Prevalence and Effects of Chronic Wasting Disease in Elk from Rocky Mountain National Park

Prevalence and Effects of Chronic Wasting Disease in Elk from Rocky Mountain National Park


Ryan Monello Biological Resource Management Division National Parks Service Ryan_Monello@nps.gov N. Thompson Hobbs Natural Resource Ecology Laboratory Department of Ecology Colorado State University Jenny G. Powers Biological Resource Management Division National Park Service Terry R. Spraker Colorado State Diagnostic Laboratory College of Veterinary Medicine Colorado State University Margaret A. Wild Biological Resource Management Division National Park Service


Chronic wasting disease (CWD) can have long-term, negative impacts on deer populations, but there is little known about the ecology of CWD in free-ranging elk (Cervus elaphus). We placed radio-collars on 136 adult female elk in Rocky Mountain National Park (RMNP) as part of a three-year study that measured the efficacy of rectal biopsies to diagnose prion infection and the impact of CWD on elk survival and population growth. Elk with biopsies that tested positive via immunohistochemistry (IHC) were euthanized, and postmortem samples were examined with IHC. Survival was monitored on a weekly basis and 20-34 study animals were resampled and euthanized annually. Specificity of rectal biopsies was 100%, while sensitivity was 74% when three or more follicles were obtained from the biopsy. Rectal biopsy test results were similar to brainstem samples, but neither tissue contained prions in the earliest stages of infection that were only detected in retropharyngeal lymph nodes. Minimum prevalence (% of elk infected) was estimated to be 9.9% (95% credible limits (CI) = 5.7, 15.7) based on rectal biopsies, but this estimate rose to 12.9% (CI = 8.0, 19.1) when we included four elk that were likely misdiagnosed at initial capture. Following removal of all known individuals with CWD, the annual survival rate was relatively high during the initial year of the study, but declined in subsequent years due to consistent increases in CWD-related mortalities (2008 survival = 0.97 [CI: 0.93, 0.99], 2009 = 0.90 [CI: 0.83, 0.95], 2010 = 0.85 [CI: 0.75, 0.93]). These results suggest that 1) rectal biopsies can be a useful research tool, but can miss elk in the earliest stages of prion infection; and 2) CWD can reduce the survival of adult females and slow the population growth of high-density elk herds.


Cervus elaphus, chronic wasting disease, Colorado, elk, mortality, prevalence, prion, survival


http://www.nps.gov/romo/parkmgmt/upload/RMNP_Conference_Proceeding_2012.pdf




National Wildlife Health Center Enhanced Surveillance Strategies for Detecting and Monitoring Chronic Wasting Disease in Free-Ranging Cervids

Open-File Report 2012–1036

snip...

In addition to locations of known CWD-positive individuals, other spatial risk factors related to CWD exposure should be considered. For example, the risk of free-ranging animals being exposed to CWD is likely greater in areas where captive cervid facilities have or had CWD-positive animals. Current evidence indicates that CWD infection rates are much higher in captive facilities than in wild populations (Keane and others, 2008), and perhaps this is driven by environmental contamination (Miller and others, 2006). This higher rate of infection in captive animals can increase the risk of disease exposure to surrounding wild populations. Furthermore, movement of infectious animals, carcasses, or other materials across the landscape, naturally or with human assistance, likely increases the risk to uninfected populations. The frequent movement of farmed elk (Cervus elaphus) and deer between production facilities, the concentration of infected animals on some facilities, and the possibility of their escape into the wild increases the risk of spreading CWD to uninfected populations of free-ranging animals. Because the infectious prions may persist in the environment for long periods, the introduction of either captive or free-ranging uninfected animals into a contaminated environment could increase their risk of infection. For example, locations from which sheep have been removed may remain contaminated with scrapie agent for more than 15 years (Georgsson and others, 2006). In a similar manner, translocation of cervids from areas that have not been documented to be CWD-free could pose a risk of disease introduction. In this situation, the risk of introduction is likely related to the probability of infected animals being moved and their ability to spread CWD to other susceptible animals or into the environment. Thus, surveillance on and around cervid farms or free-ranging populations that have received animals from known CWD areas and bordering jurisdictions with CWD-positive animals can increase the likelihood of disease spread. Additional risk factors, such as the presence of scrapie in sheep populations that are sympatric with deer and elk (Greenlee and others, 2011), feeding of animal protein to cervids (Johnson, McKenzie, and others, 2011), baiting and feeding programs (Thompson and others, 2008), or other environmental factors also may be considered, although their roles in CWD epidemiology has not been clearly established.

snip...

Baiting or feeding, which artificially increases concentrations of animals, may increase the chance of disease spread through direct contact among animals or indirect contact with environmental contamination (Thompson and others, 2008; Mathiason and others, 2009; Tamguney and others, 2009; Haley and others, 2011). Thus, variation in density of deer or infected deer across the landscape is another important spatial risk factor to consider when conducting disease surveillance or monitoring (Joly and others, 2009).

snip...

It has also been recognized that targeted surveillance of individuals demonstrating clinical signs consistent with CWD infection results an increased probability of detecting CWD. In one study, 66 percent and 43 percent of submitted deer and elk exhibiting clinical signs of CWD, respectively, were diagnosed as CWD-positive compared to 5 percent and 0.5 percent of randomly sampled deer and elk submitted for testing (Miller and others, 2000). Therefore, exhibition of clinical signs of CWD is a clearly an attribute that increases an individual’s likelihood of having CWD and is a demographic risk factor that can be exploited to increase surveillance efficiency. Targeted surveillance and investigation of clinical animals also has the added benefit of detection of other important wildlife diseases with similar clinical signs (Miller and others, 2000; Samuel and others, 2003).

Other demographic risk factors are less well understood. For example, there is evidence that genetics plays a role in individual susceptibility and rate of disease progression. Similar to other TSEs, polymorphisms of the prion protein gene (PRNP) may moderate individual susceptibility to and progression of CWD infection of elk, mule, and white-tailed deer (O’Rourke and others, 2004; Spraker and others, 2004; Jewell and others, 2005; Fox and others, 2006; Hamir and others, 2006; Goldmann, 2008; Keane and others, 2008; Perucchini and others, 2008). Therefore, it appears that certain individuals are innately at higher risk of CWD infection based solely on their PRNP genotype. For example, Wisconsin white-tailed deer with the PRNP genotype G96G have approximately four times higher rate of infection and 8 months shorter survival after infection compared to G96S deer (Robinson and others, 2012). However, unlike other TSEs, there is no evidence that any of the PRNP genotypes in wild cervids are immune to CWD infection.

snip...

Finally, high population density, which also can be considered a spatial risk factor, is generally believed to create increased risk of disease transmission through higher direct or indirect contact rates (Swinton and others, 2001; Ramsey and others, 2002). This is the basis for population reduction strategies used by many wildlife management agencies for CWD management in free-ranging cervids (Williams and others, 2002; Joly and others, 2003; Williams, 2005; Joly and others, 2006). The actual transmission route of CWD is not known, however, experimental evidence from captive cervids suggests that CWD infection occurs via horizontal transmission through both direct and indirect contact between susceptible and infected individuals (Miller and Williams, 2003; Williams and Miller, 2003), and both kinds of contact can be influenced by density. Experimental inoculation with blood, urine, feces, and saliva from CWD-infected individuals has been shown to provide viable routes of transmission, suggesting direct contact with any of these infectious materials could act as a route of infection (Miller and others, 2004; Mathiason and others, 2006; Miller and others, 2006; Trifilo and others, 2007; Safar and others, 2008; Haley and others, 2009; Mathiason and others, 2009; Tamguney and others, 2009; Haley and others, 2011). Indirect contact may play an important role in transmission dynamics via environmental contamination, because the CWD agent can persist in contaminated systems for 2 or more years (Miller and others, 2004), and if CWD is similar to scrapie, it may persist for 15 or more years (Georgsson and others, 2006). For captive cervids, the most likely route of exposure is orally through foraging activities in the immediate vicinity of fresh and decomposed carcasses or ingestion of fresh and residual excreta from infected individuals (Miller and others, 2004; Trifilo and others, 2007; Safar and others, 2008; Mathiason and others, 2009). However, the relative importance of direct and indirect transmission of CWD in wild cervids has not been determined. As previously mentioned, certain soil types can also increase oral infectivity of TSEs, which may allow environmental contamination to be problematic even in the presence of relatively low doses of the infective agent (Johnson and others, 2007). Thus, it is likely density of infected cervids can contribute to increased indirect contact rate between susceptible and infected individuals or contact with an environmental reservoir. However, it is unclear to what the extent density influences these processes.

snip...

Conclusion

We have presented a wide range of risk factors that may be considered when designing surveillance or monitoring programs. Although this is not an exhaustive list and undoubtedly other factors not yet described will come to light, the risk factors and associated references detailed herein provide a useful starting point. Many jurisdictions currently collect information on many of these factors, especially for harvested cervids. Other data related to spatial risk factors may be readily available within Geographic Information Systems (GIS). Thus, the use of the risk factors in surveillance and monitoring activities is a natural progression in continued improvement of these activities.

For jurisdictions lacking quantitative information on various risk factors, we recommend collaborating with similar entities that have available information and utilizing their data to incorporate risk factors into disease-management activities. In addition, even if information is limited or unavailable for some of the risk factors described, use of the information that is available for the remaining factors may provide gains in efficiency. However, we caution that, if possible, risk factors related to CWD infection should also consider potential differences in species of interest, differences in harvest strategies among areas, if CWD is in an early or advanced stage of epizootic (low vs. high prevalence), and how different cervid ecology and habitat features might affect estimate risk factors. At the current time, little is known about how many of these features might affect CWD prevalence and risk of infection.

Evaluation of risk factors helps to focus resources on locations or target populations with a greater likelihood of being infected and increases the efficiency of surveillance and monitoring efforts. Agencies charged with managing this disease should continue to look for efficient ways to conduct their activities. Identifying, understanding the importance of, and incorporating risk factors into surveillance and monitoring activities are potential means of meeting this need for increased efficiency.

http://pubs.usgs.gov/of/2012/1036/pdf/ofr2012_1036.pdf






Chronic Wasting Disease CWD CDC REPORT MARCH 2012


Saturday, February 18, 2012


Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting Disease



CDC Volume 18, March 2012


SNIP...


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

CWD has been identified in free-ranging cervids in 15 US states and 2 Canadian provinces and in 100 captive herds in 15 states and provinces and in South Korea (Figure 1, panel B).

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


SNIP...


Long-term effects of CWD on cervid populations and ecosystems remain unclear as the disease continues to spread and prevalence increases. In captive herds, CWD might persist at high levels and lead to complete herd destruction in the absence of human culling. Epidemiologic modeling suggests the disease could have severe effects on free-ranging deer populations, depending on hunting policies and environmental persistence (8,9). CWD has been associated with large decreases in free-ranging mule deer populations in an area of high CWD prevalence (Boulder, Colorado, USA) (5).





SNIP... see map ;




http://wwwnc.cdc.gov/eid/article/18/3/11-0685-f1.htm




full text ;



http://wwwnc.cdc.gov/eid/ahead-of-print/article/18/3/11-0685_article.htm




see much more here ;



http://chronic-wasting-disease.blogspot.com/2012/02/occurrence-transmission-and-zoonotic.html




Thursday, February 09, 2012

Colorado Farm-Raised Deer Farms and CWD there from 2012 report Singeltary et al


http://chronic-wasting-disease.blogspot.com/2012/02/colorado-farm-raised-deer-farms-and-cwd.html






50 GAME FARMS IN USA INFECTED WITH CHRONIC WASTING DISEASE CWD





Tuesday, December 20, 2011





CHRONIC WASTING DISEASE CWD WISCONSIN Almond Deer (Buckhorn Flats) Farm Update DECEMBER 2011







> > > The CWD infection rate was nearly 80%, the highest ever in a North American captive herd.





Despite the five year premise plan and site decontamination, The WI DNR has concerns over the bioavailability of infectious prions at this site to wild white-tail deer should these fences be removed. Current research indicates that prions can persist in soil for a minimum of 3 years.





However, Georgsson et al. (2006) concluded that prions that produced scrapie disease in sheep remained bioavailable and infectious for at least 16 years in natural Icelandic environments, most likely in contaminated soil.





Additionally, the authors reported that from 1978-2004, scrapie recurred on 33 sheep farms, of which 9 recurrences occurred 14-21 years after initial culling and subsequent restocking efforts; these findings further emphasize the effect of environmental contamination on sustaining TSE infectivity and that long-term persistence of prions in soils may be substantially greater than previously thought. < < <









http://dnr.wi.gov/org/nrboard/2011/december/12-11-2b2.pdf















SNIP...SEE FULL TEXT ;







http://chronic-wasting-disease.blogspot.com/2011/12/chronic-wasting-disease-cwd-wisconsin.html








Thursday, February 09, 2012





50 GAME FARMS IN USA INFECTED WITH CHRONIC WASTING DISEASE





http://chronic-wasting-disease.blogspot.com/2012/02/50-game-farms-to-date-in-usa-infected.html






 

Saturday, February 04, 2012



Wisconsin 16 age limit on testing dead deer Game Farm CWD Testing Protocol Needs To Be Revised



http://chronic-wasting-disease.blogspot.com/2012/02/wisconsin-16-age-limit-on-testing-dead.html





Chronic Wasting Disease National Program for Farmed and Captive Cervids Update

Patrice N. Klein, National Center for Animal Health Programs, USDA-APHISVS

In FY2010, APHIS received approximately $16.8 million in appropriated funding for the CWD Program, including $1.0 million in congressional earmarks. The FY2011 President’s proposed budget for the CWD Program is $14.2 million (exclusive of any congressional earmarks). In the first quarter of FY2011, the federal government is operating on a Continuing Resolution based on a quarterly percentage of the FY10 budget. CWD Rule Update: Public comments received on the proposed amendments to the 2006 CWD rule were categorized, reviewed, and responses were drafted. Issues that may impact the amended final rule and CWD Program implementation include the President’s Memo on federal preemption (May 20, 2009), budgetary constraints, and ongoing need for additional research to better understand the science for prevention and control of CWD. A draft of the amended CWD final rule is in clearance in November 2010. Surveillance testing: Through FY2009, VS conducted surveillance testing on more than 23,000 farmed and captive cervids by the immunohistochemistry (IHC) standard protocol. In FY2010, approximately 20,000 farmed and captive cervids were tested by IHC for CWD with funding to cover lab costs provided through NVSL. Status: CWD was detected in one captive white-tailed deer (WTD) herd in Missouri in February 2010. To date, 50 farmed/captive cervid herds have been identified in 11 states: CO, KS, MI, MN, MO, MT, NE, NY, OK, SD, WI. Thirty-seven were elk herds and 13 were WTD herds. At this time, six CWD positive elk herds remain in Colorado and one WTD herd remains in MO. VS has continued to offer indemnity for appraised value of the animals and to cover costs of depopulation, disposal, and testing of CWD-positive and exposed herds. Indemnity is provided based on availability of federal funding.

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

Controlling Disease at the Fence: Research Questions, Answers, and on to More Questions

Kurt VerCauteren, National Wildlife Research Center, USDA-APHIS-WS

In recent years the National Wildlife Research Center has collaborated with many privately owned elk and deer producers to investigate many aspects regarding the potential for disease transmission between freeranging and captive cervids. A suite of studies began with a fencelineinteraction evaluation designed to determine if and to what extent interactions occurred along perimeter fences. We found through 1 year of video monitoring that interactions between captive and free-ranging whitetailed deer (Odocoileus virginianus) were relatively rare (2 direct contacts and 7 indirect contacts). Interactions between captive and free-ranging elk (Cervus elaphus), though, were relatively common (77 direct contacts and 274 indirect contacts). To address this issue, we proceeded to design and evaluate a cost-effective baited-electric fence that could be added to an existing single perimeter fence to minimize potential interactions. Our case study documented that once exposed to the electric fence individual elk learned to respect it and were completely deterred thereafter. The ambiguous question of how high white-tailed deer can jump was next on our list of pursuits to further evaluate risk associated with perimeter fences.

Following a controlled evaluation involving 43 white-tailed deer motivated to jump progressively higher fences, we determined that a 2.1-m-high fence presents a considerable barrier. We also teamed up with colleagues to develop the rectal biopsy antemortem test for identifying CWD-infected individuals, collecting over 1,500 rectal biopsies from captive cervids to date. We have incorporated the procedure into our research and continue to work toward assessing its utility relative to management. To prepare for instances when disease is introduced into the wild at a pointsource, we initiated a study evaluating rapid containment of white-tailed deer and demonstrated the efficacy of 2.1-m-high polypropylene mesh fence for emergency containment. A study we hope to do will document how captive white-tailed deer respond following “escape” from a captive deer facility. The study would give us an understanding of how easily these deer can be recaptured and how readily they integrate into the local free-ranging deer herd. The progression of research that we have conducted to date has provided insight into what occurs along perimeter fences at captive cervid facilities and is enabling producers and management agencies to make more informed decisions relative to protecting valuable resources inside and outside fences. We will briefly discuss these studies and more.



http://www.usaha.org/Portals/6/Proceedings/USAHAProceedings-2010-114th.pdf




http://chronic-wasting-disease.blogspot.com/





TSS

Detection of the Abnormal Isoform of the Prion Protein Associated With Chronic Wasting Disease in the Optic Pathways of the Brain and Retina of Rocky

Detection of the Abnormal Isoform of the Prion Protein Associated With Chronic Wasting Disease in the Optic Pathways of the Brain and Retina of Rocky Mountain Elk (Cervus elaphus nelsoni)

T. R. Spraker1, K. I. O’Rourke2, T. Gidlewski3, J. G. Powers4, J. J. Greenlee5, and M. A. Wild4 Abstract Eyes and nuclei of the visual pathways in the brain were examined in 30 Rocky Mountain elk (Cervus elaphus nelsoni) representing 3 genotypes of the prion protein gene PRNP (codon 132: MM, ML, or LL).

Tissues were examined for the presence of the abnormal isoform of the prion protein associated with chronic wasting disease (PrPCWD). Nuclei and axonal tracts from a single section of brain stem at the level of the dorsal motor nucleus of the vagus nerve were scored for intensity and distribution of PrPCWD immunoreactivity and degree of spongiform degeneration. This obex scoring ranged from 0 (elk with no PrPCWD in the brain stem) to 10 (representing elk in terminal stage of disease). PrPCWD was detected in the retina of 16 of 18 (89%) elk with an obex score of > 7. PrPCWD was not detected in the retina of the 3 chronic wasting disease–negative elk and 9 elk with an obex score of < 6. PrPCWD was found in the nuclei of the visual pathways in the brain before it was found in the retina. Within the retina, PrPCWD was first found in the inner plexiform layer, followed by the outer plexiform layer. Intracytoplasmic accumulation of PrPCWD was found in a few neurons in the ganglion cell layer in the PRNP 132ML elk but was a prominent feature in the PRNP 132LL elk. Small aggregates of PrPCWD were present on the inner surface of the outer limiting membrane in PRNP 132LL elk but not in PRNP 132MM or 132ML elk. This study demonstrates PrPCWD accumulation in nuclei of the visual pathways of the brain, followed by PrPCWD in the retina.

Keywords brain, chronic wasting disease, eyes, prion protein, retina, Rocky Mountain elk, visual pathways

http://www.aphis.usda.gov/wildlife_damage/nwdp/pdf/Spraker%20et%20al%202010.pdf


PPo2-27:

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

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

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

PPo3-7:

Prion Transmission from Cervids to Humans is Strain-dependent

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

Key words: CWD, strain, human transmission

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

Acknowledgement Supported by NINDS NS052319 and NIA AG14359.



Wednesday, September 08, 2010


CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html


http://chronic-wasting-disease.blogspot.com/




The Heidenhain Variant of Creutzfeldt-Jakob Disease

Stefan Kropp, MD; Walter J. Schulz-Schaeffer, MD; Michael Finkenstaedt, MD; Christian Riedemann, MD; Otto Windl, PhD; Bernhard J. Steinhoff, MD; Inga Zerr, MD; Hans A. Kretzschmar, MD; Sigrid Poser, MD

Arch Neurol. 1999;56:55-61.

Objective To investigate whether typical neuropathological and radiological findings can be identified in patients with the clinical diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease (CJD).

Design Case study. The clinical symptoms, neuropathological findings, electroencephalograms, magnetic resonance images, and cerebrospinal fluid samples of 14 Heidenhain cases were evaluated. Neuropathological changes were compared with those in a group of 14 patients with ataxia as the leading clinical sign.

