APC Inc., PRION, typical, atypical BSE, spray dried blood, feed, and a recipe for disaster
PRION, typical, atypical BSE, aka mad cow disease, spray dried blood, feed, and a recipe for disaster
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APC, Inc.
2425 SE Oak Tree Court :: Ankeny, IA 50021
Division of Dockets Management
(HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
Response to Docket No. 2002N-0273, Proposed Rule Substances Prohibited From Use in Animal
Food or Feed
Executive Summary
APC, Inc. agrees with the conclusion of the FDA that there is no scientific evidence to suggest that BSE infectivity is present in bovine blood. Banning the use of bovine blood or blood fractions in ruminant rations will not reduce the risk of exposure of humans or animals to BSE infectivity. Animal health will be compromised if the use of bovine blood or blood proteins in ruminant feeds is restricted.
APC, Inc. is a member of the North American Spray Dried Blood and Plasma Producers Association (NASDBPP) (see Appendix A). The NASDBPP is a group of companies located in North America involved in the production and development of spray dried blood and plasma products. These companies organized a working group within the American Feed Industry Association (AFIA) with the purpose of developing Manufacturing Standards to insure that the safety of blood derived proteins is preserved. In addition, it is the intention of NASDBPP to insure that data supporting the safe nature of these proteins is communicated to industry and government officials. The NASDBPP is committed to producing safe, high quality blood products for use as an ingredient in feeds for commercial livestock and companion animals. BSE infectivity has never been detected in blood or any component of bovine blood. There is no epidemiological evidence that bovine blood or blood component carries BSE infectivity. Spray dried blood and plasma products are consumed orally, which is the least efficient method of transmission (100,000 times less efficient compared to intracranial injection). The NASDBPP developed Manufacturing Standards to insure that our blood products do not become contaminated with high-risk tissues. The Manufacturing Standards have been reviewed by internationally recognized BSE experts. Finally, the NASDBPP have agreed to and completed annual third party inspections to certify compliance to these Manufacturing Standards.
It is critically important that regulatory policy developed to prevent BSE from becoming established in the US cattle population is grounded on sound science. The NASDBPP support APHIS, FSIS and FDA in their efforts to develop policies to mitigate the risk of BSE. The NASDBPP appreciate the opportunity to comment on the questions and issues raised in the Proposed Rule, Docket No. 2002N-0273, Proposed Rule Substances Prohibited From Use in Animal Food or Feed. We will restrict our comments to the request for further comment and scientific information regarding the need to prohibit the use of blood and blood products in ruminant feed.
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APC, INC. COMMENTS
There is no scientific evidence to show that the use of bovine blood or blood products in feed pose a risk of BSE transmission in cattle and other ruminants...
snip...
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC201-Attach-1.pdf
1
North American Spray Dried Blood and Plasma Producers
Division of Dockets Management
(HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
Response to Docket No. 2002N-0273, Proposed Rule Substances Prohibited From Use in Animal
Food or Feed
Executive Summary
The North American Spray Dried Blood and Plasma Producers Association agrees with the conclusion of the FDA that there is no scientific evidence to suggest that BSE infectivity is present in bovine blood. Banning the use of bovine blood or blood fractions in ruminant rations will not reduce the risk of exposure of humans or animals to BSE infectivity. Animal health will be compromised if the use of bovine blood or blood proteins in ruminant feeds is restricted...
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http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC202-Attach-1.pdf
September 6,2007 Via Overnight Mail Robert L. Martin, Ph D. Office of Food Additive Safety (HFS-255) Center for Food Safety and Applied Nutrition Food and Drug Administration 4300 River Road College Park, Maryland 20740-3835 Re: GRAS Notification for ImmunoLinO Brand Spray-Dried Bovine Globulin Concentrate Intended for Use as an Ingredient in Food
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Importantly, while these studies indicate that transmission of vCJD to human from BSEinfected cattle via blood is a theoretical possibility, the reality is that the potential for transmissibility is substantially reduced by the cross-species barrier.
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http://www.accessdata.fda.gov/scripts/fcn/gras_notices/710670A.PDF
FDA's Comments and Corresponding Changes Made in Response 1. On pg 14, you report a protein digestibility of 93.4% for Bovine Globulin but your notice does not include information about how your calculation was derived. Additionally, the reported 94.4% digestibility value appears to conflict with the statement in Attachment 19 that the IgG in bovine globulin is resistant to digestion. Please explain how you calculated the 94.4% digestibility value and discuss how that value correlates to the high concentration of IgG in your product.
http://www.accessdata.fda.gov/scripts/fcn/gras_notices/808167A.PDF
Wednesday, March 31, 2010
Atypical BSE in Cattle
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.
This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
To date, 27 cases of L-BSE and 24 cases of H-BSE have been reported worldwide (16), thus meaning that the prevalence of atypical BSE is considerably lower than that of C-BSE. However, recent studies showed that L-BSE is easily transmissible to transgenic mice expressing human (17,18) or bovine (19,20) prion protein, as well as to non-human primates (21), with shorter incubation periods than for the transmission of C-BSE to these animals. The virulent nature of L-BSE has stimulated new concern for human public health since the transmission of C-BSE to humans resulted in variant Creutzfeldt-Jakob disease (vCJD) (4-7), a new emergent prion disease.
see full text ;
http://www.nih.go.jp/JJID/64/81.pdf
Ruminant Blood
In contrast with humans, sheep, monkeys, mice and hamsters, including sheep and mice infected with BSE and humans infected with vCJD considered identical to BSE, no infectivity has so far been demonstrated in the blood of BSE infected cattle. However, we consider it unlikely that cattle are the sole outlier to what has been a consistent finding in all other TSE diseases where the measurement has been made with sufficient sensitivity to detect the low levels of infectivity that are present in blood. Rather, this failure is more likely the result of the very small volumes of blood that were used for the inoculations (less than 1 ml), whereas whole transfusions were administered to assay animals in the published sheep scrapie/BSE experiments. If blood is infected then all vascularized tissues can be expected to contain some infectivity in proportion to the content of residual blood.
Micro emboli are a possible source of blood-borne agent that could be at much higher titer than blood itself, in slaughtered cattle carrying BSE infection. Stunning can release micro emboli of brain tissue into the circulatory system from where they can be distributed to other tissues in the few moments before the exsanguination and death. (Anil, et al, 2001a & b; Anil et al, 2002; Love, et al, 2000). This source of infection could extend a higher infectivity risk to tissues that would otherwise be at low risk, thereby allowing exposure of cattle through any of the legal exemptions and potentially producing a feed and food risk. Blood-borne contamination may be a special problem where spray-dried blood is being used as a milk replacer for calves, as it is thought that young animals are especially susceptible to infection.
Certainly, blood and blood proteins should not be used as feed without conclusive evidence that they are safe.
see full text ;
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000490-vol40.pdf
M. E., Simmons M. M., Austin A. R., & Horigan M. W. (1994) Infectivity in the ileum of cattle challenged orally with bovine spongiform encephalopathy. Vet. Rec., 135, 40-41.
Wells G.A.H., Hawkins, S.A.C., Green R. B., Austin A. R., Dexter I., Spencer, Y. I., Chaplin, M. J., Stack, M. J., & Dawson, M. (1998) Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet. Rec., 142, 103-106.
Wyatt. J. M. et al. 1991. Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Veterinary Record. 129. 233.
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[RR1] I am not sure of the point here. If they are going to use dead stock then certainly they should at a minimum remove the CNS tissue but rather I would think the point should be that we don’t want them using dead stock with or without the CNS included.
[RR2]I am not sure that the actual text of the CFR is still required to make the point. However, I am glad I had it to verify the original argument.
THE SEVEN SCIENTIST REPORT ***
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf
http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=FDA-2002-N-0031
9 December 2005 Division of Dockets Management (RFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852
Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed
Dear Sir or Madame:
Serologicals Corporation is a global provider of biological products to life science companies. The Company’s products are essential for the research, development and manufacturing of biologically based diagnostic, pharmaceutical and biological products. customers include many of the leading research institutions, diagnostic and pharmaceutical companies throughout the world. The Company’s products and technologies are used in a wide variety of applications within the areas of neurobiology, cell signaling, oncology, angiogenesis, apoptosis, developmental biology, cellular physiology, hematology, immunology, cardiology, infectious diseases and molecular biology. A number of our products are derived from bovine blood or other bovine tissues sourced in the United States, hence the overall health of the national herd is extremely important to our company as well as to our customers and their patients. Some of our bovine based products are used in the manufacture of vaccines and drugs for humans, hence it is critical that all measures are taken to assure these are safe and free from disease especially Bovine Spongiform Encephalopathy (BSE).
The most effective way to insure this is to create a system which processes cattle that are BSE free. As a company there are a number of precautions that we can take by our strict specifications but many of the needed precautions require the force of federal regulation, hence we appreciate the opportunity to submit comments to this very important proposed rule. After the identification of bovine spongiform encephalopathy (BSE) in indigenous North American cattle, the U.S. Department of Agriculture (USDA) responded rapidly to implement measures to protect public health in regard to food. Our company recognizes and supports the importance of the current feed ban which went into effect in August 1997. However, given what is known about the epidemiology and characteristically long incubation period of BSE, we urge
5655 Spalding Drive * Norcross, GA 30092 678-728-2000 * 800-842-9099 * Facsimile 678-728-2299 http://www.serologicais.com Division of Dockets Management (HFA-305) Page 2 9 December 2005
the FDA to act without further delay and implement additional measures which will reduce the risk of BSE recycling in the US cattle herd. We feel that for the FDA to provide a more comprehensive and protective feed ban, specified risk materials (SRMs) and deadstock must be removed from all animal feed and that legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk) should be discontinued. SRMs, as defined by the USDA, are tissues which, in a BSE infected animal, are known to either harbor BSE infectivity or to be closely associated with infectivity. If SRMs are not removed, they may introduce BSE infectivity and continue to provide a source of animal feed contamination. Rendering will reduce infectivity but it will not totally eliminate it. This is significant as research in the United Kingdom has shown that a calf may be infected with BSE by the ingestion of as little as .OOl gram of untreated brain. The current proposed rule falls short of this and would still leave a potential source of infectivity in the system. In fact by the FDA’s own statement the exempted tissues which are known to have infectivity (such as distal ileum, DRGs, etc) would cumulatively amount to 10% of the infectivity in an infected animal, This proposed rule would still allow for the possibility that cattle could be exposed to BSE through:
1. Feeding of materials currently subject to legal exemptions from the ban (e.g., poultry litter, plate waste)
2. Cross feeding (the feeding of non-ruminant rations to ruminants) on farms; and
3. Cross contamination of ruminant and non-ruminant feed
We are most concerned that the FDA ha chosen to include a provision which would allow tissues from deadstock into the feed chain. We do not support the provision to allow the removal of brain and spinal cord from down and deadstock over 30 months of age for several reasons. These are the animals with the highest level of infectivity in tissues which include more than brain and spinal cord. We do not feel that there can be adequate removal and enforcement of this regulation especially during warmer weather. In addition there is emerging information that at end stage disease, infectivity may also be included in additionai tissues such as peripheral nerves (Buschmann and Groschup, 2005). Leaving the tissues from these cattle in the animal feed chain will effectively nullify the intent of this regulation. This point is illustrated by the 2001 Harvard risk assessment model which demonstrated that eliminating dead and downer, 4D cattle, from the feed stream was a disproportionately effective means of reducing the risk of re-infection “The disposition of c&e that die on the farm would also have a substantial influence on the spread of BSE if the disease were in traduced. ” The base case scenario showed that the mean total number ofID.50~ (i.e., dosage sufficient to infect SO percent of exposed cattte) from healthy animals at slaughter presented to the food/feed system was 1500, The mean total number of ID.50.s from adult cattle Division of Dockets Management (HFA-305) Page 3 9 December 2005 deadstockpresented to the feed system was 3 7,000. deadstock). This illustrates the risk of “40 cattle” (i.e., From the Harvard Risk Assessment, 2001, Appendix 3A Base Case and Harvard Risk Assessment, 200 1
Executive Summary
Serologicals and companies like ours which supply components of drugs and biologicals have a responsibility to the manufacturers of these products, the medical community and their patients as well as regulatory agencies throughout the world to provide the safest products as possible. Since there is no test for BSE in live cattle or for product, the regulatory agencies throughout the world expect us to reduce or eliminate risk via suurcing criteria, These parameters may include but not be limited to country of origin, herd of origin, age of the animal, etc. The United States is no longer a country with negligible risk, hence individual animal criteria has become more important. In fact other Centers of the FDA have stated that more attention should be given to sourcing from herds likely to be a source of BSE free animals. The exemptions in the current ban as well as in the newly proposed rule make this difficult if not impossible as there are still legal avenues for ruminants to consume potentially contaminated ruminant protein. In addition, the USDA still has not implemented a system of identification and traceability. Serologicals urges agencies of the US government to work with academia and industry on research in the following areas: e Methods to inactivate TSEs agents which then may allow a product to be used and even fed to animals without risk l Alternative uses for animal byproducts which would maintain value Serologicals will continue to work with the FDA and other government agencies to implement a strong BSE risk control program, Serologicals would like to reiterate our opinion that for the FDA to provide a more comprehensive and protective feed ban, specified risk materials (SRMs) and deadstock must be removed from all animal feed and that legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk) should be discontinued. Thank you for the opportunity to submit these comments to the public record. Respectfully, SEROLOGICALS CORPORATION James J. Kramer, Ph.D. Vice President, Corporate Operations
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000435-01-vol36.pdf
03-025IFA 03-025IFA-2 Terry S. Singeltary
From: Terry S. Singeltary Sr. [flounder9@verizon.net] Sent: Thursday, September 08, 2005 6:17 PM To: fsis.regulationscomments@fsis.usda.gov Subject: [Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
see Dr. Paul Brown and Seven Scientists comments here ;
Signatories:
Paul W. Brown, M.D. Medical Director, USPHS, and Senior Investigator, NIH (retired) Consultant, TSE Risk Management 7815 Exeter Rd. Bethesda, MD 20814 Fax 301-652-4312 Email: paulwbrown@comcast.net
Neil R. Cashman MD Professor, Department of Medicine (Neurology) Diener Chair of Neurodegenerative Diseases Centre for Research in Neurodegenerative Diseases 6 Queen's Park Crescent West Toronto Ontario M5S3H2 Ph: 416-978-1875 Fax: 416-978-1878 e-mail: neil.cashman@utoronto.ca
Linda A. Detwiler, DVM Consultant, TSE Risk Management 225 Hwy 35 Red Bank, NJ 07701 Ph 732-741- 2290 Fax 732-741-7751 Email: LAVet22@aol.com
Laura Manuelidis, MD Professor and Head of Neuropathology, Department of Surgery and Faculty of Neurosciences Yale Medical School 333 Cedar St. New Haven, CT 06510 email: laura.manuelidis@yale.edu Tel: 203-785-4442 Deleted: p Deleted: 14 Formatted FDA Proposed Rule December 20, 2005
Jason C. Bartz, Ph.D. Assistant Professor Department of Medical Microbiology and Immunology Creighton University 2500 California Plaza Omaha, NE 68178 (402) 280-1811 voice (402) 280- 1875 fax jbartz@creighton.edu
Robert B. Petersen, Ph.D. Associate Professor of Pathology and Neuroscience Case Western Reserve University 5-123 Wolstein Building 2103 Cornell Road Cleveland, OH 44106-2622 Phone 216-368-6709 FAX 360-838-9226 Email rbp@cwru.edu
Robert G. Rohwer, Ph.D. Director, Molecular Neurovirology Laboratory Veterans Affairs Medical Center Medical Research Service 151 Assoc. Professor of Neurology School of Medicine University of Maryland at Baltimore 10 N. Greene St. Baltimore, MD 21201 ph. 410-605-7000 x6462 Fax 410-605-7959 email: rrohwer@umaryland.edu
FDA-2002-N-0031-0131 Paul W. Brown, et al - Comment 02/23/2009 PUBLIC SUBMISSIONS FDA-2002-N-0031-0131.1 Paul W. Brown, et al - Comment 02/23/2009
PUBLIC SUBMISSIONS
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064808b3843&disposition=attachment&contentType=pdf
http://www.regulations.gov/fdmspublic/custom/jsp/search/searchresult/docketDetail.jsp#
December 19, 2005 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852 Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Dear Sir or Madame: The McDonald's Corporation buys more beef than any other restaurant in the United States.
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SRMs, as defined by the USDA, are tissues which, in a BSE infected animal, are known to either harbor BSE infectivity or to be closely associated with infectivity. If SRMs are not removed, they may introduce BSE infectivity and continue to provide a source of animal feed contamination. Rendering will reduce infectivity but it will not totally eliminate it. This is significant, as research in the United Kingdom has shown that a calf may be infected with BSE by the ingestion of as little as .001 gram of untreated brain. The current proposed rule falls short of this and would still leave a potential source of infectivity in the system. In fact by the FDA's own statement the exempted tissues which are known to have infectivity (such as distal ileum, DRGs, etc) would cumulatively amount to approximately 10% of the infectivity in an infected animal. Leaving approximately 10% of the infectious tissues in the system is not good enough.
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http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273_emc-000134-02.pdf
9 December 2005 Division of Dockets Management (RFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852 Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Dear Sir or Madame: Serologicals Corporation is a global provider of biological products to life science companies.
We feel that for the FDA to provide a more comprehensive and protective feed ban, specified risk materials (SRMs) and deadstock must be removed from all animal feed and that legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk) should be discontinued. SRMs, as defined by the USDA, are tissues which, in a BSE infected animal, are known to either harbor BSE infectivity or to be closely associated with infectivity. If SRMs are not removed, they may introduce BSE infectivity and continue to provide a source of animal feed contamination. Rendering will reduce infectivity but it will not totally eliminate it. This is significant as research in the United Kingdom has shown that a calf may be infected with BSE by the ingestion of as little as .OOl gram of untreated brain. The current proposed rule falls short of this and would still leave a potential source of infectivity in the system. In fact by the FDA's own statement the exempted tissues which are known to have infectivity (such as distal ileum, DRGs, etc) would cumulatively amount to 10% of the infectivity in an infected animal, This proposed rule would still allow for the possibility that cattle could be exposed to BSE through:
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000383-01-vol35.pdf
2002N-0273 Animal Proteins Prohibited in Ruminant Feed
FDA Comment Number : EC240
Submitter : Mr. Masahiro Mori Date & Time: 01/04/2006 05:01:26
Organization : Embassy of Japan
Category : International Government
Issue Areas/Comments
GENERAL
GENERAL
Comments of Japan on the United States? WTO/SPS Notification (G/SPS/N/USA/1141)
The Government of Japan welcomes the opportunity to comment on the United States? notification (G/SPS/N/USA/1141) on substances prohibited from use in Animal food or feed.
