Saturday, May 30, 2015

PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS

PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS

 

THANK YOU PRION 2015 TAYLOR & FRANCIS, Professor Chernoff, and Professor Aguzzi et al, for making these PRION 2015 Congressional Poster and Oral Abstracts available freely to the public. ...Terry S. Singeltary Sr.

 

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, Val erie 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...TSS

 

===============

 

O.08: H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism: Clinical and pathologic features in wild-type and E211K cattle following intracranial inoculation

 

S Jo Moore, M Heather West Greenlee, Jodi Smith, Eric Nicholson, Cathy Vrentas, and Justin Greenlee United States Department of Agriculture; Ames, IA USA

 

In 2006 an H-type bovine spongiform encephalopathy (BSE) case was reported in an animal with an unusual polymorphism (E211K) in the prion protein gene. Although the prevalence of this polymorphism is low, cattle carrying the K211 allele are predisposed to rapid onset of H-type BSE when exposed. The purpose of this study was to investigate the phenotype of this BSE strain in wild-type (E211E) and E211K heterozygous cattle. One calf carrying the wild-type allele and one E211K calf were inoculated intracranially with H-type BSE brain homogenate from the US 2006 case that also carried one K211 allelle. In addition, one wild-type calf and one E211K calf were inoculated intracranially with brain homogenate from a US 2003 classical BSE case. All animals succumbed to clinical disease. Survival times for E211K H-type BSE inoculated catttle (10 and 18 months) were shorter than the classical BSE inoculated cattle (both 26 months). Significant changes in retinal function were observed in H-type BSE challenged cattle only. Animals challenged with the same inoculum showed similar severity and neuroanatomical distribution of vacuolation and disease-associated prion protein deposition in the brain, though differences in neuropathology were observed between E211K H-type BSE and classical BSE inoculated animals. Western blot results for brain tissue from challenged animals were consistent with the inoculum strains. ***This study demonstrates that the phenotype of E211K H-type BSE remains stable when transmitted to cattle without the E211K polymorphism, and exhibits a number of features that differ from classical BSE in both wild-type and E211K cattle.

 

==============

 

***This study demonstrates that the phenotype of E211K H-type BSE remains stable when transmitted to cattle without the E211K polymorphism, and exhibits a number of features that differ from classical BSE in both wild-type and E211K cattle.***

 

PLEASE SEE ;

 

Wednesday, May 27, 2015

 

BSE Case Associated with Prion Protein Gene Mutation

 


 

 

==============

 

P.108: Successful oral challenge of adult cattle with classical BSE

 

Sandor Dudas1,*, Kristina Santiago-Mateo1, Tammy Pickles1, Catherine Graham2, and Stefanie Czub1 1Canadian Food Inspection Agency; NCAD Lethbridge; Lethbridge, Alberta, Canada; 2Nova Scotia Department of Agriculture; Pathology Laboratory; Truro, Nova Scotia, Canada

 

Classical Bovine spongiform encephalopathy (C-type BSE) is a feed- and food-borne fatal neurological disease which can be orally transmitted to cattle and humans. Due to the presence of contaminated milk replacer, it is generally assumed that cattle become infected early in life as calves and then succumb to disease as adults.

 

Here we challenged three 14 months old cattle per-orally with 100 grams of C-type BSE brain to investigate age-related susceptibility or resistance. During incubation, the animals were sampled monthly for blood and feces and subjected to standardized testing to identify changes related to neurological disease.

 

At 53 months post exposure, progressive signs of central nervous system disease were observed in these 3 animals, and they were euthanized. Two of the C-BSE animals tested strongly positive using standard BSE rapid tests, however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE. Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

 

Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. We are further examining explanations for the unusual disease presentation in the third challenged animal.

 

========================

 

***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. ***

 

P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification

 

Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal Health; Tsukuba, Japan

 

To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).

 

Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.

 

Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, ***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.

 

================

 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. ***

 

ALSO, PLEASE SEE ;

 

31 Jan 2015 at 20:14 GMT

 

*** Ruminant feed ban for cervids in the United States? ***

 

31 Jan 2015 at 20:14 GMT

 


 


 

 

================

 

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

 

The propensity for trans-species prion transmission is related to the structural characteristics of the enciphering and heterologous PrP, but the exact mechanism remains mostly mysterious. Studies of the effects of primary or tertiary prion protein structures on trans-species prion transmission have relied primarily upon animal bioassays, making the influence of prion protein structure vs. host co-factors (e.g. cellular constituents, trafficking, and innate immune interactions) difficult to dissect. As an alternative strategy, we used real-time quakinginduced conversion (RT-QuIC) to investigate trans-species prion conversion.

 

To assess trans-species conversion in the RT-QuIC system, we compared chronic wasting disease (CWD) and bovine spongiform encephalopathy (BSE) prions, as well as feline CWD (fCWD) and feline spongiform encephalopathy (FSE). Each prion was seeded into each host recombinant PrP (full-length rPrP of white-tailed deer, bovine or feline). We demonstrated that fCWD is a more efficient seed for feline rPrP than for white-tailed deer rPrP, which suggests adaptation to the new host.

 

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.***

 

================

 

Willingham, Erin McNulty, Kelly Anderson, Jeanette Hayes-Klug, Amy Nalls, and Candace Mathiason Colorado State University; Fort Collins, CO USA

 

Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy (TSE), of free-ranging and captive cervids (deer, elk and moose).

 

The presence of infectious prions in the tissues, bodily fluids and environments of clinical and preclinical CWD-infected animals is thought to account for its high transmission efficiency. Recently it has been recognized that mother to offspring transmission may contribute to the facile transmission of some TSEs. Although the mechanism behind maternal transmission is not yet known, the extended asymptomatic TSE carrier phase (lasting years to decades) suggests that it may have implications in the spread of prions.

 

Placental trafficking and/or secretion in milk are 2 means by which maternal prion transmission may occur. In these studies we explore these avenues during early and late infection using a transgenic mouse model expressing cervid prion protein. Na€ıve and CWD-infected dams were bred at both timepoints, and were allowed to bear and raise their offspring. Milk was collected from the dams for prion analysis, and the offspring were observed for TSE disease progression. Terminal tissues harvested from both dams and offspring were analyzed for prions.

 

We have demonstrated that

 

(1) CWDinfected TgCerPRP females successfully breed and bear offspring, and

 

(2) the presence of PrPCWD in reproductive and mammary tissue from CWD-infected dams.

 

We are currently analyzing terminal tissue harvested from offspring born to CWD-infected dams for the detection of PrPCWD and amplification competent prions. These studies will provide insight into the potential mechanisms and biological significance associated with mother to offspring transmission of TSEs.

 

==============

 

P.157: Uptake of prions into plants

 

Christopher Johnson1, Christina Carlson1, Matthew Keating1,2, Nicole Gibbs1, Haeyoon Chang1, Jamie Wiepz1, and Joel Pedersen1 1USGS National Wildlife Health Center; Madison, WI USA; 2University of Wisconsin - Madison; Madison, WI USA

 

Soil may preserve chronic wasting disease (CWD) and scrapie infectivity in the environment, making consumption or inhalation of soil particles a plausible mechanism whereby na€ıve animals can be exposed to prions. Plants are known to absorb a variety of substances from soil, including whole proteins, yet the potential for plants to take up abnormal prion protein (PrPTSE) and preserve prion infectivity is not known. In this study, we assessed PrPTSE uptake into roots using laser scanning confocal microscopy with fluorescently tagged PrPTSE and we used serial protein misfolding cyclic amplification (sPMCA) and detect and quantify PrPTSE levels in plant aerial tissues. Fluorescence was identified in the root hairs of the model plant Arabidopsis thaliana, as well as the crop plants alfalfa (Medicago sativa), barley (Hordeum vulgare) and tomato (Solanum lycopersicum) upon exposure to tagged PrPTSE but not a tagged control preparation. Using sPMCA, we found evidence of PrPTSE in aerial tissues of A. thaliana, alfalfa and maize (Zea mays) grown in hydroponic cultures in which only roots were exposed to PrPTSE. Levels of PrPTSE in plant aerial tissues ranged from approximately 4 £ 10 ¡10 to 1 £ 10 ¡9 g PrPTSE g ¡1 plant dry weight or 2 £ 105 to 7 £ 106 intracerebral ID50 units g ¡1 plant dry weight. Both stems and leaves of A. thaliana grown in culture media containing prions are infectious when intracerebrally-injected into mice. ***Our results suggest that prions can be taken up by plants and that contaminated plants may represent a previously unrecognized risk of human, domestic species and wildlife exposure to prions.

 

===========

 

***Our results suggest that prions can be taken up by plants and that contaminated plants may represent a previously unrecognized risk of human, domestic species and wildlife exposure to prions.***

 

SEE ;

 

Friday, May 15, 2015 Grass Plants Bind, Retain, Uptake, and Transport Infectious Prions

 

Report

 


 

 ============

 

P.19: Characterization of chronic wasting disease isolates from freeranging deer (Odocoileus sp) in Alberta and Saskatchewan, Canada

 

Camilo Duque Velasquez1, Chiye Kim1, Nathalie Daude1, Jacques van der Merwe1, Allen Herbst1, Trent Bollinger2, Judd Aiken1, and Debbie McKenzie1 1Centre for Prions and Protein Folding Diseases; University of Alberta; Edmonton, Canada; 2Western College of Veterinary Medicine; University of Saskatchewan; Saskatoon, Canada

 

Chronic wasting disease (CWD) is an emerging prion disease of free ranging and captive species of Cervidae. In North America, CWD is enzootic in some wild cervid populations and can circulate among different deer species. The contagious nature of CWD prions and the variation of cervid PRNP alleles, which influence host susceptibility, can result in the emergence and adaptation of different CWD strains. These strains may impact transmission host range, disease diagnosis, spread dynamics and efficacy of potential vaccines. We are characterizing different CWD agents by biochemical analysis of the PrPCWD conformers, propagation in vitro cell assays1 and by comparing transmission properties and neuropathology in Tg33 (Q95G96) and Tg60 (Q95S96) mice.2 Although Tg60 mice expressing S96- PrPC have been shown resistant to CWD infectivity from various cervid species,2,3

 

***these transgenic mice are susceptible to H95 C CWD, a CWD strain derived from experimental infection of deer expressing H95G96-PrPC. The diversity of strains present in free-ranging mule deer (Odocoileus hemionus) and white-tailed deer (Odocoileus virginianus) from Alberta and Saskatchewan is being determined and will allow us to delineate the properties of CWD agents circulating in CWD enzootic cervid populations of Canada.

 

References

 

1. van der Merwe J, Aiken J, Westaway D, McKenzie D. The standard scrapie cell assay: Development, utility and prospects. Viruses 2015; 7(1):180–198; PMID:25602372; http://dx.doi.org/10.3390/v7010180

 

2. Meade-White K, Race B, Trifilo M, Bossers A, Favara C, Lacasse R, Miller M, Williams E, Oldstone M, Race R, Chesebro B. Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein. J Virol 2007; 81(9):4533–4539; PMID: 17314157; http://dx. doi.org/10.1128/JVI.02762-06

 

3. Race B, Meade-White K, Miller MW, Fox KA, Chesebro B. In vivo comparison of chronic wasting disease infectivity from deer with variation at prion protein residue 96. J Virol 2011; 85(17):9235–9238; PMID: 21697479; http://dx.doi.org/10.1128/JVI.00790-11

 

=========

 

***these transgenic mice are susceptible to H95 C CWD, a CWD strain derived from experimental infection of deer expressing H95G96-PrPC.

 

==========

 

P.136: Mother to offspring transmission of CWD—Detection in fawn tissues using the QuIC assay

 

Amy Nalls, Erin McNulty, Clare Hoover, Jeanette Hayes-Klug, Kelly Anderson, Edward Hoover, and Candace Mathiason Colorado State University; Fort Collins, CO USA

 

To investigate the role mother to offspring transmission plays in chronic wasting disease (CWD), we have employed a small, polyestrous breeding, indoor maintainable cervid model, the Reeves’ muntjac deer. Muntjac doe were inoculated with CWD and tested positive by lymphoid biopsy at 4 months post inoculation. From these CWD-infected doe, we obtained 3 viable fawns. These fawns tested IHC-positive for CWD by lymphoid biopsy as early as 40 d post birth, and all have been euthanized due to clinical disease at 31, 34 and 59 months post birth. The QuIC assay demonstrates sensitivity and specificity in the detection of conversion competent prions in peripheral IHC-positive tissues including tonsil, mandibular, partotid, retropharyngeal, and prescapular lymph nodes, adrenal gland, spleen and liver. In summary, using the muntjac deer model, we have demonstrated CWD clinical disease in offspring born to CWD-infected doe and found that the QuIC assay is an effective tool in the detection of prions in peripheral tissues. ***Our findings demonstrate that transmission of prions from mother to offspring can occur, and may be underestimated for all prion diseases.

 

===============

 

***Our findings demonstrate that transmission of prions from mother to offspring can occur, and may be underestimated for all prion diseases.

 

SEE ;

 

Friday, April 24, 2015

 

The placenta shed from goats with classical scrapie is infectious to goat kids and lambs

 


 

Tuesday, September 17, 2013

 

Mother to Offspring Transmission of Transmissible Spongiform Encephalopathy TSE prion disease

 


 

================

 

P.139: Tissue distribution and in utero transmission of chronic-wasting diseaseassociated prions in free-ranging Rocky Mountain elk

 

Anca Selariu1, Jenny G Powers2, Margaret A Wild2, Monica Brandhuber1, Amber Mayfield1, Stephenie Fullaway1, Amy Nalls1, Edward A Hoover1, and Candace K Mathiason1 1Prion Research Center; Department of Microbiology, Immunology, and Pathology; College of Veterinary Medicine and Biomedical Sciences; Colorado State University; Fort Collins, CO USA; 2National Park Service; Biological Resources Division; Fort Collins, CO USA

 

The presence of disease-associated prions in tissues and bodily fluids of chronic wasting disease (CWD)-infected cervid has received much investigation, yet little is known about CWD mother to offspring transmission. Our previous work demonstrated that mother to offspring transmission is efficient in an experimental setting (34). To address the question of relevance in a naturally-exposed free-range population, we have assessed maternal and fetal tissues derived from 19 elk dam-calf pairs harvested from Rocky Mountain National Park (RMNP), a known CWD endemic region. Conventional immunohistochemistry (IHC) identified 3/19 CWD positive dams, whereas a more sensitive assay – the serial protein misfolding cyclic amplification (sPMCA) – detected cervid prions (PrPCWD) in 15/19 dams. PrPCWD tissue distribution, as demonstrated by sPMCA, was widespread and included the central nervous system (CNS), lymphoreticular system (LRS), reproductive, secretory, excretory and adipose tissues. Interestingly, 5 of the 15 sPMCA positive dams showed no evidence of PrPCWD in either CNS or LRS, sites typically assessed in diagnosing CWD. Analysis of fetal tissues harvested from the 15 sPMCA positive dams revealed PrPCWD in 80% of fetuses (12/15), regardless of gestational stage. ***These findings demonstrate that PrPCWD is more abundant in free-range elk peripheral tissues than current diagnostic methods suggest, and that transmission of prions from mother to offspring may contribute to the efficient transmission of the CWD in native cervid populations.

 

===========

 

These findings demonstrate that PrPCWD is more abundant in free-range elk peripheral tissues than current diagnostic methods suggest, and that transmission of prions from mother to offspring may contribute to the efficient transmission of the CWD in native cervid populations.

 

===========

 

 P.142: Chronic wasting disease (CWD) transmission into hamsters

 

Elizabeth Triscott, Camilo Duque-Velasquez, Judd M Aiken, and Debbie McKenzie Center for Prions and Protein Folding Diseases; University of Alberta; Edmonton, Canada

 

KEYWORDS. chronic wasting disease, interspecies transmission, prion strains

 

Chronic wasting disease (CWD) is a contagious prion disease of cervids. The continued expansion of the disease in North America is resulting in the increasing number of mammalian species exposed to this infectious agent. As CWD is able to infect multiple cervid species, it is likely that variation of the agent might occur, due to PrP polymorphisms within and between cervid species. Using Syrian Golden hamsters as a model for interspecies transmission, we infected the hamsters with genetically defined CWD isolates from white-tailed deer as well as with hunter-harvested mule deer and white-tailed deer from Saskatchewan. ***The majority of the CWD isolates resulted in successful transmission to hamsters. Biochemical and neuropathological analyses suggests differences between the CWD isolates.

 

===========

 

P.144: Transmission of CWD to nonhuman primates: Interim results of a 6 year risk assessment study on the transmissibility to humans

 

Bianka Mussil1, Dirk Motzkus1, Georgia Hesse1, Sabine Borchert1, Barbara Schiller1, Christiane Stahl-Hennig1 , Walter Schulz-Schaeffer2, Michael Beekes3, Martin Daus3, Hermann M Schatzl5, Sandor Dudas4, Jianmin Yang4, Jean-Philippe Deslys6, and Stefanie Czub4,5 1German Primate Center; Goettingen, Germany; 2Faculty of Medicine; Department of Neuropathology; Goettingen, Germany; 3Robert Koch Institute; Berlin, Germany; 4University of Calgary; Faculty of Veterinary Medicine; Calgary, Canada; 5Canadian and OIE Reference Laboratories for BSE; Canadian Food Inspection Agency Lethbridge Laboratory; Lethbridge, Alberta, Canada; 6Commissariat a l’Energie Atomique; Fontenay-aux-Roses, France

 

Rapid spread and high prevalence of CWD in North American captive and free-ranging cervids have raised concerns about a potential risk to human health. Evidence exists that skeletal muscles might harbor significant amount of prion infectivity which is of great importance to consumers of venison, velvet and other cervid products. In order to assess the risk of primary CWD-transmission, cynomolgus macaques (Macaca fascicularis) were inoculated with high-titer brain homogenates of CWD-infected white-tailed deer material by intracerebral, intragastric and dermal scarification routes. Another group obtained a total amount of 5 kg CWD-positive muscle homogenate using a repeated low-dose regimen (each received »125 applications of 40 g muscle homogenate over a 3 y period). Risk of secondary CWD-transmission via blood or bloodderived products is judged by blood transfusion of monkey-adapted CWD to naive recipients. Based on the in vitro conversion of recombinant prion protein, a real-time quaking-induced conversion (RT-QuiC) assay was optimized by using lymph node tissues, cerebrospinal fluid samples and brain homogenate derived from BSE-inoculated macaques. Results have shown robust, sensitive, specific detection, high interand moderate intra-assay variances in samples derived from BSE-infected macaques. ***So far, all analyzed samples from CWD-inoculated macaques did not reveal any seeding activity. ***Future findings of our risk assessment study will greatly contribute to policy decisions including monitoring of human blood products, CWD surveillance and CWD control in captive and free-ranging cervids. Here we will present an update on the current state of the ongoing project.

