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1 DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 589 [Docket No. 2002N–0273] (formerly Docket No. 02N–0273) RIN 0910–AF46 Substances Prohibited From Use in Animal Food or Feed AGENCY: Food and Drug Administration, HHS. ACTION: Proposed rule. SUMMARY: The Food and Drug Administration (FDA) is proposing to amend the agency’s regulations to prohibit the use of certain cattle origin materials in the food or feed of all animals. These materials include the following: The brains and spinal cords from cattle 30 months of age and older, the brains and spinal cords from cattle of any age not inspected and passed for human consumption, the entire carcass of cattle not inspected and passed for human consumption if the brains and spinal cords have not been removed, tallow that is derived from the materials prohibited by this proposed rule that contains more than 0.15 percent insoluble impurities, and mechanically separated beef that is derived from the materials prohibited by this proposed rule. These measures will further strengthen existing safeguards designed to help prevent the spread of bovine spongiform encephalopathy (BSE) in U.S. cattle. DATES: Submit written or electronic comments by [insert date 75 days after date of publication in the Federal Register]. Submit written comments on the information collection provisions by [insert date 30 days after date of publication in the Federal Register]. 2 ADDRESSES: You may submit comments, identified by [Docket No. 2002N–0273 or RIN 0910–AF46], by any of the following methods: SNIP... 124 PAGES OF MORE BSe at the following link; http://www.fda.gov/OHRMS/DOCKETS/98fr/cv048.pdf the fda promises us hope at first, then delivers more failures and lies. promise us anything, and gives us nothing. the fda is like the usda, bought and paid for by your local cattle dealer. this is corporate and political science at it's finest hour, nothing, i mean absolutely no 'sound science' here. they just as well have kept on keeping on feeding cattle to cattle with this half @ss approach. 1862 Federal Register / Vol. 69, No. 7 / Monday, January 12, 2004 / Rules and Regulations DEPARTMENT OF AGRICULTURE Food Safety and Inspection Service 9 CFR Parts 309, 310, 311, 318, and 319 [Docket No. 03–025IF] Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle 025IF, Room 102, Cotton Annex, 300 12th and C Street, SW., Washington, DC 20250–3700. snip... This action will minimize human exposure to materials that scientific studies have demonstrated as containing the BSE agent in cattle infected with the disease. Infectivity has never been demonstrated in the muscle tissue of cattle experimentally or naturally infected with BSE at any stage of the disease. snip... http://ffas.usda.gov/info/fr/2004/011204bserisk.pdf FACT Iwamaru et al. (2005) PrPSc distribution of a natural case of bovine spongiform encephalopathy. In Prions. Food and Drug Safety. Springer- Verlag, Tokyo, 2005. 4 Buschmann & Groschup (2005) Highly Bovine Spongiform transgenic mice confirm the essential restriction of infectivity to the nervous system in clinically disease cattle. J. Infect. Dis. 192, 934-942. 3 BSE cases. SEAC noted the findings were both in single animals at the clinical stage of disease. The level of infectivity detected in PNS tissues was considerably lower than in CNS tissues. Further related research was discussed in the reserved session. spongiform encephalopathy Yoshifumi Iwamaru, Yuka Okubo, Tamako Ikeda, Hiroko Hayashi, Mori- kazu Imamura, Takashi Yokoyama and Morikazu Shinagawa Priori Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba 305-0856 Japan gan@affrc.go.jp Abstract Bovine spongiform encephalopathy (BSE) is a disease of cattle that causes progressive neurodegeneration of the central nervous system. Infectivity of BSE agent is accompanied with an abnormal isoform of prion protein (PrPSc). The specified risk materials (SRM) are tissues potentially carrying BSE infectivity. The following tissues are designated as SRM in Japan: the skull including the brain and eyes but excluding the glossa and the masse- ter muscle, the vertebral column excluding the vertebrae of the tail, spinal cord, distal illeum. For a risk management step, the use of SRM in both animal feed or human food has been prohibited. However, detailed PrPSc distribution remains obscure in BSE cattle and it has caused con- troversies about definitions of SRM. Therefore we have examined PrPSc distribution in a BSE cattle by Western blotting to reassess definitions of SRM. The 11th BSE case in Japan was detected in fallen stock surveillance. The carcass was stocked in the refrigerator. For the detection of PrPSc, 200 mg of tissue samples were homogenized. Following collagenase treatment, samples were digested with proteinase K. After digestion, PrPSc was precipitated by sodium phosphotungstate (PTA). The pellets were subjected to Western blotting using the standard procedure. Anti-prion protein monoclonal antibody (mAb) T2 conjugated horseradish peroxidase was used for the detection of PrPSc. PrPSc was detected in brain, spinal cord, dorsal root ganglia, trigeminal ganglia, sublingual ganglion, retina. In addition, PrPSc was also detected in the peripheral nerves (sciatic nerve, tibial nerve, vagus nerve). Our results suggest that the currently accepted definitions of SRM in BSE cattle may need to be reexamined. ... 