The Food safety risk assessment related to the import of beef and beef offal from the U.S.A. and Canada by the Food Safety Commission of Japan (FSC) was completed on December 8, 2005. Regarding the feed ban, the following was noted as an addendum to the conclusion on the risk assessment report of FSC:
?To prevent BSE exposure and amplification in U.S.A and Canada, the use of SRM must be prohibited completely. The ban must be applied not only to cattle feed but also to all other animal food/feed that may cause cross-contamination.?
To accomplish the effectively enforced feed ban requested in the OIE Terrestrial Animal Health Code (CHAPTER 2.3.13, Bovine Spongiform Encephalopathy), whole SRM should be excluded as high risk material from animal feed chain as the above-mentioned addendum points out. The U.S. Government should also carry out continuous BSE surveillance sufficient to verify the efficacy of U.S. feed ban and make necessary revision of its feed regulations on a basis of its results.
The Government of Japan would like to request that the U.S. Government take account of the above comments in implementing its animal food and feed regulations.
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC240.htm
Substances Prohibited From Use in Animal Food or Feed; Final Rule: Proposed Delay of Effective Date - Notice of Final Rule Send a Comment or Submission Notification Comments Due: Apr 16, 2009 11:59:59 PM EDT Docket ID: FDA-2002-N-0031
Document ID: FDA- 2002-N-0031-0132 Date Posted: Apr 9, 2009 View this Document:
http://www.regulations.gov/fdmspublic/ContentViewerobjectId=090000648094bc24&disposition=attachment&contentType=pdf
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648094bc24&disposition=attachment&contentType=html
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submit here ;
http://www.regulations.gov/fdmspublic/component/main?main=SubmitComment&o=090000648094bc24
THE SEVEN SCIENTIST REPORT ***
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf
http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=FDA-2002-N-0031
NATIONAL RENDERERS ASSOCIATION,
Inc. 801 N. Fairfax Street Suite 205 Alexandria, Virginia 22314 Tel: (703) 683-0155 Fax: (703) 683-2626
March 12, 2007 Docket No. 050-15-1 Regulatory Analysis and Development, PPD, APHIS Station 3A-03.8 4700 River Road Unit 118 Riverdale, Maryland 20737-1238 Re: Docket No. APHIS-2006-0041, Bovine Spongiform Encephalopathy; Minimal-Risk Regions; Importation of Live Bovines and Products Derived from Bovines.
To Whom It May Concern: The National Renderers Association (NRA) references APHIS’s Docket No. APHIS-2006-0041, the agency’s proposed rule to import cattle and products. NRA is the international trade association for the industry that safely and efficiently recycles animal agriculture by-products into valuable ingredients for the livestock, pet food, chemical and consumer product industries. NRA represents its members’ interests to Congress, regulatory and other government agencies, promotes greater use of rendered products, and fosters the opening and expansion of trade between North American exporters and foreign buyers. NRA’s membership represents more than 98% of the rendering capacity in both the U.S. and Canada. In the proposed rule the USDA details the criterion necessary for the importation of bovine blood products. Specifically the USDA explain: “For all the above three manners of collection, we would require that the blood be collected in a closed system or in an otherwise hygienic manner that prevents contamination of the blood with SRMs.” 1
With current line speeds in U.S. beef slaughter facilities a closed collection system (as described by the USDA in the proposed rule) is not practical and would be cost prohibitive for production of the feed ingredients spray dried bovine plasma or blood meal. Requiring such a collection system would effectively eliminate the supply of feed grade bovine plasma and blood meal. Restricting these products by requiring blood to be collected by a closed system would result in significant damage to the livestock industry both domestically and around the world. Traditional closed collection systems as suggested in the Proposed Rule may be appropriate for the collection of Fetal Calf Serum and other specialized blood products but are impractical for collection of blood used for feed application. The infective agent responsible for BSE has not been identified in bovine blood (USDA’s reference, OIE 2005). However, the North American Spray Dried Blood and Plasma Producers and the NRA recognized the potential for contamination of raw materials with SRM during collection and subsequent processing and have developed a series of Manufacturing Guidelines and a Code of Practice designed to minimize the risk of contamination. These programs include third party audits by the Facilities Certification Institute to ensure compliance with the manufacturing guidelines. These Manufacturing Guidelines have been successfully implemented at the spray dried blood facilities (including Canada) and the Code of Practice has been certified at more than 35 high volume rendering plants in the U.S. so far with many more underway. Many Canadian rendering plants operate under equally effective HACCP programs. Spray dried plasma is a unique feed ingredient. There are no effective substitutes for spray dried plasma. It is important that animal agriculture industry continues to have an adequate supply of this critical feed ingredient. A number of recognized academic and industry organizations agree that continued access to adequate supplies of spray dried bovine blood products is critical. Bovine blood meal represents a very valuable feed ingredient especially for the rations of the lactating dairy cow. It provides high levels of lysine that does not degrade in the rumen. High levels of lysine are necessary to maintain optimum levels of milk production. If bovine blood meal were removed from use in rations, the price of porcine blood meal will continue to increase, placing an additional financial burden on the dairy industry among others. In 2001, the Sparks Company evaluated the impact of prohibiting cattle derived blood meal in ruminant diets on behalf of the NRA. In 2000, 1.48 billion pounds of blood were generated from the slaughter of cattle. A resulting 121.9 million pounds of cattle blood meal and 49.8 million pounds of mixed species blood meal were manufactured. Total ruminant containing blood meal produced was 171.7 million pounds, 70% of which was utilized in ruminant diets. The study determined if the use of blood meal were prohibited in cattle diets, a product loss of $45.3 million would be realized by the cattle sector. Additional indirect losses from reduced animal productivity at the farm level were not considered by the report and are estimated below. [http://www.renderers.org/economic_impact/index.htm] 2
The unique nutritional properties of blood meal, primarily a high level of non-degradable lysine, provide a high return when used by dairy producers. Lysine is considered the first limiting amino acid vital to high milk production. Unlike poultry and swine, high producing dairy cows can’t utilize synthetic lysine, thus milk production will drop if this ingredient is removed. Typically 0.5 pounds/day of dried blood meal is fed to a dairy cow. A reduction of 4 pounds of milk/cow/day would be expected if blood meal were no longer utilized in these diets. Using the figure from the Sparks report that 70% of ruminant blood meal was utilized in dairy rations, an overall drop in milk production of 9.6 million hundredweight would occur. At $12/cwt this loss in milk production would reduce dairy farm income by $115.4 million. Thus, combined losses to the U.S. beef cattle and dairy sectors would total $160.7 million. It is critical the dairy industry continues to have access to bovine blood and bovine blood fractions. Over 41% of the heifer calves raised in the U.S. suffer from failure of passive transfer due to inadequate colostral Ig intake. Approximately 11% of heifer calves died before weaning, and half of this mortality can be attributed to inadequate supply of quality colostrum (NAHMS, 1992, 1996). Colostrum is also recognized as a vector for transmission of a number of disease-causing organisms, including Mycobacterium paratuberculosis (Johne’s disease). Published studies indicate bovine serum and fractions thereof are the only effective alternatives for colostrum (Arthington, et al., 2000 a,b; Quigley et al., 1998, 2000, 2001; McCoy et al, 1997; Holloway et al, 2002; Poulsen et al, 2003). If access to these proteins is restricted, there is no effective alternative to reduce calf mortality or to break these disease cycles. For a more complete review see the review of Quigley et al. (2004). Many studies from the involved sectors have been shared with FDA on the economic and environmental impacts of banning the use of bovine blood meal in feed, especially representatives from blood processors and the poultry industry. Collectively, the dual impacts (economic and environmental) could be very great on the industries. If these products are prohibited from animal feed, there is reduced market for such products and their disposal costs increase. This could lead to improper disposal, disposal in landfills, or by land application on farms. If feeding of blood meal were prohibited for cows, farmers would either feed higher protein levels and/or milk additional cows to maintain milk production. Either course of action would result in increased nitrogen and methane release into the environment. There is no need to stop the feeding of ruminant blood products to ruminants or any other animals because there is no science to support such a restriction. There is no scientific or peer reviewed literature linking the feeding of bovine blood in the form of blood meal or other blood products in feed to any risk of BSE transmission in cattle and other ruminants. Bovine blood has never been implicated in bovine-to-bovine transmission of either natural or experimental BSE. If there are concerns that some collection methods could allow small amounts of neural tissue to be collected with the blood, technology can be employed to remove neural tissue 3 from blood without requiring the closed system or sterile procedures. The possibility was considered in the Harvard Risk Analysis and not deemed a significant risk to spread BSE. Products resulting from processes such as filtering or centrifuging should be allowed to be imported because these steps would remove any particles or tissue residue. Any unnecessarily restrictive regulation imposed on minimum risk regions by the U.S. could easily be applied to U.S. products globally and cause severe problems with the marketing of blood products which are safe and extremely valuable to livestock and aquaculture production. The NRA urges the USDA to resume the import of blood products from minimal risk regions fo n feed applications when those products are produced in a manner consistent with the current manufacturing guidelines. Sincerely, David L. Meeker, Ph.D., MBA Vice President, Scientific Services National Renderers Association 4
http://www.animalprotein.org/news_articles/NRA_Comments_APHIS_Minmal_Risk_Rule_3-07.pdf
"Bovine blood has never been implicated in bovine-to-bovine transmission of either natural or experimental BSE"
yep, that's what they use to say about the blood from the nvCJD victims too, however they were wrong about that too. so to wait until bovine blood has been implicated, by then, it's too late. ...TSS
Fourth case of transfusion-associated vCJD infection in the United Kingdom
Editorial team (eurosurveillance.weekly@hpa.org.uk), Eurosurveillance editorial office
A case of variant Creutzfeldt-Jakob disease (vCJD) has recently been diagnosed in a patient in the United Kingdom (UK), who received a blood transfusion from a donor who later developed vCJD [1]. This is the fourth case of probable transfusion transmission of vCJD infection in the UK. Three of the four recipients developed symptoms of vCJD. The first symptomatic case of vCJD associated with blood transfusion was identified in December 2003. This individual developed vCJD six and a half years after transfusion of red cells donated by an individual who developed symptoms of vCJD three and a half years after donation.
A second case of vCJD 'infection' was identified a few months later in a person who had received red cells from a donor who developed symptoms of vCJD 18 months after donation. This patient (the second case) died from causes unrelated to vCJD five years after transfusion. Post-mortem investigations found abnormal prion protein in the spleen and a cervical lymph node., However, prion protein was not found in the brain, and no pathological features of vCJD were found.
A third case developed symptoms of vCJD six years after receiving a transfusion of red blood cells, and died two years and eight months later. The donor of the blood involved developed vCJD about 20 months after donating it.
These three cases have been published as case reports and in the findings of the ongoing collaborative study between the National Blood Services, the National CJD Surveillance Unit, and the Office for National Statistics. This study aims to collect evidence about transmission of CJD or vCJD via the blood supply [2,3,4,5].
The new, fourth case is in a patient who developed symptoms of vCJD eight and a half years after receiving a transfusion of red blood cells from a donor who developed vCJD about 17 months after this blood was donated [1]. The donor to this case also donated the vCJD-implicated blood transfused to the third case. As for all other reported clinical vCJD cases that have been tested for genotype, this patient is a methionine homozygote at codon 129 of the prion protein gene. The patient is currently alive.
All four cases had received transfusions of non-leucodepleted red blood cells between 1996 and 1999. Since October 1999, leucocytes have been removed from all blood used for transfusion in the UK. The effect of leucodepletion on the reduction of the risk of transmission of vCJD from an infective donation is uncertain.
This fourth case of vCJD infection associated with blood transfusion further increases the level of concern about the risk of vCJD transmission between humans by blood transfusion, although much remains unknown. This reinforces the importance of the existing precautions that have been introduced to reduce the risk of transmission of vCJD infection by blood and blood products [6]. No cases of vCJD have been associated with fractionated plasma products. The small group of living recipients of vCJD-implicated blood transfusion in the UK have been informed of their potential exposure to vCJD by blood transfusion, asked to take certain precautions to reduce the risk of onward person-to-person transmission of vCJD during health care, and offered specialist neurological evaluation and advice.
This article has been adapted from reference 1
References: Health Protection Agency. Fourth case of variant CJD associated with blood transfusion (press release). Press release, 18 January 2007. (http://www.hpa.org.uk/hpa/news/articles/press_releases/2007/070118_vCJD.htm) Llewelyn CA, Hewitt PE, Knight RSG, Amar K, Cousens S, Mackenzie J, et al. Possible transmission of variant CJD disease by blood transfusion. Lancet 2004; 363:417-21. Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004 ; 364: 527-9. Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, et al Clinical presentation and pre-mortem diagnosis of blood transfusion-associated variant CJD. Lancet 2006;368:2061-67. Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiology review study. Vox Sang. 2006;91(3):221-230. Department of Health [London]. Further precautions to protect blood supply. Press release 2004/0104, 16 March 2004.
(http://www.dh.gov.uk/PublicationsAndStatistics/PressReleases/PressReleasesNotices/fs/en?CONTENT_ID=4076608&chk=MTwE%2Bl)
http://www.eurosurveillance.org/ew/2007/070118.asp
http://bloodindex.org/view_news_zone.php?id=206
HARVARD BSE risk assessment was a joke as well, bought and paid for by your local cattle dealer i.e. USDA et al
*** Suppressed peer review of Harvard study October 31, 2002 ***
http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf
[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) [TSS] Date: August 26, 2006 at 12:09 pm PST
From: Terry S. Singeltary Sr. [flounder9@verizon.net]
Sent: Monday, July 24, 2006 1:09 PM
To: FSIS RegulationsComments
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
Page 1 of 98
8/3/2006
Greetings FSIS,
snip... see full text ;
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
Response to Public Commentson theHarvard Risk Assessment of Bovine SpongiformEncephalopathy Update,October 31, 2005
snip...
RESPONSE TO COMMENTS FROM TERRY S. SINGELTARY SR.
Comment #1: SINCE the first Harvard BSE Risk Assessment was so flawed and fraught with error after the PEER REVIEW assessment assessed this fact, how do you plan on stopping this from happening again, will there be another peer review with top TSE Scientists, an impartial jury so-to-speak, to assess this new and updated Harvard BSE/TSE risk assessment and will this assessment include the Atypical TSE and SRM issues?
Response: The original (October 2003) and the revised (October 2005) Harvard BSE risk assessments underwent external peer review. Subsequently, revisions were made to the analysis. In the most recent review, the most significant revisions have been:
1) theaddition of explicit modeling of the poultry litter pathway for the potential recycling ofbovine protein into cattle feed; and
2) a decrease in the assumed effectiveness of antemortem inspection in the identification of animals with BSE.
Comment #2: WITH A RECENT NATION WIDE MAD COW FEED BAN RECALL in the past few months that consisted of some 10,878.06 TONS, then another Mad Cow feed ban warning letter in May, IT should seem prudent to ask why our feed bans continue to fail in 2006, and continue to fail today?
Response: This question about feed bans is a matter for policy. As such, it is not addressed in this response.
Comment #3: WHY still now only partial ruminant feed ban, with the fact that now we seem to have 3 cases of nvCJD to humans i.e. human bovine TSE that were responsible from blood, and the fact the last 2 mad cows documented in the USA were that of an Atypical strain, would it not seem prudent to remove blood as well from ruminant feed?WOULD it not seem prudent to improve and expand the SRM list now? as per your ownthinking; If transmission occurs, tissue distribution comparisons will be made between cattle infected with the atypical BSE isolate and the U.S. BSE isolate. Differences in tissue distribution could require new regulations regarding specific risk material (SRM)removal.
Response: This comment pertains to policy. As such, it is not addressed here.
Comment #4: WHAT does USDA/FDA ET AL intend to do about the risks of atypical BSE/TSE in cattle now that infectivity shows in tissue samples other than CNS in Japan, the fact now that the last Texas mad cow and that last mad cow in Alabama were indeed of the atypical strain, the fact that the studies long ago in Mission, Texas of USA sheep scrapie transmission to the USA bovine, which proved an 'atypical tse' in the USA bovine, the fact also that USDA/FDA are still floundering on the last SRM regulations, but with the BASE strain now in cattle that is not similar to nvCJD, but very similar to the sporadic CJD, and sporadic CJD has tripled in the last few years in the USA. WHAT do you plan to do to protect human health from these atypical strains of TSE, in relations to SRMs ?
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Page 20
Response: The BSE risk assessment simulation model characterizes the disease history of BSE, including the agent's spread within the body of the animal over time. It also quantifies the agent's persistence during the feed manufacture process, and ultimately the agent's ability to cause disease in other exposed animals. There is no definitive evidence that these properties differ substantially for atypical BSE strains, compared to the typical BSE agent.
Comment #5: THE 2004 Enhanced BSE surveillance program, that tested all those cows, but then we found just how terribly flawed the program was, from testing protocols, to testing the most likely to have BSE i.e. high risk, to the geographical distribution of the testing and high risk areas, to letting the tissue samples of one mad cow sit on a shelf for 7+ months and then having to have an act of Congress to ever get that cow finally confirmed, to that other Texas mad cow they decided to not even bother testing at all, just rendered that very suspect cow, too suspect to test evidently, back to that Alabama madcow that they could only give a guess as to age with dentition where we all know that the age of that cow was so close to 10 years it could have been 9 years 7 months to 10 years 3 months, thus possibly being an BAPB i.e. USA 'born after partial ban', to all those rabies suspect cows that did not have rabies, and DID NOT get tested for BSE/TSE in that June 2004 enhanced surveillance program, even though the common lay person knows the suspect rabies negative cows are suppose to be BSE/TSE tested, how does one correct all these blatant failures and will they be corrected?
Response: This comment pertains to policy. As such, it is not addressed here.
Comment #6: WHAT happened to the test results and MOUSE BIO-ASSAYS of those imported sheep from Belgium that were confiscated and slaughtered from the Faillace's, what sort of TSE did these animals have?
Response: It is not clear how the test results referred to in this comment are relevant to the Harvard BSE Risk Assessment Update. Sheep were not considered in the risk assessment.
Comment #7: WHY is it that the Farm of the Mad Sheep of Mad River Valley were quarantined for 5 years, but none of these farms from Texas and Alabama with Atypical TSE in the Bovine, they have not been quarantined for 5 years, why not, with the real risk of BSE to sheep, whom is to say this was not BSE ?
Response: This comment pertains to policy. As such, it is not addressed here.
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snip...END
FULL TEXT ;
http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf
and just recently, private email from abroad, you can take this with how ever many grains of salt you wish ;
snip...
we had four cases of 'typical' BSE over a four year period. Herd size around 120. Two of these were half sisters, born a year apart. Their mother stayed in the herd until she died at a good age of other reasons. Friends and neighbours were hit much harder. We had four young cows 'taken' for slaughter as 'cohorts' at a later date.
