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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

Tuesday, June 07, 2016

Comparison of two US sheep scrapie isolates supports identification as separate strains

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
Title: Comparison of two US sheep scrapie isolates supports identification as separate strains
 
Authors
 
item Moore, Sarah - item Smith, Jodi item West Greenlee, Mary - item Nicholson, Eric item Richt, Juergen item Greenlee, Justin
 
Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: December 22, 2015 Publication Date: N/A
 
Interpretive Summary: Scrapie is a fatal disease of sheep and goats that causes damaging changes in the brain. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state. Whether or not a sheep will get scrapie is determined primarily by their genetics. Furthermore, different scrapie strains exist that may result in a different expression of disease such as shorter incubation periods, unusual clinical signs, or unique patterns of lesions within the brain. This study evaluated two U.S. scrapie isolates in groups of sheep with varying susceptibilities to scrapie. Our data indicates that there are differences in incubation periods, sheep genotype susceptibilities, and lesion profiles that support designating these scrapie isolates as unique strains. The identification of a new scrapie strain in the United States means that control measures, methods of decontamination, and the potential for transmission to other species may need to be reevaluated. This information is useful to sheep farmers and breeders that are selectively breeding animals with genotypes resistant to the most prevalent strain of scrapie and could impact future regulations for the control of scrapie in the United States. Technical Abstract: Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) of sheep and goats. There are different strains of sheep scrapie that are associated with unique molecular, transmission, and phenotype characteristics, but very little is known about the potential presence of scrapie strains within sheep in the US. Scrapie strain and PRNP genotype could both affect susceptibility, potential for transmission, incubation period, and control measures required for eliminating scrapie from a flock. Here we evaluate two US scrapie isolates, No. 13-7 and x124, after intranasal inoculation to compare clinical signs, incubation periods (IP), spongiform lesions, and patterns of PrPSc deposition in sheep with scrapie-susceptible PRNP genotypes (QQ171). After inoculation with x124, susceptibility and IP were associated with valine at codon 136 (V136) of the prion protein: VV136 had short IPs (6.9 months), AV136 sheep were 11.9 months, and AA136 sheep did not develop scrapie. All No.13-7 inoculated sheep developed scrapie with IP’s of 20.1 months for AA136 sheep, 22.8 months for AV136 sheep, and 26.7 months for VV136 sheep. Patterns of immunoreactivity in the brain were influenced by challenge isolate and host genotype. Differences in PrPSc profiles versus isolate were most striking when examining brains from sheep with the VV136 genotype. In summary, intranasal inoculation with isolates x124 and No. 13-7 resulted in differences in IP, sheep genotype susceptibility, and PrPSc profile that support designation as separate strains.
 
Last Modified: 6/6/2016
 
 
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. ...
 
 
also see hand written notes ;
 
 
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...
 
 
PRION 2016 CONFERENCE TOKYO
 
IL-13 Transmission of prions to non human-primates: Implications for human populations
 
Jean-Philippe Deslys, Emmanuel E. Comoy
 
CEW, Institute of Emerging Diseases and Innovative Therapies (iMETI), Division of Prions and Related Diseases (SEPIA), Fontenay-aux-Roses, France
 
Prion diseases 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 prion disease might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, prion diseases, like the other proteinopathies, are reputed to occur spontaneously (atypical animal prion strains, sporadic CJD summing 80 % of human prion cases).
 
Non-human primate models provided the first evidences supporting the transmissibility of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health1, according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the risk of primary (oral) and secondary (transfusional) risk of BSE, and also the zoonotic potential of other animal prion diseases 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' . longer incubation than BSE2. Scrapie, as recently evoked in humanized mice3, is the third potentially zoonotic prion disease (with BSE and L-type BSE4), thus questioning the origin of human sporadic cases. We also observed hidden prions transmitted by blood transfusion in primate which escape to the classical diagnostic methods and extend the field of healthy carriers. We will present an updated panorama of our different long-term transmission studies and discuss the implications on risk assessment of animal prion diseases for human health and of the status of healthy carrier5.
 
1. Chen, C. C. & Wang, Y. H. Estimation of the Exposure of the UK Population to the Bovine Spongiform Encephalopathy Agent through Dietary Intake During the Period 1980 to 1996. PLoS One 9, e94020 (2014).
 
2. Comoy, E. E. et al. Transmission of scrapie prions to primate after an extended silent incubation period. Sci Rep 5, 11573 (2015).
 
3. Cassard, H. et al. Evidence for zoonotic potential of ovine scrapie prions. Nat Commun 5, 5821-5830 (2014).
 
4. Comoy, E. E. et al. Atypical BSE (BASE) transmitted from asymptomatic aging cattle to a primate. PLoS One 3, e3017 (2008).
 
