Source: http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html
Timestamp: 2017-06-22 16:29:45
Document Index: 208333845

Matched Legal Cases: ['art 2015', 'art 2015', 'art 2016', 'art 2016', 'art 2009', 'art 2016']

Purchase options Price * Issue Purchase USD 198.00 http://www.tandfonline.com/toc/kprn20/10/sup1 Cervid to human prion transmission Kong, Qingzhong Case Western Reserve University, Cleveland, OH, United States Abstract Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans. We hypothesize that: (1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues; (2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence; (3) Reliable essays can be established to detect CWD infection in humans;and (4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches. Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of "humanized" Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental "human CWD" samples will also be generated for Aim 3. Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1. Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental "human CWD" samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions. Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans. Public Health Relevance There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans. Funding Agency Agency National Institute of Health (NIH) Institute National Institute of Neurological Disorders and Stroke (NINDS) Type Research Project (R01) Project # 1R01NS088604-01A1 Application # 9037884 Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND) Program Officer Wong, May Project Start 2015-09-30 Project End 2019-07-31 Budget Start 2015-09-30 Budget End 2016-07-31 Support Year 1 Fiscal Year 2015 Total Cost $337,507 Indirect Cost $118,756 Institution Name Case Western Reserve University Department Pathology Type Schools of Medicine DUNS # 077758407 City Cleveland State OH Country United States Zip Code 44106 http://grantome.com/grant/NIH/R01-NS088604-01A1 =========================================================== We hypothesize that: (1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues; (2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence; (3) Reliable essays can be established to detect CWD infection in humans;and (4) *** CWD transmission to humans has already occurred. *** We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches. ============================================================ Key Molecular Mechanisms of TSEs Zabel, Mark D. Colorado State University-Fort Collins, Fort Collins, CO, United States Abstract Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative diseases affecting humans, cervids, bovids, and ovids. The absolute requirement of PrPC expression to generate prion diseases and the lack of instructional nucleic acid define prions as unique infectious agents. Prions exhibit species-specific tropism, inferring that unique prion strains exist that preferentially infct certain host species and confront transmission barriers to heterologous host species. However, transmission barriers are not absolute. Scientific consensus agrees that the sheep TSE scrapie probably breached the transmission barrier to cattle causing bovine spongiform encephalopathy that subsequently breached the human transmission barrier and likely caused several hundred deaths by a new-variant form of the human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease of cervids, overcoming similar human transmission barriers. A groundbreaking discovery made last year revealed that mice infected with heterologous prion strains facing significant transmission barriers replicated prions far more readily in spleens than brains6. Furthermore, these splenic prions exhibited weakened transmission barriers and expanded host ranges compared to neurogenic prions. These data question conventional wisdom of avoiding neural tissue to avoid prion xenotransmission, when more promiscuous prions may lurk in extraneural tissues. Data derived from work previously funded by NIH demonstrate that Complement receptors CD21/35 bind prions and high density PrPC and differentially impact prion disease depending on the prion isolate or strain used. Recent advances in live animal and whole organ imaging have led us to generate preliminary data to support novel, innovative approaches to assessing prion capture and transport. We plan to test our unifying hypothesis for this proposal that CD21/35 control the processes of peripheral prion capture, transport, strain selection and xenotransmission in the following specific aims. 1. Assess the role of CD21/35 in splenic prion strain selection and host range expansion. 2. Determine whether CD21/35 and C1q differentially bind distinct prion strains 3. Monitor the effects of CD21/35 on prion trafficking in real time and space 4. Assess the role of CD21/35 in incunabular prion trafficking Public Health Relevance Transmissible spongiform encephalopathies, or prion diseases, are devastating illnesses that greatly impact public health, agriculture and wildlife in North America and around the world. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease (CWD) of cervids, overcoming similar human transmission barriers. Early this year Canada reported its first case of BSE in over a decade audits first case of CWD in farmed elk in three years, underscoring the need for continued vigilance and research. Identifying mechanisms of transmission and zoonoses remains an extremely important and intense area of research that will benefit human and other animal populations. Funding Agency Agency National Institute of Health (NIH) Institute National Institute of Allergy and Infectious Diseases (NIAID) Type High Priority, Short Term Project Award (R56) Project # 1R56AI122273-01A1 Application # 9211114 Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND) Program Officer Beisel, Christopher E Project Start 2016-02-16 Project End 2017-01-31 Budget Start 2016-02-16 Budget End 2017-01-31 Support Year 1 Fiscal Year 2016 Total Cost Indirect Cost Institution Name Colorado State University-Fort Collins Department Microbiology/Immun/Virology Type Schools of Veterinary Medicine DUNS # 785979618 City Fort Collins State CO Country United States Zip Code 80523 http://grantome.com/grant/NIH/R56-AI122273-01A1 PMCA Detection of CWD Infection in Cervid and Non-Cervid Species Hoover, Edward Arthur Colorado State University-Fort Collins, Fort Collins, CO, United States Abstract Chronic wasting disease (CWD) of deer and elk is an emerging highly transmissible prion disease now recognized in 18 States, 2 Canadian provinces, and Korea. We have shown that Infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces, and in the tissues generating those body fluids and excreta, thereby leading to facile transmission by direct contact and environmental contamination. We have also shown that CWD can infect some non-cervid species, thus the potential risk CWD represents to domestic animal species and to humans remains unknown. Whether prions borne in blood, saliva, nasal fluids, milk, or excreta are generated or modified in the proximate peripheral tissue sites, may differ in subtle ways from those generated in brain, or may be adapted for mucosal infection remain open questions. The increasing parallels in the pathogenesis between prion diseases and human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, add relevance to CWD as a transmissible protein misfolding disease. The overall goal of this work is to elucidate the process of CWD prion transmission from mucosal secretory and excretory tissue sites by addressing these questions: (a) What are the kinetics and magnitude of CWD prion shedding post-exposure? (b) Are excreted prions biochemically distinct, or not, from those in the CNS? (c) Are peripheral epithelial or CNS tissues, or both, the source of excreted prions? and (d) Are excreted prions adapted for horizontal transmission via natural/trans-mucosal routes? The specific aims of this proposal are: (1) To determine the onset and consistency of CWD prion shedding in deer and cervidized mice; (2); To compare the biochemical and biophysical properties of excretory vs. CNS prions; (3) To determine the capacity of peripheral tissues to support replication of CWD prions; (4) To determine the protease- sensitive infectious fraction of excreted vs. CNS prions; and (5) To compare the mucosal infectivity of excretory vs. CNS prions. Understanding the mechanisms that enable efficient prion dissemination and shedding will help elucidate how horizontally transmissible prions evolve and succeed, and is the basis of this proposal. Understanding how infectious misfolded proteins (prions) are generated, trafficked, shed, and transmitted will aid in preventing, treating, and managing the risks associated with these agents and the diseases they cause. Public Health Relevance Chronic wasting disease (CWD) of deer and elk is an emergent highly transmissible prion disease now recognized throughout the USA as well as in Canada and Korea. We have shown that infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces thereby leading to transmission by direct contact and environmental contamination. In that our studies have also shown that CWD can infect some non-cervid species, the potential risk CWD may represents to domestic animal species and humans remains unknown. The increasing parallels in the development of major human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, and prion diseases add relevance to CWD as a model of a transmissible protein misfolding disease. Understanding how infectious misfolded proteins (prions) are generated and transmitted will aid in interrupting, treating, and managing the risks associated with these agents and the diseases they cause. Funding Agency Agency National Institute of Health (NIH) Institute National Institute of Neurological Disorders and Stroke (NINDS) Type Research Project (R01) Project # 4R01NS061902-07 Application # 9010980 Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND) Program Officer Wong, May Project Start 2009-09-30 Project End 2018-02-28 Budget Start 2016-03-01 Budget End 2017-02-28 Support Year 7 Fiscal Year 2016 Total Cost $409,868 Indirect Cost $134,234 Institution Name Colorado State University-Fort Collins Department Microbiology/Immun/Virology Type Schools of Veterinary Medicine DUNS # 785979618 City Fort Collins State CO Country United States Zip Code 80523 http://grantome.com/grant/NIH/R01-NS061902-07 *** WDA 2016 NEW YORK *** We found that CWD adapts to a new
host more readily than BSE and that human PrP was unexpectedly prone to
region that confers unusual susceptibility to conversion by CWD prions. Student Presentations Session 2 The species barriers and public
health threat of CWD and BSE prions Ms. Kristen Davenport1, Dr. Davin
Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State
University Chronic wasting disease (CWD) is
spreading rapidly through cervid populations in the USA. Bovine spongiform
has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication
Research Contributes to Wildlife Trust Administration Exploring perceptions
about chronic wasting disease risks among wildlife and agriculture
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).*** https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249 Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