We had close links with a farm advisor and nutritionist working for a local feed compounder, and a few years later were made aware that the feed company had been given notice that blood meal inclusion would be banned in a couple of months time. As they had 200 tonnes in stock, the inclusion rate was dramatically raised (farmers later were asking for the dark brown cake that the heifers grew so well on) to use the stocks up. Two of our clinical cases were fed this cake before we knew better. Ingredient declaration was not made, only nutritional analysis. The timing also co-incided with permission being given to the big rendering companies to be allowed to lower the processing temperatures (first fuel crisis, and Mrs Thatcher's husband was on the board of the largest processor)...snip...end...TSS
Schweiz Arch Tierheilkd. 2009 Sep;151(9):433-6.
[Protease-resistant prion protein (PrPres) in the blood of offspring of cows that developed BSE].
[Article in German] Braun U, Tschuor A, Hässig M, Franitza S, Berli E, El Gedaily A, Franscini N, Matthey U, Zahn R. SourceDepartement für Nutztiere der Universität Zürich. ubraun@vetclinics.uzh.ch
Abstract The goal of the present study was to investigate whether protease-resistant prion protein (PrPres) occurs in plasma samples of offspring of cows that developed bovine spongiform encephalopathy (BSE; group A) and to compare the prevalence with that of a healthy control group in 2006 (Group B). Group A consisted of 181 offspring of cows that developed BSE and group B consisted of 240 healthy animals from a region in Switzerland where no cases of BSE occurred from 2001 to the end of 2006. All plasma samples were evaluated using Alicon PrioTrap, an antemortem test for PrPres. The time between birth of the offspring and onset of BSE in the dam was calculated to determine its relationship with the presence of PrPres in the plasma of the offspring. From 181 offspring, 29 (16.1%) had PrPres-positive plasma samples. Offspring that were born within one year of the onset of BSE in the dam had a significantly higher prevalence of PrPres-positive plasma samples than those born more than one year before the onset of BSE in the dam. Ten (4.2%) of 240 control cattle had PrPres-positive plasma samples. Thus, PrPres can be detected in bovine blood and occurs more frequently in the offspring of cows that develop BSE than in cattle of a healthy control population.
PMID:19722131[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/19722131
http://www.cabdirect.org/abstracts/20093248407.html;jsessionid=24FBC2B634B62B6FDE444A591296B3AF
http://agris.fao.org/agris-search/search/display.do?f=2010/CH/CH1001.xml;CH2010000047
COMERCIAL IN CONFIDENCE
SPREADING OF UNPROCESSED BLOOD ON LAND
http://web.archive.org/web/20040315202749/www.bseinquiry.gov.uk/files/yb/1991/02/15003001.pdf
I suppose my next concern besides the potential for transmission of TSE PrP via blood in feed, my next concern from spreading blood on the ground would be TSE infection to the soil, thus contaminating pasture land for years, and years. ...TSS
Saturday, January 24, 2009
Research Project: Detection of TSE Agents in Livestock, Wildlife, Agricultural Products, and the Environment Location: 2008 Annual Report
http://bse-atypical.blogspot.com/2009/01/research-project-detection-of-tse.html
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
Karen Fernie, Allister Smith and Robert A. Somerville The Roslin Institute and R(D)SVS; University of Edinburgh; Roslin, Scotland UK
Scrapie and chronic wasting disease probably spread via environmental routes, and there are also concerns about BSE infection remaining in the environment after carcass burial or waste 3disposal. In two demonstration experiments we are determining survival and migration of TSE infectivity when buried for up to five years, as an uncontained point source or within bovine heads. Firstly boluses of TSE infected mouse brain were buried in lysimeters containing either sandy or clay soil. Migration from the boluses is being assessed from soil cores taken over time. With the exception of a very small amount of infectivity found 25 cm from the bolus in sandy soil after 12 months, no other infectivity has been detected up to three years. Secondly, ten bovine heads were spiked with TSE infected mouse brain and buried in the two soil types. Pairs of heads have been exhumed annually and assessed for infectivity within and around them. After one year and after two years, infectivity was detected in most intracranial samples and in some of the soil samples taken from immediately surrounding the heads. The infectivity assays for the samples in and around the heads exhumed at years three and four are underway. These data show that TSE infectivity can survive burial for long periods but migrates slowly. Risk assessments should take into account the likely long survival rate when infected material has been buried.
The authors gratefully acknowledge funding from DEFRA.
PPo8-13:
Degradation of Pathogenic Prion Protein and Prion Infectivity by Lichens
Christopher J. Johnson,1 James P. Bennett,1 Steven M. Biro,1,2 Cynthia M. Rodriguez,1,2 Richard A. Bessen3 and Tonie E. Rocke1
1USGS National Wildlife Health Center; 2Department of Bacteriology; University of Wisconsin, Madison; 3Department of Veterinary Molecular Biology; Montana State University; Bozeman, MT USA
Key words: prion, lichen, bioassay, protease, degradation
Few biological systems have been identified that degrade the transmissible spongiform encephalopathy (TSE)-associated form of the prion protein (PrPTSE) and TSE infectivity. Stability of the TSE agent allows scrapie and chronic wasting disease agents to persist in the environment and cause disease for years. Naturally-occurring or engineered processes that reduce infectivity in the environment could aid in limiting environmental TSE transmission. We have previously identified that species of at least three lichens, unusual, symbiotic organisms formed from a fungus and photosynthetic partner, contain a serine protease capable of degrading PrPTSE under gentle conditions. We tested the hypothesis that lichen extracts from these three species reduce TSE infectivity by treating infected brain homogenate with extracts and examining infectivity in mice. We found lichen extracts diminished TSE infectious titer by factors of 100 to 1,000 and that reductions in infectivity were not well-correlated with the extent of PrPTSE degradation observed by immunoblotting. For example, treatment of brain homogenate with Cladonia rangiferina extract caused <100-fold reduction in PrP immunoreactivity but ~1,000-fold decrease in infectivity, suggesting that some PrPTSE remaining after extract treatment was rendered uninfectious or that the lichen protease favors more infectious forms of PrPTSE. Our data also indicate that lichen species closely related to those with prion-degrading protease activity do not necessarily degrade PrPTSE.
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Sunday, May 1, 2011
W.H.O. T.S.E. PRION Blood products and related biologicals May 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/who-tse-prion-blood-products-and.html
WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010
snip...
Finally, it is critically important to understand that categories of infectivity are not the same as categories of risk, which require consideration not only of the level of infectivity in tissue, but also of the amount of tissue to which a person or animal is exposed, and the route by which infection is transmitted. For example, although the level of tissue infectivity is the most important factor in estimating the risk of transmission by instrument crosscontamination during surgical procedures (e.g., neurosurgery versus general surgery), it will be only one determinant of the risk of transmission by blood transfusions, in which a large amount of low-infectivity blood is administered intravenously, or the risk of transmission by foodstuffs that, irrespective of high or low infectivity, involve a comparatively inefficient oral route of infection.
snip...
17. A wealth of data from studies of blood infectivity in experimental rodent models of TSE have been extended by recent studies documenting infectivity in the blood of sheep with naturally occurring scrapie and in sheep transfused with blood from BSEinfected cattle [Houston et al., 2008]; of deer with naturally occurring CWD [Mathiason et al., 2006]; and (from epidemiological observations) in the red cell fraction (which includes significant amounts of both plasma and leukocytes) of four blood donors in the pre-clinical phase of vCJD infections [reviewed in Brown, 2006;
Hewitt et al., 2006]. Plasma Factor VIII administration has also been potentially implicated in a subclinical case of vCJD in a hemophilia patient [Peden et al., 2010]. Blood has not been shown to transmit disease from humans with any form of ‘classical’ TSE [Dorsey et al., 2009], or from cattle with BSE (including fetal calf blood). A WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies
11
number of laboratories using new, highly sensitive methods to detect PrPTSE are reporting success in a variety of animal and human TSEs. However, several have experienced difficulty obtaining reproducible results in plasma, and it is not yet clear that positive results imply a potential for disease transmissibility, either because of false positives, or of ‘true’ positives that are due to sub-transmissible concentrations of PrPTSE. Because of these considerations (and the fact that no data are yet available on blinded testing of specimens from naturally infected humans or animals) the expert group felt that it was still too early to evaluate the validity of these tests with sufficient confidence to permit either a negative or positive conclusion.
18. Evidence that infectivity is not present in milk from BSE-infected bovines includes temporo-spatial epidemiologic observations failing to detect maternal transmission to calves suckled for long periods; clinical observations of over a hundred calves suckled by infected cows that have not developed BSE; and experimental observations that milk from infected cows reared to an age exceeding the minimum incubation period has not transmitted disease when administered intracerebrally or orally to mice [Middleton and Barlow, 1993; Taylor et al., 1995]. Also, PrPTSE has not been detected in milk from cattle incubating BSE following experimental oral challenge [SEAC, 2005]. However, low levels (µg to ng/L) of normal PrP have been detected in milk from both animals and humans [Franscini et al., 2006]. PrPTSE has been detected in the mammary glands of scrapie-infected sheep with chronic mastitis [Ligios et al., 2005], and very recently it has been reported that milk (which in some cases also contained colostrum) from scrapie-infected sheep transmitted disease to healthy animals [Konold et al., 2008; Lacroux et al., 2008].
snip...
please see tables and full text here ;
http://www.who.int/bloodproducts/tablestissueinfectivity.pdf
WITH the confirmed transmission of nvCJD to humans via blood, the ever so emerging strains of TSE called atypical, some much more virulent than that of the typical c-BSE, to continue the practice of feeding animals blood and the spreading of blood on land, in my opinion is a recipe for disaster. ...
layperson
Kind regards,
Terry S. Singeltary Sr. Bacliff, Texas USA
1
APC, Inc.
2425 SE Oak Tree Court :: Ankeny, IA 50021
Division of Dockets Management
(HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
Response to Docket No. 2002N-0273, Proposed Rule Substances Prohibited From Use in Animal
Food or Feed
Executive Summary
APC, Inc. agrees with the conclusion of the FDA that there is no scientific evidence to suggest that BSE infectivity is present in bovine blood. Banning the use of bovine blood or blood fractions in ruminant rations will not reduce the risk of exposure of humans or animals to BSE infectivity. Animal health will be compromised if the use of bovine blood or blood proteins in ruminant feeds is restricted.
APC, Inc. is a member of the North American Spray Dried Blood and Plasma Producers Association (NASDBPP) (see Appendix A). The NASDBPP is a group of companies located in North America involved in the production and development of spray dried blood and plasma products. These companies organized a working group within the American Feed Industry Association (AFIA) with the purpose of developing Manufacturing Standards to insure that the safety of blood derived proteins is preserved. In addition, it is the intention of NASDBPP to insure that data supporting the safe nature of these proteins is communicated to industry and government officials. The NASDBPP is committed to producing safe, high quality blood products for use as an ingredient in feeds for commercial livestock and companion animals. BSE infectivity has never been detected in blood or any component of bovine blood. There is no epidemiological evidence that bovine blood or blood component carries BSE infectivity. Spray dried blood and plasma products are consumed orally, which is the least efficient method of transmission (100,000 times less efficient compared to intracranial injection). The NASDBPP developed Manufacturing Standards to insure that our blood products do not become contaminated with high-risk tissues. The Manufacturing Standards have been reviewed by internationally recognized BSE experts. Finally, the NASDBPP have agreed to and completed annual third party inspections to certify compliance to these Manufacturing Standards.
It is critically important that regulatory policy developed to prevent BSE from becoming established in the US cattle population is grounded on sound science. The NASDBPP support APHIS, FSIS and FDA in their efforts to develop policies to mitigate the risk of BSE. The NASDBPP appreciate the opportunity to comment on the questions and issues raised in the Proposed Rule, Docket No. 2002N-0273, Proposed Rule Substances Prohibited From Use in Animal Food or Feed. We will restrict our comments to the request for further comment and scientific information regarding the need to prohibit the use of blood and blood products in ruminant feed.
2
APC, INC. COMMENTS
There is no scientific evidence to show that the use of bovine blood or blood products in feed pose a risk of BSE transmission in cattle and other ruminants...
snip...
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC201-Attach-1.pdf
1
North American Spray Dried Blood and Plasma Producers
Division of Dockets Management
(HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
Response to Docket No. 2002N-0273, Proposed Rule Substances Prohibited From Use in Animal
Food or Feed
Executive Summary
The North American Spray Dried Blood and Plasma Producers Association agrees with the conclusion of the FDA that there is no scientific evidence to suggest that BSE infectivity is present in bovine blood. Banning the use of bovine blood or blood fractions in ruminant rations will not reduce the risk of exposure of humans or animals to BSE infectivity. Animal health will be compromised if the use of bovine blood or blood proteins in ruminant feeds is restricted...
snip...
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC202-Attach-1.pdf
September 6,2007 Via Overnight Mail Robert L. Martin, Ph D. Office of Food Additive Safety (HFS-255) Center for Food Safety and Applied Nutrition Food and Drug Administration 4300 River Road College Park, Maryland 20740-3835 Re: GRAS Notification for ImmunoLinO Brand Spray-Dried Bovine Globulin Concentrate Intended for Use as an Ingredient in Food
snip...
Importantly, while these studies indicate that transmission of vCJD to human from BSEinfected cattle via blood is a theoretical possibility, the reality is that the potential for transmissibility is substantially reduced by the cross-species barrier.
snip...
http://www.accessdata.fda.gov/scripts/fcn/gras_notices/710670A.PDF
FDA's Comments and Corresponding Changes Made in Response 1. On pg 14, you report a protein digestibility of 93.4% for Bovine Globulin but your notice does not include information about how your calculation was derived. Additionally, the reported 94.4% digestibility value appears to conflict with the statement in Attachment 19 that the IgG in bovine globulin is resistant to digestion. Please explain how you calculated the 94.4% digestibility value and discuss how that value correlates to the high concentration of IgG in your product.
http://www.accessdata.fda.gov/scripts/fcn/gras_notices/808167A.PDF
Wednesday, March 31, 2010
Atypical BSE in Cattle
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.
This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
To date, 27 cases of L-BSE and 24 cases of H-BSE have been reported worldwide (16), thus meaning that the prevalence of atypical BSE is considerably lower than that of C-BSE. However, recent studies showed that L-BSE is easily transmissible to transgenic mice expressing human (17,18) or bovine (19,20) prion protein, as well as to non-human primates (21), with shorter incubation periods than for the transmission of C-BSE to these animals. The virulent nature of L-BSE has stimulated new concern for human public health since the transmission of C-BSE to humans resulted in variant Creutzfeldt-Jakob disease (vCJD) (4-7), a new emergent prion disease.
see full text ;
http://www.nih.go.jp/JJID/64/81.pdf
Ruminant Blood
In contrast with humans, sheep, monkeys, mice and hamsters, including sheep and mice infected with BSE and humans infected with vCJD considered identical to BSE, no infectivity has so far been demonstrated in the blood of BSE infected cattle. However, we consider it unlikely that cattle are the sole outlier to what has been a consistent finding in all other TSE diseases where the measurement has been made with sufficient sensitivity to detect the low levels of infectivity that are present in blood. Rather, this failure is more likely the result of the very small volumes of blood that were used for the inoculations (less than 1 ml), whereas whole transfusions were administered to assay animals in the published sheep scrapie/BSE experiments. If blood is infected then all vascularized tissues can be expected to contain some infectivity in proportion to the content of residual blood.
Micro emboli are a possible source of blood-borne agent that could be at much higher titer than blood itself, in slaughtered cattle carrying BSE infection. Stunning can release micro emboli of brain tissue into the circulatory system from where they can be distributed to other tissues in the few moments before the exsanguination and death. (Anil, et al, 2001a & b; Anil et al, 2002; Love, et al, 2000). This source of infection could extend a higher infectivity risk to tissues that would otherwise be at low risk, thereby allowing exposure of cattle through any of the legal exemptions and potentially producing a feed and food risk. Blood-borne contamination may be a special problem where spray-dried blood is being used as a milk replacer for calves, as it is thought that young animals are especially susceptible to infection.
Certainly, blood and blood proteins should not be used as feed without conclusive evidence that they are safe.
see full text ;
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000490-vol40.pdf
M. E., Simmons M. M., Austin A. R., & Horigan M. W. (1994) Infectivity in the ileum of cattle challenged orally with bovine spongiform encephalopathy. Vet. Rec., 135, 40-41.
Wells G.A.H., Hawkins, S.A.C., Green R. B., Austin A. R., Dexter I., Spencer, Y. I., Chaplin, M. J., Stack, M. J., & Dawson, M. (1998) Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet. Rec., 142, 103-106.
Wyatt. J. M. et al. 1991. Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Veterinary Record. 129. 233.
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[RR1] I am not sure of the point here. If they are going to use dead stock then certainly they should at a minimum remove the CNS tissue but rather I would think the point should be that we don’t want them using dead stock with or without the CNS included.
[RR2]I am not sure that the actual text of the CFR is still required to make the point. However, I am glad I had it to verify the original argument.
THE SEVEN SCIENTIST REPORT ***
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf
http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=FDA-2002-N-0031
9 December 2005 Division of Dockets Management (RFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852
Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed
Dear Sir or Madame:
Serologicals Corporation is a global provider of biological products to life science companies. The Company’s products are essential for the research, development and manufacturing of biologically based diagnostic, pharmaceutical and biological products. customers include many of the leading research institutions, diagnostic and pharmaceutical companies throughout the world. The Company’s products and technologies are used in a wide variety of applications within the areas of neurobiology, cell signaling, oncology, angiogenesis, apoptosis, developmental biology, cellular physiology, hematology, immunology, cardiology, infectious diseases and molecular biology. A number of our products are derived from bovine blood or other bovine tissues sourced in the United States, hence the overall health of the national herd is extremely important to our company as well as to our customers and their patients. Some of our bovine based products are used in the manufacture of vaccines and drugs for humans, hence it is critical that all measures are taken to assure these are safe and free from disease especially Bovine Spongiform Encephalopathy (BSE).