Setting A university hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study.

Patients Medical records of 169 neurologically examined patients with prospectively classified and neuropathologically confirmed CJD were analyzed.

Main Outcome Measure Difference in neuropathological and radiological findings between patients with the Heidenhain variant and other patients with CJD.

Results Of 169 patients with confirmed CJD, 20% showed characteristic clinical findings such as blurred vision, visual field restriction, metamorphopsia, or cortical blindness. Disease course of the Heidenhain group, as compared with the group of all patients with definite CJD, was significantly shorter (5.7 months vs 7.5 months; P=.02, t test). Neuropathological examination of patients with the Heidenhain variant showed most pronounced changes in the occipital lobe but less damage in the cingulate gyrus and basal ganglia compared with 14 patients with CJD who had ataxia as the leading clinical sign. Eleven (92%) of 12 genetically analyzed Heidenhain cases were homozygous for methionine at codon 129 of the prion protein gene (PRNP). In 9 of 9 cases, the 14-3-3 protein was present. In 7 (78%) of 9 cases, the level of neuron-specific enolase was elevated, with a concentration above 35 ng/mL. Periodic sharp-wave complexes were observed in 11 (78%) of the 14 cases. In 7 (63%) of 11 patients, magnetic resonance images showed symmetric hyperintensities in the basal ganglia in the T2- and proton-weighted sequence. In 4 of 11 cases the T2- and proton density–weighted images showed a pronounced signal increase confined to the gray matter of the occipital and visual cortex. Isolated atrophy of the visual cortex was noticeable in 2 of 11 cases.

Conclusions The clinical presentation of the Heidenhain variant of CJD was shown to correlate with the neuropathological findings of gliosis and nerve cell loss. In patients with visual disorders of unclear origin and signs of dementia, the differential diagnosis of a Heidenhain variant of CJD must be taken into consideration.

From the Departments of Neurology (Drs Kropp, Riedemann, Zerr, and Poser), Neuropathology (Drs Schulz-Schaeffer, Windl, and Kretzschmar), Neuroradiology (Dr Finkenstaedt), and Clinical Neurophysiology (Dr Steinhoff), Georg-August-University Göttingen, Göttingen, and the MR/CT Institute Hamburg, Hamburg (Dr Finkenstaedt), Germany.

http://archneur.ama-assn.org/cgi/content/abstract/56/1/55


full text pdf ;

http://archneur.ama-assn.org/cgi/reprint/56/1/55.pdf


Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

(hmmm, this is getting interesting now...TSS)

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

see also ;

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html


see full text ;

Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html


Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'

DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785

FAX COVER SHEET

DATE: 4-23-98

TO: Mr. Terry Singeltary @ -------

FROM: Gerald Campbell

FAX: (409) 772-5315 PHONE: (409) 772-2881

Number of Pages (including cover sheet):

Message:

*CONFIDENTIALITY NOTICE*

snip...see full text ;

http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html


Friday, August 27, 2010

NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010

http://nor-98.blogspot.com/2010/08/new-atypical-nor-98-scrapie-case.html


Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html


Scrapie USA

http://scrapie-usa.blogspot.com/


Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html


Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010 PRION 2010

International Prion Congress: From agent to disease September 8–11, 2010 Salzburg, Austria

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html


Monday, November 22, 2010

Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control

REVIEW ARTICLES

http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/atypical-transmissible-spongiform.html


Thursday, November 18, 2010

UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS

http://bse-atypical.blogspot.com/2010/11/united-states-of-america-vs-galen-j.html


Tuesday, November 02, 2010

IN CONFIDENCE ''NEED TO KNOW''

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html


Seven main threats for the future linked to prions

The NeuroPrion network has identified 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

In small ruminants, a new atypical form of scrapie currently represents up to 50% of detected cases and even involves sheep selected for resistance to classical scrapie. The consequences for animal and human health are still unknown and there may be a potential connection with atypical BSE. These atypical scrapie cases constitute a second threat not envisioned previously which could deeply modify the European approach to prion diseases.

Third threat

The species barrier between human and cattle might be weaker than previously expected and the risk of transmission of prion diseases between different species has been notoriously unpredictable. The emergence of new atypical strains in cattle and sheep together with the spread of chronic wasting disease in cervids renders the understanding of the species barrier critical. This constitutes a third threat not properly envisioned previously that could deeply modify the European approach to prion diseases.

Fourth threat

Prion infectivity has now been detected in blood, urine and milk and this has potential consequences on risk assessments for the environment and food as well as for contamination of surfaces including medical instruments. Furthermore the procedures recommended for decontamination of MBM (Meat and Bone Meal), which are based on older methodologies not designed for this purpose, have turned out to be of very limited efficacy and compromise current policies concerning the reuse of these high value protein supplements (cross-contamination of feed circuits are difficult to control). It should be noted that the destruction or very limited use of MBM is estimated to still cost 1 billion euros per year to the European economy,

whereas other countries, including the US,

Brazil, and Argentine do not have these constraints.

However, many uncertainties remain concerning the guarantees that can be reasonably provided for food and feed safety and scientific knowledge about the causative agents (prions) will continue to evolve. This decontamination and environmental issue is a fourth threat that could modify deeply the European approach to prion diseases.

Fifth threat The precise nature of prions remains elusive. Very recent data indicate that abnormal prion protein (PrPTSE) can be generated from the brains of normal animals, and under some conditions (including contaminated waste water) PrPTSE can be destroyed whereas the BSE infectious titre remains almost unchanged, a finding that underlines the possibility of having BSE without any detectable diagnostic marker. These are just two areas of our incomplete knowledge of the fundamental biology of prions which constitute a fifth threat to the European approach to prion diseases.

Sixth threat The absence of common methods and standardisation in the evaluation of multiple in vivo models with different prion strains and different transgenic mice expressing PrP from different species (different genotypes of cattle, sheep, cervids, etc) renders a complete and comprehensive analysis of all the data generated by the different scientific groups almost impossible. This deeply impairs risk assessment. Moreover, the possibility of generating PrPTSE de novo with new powerful techniques has raised serious questions about their appropriateness for use as blood screening tests. The confusion about an incorrect interpretation of positive results obtained by these methods constitutes a sixth threat to European approach to prion diseases.

Seventh Threat The detection of new or re-emerging prion diseases in animals or humans which could lead to a new crisis in consumer confidence over the relaxation of precautionary measures and surveillance programmes constitutes a seventh threat that could modify the European approach to prion diseases.

http://www.neuroprion.org/en/np-neuroprion.html


Thursday, August 12, 2010

Seven main threats for the future linked to prions

http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html


http://prionpathy.blogspot.com/


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.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156


http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF


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)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html


Wednesday, July 28, 2010

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

http://bse-atypical.blogspot.com/2010/07/re-freedom-of-information-act-project.html


Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html


Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more PRIONBALONEY ?

http://prionunitusaupdate2008.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html


PLEASE SEE the dramatic increase in sporadic CJD cases in documented BSE countries,

TOTAL CASES OF SPORADIC CJD (DEATHS) DEFINITE AND PROBABLE CASES

Australia Austria Canada France Germany Italy Netherlands Slovakia Spain Switzerland UK

http://www.eurocjd.ed.ac.uk/sporadic.htm


USA

5 Includes 16 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 21 (19 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

2010

PLEASE NOTE REFERENCE LINES 5. AND 6.

Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010) Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 51 33 28 5 0 0

1997 114 68 59 9 0 0

1998 88 52 44 7 1 0

1999 120 72 64 8 0 0

2000 146 103 89 14 0 0

2001 209 119 109 10 0 0

2002 248 149 125 22 2 0

2003 274 176 137 39 0 0

2004 325 186 164 21 0 1(3)

2005 344 194 157 36 1 0

2006 383 197 166 29 0 2(4)

2007 377 214 187 27 0 0

2008 394 231 204 25 0 0

2009 425 259 216 43 0 0

2010 204 124 85 20 0 0

TOTAL 3702(5) 2177(6) 1834 315 4 3

1 Listed based on the year of death or, if not available, on year of referral;

2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;

3 Disease acquired in the United Kingdom;

4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;

5 Includes 16 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 21 (19 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

http://www.cjdsurveillance.com/pdf/case-table.pdf


Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)

(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)

http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html


Atypical BSE in Cattle

BSE has been linked to the human disease variant Creutzfeldt Jakob Disease (vCJD). The known exposure pathways for humans contracting vCJD are through the consumption of beef and beef products contaminated by the BSE agent and through blood transfusions. However, recent scientific evidence suggests that the BSE agent may play a role in the development of other forms of human prion diseases as well. These studies suggest that classical type of BSE may cause type 2 sporadic CJD and that H-type atypical BSE is connected with a familial form of CJD.

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

snip...see full text ;

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2


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.

page 114 ;

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf



TSS

Mother to Offspring Transmission of Chronic Wasting Disease

PPo3-40:


Mother to Offspring Transmission of Chronic Wasting Disease

Candace K. Mathiason, Amy V. Nalls, Kelly Anderson, Jeanette Hayes-Klug, Nicholas Haley and Edward A. Hoover

Colorado State University, Department of Microbiology, Immunology and Pathology, Fort Collins, CO USA

Key words: Chronic wasting disease, vertical transmission, muntjac deer

We have developed a new cervid model in small Asian muntjac deer (Muntiacus reevesi) to study potential modes of vertical transmission of chronic wasting disease (CWD) from mother to offspring. Eight of eight (8/8) muntjac doe orally infected with CWD tested PrPCWD lymphoid positive by 4 months post infection. Six fawns were born to these CWD-infected doe. Six fawns were born to 6 CWD-infected doe; 4 of the fawns were non-viable. The viable fawns have been monitored for CWD infection by immunohistochemistry and sPMCA performed on serial tonsil and rectal lymphoid tissue biopsies. PrPCWD has been detected in one fawn as early as 40 days of age. Moreover, sPMCA performed on rectal lymphoid tissue has yield positive results on another fawn at 10 days of age. In addition, sPMCA assays have also demonstrated amplifiable prions in maternal placental (caruncule) and mammary tissue of the dam.

Additional pregnancy related fluids and tissues from the doe as well as tissue from the nonviable fawns are currently being probed for the presence of CWD. In summary, we have employed the muntjac deer model, to demonstrate for the first time the transmission of CWD from mother to offspring. These studies provide the foundation to investigate the mechanisms and pathways of maternal prion transfer.



PRION 2010 Meeting Report International Prion Congress: From agent to disease; September 8–11, 2010; Salzburg, Austria Volume 4, Issue 3 July/August/September 2010



http://www.landesbioscience.com/journals/prion/article/12764/




http://chronic-wasting-disease.blogspot.com/





TSS

Scientific Opinion on the results of the EU survey for Chronic Wasting Disease (CWD) in cervids EFSA Panel on Biological Hazards (BIOHAZ) (October) 20

Greetings BSE-L members et al,

I would like to post the following about the EFSA Scientific opinion on CWD in cervids in the EU, and then, a review of sorts.

let's take a look at past findings of TSE in the brains of different species over the past decades in the UK and the EU, and take a look at the testing blunders on brains, and here in the USA as well, and then ask yourself, were they really trying to find TSE, or not ???

IT's a lengthy post, i hope you find interesting. ...kindest regards, terry




SCIENTIFIC OPINION

Scientific Opinion on the results of the EU survey for Chronic Wasting Disease (CWD) in cervids1

EFSA Panel on Biological Hazards (BIOHAZ)2, 3

European Food Safety Authority (EFSA), Parma, Italy

ABSTRACT

The BIOHAZ Panel was asked to provide a scientific opinion drawing conclusions on the occurrence of CWD in the cervid population in the EU, based on the results of a survey set up by the European Commission and aimed at detecting the possible presence of CWD and other TSEs in wild and farmed cervids in the EU during years 2006 to 2010. The survey was designed taking into account recommendations from an earlier 2004 EFSA opinion and established the minimum sample size to be collected from wild and farmed red deer (Cervus elaphus elaphus) from a number of Member States and from wild white-tailed deer (Odocoileus virginianus) from Finland. It also required all Member States to collect additional samples from all cervid species. Overall, approximately 13,000 brain stem samples were collected from cervids of different species in 21 Member States and Norway. No TSE positive results were found. The opinion presents, analyses and discusses the results of the survey, explains the uncertainties involved and outlines the limitations of the survey and its results. It is concluded that the lack of one positive TSE test in the farmed and wild red deer and wild white-tailed deer which were sampled indicates that there is not a cervid TSE epidemic in the EU. It is also concluded that, considering the spreading of CWD within and from clusters in North America, the limitations of the sampling performed in the EU CWD/TSEs survey and the known susceptibility of certain cervid species to CWD, occurrence of cases of TSEs, especially in remote and presently unsampled geographic areas, may not be excluded in cervids in the EU. A few recommendations for further experimental studies and possible future monitoring of CWD/TSEs in EU cervids are also provided.

© European Food Safety Authority, 2010

KEY WORDS

Chronic Wasting Disease, Transmissible Spongiform Encephalopathies, monitoring, cervids, red deer, whitetailed deer.

1 On request from the European Commission, Question No EFSA-Q-2010-00145, adopted on 22 September 2010.

2 Panel members: Olivier Andreoletti, Herbert Budka, Sava Buncic, John D Collins, John Griffin, Tine Hald, Arie Havelaar,

James Hope, Günter Klein, James McLauchlin, Christine Müller-Graf, Christophe Nguyen-The, Birgit Noerrung, Luisa

Peixe, Miguel Prieto Maradona, Antonia Ricci, John Sofos, John Threlfall, Ivar Vågsholm and Emmanuel

Vanopdenbosch. Correspondence: biohaz@efsa.europa.eu

3 Acknowledgement: The Panel wishes to thank the members of the Working Group on the Results of EU survey for CWD in

cervids: Olivier Andreoletti, Dirk Berkvens, Christian Ducrot, Dolores Gavier-Widen, John Griffin, James Hope and

Emmanuel Vanopdenbosch for the preparatory work on this scientific opinion and the hearing expert Matthias Greiner for

the support provided to this scientific opinion.

Suggested citation: EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on the results of the EU survey for Chronic Wasting Disease (CWD) in cervids. EFSA Journal 2010;8(10):1861. [29 pp.] doi:10.2903/j.efsa.2010.1861. Available online: www.efsa.europa.eu/efsajournal.htm

SUMMARY

Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ Panel) was asked to deliver a scientific opinion on the results of the EU survey for Chronic Wasting Disease (CWD) in cervids. Following from past recommendations from the Scientific Steering Committee (SSC) and EFSA, the European Commission set up a survey aimed at detecting the possible presence of CWD and other TSEs in wild and farmed cervids in the EU. The survey was carried out mainly during the years 2007, 2008, 2009, with some samples collected during 2006 and 2010. The BIOHAZ Panel was asked to provide a scientific opinion drawing conclusions on the occurrence of CWD in the cervid population in the EU.

The survey was designed taking into account recommendations from an earlier 2004 EFSA opinion and established the minimum sample size to be collected from wild and farmed red deer (Cervus elaphus elaphus) from a number of Member States and from wild white-tailed deer (Odocoileus virginianus) from Finland. In addition, it required all Member States to collect as many samples as possible from some categories of all cervids species.

The opinion outlines the results of the survey, including animal species tested, age and risk category of the animals tested and the diagnostic tests used. Overall, approximately 13,000 brain stem samples were collected from cervids of different species in 21 Member States and Norway. No TSE positive results were found. The sampling performed did not always allow reaching the required sample size and no data at all were collected from certain Member States.

The opinion analyses and discusses the results of the survey and explains the uncertainties involved. The survey and its results have some limitations, including the limited testing performed in cervid species potentially susceptible to CWD, the lack of representativeness of samples according to the size and distribution of the EU cervid population, the sensitivity of TSE testing when carried out using obex as a target tissue and the lack of data on the PrP gene polymorphisms frequency and diversity in the EU cervid population and in the tested animals.

It is concluded that the lack of one positive TSE test in the farmed and wild red deer and wild whitetailed deer which were sampled indicates that there is not a cervid TSE epidemic in the EU. The opinion also analyses two scenarios, calculating the maximum expected prevalence of TSEs in those cervid species in the EU as a whole and in some selected EU regions. However, since the assumption of a random sampling is not fulfilled, a quantitative estimate of the true prevalence with confidence intervals has limitations and needs to be interpreted with care. This is because, with regard to TSEs in cervids, the true prevalence may be different in presently unsampled areas. The opinion also highlights that considering the practical issues inherent to collection of samples in EU wild cervids, achieving a survey that would allow a quantitative estimate of the true prevalence of TSEs in these species in the EU would remain extremely difficult. Finally, considering the spreading of CWD within and from clusters in North America, the limitations of the sampling performed in the EU CWD/TSEs survey and the known susceptibility of certain cervid species to CWD, occurrence of cases of TSEs, especially in remote and presently unsampled geographic areas, may not be excluded in cervids in the EU.

The opinion also recommends further experimental studies investigating the susceptibility of the various European cervid species to CWD/TSEs and the genetic diversity of EU cervid species in comparison with North American cervid populations. Finally, inclusion of testing for TSEs as part of wildlife disease monitoring programmes for cervids in EU Member States is recommended, and the opinion advises that the design of monitoring programmes for TSEs in cervids should take into account both the objectives to be achieved and the new scientific knowledge available.

snip...

CONCLUSIONS AND RECOMMENDATIONS

CONCLUSIONS

• The EU CWD/TSEs survey carried out in 2006-2010 was designed taking into accountrecommendations from an earlier 2004 EFSA opinion.

• Approximately 13,000 brain stem samples were collected from cervids of different species in 21 EU Member States and Norway. No TSE positive results were found.

• The lack of one positive TSE test in the farmed and wild red deer and wild white-tailed deer which were sampled indicates that there is not a cervid TSE epidemic in the EU.

• Since the assumption of a random sampling is not fulfilled, a quantitative estimate of the true

prevalence with confidence intervals has limitations and needs to be interpreted with care. This is because, with regards to TSEs in cervids, the true prevalence may be different in presently unsampled areas.

• Considering the practical issues inherent to collection of samples in EU wild cervids, achieving a survey that would allow a quantitative estimate of the true prevalence of TSEs in these species in the EU would remain extremely difficult.

• Considering the spreading of CWD within and from clusters in North America, the limitations of the sampling performed in the EU CWD/TSEs survey and the known susceptibility of certain cervid species to CWD, occurrence of cases of TSEs, especially in remote and presently unsampled geographic areas, may not be excluded in cervids in the EU.

RECOMMENDATIONS

• Further experimental studies should be considered to assess the susceptibility of the various European cervid species to CWD and other TSE agents.

• PrP genetic diversity of EU cervid species should be investigated and compared to data described in North American cervid population.

• Testing for TSEs should be incorporated as part of wildlife disease monitoring programmes for cervids carried out in different EU Member States in order to ensure a continuous vigilance on the possible emergence of TSEs in EU cervids.

• The design of monitoring programmes for TSEs in cervids should take into account both the objectives to be achieved and the new scientific knowledge available (risk categories, test sensitivity, target tissue, age of the animals, susceptibility of North American moose etc.).

see full text here ;

http://www.efsa.europa.eu/en/scdocs/doc/1861.pdf


Question number: EFSA-Q-2010-00114

Adopted: 22 April 2010

Summary (0.1 Mb)

http://www.efsa.europa.eu/en/scdocs/doc/s1591.pdf


Opinion (0.1 Mb)

http://www.efsa.europa.eu/en/scdocs/doc/1591.pdf


Annex (2.5 Mb)

http://www.efsa.europa.eu/en/scdocs/doc/1591ax1.pdf


Summary

Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on analytical sensitivity of approved TSE rapid tests – new data for assessment of two rapid tests.

On 18 December 2009 EFSA published a Scientific Opinion on analytical sensitivity of approved TSE rapid tests. With regard to approved rapid tests for the detection of BSE in cattle, the Opinion concluded that, during a comparative analytical sensitivity study performed by the Community Reference Laboratory (CRL) for TSEs, the two rapid tests, Prionics®-Check LIA and Prionics®-Check PrioSTRIP, gave unexplained and unresolved specificity problems which hampered the interpretation of their analytical sensitivity. On this basis, the BIOHAZ Panel recommended that the analytical sensitivity of those two tests with cattle BSE samples should be re-assessed by appropriate experiments, under the supervision of the CRL. Following this recommendation, a new study (“re-assessment study”) was submitted for evaluation by the European Commission to EFSA. This Opinion provides a scientific assessment of the re-assessment study and provides conclusions on the analytical sensitivity of the two above rapid tests with regard to cattle BSE.

