most top TSE Prion God in Science today is Professor Adriano Aguzzi, and he recently commented on just this, on a cwd post on my facebook page August 20 at 1:44pm, quote;
''it pains me to no end to even comtemplate the possibility, but it seems entirely plausible that CWD originated from scientist-made spread of scrapie from sheep to deer in the colorado research facility. If true, a terrible burden for those involved.'' August 20 at 1:44pm ...end
MONDAY, SEPTEMBER 25, 2017
Colorado Chronic Wasting Disease CWD TSE Prion Mandatory Submission of test samples in some areas and zoonosis
THURSDAY, OCTOBER 04, 2018
Cervid to human prion transmission 5R01NS088604-04 Update
FRIDAY, NOVEMBER 30, 2018
***> The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSEs) in 2017
Singeltary end of year report on zoonosis of tse prion
MONDAY, DECEMBER 03, 2018
***> Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients
SUNDAY, DECEMBER 09, 2018
Creutzfeldt Jakob Disease CJD, BSE, Scrapie, CWD, TSE Prion Annual Report December 14, 2018
FRIDAY, NOVEMBER 30, 2018
Minnesota DNR 11 New CWD TSE Prion Cases This Fall
FRIDAY, NOVEMBER 30, 2018
Quebec, Canada CFIA confirmed the discovery four new positive red deer Chronic Wasting Disease CWD TSE Prion in a deer farm
TUESDAY, OCTOBER 30, 2018
Québec federal officials found third case Chronic Wasting Disease CWD domestic red deer on a farm reported Boileau
SATURDAY, NOVEMBER 10, 2018
Canada Saskatchewan New Case Of CWD TSE PRION Detected Near Melfort Released on November 7, 2018
SUNDAY, OCTOBER 28, 2018
Alberta, Canada 2017 Fall CWD TSE Prion Surveillance Results
THURSDAY, OCTOBER 04, 2018
Cervid to human prion transmission 5R01NS088604-04 Update
SATURDAY, NOVEMBER 10, 2018
cwd, bse, scrapie, cjd, tse prion updated November 10 2018
THURSDAY, OCTOBER 25, 2018
***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion
CWD CWD CWD PIGS PIGS PIGS SCRAPIE SCRAPIE SCRAPIE
Scrapie, CWD, tse prion, transmit to pigs by oral route
***> 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.
MONDAY, NOVEMBER 26, 2018
***>The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP
PRION CONFERENCE 2018
O3 Experimental studies on prion transmission barrier and TSE pathogenesis in large animals
Rosa Bolea(1), Acín C(1)Marín B(1), Hedman C(1), Raksa H(1), Barrio T(1), Otero A(1), LópezPérez O(1), Monleón E(1),Martín-Burriel(1), Monzón M(1), Garza MC(1), Filali H(1),Pitarch JL(1), Garcés M(1), Betancor M(1), GuijarroIM(1), GarcíaM(1), Moreno B(1),Vargas A(1), Vidal E(2), Pumarola M(2), Castilla J(3), Andréoletti O(4), Espinosa JC(5), Torres JM(5), Badiola JJ(1).
1Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, VeterinaryFaculty, Universidad de Zaragoza; Zaragoza,Spain.2 RTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB) 3 4 INRA, ÉcoleVétérinaire, Toulouse, France.5CIC bioGUNE, Prion researchlab, Derio, Spain CISA- INIA, Valdeolmos, Madrid 28130, Spain.
Experimental transmission of Transmissible Spongiform Encephalopathies (TSE) has been understood and related with several factors that could modify the natural development of these diseases. In fact, the behaviour of the natural disease does not match exactly in each animal, being modified by parameters such as the age at infection, the genotype, the breed or the causative strain. Moreover, different TSE strains can target different animal species or tissues, what complicate the prediction of its transmissibility when is tested in a different species of the origin source. The aim of the experimental studies in large animals is to homogenize all those factors, trying to minimize as much as possible variations between individuals. These effects can be flattened by experimental transmission in mice, in which a specific strain can be selected after several passages. With this objective, several experimental studies in large animals have been developed by the presenter research team.
Classical scrapie agent has been inoculated in cow, with the aim of demonstrate the resistance or susceptibility of this species to the first well known TSE; Atypical scrapie has been inoculated in sheep (using several routes of infection), cow and pig, with the objective of evaluating the potential pathogenicity of this strain; Classical Bovine Spongiform Encephalopathy (BSE) has been inoculated in goats aiming to demonstrate if the genetic background of this species could protect against this strain; goat BSE and sheep BSE have been inoculated in goats and pigs respectively to evaluate the effect of species barrier; and finally atypical BSE has been inoculated in cattle to assess the transmissibility properties of this newly introduced strain.
Once the experiments have been carried out on large animal species, a collection of samples from animals studied were inoculated in different types of tg mice overexpressing PrPcin order to study the infectivity of the tissues, and also were studied using PMCA.
In summary, the parameters that have been controlled are the species, the strain, the route of inoculation, the time at infection, the genotype, the age, and the environmental conditions.
To date,
***> eleven of the atypical scrapie intracerebrally inoculated sheep have succumbed to atypical scrapie disease;
***> six pigs to sheep BSE;
***> one cow to classical scrapie;
***> nine goats to goat BSE and
***> five goats to classical BSE.
***> PrPSC has been demonstrated in all cases by immunohistochemistry and western blot.
=====> PRION CONFERENCE 2018
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
snip.....
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.....
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
TUESDAY, JANUARY 17, 2017
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
THIS April, 4, 2017
violation of the mad cow 21 CFR 589.2000 OAI is very serious for the great state of Michigan, some 20 years post FDA mad cow feed of August 1997. if would most likely take a FOIA request and a decade of wrangling to find out more.
TUESDAY, JANUARY 17, 2017
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
I would kindly like to comment on this FDA BSE/Ruminant Feed Inspections Firms Inventory (excel format)4 format, for reporting these breaches of BSE TSE prion protocols, from the extensive mad cow feed ban warning letters the fda use to put out for each violations. simply put, this excel format sucks, and the FDA et al intentionally made it this difficult to follow the usda fda mad cow follies. this is an intentional format to make it as difficult as possible to follow these breaches of the mad cow TSE prion safety feed protocols. to have absolutely no chronological or numerical order, and to format such violations in a way that they are almost impossible to find, says a lot about just how far the FDA and our fine federal friends will go through to hide these continued violations of the BSE TSE prion mad cow feed ban, and any breaches of protocols there from. once again, the wolf guarding the henhouse $$$
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions.
2016
ONE more thing, please remember, the label does not have to say ''deer ration'' for cervid to be pumped up with. you can get the same ''high protein'' from many sources of high protein feed for animals other than cattle, and feed them to cervid...
Saturday, August 29, 2009
FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009
Friday, September 4, 2009
FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009
WEDNESDAY, JULY 11, 2018
CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000
TUESDAY, JULY 10, 2018 CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS ***
''but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.''