The most effective way to insure this is to create a system which processes cattle that are BSE free. As a company there are a number of precautions that we can take by our strict specifications but many of the needed precautions require the force of federal regulation, hence we appreciate the opportunity to submit comments to this very important proposed rule. After the identification of bovine spongiform encephalopathy (BSE) in indigenous North American cattle, the U.S. Department of Agriculture (USDA) responded rapidly to implement measures to protect public health in regard to food. Our company recognizes and supports the importance of the current feed ban which went into effect in August 1997. However, given what is known about the epidemiology and characteristically long incubation period of BSE, we urge
5655 Spalding Drive * Norcross, GA 30092 678-728-2000 * 800-842-9099 * Facsimile 678-728-2299 http://www.serologicais.com Division of Dockets Management (HFA-305) Page 2 9 December 2005
the FDA to act without further delay and implement additional measures which will reduce the risk of BSE recycling in the US cattle herd. We feel that for the FDA to provide a more comprehensive and protective feed ban, specified risk materials (SRMs) and deadstock must be removed from all animal feed and that legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk) should be discontinued. SRMs, as defined by the USDA, are tissues which, in a BSE infected animal, are known to either harbor BSE infectivity or to be closely associated with infectivity. If SRMs are not removed, they may introduce BSE infectivity and continue to provide a source of animal feed contamination. Rendering will reduce infectivity but it will not totally eliminate it. This is significant as research in the United Kingdom has shown that a calf may be infected with BSE by the ingestion of as little as .OOl gram of untreated brain. The current proposed rule falls short of this and would still leave a potential source of infectivity in the system. In fact by the FDA’s own statement the exempted tissues which are known to have infectivity (such as distal ileum, DRGs, etc) would cumulatively amount to 10% of the infectivity in an infected animal, This proposed rule would still allow for the possibility that cattle could be exposed to BSE through:
1. Feeding of materials currently subject to legal exemptions from the ban (e.g., poultry litter, plate waste)
2. Cross feeding (the feeding of non-ruminant rations to ruminants) on farms; and
3. Cross contamination of ruminant and non-ruminant feed
We are most concerned that the FDA ha chosen to include a provision which would allow tissues from deadstock into the feed chain. We do not support the provision to allow the removal of brain and spinal cord from down and deadstock over 30 months of age for several reasons. These are the animals with the highest level of infectivity in tissues which include more than brain and spinal cord. We do not feel that there can be adequate removal and enforcement of this regulation especially during warmer weather. In addition there is emerging information that at end stage disease, infectivity may also be included in additionai tissues such as peripheral nerves (Buschmann and Groschup, 2005). Leaving the tissues from these cattle in the animal feed chain will effectively nullify the intent of this regulation. This point is illustrated by the 2001 Harvard risk assessment model which demonstrated that eliminating dead and downer, 4D cattle, from the feed stream was a disproportionately effective means of reducing the risk of re-infection “The disposition of c&e that die on the farm would also have a substantial influence on the spread of BSE if the disease were in traduced. ” The base case scenario showed that the mean total number ofID.50~ (i.e., dosage sufficient to infect SO percent of exposed cattte) from healthy animals at slaughter presented to the food/feed system was 1500, The mean total number of ID.50.s from adult cattle Division of Dockets Management (HFA-305) Page 3 9 December 2005 deadstockpresented to the feed system was 3 7,000. deadstock). This illustrates the risk of “40 cattle” (i.e., From the Harvard Risk Assessment, 2001, Appendix 3A Base Case and Harvard Risk Assessment, 200 1
Executive Summary
Serologicals and companies like ours which supply components of drugs and biologicals have a responsibility to the manufacturers of these products, the medical community and their patients as well as regulatory agencies throughout the world to provide the safest products as possible. Since there is no test for BSE in live cattle or for product, the regulatory agencies throughout the world expect us to reduce or eliminate risk via suurcing criteria, These parameters may include but not be limited to country of origin, herd of origin, age of the animal, etc. The United States is no longer a country with negligible risk, hence individual animal criteria has become more important. In fact other Centers of the FDA have stated that more attention should be given to sourcing from herds likely to be a source of BSE free animals. The exemptions in the current ban as well as in the newly proposed rule make this difficult if not impossible as there are still legal avenues for ruminants to consume potentially contaminated ruminant protein. In addition, the USDA still has not implemented a system of identification and traceability. Serologicals urges agencies of the US government to work with academia and industry on research in the following areas: e Methods to inactivate TSEs agents which then may allow a product to be used and even fed to animals without risk l Alternative uses for animal byproducts which would maintain value Serologicals will continue to work with the FDA and other government agencies to implement a strong BSE risk control program, Serologicals would like to reiterate our opinion that for the FDA to provide a more comprehensive and protective feed ban, specified risk materials (SRMs) and deadstock must be removed from all animal feed and that legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk) should be discontinued. Thank you for the opportunity to submit these comments to the public record. Respectfully, SEROLOGICALS CORPORATION James J. Kramer, Ph.D. Vice President, Corporate Operations
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000435-01-vol36.pdf
03-025IFA 03-025IFA-2 Terry S. Singeltary
From: Terry S. Singeltary Sr. [flounder9@verizon.net] Sent: Thursday, September 08, 2005 6:17 PM To: fsis.regulationscomments@fsis.usda.gov Subject: [Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
see Dr. Paul Brown and Seven Scientists comments here ;
Signatories:
Paul W. Brown, M.D. Medical Director, USPHS, and Senior Investigator, NIH (retired) Consultant, TSE Risk Management 7815 Exeter Rd. Bethesda, MD 20814 Fax 301-652-4312 Email: paulwbrown@comcast.net
Neil R. Cashman MD Professor, Department of Medicine (Neurology) Diener Chair of Neurodegenerative Diseases Centre for Research in Neurodegenerative Diseases 6 Queen's Park Crescent West Toronto Ontario M5S3H2 Ph: 416-978-1875 Fax: 416-978-1878 e-mail: neil.cashman@utoronto.ca
Linda A. Detwiler, DVM Consultant, TSE Risk Management 225 Hwy 35 Red Bank, NJ 07701 Ph 732-741- 2290 Fax 732-741-7751 Email: LAVet22@aol.com
Laura Manuelidis, MD Professor and Head of Neuropathology, Department of Surgery and Faculty of Neurosciences Yale Medical School 333 Cedar St. New Haven, CT 06510 email: laura.manuelidis@yale.edu Tel: 203-785-4442 Deleted: p Deleted: 14 Formatted FDA Proposed Rule December 20, 2005
Jason C. Bartz, Ph.D. Assistant Professor Department of Medical Microbiology and Immunology Creighton University 2500 California Plaza Omaha, NE 68178 (402) 280-1811 voice (402) 280- 1875 fax jbartz@creighton.edu
Robert B. Petersen, Ph.D. Associate Professor of Pathology and Neuroscience Case Western Reserve University 5-123 Wolstein Building 2103 Cornell Road Cleveland, OH 44106-2622 Phone 216-368-6709 FAX 360-838-9226 Email rbp@cwru.edu
Robert G. Rohwer, Ph.D. Director, Molecular Neurovirology Laboratory Veterans Affairs Medical Center Medical Research Service 151 Assoc. Professor of Neurology School of Medicine University of Maryland at Baltimore 10 N. Greene St. Baltimore, MD 21201 ph. 410-605-7000 x6462 Fax 410-605-7959 email: rrohwer@umaryland.edu
FDA-2002-N-0031-0131 Paul W. Brown, et al - Comment 02/23/2009 PUBLIC SUBMISSIONS FDA-2002-N-0031-0131.1 Paul W. Brown, et al - Comment 02/23/2009
PUBLIC SUBMISSIONS
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064808b3843&disposition=attachment&contentType=pdf
http://www.regulations.gov/fdmspublic/custom/jsp/search/searchresult/docketDetail.jsp#
December 19, 2005 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852 Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Dear Sir or Madame: The McDonald's Corporation buys more beef than any other restaurant in the United States.
snip...
SRMs, as defined by the USDA, are tissues which, in a BSE infected animal, are known to either harbor BSE infectivity or to be closely associated with infectivity. If SRMs are not removed, they may introduce BSE infectivity and continue to provide a source of animal feed contamination. Rendering will reduce infectivity but it will not totally eliminate it. This is significant, as research in the United Kingdom has shown that a calf may be infected with BSE by the ingestion of as little as .001 gram of untreated brain. The current proposed rule falls short of this and would still leave a potential source of infectivity in the system. In fact by the FDA's own statement the exempted tissues which are known to have infectivity (such as distal ileum, DRGs, etc) would cumulatively amount to approximately 10% of the infectivity in an infected animal. Leaving approximately 10% of the infectious tissues in the system is not good enough.
snip...
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273_emc-000134-02.pdf
9 December 2005 Division of Dockets Management (RFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852 Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Dear Sir or Madame: Serologicals Corporation is a global provider of biological products to life science companies.
We feel that for the FDA to provide a more comprehensive and protective feed ban, specified risk materials (SRMs) and deadstock must be removed from all animal feed and that legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk) should be discontinued. SRMs, as defined by the USDA, are tissues which, in a BSE infected animal, are known to either harbor BSE infectivity or to be closely associated with infectivity. If SRMs are not removed, they may introduce BSE infectivity and continue to provide a source of animal feed contamination. Rendering will reduce infectivity but it will not totally eliminate it. This is significant as research in the United Kingdom has shown that a calf may be infected with BSE by the ingestion of as little as .OOl gram of untreated brain. The current proposed rule falls short of this and would still leave a potential source of infectivity in the system. In fact by the FDA's own statement the exempted tissues which are known to have infectivity (such as distal ileum, DRGs, etc) would cumulatively amount to 10% of the infectivity in an infected animal, This proposed rule would still allow for the possibility that cattle could be exposed to BSE through:
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000383-01-vol35.pdf
2002N-0273 Animal Proteins Prohibited in Ruminant Feed
FDA Comment Number : EC240
Submitter : Mr. Masahiro Mori Date & Time: 01/04/2006 05:01:26
Organization : Embassy of Japan
Category : International Government
Issue Areas/Comments
GENERAL
GENERAL
Comments of Japan on the United States? WTO/SPS Notification (G/SPS/N/USA/1141)
The Government of Japan welcomes the opportunity to comment on the United States? notification (G/SPS/N/USA/1141) on substances prohibited from use in Animal food or feed.
The Food safety risk assessment related to the import of beef and beef offal from the U.S.A. and Canada by the Food Safety Commission of Japan (FSC) was completed on December 8, 2005. Regarding the feed ban, the following was noted as an addendum to the conclusion on the risk assessment report of FSC:
?To prevent BSE exposure and amplification in U.S.A and Canada, the use of SRM must be prohibited completely. The ban must be applied not only to cattle feed but also to all other animal food/feed that may cause cross-contamination.?
To accomplish the effectively enforced feed ban requested in the OIE Terrestrial Animal Health Code (CHAPTER 2.3.13, Bovine Spongiform Encephalopathy), whole SRM should be excluded as high risk material from animal feed chain as the above-mentioned addendum points out. The U.S. Government should also carry out continuous BSE surveillance sufficient to verify the efficacy of U.S. feed ban and make necessary revision of its feed regulations on a basis of its results.
The Government of Japan would like to request that the U.S. Government take account of the above comments in implementing its animal food and feed regulations.
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC240.htm
Substances Prohibited From Use in Animal Food or Feed; Final Rule: Proposed Delay of Effective Date - Notice of Final Rule Send a Comment or Submission Notification Comments Due: Apr 16, 2009 11:59:59 PM EDT Docket ID: FDA-2002-N-0031
Document ID: FDA- 2002-N-0031-0132 Date Posted: Apr 9, 2009 View this Document:
http://www.regulations.gov/fdmspublic/ContentViewerobjectId=090000648094bc24&disposition=attachment&contentType=pdf
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648094bc24&disposition=attachment&contentType=html
http://www.regulations.gov/search/search_results.jsp?css=0&&Ntk=All&Ntx=mode+matchall&Ne=2+8+11+8053+8054+8098+8074+8066+8084+8055&N=0&Ntt=Substances%20Prohibited%20From%20Use%20in%20Animal%20Food%20or%20Feed%3B%20Final%20Rule%3A%20Proposed&sid=1208CC5B88DF
submit here ;
http://www.regulations.gov/fdmspublic/component/main?main=SubmitComment&o=090000648094bc24
THE SEVEN SCIENTIST REPORT ***
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf
http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=FDA-2002-N-0031
NATIONAL RENDERERS ASSOCIATION,
Inc. 801 N. Fairfax Street Suite 205 Alexandria, Virginia 22314 Tel: (703) 683-0155 Fax: (703) 683-2626
March 12, 2007 Docket No. 050-15-1 Regulatory Analysis and Development, PPD, APHIS Station 3A-03.8 4700 River Road Unit 118 Riverdale, Maryland 20737-1238 Re: Docket No. APHIS-2006-0041, Bovine Spongiform Encephalopathy; Minimal-Risk Regions; Importation of Live Bovines and Products Derived from Bovines.
To Whom It May Concern: The National Renderers Association (NRA) references APHIS’s Docket No. APHIS-2006-0041, the agency’s proposed rule to import cattle and products. NRA is the international trade association for the industry that safely and efficiently recycles animal agriculture by-products into valuable ingredients for the livestock, pet food, chemical and consumer product industries. NRA represents its members’ interests to Congress, regulatory and other government agencies, promotes greater use of rendered products, and fosters the opening and expansion of trade between North American exporters and foreign buyers. NRA’s membership represents more than 98% of the rendering capacity in both the U.S. and Canada. In the proposed rule the USDA details the criterion necessary for the importation of bovine blood products. Specifically the USDA explain: “For all the above three manners of collection, we would require that the blood be collected in a closed system or in an otherwise hygienic manner that prevents contamination of the blood with SRMs.” 1
With current line speeds in U.S. beef slaughter facilities a closed collection system (as described by the USDA in the proposed rule) is not practical and would be cost prohibitive for production of the feed ingredients spray dried bovine plasma or blood meal. Requiring such a collection system would effectively eliminate the supply of feed grade bovine plasma and blood meal. Restricting these products by requiring blood to be collected by a closed system would result in significant damage to the livestock industry both domestically and around the world. Traditional closed collection systems as suggested in the Proposed Rule may be appropriate for the collection of Fetal Calf Serum and other specialized blood products but are impractical for collection of blood used for feed application. The infective agent responsible for BSE has not been identified in bovine blood (USDA’s reference, OIE 2005). However, the North American Spray Dried Blood and Plasma Producers and the NRA recognized the potential for contamination of raw materials with SRM during collection and subsequent processing and have developed a series of Manufacturing Guidelines and a Code of Practice designed to minimize the risk of contamination. These programs include third party audits by the Facilities Certification Institute to ensure compliance with the manufacturing guidelines. These Manufacturing Guidelines have been successfully implemented at the spray dried blood facilities (including Canada) and the Code of Practice has been certified at more than 35 high volume rendering plants in the U.S. so far with many more underway. Many Canadian rendering plants operate under equally effective HACCP programs. Spray dried plasma is a unique feed ingredient. There are no effective substitutes for spray dried plasma. It is important that animal agriculture industry continues to have an adequate supply of this critical feed ingredient. A number of recognized academic and industry organizations agree that continued access to adequate supplies of spray dried bovine blood products is critical. Bovine blood meal represents a very valuable feed ingredient especially for the rations of the lactating dairy cow. It provides high levels of lysine that does not degrade in the rumen. High levels of lysine are necessary to maintain optimum levels of milk production. If bovine blood meal were removed from use in rations, the price of porcine blood meal will continue to increase, placing an additional financial burden on the dairy industry among others. In 2001, the Sparks Company evaluated the impact of prohibiting cattle derived blood meal in ruminant diets on behalf of the NRA. In 2000, 1.48 billion pounds of blood were generated from the slaughter of cattle. A resulting 121.9 million pounds of cattle blood meal and 49.8 million pounds of mixed species blood meal were manufactured. Total ruminant containing blood meal produced was 171.7 million pounds, 70% of which was utilized in ruminant diets. The study determined if the use of blood meal were prohibited in cattle diets, a product loss of $45.3 million would be realized by the cattle sector. Additional indirect losses from reduced animal productivity at the farm level were not considered by the report and are estimated below. [http://www.renderers.org/economic_impact/index.htm] 2
The unique nutritional properties of blood meal, primarily a high level of non-degradable lysine, provide a high return when used by dairy producers. Lysine is considered the first limiting amino acid vital to high milk production. Unlike poultry and swine, high producing dairy cows can’t utilize synthetic lysine, thus milk production will drop if this ingredient is removed. Typically 0.5 pounds/day of dried blood meal is fed to a dairy cow. A reduction of 4 pounds of milk/cow/day would be expected if blood meal were no longer utilized in these diets. Using the figure from the Sparks report that 70% of ruminant blood meal was utilized in dairy rations, an overall drop in milk production of 9.6 million hundredweight would occur. At $12/cwt this loss in milk production would reduce dairy farm income by $115.4 million. Thus, combined losses to the U.S. beef cattle and dairy sectors would total $160.7 million. It is critical the dairy industry continues to have access to bovine blood and bovine blood fractions. Over 41% of the heifer calves raised in the U.S. suffer from failure of passive transfer due to inadequate colostral Ig intake. Approximately 11% of heifer calves died before weaning, and half of this mortality can be attributed to inadequate supply of quality colostrum (NAHMS, 1992, 1996). Colostrum is also recognized as a vector for transmission of a number of disease-causing organisms, including Mycobacterium paratuberculosis (Johne’s disease). Published studies indicate bovine serum and fractions thereof are the only effective alternatives for colostrum (Arthington, et al., 2000 a,b; Quigley et al., 1998, 2000, 2001; McCoy et al, 1997; Holloway et al, 2002; Poulsen et al, 2003). If access to these proteins is restricted, there is no effective alternative to reduce calf mortality or to break these disease cycles. For a more complete review see the review of Quigley et al. (2004). Many studies from the involved sectors have been shared with FDA on the economic and environmental impacts of banning the use of bovine blood meal in feed, especially representatives from blood processors and the poultry industry. Collectively, the dual impacts (economic and environmental) could be very great on the industries. If these products are prohibited from animal feed, there is reduced market for such products and their disposal costs increase. This could lead to improper disposal, disposal in landfills, or by land application on farms. If feeding of blood meal were prohibited for cows, farmers would either feed higher protein levels and/or milk additional cows to maintain milk production. Either course of action would result in increased nitrogen and methane release into the environment. There is no need to stop the feeding of ruminant blood products to ruminants or any other animals because there is no science to support such a restriction. There is no scientific or peer reviewed literature linking the feeding of bovine blood in the form of blood meal or other blood products in feed to any risk of BSE transmission in cattle and other ruminants. Bovine blood has never been implicated in bovine-to-bovine transmission of either natural or experimental BSE. If there are concerns that some collection methods could allow small amounts of neural tissue to be collected with the blood, technology can be employed to remove neural tissue 3 from blood without requiring the closed system or sterile procedures. The possibility was considered in the Harvard Risk Analysis and not deemed a significant risk to spread BSE. Products resulting from processes such as filtering or centrifuging should be allowed to be imported because these steps would remove any particles or tissue residue. Any unnecessarily restrictive regulation imposed on minimum risk regions by the U.S. could easily be applied to U.S. products globally and cause severe problems with the marketing of blood products which are safe and extremely valuable to livestock and aquaculture production. The NRA urges the USDA to resume the import of blood products from minimal risk regions fo n feed applications when those products are produced in a manner consistent with the current manufacturing guidelines. Sincerely, David L. Meeker, Ph.D., MBA Vice President, Scientific Services National Renderers Association 4
http://www.animalprotein.org/news_articles/NRA_Comments_APHIS_Minmal_Risk_Rule_3-07.pdf
"Bovine blood has never been implicated in bovine-to-bovine transmission of either natural or experimental BSE"
yep, that's what they use to say about the blood from the nvCJD victims too, however they were wrong about that too. so to wait until bovine blood has been implicated, by then, it's too late. ...TSS
Fourth case of transfusion-associated vCJD infection in the United Kingdom
Editorial team (eurosurveillance.weekly@hpa.org.uk), Eurosurveillance editorial office
A case of variant Creutzfeldt-Jakob disease (vCJD) has recently been diagnosed in a patient in the United Kingdom (UK), who received a blood transfusion from a donor who later developed vCJD [1]. This is the fourth case of probable transfusion transmission of vCJD infection in the UK. Three of the four recipients developed symptoms of vCJD. The first symptomatic case of vCJD associated with blood transfusion was identified in December 2003. This individual developed vCJD six and a half years after transfusion of red cells donated by an individual who developed symptoms of vCJD three and a half years after donation.