The BIOHAZ Panel concludes that the experimental design used in the new study is scientifically sound and can be considered equivalent to that applied during the first CRL study. The study was not hampered by specificity problems and allowed the re-assessment of the analytical sensitivity of Prionics®-Check LIA and Prionics®-Check PrioSTRIP with cattle BSE samples. The two tests performed within a maximal 2 log10 inferiority range as compared to the most sensitive test system identified in the first CRL study, as set out in the current EFSA protocols for the evaluation of TSE rapid post mortem tests.

The BIOHAZ Panel further concludes that the precise causes of the initial reactives in negative control samples observed in the first CRL study with the two rapid tests remain unidentified, since the re-assessment study was not designed for investigating them.

http://www.efsa.europa.eu/en/scdocs/scdoc/1591.htm


Transmissible Spongiform Encephalopathies (TSEs) in Deer – Advisory Notes For Farmers

PB13398 March 2010

http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bse/publications/documents/tse-deer.pdf


October 27, 2010

European Commission deletes four rapid TSE tests and recognizes one 27 Oct 2010

Four already approved rapid tests to detect TSEs in sheep and goats have been deleted from the TSE test list, as recommended by the European Food Safety Authority (EFSA). According to the EFSA opinion published in December 2009, cases of atypical scrapie can be missed when using these tests. At the same time a rapid BSE / TSE test is included in the lists of approved tests.

On the new list of rapid tests for the detection of BSE in cattle, the test "IDEXX HerdChek BSE-Scrapie Antigen Test Kit, EIA" of Idexx Laboratories is added. This test is now also listed for the detection of TSEs in sheep and goats. The tests 'Enfer TSE v2', 'Enfer TSE v3', 'Prionics-Check LIA SR "and" WB Prionics-Check Western SR have been deleted from the list.

These changes to the approved test list will come into effect in EU member stated as from January 1, 2011. This is because the member status need time to adapt their procedures for monitoring of TSE in sheep and goats.

http://www.vetsweb.com/news/european-commission-deletes-four-rapid-tse-tests-and-recognizes-one-1575.html


TSE in wild UK deer?

The first case of BSE (as we now realise) was in a nyala in London zoo and the further zoo cases in ungulates were simply thought of as being interesting transmissions of scrapie initially. The big problem started to appear with animals in 1993-5 when it became clear that there was an increase in the CJD cases in people that had eaten deer although the statistics involved must have been questionable. The reason for this was that the CJD Surveillance was well funded to look into the diet of people dying of CJD. This effect is not clear with vCJD...if only because the numbers involved are much smaller and hence it is difficult to gain enough statistics. They found that many other foods did not appear to have much association at all but that deer certainly did and as years went by the association actually became clearer. The appearance of vCJD in 1996 made all this much more difficult in that it was suddenly clearer that the cases of sporadic CJD that they had been checking up until then probably had nothing to do with beef...and the study decreased. During the period there was an increasing worry that deer were involved with CJD..see references:

http://collections.europarchive.org/tna/20080103022113/http://www.bseinquiry.gov.uk/files/yb/1991/11/20004001.pdf



DEER SPONGIFORM ENCEPHALOPATHY SURVEY

Dear Paul

I have now found time to review the 10 deer brains collected from Dr. Walker's farm via Winchester VIC. In answer to your specific question was there sufficient difference in preservation of brain tissue to warrant the extra effort involved in rapid brain removal on the farm, the answer is definitely ''Yes''. The original five brains (Winchester ref M487/11) showed varying degrees of autolytic vacuolation affecting both white and grey matter throughout the brain, vacuolation and separation of Purkinje cells and marked perivascular spaces. These artifacts made interpretation of subtle, specific pathological vacuolation more difficult. By contrast the second submission (Winchester reference M736/2 showed excellent preservation of white and grey matter. Any vacuolar change present could be CONFIDENTLY INTERPRETED AS PATHOLOGICAL, ALBEIT OF UNKNOWN PATHOGENESIS. ...

snip...

http://collections.europarchive.org/tna/20081106170644/http://www.bseinquiry.gov.uk/files/yb/1992/11/04002001.pdf



It is not clear that deer may well become infected with BSE although the rate at which this is taking place is unclear. DEFRA issued a document specifically to tell farmers what to do if they found a deer with potential symptoms:


THEY KNEW 2 DECADES AGO the damn BSE mad cow testing were not finding cases ;


Tuesday, November 17, 2009

SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1

http://bse-atypical.blogspot.com/2009/11/seac-new-results-on-idiopathic.html


BSE-NON-CONFIRMATION OF DISEASE

3. A question posed by Mr Whaley (para 2) is that classical lesions of BSE may not occur in all cases. Supposing we had a strain variant that produced it's lesions in the cerebrum these would not be detected by our current method. I think this would be unlikely but not impossible - another reason why at least a proportion of complete brains (or blocks) should be retained during the epidemic so if the problem Mr Whaley indicates escalates, it can be investigated.

snip...

5. IF you had the information what benefit would there be ? what would you do with it ?

CONCLUSION

I do not recommend any action. The situation should be accepted. I do not think the VIS can do more at present. The situation should be kept under review particularly if there is an escalation in numbers in this category.

R BRADLEY

15 MAY 1990

90/5.15/3.2

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1990/05/15003001.pdf


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1990/05/15003001.pdf


Ministry of Agriculture, Fisheries and Food Central Veterinary Laboratory New Haw Weybridge Surrey KT15 3NB Telex 262318 Telegrams Medium Addlestone Telephone Byfleet 41111 ext Director A J Stevens MA BVSc MRCVS DpBact FRSA

Mr. Ray Bicknell Your reference M132 Our reference VLO 12053/155/83 Date 10 March 1983 VI Centre Kendal Road Harlescott Shrewsbury

Dear Mr Bicknell

There was extensive wallerian degeneration in the lateral and ventral funiculi of the spinal cord. Vacuolation spread into the brainstem to diffusely involve the pons, medulla and even mesencephalon.

These changes are typical of those seen in Red Deer Ataxia.

Many thanks

Martin Jeffrey

VLO 12053

~

MS155/8

Ministry of Agriculture, Fisher and Food Agricultural Development and Advisory Service Veterinary Investigation Centro Kendal Road Harlescott Shrewsbury SY1 4HD

Telephone Shrewsbury 67621

Mr M Jeffrey Pathology Department CVL Weybridge Your reference 83/3.1/1.1 Our reference M132 Dale 1 March 1983

Dear Mr Jeffrey

Would you please examine the enclosed Black Fallow Deel brain and part spinal cord, our reference Ml32, submitted by Messrs J and L Harrington MSRCVS of Birmingham, from their client,

There has been a problem of enzootic ataxia in the deer on these premises for the last 2 years, and we have been investigating the problem in conjunction with the veterinary surgeons, and Dr McDiarmid. Marginal copper levels in the liver have been demonstrated in a number of cases of ataxia, but we have only now been able to obtain brain material. This particular animal was an adult buck, showing clinical symptoms which was shot through the heart. Head and neck were made available so that we have been able to obtain some spinal cord as well. I would be interested to know if you are able to find any typical lesions of enzootic ataxia. I have been in touch with Gwynneth Lewis on several occasions and it would be useful to see how it compares to similar problems in other deer parks.

Many Thanks

Yours sincerely

83/3.1/1.1

http://collections.europarchive.org/tna/20080102181815/http://www.bseinquiry.gov.uk/files/yb/1983/03/01001001.pdf



Experimental transmission of bovine spongiform encephalopathy to European red deer (Cervus elaphus elaphus)

Mark P Dagleish,1 Stuart Martin,2 Philip Steele,1 Jeanie Finlayson,1 Sílvia Sisó,2 Scott Hamilton,1 Francesca Chianini,1 Hugh W Reid,1 Lorenzo González,2 and Martin Jeffrey2

1Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Near Edinburgh, EH26 0PZ, UK

2Veterinary Laboratories Agency (VLA-Lasswade), Pentlands Science Park, Bush Loan, Penicuik, Near Edinburgh, EH26 0PZ, UK

Corresponding author. Mark P Dagleish: mark.dagleish@moredun.ac.uk ; Stuart Martin: S.F.Martin@vla.defra.gsi.gov.uk ; Philip Steele: philip.steele@moredun.ac.uk ; Jeanie Finlayson: jeanie.finlayson@moredun.ac.uk ; Sílvia Sisó: s.siso@vla.defra.gsi.gov.uk ; Scott Hamilton: scott.hamilton@moredun.ac.uk ; Francesca Chianini: francesca.chianini@moredun.ac.uk ; Hugh W Reid: hugh.reid@moredun.ac.uk ; Lorenzo González: l.gonzalez@vla.defra.gsi.gov.uk ; Martin Jeffrey: m.jeffrey@vla.defra.gsi.gov.uk

Received December 17, 2007; Accepted May 28, 2008.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC.

Abstract

Background

Bovine spongiform encephalopathy (BSE), a member of the transmissible spongiform encephalopathies (TSE), primarily affects cattle. Transmission is via concentrate feed rations contaminated with infected meat and bone meal (MBM). In addition to cattle, other food animal species are susceptible to BSE and also pose a potential threat to human health as consumption of infected meat products is the cause of variant Creutzfeldt-Jakob disease in humans, which is invariably fatal. In the UK, farmed and free ranging deer were almost certainly exposed to BSE infected MBM in proprietary feeds prior to legislation banning its inclusion. Therefore, although BSE has never been diagnosed in any deer species, a possible risk to human health remains via ingestion of cervine products. Chronic wasting disease (CWD), also a TSE, naturally infects several cervid species in North America and is spreading rapidly in both captive and free-ranging populations.


Results


Here we show that European red deer (Cervus elaphus elaphus) are susceptible to intra-cerebral (i/c) challenge with BSE positive cattle brain pool material resulting in clinical neurological disease and weight loss by 794–1290 days and the clinical signs are indistinguishable to those reported in deer with CWD. Spongiform changes typical of TSE infections were present in brain and accumulation of the disease-associated abnormal prion protein (PrPd) was present in the central and peripheral nervous systems, but not in lymphoid or other tissues. Western immunoblot analysis of brain material showed a similar glycosylation pattern to that of BSE derived from infected cattle and experimentally infected sheep with respect to protease-resistant PrP isoforms. However, the di-, mono- and unglycosylated bands migrated significantly (p


< href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2423184/">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2423184/




Bovine spongiform encephalopathy and scrapie Bovine spongiform encephalopathy and scrapie

Dr Danny Matthews

Veterinary Laboratories Agency, Woodham Lane

New Haw, Addlestone, Surrey KT15 3NB, United Kingdom

Tel.: (+44-1932) 359.512, Fax: (+44-1932) 354.929

d.matthews@vla.defra.gsi.gov.uk - http://www.vla.gov.uk/science-tse.htm


Summary of general activities related to the disease


1. Test(s) in use/or available for the specified disease at your laboratory Test For Specificity Total BioRad TeSeE ELISA Antigen PrP (BSE, scrapie and CWD) Approx. 240,000 (diagnostic) IHC Antigen PrP (BSE, scrapie and CWD) Approx. 30,000 (research); Approx. 1,500 (diagnostic) WB Antigen PrP (BSE and scrapie) Approx. 1000 (diagnostic) Approx. 2500 (research)


2. Production and distribution of diagnostic reagents The VLA Discriminatory Western blot kit for TSEs in small ruminants is commercially available. R145 anti-PrP rat monoclonal antibody is commercially available, and this year has been supplied to Germany, Austria and Denmark. The VLA TSE archive holds quantities of materials from BSE and scrapie-infected animals which it regularly supplies to both research groups and reference laboratories, as well as some manufacturers of commercial rapid tests. The most commonly supplied material is BSE infected brain tissue as this is used for the development and evaluation of tests, and for batch control after approval. It is also used for regular proficiency testing conducted in Europe under the laboratory’s responsibilities as EU Community Reference Laboratory. Activities specifically related to the mandate of OIE Reference Laboratories


3. International harmonisation and standardisation of methods for diagnostic testing or the production and testing of vaccines Annually the VLA organises QA rounds for all EU member states, which cover rapid tests, genotyping, discriminatory Western blot testing and confirmatory testing for bovine, ovine and – to a limited extent for the first time this year – cervine samples. We are currently establishing a system through which EQA can be offered to other countries on a cost-recovery basis. Several EU NRLs are participating in the batch release process for rapid test kits which is coordinated by the CRL. Following approval of rapid tests by the EU, the VLA approves all subsequent modifications, and ensures that further evaluation is conducted if considered necessary. All of the above underpin the laboratory’s ability to advise the OIE and member countries on these issues in relation to diagnostic test approval, and the Diagnostic Manual.


4. Preparation and supply of international reference standards for diagnostic tests or vaccines Production of BSE–infected brain reference material for use particularly in the evaluation of new confirmatory methods has progressed. Positive and negative controls are characterised by IHC, WB and ELISA, but not by infectivity titre. This reference bank will enable potential evaluation of new confirmatory test methods. Plans are under way to inoculate cattle with atypical BSE early in 2008 to enable reference material for these rare isolates to be produced for the purpose of facilitating future test evaluations. Histological material from positive cases has also been supplied for IHC positive control purposes to Austria, Ukraine, Lithuania, Spain, Portugal, USA, Poland, Indonesia, Switzerland, Peru, New Zealand, Slovak Republic, Latvia, Czech Republic. Frozen brain tissue from positive TSE cases has been supplied to National Reference Laboratories in Macedonia, Hungary, Lithuania, Finland and New Zealand, while tissue and fluid samples have been supplied to ten commercial organisations thus far in-year for diagnostic test development.


5. Research and development of new procedures for diagnosis and control The evaluation of diagnostic tests. Members of the laboratory participated in working groups of the EFSA in order to review and update protocols for the future ongoing evaluation of post-mortem and in-vivo tests for BSE in cattle and TSEs in small ruminants. The protocols were published on the EFSA web-site. The VLA will supply substantial amounts of positive brain tissue from cattle and sheep in order to enable the reference bank for the evaluation to be created. Transmission of BSE to red deer has been achieved experimentally, and comparison with CWD is ongoing. This data will be used for comparative purposes in the event of any positive animal being identified through the EU cervid surveillance programme. Unusual BSE: The CRL strain typing group met to discuss methodologies for classification of BSE isolates , and agreed terminology (C-; H-; and L-type), and to prepare a guidance document that was primarily intended for the EU, but would also be available for all other laboratories via the VLA web site. This document is currently being drafted. Atypical scrapie: The transmissibility of atypical scrapie to sheep has been confirmed by experimental inoculation (four animals to date) and it appears that the phenotypic characteristics are maintained on such sub-passage, at least within the AHQ/AHQ genotype.(Simmons et al 07). Other genotypes have been challenged, but have not yet succumbed. Similar experimental inoculations are ongoing for the production of reference material for test evaluation. An oral pathogenesis study of atypical scrapie started in early 2007. Ovine BSE. It has been shown that discriminatory WB and IHC remain able to differentiate between experimental BSE in sheep and natural scrapie up to and including the third experimental passage in sheep (paper in preparation). Scrapie transmission via milk has been demonstrated experimentally in the natural host. Publication submitted. Unusual scrapie isolates: In the context of the CRL strain typing Expert Group, several isolates identified as ‘intermediate’ between classical scrapie and BSE in diagnostic tests are being bioassayed in a variety of conventional inbred mice and transgenic models. Emerging data, in comparison with the large bioassay programmes at VLA and elsewhere, indicate that these isolates are scrapie-like in their biological behaviour, and are likely to result in a broadening of the classification parameters for ‘scrapie’. The BioRad Western blot has been evaluated as a confirmatory test, and recommendations made to the OIE and the Commission in this respect. VLA scientists evaluated variability in heart rate and further tested rectal biopsy as means of pre-clinical diagnosis of scrapie and CWD. Both resulted in publications. While none of this research directly contributes to test development it gives reassurance that the current diagnostic methods are capable of identifying BSE in the sheep population. It also underpins any amendments to the Diagnostic Manual to ensure that appropriate surveillance methods are in place for prion diseases, and facilitates the experimental production of appropriate reference materials.


6. Collection, analysis and dissemination of epizootiological data relevant to international disease control The collection and analysis of data from Europe has occurred, focusing primarily on the outcome of active surveillance for TSEs in small ruminants. This has been done in collaboration with scientists at other institutes both in the UK and in the EU, the latter particularly through the large collaborative programme of Neuroprion. One key conclusion was that the incidence of atypical scrapie in EU countries was remarkably consistent, in contrast to classical scrapie where there are between country differences, and significant variations from year to year within countries. This may indicate that atypical scrapie is non-infectious, and arises spontaneously, but natural transmissibility at low frequency cannot be ruled out. Analysis of data from elsewhere is on an ad hoc basis, on request from the member country.


7. Provision of consultant expertise to OIE or to OIE Member Countries D Matthews was a member of an OIE BSE ad hoc Group convened in November 2007 to discuss the relevance of atypical scrapie and atypical BSE to current codes. The meeting also provided advice to another ad hoc group that is involved in establishing country status for BSE. There was also consultation during the year with the OIE in relation to approval procedures for BSE tests (Dr K Webster). In addition to our role as the EU CRL through which we provide regular advice and expertise to European member states, ad hoc advice was also offered to individuals in, USA, Korea, Ukraine, New Zealand, Norway, Spain, Portugal, Canada, Brazil, Peru, Chile, Argentina and Switzerland, on a range of subjects, mostly related to surveillance and confirmatory diagnostic methods, interpretation of results, pathogenesis of BSE and acquisition of control materials. 8. Provision of scientific and technical training to personnel from other OIE Member Countries On site training has been made available to visitors from Spain, Korea,, New Zealand, Latvia, Czech Republic, Slovak Republic, Austria Canada, USA, and Japan. Training visits were also made to Poland, Denmark and Austria , to provide laboratory-specific technical advice. In addition, the VLA CRL web site is accessible to all countries, and new OIE-specific front pages enable easy access to this site. Incorporated into the web site are a series of video clips of clinical BSE and scrapie in sheep and goats, which can be downloaded without limit. These remain very popular with visitors to the site. In addition a thirty minute narrated DVD of clinical signs and examination techniques for BSE is still available to purchase through the website, They may be used for training purposes without copyright restriction provided the source is acknowledged. The web site is also populated with current methodologies for diagnostics .

The web site address is http://www.vla.gov.uk/science/science-tse.htm

Two Croatian officials were briefed about the scrapie surveillance in Great Britain with discussion about the most suitable and efficient surveillance streams for the detection of classical vs. atypical scrapie.


9. Provision of diagnostic testing facilities to other OIE Member Countries Subcontracted differential Western blotting from Cyprus. Second opinion confirmatory diagnosis for; Austria, Greece, Denmark, Cyprus, Kuwait, Ireland, Hungary.


10. Organisation of international scientific meetings on behalf of OIE or other international bodies The CRL holds an Annual Workshop for all EU NRLs at which emerging scientific issues and outcomes from the QA exercises are discussed, and future training needs identified. VLA contributed to the organisation of the international Neuroprion meeting in Edinburgh, Sept 07.


11. Participation in international scientific collaborative studies VLA scientists are involved in many international collaborative scientific studies, primarily in Europe, but increasingly with the USA, Canada, Korea and Japan. These are too numerous to list in the space available.


12. Publication and dissemination of information relevant to the work of OIE (including list of scientific publications, internet publishing activities, presentations at international conferences) Presentations have been given to UK and EU advisory groups and at various national and international scientific meetings including:


snip...see full text ;


http://www.oie.int/eng/oie/organisation/2007reports/02_Cattle/BOV_SPONGI_UK.doc


O.I.E.


http://tna.europarchive.org/20080609145105/http://www.bseinquiry.gov.uk/files/yb/1992/11/02004001.pdf


Thursday, September 10, 2009

Experimental oral transmission of CWD to red deer (Cervus elaphus elaphus): early detection and late stage distribution of protease-resistant protein


http://chronic-wasting-disease.blogspot.com/2009/09/experimental-oral-transmission-of.html



Research Project: Transmissible Spongiform Encephalopathies: the Role of Genetics, Strain Variation, and Environmental Contamination in Disease Control Location: Animal Diseases

Research Title: Experimental oral transmission of chronic wasting disease to red deer (Cervus elaphus elaphus): Early detection and late stage distribution of protease-resistant prion protein


Authors Balachandran, A - CANADIAN FOOD INSPCTN AG Harrington, Noel - CANADIAN FOOD INSPCTN AG Algire, James - CANADIAN FOOD INSPCTN AG Souyrine, Andre - CANADIAN FOOD INSPCTN AG Spraker, Terry - COLORADO ST UNIV Jeffrey, Martin - Gonzalez, Lorenzo - Orourke, Katherine Submitted to: Canadian Veterinary Journal Publication Type: Peer Reviewed Journal Publication Acceptance Date: December 1, 2008 Publication Date: March 11, 2010 Reprint URL:


http://ddr.nal.usda.gov/dspace/bitstream/10113/40677/1/IND44334511.pdf


Citation: Balachandran, A., Harrington, N., Algire, J., Souyrine, A., Spraker, T., Jeffrey, M., Gonzalez, L., Orourke, K.I. 2010.