https://cpw.state.co.us/Documents/Hunting/BigGame/CWD/PDF/ResearchArticles/EID_CDWPotTrans.pdf now, let’s see what the authors said about this casual link, personal communications years ago. see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans” From: TSS (216-119-163-189.ipset45.wt.net) Subject: CWD aka MAD DEER/ELK TO HUMANS ??? Date: September 30, 2002 at 7:06 am PST From: "Belay, Ermias" To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias" Sent: Monday, September 30, 2002 9:22 AM Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated. Ermias Belay, M.D. Centers for Disease Control and Prevention -----Original Message----- From: Sent: Sunday, September 29, 2002 10:15 AM To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS Thursday, April 03, 2008 A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ. snip... *** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***, snip... full text ; http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html CJD is so rare in people under age 30, one case in a billion (leaving out medical mishaps), that four cases under 30 is "very high," says Colorado neurologist Bosque. "Then, if you add these other two from Wisconsin [cases in the newspaper], six cases of CJD in people associated with venison is very, very high." Only now, with Mary Riley, there are at least seven, and possibly eight, with Steve, her dining companion. "It's not critical mass that matters," however, Belay says. "One case would do it for me." The chance that two people who know each other would both contact CJD, like the two Wisconsin sportsmen, is so unlikely, experts say, it would happen only once in 140 years. Given the incubation period for TSEs in humans, it may require another generation to write the final chapter on CWD in Wisconsin. "Does chronic wasting disease pass into humans? We'll be able to answer that in 2022," says Race. Meanwhile, the state has become part of an immense experiment. https://www.organicconsumers.org/old_articles/madcow/killer123103.php I urge everyone to watch this video closely...terry *** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans *** http://zoomify.uzh.ch:8080/zoomify/videos/video-004/video-004.html Envt.07: Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease ***The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans. http://www.landesbioscience.com/journals/prion/Prion5-Supp-PrionEnvironment.pdf?nocache=1333529975 Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Rachel C. Angers1,*, Shawn R. Browning1,*,†, Tanya S. Seward2, Christina J. Sigurdson4,‡, Michael W. Miller5, Edward A. Hoover4, Glenn C. Telling1,2,3,§ snip... Abstract The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure. http://www.sciencemag.org/content/311/5764/1117.long ***********CJD REPORT 1994 increased risk for consumption of veal and venison and lamb*********** CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994 Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss) These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ... Table 9 presents the results of an analysis of these data. There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01). Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal. There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51). The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02). The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08). snip... It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05). snip... In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ... snip... In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS) snip...see full report ; http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf CJD9/10022 October 1994 Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ Dear Mr Elmhirst, CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published. The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication. The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department. The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme. I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all. http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf *** 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).*** https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249 O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. *** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, ***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), ***is the third potentially zoonotic PD (with BSE and L-type BSE), ***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. =============== ***thus questioning the origin of human sporadic cases*** =============== ***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. ============== https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf 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. http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160 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 http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf ”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. http://collections.europarchive.org/tna/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf 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. ... http://web.archive.org/web/20060307063531/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf 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... http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/mb/m09/tab05.pdf http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/mb/m09a/tab01.pdf http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf 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).*** https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249 Saturday, May 30, 2015 PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf http://transmissiblespongiformencephalopathy.blogspot.com/2015/05/prion-2015-oral-and-poster.html Wednesday, June 10, 2015 Zoonotic Potential of CWD Prions LATE-BREAKING ABSTRACTS http://chronic-wasting-disease.blogspot.com/2015/06/zoonotic-potential-of-cwd-prions.html Friday, April 22, 2016 Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer http://scrapie-usa.blogspot.com/2016/04/texas-scrapie-confirmed-in-hartley.html Thursday, April 07, 2016 What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016