A second case of vCJD 'infection' was identified a few months later in a person who had received red cells from a donor who developed symptoms of vCJD 18 months after donation. This patient (the second case) died from causes unrelated to vCJD five years after transfusion. Post-mortem investigations found abnormal prion protein in the spleen and a cervical lymph node., However, prion protein was not found in the brain, and no pathological features of vCJD were found.
A third case developed symptoms of vCJD six years after receiving a transfusion of red blood cells, and died two years and eight months later. The donor of the blood involved developed vCJD about 20 months after donating it.
These three cases have been published as case reports and in the findings of the ongoing collaborative study between the National Blood Services, the National CJD Surveillance Unit, and the Office for National Statistics. This study aims to collect evidence about transmission of CJD or vCJD via the blood supply [2,3,4,5].
The new, fourth case is in a patient who developed symptoms of vCJD eight and a half years after receiving a transfusion of red blood cells from a donor who developed vCJD about 17 months after this blood was donated [1]. The donor to this case also donated the vCJD-implicated blood transfused to the third case. As for all other reported clinical vCJD cases that have been tested for genotype, this patient is a methionine homozygote at codon 129 of the prion protein gene. The patient is currently alive.
All four cases had received transfusions of non-leucodepleted red blood cells between 1996 and 1999. Since October 1999, leucocytes have been removed from all blood used for transfusion in the UK. The effect of leucodepletion on the reduction of the risk of transmission of vCJD from an infective donation is uncertain.
This fourth case of vCJD infection associated with blood transfusion further increases the level of concern about the risk of vCJD transmission between humans by blood transfusion, although much remains unknown. This reinforces the importance of the existing precautions that have been introduced to reduce the risk of transmission of vCJD infection by blood and blood products [6]. No cases of vCJD have been associated with fractionated plasma products. The small group of living recipients of vCJD-implicated blood transfusion in the UK have been informed of their potential exposure to vCJD by blood transfusion, asked to take certain precautions to reduce the risk of onward person-to-person transmission of vCJD during health care, and offered specialist neurological evaluation and advice.
This article has been adapted from reference 1
References: Health Protection Agency. Fourth case of variant CJD associated with blood transfusion (press release). Press release, 18 January 2007. (http://www.hpa.org.uk/hpa/news/articles/press_releases/2007/070118_vCJD.htm) Llewelyn CA, Hewitt PE, Knight RSG, Amar K, Cousens S, Mackenzie J, et al. Possible transmission of variant CJD disease by blood transfusion. Lancet 2004; 363:417-21. Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004 ; 364: 527-9. Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, et al Clinical presentation and pre-mortem diagnosis of blood transfusion-associated variant CJD. Lancet 2006;368:2061-67. Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiology review study. Vox Sang. 2006;91(3):221-230. Department of Health [London]. Further precautions to protect blood supply. Press release 2004/0104, 16 March 2004.
(http://www.dh.gov.uk/PublicationsAndStatistics/PressReleases/PressReleasesNotices/fs/en?CONTENT_ID=4076608&chk=MTwE%2Bl)
http://www.eurosurveillance.org/ew/2007/070118.asp
http://bloodindex.org/view_news_zone.php?id=206
HARVARD BSE risk assessment was a joke as well, bought and paid for by your local cattle dealer i.e. USDA et al
*** Suppressed peer review of Harvard study October 31, 2002 ***
http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf
[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) [TSS] Date: August 26, 2006 at 12:09 pm PST
From: Terry S. Singeltary Sr. [flounder9@verizon.net]
Sent: Monday, July 24, 2006 1:09 PM
To: FSIS RegulationsComments
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
Page 1 of 98
8/3/2006
Greetings FSIS,
snip... see full text ;
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
Response to Public Commentson theHarvard Risk Assessment of Bovine SpongiformEncephalopathy Update,October 31, 2005
snip...
RESPONSE TO COMMENTS FROM TERRY S. SINGELTARY SR.
Comment #1: SINCE the first Harvard BSE Risk Assessment was so flawed and fraught with error after the PEER REVIEW assessment assessed this fact, how do you plan on stopping this from happening again, will there be another peer review with top TSE Scientists, an impartial jury so-to-speak, to assess this new and updated Harvard BSE/TSE risk assessment and will this assessment include the Atypical TSE and SRM issues?
Response: The original (October 2003) and the revised (October 2005) Harvard BSE risk assessments underwent external peer review. Subsequently, revisions were made to the analysis. In the most recent review, the most significant revisions have been:
1) theaddition of explicit modeling of the poultry litter pathway for the potential recycling ofbovine protein into cattle feed; and
2) a decrease in the assumed effectiveness of antemortem inspection in the identification of animals with BSE.
Comment #2: WITH A RECENT NATION WIDE MAD COW FEED BAN RECALL in the past few months that consisted of some 10,878.06 TONS, then another Mad Cow feed ban warning letter in May, IT should seem prudent to ask why our feed bans continue to fail in 2006, and continue to fail today?
Response: This question about feed bans is a matter for policy. As such, it is not addressed in this response.
Comment #3: WHY still now only partial ruminant feed ban, with the fact that now we seem to have 3 cases of nvCJD to humans i.e. human bovine TSE that were responsible from blood, and the fact the last 2 mad cows documented in the USA were that of an Atypical strain, would it not seem prudent to remove blood as well from ruminant feed?WOULD it not seem prudent to improve and expand the SRM list now? as per your ownthinking; If transmission occurs, tissue distribution comparisons will be made between cattle infected with the atypical BSE isolate and the U.S. BSE isolate. Differences in tissue distribution could require new regulations regarding specific risk material (SRM)removal.
Response: This comment pertains to policy. As such, it is not addressed here.
Comment #4: WHAT does USDA/FDA ET AL intend to do about the risks of atypical BSE/TSE in cattle now that infectivity shows in tissue samples other than CNS in Japan, the fact now that the last Texas mad cow and that last mad cow in Alabama were indeed of the atypical strain, the fact that the studies long ago in Mission, Texas of USA sheep scrapie transmission to the USA bovine, which proved an 'atypical tse' in the USA bovine, the fact also that USDA/FDA are still floundering on the last SRM regulations, but with the BASE strain now in cattle that is not similar to nvCJD, but very similar to the sporadic CJD, and sporadic CJD has tripled in the last few years in the USA. WHAT do you plan to do to protect human health from these atypical strains of TSE, in relations to SRMs ?
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Page 20
Response: The BSE risk assessment simulation model characterizes the disease history of BSE, including the agent's spread within the body of the animal over time. It also quantifies the agent's persistence during the feed manufacture process, and ultimately the agent's ability to cause disease in other exposed animals. There is no definitive evidence that these properties differ substantially for atypical BSE strains, compared to the typical BSE agent.
Comment #5: THE 2004 Enhanced BSE surveillance program, that tested all those cows, but then we found just how terribly flawed the program was, from testing protocols, to testing the most likely to have BSE i.e. high risk, to the geographical distribution of the testing and high risk areas, to letting the tissue samples of one mad cow sit on a shelf for 7+ months and then having to have an act of Congress to ever get that cow finally confirmed, to that other Texas mad cow they decided to not even bother testing at all, just rendered that very suspect cow, too suspect to test evidently, back to that Alabama madcow that they could only give a guess as to age with dentition where we all know that the age of that cow was so close to 10 years it could have been 9 years 7 months to 10 years 3 months, thus possibly being an BAPB i.e. USA 'born after partial ban', to all those rabies suspect cows that did not have rabies, and DID NOT get tested for BSE/TSE in that June 2004 enhanced surveillance program, even though the common lay person knows the suspect rabies negative cows are suppose to be BSE/TSE tested, how does one correct all these blatant failures and will they be corrected?
Response: This comment pertains to policy. As such, it is not addressed here.
Comment #6: WHAT happened to the test results and MOUSE BIO-ASSAYS of those imported sheep from Belgium that were confiscated and slaughtered from the Faillace's, what sort of TSE did these animals have?
Response: It is not clear how the test results referred to in this comment are relevant to the Harvard BSE Risk Assessment Update. Sheep were not considered in the risk assessment.
Comment #7: WHY is it that the Farm of the Mad Sheep of Mad River Valley were quarantined for 5 years, but none of these farms from Texas and Alabama with Atypical TSE in the Bovine, they have not been quarantined for 5 years, why not, with the real risk of BSE to sheep, whom is to say this was not BSE ?
Response: This comment pertains to policy. As such, it is not addressed here.
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FULL TEXT ;
http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf
and just recently, private email from abroad, you can take this with how ever many grains of salt you wish ;
snip...
we had four cases of 'typical' BSE over a four year period. Herd size around 120. Two of these were half sisters, born a year apart. Their mother stayed in the herd until she died at a good age of other reasons. Friends and neighbours were hit much harder. We had four young cows 'taken' for slaughter as 'cohorts' at a later date.
We had close links with a farm advisor and nutritionist working for a local feed compounder, and a few years later were made aware that the feed company had been given notice that blood meal inclusion would be banned in a couple of months time. As they had 200 tonnes in stock, the inclusion rate was dramatically raised (farmers later were asking for the dark brown cake that the heifers grew so well on) to use the stocks up. Two of our clinical cases were fed this cake before we knew better. Ingredient declaration was not made, only nutritional analysis. The timing also co-incided with permission being given to the big rendering companies to be allowed to lower the processing temperatures (first fuel crisis, and Mrs Thatcher's husband was on the board of the largest processor)...snip...end...TSS
Schweiz Arch Tierheilkd. 2009 Sep;151(9):433-6.
[Protease-resistant prion protein (PrPres) in the blood of offspring of cows that developed BSE].
[Article in German] Braun U, Tschuor A, Hässig M, Franitza S, Berli E, El Gedaily A, Franscini N, Matthey U, Zahn R. SourceDepartement für Nutztiere der Universität Zürich. ubraun@vetclinics.uzh.ch
Abstract The goal of the present study was to investigate whether protease-resistant prion protein (PrPres) occurs in plasma samples of offspring of cows that developed bovine spongiform encephalopathy (BSE; group A) and to compare the prevalence with that of a healthy control group in 2006 (Group B). Group A consisted of 181 offspring of cows that developed BSE and group B consisted of 240 healthy animals from a region in Switzerland where no cases of BSE occurred from 2001 to the end of 2006. All plasma samples were evaluated using Alicon PrioTrap, an antemortem test for PrPres. The time between birth of the offspring and onset of BSE in the dam was calculated to determine its relationship with the presence of PrPres in the plasma of the offspring. From 181 offspring, 29 (16.1%) had PrPres-positive plasma samples. Offspring that were born within one year of the onset of BSE in the dam had a significantly higher prevalence of PrPres-positive plasma samples than those born more than one year before the onset of BSE in the dam. Ten (4.2%) of 240 control cattle had PrPres-positive plasma samples. Thus, PrPres can be detected in bovine blood and occurs more frequently in the offspring of cows that develop BSE than in cattle of a healthy control population.
PMID:19722131[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/19722131
http://www.cabdirect.org/abstracts/20093248407.html;jsessionid=24FBC2B634B62B6FDE444A591296B3AF
http://agris.fao.org/agris-search/search/display.do?f=2010/CH/CH1001.xml;CH2010000047
COMERCIAL IN CONFIDENCE
SPREADING OF UNPROCESSED BLOOD ON LAND
http://web.archive.org/web/20040315202749/www.bseinquiry.gov.uk/files/yb/1991/02/15003001.pdf
I suppose my next concern besides the potential for transmission of TSE PrP via blood in feed, my next concern from spreading blood on the ground would be TSE infection to the soil, thus contaminating pasture land for years, and years. ...TSS
Saturday, January 24, 2009
Research Project: Detection of TSE Agents in Livestock, Wildlife, Agricultural Products, and the Environment Location: 2008 Annual Report
http://bse-atypical.blogspot.com/2009/01/research-project-detection-of-tse.html
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
Karen Fernie, Allister Smith and Robert A. Somerville The Roslin Institute and R(D)SVS; University of Edinburgh; Roslin, Scotland UK
Scrapie and chronic wasting disease probably spread via environmental routes, and there are also concerns about BSE infection remaining in the environment after carcass burial or waste 3disposal. In two demonstration experiments we are determining survival and migration of TSE infectivity when buried for up to five years, as an uncontained point source or within bovine heads. Firstly boluses of TSE infected mouse brain were buried in lysimeters containing either sandy or clay soil. Migration from the boluses is being assessed from soil cores taken over time. With the exception of a very small amount of infectivity found 25 cm from the bolus in sandy soil after 12 months, no other infectivity has been detected up to three years. Secondly, ten bovine heads were spiked with TSE infected mouse brain and buried in the two soil types. Pairs of heads have been exhumed annually and assessed for infectivity within and around them. After one year and after two years, infectivity was detected in most intracranial samples and in some of the soil samples taken from immediately surrounding the heads. The infectivity assays for the samples in and around the heads exhumed at years three and four are underway. These data show that TSE infectivity can survive burial for long periods but migrates slowly. Risk assessments should take into account the likely long survival rate when infected material has been buried.
The authors gratefully acknowledge funding from DEFRA.
PPo8-13:
Degradation of Pathogenic Prion Protein and Prion Infectivity by Lichens
Christopher J. Johnson,1 James P. Bennett,1 Steven M. Biro,1,2 Cynthia M. Rodriguez,1,2 Richard A. Bessen3 and Tonie E. Rocke1
1USGS National Wildlife Health Center; 2Department of Bacteriology; University of Wisconsin, Madison; 3Department of Veterinary Molecular Biology; Montana State University; Bozeman, MT USA
Key words: prion, lichen, bioassay, protease, degradation
Few biological systems have been identified that degrade the transmissible spongiform encephalopathy (TSE)-associated form of the prion protein (PrPTSE) and TSE infectivity. Stability of the TSE agent allows scrapie and chronic wasting disease agents to persist in the environment and cause disease for years. Naturally-occurring or engineered processes that reduce infectivity in the environment could aid in limiting environmental TSE transmission. We have previously identified that species of at least three lichens, unusual, symbiotic organisms formed from a fungus and photosynthetic partner, contain a serine protease capable of degrading PrPTSE under gentle conditions. We tested the hypothesis that lichen extracts from these three species reduce TSE infectivity by treating infected brain homogenate with extracts and examining infectivity in mice. We found lichen extracts diminished TSE infectious titer by factors of 100 to 1,000 and that reductions in infectivity were not well-correlated with the extent of PrPTSE degradation observed by immunoblotting. For example, treatment of brain homogenate with Cladonia rangiferina extract caused <100-fold reduction in PrP immunoreactivity but ~1,000-fold decrease in infectivity, suggesting that some PrPTSE remaining after extract treatment was rendered uninfectious or that the lichen protease favors more infectious forms of PrPTSE. Our data also indicate that lichen species closely related to those with prion-degrading protease activity do not necessarily degrade PrPTSE.
Characterization of the lichen species-specificity of PrPTSE degradation within the genera Cladonia and Usnea and comparison with known lichen phylogeny has yielded clusters of species on which to focus searches for anti-prion agents.
TSEs And The Environment The LANCET Volume 351, Number 9110 18 April 1998
BSE: the final resting place
How to dispose of dangerous waste is a question that has vexed the human race for hundreds of years. The answer has usually been to get it out of sight--burn it or bury it. In Periclean Athens, victims of the plague were incinerated in funeral pyres; in 14th century Venice, a law stipulated that Black Death corpses should be buried to a minimum depth of 5 feet; and now, as the 20th century draws to a close, we are challenged by everything from industrial mercury to the smouldering reactors of decommissioned atomic submarines. The Irish Department of Agriculture will convene an expert panel on April 27-29 to discuss the disposal of tissues from animals with bovine spongiform encephalopathy (BSE). Proper disposal of tissues from infected cattle has implications for both human and animal safety. Safety for human beings is an issue because there is now unassailable if still indirect evidence that BSE causes infections in man in the form of "new variant" Creutzfeld-Jakob disease (nvCJD).1-3 Safety for animals is also an issue because BSE-affected cattle could possibly transmit disease to species other than cattle, including sheep, the species that was almost surely the unwitting source of the BSE epidemic. The first matter to consider is the distribution of infectivity in the bodies of infected animals. The brain (and more generally, the central nervous system) is the primary target in all transmissible spongiform encephalopathies (TSE), and it contains by far the highest concentration of the infectious agent. In naturally occuring disease, infectivity may reach levels of up to about one million lethal doses per gram of brain tissue, whether the disease be kuru, CJD, scrapie, or BSE. The infectious agent in BSE-infected cattle has so far been found only in brain, spinal cord, cervical and thoracic dorsal root ganglia, trigeminal ganglia, distal ileum, and bone marrow.4 However, the much more widespread distribution of low levels of infectivity in human beings with kuru or CJD, and in sheep and goats with scrapie, suggests that caution is advisable in prematurely dismissing as harmless other tissues of BSE-infected cattle. A second consideration relates to the routes by which TSE infection can occur. Decades of accumulated data, both natural and experimental, have shown clearly that the most efficient method of infection is by direct penetration of the central nervous system; penetration of peripheral sites is less likely to transmit disease. Infection can also occur by the oral route, and the ingestion of as little as 1 g of BSE brain tissue can transmit disease to other cattle.5 Infection by the respiratory route does not occur (an important consideration with respect to incineration), and venereal infection either does not occur or is too rare to be detected. How can tissue infectivity be destroyed before disposal? The agents that cause TSE have been known almost since their discovery to have awesome resistance to methods that quickly and easily inactivate most other pathogens. Irradiation, chemicals, and heat are the three commonest inactivating techniques. Irradiation has proved entirely ineffective, and only a handful of a long catalogue of chemicals have produced more than modest reduction in infectivity. The most active of these are concentrated solutions of sodium hypochlorite (bleach) or sodium hydroxide (lye). As for heat, even though the agent shares with most other pathogens the feature of being more effectively damaged by wet heat than by dry heat, boiling has little effect, and steam heat under pressure (autoclaving) at temperatures of 121ºC is not always sterilising. To date, the most effective heat kill requires exposure of infectious material to steam heat at 134ºC for 1 h in a porous-load autoclave.6 Exposure to dry heat even at temperatures of up to 360ºC for 1 h may leave a small amount of residual infectivity.7 The standard method of incineration, heating to about 1000ºC for at least several seconds, has been assumed to achieve total sterilisation, but needs experimental verification in the light of suggestions that rendered tissue waste might find some useful purpose as a source of heating fuel. Thus, TSE agents are very resistant to virtually every imaginable method of inactivation, and those methods found to be most effective may, in one test or another, fail to sterilise. It seems that even when most infectious particles succumb to an inactivating process, there may remain a small subpopulation of particles that exhibit an extraordinary capacity to withstand inactivation, and that, with appropriate testing, will be found to retain the ability to transmit disease. Also, almost all available inactivation data have come from research studies done under carefully controlled laboratory conditions, and it is always difficult to translate these conditions to the world of commerce. Even when the data are applied in the commercial process, the repetitive nature of the process requires vigilance in quality control and inspection to ensure adherence to its regulations. The final issue that must be addressed is the "lifespan" of the infectious agent after disposal if it has been only incompletely inactivated beforehand. Given the extraordinary resistance of the agent to decontamination measures, the epidemiological and experimental evidence indicating that TSE agents may endure in nature for a long time should come as no surprise. The first real clue to this possibility came from the Icelandic observation that healthy sheep contracted scrapie when they grazed on pastures that had lain unused for 3 years after having been grazed by scrapie-infected sheep.8 Support for this observation was obtained from an experiment in which scrapie-infected brain material was mixed with soil, placed in a container, and then allowed to "weather" in a semi-interred state for 3 years.9 A small amount of residual infectivity was detected in the contaminated soil, and most of the infectivity remained in the topmost layers of soil, where the tissue had originally been placed--in other words, there had been no significant leaching of infectivity to deeper soil layers. It is therefore plausible for surface or subsurface disposal of TSE-contaminated tissue or carcasses to result in long-lasting soil infectivity. Uncovered landfills are a favourite feeding site for seagulls, which could disperse the infectivity.10 Other animals might do likewise, and if the landfill site were later used for herbivore grazing, or tilled as arable land, the potential for disease transmission might remain. A further question concerns the risk of contamination of the surrounding water table, or even surface waste-water channels, by effluents and discarded solid waste from treatment plants. A reasonable conclusion from existing data is that there is a potential for human infection to result from environmental contamination by BSE-infected tissue residues. The potential cannot be quantified because of the huge number of uncertainties and assumptions that attend each stage of the disposal process. On the positive side, spongiform encephalopathy can be said to be not easily transmissible. Although the level of infectivity to which creatures are exposed is not known, it is probably very low, since sheep that die from scrapie, cattle that die from BSE, and human beings who die from nvCJD represent only a small proportion of their respective exposed populations. Whatever risk exists is therefore extremely small, but not zero, hence all practical steps that might reduce the risk to the smallest acceptable level must be considered. What is practical and what is acceptable are concepts that will be hammered out on the anvil of politics: scientific input, such as it is, already waits in the forge. A fairly obvious recommendation, based on the science, would be that all material that is actually or potentially contaminated by BSE, whether whole carcasses, rendered solids, or waste effluents, should be exposed to lye and thoroughly incinerated under strictly inspected conditions. Another is that the residue is buried in landfills to a depth that would minimise any subsequent animal or human exposure, in areas that would not intersect with any potable water-table source. Certainly, it has been, and will continue to be, necessary in many instances to accept less than the ideal.