 

===========

 

***So far, all analyzed samples from CWD-inoculated macaques did not reveal any seeding activity.

 

***Future findings of our risk assessment study will greatly contribute to policy decisions including monitoring of human blood products, CWD surveillance and CWD control in captive and free-ranging cervids. Here we will present an update on the current state of the ongoing project.

 

SEE ;

 

Prion

 

Volume 7, Issue 3, 2013

 

Early detection of chronic wasting disease prions in urine of pre-symptomatic deer by real-time quaking-induced conversion assay

 

Open access

 

DOI:10.4161/pri.24430Theodore R. Johna, Hermann M. Schätzlabc & Sabine Gilchad*

 

pages 253-258

 

Publishing models and article dates explained

 

Received: 7 Feb 2013 Accepted: 24 Mar 2013 Published online: 10 Apr 2013

 

Article Views: 105

 

Abstract

 

Chronic wasting disease (CWD) is a prion disease of captive and free-ranging deer (Odocoileus spp), elk (Cervus elaphus nelsonii) and moose (Alces alces shirasi). Unlike in most other prion diseases, in CWD prions are shed in urine and feces, which most likely contributes to the horizontal transmission within and between cervid species. To date, CWD ante-mortem diagnosis is only possible by immunohistochemical detection of protease resistant prion protein (PrPSc) in tonsil or recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsies, which requires anesthesia of animals. We report on detection of CWD prions in urine collected from pre-symptomatic deer and in fecal extracts by using real time quaking-induced conversion (RT-QuIC). This assay can be useful for non-invasive pre-symptomatic diagnosis and surveillance of CWD.

 

snip...

 

Introduction

 

Chronic wasting disease (CWD) is to date the most contagious prion disease and affects captive and free-ranging elk, deer and moose in North America.1 The disease is caused by the accumulation of an abnormally folded isoform of the cellular prion protein PrPc, denominated PrPSc.3 CWD is the cervid equivalent of bovine spongiform encephalopathy (BSE), scrapie in sheep and goat5 or Creutzfeldt-Jakob disease (CJD) in humans.6 Although transmission studies of CWD prions to humanized transgenic mice or non-human primates suggest a strong species barrier,7 recent in vitro studies have demonstrated that human PrP can be converted by CWD prions into PrPSc upon adaptation.10 ***Therefore, a potential for zoonotic transmission, as exemplified by BSE,11 cannot be completely excluded.

 

A huge body of evidence suggests that CWD can be efficiently transmitted horizontally within and between cervid species,12 which may be the reason for geographical spread and increase in case numbers. Horizontal transmission is explained by the rather unusual peripheral distribution of prions in CWD affected animals and the high susceptibility to the disease by oral infection.13 Unlike in most other prion diseases, CWD prions can be found in a wide variety of tissues, such as skeletal and cardiac muscle15 or kidney,17 in addition to the lymphoreticular system and blood.18 Furthermore, they are shed in significant amounts in saliva,18 ,19 urine19 or feces,20 which enables oral infection of animals by foraging on contaminated pastures. In addition, it has been demonstrated that prions can persist in soil21 and that water in endemic areas can contain CWD-associated PrPSc 22.

 


 

 ***Therefore, a potential for zoonotic transmission, as exemplified by BSE,11 cannot be completely excluded.

 

 

 

*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent

 

 *** Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP,

 

 *** indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains.

 

 PPo2-27:

 

 Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

 

 *** Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.

 

 PPo2-7:

 

 Biochemical and Biophysical Characterization of Different CWD Isolates

 

 *** The data presented here substantiate and expand previous reports on the existence of different CWD strains.

 


 

 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.

 


 

 >>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO CONVERSION OF THE HUMAN PRION PROTEIN<<<

 

 *** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***

 

 Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014

 

 Wednesday, January 01, 2014

 

 Molecular Barriers to Zoonotic Transmission of Prions

 

 *** 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.

 


 


 

 PRION2013 CONGRESSIONAL ABSTRACTS CWD

 

 Sunday, August 25, 2013

 

 HD.13: CWD infection in the spleen of humanized transgenic mice

 

 ***These results indicate that the CWD prion may have the potential to infect human peripheral lymphoid tissues.

 

 Oral.15: Molecular barriers to zoonotic prion transmission: Comparison of the ability of sheep, cattle and deer prion disease isolates to convert normal human prion protein to its pathological isoform in a cell-free system ***However, they also show that there is no absolute barrier to conversion of human prion protein in the case of chronic wasting disease.

 

 PRION2013 CONGRESSIONAL ABSTRACTS CWD

 

 Sunday, August 25, 2013

 

 ***Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission

 


 

 PPo3-7:

 

 Prion Transmission from Cervids to Humans is Strain-dependent

 

 Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi Gambetti and Liuting Qing Department of Pathology; Case western Reserve University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial Sloan-Kettering Cancer Center; New York, NY USA

 

 Key words: CWD, strain, human transmission

 

 Chronic wasting disease (CWD) is a widespread prion disease in cervids (deer and elk) in North America where significant human exposure to CWD is likely and zoonotic transmission of CWD is a concern. Current evidence indicates a strong barrier for transmission of the classical CWD strain to humans with the PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD strains. What remain unknown is whether individuals with the PrP-129VV/MV genotypes are also resistant to the classical CWD strain and whether humans are resistant to all natural or adapted cervid prion strains. Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP, indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains. Preliminary results on CWD transmission in transgenic mice expressing human PrP-129V will also be discussed.

 

 Acknowledgement Supported by NINDS NS052319 and NIA AG14359.

 

 PPo2-27:

 

 Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

 

 Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A. Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer’s disease and related Brain disorders; Dept of Neurology; University of Texas Houston Medical School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago; Chicago, IL USA

 

 Prion diseases are infectious neurodegenerative disorders affecting humans and animals that result from the conversion of normal prion protein (PrPC) into the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of cervids is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. CWD is highly contagious and its origin, mechanism of transmission and exact prevalence are currently unclear. The risk of transmission of CWD to humans is unknown. Defining that risk is of utmost importance, considering that people have been infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the infectious form by CWD PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique, which mimic in vitro the process of prion replication. Our results show that cervid PrPSc can induce the pathological conversion of human PrPC, but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, this newly generated human PrPSc exhibits a distinct biochemical pattern that differs from any of the currently known forms of human PrPSc, indicating that it corresponds to a novel human prion strain. Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.

 

 PPo2-7:

 

 Biochemical and Biophysical Characterization of Different CWD Isolates

 

 Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin, Germany

 

 Key words: CWD, strains, FT-IR, AFM

 

 Chronic wasting disease (CWD) is one of three naturally occurring forms of prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie in sheep. CWD is contagious and affects captive as well as free ranging cervids. As long as there is no definite answer of whether CWD can breach the species barrier to humans precautionary measures especially for the protection of consumers need to be considered. In principle, different strains of CWD may be associated with different risks of transmission to humans. Sophisticated strain differentiation as accomplished for other prion diseases has not yet been established for CWD. However, several different findings indicate that there exists more than one strain of CWD agent in cervids. We have analysed a set of CWD isolates from white-tailed deer and could detect at least two biochemically different forms of disease-associated prion protein PrPTSE. Limited proteolysis with different concentrations of proteinase K and/or after exposure of PrPTSE to different pH-values or concentrations of Guanidinium hydrochloride resulted in distinct isolate-specific digestion patterns. Our CWD isolates were also examined in protein misfolding cyclic amplification studies. This showed different conversion activities for those isolates that had displayed significantly different sensitivities to limited proteolysis by PK in the biochemical experiments described above. We further applied Fourier transform infrared spectroscopy in combination with atomic force microscopy. This confirmed structural differences in the PrPTSE of at least two disinct CWD isolates. The data presented here substantiate and expand previous reports on the existence of different CWD strains.

 


 


 


 

 2012

 

 Envt.06:

 

 Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates

 

 Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Aru Balachandran,2 Jürgen Richt,3 Vincent Beringue,4 Juan-Maria Torres,5 Paul Brown,1 Bob Hills6 and Jean-Philippe Deslys1

 

 1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Canadian Food Inspection Agency; Ottawa, ON Canada; 3Kansas State University; Manhattan, KS USA; 4INRA; Jouy-en-Josas, France; 5INIA; Madrid, Spain; 6Health Canada; Ottawa, ON Canada

 

 †Presenting author; Email: emmanuel.comoy@cea.fr

 

 The constant increase of chronic wasting disease (CWD) incidence in North America raises a question about their zoonotic potential. A recent publication showed their transmissibility to new-world monkeys, but no transmission to old-world monkeys, which are phylogenetically closer to humans, has so far been reported. Moreover, several studies have failed to transmit CWD to transgenic mice overexpressing human PrP. Bovine spongiform encephalopathy (BSE) is the only animal prion disease for which a zoonotic potential has been proven. We described the transmission of the atypical BSE-L strain of BSE to cynomolgus monkeys, suggesting a weak cattle-to-primate species barrier. We observed the same phenomenon with a cattleadapted strain of TME (Transmissible Mink Encephalopathy). Since cattle experimentally exposed to CWD strains have also developed spongiform encephalopathies, we inoculated brain tissue from CWD-infected cattle to three cynomolgus macaques as well as to transgenic mice overexpressing bovine or human PrP. Since CWD prion strains are highly lymphotropic, suggesting an adaptation of these agents after peripheral exposure, a parallel set of four monkeys was inoculated with CWD-infected cervid brains using the oral route. Nearly four years post-exposure, monkeys exposed to CWD-related prion strains remain asymptomatic. In contrast, bovinized and humanized transgenic mice showed signs of infection, suggesting that CWD-related prion strains may be capable of crossing the cattle-to-primate species barrier. Comparisons with transmission results and incubation periods obtained after exposure to other cattle prion strains (c-BSE, BSE-L, BSE-H and cattle-adapted TME) will also be presented, in order to evaluate the respective risks of each strain.

 

 Envt.07:

 

 Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease

 

 Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2 Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany †Presenting author; Email: dausm@rki.de

 

 Chronic wasting disease (CWD) is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE) occurring in cervids in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report a direct biochemical demonstration of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected cervids. The presence of PrPTSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrPTSE was revealed by protein misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal muscles of CWD-infected WTD was estimated to be approximately 2000- to 10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE was located in muscle- associated nerve fascicles but not, in detectable amounts, in myocytes. 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.

 


 


 

 P.10.15

 

 ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A WISCONSIN STRAIN OF CWD

 

 Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5

 

 The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.

 


 


 

 CHRONIC WASTING DISEASE CWD

 

 Transmissibility to humans.

 

 The current state of epidemiological research suggests a rather robust barrier for the transmission of CWD to humans. Particularly, the surveillance of human prion diseases in areas with a long history of endemic CWD such as Colorado and Wyoming did not reveal evidence for zoonotic transmissions of the disease to cervid hunters or consumers of meat from elk and deer.66. Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 2004; 10:977 - 984; PMID: 15207045 [CrossRef] View all references,1111. Belay ED, Abrams J, Kenfield J, Weidenbach K, Maddox RA, Lawaczeck E, et al. Monitoring the potential transmission of chronic wasting disease to humans (Abstract Oral.40, Prion 2011 Oral Presentations). Prion 2011; 5:17 Supplemental Issue April/May/June 2011 View all references

 

 However, as discussed by Belay et al.66. Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 2004; 10:977 - 984; PMID: 15207045 [CrossRef] View all references

 

 the intensity of human exposure to CWD prions may increase due to a further spread and rising prevalence of the disease in cervids. Therefore, and with the generally long latency periods of human prion diseases in mind, previous epidemiological findings cannot be readily extrapolated. Until recently, experimental studies that pursued biochemical approaches or used transgenic mice to ascertain the susceptibility of humans to CWD infections consistently seemed to corroborate current epidemiological findings: CWD-infected cervid brain tissue did not seed the conversion of PrPC into PrPres in PMCA assays using brain homogenate from macaques or transgenic mice expressing human PrPC as test substrate,1212. Kurt TD, Telling GC, Zabel MD, Hoover EA. Trans-species amplification of PrP(CWD) and correlation with rigid loop 170N. Virology 2009; 387:235 - 243; PMID: 19269662; http://dx.doi.org/10.1016/j.virol.2009.02.025 [CrossRef] View all references

 

 and transgenic mice overexpressing human PrPC were resistant to infection after intracerebral challenge with CWD prions from mule deer.1313. Sandberg MK, Al-Doujaily H, Sigurdson CJ, Glatzel M, O'Malley C, Powell C, et al. Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein. J Gen Virol 2010; 91:2651 - 2657; PMID: 20610667; http://dx.doi.org/10.1099/vir.0.024380-0 [CrossRef] View all references

 

 However, a study published by Barria et al.1414. Barria MA, Telling GC, Gambetti P, Mastrianni JA, Soto C. Generation of a new form of human PrPSc in vitro by interspecies transmission from cervid prions. J Biol Chem 2011; 286:7490 - 7495; PMID: 21209079; http://dx.doi.org/10.1074/jbc.M110.198465 [CrossRef] View all references

 

 in March 2011 found that cervid PrPTSE can seed the conversion of human PrPC into PrPres by PMCA when the CWD agent has been previously passaged in vitro or in vivo. Specifically, this was demonstrated for CWD prions from naturally affected mule deer either passaged by serial PMCA using deer PrPC as conversion substrate or in transgenic mice expressing cervid PrPC. The authors of this study pointed out that CWD prions may undergo a gradual process of change and adaptation via successive passages in the cervid population. They concluded that the reported findings, if corroborated by infectivity assays, may imply “that CWD prions have the potential to infect humans and that this ability progressively increases with CWD spreading.” Cynomolgus macaques used as a primate model for testing the susceptibility of humans to CWD as close to reality as possible have not shown clinical signs of a prion disease at nearly 6 years after intracerebral or peroral inoculation of CWD agents from white-tailed deer, Rocky Mountain elk or mule deer.1515. Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, et al. Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis 2009; 15:1366 - 1376; PMID: 19788803; http://dx.doi.org/10.3201/eid1509.090253 [CrossRef] View all references

 

 In contrast to macaques, squirrel monkeys were susceptible to CWD infection by the intracerebral route and showed even a low rate of disease transmission after oral challenge.1515. Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, et al. Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis 2009; 15:1366 - 1376; PMID: 19788803; http://dx.doi.org/10.3201/eid1509.090253 [CrossRef] View all references,1616. Marsh RF, Kincaid AE, Bessen RA, Bartz JC. Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol 2005; 79:13794 - 13796; PMID: 16227298; http://dx.doi.org/10.1128/JVI.79.21.13794-6.2005 [CrossRef] View all references

 

 Since humans are phylogenetically closer related to macaques than to squirrel monkeys, macaques are regarded as the more relevant primate model for assessing the zoonotic transmissibility of CWD.1515. Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, et al. Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis 2009; 15:1366 - 1376; PMID: 19788803; http://dx.doi.org/10.3201/eid1509.090253 [CrossRef] View all references

 

 Ongoing transmission studies in macaques. In addition to the primate study by Race et al.1515. Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, et al. Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis 2009; 15:1366 - 1376; PMID: 19788803; http://dx.doi.org/10.3201/eid1509.090253 [CrossRef] View all references

 

 two further studies in which macaques were challenged with tissue homogenates from CWD-affected cervids by intracerebral inoculation or via the oral route have been reported to be in progress.1717. Comoy E, Durand V, Correia E, Balachandran A, Richt JA, Beringue V, et al. Zoonotic potential of CWD: Experimental transmissions to non-human primates (Abstract Envt.06, Prion 2011 Poster Presentations). Prion 2011; 5:101 View all references,1818. Motzkus D, Schulz-Schaeffer WJ, Beekes M, Schätzl HM, Jirik FR, Schmädicke AC, et al. Transmission of CWD to non-human primates: Interim results of a comprehensive study on the transmissibility to humans (Abstract Envt. 22, Prion 2011 Poster Presentations). Prion 2011; 5:107 Supplemental Issue April/May/June 2011 View all references

 

 The purpose, research effort, financial investment and ethical aspects of these studies demand an utmost experimental scrutiny, careful data analysis and thorough exploitation of results. This has two immediate implications: (1) Since the incubation period of CWD may be very long in case of primary (i.e., inter-species) transmission to macaques a sustained monitoring of the animals appears mandatory for many years despite negative interim findings. (2) Increasing evidence suggests the existence of different CWD agents (see below), and theoretically, CWD prions may also change over time thereby possibly altering their potential host range. Thus, CWD isolates used in individual or pooled inocula for the challenge of macaques should be typed as precisely as possible in terms of their strain characteristics and molecular identity. Other field isolates could then be checked for their similarity or dissimilarity to the macaque-tested CWD agents in order to ascertain whether or not they are covered by the ongoing primate risk assessments. Evidence for Distinct CWD Strains Jump to section Transmissible Spongiform... Exposure of Humans to CWD Prions CWD Risk Assessments Evidence for Distinct CWD Strains Outlook Disclosure of Potential Conflicts of Interest Funding Figures and Tables Biochemical indications for isolate-dependent structural differences of PrPTSE. In 2002 it was reported that glycoform patterns of PrPTSE showed differences among individual CWD-affected cervids.1919. Race RE, Raines A, Baron TG, Miller MW, Jenny A, Williams ES. Comparison of abnormal prion protein glycoform patterns from transmissible spongiform encephalopathy agent-infected deer, elk, sheep and cattle. J Virol 2002; 76:12365 - 12368; PMID: 12414979; http://dx.doi.org/10.1128/JVI.76.23.12365-8.2002 [CrossRef] View all references

