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

Friday, January 08, 2021

Canada Scrapie Flock Certification Program

Canada Scrapie Flock Certification Program

7. Scrapie Flock Certification Program

Flocks infected with scrapie in Canada The CFIA, in co-operation with provincial governments and industry, launched a national scrapie surveillance program in 2005. Under the program, producers are encouraged to report animals that die on the farm or exhibit symptoms of the disease.

In addition, scrapie is a reportable disease under the Health of Animals Regulations. This means that all suspected cases must be reported to the CFIA.

Current as of: 2020-11-30

Sheep flocks and/or goat herds confirmed to be infected with classical scrapie in Canada Filter items

Year Date confirmed Location Animal type infected

2019 June 21 Alberta Sheep

2019 June 21 Alberta Sheep

2018 January 16 Manitoba Goat

2018 January 16 Manitoba Goat

2017 November 1 Quebec Sheep

2017 October 4 Manitoba Goat

2017 October 4 Alberta Goat

2017 September 15 Manitoba Goat

2017 September 7 Manitoba Goat

2017 August 28 Manitoba Goat

2017 July 11 Manitoba Goat

2017 June 29 Manitoba Goat

2017 April 7 Saskatchewan Sheep

2016 November 14 Quebec Sheep

2016 November 14 Quebec Sheep

2016 May 18 Ontario Goat

2015 January 5 Ontario Goat

2015 May 22 Quebec Sheep

2015 June 16 Ontario Sheep

2014 July 31 Ontario Sheep

2014 June 30 Ontario Goat

2014 June 18 Quebec Sheep

2014 June 18 Ontario Goat

2014 June 16 Ontario Goat

2014 June 4 Ontario Goat

2014 June 4 Ontario Goat

2013 December 19 Ontario Goat

2013 April 11 Quebec Sheep

2013 April 11 Quebec Sheep

2013 February 25 Quebec Sheep

2012 November 8 Quebec Sheep

2012 October 11 Ontario Sheep

2012 October 11 Ontario Sheep

2012 September 27 Ontario Sheep

2012 September 27 Quebec Sheep

2012 September 13 Ontario Sheep

2012 August 2 Ontario Sheep

2012 June 4 Table Note * Ontario Sheep

2012 May 31 Table Note * Quebec Sheep

2012 May 2 Quebec Sheep

2012 January 26 Table Note * Alberta Sheep

2011 September 26 Table Note * Nova Scotia Sheep

2011 July 14 Ontario Sheep

2011 July 13 Quebec Sheep

2011 May 5 Quebec Sheep

2011 May 3 Ontario Sheep

2011 March 30 Quebec Sheep

2011 January 19 Ontario Sheep


2010


2009


Canada atypical Nor-98 Scrapie

J Vet Diagn Invest

. 2010 May;22(3):408-11. doi: 10.1177/104063871002200310.

Identification of atypical scrapie in Canadian sheep

Gordon B Mitchell 1, Katherine I O'Rourke, Noel P Harrington, Andrei Soutyrine, Marion M Simmons, Sandor Dudas, Dongyue Zhuang, Hubert Laude, Aru Balachandran

PMID: 20453215 DOI: 10.1177/104063871002200310

Abstract

Scrapie, a transmissible spongiform encephalopathy of sheep and goats, exists in most small ruminant-producing countries of the world. A novel form of this disease was recently recognized and is known by various names, including Nor98, Nor98-like, and atypical scrapie. Differing from classic scrapie in epidemiology, histopathology, and biochemical characteristics, atypical scrapie cases have been identified throughout Europe and in the United States. Enhanced scrapie surveillance efforts recently identified 3 cases of atypical scrapie in Canada.



***> The Program certifies flocks/herds with respect to classical scrapie only, and does not cover atypical scrapie, which is clinically, pathologically, biochemically and epidemiologically unrelated to classical scrapie.