CONFIDENTIAL
SPONGIFORM ENCEPHALOPATHY OF PIGS
***2018***
Cervid to human prion transmission
Kong, Qingzhong
Case Western Reserve University, Cleveland, OH, United States
Abstract
Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans.
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.
Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of humanized Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental human CWD samples will also be generated for Aim 3.
Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1.
Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental human CWD samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.
Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.
Public Health Relevance
There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.
Funding Agency
Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS088604-04
Application #
9517118
Study Section
Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)
Program Officer Wong, May
Project Start 2015-09-30 Project End 2019-07-31 Budget Start 2018-08-01 Budget End 2019-07-31 Support Year 4 Fiscal Year 2018 Total Cost Indirect Cost Institution Name Case Western Reserve University Department Pathology Type Schools of Medicine DUNS # 077758407 City Cleveland State OH Country United States Zip Code 44106
Related projects
NIH 2018 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University
NIH 2017 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University
NIH 2016 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University
NIH 2015 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University $337,507
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. <***
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
just out CDC...see;
Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. Barria
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) M. A. Barria et al.
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.
Molecular Barriers to Zoonotic Transmission of Prions
Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. Headcorresponding author
snip...
The conversion of human PrPC by CWD brain homogenate in PMCA reactions was less efficient when the amino acid at position 129 was valine rather than methionine.
***Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.
snip...
However, we can say with confidence that under the conditions used here, none of the animal isolates tested were as efficient as C-type BSE in converting human PrPC, which is reassuring.
***Less reassuring is the finding that there is no absolute barrier to the conversion of human PrPC by CWD prions in a protocol using a single round of PMCA and an entirely human substrate prepared from the target organ of prion diseases, the brain.
Prion 2017 Conference Abstracts
CWD 2017 PRION CONFERENCE
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes.
Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product.
Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain).
Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments.
We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem.
Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes.
All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.
Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.
At present, a total of 10 animals are sacrificed and read-outs are ongoing.
Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years.
Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017
DECIPHERING NEURODEGENERATIVE DISORDERS
Subject: PRION 2017 CONFERENCE
DECIPHERING NEURODEGENERATIVE DISORDERS
VIDEO PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS
*** PRION 2017 CONFERENCE VIDEO
ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION
10. ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD DEER ELK DISEASE IN HUMANS, has it already happened, that should be the question...
''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.
snip...
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.
zoonosis zoonotic cervid tse prion cwd to humans, preparing for the storm
***An alternative to modeling the species barrier is the cell-free conversion assay which points to CWD as the animal prion disease with the greatest zoonotic potential, after (and very much less than) BSE..116***
To date there is no direct evidence that CWD has been or can be transmitted from animals to humans.
However, initial findings from a laboratory research project funded by the Alberta Prion Research Institute (APRI) and Alberta Livestock Meat Agency (ALMA), and led by a Canadian Food Inspection Agency (CFIA) scientist indicate that CWD has been transmitted to cynomolgus macaques (the non-human primate species most closely related to humans that may be used in research), through both the intracranial and oral routes of exposure.
Both infected brain and muscle tissues were found to transmit disease.
Health Canada’s Health Products and Food Branch (HPFB) was asked to consider the impact of these findings on the Branch’s current position on CWD in health products and foods.
Summary and Recommendation:
snip...
Health Portfolio partners were recently made aware of initial findings from a research project led by a CFIA scientist that have demonstrated that cynomolgus macaques can be infected via intracranial exposure and oral gavage with CWD infected muscle.
These findings suggest that CWD, under specific experimental conditions, has the potential to cross the human species barrier, including by enteral feeding of CWD infected muscle.
*** WDA 2016 NEW YORK ***
We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions.
In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species.
***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions.
Student Presentations Session 2
The species barriers and public health threat of CWD and BSE prions
Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University
Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein.
These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species.
The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time.
We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations.
We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species.
***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders
TUESDAY, SEPTEMBER 12, 2017
CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat
SATURDAY, JANUARY 27, 2018
CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018
Subject: CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018
CHRONIC WASTING DISEASE CWD TSE PRION IS THE USA AND NORTH AMERICA'S MAD COW DISEASE.
THE USDA INC ET AL WORKED VERY HARD CONCEALING BSE TSE PRION IN CATTLE. they almost succeeded $$$
BUT CWD TSE PRION IN CERVIDS IS A DIFFERENT BEAST, THE COVER UP THERE, USDA INC COULD NOT CONTAIN.
SPORADIC CJD IS 85%+ OF ALL HUMAN TSE PRION DISEASE.
SPORADIC CJD HAS NOW BEEN LINKED TO TYPICAL AND ATYPICAL BSE, SCRAPIE, AND CWD.
SPORADIC/SPONTANEOUS TSE HAS NEVER BEEN PROVEN.
***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.***
CDC CWD TSE PRION UPDATE USA JANUARY 2018
As of January 2018, CWD in free-ranging deer, elk and/or moose has been reported in at least 22 states in the continental United States, as well as two provinces in Canada. In addition, CWD has been reported in reindeer and moose in Norway, and a small number of imported cases have been reported in South Korea. The disease has also been found in farmed deer and elk. CWD was first identified in captive deer in the late 1960s in Colorado and in wild deer in 1981. By the 1990s, it had been reported in surrounding areas in northern Colorado and southern Wyoming. Since 2000, the area known to be affected by CWD in free-ranging animals has increased to at least 22 states, including states in the Midwest, Southwest, and limited areas on the East Coast.. It is possible that CWD may also occur in other states without strong animal surveillance systems, but that cases haven’t been detected yet. Once CWD is established in an area, the risk can remain for a long time in the environment. The affected areas are likely to continue to expand. Nationwide, the overall occurrence of CWD in free-ranging deer and elk is relatively low. However, in several locations where the disease is established, infection rates may exceed 10 percent (1 in 10), and localized infection rates of more than 25 percent (1 in 4) have been reported. The infection rates among some captive deer can be much higher, with a rate of 79% (nearly 4 in 5) reported from at least one captive herd. As of January 2018, there were 186 counties in 22 states with reported CWD in free-ranging cervids...
Chronic Wasting Disease Among Free-Ranging Cervids by County, United States, January 2018
snip....
*** 2017-2018 CWD TSE Prion UPDATE
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
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 (216-119-163-189.ipset45.wt.net)
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.
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).***
SEE; Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Monday, May 23, 2011
CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning
Public release date: 23-May-2011
Contact: Francesca Costanzo adajmedia@elsevier.com 215-239-3249 Elsevier Health Sciences
CDC assesses potential human exposure to prion diseases Study results reported in the Journal of the American Dietetic Association
Philadelphia, PA, May 23, 2011 – Researchers from the Centers for Disease Control and Prevention (CDC) have examined the potential for human exposure to prion diseases, looking at hunting, venison consumption, and travel to areas in which prion diseases have been reported in animals. Three prion diseases in particular – bovine spongiform encephalopathy (BSE or “Mad Cow Disease”), variant Creutzfeldt-Jakob disease (vCJD), and chronic wasting disease (CWD) – were specified in the investigation. The results of this investigation are published in the June issue of the Journal of the American Dietetic Association.