Experimental oral transmission of chronic wasting disease to red deer (Cervus elaphus elaphus): Early detection and late stage distribution of protease-resistant prion protein. Canadian Veterinary Journal. Canadian Veterinary Journal. 51:169-178.


Interpretive Summary: Farmed cervids may be exposed to the prion disorder chronic wasting disease through contact with free ranging or farmed infected Rocky Mountain elk, white tailed deer, mule deer, or moose. This is the first report of experimental transmission of chronic wasting disease to red deer, an economically important agricultural commodity in parts of North America. Brain tissue from infected Rocky Mountain elk was administered by the oral route of red deer. Deer were examined at 18 months after infection for evidence of abnormal prion protein, the marker for the disease. The abnormal protein was found throughout the brain, spinal cord and lymphoid tissues, with variable distribution in other organ systems. This finding confirms the potential susceptibility of this species to disease under natural conditions and the reliability of the current testing format for identifying the abnormal protein in the tissues routinely collected in surveillance programs. The widespread distribution of the abnormal protein in red deer indicates the potential for shedding of the agent into the environment. Technical Abstract: Chronic wasting disease CWD is the transmissible spongiform encephalopathy or prion disease of wild and farmed cervid ruminants, including Rocky Mountain elk (Cervus elaphus nelsoni), white tailed deer (Odocoileus virginianus), mule deer (Odocoileus hemionus), or moose (Alces alces). Reliable data on the susceptibility of other farmed cervid species, the distribution of the abnormal prion protein marker in brain and lymphoid tissues collected in surveillance programs, and the role of prion genotype are necessary for design of control programs for CWD in farmed cervids. In this study, red deer (Cervus elaphus elaphus) were exposed to the prion agent by oral administration of brain homogenates from infected Rocky Mountain elk. Antemortem testing was performed at 7 months post infection and the deer were euthanized when clinical disease was observed at approximately 18 months after infection. The abnormal prion protein was assayed by immunohistochemistry, enzyme linked immunosorbent assay and western blot. Abnormal prion protein was found in the spinal cord, brainstem, cerebellum, midbrain, thalamus, and cerebrum in all 4 infected red deer. Most of the lymph nodes throughout the body were positive for abnormal prion proteins. Abnromal prion protein was observed in some additional peripheral tissues in some but not all of the deer. In particular, most areas of the gastrointestinal tract were positive for abnormal prions, although the salivary glands were rarely positive. This study demonstrates the potential for oral transmission of chronic wasting disease to red deer and confirms the usefulness of the current testing methods for post mortem diagnosis of the disease in this species.


http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=228787


http://www.ncbi.nlm.nih.gov/pubmed/20436863






Subject: MAD DEER/ELK DISEASE AND POTENTIAL SOURCES

Date: Sat, 25 May 2002 18:41:46 -0700

From: "Terry S. Singeltary Sr."

Reply-To: BSE-L

To: BSE-L

8420-20.5% Antler Developer For Deer and Game in the wild Guaranteed Analysis Ingredients / Products Feeding Directions

snip...

_animal protein_

http://www.surefed.com/deer.htm

BODE'S GAME FEED SUPPLEMENT #400 A RATION FOR DEER NET WEIGHT 50 POUNDS 22.6 KG.

snip...

_animal protein_

http://www.bodefeed.com/prod7.htm

Ingredients

__Animal Protein Products__,

http://www.bodefeed.com/prod6.htm

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

MORE ANIMAL PROTEIN PRODUCTS FOR DEER

Bode's #1 Game Pellets A RATION FOR DEER F3153

GUARANTEED ANALYSIS Crude Protein (Min) 16% Crude Fat (Min) 2.0% Crude Fiber (Max) 19% Calcium (Ca) (Min) 1.25% Calcium (Ca) (Max) 1.75% Phosphorus (P) (Min) 1.0% Salt (Min) .30% Salt (Max) .70%

Ingredients

__Animal Protein Products__,

FEEDING DIRECTIONS Feed as Creep Feed with Normal Diet

http://www.bodefeed.com/prod8.htm

INGREDIENTS

__Animal Protein Products__,

DIRECTIONS FOR USE

Deer Builder Pellets is designed to be fed to deer under range conditions or deer that require higher levels of protein. Feed to deer during gestation, fawning, lactation, antler growth and pre-rut, all phases which require a higher level of nutrition. Provide adequate amounts of good quality roughage and fresh water at all times.

http://www.profilenutrition.com/Products/Specialty/deer_builder_pellets.html

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

DEPARTMENT OF HEALTH & HUMAN SERVICES PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION

April 9, 2001 WARNING LETTER

01-PHI-12 CERTIFIED MAIL RETURN RECEIPT REQUESTED

Brian J. Raymond, Owner Sandy Lake Mills 26 Mill Street P.O. Box 117 Sandy Lake, PA 16145 PHILADELPHIA DISTRICT

Tel: 215-597-4390

Dear Mr. Raymond:

Food and Drug Administration Investigator Gregory E. Beichner conducted an inspection of your animal feed manufacturing operation, located in Sandy Lake, Pennsylvania, on March 23, 2001, and determined that your firm manufactures animal feeds including feeds containing prohibited materials. The inspection found significant deviations from the requirements set forth in Title 21, code of Federal Regulations, part 589.2000 - Animal Proteins Prohibited in Ruminant Feed. The regulation is intended to prevent the establishment and amplification of Bovine Spongiform Encephalopathy (BSE) . Such deviations cause products being manufactured at this facility to be misbranded within the meaning of Section 403(f), of the Federal Food, Drug, and Cosmetic Act (the Act).

Our investigation found failure to label your swine feed with the required cautionary statement "Do Not Feed to cattle or other Ruminants" The FDA suggests that the statement be distinguished by different type-size or color or other means of highlighting the statement so that it is easily noticed by a purchaser.

In addition, we note that you are using approximately 140 pounds of cracked corn to flush your mixer used in the manufacture of animal feeds containing prohibited material. This flushed material is fed to wild game including deer, a ruminant animal. Feed material which may potentially contain prohibited material should not be fed to ruminant animals which may become part of the food chain.

The above is not intended to be an all-inclusive list of deviations from the regulations. As a manufacturer of materials intended for animal feed use, you are responsible for assuring that your overall operation and the products you manufacture and distribute are in compliance with the law. We have enclosed a copy of FDA's Small Entity Compliance Guide to assist you with complying with the regulation... blah, blah, blah...

http://www.fda.gov/foi/warning_letters/g1115d.pdf

above urls dead, go here ;

http://madcowfeed.blogspot.com/2008/07/docket-03d-0186-fda-issues-draft.html


Zoo Prion Disease: Review of Scientific Literature

http://www.mad-cow.org/zoo_cites_annotated.html




PPo3-30:

Immunohistochemical and Biochemical Characteristics of BSE and CWD in Experimentally Infected European Red Deer (Cervus Elaphus)

Stuart Martin,1 Martin Jeffrey,1 Lorenzo González,1 Sílvia Sisó,1 Hugh Reid,2 Philip Steele,2 Mark Dagleish,2 Michael Stack,1 Melanie Chaplin,1 John Spiropoulos,1 Marion Simmons,1 Wilfred Goldmann3 and Aru Balachandran4 1Veterinary Laboratories Agency; Addlestone, Surrey UK; 2Moredun Research Institute, Penicuik, Midlothian, Scotland UK; 3Neuropathology Unit; Roslin, Scotland UK; 4Canadian Food Inspection Agency

Key words: red deer, BSE, CWD, IHC, WB, polymorphism, bioassay

Thirty-two deer were orally or intra-cerebrally dosed with homogenate from a pool of five BSE-positive bovine brains and negative control animals underwent identical procedures with sterile saline buffer. An extensive range of samples was tested by immunohistochemistry (IHC), western blot (WB, brainstem only) and mouse bioassay (2 positive deer). In the absence of clinical signs, none of the 12 orally-dosed deer culled after 6 or 12 months, nor 5 of 6 culled at the termination of the experiment (72 months), showed any evidence of abnormal PrP accumulation by IHC or WB. In contrast, all the 6 intra-cerebrally challenged and 1 of 6 orally dosed deer developed clinical disease at various times after infection. These deer showed widespread accumulation of disease specific PrP in the CNS, PNS and ENS but none in the LRS. Both IHC and WB features were similar to those of BSE in sheep, goats and cattle but unlike those seen in CWD in elk or scrapie in sheep. Analysis of the PrP ORF of all deer in the experiment identified a Q to E polymorphism at codon 226. Interestingly, the single deer that succumbed to oral BSE infection was the only QQ deer of the 6 allowed to develop clinical disease, suggesting that such polymorphism may influence the susceptibility of deer to oral BSE. Brain homogenates from positive deer were inoculated into panels of 20 Tg(cerPrP) 1536+/- mice, which developed neurological signs with an incubation period of 202–298 days post inoculation and attack rates of 90–95%.



http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099



see ;

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010 PRION 2010

International Prion Congress: From agent to disease September 8–11, 2010 Salzburg, Austria


http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html



LET's look at some other mix-up of brains in the ever revolving doors of TSE, prion, prionpathy, prionopathy, prionoids, saga. ...

Besides the Deer brains, let's take a look at the infamous hound ataxia, and the BSE to sheep brains......oops, cow brains, or what ?

Subject: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY

Date: Thu, 17 Oct 2002 17:04:51 -0700

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L

Greetings BSE-L,

is there any other CWD surveys/testing in the UK on their deer? what sort of testing has been done to date on UK/EU deer? any input would be helpful... thank you

DEER SPONGIFORM ENCEPHALOPATHY SURVEY

3. This will be a low key study with no publicity to avoid unnecessary media interest. It will be carried out in two stages ;

(I) A small scale examination of around 30 deer brains to establish the normal histology of the healthy brain; and

(II) A larger scale random examination of 300 or more adult deer brains drawn from both deer farms and parks to establish whether there is any evidence of a cervine spongiform encephalopathy. ...

http://collections.europarchive.org/tna/20080103022113/http://www.bseinquiry.gov.uk/files/yb/1991/11/20004001.pdf



Ministry of Agriculture Fisheries and Food Veterinary Investigation Centre West House. Station Road. Thirsk Y07 IPZ Telephone: 0845·522065 Fax: 0845·525224

Your reference

Our reference RJH/ASB

Date 4 November 1992

DEER SPONGIFORM ENCEPHALOPATHY SURVEY

Dear Paul

I have now found time to review the 10 deer- brains collected from Mr Walker farm··via Winchester Via Winchester VIC. In answer to your specific question was there sufficient difference in preservation of brain tissue to warrant the extra effort involved in rapid brain removal on the farm, the answer is definitely "Yes." The original five brains (Winchester ref M487/11) showed varying degrees of autolytic vacuolation affecting both white and grey matter throughout the brain. vacuolation and separation of Purkinje cells and marked perivascular spaces. These artifacts made interpretation of subtle, specific pathological vacuolation more difficult. By contrast the second submission (Winchester reference N736/2) showed excellent preservation of white and grey matter. Any vacuolar Change present could be confidently interpreted as pathological albeit of unknown pathogenesis.

I can only reiterate the comments made by Gerald Wells and myself at the preliminary discussion at Weybridge in Autumn 1991. If the survey's purpose is an accurate histopathological interpretation of brain tissue. the material must be collected in a pristine state. This is particularly valid when looking for ar unrecognised and undefined spongiform encephalopathy in a new species. Deer brains are very large structures which take a lot of fixation and therefore must be handled sympathetically from the start. We have already seen the problems encountered in comparatively smaller hound brains where delayed fixation was a major limitation on interpretation of true pathological change.

The bottom line must be that if a pathologist's expertise is to be used, it is critical to collect artefact free brain material. If the politics or economics do not allow this, then I would suggest that an electron microscopy survey in­volving detection of scrapie associated fibrils would be much more appropriate.

Best wishes Yours sincerely

R J HIGGINS VIO 92/11.4/2.1

http://collections.europarchive.org/tna/20081106170644/http://www.bseinquiry.gov.uk/files/yb/1992/11/04002001.pdf



SEE DEER ON STENT FARM (cattle feed i.e. animal protein to deer ???)

http://tna.europarchive.org/20080609145105/http://www.bseinquiry.gov.uk/files/yb/1987/08/05003001.pdf



HOUND SURVEY

I am sorry, but I really could have been a co-signatory of Gerald's minute.

I do NOT think that we can justify devoting any resources to this study, especially as larger and more important projects such as the pathogenesis study will be quite demanding.

If there is a POLITICAL need to continue with the examination of hound brains then it should be passed entirely to the VI Service.

J W WILESMITH Epidemiology Unit 18 October 1991

Mr. R Bradley

cc: Mr. G A H Wells

http://collections.europarchive.org/tna/20081106102318/http://www.bseinquiry.gov.uk/files/yb/1991/10/18001001.pdf



3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would by the end of the year, indentify the three brains that were from the ''POSITIVE'' end of the lesion spectrum.

http://collections.europarchive.org/tna/20080103034308/http://www.bseinquiry.gov.uk/files/yb/1993/12/06001001.pdf



37. Putative TSE in hounds - work started 1990 -(see para 41)

Robert Higgins, a Veterinary Investigation Officer at Thirsk, had been working on a hound survey in 1990. Gerald Wells and I myself received histological sections from this survey along with the accompanying letter (YB90/11.28/1.1) dated November 1990. This letter details spongiform changes found in brains from hunt hounds failing to keep up with the rest of the pack, along with the results of SAF extractions from fresh brain material from these same animals. SAFs were not found in brains unless spongiform changes were also present. The spongiform changes were not pathognomonic (ie. conclusive proof) for prion disease, as they were atypical, being largely present in white matter rather than grey matter in the brain and spinal cord. However, Tony Scott, then head of electron microscopy work on TSEs, had no doubt that these SAFs were genuine and that these hounds therefore must have had a scrapie-like disease. I reviewed all the sections myself (original notes appended) and although the pathology was not typical, I could not exclude the possibility that this was a scrapie-like disorder, as white matter vacuolation is seen in TSEs and Wallerian degeneration was also present in the white matter of the hounds, another feature of scrapie.

38.I reviewed the literature on hound neuropathology, and discovered that micrographs and descriptive neuropathology from papers on 'hound ataxia' mirrored those in material from Robert Higgins' hound survey. Dr Tony Palmer (Cambridge) had done much of this work, and I obtained original sections from hound ataxia cases from him. This enabled me provisionally to conclude that Robert Higgins had in all probability detected hound ataxia, but also that hound ataxia itself was possibly a TSE. Gerald Wells confirmed in 'blind' examination of single restricted microscopic fields that there was no distinction between the white matter vacuolation present in BSE and scrapie cases, and that occurring in hound ataxia and the hound survey cases.

39.Hound ataxia had reportedly been occurring since the 1930's, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.

40.The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.

41.The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.

Histopathological support to various other published MAFF experiments

42.These included neuropathological examination of material from experiments studying the attempted transmission of BSE to chickens and pigs (CVL 1991) and to mice (RVC 1994).

http://www.bseinquiry.gov.uk/witness/htm/stat067.htm


1. I have had no further submission of material or communication regarding this survey since January 1991.

http://collections.europarchive.org/tna/20080103024918/http://www.bseinquiry.gov.uk/files/yb/1991/10/17001001.pdf


HOUND SURVEY PATHOLOGICAL REPORT (see positive results)

http://web.archive.org/web/20030605233318/http://www.bseinquiry.gov.uk/files/yb/1990/11/28001001.pdf


kind regards, terry

###########bse-l ############

Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY

Date: Fri, 18 Oct 2002 23:12:22 +0100

From: Steve Dealler

Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member T

o: BSE-L@ References: <3daf5023.4080804@wt.net>

Dear Terry,

An excellent piece of review as this literature is desparately difficult to get back from Government sites.

What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!

Steve Dealler


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



Incubation periods for BSE are proportional to the life expectancy of the animal affected. The disease's incubation period is 18% of a cow's life expectancy and would be expected to about double when crossing to another species [---] that is, to 36% of 70 years in humans.

Steve Dealler, consultant in medical microbiology. Burnley General Hospital, Burnley BB10 2PQ deal@airtime.co.uk


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


http://caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html



HOUND STUDY

AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.

snip...

http://web.archive.org/web/20010305222642/www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf



2005 DEFRA Department for Environment, Food & Rural Affairs

Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk

GTN: FAX:

Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518

21 November 2001

Dear Mr Singeltary

TSE IN HOUNDS

Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.

As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.

Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.

Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less

critical. For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf


As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.

Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK

You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.

I hope this is helpful

Yours sincerely 4

HUGH MCDONAGH BSE CORRESPONDENCE SECTION

IN CONFIDENCE

CONCEPT NOT FOR FURTHER STUDY OF MATERIAL OBTAINED IN A SURVEY OF HOUNDS FOR EVIDENCE OF A SCRAPIE-LIKE SPONGIFORM ENCEPHALOPATHY (SE)

snip...

b) Fibrillar material closely similar to SAF, found in BSE/Scrapie, was observed in 19 (4.3%) cases, all of which were hounds > 7 years of age. 14/19 of these suspected SAF results correlated with cases in the unresolveable histopathological category.

snip...

The following proposals address the hypothesis that the hound survey observations represent a PrP related or scrapie-like disease of dogs in which the pathological response, and possible the spread of infectivity, is neuroanatomically localized. By inference this could also mean that the disorder is clinically silent and non-progressive.

http://collections.europarchive.org/tna/20080102212426/http://www.bseinquiry.gov.uk/files/yb/1995/02/09001001.pdf



In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

http://collections.europarchive.org/tna/20090114025254/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf




MADTOM said it best way back, and it still holds true today ;


Opinion (webmaster): It was politically unacceptable to find TSE in dogs. However, hunting dogs in particular received horrific exposure to terminal downer BSE cows, including skull and spinal column. The most interesting aspect is that hound ataxia, taken above as a proxy for dog TSE, goes back to the 1930's, the time of the louping ill vaccine accident causing tens of thousands of sheep to develop scrapie. Some of the dog cases could be due in fact to consumption of sheep scrapie.

TSE in dogs: new details emerge

http://www.mad-cow.org/00/aug00_late_news.html#ggg


http://www.mad-cow.org/Dec98_news.html#bbb


http://www.mad-cow.org/00/nov00_late_news.html#fff




NOW, what about those BSE to sheep brains, oops, cow brains, or what ???



News Nature 413, 760 (25 October 2001) doi:10.1038/35101729

Brain mix-up leaves BSE research in turmoil Declan Butler

In a report that could have plunged the British meat industry back into crisis, parliament was due to receive research results this week confirming that traces of bovine spongiform encephalopathy (BSE) had been found in sheep.But at the eleventh hour, the Department for Environment, Food and Rural Affairs (DEFRA) declared that the experiments conducted by the Institute for Animal Health (IAH) near Newbury, Berkshire, were suspect.

http://www.nature.com/nature/journal/v413/n6858/full/413760a0.html



Subject: Re: No sign of BSE in sheep ??? [tests terribly flawed]

Date: Thu, 18 Oct 2001 21:38:12 -0700

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de

References: 1

######## Bovine Spongiform Encephalopathy #########

18 October 2001

FSA UPDATE ON THE RISK OF BSE IN SHEEP

The FSA has previously issued advice on the theoretical risk of BSE being in sheep.

The FSA is not advising against the consumption of lamb. However, the theoretical risk of BSE in sheep remains, although on-going studies of the current sheep flock indicate that no sheep have tested positive for BSE.

The FSA has previously publicised the potential problems in relation to an experiment on sheep brains from the early 1990s to determine whether sheep had BSE then. The Agency agrees with DEFRA that there are now significant doubts about the validity of the original sample that prevents it from being further considered in relation to the presence of BSE in sheep in the early 1990s.

The Agency will discuss its current position at an open Board meeting in London on Monday 22 October 2001.