179 T. Kitamoto (Ed.) PRIONS Food and Drug Safety ================ International Symposium of Prion Diseases held in Sendai, October 31, to November 2, 2004 http://docket.epa.gov/edkfed/do/EDKStaffAttachDownloadPDF?objectId=090007d480993808 ============================================= I GUESS my next question is about blood from cattle being fed back to cattle. SINCE it has now been proven that nvCJD in humans (which in there terms is the only TSE related to BSE in cattle) that nvCJD in humans transmits to humans via blood, then why no concern about blood from BSE infected cattle being fed back to cattle$ i guess you could trace it back to big business making corporate decisions on scientific matters. BSE tainted blood is just a small part of it. course, if you have no mad cows as Johanns is so sure of himself, you have no problems, unless, the 'fong syndrome' strikes. and we all know how to take care of that, just let the tissue samples sit up on the shelf for 4 months or so in preservative this time... STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995 snip... To minimise the risk of farmers' claims for compensation from feed To minimise the potential damage to compound feed markets through adverse publicity. To maximise freedom of action for feed compounders, notably by snip... THE FUTURE 4.......... MAFF remains under pressure in Brussels and is not skilled at 5. Tests _may_ show that ruminant feeds have been sold which 6. The threat remains real and it will be some years before feed SEE full text ; http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf NO need to worry about the fact that BSE blood transmits to sheep either; Research letters Transmission of BSE by blood transfusion See Commentary We have shown that it is possible to transmit The demonstration that the new variant of We report preliminary data from a study We have seen BSE clinical signs and pathological PrPSc (proteinase K treated) analysed by SDS-PAGE, All lanes are from the same gel with different We thank Karen Brown, Moira Bruce, Calum 1 Bruce ME, Will RG, Ironside JW, et al. 2 Schmerr MJ, Jenny A, Cutlip RC. Use of 3 Foster JD, Bruce M, McConnell I, Chree A, 4 Hill AF, Zeidler M, Ironside J, Collinge J. 5 Goldmann W, Hunter N, Smith G, Foster J, ======================= Commentary BSE and transmission through blood Blood, especially the buffy-coat component, In naturally infected animals (sheep and goats Blood from four of 37 human beings with Epidemiological data have not revealed a No comparable information about vCJD is available. In this issue of The Lancet, F Houston and co-workers Is it appropriate to publish an experimental Paul Brown 1 Ghani AC, Ferguson NM, Donnelly CA, Anderson RM. 2 Brown P. Can Creutzfeldt-Jakob disease be 3 Brown P, Cervenáková L, McShane LM, Barber P, 4 Rohwer RG. Titer, distribution, and transmissibility 5 Hill AF, Butterworth RJ, Joiner S, et al. Investigation http://www.thelancet.com/ From: Terry S. Singeltary Sr. (216-119-130-97.ipset10.wt.net) In Reply to: Transmission of BSE by blood transfusion in sheep... posted by Terry S. Singeltary Sr. on September 15, 2000 at 9:29 am: Transmission of Creutzfeldt-Jakob Disease from Blood and Urine Into Mice The Lancet, November 9, 1985 Sir,--Professor Manuelidis and his colleagues (Oct 19, p896) report A 70-year-old man was noted to have a slowing of speech and writing Results of innoculation in Mice Inocula NO* Incubation period (days)+ * Number of mice with CJD change/number examined histologically. + means + or - SD Samples were taken aseptically at necropsy. 10% crude homogenates In our long-term experiments, inoculating materials taken from As viraemia has been proved in guineapigs,6 mice,1,7 and lately Department of Neuropathology, JUN TATEISHI 1. Tateishi J, Sato Y, Kaga M. Doi H, Ohta M. Experimental transmission 2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakob 3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in the 4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D. 5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L. 6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimental 7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC. 8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiform 9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob disease Subject: Transmission of TSEs through blood ######### Bovine Spongiform Encephalopathy ######### The Lord Lucas asked Her Majesty's Government: Whether there is any evidence that any Transmissible Spongiform Some animal studies have shown that certain transmissible spongiform Copies of the following relevant scientific papers are being placed in the Library. Brown P, 1995, "Can Creutzfeldt-Jakob Disease be transmitted by Brown et al 1999, Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt - Jakob