“While prion diseases are rare, they are generally fatal for anyone who becomes infected. More than anything else, the results of this study support the need for continued surveillance of prion diseases,” commented lead investigator Joseph Y. Abrams, MPH, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta.”But it’s also important that people know the facts about these diseases, especially since this study shows that a good number of people have participated in activities that may expose them to infection-causing agents.”
Although rare, human prion diseases such as CJD may be related to BSE. Prion (proteinaceous infectious particles) diseases are a group of rare brain diseases that affect humans and animals. When a person gets a prion disease, brain function is impaired. This causes memory and personality changes, dementia, and problems with movement. All of these worsen over time. These diseases are invariably fatal. Since these diseases may take years to manifest, knowing the extent of human exposure to possible prion diseases could become important in the event of an outbreak.
CDC investigators evaluated the results of the 2006-2007 population survey conducted by the Foodborne Diseases Active Surveillance Network (FoodNet). This survey collects information on food consumption practices, health outcomes, and demographic characteristics of residents of the participating Emerging Infections Program sites. The survey was conducted in Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and Tennessee, as well as five counties in the San Francisco Bay area, seven counties in the Greater Denver area, and 34 counties in western and northeastern New York.
Survey participants were asked about behaviors that could be associated with exposure to the agents causing BSE and CWD, including travel to the nine countries considered to be BSE-endemic (United Kingdom, Republic of Ireland, France, Portugal, Switzerland, Italy, the Netherlands, Germany, Spain) and the cumulative length of stay in each of those countries. Respondents were asked if they ever had hunted for deer or elk, and if that hunting had taken place in areas considered to be CWD-endemic (northeastern Colorado, southeastern Wyoming or southwestern Nebraska). They were also asked if they had ever consumed venison, the frequency of consumption, and whether the meat came from the wild.
The proportion of survey respondents who reported travel to at least one of the nine BSE endemic countries since 1980 was 29.5%. Travel to the United Kingdom was reported by 19.4% of respondents, higher than to any other BSE-endemic country. Among those who traveled, the median duration of travel to the United Kingdom (14 days) was longer than that of any other BSE-endemic country.. Travelers to the UK were more likely to have spent at least 30 days in the country (24.9%) compared to travelers to any other BSE endemic country. The prevalence and extent of travel to the UK indicate that health concerns in the UK may also become issues for US residents.
The proportion of survey respondents reporting having hunted for deer or elk was 18.5% and 1.2% reported having hunted for deer or elk in CWD-endemic areas. Venison consumption was reported by 67.4% of FoodNet respondents, and 88.6% of those reporting venison consumption had obtained all of their meat from the wild. These findings reinforce the importance of CWD surveillance and control programs for wild deer and elk to reduce human exposure to the CWD agent. Hunters in CWD-endemic areas are advised to take simple precautions such as: avoiding consuming meat from sickly deer or elk, avoiding consuming brain or spinal cord tissues, minimizing the handling of brain and spinal cord tissues, and wearing gloves when field-dressing carcasses.
According to Abrams, “The 2006-2007 FoodNet population survey provides useful information should foodborne prion infection become an increasing public health concern in the future. The data presented describe the prevalence of important behaviors and their associations with demographic characteristics. Surveillance of BSE, CWD, and human prion diseases are critical aspects of addressing the burden of these diseases in animal populations and how that may relate to human health.”
###
The article is “Travel history, hunting, and venison consumption related to prion disease exposure, 2006-2007 FoodNet population survey” by Joseph Y. Abrams, MPH; Ryan A. Maddox, MPH; Alexis R Harvey, MPH; Lawrence B. Schonberger, MD; and Ermias D. Belay, MD. It appears in the Journal of the American Dietetic Association, Volume 111, Issue 6 (June 2011) published by Elsevier.
In an accompanying podcast CDC’s Joseph Y. Abrams discusses travel, hunting, and eating venison in relation to prion diseases. It is available at http://adajournal.org/content/podcast. ;
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Joseph Y. Abrams, MPH, Ryan A. Maddox, MPH , Alexis R. Harvey, MPH , Lawrence B. Schonberger, MD , Ermias D. Belay, MD
Accepted 15 November 2010. Abstract Full Text PDF References .
Abstract
The transmission of bovine spongiform encephalopathy (BSE) to human beings and the spread of chronic wasting disease (CWD) among cervids have prompted concerns about zoonotic transmission of prion diseases. Travel to the United Kingdom and other European countries, hunting for deer or elk, and venison consumption could result in the exposure of US residents to the agents that cause BSE and CWD. The Foodborne Diseases Active Surveillance Network 2006-2007 population survey was used to assess the prevalence of these behaviors among residents of 10 catchment areas across the United States. Of 17,372 survey respondents, 19.4% reported travel to the United Kingdom since 1980, and 29.5% reported travel to any of the nine European countries considered to be BSE-endemic since 1980. The proportion of respondents who had ever hunted deer or elk was 18.5%, and 1.2% had hunted deer or elk in a CWD–endemic area. More than two thirds (67.4%) reported having ever eaten deer or elk meat. Respondents who traveled spent more time in the United Kingdom (median 14 days) than in any other BSE-endemic country. Of the 11,635 respondents who had consumed venison, 59.8% ate venison at most one to two times during their year of highest consumption, and 88.6% had obtained all of their meat from the wild. The survey results were useful in determining the prevalence and frequency of behaviors that could be important factors for foodborne prion transmission.
PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
NOR IS THE FDA recalling this CWD positive elk meat for the well being of the dead elk ;
Wednesday, March 18, 2009
Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II
Transmissible Spongiform Encephalopathies
Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
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 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). ***
*** 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). ***
*** 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/20170126073306/http://collections..europarchive..org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
MONDAY, NOVEMBER 26, 2018
***> Wisconsin CWD spreads on deer and elk farms as control efforts stumble
WITH the recent findings that Scrapie will transmit to Macaque by oral route, that Scrapie and CWD TSE Prion will transit to pigs orally, recent outbreak documented of TSE Prion Disease in Dromedary Camels, Algeria, atypical TSE Prion still being documented, and again just recently in the USA, of another atypical BSE case, and this discovery was only documented by testing 20k head of cattle from some 100M head of cattle in any given year in the USA, the continued denial that atypical BSE and atypical Scrapie are a transmissible disease (science has shown otherwise) this is concerning to me. Science and scientific policy makers have forgotten what Gibbs, Gajdusek, Hadlow, Alper, Zigas, even Gordon with the infamous Scrapie vaccine blunder, a discovery of valuable importance, and so many others i am failing to remember now, what some found long ago, like Dr. Gibbs, he tried to warn us about scrapie zoonosis potential, yet that went ignored for decades and decades. we/scientist/officials/the world, knows the USA FDA PART 589 TSE PRION FEED ban has failed terribly, the BSE testing has failed terribly, and the surveillance there from has failed, SRM removal breaches, all proven by the OIG or the GAO, and others. But yet, we find ourselves now debating the issue of these same risk factors for scrapie, the same risk factors that we all knew were there, with science staring us in the face, we still deny scientific facts all in the name of corporate interest. let's not continue to make these same mistakes. human and animal life is at stake here. we must remove corporate/government/lobbyist interest from the scientific policy making and regulations there from for the TSE Prion, all of them. ...Terry S. Singeltary SR.