5. Gill O. N. et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ. 347, f5675 (2013).
 
Curriculum Vitae
 
Dr. Deslys co-authored more than one hundred publications in international scientific journals on main aspects of applied prion research (diagnostic, decontamination techniques, risk assessment, and therapeutic approaches in different experimental models) and on underlying pathological mechanisms. He studied the genetic of the first cases of iatrogenic CJD in France. His work has led to several patents including the BSE (Bovine Spongiform Encephalopathy) diagnostic test most widely used worldwide. He also wrote a book on mad cow disease which can be downloaded here for free (http://www.neuroprion.org/pdf_docs/documentation/madcow_deslys.pdf). His research group is Associate Laboratory to National Reference Laboratory for CJD in France and has high security level microbiological installations (NeuroPrion research platform) with different experimental models (mouse, hamster, macaque). The primate model of BSE developed by his group with cynomolgus macaques turned out to mimick remarkably well the human situation and allows to assess the primary (oral) and secondary (transfusional) risks linked to animal and human prions even after very long silent incubation periods. For several years, his interest has extended to the connections between PrP and Alzheimer and the prion mechanisms underlying neurodegenerative diseases. He is coordinating the NeuroPrion international association (initially european network of excellence now open to all prion researchers).
 
- 59-
 
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.
 
WS-02
 
Scrapie in swine: A diagnostic challenge
 
Justin J Greenlee1, Robert A Kunkle1, Jodi D Smith1, Heather W. Greenlee2
 
1National Animal Disease Center, US Dept. of Agriculture, Agricultural Research Service, United States; 2Iowa State University College of Veterinary Medicine
 
A naturally occurring prion disease has not been recognized in swine, but the agent of bovine spongiform encephalopathy does transmit to swine by experimental routes. Swine are thought to have a robust species barrier when exposed to the naturally occurring prion diseases of other species, but the susceptibility of swine to the agent of sheep scrapie has not been thoroughly tested.
 
Since swine can be fed rations containing ruminant derived components in the United States and many other countries, we conducted this experiment to test the susceptibility of swine to U.S. scrapie isolates by intracranial and oral inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the brains of clinically ill sheep from the 4th passage of a serial passage study of the U.S scrapie agent (No. 13-7) through susceptible sheep that were homozygous ARQ at prion protein residues 136, 154, and 171, respectively. Pigs were inoculated intracranially (n=19) with a single 0.75 ml dose or orally (n=24) with 15 ml repeated on 4 consecutive days. Necropsies were done on a subset of animals at approximately six months post inoculation (PI), at the time the pigs were expected to reach market weight. Remaining pigs were maintained and monitored for clinical signs of TSE until study termination at 80 months PI or when removed due to intercurrent disease (primarily lameness). Brain samples were examined by immunohistochemistry (IHC), western blot (WB), and enzyme-linked immunosorbent assay (ELISA). Brain tissue from a subset of pigs in each inoculation group was used for bioassay in mice expressing porcine PRNP.
 
At six-months PI, no evidence of scrapie infection was noted by any diagnostic method. However, at 51 months of incubation or greater, 5 animals were positive by one or more methods: IHC (n=4), WB (n=3), or ELISA (n=5). Interestingly, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study).
 
Swine inoculated with the agent of scrapie by the intracranial and oral routes do not accumulate abnormal prion protein (PrPSc) to a level detectable by IHC or WB by the time they reach typical market age and weight. However, strong support for the fact that swine are potential hosts for the agent of scrapie comes from positive bioassay from both intracranially and orally inoculated pigs and multiple diagnostic methods demonstrating abnormal prion protein in intracranially inoculated pigs with long incubation times.
 
Curriculum Vitae
 
Dr. Greenlee is Research Veterinary Medical Officer in the Virus and Prion Research Unit at the National Animal Disease Center, US Department of Agriculture, Agricultural Research Service. He applies his specialty in veterinary anatomic pathology to focused research on the intra- and interspecies transmission of prion diseases in livestock and the development of antemortem diagnostic assays for prion diseases. In addition, knockout and transgenic mouse models are used to complement ongoing experiments in livestock species. Dr. Greenlee has publications in a number of topic areas including prion agent decontamination, effects of PRNP genotype on susceptibility to the agent of sheep scrapie, characterization of US scrapie strains, transmission of chronic wasting disease to cervids and cattle, features of H-BSE associated with the E211 K polymorphism, and the development of retinal assessment for antemortem screening for prion diseases in sheep and cattle. Dr. Greenlee obtained his DVM degree and completed the PhD/residency program in Veterinary Pathology at Iowa State University. He is a Diplomate of the American College of Veterinary Pathologists.
 