Background information

The theoretical risk of BSE in sheep has long been known and has been publicly recognised by the Food Standards Agency and was raised in the Agency’s review of BSE controls. This theoretical risk was originally identified as a result of experiments in which it was shown that sheep deliberately fed BSE-infected cows’ brains were susceptible to infection. Despite the fact that sheep as well as cows are known to have eaten the same feed that caused the BSE epidemic in cows, evidence to date has not shown that any sheep have contracted BSE except experimentally.

http://www.foodstandards.gov.uk/press_releases/statements/st011018.htm



Letter to the Committee Chairman from Dr A G Dickinson (R 11)

I have not submitted any evidence to your Committee and this letter is intended to explain why. The enclosed copy of Hugh Pennington's Review of the Phillips Report [not printed] explains my involvement with TSE research, which has been longer than for anyone else world-wide.

I was one of the half-dozen who put a great deal of effort into arguing for a BSE Inquiry to be set up, as I had been close to the subject over several decades. The Phillips Report has, with one major exception, been widely regarded as excellent—unfortunately, its science section is unsatisfactory in many respects. This is not surprising because this subject is at the frontier of knowledge and Lord Phillips deliberately excluded from his team anyone with direct involvement in TSE research (he rightly criticises various BSE committees for doing this).

Some still disapprove of there having been a public inquiry, but they do not realise that the alternative was that we would now be half way through a High Court action lasting twice as long as Phillips took, with adversarial methods potentially doing untold co-lateral damage to both groups of victims (livestock farmers and vCJD families), but almost certainly failing to reveal the main aspects leading to the epidemic (I speak from the experience of having raised the warning, seven years in advance, that human growth hormone could be CJD-contaminated).

From the wording of your Committee's invitation for the submission of written evidence, the Phillips Report is being assumed to be a sound basis from which to asses the "scale and focus of MAFF's research into TSEs". Because I am trying to be as constructive as possible, I hope that you will not be offended by commenting that it seems to me that the nearly impossible is being attempted. Unless the breadth of this subject is thoroughly understood by those concerned, along with all the technical limitations involved in interpreting the research, "scope and focus" cannot be judged. With the aim of being helpful, I will include a few examples of important unresolved issues which could provide a constructive basis for your inquiry.

Since I started in this research in 1955, of the many committees intended to appraise or fund TSE work, there have been hardly any that have been of value. Many have had very wasteful or harmful consequences, because they comprised busy "experts" from other fields, who recommended the current scientific band-wagons (in 1955 for a scrapie vaccine or in 1988-89 ill-considered overemphasis on PrP) or the blatantly obvious (the need since 1960 for diagnostic tests). However, by making recommendations they succeeded in deflecting funds from other important aspects. During the BSE epidemic there has been extensive waste of the large, mainly MAFF-controlled, research funds. This is a view shared by many of those with proven TSE-research expertise, some of whom are still involved in the research and therefore too prudent or intimidated to publicise their opinions.

There were two types of reason why BSE funding has been very wastefully focused. One, from the late 1980s, was the plethora of research committees controlling the policy and funds, hardly any of whose members were familiar with the subject, but who were mesmerised by the hype surrounding the protein, PrP. In 1971 I discovered the crucial role of this protein in the pathogenesis of the disease and published this along with a range of predictions, most of which have now been confirmed. You may be assuming that the molecular nature of TSE agents has been "proved" to be, simply, a modified form of this protein (a so-called "rogue protein"), but the number of those who doubt this is steadily growing, if only for the reason that this hypothesis has never been able to explain the facts, and such anomalies progressively increase in number. This short-sighted view of molecular aspects deflected funding away from several important areas. One vital aspect from which work was deflected for a decade after 1988 was the investigation of substances (polyanions) which have the prospect of providing therapies for TSE infections—I drew the Inquiry's attention to this lapse in my Statement.

The second reason for considerable waste of funds was that staff at the Central Veterinary Lab, who were inexperienced with TSE research, controlled early decisions. An example of where this proved very costly was their misjudged decision to base routine BSE diagnosis on neuropathology, rather than on our quick, cheap 1986 biochemical assay, which would, importantly, also have been applicable to tissue from dead cattle that was unsuitable for neuropathology.

The foregoing relates to the past but is symptomatic of the present. Three current examples are given below under separate headings. The first example still remains as the most important issue needing active debate and good experiments, because it may become necessary to undo public misconceptions about whether or not the BSE strain of agent per se is more dangerous to humans than other TSE strains. The impression created since 1996 by governments and the media has certainly been that it is a more dangerous strain, but where is the hard evidence?

(1) The unresolved question is whether the TSE strain that causes BSE and vCJD is intrinsically more easily transmitted to other species, including humans, than other TSE strains. [This issue was presented to the BSE Inquiry in paragraphs 4-9 of my Statement.]

The misleading word that has been most popular with the media in recent years to describe BSE being transferred to another species is that it "jumped". I am certain that a more accurate term is that it was "pushed". In order to "push" one of these types of agents across to another species, the greater the amount of infective agent involved, the more likely it is to achieve infection of the other species. My assessment of the current situation with the transfer of BSE to humans, is that the whole picture could be explained solely in terms of the enormous scale of the BSE epidemic having massively exposed people to the otherwise very small risk of being infected.

It is only because of the precautionary principle that the provisional assumption has to be made that the BSE strain is very much more liable to infect humans than strains that have been present in sheep for hundreds of years. For 15 years we have urgently needed to know the relative risk of the BSE strain to humans—relative, that is, compared with other strains of TSEs. I am not aware of any properly designed experiments with this objective: enquiries whether some are, at last, in progress have been unproductive.

It is often claimed that no scrapie strain has infected humans, but this is an unjustified extrapolation. What has been well established is that if any scrapie strain has passed from sheep to humans, this must be such a rare event that it has not been detected as a component of the 1:50,000 rate of incidence of CJD in humans. It seems reasonable to conclude that the scale of exposure of humans to scrapie strains during the 20th century will have been vastly less than that to the BSE strain during the epidemic. The simple observation that humans and several other species have become infected with BSE proves nothing about whether it transmits more easily to other species when the same doses of different strains of infective agent are compared. The cases seen in other species can be explained either by the massive scale of exposure to BSE agent afforded by the epidemic, or by the BSE strain having "higher infectiousness" for other species, or both. Its known greater thermal stability than other strains may well be an important aspect of this. The Phillips Report, unfortunately, jumps to a premature conclusion on this whole question, but that is not their only lapse.

I am certainly not arguing that the BSE strain will prove to be no more dangerous to other species than most TSE strains—we must have hard facts. An extensive range of experiments is urgently needed, comparing the relative transmissibilities of various TSE strains with the BSE strain: these must cover a full range of doses of agent and species sources, and must examine several routes of potential infection. The work will need to be done in several species.

(2) The search for the BSE strain in the sheep population

Whether or not it should be a very high priority to search for the BSE strain in British sheep (or even world-wide) depends on the outcome of work under the previous heading. There have been hints of MAFF contingency plans to deal with British flocks on a draconian scale should the BSE strain be found, which heightens the urgency of answering the underlying question. But, at least, the Phillips Report kills off over a decade of MAFF propagation of the unsupported claim that the BSE strain originated on many occasions from scrapie strains being transferred to cattle in Meat and Bone Meal. (Unfortunately, the Report backs an origin for BSE that is implausible in the extreme.)

I was responsible for devising the type of strain-typing test needed for identifying different TSE strains and, with former colleagues at the Neuropathogenesis Unit (NPU), devised various means of separating component strains from mixtures. Nowhere else is there any such experience. It was a cause for amazement, therefore, when I heard that MAFF was funding attempts to search for particular strains in the UK sheep population by pooling the brains of sheep in batches, to economise this search. They will need considerable good luck with any such approach. I hope that they have run pilot trials with deliberate mixtures of a dozen known strains, along with the BSE strain, to test the proposition. At least, the NPU have declined to adopt any such method.

This brain-pool approach sounds like another MAFF-associated emulation of the botched CVL design for cattle "maternal transmission" experiments, which largely wasted several million pounds and many years. Is it fair comment to recall that in 1986-87, as director of the NPU, I only had £75,000 for all our TSE research experiments, after paying salaries and overheads for nearly 40 staff?

(3) The National Scrapie Eradication Plan for GB

The National Sheep Association know of my long-standing concern about the often unfounded speculations that have been damaging to their industry during the last decade.

Late last year, I was shown a copy of the glossy MAFF booklet dealing with the scheme aimed to eradicate scrapie from British sheep by breeding from rams carrying a particular version of the gene which codes for the PrP protein. As I had done the pre-molecular groundwork for this, by 20 years of selecting sheep genetically for some variants of this gene, I am in a position to understand the potential complications. Indeed, it was long realised that the notion of a version of the gene that would "resist" all known (and future) strains of TSEs, may not be realistic. This was underlined by the fact that in 10 years of searching for a strain of scrapie agent that could break such a barrier, I had been lucky enough to find one, with approximately this property. Furthermore, this finding was not a surprise because the work with scrapie in mice had taught me to avoid the notion of genetic "resistance" to TSEs: this complication is fundamental to understanding of the whole subject and is widely unrecognised, for example on occasion by leading members of SEAC. The nagging possibility of "carrier-infections" with TSE agents is one aspect of this complication.

Where the balance of judgement lies in the present context is dealt with in the response to the MAFF document appended to this letter, which is signed by four senior animal-disease scientists [not printed]. It came as a surprise that the booklet was issued as a "Consultation on proposals for Phase 1—a Ram Genotyping Scheme" when there appeared to have been several years of active support by MAFF for implementing this scheme. It seems to have the de facto status of an ongoing programme.

In closing, I must query the implication underlying the stated objective of your Committee. A subject like BSE is far bigger than any single department should attempt to handle. A very significant error was that MAFF was intent on keeping exclusive control, for example, by their early determination to exclude the Government Chief Scientist.

I consider it entirely inappropriate that any government department or group of departments (or their agencies) should control research on basic scientific issues, especially areas so near the frontier of knowledge. Such direct control should only involve practical and applied topics in well known areas. The research role of departments should focus almost entirely on having first-hand, comprehensive information about "who and where" there is success, but this must be staffed on criteria very different from present ones. Whitehall norms will need to be changed radically, where science is involved.

The basic research should be funded so as to ensure its objectivity and freedom from coercion—the Research Councils, as originally created, were well conceived to achieve this. Radical changes are needed to avoid the administrative traps into which MAFF fell headlong, when it allowed a disease outbreak to turn into a huge epidemic.

25 January 2001

http://www.parliament.the-stationery-office.co.uk/pa/cm200001/cmselect/cmagric/388/388m11.htm



Transmission studies of BSE to sheep;

http://collections.europarchive.org/tna/20090114023943/http://www.bseinquiry.gov.uk/files/mb/m09/tab01.pdf



Using transmission to sheep of known PrP genotype as our criterion for agent strain typing, we have found a link between BSE and CH1641, a c-group strain of scrapie.

http://collections.europarchive.org/tna/20090114025858/http://www.bseinquiry.gov.uk/files/mb/m09/tab11.pdf



TSS

"Terry S. Singeltary Sr." wrote:

######## Bovine Spongiform Encephalopathy #########


No sign of BSE in sheep - Defra

Tests to discover whether BSE is affecting currently sheep have so far shown no signs of the disease, according to Government scientists.

But further research to establish whether it was in the UK flock in the early 1990s may be flawed, according to the Department for the Environment, Food and Rural Affairs (Defra).

Samples taken from sheep at the time may have become contaminated and the release of the test results, scheduled for Friday, has now been postponed.

Scientists have previously expressed fears that BSE may have been passed between cows and sheep because it behaves like the sheep disease scrapie.

Lucian Hudson, director of the communications directorate at Defra, said: "Research has been under way for some time to see if it can be established whether BSE might have been present in the sheep flock in the early 1990s and masked as scrapie.

"Some work has also been undertaken by the Veterinary Laboratories Agency. They have been seeking to establish whether BSE might be in sheep now.

"The results so far on about 180 TSE (Transmissible Spongiform Encephalopathy) affected brains have not shown BSE.

"The work on material from the early 1990s has been conducted by the Institute for Animal Health (IAH) and it was anticipated that some results would be ready to present to the Spongiform Encephalopathy Advisory Committee (SEAC) on Friday.

"However Defra, who commissioned the work, also commissioned cross-checking to guard against the possibility of material being contaminated by cattle brains, not least because it had been collected for entirely different experiments.

"This cross-checking has indeed raised doubts about the viability of the original sample and the SEAC chairman decided that Friday's meeting should be postponed."

Story filed: 00:40 Thursday 18th October 2001

http://www.ananova.com/news/story/sm_426645.html




could someone please explain to me why these tests may have been flawed, and why after so many years of waiting for these results, how/why would something this important be postponed again, especially since we know BSE _can_ transmit to sheep in the lab?

to continue to postpone and put off this important research, is beyond me.

i know they tried explaining in this article the why/how, just after so many years of waiting, just smells to high heaven to me to still have no definate results, one way or the other. we will wait another decade or so i guess.

more tea and coffee anyone...

kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA

########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############


From: TSS (216-119-130-106.ipset10.wt.net) Subject: Re: NO BSE IN SHEEP? (don't count your sheep, before they lamb) Date: October 19, 2001 at 9:57 am PST

In Reply to: NO BSE IN SHEEP? (don't count your sheep, before they lamb) posted by TSS on October 19, 2001 at 9:30 am:

Scientists in vital BSE experiment tested wrong animal brains

By Steve Connor Science Editor

Independent, 19 October 2001

An inquiry has been launched into how a crucial experiment into whether BSE has infected sheep fell apart in disarray after an astonishing mix up in which scientists discovered that they have been testing the wrong animal brains.

The discovery, leaked on Wednesday night by embarrassed government officials, calls into question the quality of some of the science on which Britain's anti-BSE strategy is based. Scientists at the government-funded Institute for Animal Health in Edinburgh discovered that instead of testing sheep brains for BSE they had inadvertently been testing cattle brains for the past five years, making the entire £217,000 study null and void.

The results of the experiment were about to be made public and it is understood that civil servants were bracing themselves for an announcement that BSE had been found in sheep.

But three days before the results were due to be made public today – demonstrating that the cattle disease

had jumped the "species barrier" into sheep – DNA tests on the material showed that it was composed entirely of cattle brains with no detectable sheep tissue.

"Extraordinary is a fair description of this," said Professor Peter Smith, chairman of the Government's Spongiform Encepthalopathy Advisory Committee. "Everyone who's seen these results has been taken aback. It is amazing."

Professor Chris Bostock, a member of Seac and the director of the Institute for Animal Health, said he was also surprised when he was told on Wednesday that another government laboratory had failed to find any DNA material that could have come from sheep brains in the samples undergoing the tests for BSE.

"I was completely flabbergasted when told yesterday morning of what they had found. I've taken steps to set up our own independent audit into the tissue samples and I'm told that Defra [Department for Environment, Food and Rural Affairs] will establish its own audit," Professor Bostock said.

"We were certainly of the view that the samples were fundamentally of sheep origin. I'm not prepared to discuss the results of the [BSE in sheep] experiment because they are now uninterpretable," he said.

However, Professor Smith said that although the experiment was not simple to interpret, some of the features of the results that he is aware of indicated that a "BSE-like" agent was present in the brain tissue. "But that now goes out of the window," Professor Smith said.

The experiment began in early 1997 and involved testing for the presence of BSE in what was then believed to be a pooled collection of 2,860 brains of sheep that had died of scrapie, a related brain disease to BSE, between 1990 and 1992.

If BSE had spread to sheep during the late 1980s, when sheep were fed the same contaminated feed that infected cattle, there was a strong possibility that the pooled collection of brains would indicate the presence of BSE.

The complicated experiment was carried out by scientists at the Institute for Animal Health's Neuropathogenesis Unit in Edinburgh. It involved injecting the brain material into different strains of laboratory mice which would incubate the disease in a precise pattern if BSE was present.

Professor Bostock said that two tests early on in the experiment indicated that the material was at least predominantly sheep brains as there had always been a concern of cross contamination given that the brains were collected for another experiment at a time when scientists used the same instruments to collect both sheep and cattle brains.

However, early in September samples of the brain material were sent to the Laboratory of the Government Chemist for DNA analysis. It is these results that demonstrated unequivocally that the brain tissue came only from cattle, with no traces of sheep tissue present.

http://news.independent.co.uk/uk/science/story.jsp?story=100316


Subject: Re: No sign of BSE in sheep ??? [tests terribly flawed]

Date: Fri, 19 Oct 2001 13:57:55 -0700

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de

References: 1 , 2

######## Bovine Spongiform Encephalopathy #########



Greeting List,

How in the world can these so called prion gods continue to be trusted, after such incompetence?

they said BSE could not transmit to man, IT DID.

they insist scrapie/cwd can not transmit to man. they insist this without any proof. in fact, just the opposite is very real.

they said BSE could not transmit to chickens, but if you look at the ostrich autopsy, there should be great concern with this, because some sort of SE was present.

if we go back and look at the old studies, who is to say they were not terribly flawed as well. what about the domestic fowl studies, and all the rest of the studies. someone's ass should be held to the fire because of this. and these so called 'prion gods' should be sent out to pasture.

MY GOSH, they have been at this for how long, and in 2001 find out they had the wrong brains? gimmie a break. you leave these same clowns in there, and the incubation period could very well catch up to 2001, and a 'real' epidemic

could occur, with the same old data we had 25 or 30 years ago. this is disgusting and now we will have to go through another stupid inquiry where _nothing_ happens.

My sincere apologize if i offended anyone, but there is no excuse for the continued incompetence of these agencies and their 'prion gods'. as i said, if you are not going to reprimand them, then do as they do in the USA, give them a fat pension, and SEND THEM OUT TO PASTURE.

or, another possibility is that they made up this hoaky story about it being cow brains at the last minute because they did not want to slaughter 40 million sheep. may have had sheep with BSE but turned it around, by lying about it being cow brain dna.

naaa, they would not do that, would they?


SUMMARY REPORTS OF MAFF BSE TRANSMISSION STUDIES AT THE CVL ;

http://collections.europarchive.org/tna/20090114023010/http://www.bseinquiry.gov.uk/files/sc/seac18/tab02b.pdf



THE RISK TO HUMANS FROM SHEEP;

http://collections.europarchive.org/tna/20090114022915/http://www.bseinquiry.gov.uk/files/sc/seac24/tab03.pdf



EXPERIMENTAL TRANSMISSION OF BSE TO SHEEP

http://collections.europarchive.org/tna/20090114023211/http://www.bseinquiry.gov.uk/files/sc/seac25/tab05.pdf




RISK OF BSE TO SHEEP VIA FEED

http://collections.europarchive.org/tna/20090114022605/http://www.bseinquiry.gov.uk/files/sc/seac31/tab01.pdf



SHEEP AND BSE PERSONAL AND CONFIDENTIAL


SHEEP AND BSE

A. The experimental transmission of BSE to sheep.

Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).

http://collections.europarchive.org/tna/20090506010048/http://www.bseinquiry.gov.uk/files/sc/seac33/tab02.pdf




RB264

BSE - TRANSMISSION STUDIES

http://collections.europarchive.org/tna/20090113230127/http://www.bseinquiry.gov.uk/files/sc/Seac06/tab06.pdf




BOV 92 A

SEAC 10/7

MAFF Translation from German T301/91/JS/41-4

Source: Tierarztl. Prax. 19, 1991, pp. 263-265

Author: H A Schoon, D Brunckhorst, J Pohlenz

Title: Sponqiform encephalopathy in a red-necked ostrich (Struthio camelus) A case history

Sides: 4

Case history

The adult female 150-kg red-necked ostrich came from a zoo in north-western Germany. In autumn 1986, the bird showed protracted- central nervous symptoms with ataxia, balance disorders and uncoordinated feedinq. The stock had recently lost a male bird with identical symptoms, but in that case a post­mortem examination was not carried out. Food was based on vegetable feedingstuffs, supplemented by commercially available mixed feed for poultry together with raw meat, which was sometimes obtained from small-scale emergency slaughterhouses in the vicinity. The remaining ostriches in the stock were clinically healthy.

Post-mortem findings

It was not possible to find anything unusual as a result of a pathological anatomical examination, other than distinct adiposis together with multiple excoriations of the skin in the area of the two rear extremities.

For the purposes of histopathological examination, tissue material from all the internal organs, includinq the vascular system, skeletal muscles and brain (both hemispheres of the cerebrum, cerebellum, two sections at the level of the Lobi optici of the brain stem, four sections from the Medulla oblongata), was fixed in formalin and, after standard emhedding in paraplast, was studied by means of qeneral and special staininq.