O3 Experimental studies on prion transmission barrier and TSE pathogenesis in large animals
Rosa Bolea(1), Acín C(1)Marín B(1), Hedman C(1), Raksa H(1), Barrio T(1), Otero A(1), LópezPérez O(1), Monleón E(1),Martín-Burriel(1), Monzón M(1), Garza MC(1), Filali H(1),Pitarch JL(1), Garcés M(1), Betancor M(1), GuijarroIM(1), GarcíaM(1), Moreno B(1),Vargas A(1), Vidal E(2), Pumarola M(2), Castilla J(3), Andréoletti O(4), Espinosa JC(5), Torres JM(5), Badiola JJ(1).
1Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, VeterinaryFaculty, Universidad de Zaragoza; Zaragoza,Spain.2 RTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB) 3 4 INRA, ÉcoleVétérinaire, Toulouse, France.5CIC bioGUNE, Prion researchlab, Derio, Spain CISA- INIA, Valdeolmos, Madrid 28130, Spain.
Experimental transmission of Transmissible Spongiform Encephalopathies (TSE) has been understood and related with several factors that could modify the natural development of these diseases. In fact, the behaviour of the natural disease does not match exactly in each animal, being modified by parameters such as the age at infection, the genotype, the breed or the causative strain. Moreover, different TSE strains can target different animal species or tissues, what complicate the prediction of its transmissibility when is tested in a different species of the origin source. The aim of the experimental studies in large animals is to homogenize all those factors, trying to minimize as much as possible variations between individuals. These effects can be flattened by experimental transmission in mice, in which a specific strain can be selected after several passages. With this objective, several experimental studies in large animals have been developed by the presenter research team.
Classical scrapie agent has been inoculated in cow, with the aim of demonstrate the resistance or susceptibility of this species to the first well known TSE; Atypical scrapie has been inoculated in sheep (using several routes of infection), cow and pig, with the objective of evaluating the potential pathogenicity of this strain; Classical Bovine Spongiform Encephalopathy (BSE) has been inoculated in goats aiming to demonstrate if the genetic background of this species could protect against this strain; goat BSE and sheep BSE have been inoculated in goats and pigs respectively to evaluate the effect of species barrier; and finally atypical BSE has been inoculated in cattle to assess the transmissibility properties of this newly introduced strain.
Once the experiments have been carried out on large animal species, a collection of samples from animals studied were inoculated in different types of tg mice overexpressing PrPcin order to study the infectivity of the tissues, and also were studied using PMCA.
In summary, the parameters that have been controlled are the species, the strain, the route of inoculation, the time at infection, the genotype, the age, and the environmental conditions.
To date,
***> eleven of the atypical scrapie intracerebrally inoculated sheep have succumbed to atypical scrapie disease;
***> six pigs to sheep BSE;
***> one cow to classical scrapie;
***> nine goats to goat BSE and
***> five goats to classical BSE.
***> PrPSC has been demonstrated in all cases by immunohistochemistry and western blot.
=====> PRION CONFERENCE 2018
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...
ZOONOSIS OF SCRAPIE TSE PRION
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
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
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion... Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
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...
R. BRADLEY
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.
***> 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. <***
Transmission of scrapie prions to primate after an extended silent incubation period
Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.
SNIP...
Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.
The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.
We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.
Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.
The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.
Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.
Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.
Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.
Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.
In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
Singeltary on Scrapie and human transmission way back, see;
O3 Experimental studies on prion transmission barrier and TSE pathogenesis in large animals
Rosa Bolea(1), Acín C(1)Marín B(1), Hedman C(1), Raksa H(1), Barrio T(1), Otero A(1), LópezPérez O(1), Monleón E(1),Martín-Burriel(1), Monzón M(1), Garza MC(1), Filali H(1),Pitarch JL(1), Garcés M(1), Betancor M(1), GuijarroIM(1), GarcíaM(1), Moreno B(1),Vargas A(1), Vidal E(2), Pumarola M(2), Castilla J(3), Andréoletti O(4), Espinosa JC(5), Torres JM(5), Badiola JJ(1).
1Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, VeterinaryFaculty, Universidad de Zaragoza; Zaragoza,Spain.2 RTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB) 3 4 INRA, ÉcoleVétérinaire, Toulouse, France.5CIC bioGUNE, Prion researchlab, Derio, Spain CISA- INIA, Valdeolmos, Madrid 28130, Spain.
Experimental transmission of Transmissible Spongiform Encephalopathies (TSE) has been understood and related with several factors that could modify the natural development of these diseases. In fact, the behaviour of the natural disease does not match exactly in each animal, being modified by parameters such as the age at infection, the genotype, the breed or the causative strain. Moreover, different TSE strains can target different animal species or tissues, what complicate the prediction of its transmissibility when is tested in a different species of the origin source. The aim of the experimental studies in large animals is to homogenize all those factors, trying to minimize as much as possible variations between individuals. These effects can be flattened by experimental transmission in mice, in which a specific strain can be selected after several passages. With this objective, several experimental studies in large animals have been developed by the presenter research team.
Classical scrapie agent has been inoculated in cow, with the aim of demonstrate the resistance or susceptibility of this species to the first well known TSE; Atypical scrapie has been inoculated in sheep (using several routes of infection), cow and pig, with the objective of evaluating the potential pathogenicity of this strain; Classical Bovine Spongiform Encephalopathy (BSE) has been inoculated in goats aiming to demonstrate if the genetic background of this species could protect against this strain; goat BSE and sheep BSE have been inoculated in goats and pigs respectively to evaluate the effect of species barrier; and finally atypical BSE has been inoculated in cattle to assess the transmissibility properties of this newly introduced strain.
Once the experiments have been carried out on large animal species, a collection of samples from animals studied were inoculated in different types of tg mice overexpressing PrPcin order to study the infectivity of the tissues, and also were studied using PMCA.
In summary, the parameters that have been controlled are the species, the strain, the route of inoculation, the time at infection, the genotype, the age, and the environmental conditions.
To date,
***> eleven of the atypical scrapie intracerebrally inoculated sheep have succumbed to atypical scrapie disease;
***> six pigs to sheep BSE;
***> one cow to classical scrapie;
***> nine goats to goat BSE and
***> five goats to classical BSE.
***> PrPSC has been demonstrated in all cases by immunohistochemistry and western blot.
=====> PRION CONFERENCE 2018
1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
***> Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
***> CONGRESSIONAL ABSTRACTS PRION CONFERENCE 2018
P69 Experimental transmission of CWD from white-tailed deer to co-housed reindeer
Mitchell G (1), Walther I (1), Staskevicius A (1), Soutyrine A (1), Balachandran A (1)
(1) National & OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada.