 
Wednesday, May 25, 2016
 
USDA APHIS National Scrapie TSE Prion Eradication Program April 2016 Monthly Report Prion 2016 Tokyo Update
 
 
Saturday, April 23, 2016
 
Prion 2016 Tokyo Update
 
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
 
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
 
 
Friday, April 22, 2016
 
*** Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer ***
 
 
Friday, June 03, 2016
 
*** Chronic Wasting Disease CWD TSE Prion Surveillance and Testing in Texas, a very concerning situation ***
 
 
Saturday, May 28, 2016
 
*** TPWD gives in to Breeders again and postponed their decision regarding proposed changes to state regulations for managing CWD allowing the TSE Prion to spread further ***
 
 
Saturday, May 28, 2016
 
*** Infection and detection of PrPCWD in soil from CWD infected farm in Korea Prion 2016 Tokyo ***
 
 
PRION 2016 TOKYO
 
Zoonotic Potential of CWD Prions: An Update
 
Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3, Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6, Pierluigi Gambetti1, Qingzhong Kong1,5,6
 
1Department of Pathology, 3National Prion Disease Pathology Surveillance Center, 5Department of Neurology, 6National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
 
4Department of Biological Sciences and Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada,
 
2Encore Health Resources, 1331 Lamar St, Houston, TX 77010
 
Chronic wasting disease (CWD) is a widespread and highly transmissible prion disease in free-ranging and captive cervid species in North America. The zoonotic potential of CWD prions is a serious public health concern, but the susceptibility of human CNS and peripheral organs to CWD prions remains largely unresolved. We reported earlier that peripheral and CNS infections were detected in transgenic mice expressing human PrP129M or PrP129V. Here we will present an update on this project, including evidence for strain dependence and influence of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of experimental human CWD prions.
 
PRION 2016 TOKYO
 
In Conjunction with Asia Pacific Prion Symposium 2016
 
PRION 2016 Tokyo
 
Prion 2016
 
 
Prion 2016
 
Purchase options Price * Issue Purchase USD 198.00
 
 
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
 
Taylor & Francis
 
Prion 2016 Animal Prion Disease Workshop Abstracts
 
WS-01: Prion diseases in animals and zoonotic potential
 
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
 
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
 
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
 
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
 
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
 
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
 
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
 
 
IL-13 Transmission of prions to non human-primates: Implications for human populations
 
Jean-Philippe Deslys, Emmanuel E. Comoy
 
CEW, Institute of Emerging Diseases and Innovative Therapies (iMETI), Division of Prions and Related Diseases (SEPIA), Fontenay-aux-Roses, France
 
Prion diseases 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 prion disease might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, prion diseases, like the other proteinopathies, are reputed to occur spontaneously (atypical animal prion strains, sporadic CJD summing 80 % of human prion cases).
 
Non-human primate models provided the first evidences supporting the transmissibility of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health1, according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the risk of primary (oral) and secondary (transfusional) risk of BSE, and also the zoonotic potential of other animal prion diseases 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' . longer incubation than BSE2. Scrapie, as recently evoked in humanized mice3, is the third potentially zoonotic prion disease (with BSE and L-type BSE4), thus questioning the origin of human sporadic cases. We also observed hidden prions transmitted by blood transfusion in primate which escape to the classical diagnostic methods and extend the field of healthy carriers. We will present an updated panorama of our different long-term transmission studies and discuss the implications on risk assessment of animal prion diseases for human health and of the status of healthy carrier5.
 
1. Chen, C. C. & Wang, Y. H. Estimation of the Exposure of the UK Population to the Bovine Spongiform Encephalopathy Agent through Dietary Intake During the Period 1980 to 1996. PLoS One 9, e94020 (2014).
 
2. Comoy, E. E. et al. Transmission of scrapie prions to primate after an extended silent incubation period. Sci Rep 5, 11573 (2015).
 
3. Cassard, H. et al. Evidence for zoonotic potential of ovine scrapie prions. Nat Commun 5, 5821-5830 (2014).
 
4. Comoy, E. E. et al. Atypical BSE (BASE) transmitted from asymptomatic aging cattle to a primate. PLoS One 3, e3017 (2008).
 
5. Gill O. N. et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ. 347, f5675 (2013).
 
Curriculum Vitae
 
Dr. Deslys co-authored more than one hundred publications in international scientific journals on main aspects of applied prion research (diagnostic, decontamination techniques, risk assessment, and therapeutic approaches in different experimental models) and on underlying pathological mechanisms. He studied the genetic of the first cases of iatrogenic CJD in France. His work has led to several patents including the BSE (Bovine Spongiform Encephalopathy) diagnostic test most widely used worldwide. He also wrote a book on mad cow disease which can be downloaded here for free (http://www.neuroprion.org/pdf_docs/documentation/madcow_deslys.pdf). His research group is Associate Laboratory to National Reference Laboratory for CJD in France and has high security level microbiological installations (NeuroPrion research platform) with different experimental models (mouse, hamster, macaque). The primate model of BSE developed by his group with cynomolgus macaques turned out to mimick remarkably well the human situation and allows to assess the primary (oral) and secondary (transfusional) risks linked to animal and human prions even after very long silent incubation periods. ***For several years, his interest has extended to the connections between PrP and Alzheimer and the prion mechanisms underlying neurodegenerative diseases. He is coordinating the NeuroPrion international association (initially european network of excellence now open to all prion researchers).
 
