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.
http://ars.usda.gov/research/projects/p ... ue&fy=2011
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:
[email protected] 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.
http://jcm.asm.org/content/early/2012/0 ... 2.abstract
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
Saturday, August 4, 2012
Final Feed Investigation Summary - California BSE Case - July 2012
http://transmissiblespongiformencephalo ... mmary.html
Wednesday, May 2, 2012
ARS FLIP FLOPS ON SRM REMOVAL FOR ATYPICAL L-TYPE BASE BSE RISK HUMAN AND ANIMAL HEALTH
http://transmissiblespongiformencephalo ... l-for.html
snip...
see much more (cwd, scrapie, bse) here ;
Saturday, October 6, 2012
TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2011 Annual Report
http://transmissiblespongiformencephalo ... n-and.html