Paul Brown Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA 1 Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347: 921-25 [PubMed]. 2 Bruce M, Will RG, Ironside JW, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997: 389: 498-501. 3 Collinge J, Sidle KCL, Heads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996; 383: 685-90 [PubMed]. 4 Wells GAH, Hawkins SAC, Green RB, et al. Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet Rec 1998; 142: 103-06 [PubMed]. 5 Collee JG, Bradley R. BSE: a decade on--part 2. Lancet 1997; 349: 715-21 [PubMed]. 6 Taylor DM. Exposure to, and inactivation of, the unconventional agents that cause transmissible degenerative encephalopathies. In: Baker HF, Ridley RM, eds. Methods in molecular medicine: prion diseases. Totawa NJ: Humana Press, 1996: 105-18. 7 Brown P, Liberski PP, Wolff A, Gajdusek DC. Resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360°C: practical and theoretical implications, J Infect Dis 1990; 161: 467-72 [PubMed]. 8 Palsson PA. Rida (scrapie) in Iceland and its epidemiology. In: Prusiner SB, Hadlow WJ, eds. Slow transmissible diseases of the nervous system, vol I. New York: Academic Press, 1979: 357-66. 9 Brown P, Gajdusek DC. Survival of scrapie virus after 3 years' interment. Lancet 1991; 337; 269-70. 10 Scrimgoeur EM, Brown P, Monaghan P. Disposal of rendered specified offal. Vet Rec 1996; 139: 219-20 [PubMed]. http://www.thelancet.com/newlancet/sub/issues/vol351no9110/body.commentary1146.html
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88. Natural decay: Infectivity persists for a long time in the environment. A study by Palsson in 1979 showed how scrapie was contracted by healthy sheep, after they had grazed on land which had previously been grazed by scrapie-infected sheep, even though the land had lain fallow for three years before the healthy sheep were introduced. Brown also quoted an early experiment of his own (1991), where he had buried scrapie-infected hamster brain and found that he could still detect substantial infectivity three years later near where the material had been placed. 89. Potential environmental routes of infection: Brown discusses the various possible scenarios, including surface or subsurface deposits of TSE-contaminated material, which would lead to a build-up of long-lasting infectivity. Birds feeding on animal remains (such as gulls visiting landfill sites) could disperse infectivity. Other animals could become vectors if they later grazed on contaminated land. "A further question concerns the risk of contamination of the surrounding water table or even surface water channels, by effluents and discarded solid wastes from treatment plants. A reasonable conclusion is that there is a potential for human infection to result from environmental contamination by BSE-infected tissue residues. The potential cannot be quantified because of the huge numbers of uncertainties and assumptions that attend each stage of the disposal process". These comments, from a long established authority on TSEs, closely echo my own statements which were based on a recent examination of all the evidence. 90. Susceptibility: It is likely that transmissibility of the disease to humans in vivo is probably low, because sheep that die from scrapie and cattle that die from BSE are probably a small fraction of the exposed population. However, no definitive data are available. 91. Recommendations for disposal procedures: Brown recommends that material which is actually or potentially contaminated by BSE should be: 1) exposed to caustic soda; 2) thoroughly incinerated under carefully inspected conditions; and 3) that any residue should be buried in landfill, to a depth which would minimise any subsequent animal or human exposure, in areas that would not intersect with any potable water-table source. 92. This review and recommendations from Brown have particular importance. Brown is one of the world's foremost authorities on TSEs and is a senior researcher in the US National Institutes of Health (NIH). It is notable that such a respected authority is forthright in acknowledging the existence of potential risks, and in identifying the appropriate measures necessary to safeguard public health. Paper by SM Cousens, L Linsell, PG Smith, Dr M Chandrakumar, JW Wilesmith, RSG Knight, M Zeidler, G Stewart, RG Will, "Geographical distribution of variant CJD in the UK (excluding Northern Ireland)". Lancet 353:18-21, 2 nd January 1999 93. The above paper {Appendix 41 (02/01/99)} (J/L/353/18) examined the possibility that patients with vCJD (variant CJD) might live closer to rendering factories than would be expected by chance. All 26 cases of vCJD in the UK with onset up to 31 st August 1998 were studied. The incubation period of vCJD is not known but by analogy with other human TSEs could lie within the range 5-25 years. If vCJD had arisen by exposure to rendering products, such exposure might plausibly have occurred 8-10 years before the onset of symptoms. The authors were able to obtain the addresses of all rendering plants in the UK which were in production in 1988. For each case of vCJD, the distance from the place of residence on 1st January 1998 to the nearest rendering plant was calculated
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http://web.archive.org/web/20030326042814/http://www.bseinquiry.gov.uk/files/ws/s019b.pdf
Infectivity surviving ashing to 600*C is (in my opinion) degradable but infective. based on Bown & Gajdusek, (1991), landfill and burial may be assumed to have a reduction factor of 98% (i.e. a factor of 50) over 3 years. CJD-infected brain-tissue remained infectious after storing at room-temperature for 22 months (Tateishi et al, 1988). Scrapie agent is known to remain viable after at least 30 months of desiccation (Wilson et al, 1950). and pastures that had been grazed by scrapie-infected sheep still appeared to be contaminated with scrapie agent three years after they were last occupied by sheep (Palsson, 1979).
http://europa.eu.int/comm/food/fs/sc/ssc/out58_en.pdf
PAUL BROWN SCRAPIE SOIL TEST
http://collections.europarchive.org/tna/20080102120203/http://www.bseinquiry.gov.uk/files/sc/seac07/tab03.pdf
Some unofficial information from a source on the inside looking out -
Confidential!!!! As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts bot
h heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!! ----------
snip...
http://web.archive.org/web/20030326042814/http://www.bseinquiry.gov.uk/files/ws/s019b.pdf
Infectivity surviving ashing to 600*C is (in my opinion) degradable but infective. based on Bown & Gajdusek, (1991), landfill and burial may be assumed to have a reduction factor of 98% (i.e. a factor of 50) over 3 years. CJD-infected brain-tissue remained infectious after storing at room-temperature for 22 months (Tateishi et al, 1988). Scrapie agent is known to remain viable after at least 30 months of desiccation (Wilson et al, 1950). and pastures that had been grazed by scrapie-infected sheep still appeared to be contaminated with scrapie agent three years after they were last occupied by sheep (Palsson, 1979).
http://europa.eu.int/comm/food/fs/sc/ssc/out58_en.pdf
PAUL BROWN SCRAPIE SOIL TEST
http://collections.europarchive.org/tna/20080102120203/http://www.bseinquiry.gov.uk/files/sc/seac07/tab03.pdf
Some unofficial information from a source on the inside looking out -
Confidential!!!! As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts bot
h heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!! ----------
You can also take that with however many grains of salt you wish, and we can debate these issues all day long, but the bottom line, this is not rocket-science, all one has to do is some experiments and case studies. But for the life of me, I don't know what they are waiting on? Einstein once said, 'The definition of insanity is doing the same thing over and over again and expecting different results.' re-transmission studies on TSE's...TSS and as late as 2007,
10 MILLION POUNDS of blood laced MBM went into commerce in the USA ; "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."
WHAT about that partial and voluntary ruminant to ruminant mad cow feed ban of August 4, 1997 ? lets take a look at progress 10 years later, fast forward 2007 ; 10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007 Date: March 21, 2007 at 2:27 pm PST RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II ___________________________________ PRODUCT Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007 CODE Cattle feed delivered between 01/12/2007 and 01/26/2007 RECALLING FIRM/MANUFACTURER Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007. Firm initiated recall is ongoing. REASON Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI ___________________________________ PRODUCT Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007 CODE The firm does not utilize a code - only shipping documentation with commodity and weights identified. RECALLING FIRM/MANUFACTURER Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete. REASON Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 9,997,976 lbs. DISTRIBUTION ID and NV END OF ENFORCEMENT REPORT FOR MARCH 21, 2007 http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm Subject: Calf Claimer Powder with prohibited bovine blood meal which did not bear the cautionary BSE statement DISTRIBUTION NATIONWIDE Date: June 13, 2007 at 10:59 am PST RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE - CLASS II ___________________________________ PRODUCT O-NO-MORE (Formerly ORPHAN-NO-MORE) Calf Claimer Powder, packaged in 11-oz. bottles, For Animal Use Only. Recall # V-043-2007 CODE A06 RECALLING FIRM/MANUFACTURER Springer Magrath Co., Mc Cook, NE, by telephone on January 2, 2007, fax dated January 9, 2007, by letters on February 22, 2007, March 12, March 14 and March 21, 2007. Firm initiated recall is ongoing. REASON The finished product was manufactured with prohibited bovine blood meal and did not bear the cautionary BSE statement that the product should not be fed to ruminants. VOLUME OF PRODUCT IN COMMERCE Approximately 13,255 bottles DISTRIBUTION Nationwide END OF ENFORCEMENT REPORT FOR JUNE 13, 2007 ### http://www.fda.gov/bbs/topics/enforce/2007/ENF01008.html Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)
PRION DISEASE UPDATE 2010 (11)
SEE;
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://www.promedmail.org/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
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
http://www.aphis.usda.gov/import_export/plants/manuals/ports/downloads/apm_pdf/03_18petfoodsandfeed.pdf
http://www.dardni.gov.uk/index/animal-health/animal-diseases/bse/bse-feed-ban.htm
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
NOW, back to August 1995 ;
STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995
snip...
To minimise the risk of farmers' claims for compensation from feed compounders.
To minimise the potential damage to compound feed markets through adverse publicity.
To maximise freedom of action for feed compounders, notably by maintaining the availability of meat and bone meal as a raw material in animal feeds, and ensuring time is available to make any changes which may be required.
snip...
THE FUTURE
4..........
MAFF remains under pressure in Brussels and is not skilled at handling potentially explosive issues.
5. Tests _may_ show that ruminant feeds have been sold which contain illegal traces of ruminant protein. More likely, a few positive test results will turn up but proof that a particular feed mill knowingly supplied it to a particular farm will be difficult if not impossible.
6. The threat remains real and it will be some years before feed compounders are free of it. The longer we can avoid any direct linkage between feed milling _practices_ and actual BSE cases, the more likely it is that serious damage can be avoided. ...
SEE full text ;
http://collections.europarchive.org/tna/20080102153800/http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf
PPo4-15:
A Surprisingly High Number of the Plaque-Like VV sCJD Subtype Among the Polish sCJD—is There a Connection with BASE?
Beata Sikorska and Pawel P. Liberski Department of Molecular Pathology and Neuropathology; Medical University of Lodz; Lodz, Poland
Recently described bovine amyloidotic spongiform encephalopathy (BASE) or L type BSE—was is overrepresented in Poland (15% of all cases of BSE). Moreover, the number of BASE cases in Poland per million bovines is the highest in Europe. A potential human risk from BASE is evident from experimental transmission to “humanized” transgenic animals and primates. Taking into consideration that non-human primate inoculated with BASE had a shorter incubation period than monkeys infected with classical BSE, and that humanized Tg mice have been found to be highly susceptible to infection with atypical form of BSE, it seems probable that BASE may be more pathogenic for humans than BSE, but the transmitted disease may differ from BSE-derived vCJD. Among 47 cases which have been diagnosed as definite in our laboratory, in 19 cases complete histopathological examination and codon 129 status were available. On the basis of the histological pattern and codon 129 status the cases of sCJD were divided into subtypes according to the Parchi&Gambetti classification. The results are as follows: type 1 (MMorMV)- 42%, type 2 (VV)-32%, type 3 (MV)-10.5%, type 4c (MM)- 10.5% and type 5 (VV)-5 %. Although the number of cases is too low to conclude a significantly different distribution of sCJD subtypes in Polish population those data show surprisingly high number of the plaque-like VV sCJD subtype. Interestingly, it was shown before that Tg mice inoculated with BASE showed granular and plaque-like aggregates or PrPSc in brains resembling those observed in VV2 subtype of sCJD.
PPo2-26:
Transmission of Classical and Atypical (L-type) Bovine Spongiform Encephalopathy (BSE) Prions to Cynomolgus macaques
Fumiko Ono,1 Yoshio Yamakawa,2 Minoru Tobiume,3 Yuko Sato,3 Harutaka Katano,3 Kenichi Hagiwara,2 Iori Itagaki,1 Akio Hiyaoka,1 Katuhiko Komatuzaki,1 Yasunori Emoto,1 Hiroaki Shibata,4 Yuichi Murayama,5 Keiji Terao,4 Yasuhiro Yasutomi4 and Tetsutaro Sata3
1The Corporation for Production and Research of Laboratory Primates; Tsukuba City, Japan; 2Departments of Cell Biology and Biochemistry; and 3Pathology; National Institute of Infectious Diseases; Tokyo, Japan; 4Tsukuba Primate Research Center; National Institute of Biomedical Innovation; Tsukuba City, Japan; 5Prion Disease Research Team; National Institute of Animal Health; Tsukuba City, Japan
Key words: L-type BSE, cBSE, cynomolgus macaques, transmission
BSE prion derived from classical BSE (cBSE) or L-type BSE was characterized by inoculation into the brain of cynomolgus macaques. The neurologic manifestation was developed in all cynomolgus macaques at 27–43 months after intracerebral inoculation of brain homogenate from cBSE-affected cattle (BSE JP/6). Second transmission of cBSE from macaque to macaque shortened incubation period to 13–18 months. cBSE-affected macaques showed the similar clinical signs including hyperekplexia, tremor and paralysis in both primary and second transmission.
Two macaques were intracerebrally inoculated brain homogenate from the L-type BSE-affected cattle (BSE JP/24). The incubation periods were 19–20 months in primary transmission.
The clinical course of the L-type BSE-affected macaques differed from that in cBSE-affected macaques in the points of severe myoclonus without hyperekplexia. The glycoform profile of PrPSc detected in macaque CNS was consistent with original pattern of either cBSE or L-typeBSE PrPSc, respectively. Although severe spongiform change in the brain was remarkable in all BSE-affected macaques, severe spongiform spread widely in cerebral cortex in L-type BSE-affected macaques. Heavy accumulation of PrPSc surrounded by vacuola formed florid plaques in cerebral cortex of cBSE-affected macaques. Deposit of PrPSc in L-type BSE-affected macaque was weak and diffuse synaptic pattern in cerebrum, but large PrPSc plaques were evident at cerebellum. MRI analysis, T2, T1, DW and flair sequences, at the time of autopsy revealed that brain atrophy and dilatation of cerebral ventricles were significantly severe in L-type BSE-affected macaques. These results suggest that L-type BSE is more virulent strain to primates comparing to cBSE.
SP1-4:
Evidence from Molecular Strain Typing
Gianluigi Zanusso Department of Neurological and Visual Sciences; Section of Clinical Neurology; University of Verona; Verona, Italy
Key words: molecular analysis, strain typing, atypical BSE, CJD
In 2001, active surveillance for bovine spongiform encephalopathy (BSE) led to the discovery of atypical BSE phenotypes in aged cattle distinct from classical BSE (C-type). These atypical BSE cases had been classified as low L-type (BASE) or high H-type BSE based on the molecular mass and the degree of glycosylation of of the pathological prion protein (PrPSc). Transmission studies in TgBov mice showed that H-type BSE, C-type BSE and BASE behave as distinct prion strains with different incubation periods, PrPSc molecular patterns and pathological phenotypes. A still unclear issue concerns the potential transmissibility and phenotypes of atypical BSEs in humans. We previously indicated that BASE was similar to a distinct subgroup of sporadic form of Creutzfeldt-Jakob disease (sCJD) MV2, based on molecular similarities and on neuropathological pattern of PrP deposition. To investigate a possible link between BASE and sCJD, Kong et al. and Comoy et al. experimentally inoculated TgHu mice (129MM) and a non-human primate respectively, showing in both models that BASE was more virulent compare to BSE. Further, non-human primate reproduced a clinical phenotype resembling to that of sCJD subtype MM2. Here, we presented a comparative analysis of the biochemical fingerprints of PrPSc between the different sCJD subtypes and animal TSEs and after experimental transmission to animals.
http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099
Opinion of the Scientific Steering Committee on the GEOGRAPHICAL RISK OF BOVINE SPONGIFORM ENCEPHALOPATHY (GBR) in POLAND Adopted on 30/03/2001
It is concluded that it is likely but not confirmed that one or several cattle that are (pre-clinically or clinically) infected with the BSE agent are currently present in the domestic herd of Poland (GBR III).
http://ec.europa.eu/food/fs/sc/ssc/out185_en.pdf
http://bse-atypical.blogspot.com/2010/09/atypical-bse-strains-and-sporadic-cjd.html
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate
Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1, Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1, Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4, Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4, Jean-Philippe Deslys1
1 Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps Florida, Jupiter, Florida, United States of America, 5 Genetics Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
Abstract Top Background Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.