***> The program certifies flocks/herds with respect to classical scrapie only, and does not cover "atypical" scrapie which is clinically, pathologically, biochemically and epidemiologically unrelated to classical scrapie. Atypical scrapie may, in fact, be a non-contagious, spontaneous degenerative condition of older sheep. As such, throughout this document, when the term "scrapie" is used, it refers to classical scrapie only.

https://www.inspection.gc.ca/animal-health/terrestrial-animals/diseases/accredited-veterinarian-s-manual/chapter-7/eng/1345472078870/1345472451638?chap=0

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

Justin J. Greenlee First Published September 10, 2018 Review Article Find in PubMed


PRNP genotype is a major factor in atypical scrapie cases with polymorphisms at codons 141 (F, phenylalanine) and 154 (H) being highly associated with identified cases. Sheep in the original report carried at least 1 AHQ allele.16 Atypical scrapie has been transmitted experimentally to AHQ sheep by the intracranial145 and oral146 routes. An increased risk of atypical scrapie has also been identified in sheep with the AF141RQ haplotype.137 Atypical scrapie does experimentally transmit to sheep with the AL141RQ haplotype but with very long incubation periods without clinical signs.123 Furthermore, sheep with the ARR haplotype, which confers resistance to classical scrapie and is the cornerstone of genotype-based eradication programs, do not appear to be protected against developing atypical scrapie.41,137

Atypical scrapie has also been reported in goats,103,142 where the molecular profile on western blot is similar to atypical scrapie in sheep, but the distribution of lesions within the brain is more rostral (thalamus and midbrain) than atypical scrapie of sheep.142 Similar to sheep with atypical scrapie, histidine substitution at PRNP codon 154 is a risk factor for atypical scrapie in goats,32 and PrPSc has not been demonstrated in the lymphoid tissues of affected goats.142


Front. Bioeng. Biotechnol., 12 March 2020 | https://doi.org/10.3389/fbioe.2020.00164

The Scrapie Prevalence in a Goat Herd Is Underestimated by Using a Rapid Diagnostic Test

Two scrapie types exist, atypical and classical scrapie, which are epidemiologically distinct and produce different disease phenotypes. Contrary to classical scrapie, atypical scrapie usually affects single and older animals, the agent is less resistant to proteolytic digestion with proteinase K, PrPSc is not detectable in lymphoid tissue by immunohistochemical examination (IHC) and relatively absent in the brainstem. Different biochemical profiles are also identified on Western blot examination of brain (Benestad et al., 2008). Scrapie is a World Organization for Animal Health (OIE) listed disease, although management of the animal health risks associated with the scrapie agent in the OIE’s Terrestrial Animal Health Code (OIE, 2018) only applies to classical scrapie, due to the known contagious nature of this disease type. 


RESEARCH ARTICLE

The emergence of classical BSE from atypical/Nor98 scrapie

Alvina Huor, View ORCID ProfileJuan Carlos Espinosa, View ORCID ProfileEnric Vidal, Hervé Cassard, View ORCID ProfileJean-Yves Douet, Séverine Lugan, Naima Aron, View ORCID ProfileAlba Marín-Moreno, Patricia Lorenzo, Patricia Aguilar-Calvo, Juan Badiola, Rosa Bolea, Martí Pumarola, Sylvie L. Benestad, Leonore Orge, Alana M. Thackray, Raymond Bujdoso, View ORCID ProfileJuan-Maria Torres, and View ORCID ProfileOlivier Andreoletti PNAS December 26, 2019 116 (52) 26853-26862; first published December 16, 2019; https://doi.org/10.1073/pnas.1915737116 Edited by Michael B. A. Oldstone, Scripps Research Institute, La Jolla, CA, and approved November 15, 2019 (received for review September 11, 2019)

Article Figures & SI Info & Metrics PDF

Significance

The origin of transmissible BSE in cattle remains unestablished. Sheep scrapie is a potential source of this known zoonotic. Here we investigated the capacity of sheep scrapie to propagate in bovine PrP transgenic mice. Unexpectedly, transmission of atypical but not classical scrapie in bovine PrP mice resulted in propagation of classical BSE prions. Detection of prion seeding activity by in vitro protein misfolding cyclic amplification demonstrated BSE prions in the original atypical scrapie isolates. BSE prion seeding activity was also detected in ovine PrP mice inoculated with limiting dilutions of atypical scrapie. Our data demonstrate that classical BSE prions can emerge during intra- and interspecies passage of atypical scrapie and provide an unprecedented insight into the evolution of mammalian prions.

