Saturday, October 6, 2012

TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2011 Annual Report

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research Unit



2011 Annual Report



1a.Objectives (from AD-416) Obj. 1. Assess the cross species transmissibility of transmissible spongiform encephalopathies (TSEs) in livestock and wildlife. Obj. 2. Investigate the pathobiology of TSEs in natural and secondary hosts. Obj. 3. Investigate pathogenesis and ante mortem detection of bovine spongiform encephalopathy (BSE). Obj. 4. Develop a method to detect central nervous system (CNS) tissue contamination on carcasses. Obj. 5. Discover effective methods to inactivate TSE agents in agricultural settings.



1b.Approach (from AD-416) Studies are focused on the four animal Transmissible Spongiform Encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; and transmissible mink encephalopathy (TME). These agents will be tested for cross-species transmissibility into various livestock and cervid species using both oral and intracerebral inoculation. Sites of accumulation, routes of infection, methods of isolate differentiation, and in the case of BSE, genetics of susceptibility and ante-mortem diagnostics, will be investigated. Existing technology developed at the National Animal Disease Center and those used in the meat packing industry for the detection of fecal contamination on carcasses will be adapted to detect CNS tissue contamination on carcasses. Methods of TSE inactivation will be evaluated for efficacy in agricultural settings.



3.Progress Report This is the final report for project 3625-32000-086-00D, terminated in September 2011 and replaced by 3625-32000-103-00D. The project plan involved 5 objectives.



In Objective 1, Assess cross-species transmissibility of transmissible spongiform encephalopathies (TSEs) in livestock and wildlife, numerous experiments assessing the susceptibility of various TSEs in different host species were conducted. Most notable is deer inoculated with scrapie, which exhibits similarities to chronic wasting disease (CWD) in deer suggestive of sheep scrapie as an origin of CWD.



In Objective 2, Investigate the pathobiology of TSEs in natural and secondary hosts, deer were inoculated with CWD-infected blood. Several animals developed clinical signs, a result consistent with CWD infectivity in blood. Also, biochemical strain typing commonly used for rodent models of TSE was investigated to assess the importance of genetic variability in natural hosts and how to apply these methods to natural hosts.



Objective 3, Investigate pathogenesis and antemortem detection of bovine spongiform encephalopathy (BSE), involves several different research areas. Our results in genetic susceptibility of BSE support the now widely accepted conclusion that atypical BSE is a spontaneous TSE in cattle. This has important implications for the ruminant feed ban, food safety, and our understanding of the origins of BSE. Also as part of Obj. 3, we identified the first recognized case of genetic BSE where a natural case of BSE was identified in an animal containing a polymorphism analogous to a human polymorphism that causes a genetic TSE. Bovine spongiform encephalopathy has long been believed to only be a feed-borne disease. Together, our results show for the first time the presence of three different etiologies for BSE as are known to occur in humans. As part of our investigation, classical, and atypical BSE isolates were inoculated into cattle. Upon completion, this work will represent the first thorough comparison of domestic and international BSE isolates, including both classical and atypical BSE. An antemortem diagnostic technique based upon retinal function was developed and is routinely applied to experimental animals on site. This technique detects a TSE before the onset of clinical signs. Work is ongoing to increase the number of animals containing the E211K polymorphism, a potential cause of genetic BSE; this will provide the only means by which to prove the novel allele may cause BSE. The unusual E211K BSE material has also been successfully amplified in one of these animals.



Objective 4, Develop a method to detect CNS tissue contamination on carcasses, resulted in a successful method that may be applied through adaptation of existing technology currently used to detect fecal contamination on carcasses.



In Objective 5, Determine effective methods to inactivate TSE agents in agricultural settings, compounds applicable to agricultural settings were evaluated; the results are being prepared for publication. As part of this objective, a natural host model for assessing inactivation was developed. Despite experimental success the model is not suitable due to incubation time.



4.Accomplishments 1. Deer inoculated with domestic isolates of sheep scrapie. Scrapie-affected deer exhibit 2 different patterns of disease associated prion protein. In some regions of the brain the pattern is much like that observed for scrapie, while in others it is more like chronic wasting disease (CWD), the transmissible spongiform encephalopathy typically associated with deer. This work conducted by ARS scientists at the National Animal Disease Center, Ames, IA suggests that an interspecies transmission of sheep scrapie to deer may have been the origin of CWD. This is important for husbandry practices with both captive deer, elk and sheep for farmers and ranchers attempting to keep their herds and flocks free of CWD and scrapie.



2. Demonstrated transmissibility of K211 BSE, a rare genetic form of bovine spongiform encephalopathy (BSE), to cattle. Cattle containing the rare K211 PRNP gene have been produced in-house and used in this study conducted by ARS scientists at the National Animal Disease Center, Ames, IA. These animals have been inoculated with both K211 BSE and classical BSE. The K211 BSE is transmissible and progresses far more rapidly in K211 cattle than does classical BSE. Because of their genetic susceptibility to BSE, K211 PRNP cattle have a very rapid incubation time and may be more susceptible to TSEs, which are two characteristics that make them highly desirable for future studies of antemortem diagnostics and residual infectivity or risk materials after decontamination. The possibility remains that K211 BSE transmitted to conventional cattle will result in a disease phenotype similar to classical BSE. If this turns out to be true, then it will be very important in that it suggests a very rare genetic form of BSE could have been the original source of brain material responsible for the U.K. BSE epidemic. Current human and animal feed bans regarding specified risk materials from cattle protect humans and animals from a recurrence of such an epidemic.



Review Publications Hamir, A.N., Greenlee, J.J., Stanton, T.B., Smith, J.D., Doucette, S., Kunkle, R.A., Stasko, J.A., Richt, J.A., Kehrli, Jr., M.E. 2011. Experimental inoculation of raccoons (Procyon lotor) with Spiroplasma mirum and transmissible mink encephalopathy (TME). Canadian Journal of Veterinary Research. 75(1):18–24.