Methodology/Principal Findings Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.
Conclusion/Significance Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.
Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017
Editor: Neil Mabbott, University of Edinburgh, United Kingdom
Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20, 2008
Copyright: © 2008 Comoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work has been supported by the Network of Excellence NeuroPrion.
Competing interests: CEA owns a patent covering the BSE diagnostic tests commercialized by the company Bio-Rad.
* E-mail: emmanuel.comoy@cea.fr
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003017
Session I - Prions: Structure, Strain and Detection (II)
Searching for BASE Strain Signature in Sporadic Creutzfedlt-Jakob Disease
Gianluigi Zanusso
Department of Neurological and Visual Sciences, Section of Clinical Neurology University of Verona, Verona, Italy.
Bovine amyloidotic spongiform encephalopathy (BASE) is a newly recognized form of bovine prion disease, which was originally detected in Italy in 2004 as an effect of active surveillance. BASE or BSE L-type (L is referred to the lower electrophoretic PrPSc migration than classical BSE) has now been reported in several countries, including Japan. All field cases of BASE were older than 8 years and neurologically normal at the time of slaughtered. By experimental transmission, we defined the disease phenotype of cattle BASE, which is quite distinct from that seen in typical BSE and characterized by mental dullness and amyotrophy. Surprisingly, following intraspecies and interspecies transmission the incubation period of BASE was shorter than BSE. The relatively easy transmission of BASE isolate as well as the molecular similarity with sporadic Creutzfeldt-Jakob disease (sCJD) have raised concern regarding its potential passage to humans. Tg humanized mice Met/Met at codon 129 challenged with both BSE and BASE isolates, showed a resistance to BSE but a susceptibility to BASE at a 60% rate; in addition, BASE-inoculated Cynomolgus (129 Met/Met) had shorter incubation periods than BSE-inoculated primates. In this study we compared the biochemical properties of PrPSc in Cynomolgus and in TgHu Met/Met mice challenged with BSE and BASE strains, by conventional SDS-PAGE analysis and 2D separation. The results obtained disclose distinct conformational changes in PrPSc, which are dependent on the inoculated host but not on the codon 129 genotype.
This work was supported by Neuroprion contract n. FOOD CT 2004 -506579 (NOE)
http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf
P02.35
Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK-resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf
Thursday, October 07, 2010
Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice
Thursday, October 07, 2010 Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice
Vet Pathol 0300985810382672, first published on October 4, 2010
Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice
H. Okada okadahi@affrc.go.jp Prion Disease Research Center, National Institute of Animal Health, Tsukuba, K. Masujin Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Y. Imamaru Prion Disease Research Center, National Institute of Animal Health, Tsukuba, M. Imamura Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Y. Matsuura Prion Disease Research Center, National Institute of Animal Health, Tsukuba, S. Mohri Prion Disease Research Center, National Institute of Animal Health, Tsukuba, S. Czub Animal Disease Research Institute, Canadian Food Inspection Agency, T. Yokoyama Prion Disease Research Center, National Institute of Animal Health, Tsukuba,
Abstract
To characterize the biological and biochemical properties of H-type bovine spongiform encephalopathy (BSE), a transmission study with a Canadian H-type isolate was performed with bovinized transgenic mice (TgBoPrP), which were inoculated intracerebrally with brain homogenate from cattle with H-type BSE. All mice exhibited characteristic neurologic signs, and the subsequent passage showed a shortened incubation period. The distribution of disease-associated prion protein (PrPSc) was determined by immunohistochemistry, Western blot, and paraffin-embedded tissue (PET) blot. Biochemical properties and higher molecular weight of the glycoform pattern were well conserved within mice. Immunolabeled granular PrPSc, aggregates, and/or plaque-like deposits were mainly detected in the following brain locations: septal nuclei, subcallosal regions, hypothalamus, paraventricular nucleus of the thalamus, interstitial nucleus of the stria terminalis, and the reticular formation of the midbrain. Weak reactivity was detected by immunohistochemistry and PET blot in the cerebral cortex, most thalamic nuclei, the hippocampus, medulla oblongata, and cerebellum. These findings indicate that the H-type BSE prion has biological and biochemical properties distinct from those of C-type and L-type BSE in TgBoPrP mice, which suggests that TgBoPrP mice constitute a useful animal model to distinguish isolates from BSE-infected cattle.
© 2010 Sage Publications, Inc.
http://vet.sagepub.com/content/early/2010/10/02/0300985810382672.abstract
let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.
This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$
ALABAMA MAD COW g-h-BSEalabama
In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.
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
Sunday, May 01, 2011
STUDY OF ATYPICAL BSE 2010 Annual Report May 2011
http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html
Sunday, May 1, 2011
W.H.O. T.S.E. PRION Blood products and related biologicals May 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/who-tse-prion-blood-products-and.html
Sunday, January 30, 2011
Vaccines and Transmissible Spongiform Encephalopathy the Prion Disease, what if ?
COMMERCIAL IN CONFIDENCE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/vaccines-and-transmissible-spongiform.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Blood products and related biologicals
Transmissible spongiform encephalopathies (TSE) The appearance of a variant form of human Creutzfeldt-Jakob Disease (CJD) in the mid-1990s, as a result of the Bovine Spongiform Encephalopathy (BSE) epidemic in the United Kingdom, has increased the profile of transmissible spongiform encephalopathies as a risk to human health and has already affected public health policy worldwide. It is assumed that the variant CJD (vCJD) results from the consumption of meat products from cattle infected with BSE and that there is a relation of the incidence of vCJD to the incidence of BSE in the countries where the disease has occurred. Since 1996, over 140 cases of vCJD have occurred in UK, seven in France and one each in Ireland, Italy, USA and Canada.
Policies related to vCJD and the potential risk of human to human transmission are based on three main factors:
an unknown number of individuals who might be infected with the BSE agent;
presence of the pathological prion protein in many peripheral tissues from vCJD terminal patients and
evidence of experimental transmission in animals from blood of rodents and sheep infected with vCJD and BSE respectively.
There is increasing concern about the troubling possibility that blood or blood products, vaccines and other pharmaceutical products could spread the agent of variant CJD (vCJD) worldwide, especially in countries where BSE has not yet been reported. Bovine derived materials involved in the production of vaccines and other pharmaceutical products could represent a way of potential transmission of the disease. Moreover, the possibility that human blood and plasma could be a vehicle for the transmission and spread of the disease have led to a number of donor deferral policies aimed at minimizing the risk of accepting a blood donor who might be incubating the human form of BSE. In addition, blood fractionated products such as albumin are used as stabilizers in the production of vaccines and recombinant pharmaceutical products. There is, therefore, a need to ensure that regulatory authorities with limited resources can have reliable information when making their risk assessment and evaluation of product safety to prevent the transmission of TSE to human via biological and pharmaceutical products.
A WHO Consultation was held in February 2003 to update the WHO Recommendations on Medicinal Products in relation to Human TSEs which were prepared in 1997, following a WHO Consultation on the same subject.
This Consultation complemented other important efforts of WHO in the follow up of the scientific and epidemiological developments in TSEs such as the Joint WHO/FAO/OIE Technical Consultation on BSE organized by the WHO Department of Communicable Disease Surveillance and Response (CSR) and the activities of the "Working Group on International Reference Materials for Diagnosis and Study of TSEs", established in 1999 as a scientific forum to advance development of diagnostic tests based on available research methods and their application in health technology and pharmaceuticals.
The primary aim of this Consultation was to provide evidence-based information to medicines regulatory authorities of Member States, specially to those where BSE has not yet been reported, with regard to risk assessment, precautionary and control measures of medicinal products.
The Recommendations of the Consultation form the basis of the WHO Guidance Document to support regulatory decisions by National Regulatory Authorities in developing countries. Based on scientific information available, a tissue infectivity category was developed for the first time, that serves as a global basis for the development of risk assessment models for biological and pharmaceutical products derived from human or animal tissues or body fluids in relation to the transmission of TSE agents.
Creutzfeldt-Jakob Disease reagents
WHO Reference Reagents for In Vitro Assays of CJD Specimens. ECBS 2003. WHO/BS/03.1965 Rev.1 pdf, 127kb Catalogue of WHO International Reference Materials (for CJD specimens see Miscellaneous) Distribution of WHO International Reference Materials The characteristics of all reference preparations as well as the information regarding establishment can be found in the WHO Reference Material section.
Related documents WHO Guidelines on Tissue Infectivity Distribution in TSEs 2006 pdf, 638kb Report on International Reference Materials for Diagnosis and Study of Transmissible Spongiform Encephalopathies (TSEs). Working group fourth meeting, Geneva, Switzerland (April 2002) pdf, 99kb Report on International Reference Materials for Diagnosis and Study of Transmissible Spongiform Encephalopathies (TSEs). Working group third meeting, Geneva, Switzerland (March 2001) pdf, 81kb Report on International Reference Materials for Diagnosis and Study of Transmissible Spongiform Encephalopathies (TSEs). Working group second meeting, Geneva, Switzerland (May 2000) pdf, 86kb Report on International Reference Materials for Diagnosis and Study of Transmissible Spongiform Encephalopathies (TSEs). Working group first meeting, Geneva, Switzerland (Sep 1999) pdf, 62kb Report on WHO Consultation on Diagnostic Procedures for Transmissible Spongiform Encephalopathies (TSEs): Need for Reference Reagents and Reference Panels. Geneva, Switzerland (March 1999) pdf, 77kb Related links
http://www.who.int/bloodproducts/tse/en/
The documents below were provided by Terry S. Singeltary Sr on 8 May 2000.
They are optically character read (scanned into computer) and so may contain typos and unreadable parts.
TIP740203/l 0424 CONFIDENTIAL
snip...
The responses by the companies were presented by Ms Turner and were categorised by MCA standards, the products that were discussed were all low volume usage products eg sutures, heart valves.
8. As the responses included some materials of human origin it was decided that more information should be sought about CJD. There had been 2 recent deaths reported associated with human growth hormone. These were being investigated.
snip...
http://www.mad-cow.org/00/may00_news.html#aaa
5.3.3 The greatest risk, in theory, would be from parenteral injection of material derived from bovine brain or lymphoid tissue. Medicinal products for injection or surgical implantation which are prepared from bovine tissues, or which utilise bovine serum albumin or similar agents in their manufacture, might also be capable of transmitting infectious agents. All medicinal products are licensed under the Medicines Act by the Licensing Authority following guidance, for example from the Committee on Safety of Medicines (CSM), the Committee on Dental and Surgical Materials (CDSM) and their subcommittees. The Licensing Authority have been alerted to potential concern about BSE in medicinal products and will ensure that scrutiny of source materials and manufacturing processes now takes account of BSE agent.
see all 76 pages ;
http://collections.europarchive.org/tna/20080102132706/http://www.bseinquiry.gov.uk/files/ib/ibd1/tab02.pdf
EXPORT OF BRITISH BIOLOGICAL PHARMACEUTICALS...
snip...please see full text ;
Sunday, January 30, 2011
Vaccines and Transmissible Spongiform Encephalopathy the Prion Disease, what if ?
COMMERCIAL IN CONFIDENCE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/vaccines-and-transmissible-spongiform.html
Saturday, February 26, 2011
Supreme Court Protects Vaccine Manufacturers, Not Injured Children there from Bruesewitz vs Wyeth
http://vcjdtransfusion.blogspot.com/2011/02/supreme-court-protects-vaccine.html
Sunday, May 18, 2008
10 MILLION POUNDS of blood laced MBM went into commerce in the USA ; "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."
WHAT about that partial and voluntary ruminant to ruminant mad cow feed ban of August 4, 1997 ? lets take a look at progress 10 years later, fast forward 2007 ; 10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007 Date: March 21, 2007 at 2:27 pm PST RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II ___________________________________ PRODUCT Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007 CODE Cattle feed delivered between 01/12/2007 and 01/26/2007 RECALLING FIRM/MANUFACTURER Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007. Firm initiated recall is ongoing. REASON Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI ___________________________________ PRODUCT Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007 CODE The firm does not utilize a code - only shipping documentation with commodity and weights identified. RECALLING FIRM/MANUFACTURER Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete. REASON Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 9,997,976 lbs. DISTRIBUTION ID and NV END OF ENFORCEMENT REPORT FOR MARCH 21, 2007 http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm Subject: Calf Claimer Powder with prohibited bovine blood meal which did not bear the cautionary BSE statement DISTRIBUTION NATIONWIDE Date: June 13, 2007 at 10:59 am PST RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE - CLASS II ___________________________________ PRODUCT O-NO-MORE (Formerly ORPHAN-NO-MORE) Calf Claimer Powder, packaged in 11-oz. bottles, For Animal Use Only. Recall # V-043-2007 CODE A06 RECALLING FIRM/MANUFACTURER Springer Magrath Co., Mc Cook, NE, by telephone on January 2, 2007, fax dated January 9, 2007, by letters on February 22, 2007, March 12, March 14 and March 21, 2007. Firm initiated recall is ongoing. REASON The finished product was manufactured with prohibited bovine blood meal and did not bear the cautionary BSE statement that the product should not be fed to ruminants. VOLUME OF PRODUCT IN COMMERCE Approximately 13,255 bottles DISTRIBUTION Nationwide END OF ENFORCEMENT REPORT FOR JUNE 13, 2007 ### http://www.fda.gov/bbs/topics/enforce/2007/ENF01008.html Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)
PRION DISEASE UPDATE 2010 (11)
SEE;
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://www.promedmail.org/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
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
http://www.aphis.usda.gov/import_export/plants/manuals/ports/downloads/apm_pdf/03_18petfoodsandfeed.pdf
http://www.dardni.gov.uk/index/animal-health/animal-diseases/bse/bse-feed-ban.htm
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
NOW, back to August 1995 ;
STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995
snip...
To minimise the risk of farmers' claims for compensation from feed compounders.
To minimise the potential damage to compound feed markets through adverse publicity.
To maximise freedom of action for feed compounders, notably by maintaining the availability of meat and bone meal as a raw material in animal feeds, and ensuring time is available to make any changes which may be required.
snip...
THE FUTURE
4..........
MAFF remains under pressure in Brussels and is not skilled at handling potentially explosive issues.
5. Tests _may_ show that ruminant feeds have been sold which contain illegal traces of ruminant protein. More likely, a few positive test results will turn up but proof that a particular feed mill knowingly supplied it to a particular farm will be difficult if not impossible.
6. The threat remains real and it will be some years before feed compounders are free of it. The longer we can avoid any direct linkage between feed milling _practices_ and actual BSE cases, the more likely it is that serious damage can be avoided. ...
SEE full text ;
http://collections.europarchive.org/tna/20080102153800/http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf
PPo4-15:
A Surprisingly High Number of the Plaque-Like VV sCJD Subtype Among the Polish sCJD—is There a Connection with BASE?
Beata Sikorska and Pawel P. Liberski Department of Molecular Pathology and Neuropathology; Medical University of Lodz; Lodz, Poland
Recently described bovine amyloidotic spongiform encephalopathy (BASE) or L type BSE—was is overrepresented in Poland (15% of all cases of BSE). Moreover, the number of BASE cases in Poland per million bovines is the highest in Europe. A potential human risk from BASE is evident from experimental transmission to “humanized” transgenic animals and primates. Taking into consideration that non-human primate inoculated with BASE had a shorter incubation period than monkeys infected with classical BSE, and that humanized Tg mice have been found to be highly susceptible to infection with atypical form of BSE, it seems probable that BASE may be more pathogenic for humans than BSE, but the transmitted disease may differ from BSE-derived vCJD. Among 47 cases which have been diagnosed as definite in our laboratory, in 19 cases complete histopathological examination and codon 129 status were available. On the basis of the histological pattern and codon 129 status the cases of sCJD were divided into subtypes according to the Parchi&Gambetti classification. The results are as follows: type 1 (MMorMV)- 42%, type 2 (VV)-32%, type 3 (MV)-10.5%, type 4c (MM)- 10.5% and type 5 (VV)-5 %. Although the number of cases is too low to conclude a significantly different distribution of sCJD subtypes in Polish population those data show surprisingly high number of the plaque-like VV sCJD subtype. Interestingly, it was shown before that Tg mice inoculated with BASE showed granular and plaque-like aggregates or PrPSc in brains resembling those observed in VV2 subtype of sCJD.
PPo2-26:
Transmission of Classical and Atypical (L-type) Bovine Spongiform Encephalopathy (BSE) Prions to Cynomolgus macaques
Fumiko Ono,1 Yoshio Yamakawa,2 Minoru Tobiume,3 Yuko Sato,3 Harutaka Katano,3 Kenichi Hagiwara,2 Iori Itagaki,1 Akio Hiyaoka,1 Katuhiko Komatuzaki,1 Yasunori Emoto,1 Hiroaki Shibata,4 Yuichi Murayama,5 Keiji Terao,4 Yasuhiro Yasutomi4 and Tetsutaro Sata3
1The Corporation for Production and Research of Laboratory Primates; Tsukuba City, Japan; 2Departments of Cell Biology and Biochemistry; and 3Pathology; National Institute of Infectious Diseases; Tokyo, Japan; 4Tsukuba Primate Research Center; National Institute of Biomedical Innovation; Tsukuba City, Japan; 5Prion Disease Research Team; National Institute of Animal Health; Tsukuba City, Japan
Key words: L-type BSE, cBSE, cynomolgus macaques, transmission
BSE prion derived from classical BSE (cBSE) or L-type BSE was characterized by inoculation into the brain of cynomolgus macaques. The neurologic manifestation was developed in all cynomolgus macaques at 27–43 months after intracerebral inoculation of brain homogenate from cBSE-affected cattle (BSE JP/6). Second transmission of cBSE from macaque to macaque shortened incubation period to 13–18 months. cBSE-affected macaques showed the similar clinical signs including hyperekplexia, tremor and paralysis in both primary and second transmission.
Two macaques were intracerebrally inoculated brain homogenate from the L-type BSE-affected cattle (BSE JP/24). The incubation periods were 19–20 months in primary transmission.