What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016 http://chronic-wasting-disease.blogspot.com/2016/04/what-is-risk-of-chronic-wasting-disease.html Tuesday, April 12, 2016 *** The first detection of Chronic Wasting Disease (CWD) in Europe
http://chronic-wasting-disease.blogspot.com/2016/04/the-first-detection-of-chronic-wasting.html Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission Greetings again FDA and Mr. Pritchett et al, I would kindly like to comment on ; Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission #158 Guidance for Industry Use of Material from Deer and Elk in Animal Feed This version of the guidance replaces the version made available September15, 2003. This document has been revised to update the docket number, contact information, and standard disclosures. Submit comments on this guidance at any time. Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified with the Docket No. FDA-2003-D-0432 (formerly 03D-0186). For further information regarding this guidance, contact Burt Pritchett, Center for Veterinary Medicine (HFV-222), Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, 240-402-6276, E-mail: burt.pritchett@fda.hhs.gov. Additional copies of this guidance document may be requested from the Policy and Regulations Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, and may be viewed on the Internet at either http://www.fda.gov/AnimalVeterinary/default.htm or http://www.regulations.gov. U.S. Department of Health and Human Services Food and Drug Administration Center for Veterinary Medicine March 2016 Contains Nonbinding Recommendations 2 Guidance for Industry Use of Material from Deer and Elk in Animal Feed This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title page. I. Introduction Under FDA’s BSE feed regulation (21 CFR 589.2000) most material from deer and elk is prohibited for use in feed for ruminant animals. This guidance document describes FDA’s recommendations regarding the use in all animal feed of all material from deer and elk that are positive for Chronic Wasting Disease (CWD) or are considered at high risk for CWD. The potential risks from CWD to humans or non-cervid animals such as poultry and swine are not well understood. However, because of recent recognition that CWD is spreading rapidly in white-tailed deer, and because CWD’s route of transmission is poorly understood, FDA is making recommendations regarding the use in animal feed of rendered materials from deer and elk that are CWD-positive or that are at high risk for CWD. In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required. II. Background CWD is a neurological (brain) disease of farmed and wild deer and elk that belong in the animal family cervidae (cervids). Only deer and elk are known to be susceptible to CWD by natural transmission. The disease has been found in farmed and wild mule deer, white-tailed deer, North American elk, and in farmed black-tailed deer. CWD belongs to a family of animal and human diseases called transmissible spongiform encephalopathies (TSEs). These include bovine spongiform encephalopathy (BSE or “mad cow” disease) in cattle; scrapie in sheep and goats; and classical and variant Creutzfeldt-Jakob diseases (CJD and vCJD) in humans. There is no known treatment for these diseases, and there is no vaccine to prevent them. In addition, although validated postmortem diagnostic tests are available, there are no validated diagnostic tests for CWD that can be used to test for the disease in live animals. Contains Nonbinding Recommendations III. Use in animal feed of material from CWD-positive deer and elk Material from CWD-positive animals may not be used in any animal feed or feed ingredients. Pursuant to Sec. 402(a)(5) of the Federal Food, Drug, and Cosmetic Act, animal feed and feed ingredients containing material from a CWD-positive animal would be considered adulterated. FDA recommends that any such adulterated feed or feed ingredients be recalled or otherwise removed from the marketplace. IV. Use in animal feed of material from deer and elk considered at high risk for CWD Deer and elk considered at high risk for CWD include: (1) animals from areas declared by State officials to be endemic for CWD and/or to be CWD eradication zones; and (2) deer and elk that at some time during the 60-month period immediately before the time of slaughter were in a captive herd that contained a CWD-positive animal. FDA recommends that materials from deer and elk considered at high risk for CWD no longer be entered into the animal feed system. Under present circumstances, FDA is not recommending that feed made from deer and elk from a non-endemic area be recalled if a State later declares the area endemic for CWD or a CWD eradication zone. In addition, at this time, FDA is not recommending that feed made from deer and elk believed to be from a captive herd that contained no CWD-positive animals be recalled if that herd is subsequently found to contain a CWD-positive animal. V. Use in animal feed of material from deer and elk NOT considered at high risk for CWD FDA continues to consider materials from deer and elk NOT considered at high risk for CWD to be acceptable for use in NON-RUMINANT animal feeds in accordance with current agency regulations, 21 CFR 589.2000. Deer and elk not considered at high risk include: (1) deer and elk from areas not declared by State officials to be endemic for CWD and/or to be CWD eradication zones; and (2) deer and elk that were not at some time during the 60-month period immediately before the time of slaughter in a captive herd that contained a CWD-positive animal. 