SCRAPIE USA

Transmissible Spongiform Encephalopathy TSE Prion PrP sheep and goats

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Location: BACLIFF, Texas, United States

My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS

Saturday, December 04, 2021

Final rule on the Importation of Sheep, Goats, and Certain Other Ruminants (APHIS-2009-0095) Scrapie, BSE, CWD, TSE Prion

Final rule on the Importation of Sheep, Goats, and Certain Other Ruminants (APHIS-2009-0095) Scrapie, BSE, CWD, TSE Prion


This is an incredibly bad idea, based on trade, not science, imo...terry

United States Senate

Washington DC 20510

February 5, 2021

Robert Fairweather Acting Director United States Office of Management and Budget

725 17th Street NW Washington, DC 20503

Dear Acting Director Fairweather,

We write to urge you to withdraw the final rule on the Importation of Sheep, Goats, and Certain Other Ruminants (APHIS-2009-0095) until its impact on current market conditions has been fully evaluated. The rule seeks to remove bovine spongiform encephalopathy (BSE) related import restrictions on sheep, goats, and most of their products. 

The existing BSE-related import restrictions function as a necessary protection against the introduction of other transmissible spongiform encephalopathies (TSEs), such as scrapie.TSEs are a group of rare degenerative brain disorders. Scrapie and BSE are both TSEs. BSE, commonly known as “mad cow disease,” is a progressive neurologic disease of cows. 

Scrapie is a fatal, degenerative disease which affects the central nervous system of sheep and goats. 

There is no cure or treatment for either disease.The federal government has invested over $200 million into scrapie eradication since the early 2000s. 

This investment has yielded tremendous results, lowering the percentage of scrapie-positive cull sheep at slaughter by 99 percent since FY2003. 

By allowing scrapie positive animals and genetic materials into the United States, we risk reintroducing the very disease we have nearly eradicated. 

If disease is reintroduced into domestic flocks, opportunities for export will rapidly decline. 

Prior to a domestic BSE occurrence in cattle in 2003, Japan was the primary export market for U.S. lamb. 

Japan quickly closed American access to its market and the U.S. did not recoup it until 2018.

The rule should not precede accomplishing increased market access for American lamb, goats, and their products. 

By removing BSE-related restrictions, the United States would be increasing foreign imports while trade obstructions from countries such as the United Kingdom, European Union, and China remain in place.

For these reasons, we urge you to withdraw the final rule on the Importation of Sheep, Goats, and Certain Other Ruminants. 

Thank you for your time and consideration of our request.

Sincerely,

________________________________________

Kevin Cramer John Cornyn United States Senator United States Senator


Volume 27, Number 12—December 2021

Dispatch

Experimental Oronasal Transmission of Chronic Wasting Disease Agent from White-Tailed Deer to Suffolk Sheep

Eric D. Cassmann, S. Jo Moore, and Justin J. GreenleeComments to Author 

Author affiliation: US Department of Agriculture, Ames, Iowa, USA

Abstract

Chronic wasting disease (CWD) is a fatal prion disease of cervids. We examined host range of CWD by oronasally inoculating Suffolk sheep with brain homogenate from a CWD-positive white-tailed deer. Sixty months after inoculation, 1/7 sheep had immunoreactivity against the misfolded form of prion protein in lymphoid tissue. Results were confirmed by mouse bioassay.

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of fatal neurologic diseases caused by a misfolded form of the prion protein (PrPSc). Several TSEs affect livestock, including scrapie in sheep and chronic wasting disease (CWD) in cervids.

Susceptibility of sheep to the agent of scrapie is determined by the host prion protein genotype. Three polymorphisms at codons 136, 154, and 171 of the prion protein gene occur in sheep. The haplotype A136R154R171 is associated with resistance to scrapie, whereas VRQ is linked with susceptibility. Likewise, the deer prion protein genotype GG96 is overrepresented in cases of CWD.

CWD was identified in captive mule deer in Colorado, USA, in 1967 (1). Since then, CWD has been reported in >24 states in the United States, 2 provinces in Canada, and South Korea (2,3). During 2016, CWD was reported in Europe, and it has since been detected in 3 Nordic countries (Norway, Sweden, and Finland), although CWD strains in Europe were recently shown to be distinct from strains in North America (4). Because of human consumption of cervid meat products and intermingling of various livestock species with wild cervid populations, there is major interest in characterizing the possible host range of CWD.

Scrapie has been implicated as the possible source of CWD in cervids (5). This finding is supported by in vitro conversion of sheep prion protein by infectious CWD prions (6) and glycoprofile similarities between scrapie and CWD prions (7). Another similarity between scrapie and CWD is prominent lymphoid accumulation of PrPSc in both species affected (5). Experimental transmission of mule deer CWD to Suffolk sheep by intracranial inoculation, a highly artificial route of transmission, has been performed (8). Widespread peripheral lymphoid accumulation of PrPSc is retained in intracranially CWD inoculated sheep.

The objective of this study was to test the oronasal susceptibility of sheep to the agent of CWD. We report the preliminary findings of an ongoing multiyear study.

The Study Initially, we oronasally inoculated (9) seven Suffolk lambs (3‒4 months of age) with the V136R154Q171/ARQ (n = 2), ARQ/ARQ (n = 4), or ARQ/ARR (n = 1) prion protein genotype and 0.1 g of 10% (wt/vol) brain homogenate from a GG96 white-tailed deer that had CWD. The sheep were housed indoors in a Biosafety Level 2 agriculture facility separate from scrapie-affected sheep. At 60 months postinoculation, the initial experimental endpoint, sheep were asymptomatic, and all 7 sheep were culled.

We performed a postmortem examination on each sheep and collected a full spectrum of tissues, which we froze and stored in 10% neutral-buffered formalin. To evaluate lymphoinvasion and neuroinvasion, we tested tissues from the brainstem at the obex and pons, third eyelid, palatine tonsil, lymph nodes (mesenteric and retropharyngeal), spleen, and ileum. We processed the formalin-fixed tissues, embedded in paraffin, and sectioned at optimal thickness (brain, 4 µm; lymphoid, 3 µm; and other tissues, 5 µm) for subsequent staining with hematoxylin and eosin and immunohistochemical (IHC) analysis. We used a cocktail of PrPSc monoclonal antibodies (F89/160.1.5 and F99/97.6.1; 5 μg/mL) for IHC.

Immunoreactivity against misfolded form of the prion protein (red) in lymphoid tissue from a sheep oronasally inoculated with the agent of chronic wasting disease from white-tailed deer. A) Retropharyngeal lymph node (original magnification ×100.) B) Palatine tonsil (original magnification ×40). We used a cocktail of monoclonal antibodies (F89/160.1.5 and F99/97.6.1). Figure 1. Immunoreactivity against misfolded form of the prion protein (red) in lymphoid tissue from a sheep oronasally inoculated with the agent of chronic wasting disease from white-tailed deer. A) Retropharyngeal lymph...

Examination of IHC-stained tissues showed PrPSc in the retropharyngeal lymph node (Figure 1, panel A) and palatine tonsil (Figure 1, panel B) of 1 sheep inoculated with the ARQ/ARQ genotype. The retropharyngeal lymph node was also positive by enzyme immunoassay (EIA) (HerdChek; IDEXX Laboratories, https://www.idexx.comExternal Link) at initial (optical density 0.99; negative cutoff value 0.186) and repeat (optical density 0.559; negative cutoff value 0.178) tests. The palatine tonsil was negative by EIA.

To confirm prion disease infectivity in the retropharyngeal lymph node, we performed bioassays in Tg12 cervidized (10) and Tg338 ovinized (11) transgenic mice. Mice expressed the transgene for the elk prion protein polymorphism MM132 (Tg12) and the ovine prion protein polymorphisms V136R154Q171 (Tg338). We homogenized fresh frozen lymph nodes to 10% (wt/vol) and enriched them by repeated rounds of differential centrifugation; we intracranially inoculated mice with 20 μL of 10% (wt/vol) equivalent enriched homogenate. The Tg12 bioassay had a partial attack rate of 5/9 mice. Most (4/5) dead Tg12 mice were strongly positive by EIA (optical density 4.0) and had an average incubation period of 511 days.

Western blot analysis showing proteinase K‒resistant misfolded form of the prion protein (PrPSc) in brains of 4 Tg12 mice. Mice were intracranially inoculated with a homogenate made from retropharyngeal lymph node of a sheep oronasally inoculated with the agent of chronic wasting disease. Tg12 brain was prepared as a 10% (wt/vol) homogenate with phosphate-buffered saline. A total of 1 mg of tissue equivalent was treated with proteinase K (90 μg/mL) before electrophoresis. Immunodetection of PrPSc was performed overnight at 4°C with monoclonal antibody Sha31 (dilution 1:10,000). Left lane, molecular mass ladder. kDa, kilodaltons. Figure 2. Western blot analysis showing proteinase K‒resistant misfolded form of the prion protein (PrPSc) in brains of 4 Tg12 mice. Mice were intracranially inoculated with a homogenate made from...

Western blots of these 4 Tg12 mice confirmed the presence of proteinase K‒resistant PrPSc in the brains (Figure 2). The positive EIA results were obtained from brain homogenates in Tg12 mice; the spleens were negative for PrPSc. For the Tg338 bioassay (n = 15), brains and spleens were negative by EIA. Four Tg338 mice that died or were euthanized because of intercurrent disease at 254, 462, 629, and 657 days postinoculation were negative by EIA. The rest of the Tg338 mice were negative at the study endpoint, 700 days postinoculation.

Top

Conclusions The oronasal susceptibility of sheep to the agent of CWD is a major finding in light of its possible effect on risk assessment and understanding possible transmission of CWD to noncervid species in field conditions. Interspecies transmission of TSEs is less likely when the experimental species barrier between hosts is strong (12). One study demonstrated that the CWD agent does not readily transmit to transgenic ovinized mice (13). However, another study reported lifelong replication of PrPSc in the spleen after intracranial inoculation of the CWD agent in Tg338 ovinized mice (14). The finding of extraneuronal PrPSc in 1 sheep 5 years after oral inoculation suggests that sheep are unlikely to develop neurologic disease after natural exposure to the agent of CWD, but they might serve as asymptomatic carriers under the right conditions.

In this study, we used a relatively low dose (0.1 g) of brain homogenate. These results are intriguing, but they do not assess potential modes of transmission that could occur in the field, such as nose-to-nose contact or environmental contamination. In our ongoing multiyear study, 1 sheep had PrPSc-positive lymphoid tissue but no evidence of neuroinvasion 5 years postinoculation. This time interval is an extremely protracted incubation period. Had we continued this experiment, it is unknown how long the sheep would have remained asymptomatic or whether they would have eventually developed clinical disease. Because PrPSc was detected in lymphoid tissues of the head, the possibility that this sheep might have been shedding infectivity into the environment cannot be ruled out.

Positive bioassay results in Tg12 mice confirm CWD infectivity in the lymph node. Negative results in Tg338 mice could be explained by a donor/host mismatch between the ARQ donor sheep and VRQ expressing mice. Pursuing bioassays in A136-expressing transgenic mice could be more fruitful.

Interspecies transmission events might increase the pathogenicity of an infectious prion on subsequent transmission to other species (15). Thus, exploration of potential new host ranges of this CWD isolate and performing human health risk assessments will provide useful information for this prion. 

Dr. Cassmann is a research veterinary medical officer at the National Animal Disease Center, Ames, IA. His primary research interests are veterinary pathology, animal prion diseases, interspecies transmission, host ranges, host genetic susceptibility, and diagnostics. 

Acknowledgments

snip...


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

Title: Experimental oronasal transmission of the CWD agent from whitetail deer to Suffolk sheep

Author item Cassmann, Eric item MOORE, SARA JO - Orise Fellow item Greenlee, Justin Submitted to: Emerging Infectious Diseases Publication Type: Peer Reviewed Journal Publication Acceptance Date: 8/20/2021 Publication Date: N/A Citation: N/A Interpretive 

Summary: Transmissible spongiform encephalopathies (TSEs) are a group of fatal diseases caused by the accumulation of misfolded prion protein in the brain. Several livestock species including sheep, deer, and elk are afflicted by prion diseases. In sheep the disease is called scrapie. In deer and elk, the disease is called chronic wasting disease (CWD). The source of CWD is unknown, but it is speculated that the origin of CWD may have been due to a species jump of scrapie in sheep to deer. Due to the human consumption of cervid meat products and intermingling of various livestock species with wild cervid populations, there is significant interest in characterizing the possible host range of CWD. This study reports preliminary results of an ongoing multi-year experiment on the oronasal transmission of CWD from white-tailed deer to sheep. After a five-year period, 1/7 sheep had detectable CWD prions in the retropharyngeal lymph nodes and tonsil. Infectivity of these prions was confirmed using a bioassay with transgenic mice expressing cervid prion protein. These results demonstrate the susceptibility of sheep to the agent of CWD after a prolonged incubation period. Since the original experiment ended after five years, it is unknown if the sheep would have remained asymptomatic or developed clinical prion disease given a longer incubation period. It is also unknown if sheep are capable of shedding or transmitting CWD prions. Additional work is necessary to further characterize the transmission properties of the CWD agent in sheep and other species.

Technical Abstract: CWD is a fatal prion disease of cervids. This study examined the host range of CWD by orally inoculating Suffolk sheep with brain homogenate from a CWD positive white-tailed deer. Sixty-months after oronasal inoculation, 1/7 sheep had immunoreactivity against PrPSc in the lymphoid tissue that was confirmed by mouse bioassay.


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

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

Author 

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

Interpretive Summary:

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


***> “In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.”

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

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

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

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

ABSTRACT

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


***> “The scrapie agent readily transmits between sheep and deer after oronasal exposure. This could confound the identification of CWD strains in deer and the eradication of scrapie from sheep.”

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


J Vet Diagn Invest . 2021 Jul;33(4):711-720. doi: 10.1177/10406387211017615. Epub 2021 May 28. D Cassmann 1, Rylie D Frese 1, Justin J Greenlee 1

Affiliations expand PMID: 34047228 PMCID: PMC8229824 (available on 2022-05-28)DOI: 10.1177/10406387211017615 Full text linksCite Abstract

The origin of chronic wasting disease (CWD) in cervids is unclear. One hypothesis suggests that CWD originated from scrapie in sheep. We compared the disease phenotype of sheep-adapted CWD to classical scrapie in sheep. We inoculated sheep intracranially with brain homogenate from first-passage mule deer CWD in sheep (sCWDmd). The attack rate in second-passage sheep was 100% (12 of 12). Sheep had prominent lymphoid accumulations of PrPSc reminiscent of classical scrapie. The pattern and distribution of PrPSc in the brains of sheep with CWDmd was similar to scrapie strain 13-7 but different from scrapie strain x124. The western blot glycoprofiles of sCWDmd were indistinguishable from scrapie strain 13-7; however, independent of sheep genotype, glycoprofiles of sCWDmd were different than x124. When sheep genotypes were evaluated individually, there was considerable overlap in the glycoprofiles that precluded significant discrimination between sheep CWD and scrapie strains. Our data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given our results, current detection techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally. It is unknown if sheep are naturally vulnerable to CWD; however, the susceptibility of sheep after intracranial inoculation and lymphoid accumulation indicates that the species barrier is not absolute.

Keywords: PrPSc proteins; chronic wasting disease; deer; prions; scrapie; sheep.


***> ”Our data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given our results, current detection techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally.”



Title: Second passage of chronic wasting disease of mule deer in sheep compared to classical scrapie after intracranial inoculation

Taken together, these data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. 


''We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation.''

Title: Passage of scrapie to deer results in a new phenotype upon return passage to sheep


Title: Transmission of the agent of sheep scrapie to deer results in PrPSc with two distinct molecular profiles 

***> In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile type readily passes to deer. 




cwd scrapie pigs oral routes 

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

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

***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). 

***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains. 




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.


CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

LINE TO TAKE

3. If questions on pharmaceuticals are raised at the Press conference, the suggested line to take is as follows:- 

 "There are no medicinal products licensed for use on the market which make use of UK-derived porcine tissues with which any hypothetical “high risk" ‘might be associated. The results of the recent experimental work at the CSM will be carefully examined by the CSM‘s Working Group on spongiform encephalopathy at its next meeting.

DO Hagger RM 1533 MT Ext 3201


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


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


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


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


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


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


***> cattle, pigs, sheep, cwd, tse, prion, oh my! 

***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). 
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable. 


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..... 


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

PLEASE NOTE;

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

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

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


FRIDAY, NOVEMBER 19, 2021 

EFSA Annual Report of the Scientific Network on BSE-TSE 2021


TUESDAY, SEPTEMBER 07, 2021 

Atypical Bovine Spongiform Encephalopathy BSE OIE, FDA 589.2001 FEED REGULATIONS, and Ingestion Therefrom


Terry S. Singeltary Sr.

MONDAY, NOVEMBER 29, 2021 

Experimental Oronasal Transmission of Chronic Wasting Disease Agent from White-Tailed Deer to Suffolk Sheep Volume 27, Number 12—December 2021 Dispatch



SENATORS URGE BIDEN TO WITHDRAW SHEEP IMPORT RULE DUE TO SCRAPIE TSE Prion CONCERNS

Wed, Feb 10, 2021 12:55 pm

From Terry Singeltary flounder9@verizon.net

To 

Greetings Senator Fairweather, Senators John Cornyn (R-TX), Steve Daines (R-MT), John Barrasso (R-WY), Cynthia Lummis (R-WY), John Thune (R-SD), John Hoeven (R-ND), and Mike Rounds (R-SD), et al, 

I wish to make this urgent statement/plea, with updated science on the Scrapie TSE Prion. i have been involved with this research daily for 23 years, and would like to kindly send this information for you all. i have always been non-partisan when it comes to the Transmissible Spongiform Encephalopathy TSE Prion disease, and in fact Senator Cornyn kindly helped me out years ago get the NIH et al to stop destroying the brain tissue of the dead from tse prion disease that we had so much pain in donating, and that's another story. Sadly today, his office rudely did not have time for me, did not want to hear about this information, and would not give me contact information. i called and they were not interested in me getting in contact with Senator Cornyn. damn shame now you can't even get in touch with politicians by email. Regardless if this is a political move or not, because each one of you Senators that are now concerned, were not concerned before, that i am aware of. regardless, i am glad attention is now being brought forth by these risk factors for Scrapie, and you better be concerned with atypical Nor-98 Scrapie, due to what it does when it cross overs into other species. for this, you should all study the recent peer review and transmission studies that have come forth over the past decade. as a Democrat, i was not happy with President Bidens pick Tom Vilsacki i.e. been there, done that, with the first round of mad cow follies. i have been doing this daily for 23 years, since losing my mother to the hvCJD i.e. the Heidenhain Variant of CJD, another strain of the infamous sporadic spontaneous CJD...LOL, there is no such thing. just made a promise to mom, never forget, and never let them forget. i have documented every move of the USDA/APHIS/FSIS/FDA et al on the BSE, Scrapie, and CWD saga. i just wrote a report on the history of scrapie here in the USA, the spread of the atypical Nor-98 Scrapie here in the USA, and other strains of Scrapie and TSE prion disease here in the USA, and why it is paramount that we stop any other foreign or domestic TSE Prion disease from coming to the USA. Most of you probably don't know about the new livestock TSE Prion disease in Camels now i.e. CPD or mad camel disease, they hate that name, that is very concerning. i will supply you all with this information, please do me a favor though, no, i am not asking for a reply or thanks for all this work, just please, please read and study it. what you have been told in the past, is not the case today, and science proves this. when this was stated;

''By allowing scrapie positive animals and genetic materials into the United States, we risk reintroducing the very disease we have nearly eradicated.''

YOU ALL can take that to the bank, but be very careful, it work both ways, and with what i am going to prove to you here, it's not pretty. 

with kindest regards, i am sincerely, Terry S. Singeltary, Bacliff, Texas 77518 <flounder9@verizon.net)

p.s. i will start with the updated science and then my recent report of the HISTORY OF SCRAPIE IN THE USA toward the bottom...terry

SENATORS URGE BIDEN TO WITHDRAW SHEEP IMPORT RULE DUE TO SCRAPIE TSE Prion CONCERNS

February 5, 2021

Robert Fairweather Acting Director United States Office of Management and Budget 725 17thStreet NW Washington, DC 20503

Dear Acting Director Fairweather, We write to urge you to withdraw the final rule on the Importation of Sheep, Goats, and Certain Other Ruminants (APHIS-2009-0095) until its impact on current market conditions has been fully evaluated. The rule seeks to remove bovine spongiform encephalopathy (BSE) related import restrictions on sheep, goats, and most of their products. The existing BSE-related import restrictions function as a necessary protection against the introduction of other transmissible spongiform encephalopathies (TSEs), such as scrapie.

TSEs are a group of rare degenerative brain disorders. Scrapie and BSE are both TSEs. BSE, commonly known as “mad cow disease,” is a progressive neurologic disease of cows. Scrapie is a fatal, degenerative disease which affects the central nervous system of sheep and goats. There is no cure or treatment for either disease.

The federal government has invested over $200 million into scrapie eradication since the early 2000s. This investment has yielded tremendous results, lowering the percentage of scrapie-positive cull sheep at slaughter by 99 percent since FY2003. By allowing scrapie positive animals and genetic materials into the United States, we risk reintroducing the very disease we have nearly eradicated. 

If disease is reintroduced into domestic flocks, opportunities for export will rapidly decline. Prior to a domestic BSE occurrence in cattle in 2003, Japan was the primary export market for U.S. lamb. Japan quickly closed American access to its market and the U.S. did not recoup it until 2018.

The rule should not precede accomplishing increased market access for American lamb, goats, and their products. By removing BSE-related restrictions, the United States would be increasing foreign imports while trade obstructions from countries such as the United Kingdom, European Union, and China remain in place.

For these reasons, we urge you to withdraw the final rule on the Importation of Sheep, Goats, and Certain Other Ruminants. Thank you for your time and consideration of our request.

Sincerely,

________________________________________

Kevin Cramer John Cornyn United States Senator United States Senator
________________________________________

Steve Daines John Barrasso, M.D. United States Senator United States Senator 
________________________________________

Cynthia M. Lummis John Thune United States Senator United States Senator 
________________________________________ 

John Hoeven M. Michael Rounds United States Senator United States Senator

Cc: Acting Secretary Kevin Shae, U.S. Department of Agriculture

Acting U.S. Trade Representative Maria Pagan, Office of the U.S. Trade Representative


SENATORS URGE BIDEN TO WITHDRAW SHEEP IMPORT RULE

Posted By: i3gradiopushbin February 10, 2021 @ 5:09 am 

Ag Central News

WASHINGTON, D.C. (NAFB) – A Senator from North Dakota wants the Biden administration to withdraw a final rule on the importation of sheep and goats.

Republican Kevin Cramer made the request in a letter to the Department of Agriculture this week, asking the rule be withdrawn until its impact on current market conditions can be fully evaluated. The rule, finalized on January 14, would remove brain disorder-related import restrictions on sheep, goats, and most of their products. Cramer says the existing import restrictions function as a necessary protection against the introduction of other brain disorders, such as scrapie or mad cow disease.

Republican Senators Steve Daines of Montana, John Cornyn of Texas, John Barrasso and Cynthia Lummis of Wyoming, John Thune and Michael Rounds of South Dakota, and John Hoeven of North Dakota joined Cramer on the letter.