 
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
 
 
Friday, April 22, 2016
 
*** Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer ***
 
 
LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$
 
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
 
 
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
 
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
 
O18
 
Zoonotic Potential of CWD Prions
 
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA
 
*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.
 
==================
 
***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***
 
==================
 
P.105: RT-QuIC models trans-species prion transmission
 
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA
 
Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.
 
***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.
 
================
 
***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***
 
================
 
 
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
 
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
 
*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.
 
*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.
 
 
 
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
 
 
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
 
 
Monday, May 02, 2016
 
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
 
 
Wednesday, May 25, 2016
 
USDA APHIS National Scrapie TSE Prion Eradication Program April 2016 Monthly Report Prion 2016 Tokyo Update
 
 
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.
 
==============
 
 
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
Title: Transmission of scrapie prions to primate after an extended silent incubation period
 
Authors
 
item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -
 
Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.
 
Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans. Technical Abstract: Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health.
 
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
 
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
 
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
 
 
1: J Infect Dis 1980 Aug;142(2):205-8
 
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
 
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
 
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
 
snip...
 
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
 
PMID: 6997404
 
 
12/10/76
 
AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE
 
Office Note CHAIRMAN: PROFESSOR PETER WILDY
 
snip...
 
A The Present Position with respect to Scrapie A] The Problem
 
Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.
 
The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.
 
It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.
 
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).
 
 
Epidemiology of Scrapie in the United States 1977
 
 image
 
 
NEW URL ;
 
 
OPII-1
 
Disease incidence and incubation period of BSE and CH1641 in sheep is associated with PrP gene polymorphisms.
 
Goldman WI, Hunter N., Benson G., Foster J. and Hope J. AFRC&MRC Neuropathogenesis Unit, Institute for Animal Health, West Mains Rd. Edinburgh EH9 3JF. U.K.
 
The relative survival periods of mice with different Sine genotype have long been used for scrapie strain typing. The PrP protein. a key molecule in the pathogenesis of scrapie and related diseases, is a product of the Sine locus and homologous proteins are also linked to disease-incidence loci in sheep and man. In sheep alleles of this locus (Sip) encode several PrP protein variants, of which one has been associated with short incubation periods of Cheviot sheep infected with SSBP/1 scrapie. Other isolates, i.e. BSE or CH1641. cause a different pattern of incubation periods and a lower disease incidence in the same flock of Cheviot sheep. Using transmission to sheep of known PrP genotype as our criterion for agent strain typing. we have found a link between BSE and CH1641. a C-group strain of scrapie. Disease susceptibility of sheep to these isolates is associated with different PrP genotypes compared to SSBP/1 scrapie.
 
OPII –2
 
Transmission of Bovine Spongiform Encephalopathy in sheep, goats and mice.
 
Foster J., Hope J., McConnell I. and Fraser H. Institute for Animal Health, AFRC and MRC Neuropathogenesis Unit, Kings Buildings, West Mains Road, Edinburgh EH9 3JF
 
Bovine Spongiform Encephalopathy (BSE) has been transmitted in two lines of genetically selected sheep [differing in their susceptibilities to the SSBP/1 source of scrapie), and to goats by intracerebral injection and by oral dosing. Incubation periods in sheep for both routes of challenge ranged from 440-994 days. In goats this range was 506-1508 days. Both routes of infection in sheep and goats were almost equally efficient. In mice, primary transmission of BSE identified a sinc-independant genetic control of incubation period. Also, intermediate passage of BSE in sheep or goats did not alter these primary transmission properties. Hamsters were susceptible to BSE only after intervening passage through mice.
 
 
However, I became increasingly aware after 1988 that questioning official dogma about BSE brought difficulties to one’s career. I was myself about to retire from the Charing Cross Hospital, where I worked as a Consultant Neuropathologist, but I observed with horror that the good reputations of dissenting scientists in the field, not least Dr Stephen Dealler and especially Dr Harash Narang were systematically undermined.
 
 
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.
 
snip...
 
 
ANNEX 1 to witness statement 410 of Dr. Helen Grant
 
Annex 1
 
Unique Properties of the scrapie/BSE/CJD Agent, the so-called "prion"
 
A. The transmissible organism which causes all the transmissible spongiform encephalopathies (TSEs) -- scrapie, BSE, CJD and Kuru – is almost indestructible, unlike any other virus, bacterium, protozoon, fungus or parasite. For example, it still transmits scrapie after being 'fixed' in formaldehyde for ten years. Heating it to a very high temperature, exposing it to enormous doses of ultraviolet light, or to ionising radiation, do not affect it. Incineration is the only way of destroying it and even then the temperature must be very high indeed.
 