Chronic wasting disease (CWD) continues to be detected in wild and farmed cervid populations of North America, affecting predominantly white-tailed deer, mule deer and elk. Extensive herds of wild caribou exist in northern regions of Canada, although surveillance has not detected the presence of CWD in this population. Oral experimental transmission has demonstrated that reindeer, a species closely related to caribou, are susceptible to CWD. Recently, CWD was detected for the first time in Europe, in wild Norwegian reindeer, advancing the possibility that caribou in North America could also become infected. Given the potential overlap in habitat between wild CWD-infected cervids and wild caribou herds in Canada, we sought to investigate the horizontal transmissibility of CWD from white-tailed deer to reindeer.
Two white-tailed deer were orally inoculated with a brain homogenate prepared from a farmed Canadian white-tailed deer previously diagnosed with CWD. Two reindeer, with no history of exposure to CWD, were housed in the same enclosure as the white-tailed deer, 3.5 months after the deer were orally inoculated. The white-tailed deer developed clinical signs consistent with CWD beginning at 15.2 and 21 months post-inoculation (mpi), and were euthanized at 18.7 and 23.1 mpi, respectively. Confirmatory testing by immunohistochemistry (IHC) and western blot demonstrated widespread aggregates of pathological prion protein (PrPCWD) in the central nervous system and lymphoid tissues of both inoculated white-tailed deer. Both reindeer were subjected to recto-anal mucosal associated lymphoid tissue (RAMALT) biopsy at 20 months post-exposure (mpe) to the white-tailed deer. The biopsy from one reindeer contained PrPCWD confirmed by IHC. This reindeer displayed only subtle clinical evidence of disease prior to a rapid decline in condition requiring euthanasia at 22.5 mpe. Analysis of tissues from this reindeer by IHC revealed widespread PrPCWD deposition, predominantly in central nervous system and lymphoreticular tissues. Western blot molecular profiles were similar between both orally inoculated white-tailed deer and the CWD positive reindeer. Despite sharing the same enclosure, the other reindeer was RAMALT negative at 20 mpe, and PrPCWD was not detected in brainstem and lymphoid tissues following necropsy at 35 mpe. Sequencing of the prion protein gene from both reindeer revealed differences at several codons, which may have influenced susceptibility to infection.
Natural transmission of CWD occurs relatively efficiently amongst cervids, supporting the expanding geographic distribution of disease and the potential for transmission to previously naive populations. The efficient horizontal transmission of CWD from white-tailed deer to reindeer observed here highlights the potential for reindeer to become infected if exposed to other cervids or environments infected with CWD.
Infectious agent of sheep scrapie may persist in the environment for at least 16 years
Gudmundur Georgsson,1 Sigurdur Sigurdarson2 and Paul Brown3
Correspondence
Gudmundur Georgsson ggeorgs@hi.is
1 Institute for Experimental Pathology, University of Iceland, Keldur v/vesturlandsveg, IS-112 Reykjavı´k, Iceland
2 Laboratory of the Chief Veterinary Officer, Keldur, Iceland
3 Bethesda, Maryland, USA
Received 7 March 2006 Accepted 6 August 2006
In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2–3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheephouse that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.
21 YEARS!
***>>>Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded...tss
***> CONGRESSIONAL ABSTRACTS PRION CONFERENCE 2018
P69 Experimental transmission of CWD from white-tailed deer to co-housed reindeer
Mitchell G (1), Walther I (1), Staskevicius A (1), Soutyrine A (1), Balachandran A (1)
(1) National & OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada.
Chronic wasting disease (CWD) continues to be detected in wild and farmed cervid populations of North America, affecting predominantly white-tailed deer, mule deer and elk. Extensive herds of wild caribou exist in northern regions of Canada, although surveillance has not detected the presence of CWD in this population. Oral experimental transmission has demonstrated that reindeer, a species closely related to caribou, are susceptible to CWD. Recently, CWD was detected for the first time in Europe, in wild Norwegian reindeer, advancing the possibility that caribou in North America could also become infected. Given the potential overlap in habitat between wild CWD-infected cervids and wild caribou herds in Canada, we sought to investigate the horizontal transmissibility of CWD from white-tailed deer to reindeer.
Two white-tailed deer were orally inoculated with a brain homogenate prepared from a farmed Canadian white-tailed deer previously diagnosed with CWD. Two reindeer, with no history of exposure to CWD, were housed in the same enclosure as the white-tailed deer, 3.5 months after the deer were orally inoculated. The white-tailed deer developed clinical signs consistent with CWD beginning at 15.2 and 21 months post-inoculation (mpi), and were euthanized at 18.7 and 23.1 mpi, respectively. Confirmatory testing by immunohistochemistry (IHC) and western blot demonstrated widespread aggregates of pathological prion protein (PrPCWD) in the central nervous system and lymphoid tissues of both inoculated white-tailed deer. Both reindeer were subjected to recto-anal mucosal associated lymphoid tissue (RAMALT) biopsy at 20 months post-exposure (mpe) to the white-tailed deer. The biopsy from one reindeer contained PrPCWD confirmed by IHC. This reindeer displayed only subtle clinical evidence of disease prior to a rapid decline in condition requiring euthanasia at 22.5 mpe. Analysis of tissues from this reindeer by IHC revealed widespread PrPCWD deposition, predominantly in central nervous system and lymphoreticular tissues. Western blot molecular profiles were similar between both orally inoculated white-tailed deer and the CWD positive reindeer. Despite sharing the same enclosure, the other reindeer was RAMALT negative at 20 mpe, and PrPCWD was not detected in brainstem and lymphoid tissues following necropsy at 35 mpe. Sequencing of the prion protein gene from both reindeer revealed differences at several codons, which may have influenced susceptibility to infection.
Natural transmission of CWD occurs relatively efficiently amongst cervids, supporting the expanding geographic distribution of disease and the potential for transmission to previously naive populations. The efficient horizontal transmission of CWD from white-tailed deer to reindeer observed here highlights the potential for reindeer to become infected if exposed to other cervids or environments infected with CWD.
TITLE: PATHOLOGICAL FEATURES OF CHRONIC WASTING DISEASE IN REINDEER AND DEMONSTRATION OF HORIZONTAL TRANSMISSION
*** DECEMBER 2016 CDC EMERGING INFECTIOUS DISEASE JOURNAL CWD HORIZONTAL TRANSMISSION
SEE;
Back around 2000, 2001, or so, I was corresponding with officials abroad during the bse inquiry, passing info back and forth, and some officials from here inside USDA aphis FSIS et al. In fact helped me get into the USA 50 state emergency BSE conference call way back. That one was a doozy. But I always remember what “deep throat” I never knew who they were, but I never forgot;
Some unofficial information from a source on the inside looking out -
Confidential!!!!
As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!
---end personal email---end...tss
Infectivity surviving ashing to 600*C is (in my opinion) degradable but infective. based on Bown & Gajdusek, (1991), landfill and burial may be assumed to have a reduction factor of 98% (i.e. a factor of 50) over 3 years. CJD-infected brain-tissue remained infectious after storing at room-temperature for 22 months (Tateishi et al, 1988). Scrapie agent is known to remain viable after at least 30 months of desiccation (Wilson et al, 1950). and pastures that had been grazed by scrapie-infected sheep still appeared to be contaminated with scrapie agent three years after they were last occupied by sheep (Palsson, 1979).