The clinical course of the L-type BSE-affected macaques differed from that in cBSE-affected macaques in the points of severe myoclonus without hyperekplexia. The glycoform profile of PrPSc detected in macaque CNS was consistent with original pattern of either cBSE or L-typeBSE PrPSc, respectively. Although severe spongiform change in the brain was remarkable in all BSE-affected macaques, severe spongiform spread widely in cerebral cortex in L-type BSE-affected macaques. Heavy accumulation of PrPSc surrounded by vacuola formed florid plaques in cerebral cortex of cBSE-affected macaques. Deposit of PrPSc in L-type BSE-affected macaque was weak and diffuse synaptic pattern in cerebrum, but large PrPSc plaques were evident at cerebellum. MRI analysis, T2, T1, DW and flair sequences, at the time of autopsy revealed that brain atrophy and dilatation of cerebral ventricles were significantly severe in L-type BSE-affected macaques. These results suggest that L-type BSE is more virulent strain to primates comparing to cBSE.
SP1-4:
Evidence from Molecular Strain Typing
Gianluigi Zanusso Department of Neurological and Visual Sciences; Section of Clinical Neurology; University of Verona; Verona, Italy
Key words: molecular analysis, strain typing, atypical BSE, CJD
In 2001, active surveillance for bovine spongiform encephalopathy (BSE) led to the discovery of atypical BSE phenotypes in aged cattle distinct from classical BSE (C-type). These atypical BSE cases had been classified as low L-type (BASE) or high H-type BSE based on the molecular mass and the degree of glycosylation of of the pathological prion protein (PrPSc). Transmission studies in TgBov mice showed that H-type BSE, C-type BSE and BASE behave as distinct prion strains with different incubation periods, PrPSc molecular patterns and pathological phenotypes. A still unclear issue concerns the potential transmissibility and phenotypes of atypical BSEs in humans. We previously indicated that BASE was similar to a distinct subgroup of sporadic form of Creutzfeldt-Jakob disease (sCJD) MV2, based on molecular similarities and on neuropathological pattern of PrP deposition. To investigate a possible link between BASE and sCJD, Kong et al. and Comoy et al. experimentally inoculated TgHu mice (129MM) and a non-human primate respectively, showing in both models that BASE was more virulent compare to BSE. Further, non-human primate reproduced a clinical phenotype resembling to that of sCJD subtype MM2. Here, we presented a comparative analysis of the biochemical fingerprints of PrPSc between the different sCJD subtypes and animal TSEs and after experimental transmission to animals.
http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099
Opinion of the Scientific Steering Committee on the GEOGRAPHICAL RISK OF BOVINE SPONGIFORM ENCEPHALOPATHY (GBR) in POLAND Adopted on 30/03/2001
It is concluded that it is likely but not confirmed that one or several cattle that are (pre-clinically or clinically) infected with the BSE agent are currently present in the domestic herd of Poland (GBR III).
http://ec.europa.eu/food/fs/sc/ssc/out185_en.pdf
http://bse-atypical.blogspot.com/2010/09/atypical-bse-strains-and-sporadic-cjd.html
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate
Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1, Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1, Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4, Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4, Jean-Philippe Deslys1
1 Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps Florida, Jupiter, Florida, United States of America, 5 Genetics Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
Abstract Top Background Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.
Methodology/Principal Findings Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.
Conclusion/Significance Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.
Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017
Editor: Neil Mabbott, University of Edinburgh, United Kingdom
Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20, 2008
Copyright: © 2008 Comoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work has been supported by the Network of Excellence NeuroPrion.
Competing interests: CEA owns a patent covering the BSE diagnostic tests commercialized by the company Bio-Rad.
* E-mail: emmanuel.comoy@cea.fr
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003017
Session I - Prions: Structure, Strain and Detection (II)
Searching for BASE Strain Signature in Sporadic Creutzfedlt-Jakob Disease
Gianluigi Zanusso
Department of Neurological and Visual Sciences, Section of Clinical Neurology University of Verona, Verona, Italy.
Bovine amyloidotic spongiform encephalopathy (BASE) is a newly recognized form of bovine prion disease, which was originally detected in Italy in 2004 as an effect of active surveillance. BASE or BSE L-type (L is referred to the lower electrophoretic PrPSc migration than classical BSE) has now been reported in several countries, including Japan. All field cases of BASE were older than 8 years and neurologically normal at the time of slaughtered. By experimental transmission, we defined the disease phenotype of cattle BASE, which is quite distinct from that seen in typical BSE and characterized by mental dullness and amyotrophy. Surprisingly, following intraspecies and interspecies transmission the incubation period of BASE was shorter than BSE. The relatively easy transmission of BASE isolate as well as the molecular similarity with sporadic Creutzfeldt-Jakob disease (sCJD) have raised concern regarding its potential passage to humans. Tg humanized mice Met/Met at codon 129 challenged with both BSE and BASE isolates, showed a resistance to BSE but a susceptibility to BASE at a 60% rate; in addition, BASE-inoculated Cynomolgus (129 Met/Met) had shorter incubation periods than BSE-inoculated primates. In this study we compared the biochemical properties of PrPSc in Cynomolgus and in TgHu Met/Met mice challenged with BSE and BASE strains, by conventional SDS-PAGE analysis and 2D separation. The results obtained disclose distinct conformational changes in PrPSc, which are dependent on the inoculated host but not on the codon 129 genotype.
This work was supported by Neuroprion contract n. FOOD CT 2004 -506579 (NOE)
http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf
P02.35
Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK-resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf
Thursday, October 07, 2010
Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice
Thursday, October 07, 2010 Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice
Vet Pathol 0300985810382672, first published on October 4, 2010
Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice
H. Okada okadahi@affrc.go.jp Prion Disease Research Center, National Institute of Animal Health, Tsukuba, K. Masujin Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Y. Imamaru Prion Disease Research Center, National Institute of Animal Health, Tsukuba, M. Imamura Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Y. Matsuura Prion Disease Research Center, National Institute of Animal Health, Tsukuba, S. Mohri Prion Disease Research Center, National Institute of Animal Health, Tsukuba, S. Czub Animal Disease Research Institute, Canadian Food Inspection Agency, T. Yokoyama Prion Disease Research Center, National Institute of Animal Health, Tsukuba,
Abstract
To characterize the biological and biochemical properties of H-type bovine spongiform encephalopathy (BSE), a transmission study with a Canadian H-type isolate was performed with bovinized transgenic mice (TgBoPrP), which were inoculated intracerebrally with brain homogenate from cattle with H-type BSE. All mice exhibited characteristic neurologic signs, and the subsequent passage showed a shortened incubation period. The distribution of disease-associated prion protein (PrPSc) was determined by immunohistochemistry, Western blot, and paraffin-embedded tissue (PET) blot. Biochemical properties and higher molecular weight of the glycoform pattern were well conserved within mice. Immunolabeled granular PrPSc, aggregates, and/or plaque-like deposits were mainly detected in the following brain locations: septal nuclei, subcallosal regions, hypothalamus, paraventricular nucleus of the thalamus, interstitial nucleus of the stria terminalis, and the reticular formation of the midbrain. Weak reactivity was detected by immunohistochemistry and PET blot in the cerebral cortex, most thalamic nuclei, the hippocampus, medulla oblongata, and cerebellum. These findings indicate that the H-type BSE prion has biological and biochemical properties distinct from those of C-type and L-type BSE in TgBoPrP mice, which suggests that TgBoPrP mice constitute a useful animal model to distinguish isolates from BSE-infected cattle.
© 2010 Sage Publications, Inc.
http://vet.sagepub.com/content/early/2010/10/02/0300985810382672.abstract
let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.
This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$
ALABAMA MAD COW g-h-BSEalabama
In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.
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
Sunday, May 01, 2011
STUDY OF ATYPICAL BSE 2010 Annual Report May 2011
http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html
Sunday, May 1, 2011
W.H.O. T.S.E. PRION Blood products and related biologicals May 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/who-tse-prion-blood-products-and.html
Sunday, January 30, 2011
Vaccines and Transmissible Spongiform Encephalopathy the Prion Disease, what if ?
COMMERCIAL IN CONFIDENCE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/vaccines-and-transmissible-spongiform.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Blood products and related biologicals
Transmissible spongiform encephalopathies (TSE) The appearance of a variant form of human Creutzfeldt-Jakob Disease (CJD) in the mid-1990s, as a result of the Bovine Spongiform Encephalopathy (BSE) epidemic in the United Kingdom, has increased the profile of transmissible spongiform encephalopathies as a risk to human health and has already affected public health policy worldwide. It is assumed that the variant CJD (vCJD) results from the consumption of meat products from cattle infected with BSE and that there is a relation of the incidence of vCJD to the incidence of BSE in the countries where the disease has occurred. Since 1996, over 140 cases of vCJD have occurred in UK, seven in France and one each in Ireland, Italy, USA and Canada.
Policies related to vCJD and the potential risk of human to human transmission are based on three main factors:
an unknown number of individuals who might be infected with the BSE agent;
presence of the pathological prion protein in many peripheral tissues from vCJD terminal patients and
evidence of experimental transmission in animals from blood of rodents and sheep infected with vCJD and BSE respectively.
There is increasing concern about the troubling possibility that blood or blood products, vaccines and other pharmaceutical products could spread the agent of variant CJD (vCJD) worldwide, especially in countries where BSE has not yet been reported. Bovine derived materials involved in the production of vaccines and other pharmaceutical products could represent a way of potential transmission of the disease. Moreover, the possibility that human blood and plasma could be a vehicle for the transmission and spread of the disease have led to a number of donor deferral policies aimed at minimizing the risk of accepting a blood donor who might be incubating the human form of BSE. In addition, blood fractionated products such as albumin are used as stabilizers in the production of vaccines and recombinant pharmaceutical products. There is, therefore, a need to ensure that regulatory authorities with limited resources can have reliable information when making their risk assessment and evaluation of product safety to prevent the transmission of TSE to human via biological and pharmaceutical products.
A WHO Consultation was held in February 2003 to update the WHO Recommendations on Medicinal Products in relation to Human TSEs which were prepared in 1997, following a WHO Consultation on the same subject.
This Consultation complemented other important efforts of WHO in the follow up of the scientific and epidemiological developments in TSEs such as the Joint WHO/FAO/OIE Technical Consultation on BSE organized by the WHO Department of Communicable Disease Surveillance and Response (CSR) and the activities of the "Working Group on International Reference Materials for Diagnosis and Study of TSEs", established in 1999 as a scientific forum to advance development of diagnostic tests based on available research methods and their application in health technology and pharmaceuticals.
The primary aim of this Consultation was to provide evidence-based information to medicines regulatory authorities of Member States, specially to those where BSE has not yet been reported, with regard to risk assessment, precautionary and control measures of medicinal products.
The Recommendations of the Consultation form the basis of the WHO Guidance Document to support regulatory decisions by National Regulatory Authorities in developing countries. Based on scientific information available, a tissue infectivity category was developed for the first time, that serves as a global basis for the development of risk assessment models for biological and pharmaceutical products derived from human or animal tissues or body fluids in relation to the transmission of TSE agents.
Creutzfeldt-Jakob Disease reagents
WHO Reference Reagents for In Vitro Assays of CJD Specimens. ECBS 2003. WHO/BS/03.1965 Rev.1 pdf, 127kb Catalogue of WHO International Reference Materials (for CJD specimens see Miscellaneous) Distribution of WHO International Reference Materials The characteristics of all reference preparations as well as the information regarding establishment can be found in the WHO Reference Material section.
Related documents WHO Guidelines on Tissue Infectivity Distribution in TSEs 2006 pdf, 638kb Report on International Reference Materials for Diagnosis and Study of Transmissible Spongiform Encephalopathies (TSEs). Working group fourth meeting, Geneva, Switzerland (April 2002) pdf, 99kb Report on International Reference Materials for Diagnosis and Study of Transmissible Spongiform Encephalopathies (TSEs). Working group third meeting, Geneva, Switzerland (March 2001) pdf, 81kb Report on International Reference Materials for Diagnosis and Study of Transmissible Spongiform Encephalopathies (TSEs). Working group second meeting, Geneva, Switzerland (May 2000) pdf, 86kb Report on International Reference Materials for Diagnosis and Study of Transmissible Spongiform Encephalopathies (TSEs). Working group first meeting, Geneva, Switzerland (Sep 1999) pdf, 62kb Report on WHO Consultation on Diagnostic Procedures for Transmissible Spongiform Encephalopathies (TSEs): Need for Reference Reagents and Reference Panels. Geneva, Switzerland (March 1999) pdf, 77kb Related links
http://www.who.int/bloodproducts/tse/en/
The documents below were provided by Terry S. Singeltary Sr on 8 May 2000.
They are optically character read (scanned into computer) and so may contain typos and unreadable parts.
TIP740203/l 0424 CONFIDENTIAL
snip...
The responses by the companies were presented by Ms Turner and were categorised by MCA standards, the products that were discussed were all low volume usage products eg sutures, heart valves.
8. As the responses included some materials of human origin it was decided that more information should be sought about CJD. There had been 2 recent deaths reported associated with human growth hormone. These were being investigated.
snip...
http://www.mad-cow.org/00/may00_news.html#aaa
5.3.3 The greatest risk, in theory, would be from parenteral injection of material derived from bovine brain or lymphoid tissue. Medicinal products for injection or surgical implantation which are prepared from bovine tissues, or which utilise bovine serum albumin or similar agents in their manufacture, might also be capable of transmitting infectious agents. All medicinal products are licensed under the Medicines Act by the Licensing Authority following guidance, for example from the Committee on Safety of Medicines (CSM), the Committee on Dental and Surgical Materials (CDSM) and their subcommittees. The Licensing Authority have been alerted to potential concern about BSE in medicinal products and will ensure that scrutiny of source materials and manufacturing processes now takes account of BSE agent.
see all 76 pages ;
http://collections.europarchive.org/tna/20080102132706/http://www.bseinquiry.gov.uk/files/ib/ibd1/tab02.pdf
EXPORT OF BRITISH BIOLOGICAL PHARMACEUTICALS...
snip...please see full text ;
Sunday, January 30, 2011
Vaccines and Transmissible Spongiform Encephalopathy the Prion Disease, what if ?
COMMERCIAL IN CONFIDENCE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/vaccines-and-transmissible-spongiform.html
Saturday, February 26, 2011
Supreme Court Protects Vaccine Manufacturers, Not Injured Children there from Bruesewitz vs Wyeth
http://vcjdtransfusion.blogspot.com/2011/02/supreme-court-protects-vaccine.html
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
TIP740203/l 0424 CONFIDENTIAL
http://bseinquiry.blogspot.com/2008/05/mad-cow-disease-bse-cjd-children.html
Saturday, April 30, 2011
Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed APRIL 27, 2011
http://vcjdtransfusion.blogspot.com/2011/04/blood-product-collected-from-donor-who.html
Sunday, January 30, 2011
Vaccines and Transmissible Spongiform Encephalopathy the Prion Disease, what if ?
COMMERCIAL IN CONFIDENCE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/vaccines-and-transmissible-spongiform.html
MAD COW DISEASE BSE CJD CHILDREN VACCINES
TIP740203/l 0424 CONFIDENTIAL
http://bseinquiry.blogspot.com/2008/05/mad-cow-disease-bse-cjd-children.html
Saturday, April 30, 2011
Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed APRIL 27, 2011
http://vcjdtransfusion.blogspot.com/2011/04/blood-product-collected-from-donor-who.html
Sunday, January 30, 2011
Vaccines and Transmissible Spongiform Encephalopathy the Prion Disease, what if ?
COMMERCIAL IN CONFIDENCE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/vaccines-and-transmissible-spongiform.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Sunday, May 1, 2011
W.H.O. T.S.E. PRION Blood products and related biologicals May 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/who-tse-prion-blood-products-and.html
WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010
snip...
Finally, it is critically important to understand that categories of infectivity are not the same as categories of risk, which require consideration not only of the level of infectivity in tissue, but also of the amount of tissue to which a person or animal is exposed, and the route by which infection is transmitted. For example, although the level of tissue infectivity is the most important factor in estimating the risk of transmission by instrument crosscontamination during surgical procedures (e.g., neurosurgery versus general surgery), it will be only one determinant of the risk of transmission by blood transfusions, in which a large amount of low-infectivity blood is administered intravenously, or the risk of transmission by foodstuffs that, irrespective of high or low infectivity, involve a comparatively inefficient oral route of infection.
snip...
17. A wealth of data from studies of blood infectivity in experimental rodent models of TSE have been extended by recent studies documenting infectivity in the blood of sheep with naturally occurring scrapie and in sheep transfused with blood from BSEinfected cattle [Houston et al., 2008]; of deer with naturally occurring CWD [Mathiason et al., 2006]; and (from epidemiological observations) in the red cell fraction (which includes significant amounts of both plasma and leukocytes) of four blood donors in the pre-clinical phase of vCJD infections [reviewed in Brown, 2006;
Hewitt et al., 2006]. Plasma Factor VIII administration has also been potentially implicated in a subclinical case of vCJD in a hemophilia patient [Peden et al., 2010]. Blood has not been shown to transmit disease from humans with any form of ‘classical’ TSE [Dorsey et al., 2009], or from cattle with BSE (including fetal calf blood). A WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies
11
number of laboratories using new, highly sensitive methods to detect PrPTSE are reporting success in a variety of animal and human TSEs. However, several have experienced difficulty obtaining reproducible results in plasma, and it is not yet clear that positive results imply a potential for disease transmissibility, either because of false positives, or of ‘true’ positives that are due to sub-transmissible concentrations of PrPTSE. Because of these considerations (and the fact that no data are yet available on blinded testing of specimens from naturally infected humans or animals) the expert group felt that it was still too early to evaluate the validity of these tests with sufficient confidence to permit either a negative or positive conclusion.
18. Evidence that infectivity is not present in milk from BSE-infected bovines includes temporo-spatial epidemiologic observations failing to detect maternal transmission to calves suckled for long periods; clinical observations of over a hundred calves suckled by infected cows that have not developed BSE; and experimental observations that milk from infected cows reared to an age exceeding the minimum incubation period has not transmitted disease when administered intracerebrally or orally to mice [Middleton and Barlow, 1993; Taylor et al., 1995]. Also, PrPTSE has not been detected in milk from cattle incubating BSE following experimental oral challenge [SEAC, 2005]. However, low levels (µg to ng/L) of normal PrP have been detected in milk from both animals and humans [Franscini et al., 2006]. PrPTSE has been detected in the mammary glands of scrapie-infected sheep with chronic mastitis [Ligios et al., 2005], and very recently it has been reported that milk (which in some cases also contained colostrum) from scrapie-infected sheep transmitted disease to healthy animals [Konold et al., 2008; Lacroux et al., 2008].
snip...
please see tables and full text here ;
http://www.who.int/bloodproducts/tablestissueinfectivity.pdf
WITH the confirmed transmission of nvCJD to humans via blood, the ever so emerging strains of TSE called atypical, some much more virulent than that of the typical c-BSE, to continue the practice of feeding animals blood and the spreading of blood on land, in my opinion is a recipe for disaster. ...
layperson
Kind regards,
Terry S. Singeltary Sr. Bacliff, Texas USA
posted by Terry S. Singeltary Sr. at
4:45 PM
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