B. It proliferates only in the brain, eyes, spinal cord, pituitary and, in some mammals, the placenta. The transmission of these diseases is dose-related and although the virus usually enters the bloodstream from the stomach, and then visits all tissues for a few hours, it lingers and proliferates only in the brain etc. The red meat (muscle) of BSE-infected cattle has never transmitted the disease in the laboratory and we have not had any trouble from eating scrapie-infected muscle over the centuries.
 
C. It lurks for years in an outwardly completely healthy individual.
 
D. During this long 'incubation period' the brain etc. is infective which is why it was necessary to ban the brains etc. of all cattle from human foods.
 
E. It raises no antibodies -- which might then be tested for -- in the infected host.
 
F. There is officially no live test to reveal infected individuals. "Officially" because a live (urine) test has recently been devised and has been used successfully in 15 out of 15 humans who were subsequently shown to have suffered CJD. MAFF's vets refuse to make use of this live test and denigrate it whenever they are asked about it. It could also be used to screen blood donors.
 
G. Individuals' susceptibility to this organism is genetically determined. Not all types of sheep develop scrapie; not all types of cattle develop BSE and only some humans -- those of an unusual genotype -- will, if infected, develop CJD.
 
H. Scrapie, the orginal disease in sheep, has been easily transmitted by mouth to many experimental mammals including primates. Humans are primates.
 
Items b (placenta), c, d and f establish that the Government's present 'culling' policy, which is not based on science, cannot possibly eradicate BSE.
 
______________________________________________________________________
 
[I don't have the time to print all of the text from the Discussion document for session on epidemiology of BSE 14 October 1999, but I would like to point out a few things.....TSS]...2016, wish I would have taken the time to print it out...tss
 
 
 
BSE: TIME TO TAKE H.B. PARRY SERIOUSLY
 
If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...
 
 
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
 
 
”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” page 26.
 
 
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. ...
 
 
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...
 
 
 
 
Wednesday, May 30, 2012
 
PO-028: Oral transmission of L-type bovine spongiform encephalopathy (L-BSE) in primate model Microcebus murinus
 
 
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
 
Emmanuel Comoy,1,? Valérie Durand,1 Evelyne Correia,1 Sophie Freire,1 Jürgen Richt,2 Justin Greenlee,3 Juan-Maria Torres,4 Paul Brown,1 Bob Hills5 and Jean-Philippe Deslys1
 
1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Kansas State University; Manhattan, KS USA; 3USDA; Ames, IA USA; 4INIA; Madrid, Spain; 5Health Canada; Ottawa, ON Canada?Presenting author; Email: emmanuel.comoy@cea.fr.
 
The epidemiology of Transmissible mink encephalopathy (TME) indicates an alimentary origin. Several inter-species transmission experiments have not succeeded in establishing with certainty any natural reservoir of this prion strain, although both ovine and bovine sources have been suspected. Cattle exposed to TME develop a spongiform encephalopathy that is distinct from classical Bovine Spongiform Encephalopathy (c-BSE).
 
Inoculation of c-BSE to cynomolgus macaque provided early evidence of a possible risk to humans, and remains an important model to define the risk of both primary (oral transmission from cattle to primate) and secondary (intravenous intra-species transmission) exposures. We have also evaluated the transmissibility of other cattle prion strains to macaques, including L- and H- atypical forms of BSE, namely BSE-L and BSE-H, and cattle-adapted TME.
 
BSE-L induced a neurological disease distinct from c-BSE. Peripheral exposures demonstrate the transmissibility of BSE-L by oral, intravenous, and intra-cerebral routes, with incubation periods similar to c-BSE. Cattle-adapted TME also induced a rapid disease in cynomolgus macaque. The clinical features, lesion profile, and biochemical signature of the induced disease was similar to the features observed in animals exposed to BSE-L, suggesting a link between the two prion strains. Secondary transmissions to a common host (transgenic mouse overexpressing bovine PrP) of cattle-TME and BSE-L before or after passage in primates induced diseases with similar incubation periods: like the c-BSE strain, these cattle strains maintained their distinctive features regardless of the donor species and passages.
 
*** If the link between TME and BSE-L is confirmed, our results would suggest that BSE-L in North America may have existed for decades, and highlight a possible preferential transmission of animal prion strains to primates after passage in cattle.
 
==================================================end...tss============================================
 
Risk.16: Clinical Disease in Cattle Experimentally Inoculated with All Types of BSE
 
Catherine Graham,1,? Michel Levy,2 Ed Pajor,2 Garth McGregor,1 Rheana Flitton1 and Stefanie Czub1
 
1Canadian Food Inspection Agency; Lethbridge, AB Canada; 2Faculty of Veterinary Medicine; University of Calgary; Calgary, AB Canada?Presenting author; Email: catherine.graham@inspection.gc.ca.
 