The Senators state, “By allowing scrapie-positive animals and genetic materials into the United States, we risk reintroducing the very disease we have nearly eradicated.”


North Dakota Senator Kevin Cramer led a letter to Robert Fairweather, Acting Director of the Office of Management and Budget, requesting USDA’s final rule on the importation of sheep, goats, and certain other ruminants be withdrawn until its impact on current market conditions has been fully evaluated.

The rule, finalized on January 14, would remove brain disorder-related import restrictions on sheep, goats, and most of their products. The existing import restrictions function as a necessary protection against the introduction of other brain disorders, such as scrapie or mad cow disease.

The senators wrote, “The federal government has invested over $200 million into scrapie eradication since the early 2000s. This investment has yielded tremendous results, lowering the percentage of scrapie-positive cull sheep at slaughter by 99 percent since FY2003.  By allowing scrapie positive animals and genetic materials into the United States, we risk reintroducing the very disease we have nearly eradicated. If the disease is reintroduced into domestic flocks, opportunities for export will rapidly decline.”

Joining Senator Cramer on his letter are Senators John Cornyn (R-TX), Steve Daines (R-MT), John Barrasso (R-WY), Cynthia Lummis (R-WY), John Thune (R-SD), John Hoeven (R-ND), and Mike Rounds (R-SD).
Office of Senator Cramer


“The federal government has invested over $200 million into scrapie eradication since the early 2000s. This investment has yielded tremendous results, lowering the percentage of scrapie-positive cull sheep at slaughter by 99 percent since FY2003,” the senators wrote. “By allowing scrapie positive animals and genetic materials into the United States, we risk reintroducing the very disease we have nearly eradicated. If the disease is reintroduced into domestic flocks, opportunities for export will rapidly decline.”


SENATORS URGE BIDEN TO WITHDRAW SHEEP IMPORT RULE DUE TO SCRAPIE TSE Prion CONCERNS

***> 2019, 2020, 2021, UPDATED SCIENCE TSE PRION <***

CHRONIC WASTING DISEASE OF CERVID AND SCRAPIE OF SHEEP AND GOATS TRANSMIT TO PIGS BY ORAL ROUTES, OH MY!

***> cwd scrapie pigs oral routes <***

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

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

***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). 

***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains. 




Transmissible Spongiform Encephalopathy TSE Prion End of Year Report

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

zoonotic potential of PMCA-adapted CWD PrP 96SS inoculum


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


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

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

HYPOTHOSIS AND SPECIFIC AIMS

HYPOTHOSIS 

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


Final Report – CJD Foundation Grant Program A. 

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


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

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



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

Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease 

Author item MOORE, SARAH - Orise Fellow item Kunkle, Robert item KONDRU, NAVEEN - Iowa State University item MANNE, SIREESHA - Iowa State University item SMITH, JODI - Iowa State University item KANTHASAMY, ANUMANTHA - Iowa State University item WEST GREENLEE, M - Iowa State University item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:

Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent. 

Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 month challenge groups). The remaining pigs (>6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC. 

Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). 

Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.



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

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

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

Interpretive Summary:

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


WEDNESDAY, MAY 29, 2019 

***> Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures 


THURSDAY, DECEMBER 31, 2020 

Autoclave treatment of the classical scrapie agent US No. 13-7 and experimental inoculation to susceptible VRQ/ARQ sheep via the oral route results in decreased transmission efficiency


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

PLEASE NOTE;

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

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

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


THURSDAY, SEPTEMBER 24, 2020 

The emergence of classical BSE from atypical/ Nor98 scrapie


FRIDAY, OCTOBER 30, 2020 

Efficient transmission of US scrapie agent by intralingual route to genetically susceptible sheep with a low dose inoculum


SUNDAY, OCTOBER 11, 2020 

Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ 


WEDNESDAY, JULY 31, 2019 

The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L


MONDAY, JULY 27, 2020 

APHIS USDA Nor98-like scrapie was confirmed in a sheep sampled at slaughter in May 2020


WEDNESDAY, OCTOBER 28, 2020 

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


SUNDAY, OCTOBER 11, 2020 

Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ 


*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;


A REVIEW of facts and science on scrapie zoonosis potential/likelihood and the USA incredible failure of the BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham) 

***> 1st up BSE 589.2001 FEED REGULATIONS 


IBNC Tauopathy or TSE Prion disease, it appears, no one is sure 

Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT

PLOS ONE Journal 

IBNC Tauopathy or TSE Prion disease, it appears, no one is sure 

Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT

***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 ***


WEDNESDAY, DECEMBER 23, 2020 

Idiopathic Brainstem Neuronal Chromatolysis IBNC BSE TSE Prion a Review 2020


***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.

snip... 

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.


CH1641


WEDNESDAY, JULY 31, 2019

The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L

49. The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L

E. D. Cassmanna,b, S. J. Moorea,b, R. D. Kokemullera, A. Balkema-Buschmannc, M. H. Groschupcand J. J. Greenleea

aVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA (EDC, SJM, RDK, JJG); bOak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Department of Agriculture (USDA). ORISE is managed by ORAU under DOE contract number DE-SC0014664. (EDC, SJM), Department of Veterinary Pathology, Iowa State University, Ames, IA, USA (JDS); cInstitute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald – Isle of Riems, Germany (ABB, MHG)

CONTACT E. D. Cassmann eric.cassmann@usda.gov

ABSTRACT

Introduction: Transmissible mink encephalopathy (TME) is a fatal neurologic prion disease of farmed mink. Epidemiologic and experimental evidence following a Wisconsin outbreak in 1985 has linked TME to low-type bovine spongiform encephalopathy (BSE-L). Evidence suggests that farmed mink were likely exposed through feeding of BSE-L infected downer cattle. The interspecies transmission of TME to cattle has been documented. Recently, we demonstrated the susceptibility of sheep to cattle passaged TME by intracranial inoculation. The aim of the present study was to compare ovine passaged cattle TME to other prion diseases of food-producing animals. Using a bovine transgenic mouse model, we compared the disease phenotype of sheep TME to BSE-C and BSE-L.

Materials and Methods: Separate inoculants of sheep passaged TME were derived from animals with the VRQ/VRQ (VV136) and ARQ/VRQ (AV136) prion protein genotype. Transgenic bovinized mice (TgBovXV) were intracranially inoculated with 20 µl of 1% w/v brain homogenate. The disease phenotypes were characterized by comparing the attack rates, incubation periods, and vacuolation profiles in TgBovXV mice.

Results: The attack rate for BSE-C (13/13), BSE-L (18/18), and TMEVV (21/21) was 100%; whereas, the TMEAV group (15/19) had an incomplete attack rate. The average incubation periods were 299, 280, 310, and 541 days, respectively. The vacuolation profiles of BSE-L and TMEVV were most similar with mild differences observed in the thalamus and medulla. Vacuolation profiles from the BSE-C and TMEAV experimental groups were different than TMEVVand BSE-L.

Conclusion: Overall the phenotype of disease in TME inoculated transgenic mice was dependent on the sheep donor genotype (VV vs AV). The results of the present study indicate that TME isolated from VRQ/VRQ sheep is similar to BSE-L with regards to incubation period, attack rate, and vacuolation profile. Our findings are in agreement with previous research that found phenotypic similarities between BSE-L and cattle passaged TME in an ovine transgenic rodent model. In this study, the similarities between ovine TME and BSE-L are maintained after multiple interspecies passages.

Prion2019 Conference


2007


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

June 17, 2019

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

Greetings APHIS et al, 

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

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

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

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

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

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

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






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

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


PLEASE UNDERSTAND OUR MAD COW FEED BAN, SURVEILLANCE, TESTING, SRM, THEY HAVE ALL FAILED TERRIBLY, and with the recent findings of cwd and scrapie transmitting to pigs by oral routes, the price of tse prion poker goes up dramatically. but who cares, right?

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..... 


***> READ THIS VERY, VERY, CAREFULLY, AUGUST 1997 MAD COW FEED BAN WAS A SHAM, AS I HAVE STATED SINCE 1997! 3 FAILSAFES THE FDA ET AL PREACHED AS IF IT WERE THE GOSPEL, IN TERMS OF MAD COW BSE DISEASE IN USA, AND WHY IT IS/WAS/NOT A PROBLEM FOR THE USA, and those are; 

BSE TESTING (failed terribly and proven to be a sham) 

BSE SURVEILLANCE (failed terribly and proven to be a sham) 

BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham) 

these are facts folks. trump et al just admitted it with the feed ban. 

see; 

FDA Reports on VFD Compliance 

John Maday 

August 30, 2019 09:46 AM VFD-Form 007 (640x427) 

Before and after the current Veterinary Feed Directive rules took full effect in January, 2017, the FDA focused primarily on education and outreach. ( John Maday ) Before and after the current Veterinary Feed Directive (VFD) rules took full effect in January, 2017, the FDA focused primarily on education and outreach to help feed mills, veterinarians and producers understand and comply with the requirements. Since then, FDA has gradually increased the number of VFD inspections and initiated enforcement actions when necessary. On August 29, FDA released its first report on inspection and compliance activities. The report, titled “Summary Assessment of Veterinary Feed Directive Compliance Activities Conducted in Fiscal Years 2016 – 2018,” is available online.


SUNDAY, SEPTEMBER 1, 2019 

***> FDA Reports on VFD Compliance 


TUESDAY, APRIL 18, 2017 

*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP *** 


Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. 

snip... 

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle... 




I URGE EVERYONE TO READ IN FULL, THE OIE REPORT 2019 ABOUT ATYPICAL BSE TSE PRION, SRMs, SBOs, and feed...tss

''Experts could not rule out other causes due to the difficulty of investigating individual cases. Some constraints are the long incubation period of the disease and the lack of detailed information available from farms at the time of the trace-back investigation.''

Scientists investigate origin of isolated BSE cases 

The European response to bovine spongiform encephalopathy (BSE) after the crisis of the 1980s has significantly reduced prevalence of the disease in cattle. However, isolated cases are still being reported in the EU and for this reason the European Commission asked EFSA to investigate their origin.

The key measure for controlling BSE in the EU is a ban on the use of animal proteins in livestock feed. This is because BSE can be transmitted to cattle through contaminated feed, mainly in the first year of life.

Sixty cases of classical BSE have been reported in cattle born after the EU ban was enforced in 2001. None of these animals entered the food chain. Classical BSE is the type of BSE transmissible to humans. The Commission asked EFSA to determine if these cases were caused by contaminated feed or whether they occurred spontaneously, i.e. without an apparent cause.

EFSA experts concluded that contaminated feed is the most likely source of infection. This is because the infectious agent that causes BSE has the ability to remain active for many years. Cattle may have been exposed to contaminated feed because the BSE infectious agent was present where feed was stored or handled. A second possibility is that contaminated feed ingredients may have been imported from non-EU countries.

Experts could not rule out other causes due to the difficulty of investigating individual cases. Some constraints are the long incubation period of the disease and the lack of detailed information available from farms at the time of the trace-back investigation.

EFSA experts made a series of recommendations to maintain and strengthen the EU monitoring and reporting system, and to evaluate new scientific data that become available.

The European response to BSE

The coordinated European response to BSE has succeeded in reducing the prevalence of the disease. Between 2005 and 2015 about 73,000,000 cattle were tested for BSE in the EU, out of which 60 born after the ban tested positive for classical BSE. The number of affected animals rises to 1,259 if cattle born before the ban are included. The number of classical BSE cases has dropped significantly in the EU over time, from 554 cases reported in 2005 to just two in 2015 (both animals born after the ban). Moreover the EU food safety system is designed to prevent the entry of BSE-contaminated meat into the food chain.


MONDAY, NOVEMBER 30, 2020 

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

see updated concerns with atypical BSE from feed and zoonosis...terry


WEDNESDAY, DECEMBER 23, 2020 

BSE research project final report 2005 to 2008 SE1796 SID5


TUESDAY, JANUARY 5, 2021 

Exploration of genetic factors resulting in abnormal disease in cattle experimentally challenged with bovine spongiform encephalopathy


THURSDAY, SEPTEMBER 26, 2019 

Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics


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

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

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

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy


snip...

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

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

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

[host Richard] could you repeat the question?

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

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

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

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

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

[not sure whom speaking] NO

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



SUNDAY, APRIL 14, 2019 

Estimation of prion infectivity in tissues of cattle infected with atypical BSE by real time-quaking induced conversion assay


WEDNESDAY, APRIL 24, 2019 

USDA Announces Atypical Bovine Spongiform Encephalopathy Detection Aug 29, 2018 A Review of Science 2019


SUNDAY, OCTOBER 4, 2020 

Cattle Meat and Offal Imported from the United States of America, Canada and Ireland to Japan (Prions) Food Safety Commission of Japan


SEE HADLOW AND SCRAPIE !



 Monday, December 1, 2008 

 When Atypical Scrapie cross species barriers 

 Authors 

 Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France. 

 Content 

 Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.

Neuroprion 2008 Abstract Book

WEDNESDAY, JUNE 10, 2020 

Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice

Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.

our results clearly indicate that atypical BSE adaptation to an ovine-PrP sequence could modify the prion agent to potentially infect humans, showing strain features indistinguishable from those of classic sCJD prions, even though they might or might not be different agents.

However, the expanding range of TSE agents displaying the capacity to transmit in human-PrP–expressing hosts warrants the continuation of the ban on meat and bone meal recycling and underscores the ongoing need for active surveillance


The identification of a new prion disease in dromedary camels in Algeria and Tunisia, called camel prion disease (CPD), extends the spectrum of animal species naturally susceptible to prion diseases and opens up new research areas for investigation.

Camel prion disease was identified in 2018 in adult camels showing clinical signs at the ante mortem inspection at slaughterhouses in the region of Ouargla (Algeria), and in 2019 in the region of Tataouine (Tunisia). It adds to the group of existing animal prion diseases, including scrapie in sheep and goats, chronic wasting disease (CWD) in cervids and BSE (mainly in bovines). The detection of a new prion disease in the dromedary population requires attention and investigation needs to be carried out to assess the risks of this disease to animal and public health. As of today, very limited epidemiological information is available to assess the prevalence, geographical distribution and dynamic of the transmission of the disease.

Based on the clinical signs suggesting prion disease, CPD seems to have occurred in 3.1% of the dromedaries brought to the abattoir in Ouargla. Pathognomonic neurodegeneration and diseasespecific prion protein (PrPSc) were detected in brain tissue from three symptomatic animals (source: CDC article wwwnc.cdc.gov/eid/article/24/6/17-2007_article). 

In May 2019, the OIE received a report from Tunisia on a single case of a 12-year-old slaughtered dromedary camel showing neurological signs confirmed as CPD by the Istituto Superiore di Sanità (ISS) based in Italy.

©B. Babelhadj/University Kasdi Merbah, Algeria www.oiebulletin.com 2

Is camel prion disease transmissible in natural conditions?

The involvement of lymphoid tissue in prion replication, observed both in the Algeria and Tunisia cases, is suggestive of a peripheral pathogenesis, which is thought to be a prerequisite for prion shedding into the environment. As with other animal prion diseases, such as scrapie and CWD, in which lymphoid tissues are extensively involved and horizontal transmission occurs efficiently under natural conditions, the detection of prion proteins in lymph nodes is suggestive of the infectious nature of CPD and concurs to hypothesise the potential impact of CPD on animal health. No evidence is currently available with which to argue for the relevance of CPD for human health. However, no absolute species barrier exists in prion diseases and minimising the exposure of humans to prion-infected animal products is an essential aspect of public health protection. As for the relationship between CPD and other animal prion diseases, preliminary analyses suggest that CPD prions have a different molecular signature from scrapie and BSE.

Actions on the follow up of CPD

Since the first description of CPD, the OIE promoted discussions on the impact of this new disease through the OIE Scientific Commission for Animal Diseases (Scientific Commission). The Scientific Commission consulted two OIE ad hoc Groups, one on BSE risk status evaluation of Members and the other on camelids. It analysed the information available from the Algeria and Tunisia cases to evaluate if CPD should be considered an ‘emerging disease’ based on the criteria listed in the Terrestrial Animal Health Code1

. The OIE Scientific Commission noted that limited surveillance data were available on the prevalence of CPD and that the evidence was not sufficient to measure, at that time, the impact of the disease on animal or public health. Therefore, it was concluded that, with the current knowledge, CPD did not currently meet the criteria to be considered an emerging disease. Nonetheless, it was emphasised that CPD should be considered as a new disease not to be overlooked and called for the collection of further scientific evidence through research and surveillance in the affected countries and in countries with dromedary camel populations to measure the impact of the disease. As new scientific evidence becomes available,the OIE Scientific Commission will reassess whether this disease should be considered as an emerging disease.

The worldwide camel population is ~35 million head (FAO, 2019), 88% of which is found in Africa. The camel farming system is evolving rapidly, and these animals represent vital sources of meat, milk and transportation for millions of people living in the most arid regions of the world. This makes it necessary to assess the risk for animal and human health and to develop evidence-based policies to control and limit the spread of the disease in animals, and to minimise human exposure. As a first step, the awareness of Veterinary Services about CPD and its diagnostic capacity needs to be improved in all countries where dromedaries are part of the domestic livestock.

At the regional level, CPD was first discussed in the 18th Joint Permanent Committee of the Mediterranean Animal Health Network (REMESA) held in Cairo, Egypt, in June 2019 where an expert 1 a new occurrence in an animal of a disease, infection or infestation, causing a significant impact on animal or public health resulting from a) a change of a known pathogenic agent or its spread to a new geographic area or species, or b) a previously unrecognised pathogenic agent or disease diagnosed for the first time www.oiebulletin.com

3

from ISS, Italy, shared the knowledge available on the new disease with the 15 REMESA Member Countries. The discussion highlighted the need to strengthen surveillance systems in order to collect epidemiological data to inform the risk assessments. The results of these risk assessments will support the implementation of evidence-based policies to manage the risks in both animals and humans.

CPD was recently discussed at the 15thConference of the OIE Regional Commission for the Middle East in November. During this conference, the CAMENET (Camel Middle East Network) launched a wideranging proposal for training, coordinated surveillance and research on CPD. In addition, the ERFAN (Enhancing Research forAfrica Network), a platform aimed at enhancing scientific cooperation between Africa and Italy, during its 2nd ERFAN meeting for North Africa, presented a project on CPD with the objective of increasing CPD coordinated surveillance in North Africa.

The OIE, through its Reference Laboratories for prion diseases, and by involving the above scientific initiatives, is keeping a close watch on the evolution of the disease to gather scientific evidence and to allow a proper and more thorough assessment of the risk associated with this novel disease.

◼ December 2019


THURSDAY, AUGUST 06, 2020 

Scrapie Documented in Tunisia


Thursday, August 1, 2019 

Camel prion disease detected in Tunisian camels Camel prion disease detected in Tunisian camels

A novel prion disease first reported in three dromedary camels in Algeria in 2018 has now been detected in dromedaries in Tunisia, the second country to be affected within a year, ProMED Mail, the online reporting system of the International Society for Infectious Diseases, reported yesterday.

The Tunisian detection and the latest information about the disease, called camel prion disease (CPD) and sometimes referred to as "mad camel disease", came from a presentation at the Mediterranean Animal Health Network meeting, held in Cairo on Jun 26 and 27. According to the meeting presentation, CPD is spreading rapidly in the Ouargla region of Algeria where the disease was first identified in older camels at a slaughterhouse.

The scientists who presented at the meeting also said preliminary results suggest that the CPD prion is different from scrapie and bovine spongiform encephalitis (BSE, or "mad cow disease").

A comment from the ProMED Mail moderator Arnon Shimshony, DVM, associate professor of veterinary medicine at Hebrew University of Jerusalem, notes that the area where CPD was first found in Algeria is about 174 miles from the Tunisian border.

In the initial report on the first detection in Algerian camels, published in April 2018 in Emerging Infectious Diseases, described disease-specific prion protein in brain tissues from symptomatic camels, including positive samples in lymph nodes, suggesting infection. The moderator also requested more details about the detections in Tunisia, including location, clinical signs, and ages and origins of affected camels. Jul 29 ProMED Mail post Apr 18, 2018, CIDRAP News story "'Mad camel' disease? New prion infection causes alarm"



***> NEW TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE (MAD CAMEL DISEASE) IN A NEW SPECIES <***

NEW OUTBREAK OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE IN A NEW SPECIES

Subject: Prion Disease in Dromedary Camels, Algeria

Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.



Wednesday, May 30, 2018 

Dromedary camels in northern Africa have a neurodegenerative prion disease that may have originated decades ago


***> IMPORTS AND EXPORTS <***

***> SEE MASSIVE AMOUNTS OF BANNED ANIMAL PROTEIN AKA MAD COW FEED IN COMMERCE USA DECADES AFTER POST BAN

Saturday, April 14, 2018

Dromedary Camels Algeria Prion (Mad Camel Disease) TSE BSE MRR Import Export Risk Factors Excluding Grains and Plants

Dromedary Camels Algeria Prion (Mad Camel Disease) TSE BSE MRR Import Export Risk Factors Excluding Grains and Plants

(Grains and Plants Materials Could Harbor the Transmissible Spongiform Encephalopathy TSE Prion agent...TSS)

Dromedary Camels Algeria Prion (Mad Camel Disease) TSE BSE MRR Import Export Risk Factors Excluding Grains and Plants



Microb Risk Anal . 2020 Aug 15;100134. doi: 10.1016/j.mran.2020.100134. Online ahead of print. 

Assessing the aggregated probability of entry of a novel prion disease agent into the United Kingdom 



''Why is USDA "only" testing 25,000 samples a year? 

TUESDAY, AUGUST 18, 2020 

Sheep Scrapie, Bovine BSE, Cervid CWD, ZOONOSIS, TSE Prion Roundup August 18, 2020 


***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.


O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). 

Non-human primate models provided the first evidences supporting the 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. 

============== 

Reference Prion 2015 Conference Abstract Book

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 


PRION 2016 TOKYO

Saturday, April 23, 2016

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 


Title: Transmission of scrapie prions to primate after an extended silent incubation period) 

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. 


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

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

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

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

snip...

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

PMID: 6997404


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

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

snip...

76/10.12/4.6


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

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

Gibbs CJ Jr, Gajdusek DC.

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

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

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

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

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



THURSDAY, JANUARY 7, 2021 

Atypical Nor-98 Scrapie TSE Prion USA State by State Update January 2021


P03.141 

 Aspects of the Cerebellar Neuropathology in Nor98 

 Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute, 

 Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans. 

 ***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans. 

Prion Conference 2007 Abstract Book

 PR-26 

 NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS 

 R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway 

 Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion. 

 *** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease. 

 119 

Neuroprion 2006 Conference Abstract Book

A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes 

 Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,? +Author Affiliations 

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway 

***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005) 

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. *** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health. 


WEDNESDAY, NOVEMBER 20, 2019 

Review: Update on Classical and Atypical Scrapie in Sheep and Goats 


FRIDAY, FEBRUARY 11, 2011 

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues 


SEE HADLOW AND SCRAPIE !



WEDNESDAY, JUNE 10, 2020 

Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice

Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.

our results clearly indicate that atypical BSE adaptation to an ovine-PrP sequence could modify the prion agent to potentially infect humans, showing strain features indistinguishable from those of classic sCJD prions, even though they might or might not be different agents.

However, the expanding range of TSE agents displaying the capacity to transmit in human-PrP–expressing hosts warrants the continuation of the ban on meat and bone meal recycling and underscores the ongoing need for active surveillance


FRIDAY, OCTOBER 23, 2020 

Scrapie TSE Prion Zoonosis Zoonotic, what if?