Hamir, A.N., Greenlee, J.J., Nicholson, E.M., Kunkle, R.A., Richt, J.A., Miller, J.M., Hall, M. 2011. Experimental transmission of chronic wasting disease (CWD) from elk and white-tailed deer to fallow deer by intracerebral route: final report. Canadian Journal of Veterinary Research. 75(2):152-156.



Smith, J.D., Hamir, A.N., Greenlee, J.J. 2011. Cartilaginous metaplasia in the sclera of Suffolk sheep. Veterinary Pathology. 48(4):827-829.



Loiacono, C.M., Beckwith, N., Kunkle, R.A., Orcutt, D., Hall, S.M. 2010. Detection of PrPSc in formalin-fixed, paraffin embedded tissue by Western blot differentiates classical scrapie, Nor98 scrapie, and bovine spongiform encephalopathy. Journal of Veterinary Diagnostic Investigation. 22(5):684-689.



Hamir, A.N., Kehrli, Jr., M.E., Kunkle, R.A., Greenlee, J.J., Nicholson, E.M., Richt, J.A., Miller, J.M., Cutlip, R.C. 2011. Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle. Journal of Veterinary Diagnostic Investigation. 23(3):407-420.



Nicholson, E.M. 2011. Enrichment of PrPSc in formalin-fixed, paraffin-embedded tissues prior to analysis by Western blot. Journal of Veterinary Diagnostic Investigation. 23(4):790-792.










Atypical H-Type Bovine Spongiform Encephalopathy in a Cow Born after the Reinforced Feed-Ban on Meat-and-Bone-Meal



Claudia Guldimann1, Michaela Gsponer1, Cord Drögemüller2, Anna Oevermann1 and Torsten Seuberlich1,*



+ Author Affiliations



1NeuroCentre, National and OIE Reference Laboratory for BSE and Scrapie



2Institute of Genetics, Vetsuisse Faculty, University of Berne, Berne, Switzerland




ABSTRACT



The significance of atypical bovine spongiform encephalopathies (BSE) in cattle for controlling the BSE epidemic is poorly understood. Here we report a case of atypical H-type BSE born after the implementation of the reinforced feed-ban in Europe. This supports an etiology of H-type BSE unrelated to that of classical BSE.




FOOTNOTES ↵* Corresponding author. Mailing address: NeuroCentre, DCR-VPH, Bremgartenstrasse 109a, CH-3001 Berne, Switzerland. Phone: 41 31 631 2206. Fax: 41 31 631 2538. E-mail: torsten.seuberlich@vetsuisse.unibe.ch Copyright © 2012, American Society for Microbiology. All Rights Reserved.




snip...





In contrast, the animal described here was 6.5 years old, CNS specific neurological signs were not observed, and spongiform lesions as well as PrPd deposits in the brain were minimal. All this supports that it was in an early, preclinical stage of the disease. In this regard it is important to point out that these minimal lesions and PrPd deposits were found in the grey matter structures of the obex region of the medulla oblongata, the midbrain and the thalamus. These findings are essentially similar to those in preclinical C-type BSE (1,12,13,22) and support that sampling of the obex region in surveillance schemes implemented for C98 type BSE might be similarly suitable for detection of naturally occurring H-type BSE.



The main disease-control measure of C-type BSE is the ban on mammalian MBM in ruminant feed. This feed-ban was enforced in Switzerland and the European Union in the early 1990s and considerably reduced the number of newly infected cattle. However, the recycling of the C-type BSE agent in the cattle population was not blocked until the MBM feed-ban was reinforced in 2001, now excluding the use of animal proteins in feed of all farmed animals (10).



It remains unknown, whether H-type BSE similarly transmits orally in the cattle population with MBM as a vehicle or not. If oral transmission occurs and is the sole etiology, the reinforced MBM feed-ban should be an appropriate measure to prevent the spread of H-type BSE also and no cases should be born after its implementation, i.e., after 2001 in Switzerland and Germany.



To our knowledge, this is the first report of an H-type BSE affected animal being born after the reinforced MBM feed-ban in the respective country. Therefore, this case provides further evidence that the etiology of H-type BSE may be unrelated to the ingestion of prion contaminated meat-and-bone meal. Taken together, this supports the widely expressed postulate that H-type BSE originates from a spontaneous misfolding of cellular PrP with a pathophysiology similar to sporadic Creutzfeld-Jakob disease in humans (7,20).



Alternatively, other yet unknown routes of transmission or genetic determinants must be considered. This said, H-type BSE might persist after eradication of C-type BSE. What are the implications of this scenario? Studies in mice provided experimental evidence that H-type BSE may shift its disease phenotype to that of C-type BSE (3) upon transmission. It has therefore been hypothesized that the C-type BSE epidemic originated from spontaneously occurring H-type BSE cases. If this was the case there would be a constant risk that C-type BSE re-emerges in the cattle population once the feed-ban is discontinued. Consequently, some measures of disease control would need to be maintained indefinitely. Since the standards for the determination of a countries’ BSE risk status currently do not differentiate between BSE subtypes (28), BSE risk assessments will certainly need to take such considerations into account. This highlights the need for continuing research into the relationship between classical and atypical BSE variants to provide the scientific basis for future disease surveillance and control policies.








re-Atypical H-Type Bovine Spongiform Encephalopathy in a Cow Born after the Reinforced Feed-Ban on Meat-and-Bone-Meal


please note, one decade (10 years), post USA mad cow partial and voluntary mad cow feed ban of August 4, 1997, the USA was still feeding cows to cows, with some 10,000,000 pounds of banned blood laced meat and bone meal fed out into commerce in 2007. 2006 was a banner year for mad cow protein into commerce as well.


please see banned mad cow feed in commerce USA 1997 to 2007 ;





2007




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



RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II



PRODUCT



Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007



CODE



Cattle feed delivered between 01/12/2007 and 01/26/2007



RECALLING FIRM/MANUFACTURER



Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.



Firm initiated recall is ongoing.



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



___________________________________




PRODUCT



Custom dairy premix products:



MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007



CODE



The firm does not utilize a code - only shipping documentation with commodity and weights identified.



RECALLING FIRM/MANUFACTURER



Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.