Abstract

Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form of prion disease, and, importantly, the zoonotic potential and the risk that AS might represent for other farmed animal species remains largely unknown. In this study, we investigated the capacity of AS to propagate in bovine PrP transgenic mice. Unexpectedly, the transmission of AS isolates originating from 5 different European countries to bovine PrP mice resulted in the propagation of the classical BSE (c-BSE) agent. Detection of prion seeding activity in vitro by protein misfolding cyclic amplification (PMCA) demonstrated that low levels of the c-BSE agent were present in the original AS isolates. C-BSE prion seeding activity was also detected in brain tissue of ovine PrP mice inoculated with limiting dilutions (endpoint titration) of ovine AS isolates. These results are consistent with the emergence and replication of c-BSE prions during the in vivo propagation of AS isolates in the natural host. These data also indicate that c-BSE prions, a known zonotic agent in humans, can emerge as a dominant prion strain during passage of AS between different species. These findings provide an unprecedented insight into the evolution of mammalian prion strain properties triggered by intra- and interspecies passage. From a public health perspective, the presence of c-BSE in AS isolates suggest that cattle exposure to small ruminant tissues and products could lead to new occurrences of c-BSE.

snip...

Discussion The mechanism(s) that lead to an alteration in the phenotype of prion strains as these transmissible entities undergo transmission between different host species remain uncertain. This is despite the identification that differences in amino acid sequence between host PrPC and donor PrPSc, together with prion strain identity, are principal determinants of the transmission barrier (9, 10). Based on the concept that conformation of PrPSc molecules/aggregates encode prion strain information (2, 4, 5, 30, 31), at least 2 nonexclusive hypotheses, “deformed templating” (32, 33) and the “conformational selection model” (32⇓⇓–35), have been proposed to explain the mutation of prion strains.

The deformed templating hypothesis postulates that a prion strain replicates as a clone of PrPSc molecules/aggregates. When confronted by a transmission barrier that does not allow clonal prion replication, the propagation process is modified so that “altered” PrPSc structural variants are generated in an attempt to convert the new host PrPC. While the majority of these presumably fail to replicate efficiently in the new host, variants eventually emerge that are successful and adapt to the new PrP environment through multiple trial-and-error replication events. In this deformed templating model, confrontation of the transmission barrier serves as the triggering event that initiates the generation of new prion variant(s) and as a filter for their selection (35).

The conformational selection model proposes that a prion strain naturally propagates in its host as an ensemble of PrPSc conformers dominated by a stable energetically favorable conformation responsible for the observed prion strain phenotype. Furthermore, this model predicts that the number of stable PrPSc conformers is limited for each PrP amino acid sequence, which would explain the existence of a finite number of stable prion strains that can propagate in a given species. It is further proposed that, during transmission of a prion strain to a new host, one of the less dominant PrPSc conformers of those present in the ensemble is selected with a resultant change, or mutation, in the properties of the newly propagating prion strain. In the conformational selection model, the transmission barrier acts simply as a selective filter for new prion variants, and ease of permeation of the barrier results from the extent of overlap of PrPSc conformers that exist between the interacting species (32, 33).

Our data reported here showed that c-BSE prions are present as a minor variant in natural isolates of ovine AS. In addition, transmission of ovine AS to bovine PrP mice demonstrated that c-BSE can emerge during these transmissions as the dominant prion strain. These results provide a cogent argument in favor of the conformational selection model as the mechanism for prion strain mutation during interspecies prion transmission. This would be expected to occur by selection of a preexisting PrPSc variant in AS isolates, one best suited to the new replicative environment. Within this conceptual framework, the occurrence of prion strain mutation is dependent upon the particular repertoire of PrPSc variants associated with distinct prion strains. This notion is supported by our observation that c-BSE prions emerged during serial transmission of ovine AS in tgBov mice but not from serial passage of classical scrapie in the same mouse line [Table 1 and Cassard et al. (15)].