***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.


O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). 

Non-human primate models provided the first evidences supporting the 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. 

============== 

Reference 2015 Prion Conference Abstract Book

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 


PRION 2016 TOKYO

Saturday, April 23, 2016

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 


Title: Transmission of scrapie prions to primate after an extended silent incubation period) 

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. 


MONDAY, NOVEMBER 30, 2020 

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

see updated concerns with atypical BSE from feed and zoonosis...terry


THE tse prion aka mad cow type disease is not your normal pathogen. 

The TSE prion disease survives ashing to 600 degrees celsius, that’s around 1112 degrees farenheit. 

you cannot cook the TSE prion disease out of meat. 

you can take the ash and mix it with saline and inject that ash into a mouse, and the mouse will go down with TSE. 

Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production as well. 

the TSE prion agent also survives Simulated Wastewater Treatment Processes. 

IN fact, you should also know that the TSE Prion agent will survive in the environment for years, if not decades. 

you can bury it and it will not go away. 

The TSE agent is capable of infected your water table i.e. Detection of protease-resistant cervid prion protein in water from a CWD-endemic area. 

it’s not your ordinary pathogen you can just cook it out and be done with. 

***> that’s what’s so worrisome about Iatrogenic mode of transmission, a simple autoclave will not kill this TSE prion agent.

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] 


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 

PPo4-4:

Survival and Limited Spread of TSE Infectivity after Burial

Karen Fernie, Allister Smith and Robert A. Somerville The Roslin Institute and R(D)SVS; University of Edinburgh; Roslin, Scotland UK

Scrapie and chronic wasting disease probably spread via environmental routes, and there are also concerns about BSE infection remaining in the environment after carcass burial or waste 3disposal. In two demonstration experiments we are determining survival and migration of TSE infectivity when buried for up to five years, as an uncontained point source or within bovine heads. Firstly boluses of TSE infected mouse brain were buried in lysimeters containing either sandy or clay soil. Migration from the boluses is being assessed from soil cores taken over time. With the exception of a very small amount of infectivity found 25 cm from the bolus in sandy soil after 12 months, no other infectivity has been detected up to three years. Secondly, ten bovine heads were spiked with TSE infected mouse brain and buried in the two soil types. Pairs of heads have been exhumed annually and assessed for infectivity within and around them. After one year and after two years, infectivity was detected in most intracranial samples and in some of the soil samples taken from immediately surrounding the heads. The infectivity assays for the samples in and around the heads exhumed at years three and four are underway. These data show that TSE infectivity can survive burial for long periods but migrates slowly. Risk assessments should take into account the likely long survival rate when infected material has been buried.

The authors gratefully acknowledge funding from DEFRA.

PRION CONFERENCE 2010 ABSTRACT REFERENCE

2018 - 2019

***> This is very likely to have parallels with control efforts for CWD in cervids.

Rapid recontamination of a farm building occurs after attempted prion removal


Kevin Christopher Gough, BSc (Hons), PhD1, Claire Alison Baker, BSc (Hons)2, Steve Hawkins, MIBiol3, Hugh Simmons, BVSc, MRCVS, MBA, MA3, Timm Konold, DrMedVet, PhD, MRCVS3 and Ben Charles Maddison, BSc (Hons), PhD2

Abstract

The transmissible spongiform encephalopathy scrapie of sheep/goats and chronic wasting disease of cervids are associated with environmental reservoirs of infectivity. 

Preventing environmental prions acting as a source of infectivity to healthy animals is of major concern to farms that have had outbreaks of scrapie and also to the health management of wild and farmed cervids. 

Here, an efficient scrapie decontamination protocol was applied to a farm with high levels of environmental contamination with the scrapie agent. 

Post-decontamination, no prion material was detected within samples taken from the farm buildings as determined using a sensitive in vitro replication assay (sPMCA). 

A bioassay consisting of 25 newborn lambs of highly susceptible prion protein genotype VRQ/VRQ introduced into this decontaminated barn was carried out in addition to sampling and analysis of dust samples that were collected during the bioassay. 

Twenty-four of the animals examined by immunohistochemical analysis of lymphatic tissues were scrapie-positive during the bioassay, samples of dust collected within the barn were positive by month 3. 

The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease.

snip...

As in the authors' previous study,12 the decontamination of this sheep barn was not effective at removing scrapie infectivity, and despite the extra measures brought into this study (more effective chemical treatment and removal of sources of dust) the overall rates of disease transmission mirror previous results on this farm. With such apparently effective decontamination (assuming that at least some sPMCA seeding ability is coincident with infectivity), how was infectivity able to persist within the environment and where does infectivity reside? Dust samples were collected in both the bioassay barn and also a barn subject to the same decontamination regime within the same farm (but remaining unoccupied). Within both of these barns dust had accumulated for three months that was able to seed sPMCA, indicating the accumulation of scrapie-containing material that was independent of the presence of sheep that may have been incubating and possibly shedding low amounts of infectivity.

This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapiepositive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.

Acknowledgements The authors thank the APHA farm staff, Tony Duarte, Olly Roberts and Margaret Newlands for preparation of the sheep pens and animal husbandry during the study. The authors also thank the APHA pathology team for RAMALT and postmortem examination.

Funding This study was funded by DEFRA within project SE1865. 

Competing interests None declared. 






Saturday, January 5, 2019 

Rapid recontamination of a farm building occurs after attempted prion removal 


The effectiveness of on-farm decontamination methods for scrapie - SE1865

Description

Scrapie infectivity persists on farms where infected animals have been removed1. Recently we have demonstrated that it is possible to detect environmental scrapie contamination biochemically using serial Protein Misfolding Cyclic Amplification (sPMCA)2, allowing the monitoring of scrapie infectivity on farm premises. Ongoing Defra study SE1863 has compared pen decontamination regimes on a scrapie-infected farm by both sheep bioassay and sPMCA. For bioassay, scrapie-free genetically susceptible lambs were introduced into pens decontaminated using distinct methodologies, all pens contained scrapie-positive lambs within 1 year. Remarkably this included lambs housed within a pen which had been jet washed/chloros treated, followed by regalvanisation/ replacement of all metalwork and painting of all other surfaces.

We have recently demonstrated using sPMCA, that material collected on swabs from vertical surfaces at heights inaccessible to sheep within a barn on the same scrapie affected farm contained scrapie prions (unpublished observations). We hypothesise that scrapie prions are most likely to have been deposited in these areas by bioaerosol movement. We propose that this bioaerosol movement contributes to scrapie transmission within the barn, and could account for the sheep that became positive within the pen containing re-galvanised/new metalwork and repainted surfaces (project SE1863). It is proposed that a thorough decontamination that would minimise prion-contaminated dust, both within the building and its immediate vicinity, is likely to increase the effectiveness of current methods for decontaminating farm buildings following outbreaks of scrapie. The proposed study builds on our previous data and will thoroughly investigate the potential for farm building scrapie-contamination via the bioaerosol route, a previously unrecognised route for dissemination of scrapie infectivity. This route could lead to the direct infection of healthy animals and/or indirect transmission of disease via contamination of surfaces within animal pens. The proposed study would analyse material collected using air samplers set up within “scrapie-infected” barns and their immediate vicinity, to confirm that prion containing material can be airborne within a scrapie infected farm environment. The study would incorporate a biochemical assessment of different surface decontamination methods, in order to demonstrate the best methodology and then the analysis of air and surface samples after a complete building decontamination to remove sources of dust and surface bound prions from both the building and its immediate vicinity. Analysis of such surface and air samples collected before and after treatment would measure the reduction in levels of infectivity. It is envisaged that the biochemical demonstration of airborne prions and the effective reduction in such prion dissemination would lead to a sheep bioassay experiment that would be conducted after a full farm decontamination. This would fully assess the effectiveness of an optimised scrapie decontamination strategy.

This study will contribute directly to Defra policy on best practice for on-farm decontamination after outbreaks of scrapie; a situation particularly relevant to decontamination after scrapie cases on goat farms where no genetic resistance to scrapie has currently been identified, and where complete decontamination is essential in order to stop recurrence of scrapie after restocking.

Objective

Phase 1

• Determine the presence and relative levels of airborne prions on a scrapie infected farm.

• Evaluate different pen surface decontamination procedures.

Phase 2

• Determine the presence of any airborne prions in a barn after a full decontamination.

Phase 3

• Further assess the efficacy of the decontamination procedure investigated in phase 2 by sheep bioassay.

Time-Scale and Cost

From: 2012 

To: 2016 

Cost: £326,784

Contractor / Funded Organisations

A D A S UK Ltd (ADAS)

Keywords Animals Fields of Study Animal Health


The Effectiveness of on-Farm Decontamination Methods for Scrapie

Institutions ADAS

Start date 2012

End date 2016

Objective Phase 1

Determine the presence and relative levels of airborne prions on a scrapie infected farm. Evaluate different pen surface decontamination procedures.

Phase 2

Determine the presence of any airborne prions in a barn after a full decontamination.

Phase 3

Further assess the efficacy of the decontamination procedure investigated in phase 2 by sheep bioassay.

More information

Scrapie infectivity persists on farms where infected animals have been removed1. Recently we have demonstrated that it is possible to detect environmental scrapie contamination biochemically using serial Protein Misfolding Cyclic Amplification (sPMCA)2, allowing the monitoring of scrapie infectivity on farm premises. Ongoing Defra study SE1863 has compared pen decontamination regimes on a scrapie-infected farm by both sheep bioassay and sPMCA. For bioassay, scrapie-free genetically susceptible lambs were introduced into pens decontaminated using distinct methodologies, all pens contained scrapie-positive lambs within 1 year. Remarkably this included lambs housed within a pen which had been jet washed/chloros treated, followed by regalvanisation/replacement of all metalwork and painting of all other surfaces.

We have recently demonstrated using sPMCA, that material collected on swabs from vertical surfaces at heights inaccessible to sheep within a barn on the same scrapie affected farm contained scrapie prions (unpublished observations). We hypothesise that scrapie prions are most likely to have been deposited in these areas by bioaerosol movement. We propose that this bioaerosol movement contributes to scrapie transmission within the barn, and could account for the sheep that became positive within the pen containing re-galvanised/new metalwork and repainted surfaces (project SE1863). It is proposed that a thorough decontamination that would minimise prion-contaminated dust, both within the building and its immediate vicinity, is likely to increase the effectiveness of current methods for decontaminating farm buildings following outbreaks of scrapie. The proposed study builds on our previous data and will thoroughly investigate the potential for farm building scrapie contamination via the bioaerosol route, a previously unrecognised route for dissemination of scrapie infectivity. This route could lead to the direct infection of healthy animals and/or indirect transmission of disease via contamination of surfaces within animal pens. The proposed study would analyse material collected using air samplers set up within “scrapie-infected” barns and their immediate vicinity, to confirm that prion containing material can be airborne within a scrapie infected farm environment. The study would incorporate a biochemical assessment of different surface decontamination methods, in order to demonstrate the best methodology and then the analysis of air and surface samples after a complete building decontamination to remove sources of dust and surface bound prions from both the building and its immediate vicinity. Analysis of such surface and air samples collected before and after treatment would measure the reduction in levels of infectivity. It is envisaged that the biochemical demonstration of airborne prions and the effective reduction in such prion dissemination would lead to a sheep bioassay experiment that would be conducted after a full farm decontamination. This would fully assess the effectiveness of an optimised scrapie decontamination strategy.

This study will contribute directly to Defra policy on best practice for on-farm decontamination after outbreaks of scrapie; a situation particularly relevant to decontamination after scrapie cases on goat farms where no genetic resistance to scrapie has currently been identified, and where complete decontamination is essential in order to stop recurrence of scrapie after restocking.

Funding Source

Department for Environment, Food and Rural Affairs

Project source

View this project

Project number

SE1865

Categories

Foodborne Disease

Policy and Planning 


Circulation of prions within dust on a scrapie affected farm

Kevin C Gough1 , Claire A Baker2 , Hugh A Simmons3 , Steve A Hawkins3 and Ben C Maddison2*

Abstract

Prion diseases are fatal neurological disorders that affect humans and animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk are contagious prion diseases where environmental reservoirs have a direct link to the transmission of disease. Using protein misfolding cyclic amplification we demonstrate that scrapie PrPSc can be detected within circulating dusts that are present on a farm that is naturally contaminated with sheep scrapie. The presence of infectious scrapie within airborne dusts may represent a possible route of infection and illustrates the difficulties that may be associated with the effective decontamination of such scrapie affected premises.

snip... 

Discussion We present biochemical data illustrating the airborne movement of scrapie containing material within a contaminated farm environment. We were able to detect scrapie PrPSc within extracts from dusts collected over a 70 day period, in the absence of any sheep activity. We were also able to detect scrapie PrPSc within dusts collected within pasture at 30 m but not at 60 m distance away from the scrapie contaminated buildings, suggesting that the chance of contamination of pasture by scrapie contaminated dusts decreases with distance from contaminated farm buildings. PrPSc amplification by sPMCA has been shown to correlate with infectivity and amplified products have been shown to be infectious [14,15]. These experiments illustrate the potential for low dose scrapie infectivity to be present within such samples. We estimate low ng levels of scrapie positive brain equivalent were deposited per m2 over 70 days, in a barn previously occupied by sheep affected with scrapie. This movement of dusts and the accumulation of low levels of scrapie infectivity within this environment may in part explain previous observations where despite stringent pen decontamination regimens healthy lambs still became scrapie infected after apparent exposure from their environment alone [16]. The presence of sPMCA seeding activity and by inference, infectious prions within dusts, and their potential for airborne dissemination is highly novel and may have implications for the spread of scrapie within infected premises. The low level circulation and accumulation of scrapie prion containing dust material within the farm environment will likely impede the efficient decontamination of such scrapie contaminated buildings unless all possible reservoirs of dust are removed. Scrapie containing dusts could possibly infect animals during feeding and drinking, and respiratory and conjunctival routes may also be involved. It has been demonstrated that scrapie can be efficiently transmitted via the nasal route in sheep [17], as is also the case for CWD in both murine models and in white tailed deer [18-20].

The sources of dust borne prions are unknown but it seems reasonable to assume that faecal, urine, skin, parturient material and saliva-derived prions may contribute to this mobile environmental reservoir of infectivity. This work highlights a possible transmission route for scrapie within the farm environment, and this is likely to be paralleled in CWD which shows strong similarities with scrapie in terms of prion dissemination and disease transmission. The data indicate that the presence of scrapie prions in dust is likely to make the control of these diseases a considerable challenge.


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

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

Author 

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

Interpretive Summary:

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


THURSDAY, FEBRUARY 28, 2019 

BSE infectivity survives burial for five years with only limited spread


***> 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. 

SOURCE REFERENCE 2018 PRION CONFERENCE ABSTRACT

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

Title: Horizontal transmission of chronic wasting disease in reindeer

Author

item MOORE, SARAH - ORISE FELLOW item KUNKLE, ROBERT item WEST GREENLEE, MARY - IOWA STATE UNIVERSITY item Nicholson, Eric item RICHT, JUERGEN item HAMIR, AMIRALI item WATERS, WADE item Greenlee, Justin

Submitted to: Emerging Infectious Diseases

Publication Type: Peer Reviewed Journal

Publication Acceptance Date: 8/29/2016

Publication Date: 12/1/2016

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

Interpretive Summary: Chronic wasting disease (CWD) is a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America and was recently diagnosed in a single free-ranging reindeer (Rangifer tarandus tarandus) in Norway. CWD is a transmissible spongiform encephalopathy (TSE) that is caused by infectious proteins called prions that are resistant to various methods of decontamination and environmental degradation. Little is known about the susceptibility of or potential for transmission amongst reindeer. In this experiment, we tested the susceptibility of reindeer to CWD from various sources (elk, mule deer, or white-tailed deer) after intracranial inoculation and tested the potential for infected reindeer to transmit to non-inoculated animals by co-housing or housing in adjacent pens. Reindeer were susceptible to CWD from elk, mule deer, or white-tailed deer sources after experimental inoculation. Most importantly, non-inoculated reindeer that were co-housed with infected reindeer or housed in pens adjacent to infected reindeer but without the potential for nose-to-nose contact also developed evidence of CWD infection. This is a major new finding that may have a great impact on the recently diagnosed case of CWD in the only remaining free-ranging reindeer population in Europe as our findings imply that horizontal transmission to other reindeer within that herd has already occurred. Further, this information will help regulatory and wildlife officials developing plans to reduce or eliminate CWD and cervid farmers that want to ensure that their herd remains CWD-free, but were previously unsure of the potential for reindeer to transmit CWD.

Technical Abstract: Chronic wasting disease (CWD) is a naturally-occurring, fatal prion disease of cervids. Reindeer (Rangifer tarandus tarandus) are susceptible to CWD following oral challenge, and CWD was recently reported in a free-ranging reindeer of Norway. Potential contact between CWD-affected cervids and Rangifer species that are free-ranging or co-housed on farms presents a potential risk of CWD transmission. The aims of this study were to 1) investigate the transmission of CWD from white-tailed deer (Odocoileus virginianus; CWDwtd), mule deer (Odocoileus hemionus; CWDmd), or elk (Cervus elaphus nelsoni; CWDelk) to reindeer via the intracranial route, and 2) to assess for direct and indirect horizontal transmission to non-inoculated sentinels. Three groups of 5 reindeer fawns were challenged intracranially with CWDwtd, CWDmd, or CWDelk. Two years after challenge of inoculated reindeer, non-inoculated negative control reindeer were introduced into the same pen as the CWDwtd inoculated reindeer (direct contact; n=4) or into a pen adjacent to the CWDmd inoculated reindeer (indirect contact; n=2). Experimentally inoculated reindeer were allowed to develop clinical disease. At death/euthanasia a complete necropsy examination was performed, including immunohistochemical testing of tissues for disease-associated CWD prion protein (PrPcwd). Intracranially challenged reindeer developed clinical disease from 21 months post-inoculation (months PI). PrPcwd was detected in 5 out of 6 sentinel reindeer although only 2 out of 6 developed clinical disease during the study period (< 57 months PI). We have shown that reindeer are susceptible to CWD from various cervid sources and can transmit CWD to naïve reindeer both directly and indirectly.


***> Infectious agent of sheep scrapie may persist in the environment for at least 16 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. 

JOURNAL OF GENERAL VIROLOGY Volume 87, Issue 12

Infectious agent of sheep scrapie may persist in the environment for at least 16 years Free

Gudmundur Georgsson1, Sigurdur Sigurdarson2, Paul Brown3

First Published: 01 December 2006 https://doi.org/10.1099/vir.0.82011-0 ABSTRACT 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 sheep-house 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.


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.

 
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. 

source reference Prion Conference 2015 abstract book

Grass Plants Bind, Retain, Uptake, and Transport Infectious Prions

Sandra Pritzkow,1 Rodrigo Morales,1 Fabio Moda,1,3 Uffaf Khan,1 Glenn C. Telling,2 Edward Hoover,2 and Claudio Soto1, * 1Mitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA

2Prion Research Center, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA

3Present address: IRCCS Foundation Carlo Besta Neurological Institute, 20133 Milan, Italy *Correspondence: claudio.soto@uth.tmc.edu http://dx.doi.org/10.1016/j.celrep.2015.04.036

SUMMARY

Prions are the protein-based infectious agents responsible for prion diseases. Environmental prion contamination has been implicated in disease transmission. Here, we analyzed the binding and retention of infectious prion protein (PrPSc) to plants. Small quantities of PrPSc contained in diluted brain homogenate or in excretory materials (urine and feces) can bind to wheat grass roots and leaves. Wild-type hamsters were efficiently infected by ingestion of prion-contaminated plants. The prion-plant interaction occurs with prions from diverse origins, including chronic wasting disease. Furthermore, leaves contaminated by spraying with a prion-containing preparation retained PrPSc for several weeks in the living plant. Finally, plants can uptake prions from contaminated soil and transport them to aerial parts of the plant (stem and leaves). These findings demonstrate that plants can efficiently bind infectious prions and act as carriers of infectivity, suggesting a possible role of environmental prion contamination in the horizontal transmission of the disease.

INTRODUCTION

snip...

DISCUSSION

This study shows that plants can efficiently bind prions contained in brain extracts from diverse prion infected animals, including CWD-affected cervids. PrPSc attached to leaves and roots from wheat grass plants remains capable of seeding prion replication in vitro. Surprisingly, the small quantity of PrPSc naturally excreted in urine and feces from sick hamster or cervids was enough to efficiently contaminate plant tissue. Indeed, our results suggest that the majority of excreted PrPSc is efficiently captured by plants’ leaves and roots. Moreover, leaves can be contaminated by spraying them with a prion-containing extract, and PrPSc remains detectable in living plants for as long as the study was performed (several weeks). Remarkably, prion contaminated plants transmit prion disease to animals upon ingestion, producing a 100% attack rate and incubation periods not substantially longer than direct oral administration of sick brain homogenates.

Finally, an unexpected but exciting result was that plants were able to uptake prions from contaminated soil and transport them to aerial parts of the plant tissue. Although it may seem farfetched that plants can uptake proteins from the soil and transport it to the parts above the ground, there are already published reports of this phenomenon (McLaren et al., 1960; Jensen and McLaren, 1960;Paungfoo-Lonhienne et al., 2008). The high resistance of prions to degradation and their ability to efficiently cross biological barriers may play a role in this process. The mechanism by which plants bind, retain, uptake, and transport prions is unknown. We are currently studying the way in which prions interact with plants using purified, radioactively labeled PrPSc to determine specificity of the interaction, association constant, reversibility, saturation, movement, etc.

Epidemiological studies have shown numerous instances of scrapie or CWD recurrence upon reintroduction of animals on pastures previously exposed to prion-infected animals. Indeed, reappearance of scrapie has been documented following fallow periods of up to 16 years (Georgsson et al., 2006), and pastures were shown to retain infectious CWD prions for at least 2 years after exposure (Miller et al., 2004). It is likely that the environmentally mediated transmission of prion diseases depends upon the interaction of prions with diverse elements, including soil, water, environmental surfaces, various invertebrate animals, and plants.

However, since plants are such an important component of the environment and also a major source of food for many animal species, including humans, our results may have far-reaching implications for animal and human health. Currently, the perception of the riskfor animal-to-human prion transmission has beenmostly limited to consumption or exposure to contaminated meat; our results indicate that plants might also be an important vector of transmission that needs to be considered in risk assessment. 


RIGINAL RESEARCH ARTICLE

Front. Vet. Sci., 14 September 2015 | https://doi.org/10.3389/fvets.2015.00032

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

imageTimm Konold1*, imageStephen A. C. Hawkins2, imageLisa C. Thurston3, imageBen C. Maddison4, imageKevin C. Gough5, imageAnthony Duarte1 and imageHugh A. Simmons1

1Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK

2Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK

3Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK

4ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK

5School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK

Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie-affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.

snip...

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, MARCH 13, 2019 

CWD, TSE, PRION, MATERNAL mother to offspring, testes, epididymis, seminal fluid, and blood
Subject: Prion 2019 Conference

See full Prion 2019 Conference Abstracts


Transmissible Spongiform Encephalopathies in exotic species

In exotic species, the last one was in 2007.