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










please see 2006 and more here ;







Saturday, August 4, 2012



Final Feed Investigation Summary - California BSE Case - July 2012








Wednesday, May 30, 2012



PO-028: Oral transmission of L-type bovine spongiform encephalopathy (L-BSE) in primate model Microcebus murinus








Wednesday, May 2, 2012



ARS FLIP FLOPS ON SRM REMOVAL FOR ATYPICAL L-TYPE BASE BSE RISK HUMAN AND ANIMAL HEALTH








Wednesday, July 28, 2010



re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010



Sent: Wednesday, July 28, 2010 11:42 AM



Subject: re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE




Greetings again Ms Williams et al at FOIA USDA,





Thank You again for your kind reply on this important information. However, I am concerned that you may not be aware of new transmission studies. You (USDA et al) state Ma'am ;




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





The SCA with Italy was mainly to confirm our respective country’s diagnostic tests would detect the various atypical BSE cases as seen in each country), in the meantime, the Italians have published their transmissibility and pathogenesis work on their BASE cases in the following article:




Lombardi G, Casalone C, A DA, Gelmetti D, Torcoli G, Barbieri I, Corona C, Fasoli E, Farinazzo A, Fiorini M, Gelati M, Iulini B, Tagliavini F, Ferrari S, Caramelli M, Monaco S, Capucci L, Zanusso G (2008) Intraspecies transmission of BASE induces clinical dullness and amyotrophic changes. PLoS Pathog 4:e1000075




The above mentioned paper concludes, “In all experimentally infected animals, no PrP**TSE was detected in peripheral tissues, including cervical and mesenteric lymph nodes, spleen, thymus, liver, lung, peripheral nerves and forelimb and limb muscles, either by standard Western blot analysis or following phosphotungstic acid precipitation.“




It is not necessary to change SRM removal due to any different tissue infectivity distribution between classical BSE and atypical BSE. At this time, there is no scientific evidence to suggest a need for expanding the list of tissues included in the Specified Risk Material (SRM) ban as a result of published studies on atypical BSE.




snip...




Moreover, in the paper by Buschmann A, Groschup MH (2005,) Highly bovine spongiform encephalopathy-sensitive transgenic mice confirm the essential restriction of infectivity to the nervous system in clinically diseased cattle. J Infect Dis 192:934-942; the authors, when speaking about the classical BSE food-borne epidemic in Europe, concluded their “results provide further indication that the pathogenesis of BSE in cattle is fundamentally different from that in sheep and mice, due to an exclusive intraneuronal spread of infectivity from the gut to the central nervous system.”




end...





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





Again, in my opinion, the USDA is cherry picking the science they want to use, and in doing so, I believe they are putting human lives at risk.



I disagree for the following reasons. New studies indeed show that ;




July 10, 2010



see full text ;




Wednesday, July 28, 2010



re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010








USDA TRIPLE BSE MAD COW FIREWALL, SRM, FEED, AND SURVEILLANCE





2012





***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...








MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...



***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model








***Infectivity in skeletal muscle of BASE-infected cattle








***feedstuffs- It also suggests a similar cause or source for atypical BSE in these countries.








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








The present study demonstrated successful intraspecies transmission of H-type BSE to cattle and the distribution and immunolabeling patterns of PrPSc in the brain of the H-type BSE-challenged cattle. TSE agent virulence can be minimally defined by oral transmission of different TSE agents (C-type, L-type, and H-type BSE agents) [59]. Oral transmission studies with H-type BSEinfected cattle have been initiated and are underway to provide information regarding the extent of similarity in the immunohistochemical and molecular features before and after transmission.



In addition, the present data will support risk assessments in some peripheral tissues derived from cattle affected with H-type BSE.









Friday, May 11, 2012



Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits



***support risk assessments in some peripheral tissues derived from cattle affected with H-type BSE








Thursday, June 21, 2012



Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy Associated with E211K Prion Protein Polymorphism



Justin J. Greenlee1*, Jodi D. Smith1, M. Heather West Greenlee2, Eric M. Nicholson1



1 National Animal Disease Center, United States Department of Agriculture, Agricultural Research Service, Ames, Iowa, United States of America, 2 Iowa State University, Ames, Iowa, United States of America



Abstract



The majority of bovine spongiform encephalopathy (BSE) cases have been ascribed to the classical form of the disease. Htype and L-type BSE cases have atypical molecular profiles compared to classical BSE and are thought to arise spontaneously. However, one case of H-type BSE was associated with a heritable E211K mutation in the prion protein gene. The purpose of this study was to describe transmission of this unique isolate of H-type BSE when inoculated into a calf of the same genotype by the intracranial route. Electroretinograms were used to demonstrate preclinical deficits in retinal function, and optical coherence tomography was used to demonstrate an antemortem decrease in retinal thickness. The calf rapidly progressed to clinical disease (9.4 months) and was necropsied. Widespread distribution of abnormal prion protein was demonstrated within neural tissues by western blot and immunohistochemistry. While this isolate is categorized as BSE-H due to a higher molecular mass of the unglycosylated PrPSc isoform, a strong labeling of all 3 PrPSc bands with monoclonal antibodies 6H4 and P4, and a second unglycosylated band at approximately 14 kDa when developed with antibodies that bind in the C-terminal region, it is unique from other described cases of BSE-H because of an additional band 23 kDa demonstrated on western blots of the cerebellum. This work demonstrates that this isolate is transmissible, has a BSE-H phenotype when transmitted to cattle with the K211 polymorphism, and has molecular features that distinguish it from other cases of BSE-H described in the literature.



snip...



Most significantly it must be determined if the molecular phenotype of this cattle TSE remains stable when transmitted to cattle without the E211K polymorphism as several other isolates of atypical BSE have been shown to adopt a molecular profile consistent with classical BSE after passage in transgenic mice expressing bovine PrPC [40] or multiple passages in wild type mice [23]. Results of ongoing studies, namely passage of the E211K Htype isolate into wild-type cattle, will lend further insight into what role, if any, genetic and sporadic forms of BSE may have played in the origins of classical BSE. Atypical cases presumably of spontaneous or, in the case of E211K BSE-H, genetic origins highlight that it may not be possible to eradicate BSE entirely and that it would be hazardous to remove disease control measures such as prohibiting the feeding of meat and bone meal to ruminants.