Background. Classical, or C-type, bovine spongiform encephalopathy (BSE) has been extensively described in the literature. Recently, two novel forms of BSE, termed atypical BSE, have been reported in a number of countries. These new forms show differences in the biochemical characteristics of the prion protein and, where reported, tend to occur in aged animals but descriptions of clinical presentation are incomplete or absent.
 
Materials and Methods. Female Hereford/Angus cross calves were intracranially challenged at approximately five months of age with 1 ml of a 10% brain homogenate originating from Canadian field cases of BSE which had been previously classified as C-, L-, or H- type.
 
The animals were monitored during incubation period, and clinical disease is described using a standardized examination protocol. Incubation period, description and progression of clinical signs was recorded and videotaped for objective evaluation.
 
Results. All L- and H- type atypical BSE challenged animals began to display signs of clinical disease at approximately 11 months post inoculation, and disease progression was slow but constant until animals were euthanized. Clinical signs in all atypical BSE inoculated animals included hesitation at doors and gates, spontaneous muscle fasciculations and sensitivity to touch. Teeth grinding and excessive salivation are occasionally noted. Animals with L-type BSE are very anxious and show high levels of sensitivity to hand movement. One H-type animal shows periods of somnolence. Both H-type inoculated animals go down during handling and have difficulty rising and show sensitivity to movement around their head and neck area, but to a lesser degree than the L-type BSE inoculated animals. Interestingly, no locomotor abnormalities have been observed in either group.
 
C-type challenged animals remain normal at approximately 18 months post inoculation. Clinical disease in C-type inoculated animals from a previous transmission study was typically slow and intermittently displayed during the initial stages and after a period of two to four months was more consistent and progressive. Clinical signs in C-type BSE were as previously reported in the literature.
 
Discussion. The spectrum of clinical signs for all three types of BSE examined is similar. Incubation period is shorter for H- and L-type BSE as compared with C-type. Once clinical signs begin, progression is slow but relentless in atypical BSE, and more insidious in classical BSE. A summary of clinical signs presented in the three different types of BSE will be presented, and video of clinical disease will be displayed.
 
link url not available, please see PRION 2011 ;
 
 
 
 
 
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
Title: Bovine Spongiform Encephalopathy: Docket_No_APHIS-2014-0107_BSE.pdf (236.79 KB) Authors
 
item Kehrli Jr, Marcus item Greenlee, Justin item Nicholson, Eric
 
Submitted to: Proceedings of the California Animal Nutrition Conference Publication Type: Proceedings Publication Acceptance Date: May 1, 2014 Publication Date: May 9, 2014 Citation: Kehrli Jr, M.E., Greenlee, J.J., Nicholson, E.M. 2014. Bovine Spongiform Encephalopathy: Atypical Pros and Cons. Proceedings of the California Animal Nutrition Conference, May 13-16, 2014, Fresno, California. p. 70-81.
 
Technical Abstract:
 
Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases that affect several mammalian species including human beings. Four animal TSE agents have been reported: scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; transmissible mink encephalopathy (TME) and bovine spongiform encephalopathy (BSE). In comparison with contagious bacterial, viral and parasitic infectious diseases, TSEs typically do not present with high morbidity or mortality rates in livestock, wildlife or human populations. The TSEs, however, remain important because of public health and international or domestic trade issues involving movement of animals. In response to the discovery of BSE, governments around the world began investing in research to determine the origin of BSE and the host range of the recognized TSEs. The prevailing theory at the time of the BSE discovery was that it had resulted from transmission of scrapie from sheep to cattle 82. Once the original interspecies transmission event had occurred it was then amplified by the subsequent feeding of meat and bone meal (MBM), a supplement that normally contains central nervous system (CNS) tissues, which inevitably became contaminated with CNS tissues from BSE affected cattle. Such practice precipitated more BSE cases, thus resulting in greater volumes of contaminated MBM supplement assisted by growing inventories of contaminated MBM prior to its discovery. Epidemiological studies suggest that classical BSE spreads through contaminated feedstuffs, and early in the UK epizootic it was suspected that the origin of the disease was scrapie,82,83 a TSE known to exist in sheep for over 200 years. However, experimental transmission of scrapie to cattle by a natural route has failed to produce disease, and while transmission of scrapie or CWD to cattle by the intracranial route produces a disease in cattle, they fail to accurately reproduce the clinical and pathologic features of BSE in cattle.25,27 Thus the origin of classical BSE remains unclear. In humans, TSEs can be acquired through exposure to infectious material, inherited as germline polymorphisms in the prion gene (PRNP), or occur spontaneously. This appears to be true in cattle as well with the belief that atypical BSE is of either spontaneous or genetic origin, and classical BSE was the form transmitted through the feeding of contaminated MBM. The original contamination of MBM in the UK remains unknown but presumably was contaminated with some form of either a spontaneous or genetic form of BSE or another not yet evaluated TSE from another host.
 