SPECIES No. DATES AFFECTED

Ankole cow 2 1991, 95

Bison 1 1996

Cheetah 5 1992 – 98

Eland 6 1989 – 95

Gemsbok 1 1987

Kudu 6 1989 – 92

Asian Leopard Cat1 1 2005

Lion 5 1998 - 2007

Nyala 1 1986

Ocelot 3 1994 – 99

Oryx 2 1989, 92

Puma 3 1992 – 95

Tiger 3 1995 – 99

Data valid to 30 September 2019

1Felis (Prionailurus) bengalensis. 


ZOO ANIMALS AND TSE PRION DISEASE

The 82 zoo animals with BSE:

Id TSE Genus Species Subsp Birth Origin Death Place of Death

654 x Microcebus murinus - 1997 U.Montpellier 1998 U.Montpellier

656 x Microcebus murinus - 1997 U.Montpellier 1998 U.Montpellier

481 + Eulemur fulvus mayottensis 1974 Madagascar 1992 Montpellier zoo

474 + Eulemur fulvus mayottensis 1974 Madagascar 1990 Montpellier zoo

584 - Eulemur fulvus mayottensis 1984 Montpellier 1991 Montpellier zoo

455 + Eulemur fulvus mayottensis 1983 Montpellier 1989 Montpellier zoo

 - + Eulemur fulvus mayottensis 1988 Montpellier 1992 Montpellier zoo

 - + Eulemur fulvus mayottensis 1995 Montpellier 1996 Montpellier zoo

 - + Eulemur fulvus albifrons 1988 Paris 1992 Montpellier zoo

 - + Eulemur fulvus albifrons 1988 Paris 1990 Montpellier zoo

 - + Eulemur fulvus albifrons 1988 Paris 1992 Montpellier zoo

456 + Eulemur fulvus albifrons 1988 Paris 1990 Montpellier zoo

586 + Eulemur mongoz - 1979 Madagascar 1998 Montpellier zoo

 - p Eulemur mongoz - 1989 Mulhouse 1991 Montpellier zoo

 - p Eulemur mongoz - 1989 Mulhouse 1990 Montpellier zoo

 - p Eulemur macaco - 1986 Montpellier 1996 Montpellier zoo

 - p Lemur catta - 1976 Montpellier 1994 Montpellier zoo

 - p Varecia variegata variegata 1985 Mulhouse 1990 Montpellier zoo

 - p Varecia variegata variegata 1993 xxx 1994 Montpellier zoo

455 + Macaca mulatta - 1986 Ravensden UK 1992 Montpellier zoo

 - p Macaca mulatta - 1986 Ravensden UK 1993 Montpellier zoo

 - p Macaca mulatta - 1988 Ravensden UK 1991 Montpellier zoo

 - p Saimiri sciureus - 1987 Frejus France 1990 Frejus zoo

700 pc eulemur hybrid - - Besancon zoo 1998 Besancon zoo

701 pc eulemur hybrid - - Besancon zoo 1998 Besancon zoo

702 pc eulemur hybrid - - Besancon zoo 1998 Besancon zoo

703 pc eulemur hybrid - - Besancon zoo 1998 Besancon zoo

704 pc eulemur hybrid - - Besancon zoo 1998 Besancon zoo

705 pc eulemur hybrid - - Besancon zoo 1998 Besancon zoo

706 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

707 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

708 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

709 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

710 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

711 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

712 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

713 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

714 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

715 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

716 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

717 pc eulemur hybrid - - Strasbourg zoo 1998 Strasbourg zoo

 x p genus species - - Lille zoo 1996 Lille zoo

 y p genus species - - Lille zoo 1996 Lille zoo

 z p genus species - - Lille zoo 1996 Lille zoo 

1 + Actinonyx jubatus cheetah 1986 Marwell zoo 1991 Pearle Coast AU

Duke + Actinonyx jubatus cheetah 1984 Marwell zoo 1992 Colchester zoo? UK

Saki + Actinonyx jubatus cheetah 1986 Marwell zoo 1993 unknown UK

Mich + Actinonyx jubatus cheetah 1986 Whipsnade 1993 Whipsnade UK

Fr1 + Actinonyx jubatus cheetah 1987 Whipsnade 1997 Safari de Peaugres FR

Fr2 + Actinonyx jubatus cheetah 1991 Marwell zoo 1997 Safari de Peaugres Fr

xx + Actinonyx jubatus cheetah 19xx xxx zoo 199x Fota zoo IR

yy + Actinonyx jubatus cheetah 19xx yyy zoo 1996+ yyyy zoo UK

zz + Actinonyx jubatus cheetah 19xx zzz zoo 1996+ yyyy zoo UK

aaa + Felis concolor puma 1986 Chester zoo 1991 Chester zoo UK

yy + Felis concolor puma 1980 yyy zoo 1995 yyyy zoo UK

zz + Felis concolor puma 1978 zzz zoo 1995 zzzz zoo UK

xxx + Felis pardalis ocelot 1987 xxx 1994 Chester zoo UK

zzz + Felis pardalis ocelot 1980 zzz 1995 zzzz zoo UK

85 + Felis catus cat 1990+ various 1999+ various UK LI NO 

19 + Canis familia. dog 1992+ various 1999+ various UK 

Fota + Panthera tigris tiger 1981 xxx zoo 1995 xxxx zoo UK

yy + Panthera tigris tiger 1983 yyy zoo 1998 yyyy zoo UK

Lump + Panthera leo lion 1986 Woburn SP 1998 Edinburgh zoo UK [since 1994]

1 + Taurotragus oryx eland 1987 Port Lympne 1989 Port Lympne zoo UK

Moll + Taurotragus oryx eland 1989 xx UK 1991 not Port Lympne UK

Nedd + Taurotragus oryx eland 1989 xx UK 1991 not Port Lympne UK

Elec + Taurotragus oryx eland 1990 xx UK 1992 not Port Lympne Uk

Daph p Taurotragus oryx eland 1988 xx UK 1990 not Port Lympne UK

zzz + Taurotragus oryx eland 1991 zz UK 1994 zzz UK 

yyy + Taurotragus oryx eland 1993 yy UK 1995 yyy UK 

Fran p Tragelaphus strepsi. kudu 1985 London zoo 1987 London zoo UK

Lind + Tragelaphus strepsi. kudu 1987 London zoo 1989 London zoo UK

Karl + Tragelaphus strepsi. kudu 1988 London zoo 1990 London zoo UK

Kaz + Tragelaphus strepsi. kudu 1988 London zoo 1991 London zoo UK

Bamb pc Tragelaphus strepsi. kudu 1988 London zoo 1991 London zoo UK

Step - Tragelaphus strepsi. kudu 1984 London zoo 1991 London zoo UK

346 pc Tragelaphus strepsi. kudu 1990 London zoo 1992 London zoo UK

324 + Tragelaphus strepsi. kudu 1989 Marwell zoo 1992 London zoo UK

xxx + Tragelaphus angasi nyala 1983 Marwell zoo 1986 Marwell zoo UK

yy + Oryx gazella gemsbok 1983 Marwell zoo 1986 Marwell zoo UK

zz + Oryx gazella gemsbok 1994+ zzz zoo 1996+ zzzz zoo UK

xx + Oryx dammah scim oryx 1990 xxxx zoo 1993 Chester zoo UK

yy + Oryx leucoryx arab oryx 1986 Zurich zoo 1991 London zoo UK

yy + Bos taurus ankole cow 1987 yyy zoo 1995 yyyy zoo UK

zz + Bos taurus ankole cow 1986 zzz zoo 1991 zzzz zoo UK

xx + Bison bison Eu bison 1989 xxx zoo 1996 xxxx zoo UK






THURSDAY, DECEMBER 19, 2019

TSE surveillance statistics exotic species and domestic cats Update December 2019


172. Establishment of PrPCWD extraction and detection methods in the farm soil

Kyung Je Park, Hoo Chang Park, In Soon Roh, Hyo Jin Kim, Hae-Eun Kang and Hyun Joo Sohn
Foreign Animal Disease Division, Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbuk-do, Korea
ABSTRACT
Introduction: Transmissible spongiform encephalopathy (TSE) is a fatal neurodegenerative disorder, which is so-called as prion diseases due to the causative agents (PrPSc). TSEs are believed to be due to the template-directed accumulation of disease-associated prion protein, generally designated PrPSc. Chronic wasting disease (CWD) is the prion disease that is known spread horizontally. CWD has confirmed last in Republic of Korea in 2016 since first outbreak of CWD in 2001. The environmental reservoirs mediate the transmission of this disease. The significant levels of infectivity have been detected in the saliva, urine, and faeces of TSE-infected animals. Soil can serve as a stable reservoir for infectious prion proteins. We found that PrPCWD can be extracted and detected in CWD contaminated soil which has kept at room temperature until 4 years after 0.001 ~ 1% CWD exposure and natural CWD-affected farm soil through PBS washing and sPMCAb.
Materials and Methods: Procedure of serial PMCAb. CWD contaminated soil which has kept at room temperature (RT) for 1 ~ 4 year after 0.001%~1% CWD brain homogenates exposure for 4 months collected 0.14 g. The soil was collected by the same method once of year until 4 year after stop CWD exposure. We had conducted the two steps. There are two kinds of 10 times washing step and one amplification step. The washing step was detached PrPSc from contaminated soil by strong vortex with maximum rpm. We harvest supernatant every time by 10 times. As the other washing step, the Washed soil was made by washing 10 times soil using slow rotator and then harvest resuspended PBS for removing large impurity material. Last step was prion amplification step for detection of PrPCWD in soil supernatant and the washed soil by sPMCAb. Normal brain homogenate (NBH) was prepared by homogenization of brains with glass dounce in 9 volumes of cold PBS with TritonX-100, 5 mM EDTA, 150 mM NaCl and 0.05% Digitonin (sigma) plus Complete mini protease inhibitors (Roche) to a final concentration of 5%(w/v) NBHs were centrifuged at 2000 g for 1 min, and supernatant removed and frozen at −70 C for use. CWD consisted of brain from natural case in Korea and was prepared as 10%(w/v) homogenate. Positive sample was diluted to a final dilution 1:1000 in NBH, with serial 3:7 dilutions in NBH. Sonication was performed with a Misonix 4000 sonicator with amplitude set to level 70, generating an average output of 160W with two teflon beads during each cycle. One round consisted of 56 cycles of 30 s of sonication followed 9 min 30 s of 37°C incubation. Western Blotting (WB) for PrPSc detection. The samples (20 µL) after each round of amplification were mixed with proteinase K (2 mg/ml) and incubated 37°C for 1 h. Samples were separated by SDS-PAGE and transferred onto PVDF membrane. After blocking, the membrane was incubated for 1 h with 1st antibody S1 anti rabbit serum (APQA, 1:3000) and developed with enhanced chemiluminescence detection system.
Results: We excluded from first to third supernatant in view of sample contamination. It was confirmed abnormal PrP amplification in all soil supernatants from fourth to tenth. From 0.01% to 1% contaminated washed soils were identified as abnormal prions. 0.001% contaminated washed soil did not show PrP specific band (Fig 1). The soil was collected by the same method once of year until 4 year after stop CWD exposure. After sPMCAb, there were no PrPCWD band in from second to fourth year 0.001% washed soil. but It was confirmed that the abnormal prion was amplified in the washing supernatant which was not amplified in the washed soil. we have decided to use soil supernatant for soil testing (Fig. 2). After third rounds of amplification, PrPSc signals observed in three out of four sites from CWD positive farm playground. No signals were observed in all soil samples from four CWD negative farm (Fig. 3).
Conclusions: Our studies showed that PrPCWD persist in 0.001% CWD contaminated soil for at least 4 year and natural CWD-affected farm soil. When cervid reintroduced into CWD outbreak farm, the strict decontamination procedures of the infectious agent should be performed in the environment of CWD-affected cervid habitat.
===

186. Serial detection of hematogenous prions in CWD-infected deer

Amy V. Nalls, Erin E. McNulty, Nathaniel D. Denkers, Edward A. Hoover and Candace K. Mathiason
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA
CONTACT Amy V. Nalls amy.nalls@colostate.edu
ABSTRACT
Blood contains the infectious agent associated with prion disease affecting several mammalian species, including humans, cervids, sheep, and cattle. It has been confirmed that sufficient prion agent is present in the blood of both symptomatic and asymptomatic carriers to initiate the amyloid templating and accumulation process that results in this fatal neurodegenerative disease. Yet, to date, the ability to detect blood-borne prions by in vitro methods remains difficult.
We have capitalized on blood samples collected from longitudinal chronic wasting disease (CWD) studies in the native white-tailed deer host to examine hematogenous prion load in blood collected minutes, days, weeks and months post exposure. Our work has focused on refinement of the amplification methods RT-QuIC and PMCA. We demonstrate enhanced in vitro detection of amyloid seeding activity (prions) in blood cell fractions harvested from deer orally-exposed to 300 ng CWD positive brain or saliva.
These findings permit assessment of the role hematogenous prions play in the pathogenesis of CWD and provide tools to assess the same for prion diseases of other mammalian species.
Considering the oral secretion of prions, saliva from CWD-infected deer was shown to transmit disease to other susceptible naïve deer when harvested from the animals in both the prions in the saliva and blood of deer with chronic wasting disease
 and preclinical stages69
 of infection, albeit within relatively large volumes of saliva (50 ml). In sheep with preclinical, natural scrapie infections, sPMCA facilitated the detection of PrPSc within buccal swabs throughout most of the incubation period of the disease with an apparent peak in prion secretion around the mid-term of disease progression.70
 The amounts of prion present in saliva are likely to be low as indicated by CWD-infected saliva producing prolonged incubation periods and incomplete attack rates within the transgenic mouse bioassay.41
snip...
Indeed, it has also been shown that the scrapie and CWD prions are excreted in urine, feces and saliva and are likely to be excreted from skin. While levels of prion within these excreta/secreta are very low, they are produced throughout long periods of preclinical disease as well as clinical disease. Furthermore, the levels of prion in such materials are likely to be increased by concurrent inflammatory conditions affecting the relevant secretory organ or site. Such dissemination of prion into the environment is very likely to facilitate the repeat exposure of flockmates to low levels of the disease agent, possibly over years.
snip...
Given the results with scrapie-contaminated milk and CWD-contaminated saliva, it seems very likely that these low levels of prion in different secreta/excreta are capable of transmitting disease upon prolonged exposure, either through direct animal-to-animal contact or through environmental reservoirs of infectivity.
the other part, these tissues and things in the body then shed or secrete prions which then are the route to other animals into the environment, so in particular, the things, the secretions that are infectious are salvia, feces, blood and urine. so pretty much anything that comes out of a deer is going to be infectious and potential for transmitting disease.
HUNTERS, CWD TSE PRION, THIS SHOULD A WAKE UP CALL TO ALL OF YOU GUTTING AND BONING OUT YOUR KILL IN THE FIELD, AND YOUR TOOLS YOU USE...

* 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]
Wednesday, September 11, 2019 

Is the re-use of sterilized implant abutments safe enough? (Implant abutment safety) iatrogenic TSE Prion

SATURDAY, MARCH 16, 2019 

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) Guidance for Industry and Food and Drug Administration Staff Document issued on March 15, 2019 Singeltary Submission


MONDAY, NOVEMBER 23, 2020 

***> Chronic Wasting Disease CWD TSE Prion Cervid State by State and Global Update November 2020


MONDAY, NOVEMBER 30, 2020 

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

see updated concerns with atypical BSE from feed and zoonosis...terry

Monday, November 30, 2020 

Tunisia has become the second country after Algeria to detect a case of CPD within a year


TUESDAY, NOVEMBER 17, 2020 

The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSE) in 2019 First published 17 November 2020


WEDNESDAY, OCTOBER 28, 2020 

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


WEDNESDAY, OCTOBER 28, 2020 

EFSA Scientific Opinion Potential BSE risk posed by the use of ruminant collagen and gelatine in feed for non‐ruminant farmed animals


WEDNESDAY, DECEMBER 2, 2020

EFSA Evaluation of public and animal health risks in case of a delayed post-mortem inspection in ungulates EFSA Panel on Biological Hazards (BIOHAZ) ADOPTED: 21 October 2020

i wonder if a 7 month delay on a suspect BSE case in Texas is too long, on a 48 hour turnaround, asking for a friend???


> However, to date, no CWD infections have been reported in people.
key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;
(3) Reliable essays can be established to detect CWD infection in humans; and
(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
Prion 2017 Conference
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 
This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 
At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS 
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.
After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.
The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD..
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD
states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,
AND
included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),
AND
THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
snip…
see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below…terry
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
International Conference on Emerging Diseases, Outbreaks & Case Studies & 16th Annual Meeting on Influenza March 28-29, 2018 | Orlando, USA
Qingzhong Kong
Case Western Reserve University School of Medicine, USA
Zoonotic potential of chronic wasting disease prions from cervids
Chronic wasting disease (CWD) is the prion disease in cervids (mule deer, white-tailed deer, American elk, moose, and reindeer). It has become an epidemic in North America, and it has been detected in the Europe (Norway) since 2016. The widespread CWD and popular hunting and consumption of cervid meat and other products raise serious public health concerns, but questions remain on human susceptibility to CWD prions, especially on the potential difference in zoonotic potential among the various CWD prion strains. We have been working to address this critical question for well over a decade. We used CWD samples from various cervid species to inoculate transgenic mice expressing human or elk prion protein (PrP). We found infectious prions in the spleen or brain in a small fraction of CWD-inoculated transgenic mice expressing human PrP, indicating that humans are not completely resistant to CWD prions; this finding has significant ramifications on the public health impact of CWD prions. The influence of cervid PrP polymorphisms, the prion strain dependence of CWD-to-human transmission barrier, and the characterization of experimental human CWD prions will be discussed.
Speaker Biography Qingzhong Kong has completed his PhD from the University of Massachusetts at Amherst and Post-doctoral studies at Yale University. He is currently an Associate Professor of Pathology, Neurology and Regenerative Medicine. He has published over 50 original research papers in reputable journals (including Science Translational Medicine, JCI, PNAS and Cell Reports) and has been serving as an Editorial Board Member on seven scientific journals. He has multiple research interests, including public health risks of animal prions (CWD of cervids and atypical BSE of cattle), animal modeling of human prion diseases, mechanisms of prion replication and pathogenesis, etiology of sporadic Creutzfeldt-Jacob disease (CJD) in humans, normal cellular PrP in the biology and pathology of multiple brain and peripheral diseases, proteins responsible for the α-cleavage of cellular PrP, as well as gene therapy and DNA vaccination.
SATURDAY, FEBRUARY 23, 2019 

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


TUESDAY, NOVEMBER 04, 2014 

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

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


Transmission Studies

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

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

snip.... 


Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿ 

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

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


Prions in Skeletal Muscles of Deer with Chronic Wasting Disease 

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


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

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

From: TSS 

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

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

From: "Belay, Ermias"

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

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

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

Dear Sir/Madam,

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

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

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

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


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

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

Thursday, April 03, 2008

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

snip...

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

snip... full text ; 


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

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

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



key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry 

*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).*** 




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

FRIDAY, JULY 26, 2019 

Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species

TUESDAY, JANUARY 21, 2020 

***> 2004 European Commission Chronic wasting disease AND TISSUES THAT MIGHT CARRY A RISK FOR HUMAN FOOD AND ANIMAL FEED CHAINS REPORT UPDATED 2020


CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL

Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY 

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

From: Steve Dealler 

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

To: BSE-L@ References: <3daf5023 .4080804="" wt.net="">

Dear Terry,

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

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

Steve Dealler =============== 


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

BSE Inquiry Steve Dealler

Management In Confidence

BSE: Private Submission of Bovine Brain Dealler

snip...see full text;

MONDAY, FEBRUARY 25, 2019

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


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

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

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

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

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


TUESDAY, NOVEMBER 17, 2020 

The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSE) in 2019 First published 17 November 2020


FRIDAY, OCTOBER 30, 2020 

Efficient transmission of US scrapie agent by intralingual route to genetically susceptible sheep with a low dose inoculum

SENATORS URGE BIDEN TO WITHDRAW SHEEP IMPORT RULE DUE TO SCRAPIE TSE Prion CONCERNS

Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al

Tue, Feb 2, 2021 4:40 pm

Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al

SCRAPIE USA MAP 1947 1977 MAP

scan0001.jpg

Epidemiology of Scrapie in the United States 1977

Slow Transmissible Diseases of the Nervous System: Volume 1

EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES

James Hourrigan1, Albert Klingsporn2, W. W. Clark3, and M. de Camp4

United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services

ABSTRACT Observations and experiences with scrapie in the United States during the past 25 years have consistently shown it was a disease that spreads from flock to flock, state to state, or from country to country by movement of infected, but apparently normal sheep which were incubating the disease but had not yet reached the age of clinical manifestation. The disease progressed relentlessly until the animal reached the age of manifestation, irrespective of whether the animal remained in the parent flock or had been moved to another flock, state, or country.

The means of spread from animal to animal was more difficult to explain. A close study of parent-progeny relationships suggested that maternal transmission played a dominant role and that there is an inherited component in the level of incidence. When previously unexposed Angora or dairy goats or sheep of the Suffolk, Hampshire, Rambouillet, or Targhee breeds were placed in contact with natural cases of scrapie, and subsequently bred within their own groups, scrapie developed in a few of the sheep first exposed at 3 to 9 months of age and in 14 to 39% of the sheep progeny, born and reared in the infected environment. Scrapie occurred in the progeny of all breeds of goats so exposed. The incidence in Angora goat progeny was 26% and in dairy goat progeny 61%. Dairy goats removed from scrapie exposure at 6 months of age or older developed scrapie, however, those removed at birth did not. Sheep removed from exposure at birth or at 4, 9, or 20 months of age developed scrapie. There was a progressive increase in scrapie incidence among those removed at older ages.

1Federal Center Building, Hyattsville, Maryland

2Federal Center Building, Hyattsville, Maryland

3Scrapie Field Trial, Mission, Texas

4Scrapie Field Trial, Mission, Texas 

INTRODUCTION’

Scrapie is a naturally occurring, fatal disease of sheep and goats caused by a filterable, transmissible, self-replicating agent considered by some workers to be a small virus. The virus is unusually resistant to heat and other physical and chemical abuse, including formaldehyde, and to ultraviolet and ionizing radiation. The early signs of natural scrapie are usually subtle changes in behavior or temperament followed by more obvious clinical signs which are progressive and include pruritus, debilitation, rubbing against fixed objects often accompanied by rapid movements of the tongue and lips, grinding of teeth, biting of feet and limbs, locomotor incoordination and, usually, loss of wool, condition, and weight. The course of the clinical disease varies from 1 to 8 months, but may be much longer. Suspicious signs, which on rare occasions persisted or recurred over a period of more than 2 years, were seen. Recovery in an obvious clinical case was not observed. In Icelandic sheep, the signs were primarily those of incoordination of gait without prominent pruritus, Palsson and Sigurdsson, 1958 (1). Recently, pruritus was more evident, Palsson, Personal Communications, 1978. In northern India, sheep showed a severe pruritus but not a protracted period of locomotor incoordination, Zlotnik and Katiyar, 1961 (2). In Suffolk sheep in Britain, there was usually both pruritus and incoordination; however, either could be absent, and extensive neurological lesions could be present in the absence of unequivocal signs of both, Dickinson et al., 1965 (3).