 

 In a variety of studies the glycosylation of PrPTSE had been previously established as a biochemical feature that may differ between distinct TSE agents.2020. Parchi P, Capellari S, Chen SG, Petersen RB, Gambetti P, Kopp N, et al. Typing prion isoforms. Nature 1997; 386:232 - 234; PMID: 9069279; http://dx.doi.org/10.1038/386232a0 [CrossRef] View all references,2121. Aguzzi A, Heikenwalder M, Polymenidou M. Insights into prion strains and neurotoxicity. Nat Rev Mol Cell Biol 2007; 8:552 - 561; PMID: 17585315; http://dx.doi.org/10.1038/nrm2204 [CrossRef] View all references

 

 Accordingly, the finding by Race et al. possibly indicated CWD infections with different or multiple strains of agent, although, alternatively, it could also be explained by random selection from a heterogeneous population of CWD-affected ruminants.1919. Race RE, Raines A, Baron TG, Miller MW, Jenny A, Williams ES. Comparison of abnormal prion protein glycoform patterns from transmissible spongiform encephalopathy agent-infected deer, elk, sheep and cattle. J Virol 2002; 76:12365 - 12368; PMID: 12414979; http://dx.doi.org/10.1128/JVI.76.23.12365-8.2002 [CrossRef] View all references

 

 Using a conformation-dependent immunoassay (CDI), Safar et al. found evidence for different conformations of PrPTSE in elk CWD as compared with white-tailed and mule deer CWD.2222. Safar JG, Scott M, Monaghan J, Deering C, Didorenko S, Vergara J, et al. Measuring prions causing bovine spongiform encephalopathy or chronic wasting disease by immunoassays and transgenic mice. Nat Biotechnol 2002; 20:1147 - 1150; PMID: 12389035; http://dx.doi.org/10.1038/nbt748 [CrossRef] View all references

 

 However, the amino acid sequences of elk and deer PrPC differ at residues 226 (glutamic acid in elk and glutamine in deer), and it remained to be established whether the structural differences detected by CDI were related to biologically distinct CWD strains. Isolation of CWD-associated agents causing distinct phenotypes in laboratory rodents. Classically, prion strains are differentiated based on their incubation periods in inbred mice with distinct PrP genotypes and by lesion profiles of the vacuolation in selected brain areas of reporter animals.2323. Bruce ME, Fraser H. Scrapie strain variation and its implications. Curr Top Microbiol Immunol 1991; 172:125 - 138; PMID: 1810707 [CrossRef] View all references

 

 When Raymond et al. serially passaged a CWD inoculum from mule deer either in Syrian hamsters or first into transgenic mice expressing hamster PrPC, and then further on in hamsters, they obtained two distinct isolates termed SghaCWDmd-f and SghaCWDmd-s, respectively.2424. Raymond GJ, Raymond LD, Meade-White KD, Hughson AG, Favara C, Gardner D, et al. Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. J Virol 2007; 81:4305 - 4314; PMID: 17287284; http://dx.doi.org/10.1128/JVI.02474-06 [CrossRef] View all references

 

 The first isolate showed an about 5-fold shorter incubation period in Syrian hamsters than the latter, and the cerebral patterns of PrPTSE deposition and gliosis in clinically affected hamsters were also different. Based on their findings the authors concluded that the “cervid-derived inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.” Angers et al. transmitted CWD inocula from elk and deer to transgenic mice expressing cervid PrP and found that these mice were affected by one of two strains, referred to as CWD1 and CWD2, that caused different incubation times and lesion profiles.2525. Angers RC, Kang HE, Napier D, Browning S, Seward T, Mathiason C, et al. Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science 2010; 328:1154 - 1158; PMID: 20466881; http://dx.doi.org/10.1126/science.1187107 [CrossRef] View all references

 

 The results of this study “appear to reflect strain constitutions in the natural host, rather than adaptation and divergence of progenitor strains in recipient mice,” according to the authors. Interestingly, CWD1 and CWD2 did not show recognizably different biochemical properties of their PrPTSE. The electrophoretic migration and glycosylation patterns as well as the stability characteristics after treatment with guanidine hydrochloride were indistinguishable for CWD1- and CWD2-associated PrPTSE. Consistent with these findings it has been previously reported that biologically distinct prion strains cannot always be differentiated by biochemical PrPTSE-typing or characterization of the conformational stability of PrPTSE.2626. Thomzig A, Spassov S, Friedrich M, Naumann D, Beekes M. Discriminating scrapie and bovine spongiform encephalopathy isolates by infrared spectroscopy of pathological prion protein. J Biol Chem 2004; 279:33847 - 33854; PMID: 15155741; http://dx.doi.org/10.1074/jbc.M403730200 [CrossRef] View all references,2727. Peretz D, Scott MR, Groth D, Williamson RA, Burton DR, Cohen FE, et al. Strain-specified relative conformational stability of the scrapie prion protein. Protein Sci 2001; 10:854 - 863; PMID: 11274476; http://dx.doi.org/10.1110/ps.39201 [CrossRef] View all references

 


 

 UPDATED DATA ON 2ND CWD STRAIN Wednesday, September 08, 2010 CWD PRION CONGRESS SEPTEMBER 8-11 2010

 


 

 OR-12: Chronic wasting disease transmission and pathogenesis in cervid and non-cervid Species

 

 Edward A. Hoover, Candace K. Mathiason, Nicholas J. Haley, Timothy D. Kurt, Davis M. Seelig, Nathaniel D. Denkers, Amy V. Nalls, Mark D. Zabel, and Glenn C. Telling

 

 Prion Research Program, Department of Microbiology, Immunology, and Pathology; Colorado State University; Fort Collins, CO USA

 

 Since its recognition as a TSE in the late 1970s, chronic wasting disease (CWD) of cervids has been distinguished by its facile spread and is now recognized in 18 states, 2 Canadian provinces, and South Korea. The efficient horizontal spread of CWD reflects a prion/host relationship that facilitates efficient mucosal uptake, peripheral lymphoid amplification, and dissemination by exploiting excretory tissues and their products, helping to establish indirect/environmental and well as direct (e.g., salivary) transmission. Recent studies from our group also support the likelihood of early life mother to offspring and aerosol CWD prion transmission. Studies of cervid CWD exposure by natural routes indicate that incubation period for detection of overt infection, while still uncertain, may be much longer than originally thought.

 

 Several non-cervid species can be infected by CWD experimentally (e.g., ferrets, voles, cats) with consequent species-specific disease phenotypes. The species-adapted prions so generated can be transmitted by mucosal, i.e., more natural, routes. Whether non-cervid species sympatric with deer/elk can be infected in nature, however, remains unknown. In vitro CWD prion amplification studies, in particular sPMCA, can foreshadow in vivo susceptibility and suggest the importance of the PrPC rigid loop region in species barrier permissiveness. Trans-species CWD amplification appears to broaden the host range/strain characteristics of the resultant prions. The origins of CWD remain unknown, however, the existence of multiple CWD prion strains/ quasi-species, the mechanisms of prion shedding/dissemination, and the relationship between sheep scrapie and CWD merit further investigation.

 


 

 Monday, May 23, 2011

 

 CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning

 

 Public release date: 23-May-2011

 

 Contact: Francesca Costanzo adajmedia@elsevier.com 215-239-3249 Elsevier Health Sciences

 

 CDC assesses potential human exposure to prion diseases Study results reported in the Journal of the American Dietetic Association Philadelphia, PA, May 23, 2011 – Researchers from the Centers for Disease Control and Prevention (CDC) have examined the potential for human exposure to prion diseases, looking at hunting, venison consumption, and travel to areas in which prion diseases have been reported in animals. Three prion diseases in particular – bovine spongiform encephalopathy (BSE or “Mad Cow Disease”), variant Creutzfeldt-Jakob disease (vCJD), and chronic wasting disease (CWD) – were specified in the investigation. The results of this investigation are published in the June issue of the Journal of the American Dietetic Association.

 

 “While prion diseases are rare, they are generally fatal for anyone who becomes infected. More than anything else, the results of this study support the need for continued surveillance of prion diseases,” commented lead investigator Joseph Y. Abrams, MPH, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta.”But it’s also important that people know the facts about these diseases, especially since this study shows that a good number of people have participated in activities that may expose them to infection-causing agents.”

 

 Although rare, human prion diseases such as CJD may be related to BSE. Prion (proteinaceous infectious particles) diseases are a group of rare brain diseases that affect humans and animals. When a person gets a prion disease, brain function is impaired. This causes memory and personality changes, dementia, and problems with movement. All of these worsen over time. These diseases are invariably fatal. Since these diseases may take years to manifest, knowing the extent of human exposure to possible prion diseases could become important in the event of an outbreak.

 

 CDC investigators evaluated the results of the 2006-2007 population survey conducted by the Foodborne Diseases Active Surveillance Network (FoodNet). This survey collects information on food consumption practices, health outcomes, and demographic characteristics of residents of the participating Emerging Infections Program sites. The survey was conducted in Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and Tennessee, as well as five counties in the San Francisco Bay area, seven counties in the Greater Denver area, and 34 counties in western and northeastern New York.

 

 Survey participants were asked about behaviors that could be associated with exposure to the agents causing BSE and CWD, including travel to the nine countries considered to be BSE-endemic (United Kingdom, Republic of Ireland, France, Portugal, Switzerland, Italy, the Netherlands, Germany, Spain) and the cumulative length of stay in each of those countries. Respondents were asked if they ever had hunted for deer or elk, and if that hunting had taken place in areas considered to be CWD-endemic (northeastern Colorado, southeastern Wyoming or southwestern Nebraska). They were also asked if they had ever consumed venison, the frequency of consumption, and whether the meat came from the wild.

 

 The proportion of survey respondents who reported travel to at least one of the nine BSE endemic countries since 1980 was 29.5%. Travel to the United Kingdom was reported by 19.4% of respondents, higher than to any other BSE-endemic country. Among those who traveled, the median duration of travel to the United Kingdom (14 days) was longer than that of any other BSE-endemic country. Travelers to the UK were more likely to have spent at least 30 days in the country (24.9%) compared to travelers to any other BSE endemic country. The prevalence and extent of travel to the UK indicate that health concerns in the UK may also become issues for US residents.

 

 The proportion of survey respondents reporting having hunted for deer or elk was 18.5% and 1.2% reported having hunted for deer or elk in CWD-endemic areas. Venison consumption was reported by 67.4% of FoodNet respondents, and 88.6% of those reporting venison consumption had obtained all of their meat from the wild. These findings reinforce the importance of CWD surveillance and control programs for wild deer and elk to reduce human exposure to the CWD agent. Hunters in CWD-endemic areas are advised to take simple precautions such as: avoiding consuming meat from sickly deer or elk, avoiding consuming brain or spinal cord tissues, minimizing the handling of brain and spinal cord tissues, and wearing gloves when field-dressing carcasses.

 

 According to Abrams, “The 2006-2007 FoodNet population survey provides useful information should foodborne prion infection become an increasing public health concern in the future. The data presented describe the prevalence of important behaviors and their associations with demographic characteristics. Surveillance of BSE, CWD, and human prion diseases are critical aspects of addressing the burden of these diseases in animal populations and how that may relate to human health.”

 

 ###

 

 The article is “Travel history, hunting, and venison consumption related to prion disease exposure, 2006-2007 FoodNet population survey” by Joseph Y. Abrams, MPH; Ryan A. Maddox, MPH; Alexis R Harvey, MPH; Lawrence B. Schonberger, MD; and Ermias D. Belay, MD. It appears in the Journal of the American Dietetic Association, Volume 111, Issue 6 (June 2011) published by Elsevier.

 

 In an accompanying podcast CDC’s Joseph Y. Abrams discusses travel, hunting, and eating venison in relation to prion diseases. It is available at http://adajournal.org/content/podcast.

 


 

 Thursday, May 26, 2011

 

 Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

 

 Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

 

 Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

 

 Joseph Y. Abrams, MPH, Ryan A. Maddox, MPH , Alexis R. Harvey, MPH , Lawrence B. Schonberger, MD , Ermias D. Belay, MD

 

 Accepted 15 November 2010. Abstract Full Text PDF References .

 

 Abstract

 

 The transmission of bovine spongiform encephalopathy (BSE) to human beings and the spread of chronic wasting disease (CWD) among cervids have prompted concerns about zoonotic transmission of prion diseases. Travel to the United Kingdom and other European countries, hunting for deer or elk, and venison consumption could result in the exposure of US residents to the agents that cause BSE and CWD. The Foodborne Diseases Active Surveillance Network 2006-2007 population survey was used to assess the prevalence of these behaviors among residents of 10 catchment areas across the United States. Of 17,372 survey respondents, 19.4% reported travel to the United Kingdom since 1980, and 29.5% reported travel to any of the nine European countries considered to be BSE-endemic since 1980. The proportion of respondents who had ever hunted deer or elk was 18.5%, and 1.2% had hunted deer or elk in a CWD–endemic area. More than two thirds (67.4%) reported having ever eaten deer or elk meat. Respondents who traveled spent more time in the United Kingdom (median 14 days) than in any other BSE-endemic country. Of the 11,635 respondents who had consumed venison, 59.8% ate venison at most one to two times during their year of highest consumption, and 88.6% had obtained all of their meat from the wild. The survey results were useful in determining the prevalence and frequency of behaviors that could be important factors for foodborne prion transmission.

 


 

 CDC

 

 Saturday, February 18, 2012

 

 Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting Disease

 

 CDC Volume 18, Number 3—March 2012

 

 SNIP…

 

 Interspecies transmission of CWD to noncervids has not been observed under natural conditions. CWD infection of carcass scavengers such as raccoons, opossums, and coyotes was not observed in a recent study in Wisconsin (22). In addition, natural transmission of CWD to cattle has not been observed in experimentally controlled natural exposure studies or targeted surveillance (2). However, CWD has been experimentally transmitted to cattle, sheep, goats, mink, ferrets, voles, and mice by intracerebral inoculation (2,29,33).

 

 CWD is likely transmitted among mule, white-tailed deer, and elk without a major species barrier (1), and other members of the cervid family, including reindeer, caribou, and other species of deer worldwide, may be vulnerable to CWD infection. Black-tailed deer (a subspecies of mule deer) and European red deer (Cervus elaphus) are susceptible to CWD by natural routes of infection (1,34). Fallow deer (Dama dama) are susceptible to CWD by intracerebral inoculation (35). Continued study of CWD susceptibility in other cervids is of considerable interest.

 

 Reasons for Caution There are several reasons for caution with respect to zoonotic and interspecies CWD transmission. First, there is strong evidence that distinct CWD strains exist (36). Prion strains are distinguished by varied incubation periods, clinical symptoms, PrPSc conformations, and CNS PrPSc depositions (3,32). Strains have been identified in other natural prion diseases, including scrapie, BSE, and CJD (3). Intraspecies and interspecies transmission of prions from CWD-positive deer and elk isolates resulted in identification of >2 strains of CWD in rodent models (36), indicating that CWD strains likely exist in cervids. However, nothing is currently known about natural distribution and prevalence of CWD strains. Currently, host range and pathogenicity vary with prion strain (28,37). Therefore, zoonotic potential of CWD may also vary with CWD strain. In addition, diversity in host (cervid) and target (e.g., human) genotypes further complicates definitive findings of zoonotic and interspecies transmission potentials of CWD.

 

 Intraspecies and interspecies passage of the CWD agent may also increase the risk for zoonotic CWD transmission. The CWD prion agent is undergoing serial passage naturally as the disease continues to emerge. In vitro and in vivo intraspecies transmission of the CWD agent yields PrPSc with an increased capacity to convert human PrPc to PrPSc (30). Interspecies prion transmission can alter CWD host range (38) and yield multiple novel prion strains (3,28). The potential for interspecies CWD transmission (by cohabitating mammals) will only increase as the disease spreads and CWD prions continue to be shed into the environment. This environmental passage itself may alter CWD prions or exert selective pressures on CWD strain mixtures by interactions with soil, which are known to vary with prion strain (25), or exposure to environmental or gut degradation.

 

 Given that prion disease in humans can be difficult to diagnose and the asymptomatic incubation period can last decades, continued research, epidemiologic surveillance, and caution in handling risky material remain prudent as CWD continues to spread and the opportunity for interspecies transmission increases. Otherwise, similar to what occurred in the United Kingdom after detection of variant CJD and its subsequent link to BSE, years of prevention could be lost if zoonotic transmission of CWD is subsequently identified, CWD will likely continue to emerge in North America. …

 

 SNIP…

 


 


 

 Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions

 

 Our results have far-reaching implications for human health, since they indicate that cervid PrPSc can trigger the conversion of human PrPC into PrPSc, suggesting that CWD might be infectious to humans. Interestingly our findings suggest that unstable strains from CWD affected animals might not be a problem for humans, but upon strain stabilization by successive passages in the wild, this disease might become progressively more transmissible to man.

 


 

 Our results also have profound implications for understanding the mechanisms of the prion species barrier and indicate that the transmission barrier is a dynamic process that depends on the strain and moreover the degree of adaptation of the strain. If our findings are corroborated by infectivity assays, they will imply that CWD prions have the potential to infect humans and that this ability progressively increases with CWD spreading.

 


 


 

 I thought your readers and hunters and those that consume the venison, should have all the scientific facts, personally, I don’t care what you eat, but if it effects me and my family down the road, it should then concern everyone, and the potential of iatrogenic transmission of the TSE prion is real i.e. ‘friendly fire’, medical, surgical, dental, blood, tissue, and or products there from...like deer antler velvet and TSE prions and nutritional supplements there from, all a potential risk factor that should not be ignored or silenced. ...

 

 the prion gods at the cdc state that there is ;

 

 ''no strong evidence''

 

 but let's see exactly what the authors of this cwd to human at the cdc state ;

 

 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 ;

 


 


 


 

 ***********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 ;

 


 

 Thursday, October 10, 2013

 

 *************CJD REPORT 1994 increased risk for consumption of veal and venison and lamb**************

 


 

 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.

