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, May 29, 2021

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

''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.''

J Vet Diagn Invest. 

2021 May 28;10406387211017615. doi: 10.1177/10406387211017615. Online ahead of print.

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

Eric D Cassmann 1, Rylie D Frese 1, Justin J Greenlee 1

Affiliations expand


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.


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. 


2011 

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


Sunday, October 25, 2015 

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


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

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. 




WEDNESDAY, MAY 05, 2021 

Scrapie infected sheep and goat herd was identified in Wisconsin on March 16, 2021


Ohio Scrapie Cases in Goats FY 2002 – FY 2021


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


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 Field Trial Experiments Mission, Texas, The Moore Air Force Base Scrapie TSE Prion Experiment 1964 Terry S. Singeltary Goal: Thursday, June 09, 2016

Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base Scrapie TSE Prion Experiment 1964

How Did CWD Get Way Down In Medina County, Texas?

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 absent 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...




THURSDAY, JANUARY 7, 2021 

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


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 ;


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


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


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


August 1988

Evidence That Transmissible Mink Encephalopathy Results From Feeding Infected Cattle


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... 




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



31

Appendix I VISIT TO USA - OR A E WRATHALL — INFO ON BSE AND SCRAPIE

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 SAF were given.

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).

Prof. A Robertson gave a brief accout of BSE. The us approach was to

32

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

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.

33

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

http://webarchive.nationalarchives.gov.uk/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf


Thursday, June 09, 2016 

Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base Scrapie Experiment 1964 

How Did CWD Get Way Down In Medina County, Texas? 

Confucius ponders... 

Could the Scrapie experiments back around 1964 at Moore Air Force near Mission, Texas, could this area have been ground zero for CWD TSE Prion (besides the CWD cases that have waltzed across the Texas, New Mexico border near WSMR Trans Pecos region since around 2001)? 

Epidemiology of Scrapie in the United States 1977 

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 ; 


Thursday, June 09, 2016 

Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base Scrapie TSE Prion Experiment 1964 How Did CWD Get Way Down In Medina County, Texas? 



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 !



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. 


 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 


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. 


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.


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


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

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

https://www.nature.com/articles/srep11573 

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

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

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. 

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. 

=============== 

***thus questioning the origin of human sporadic cases*** 

=============== 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 

============== 

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf 

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

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

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

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20 

PRION 2016 TOKYO

Saturday, April 23, 2016

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

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

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

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

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

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

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

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

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

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

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

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

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

snip...

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

PMID: 6997404


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

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

snip...

76/10.12/4.6


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

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

Gibbs CJ Jr, Gajdusek DC.

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

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

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

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

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



WEDNESDAY, 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


Like lambs to the slaughter 

* 31 March 2001 * 

Debora MacKenzie * 

Magazine issue 2284 

Suspect symptoms 

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie? 

Exclusive from New Scientist magazine 

Four years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. 

The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease. 

Photo: Murdo McLeod 

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. 

He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. 

Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America. 

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. 

To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD. 

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. 

Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb. 

Brain damage Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. 

But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE. 

Deslys and colleagues were originally studying vCJD, not sCJD. 

They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. 

Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms. 

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. 

As expected, they all affected the brain in a different way from BSE and vCJD. 

But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology. Multiple strains "The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. 

"You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie," she says. 

In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar. But there are more than 20 strains of scrapie, and six of sCJD. 

"You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. 

Bruce is cautious about the mouse results, but agrees they require further investigation. 

Other trials of scrapie and sCJD in mice, she says, are in progress. 

Deformed proteins People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. 

Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD. But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. 

"If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection." 

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. 

Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. 

Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted. 

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. 

And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments. 

More at: Proceedings of the National Academy of Sciences (vol 98, p 4142) 

 Correspondence about this story should be directed to letters@newscientist.com 1900 GMT, 28 March 2001 

* New Scientist 





2001 Mar 27;98(7):4142-7. doi: 10.1073/pnas.041490898. Epub 2001 Mar 20.

Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-- Jakob disease: implications for human health

C I Lasmézas 1, J G Fournier, V Nouvel, H Boe, D Marcé, F Lamoury, N Kopp, J J Hauw, J Ironside, M Bruce, D Dormont, J P Deslys

Affiliations expand

PMID: 11259641 PMCID: PMC31193 DOI: 10.1073/pnas.041490898

Abstract

There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.

snip...

We found that the BSE agent in nonhuman primates is similar to that causing vCJD in humans and tends to evolve rapidly toward a primate-adapted variant. Furthermore, we showed that the strain responsible for iCJD is closely related to that of one patient with sCJD, and, more unexpectedly, that these agents were similar to the French scrapie strain studied (but different from the U.S. scrapie strain). This finding requires a cautious interpretation for several reasons, not least because of the inevitably limited number of TSE strains that can be studied by such a cumbersome method as strain typing. Nonetheless, it also prompts reconsideration of the possibility that, in some instances, sheep and human TSEs can share a common origin. 


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

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

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

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

snip...

R. BRADLEY


FRIDAY, OCTOBER 23, 2020 

Scrapie TSE Prion Zoonosis Zoonotic, what if?


terry

''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.''

posted by Terry S. Singeltary Sr. | 11:31 AM

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