Fig. 1 showed the countries in which scrapie has been reported. The disease was recognized in England, Scotland, Wales, and continental Europe, including Germany, France, and Spain, about 250 years ago and has been reported there in many breeds of sheep. In Iceland, scraple is called rida, Sigurdsson, 1954 (4). Reports of scrapie outbreaks in other countries, largely due to the importation of sheep from Britain, included those in New Zealand, Brash, 1952 (5), and Brash, 1952 (6); Australia, Bull and Murnane, 1958 (7); India, Zlotnik and Katiyar, 1961 (2); Hungary, Aldasy and Suveges, 1964 (8); the Netherlands, Van der Akker et al., 1968 (9); Bulgaria, Ivanov and Haralambiev, 1970 (10); Belgium, Hoorens and Oyaert, 1966 (11); Republic of South Africa, Van der Merwe, 1966 (12); and Kenya, Cooper, 1973 (13). Outbreaks have also occurred in The Federal’ Republic of Germany (West), Von Hiepe et al., 1973 (14); Isle of Man, Italy, Lebanon, Somalia, United Arab Emirates, Yemen, Norway, Ireland, Northern Ireland, and Colombia, South America (FAO-WHO-OIE, 1975, 1976, and 1977, Annual Health Yearbook) and in Austria and former East Prussia. 

In the Western Hemisphere, scrapie was first reported in Canada in 1938, Schofield, 1938 (15), and in the United States in Michigan, in 1947, Thorp et al., 1952 (16). The basic source of scrapie in these countries was also British sheep. More extensive outbreaks were disclosed in the United States, in 1952, in California, Stuart et al., 1952 (17), and Ohio, Wagner et al., 1954 (18).

Scrapie has now been reported in the United States in 203 Suffolk flocks, 10 Cheviot flocks, 3 Hampshire flocks, 2 Montadale flocks, and 1 mixed breed flock, Klingsporn and Hourrigan, 1978 (19).

The States and counties involved in scrapie outbreaks were shown in Fig. 2. Although the 219 outbreaks were widespread geographically with 31 States involved, it was encouraging to note that the eradication program restricted further spread. For example, California had 13 outbreaks, but none since 1969. Indiana had 28 outbreaks but none since 1973, and Ohio with a total of 13 outbreaks had reported none since 1966.

Fig. 3 illustrated the spread of scrapie through the movement of sheep incubating the disease. In this particular Situation the disease became entrenched in particular flocks and spread to many other flocks in other States. In a typical situation, the disease became established, most often in purebred flocks, and spread by sheep sold at 2 or 3 or fewer years of age. When the index case was disclosed, all possibly-exposed sheep were traced often disclosing additional scrapied animals in other receiving flocks. Although there was substantial circumstantial evidence against certain suspected source flocks, it was often difficult to prove the disease was present in such flocks. This could have been because sheep were usually sold prior to the age of manifestation or perhaps the owners innocently or deliberately failed to report suspect cases for fear of jeopardizing customary markets.

Evidence of natural scrapie in goats is accumulating. The disease was reported in 1942 in a goat reared with a flock of scrapied sheep in France, Chellé, 1942 (20). In Scotland, 4 of 6 dairy goats maintained in a stall, in contact from the time they were less than 1 week old with a succession of natural cases (mainly Suffolks), developed scrapie at 39, 39, 39, and 47 months of age. In a second similar experiment, 55% of 11 exposed goats developed serapie at 29, 32, 32, 32, 36, and 37 months of age, Brotherston et al., 1968 (21).

Three goats developed scrapie when held in contact from 1 day of age with scrapled sheep for 40 months, Stamp, 1962 (22).

Scrapie was diagnosed in a 5-year-old goat reared in a scrapied flock of Suffolk sheep in Missouri, Hourrigan et al., 1969 (23). In Canada, scrapie was diagnosed in a 7- or 8-year-old goat born in a flock where scrapie had occurred in sheep, Stemshorn, 1975 (24). In Britain, scrapie was reported in a 4-year-old and an 8-year-old Saanan goat which had very little contact with any sheep, Harcourt and Anderson, 1974 (25). Scrapie was diagnosed in an uninoculated control adult goat purchased at 3 years of age from a dealer, MacKay and Smith, 1961 (26).

Indirect transmission of natural scrapie to 10 of 25 test sheep following exposure on a rotational basis to pastures used by scrapied sheep was reported, Greig, 1940 (27).

Following exposure indoors to a succession of naturally scrapied sheep, 43% of 7 Scottish Blackface lambs, developed scrapie at 42 to 44 months of age, Brotherston et.al., 1968 (21).

Scrapie occurred in 28% of purebred Scottish Blackface sheep due to lateral transmission under lifetime contact, Dickinson et al., 1974 (28).

METHODS

A Scrapie Field Trial was developed at Mission, Texas, to provide additional information for the eradication program on the epidemiology of natural scrapie. The Mission Field Trial Station is located on 450 acres of pastureland, part of the former Moore Air Force Base, near Mission, Texas. It was designed to bring previously exposed, and later also unexposed, sheep or goats to the Station and maintain and breed them under close observation for extended periods to determine which animals would develop scrapie and define more closely the natural spread and other epidemiological aspects of the disease.

The 547 previously exposed sheep brought to the Mission Station beginning in 1964 were of the Cheviot, Hampshire, Montadale, or Suffolk breeds. They were purchased as field outbreaks occurred, and represented 21 bloodlines in which scrapie had been diagnosed. Upon arrival at the Station, the sheep were maintained on pasture, with supplemental feeding as necessary. The station was divided into 2 areas: (1) a series of pastures and-pens occupied by male animals only, and (2) a series of pastures and pens occupied by females and young progeny of both sexes. Lambing and kidding occurred in the female area, with lambs remaining with the dams until weaning. At weaning, young males were removed to the male area, and females were temporarily separated from their dams, but remained in the female area. (?) weaning, males and females were kept separated and not allowed to mix or use the same pastures or facilities, except for those males which were chosen for breeding and taken temporarily to the breeding pens. To study familial relationships of the disease, a particular ram was bred to a selected ewe and re- bred to the same ewe in succeeding years to produce as many full sibs as possible.

Numbered duplicate ear tags were placed in both ears of each animal. Sheep were also wool-branded with a number, corresponding to the ear tag number, and rebranded after each semiannual shearing.

Prior to the arrival of exposed sheep, in November 1964, the premises were considered free of contamination by scrapie virus. No livestock had occupied the pastures since 1942, when the Air Base had been established.

Previously unexposed animals were also taken to the Station beginning in 1965 and were placed in direct contact with the infected flock, The previously unexposed animals included 11 Angora goats, 6 Nubian or Toggenburg dairy goats, and 31 Rambouillet, 31 Targhee, 33 Hampshire, and 28 Suffolk sheep. These animals were carefully selected to assure freedom from previous exposure to scrapie. No field cases of scrapie have been found in Rambouillet or Targhee sheep or Angora goats in the United States. Only 1 field case has been reported in a dairy goat, Hourrigan et al., 1969 (23), and 3 field cases in Hampshire sheep. These 4 cases had been raised in flocks containing Suffolk sheep. Twenty of the Suffolks were imported from New Zealand, which had been scrapie-free for more than 20 years.

Later, certain sheep or goats born at the Station were removed from exposure at birth and at 4, 6, 9, or 20 months of age and placed in isolation pens at the Station for long term observation. 

Scrapie incidence (percentage of scrapie) was calculated by dividing the number of scrapied animals by the number of animals at risk. Animals were not diagnosed as scrapied unless confirmed by histological examination, McDaniel et al., 1966 (29) and/or by inoculation into mice. 

To be considered at risk and scrapie-free, animals had to have reached at Least 24 months of age, and if they had died, high quality brain tissue was submitted to the laboratory and found to be histologically negative for scrapie. Animals brought to the Station and still alive had to reach at least 100 months of age and those born at the Station 60 months of age to be considered at risk and scrapie free.

The age (months) of scrapied animals at death or sacrifice was used as “age scrapied" in all calculations. Animals of doubtful category (clinically : -cious, histologically inconclusive, or showing post-mortem autolytic brain damage were not considered at risk insofar as these calculations were concerned.

RESULTS

Table 1 indicated that previously exposed sheep brought to the Station at various times and ages (1 to 89 months old) included 333 Suffolks at risk. Of these, 98 (29%) developed scrapie. This demonstrated the necessity to slaughter such sheep to prevent further Spread of the disease, These previously exposed Suffolks were bred at the Station and produced 446 progeny at risk. Of these 153 (34%) developed scrapie.

Although the minimum and average ages when scrapied were similar for both groups, some of the previously exposed Suffolks brought to the Station developed scrapie when much older--ewes 60 to 142 months old and rams 67 to 102 months old. Of the 153 Suffolks born at the Station, only 3 were more than 60 months of age (65, 66, and 69 months old).

This difference in age scrapied was attributed to the fact that the Suffolks born at the Station may have been subject to a greater exposure from birth.

It was also observed that when both dam and progeny were scrapied, the progeny nearly always developed clinical disease at a younger age than their respective dam. Thirty-two dams were scrapied at an average of 60 months of age. Forty-six of their progeny developed the disease at an average of 38 months (range 25 to 53 months). Thirty-seven of the 46 progeny were younger than the dam (average 20 months younger, range 2 to 99 months younger). Two were scrapied at the same age as their dams, and 8 were older (average 5 months, range 1 to 13 months older).

Although the incidence of scrapie was considerably Greater in the progeny of scrapied compared to free dams, the progeny of either scrapied or free dams manifested scrapie at the typical age and irrespective of the age their respective dams were scrapied. The differences in ages that dams and progeny were scrapied was believed due to difference of exposure, particularly whether they were exposed at an early age,

Table 2 summarized the data on exposed Suffolks and was Prepared so as to show scrapie incidence in the progeny of dams and sires of known Scrapie status. The scrapie incidence in the progeny of Free X Free parents was 25%, progeny of scrapied Sires 39%, and scrapied dams 42%. When both sire and dam were scrapied, the scrapie incidence in 18 Progeny at risk was 78%,

When the scrapie status of the sire was ignored, scrapie incidence in the progeny of free dams was 34% and in pre y of scrapied da as 62%. When the scrapie status of the dam was ignored, scrapie incidence in the progeny of free sires was 26% and in the progeny of scrapied sires was 45%.

Although the scrapie incidence was nearly double in the progeny of scrapied compared to free dams, the latter con- tributed a greater number of scrapied progeny, 116, compared to only 51 cases which had scrapied dams. This was because free dams made a considerably heavier contribution to the progeny at risk4-342 compared to 82. It was felt that in farm flocks a similar situation could exist.

It was possible that free dams could have been misclassified; however, this was unlikely to have been significant, unless "nonclinical or carrier" dams exist. In this Suffolk group, the ages of 100 free dams of scrapied progeny ranged from 25 to 160 (average 97) months. These free dams did not show clinical signs of scrapie, and there were no histopathological lesions suggesting scrapie in those which died. If one cannot classify as free, ewes which have reached 97 months (average) and did not develop the disease, from a practical standpoint, it is not possible to classify sheep as free, at least on the basis of clinical signs and histology. The free dams of 50% of the scrapied progeny were more than 100 months of age, averaging 126 months.

Upon arrival at the Mission Station at 3 to 9 months of age, the 140 previously unexposed sheep and goats were placed in infected pastures and corrals and were subjected to contact with a succession of natural cases of scrapie in sheep, and eventually also in goats. These animals were bred only within their respective groups and were not crossbred to other breeds of sheep or those brought to the Station from infected flocks or their progeny. The male or female animals mixed freely with animals of their respective sex of the infected Flock and were similarly identified and subjected to similar flock management and diagnostic procedures.

Table 3 indicated that natural scrapie had occurred in 5 of the 140 previously unexposed sheep. One case each occurred in Rambouillet, Targhee, and Hampshire ewes at 88, 89, and 89 months of age and in 2 Suffolk ewes at 73 and 102 months of age, and 85, 82, 80, 64, and 93 months following initial natural exposure. This represented a natural situation involving lateral spread, under the circumstances involved, when sheep were not exposed when very young. Scrapie was not detected clinically or histologically in any of the dairy or Angora goats brought to the Station. The disease occurred in an average of 27% of the progeny of previously unexposed sheep or goats born at the Station and included cases in progeny of all breeds of sheep or goats taken there, The incidence in the progeny ranged from 14% in Rambouillet sheep to 61% in dairy goats. 

These data showed that scrapie spread laterally, by contact exposure, from scrapied te previously free animals, but at an apparently lower rate when exposure was first received at the age of 3 te 9 months. These animals were presumed to be susceptible to the disease, as their progeny developed scrapie at rates and ages similar (on the average) to the progeny, pf previously exposed Suffolk sheep born and reared in the same environment.

It was suggested that the progeny of previously unexposed animals developed scrapie at a much higher rate than their parents, and at a younger age, because they were subjected to exposure from birth. The data did not rule out the possibility that the animals born at the Station could have also received the virus from their dams "vertically" prior to, at, or following birth.

Table 4 summarized the scrapie incidence in the progeny, born at the Station, of previously unexposed dairy goats. The data were prepared so as to show scrapie incidence in the progeny of dams and sires of known scrapie status.

The 58% incidence in the progeny (24 at risk) of Free X Free parents was more than twice the 25% seen in the Suffolk group (Table 2). Scrapied sires did not increase the incidence in goat progeny (it was 44%); scrapied dams increased the incidence to 71%. When both sire and dam were scrapied the incidence was 89%, with only 9 goat progeny at risk.

When the scrapie status of the sire was ignored, the scrapie incidence in the progeny of free dams was 56% and in the progeny of scrapied dams it was 74%.

Free dams contributed 34 progeny at risk and scrapied dams 31 progeny.

When the scrapie status of the dam was ignored, scrapie incidence was 64% in the progeny of free sires and a similar 66% in the progeny of scrapied sires.

A total of 244 sheep (127 Suffolk, 59 Rambouillet, and 58 Targhee) were removed from scrapie exposure within a few hours of birth or at 4, 9, or 20 months of age and placed in isolation pens. Removal of sheep from exposure at these ages was selected as being representative of usual flock operations when sheep might be sold from an infected flock at weaning, the first fall or the second fall after their birth.

Table 5 reflected the fate of such animals. Four of the 6 scrapied sheep which had been isolated at birth were Suffolks and the 2 older animals were Targhees. The first case in the group isolated at birth was a Targhee, progeny of a ewe that did not develop clinical scrapie. The scrapie incidence in 36 at risk Suffolks removed from exposure at birth was 11%, considerably less then that expected had these animals remained in an infected environment.

Table 6 reflected the status of 51 goats isolated from scrapie exposure at birth, and at 6, 8 to 10, 20, 32 to 59 and 60 to 82 months of age.

None of the goats removed at birth developed scrapie, although all 5 of those alive at 5 years of age had scrapied dams and 1 also had a scrapied sire. The sire of the remaining 4 had sired 7 scrapied progeny. Under such circumstances, had they remained in an infected environment nearly all of these goats would have been expected to develop scrapie. With the exception of the 20 month group, scrapie occurred at an incidence of 25 to 100% in all other groups and at the expected age. A further observation was that 4 of the progeny of these dairy goats, born and kept apart from any sheep, developed scrapie which suggested that goats were not "dead- end hosts" insofar as scrapie was concerned.

Table 7 recorded the fate of progeny of certatn selected scrapied or free Suffolk sheep or dairy goat dams.

Suffolk ewe G298 was scrapied at 46 months of age. She had twin lambs in 1969 and 1 lamb in 1970. All 3 lambs developed scrapie. Suffolk ewe G27a was scrapied at 39 months. Her lamb born in 1966 was serapied at 53 months; however, her lambs born in 1967 and 1968 remained free--l*lived to 102 months of age.

Suffolk ewe G25a died at 131] months of age and was negative clinically and histologically. Mice remained negative following intracerebral inoculation of brain, spleen, and lymph nodes from this ewe. This ewe had 9 progeny at risk, of which 4 developed scrapie and 5 did not. There was no discernible pattern to the cases. In two instances, 1 twin was scrapied and 1 remained free.

Goat B259 was scrapied when 43 months old. All of her 6 progeny at risk developed scrapie.

Goat B14a remained free and died at 101 months of age. Of her 11 progeny at risk, 7 were scrapied and 4 were not.

It was observed at the Station that when scrapied dams had several progeny at risk, 1 or more progeny usually developed the disease. However, many such scrapied dams also had progeny which lived, or are living, considerably beyond the age of their dams and beyond the age animals born at the Station manifested the disease.

It was also observed that individual free dams had free progeny in earlier years followed by scrapied progeny when they were older, or had scrapied progeny when young followed by free progeny when older, or scrapie and free progeny dispersed throughout the dam's breeding life. The same situation occurred in progeny of scrapied dams; however, the pattern was less irregular due to the smaller number of progeny from each scrapied dam and the higher incidence of scrapie in such progeny. circumstances prevented breeding all ewes every year and, thus, many had only 1 progeny at risk. Scrapie developed in 100% of the single progeny at risk of 11 scrapied and 15 free dams. The 26 scrapied progeny were equally divided between ewes and rams.

Table 8 reflected the difference in age scrapied of sheep brought to the Station compared to the age scrapied of those born there. Although the average age of previously exposed sheep (Suffolks) brought to the Station did not differ greatly from the overall average, several animals brought to the Station developed the disease at quite advanced ages. The previously unexposed scrapied animals brought to the Station were also considerably older than animals born there. Progeny of scrapied dams developed the disease at a slightly younger age than did progeny of free dams. The average age was nearly the same for males and females.

DISCUSSION

Observations of natural outbreaks of scrapie indicated that the disease spread from flock to flock by the movement of infected, but apparently normal, sheep which were incubating the disease.

There was no evidence that the disease spread to adjacent flocks in the absence of such movements or that vectors or other host species were involved in the spread of scrapie to sheep or goats; however, these possibilities should be kept open.

In countries where scrapie occurred, it was difficult to know with certainty that sheep or goats were not incubating the disease and would not manifest the disease at some future time. This concept was supported when sheep removed from scrapie exposure at birth, and at 4, 9, or 20 months of age developed scrapie at the expected ages. Thus, sheep born in a contaminated environment had been sufficiently infected so as to develop the disease when they reached the age of manifestation. Unpublished data at the Station demonstrated that scrapie virus could be isolated by intracerebral inoculation of mice from an apparently normal Suffolk sheep as young as 4 months and goats as young as 11 months of age. The dams of both such animals had been scrapied. Attempts to isolate scrapie virus from younger progeny or fetal tissues from scrapied dams had been negative. Histological evidence of natural scrapie in apparently normal sheep had been reported in lambs as young as 11 months, Dickinson et al., 1965 (3). Natural scrapie virus was recovered in Cheviot sheep 8 months old. Renwick and Zlotnik, 1965 (30) claimed to have isolated the agent from apparently normal 4 1/2 month old Bord Leicester lamb ... of a scrapied dam. 

Goats removed from exposure at birth had not developed scrapie at 5 years of age, although all had scrapied dams. Had they remained with their dams in the infected environment, nearly all of these 5 goats would have been expected to develop scrapie. However, goats isolated at 6 months of age or older developed scrapie at the expected age. Goats born and kept apart from all sheep, but in contact with scrapied goats, developed scrapie suggesting goats were not dead-end hosts.

When previously unexposed animals 3 to 9 months old were placed on premises where clinical cases were occurring, a small number of such test sheep developed clinical scrapie at rather advanced ages of 73 to 102 months. However, 14 to 61% of the progeny of such sheep or goats developed scrapie at the customary 30 to 60 months of age. This was observed when progeny of previously unexposed Suffolk, Ramboillet, Targhee, or Hampshire sheep or Angora or dairy goats were exposed to scrapied sheep, mainly Suffolks.

Suffolk sheep showed definite familial patterns, suggesting an inherited component and/or maternal transmission of scrapie. Morbidity in the progeny born on infected premises of free sires and free dams was 25% with 105 at risk (58% for dairy goats with 24 at risk) and increased to about 80% or more if both parents were scrapied.

The overall incidence in 283 Suffolk progeny at risk was 36%. Although the incidence was 62% in the progeny of scrapied and 34% in the progeny of free dams, the latter contributed a much greater number of progeny at risk and actually had a larger number of scrapied progeny.

Under similar exposure, the incidence in mixed dairy goats was 61% in 72 progeny at risk. Morbidity was 58% in progeny of free dams and free sires, 44% if the sire only was scrapied, 71% 1f the dam only was scrapied, and 89% if both sire and dam were scrapied.

Limited attempts to isolate scrapie virus from materials which might provide clues for animal to animal spread have been largely negative at the Mission Station. Tissues from scrapied sheep or goats or other materials inoculated intracerebrally or subcutaneously or fed to swiss white outbred mice included feces, urine, saliva, milk, semen, testes, colostrum, and ovary. Mice were also exposed to grass from pastures and manure from sheds believed to be contaminated. Preliminary results were negative. In only 2 instances did inoculated mice develop scrapie, This involved 1 cage of mice inoculated with internal parasites, Haemonchus contortus, and 1 cage of mice inoculated with fetal cotyledon from scrapled goats.

The average age of previously exposed scrapied sheer brought to the ...Station did not differ greatly from the overall average. However, several of these animals showed clinical evidence of the disease at advanced ages, up to 142 months. Previously unexposed animals brought to Mission also developed clinical signs at 73 to 102 months of age, considerably older than their progeny born at Mission.

In the United States, sheep with natural scrapie have on rare occasions shown clinical signs as young as 18 months.of age, Scrapied ewes as old as 142 months and scrapied rams as old as 102 months of age were recorded at the Mission Station; however, the great majority of scrapied sheep and goats were from 30 to 60 months of age. Field cases in younger animals were more likely to be seen when the disease was firmly established in a flock, Clinical natural scrapie was not observed in sheep or goats less than 18 months of age and rarely in animals that young; however, Katiyar, 1962 (31) and Joubert et al., 1972 (32) reported natural scrapie in India and in France in sheep as young as 10 to 12 months of age.

REFERENCES .

snip...


Scrapie Field Trial Experiments Mission, Texas

A Scrapie Field Trial was developed at Mission, Texas, to provide additional information for the eradication program on the epidemiology of natural scrapie. The Mission Field Trial Station is located on 450 acres of pastureland, part of the former Moore Air Force Base, near Mission, Texas. It was designed to bring previously exposed, and later also unexposed, sheep or goats to the Station and maintain and breed them under close observation for extended periods to determine which animals would develop scrapie and define more closely the natural spread and other epidemiological aspects of the disease.

The 547 previously exposed sheep brought to the Mission Station beginning in 1964 were of the Cheviot, Hampshire, Montadale, or Suffolk breeds. They were purchased as field outbreaks occurred, and represented 21 bloodlines in which scrapie had been diagnosed. Upon arrival at the Station, the sheep were maintained on pasture, with supplemental feeding as necessary. The station was divided into 2 areas: (1) a series of pastures and-pens occupied by male animals only, and (2) a series of pastures and pens occupied by females and young progeny of both sexes. ...

snip...see full text ;


Mission, Texas Scrapie transmission to cattle study

Wilbur Clarke (reference the Mission, Texas scrapie transmission transmission to cattle study) is now the State Veterinarian for Montana based at Helena.