P.4.23



Transmission of atypical BSE in humanized mouse models



Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA



Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.



Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.



Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.



Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.



Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.











P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS



Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA



Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.



III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)
















I ask Professor Kong ;



Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment



''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''



Professor Kong reply ;



.....snip




''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''




Best regards,




Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA





END...TSS





Thursday, December 04, 2008 2:37 PM



"we have found that H-BSE can infect humans."



personal communication with Professor Kong. ...TSS





BSE-H is also transmissible in our humanized Tg mice.



The possibility of more than two atypical BSE strains will be discussed.



Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.


















let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.





This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$




ALABAMA MAD COW g-h-BSEalabama




In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.














her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).




This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine–human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.




Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA




NATURE|Vol 457|26 February 2009










Saturday, August 14, 2010



BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY



(see mad cow feed in COMMERCE IN ALABAMA...TSS)









P.9.21



Molecular characterization of BSE in Canada



Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada



Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.



Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.



Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.



Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.



*** It also suggests a similar cause or source for atypical BSE in these countries.









Saturday, May 26, 2012



Are USDA assurances on mad cow case 'gross oversimplification'?




SNIP...



What irks many scientists is the USDA’s April 25 statement that the rare disease is “not generally associated with an animal consuming infected feed.”



The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown, one of the world’s experts on this type of disease who retired recently from the National Institutes of Health. "(The agency) has no foundation on which to base that statement.”



“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an official with the USDA during the Clinton Administration now at Mississippi State.



In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the origins of atypical cases of BSE,” she said



The argument about feed is critical because if feed is the cause, not a spontaneous mutation, the California cow could be part of a larger outbreak.



SNIP...








2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006








in the url that follows, I have posted



SRM breaches first, as late as 2011.



then



MAD COW FEED BAN BREACHES AND TONNAGES OF MAD COW FEED IN COMMERCE up until 2007, when they ceased posting them.



then,



MAD COW SURVEILLANCE BREACHES.





Friday, May 18, 2012



Update from APHIS Regarding a Detection of Bovine Spongiform Encephalopathy (BSE) in the United States Friday May 18, 2012








Wednesday, March 28, 2012



VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion poker goes up again $



OR-10 15:25 - 15:40 VARIABLY PROTEASE-SENSITIVE PRIONOPATHY IS TRANSMISSIBLE IN BANK VOLES Nonno




OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles



Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1



1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA



Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.



Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.



Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases. In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.



Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109. The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.












Saturday, August 14, 2010



BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY



(see mad cow feed in COMMERCE IN ALABAMA...TSS)









There have been two molecular types of "atypical" BSE isolates described in the literature so far:


(i) a type with a lower molecular mass of the unglycosylated isoform also called the L-type and


(ii) a type with a higher molecular mass of the unglycosylated isoform, also called the H-type.


The L-type has been found in cattle in Italy (10), Japan (11), Germany (12) and Belgium (13).


So far, the H-type has been described in cattle from France (14), Germany (12) and the United States (15).


The U.S. cases were animals born and raised in the U.S. (Texas, Alabama). Unusual cases of BSE are an


unexpected finding since it was previously believed that BSE disease in cattle is caused by a single strain of


infectious agent, which has been shown to be very consistent and uniform in appearance, even after


transmission to other species. The reports of unusual phenotypes of BSE in cattle suggest that different PrPSc


phenotypes exist in cattle with BSE.




There are several hypotheses which can explain these findings:



(i) there are variants of the BSE agent with different molecular features in cattle;



(ii) cattle may have been infected by another source of an infectious prion agent (e.g. scrapie or CWD); or



(iii) a rare sporadic or genetic form of TSE disease could exist in cattle as described for humans.









DR. CLIFFORD: "Basically the IHC test, besides looking at location of the brain stem you're also doing a staining technique to identify abnormal prion proteins. In this case they had some staining, but the staining did not match up with what they would typically see in a BSE case. It didn't have the normal distribution it would see within the samples. So basically that's why the request for doing additional testing, and that's why we're sending it to Weybridge as well."



DR. CLIFFORD: "There was some staining present. But it did not match a normal pattern, and we're taking through that to do additional tests in additional parts of the brain stem to try to see if we can find a normal staining pattern as well as sending that sample to Weybridge to run against their IHC."









Atypical BSE



Atypical BSE, is a rare type of “madcow” disease that is not linked to the consumption of contaminated feed.The second (Texas) and third (Alabama) announced cases of U.S. BSE were atypical. ...








Subject: BSE, BOVINE - USA: ATYPICAL STRAIN Date: June 1, 2006 at 11:09 am PST BSE, BOVINE - USA: ATYPICAL STRAIN




**********************************



A ProMED-mail post



ProMED-mail, a program of the International Society for Infectious Diseases


Date: 31 May 2006 From: Terry S. Singletary and Mary Marshall


Source: Rapid City Journal [edited]


The 2 cases of bovine spongiform encephalopathy found in U.S. cattle over the past year came from a rare strain of BSE found largely in Europe that scientists are only beginning to identify, according to research by a French scientist.


Researchers in France and Italy who presented their work at an international conference in London reported 2 rare strains of bovine spongiform encephalopathy that are harder to detect and affect mainly older cattle.


Thierry Baron of the French Food Safety Agency presented research indicating that a 12-year-old Texas cow testing positive for BSE in June 2005, and the 10-year-old Alabama cow that tested positive in March [2006?], showed identical testing patterns to a small number of BSE cases in France, Sweden and Poland.


Animal scientists are calling such strains "atypical" BSE, which is different from the "typical" BSE caused by cattle eating feed with ruminant offal contaminated with a BSE protein.


They don't know whether the atypical strains are caused by something else or simply appear spontaneously in older, susceptible cattle.


Art Davis, a U.S. Department of Agriculture (USDA) scientist for the Animal and Plant Health Inspection Service (APHIS) at the National Veterinary Services Laboratory in Ames, Iowa, said in his presentation Sunday at the London conference that the Texas and Alabama test results showed completely different prion patterns than the Washington state case discovered in December 2003.