The diversity of prion strains that exist in small ruminants remains undefined, although it is established that at least 5 different natural ovine prion strains exist, including AS (6, 36⇓⇓–39). According to the conformational selection model, each of these different ovine prion strains is associated with a unique and stable PrPSc conformer and a distinct set of minor variants. The tgBov mouse line has previously been reported to support the propagation of a variety of natural ovine prions, of which several displayed significantly shorter incubation periods than c-BSE (15). Strikingly, in our experiments, the diversity of prion variants in the AS isolates (7 different cases) revealed by the serial passage in tgBov was restricted to the c-BSE agent (Table 1). This consistent emergence of a single prion strain argues against the view that AS prion replication in sheep can randomly generate all of the existing stable PrPSc variants associated with a particular ovine PrPC amino acid sequence. Instead, our data support the view that individual prion strains are associated with a restricted repertoire of stable PrPSc variants in a given host. Whether AS is unique in its ability to generate c-BSE prion particles during its replication process remains to be established.

Classical BSE was first recognized in 1984 and 1985 as a novel prion disease affecting cattle in the United Kingdom (40). Epidemiological data clearly established that the number of cases of c-BSE was amplified by the recycling of infected animal carcasses into cattle feed in the form of meat and bone meal (MBM) (41). Since bovine prion disease had not been recognized in cattle prior to the c-BSE epizootic and the disease is apparently noncontagious between cattle, several hypotheses were proposed to explain its emergence. These range from the spontaneous occurrence of c-BSE in cattle to the passage and adaptation of a prion originating from another species (42, 43). Our studies here that show the presence of c-BSE prions in AS isolates, combined with the demonstrated presence of AS in the United Kingdom long before the appearance of the c-BSE epizootic in cattle, suggests that the recycling of AS cases in MBM might be a source of bovine prion disease (20). In addition to its potential role in the initial emergence of c-BSE in cattle, the presence of c-BSE prions in natural cases of AS has current and direct implications for both the continued risk of this ovine prion disease to other farmed animals and for human exposure risks. The distribution of AS cases are widespread across the world (17⇓–19). A recent retrospective analysis of surveillance data collected over a period exceeding 10 y in the European Union (EU) concluded that the prevalence of detected AS cases has remained relatively stable in the different member states, with between 2 and 6 positive cases per 10,000 tested animals per year. This implies that a substantial number of AS-infected animals could enter either the animal or human food chain each year (44, 45), and each case represents a potential source of exposure to the c-BSE agent for farmed animals (MBM derived from rendered small ruminants) and human consumers (consumption of healthy slaughtered animals), respectively. The epidemiological features of AS within the EU is likely to reflect the situation of the disease in other countries that breed and maintain small ruminants.

In Europe, the c-BSE crisis and the emergence of vCJD resulted in the implementation of a strong and coherent policy (EU regulation 999/2001) aimed at control and eradication of this animal prion disease. The total feed ban on the use of MBM in animal feed and the systematic retrieval from the food chain of ruminant tissues that have the potential to contain high levels of prion infectivity, so-called Specified Risk Material (SRM) measures, were instrumental for control of c-BSE in cattle and prevention of dietary human exposure to these bovine prions (46, 47). As a side effect, these measures also strongly limited the exposure of farmed animals and human consumers to the other TSE agents circulating in farmed animal species, including AS.