I was given confidential access to sections from the Clarke scrapie-cattle transmission experiment. Details of the experimental design were as supplied previously by Dr. Wrathall (copy of relevant information appended). Only 3 animals (2 inoculated with 2nd pass Suffolk scrapie and 1 inoculated with Angora goat passaged scrapie) showed clinical signs. Clinical signs were characterised by weakness, ''a stilted hindlimb gait'', disorientation, ataxia and, terminally, lateral recumbency. The two cattle from which I examined material were inocluated at 8 months of age and developed signs 36 months pi (goat scrapie inoculum) and 49 months pi (one of the Suffolk scrapie inoculated) respectively. This latter animal was killed at 58 months of age and so the clinical duration was only 1 month. The neuropathology was somewhat different from BSE or the Stetsonville TME in cattle. Vacuolar changes were minimal, to the extent that detection REQUIRED CAREFUL SEARCHING. Conversely astrocyte hypertrophy was a widespread and prominent feature. The material requires DETAILED NEUROPATHOLOGICAL ASSESSMENT BUT WHETHER OR NOT THIS WILL BE DONE REMAINS A QUESTION.

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...

Appendix 3

VISIT TO USA - DR A E WRATHALL - INFO OH BSE AND SCRAPIE

1. Dr Clark lately of the Scrapie Research Unit, Mission Texas has successfully transmitted ovine and caprine scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978.

A summary of it is:-

Expt A

6 Her x Jer calves born in 1978 were inoculated as follows with

a 2nd Suffolk scrapie passage:-

i/c 1ml; i/m, 5ml; s/c 5ml; oral 30ml.

1/6 went down after 48 months with a scrapie/BSE-like disease.

Expt B

6 Her or Jer or HxJ calves were inoculated with angora Goat

virus 2/6 went down similarly after 36 months.

Expt C

Mice inoculated from brains of calves/cattle in expts A • B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.

Diagnosis in A, B, C was by histopath. No reports on SAT were given.

2. Dr Warren Foote indicated success so far in eliminating scrapie in offspring from experimentally- (and naturally) infected sheep by ET. He had found difficulty in obtaining embryos from naturally infected sheep (cf SPA).

3. Prof. A Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr A Thiermann showed the picture in the "Independent" with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. BSE was not reported in USA.

4. Scrapie incidents (ie affected flocks) have shown a dramatic increase since 1978. In 1953 when the National Control Scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.

5. Scrapie agent was reported to have been isolated from a solitary fetus.

6. A western blotting diagnostic technique (? on PrP) shows some promise.

7. Results of a questionnaire sent to 33 states on the subject of the national sheep scrapie programme survey indicated

17/33 wished to drop it

6/33 wished to develop it

9/13/2005

33

Page 15 of 17

8/33 had few sheep and were neutral

Information obtained from Dr Wrathall's notes of a meeting of the U.S. Animal Health Association at Little Rock, Arkansas Nov. 1988.

end...TSS



NOW, in 1979, it was proven that indeed U.S. scrapie strain that was transmitted to U.S. cattle, did NOT produce a Transmissible Spongiform Encephalopathy (TSE) like the U.K. B.S.E., but a TSE unlike the U.K. B.S.E. SO what does all this tell us? it tells me that there is a possibility that a strain of mad cow disease was circulating in the U.S.A. long, long, before originally thought, only left to be ignored, while incubating and spreading. 

3.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE.339 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture.340 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre.341 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle, did not produce the same clinical signs of brain lesions characteristic of BSE.

3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345

3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility. 

337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells, G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice, Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I., Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I., Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4



In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...


VISIT TO USA - DR AE WRATHALL - INFO ON BSE AND SCRAPIE

1. Dr. Clark lately of the Scrapie Research Unit, Mission Texas has successfully transmitted ovine & caprine Scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978. A summary of it is;

snip...see handwritten notes from this here;



IN CONFIDENCE

Perceptions of an unconventional slow virus diseases of animals in the U.S.A. G A H Wells

Report of a Visit to the USA April-May 1989



Transmissible Spongiform Encephalopathy

Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY


Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. snip... The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle... 




Scrapie USAHA


Scrapie USA 1997

PROCEEDINGS ONEHUNDREDANDFIRST ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION

October 18-24,1997 

8. SCRAPIE: Whereas in 1994 and 1995,102 brains of sheep showing various neuromotor clinical signs had been examined in Israel, all with negative results, one case was confirmed in October 1996. In Norway, since 1991 , the disease has remained confined to Hordaland and Rogaland districts. A new control program was launched in May 1996, which encourages the slaughter of animals having come into contact with infected flocks. In June 1996, scrapie was diagnosed in a sheep on the island of Hokkaido in Japan. This was the first case to be reported in the country since November 1994. 

Sheep 


Dr. John Clifford, USDA APHIS VS, reported on identification in the voluntary scrapie program. EID was not readable 20-30% of the time in some flocks. Tamper resistant eartags bearing premise ID issued by VS is being used in several flocks. VS maintains the database for these premise numbers. 


Scrapie USA 2000

PROCEEDINGS ONE HUNDRED AND FOURTH ANNUALMEETING of the UNITED STATESANIMAL HEALTH ASSOCIATION

October 20-27, 2000

On February IO, 2000, there were 48 flocks in the United States listed as infected with scrapie. A national surveillance plan is being developed for scrapie. On December 31,1999, there were 222 pseudorabies infected herds in the country.


Scrapie USA 2001


Scrapie USA 2002

PROCEEDINGS ONE HUNDRED AND SIXTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION

2002

Scrapie Infected and Source Flocks (Dianne Sutton): As of 9/30/02, there was 42 scrapie infected and source flocks. In FY 2002, 94 infected flocks were newly detected and over 259 scrapie cases were confirmed and reported by NVSL. Eighty-six flocks have been released from infected or source status or put on clean-up plans in FY 2002. Five cases of scrapie in goats were reported in FY 2002. During FY 2002, 11,751 animals were tested for scrapie. Laboratory testing has been taking 10 to 11 days on average. During FY 2002, 9.9 million plastic and 6.0 million metal tags were distributed by APHIS.


Scrapie USA 2003

PROCEEDINGS ONE HUNDRED AND SEVENTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION

2003

RESOLUTION NUMBER: 15 APPROVED SOURCE: COMMITTEE ON SHEEP AND GOATS SUBJECT MATTER: SCRAPIE BACKGROUND INFORMATION:

A significant number of sheep in the United States have been identified as immunohistochemistry (IHC) positive on tonsil and/or lymph nodes and IHC negative on obex. This number includes 24% of the sheep that tested positive on one or more tissues as part of Regulatory Slaughter Surveillance. This makes it important that IHC testing on tonsil and lymph nodes be approved as an official test. The United States Department of Agriculture (USDA), Agricultural Research Service (ARS) and Animal and Plant Health Inspection Service (APHIS), Veterinary Services (VS) have compiled data on 2,523 sheep of which 467 were positive on at least one tissue and for which results were available for obex or third eyelid and for tonsil or lymph node. The Kappa analysis showed the concordance between the currently approved tests and lymphoid nodes or tonsil to be 0.91 in the test validation data set and 0.93 for the National Veterinary Services Laboratory (NVSL) data set. As would be expected based on pathogenesis studies, the discrepant positive lymphoid tests were most often seen in young animals. The scientific literature supports the correlation between the detection of PrPsc and the presence of infectivity.

RESOLUTION:

The United States Animal Health Association (USAHA) recommends that the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Veterinary Services (VS) to approve immunohistochemistry on specific lymphoid tissues as an official test for the determination of a scrapie positive animal in live and dead sheep and goats.

APHIS RESPONSE:

The U.S. Department of Agriculture has approved immunohistochemistry testing on lymph node or tonsil as an official test when conducted at the National Veterinary Services Laboratories or its cooperating laboratories. Animals determined to be lymph node or tonsil

REPORT OF THE COMMITTEE

positive on or after November 7, 2003, at an approved laboratory will be designated scrapie-positive animals.

Infected and Source Flocks

As of September 30, 2003, there were 50 scrapie infected and source flocks (figure 3). There were 73 newly infected flocks reported in FY 2003 (figure 4). In addition, 351 Scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2003 (figure 5). These included 249 regular necropsy cases, 66 validation necropsy

475 SCRAPIE SUB-COMMITTEE REPORT

cases, 32 regulatory third eyelid cases, and 4 validation third eyelid cases. No cases of scrapie in goats were reported in FY 2003. The last case was confirmed in August 2002. New infected and source flocks numbers and the number of these flocks released in FY 2003 are depicted in chart 4. Sixty flocks, or 82 percent of the scrapie infected and source flocks present in FY 2003, were released or put on clean-up plans in FY 2003.

Scrapie: Ovine Slaughter Surveillance (SOSS)

The Center for Epidemiology and Animal Health, has released the first results of the SOSS study. The objective of SOSS was to estimate the national and regional prevalence of Scrapie in mature cull ewes. Prior to the SOSS study, the prevalence of Scrapie in the United States was estimated to be 0.07 percent (based on information from NAHMS Sheep ’96, unpublished data). The SOSS study estimate for the national Scrapie prevalence in mature ewes is 0.20 percent. The prevalence phase of the SOSS study started April 1, 2002, and continued through March 31, 2003. Samples were collected from 12,508 mature sheep at 22 slaughter facilities and a major livestock market during this time period.

The country was divided into four regions: West (CA,OR,WA); Mountain (AZ,CO,ID,MT,NV, NM,OK,TX,UT,WY); Central (IA,KS,MN, MO,NE,ND,SD); and East (AL,AR,CT,DE,FL,GA,KY, IL,IN,LA,MA, ME,MD,MI,MS,NH,NJ,NY,NC,OH,PA,RI,SC,TN,VA,VT,WI,WV). Sheep that could not be traced to a region were grouped as Multi-region. The regions are illustrated in figure 6. The weighted regional prevalence estimates (percent positive) for scrapie in mature sheep are: West = sample size was too small for prevalence estimation - no positives were found in the 670 sheep tested; Mountain = .14%; Central = .21%; East = .52%; and Multi-Region = .13%

Of the 12,508 sheep tested, 34 were found to be scrapie positive of which there were 27 black face, 3 mottled face, 2 white face, and 2 unknown face color. A complete report and analysis will be available in January 2004. Note: The raw prevalence is higher than the weighted prevalence. The difference is the result of weighting each positive based on the number of sheep sampled and the number of sheep killed at each plant.

Regulatory Scrapie Slaughter Surveillance (RSSS)

RSSS started April 1, 2003. RSSS is targeted slaughter surveillance which is designed to identify infected flocks for clean up. Six thousand and six hundred (6600) sheep were sampled during FY 2003, of which test results have been reported for 5,160. There were 17 positive or suspect sheep of which 3 were white face and 14 were black face. Seventeen plants submitted samples.

Scrapie Testing Summary

During FY 2003, 16,803 animals have been sampled or tested for

476

SHEEP AND GOATS

scrapie, which includes: 3,724 regular necropsy cases, 42 third eyelid biopsies for the test validation project, 244 necropsy test validations, 579 third eyelid biopsies for the regulatory program, and approximately 12,214 animals for SOSS and RSSS (chart 5).


Scrapie USA 2004

PROCEEDINGS ONE HUNDRED AND EIGHTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION

2004

There were seventy infected and source flocks identified as of September 30, 2004. In FY2004 a total of 103 new infected and source flocks reported with seventy-seven of those released in FY2004. As of September 30, 2004, 368 scrapie cases had been confirmed and reported by the National Veterinary Services Laboratories (NVSL), of which fifty-four were RSSS cases. One new goat case was reported. Approximately 3,058 animals were indemnified. Dr. Sutton also reported on the Scrapie ovine slaughter surveillance study and the Regulatory Slaughter Surveillance program. Scrapie testing was done on 25,006 animals in FY2004. As of September 30, 2004, 90,322 sheep and goat premises have been assigned identification (ID) numbers in the Scrapie National Generic Database. Official eartags have been issued to 64,040 of the premises.


Scrapie USA 2005

PROCEEDINGS ONE HUNDRED AND NINTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION

2005

For the period of time from January 1, 2005, until October 15, 2005, there were 23 instances of discrepancies in results from 35 flocks. Of those 23 instances, 14 were caused by laboratory error (paperwork or sample mix-up), 3 results from field error, 5 were not completely resolved, and 1 originated from the use of a non-approved laboratory for the first test. As a result of inconsistencies, one laboratory’s certification was revoked by APHIS-VS.

To reduce/eliminate these problems, the Program has placed additional quality requirements on the testing laboratories: additional review of final reports, additional coding systems for testing operations, strict follow-up and reports to NVSL on corrective actions, dual data entry systems, and more frequent inspections.

Infected and Source Flocks

As of September 30, 2005, there were 105 scrapie infected and source flocks. There were a total of 165** new infected and source flocks reported for FY 2005. The total infected and source flocks that have been released in FY 2005 was 128. The ratio of infected and source flocks cleaned up or placed on clean up plans vs. new infected and source flocks discovered in FY 2005 was 1.03 : 1*. In addition 622 scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2005, of which 130 were RSSS cases. Fifteen cases of scrapie in goats have been reported since 1990. The last goat case was reported in May 2005. Approximately 5,626 animals were indemnified comprised of 49% non-registered sheep, 45% registered sheep, 1.4% non-registered goats and 4.6% registered goats.

Regulatory Scrapie Slaughter Surveillance (RSSS) RSSS was designed to utilize the findings of the Center for Epidemiology and Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at http://www.aphis.usda.gov/vs/ceah/cahm/Sheep/sheep.htm. RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks for clean-up. During FY 2005 collections increased by 32% overall and by 90% for black and mottled faced sheep improving overall program effectiveness and efficiency as demonstrated by the 26% decrease in percent positive black faced sheep compared to FY 2004. Samples have been collected from 62,864 sheep since April 1, 2003, of which results have been reported for 59,105 of which 209 were confirmed positive. During FY 2005, 33,137 samples were collected from 81 plants. There have been 130 NVSL confirmed positive cases (30 collected in FY 2004 and confirmed in FY 2005 and 100 collected and confirmed in FY 2005) in FY 2005. Face colors of these positives were 114 black, 14 mottled, 1 white and 1 unknown. The percent positive by face color is shown in the chart below.

Scrapie Testing

In FY 2005, 35,845 animals have been tested for scrapie: 30,192 RSSS; 4,742 regulatory field cases; 772 regulatory third eyelid biopsies; 10 third eyelid validations; and 129 necropsy validations (Chart 9). 


Scrapie USA 2006

PROCEEDINGS ONE HUNDRED AND TENTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION

2006

Infected and Source Flocks

As of September 30, 2006, there were 85 scrapie-infected and source flocks (48 infected and 37 source). There were a total of 116 new infected and source flocks reported for FY 2006. Figure 1 shows the number of new infected and source flocks by year. The total infected and source flock statuses that were released in FY 2006 was 100. A total of 343 positive scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL). Of these, 70 were RSSS cases, (collected in FY 2006 and confirmed in FY 2006 or FY 2007), and 222 positive field necropsy cases (most of these cases were found during depopulations of scrapie exposed animals in infected/source flocks), 14 necropsies of field cases retained long term for test evaluation, and 37 third eyelid regulatory tests confirmed in FY 2006. Three of the field cases were goats. One goat case, in Colorado, could not be linked to exposure in sheep as a result Colorado goats no longer meet the requirements to be classified as lowrisk goats or low-risk commercial goats for interstate movement. Approximately 3,822 animals were indemnified comprised of 62% nonregistered sheep, 30% registered sheep, 5% non-registered goats and 3% registered goats. This represents a 26% decrease over FY 2005 with a significant shift from registered to grade animals.

Regulatory Scrapie Slaughter Surveillance (RSSS) RSSS was designed based on the findings of the Center for Epidemiology and Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at http://www.aphis.usda.gov/vs/ ceah/cahm/Sheep/sheep.htm.

RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks for clean-up. During FY 2006, collections increased by 9% overall and by 16% for black and mottled faced sheep compared to FY 2005. Improvement in the overall program effectiveness and efficiency is demonstrated by the 33% decrease in percent positive black-faced sheep compared to FY 2005 (0.67 to 0.45%, based on test results posted before November 6, 2006). During FY 2006, 37,167 samples were collected. The distribution of these samples is shown in figure 2. There have been 70 NVSL confirmed positive cases that were collected in FY 2006. Face colors of these positives were 62 black and eight mottled. The percent positive by face color is shown in the figure 3 below.

Scrapie Testing

In FY 2006, 42,823 animals were sampled for scrapie testing: 37,167 RSSS; 3,649 regulatory field cases, 1,934 regulatory third eyelid biopsies, and 73 necropsy validations.


Scrapie USA 2007

PROCEEDINGS ONE HUNDRED AND ELEVENTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION

2007

Infected and Source Flocks

As of September 30, 2007, there were 37 scrapie infected and source flocks, a decrease of 56 percent from September 30, 2006. There were a total of 72 new infected and source flocks reported for fiscal year (FY) 2007, a decrease of 38 percent from FY 2006. Chart 1 shows the number of new infected and source flocks by year. The total infected and source flock statuses that were released in FY 2007 was 83. Three hundred, thirty-one positive scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) for FY 2007. Of these, 59 were RSSS cases, collected in FY 2007, 253 positive field cases, six test validation necropsies, and 13 third eyelids tests. One of the field cases was a goat. Five cases were consistent with Nor98 scrapie (Figure 1).

Approximately 3,622 animals were indemnified comprised of 61 percent non-registered sheep, 35 percent registered sheep, 2.3 percent non-registered goats and 1.7 percent registered goats. Regulatory Scrapie Slaughter Surveillance (RSSS) RSSS was designed based on the findings of the Center for Epidemiology and Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at www.aphis.usda.gov/vs/ceah/cahm/sheep/sheep.htm. RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks for cleanup. During FY 2007, collections increased by 11 percent overall and by 16 percent for black and mottled faced sheep compared to FY2006. Improvement in the overall program effectiveness and efficiency is demonstrated by the 34 percent decrease in percent positive black faced sheep compared to FY 2006 (.44 to .29 percent, based on test results posted before October 12, 2007). During FY 2007, 41,244 samples were collected (Figure 2). There have been 59 NVSL confirmed positive cases collected in FY2007. Face colors of these positives were 46 black, 11 mottled, one white and one unknown. The percent positive by face color is shown in Figure 3 below.

Caprine Scrapie Prevalence Study (CSPS)

CSPS was initiated in May 2007, to estimate the national prevalence of scrapie in adult goats at slaughter. If no scrapie is found we will be able to conclude that the prevalence is less than 0.1 percent. As of September 30, 2007, 1,515 goats were sampled for scrapie testing. None had tested positive for scrapie.

Scrapie Testing

As of September 30, 2007, 47,697 animals have been sampled for scrapie testing: 41,244 RSSS, 1,515 goats for the CSPS, 3,557 regulatory field cases, 139 necropsy validations, and 1,242 regulatory third eyelid biopsies.


Scrapie USA 2008

Infected and Source Flocks As of September 30, 2008, there were 31 scrapie infected and source flocks, a decrease of 16 percent from September 30, 2007. There were a total of 61 new infected and source flocks reported for FY 2008, a decrease of 15 percent from FY 2008. Chart 1 shows the number of new infected and source flocks by year. The total infected and source flock statuses that were released in FY 2008 was 64. 174 positive scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) for FY 2008. Of these, 40 were RSSS cases, (collected in FY 2008), 128 positive field necropsy cases, 4 rectal biopsy and 2 third eyelid tests. Five of the field cases were goats that originated from the same herd. One RSSS case was consistent with Nor98 scrapie. NOTE: Ante-mortem scrapie testing in sheep and goats using rectal biopsy was approved for program use by USDA for in January 2008. Approximately 2,438 animals were indemnified comprised of 51.4 percent non-registered sheep, 30.5 percent registered sheep, 9.6 percent non-registered goats and 8.5 percent registered goats. 




Scrapie USA 2009

PROCEEDINGS ONE HUNDRED AND THIRTEENTH ANNUAL MEETING of the United States Animal Health Association

2009

National Scrapie Surveillance Plan Implementation: The National Scrapie Surveillance Plan is posted at http://www.aphis.usda.gov/vs/nahss/sheep/national_scrapie_surveillance_plan_08192008.pdf.

The plan provides a comprehensive review of scrapie surveillance in the U.S., explains the basis for implementing state-of-origin sampling targets and ultimately flock level surveillance, and establishes minimum targets for FY 2009 and 2010. In FY 2009, Area Action Plans were developed to help meet state-of-origin sampling and ID compliance targets identified by the National Scrapie Surveillance Plan. This activity resulted in increased sampling in states not meeting plan targets.

Infected and Source Flocks: Thirty-three percent fewer newly infected and source flocks were identified in FY 2009 through July compared to the same month in FY 2008 (Figure 1). As of July 31, 2009, there were 21 scrapie infected and source flocks with open statuses. In FY 2009, 21 new source flocks and 8 new infected flocks had been reported; 26 flocks had completed a clean-up plan and been released. The ratio of infected and source flocks released to newly identified infected and source flocks for FY 2009 = 0.9 : 1.

Positive Scrapie Cases: As of July 31, 2009, 65 positive cases in sheep or goats were reported by the National Veterinary Services Laboratories (NVSL); 34 were field cases and 31 were RSSS cases collected between October 1, 2008 and July 31, 2009 and confirmed by August 20, 2009. Field cases are positive animals tested as part of a disease investigation including potentially exposed, exposed and suspect animals. Twenty cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002. The most recent positive goat case was confirmed in July 2009 and is epidemiologically linked to the same herd in Michigan as the positive goat cases that were found in FY 2008. The positive goat was a pet animal quarantined as part of the FY 2008 investigation. No additional animals were exposed.

Regulatory Scrapie Slaughter Surveillance (RSSS): RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks. Samples have been collected from 223,452 animals since April 1, 2003: this total includes 695 rectal biopsies collected in Texas as part of a surveillance pilot project. There have been 415 NVSL confirmed positive animals since the beginning of RSSS. As of July 31, 2009, 34,193 samples, including 513 rectal biopsies, have been collected in FY 2009. Thirty one samples collected in FY 2009 have tested positive for scrapie; 28 of these were from black-faced sheep and 3 from mottle-faced sheep. Two of these RSSS cases originated from a source flock identified at the end of FY 2008. Four other animals originated from flocks containing other RSSS positive sheep. There was an 11% decrease in percent positive black face sheep sampled at slaughter (.18 to .16%) between FY 2008 and FY 2009 as of July 31, 2009 if multiple positives from the same flock are excluded (Figure 2). RSSS was designed based on the findings of the Center for Epidemiology and Animal Health (CEAH), Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at http://www.aphis.usda.gov/vs/ceah/cahm/Sheep/sheep.htm.

Scrapie Testing: As of July 31, 2009, 36,524 animals have been sampled for scrapie testing: 34,193 RSSS samples (number includes 513 rectal biopsies from Texas), 1,663 regulatory field cases, and 668 liveanimal biopsies. 


Scrapie USA 2010

Positive Scrapie Cases:

• As of September 30, 2010, 72 cases of classical scrapie and 5 cases of Nor98-like scrapie were confirmed by the National Veterinary Services Laboratories (NVSL); 53 were field cases and 24 were RSSS cases collected between October 1, 2009 and September 30, 2010 and confirmed by November 8, 2010. Of the five Nor98-like scrapie cases, four were RSSS cases that originated from flocks in Ohio, Pennsylvania, Oregon, and Idaho and one was a field case form Maine. This brings the total number of Nor98-like cases detected in the United States to 11. Field cases are positive animals tested as part of a disease investigation including potentially exposed, exposed, and suspect animals or tested as part of on farm surveillance. 


Scrapie USA 2011

Positive Scrapie Cases: ???