 


 

 *** our results raise the possibility that CJD cases classified as VV1 may include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne infection by type 1 prions from animals, e.g., chronic wasting disease prions in cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have been reported (40, 41). The results of the present study emphasize the need for traceback studies and careful re-examination of the biochemical properties of sCJD-VV1 prions. ***

 


 

 snip...see full text ;

 


 

 Thursday, January 2, 2014

 

 *** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ??? ***

 


 

 *** 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.

 


 

 *** We hypothesize that both BSE prions and CWD prions passaged through felines will seed human recPrP more efficiently than BSE or CWD from the original hosts, evidence that the new host will dampen the species barrier between humans and BSE or CWD. The new host effect is particularly relevant as we investigate potential means of trans-species transmission of prion disease.

 


 

 *** We hypothesize that both BSE prions and CWD prions passaged through felines will seed human recPrP more efficiently than BSE or CWD from the original hosts, evidence that the new host will dampen the species barrier between humans and BSE or CWD. The new host effect is particularly relevant as we investigate potential means of trans-species transmission of prion disease.

 


 

 Monday, August 8, 2011

 

 *** Susceptibility of Domestic Cats to CWD Infection ***

 

 Oral.29: Susceptibility of Domestic Cats to CWD Infection

 

 Amy Nalls, Nicholas J. Haley, Jeanette Hayes-Klug, Kelly Anderson, Davis M. Seelig, Dan S. Bucy, Susan L. Kraft, Edward A. Hoover and Candace K. Mathiason†

 

 Colorado State University; Fort Collins, CO USA†Presenting author; Email: ckm@lamar.colostate.edu

 

 Domestic and non-domestic cats have been shown to be susceptible to one prion disease, feline spongiform encephalopathy (FSE), thought to be transmitted through consumption of bovine spongiform encephalopathy (BSE) contaminated meat. Because domestic and free ranging felids scavenge cervid carcasses, including those in CWD affected areas, we evaluated the susceptibility of domestic cats to CWD infection experimentally. Groups of n = 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD deer brain homogenate. Between 40–43 months following IC inoculation, two cats developed mild but progressive symptoms including weight loss, anorexia, polydipsia, patterned motor behaviors and ataxia—ultimately mandating euthanasia. Magnetic resonance imaging (MRI) on the brain of one of these animals (vs. two age-matched controls) performed just before euthanasia revealed increased ventricular system volume, more prominent sulci, and T2 hyperintensity deep in the white matter of the frontal hemisphere and in cortical grey distributed through the brain, likely representing inflammation or gliosis. PrPRES and widely distributed peri-neuronal vacuoles were demonstrated in the brains of both animals by immunodetection assays. No clinical signs of TSE have been detected in the remaining primary passage cats after 80 months pi. Feline-adapted CWD was sub-passaged into groups (n=4 or 5) of cats by IC, PO, and IP/SQ routes. Currently, at 22 months pi, all five IC inoculated cats are demonstrating abnormal behavior including increasing aggressiveness, pacing, and hyper responsiveness.

 

 *** Two of these cats have developed rear limb ataxia. Although the limited data from this ongoing study must be considered preliminary, they raise the potential for cervid-to-feline transmission in nature.

 


 


 

 AD.63:

 

 Susceptibility of domestic cats to chronic wasting disease

 

 Amy V.Nalls,1 Candace Mathiason,1 Davis Seelig,2 Susan Kraft,1 Kevin Carnes,1 Kelly Anderson,1 Jeanette Hayes-Klug1 and Edward A. Hoover1 1Colorado State University; Fort Collins, CO USA; 2University of Minnesota; Saint Paul, MN USA

 

 Domestic and nondomestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE), almost certainly caused by consumption of bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and free-ranging nondomestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD-infected deer brain. At 40 and 42 mo post-inoculation, two IC-inoculated cats developed signs consistent with prion disease, including a stilted gait, weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail tremors, and ataxia, and progressed to terminal disease within 5 mo. Brains from these two cats were pooled and inoculated into cohorts of cats by IC, PO, and intraperitoneal and subcutaneous (IP/SC) routes. Upon subpassage, feline-adapted CWD (FelCWD) was transmitted to all IC-inoculated cats with a decreased incubation period of 23 to 27 mo. FelCWD was detected in the brains of all the symptomatic cats by western blotting and immunohistochemistry and abnormalities were seen in magnetic resonance imaging, including multifocal T2 fluid attenuated inversion recovery (FLAIR) signal hyper-intensities, ventricular size increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4 IP/SQ and 2 of 4 PO inoculared cats have developed abnormal behavior patterns consistent with the early stage of feline CWD.

 

 *** These results demonstrate that CWD can be transmitted and adapted to the domestic cat, thus raising the issue of potential cervid-to- feline transmission in nature.

 


 

 Tuesday, November 04, 2014

 

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

 


 

 www.landesbioscience.com

 

 PO-081: Chronic wasting disease in the cat— Similarities to feline spongiform encephalopathy (FSE)

 


 


 

 FELINE SPONGIFORM ENCEPHALOPATHY FSE

 


 


 

 Thursday, July 03, 2014

 

 *** How Chronic Wasting Disease is affecting deer population and what’s the risk to humans and pets?

 


 

 Saturday, January 31, 2015

 

 European red deer (Cervus elaphus elaphus) are susceptible to Bovine Spongiform Encephalopathy BSE by Oral Alimentary route

 


 

 *** Singeltary reply ;

 

 ruminant feed ban for cervids in the United States ?

 

 31 Jan 2015 at 20:14 GMT

 


 

 Friday, January 30, 2015

 

 *** Scrapie: a particularly persistent pathogen ***

 


 

===========

 

P.153: An independent and blinded confirmation of real-time quakinginduced conversion (RT-QuIC) analysis of cervid rectal biopsies for detection of chronic wasting disease

 

Sireesha Manne1,*, Naveen Kondru1, Nicholas Haley2, Tracy Nichols3, Bruce Thomsen4, Roger Main5, Patrick Halbur5, Arthi Kanthasamy1, and Anumantha Kanthasamy1 1Biomedical Sciences; Iowa State University; Ames, IA USA; 2Kansas State University; Manhattan, KS USA; 3United States Department of Agriculture; Fort Collins, CO USA; 4National Veterinary Service Laboratories; Ames, IA USA; 5VDPAM; Iowa State University; Ames, IA USA

 

Prion diseases are transmissible spongiform encephalopathies (TSEs) characterized by an always fatal, progressive neuronal degeneration in the brain due to infectious misfolded prion proteins whose prolonged incubation periods often make ante-mortem diagnosis difficult. Chronic wasting disease (CWD) is a TSE affecting both wild and captive populations of mule deer, whitetailed deer, elk and moose. CWD in cervids was first identified in Rocky Mountain States and has recently spread to several other states including Iowa. In this current study, we attempted to independently confirm the results of a Real-Time Quaking-Induced Conversion (RT-QuIC) assay to diagnose CWD using rectal biopsy sections from farmed white-tailed deer. First, we generated recombinant prion protein substrate and then validated the quality of protein for RT-QuIC using a reference prion protein kindly provided by Dr. Caughey’s lab. After validating the assay, we blindly evaluated approximately 350 rectal biopsy samples analyzed previously by another institution. All assay plates included positive and negative controls and were analyzed in triplicate. Samples were analyzed using the Biotek Cytation-3 multimode plate reader for 24-hrs duration. Our RT-QuIC assays showed 55% positivity for 356 rectal samples analyzed. Comparison of RT-QuIC results with the immunohistochemical results of obex revealed 93% sensitivity (95% confidence limits: 88.05–95.78%) and 96% specificity (95% CL: 91–99%), confirming that the RT-QuIC assay may be one of the most promising rapid assays for detecting CWD prions. We are currently working on applying the RT-QuIC assay to other test samples (ISU Presidential Wildlife initiative, ISU-CVM Diagnostic lab and ES10586).

 

==========

 

P.154: Brain derived lipids inhibit prion amyloid formation in vitro

 

Clare Hoover, Davin Henderson, Mark Zabel, and Edward Hoover Colorado State University; Fort Collins, CO USA

 

The normal cellular prion protein (PrPC) resides in cellular outer membrane lipid rafts and conversion from PrPC to the pathogenic misfolded isoform is believed to occur at the lipid membrane. In vitro assays have demonstrated the intimate association between prion conversion and lipids, specifically phosphatidylethanolamine, which is a critical cofactor in the formation of synthetic infectious prions. In the current work, we demonstrate an opposing property of lipids, the ability to inhibit amyloid formation in vitro. The real-time quakinginduced conversion assay (RT-QuIC) was used to investigate whole brain lipid effects on prion amyloid formation. An alcohol based extraction technique was used to remove the lipid content from terminal chronic wasting disease (CWD)- infected white tailed deer brain homogenates. Eliminating lipids increased the sensitivity of RT-QuIC detection of CWD in brain samples one hundred-fold. Addition of brain-derived lipid extracts to CWD prion samples inhibited amyloid formation in a dose-dependent manner. Brain-derived lipids also inhibited prion amyloid formation in RT-QuIC reaction seeds derived from lymphoid tissues. This is the first demonstration of brain derived lipids directly inhibiting prion amyloid formation in vitro and highlights the diverse roles lipids play in the conversion process. Further experiments will identify the individual lipid species or groups of lipids responsible for this inhibitory activity.

 

============

 

P.160: Detecting the temporal status of prionemia in transmissible spongiform encephalopathy-infected hosts

 

Alan Elder1, Davin Henderson1, Amy Nalls1, Kristen Davenport1, Anthony Kincaid2, Edward Hoover1, Jason Bartz2, and Candace Mathiason1 1Colorado State University; Fort Collins, CO USA; 2Creighton University; Omaha, NE USA

 

Infectious prions can traverse epithelial barriers and gain access to the circulatory system early in infection. The details of prion entry, temporal status, and persistence in the blood remain unknown. Furthermore, it is unknown if the route of inoculation plays a role in the development of prionemia. We previously demonstrated PrPC amyloid conversion activity in the blood (prionemia) of deer and hamsters infected with transmissible spongiform encephalopathies (TSEs) using whole blood real-time quaking-induced conversion (wbRT-QuIC). In this study we analyzed the temporal status of prionemia, spanning 0–100% of the disease course, in hosts exposed to TSEs via blood transfusion or other peripheral means (i.e. oral, aerosol, extranasal, and subcutaneous). Our results demonstrate the presence of PrPC amyolid conversion activity in the blood of all TSE-inoculated hosts as early as 15 minutes post inoculation likely-representing the point source inoculum–which was cleared from the circulatory system by 72 hours post exposure. De novo host generated hematogenous PrPC amyloid conversion activity, or prionemia, was identified at 4–5% of the TSE disease course and persisted throughout disease. ***Our results indicate that hematogenous prions can traverse mucosal surfaces and enter the circulatory system with the same speed and efficiency as those entering the blood directly by blood transfusion, and that an asymptomatic carrier state is established within minutes of TSE exposure.

 

==========

 

***Our results indicate that hematogenous prions can traverse mucosal surfaces and enter the circulatory system with the same speed and efficiency as those entering the blood directly by blood transfusion, and that an asymptomatic carrier state is established within minutes of TSE exposure.***

 

===========

 

P.161: Prion soil binding may explain efficient horizontal CWD transmission

 

Nathaniel Denkers1, Davin Henderson1, Shannon Bartelt-Hunt2, Jason Bartz3, and Edward Hoover1 1Colorado State University; Fort Collins, Colorado USA; 2University of Nebraska-Lincoln; Omaha, Nebraska USA; 3Creighton University; Omaha, Nebraska USA

 

Background. Chronic wasting disease (CWD) is unique due to the facile spread in nature. The interaction of excreted CWD prions and soil is a hypothesized contributor in environmental transmission. The present study examines whether and to what degree CWD prions bind to silty clay loam (SCL) using an adapted version of real-time quaking-induced conversion (RT-QuIC) methodology.

 

Materials and Methods. Varying amounts (50–3.12 mg) of SCL were incubated with 1 mL-serial dilutions of CWD (C), CWD (¡), or no brain homogenate (BH). Samples were centrifuged, washed, diluted 1:10 in 0.1% SDS, and 2.5 uL seeded in RT-QuIC assays employing recombinant Syrian hamster prion PrP substrate. Multiple well replicates of sample and supernatant fractions were assayed for positive seeding activity (recorded as thioflavin T fluorescence emission; 480 nm). Samples were considered positive if they crossed a threshold of 25,000. Reaction rates (RR) were calculated, averaged, and expressed as 1/RR.

 

Results. Positive seeding activity was detected for most SCL samples incubated with CWD (C) BH dilutions. Higher SCL concentrations (50 mg) produced low fluorescent readings due to optical interference. Lower SCL concentrations (6.25 mg) produced minimal optical interference and removed the vast majority of seeding activity from CWDC BH in a concentration-dependent manner; determined by seeding activity in residual BH supernatants. Control SCL and supernatants produced minimal falsepositive reactions (8 of 240 replicates; 3.3%). We estimated the prion binding capacity of SCL to be 0.16 ng/mg.

 

***Conclusion. Silty clay loam exhibits highly efficient prion binding, inferring a durable environmental reservoir, and an efficient mechanism for indirect horizontal CWD transmission.

 

==============

 

***Conclusion. Silty clay loam exhibits highly efficient prion binding, inferring a durable environmental reservoir, and an efficient mechanism for indirect horizontal CWD transmission.

 

=============

 

P.66: Transport of CWD prions in Alberta soils

 

Alsu Kuznetsova1, Debbie McKenzie2, Tariq Siddique1, and Judd Aiken2 1University of Alberta; Department of Renewable Resources; Edmonton, Canada; 2University of Alberta; Centre for Prions and Protein Folding Diseases; Edmonton, Canada

 

The transmission of chronic wasting disease (CWD) includes environmental pathways, particularly soils as disease reservoirs. Soils differ dramatically in their capacity to adsorb PrPCWD due to differences in mineral composition, humus content and particle surface area. Mineral and organic compounds have the ability to bind PrPCWD impacting infectious properties. The extreme variability of these soil constituents suggests that the PrPCWD fate and behavior will depend on specific soil properties. The soil moisture regime also has the potential to affect transportation of compounds through a soil profile. PrPCWD can be bound to soil particles with Prion 2015 Poster Abstracts S45 3 hypothetical scenarios for prion fate: (i) prions stay in the surface soil horizon and remain bioavailable for grazing animals; (ii) prions can be transported into lower soil horizons and become unavailable for consumption; or (iii) prions can migrate through the soil profile and end up in ground water. We performed bench-scale experiments with soil columns to evaluate the potential for transportation of PrPCWD using soils from different regions of Alberta, Canada. The Luvisols found in northern Alberta have an ustic/udic moisture regime and illite as a predominant clay mineral. The prion binding capacity of illite is poor suggesting it cannot contribute to prion binding and PrPCWD can migrate through the soil profile. Chernozems are found in the CWD-endemic region in southern Alberta and have an aridic soil moisture regime, high amount of humus content and contain montmorillonite. In the Chernozem soil columns PrPCWD remains on the soil surface and does not migrate in lower horizons.

 

===========

 

PLEASE SEE;

 

 

Friday, May 22, 2015

 

Chronic Wasting Disease and Program Updates - 2014 NEUSAHA Annual Meeting 12-14 May 2014

 


 

============

 

P.70: Experimental transmission of chronic wasting disease to sheep and goats

 

Gordon Mitchell, Nishandan Yogasingam, Ines Walther, and Aru Balachandran National and OIE Reference Laboratory for Scrapie and CWD; Canadian Food Inspection Agency; Ottawa, ON, Canada

 

The persistence of chronic wasting disease (CWD) in North American cervids, coupled with efforts to eradicate scrapie in sheep and goats, necessitates an understanding of the transmission, clinical and diagnostic characteristics of CWD in small ruminants. Oral and intracerebral transmission studies were conducted in sheep and goats using tissues from CWD-infected elk. Four lambs and 4 goats were orally inoculated with a pooled brain and lymph node homogenate from a group of farmed elk with clinical CWD. At study endpoint, there was no evidence of primary CWD transmission in the sheep or goat tissues examined by ELISA, western blot and immunohistochemistry (IHC). Two lambs which were challenged intracerebrally with the same pooled elk inoculate displayed neurological signs beginning at 27 months postinoculation (mpi) and were euthanized within 10 d of each other at 28 mpi. Testing of tissues by ELISA and IHC confirmed disease transmission and revealed differences in the distribution and intensity of PrPd deposition between animals. Western immunoblot analysis identified characteristics permitting the differentiation of CWD in sheep from other prion diseases in small ruminants. CWD-infected tissue from the intracerabrally-inoculated sheep has undergone secondary passage into sheep and goats and currently shows no evidence of oral transmission in rectal mucosa biopsies at 20 mpi. These findings corroborate evidence of a significant species barrier preventing the oral transmission of CWD to sheep and goats, and identify diagnostic characteristics to enable the differentiation of prion diseases affecting small ruminants.

 

===========

 

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.