Nothing unusual could be found in the cerebrum or cerebellum other than sliqht oedema of the neuropil. On the other hand serious, bilaterally symmetrical changes were found in the brain stem and Medulla oblongata. In addition to marked vacuolation of the neuropil, apparently [lit.: "optically"] empty, ovoid to spherical vacuoles of varyinq sizes occurred in numerous neurons in the nuclei Nucleus ruber, Nucleus vestibularis and Formatio reticularis. In some cases these vacuoles were forcinq the Nissl bodies to a narrow margin (Fiqs. 1-3). Moreover, the perikaryons of many neurons contained fine-qrained piqments which appeared qolden brownish in the haematoxylin and eosin stained specimen, reacted positively in both PAS (Fig. 4) and Ziehl-Neelsen and, in addition, showed yellowish-qreen spontaneous autofluorescence when examined under a fluorescence microscope. Lillie1 staininq to show neuromelanin produced negative results. The piqments were therefore described as lipofuscin. Only in the cranial locations of the brain stem were mild gliosis, isolated necrotic neurons and neuronophagia observed.

The heart and skeletal muscles showed moderate, fine adiposis, and multifocal arteriosclerotic plaques were found in the coronary and limb arteries.

1 [Not traced; presumably a proper name - Trans.)

Discussion

Investigations into the occurrence, diagnosis, differential diagnosis and epidemiology of spongiform encephalopathy in human beings and animals have been a focus of medical and general interest since BSE first occurred in the British Isles in 1985 (summary in Truyen and Kaaden 1990).

As a result of an increasing number of reports of "new" susceptible species and the related questions regarding the causative agent and its transmissibility, it appears necessary to describe individual cases within this problem area even when the causative agent is unclear [lit. "even aetiopathogenically unclear individual cases"].

There are no detailed descriptions of neurological problems in zoo ostriches in the literature available to us. The findings, in this ostrich do not correspond either to those which are caused by typical virus infections of domestic and wild poultry or to those which are observed as a result of Vitamin E deficiency in chickens (Gratzl and Kohler 1957, Cheville 1966). Instead there is a high degree of correspondence as regards light microscopy findings (relating to both quality and distribution pattern in the central nervous system) with the findings as described in the case of transmissible spongiform encephalopathy of mammals (scrapie, BSE, transmissible mink encephalopathy, chronic wasting disease of captive mule deer and elk) (Hadlow 1961, Hartsough and Burqer 1965, Williams and Young 1980, Wells et al. 1987, 1989). Whether and to what extent neuropathological findings in the omnivorous ostrich are comparable to those in mammals as regards the causative agent [lit.: "aetiopathogenically"] cannot at present be determined. There have been no references to any basic susceptibility of birds in the literature to date. Moreover the Federal Republic of Germany was regarded as free from scrapie and BSE in 1986. The reader is referred to the article by Truyen and Kaaden (1990) for a discussion of the problem of possible contamination of meat-and­-bone meal.

In spite of the reliability of histopathological findings in cattle which was emphasised by Wells et al. (1989), definitive diagnosis in this case requires both electron microscopy detection of so-called scrapie-related fibrils (Scott et al. 1987, Hope at al. 1988) and an experiment to transmit the disease to mice by means of intracerebral inoculation of suspect brain material (Truyen and Kaaden 1990). The available formalin-fixed tissue which has been embedded in paraplast is currently being worked up for appropriate experiments with the aid of modified processes.

Other aetiological factors to be taken into consideration are: toxic influences which cannot retrospectively be characterised in greater detail, unknown deficiency disorders specific to the species and metabolic situations with uncertain effects which manifest themselves in the central nervous [system].

[Captions)

Fig. 1 High level of vacuolation of the neuropil in the grey matter area, individual neurons with vacuoles in the perikaryon. Brain stem. Haematoxylin and eosin stain. Magnification x 120.

Fig. 2 In addition to marked vacuolation of the neuropil, there are numerous neurons with apparently empty vacuoles of varying sizes. Medulla oblongata. Haematoxylin and eosin stain. Magnification x 300.

Fig. 3 Neuropil with oedema and numerous neurons with vacuoles in the perikaryon. Medulla oblongata. Haematoxylin and eosin stain. Magnification x 300.

Fig. 4 "Ballooning" degeneration of a nerve cell, PAS-positive lipofuscin granules in perikaryon of the remaining neruons. Medulla oblongata. PAS reaction [stain]. Maqnification x 300.

http://collections.europarchive.org/tna/20090113230726/http://www.bseinquiry.gov.uk/files/sc/Seac10/tab07.pdf




RED NECK OSTRICH

http://collections.europarchive.org/tna/20090505211737/http://www.bseinquiry.gov.uk/files/sc/Seac10/tab06.pdf




Dutch say German beef posed BSE risk for years Thu, Dec 28, 2000 Reuters World Report


http://www.mad-cow.org/00/01jan_news.html#kkk



http://www.mad-cow.org/00/aug00_last_news.html#fff



German policy-makers never asserted full certainty with respect to the risks posed by BSE and British beef, but they did assert that German beef was perfectly safe. Italian and Finnish policy-makers insisted that BSE was a "foreign" problem and that BSE was being kept out of their jurisdictions, and that beef on sale in those countries was entirely safe.

The experiences described in this chapter suggest that risk communication strategies that assert full certainty when significant uncertainties remain are unlikely to be sustainable in the long run. Risk communication strategies that assert risks to be zero, or virtually zero, are also unlikely to be sustainable in the long run. Any risk communication strategy that combines those two shortcomings is likely to become especially problematic, particularly as and when new evidence emerges.

snip...

The British Government's pre-March 1996 risk communication narrative backfired dramatically after evidence emerged showing that such claims had been premised on false assumptions about both the science of BSE and policy-making processes. Trust, on the part both of domestic consumers and of international consumers, in British regulatory institutions and their expert advisers evaporated. Prior to March 1996 those risk communication practices had also had an adverse impact on the substance of policy, by diminishing the scope for policymakers to appreciate the need to make judgements about the extent to which precaution was appropriate, and the scope for exercising precaution. Having started with a risk communication strategy of consumer reassurance that asserted that British beef was safe, policymakers were inhibited from learning about the risks or responding to new evidence. The reassuring, and nationalistic, risk communication narratives adopted by German and Italian policy-makers in the 1990s were also ruined by the discovery of cases of BSE in cattle in German and Italian animals in late 2000 and early 2001; these events were closely followed by dramatic and abrupt reductions in beef sales within those jurisdictions. In Germany it became evident that, despite the rhetoric about having a pre-eminently precautionary policy regime, agricultural policy-makers had been at least as preoccupied with promoting the interests of the cattle farmers and animal-feed producers as with protecting public health. In Italy, once the domestic crisis broke, the authorities were unable to provide a coherent or consistent message about the risks that BSE posed in Italy, or to deal effectively with the media. Consumers therefore drew the conclusion that they had not been, and were not being, properly informed about BSE.

http://www.bvsde.paho.org/bvsacd/cd65/E87919/cap9.pdf



*This case study accompanies the IRGC report “Risk Governance Deficits: An analysis and illustration of the most common deficits in risk governance”.

The Bovine Spongiform Encephalopathy (BSE) Epidemic in the United Kingdom

By Belinda Cleeland1

The emergence of Bovine spongiform encephalopathy (BSE) in the UK and the handling of the epidemic in British cattle in the late 1980s-early 1990s, especially as regards the risks posed by BSE to humans, is an example of inadequate risk governance. The epidemic resulted in the infection of 170,000 cattle, the killing of 4.4 million cattle as a precaution and the deaths of 164 people to date in Britain from New Variant Creutzfeld-Jacob disease (vCJD), the human form of BSE. It was also disastrous for the UK beef trade.

snip...

Early warnings that BSE might be transmissible to humans were, in fact, observed by scientists and government officials throughout the period from 1986 (the time of first diagnosis in cattle) to 1995 (when vCJD was first observed in humans). Such observations are noted in, for example, the minutes of a meeting of the National Institute for Biological Standards and Control in May 1988, where the probability of transmission of BSE to humans is assessed as more than remote. The diagnosis in 1990 of a domestic cat with a previously unknown spongiform encephalopathy resembling BSE indicated that the disease could infect a wider range of hosts. Responses to such early warnings of potential dangers to human health were either too weak or came too late. This may have been partly a result of an ‘unwillingness to know’ due to the economic harm this knowledge would cause the UK beef industry (related to deficit A6); and partly due to institutional capacities and procedures (related to deficits B5, 9 and 10).

BSE in Germany: Lessons learned from the UK experience?

As of 2007, there have been 415 cases of BSE identified in Germany. The first case was isolated and appeared in 1992. This was followed by 3 cases in 1994 and 2 more in 1997 [OIE, 2008]. All of these cases occurred in cows that had been imported from either the UK or Switzerland, and thus were not deemed to signify an outbreak of the disease in Germany.

Although the German Health Minister at the time, Horst Seehofer, did suggest to the European Commission in 1994 that they ban the import of all British Beef; in light of other actions the German government had taken with regards to BSE-related risks, the motivation for this move 8

was almost certainly political rather than scientific or precautionary [Abbott, 1994]. For example, whilst the UK had banned the use of meat and bone meal (MBM) in all animal feed in 1988 as an effort to halt the disease’s spread, Germany did not go so far in its precautionary measures and only banned its use for cattle, allowing MBM to continue to be fed to poultry and pigs [Abbott & Schiermeier, 2000]. Indeed, Germany was proud to declare itself "BSE free" due to its superior testing, its tighter controls and stricter standards for the treatment of animal feedstuffs. The fact that German farmers had not traditionally fed their cattle on MBM was one of the reasons for the certainty of the government in declaring itself immune [Abbott & Schiermeier, 2000].

On 24 November 2000, however, the first case of native BSE was identified in Germany. When this occurred, there was a very strong public reaction, with many heavily criticising the government for being complacent in its approach to risk management with regards to the spread of BSE, and beef consumption falling 75% over the next few months. The reaction in Germany was even more intense than that in the UK, and suggests that the government, when formulating its response to BSE, had failed to properly gauge the public sensitivity to health and environmental threats [Imort, 2001] (A3).

Despite its failure to observe early warnings (A1) and its over certainty that it would not be affected by the epidemic (only one week prior to the discovery of the first BSE case, the Agriculture Minister had publicly declared himself "absolutely convinced" that Germany was immune to BSE), the government’s reaction once native BSE had been discovered was swift and far-reaching:

24 Nov 2000 First case of native BSE discovered

25 Nov 2000 Emergency measures to fight BSE agreed by German officials (including an immediate ban on the use of MBM in all animal feed)

25-30 Nov 2000 Federal Minister of Agriculture announces creation of a new department devoted to food safety

The Bundesrat asks the government to push the EC for a Europe-wide ban on British beef

1 Dec 2000 The Bundesrat passes the bill banning the import, export or use of MBM in animal feed – one of the fastest pieces of legislation enacted in Federal Germany [BBC News, 2000]

4 Dec 2000 EC puts a temporary ban on the feeding of processed animal proteins to farmed animals kept for food production (Germany had pushed for this measure)

Jan 2001 Andrea Fischer (Federal Health Minister) and Karl-Heinz Funke (Federal Agriculture Minister) resign over allegations that they mismanaged the BSE crisis [Hooper, 2001]…the Ministries are then rearranged.

The Ministry for Food Agriculture and Forestry becomes the Ministry of Consumer Protection, Food and Agriculture (consumer protection was formerly a responsibility of the health ministry) and the new Minister is neither a farmer nor a member of a large political party, so as to lessen the influence of the agricultural lobby. Within this Ministry, there is a whole department created to handle BSE [Abbott, 2001].

Introduction of compulsory BSE testing for all cows 24 months or older. 9

31 Jan 2001 Government approves the slaughter of 400,000 cows over 30 months to help stabilise the German beef market (EU’s purchase for destruction programme)

Spring 2001 27 million DM of federal money is earmarked for BSE research (despite budget cutbacks in other areas)

The great advantage that Germany had over the UK when dealing with BSE was that, by the time the disease reached Germany, its pathology was well known and the risks it posed to humans were better understood.

On the one hand, the improved knowledge of BSE, its spread across Europe, and the discovery that it had probably been transmitted to humans should have prompted Germany to take more serious measures to prevent the disease reaching it. Perhaps in an effort to protect its industries (Germany is one of Europe’s largest beef producers) [EC, 2000b], Germany, like the UK before it, had prioritised economic interests over public health (B2/B3). Warnings from Brussels in March 2000 that BSE was likely to reach Germany went unheeded, and the European Commissioner for Health and Consumer Protection criticised Germany for consistently opposing EU legislation to reduce the risks of BSE [EC, 2000a].3

On the other hand, Germany’s quick move to make fundamental changes to the structure and competencies of its health and agriculture ministries may reflect a recognition of some of the problems encountered between ministries in the UK. Distancing the ministry further from the agricultural lobby was designed to avoid problems relating to the promotion of special interests (which can be one reason for the occurrence of deficit A6); and creating a separate department to deal with BSE would lower the probability of implementation failures (B5) and help eliminate problems stemming from dispersed responsibilities (B10). Allocating large amounts of funding to BSE research also helps to remedy any problems arising from (A2) lack of knowledge about the physical facts, so as to better inform future policy responses.

Overall, the situation in Germany was very different to that in the UK. The reactions of these two governments must not be compared without keeping in mind that there were important differences between the two cases which would have strongly influenced any actions taken: differences in political culture, values and perceptions, scientific knowledge about BSE at the time of outbreak, and the scale of the problem. Nevertheless, the fact that Germany, despite its different culture and circumstances, experienced (or identified, in trying to avoid them) many of the same risk governance deficits as the UK points to the importance of these distortions in the risk governance process and the need to find ways to avoid them in future.

3 In 1997, Germany, along with Spain, opposed the banning from the food chain of all parts of the animal likely to carry infection (brain, spinal cord, etc.). Due to support from other member states, the legislation came into effect on 1 October 2000.

snip...

International Risk Governance Council

Chemin de Balexert 9

1219 Châtelaine

Geneva – Switzerland

www.irgc.org

Tel.: +41 22 795 17 30

Fax: +41 22 795 17 39

© All rights reserved, International Risk Governance Council, Geneva, 2009.


http://www.irgc.org/IMG/pdf/BSE_full_case_study_web.pdf



IN CONFIDENCE

BSE TRANSMISSION STUDIES


http://collections.europarchive.org/tna/20090113230340/http://www.bseinquiry.gov.uk/files/sc/seac11/tab10.pdf



http://collections.europarchive.org/tna/20090505211647/http://www.bseinquiry.gov.uk/files/sc/seac13/tab09.pdf



BSE TO FELINE (let's hope they did not have the feline brain mixed up with cow brain)


http://collections.europarchive.org/tna/20090113230941/http://www.bseinquiry.gov.uk/files/sc/seac12/tab04.pdf



http://collections.europarchive.org/tna/20090113230854/http://www.bseinquiry.gov.uk/files/sc/seac13/tab04.pdf




BSE TO HOUNDS


http://collections.europarchive.org/tna/20090506010345/http://www.bseinquiry.gov.uk/files/sc/seac16/tab04.pdf




disgusted again, Terry S. Singeltary Sr., Bacliff, Texas USA


From: TSS (216-119-138-181.ipset18.wt.net) Subject: Re: NO BSE IN SHEEP? (don't count your sheep, before they lamb) ''MEDIA REPORTS'' Date: October 20, 2001 at 8:47 am PST

In Reply to: Re: NO BSE IN SHEEP? (don't count your sheep, before they lamb) posted by TSS on October 19, 2001 at 1:23 pm:

Beckett in firing line over brains fiasco M. Beckett was under pressure yesterday to make an emergency Commons statement over how researchers wasted four years testing the wrong animal brains for BSE.

http://www.thetimes.co.uk/article/0,,10-2001364049,00.html



Mad! BSE experts study wrong brains The credibility of Environment Secretary Margaret Beckett was on the line today after it emerged that her department tried to cover up a disastrous bungle over BSE.

http://uk.news.yahoo.com/011019/27/cb8ya.html



Research short cut led to cow brains blunder The inquest into the BSE test blunder began in earnest yesterday. The investigation of how what were thought to be sheep brains turned out to be cattle brains will consider if a simple error, such as missing out a "b" on a container - so "bovine" became "ovine", led to the fiasco. BSE fiasco : James Meikle, health correspondent Guardian

http://www.guardian.co.uk/Archive/Article/0,4273,4281297,00.html



BSE experiments end in farce A five year study to establish whether BSE has infiltrated the British sheep flock has ended in farce when it emerged that the scientists had been testing samples from cattle all along. The experiments were supposed to use 2867 sheep brains from animals that died between 1990 and 1992 of suspected scrapie. James Randerson, New Scientist.

http://www.newscientist.com/news/news.jsp?id=ns99991454



BSE test on sheep ends in fiasco : réalité ou calcul ? By Charles Clover, Environment Editor, Telegraph

http://www.portal.telegraph.co.uk/news/main.jhtml?xml=/news/2001/10/19/nrur19.xml&sSheet=/news/2001/10/19/ixhome.html



British government admits mad cow test fiasco London (AFP) - Britain's food standards watchdog on Friday blasted a four-year government study as a "cock-up"

http://asia.dailynews.yahoo.com/headlines/world/afp/article.html?s=asia/headlines/011019/world/afp/British_government_admits_mad_cow_test_fiasco.html



Storm over Government 'burial' of brain blunder over BSE tests Farming bodies and MPs were asking yesterday how a Government that ordered a £26 million inquiry into its predecessor's handling of the BSE epidemic came to post its own BSE blunder on its website at 10.30 on Wednesday evening. Charles Clover, Environment Editor, Telegraph.

http://www.portal.telegraph.co.uk/news/main.jhtml?xml=/news/2001/10/19/nrur119.xml&sSheet=/news/2001/10/19/ixhome.html



Study of BSE in sheep collapses in tests blunder The food standards agency was urged to consider banning all British lamb from baby food last night as a four year experiment to establish if BSE had ever spread to sheep teetered on collapse. "This raises serious questions about scientific competence. It has wasted years as this experiment has proved to be potentially useless." James Meikle, Health Correspondent, Guardian

http://www.guardian.co.uk/bse/article/0,2763,576875,00.html



Six key questions Are there "mad sheep" out there, like "mad cows"? Sandra Barwick, Telegraph

http://portal.telegraph.co.uk/news/main.jhtml?xml=/news/2001/10/20/nbse220.xml&sSheet=/news/2001/10/20/ixhome.html



Label blunder as brains were mixed to paste A famous institute that advises the Government on livestock diseases. Charles Clover, Telegraph

http://portal.telegraph.co.uk/news/main.jhtml?xml=/news/2001/10/20/nbse120.xml&sSheet=/news/2001/10/20/ixhome.html



Labour 'buried report of BSE inquiry' How did top scientists mix up brains from cattle and sheep? The Government was accused of spreading "the Jo Moore syndrome" after apparently trying to hide details of the disastrous scientific investigation into BSE in sheep by releasing them in a misleading statement late at night. Marie Woolf Chief Political Correspondent, Independent

http://news.independent.co.uk/uk/politics/story.jsp?story=100484



Inquiries launched into BSE blunder 'Dreadful mistake' : samples came from the wrong animal (Defra)

http://news.bbc.co.uk/hi/english/sci/tech/newsid_1607000/1607915.stm



From: TSS (216-119-138-136.ipset18.wt.net)

Subject: Re: NO BSE IN SHEEP? (don't count your sheep, before they lamb) ''MEDIA REPORTS''

Date: October 22, 2001 at 1:37 pm PST

In Reply to: Re: NO BSE IN SHEEP? (don't count your sheep, before they lamb) ''MEDIA REPORTS'' posted by TSS on October 20, 2001 at 8:47 am:

Subject: STATEMENT BY SIR JOHN KREBS FOLLOWING FSA BOARD DISCUSSION ON BSE AND SHEEP ! Date: Mon, 22 Oct 2001 15:04:53 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de


######## Bovine Spongiform Encephalopathy #########


FSA

22 October 2001

STATEMENT BY SIR JOHN KREBS FOLLOWING FSA BOARD DISCUSSION ON BSE AND SHEEP

It is important to act quickly and effectively to provide public reassurance on BSE in sheep. Agency advice has been consistent - there is no reason to avoid the consumption of lamb. But the theoretical risk remains and there is an urgent need to reduce the uncertainty on BSE in sheep and look at whether further precautionary measures are needed. This can only be resolved through effective public action.