3 http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM052506.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission Greetings again FDA and Mr. Pritchett et al, MY comments and source reference of sound science on this very important issue are as follows ; Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission I kindly wish to once again submit to Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed. Thank you kindly for allowing me to comment again, ...and again...and again, on a topic so important, why it is ‘NON-BINDING’ is beyond me. this should have been finalized and made ‘BINDING’ or MANDATORY OVER A DECADE AGO. but here lay the problem, once made ‘BINDING’ or ‘MANDATORY’, it is still nothing but ink on paper. we have had a mad cow feed ban in place since August 1997, and since then, literally 100s of millions of pounds BANNED MAD COW FEED has been sent out to commerce and fed out (see reference materials). ENFORCEMENT OF SAID BINDING REGULATIONS HAS FAILED US TOO MANY TIMES. so, in my opinion, any non-binding or voluntary regulations will not work, and to state further, ‘BINDING’ or MANDATORY regulations will not work unless enforced. with that said, we know that Chronic Wasting Disease CWD TSE Prion easily transmits to other cervid through the oral route. the old transmission studies of BSE TSE floored scientist once they figured out what they had, and please don’t forget about those mink that were fed 95%+ dead stock downer cow, that all came down with TME. please see ; It is clear that the designing scientists must also have shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection. http://web.archive.org/web/20061003022720/http://www.bseinquiry.gov.uk/files/ws/s145d.pdf it is clear that the designing scientists must have also shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection. http://web.archive.org/web/20030526212610/http://www.bseinquiry.gov.uk/files/ws/s147f.pdf 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... http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/mb/m09/tab05.pdf *** PLEASE SEE THIS URGENT UPDATE ON CWD AND FEED ANIMAL PROTEIN *** Sunday, March 20, 2016 Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed ***UPDATED MARCH 2016*** Singeltary Submission http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM052506.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery http://chronic-wasting-disease.blogspot.com/2016/03/docket-no-fda-2003-d-0432-formerly-03d.html Sunday, March 20, 2016 UPDATED MARCH 2016 URGENT Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission http://chronic-wasting-disease.blogspot.com/2016/03/docket-no-fda-2003-d-0432-formerly-03d.html Tuesday, April 19, 2016 Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission http://madcowfeed.blogspot.com/2016/04/docket-no-fda-2013-n-0764-for-animal.html
http://www.plosone.org/annotation/listThread.action?root=85351 Thursday, March 31, 2016 *** Chronic Wasting Disease CWD TSE Prion Roundup USA 2016 ***
http://chronic-wasting-disease.blogspot.com/2016/03/chronic-wasting-disease-cwd-tse-prion.html *** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ; http://www.plosone.org/annotation/listThread.action;jsessionid=635CE9094E0EA15D5362B7D7B809448C?root=7143 *** It also suggests a similar cause or source for atypical BSE in these countries. *** Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. *** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *** It also suggests a similar cause or source for atypical BSE in these countries. *** see page 176 of 201 pages...tss http://www.neuroprion.org/resources/pdf_docs/conferences/prion2009/prion2009_bookofabstracts.pdf Saturday, April 16, 2016 APHIS [Docket No. APHIS-2016-0029] Secretary's Advisory Committee on Animal Health; Meeting May 2, 2016, and June 16, 2016 Singeltary Submission http://animalhealthreportpriontse.blogspot.com/2016/04/aphis-docket-no-aphis-2016-0029.html Sunday, May 1, 2016 Center for Biologics Evaluation and Research 25th Meeting of: The Transmissible Spongiform Encephalopathies Advisory Committee June 1, 2015 Transcript AND DRUG ADMINISTRATION
Please note, I do not advertise or make money from these blogs full of TSE Prions. they are for educational use, just made a promise to Mom, never forget, and never let them forget. MOM DOD 12/14/97 confirmed Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD...
Strikingly PMCA also revealed the presence of consistent level of vCJD prion in various other tissues like liver, salivary gland, kidney or bone marrow. Bioassays carried out using certain of these tissues confirmed the presence of vCJD infectivity. These data confirm the possibility of a vCJD transmission risk that could be associated to various medical procedures (surgery, tissue grafts). They also represent an important contribution towards developing adapted prevention measures to mitigate the risk of vCJD iatrogenic transmission. http://www.tandfonline.com/doi/suppl/10.1080/19336896.2016.1173501 *** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract Saturday, April 23, 2016
v-CJD prion distribution in the tissues of patients at preclinical and clinical stage of the disease http://vcjd.blogspot.com/2016/04/v-cjd-prion-distribution-in-tissues-of.html Terry S. Singeltary Sr., Bacliff, Texas USA 77518 flounder9@verizon.net
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