 

=================

 

*** 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. ***

 

================

 

P.128: Bioassay using ovine and cervid PrP transgenic mice for discrimination of scrapie and CWD origins in sheep and goats

 

Sally Madsen-Bouterse1,*, Dongyue Zhuang2, David Schneider2, Rohana Dassanayake1, Aru Balachandran3, Gordon Mitchell3, and Katherine O’Rourke1 1Department of Veterinary Microbiology and Pathology; College of Veterinary Medicine; Washington State University; Pullman, WA USA; 2Animal Disease Research Unit; Agricultural Research Service; US. Department of Agriculture; Pullman, WA USA; 3National and OIE Reference Laboratory for Scrapie and CWD; Canadian Food Inspection Agency; Ottawa Laboratory– Fallowfield; Ottawa, ON Canada

 

As the United States works toward the eradication of scrapie, identifying TSE reservoirs that could lead to disease re-emergence is imperative. Development of transgenic mice expressing either the ovine or cervid prion protein has aided characterization of scrapie and CWD, respectively. We hypothesize that transgenic mouse models will discern whether new incidents of scrapie in sheep and goats with clinical disease originated from CWD exposure. Two transgenic mouse lines (Tg338 and TgElk; minimum 5 mice/strain) were inoculated with brain homogenate from clinically affected animals including sheep or goats with naturally acquired classical scrapie, white-tailed deer with naturally acquired CWD (WTD-CWD), or sheep experimentally inoculated with elk-CWD (sheepelk- CWD). Transmission was assessed via survival analysis and western blot characterization of brain PrPres. WTD-CWD transmitted efficiently to TgElk with all mice culled due to clinical disease, whereas all Tg338 remained asymptomatic at endpoint with no PrPres detected in the brain. Ovine and caprine scrapie transmitted poorly to TgElk with all mice asymptomatic at endpoint and 6.8% brain-positive for PrPres, whereas all Tg338 were culled due to clinical disease. Sheep elk-CWD yielded Tg338 that were all asymptomatic at endpoint and were all brainpositive for PrPres. However, sheepelk-CWD yielded TgElk with 5/22 displaying clinical disease near endpoint but 16/22 brain-positive for PrPres. Furthermore, TgElk-PrPres molecular mass appeared lower when inoculated with caprine scrapie versus WTD-CWD and both molecular masses were yielded when inoculated with sheepelk-CWD. ***These findings suggest primary passage in Tg338 and TgElk could discern whether scrapie in sheep and goats originated from CWD exposure.

 

===========

 

P.73: Oral challenge of goats with atypical scrapie

 

Silvia Colussi1, Maria Mazza1, Francesca Martucci1, Simone Peletto1, Cristiano Corona1, Marina Gallo1, Cristina Bona1, Romolo Nonno2, Michele Di Bari2, Claudia D’Agostino2, Nicola Martinelli3, Guerino Lombardi3, and Pier Luigi Acutis1 1Istituto Zooprofilattico Sperimentale del Piemonte; Liguria e Valle d’Aosta; Turin, Italy; 2Istituto Superiore di Sanit a; Rome, Italy; 3Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna; Brescia, Italy

 

Atypical scrapie transmission has been demonstrated in sheep by intracerebral and oral route (Simmons et al., Andreoletti et al., 2011) but data about goats are not available yet. In 2006 we orally challenged four goats, five months old, with genotype R/H and R/R at codon 154. Animals died starting from 24 to 77 months p.i. without clinical signs. They all resulted negative for scrapie in CNS and peripheral tissues using Western blot and immunohistochemistry. Nevertheless these goats could still represent carriers. This hypothesis was investigated through bioassay in tg338 mice, a sensitive animal model for atypical scrapie infectivity. By end-point dilution titration, the starting inoculum contained 106.8 ID50/g. In contrast, all tissues from challenged goats were negative by bioassay. These negative results could be explained with the low infectivity of the starting inoculum, which could have been unable to induce disease or infectivity within our period of observation. However the challenge conditions could have been a bias too: as the matter of the fact, while the oral challenge of classical scrapie is still effective in sheep 6–10 months old (Andreoletti et al., 2011), Simmons et al. (2011) demonstrated a very short efficacy period for atypical scrapie (24 hours after birth), hypothesizing that natural transmission could occur mainly via milk. ***Our work suggests that this could be true also for goats and it should be taken into account in oral challenges. However a low susceptibility of goats to atypical scrapie transmission via oral route cannot be excluded.

 

=============

 

P.74: Transmission of experimental CH1641 scrapie to wild-type mice

 

Lucien van Keulen1,*, Jan Langeveld1, Corry Dolstra1, Jorg Jacobs1, Alex Bossers1, and Fred van Zijderveld2 1Department of Infection Biology; Central Veterinary Institute of Wageningen UR, Lelystad, The Netherlands; 2Department of Bacteriology and TSEs; Central Veterinary Institute of Wageningen UR, Lelystad, The Netherlands

 

Introduction. CH1641 was isolated in the UK in 1970 from a natural case of scrapie in a Cheviot sheep and was further passaged intracerebrally in sheep. CH1641 has been the subject of extensive research because of the biochemical similarities of PrPres from CH1641- and BSE-affected sheep brains. Previous attempts to transmit CH1641 to wild type mice have been unsuccessful. We report here for the first time, the positive transmission of experimental CH1641 to RIII mice and compare the incubation period, PrPSc profile and PrPres Western blot properties to those of known scrapie and BSE reference strains.

 

Methods. The CH1641 brain homogenate used in this study came from a pool a 5 sheep brains which had been challenged intracerebrally with brain material from the third passage of CH1641 in sheep. Groups of 15–20 RIII mice were inoculated intracerebrally with a 10% brain homogenate of CH1641. The brains of the mice were examined by PrPSc profiling and triplex Western blot as reported previously.

 

Results. Surprisingly CH1641 transmitted to RIII mice with a 100% attack rate although with a long incubation period (794 § 149 d). The resulting PrPSc profile was unlike any of the profiles of the scrapie and BSE reference strains reported previously. Triplex Western blot pointed after first passage to a very low PrPres level. We observed a reduction of molecular mass of the non-glycosyl PrPres moiety and concomittant N-terminal 12B2 epitope signal. In comparison to the original CH1641 inoculum there was a lack of a dual population of PrPres.

 

===========

 

***The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans.

 

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

 

Subject terms: Biological sciences• Medical research At a glance

 


 

Wednesday, January 18, 2012

 

Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie

 

Journal of Neuropathology & Experimental Neurology: February 2012 - Volume 71 - Issue 2 - p 140–147

 


 

Thursday, July 14, 2011

 

Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)

 


 

===========

 

P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study

 

 Paul Brown1, Diane Ritchie2, James Ironside2, Christian Abee3, Thomas Kreil4, and Susan Gibson5 1NIH (retired); Bethesda, MD USA; 2University of Edinburgh; Edinburgh, UK; 3University of Texas; Bastrop, TX USA; 4Baxter Bioscience; Vienna, Austria; 5University of South Alabama; Mobile, AL USA

 

Five vCJD disease transmissions and an estimated 1 in 2000 ‘silent’ infections in UK residents emphasize the continued need for information about disease risk in humans. A large study of blood component infectivity in a non-human primate model has now been completed and analyzed. Among 1 GSS, 4 sCJD, and 3 vCJD cases, only GSS leukocytes transmitted disease within a 5–6 year surveillance period. A transmission study in recipients of multiple whole blood transfusions during the incubation and clinical stages of sCJD and vCJD in ic-infected donor animals was uniformly negative. These results, together with other laboratory studies in rodents and nonhuman primates and epidemiological observations in humans, ***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. The issue of decades-long incubation periods in ‘silent’ vCJD carriers remains open.

 

=============

 

***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD...see;

 

Wednesday, December 11, 2013

 

*** Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease ***

 


 

THE BAXTER STUDY...SEE MORE HERE ;

 


 

==============

 

 P.23: An improved test for the detection of Creutzfeldt-Jakob Disease from human CSF using new RT-QuIC conditions

 

Bradley R Groveman1, Christina D Orr u1, Andrew G Hughson1, Gianluigi Zanusso2, Maurizio Pocchiari3, Michael B Coulthart4, and Byron Caughey1 1Laboratory of Persistent Viral Diseases; Rocky Mountain Laboratories; NIAID; NIH; Hamilton, MT USA; 2Department of Neurological and Movement Sciences; University of Verona; Verona, Italy; 3Department of Cell Biology and Neurosciences; Istituto Superiore di Sanit a; Rome, Italy; 4Canadian CJD Surveillance System; Public Health Agency of Canada; Ottawa, ON Canada

 

Neurodegenerative protein misfolding diseases are difficult to diagnose early and accurately. This is particularly worrisome with human prion diseases, such as Creutzfeldt- Jakob disease (CJD), because prions are transmissible, deadly, and unusually resistant to decontamination. Real-time quaking-induced conversion (RT-QuIC) assays allow highly sensitive and specific testing for CJD using human cerebrospinal fluid (CSF) or nasal brushings and are being widely implemented as important diagnostic tools. However, such laboratory analyses have required 2.5 to 5 d to complete. Furthermore, CSF testing using previously evaluated RT-QuIC conditions still yields false negative results in 11 to 23% of CJD cases. We have now developed an improved RT-QuIC assay which can identify positive CSF samples within 4 to 14 h with better analytical and diagnostic sensitivity. Analysis of CSF samples from 11 CJD patients demonstrated that while 7 were RT-QuIC positive using previous conditions, an additional 3 samples were positive using the new assay. In these and subsequent analyses, a total of 46 of 48 CSF samples from sporadic CJD patients gave positive RT-QuIC responses, while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity. This diagnostic sensitivity was significantly better than that obtained using the previous conditions. We continue to expand the testing of CJD-positive and -negative CSF samples to further establish the diagnostic utility of this new assay for various human prion diseases. So far, our improved RT-QuIC assay appears to allow for much faster, more accurate and practical antemortem testing for CJD using CSF samples.

 

===========

 

P.159: Improvements of nasal brushing procedure for Creutzfeldt-Jakob disease diagnosis

 

Matilde Bongianni1, Christina Orr u2, Giovanni Tonoli3, Bradley Groveman2, Giorgo Triva4, Santina Castriciano4, Luca Sacchetto1, Andrew Hughson2, Annachiara Cagnin5, Stefano Capaldi1, Sergio Ferrari1, Michele Fiorini1, Salvatore Monaco1, Maurizio Pocchiari6, Byron Caughey2, and Gianluigi Zanusso1 1University of Verona; Verona, Italy; 2Rocky Montain Laboratories; Hamilton, MT USA; 3Ospedale “Santa Maria della Misericordia”; Rovigo, Italy; 4Copan Italia S.P.A.; Brescia, Italy; 5University of Padua; Padua, Italy; 6Istituto Superiore di Sanit a; Rome, Italy

 

Introduction. We previously identified prion seeding activity in olfactory mucosa (OM) of CJD patients using nasal brushings coupled with Real Time Quaking induced Conversion (RT-QuIC) with 100% specificity and >97% sensitivity. OM samples were collected using a sterile disposable Cyto-brush (Kito-Brush, Kaltek) which might provoke a mild discomfort for patients. Therefore, we aimed to use a more gentle tool for OM samplings such as short nylon fiber Flocked swabs (Copan technologies).

 

Materials and Methods. We collected OM and CSF samples in 43 CJD patients. To ensure efficient OM sample collection, each patient underwent to two OM samplings using flocked swabs one in each nostril and a final with Cytobrush. OM samples were processed and analyzed by RT-QuIC, as previously described.

 

Results. Using Cyto-brushes 32 out of 35 OM samples were positive by RT-QuIC analysis, while flocked swabs in 40 out of 43 OM samples. In contrast, CSF samples were positive in 33 out of 43. Two OM samples resulted negative for both Cyto-brush and Flocked swab. Neither OM sampling technique or CSF produced false positives.

 

***Conclusion. This study demonstrates that OM brushing following RT-QuIC ssay is 95% sensitive and 100% specific in CJD diagnosis while CSF resulted 77% sensitive. OM collection using flocked swabs is preferred and provides same sensitivity as cyto-brush. These data recommend four separate samplings possibly from both nostrils to maximize the sensitivity, using three Flocked swabs and lastly a brush.

 

============

 

P.24: A comparative study of dura mater graft-associated Creutzfeldt-Jakob disease between Japan and other countries

 

Tsuyoshi Hamaguchi1, Kenji Sakai1, Moeko Noguchi-Shinohara1, Ichiro Nozaki1, Ichiro Takumi2, Nobuo Sanjo3, Yosikazu Nakamura4, Tetsuyuki Kitamoto5, Nobuhito Saito6, Hidehiro Mizusawa7, and Masahito Yamada1 1Department of Neurology and Neurobiology of Aging; Kanazawa University Graduate School of Medical Science; Kanazawa, Japan; 2Department of Neurosurgery; Nippon Medical School Musashi Kosugi Hospital; Kawasaki, Japan; 3Department of Neurology and Neurological Science; Graduate School; Tokyo Medical and Dental University; Tokyo, Japan; 4Department of Public Health; Jichi Medical University; Shimotsuke, Japan; 5Departments of Prion Protein Research; Division of CJD Science and Technology; Tohoku University Graduate School of Medicine; Sendai, Japan; 6Department of Neurosurgery; Faculty of Medicine; The University of Tokyo; Tokyo, Japan; 7National Center Hospital; National Center of Neurology and Psychiatry; Tokyo, Japan

 

Objective. More than 60% of patients worldwide diagnosed with Creutzfeldt-Jakob disease

 

(CJD) associated with dura mater graft (dCJD) have been identified in Japan. The remarkable frequency of dura mater graft use in Japan might contribute to the elevated incidence of dCJD, but the possible reasons for the disproportionate use of this procedure in Japan remain unclear. We investigated the differences between dCJD patients in Japan and those elsewhere to help uncover an explanation for the unusually more frequent use of cadaveric dura mater and high incidence of dCJD in Japan.

 

Methods. We obtained data of dCJD patients in Japan from the nationwide surveillance of CJD in Japan and of those in other countries from extant literature. We compared demographic, clinical, and pathological features of dCJD patients between Japan and elsewhere.

 

Results. Data from 142 dCJD patients in Japan and 53 in other countries were obtained. The medical conditions precipitating dura mater graft were significantly different between Japan and other countries (P < 0.001); in Japan, there were more cases of cerebrovascular disease and hemifacial spasm or trigeminal neuralgia. Patients with dCJD in Japan received dura mater graft more often for non-life-threatening conditions, such as meningioma, hemifacial spasm and trigeminal neuralgia, than those in other countries.

 

Conclusion. Differences in the medical conditions precipitating dura mater graft may contribute to the frequent use of cadaveric dura mater and the higher incidence of dCJD in Japan.

 

===============

 

P.34: Preliminary study of Alzheimer’s disease transmission to bank vole

 

Guido Di Donato1, Geraldina Riccardi1, Claudia D’Agostino1, Flavio Torriani1, Maurizio Pocchiari2, Romolo Nonno1, Umberto Agrimi1, and Michele Angelo Di Bari1 1Department of Food Safety and Veterinary Public Health Istituto Superiore di Sanit a, Rome, Italy; 2Department of Cellular Biology and Neuroscience; Istituto Superiore di Sanit a, Rome, Italy

 

Extensive experimental findings indicate that prion-like mechanisms underly the pathogenesis of Alzheimer disease (AD). Transgenic mice have been pivotal for investigating prionlike mechanisms in AD, still these models have not been able so far to recapitulate the complex clinical-pathological features of AD. Here we aimed at investigating the potential of bank vole, a wild-type rodent highly susceptible to prions, in reproducing AD pathology upon experimental inoculation.

 

Voles were intracerebrally inoculated with brain homogenate from a familial AD patient. Animals were examined for the appearance of neurological signs until the end of experiment (800 d post-inoculation, d.p.i.). Brains were studied by immunohistochemistry for pTau Prion 2015 Poster Abstracts S29 (with AT180 and PHF-1 antibodies) and b-amyloid (4G8).

 

Voles didn’t show an overt clinical signs, still most of them (11/16) were found pTau positive when culled for intercurrent disease or at the end of experiment. Interestingly, voles culled as early as 125 d.p.i. already showed pTau aggregates. Deposition of pTau was similar in all voles and was characterized by neuropil threads and coiled bodies in the alveus, and by rare neurofibrillary tangles in gray matter. Conversely, b-amyloid deposition was rather rare (2/16). Nonetheless, a single vole showed the contemporaneous presence of pTau in the alveus and a few Ab plaque-like deposits in the subiculum. Uninfected age-matched voles were negative for pTau and Ab.

 

These findings corroborate and extend previous evidences on the transmissibility of pTau and Ab aggregation. Furthermore, the observation of a vole with contemporaneous propagation of pTau and Ab is intriguing and deserves further studies.

 

=================

 

PLEASE SEE ;

 

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

 

Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014

 


 

Singeltary comment ;

 


 

===============

 

P.36: Spontaneous in vitro conversion of full length recombinant human prion protein in unseeded RT-QuIC reactions

 

 Marcelo Barria Matus, Alexander Peden, Richard Knight, James Ironside, and Mark Head National CJD Research & Surveillance Unit; The University of Edinburgh, Edinburgh, UK

 

Sporadic Creutzfeldt–Jakob disease (sCJD) is the most common human prion disease, affecting approximately 1–2 persons per one million of the population per year. It is thought to arise as a result of spontaneous conversion of PrPC to PrPSc, which becomes self-propagating. The prion protein polymorphism at codon 129 encodes either methionine (M) or valine (V). Comparison of the codon 129 genotype distribution in sCJD cohorts with that of the normal Caucasian population suggests that heterozygosity (MV) protects against sCJD and the comparison has also been widely interpreted to mean that methionine homozygosity predisposes to CJD.

 

We have used real-time quaking induced conversion (RT-QuIC) to model the S30 Prion 2015 Poster Abstracts spontaneous formation of the abnormal form of human PrP and to determine whether methionine or valine at the position 129 of PrPC confers a greater susceptibility to spontaneous conversion to PrP amyloid.

 

Unseeded RT-QuIC reactions using fulllength recombinant human prion protein with either methionine or valine at position 129 both resulted in spontaneous amyloid formation. The process appeared to have a pronounced stochastic element, but when a sufficient number of replicates were performed a clear and reproducible effect of codon 129 genotype was also evident, in which PrPC with valine at codon 129 showed a greater predisposition to form amyloid than its allelic counterpart containing methionine.

 

***These results question whether methionine at position 129 in PrPC can be considered an intrinsic susceptibility factor for conversion to PrPSc, at least in terms of the initiation of spontaneous, as opposed to seeded PrP amyloid formation.