PROCEEDINGS ONE HUNDRED AND FIFTEENTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION 

2011

National Scrapie Eradication Program

Diane Sutton, United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services (USDA-APHIS-VS) gave the following update of the scrapie eradication program:

Scrapie Eradication Program Results

• There has been a 96% decrease in the percent positive sheep sampled at slaughter adjusted for face color, from 0.16 to 0.0067%, since the start of Regulatory Scrapie Slaughter Surveillance (RSSS) in FY 2003 thru Aug. 31, 2011.

• A decrease of 40% newly infected and source flocks was reported in FY 2011 through August compared to the same date in FY 2010. • At the current rate of progress, we expect the prevalence to be at or near zero for FY 2017.

Slaughter Surveillance

• The number of animals sampled through slaughter surveillance in FY 2011, through Aug. 31, 2011, was 34,146 a decrease from 42,104 in FY 2010 — a decrease of 19%. The decline was primarily due to strict adherence to targeting criteria to reduce testing costs.


2011 

*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie. 


Scrapie USA 2012

Positive Scrapie Cases ???

Scrapie Eradication Program Results

• There has been a 96 percent decrease in the percent positive sheep sampled at slaughter adjusted for face color, from 0.15 to 0.0057 percent, since the start of Regulatory Scrapie Slaughter Surveillance (RSSS) in FY2003 thru September 30, 2012.

• There were eight new infected or source flocks reported in FY2012 as of September 30, 2012. A decrease of 47 percent compared to the same date in FY 2011.

Slaughter Surveillance

• The number of animals sampled through slaughter surveillance in FY 2012 through September 30, 2012 was 40,776 compared to 37,192 in FY2011; this represents an increase of 10 percent. The increase was due in part to increased sampling of goats. 


Scrapie 2013

Positive Scrapie Cases: ???

Scrapie Surveillance Projects:

• Since the start of slaughter surveillance in 2003 the prevalence of scrapie in sheep has declined 85 percent from 0.2 percent to less than 0.03 percent. The prevalence in goats is estimated to be less than 0.02 percent.

• APHIS continues to find new approaches to increase flock level surveillance.

• In FY 2013 APHIS initiated an effort to provide information on sample collection and to encourage producer and accredited veterinarian submission of samples.

• Instructions for producers and veterinarians to submit samples are now available on the APHIS Scrapie Web Page.

• In FY 2014 APHIS will conduct pilot projects in New Jersey and Arkansas to evaluate the efficiency of working with accredited veterinarians to collect samples for scrapie testing.

Update from Agriculture Research Service

David Schneider

USDA, Agriculture Research Service (ARS), Animal Disease Research Unit

(ADRU)

The USDA-ARS unit in Pullman, Washington, conducts an integrated research program involving studies on scrapie transmission, diagnosis and susceptibility genetics in domestic sheep and goats. Accumulation of diseaseassociated prion protein (PrPSc) in the placenta of sheep is a recognized source for natural transmission of classical scrapie disease and environmental contamination. Much less is known about prion accumulation in the placenta of goats but our recent study demonstrated much less PrPSc accumulates in the placenta in goats, which calls into question its role in natural transmission. In a recent follow-up study, we now demonstrate that the placenta of goats does harbor prions infectious to other goats and sheep when exposed by the oral route. A study on Nor98-like scrapie in breeding ewes is now in its 6th year. 

REPORT OF THE COMMITTEE

344

Ewes were experimentally inoculated with brain homogenate obtained from a U.S. sheep with clinical Nor98-like scrapie. Recipient ewes are bred annually to examine the placenta for evidence of a transmissible agent. Placentas shed 2009-2013 were negative. In 2013, one recipient ewe developed an unrelated disease. At postmortem examination, abundant accumulation of PrPSc was observed only in the cerebellum of this ewe with much less accumulation in the hindbrain obex. This confirms that initial inoculation of these ewes has been successful. Monitoring continues in the remaining ewes of this study. Improvements in tissue-based (rectal biopsy) live animal testing for scrapie with focus on application to goats continue. In addition, efforts toward developing a live-animal blood test have demonstrated the presence of prions (infectivity) in the blood of sheep and goats, even those with preclinical disease and within blood sample volumes routinely used in veterinary diagnostic work. A recent study also demonstrates PrPSc accumulation in lymphoid tissues of hemal nodes, small lymphoid organs that filter blood but not lymph.

Collectively, these findings confirm that blood is a relevant target for continued assay development. We continue to develop methods for enriching the relevant blood fractions for assay and are now making efforts to adapt novel in vitro assays for detecting infectivity and prion-associated misfolding activity. A long term study examining the effect of prion genotype on susceptibility to goat scrapie and the effect of genetic changes on accuracy of live animal testing continue. Following oral infection at birth with placenta and brain-derived scrapie, goats with the highly susceptible genotype all developed clinical disease around 24 months. Goats with the less susceptible or long incubation genetics today remain clinically normal. Monitoring continues.

Prion Transmission Through Milk

Christina Sigurdson

University of California, San Diego School of Medicine, Department of Pathology

Prion disorders are caused by misfolded proteins that are naturally transmitted, causing a fatal neurological disease in animals. In sheep with classical scrapie, prions accumulate in the follicles of lymphoid tissues in addition to the brain and spinal cord. Follicular dendritic cells (FDCs) form a network within the follicles and accumulate high levels of prions during disease. Previous work in mice has revealed that follicular inflammation in nonlymphoid organs, such as kidney, results in prion accumulation and can lead to prion shedding, such as into the urine. We have found sheep with follicular mastitis and scrapie that have accumulated prions within the follicles of the mammary gland.

In follow-up studies, we found that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs. Taken together, lentiviruses may enhance prion transmission and conceivably sustain prion infections in flocks for generations. Work by other groups has also shown prion infectivity in all three milk fractions, cells, casein whey, and 

SCRAPIE 345

cream. Prion infectivity has also been detected in milk from sheep having the VRQ/VRQ genotype with no evidence of mastitis.

References

1. Konold, T., Moore, S.J., Bellworthy, S.J. & Simmons, H.A. Evidence of scrapie transmission via milk. BMC Vet Res 4, 14 (2008). 2. Konold, T., et al. Evidence of effective scrapie transmission via colostrum and milk in sheep. BMC Vet Res 9, 99 (2013). 3. Ligios, C., et al. Sheep with Scrapie and Mastitis Transmit Infectious Prions through the Milk. J Virol 85, 1136-1139 (2011). 4. Ligios, C., et al. PrPSc in mammary glands of sheep affected by scrapie and mastitis. Nat Med 11, 1137-1138 (2005). 5. Lacroux, C., et al. Prions in milk from ewes incubating natural scrapie. PLoS Pathog 4, e1000238 (2008).

Committee Business:

The final response from the Committee’s 2012 Resolution (26, 9 and 30 Combined) relating to the export of sheep and goats was reviewed. In this response the USDA-APHIS-VS agreed to ask the World Organization for Animal Health (OIE) to modify the Scrapie Chapter to consider options such as genotyping to qualify animals for export. USDA-APHIS-VS agreed to make this request by Spring 2014, and would expect to see the Scrapie Chapter amended in Spring 2015 or 2016 if their revisions were to be accepted by OIE. One of the Committee members updated the group on progress related to a 2010 Resolution #48. This resolution requested USDA, Food Safety Inspection Service (FSIS) to work with USDA-APHIS-VS and industry to identify and approve appropriate sites for radio frequency identification implants for goats and sheep. As a result, both the underside of the tail and the base of the ear are now approved sites for these implants. No new resolutions or recommendations were introduced. The Committee briefly discussed the challenges of obtaining scrapie surveillance samples from certain flocks and herds. Several members mentioned that one barrier to sample collection is the problem that the producers have with carcass disposal after the head has been removed. Members agreed that offering options to producers to help them properly dispose of these carcasses could significantly increase voluntary participation in surveillance. Options include to transporting carcasses to diagnostic laboratories or providing payment to the producers to offset the cost of carcass disposal. 


Scrapie 2015

Positive Scrapie Cases ???

Scrapie Eradication Program Results

• The National Scrapie Eradication Program continued to make progress in FY 2015.

• At the end of FY 2014, the percent of cull sheep found positive at slaughter and adjusted for face color was 0.018 percent and is currently at 0.004 percent for FY 2015. This measure has decreased by 80 percent compared to FY 2014 and by 98 percent compared to FY 2003.

• Three source flocks and 3 infected flocks were designated in FY 2014. One infected and three source flocks have been designated in FY 2015, a decrease of 30 percent.

• In November 2014, the first positive goat found through RSSS was identified. Based on the goats sampled at slaughter to date, the prevalence of scrapie in U.S. cull goats (2003 – 2015) was 0.0037 percent with an upper 95 percent confidence limit of 0.0097 percent.

• In FY 2015 there was a decrease in the number of States meeting their sampling minimums for sheep and goats. This was likely due in part to the impact of Highly Pathogenic Avian Influenza response on resources.

Slaughter Surveillance

As of September 30, 2015, 40,862 animals were sampled for scrapie testing in FY 2015:

• 38,671 RSSS samples and 2,191 on-farm samples;

• Of which 33,698 were sheep and 7,164 were goats.


Sunday, October 25, 2015 

USAHA Detailed Events Schedule – 119th USAHA Annual Meeting CAPTIVE LIVESTOCK CWD SCRAPIE TSE PRION 


Scrapie USA 2016

Scrapie Eradication Program Results*

 The National Scrapie Eradication Program continued to make progress in FY 2016.

 As a result of the hard work of industry, the states and APHIS, we have decreased scrapie prevalence in cull sheep from 1 in 500 to less than 1 in 20,000 (based on upper confidence level). At the end of FY 2015, the percent of cull sheep found positive at slaughter and adjusted for face color was 0.0036 percent. As of September 30, 2016, this measure was 0.0014 percent (upper confidence limit 0.005%) a 61 percent decrease; however, due to sample size this is not significantly different from FY 2015.

 At the end of FY 2015, the percent of cull black face sheep found positive at slaughter was 0.025 percent. The current value of this measure is 0.009 percent, a 99 percent decrease compared to FY 2003 and a 62 percent decrease from FY 2015. The upper confidence limit of the measure is 0.025 percent so the change from FY 2015 is not statistically significant.

 One infected and three source flocks were designated in FY 2015. Two infected and three source flocks have been designated in FY 2016.

 In November 2014, the first positive goat found through Regulatory Scrapie Slaughter Surveillance (RSSS) was identified. Based on all goats sampled at slaughter, the prevalence of scrapie in U.S. cull goats is 0.003 percent with an upper 95 percent confidence limit of 0.011 percent. To date, no other goats have tested positive at slaughter.

Slaughter Surveillance*

As of September 30, 2016, 39,978 animals have been sampled for scrapie testing in FY 2016:

• 37,878 RSSS samples and 2,100 on-farm samples;

• Of which 32,356 were sheep and 7,622 were goats. 



Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer

April 22, 2016

Scrapie Confirmed in a Hartley County Sheep

AUSTIN - Texas Animal Health Commission (TAHC) officials have confirmed scrapie in a Hartley County ewe. The ewe was tested by TAHC after the owner reported signs of weight loss and lack of coordination to their local veterinarian. The premises was quarantined and a flock plan for monitoring is being developed by the TAHC and USDA.

"The TAHC is working closely with the flock owner, sharing all of the options for disease eradication," said Dr. David Finch, TAHC Region 1 Director. "We are thankful the producer was proactive in identifying a problem and seeking veterinary help immediately."

Texas leads the nation in sheep and goat production. Since 2008, there have been no confirmed cases of scrapie in Texas. The last big spike in Texas scrapie cases was in 2006 when nine infected herds were identified and the last herd was released from restrictions in 2013.

According to USDA regulations, Texas must conduct adequate scrapie surveillance by collecting a minimum of 598 sheep samples annually. Since USDA slaughter surveillance started in FY 2003, the percent of cull sheep found positive for scrapieat slaughter (once adjusted for face color) has decreased 90 percent.

Scrapie is the oldest known transmissible spongiform encephalopathies, and under natural conditions only sheep and goats are known to be affected by scrapie. It is a fatal disease that affects the central nervous system of sheep and goats. It is not completely understood how scrapie is passed from one animal to the next and apparently healthy sheep infected with scrapie can spread the disease. Sheep and goats are typically infected as young lambs or kids, though adult sheep and goats can become infected.

The most effective method of scrapie prevention is to maintain a closed flock. Raising replacement ewes, purchasing genetically resistant rams and ewes,or buying from a certified-free scrapie flock are other options to reduce the risk of scrapie. At this time the resistant genetic markers in goats have not been identified, therefore it is important to maintain your sheep and goat herds separately.

The incubation period for Scrapie is typically two to five years. Producers should record individual identification numbers and the seller's premise identification number on purchase and sales records. These records must be maintained for a minimum of five years.

Producers should notify the Texas Animal Health Commission (800-550-8242) or the USDA-Austin Office (512-383-2400) if they have an adult sheep or goat with neurologic signs such as incoordination, behavioral changes, or intense itching with wool loss. Producers may order scrapie identification tags by calling 866-873-2824. For more information, please visit our website at:



TEXAS Sheep and Goats

• Most recent scrapie positive animal in Texas was found in April, 2008.

• USDA-APHIS-VS set the national goal for surveillance at 46,000 traceable, mature sheep or goats. Target for Texas is 1,472.

• The Scrapie Program Review is being scheduled for this summer. No problems expected.



Scrapie USA 2017

 REPORT OF THE SUBCOMMITTEE ON SCRAPIE

Chair: Cheryl Miller, IN

Vice Chair: Larry Forgey, MO

The Subcommittee met on October 18, 2017 at the Town and Country Hotel in San Diego, California from 9:00 a.m. to 12:35 p.m. There were 21 members and 14 guests present. Meeting was called to order by the chairman, Dr. Cheryl Miller. All attendees were asked to sign in.

Presentations and Reports

Scrapie Program Updates

Diane Sutton, USDA-APHIS-VS

Scrapie Eradication Program Results*

• The National Scrapie Eradication Program made tremendous progress in FY2017.

• Other than a goat that resided in a herd that was under quarantine since 2005 there have been no classical scrapie positive animals in the United States since April 2016. This goat herd was depopulated in July and the remaining goats moved to the Agricultural Research Service (ARS).

• There were two Nor98-like cases confirmed by the National Veterinary Services Laboratory (NVSL) one from Colorado and one with a Montana tag pending trace back.

• The last two known scrapie infected/source flocks have been depopulated and the premises are pending disinfection. No high-risk animals exist in the United States outside of research facilities. Surveillance*

• As of September 30, 2017, 42,030 animals had been sampled for scrapie testing in FY2017:

• 6 percent were collected on-farm and 94 percent through Regulatory Scrapie Slaughter Surveillance (RSSS)

• 19 percent of the samples collected were from goats and the 81 percent from sheep

• Implementation FY2018

• States with RSSS collection sites will continue to sample targeted sheep and goats.

• The State sampling minimums for FY2018 have been provided to the States and will be made public in the October monthly report. Note: These are minimums. The plan is to continue to collect samples from the maximum number of targeted animals given the available budget.


Scrapie USA 2018

Scrapie Program Updates

Diane Sutton, USDA-APHIS, Veterinary Services (VS)

Scrapie Eradication Program Results*

• The National Scrapie Eradication Program made progress in FY2018.

• The last confirmed classical scrapie positive sheep was in April 2016.

• In April 2018, APHIS identified scrapie in a 171 RR sheep from a flock in North Carolina. There was insufficient positive tissue available to rule out non-classical scrapie; the flock has been depopulated and no other sheep in the flock have tested positive for scrapie. USDA continues to conduct additional testing, before determining whether to classify the case as classical or non-classical scrapie.

• In August 2018, a Pennsylvania goat sampled at slaughter in July was confirmed positive for classical scrapie. The flock is scheduled for high-risk animal depopulation in October 2018. The only other positive goat found through slaughter surveillance was in November 2014.

• One Nor98-like case sampled in October 2017 was confirmed positive. Unlike classical scrapie, non-classical scrapie (Nor98-like) is either not laterally transmissible or is transmissible at a very low rate. The World Animal Health Organisation (OIE) and APHIS have determined that it is not a disease of trade concern Surveillance*

• Since the scrapie slaughter surveillance program began in FY2003, over 600,000 samples have been collected.

• As of September 30, 2018, 43,625 animals had been sampled for scrapie testing in FY2018:

o 5% were collected on-farm and 95 percent through RSSS

o 21% of the samples collected were from goats and the 79% from sheep

• When first measured in FY2002-2003, the percentage of cull sheep sampled at slaughter that tested positive for classical scrapie was 1 in 500. Since the last case in April 2016, APHIS has tested 82,199 sheep and no cases of classical scrapie have been confirmed.

• Since the slaughter surveillance program began, only two goats sampled at slaughter have been confirmed positive for classical scrapie, one sampled in FY2015 and one in FY2018. Since the detection in FY2015, 25,618 goats have been tested through slaughter surveillance. 


USDA-APHIS FY 2018 Cervid Health Program Update

Tracy Nichols, USDA-APHIS, Veterinary Services (VS)

The USDA Chronic Wasting Disease (CWD) Herd Certification Program (HCP) is a voluntary program in which herd certification is required for interstate movement of farmed cervids. Certification requires five years of 100 percent CWD post mortem testing of all herd mortalities over 12 months of age and zero CWD detection. This program was implemented in 2014 after the approval of the final CWD rule.

Management of this program is a collaborative effort between USDAAPHIS and States, with State participation being voluntary. Currently 28 states participate in the program encompassing 2,393 enrolled herds, and 1,875 certified herds. Of the certified herds, 1,434 are deer, 344 elk, and 97 mixed (containing both deer and elk). In fiscal year 2018 there were 15 newly identified farmed cervid herds (11 deer, 1 elk, 1 reindeer, and 2 mixed). Six of the 15 herds were HCP-certified, and two were enrolled. The remaining seven were not part of the program. Ten of the newly identified herds were located in areas endemic with CWD.

snip...

Interspecies Transmission of the Scrapie Agent

Justin Greenlee, National Animal Disease Center (NADC), Agricultural Research Service (ARS), USDA

The Virus and Prion Research Unit at the National Animal Disease Center has ongoing research projects with the agents of scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD). Numerous studies have been done to better understand scrapie strains and their potential to transmit to other species. We acknowledge at least two scrapie strains present in the U.S. In previous studies we used two scrapie isolates: No. 13-7 that was isolated from ARQ/ARQ black-faced sheep and x124 that has a rapid incubation time in sheep with the V136 allele. Studies that have been conducted in cats, cattle, pigs, and raccoons suggest a substantial barrier to transmission based upon incomplete attack rates, prolonged incubation, or limited distribution of abnormal prion protein in the body. However, the No. 13-7 scrapie agent transmits to white-tailed deer after intracranial of oronasal challenge with a 100% attack rate. We conducted a study to determine if deer infected with the scrapie agent could serve as a reservoir of scrapie infectivity to sheep. The scrapie agent from deer did transmit to sheep by the oronasal route, but with more rapid incubation periods in sheep with the V136 genotype and with lesions consistent with x124 scrapie rather than the original No. 13-7 inoculum. Very low incidence of scrapie in the U.S. suggests that exposure of deer to the scrapie agent is unlikely. If sheep were exposed to the scrapie agent from deer, current genotype-based methods for scrapie eradication would remain effective.

Update on Scrapie Research at the Animal Disease Research Unit David Schneider, USDA, Agricultural Research Service (ARS)

The USDA-ARS Animal Disease Research Unit in Pullman, Washington, conducts an integrated research program involving studies on scrapie diagnostics, the role of Prion Protein (PRNP) genetics, and modes of transmission in domestic sheep and goats. In this update, we report on the role of goat milk and concurrent SRLV-infection on transmissibility of scrapie to goat kids and lambs; an update of ongoing research to determine the role of PRNP genetics on susceptibility and disease on diagnostics in goats and sheep; and initiation of an attempt to isolate a prion (infectious particle) from of a young resistant-genotype sheep with peripheral accumulation of PrP-Sc.

Classical scrapie was transmitted to goat kids and lambs after lowvolume, short-duration bottle feeding of mid-lactation milk from goat does with naturally acquired scrapie and small ruminant lentivirus (SRLV) infections. The potential role of concurrent SRLV infection was explored and results were consistent with a virus-associated increase in PrP-Sc accumulation in the mammary glands of the milk donor goats and the likelihood of scrapie transmission. SRLV was also transmitted to some of the goat kids but not lamb milk recipients, however, SRLV transmission did not appear to be necessary for scrapie transmission.

Goats bearing the PRNP codons NS146 or QK222 and orally inoculated at birth with goat-derived scrapie continued to be monitored for signs of scrapie transmission. At more than eight years post-inoculation, four of eight NS146 goats still survive and are in good health. However, the last two of eight QK222 goats were euthanized because of ageing dentition. No evidence of PrP-Sc accumulation has been observed. Monitoring of the surviving NS146 goats continues.

A survey study on archived tissue of classical scrapie in U.S. sheep covering the years 2000-2007 was completed. The PRNP genotype of these sheep was expanded to include the amino acid at codon 112 (M or T). Diagnosis of scrapie was significantly less likely in heterozygous MT112 sheep (7% prevalence) than in homozygous MM112 (wild type) sheep (37% prevalence) and no cases of scrapie were detected in 27 sheep genotyped to be homozygous TT112. While uniformity of exposure cannot be known, the data suggest the T112 allele confers some resistance to scrapie infection, but not strong enough to fully protect the heterozygous animal. Other data suggest that the T112 allele may reduce the peripheral accumulation of PrPSc, perhaps making these animals more difficult to detect early in disease progression.

Subcommittee Business:

snip...


Ohio Scrapie Cases in Goats FY 2002 – FY 2021


Ohio atypical scrapie Nor-98 TSE Prion detected 2010 1 case documented


THURSDAY, JANUARY 7, 2021 

Atypical Nor-98 Scrapie TSE Prion USA State by State Update January 2021



Second passage of chronic wasting disease of mule deer in sheep compared to classical scrapie after intracranial inoculation

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

Title: Second passage of chronic wasting disease of mule deer in sheep compared to classical scrapie after intracranial inoculation

Author item Cassmann, Eric item FRESE, RYLIE - Orise Fellow item Greenlee, Justin Submitted to: Journal of Veterinary Diagnostic Investigation Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/25/2020 Publication Date: N/A Citation: N/A

Interpretive Summary: Chronic wasting disease (CWD) is a fatal and uncurable brain disease of deer and elk that is related to a similar disease in sheep called scrapie. Both diseases are cause by a misfolded protein called a prion. The exact origin of CWD is unknown, but a possible origin could have been spread of sheep scrapie to deer. Previous research found indistinguishable traits in common between CWD in deer and scrapie in sheep. Additionally, it is unknown if deer CWD can naturally transmit to sheep. In this research, we show that abnormal prions spread throughout the body of sheep intracranially infected with CWD similar to how scrapie spreads in sheep. We compared two US classical scrapie strains to CWD in sheep and found that one of these strains is indistinguishable from sheep CWD. These results demonstrate that current diagnostic techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred in a natural setting. This research reinforces the need to continue ongoing cross-species transmission studies focusing on oral susceptibility of sheep to CWD and develop techniques to discriminate sheep CWD from sheep scrapie.