Dr. Paul Brown Scrapie Soil Test BSE Inquiry Document
Using in vitro Prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission.
Claudio Soto Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston.
Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.
=========================
***>>> Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.
========================
Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing
Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
Discussion Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20).
Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22).
Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23).
Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing.
Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building.
Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9).
The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture.
When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier.
This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep.
Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease.
It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled.
Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases.
Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA.
Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions.
PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice.
In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals.
In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions).
As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay.
False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28).
This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm.
This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc.
In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc.
Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing.
The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material.
In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12).
A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30).
This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model.
Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions.
In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination.
These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes.
Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification
Wednesday, December 16, 2015
*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission ***
***> 2018 URGENT DATA <***
THURSDAY, OCTOBER 25, 2018
***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion
JUST OUT CDC;
Tuesday, November 20, 2018
Eyes of CJD patients show evidence of prions Finding could help early diagnosis, raise concern for eye exams and transplants.
Singeltary 1999
***> THE EYES HAVE IT, CJD, AND THEY COULD BE STEALING THEM FROM YOUR LOVED ONE!...year 1999
i said that 20 years ago about this very thing. but did anyone listen...no!
prepare for the storm...terry
year 1999 to 2000
Subject: RE-The Eyes Have It (cjd) and they could be stealing them from your loved one... "pay back time"
Date: Sat, 16 Sep 2000 10:04:26 -0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
Greetings List Members,
I hate to keep kicking a madcow, but this still is very disturbing to me. Not only for the recipient of the cornea's, but as well, for the people whom would be operated on, using the same tools that were used to put those stolen cornea's in the recipient with. No history of this donor or his family (re-ffi), or anything would be known, using stolen organs and or tissue's. I just think this is not only wrong, but very dangerous to a great many other people, as this is one of the most infectious tissues of TSE's. It seems that this practice of stealing organ/tissue happens more than we think. Anyway, the family of the victim which had their cornea's stolen, are now suing. In the example I used with my Mother, if 3 months before, she would have been in a catastrophic accident (car wreck, whatever), no autopsy (for whatever reason), no family (for whatever reason), she lay in the morgue, and after 4 hours, they come steal the cornea's, lot of people could have been infected, just because of lack of medical history of donor/family. It may be hypothetical, but very real. We need to stop the spread of this disease.
kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA
===========================================
Previous story--
Cadaver corneal transplants -- without family permission...
Cadaver corneal transplants -- without family permission Houston, Texas channel 11 news 28 Nov 99
Reported by Terry S. Singeltary Sr.son of CJD victim
"It was a story about how the Lions eye bank were harvesting corneas from victims in the Morgue, without their consent. Under Texas law, this appears to be legal (remember Texas has the Veggie liable law). Even if Family says no, this appears to happen, from what the news story said.
They said the only way to prevent this, is to fill out a form, stating not to have this done. So if you don't fill out the form, they can do this. How many people don't know about the form?
This is not only disgusting and appalling, it could be highly infectious. Without proper background checking of the donors, on their physical history, checking on past dementia, and/or family history, some of these unfortunate victims, could be passing a human TSE.
Response Jill Spitler Clevelland Eye Bank:
"No, we are not stealing.........Yes, you do have such a law in the state of Texas, but not all your state Eye Banks utilize the law. The Eye Bank that you're speaking of is only one of 43 certified Eye Bank throughout the USA.
And there are measure taken per the Medical Standards of the Eye Bank Association of America, the certifying body for eye banks and per FDA regulations to address those concerns that you speak of.
I would suggest that those interested/concern with transplant contact their local agencies. The Eye Bank Association of America has a web. site . Further if anyone has problems contacting or finding out about their local organization(s), call me or e-mail me I would be glad to help. My e-mail address is jill@clevelandeyebank.org"
Terry Singeltary responds:
"Explain this to the family in Houston who went to their loved ones funeral, only to find out that the loved one that was in the casket, had their corneas removed without their permission, without the consent of the victim or it's family. They would not have known it, only for the funny look the victim had. So, they questioned, only to find out, the corneas, had in fact, been removed without consent.
I call that stealing, regardless what the law states. This type of legal grave robbing is not a logical thing to do without knowing any type of background of the victims medical past, which really will not prove anything due to the incubation period. Eye tissue being potentially a highly infective source, there are risks here.
Should they not at least know of the potential ramifications of TSE's (the person receiving the corneas)?
Should there not be some sort of screening?
Should there be some sort of moral issue here?
If this is the case, and in fact, they can come take your corneas, without your consent, then what will they start taking next, without your consent?
Lets look at a hypothetical situation:
What would happen if my Mom (DOD 12-14-97 hvCJD) would have gotten into a car wreck and died, before the symptoms of CJD appeared. Not much money, so there was no autopsy. What would have happened to that recipient of those infecting corneas?"
Comment (webmaster): Actual transmission of CJD by means of corneal transplant may or may not be rare. The incidence of infectivity in older people could be fairly high; this is not to be confused with the lower incidence of symptomatic (clinical) CJD. It is very unlikely that familial CJD would have been diagnosed in earlier generations; however, without interviewing the family even known kindreds would not be excluded.
In blood donation, a much stricter policy is followed, even though corneal transplant may be far more dangerous (being a direct link to the brain and not going through purification steps).
Since highly sensitive tests for pre-clinical CJD are now available, it would make sense to screen corneas for CJD, just as they are screened for AIDS, hepatitus, and a host of other conditions.
Eye procedure raises CJD concerns
BySTEVE MITCHELL, Medical Correspondent
WASHINGTON, Nov. 18 (UPI) -- A New York man who died from a rare brain disorder similar to mad cow disease in May underwent an eye procedure prior to his death that raises concerns about the possibility of transmitting the fatal disease to others, United Press International has learned.
The development comes on the heels of the announcement Thursday by U.S. Department of Agriculture officials of a possible second case of mad cow disease in U.S. herds.
Richard Da Silva, 58, of Orange County, N.Y., died from Creutzfeldt Jakob disease, an incurable brain-wasting illness that strikes about one person per million.
Richard's wife Ann Marie Da Silva told UPI he underwent a check for the eye disease glaucoma in 2003, approximately a year before his death. The procedure involves the use of a tonometer, which contacts the cornea -- an eye tissue that can contain prions, the infectious agent thought to cause CJD.
Ann Marie's concern is that others who had the tonometer used on them could have gotten infected.
A 2003 study by British researchers suggests her concerns may be justified. A team led by J.W. Ironside from the National Creutzfeldt-Jakob Disease Surveillance Unit at the University of Edinburgh examined tonometer heads and found they can retain cornea tissue that could infect other people -- even after cleaning and decontaminating the instrument.
"Retained corneal epithelial cells, following the standard decontamination routine of tonometer prisms, may represent potential prion infectivity," the researchers wrote in the British Journal of Ophthalmology last year. "Once the infectious agent is on the cornea, it could theoretically infect the brain."