disease in humans. Transfusion Vol. 39, November/December 1169 - 1178. >>>>>What, therefore, is the Paul Brown <<<<<< SEAC May 2005 1 POSITION STATEMENT EARLY PHASE OF vCJD INFECTION IN BLOOD TRANSFUSION RECIPIENTS Issue 1. The Committee on Microbiological Safety of Blood, Tissue and Organs has requested advice from SEAC on whether a scientific distinction can be drawn between historic and recent blood transfusion recipients in terms of the relative load of the vCJD agent that may be present in the bone, tissues or organs of the blood transfusion recipient. In the context of this question, a recent recipient is defined as having received a blood transfusion within the week prior to bone, tissue or organ donation. A historic recipient is defined as having received a blood transfusion in the more distant past. Background 2. A pre-symptomatic diagnostic test for vCJD is currently not available. Therefore, blood, bone, tissue or organ donors with a sub- or pre-clinical vCJD infection cannot be identified prior to donation. Two cases of vCJD infection in recipients of blood from donors that subsequently developed vCJD suggest that the disease may be transmitted from asymptomatic individuals via blood transfusion. Epidemiological evidence of iatrogenic transmission of sCJD suggests there is a potential risk of vCJD transmission via tissue/organ transplantation. 3. There are no data on the tissue distribution of vCJD infectivity in humans in the first week following infection by blood transfusion. There is some, albeit very limited, information from mouse studies on prion replication and spread in the early phase of infection. However, these studies used inocula, routes of administration and prion strains not directly applicable to the human blood transfusion situation. 2 Early phase tissue accumulation of abnormal prions 4. On the basis of the very limited information available, it is considered unlikely that significant prion replication would occur in tissues in the first week following transfusion with infected blood. Thus, the level of abnormal prions accumulating in a tissue would probably correlate with the level of vascularisation of that tissue. Highly vascularised organs such as the liver, lung and spleen, as well as bone, would be more likely to contain the agent compared with other organs. At later times in the incubation period (likely to be well in excess of one week), the accumulation of abnormal prion protein and infectivity would be expected to correlate with the ability of various tissues to support prion replication, with the central nervous system containing the highest levels of infectivity. Relative risks 5. Data are too limited to allow quantification of the risks of transplant associated vCJD transmission from donors that have received a blood transfusion. 6. The number of pre- and sub-clinical vCJD infections in the population is believed to be small. Therefore, there is a small risk of vCJD transmission from transplantation of tissues/organs from all donors, irrespective of whether they have received a blood transfusion prior to donation. The additional risk resulting from a tissue/organ donor having received a blood transfusion at any time prior to donation is likely to be small. Furthermore, the introduction of precautionary safety measures to protect the blood supply, such as leucodepletion and exclusion of previously transfused blood donors, means that, in general, the risk of blood transfusionassociated transmission of vCJD from tissue/organ donation is, if anything, likely to be lower if the transfusion is recent rather than historic. However, it is not possible to define a threshold of lowest risk in terms of a specific date of, or period of time following, a blood transfusion. Possible risk reduction measures 7. Screening cadaveric donors for markers of infection would allow, depending on the sensitivity of the test used, pre- or sub-clinically infected donors to be identified prior to the use of the donated tissues/organs. Retrospective screening of donors would also help to inform assessment of transmission risks. 3 8. On the basis that tissue/organ infectivity levels in the very early stage of infection are associated with the blood content of tissues/organs, washing or perfusing tissues to remove blood could reduce the infectious load. In this respect, it would be important to consider processes that efficiently remove bone marrow and blood from bone. 9. Avoiding the pooling of tissues from different donors to be transplanted into one individual reduces transmission risks to that individual. Summary 10. There is no clinical evidence that vCJD has been transmitted through tissue/organ transplantation. However, a potential risk of transmission via this route exists. Relevant data are extremely limited but suggest that in the early phase of infection, significant prion replication is unlikely to occur and that, therefore, tissue levels of abnormal prions following recent transfusions are likely to be related to the blood supply to each specific tissue. 