"The classical lesions were not there," Davis said of the cases. The Washington state cow originated in Alberta, Canada, near where several other BSE cases have been found.


The "typical" BSE strain caused a mad cow disease epidemic in Great Britain beginning in the mid-1980s that killed 184 000 cattle and more than 100 people who contracted a human form of the disease caused by eating contaminated beef products.


The scientific evidence shows that in almost all cattle cases, the fatal neurological disorder was contracted through contaminated meat and bone meal fed to the cow, typically at a young age.


However, scientists finding atypical cases of BSE are beginning to question if there has been a change in the abnormal protein that causes BSE or if cattle might be susceptible to a sporadic BSE affecting older cattle.


Danny Matthews, head of transmissible spongiform encephalopathies at England's Veterinary Laboratories Agency, said recent research on atypical cases of BSE raises questions over whether older cattle can sporadically get the disease or if there are more strains of BSE than previously understood. Scientists might also be facing something new, such as "son of BSE," he said.


"We don't fully understand what atypical BSE means," Matthews said. "Is it spontaneous or another source causing it? Time will tell."


Although the test patterns in the U.S. cases and atypical cases in Europe closely matched, Baron said there were no known links among any of the positive animals. The French Food Safety Agency sent a researcher to the United States to study the positive Texas case and compare its results to known cases in France that did not match the typical BSE positive tests.


"You could place them side-by-side and not tell the difference," Baron said.


Baron also raised the prospect that the disease could be sporadic in at least a small number of older cattle. He said, however, such a conclusion would be hard to determine because of the small number of cattle with this atypical strain globally.


Dr. Sam Holland, South Dakota's state veterinarian, said there are many strains of BSE and varying degrees of infectiousness of the agent.


"What if the scenario is there is an atypical prion out there that is much less infective, has a longer incubation period and has not been recognized as part of the Great Britain BSE experience identified in 1985 and '86?" Holland said. "There could be others out there that we haven't recognized yet."


He said it is possible the atypical strains are not caused by contaminated feed and that it still makes sense to continue the ban on ruminant offal in cattle feed to prevent the spread of typical BSE and eventually to eliminate that disease.


"Based on what we know about BSE, it makes good sense to -- number one -- keep some surveillance in place; number 2, watch what we import and restrict shipments and movements from places that have had those syndromes; and, number 3, with what we know about BSE, it seems to be very prudent to keep our ruminant offal ban in place," Holland said.


"At least for typical BSE's, it seems to be very effective. It's probably reasonable to continue the ruminant offal ban even after the last typical BSE case has been eliminated."


Editor's note: DTN, a private company based in Omaha, Neb., provides information to agriculture, energy trading markets and other weather-sensitive industries. The Rapid City Journal received a copy of DTN's story and expanded on it.


[Byline: Chris Clayton]


-- Terry S. Singletary and Mary Marshall


[An atypical form has been found in sheep with scrapie. Other countries have indicated an atypical form of BSE. It seems logical that the US would have an a atypical form as well. The case might even be made that new variant CJD is an atypical form of CJD. Clearly there is more to the TSE diseases than we fully comprehend. - Mod.TG]


[see also: 2005 ---- Scrapie, atypical, ovine - Falkland Islands 20051120.3371 2004 ---- Scrapie, atypical, sheep - UK and Ireland 20041210.3274 Scrapie, atypical, sheep - UK (02) 20040409.0965 Scrapie, atypical, sheep - UK20040408.0952 BSE, atypical - France: OIE 20040201.0391 Scrapie, atypical, sheep - France: OIE 20040201.0390 BSE - France: distinct molecular phenotypes 20040107.0076 2003 ---- Scrapie - Norway: new phenotype 20031117.2857 BSE - Japan (08): 9th case, lab findings 20031115.2838 BSE, atypical case - Italy: OIE 20031022.2649 BSE - Italy: atypical, suspected 20031012.2576 BSE - Japan (06): atypical 20031009.2547 BSE - Japan (05): atypical 20031008.2526 BSE - Japan (04): atypical 20031007.2511 2002 ---- BSE? Sheep - USA (Vermont) 20020412.3937 2000 ---- BSE? sheep - USA (Vermont) (06) 20000724.1223 BSE? sheep - USA (Vermont) 20000717.1184 1996 ---- CJD sporadic vs variant differences 19960526.0990] ...............tg/pg/lm




*##########################################################*



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END...TSS




2012




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



Saturday, August 4, 2012



Final Feed Investigation Summary - California BSE Case - July 2012







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





SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE INVESTIGATION JULY 2012



Summary Report BSE 2012



Executive Summary









Saturday, August 4, 2012



Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation









CENSORSHIP IS A TERRIBLE THING $$$





Canada has had a COVER-UP policy of mad cow disease since about the 17th case OR 18th case of mad cow disease. AFTER THAT, all FOIA request were ignored $$$



THIS proves there is indeed an epidemic of mad cow disease in North America, and it has been covered up for years and years, if not for decades, and it’s getting worse $$$





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









Reasons for the New Regulation Order No. 23 (as well as amending Order No. 149) of the State Committee for Veterinary Medicine name BSE as the reason for new import requirement. The legal title for Order No. 23 is "On Urgent Measures Aimed at Prevention and Elimination of BSE and Other Prion Infections in Cattle”. Neither Order explains how the threat of introduction of BSE can be addressed through the inspection of producers of all products of animal origin including fish, dairy products, poultry and pork. It is not clear what other concerns are addressed through the proposed inspections. Formal Notification of Trading Partners On August 3rd, Ukraine's Notification and Enquiry Point issued a legal Notification G/SPS/N/UKR/3/Rev.1 found on the Official WTO Website (Committee on Sanitary and Phytosanitary Measures)









Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research Unit


2011 Annual Report


1a.Objectives (from AD-416) Obj. 1. Assess the cross species transmissibility of transmissible spongiform encephalopathies (TSEs) in livestock and wildlife. Obj. 2. Investigate the pathobiology of TSEs in natural and secondary hosts. Obj. 3. Investigate pathogenesis and ante mortem detection of bovine spongiform encephalopathy (BSE). Obj. 4. Develop a method to detect central nervous system (CNS) tissue contamination on carcasses. Obj. 5. Discover effective methods to inactivate TSE agents in agricultural settings.