With the decline of the c-BSE epizootic in cattle and the combined increase in pressure from industry, EU authorities have begun to consider discontinuing certain TSE control measures. The abrogation of the SRM measures for small ruminants and the partial reauthorization of the use of processed animal protein, formerly known as MBM, in animal feed are part of the EU authorities’ agenda. Our observation of the presence of the c-BSE agent in AS-infected small ruminants suggests that modification of the TSE control measures could result in an increased risk of exposure to c-BSE prions for both animals and humans. Whether or not this exposure will result in further c-BSE transmission in cattle and/or humans remains an open and important question.


MONDAY, JULY 13, 2020 

Efficient transmission of classical scrapie agent x124 by intralingual route to genetically susceptible sheep with a low dose inoculum


*** 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


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


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? 



doi:10.1016/S0021-9975(97)80022-9 Copyright © 1997 Published by Elsevier Ltd.

Second passage of a US scrapie agent in cattle

R.C. Cutlip, J.M. Miller and H.D. Lehmkuhl

United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Ames, Iowa, USA

Received 10 September 1996; accepted 31 July 1997. Available online 25 May 2006.

Summary

Scrapie and bovine spongiform encephalopathy are similar chronic neurodegenerative diseases of sheep and cattle. An earlier study showed that, on first passage in cattle, a US scrapie agent caused an encephalopathy that was distinct from bovine spongiform encephalopathy (BSE). The present report describes a second passage in cattle, carried out because diseases caused by the spongiform encephalopathy agents often change in character with additional passages in abnormal hosts. For this work, young calves were inoculated intracerebrally with a pooled suspension of brain from cattle that had died of encephalopathy after experimental inoculation with brain from scrapie-affected sheep. The second passage disease was essentially identical with the first passage disease, as judged by clinical signs, histopathological findings and distribution of "prion protein scrapie" (PrPsc). This represents additional evidence to suggest that the US sheep scrapie agent tested is incapable of causing BSE in cattle.


(b) the epidemiological and laboratory studies in the USA suggest the possibility of an occurrence of BSE infection in cattle as the origin of outbreaks of TME.

{c) there is also evidence from two experiments conducted in the USA that cattle, though susceptible to scrapie inocula prepared from sheep, express a pathology quite different from that of BSE and not convincingly diagnostic of an SE by histopathological criteria. Furthermore, neither of these studies can be regarded as a basis for extrapolation to the situation in the UK because the inocula used were either experimentally passaged or natural scrapie originating from Suffolk sheep; a minority breed in this country.


Is There a Scrapie-Like Disease in Cattle? R.F. Marsh*, DVM, PhD and G.R. Hartsough, DVM

Transmissible mink encephalopathy (TME) is a rare disease of ranch-reared mink which is indistinguishable from sheep scrapie. Previous studies on the epidemiology of TME have not identified a definite source of infection for mink. Studies on experimental transmission have shown that mink are susceptible to intracerebral inoculation of American Suffolk scrapie, but that the incubation periods are longer (>1 year) than those observed in natural outbreaks of TME (<1 year).

In April of 1985, a mink rancher in Wisconsin reported a debilitating neurologic disease in his herd which we diagnosed as TME by histopathologic findings confirmed by experimental transmission to mink and squirrel monkeys. The rancher was a “dead stock" feeder using mostly (>95%) downer or dead dairy cattle and a few horses. Sheep had never been fed.

We believe that these findings may indicate the presence of a previously unrecognized scrapie-like disease in cattle and wish to alert dairy practitioners to this possibility.

* Department of Veterinary Science, University of Wisconsin-

- Madison, Madison, WI 53706, .

* Director of the GLMA/EMBA Ranch Service, P.0. Box 342, Thiensville, WI 53092.

PROCEEDINGS OF THE SEVENTH ANNUAL WESTERN CONFERENCE FOR FOOD ANIMAL VETERINARY MEDICINE, University of Arizona, March 17-19, 1986 

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... 




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


FRIDAY, OCTOBER 23, 2020 

Scrapie TSE Prion Zoonosis Zoonotic, what if?


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, JANUARY 7, 2021 

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


Terry S. Singeltary Sr.

posted by Terry S. Singeltary Sr. | 3:42 PM

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