 

==========

 

P.69: Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone

 

Ignazio Cali1,2, Cathleen Miller3, Tetsuyuky Kitamoto4, Joseph Parisi5, Michael Geschwind6, Pierluigi Gambetti1, and Lawrence Schonberger7 1National Prion Disease Pathology Surveillance Center (NPDPSC); Department of Pathology; Case Western Reserve University; School of Medicine; Cleveland, OH USA; 2Department of Clinical and Experimental Medicine; Second University of Naples; Naples, Italy; 3Kaiser Permanente Vancouver Medical Center; Vancouver, WA USA; 4Graduate School of Medicine; Tohoku University; Sendai, Japan; 5Departments of Laboratory Medicine & Pathology and Neurology; Mayo Clinic; Rochester, MN USA; 6Department of Neurology; Memory and Aging Center; University of California; San Francisco, CA USA; 7National Center for Emerging and Zoonotic Infectious Diseases; Centers for Disease Control and Prevention; Atlanta, GA USA

 

The peripheral administration of growth hormone (GH) from prion-contaminated cadaveric pituitary glands is believed to be causative of iatrogenic Creutzfeldt-Jakob disease (iCJD) in more than 225 subjects worldwide. The present study describes the neuropathology and molecular features of 3 of the 30 identified iCJD cases among the approximately 7,700 recipients of cadaveric pituitary hormone in the US National Hormone and Pituitary Program (NHPP). All three cases were methionine (M) homozygous at codon 129 of the prion protein (PrP) gene (GH-CJDMM) and all received NHPP hormone produced before 1977 when a new hormone purification protocol was introduced that reduced the risk of prion contamination. Neuropathological examination revealed divergent phenotypes. The first phenotype, observed in the most recent US NHPP GH-CJD case, was characterized by the presence of amyloid plaques and reminiscent of sCJDMV2-K and, to some extent, variant CJD (vCJD). The second phenotype showed no plaques and shared several, but not all, characteristics with the sCJDMM(MV)1 subtype. However, PKresistant PrPSc (resPrPSc) from GH-CJDMM co-migrated with resPrPSc type 1 (GHCJDMM1) of sCJDMM1, but not with type 2 of sCJDMV2-K. Histopathological phenotypes with or without plaques also have been described in 2 groups of Japanese dura mater (d) graft-associated CJD (dCJD) with the same 129MM genotype but apparently different gel mobility of resPrPSc type 1. ***Our study suggests that phenotypic diversity in these iatrogenic diseases reflects adaptation of different exogenous prion strains to the 129MM host and/or to different locations of the initial PrPC to PrPSc conversion.

 

===========

 

P.75: Development of pre-mortem diagnosis for suspected Creutzfeldt- Jakob diseases’ patients

 

SuYeon Kim, JaeWook Hyeon, YeongRan Ju, JiYeon Lee, WonCheol Lee, and YeongSeon Lee Korea NIH (KCDC); Cheonju, Chungcheongbukdo, Republic of Korea

 

Creutzfeldt-Jakob disease (CJD) is the most representative human prion disease caused by abnormal accumulation of misfolding prion protein. The diagnosis is performed with features of magnetic resonance imaging, electroencephalogram and elevated the 14-3-3 protein findings, prion protein gene polymorphisms. In laboratory, the protein detection and analysis of the gene polymorphisms have been monitored, and then clinicians determined as CJD patient or not CJD case combining specific clinical opinions in Korea. We aimed evaluate the epidemiological tendency, and the possibility of early diagnosis through the application of clinical features included the protein tests and genetic analysis. We detected 14-3-3 protein, and analyzed PRNP genotypes for suspected cases (2010–2014). The results were combined with progressive dementia, myoclonus, and memory decline, and their relationships were analyzed. They were almost within the age range of 60–80 years, and the numbers of male and female were similar. Approximately 49% showed positive for 14-3-3 protein, and the polymorphisms reported to genetic pathogenic factor inherited CJD showed in 11 patients. Three definite and 14 possible sCJD patients defined except for one were positive for 14-3-3, and several probable sporadic cases had pathogenic genetic factors like P102L, E200K and V180I. The clinical presentations showed progressive dementia, visual illusion, myoclonus, ataxia, akinetic mutism, and memory decline. Some MRI and EEG findings showed high signal abnormalities in the fronto-temporal cortex and typical periodic sharp wave complexes. We consider that the active following surveillance for patients would be added to improve the specificity of early CJD diagnosis.

 

===============

 


 

==============

 

P.13: Detection of sCJD prions in human saliva by RT-QuIC

 

Matteo Manca1, Gianluigi Zanusso2, and Byron Caughey1 1Laboratory of Persistent Viral Diseases; Rocky Mountain Laboratories (RML); National Institute of Allergy and Infectious Disease (NIAID); National Institutes of Health (NIH); Hamilton, MT USA; 2Department of Neurological and Movement Sciences; University of Verona; Verona, Verona, Italy

 

Sporadic Creutzfeldt-Jakob Disease (sCJD) is the most common form of human prion disease. A recent study showed that prion seeding activity is RT-QuIC-detectable in the olfactory neuroepithelium of sCJD patients. Relatively rapid turnover of the olfactory neuroepithelium and nasal mucus clearance systems might lead to the transportation of prion seeds into the oral cavity and shedding through saliva. Pooled human saliva was spiked with sCJD prions and subjected to different treatments to investigate the suitability of such a sample as a new and non-invasive diagnostic specimen. Our findings highlighted the presence of yet unidentified factor( s) that could lead to spontaneous conversion in the RT-QuIC assay. We will show our ongoing results on the attempt to identify the factor (s) and eliminate it/them.

 

=================

 

P.85: Improving Creutzfeldt-Jakob disease incidence estimates by incorporating results of neuropathological analyses, United States, 2003–2011

 

Ryan Maddox1, Marissa Person1, Arialdi Minino2, Janis Blevins3, Lawrence Schonberger1, and Ermias Belay1 1National Center for Emerging and Zoonotic Infectious Diseases; Centers for Disease Control and Prevention, Atlanta GA USA; 2National Center for Health Statistics; Centers for Disease Control and Prevention; Hyattsville, MD USA; 3National Prion Disease Pathology Surveillance Center; Case Western Reserve University; Cleveland, OH USA

 

Introduction. The incidence of invariably fatal prion diseases such as Creutzfeldt-Jakob disease (CJD) can be estimated by analyzing death certificate data, but there are limitations.

 

Methods. Prion disease decedents were identified from the US national multiple cause-ofdeath data and the National Prion Disease Pathology Surveillance Center (NPDPSC) database for 2003–2011. Due to limited personal identifying information, an algorithm was constructed to determine likely decedent matches between the 2 databases. NPDPSC decedents with a positive prion disease autopsy or biopsy result or genetic mutation for whom no match was found in the multiple cause-of-death data were added as cases for incidence calculations; those with negative neuropathology results but

 

Prion 2015 Poster Abstracts S55

 

with a death certificate indicating prion disease were removed. The resulting average annual age-adjusted incidence was then calculated. Results. A total of 2986 decedents were identified as having prion disease indicated as a cause of death in the multiple cause-of-death data; 469 additional NPDPSC decedents were identified with positive neuropathology and/or genetic findings, while 140 decedents with death certificates indicating prion disease had negative neuropathology results. Incorporating the matched data, the average annual age adjusted incidence of CJD in the United States was 1.2 per million.

 

Conclusion. Analysis of multiple cause-ofdeath data is an efficient means of conducting CJD surveillance. However, not all decedents are captured as the death certificate may not list the diagnosis; conversely, a CJD diagnosis on the certificate may be contradicted by neuropathology results. Incorporating findings from NPDPSC neuropathological and genetic analyses produces an estimate closer to the true incidence of the disease.

 


 


 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

 Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

 Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

 To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

 

 Terry S. Singeltary, Sr Bacliff, Tex

 

 1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

 


 

 26 March 2003

 

 Terry S. Singeltary, retired (medically) CJD WATCH

 

 I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?

 


 

 2 January 2000

 

 British Medical Journal

 

 U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

 


 

 15 November 1999

 

 British Medical Journal

 

 vCJD in the USA * BSE in U.S.

 


 

 The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI

 

 Tracking spongiform encephalopathies in North America

 

 Original

 

 Xavier Bosch

 

 “My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt—Jakob ...

 


 

 Suspect symptoms

 

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

 

 28 Mar 01 Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 

 Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

 

 "This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...

 


 

 Tuesday, December 16, 2014

 

 Evidence for zoonotic potential of ovine scrapie prions

 

 Scrapie from sheep could infect humans with 'mad cow disease', study finds

 


 


 

 The Pathological Protein:

 

 Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases

 

 Philip Yam

 

 ''Answering critics like Terry Singeltary, who feels that the US undercounts CJD, Schonberger _conceded_ that the current surveillance system has errors but stated that most of the errors will be confined to the older population''....end

 

 snip...

 

 His combative, blunt, opinion- ated style sometimes borders on obsessive ranting that earns praise from some officials and researchers but infuriates others especially when he repeats his conviction that "the government has lied to us, the feed industry has lied to us all over a buck." As evidence, Singeltary cites the USDA's testing approach, which targets downer cows and examined 19,900 of them in 2002. To him, the USDA should test 1 mil- lion cattle, because the incidence of BSE may be as low as one in a mil- lion, as it was in some European countries. That the U.S. does not, he thinks, is a sign that the government is really not interested in finding mad cows because of fears of an economic disaster.

 

 Singeltary got into the field of transmissible spongiform encepha- lopathy in 1997, just after his mother died of sporadic CJD. She had an especially aggressive version the Heidenhain variant that first causes the patient to go blind and then to deteriorate rapidly She died just ten weeks after her symptoms began. Singeltary, who said he had watched his grandparents die of cancer, considered her death by CJD to be much, much worse: "It's something you never forget." Her uncon- trollable muscle twitching became so bad "that it took three of us to hold her one time," Singeltary recalled. "She did everything but levitate in bed and spin her head."

 


 

 14th ICID International Scientific Exchange Brochure -

 

 Final Abstract Number: ISE.114

 

 Session: International Scientific Exchange

 

 Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

 

 T. Singeltary

 

 Bacliff, TX, USA

 

 Background:

 

 An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.

 

 Methods:

 

 12 years independent research of available data

 

 Results:

 

 I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.

 

 Conclusion:

 

 I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

 


 

 re-Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

 

 Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014

 

 Singeltary comment ;

 


 

 RE: re-Human Prion Diseases in the United States

 

 part 2 flounder replied to flounder on 02 Jan 2010 at 21:26 GMT

 

 No competing interests declared.

 

 No competing interests declared.

 

 see full text ;

 


 

 *** PLOS Singeltary reply ;

 

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

 


 

 PLOS Singeltary reply ;

 

ruminant feed ban for cervids in the United States ?

 

 Singeltary T. S.

 

31 Jan 2015 at 20:14 GMT

 


 

 "Löcher wie in einem Schweizer Käse" hat auch Terry Singeltary im Regelwerk der FDA ausgemacht. Der Texaner kam auf einem tragischen Umweg zu dem Thema: Nachdem seine Mutter 1997 binnen weniger Wochen an der Creutzfeldt-Jakob-Krankheit gestorben war, versuchte er, die Ursachen der Infektion aufzuspüren. Er klagte auf die Herausgabe von Regierungsdokumenten und arbeitete sich durch Fachliteratur; heute ist er überzeugt, dass seine Mutter durch die stetige Einnahme von angeblich kräftigenden Mitteln erkrankte, in denen - völlig legal - Anteile aus Rinderprodukten enthalten sind.

 

 Von der Fachwelt wurde Singeltary lange als versponnener Außenseiter belächelt. Doch mittlerweile sorgen sich auch Experten, dass ausgerechnet diese verschreibungsfreien Wundercocktails zur Stärkung von Intelligenz, Immunsystem oder Libido von den Importbeschränkungen ausgenommen sind. Dabei enthalten die Pillen und Ampullen, die in Supermärkten verkauft werden, exotische Mixturen aus Rinderaugen; dazu Extrakte von Hypophyse oder Kälberföten, Prostata, Lymphknoten und gefriergetrocknetem Schweinemagen. In die USA hereingelassen werden auch Blut, Fett, Gelatine und Samen. Diese Stoffe tauchen noch immer in US-Produkten auf, inklusive Medizin und Kosmetika. Selbst in Impfstoffen waren möglicherweise gefährliche Rinderprodukte enthalten. Zwar fordert die FDA schon seit acht Jahren die US-Pharmaindustrie auf, keine Stoffe aus Ländern zu benutzen, in denen die Gefahr einer BSE-Infizierung besteht. Aber erst kürzlich verpflichteten sich fünf Unternehmen, darunter Branchenführer wie GlaxoSmithKline, Aventis und American Home Products, ihre Seren nur noch aus unverdächtigem Material herzustellen.

 

 "Its as full of holes as Swiss Cheese" says Terry Singeltary of the FDA regulations. ...

 


 

 New York Times Magazine The Case of the Cherry Hill Cluster By D.T. MAX

 

 Published: March 28, 2004

 

 snip...

 

 Skarbek did not know how to surmount this objection. But she was a go-getter. She wasn't about to give up on her cluster so easily. Fortunately, she was in contact with Terry Singeltary. She had seen his name quoted often on the Web in articles on C.J.D. and mad cow. Singeltary lost his mother to an extremely rare strain of sporadic C.J.D. in 1997. Soon after, he learned that a year earlier to the day, the mother of his next-door neighbor died of the disease. Since that time, he has become convinced that these sporadic cases are not sporadic at all, that mad cow is now a disease of humans in America. He said he believes that his mother was accidentally infected during surgery and the mother of his neighbor from taking nutritional supplements made from high-risk bovine tissue, which he calls ''mad cow in a pill.''

 

 Singeltary has a sloping face and slicked-back hair. He is nearsighted, with small blue eyes. He looks like Lewis Carroll's White Rabbit. From his living room in Bacliff, Tex., he dominates the listservs and message boards of an online debate over sporadic C.J.D. -- the scientists who say it exists; the heartbroken family members who doubt it. Early, deep in his grief, he would sign his e-mail messages to scientists, ''I am the madson of a deadmom who died of madcow.'' Singeltary turned out to be helpful for Skarbek. He pointed her to a paper that was published in 2002 in the journal of the European Molecular Biology Organization by John Collinge, the premier prion researcher in England. Collinge argued that experiments conducted in mice suggest that infections with mad cow can sometimes look like sporadic C.J.D. Collinge accepted the implications: he recommended that ''serious consideration should be given'' to the idea that some of the more recent sporadic C.J.D. cases in Europe were in fact related to mad cow disease.

 


 

 2014

 

 ***Moreover, L-BSE has been transmitted more easily to transgenic mice overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.

 

 ***It has been suggested that some sporadic CJD subtypes in humans may result from an exposure to the L-BSE agent.

 

 *** Lending support to this hypothesis, pathological and biochemical similarities have been observed between L-BSE and an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and another sCJD subtype (MM genotype) [15].

 

 snip...

 


 

 BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein

 

 *** Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2.

 

 These data suggest that more than one BSEderived prion strain might infect humans;

 

 ***it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.

 

 snip...

 

 These studies further strengthen the evidence that vCJD is caused by a BSE-like prion strain.

 

 Also, remarkably, the key neuropathological hallmark of vCJD, the presence of abundant florid PrP plaques, can be recapitulated on BSE or vCJD transmission to these mice.

 

 ***However, the most surprising aspect of the studies was the finding that an alternate pattern of disease can be induced in 129MM Tg35 mice from primary transmission of BSE, with a molecular phenotype indistinguishable from that of a subtype of sporadic CJD. This finding has important potential implications as it raises the possibility that some humans infected with BSE prions may develop a clinical disease indistinguishable from classical CJD associated with type 2 PrPSc. This is, in our experience, the commonest molecular sub-type of sporadic CJD. In this regard, it is of interest that the reported incidence of sporadic CJD has risen in the UK since the 1970s (Cousens et al., 1997)...

 


 

 To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE.

 

 ***In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

 


 

 -------- Original Message --------

 

 Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD

 

 Date: Thu, 28 Nov 2002 10:23:43 -0000

 

 From: "Asante, Emmanuel A" e.asante@ic.ac.uk

 

 To: "'flounder@wt.net'" flounder@wt.net

 

 Dear Terry,

 

 I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention.

 

 Thank you for your interest in the paper.

 

 In respect of your first question, the simple answer is, ***yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.

 

 I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.

 

 Emmanuel Asante

 

 <>

 

 ____________________________________

 

 Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)

 

 ____________________________________ END

 

 Aug. 5, 2001, 12:25AM

 

 Mad cow disease: Could it be here?

 

 Man's stubborn crusade attracts experts' notice

 

 By CAROL CHRISTIAN Copyright 2001 Houston Chronicle

 

 Like Paul Revere with e-mail, Terry Singeltary Sr. is on a mission to sound an alarm: Beware of mad cow disease.

 

 As is true of many crusaders, however, his pleas often fall on deaf ears. Health officials here and abroad insist that bovine spongiform encephalopathy -- popularly known as mad cow disease, a fatal brain disorder that can make cows shake uncontrollably -- has been kept out of this country through surveillance of the cattle industry.

 

 But since his mother's death in December 1997, the Galveston County man has been obsessed with possible connections between her deadly brain disorder, sporadic Creutzfeldt-Jakob Disease, and mad cow disease.

 

 And after much persistence on his part, people are taking notice of this former machinist and high school dropout who jokes that he has a Ph.D. -- a Pool Hall Degree.

 

 "They called me Chicken Little for four years," he said. "Now they're calling back, asking for more information."

 

 For the past year he has been U.S. co-coordinator of an international monitoring group called CJD Watch. He regularly gets e-mail from scientists and journalists around the world.

 

 Debora MacKenzie, a reporter for the British magazine New Scientist, described Singeltary, 47, as a "dogged unearther and tabulator of government documents." Singeltary monitors "every word written about CJD/BSE," said Anita Manning of USA Today, also by e-mail.

 

 "He's passionate, opinionated and not always tactful, although I like him because he's such a character and he is so transparent," Manning said. "He is what he appears to be."

 

 Science and environment writer Jonathan Leake of the Sunday Times in London said Singeltary has helped him track down families of people with CJD along with academic research papers.

 

 "I strongly suspect he is right in thinking the USA has had BSE cases," Leake said by e-mail.