 
Tuesday, July 21, 2009
 
Transmissible mink encephalopathy - review of the etiology
 
 
Saturday, December 01, 2007
 
Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model
 
 
Sunday, December 10, 2006
 
Transmissible Mink Encephalopathy TME
 
 
 
Saturday, June 25, 2011
 
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
 
"BSE-L in North America may have existed for decades"
 
 
 
SUMMARY REPORT CALIFORNIA ATYPICAL L-TYPE BOVINE SPONGIFORM ENCEPHALOPATHY CASE INVESTIGATION JULY 2012 CALIFORNIA
 
Summary Report BSE 2012
 
Executive Summary
 
 
Saturday, August 4, 2012
 
Final Feed Investigation Summary - California atypical L-type BSE Case - July 2012
 
 
Saturday, August 4, 2012
 
Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation
 
 
Thursday, March 29, 2012
 
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012 NIAA Annual Conference April 11-14, 2011 San Antonio, Texas
 
 
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, I believe around Hidalgo county, could this be ground zero?
 
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 ;
 
 
P.97: 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
 
Justin Greenlee1, S Jo Moore1, Jodi Smith1, M Heather West Greenlee2, and Robert Kunkle1
 
1National Animal Disease Center; Ames, IA USA;
 
2Iowa State University; Ames, IA USA
 
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 D 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 2 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, 2 distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.
 
 
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.
 
 
 
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.
 
 
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 ;
 
 
Friday, April 22, 2016
 
*** Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer
 
 
Saturday, April 02, 2016
 
TEXAS TAHC BREAKS IT'S SILENCE WITH TWO MORE CASES CWD CAPTIVE DEER BRINGING TOTAL TO 10 CAPTIVES REPORTED TO DATE
 
 
Friday, February 26, 2016
 
TEXAS Hartley County Mule Deer Tests Positive for Chronic Wasting Disease CWD TSE Prion
 
 
Tuesday, July 21, 2015
 
*** Texas CWD Medina County Herd Investigation Update July 16, 2015 ***
 
 
Thursday, July 09, 2015
 
TEXAS Chronic Wasting Disease (CWD) Herd Plan for Trace-Forward Exposed Herd with Testing of Exposed Animals
 
 
Wednesday, July 01, 2015
 
TEXAS Chronic Wasting Disease Detected in Medina County Captive Deer
 
 
Wednesday, March 18, 2015
 
Chronic Wasting Disease CWD Confirmed Texas Trans Pecos March 18, 2015
 
 
Wednesday, March 25, 2015
 
Chronic Wasting Disease CWD Cases Confirmed In New Mexico 2013 and 2014 UPDATE 2015
 
 
Thursday, May 02, 2013
 
*** Chronic Wasting Disease (CWD) Texas Important Update on OBEX ONLY TEXTING
 
 
Monday, February 11, 2013
 
TEXAS CHRONIC WASTING DISEASE CWD Four New Positives Found in Trans Pecos
 
 
Tuesday, July 10, 2012
 
Chronic Wasting Disease Detected in Far West Texas
 
 
Monday, March 26, 2012
 
Texas Prepares for Chronic Wasting Disease CWD Possibility in Far West Texas
 
 
Wednesday, February 10, 2016
 
*** Wisconsin Two deer that escaped farm had chronic wasting disease CWD ***
 
 
Sunday, January 17, 2016
 
*** Wisconsin Captive CWD Lotto Pays Out Again indemnity payment of $298,770 for 228 white-tailed deer killed on farm ***
 
 
WISCONSIN CHRONIC WASTING DISEASE CWD TSE PRION SPIRALING FURTHER INTO THE ABYSS UPDATE
 
 
Arkansas Chronic Wasting Disease CWD TSE Prion and Elk Restoration Project and Hunkering Down in the BSE Situation Room USDA 1998
 
 
Monday, April 25, 2016
 
Arkansas AGFC Phase 2 sampling reveals CWD positive deer in Madison and Pope counties
 
 
Tuesday, April 19, 2016
 
Arkansas First Phase of CWD sampling reveals 23 percent prevalence rate in focal area With 82 Confirmed to Date
 
 
PENNSYLVANIA TWELVE MORE CASES OF CWD FOUND: STATE GEARS UP FOR ADDITIONAL CONTROL MEASURES
 
 
Friday, April 22, 2016
 
Missouri MDC finds seven new cases of ChronicWasting Disease CWD during past‐season testing
 
 
Friday, April 22, 2016
 
COLORADO CHRONIC WASTING DISEASE CWD TSE PRION SURVEILLANCE AND TESTING PROGRAM IS MINIMAL AND LIMITED
 
 
KANSAS CWD CASES ALARMING
 
Wednesday, March 02, 2016 Kansas Chronic Wasting Disease CWD TSE Prion 52 cases 2015 updated report 'ALARMING'
 
 
Tuesday, February 02, 2016
 
Illinois six out of 19 deer samples tested positive for CWD in the Oswego zone of Kendall County
 