Prions, misfolded proteins thought to be the cause of mad cow, CJD and similar diseases, are notoriously difficult to destroy and are capable of withstanding most sterilization procedures.
Laura Manuelidis, an expert on these diseases and section chief of surgery in the neuropathology department at Yale University, agreed with the British researchers that tonometers represent a potential risk of passing CJD to other people.
Manuelidis told UPI she has been voicing her concern about the risks of corneas since 1977 when her own study, published in the New England Journal of Medicine, showed the eye tissue, if infected, could transmit CJD.
At the time the procedure was done on Richard Da Silva, about a year before he died, she said it was "absolutely" possible he was infectious.
The CJD Incidents Panel, a body of experts set up by the U.K. Department of Health, noted in a 2001 report that procedures involving the cornea are considered medium risk for transmitting CJD. The first two patients who have a contaminated eye instrument used on them have the highest risk of contracting the disease, the panel said.
In 1999, the U.K. Department of Health banned opticians from reusing equipment that came in contact with patients' eyes out of concern it could result in the transmission of variant CJD, the form of the disease humans can contract from consuming infected beef products.
Richard Da Silva was associated with a cluster of five other cases of CJD in southern New York that raised concerns about vCJD.
None of the cases have been determined to stem from mad cow disease, but concerns about the cattle illness in the United States could increase in light of the USDA announcement Thursday that a cow tested positive on initial tests for the disease. If confirmed, this would be the second U.S. case of the illness; the first was detected in a Washington cow last December. The USDA said the suspect animal disclosed Thursday did not enter the food chain. The USDA did not release further details about the cow, but said results from further lab tests to confirm the initial tests were expected within seven days.
Ann Marie Da Silva said she informed the New York Health Department and later the eye doctor who performed the procedure about her husband's illness and her concerns about the risk of transmitting CJD via the tonometer.
The optometrist -- whom she declined to name because she did not want to jeopardize his career -- "didn't even know what this disease was," she said.
"He said the health department never called him and I called them (the health department) back and they didn't seem concerned about it," she added. "I just kept getting angrier and angrier when I felt I was being dismissed."
She said the state health department "seems to have an attitude of don't ask, don't tell" about CJD.
"There's a stigma attached to it," she said. "Is it because they're so afraid the public will panic? I don't know, but I don't think that the answer is to push things under the rug."
New York State Department of Health spokeswoman Claire Pospisil told UPI she would look into whether the agency was concerned about the possibility of transmitting CJD via tonometers, but she had not called back prior to story publication.
Disposable tonometers are readily available and could avoid the risk of transmitting the disease, Ironside and colleagues noted in their study. Ann Marie Da Silva said she asked the optometrist whether he used disposable tonometers and "he said 'No, it's a reusable one.'"
Ironside's team also noted other ophthalmic instruments come into contact with the cornea and could represent a source of infection as they are either difficult to decontaminate or cannot withstand the harsh procedures necessary to inactivate prions. These include corneal burrs, diagnostic and therapeutic contact lenses and other coated lenses.
Terry Singletary, whose mother died from a type of CJD called Heidenhain Variant, told UPI health officials were not doing enough to prevent people from being infected by contaminated medical equipment.
"They've got to start taking this disease seriously and they simply aren't doing it," said Singletary, who is a member of CJD Watch and CJD Voice -- advocacy groups for CJD patients and their families.
U.S. Centers for Disease Control and Prevention spokeswoman Christine Pearson did not return a phone call from UPI seeking comment. The agency's Web site states the eye is one of three tissues, along with the brain and spinal cord, that are considered to have "high infectivity."
The Web site said more than 250 people worldwide have contracted CJD through contaminated surgical instruments and tissue transplants. This includes as many as four who were infected by corneal grafts. The agency noted no such cases have been reported since 1976, when sterilization procedures were instituted in healthcare facilities.
Ironside and colleagues noted in their study, however, many disinfection procedures used on optical instruments, such as tonometers, fail. They wrote their finding of cornea tissue on tonometers indicates that "no current cleaning and disinfection strategy is fully effective."
Singletary said CDC's assertion that no CJD cases from infected equipment or tissues have been detected since 1976 is misleading.
"They have absolutely no idea" whether any cases have occurred in this manner, he said, because CJD cases often aren't investigated and the agency has not required physicians nationwide report all cases of CJD.
"There's no national surveillance unit for CJD in the United States; people are dying who aren't autopsied, the CDC has no way of knowing" whether people have been infected via infected equipment or tissues, he said.
Ann Marie Da Silva said she has contacted several members of her state's congressional delegation about her concerns, including Rep. Sue Kelly, R-N.Y., and Sen. Charles Schumer, D-N.Y.
"Basically, what I want is to be a positive force in this, but I also want more of a dialogue going on with the public and the health department," she said.
Friday, December 04, 2009
New guidance on decontamination of trial contact lenses and other contact devices has been revealed for CJD AND vCJD
SUNDAY, JANUARY 17, 2016
Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease
TUESDAY, NOVEMBER 20, 2018
CDC Eyes of CJD patients show evidence of prions concerns for iatrogenic transmission
MONDAY, NOVEMBER 19, 2018
Benefit cuts hit mad cow disease sufferer A girl born severely disabled from vCJD may lose her home under universal credit
2006-2007
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory
TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption.
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007.
With all the science to date refuting it, to continue to validate this myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, surgical, blood, medical, cosmetics etc.
I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down.
Accumulation and Transmission are key to the threshold from subclinical to clinical disease, and of that, I even believe that physical and or blunt trauma may play a role of onset of clinical symptoms in some cases, but key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain.
BUT, to continue with this myth that the U.K. strain of BSE one strain in cows, and the nv/v CJD, one strain in humans, and that all the rest of human TSE is one single strain i.e. sporadic CJD (when to date there are 6 different phenotypes of sCJD), and that no other animal TSE transmits to humans, to continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come.
ONE was enough for me, My Mom, hvCJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human.
WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE?
Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE.
There must be a proper classification that will differentiate between all these human TSE in order to do this.
With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously.
My name is Terry S. Singeltary Sr. and I am no scientist, no doctor and have no PhDs, but have been independently researching human and animal TSEs since the death of my Mother to the Heidenhain Variant of Creutzfeldt Jakob Disease on December 14, 1997 'confirmed'.
...END
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor:
In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734.
BRITISH MEDICAL JOURNAL
BMJ
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well....
02 January 2000
Terry S Singeltary
retired
US scientists develop a possible test for BSE
BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7220.1312b (Published 13 November 1999) Cite this as: BMJ 1999;319:1312
Rapid responses Response
Re: vCJD in the USA * BSE in U.S.