1b.Approach (from AD-416) Studies are focused on the four animal Transmissible Spongiform Encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; and transmissible mink encephalopathy (TME). These agents will be tested for cross-species transmissibility into various livestock and cervid species using both oral and intracerebral inoculation. Sites of accumulation, routes of infection, methods of isolate differentiation, and in the case of BSE, genetics of susceptibility and ante-mortem diagnostics, will be investigated. Existing technology developed at the National Animal Disease Center and those used in the meat packing industry for the detection of fecal contamination on carcasses will be adapted to detect CNS tissue contamination on carcasses. Methods of TSE inactivation will be evaluated for efficacy in agricultural settings.


3.Progress Report This is the final report for project 3625-32000-086-00D, terminated in September 2011 and replaced by 3625-32000-103-00D. The project plan involved 5 objectives.


In Objective 1, Assess cross-species transmissibility of transmissible spongiform encephalopathies (TSEs) in livestock and wildlife, numerous experiments assessing the susceptibility of various TSEs in different host species were conducted. Most notable is deer inoculated with scrapie, which exhibits similarities to chronic wasting disease (CWD) in deer suggestive of sheep scrapie as an origin of CWD.


In Objective 2, Investigate the pathobiology of TSEs in natural and secondary hosts, deer were inoculated with CWD-infected blood. Several animals developed clinical signs, a result consistent with CWD infectivity in blood. Also, biochemical strain typing commonly used for rodent models of TSE was investigated to assess the importance of genetic variability in natural hosts and how to apply these methods to natural hosts.


Objective 3, Investigate pathogenesis and antemortem detection of bovine spongiform encephalopathy (BSE), involves several different research areas. Our results in genetic susceptibility of BSE support the now widely accepted conclusion that atypical BSE is a spontaneous TSE in cattle. This has important implications for the ruminant feed ban, food safety, and our understanding of the origins of BSE. Also as part of Obj. 3, we identified the first recognized case of genetic BSE where a natural case of BSE was identified in an animal containing a polymorphism analogous to a human polymorphism that causes a genetic TSE. Bovine spongiform encephalopathy has long been believed to only be a feed-borne disease. Together, our results show for the first time the presence of three different etiologies for BSE as are known to occur in humans. As part of our investigation, classical, and atypical BSE isolates were inoculated into cattle. Upon completion, this work will represent the first thorough comparison of domestic and international BSE isolates, including both classical and atypical BSE. An antemortem diagnostic technique based upon retinal function was developed and is routinely applied to experimental animals on site. This technique detects a TSE before the onset of clinical signs. Work is ongoing to increase the number of animals containing the E211K polymorphism, a potential cause of genetic BSE; this will provide the only means by which to prove the novel allele may cause BSE. The unusual E211K BSE material has also been successfully amplified in one of these animals.


Objective 4, Develop a method to detect CNS tissue contamination on carcasses, resulted in a successful method that may be applied through adaptation of existing technology currently used to detect fecal contamination on carcasses.


In Objective 5, Determine effective methods to inactivate TSE agents in agricultural settings, compounds applicable to agricultural settings were evaluated; the results are being prepared for publication. As part of this objective, a natural host model for assessing inactivation was developed. Despite experimental success the model is not suitable due to incubation time.


4.Accomplishments 1. Deer inoculated with domestic isolates of sheep scrapie. Scrapie-affected deer exhibit 2 different patterns of disease associated prion protein. In some regions of the brain the pattern is much like that observed for scrapie, while in others it is more like chronic wasting disease (CWD), the transmissible spongiform encephalopathy typically associated with deer. This work conducted by ARS scientists at the National Animal Disease Center, Ames, IA suggests that an interspecies transmission of sheep scrapie to deer may have been the origin of CWD. This is important for husbandry practices with both captive deer, elk and sheep for farmers and ranchers attempting to keep their herds and flocks free of CWD and scrapie.


2. Demonstrated transmissibility of K211 BSE, a rare genetic form of bovine spongiform encephalopathy (BSE), to cattle. Cattle containing the rare K211 PRNP gene have been produced in-house and used in this study conducted by ARS scientists at the National Animal Disease Center, Ames, IA. These animals have been inoculated with both K211 BSE and classical BSE. The K211 BSE is transmissible and progresses far more rapidly in K211 cattle than does classical BSE. Because of their genetic susceptibility to BSE, K211 PRNP cattle have a very rapid incubation time and may be more susceptible to TSEs, which are two characteristics that make them highly desirable for future studies of antemortem diagnostics and residual infectivity or risk materials after decontamination. The possibility remains that K211 BSE transmitted to conventional cattle will result in a disease phenotype similar to classical BSE. If this turns out to be true, then it will be very important in that it suggests a very rare genetic form of BSE could have been the original source of brain material responsible for the U.K. BSE epidemic. Current human and animal feed bans regarding specified risk materials from cattle protect humans and animals from a recurrence of such an epidemic.


Review Publications Hamir, A.N., Greenlee, J.J., Stanton, T.B., Smith, J.D., Doucette, S., Kunkle, R.A., Stasko, J.A., Richt, J.A., Kehrli, Jr., M.E. 2011. Experimental inoculation of raccoons (Procyon lotor) with Spiroplasma mirum and transmissible mink encephalopathy (TME). Canadian Journal of Veterinary Research. 75(1):18–24.


Hamir, A.N., Greenlee, J.J., Nicholson, E.M., Kunkle, R.A., Richt, J.A., Miller, J.M., Hall, M. 2011. Experimental transmission of chronic wasting disease (CWD) from elk and white-tailed deer to fallow deer by intracerebral route: final report. Canadian Journal of Veterinary Research. 75(2):152-156.