Technical Abstract: The origin of chronic wasting disease (CWD) in cervids is unclear. One hypothesis suggests that CWD originated from scrapie in sheep. In this experiment, we had two main objectives. The first objective was to determine if CWD adaptation in sheep alters the disease phenotype. The second objective was to determine if the disease phenotype of sheep adapted CWD is distinct from classical scrapie. We intracranially inoculated sheep with brain homogenate from first passage mule deer CWD in sheep (sCWDmd). The attack rate in second passage sheep was 100% (12/12). Sheep had prominent lymphoid accumulations of PrPSc reminiscent of classical scrapie. The pattern and distribution of PrPSc in the brains of sheep with CWDmd was similar to scrapie strain 13-7 but different from scrapie strain x124. The western blot glycoprofiles of sCWDmd were indistinguishable from scrapie strain 13-7; however, independent of sheep genotype, glycoprofiles of sCWDmd were different than x124. When sheep genotypes were evaluated individually, there was considerable overlap in the glycoprofiles that precluded significant discrimination between sheep CWD and scrapie strains. Taken together, these data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given the results of this study, current diagnostic techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally. It is unknown if sheep are naturally vulnerable to CWD; however, the susceptibility of sheep after intracranial inoculation and lymphoid accumulation indicates that the species barrier is not absolute.


''We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation.'' Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

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

item Greenlee, Justin item Moore, S – item Smith, Jodi – item Kunkle, Robert item West Greenlee, M –

Submitted to: American College of Veterinary Pathologists Meeting Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015 Publication Date: N/A

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

In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.


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

Location: Virus and Prion Research

Title: Passage of scrapie to deer results in a new phenotype upon return passage to sheep) Author 

item Greenlee, Justin item Kokemuller, Robyn item Moore, Sarah item West Greenlee, N

Submitted to: Prion 

Publication Type: Abstract Only 

Publication Acceptance Date: 3/15/2017 

Publication Date: N/A 

Citation: N/A

Interpretive Summary:

Technical Abstract: Aims: We previously demonstrated that scrapie has a 100% attack rate in white-tailed deer after either intracranial or oral inoculation. Samples from deer that developed scrapie had two different western blot patterns: samples derived from cerebrum had a banding pattern similar to the scrapie inoculum, but samples from brainstem had a banding pattern similar to CWD. In contrast, transmission of CWD from white-tailed deer to sheep by the intracranial route has a low attack rate and to-date oronasal exposure has been unsuccessful. The purpose of this study was to determine if sheep are susceptible to oronasal exposure of the scrapie agent derived from white-tailed deer. 

Methods: At approximately 5 months of age, Suffolk sheep of various PRNP genotypes were challenged by the oronasal route with 10% brain homogenate derived from either the cerebrum or the brainstem of scrapie-affected deer. Genotypes represented in each inoculation group were VV136RR154QQ171 (n=2), AA136RR154QQ171 (n=2), and AV136RR154QR171 (n=1). After inoculation, sheep were observed daily for clinical signs. Upon development of clinical signs, sheep were killed with an overdose of pentobarbital sodium and necropsied. Tissue samples were tested for the presence of PrPSc by EIA, western blot, and immunohistochemistry (IHC). The No. 13-7 scrapie inoculum used for the deer has a mean incubation period of 20.1 months in sheep with the AA136RR154QQ171 genotype and 26.7 months in sheep with the VV136RR154QQ171 genotype. 

Results: Sheep inoculated oronasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum from the cerebrum that had a scrapie-like profile. The first sheep to develop clinical signs at approximately 29 months post inoculation had the VV136RR154QQ171 genotype. Eventually sheep of the AA136RR154QQ171 genotype developed clinical signs, but at a mean incubation of 52 months. At 62 months post-inoculation, none of the sheep inoculated with material from the deer brainstem have developed clinical disease. 

Conclusions: The No. 13-7 inoculum used in the original deer experiment readily infects white-tailed deer and sheep of various genotypes by the oronasal route. When inoculum is made from different brain regions of No 13-7 scrapie-infected deer from either cerebrum with a scrapie-like western blot pattern or brainstem with a CWD-like western blot pattern, sheep with the VV136RR154QQ171 genotype are the first to develop clinical signs. This is in contrast to the original No. 13-7 inoculum that has a faster incubation period in sheep with the AA136RR154QQ171 genotype. Similar to experiments conducted with CWD, sheep oronasally inoculated with brainstem material from deer with a CWD-like molecular profile have no evidence of disease after 62 months of incubation. While scrapie is not known to occur in free-ranging populations of white-tailed deer, experimental cases are difficult to differentiate from CWD. This work raises the potential concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as scrapie from deer seems to be transmissible to sheep by the oronasal route.


Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 

Title: Transmission of the agent of sheep scrapie to deer results in PrPSc with two distinct molecular profiles 

Authors item Greenlee, Justin item Moore, Sarah - item Smith, Jodi item West Greenlee, Mary - item Kunkle, Robert Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: March 31, 2015 Publication Date: May 25, 2015 Citation: Greenlee, J., Moore, S.J., Smith, J.., West Greenlee, M.H., Kunkle, R. 2015. 

Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease and distinct from the scrapie inoculum. 

Prion 2015. p. S62. 

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

In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile type readily passes to deer. 


White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection 

Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS 

Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. Previous experiments demonstrated that white-tailed deer are susceptible to sheep-derived scrapie by intracranial inoculation. The purpose of this study was to determine susceptibility of white-tailed deer to scrapie after a natural route of exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal (1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with scrapie. Non-inoculated deer were maintained as negative controls. All deer were observed daily for clinical signs. Deer were euthanized and necropsied when neurologic disease was evident, and tissues were examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and western blot (WB). One animal was euthanized 15 months post-inoculation (MPI) due to an injury. At that time, examination of obex and lymphoid tissues by IHC was positive, but WB of obex and colliculus were negative. Remaining deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by potential natural routes of inoculation. In-depth analysis of tissues will be done to determine similarities between scrapie in deer after intracranial and oral/intranasal inoculation and chronic wasting disease resulting from similar routes of inoculation. 

see full text ; 


PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer 

Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA 


White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation 

snip... 

It is unlikely that CWD will be eradicated from free-ranging cervids, and the disease is likely to continue to spread geographically [10]. However, the potential that white-tailed deer may be susceptible to sheep scrapie by a natural route presents an additional confounding factor to halting the spread of CWD. This leads to the additional speculations that 

1) infected deer could serve as a reservoir to infect sheep with scrapie offering challenges to scrapie eradication efforts and 

2) CWD spread need not remain geographically confined to current endemic areas, but could occur anywhere that sheep with scrapie and susceptible cervids cohabitate. 

This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation with a high attack rate and that the disease that results has similarities to CWD. 

These experiments will be repeated with a more natural route of inoculation to determine the likelihood of the potential transmission of sheep scrapie to white-tailed deer. If scrapie were to occur in white-tailed deer, results of this study indicate that it would be detected as a TSE, but may be difficult to differentiate from CWD without in-depth biochemical analysis. 



2012 PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer 

Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA 

snip... 

The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. 

Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like. 

*** After a natural route of exposure, 100% of WTD were susceptible to scrapie. 

Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. 

Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. 

This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD. 


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 


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

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

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

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

snip...

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

PMID: 6997404


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

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

snip...

76/10.12/4.6


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

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

Gibbs CJ Jr, Gajdusek DC.

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

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

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

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

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



WEDNESDAY, NOVEMBER 20, 2019 

Review: Update on Classical and Atypical Scrapie in Sheep and Goats 


FRIDAY, FEBRUARY 11, 2011 

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues 


Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE


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

PLEASE NOTE;

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

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

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


Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE


FRIDAY, OCTOBER 23, 2020 

Scrapie TSE Prion Zoonosis Zoonotic, what if?


TUESDAY, SEPTEMBER 22, 2020 

APHIS USDA MORE SCRAPIE ATYPICAL Nor-98 Confirmed USA September 15 2020

Personal Communication from USDA et al Mon, Jan 4, 2021 11:37 am...terry

17 cases of the Nor98 in the USA to date

17 Nor98-like cases since the beginning of RSSS.


TUESDAY, JANUARY 12, 2021 

Annual Scrapie Report Available for Fiscal Year 2020 USA October 1, 2019 to September 30, 2020


THURSDAY, JANUARY 7, 2021 

Atypical Nor-98 Scrapie TSE Prion USA State by State Update January 2021


MONDAY, JANUARY 11, 2021 

North Dakota 18 deer tested positive for CWD during the 2020 hunting season, with most testing completed


FRIDAY, FEBRUARY 05, 2021 

USA 50 STATE CWD TSE Prion UPDATE FEBRUARY 2021


MONDAY, NOVEMBER 23, 2020 

Chronic Wasting Disease CWD TSE Prion Cervid State by State and Global Update November 2020


THURSDAY, FEBRUARY 4, 2021 

Guidance for reporting 2021 surveillance data on Transmissible Spongiform Encephalopathies (TSE) 

APPROVED: 1 February 2021


Wednesday, February 3, 2021 

Wide distribution of prion infectivity in the peripheral tissues of vCJD and sCJD patients


Friday, January 29, 2021 
Scientists identify locations of early prion protein deposition in retina, what if?
FRIDAY, JANUARY 22, 2021 

Creutzfeldt Jakob Disease TSE Prion and Nutritional Supplements, Porcine Products, what you need to know 

***> FDA DOES NOT have mandatory established specifications for animal-derived ingredients to ensure they are BSE free in Nutritional Supplements

Saturday, January 23, 2021 

Improved surveillance of surgical instruments reprocessing following the variant Creutzfeldt-Jakob disease crisis in England: findings from a 3-year survey 


***>''Implementing recent national guidelines to address the prions concern proved an eye-opener. Microscopic levels of proteins remain on many reprocessed instruments. The impact most of these residues, potentially including prions, may have on subsequent patients after sterilization remains debatable.''<***

DEAD people can't debate this, and it's a damn shame that after 5 decades, or more, of discussing this, we now know what to do, but still refuse to do it i.e. disposable instruments,  jiminy cricket what the hell does it take, how many body bags of iatrogenic cjd (now called sporadic cjd in most cases still) does it take, i guess it's just too easy to call it sporadic cjd and go on down the road.

all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, provern, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd, PLUS, SPORADIC CJD HAS NOW BEEN LINKED TO ATYPICAL AND TYPICAL BSE, SCRAPIE, AND NOW CWD. ...terry

TUESDAY, DECEMBER 01, 2020 

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


WEDNESDAY, OCTOBER 21, 2020 

Human Prion Disease Surveillance in Washington State, 2006-2017


Sunday, December 27, 2020 

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


TUESDAY, DECEMBER 01, 2020 

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


FRIDAY, JANUARY 22, 2021 
Creutzfeldt Jakob Disease TSE Prion and Nutritional Supplements, Porcine Products, what you need to know 
***> FDA DOES NOT have mandatory established specifications for animal-derived ingredients to ensure they are BSE free in Nutritional Supplements 
FRIDAY, JANUARY 15, 2021 

CJD TSE Prion Questionnaire USA, UK, and the history there from, have you filled out this questionnaire?


JOHN CORNYN TEXAS UNITED STATES SENATE WASHINGTON, DC 20510-4305 April 26,2005

Mr. Terry Singeltary

P.O. Box 

Bacliff, Texas 77518

Dear Mr. Singeltary:

In response to your recent request for my assistance, I have contacted the National Institutes ofHealth. I will write you again as soon as I receive a reply. I appreciate having the opportunity to represent you in the United States Senate and to be ofservice in this matter.

Sincerely,

JOHN CORNYN United States Senator JC:djl 

=============== 

JOHN CORNYN TEXAS UNITED STATES SENATE WASHINGTON, DC 20510-4305

May 18,2005

Mr. Terry Singeltary

P.O. Box 

Bacliff, Texas 77518

Dear Mr. Singeltary:

Enclosed is the reply I received from the Department of Health and Human Services in response to my earlier inquiry on your behalf. I hope this will be useful to you. I appreciate having the opportunity to represent you in the United States Senate. Thank you for taking time to contact me. Sincerely,

JOHN CORNYN United States Senate JC:djl Enclosure

DEPARTMENT OF HEALTH & HUMAN SERVICES National Institutes of HealthNational Institute of NeurologicalDisorders and Stroke NINDS Building 31, Room 8A52 31 Center Dr., MSC 2540 Bethesda, Maryland 20892-2540 Phone: 301-496-9746 Fax: 301-496-0296 Email: [log in to unmask]

May 10, 2005

The Honorable John CornynUnited States SenatorOccidental Tower5005 LBJ Freeway, Suite 1150Dallas, Texas 75244-6199

Dear Senator Cornyn:

Your letter to the National Institutes of Health (NIH) forwarding correspondence from Mr. Terry S. Singeltary, Sr., has been forwarded to me for reply. Mr. Singeltary is concerned about thepreservation of Creutzfeldt-Jakob disease (CJD) brain samples that have been maintained by theNational Institute of Neurological Disorders and Stroke (NINDS) Intramural Research programfor many years. I am sorry to learn that Mr. Singeltary's mother died of CJD and can certainly understand hisdesire that any tissues that could help investigators unravel the puzzle of this deadly disease arepreserved. I hope he will be pleased to learn that all the brains and other tissues with potential tohelp scientists learn about CJD are, and will continue to be, conserved. (The tissues that arediscarded are those that have either decayed to an extent that renders them no longer appropriatefor research or those for which we do not have sufficient identification.) The purpose of gathering these brains and tissues is to help scientists learn about CJD. To that end, some of the NINDS-held samples are distributed to investigators who can demonstrate thatthey have a compelling research or public health need for such materials. For example, sampleshave been transferred to NIH grantee Dr. Pierluigi Gambetti, who heads the National PrionDiseases Pathology Surveillance Center at Case Western Reserve University in Ohio and workswith the Centers for Disease Control and Prevention to monitor all cases of CJD in the UnitedStates. Dr. Gambetti studies the tissues to learn about the formation, physical and chemicalproperties, and pathogenic mechanisms of prion proteins, which are believed to be involved inthe cause of CJD. Samples have also been transferred to Dr. David Asher, at the U.S. Food andDrug Administration, for use in assessing a potential diagnostic test for CJD.

Page 2 - The Honorable John Cornyn

in closing, we know that donating organs and tissue from loved ones is a very difficult andpersonal choice that must often be made at the most stressful of times. We at the NINDS aregrateful to those stalwart family members who make this choice in the selfless hope that it willhelp others afflicted with CJD. We also know the invaluable contribution such donations maketo the advancement of medical science, and we are dedicated to the preservation of all of thetissue samples that can help in our efforts to overcome CJD.

I hope this information is helpful to you in responding to Mr. Singeltary. Sincerely,

Story C. Landis, Ph.D. Director, National Institute ofNeurological Disorders and Stroke

snip...see full text;



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. 
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..” 



January 28, 2003; 60 (2) VIEWS & REVIEWS

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?


SPORADIC CJD LAYING ODDS


In brief

BMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7226.8/b (Published 01 January 2000)

Cite this as: BMJ 2000;320:8

Rapid Response:

02 January 2000

Terry S Singeltary

retired

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well... In reading your short article about 'Scientist warn of CJD epidemic' news in brief Jan. 1, 2000. I find the findings in the PNAS old news, made famous again. Why is the U.S. still sitting on their butts, ignoring the facts? We have the beginning of a CJD epidemic in the U.S., and the U.S. Gov. is doing everything in it's power to conceal it.

The exact same recipe for B.S.E. existed in the U.S. for years and years. In reading over the Qualitative Analysis of BSE Risk Factors-1, this is a 25 page report by the USDA:APHIS:VS. It could have been done in one page. The first page, fourth paragraph says it all;

"Similarities exist in the two countries usage of continuous rendering technology and the lack of usage of solvents, however, large differences still remain with other risk factors which greatly reduce the potential risk at the national level."

Then, the next 24 pages tries to down-play the high risks of B.S.E. in the U.S., with nothing more than the cattle to sheep ratio count, and the geographical locations of herds and flocks. That's all the evidence they can come up with, in the next 24 pages.

Something else I find odd, page 16;

"In the United Kingdom there is much concern for a specific continuous rendering technology which uses lower temperatures and accounts for 25 percent of total output. This technology was _originally_ designed and imported from the United States. However, the specific application in the production process is _believed_ to be different in the two countries."

A few more factors to consider, page 15;

"Figure 26 compares animal protein production for the two countries. The calculations are based on slaughter numbers, fallen stock estimates, and product yield coefficients. This approach is used due to variation of up to 80 percent from different reported sources. At 3.6 million tons, the United States produces 8 times more animal rendered product than the United Kingdom."

"The risk of introducing the BSE agent through sheep meat and bone meal is more acute in both relative and absolute terms in the United Kingdom (Figures 27 and 28). Note that sheep meat and bone meal accounts for 14 percent, or 61 thousand tons, in the United Kingdom versus 0.6 percent or 22 thousand tons in the United States. For sheep greater than 1 year, this is less than one-tenth of one percent of the United States supply."

"The potential risk of amplification of the BSE agent through cattle meat and bone meal is much greater in the United States where it accounts for 59 percent of total product or almost 5 times more than the total amount of rendered product in the United Kingdom."

Considering, it would only take _one_ scrapie infected sheep to contaminate the feed. Considering Scrapie has run rampant in the U.S. for years, as of Aug. 1999, 950 scrapie infected flocks. Also, Considering only one quarter spoonful of scrapie infected material is lethal to a cow.

Considering all this, the sheep to cow ration is meaningless. As I said, it's 24 pages of B.S.e.

To be continued...

Terry S. Singeltary Sr.

Bacliff, Texas USA

Competing interests: No competing interests


Rapid response to:

US scientists develop a possible test for BSE

15 November 1999

Terry S Singeltary

NA

BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7220.1312b (Published 13 November 1999)

Cite this as: BMJ 1999;319:1312

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Response Rapid Response: Re: vCJD in the USA * BSE in U.S. In reading the recent article in the BMJ about the potential BSE tests being developed in the U.S. and Bart Van Everbroeck reply. It does not surprize me, that the U.S. has been concealing vCJD. There have been people dying from CJD, with all the symptoms and pathological findings that resemble U.K. vCJD for some time. It just seems that when there is one found, they seem to change the clarical classification of the disease, to fit their agenda. I have several autopsies, stating kuru type amyloid plaques, one of the victims was 41 years of age. Also, my Mom died a most hideous death, Heidenhain Variant Creutzfeldt Jakob disease. Her symptoms resemble that of all the U.K. vCJD victims. She would jerk so bad at times, it would take 3 of us to hold her down, while she screamed "God, what's wrong with me, why can't I stop this." 1st of symptoms to death, 10 weeks, she went blind in the first few weeks. But, then they told me that this was just another strain of sporadic CJD. They can call it what ever they want, but I know what I saw, and what she went through. Sporadic, simply means, they do not know. My neighbors Mom also died from CJD. She had been taking a nutritional supplement which contained the following; vacuum dried bovine BRAIN, bone meal, bovine EYE, veal bone, bovine liver powder, bovine adrenal, vacuum dried bovine kidney, and vacuum dried porcine stomach. As I said, this woman taking these nutritional supplements, died from CJD. The particular batch of pills that was located, in which she was taking, was tested. From what I have heard, they came up negative, for the prion protein. But, in the same breath, they said their testing, may not have been strong enough to pick up the infectivity. Plus, she had been taking these type pills for years, so, could it have come from another batch?

CWD is just a small piece of a very big puzzle. I have seen while deer hunting, deer, squirrels and birds, eating from cattle feed troughs where they feed cattle, the high protein cattle by products, at least up until Aug. 4, 1997.

So why would it be so hard to believe that this is how they might become infected with a TSE. Or, even by potentially infected land. It's been well documented that it could be possible, from scrapie. Cats becoming infected with a TSE. Have you ever read the ingredients on the labels of cat and dog food? But, they do not put these tissues from these animals in pharmaceuticals, cosmetics, nutritional supplements, hGH, hPG, blood products, heart valves, and the many more products that come from bovine, ovine, or porcine tissues and organs. So, as I said, this CWD would be a small piece of a very big puzzle. But, it is here, and it most likely has killed. You see, greed is what caused this catastrophe, rendering and feeding practices. But, once Pandora's box was opened, the potential routes of infection became endless.

No BSE in the U.S.A.? I would not be so sure of that considering that since 1990;

Since 1990 the U.S. has raised 1,250,880,700 cattle;

Since 1990 the U.S. has ONLY checked 8,881 cattle brains for BSE, as of Oct. 4, 1999;

There are apprx. 100,000 DOWNER cattle annually in the U.S., that up until Aug. 4, 1997 went to the renders for feed;

Scrapie running rampant for years in the U.S., 950 infected FLOCKS, as of Aug. 1999;

Our feeding and rendering practices have mirrored that of the U.K. for years, some say it was worse. Everything from the downer cattle, to those scrapie infected sheep, to any roadkill, including the city police horse and the circus elephant went to the renders for feed and other products for consumption. Then they only implemented a partial feed ban on Aug. 4, 1997, but pigs, chickens, dogs, and cats, and humans were exempt from that ban. So they can still feed pigs and chickens those potentially TSE tainted by-products, and then they can still feed those by-products back to the cows. I believe it was Dr. Joe Gibbs, that said, the prion protein, can survive the digestinal track. So you have stopped nothing. It was proven in Oprah Winfrey's trial, that Cactus Cattle feeders, sent neurologically ill cattle, some with encephalopathy stamped on the dead slips, were picked up and sent to the renders, along with sheep carcasses. Speaking of autopsies, I have a stack of them, from CJD victims. You would be surprised of the number of them, who ate cow brains, elk brains, deer brains, or hog brains.

I believe all these TSE's are going to be related, and originally caused by the same greedy Industries, and they will be many. Not just the Renders, but you now see, that they are re-using medical devices that were meant for disposal. Some medical institutions do not follow proper auto- claving procedures (even Olympus has put out a medical warning on their endescopes about CJD, and the fact you cannot properly clean these instruments from TSE's), and this is just one product. Another route of infection.

Regardless what the Federal Government in the U.S. says. It's here, I have seen it, and the longer they keep sweeping it under the rug and denying the fact that we have a serious problem, one that could surpass aids (not now, but in the years to come, due to the incubation period), they will be responsible for the continued spreading of this deadly disease.

It's their move, it's CHECK, but once CHECKMATE has been called, how many thousands or millions, will be at risk or infected or even dead. You can't play around with these TSE's. I cannot stress that enough. They are only looking at body bags, and the fact the count is so low. But, then you have to look at the fact it is not a reportable disease in most states, mis-diagnosis, no autopsies performed. The fact that their one-in-a- million theory is a crude survey done about 5 years ago, that's a joke, under the above circumstances. A bad joke indeed........

The truth will come, but how many more have to die such a hideous death. It's the Government's call, and they need to make a serious move, soon. This problem, potential epidemic, is not going away, by itself.

Terry S. Singeltary Sr.

Bacliff, Texas 77518 USA

flounder@wt.netWEDNESDAY, FEBRUARY 10, 2021 

SENATORS URGE BIDEN TO WITHDRAW SHEEP IMPORT RULE DUE TO SCRAPIE TSE Prion CONCERNS


Competing interests: No competing interests


WEDNESDAY, FEBRUARY 10, 2021 

SENATORS URGE BIDEN TO WITHDRAW SHEEP IMPORT RULE DUE TO SCRAPIE TSE Prion CONCERNS


Terry S. Singeltary Sr., Bacliff, Texas USA, 7718 <flounder9@verizon.net>

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