 

 "The American government is making the same mistake as the British in putting the short-term commercial interests of its farmers before health considerations," he added.

 

 "It should start formal and widespread testing of cattle plus compulsory autopsies for all human CJD victims at the state's expense. If there is BSE, then leaving it to spread will kill people -- and that would eventually destroy the industry, too."

 

 Texas Department of Health epidemiologist Julie Rawlings said Singeltary's careful monitoring of the disease had proven useful.

 

 "Terry has been helpful in providing contact information regarding suspect CJD cases so that the Health Department can initiate case investigations and learn more about CJD in Texas," she said.

 

 Noting that the department cannot release records on individual patients, she added, "I think we learn more from him than he does from us."

 

 Mad cow disease surfaced in England in 1986 and quickly became an epidemic. It since has been reported in 15 European countries, most recently Greece on July 2, and the Czech Republic on June 14. Two German-born cows tested positive for BSE in November.

 

 Singeltary said he became convinced that BSE is here as he watched his mother, Barbara Poulter of Crystal Beach, dying of sporadic Creutzfeldt-Jakob Disease. The rare, fatal brain disease is sometimes accompanied by severe jerking.

 

 "She would jerk so bad at times, it would take three of us to hold her down," Singeltary said. "They can call it whatever they want, but I know what I saw, and what she went through. `Sporadic' simply means they don't know."

 

 Poulter, a retired telephone-company field worker, had a form of sporadic CJD -- Haidenhain variant -- that is even less common than the typical sporadic case. One of its first symptoms is loss of vision.

 

 She started seeing brown spots in September 1997 and was virtually blind within two weeks. By the eighth week of the illness Poulter was bedridden, and in the 10th week she died. Before that she had been in good health.

 

 In many countries and most U.S. states, physicians are not required to report CJD cases to health officials. Texas made the disease reportable in 1998. Through 2000, there were 17 probable or confirmed cases, according to the Texas Department of Health.

 

 In mid-June, a case of sporadic CJD was confirmed through brain biopsy at Christus Spohn Hospital Shoreline in Corpus Christi, said Jane Bakos, hospital vice president. The patient has since died, the hospital reported.

 

 CJD and mad cow disease leave their victims' brains full of holes like a sponge.

 

 Although not contagious, the illnesses are thought to be transmissible through prions, or nearly indestructible abnormal proteins.

 

 Because the prion protein is not killed by standard sterilization, sporadic CJD can be spread by contaminated surgical instruments.

 

 In March 1996, the British government announced the discovery of a new variant of CJD, most likely explained by exposure to bovine spongiform encephalopathy.

 

 Through June, 101 cases of new-variant CJD have been reported in the United Kingdom, three in France and one in Ireland. In contrast to sporadic CJD, the new variant usually affects younger patients and lasts longer.

 

 No cases of new-variant CJD or BSE have been reported in the United States. No relationship has been shown between sporadic CJD and mad cow disease.

 

 There is no indication that new-variant CJD can be spread through blood transfusions, but a U.S. Food and Drug Administration advisory committee voted in June to broaden the categories for excluding potential donors. The recommendations have not yet been approved by the FDA.

 

 The American Red Cross has announced that on Sept. 17 it will begin rejecting potential blood donors who, since 1980, have spent at least three months in the United Kingdom or at least six months in any European country or combination of countries. Those who have received a blood transfusion in Britain since 1980 also will be rejected.

 

 The primary collector of local blood donations is the Gulf Coast Regional Blood Center, which will follow the FDA's guidelines, said Bill Teague, president and chief executive officer.

 

 Singeltary said it's naive to think that U.S. prevention efforts have kept mad cow and new-variant CJD out of the United States.

 

 "They haven't found it," he said, "because they haven't looked."

 

 For one thing, he said, too few cows are tested for the disease. In the first six months of this year, the European Union tested more than 3.2 million cows, David Byrne of the European Commission said in a speech last month.

 

 By contrast, it took the U.S. Department of Agriculture nearly 10 years to analyze about 13,000 cow brains, according to the department's Web site.

 

 With more than 68 million cattle slaughtered since 1990 in the United States, according to the USDA, checking about 13,000 falls far short, Singeltary said.

 

 Though not a scholar, Singeltary has collected voluminous material on mad cow and CJD. Disabled from a neck injury, Singeltary never used a computer until 1998.

 

 He now spends hours each day on the Internet while his wife, Bonnie Singeltary, runs a flower shop in their home in Bacliff, in north Galveston County.

 

 His challenge to the CJD/BSE establishment is courageous and refreshing, said Dr. Lynette Dumble, former visiting professor of surgery at University of Texas Medical School at Houston and a former senior research fellow in the history and philosophy of science at the University of Melbourne in Australia.

 

 "I certainly have no problem with Terry's ideas on BSE/CJD," said Dumble, who coordinates the Global Sisterhood Network, a computer service that posts media reports on developments affecting women. "His research skills are excellent, and he is abreast of each and every development in the field."

 

 Among Singeltary's worries now, he said, are widespread violations of an August 1997 ban on feeding animal products to U.S. cattle. The FDA reported in January that hundreds of feed manufacturers were not complying with regulations designed to keep BSE out of this country.

 

 (That same month, a Purina Mills feedlot near San Antonio told the FDA that a "very low level" of cow parts had been found in cattle feed. The company voluntarily removed 1,222 animals who had been fed the prohibited materials.)

 

 He obtained copies of FDA letters to various feed mills that had been found in violation of the regulations and immediately sent them by e-mail to hundreds of people around the world.

 

 Singeltary might not be so zealous in getting the word out if he weren't convinced that someone is covering up the truth.

 

 "They used to say BSE would never transmit to humans," he said, "and it has. They lied about the feed ban being in place.

 

 "I've lost faith in the whole process. I've discovered too many things."

 


 

 Tuesday, March 16, 2010

 

 COMMONWEALTH OF AUSTRALIA Hansard Import restrictions on beef FRIDAY, 5 FEBRUARY 2010 AUSTRALIA

 

 COMMONWEALTH OF AUSTRALIA

 

 Proof Committee Hansard

 

 RRA&T 2 Senate Friday, 5 February 2010

 

 RURAL AND REGIONAL AFFAIRS AND TRANSPORT

 

 [9.03 am]

 

 BELLINGER, Mr Brad, Chairman, Australian Beef Association CARTER, Mr John Edward, Director, Australian Beef Association CHAIR—Welcome. Would you like to make an opening statement? Mr Bellinger—Thank you. The ABA stands by its submission, which we made on 14 December last year, that the decision made by the government to allow the importation of beef from BSE affected countries is politically based, not science based. During this hearing we will bring forward compelling new evidence to back up this statement. When I returned to my property after the December hearing I received a note from an American citizen. I will read a small excerpt from the mail he sent me in order to reinforce the dangers of allowing the importation of beef from BSE affected countries. I have done a number of press releases on this topic, and this fellow has obviously picked my details up from the internet. His name is Terry Singeltary and he is from Bacliff, Texas. He states, and rightfully so: You should be worried. Please let me explain. I’ve kept up with the mad cow saga for 12 years today, on December 14th 1997, some four months post voluntary and partial mad cow feed ban in the USA, I lost my mother to the Heinemann variant Creutzfeldt-Jakob disease (CJD). I know this is just another phenotype of the infamous sporadic CJDs. Here in the USA, when USA sheep scrapie was transmitted to USA bovine, the agent was not UK BSE—it was a different strain. So why then would human TSE from USA cattle look like UK CJD from UK BSE? It would not. So this accentuates that the science is inconclusive still on this devastating disease. He goes on to state:

 

 snip...see full text 110 pages ;

 


 

 for those interested, please see much more here ;

 


 


 


 

 This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

 


 

 Owens, Julie From: Terry S. Singeltary Sr. [flounder9@verizon.net]

 

 Sent: Monday, July 24, 2006 1:09 PM To: FSIS RegulationsComments

 

 Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Page 1 of 98 8/3/2006

 

 Greetings FSIS, I would kindly like to comment on the following ;

 


 

 Nature | Editorial

 

 Needless conflict Nature 485, 279–280 (17 May 2012) doi:10.1038/485279b Published online 16 May 2012

 


 

 Tuesday, December 2, 2014

 

 UK EXPORTS OF MBM TO WORLD Bovine Spongiform Encephalopathy BSE TSE Prion aka Mad Cow Disease

 

 USA, NORTH AMERICA, MBM (or any potential TSE prion disease) EXPORTS TO THE WORLD (?) [protected by the BSE MRR policy] $$$

 


 

 *** Qualitative Analysis of BSE Risk Factors in the United States

 

 February 13, 2000 at 3:37 pm PST (BSE red book)

 


 

 Tuesday, July 14, 2009 U.S.

 

 *** Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book

 

 Date: February 14, 2000 at 8:56 am PST

 

 WHERE did we go wrong $$$

 


 

 Friday, November 22, 2013

 

 Wasting disease is threat to the entire UK deer population CWD TSE PRION disease in cervids

 

 ***SINGELTARY SUBMISSION

 

 The Scottish Parliament’s Rural Affairs, Climate Change and Environment Committee has been looking into deer management, as you can see from the following press release,

 

 ***and your email has been forwarded to the committee for information:

 


 


 

 Sunday, July 21, 2013

 

 Welsh Government and Food Standards Agency Wales Joint Public Consultation on the Proposed Transmissible Spongiform Encephalopathies (Wales) Regulations 2013

 

 *** Singeltary Submission WG18417

 


 

 *** 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.

 


 


 

 Subject: OIE cuts six European countries' mad cow risk level, while increasing risk factors for humans to the BSE TSE PRION DISEASE around the globe

 

Published May 27, 2015, 03:42 PM

 

OIE cuts six European countries' mad cow risk level

 

The World Organization for Animal Health said on Wednesday it had lowered to the safest level the official risk of six countries for mad cow disease, a move expected to open international market access for their beef exports. By: Reuters ,

 

PARIS -- The World Organization for Animal Health said on Wednesday it had lowered to the safest level the official risk of six countries for mad cow disease, a move expected to open international market access for their beef exports.

 

These countries are France, Ireland, Switzerland, the Czech Republic, Cyprus and the Lichtenstein.

 

OIE members in Paris eased their status on bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, to "negligible risk" from "controlled risk".

 

One of the OIE criteria to be categorized as a negligible BSE risk country is to demonstrate that the last infected native animal was born more than 11 years ago, it said.

 

"The main advantage will be at international trade level because many countries insist on limiting trade exchange to countries that have the same risk status," Karin Schwabenbauer, head the OIE Council and World Assembly, told reporters.

 

France welcomed the decision, noting that the BSE epidemic that spread from Britain to mainland Europe in the 1980s because of contaminated meal had prompted consumer distrust and trade restrictions.

 

"I appeal to countries that still have an embargo on exports of this sector to lift it very quickly," French Agriculture Minister Stephane Le Foll said in a statement.

 

Thirteen countries ban French beef and beef products because of BSE - Brazil, China, Argentina, Saudi Arabia, Taiwan, South Africa, Botswana, Mali, Uganda, South Korea, Iraq, Syria and Qatar - a Farm Ministry spokesman said. Japan, Vietnam and Singapore ban meat from cattle older than 30 months.

 

Ireland earlier this year signed export deals with China and the United States, making it the only European country to be allowed to export beef to both countries.

 

Tags: mad cow, livestock, agribusiness, updates, cattle - See more at: http://www.agweek.com/event/article/id/26479/#sthash.2opRk32H.dpuf

 


 


 


 


 


 

 it’s all about trade now, nothing else matters $$$

 

>>>PARIS -- The World Organization for Animal Health said on Wednesday it had lowered to the safest level the official risk of six countries for mad cow disease, a move expected to open international market access for their beef exports. These countries are France, Ireland, Switzerland, the Czech Republic, Cyprus and the Lichtenstein.<<<

 

THIS move is _not_ based on science, but on corporate profits and big ag. to say now that France is a "negligible risk", would be like saying North America is a "negligible risk", which is preposterous. not based on sound science, but on greed and special interest. the only _move_ this ‘’BSE mad cow negligible risk’’ assessment makes, is a move to increase global Transmissible Spongiform Encephalopathy prion mad cow type disease, via the legal trading of the TSE prion aka mad cow type disease via the BSE MRR i.e. Minimal Risk Region policy, a policy set up to fail from the start. please, for whatever God you pray to sake, please be warned.

 

‘’AS i said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization.’’

 

IN A NUT SHELL ;

 

(Adopted by the International Committee of the OIE on 23 May 2006)

 

11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,

 


 

Wednesday, March 11, 2015

 

OIE and Centers for Disease Control and Prevention Reinforce Collaboration

 


 

Friday, April 4, 2014

 

China, Australia, Argentina, Brazil, Uruguay, Morocco, Israel, South Africa and Saudi Arabia still retain BSE-related closures

 


 

Thursday, May 30, 2013

 

World Organization for Animal Health (OIE) has upgraded the United States' risk classification for mad cow disease to "negligible" from "controlled", and risk further exposing the globe to the TSE prion mad cow type disease

 

U.S. gets top mad-cow rating from international group and risk further exposing the globe to the TSE prion mad cow type disease

 


 


 

The OIE is nothing more than a trading brokerage for the Transmissible Spongiform Encephalopathy TSE prion disease aka mad cow type disease. Frances is still in the midst of a mad cow disease outbreak with atypical BSE cases still growing. mad cow disease is so bad in France, as with the USA, they stopped testing for mad cow disease (France altogether and the USA to figures so low, you would only detect a case of mad cow disease, only by chance).

 

from the inside looking out ;

 

Quote: Maybe familirise yourself with the OIE. The primary concern is animal health of the world they are the animal version of the WHO. It is a long way down from that ivory tower but here we go, until pressured by the USA repesentatives a country could not export animals for 6 years after finding a BSE/BASE positive animal so under the old rules the US would not be able to export anywhere in the world for another 4 1/2 years. Who got the risk levels system put in to allow some trade - your US representatives. You guys want to change rules - OK , but you do not get special rules that only apply to the US. As i have told you before Sand h I market all my own slaughter animals and you know that, so don't do the whole holier than thow act.

 

With all due respect, it is obvious that you know little about the OIE and how it actually works. Having been to their offices in Paris and talked personally with the Head of the Animal Test Section, you would choke if you knew how many lobby groups attend that office daily. There is a steady stream of paid lobby groups that have one goal in life and that is to sway the Section Heads of each department within the OIE to suit the needs of different juristictions around the world, which curiously enough, also includes the USA and Canada. Anyone can go there and chat with them - providing they can privide valid cause to be let in. To say that the only goal of the OIE is animal health is actually only part of their function. They are more than that and my discussions with Dr. Diaz there has showed me that. But to blindly make a statement regarding what they do when you have no idea what they actually do is like eating the skin of the orange and not knowing what is actually under.

 

Interstingly you state that the US Government applied pressure (to the OIE) I assume and that is a great example of the lobby groups doing their job. So, at the end of the day, one can safely assume that it is the pressure applied by certain influential lobby groups that will determine a likely aoutcome to an apparent OIE directive. Man alive, isn't it great to live in a democracy wherein the people get to make the choices and not just some "other" interested party or group - say like........Cargyll or Tyson for example?

 

So, one last question, question?

 

Who wags the tail of that dog?? And for what reason other than one that is purely associated with trade and international agreements and greed?

 

And you think it is so simply explainable.

 

end...tss

 

please see ;

 

spontaneous atypical BSE ???

 

don’t let anyone fool you. spontaneous TSE prion disease is a hoax in natural cases, never proven.

 

all one has to do is look at France. France is having one hell of an epidemic of atypical BSE, probably why they stopped testing for BSE, problem solved $$$ same as the USA, that’s why they stopped testing for BSE mad cow disease in numbers they could find any with, after those atypical BSE cases started showing up. shut down the testing to numbers set up by OIE that are so low, you could only by accident find a case of BSE aka mad cow disease. and this brilliant idea by the WHO et al, to change the name of mad cow disease, thinking that might change things is preposterous. it’s all about money now folks, when the OIE, USDA and everyone else went along and made the TSE prion disease aka mad cow type disease a legal trading commodity by the BSE MRR policy, I would say everyone bit off more then they can chew, and they will just have to digest those TSE Prions coming from North America, and like it, and just prey you don’t get a mad cow type disease i.e. Transmissible Spongiform Encephalopathy TSE prion disease in the decades to come, and or pass it to some other poor soul via the iatrogenic medical surgical tissue friendly fire mode of transmission i.e. second hand transmission. it’s real folks, just not documented much, due to lack of trace back efforts. all iatrogenic cjd is, is sporadic cjd, until the iatrogenic event is tracked down and documented, and put into the academic and public domain, which very seldom happens. ...

 

As of December 2011, around 60 atypical BSE cases have currently been reported in 13 countries, *** with over one third in France.

 


 

FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many spontaneous events of mad cow disease $$$

 

so 20 cases of atypical BSE in France, compared to the remaining 40 cases in the remaining 12 Countries, divided by the remaining 12 Countries, about 3+ cases per country, besides Frances 20 cases. you cannot explain this away with any spontaneous BSe. ...TSS

 

Sunday, October 5, 2014

 

France stops BSE testing for Mad Cow Disease

 


 

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

 


 

Saturday, May 09, 2015

 

Expression of genes involved in the T cell signalling pathway in circulating immune cells of cattle 24 months following oral challenge with Bovine Amyloidotic Spongiform Encephalopathy (BASE)

 


 

(c) The commonest form of CJD occurs as a sporadic disease, the cause of which is unknown, although genetic factors (particularly the codon 129 polymorphism in the prion protein gene (PRNP)) influence disease susceptibility. The familial forms of human TSEs (see Box 1) appear to have a solely genetic origin and are closely associated with mutations or insertions in the PRNP gene. Most, but not all, of the familial forms of human TSEs have been transmitted experimentally to animals. There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease. (

 


 

31 Jan 2015 at 20:14 GMT

 

*** Ruminant feed ban for cervids in the United States? ***

 

31 Jan 2015 at 20:14 GMT

 


 

Wednesday, May 27, 2015

 

*** BSE Case Associated with Prion Protein Gene Mutation ***

 


 

Saturday, May 09, 2015

 

Expression of genes involved in the T cell signalling pathway in circulating immune cells of cattle 24 months following oral challenge with Bovine Amyloidotic Spongiform Encephalopathy (BASE)

 


 

Tuesday, May 19, 2015

 

COUNTRY OF ORIGIN LABELING COOL H.R. 2393 Agriculture Chairman K. Michael Conaway (R-TX) Fears of US imports infected with mad cow disease is emerging as an issue in trans-Pacific trade talks

 


 

Tuesday, December 16, 2014

 

Evidence for zoonotic potential of ovine scrapie prions

 

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics

 

Abstract

 

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

 

Subject terms: Biological sciences• Medical research At a glance

 


 

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

 


 

Suspect symptoms

 

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

 

28 Mar 01 Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

 

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...