Smith, J.D., Hamir, A.N., Greenlee, J.J. 2011. Cartilaginous metaplasia in the sclera of Suffolk sheep. Veterinary Pathology. 48(4):827-829.


Loiacono, C.M., Beckwith, N., Kunkle, R.A., Orcutt, D., Hall, S.M. 2010. Detection of PrPSc in formalin-fixed, paraffin embedded tissue by Western blot differentiates classical scrapie, Nor98 scrapie, and bovine spongiform encephalopathy. Journal of Veterinary Diagnostic Investigation. 22(5):684-689.


Hamir, A.N., Kehrli, Jr., M.E., Kunkle, R.A., Greenlee, J.J., Nicholson, E.M., Richt, J.A., Miller, J.M., Cutlip, R.C. 2011. Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle. Journal of Veterinary Diagnostic Investigation. 23(3):407-420.


Nicholson, E.M. 2011. Enrichment of PrPSc in formalin-fixed, paraffin-embedded tissues prior to analysis by Western blot. Journal of Veterinary Diagnostic Investigation. 23(4):790-792.








Tuesday, July 17, 2012



O.I.E. BSE, CWD, SCRAPIE, TSE PRION DISEASE Final Report of the 80th General Session, 20 - 25 May 2012







CHRONIC WASTING DISEASE, CWD, AND THE DEER PENS AT THE FOOT HILLS CAMPUS




page 30,



*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or about that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.



(PLEASE NOTE SOME OF THESE OLD UK GOVERNMENT FILE URLS ARE SLOW TO OPEN, AND SOMETIMES YOU MAY HAVE TO CLICK ON MULTIPLE TIMES, PLEASE BE PATIENT, ANY PROBLEMS PLEASE WRITE ME PRIVATELY, AND I WILL TRY AND FIX OR SEND YOU OLD PDF FILE...TSS)





IN CONFIDENCE



PERCEPTIONS OF UNCONVENTIONAL SLOW VIRUS DISEASES OF ANIMALS IN USA



GAH WELLS



REPORT OF A VISIT TO THE USA APRIL-MAY 1989







now, years later, see the latest studies here on scrapie and cwd ;






PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer



Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA



Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. The purpose of these experiments was to determine susceptibility of white-tailed deer (WTD) to scrapie and to compare the resultant clinical signs, lesions, and molecular profiles of PrPSc to those of chronic wasting disease (CWD). We inoculated WTD intracranially (IC; n = 5) and by a natural route of exposure (concurrent oral and intranasal (IN); n = 5) with a US scrapie isolate. All deer were inoculated with a 10% (wt/vol) brain homogenate from sheep with scrapie (1ml IC, 1 ml IN, 30 ml oral). All deer inoculated by the intracranial route had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues as early as 7 months-post-inoculation (PI) and a single deer that was necropsied at 15.6 months had widespread distribution of PrPSc highlighting that PrPSc is widely distributed in the CNS and lymphoid tissues prior to the onset of clinical signs. IC inoculated deer necropsied after 20 months PI (3/5) had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like. After a natural route of exposure, 100% of WTD were susceptible to scrapie. Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.








White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection



Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS



Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. Previous experiments demonstrated that white-tailed deer are susceptible to sheep-derived scrapie by intracranial inoculation. The purpose of this study was to determine susceptibility of white-tailed deer to scrapie after a natural route of exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal (1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with scrapie. Non-inoculated deer were maintained as negative controls. All deer were observed daily for clinical signs. Deer were euthanized and necropsied when neurologic disease was evident, and tissues were examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and western blot (WB). One animal was euthanized 15 months post-inoculation (MPI) due to an injury. At that time, examination of obex and lymphoid tissues by IHC was positive, but WB of obex and colliculus were negative. Remaining deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by potential natural routes of inoculation. In-depth analysis of tissues will be done to determine similarities between scrapie in deer after intracranial and oral/intranasal inoculation and chronic wasting disease resulting from similar routes of inoculation.




see full text ;








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.









Sunday, January 22, 2012



Chronic Wasting Disease CWD cervids interspecies transmission












Friday, August 24, 2012



Diagnostic accuracy of rectal mucosa biopsy testing for chronic wasting disease within white-tailed deer (Odocoileus virginianus) herds in North America








Saturday, September 01, 2012



Resistance of Soil-Bound Prions to Rumen Digestion









Monday, September 17, 2012



Rapid Transepithelial Transport of Prions Following Inhalation









Thursday, September 27, 2012



Genetic Depletion of Complement Receptors CD21/35 Prevents Terminal Prion Disease in a Mouse Model of Chronic Wasting Disease









CDC



October 2012



Synopsis Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting Disease



Controlling the spread of CWD, especially by human action, is a more attainable goal than eradication. Human movement of cervids has likely led to spread of CWD in facilities for captive animals, which has most likely contributed to establishment of new disease foci in free-ranging populations (Figure 1, panel A). Thus, restrictions on human movement of cervids from disease-endemic areas or herds continue to be warranted. Anthropogenic factors that increase cervid congregation such as baiting and feeding should also be restricted to reduce CWD transmission. Appropriate disposal of carcasses of animals with suspected CWD is necessary to limit environmental contamination (20), and attractive onsite disposal options such as composting and burial require further investigation to determine contamination risks. The best options for lowering the risk for recurrence in facilities for captive animals with outbreaks are complete depopulation, stringent exclusion of free-ranging cervids, and disinfection of all exposed surfaces. However, even the most extensive decontamination measures may not be sufficient to eliminate the risk for disease recurrence (20; S.E. Saunders et al. unpub. data)










UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF THE STUDIES ON CWD TRANSMISSION TO CATTLE ;




CWD to cattle figures CORRECTION





Greetings,



I believe the statement and quote below is incorrect ;



"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."



Please see ;



Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.







" although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). "



shouldn't this be corrected, 86% is NOT a low rate. ...



kindest regards,





Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518




Thank you!