 
*** SEE CWD HIGH INFECTION RATE MAPS FOR COLORADO ! ***
 
 
I could go on, for more see ;
 
Thursday, March 31, 2016
 
*** Chronic Wasting Disease CWD TSE Prion Roundup USA April 1, 2016 ***
 
 
 
*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr. Submission ***
 
Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats
 
SUMMARY: We are reopening the comment period for our proposed rule that would revise completely the scrapie regulations, which concern the risk groups and categories established for individual animals and for flocks, the use of genetic testing as a means of assigning risk levels to animals, movement restrictions for animals found to be genetically less susceptible or resistant to scrapie, and recordkeeping requirements. This action will allow interested persons additional time to prepare and submit comments.DATES: The comment period for the proposed rule published on September 10, 2015 (80 FR 54660-54692) is reopened. We will consider all comments that we receive on or before December 9, 2015. ...
 
 
 
 
Comment from Terry Singeltary This is a Comment on the Animal and Plant Health Inspection Service (APHIS) Proposed Rule: Scrapie in Sheep and Goats
 
For related information, Open Docket Folder Docket folder icon
 
--------------------------------------------------------------------------------
 
Show agency attachment(s) AttachmentsView All (0)
 
--------------------------------------------------------------------------------
 
Comment View document:Indeed, much science has changed about the Scrapie TSE prion, including more science linking Scrapie to humans. sadly, politics, industry, and trade, have not changed, and those usually trump sound science, as is the case with all Transmissible Spongiform Encephalopathy TSE Prion disease in livestock producing animals and the OIE. we can look no further at the legal trading of the Scrapie TSE prion both typical and atypical of all strains, and CWD all stains. With as much science of old, and now more new science to back this up, Scrapie of all types i.e. atypical and typical, BSE all strains, and CWD all strains, should be regulated in trade as BSE TSE PRION. In fact, I urge APHIS et al and the OIE, and all trading partners to take heed to the latest science on the TSE prion disease, all of them, and seriously reconsider the blatant disregards for human and animal health, all in the name of trade, with the continued relaxing of TSE Prion trade regulations through the 'NEGLIGIBLE BSE RISK' PROGRAM, which was set up to fail in the first place. If the world does not go back to the 'BSE RISK ASSESSMENTS', enhance, and or change that assessment process to include all TSE prion disease, i.e. 'TSE RISK ASSESSMENT', if we do not do this and if we continue this farce with OIE and the USDA et al, and the 'NEGLIGIBLE BSE RISK' PROGRAM, we will never eradicate the TSE prion aka mad cow type disease, they will continue to mutate and spread among species of human and animal origin, and they will continue to kill. ...
 
please see ;
 
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 longe 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***
 
===============
 
 
***This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans.
 
***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.
 
 
please see file attachment for full submission and recent science and my deep concerns on the TSE Prion disease... No documents available. AttachmentsView All (1) scrapie-usa-blogspot-com View Attachment:
 
 
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 about 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. Whether they were scrapie infected sheep or not is unclear. There were domestic sheep and goats present in the facility also in the 1960's but there is no evidence that these animals developed scrapie. During the 60's hybridization studies between the Bighorn and domestic sheep were carried out, again, without evidence of scrapie. Domestic goats were also kept at Sybille in the 1960's. ...
 
snip...see full text ;
 
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. ...
 
 
snip...see full text ;
 
Colorado CWD
 
SEE CWD HIGH INFECTION RATE MAPS FOR COLORADO !
 
 
P.97: 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
 
Justin Greenlee1, S Jo Moore1, Jodi Smith1, M Heather West Greenlee2, and Robert Kunkle1
 
1National Animal Disease Center; Ames, IA USA;
 
2Iowa State University; Ames, IA USA
 
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 D 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 2 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, 2 distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.
 
 
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.
 
 
 
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.
 
 
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 ;
 
 
Thursday, April 07, 2016
 
What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016
 
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008).
 
***In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research, however, suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008). It is apparent, though, that CWD is affecting wild and farmed cervid populations in endemic areas with some deer populations decreasing as a result.
 
snip...
 
SNIP...
 
 
Tuesday, May 31, 2016
 
New insights in the transfusional risk assessment of variant Creutzfeldt-Jakob Disease: Transfusional transmission of vCJD prions in the absence of detectable abnormal prion protein Prion 2016 Tokyo
 
 
Tuesday, May 31, 2016
 
Priority Interim Position Paper PROTECTING THE FOOD CHAIN FROM PRIONS Perspectives
 
 
Sent: Monday, January 08,2001 3:03 PM
 
TO: freas@CBS5055530.CBER.FDA.GOV
 
FDA CJD BSE TSE Prion Scientific Advisors and Consultants Staff January 2001 Meeting Singeltary Submission
 
2001 FDA CJD TSE Prion Singeltary Submission
 
 
Terry S. Singeltary Sr.

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