The Food Standards Agency proposes to review the precautionary measures and, with SEAC, current research into BSE in sheep. This review will be part of a process that will include a public stakeholder meeting to be held before Christmas. The Agency reaffirms its view, acknowledging the practical difficulties, that:

- The current screening programme for TSEs should be expanded - The national scrapie plan should be accelerated with clear statements of what is deliverable - There is an urgent requirement to develop a validated rapid test to detect the possible presence of BSE in sheep - European-wide TSE surveillance should be undertaken on sheep

And that there is a need for an audit on the Institute of Animal Health (IAH) sheep experiments that is thoroughly independent and transparent.

Notes to editors

1) SEAC, the Spongiform Encephalopathy Advisory Committee, was set up in 1990. It provides independent scientific advice to the Food Standards Agency and other Government Departments on BSE and other spongiform encephalopathies.

2) TSE, Transmissible Spongiform Encephalopathy, is a disease

of the neurological system where there is spongy degeneration of the brain and progressive dementia. Both scrapie and BSE are examples of TSE's in animals.

3) The national scrapie plan is a Department of the Environment, Food and Rural Affairs (DEFRA) initiative. A key element of the plan is a breeding programme to produce sheep resistant to TSE's.

4) The IAH experiment involved testing for the presence of BSE-like strains in the pooled homogenised brains of nearly 3,000 scrapie-infected sheep collected in the early 1990s. It is this experiment that has been called into question by the Laboratory of the Government Chemist, which has concluded that the samples were bovine tissue not sheep tissue.

FSA UPDATE ON THE RISK OF BSE IN SHEEP - QUESTIONS AND ANSWERS

Is lamb safe to eat? The FSA is not advising against the consumption of lamb. The risk of BSE in sheep is theoretical but we think people have the right to be aware of it.

Does that advice include giving lamb to babies and children? Our advice applies to all consumers and all age groups.

Surely babies and children are more vulnerable? The current expert view is that this is not the case.

Why are some manufacturers of baby food not using British lamb? This is not for safety reasons. It does not give the Agency any cause for concern, nor should it alarm consumers.

Why is the FSA saying there is a theoretical risk of BSE in sheep? Experiments have shown that it is possible to infect sheep with BSE by feeding or injecting them with brain tissue from cattle infected by BSE. Sheep as well as cows are known to have eaten feed that contained meat and bonemeal. This is believed to be the most likely cause of the BSE epidemic in cows.

In that case why is the FSA saying there remains a theoretical risk of BSE in sheep? Perhaps up to 10,000 sheep a year in the UK are thought to develop scrapie. Sheep identified with scrapie are banned from entering the food chain. Scrapie could be concealing BSE or something like BSE in sheep. It is not known how scrapie is spread in sheep but it is known to have been present for at least 200 years and spreads naturally between sheep. Therefore, sheep could have contracted BSE from infected animal feed and it could have spread from sheep to sheep. But the fact is nobody knows.

When was it first known that there was a theoretical risk of BSE in sheep? It became a possibility when cows became infected with BSE in the 1980's. It became a theoretical risk when sheep were shown to contract BSE when artificially fed cow brain with BSE in the early 1990's.

When did the FSA publicise this? The FSA undertook a review of BSE controls when it was set up in April 2000. The Agency published a draft of the review in September 2001 and pointed to the theoretical risk of BSE in sheep in the review and at a press conference.

When did the FSA alert the public to the experiment where they tested cows brains instead of sheep's brains? The FSA announced in August 2001 that emerging results from that experiment could be compatible with BSE having been in sheep at that time. However, the FSA made it very clear that there was a risk of contamination and that it was not possible to draw conclusions from an incomplete experiment.

Why did the FSA publicise the experiment? The Agency has a duty to ensure that the public is kept informed on developments relating to food safety. This is especially important when there is so much uncertainty.

Why didn't the FSA check the experiment? The FSA did not commission this particular experiment. The Department of Environment, Food and Rural Affairs commissioned this experiment.

How do you know that BSE isn't in sheep now? All the recent sheep brains that have been screened so far for BSE, 160+, have not tested positive. However, as the number of these is relatively low and the tests are incomplete we cannot exclude the possibility that BSE may be present in sheep now.

How do the risks from lamb compare with the risks from beef? We cannot make a comparison between the risk of BSE in beef and lamb, because no cases of BSE have been found in sheep.

Is it more likely that people got vCJD from eating lamb rather than beef? It is currently considered that the most likely explanation of the present cases of vCJD is the consumption of BSE infected beef before the specified bovine offal ban came into force in 1989. We don't know whether sheep have ever had BSE, let alone what impact that would have made on vCJD if it had occurred.

What should consumers do if they want to avoid all risk of BSE from sheep? The FSA is not advising against eating lamb. Our role is to ensure that consumers have the best available information with which to make informed decisions about the food that they eat. Consumers have the option, if they are concerned, of seeking to buy lamb from countries without cases of both BSE and scrapie.

What measures are in place in case BSE is present in sheep? Specified risk material (SRM) controls are in place as a precautionary measure to reduce the risk of BSE-infected sheep meat from entering the food chain. SRM in sheep includes the skull, including the brain and eyes, tonsils and spinal cord of animals over 12 months old and the spleens of all sheep. The SRM controls mean these parts of the sheep would be removed and destroyed. However, if BSE were found to be present in sheep, the current SRM controls would not be adequate to eliminate the risk of infected sheep meat from entering the food chain. It has been shown that it is impossible to remove all infectivity from a sheep.

The FSA would consider any further SEAC opinion and in keeping with the FSA Board's commitment to open debate on food safety issues, will publicly consider whether it is appropriate to update its advice.

Is there a simple test to detect BSE in sheep? There is, as yet, no rapid validated test available that is capable of distinguishing BSE in sheep from scrapie.

What would have to happen now for the FSA to advise consumers to stop eating lamb altogether? The FSA would advise consumers to stop eating lamb only if there was a firm basis, taking into account SEAC's expert advice for judging that BSE was in the national flock.

http://213.38.88.195/coi/coipress.nsf



some thoughts;

the more i think about this, it is totally unbelievable that the govt would request a dna study of sheep/cow at such a late stage in the study, given that they knew this had been done at the start. i never heard of a govt getting involved in the details of routine control expts.

what happened is that the study had results saying sheep had bse. the govt didn't like the implications and looked for a way to discredit the study at the last minute. they decided an "independent" lab could find cow brains instead. whether the lab participated in the fraud, whether samples were switched on them, or more far-fetchedly edinburg sent them the wrong samples (these would have id tags) has not been settled.

the delfa minister is wholly ignorant of the scientific process. this idea for a coverup would only occur to a complete idiot because it is a lie with a very short lifespan. basically there saying, we still have the power and arrogance to rub your nose in it, we are not getting rid of the 40m sheep, we don't give a hoot how much BSE the public is still eating, and we will stand behind the silliest of pretexts to do so...not the first time///

TSS

########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############



From: TSS (216-119-138-161.ipset18.wt.net)

Subject: BSE SHEEP WARNINGS IGNORED FOR YEARS $ ANOTHER FOOD FARCE (BABY FOODS AND BSE)

Date: October 21, 2001 at 9:19 am PST

From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de

######## Bovine Spongiform Encephalopathy #########

October 21 2001 BRITAIN

Scientists scorn government tests

BSE sheep warnings ignored for years

Jonathan Leake, Science Editor

THE government was yesterday accused by top scientists of putting the public's health at risk by ignoring repeated requests that it carry out a nationwide survey of sheep for evidence of BSE.

Professor Roy Anderson, an epidemiologist at Imperial College, London, and Professor John Collinge, director of the Medical Research Council's prion research unit, told the government yesterday that it should have initiated the study years ago, that its research has been deeply flawed and that it has failed to grasp the potential size of the problem.

They say they have persistently told ministers that BSE could have spread among sheep just as it spread through cattle - but that nobody would know because it is masked by scrapie, a similar condition already common in sheep.

The call follows the fiasco of last week when Margaret Beckett, the environment and rural affairs minister, announced that a large-scale study on sheep commissioned by the government appeared to be fundamentally flawed. Instead of sampling sheep brains, as was intended, her department is thought to have overseen a five-year £217,000 analysis of bovine tissue that was riddled with BSE by mistake.

Only a last-minute check of the samples by an independent laboratory prevented Beckett from announcing that the British sheep population was infected and possibly ordering a national cull.

Anderson and Collinge are furious with the government for relying on a complex study when other simpler checks could have been run in parallel.

They point out that almost all the testing done on sheep has relied on injecting genetically modified mice with material extracted from the brains of suspect animals. A single animal's brain material must be injected into the heads of 100-120 mice, which are then kept under observation for up to three years to see what disease they develop.

Such tests, the scientists point out, are labour-intensive, time-consuming and need huge premises to house all the mice. Collinge has persistently recommended that the government uses a much speedier chemical testing method that he has perfected, which takes just two weeks to give a definite result.

In a paper published in The Lancet two years ago, Collinge warned: "The possibility that BSE may have been transmitted to sheep has caused concern. BSE that has been transmitted is clinically indistinguishable from scrapie."

Anderson concedes that the government did carry out a survey of 180 sheep infected with scrapie outside its main study, but believes it was far too small to produce statistically valid results. Civil servants, he said, had persistently ignored his calls to expand the work.

"Scrapie is found in only a few per cent of sheep. The fraction with BSE will be even smaller, so to detect it you need to sample thousands of sheep brains - but Defra [the Department for the Environment, Food and Rural Affairs] has looked at only 180. We have made this clear to Defra to no avail, which I find really very disturbing," he said.

Collinge has expressed similar fears for even longer. He first raised them in 1996 when the Tories were in power, telling his fellow members of the Spongiform Encephalopathy Advisory Committee (Seac), which advises the government, that widespread testing on sheep was urgently needed.

No action was taken but Collinge was so worried that he raised the matter with ministers - again to no avail.

Collinge has also protested strongly at the government's failure to commission research into the possibility that there are different types of BSE - an extremely serious issue since alternative strains could vary enormously in infectivity.

"Only nine cattle brains, from more than 170,000, have been strain-typed, so the existence of other less common BSE strains is possible," he said.

The issue was thrown into further chaos this weekend when Professor Chris Bostock, director of the Institute for Animal Health which carried out the main study, said there was still a 50% chance that the study would be proved safe. He said the material his team had used had been fully tested and had been confirmed as coming from sheep. "This means the real error could have been in the material we sent for the final checking. If so, then the work will still be valid," Bostock said.

Experiments show that sheep can develop BSE when they are given the same feed that infected 1m cattle.

Bostock also warned that research into the 180 sheep diagnosed with scrapie, from 1997 to 2000, had not, as the government claimed last week, cleared them of suffering from BSE. "Material was injected into mice, some of which came down with a disease that could be scrapie or BSE," he said.

A positive finding of BSE in even one of the 180 brains would be devastating, since it would suggest that not only did BSE transmit to millions of sheep in the early 1990s, but that it has also been transmitted down the generations in the same way as scrapie.

The only way of getting rid of it would be to slaughter every sheep in Britain. Worse, it would mean that millions more consumers than expected have been exposed to BSE.

This weekend Beckett acknowledged the criticisms after Defra plunged the government into a public relations disaster with a bland press release that gave no hint of the devastating details. She also announced a complete review of her department's research into BSE.

Defra had briefed the Press Association to put out a release, now acknowledged as misleading, saying, "No sign of BSE in sheep - Defra".

Beckett confirmed that she had put out the release against the advice of her officials. "We could have done it a lot better. One result is that we are going to review all the science being done on BSE," she said.

http://www.sunday-times.co.uk/news/pages/sti/2001/10/21/stinwenws01008.html



October 21 2001 EDITORIAL

Another food farce

The war pace quickens

The latest scandal over botched research into possible BSE in sheep confirms our worst fears about the way Whitehall fulfils its responsibilities for food safety. Anybody relying on government assurances that all was well had their confidence shaken during the BSE disaster in the beef industry. Now we learn that our sheep flock may also have been infected with bovine spongiform encephalopathy in the early 1990s. Experts cannot be sure, however, because they may have been testing the wrong samples, possibly in the wrong way. Officialdom's grudging admission of this laboratory farce would be alarming enough if it were an isolated incident. But it follows a decade of evasions, cover-ups, errors and misjudgments that has culminated in the payment of £4 billion compensation from the taxpayer.

Yet anybody listening to Margaret Beckett defending her reaction to the latest mix-up, in which cow brain samples were mixed up with those from sheep, would imagine she was dealing with an issue of unfortunate news management instead of a matter of vital concern to consumers. Parents were specifically told they had nothing to worry about because British baby food contained no British lamb. Next day, they were told by food manufacturers that it did, and when the Food Standards Agency (FSA) was told so earlier this year, it said there was no need to stop the practice.

What are the FSA and its uninformed chairman, Sir John Krebs, playing at? The agency was set up last year to reassure the public after years of plummeting confidence in the old Ministry of Agriculture, to put the consumer first and reassure us that "the food you eat is safe". It admitted last August that there was "a theoretical risk" of BSE in sheep but did not advise people to stop eating lamb. The baby food industry always denied using suspect beef from heavily infected areas in its products. The question parents urgently want answering now is whether their baby jars of lamb contain a hidden danger, however small. They will not be reassured by Professor Harriet Kimbell, the consumer representative on the government's BSE advisory committee, who says she does not feed British lamb to her teenagers and that the FSA should advise parents about the risks involved.

If she believes that, why has it not done so already? And why did Professor John Collinge, who discovered that the killer disease variant CJD was the human variety of BSE, not get a reply when he urged ministers two years ago to adopt his two-day test for BSE in sheep? Was it because they had already commissioned the research project that Mrs Beckett was told last Wednesday had gone disastrously wrong?

Every time a food safety scandal erupts, we find a trail of unanswered questions and official incompetence. Mrs Beckett's announcement that a scientific audit is to be held is the least she could do. Her comment yesterday that "as far as" she was aware, people were "trying to find out what happened" and "whether there's still anything to learn from the [failed] experiment" sounds alarmingly complacent.

Her new environment, farm and rural affairs department (Defra) was set up to end the culture of cover-up that placed the short-term commercial interests of British agriculture above the overriding concerns of the consumer. That order of priorities crashed in the collapse of consumer confidence and the loss of British markets overseas after the BSE crisis and the foot and mouth epidemic. Mrs Beckett's task as the new minister at Defra is to get to the bottom of this latest scandal before consumers decide that safety is the best policy and that weasel words by the so-called experts are not enough.

A contingency plan already exists to slaughter 40m sheep and ban the eating of lamb if evidence of infection is found. That would be 10 times the size of the foot and mouth slaughter programme and yet another hammer blow to British farming. If exhaustive research proves the British sheep flock to be clear of BSE, all will be well. But the government will have to move fast to convince a worried public.

http://www.sunday-times.co.uk/news/pages/sti/2001/10/21/stinwcldr01002.html



TSS

########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############



From: TSS (216-119-138-135.ipset18.wt.net)

Subject: BSE IN SHEEP? COVER-UP OR STUPIDITY OR BOTH? (Lord Hansard)

Date: October 25, 2001 at 8:26 am PST

Subject: BSE IN SHEEP? COVER-UP OR STUPIDITY OR BOTH? (Lord Hansard)

Date: Thu, 25 Oct 2001 10:22:40 -0700

From: "Terry S. Singeltary Sr." To: BSE-L@uni-karlsruhe.de

Table of Contents for Monday 22 Oct 2001

Volume No. 627 Part No. 30

snip...

I understand from the Statement that it was decided that the announcement would be left and that there was not a cover-up. Many of us are very concerned that, by not making a Statement, a cover-up has in fact happened. The Statement itself goes on to say that there was little press interest following the announcement by Margaret Beckett. We are then told that the experiment may not be conclusive and that it does not always excite the media. Do the Government read the news? Certainly in the past few days the press reports have highlighted this problem, and it does indeed look as though there has been a cover-up.

We acknowledge the fact and are pleased that many of the 3,000 abattoir sheep brains have indicated no scrapie cases at all. Contingency plans published on 28th September estimate that the testing of the some 20 million lambs or so entering the food chain might cost £400 million annually and question whether that would be feasible. The date of 28th September brought to mind the fact that Elliot Morley made an announcement that day, saying that in all matters relating to BSE and animal health the Government's handling had been open and transparent. I question that. On the same day Mr Morley also announced that it was a possibility that all the sheep in the country might have to be culled. Does it not seem very strange that various announcements and suggestions have been made, and yet there has been no open statement until today?

I accept that it is too early for us to have firm conclusions from the experiments that are going on. However, does the noble Lord agree that Professor Bostock said almost a year ago that he was concerned that there might be a mix-up between the brains being tested? If there was concern, why did nothing happen until just recently? Either there was concern and the Government took action, or the Government were not aware of the need for action; in which case it begs the question as to how MAFF was running its department.

Another statement was made was that British baby food did not contain British lamb. I should be grateful if the Minister would offer clarification on that point. My understanding is that on one day it was said that baby food did not contain any British lamb and the next day the manufacturers said that it did. Can the noble Lord clarify for us whether it is safe for British babies

to eat British lamb? 22 Oct 2001 : Column 832

snip...

http://www.publications.parliament.uk/pa/ld199697/ldhansrd/pdvn/lds01/text/11022-06.htm#11022-06_head0



also;

http://www.publications.parliament.uk/pa/ld199697/ldhansrd/pdvn/lds01/text/11022-07.htm



also;

http://www.publications.parliament.uk/pa/ld199697/ldhansrd/pdvn/lds01/text/11022-08.htm



From: TSS (216-119-138-125.ipset18.wt.net)

Subject: BSE-SSC PUBLISHES OPINION ON POTENTIAL RISK OF BSE IN SHEEP AND GOATS...

Date: October 25, 2001 at 7:47 am PST

Brussels, 24 octobre 2001

BSE - Scientific Steering Committee publishes opinion on potential risk of BSE in sheep and goats

The Scientific Steering Committee, advising the European Commission on Bovine Spongiform Encephalopathies (BSE) and other multi-disciplinary consumer health issues today published an opinion about the safety of sheep and goat products if BSE were to be confirmed or become probable in these small ruminants. The SSC had been asked to address these questions in view of a possible confirmation of the presence of BSE in sheep brains in ongoing experiments in the UK as announced by the UK Food Standards Agency in August this year. The UK government department responsible for the experiments however informed on October 18th that the brain materials from the early 1990's that were used in the tests were unsuitable for the purpose.

Up to date there is no evidence that BSE is present in small ruminants under field conditions. The scientists however do not exclude that sheep were fed with potentially infected meat-and-bone meal in the past and therefore reaffirm their view that the risk that BSE is present in sheep cannot be excluded. They call for more research in a number of specific fields to fill in current gaps in scientific knowledge, and confirm that their previous opinions dealing with the risk of TSE in small ruminants remain valid.

The scientists recommend that urgent action be taken to validate and introduce rapid tests on sheep and goats to detect whether an animal is infected with a Transmissable Spongiform Encephalopathy (TSE), which can be either BSE or scrapie. This would allow to compile essential data on the real TSE incidence and geographical spread which are badly needed. The rapid tests should preferably be done on lymphoid tissues that show infectivity in sheep in the early stages of incubation instead of brain tissue.

Testing efforts should be linked to genotyping of the animals tested, so that the possible genetic resistance to TSE of certain types of sheep can be ascertained. For the moment the scientists consider there are insufficient guarantees that certain scrapie-resistant genetic sheep strains are not silent carriers of TSEs. A combined rapid testing and genotyping programme would provide the scientific basis for confirming that scrapie-resistant sheep genotypes do not harbour any TSEs. Certification of flocks that are scrapie- and TSE free, in combination with better identification and tracing of small ruminants will, according to the SSC, offer the best policy option for the safe sourcing of sheep and goat products and consumer protection in the longer term. The scientists however recommend that the existing uncertainties about TSE resistance in sheep are addressed before the possible EU-wide introduction of breeding programmes of TSE resistant animals.

The SSC considers that its previous opinions on specified risk materials that need to be taken out of the food chain will require updating if BSE were to become probable in sheep and goats. The Committee however reaffirms its view that sheep and goat milk and milk products do not present a possible risk, provided milk of suspect animals is excluded from the food chain.