Thanks so much for your updates/comments. We intend to publish as rapidly as possible all updates/comments that contribute substantially to the topic under discussion.







re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations



1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu







Mule deer, white-tailed deer, and elk have been reported to develop CWD. As the only prion disease identified in free-ranging animals, CWD appears to be far more communicable than other forms of prion disease. CWD was first described in 1967 and was reported to be a spongiform encephalopathy in 1978 on the basis of histopathology of the brain. Originally detected in the American West, CWD has spread across much of North America and has been reported also in South Korea. In captive populations, up to 90% of mule deer have been reported to be positive for prions (Williams and Young 1980). The incidence of CWD in cervids living in the wild has been estimated to be as high as 15% (Miller et al. 2000). The development of transgenic (Tg) mice expressing cervid PrP, and thus susceptible to CWD, has enhanced detection of CWD and the estimation of prion titers (Browning et al. 2004; Tamgüney et al. 2006). Shedding of prions in the feces, even in presymptomatic deer, has been identified as a likely source of infection for these grazing animals (Williams and Miller 2002; Tamgüney et al. 2009b). CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures.



snip...








----- Original Message -----




From: David Colby To: flounder9@verizon.net






Sent: Tuesday, March 01, 2011 8:25 AM



Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations



Dear Terry Singeltary,



Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter. Warm Regards, David Colby -- David Colby, PhDAssistant Professor Department of Chemical Engineering University of Delaware




===========END...TSS==============



SNIP...SEE FULL TEXT ;








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








Sunday, August 19, 2012



Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation 2012



Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research Unit








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

















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











Thursday, May 31, 2012



CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission, Scrapie, cats, species barrier, burial, and more








PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;



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.








NOR IS THE FDA recalling this CWD positive elk meat for the well being of the dead elk ;





Wednesday, March 18, 2009



Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II








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 ;








CWD ongoing experiment on humans, long term $$$





Monday, November 14, 2011



WYOMING Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011








Wednesday, November 16, 2011



Wisconsin Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011








Sunday, November 13, 2011



COLORADO CWD CJD TSE PRION REPORTING 2011














Thursday, March 29, 2012



atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012



NIAA Annual Conference April 11-14, 2011San Antonio, Texas








Monday, November 30, 2009



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








Wednesday, February 16, 2011



IN CONFIDENCE SCRAPIE TRANSMISSION TO CHIMPANZEES



IN CONFIDENCE



reference...



RB3.20



TRANSMISSION TO CHIMPANZEES



1. Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.


2. We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, ilp and i/v) :


3. I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. Proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.


4. In view of Dr Gibbs' probable use of chimpazees Mr Wells' comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.


5. A positive result from a chimpanzee challenged severely 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.


6. A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans' susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive. We may learn more about public reactions following next Monday' s meeting.


R. Bradley


23 September 1990


CVO (+Mr Wells' comments)


Dr T W A Little


Dr B J Shreeve


90/9.23/1.1.









see full text ;








Thursday, March 29, 2012



atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012



NIAA Annual Conference April 11-14, 2011San Antonio, Texas








Monday, November 30, 2009



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








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...








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



This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;




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...











see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;









2011 Monday, September 26, 2011



L-BSE BASE prion and atypical sporadic CJD








Saturday, March 5, 2011



MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA








Wednesday, August 01, 2012



Behavioural and Psychiatric Features of the Human Prion Diseases: Experience in 368 Prospectively Studied Patients








Monday, August 06, 2012



Atypical neuropathological sCJD-MM phenotype with abundant white matter Kuru-type plaques sparing the cerebellar cortex








Tuesday, June 26, 2012



Creutzfeldt Jakob Disease Human TSE report update North America, Canada, Mexico, and USDA PRION UNIT as of May 18, 2012



type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the rise in Canada and the USA








Friday, August 24, 2012



Iatrogenic prion diseases in humans: an update









Monday, July 23, 2012



The National Prion Disease Pathology Surveillance Center July 2012








2011 Monday, September 26, 2011



L-BSE BASE prion and atypical sporadic CJD








Saturday, March 5, 2011



MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA








Wednesday, August 01, 2012



Behavioural and Psychiatric Features of the Human Prion Diseases: Experience in 368 Prospectively Studied Patients








Monday, August 06, 2012



Atypical neuropathological sCJD-MM phenotype with abundant white matter Kuru-type plaques sparing the cerebellar cortex








Tuesday, June 26, 2012



Creutzfeldt Jakob Disease Human TSE report update North America, Canada, Mexico, and USDA PRION UNIT as of May 18, 2012



type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the rise in Canada and the USA








Friday, August 24, 2012



Iatrogenic prion diseases in humans: an update









Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis













full text with source references ;








re-Human Prion Diseases in the United States Posted by flounder on 01 Jan 2010 at 18:11 GMT I kindly disagree with your synopsis for the following reasons ;








Tuesday, November 08, 2011



Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011 Original Paper



Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.








Views & Reviews



Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States



Ermias D. Belay, MD, Ryan A. Maddox, MPH, Pierluigi Gambetti, MD and Lawrence B. Schonberger, MD



+ Author Affiliations



From the Division of Viral and Rickettsial Diseases (Drs. Belay and Schonberger and R.A. Maddox), National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA; and National Prion Disease Pathology Surveillance Center (Dr. Gambetti), Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH.



Address correspondence and reprint requests to Dr. Ermias D. Belay, 1600 Clifton Road, Mailstop A-39, Atlanta, GA 30333.









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?








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. FREE FULL TEXT









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.








Saturday, January 2, 2010



Human Prion Diseases in the United States January 1, 2010 ***FINAL***









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-Human Prion Diseases in the United States Posted by flounder on 01 Jan 2010 at 18:11 GMT I kindly disagree with your synopsis for the following reasons ;









Wednesday, May 16, 2012



Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?



Proposal ID: 29403










Monday, August 20, 2012



CASE REPORTS CREUTZFELDT-JAKOB DISEASE: AN UNDER-RECOGNIZED CAUSE OF DEMENTIA








Friday, October 05, 2012



Differential Diagnosis of Jakob-Creutzfeldt Disease








see the Duke, Pa, Yale, and Mexican study here, showing the misdiagnosis of CJD TSE prion disease as Alzheimers ;








Monday, July 23, 2012



The National Prion Disease Pathology Surveillance Center July 2012



 


TSS


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