 

2001

 

Suspect symptoms

 

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

 

28 Mar 01

 

Like lambs to the slaughter

 

31 March 2001

 

by Debora MacKenzie Magazine issue 2284.

 

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

 

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

 

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

 

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

 

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

 

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

 

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

 

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

 

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

 

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

 

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

 

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

 


 

Friday, January 30, 2015

 

*** Scrapie: a particularly persistent pathogen ***

 


 

Monday, November 30, 2009

 

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

 


 

I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS

 

Sunday, April 12, 2015

 

*** Research Project: Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies 2014 Annual Report ***

 


 

Friday, May 22, 2015

 

Chronic Wasting Disease and Program Updates - 2014 NEUSAHA Annual Meeting 12-14 May 2014

 


 

Comment from Terry Singeltary This is a Comment on the Food and Drug Administration (FDA) Notice: Draft Guidance for Industry on Ensuring Safety of Animal Feed Maintained and Fed On-Farm; Availability

 

For related information, Open Docket Folder Docket folder icon

 

--------------------------------------------------------------------------------

 

Show agency attachment(s) Attachments View All (0)

 

--------------------------------------------------------------------------------

 

Comment View document:

 


 


 

WI

 

REASON

 

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

 

VOLUME OF PRODUCT IN COMMERCE

 

9,997,976 lbs.

 

DISTRIBUTION

 

ID and NV

 

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

 


 

Terry S. Singeltary Sr.

 

*** See attached file(s) No documents available. Attachments View All (1) Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm Terry Singeltary Comment View Attachment:

 


 

Sunday, April 5, 2015

 

*** Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180 ***

 


 

Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180 Singeltary Comment

 

Greetings FDA et al,

 

I wish to comment on Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180.

 

Once again, I wish to kindly bring up the failed attempt of the FDA and the ruminant to ruminant mad cow feed ban of August 4, 1997. This feed ban is still failing today, as we speak. Even more worrisome, is the fact it is still legal to feed cervids to cervids in the USA, in fact, the FDA only _recommends_ that deer and elk considered to be of _high_ risk for CWD do not enter the animal food chain, but there is NO law, its only voluntary, a recipe for a TSE prion disaster, as we have seen with the ruminant to ruminant feed ban for cattle, where in 2007, one decade post August 1997 mad cow feed ban, where in 2007 10,000,000 POUNDS OF BANNED BLOOD LACED MEAT AND BONE MEAL WHEN OUT INTO COMMERCE, TO BE FED OUT. Since 2007, these BSE feed ban rules have been breached time and time again. tons and tons of mad cow feed went out in Alabama as well, where one of the mad cows were documented, just the year before in 2006, and in 2013 and 2014, breaches so bad (OAI) Official Action Indicated were issued. those are like the one issued where 10 million pounds of banned blood laced meat and bone meal were fed out.

 

What is the use of having a Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180, if it cannot be enforced, as we have seen with a mandatory ruminant to ruminant feed ban?

 

I strenuously once again urge the FDA and its industry constituents, to make it MANDATORY that all ruminant feed be banned to all ruminants, and this should include all cervids as soon as possible for the following reasons...

 

======

 

In the USA, under the Food and Drug Administrations BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system.

 

***However, this recommendation is guidance and not a requirement by law.

 

======

 

31 Jan 2015 at 20:14 GMT

 

*** Ruminant feed ban for cervids in the United States? ***

 

31 Jan 2015 at 20:14 GMT

 


 

19 May 2010 at 21:21 GMT

 

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

 


 

Tuesday, December 23, 2014

 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION

 


 

2013

 

Sunday, December 15, 2013

 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2013 UPDATE

 


 

DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability Date: Fri, 16 May 2003 11:47:37 0500 EMC 1 Terry S. Singeltary Sr. Vol #: 1

 


 


 

PLEASE SEE FULL TEXT SUBMISSION ;

 


 

10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

 

Date: March 21, 2007 at 2:27 pm PST

 

REASON

 

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

 

VOLUME OF PRODUCT IN COMMERCE

 

42,090 lbs.

 

DISTRIBUTION

 

WI

 

REASON

 

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

 

VOLUME OF PRODUCT IN COMMERCE

 

9,997,976 lbs.

 

DISTRIBUTION

 

ID and NV

 

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

 


 

Terry S. Singeltary Sr.

 

*** See attached file(s) No documents available. Attachments View All (1) Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm Terry Singeltary Comment View Attachment:

 


 

Sunday, April 5, 2015

 

*** Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180 ***

 


 

Sunday, January 11, 2015

 

Docket No. APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of Animals and Animal Products Singeltary Submission

 


 

This is a Comment on the Animal and Plant Health Inspection Service (APHIS) Notice: Agency Information Collection Activities; Proposals, Submissions, and Approvals: Bovine Spongiform Encephalopathy; Importation of Animals and Animal Products

 

For related information, Open Docket Folder Docket folder icon

 

--------------------------------------------------------------------------------

 

Show agency attachment(s) AttachmentsView All (0) Empty

 

--------------------------------------------------------------------------------

 

Comment View document:Docket No. APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of Animals and Animal Products Singeltary Submission ;

 

I believe that there is more risk to the world from Transmissible Spongiform Encephalopathy TSE prion aka mad cow type disease now, coming from the United States and all of North America, than there is risk coming to the USA and North America, from other Countries. I am NOT saying I dont think there is any risk for the BSE type TSE prion coming from other Countries, I am just saying that in 2015, why is the APHIS/USDA/FSIS/FDA still ignoring these present mad cow risk factors in North America like they are not here?

 

North America has more strains of TSE prion disease, in more species (excluding zoo animals in the early BSE days, and excluding the Feline TSE and or Canine TSE, because they dont look, and yes, there has been documented evidence and scientific studies, and DEFRA Hound study, that shows the canine spongiform encephalopathy is very possible, if it has not already happened, just not documented), then any other Country in the world. Mink TME, Deer Elk cervid CWD (multiple strains), cBSE cattle, atypical L-type BSE cattle, atypical H-type BSE cattle, atyical HG type BSE cow (the only cow documented in the world to date with this strain), typical sheep goat Scrapie (multiple strains), and the atypical Nor-98 Scrapie, which has been linked to sporadic CJD, Nor-98 atypical Scrapie has spread from coast to coast. sporadic CJD on the rise, with different strains mounting, victims becoming younger, with the latest nvCJD human mad cow case being documented in Texas again, this case, NOT LINKED TO EUROPEAN TRAVEL CDC.

 

typical BSE can propagate as nvCJD and or sporadic CJD (Collinge et al), and sporadic CJD has now been linked to atypical BSE, Scrapie and atypical Scrapie, and scientist are very concerned with CWD TSE prion in the Cervid populations. in my opinion, the BSE MRR policy, which overtook the BSE GBR risk assessments for each country, and then made BSE confirmed countries legal to trade mad cow disease, which was all brought forth AFTER that fateful day December 23, 2003, when the USA lost its gold card i.e. BSE FREE status, thats the day it all started. once the BSE MRR policy was shoved down every countries throat by USDA inc and the OIE, then the legal trading of Scrapie was validated to be a legal trading commodity, also shoved through by the USDA inc and the OIE, the world then lost 30 years of attempted eradication of the BSE TSE prion disease typical and atypical strains, and the BSE TSE Prion aka mad cow type disease was thus made a legal trading commodity, like it or not. its all about money now folks, trade, to hell with human health with a slow incubating disease, that is 100% fatal once clinical, and forget the fact of exposure, sub-clinical infection, and friendly fire there from i.e. iatrogenic TSE prion disease, the pass it forward mode of the TSE PRION aka mad cow type disease. its all going to be sporadic CJD or sporadic ffi, or sporadic gss, or now the infamous VPSPr. ...problem solved $$$

 

the USDA/APHIS/FSIS/FDA triple mad cow BSE firewall, well, that was nothing but ink on paper.

 

for this very reason I believe the BSE MRR policy is a total failure, and that this policy should be immediately withdrawn, and set back in place the BSE GBR Risk Assessments, with the BSE GBR risk assessments set up to monitor all TSE PRION disease in all species of animals, and that the BSE GBR risk assessments be made stronger than before.

 

lets start with the recent notice that beef from Ireland will be coming to America.

 

Ireland confirmed around 1655 cases of mad cow disease. with the highest year confirming about 333 cases in 2002, with numbers of BSE confirmed cases dropping from that point on, to a documentation of 1 confirmed case in 2013, to date. a drastic decrease in the feeding of cows to cows i.e. the ruminant mad cow feed ban, and the enforcement of that ban, has drastically reduced the number of BSE cases in Europe, minus a few BABs or BARBs. a far cry from the USDA FDA triple BSE firewall, which was nothing more than ink on paper, where in 2007, in one week recall alone, some 10 MILLION POUNDS OF BANNED POTENTIAL MAD COW FEED WENT OUT INTO COMMERCE IN THE USA. this is 10 years post feed ban. in my honest opinion, due to the blatant cover up of BSE TSE prion aka mad cow disease in the USA, we still have no clue as to the true number of cases of BSE mad cow disease in the USA or North America as a whole. ...just saying.

 

Number of reported cases of bovine spongiform encephalopathy (BSE) in farmed cattle worldwide* (excluding the United Kingdom)

 

Country/Year

 

snip...please see attached pdf file, with references of breaches in the USA triple BSE mad cow firewalls, and recent science on the TSE prion disease. ...TSS

 

No documents available. AttachmentsView All (1) Empty Docket No. APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of Animals and Animal Products Singeltary Submission View Attachment:

 


 

Sunday, January 11, 2015

 

Docket No. APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of Animals and Animal Products Singeltary Submission

 


 

Tuesday, February 17, 2015

 

*** Could we spot the next BSE?, asks BVA President ***

 


 

UK EXPORTS OF MBM TO WORLD

 


 


 


 

OTHERS BEEF AND VEAL

 


 


 


 


 


 


 


 


 


 

Tuesday, September 2, 2014

 

COOL UPDATE September 2, 2014

 


 

Monday, February 23, 2015

 

20th BSE Case Raises New Concerns about Canada's Feeding Practices and Voluntary Testing Program; Highlights Importance of COOL

 


 

Friday, February 20, 2015

 

A BSE CANADIAN COW MAD COW UPDATE Transcript - Briefing (February 18, 2015)

 


 

EDMONTON - Some of former Alberta premier Ralph Klein's most colourful quotes — and the reactions they elicited:

 

SNIP...

 

"This all came about through the discovery of a single, isolated case of mad cow disease in one Alberta cow on May 20th. The farmer — I think he was a Louisiana fish farmer who knew nothing about cattle ranching. I guess any self-respecting rancher would have shot, shovelled and shut up, but he didn't do that." — Klein recalls how the mad cow crisis started and rancher Marwyn Peaster's role. The premier was speaking at the Western Governors Association meeting in Big Sky, Mont. September 2004.

 

"The premier meant that in an ironic or almost a sarcastic way." — Klein spokesman Gordon Turtle.

 

---

 

"You would have to eat 10 billion meals of brains, spinal cords, ganglia, eyeballs and tonsils." — Klein speaking in Montreal in January 2005 on the risk of humans contracting mad cow disease.

 

---

 

"I would offer $5 billion to have a Japanese person to come over here and eat nothing but Alberta beef for a year. And if he gets mad cow disease, I would be glad to give him $5 billion — make it $10 billion — Canadian." — Klein speaking after Japan closed its borders to Canadian beef.

 

---

 


 


 

Thursday, February 10, 2011

 

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011 and how to hide mad cow disease in Canada Current as of: 2011-01-31

 


 

Wednesday, August 11, 2010

 

REPORT ON THE INVESTIGATION OF THE SIXTEENTH CASE OF BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN CANADA

 


 

Thursday, August 19, 2010

 

REPORT ON THE INVESTIGATION OF THE SEVENTEENTH CASE OF BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN CANADA

 


 

Friday, March 4, 2011

 

Alberta dairy cow found with mad cow disease

 


 

Tuesday, May 21, 2013

 

Canada, USA, Bad feed, mad cows: Why we know three BSE cases had a common origin and why the SSS policy is in full force $$$

 


 

Increased Atypical Scrapie Detections

 

Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.

 


 

Current as of: 2015-01-31

 

Sheep flocks and/or goat herds confirmed to be infected with classical scrapie in Canada in 2015 Date confirmed Location Animal type infected January 5 Ontario Goat

 


 


 

Tuesday, February 10, 2015

 

Alberta Canada First case of chronic wasting disease found in farm elk since 2002

 


 

Saturday, March 21, 2015

 

***Canada and United States Creutzfeldt Jakob TSE Prion Disease Incidence Rates Increasing

 


 

Tuesday, May 26, 2015

 

*** Minimise transmission risk of CJD and vCJD in healthcare settings Last updated 15 May 2015 ***

 


 

Tuesday, April 21, 2015

 

Transmissible Spongiform Encephalopathy Advisory Committee TSEAC MEETING SCHEDULED FOR June 1, 2015

 


 

Saturday, April 18, 2015

 

*** vCJD TEXAS CDC Emerging Infectious Diseases May 2015 Baylor College of Medicine Neuroscience 2014 case of human form of “mad cow disease” highlights need for continued surveillance

 


 

Saturday, May 09, 2015

 

*** Psychiatric Symptoms in Patients With Sporadic Creutzfeldt-Jakob Disease ***

 


 

Sunday, May 3, 2015

 

PRION2015 FORT COLLINS

 


 

Transmissible Spongiform Encephalopthy TSE Prion Disease

 

*** Kuru Video

 

Kuru: The Science and The Sorcery

 


 

*** Scrapie Video

 


 

*** Human Mad Cow Video

 


 

*** USA sporadic CJD MAD COW DISEASE HAS HUGE PROBLEM Video

 


 

2014

 

***Moreover, L-BSE has been transmitted more easily to transgenic mice overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.

 

***It has been suggested that some sporadic CJD subtypes in humans may result from an exposure to the L-BSE agent.

 

*** Lending support to this hypothesis, pathological and biochemical similarities have been observed between L-BSE and an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and another sCJD subtype (MM genotype) [15].

 

snip...

 


 

Monday, October 10, 2011

 

EFSA Journal 2011 The European Response to BSE: A Success Story

 

snip...

 

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far

 

*** but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded.

 

*** Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

 

snip...

 


 


 

Thursday, August 12, 2010

 

Seven main threats for the future linked to prions

 

First threat

 

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

 

*** Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans.

 

*** These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

 

Second threat

 

snip...

 


 

Sunday, November 23, 2014

 

*** Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European ***

 


 

Monday, November 3, 2014

 

USA CJD TSE PRION UNIT, TEXAS, SURVEILLANCE UPDATE NOVEMBER 2014

 

National Prion Disease Pathology Surveillance Center Cases Examined1 (October 7, 2014)

 

***6 Includes 11 cases in which the diagnosis is pending, and 19 inconclusive cases;

 

***7 Includes 12 (11 from 2014) cases with type determination pending in which the diagnosis of vCJD has been excluded.

 

***The sporadic cases include 2660 cases of sporadic Creutzfeldt-Jakob disease (sCJD),

 

***50 cases of Variably Protease-Sensitive Prionopathy (VPSPr)

 

***and 21 cases of sporadic Fatal Insomnia (sFI).

 


 

Thursday, January 15, 2015

 

41-year-old Navy Commander with sporadic Creutzfeldt–Jakob disease CJD TSE Prion: Case Report

 


 

Subject: *** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease aka mad cow type disease

 

what is CJD ? just ask USDA inc., and the OIE, they are still feeding the public and the media industry fed junk science that is 30 years old.

 

why doesn’t some of you try reading the facts, instead of rubber stamping everything the USDA inc says.

 

sporadic CJD has now been linked to BSE aka mad cow disease, Scrapie, and there is much concern now for CWD and risk factor for humans.

 

My sincere condolences to the family and friends of the House Speaker Becky Lockhart. I am deeply saddened hear this.

 

with that said, with great respect, I must ask each and every one of you Politicians that are so deeply saddened to hear of this needless death of the Honorable House Speaker Becky Lockhart, really, cry me a friggen river. I am seriously going to ask you all this...I have been diplomatic for about 17 years and it has got no where. people are still dying. so, are you all stupid or what??? how many more need to die ??? how much is global trade of beef and other meat products that are not tested for the TSE prion disease, how much and how many bodies is this market worth?

 

Saturday, January 17, 2015

 

*** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease

 


 

*** ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD strains, TSE prion aka Mad Cow Disease United States of America Update December 14, 2014 Report ***

 


 

*** Creutzfeldt-Jakob Disease Public Health Crisis VIDEO

 


 


 


 


 

Saturday, December 13, 2014

 

Terry S. Singeltary Sr. Publications TSE prion disease

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

snip...

 


 

lost my mom to the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD 12/14/97 confirmed. I just made a promise to mom, never forget (I could never ever forget what I saw), and never let them forget...

 

layperson

 

Terry S. Singeltary Sr., Bacliff, Texas USA 77518 flounder9@verizon.net

 

Thursday, May 28, 2015

 

OIE cuts six European countries' mad cow risk level, while increasing risk factors for humans to the BSE TSE PRION DISEASE around the globe

 


 

 

 

 


 

 

 


 

No comments:

Post a Comment