15 November 1999
Terry S Singeltary
NA
medically retired
January 28, 2003; 60 (2) VIEWS & REVIEWS
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Ermias D. Belay, Ryan A. Maddox, Pierluigi Gambetti, Lawrence B. Schonberger
First published January 28, 2003, DOI: https://doi.org/10.1212/01.WNL.0000036913.87823.D6
Abstract
Transmissible spongiform encephalopathies (TSEs) attracted increased attention in the mid-1980s because of the emergence among UK cattle of bovine spongiform encephalopathy (BSE), which has been shown to be transmitted to humans, causing a variant form of Creutzfeldt-Jakob disease (vCJD). The BSE outbreak has been reported in 19 European countries, Israel, and Japan, and human cases have so far been identified in four European countries, and more recently in a Canadian resident and a US resident who each lived in Britain during the BSE outbreak. To monitor the occurrence of emerging forms of CJD, such as vCJD, in the United States, the Centers for Disease Control and Prevention has been conducting surveillance for human TSEs through several mechanisms, including the establishment of the National Prion Disease Pathology Surveillance Center. Physicians are encouraged to maintain a high index of suspicion for vCJD and use the free services of the pathology center to assess the neuropathology of clinically diagnosed and suspected cases of CJD or other TSEs.
Received May 7, 2002. Accepted August 28, 2002.
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Terry S. Singeltary, retired (medically)
Published March 26, 2003
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
Reply to Singletary Ryan A. Maddox, MPH Other Contributors: Published March 26, 2003
Mr. Singletary raises several issues related to current Creutzfeldt- Jakob disease (CJD) surveillance activities. Although CJD is not a notifiable disease in most states, its unique characteristics, particularly its invariably fatal outcome within usually a year of onset, make routine mortality surveillance a useful surrogate for ongoing CJD surveillance.[1] In addition, because CJD is least accurately diagnosed early in the course of illness, notifiable-disease surveillance could be less accurate than, if not duplicative of, current mortality surveillance.[1] However, in states where making CJD officially notifiable would meaningfully facilitate the collection of data to monitor for variant CJD (vCJD) or other emerging prion diseases, CDC encourages the designation of CJD as a notifiable disease.[1] Moreover, CDC encourages physicians to report any diagnosed or suspected CJD cases that may be of special public health importance (e.g., vCJD, iatrogenic CJD, unusual CJD clusters).
As noted in our article, strong evidence is lacking for a causal link between chronic wasting disease (CWD) of deer and elk and human disease,[2] but only limited data seeking such evidence exist. Overall, the previously published case-control studies that have evaluated environmental sources of infection for sporadic CJD have not consistently identified strong evidence for a common risk factor.[3] However, the power of a case-control study to detect a rare cause of CJD is limited, particularly given the relatively small number of subjects generally involved and its long incubation period, which may last for decades. Because only a very small proportion of the US population has been exposed to CWD, a targeted surveillance and investigation of unusual cases or case clusters of prion diseases among persons at increased risk of exposure to CWD is a more efficient approach to detecting the possible transmission of CWD to humans. In collaboration with appropriate local and state health departments and the National Prion Disease Pathology Surveillance Center, CDC is facilitating or conducting such surveillance and case- investigations, including related laboratory studies to characterize CJD and CWD prions.
Mr. Singletary also expresses concern over a recent publication by Asante and colleagues indicating the possibility that some sporadic CJD cases may be attributable to bovine spongiform encephalopathy (BSE).[4] The authors reported that transgenic mice expressing human prion protein homozygous for methionine at codon 129, when inoculated with BSE prions, developed a molecular phenotype consistent with a subtype of sporadic CJD. Although the authors implied that BSE might cause a sporadic CJD-like illness among persons homozygous for methionine, the results of their research with mice do not necessarily directly apply to the transmission of BSE to humans. If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic CJD cases would be expected to first occur in the United Kingdom, where the vast majority of vCJD cases have been reported. In the United Kingdom during 1997 through 2002, however, the overall average annual mortality rate for sporadic CJD was not elevated; it was about 1 case per million population per year. In addition, during this most recent 6-year period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of UK sporadic CJD deaths.[3, 5] Furthermore, surveillance in the UK has shown no increase in the proportion of sporadic CJD cases that are homozygous for methionine (Will RG, National CJD Surveillance Unit, United Kingdom, 2003; personal communication).
References
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Diagnosis and reporting of Creutzfeldt-Jakob disease. JAMA 2001;285:733-734.
2. Belay ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States. Neurology 2003;60:176-181.
3. Belay ED. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol 1999;53:283-314.
4. Asante EA, Linehan JM, Desbruslais M, et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 2002;21:6358-6366.
5. The UK Creutzfeldt-Jakob Disease Surveillance Unit. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm. Accessed February 18, 2003.
Competing Interests: None declared.
doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003.
Volume 3, Issue 8, August 2003, Page 463
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem..” ............................
SUNDAY, DECEMBER 02, 2018
CWD TSE PRION, REGULATORY LEGISLATION, PAY TO PLAY, and The SPREAD of Chronic Wasting Disease
PREPARE FOR THE STORM...
FRIDAY, NOVEMBER 30, 2018
***>>>The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSEs) in 2017 Published November 2018
COLORADO THE ORIGIN OF CHRONIC WASTING DISEASE CWD TSE PRION?
*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.
IN CONFIDENCE, REPORT OF AN UNCONVENTIONAL SLOW VIRUS DISEASE IN ANIMALS IN THE USA 1989
ALSO, one of the most, if not the most top TSE Prion God in Science today is Professor Adriano Aguzzi, and he recently commented on just this, on a cwd post on my facebook page August 20 at 1:44pm, quote;
''it pains me to no end to even comtemplate the possibility, but it seems entirely plausible that CWD originated from scientist-made spread of scrapie from sheep to deer in the colorado research facility. If true, a terrible burden for those involved.'' August 20 at 1:44pm ...end
MONDAY, SEPTEMBER 25, 2017
Colorado Chronic Wasting Disease CWD TSE Prion Mandatory Submission of test samples in some areas and zoonosis
MONDAY, DECEMBER 10, 2018
Wisconsin DATCP Confirms 11 additional animals from a deer farm in Washington County tested positive for CWD TSE Prion
MONDAY, DECEMBER 10, 2018
BOONE AND CROCKETT CLUB POSITION STATEMENT CHRONIC WASTING DISEASE AND THE TRANSPORTATION OF LIVE CERVIDS
MONDAY, DECEMBER 10, 2018
Wisconsin DATCP Confirms 11 additional animals from a deer farm in Washington County tested positive for CWD TSE Prion
FRIDAY, NOVEMBER 30, 2018
The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSEs) in 2017
Friday, December 14, 2018
FSIS Recalling 10,828 pounds raw intact bone-in beef quarters cattle Products may contain Specified Risk Materials (SRM) MOST HIGH RISK FOR BSE MAD COW DISEASE
FRIDAY, DECEMBER 14, 2018
MAD COW USA FLASHBACK FRIDAY DECEMBER 14, 2018
THURSDAY, OCTOBER 04, 2018
Cervid to human prion transmission 5R01NS088604-04 Update
Singeltary end of year report on zoonosis of tse prion
SUNDAY, DECEMBER 09, 2018
Creutzfeldt Jakob Disease CJD, BSE, Scrapie, CWD, TSE Prion Annual Report December 14, 2018
FRIDAY, DECEMBER 14, 2018
Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
3:06 PM
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