The full text of today's opinion is available at:

http://europa.eu.int/comm/food/fs/sc/ssc/outcome_en.html



Previous SCC opinions on TSE in Sheep are available at the same address.

http://europa.eu.int/comm/dgs/health_consumer/library/press/press200_en.html



Delay after delay after delay in the Inquiry Report release were announced. It now appears that opposing lawyers were having internal aspects of the Report rewritten to better suit their clients. A more immediate effect was the removal of vast amounts of embarassing archival and draft factual account material from the Inquiry web site (although this was captured and stored offshore). Indeed, Terry S. Singeltary has obtained and subsequently posted a fair amount of additional documents that were intended for, but blocked from, the Inquiry web site. Not everyone on the Inquiry staff was willing to join the cover-up.

http://www.mad-cow.org/00/oct00_inquiry_final.html



*****$$$$$$$******



NOW, what about the 'obex only' mode of testing used by the USDA et al for TSE, prions $$$ works for them too, a sure fire way NOT TO FIND MAD COW DISEASE $$$

Tuesday, November 17, 2009

SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1

http://bse-atypical.blogspot.com/2009/11/seac-new-results-on-idiopathic.html



NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" 2009

http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html





****************$$$$$$$$$$$$$***************



NOW, read the following please, and then ask yourself, WHY the USDA et al were ONLY TESTING THE OBEX PART OF THE BRAIN in USA cattle for BSE $$$

BECAUSE they knew that would be the least likely way to find BSE/TSE in USA cattle $$$...TSS

Discussion

In the five cats in this study with a spongiform encephalopathy, fibrils were observed by electron microscopy and their major protein, Prpsc, was identified by SDS-PAGE and Western blot. The fibrils were similar to those described in sheep with scrapie (Rubenstein and others 1987, Gibson and others 1987, Scott and others 1987, Dawson and others 1987), cattle with bovine spongiform encephalopathy (Wells and others 1987, Hope and others 1988, Scott and others 1990) and humans with Creutzfeldt-Jakob disease (Merz and others 1984).

In sheep with scrapie, fibrils can be readily detected in several areas of the brain, including cerebral cortex (Stack and others 1991).

By contrast, the frequency with which fibrils were detected in cattle with BSE, DEPENDED ON THE REGION OF THE BRAIN SAMPLED; THE HIGHEST YIELD BEING OBTAINED FROM MEDULLA, MIDBRAIN, THALAMUS AND BASAL NUCLEI WHERE VACUOLA CHANGES ARE PRESENT (Scott and others 1990). This correlation between PrPsc accumulation and vacuolar pathology is also well established in laboratory animal models of scrapie (Bruce and others 1989). Because of the widespread distribution of changes in FSE (Whatt and others 1991) and the requirement, in the present study, not to compromise the histopathological examination of the brain, the frontal region of the cerebrum was therefore selected for fibril and PrPsc examinations. However, studies of the sensitivity of fibril detection in different parts of the brain in cats with FSE are required to determine whether detection can be made as readliy in other regions as in the frontal cerebral cortex.

IT IS OF INTEREST, that fibrils were detected in the brains of 3 cats (cases 9, 13, & 18) WITHOUT histopathological evidence of spongiform encephalopathy, and that in only one of them, (case 9), a Western blot for modified PrP was positive. There are precedents for the occurrence of abnormal PrP in the organs of animals incubation scrapie prior to clinical signs and/or spongiform encephalopathy...

snip...

(please see full text (and one might start downloading these documents for future use, as some disappear never to re-appear, as in some of the FDA's. ...TSS)

http://collections.europarchive.org/tna/20090113230941/http://www.bseinquiry.gov.uk/files/sc/seac12/tab04.pdf



PLEASE NOTE *

Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...


http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf




AND THE USDA ET AL KNEW IT TOO ;



""These 9,200 cases were different because brain tissue samples were preserved with formalin, which makes them suitable for only one type of test--immunohistochemistry, or IHC."


THIS WAS DONE FOR A REASON!


THE IHC test has been proven to be the LEAST LIKELY to detect BSE/TSE in the bovine, and these were probably from the most high risk cattle pool, the ones the USDA et al, SHOULD have been testing. ...TSS


USDA 2003

We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back. Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS.

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.

snip.............

Dr. Detwiler: It seems a good idea, but I'm not aware of it. Another important thing to get across to the public is that the negatives do not guarantee absence of infectivity. The animal could be early in the disease and the incubation period. Even sample collection is so important. If you're not collecting the right area of the brain in sheep, or if collecting lymphoreticular tissue, and you don't get a good biopsy, you could miss the area with the PRP in it and come up with a negative test. There's a new, unusual form of Scrapie that's been detected in Norway. We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back.

Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS .

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.

snip...

FULL TEXT;

Completely Edited Version PRION ROUNDTABLE

Accomplished this day, Wednesday, December 11, 2003, Denver, Colorado

END...TSS



Subject: USDA OIG SEMIANNUAL REPORT TO CONGRESS FY 2007 1st Half (bogus BSE sampling FROM HEALTHY USDA CATTLE)

Date: June 21, 2007 at 2:49 pm PST

Owner and Corporation Plead Guilty to Defrauding Bovine Spongiform Encephalopathy (BSE) Surveillance Program

An Arizona meat processing company and its owner pled guilty in February 2007 to charges of theft of Government funds, mail fraud, and wire fraud. The owner and his company defrauded the BSE Surveillance Program when they falsified BSE Surveillance Data Collection Forms and then submitted payment requests to USDA for the services. In addition to the targeted sample population (those cattle that were more than 30 months old or had other risk factors for BSE), the owner submitted to USDA, or caused to be submitted, BSE obex (brain stem) samples from healthy USDA-inspected cattle. As a result, the owner fraudulently received approximately $390,000. Sentencing is scheduled for May 2007.

snip...

Topics that will be covered in ongoing or planned reviews under Goal 1 include:

soundness of BSE maintenance sampling (APHIS),

implementation of Performance-Based Inspection System enhancements for specified risk material (SRM) violations and improved inspection controls over SRMs (FSIS and APHIS),

snip...

The findings and recommendations from these efforts will be covered in future semiannual reports as the relevant audits and investigations are completed.

4 USDA OIG SEMIANNUAL REPORT TO CONGRESS FY 2007 1st Half

http://www.usda.gov/oig/webdocs/sarc070619.pdf




THE USDA JUNE 2004 ENHANCED BSE SURVEILLANCE PROGRAM WAS TERRIBLY FLAWED ;


CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006

In an article today for United Press International, science reporter Steve Mitchell writes:

Analysis: What that mad cow means

By STEVE MITCHELL UPI Senior Medical Correspondent

WASHINGTON, March 15 (UPI) -- The U.S. Department of Agriculture was quick to assure the public earlier this week that the third case of mad cow disease did not pose a risk to them, but what federal officials have not acknowledged is that this latest case indicates the deadly disease has been circulating in U.S. herds for at least a decade.

The second case, which was detected last year in a Texas cow and which USDA officials were reluctant to verify, was approximately 12 years old.

These two cases (the latest was detected in an Alabama cow) present a picture of the disease having been here for 10 years or so, since it is thought that cows usually contract the disease from contaminated feed they consume as calves. The concern is that humans can contract a fatal, incurable, brain-wasting illness from consuming beef products contaminated with the mad cow pathogen.

"The fact the Texas cow showed up fairly clearly implied the existence of other undetected cases," Dr. Paul Brown, former medical director of the National Institutes of Health's Laboratory for Central Nervous System Studies and an expert on mad cow-like diseases, told United Press International. "The question was, 'How many?' and we still can't answer that."

Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive.

USDA officials finally retested the cow and confirmed it was infected seven months later, but only at the insistence of the agency's inspector general.

"Everything they did on the Texas cow makes everything they did before 2005 suspect," Brown said.

Despite this, Brown said the U.S. prevalence of mad cow, formally known as bovine spongiform encephalopathy, or BSE, did not significantly threaten human or cattle health.

"Overall, my view is BSE is highly unlikely to pose any important risk either in cattle feed or human feed," he said.

However, Jean Halloran of Consumers Union in Yonkers, N.Y., said consumers should be troubled by the USDA's secrecy and its apparent plan to dramatically cut back the number of mad cow tests it conducts.

"Consumers should be very concerned about how little we know about the USDA's surveillance program and the failure of the USDA to reveal really important details," Halloran told UPI. "Consumers have to be really concerned if they're going to cut back the program," she added.

Last year the USDA tested more than 300,000 animals for the disease, but it has proposed, even in light of a third case, scaling back the program to 40,000 tests annually.

"They seem to be, in terms of actions and policies, taking a lot more seriously the concerns of the cattle industry than the concerns of consumers," Halloran said. "It's really hard to know what it takes to get this administration to take action to protect the public."

The USDA has insisted that the safeguards of a ban on incorporating cow tissue into cattle feed (which is thought to spread the disease) and removal of the most infectious parts of cows, such as the brain and spinal cord, protect consumers. But the agency glosses over the fact that both of these systems have been revealed to be inadequately implemented.

The feed ban, which is enforced by the Food and Drug Administration, has been criticized by the Government Accountability Office in two reports, the most recent coming just last year. The GAO said the FDA's enforcement of the ban continues to have weaknesses that "undermine the nation's firewall against BSE."

USDA documents released last year showed more than 1,000 violations of the regulations requiring the removal of brains and spinal cords in at least 35 states, Puerto Rico and the Virgin Islands, with some plants being cited repeatedly for infractions. In addition, a violation of similar regulations that apply to beef exported to Japan is the reason why Japan closed its borders to U.S. beef in January six weeks after reopening them.

Other experts also question the adequacy of the USDA's surveillance system. The USDA insists the prevalence of mad cow disease is low, but the agency has provided few details of its surveillance program, making it difficult for outside experts to know if the agency's monitoring plan is sufficient.

"It's impossible to judge the adequacy of the surveillance system without having a breakdown of the tested population by age and risk status," Elizabeth Mumford, a veterinarian and BSE expert at Safe Food Solutions in Bern, Switzerland, a company that provides advice on reducing mad cow risk to industry and governments, told UPI.

"Everybody would be happier and more confident and in a sense it might be able to go away a little bit for (the USDA) if they would just publish a breakdown on the tests," Mumford added.

UPI requested detailed records about animals tested under the USDA's surveillance plan via the Freedom of Information Act in May 2004 but nearly two years later has not received any corresponding documents from the agency, despite a federal law requiring agencies to comply within 30 days. This leaves open the question of whether the USDA is withholding the information, does not have the information or is so haphazardly organized that it cannot locate it.

Mumford said the prevalence of the disease in U.S. herds is probably quite low, but there have probably been other cases that have so far gone undetected. "They're only finding a very small fraction of that low prevalence," she said.

Mumford expressed surprise at the lack of concern about the deadly disease from American consumers. "I would expect the U.S. public to be more concerned," she said.

Markus Moser, a molecular biologist and chief executive officer of Prionics, a Swiss firm that manufactures BSE test kits, told UPI one concern is that if people are infected, the mad cow pathogen could become "humanized" or more easily transmitted from person to person.

"Transmission would be much easier, through all kinds of medical procedures" and even through the blood supply, Moser said.

© Copyright 2006 United Press International, Inc. All Rights Reserved

http://www.upi.com/ConsumerHealthDaily/view.php?StoryID=20060315-055557-1284r


http://www.upi.com/Science_News/2003/12/30/Mad-Cow-Linked-to-thousands-of-CJD-cases/UPI-47861072816318/




CDC - Bovine Spongiform Encephalopathy and Variant Creutzfeldt ... Dr. Paul Brown is Senior Research Scientist in the Laboratory of Central Nervous System ... Address for correspondence: Paul Brown, Building 36, Room 4A-05, ...

http://www.cdc.gov/ncidod/eid/vol7no1/brown.htm




PAUL BROWN COMMENT TO ME ON THIS ISSUE

Tuesday, September 12, 2006 11:10 AM

"Actually, Terry, I have been critical of the USDA handling of the mad cow issue for some years, and with Linda Detwiler and others sent lengthy detailed critiques and recommendations to both the USDA and the Canadian Food Agency." ........TSS

http://madcowtesting.blogspot.com/2009/07/mad-cow-cover-up-usa-masked-as-sporadic.html




OR, what the Honorable Phyllis Fong of the OIG found ;

Audit Report Animal and Plant Health Inspection Service Bovine Spongiform Encephalopathy (BSE) Surveillance Program ­ Phase II and Food Safety and Inspection Service

Controls Over BSE Sampling, Specified Risk Materials, and Advanced Meat Recovery Products - Phase III

Report No. 50601-10-KC January 2006

Finding 2 Inherent Challenges in Identifying and Testing High-Risk Cattle Still Remain


http://www.usda.gov/oig/webdocs/50601-10-KC.pdf




THIS is just ONE month report, of TWO recalls of prohibited banned MBM, which is illegal, mixed with 85% blood meal, which is still legal, but yet we know the TSE/BSE agent will transmit blood. we have this l-BSE in North America that is much more virulent and there is much concern with blood issue and l-BSE as there is with nvCJD in humans. some are even starting to be concerned with sporadic CJD and blood, and there are studies showing transmission there as well. ... this is one month recall page, where 10 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE, TO BE FED OUT. very little of the product that reaches commerce is ever returned via recall, very, very little. this was 2007, TEN YEARS AFTER THE AUGUST 4, 1997, PARTIAL AND VOLUNTARY MAD COW FEED BAN IN THE USA, that was nothing but ink on paper. i have listed the tonnage of mad cow feed that was in ALABAMA in one of the links too, this is where the infamous g-h-BSEalabama case was, a genetic relation matching the new sporadic CJD in the USA. seems this saga just keeps getting better and better.......$$$

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

http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm



Wednesday, September 22, 2010

Docket APHIS-2010-0056 National Veterinary Services Laboratories; Bovine Spongiform Encephalopathy Surveillance Program Documents COMMENT SUBMISSION

Docket No. APHIS-2010-0056

http://madcowtesting.blogspot.com/2010/09/docket-aphis-2010-0056-national.html



Suppressed peer review of Harvard study October 31, 2002.

October 31, 2002 Review of the Evaluation of the Potential for Bovine Spongiform Encephalopathy in the United States Conducted by the Harvard Center for Risk Analysis, Harvard School of Public Health and Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Final Report Prepared for U.S. Department of Agriculture Food Safety and Inspection Service Office of Public Health and Science Prepared by RTI Health, Social, and Economics Research Research Triangle Park, NC 27709 RTI Project Number 07182.024

http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf



Sunday, February 14, 2010

[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

http://bseusa.blogspot.com/2010/02/docket-no-fsis-2006-0011-fsis-harvard.html



PLEASE SEE FULL TEXT 98 PAGES HERE ;

[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf



Response to Public Comments on the Harvard Risk Assessment of Bovine Spongiform Encephalopathy

Update, October 31, 2005 INTRODUCTION The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website: http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp). Comments on technical aspects of the risk assessment were then submitted to FSIS. Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary. This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf



Friday, August 27, 2010

NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010

http://nor-98.blogspot.com/2010/08/new-atypical-nor-98-scrapie-case.html



Technical Abstract:

Prion strains may vary in their ability to transmit to humans and animals. Few experimental studies have been done to provide evidence of differences between U.S. strains of scrapie, which can be distinguished by incubation times in inbred mice, microscopic lesions, immunoreactivity to various antibodies, or molecular profile (electrophoretic mobility and glycoform ratio). Recent work on two U.S. isolates of sheep scrapie supports that at least two distinct strains exist based on differences in incubation time and genotype of sheep affected. One isolate (No. 13-7) inoculated intracerebrally caused scrapie in sheep AA at codon 136 (AA136) and QQ at codon 171 (QQ171) of the prion protein in an average of 19 months post-inoculation (PI) whereas a second isolate (No. x124) caused disease in less than 12 months after oral inoculation in AV136/QQ171 sheep. Striking differences were evident when further strain analysis was done in R111, VM, C57Bl6, and C57Bl6xVM (F1) mice. No. 13-7 did not induce disease in any mouse strain at any time post-inoculation (PI) nor were brain tissues positive by western blot (WB). Positive WB results were obtained from mice inoculated with isolate No. x124 starting at day 380 PI. Incubation times averaged 508, 559, 601, and 633 days PI for RIII, C57Bl6, VM, and F1 mice, respectively. Further passage will be required to characterize these scrapie strains in mice. This work provides evidence that multiple scrapie strains exist in U.S. sheep.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=227516



One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.

http://jvi.asm.org/cgi/content/full/81/13/7230?view=long&pmid=17442721



In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=182469



REPORT OF THE WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY 1989

snip...

4.2.9 ...Also, if it resulted from a localised chance transmission of the scrapie strain from sheep to cattle giving rise to a mutant, a different pattern of disease would have been expected: its range would have increased with time. Thus the evidence from Britain is against the disease being due to a new strain of the agent, but we note that in the United States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to have Increased markedly, now being nearly 3 times as high as during any previous period (18).



http://collections.europarchive.org/tna/20080102132706/http://www.bseinquiry.gov.uk/files/ib/ibd1/tab02.pdf



http://collections.europarchive.org/tna/20080102193106/http://www.bseinquiry.gov.uk/files/mb/m12/tab12.pdf



If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...



http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf



http://scrapie-usa.blogspot.com/2007/12/scrapie-hb-parry-seriously-yb886841.html




EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........



http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf




1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract




12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie A] The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6



http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf




Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis). Gibbs CJ Jr, Gajdusek DC.

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).


http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html



Epidemiology of Scrapie in the United States 1977


http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf



Monday, December 1, 2008

When Atypical Scrapie cross species barriers

Authors

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

Content

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf



P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf



PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119

http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf



A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. *** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

http://www.pnas.org/content/102/44/16031.abstract



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)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html



Thursday, October 07, 2010

Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice

http://bse-atypical.blogspot.com/2010/10/experimental-transmission-of-h-type.html



The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.

http://www.oie.int/boutique/extrait/06heim937950.pdf



Rare BSE mutation raises concerns over risks to public health

SIR — Atypical forms (known as H- and L-type) of bovine spongiform encephalopathy (BSE) have recently appeared in several European countries as well as in Japan, Canada and the United States. This raises the unwelcome possibility that variant Creutzfeldt–Jakob disease (vCJD) could increase in the human population. Of the atypical BSE cases tested so far, a mutation in the prion protein gene (PRNP) has been detected in just one, a cow in Alabama with BSE;

http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF



http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html



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

NATUREVol 45726 February 2009

http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html



Monday, May 11, 2009

Rare BSE mutation raises concerns over risks to public health

http://bse-atypical.blogspot.com/2009/05/rare-bse-mutation-raises-concerns-over.html



Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.

The key word here is diverse. What does diverse mean?

If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

SEE FULL TEXT ;

http://www.promedmail.org/pls/apex/f?p=2400:1001:568933508083034::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,82101



.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE. 32 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture. 33 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre. 34 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle, did not produce the same clinical signs of brain lesions characteristic of BSE.

32 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606-12

33 YB88/10.00/1.1

http://web.archive.org/web/20040823105233/www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf



Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010


http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html



http://chronic-wasting-disease.blogspot.com/




SEE where sporadic cjd in the USA went from 59 cases in 1997, to 216 cases in 2009. a steady increase since 1997. ...TSS


Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)

(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1997 114 68 59 9 0 0

to

2009 425 259 216 43 0 0

http://www.cjdsurveillance.com/pdf/case-table.pdf



see full text ;

http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html



Sunday, July 11, 2010

CJD 2 CASES McLennan County Texas population 230,213 both cases in their 40s

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/cjd-2-cases-mclennan-county-texas.html



Tuesday, June 1, 2010

USA cases of dpCJD rising with 24 cases so far in 2010

http://cjdtexas.blogspot.com/2010/06/usa-cases-of-dpcjd-rising-with-24-cases.html



Monday, September 13, 2010

atypical BSE strains and sporadic CJD strains, is there a connection and why shouldn't there be $

http://bse-atypical.blogspot.com/2010/09/atypical-bse-strains-and-sporadic-cjd.html



Thursday, July 08, 2010

GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/global-clusters-of-creutzfeldt-jakob.html



Tuesday, August 03, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html



Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more Prionbaloney ?

http://prionunitusaupdate2008.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html



Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION

http://cjdquestionnaire.blogspot.com/



Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html



Wednesday, October 27, 2010

A novel variant of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

http://creutzfeldt-jakob-disease.blogspot.com/2010/10/novel-variant-of-human-disease-with.html



Wednesday, September 08, 2010

Emerging Infectious Diseases: CJD, BSE, SCRAPIE, CWD, PRION, TSE Evaluation to Implementation for Transfusion and Transplantation September 2010

http://vcjdtransfusion.blogspot.com/2010/09/emerging-infectious-diseases-cjd-bse.html




Thursday, August 12, 2010

Seven main threats for the future linked to prions

http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html



layperson


Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
flounder9@verizon.net