11. A risk of transplant associated transmission of vCJD exists from tissue/organ donors that have not received blood transfusions. The additional risk as a result of a donor having received a recent blood transfusion is likely to be very small. Post mortem assessment of donor infection would provide the best method of risk reduction and enable these risks to be quantified. 12. In assessing and communicating the risks a balance must be struck between the small risk of vCJD transmission by transplantation and the benefits to patients receiving a transplant, especially where tissues/organs are scarce and are required for (potentially) life-saving procedures. SEAC May 2005 http://www.seac.gov.uk/pdf/cjd.pdf SEAC Statement 7th August 2004 -------------------------------------------------------------------------------- Summary of SEAC’s discussion on the second presumed case of blood transfusion-associated infection with vCJD 1. The Department of Health sought advice from the committee on a presumed second instance of blood transfusion-associated transmission of the variant Creutzfeldt-Jakob disease (vCJD) agent. The first case of probable blood transfusion-associated transmission of vCJD1 was considered by SEAC in February 2004. 2. The National CJD Surveillance Unit (NCJDSU) had investigated this second patient after death, as the patient was a known recipient of blood from a donor incubating vCJD. Patient confidentiality and medico-legal issues surrounding the patient at the time of reporting required that the issue was considered in the reserved session of the meeting. 3. The elderly patient died in 2004, showed no clinical signs of vCJD at the time of death, which was from an unrelated cause. The patient had received a single unit of non-leucodepleted blood in 1999 that had been donated by an individual who was confirmed in 2001 as a definite vCJD case. The donor’s disease onset was in 2000. 4. The NCJDSU had investigated the neuropathology, accumulation of prion protein and PrPres in autopsied tissues in the case. The PRPN genotype had also been determined. The following details were reported: No evidence of a spongiform encephalopathy in an examination of brain material. 6. The Department of Health (DH) asked SEAC to assess the data available on this case, and to advise on the implications this finding may have on the risk associated with blood, and on any additional concerns for public health. 8. The committee agreed that the statistical analysis suggested that the presence of PrPres in the case was attributable to a vCJD infection acquired via blood transfusion rather than a primary infection resulting from a food borne exposure. 9. SEAC agreed that this second patient with apparent vCJD infection added to the evidence that the vCJD agent can be transmitted by blood. However the committee noted that in this instance, although vCJD infection appeared to have been transmitted, it was not known if clinical vCJD would have developed if the patient had lived longer. 10. SEAC agreed that this case added support to its view on the risk associated with blood transfusion. The finding was consistent with there being a substantial risk associated with receipt of non-leucodepleted blood from a donor incubating vCJD. The extent to which leucodepletion reduces that risk is not known. 11. The committee agreed that it should be a public health priority for all recipients of blood (leucodepleted or not) from donors incubating vCJD to be subject to the kind of careful post-mortem examination that had been possible in this case. This would help to quantify the nature and magnitude of the risks of transmission of the vCJD agent through blood [donated by preclinical cases of vCJD]. The committee re-iterated the continuing importance of the Transfusion Medicine Epidemiology Review (TMER) to identify vCJD cases who have been donors and the recipients of such donations. 12. SEAC noted that the detection of PrPres in lymphoreticular tissues of vCJD cases and the presence of infection in the spleen of this case was compatible with the lymphoreticular system being involved in the early spread of infection before entering the CNS. SEAC agreed that the detection of prion protein in the spleen but not in the tonsil of the case has implications for the national anonymous tonsil archive. The SEAC chair agreed to refer this finding to the DH/MRC steering group overseeing the archive. 13. SEAC noted that the patient was heterozygous at codon 129 of the PRNP gene and that this was the first time infection with the vCJD agent had been reported in an individual not methionine homozygous. This indicated that genotypes other than the methionine homozygous were susceptible to infection with the vCJD agent. Uncertainties remain as to the relative susceptibility of heterozygotes to food borne (or other) infection or the possible outcomes of infection. The committee agreed that the similarities between the western blot band analysis and PrPres glycoprofile seen in this case and in cases of vCJD who were methionine homozygous was reassuring with respect to the ability to make the diagnosis of vCJD in those of genotypes other than methionine homozygous. 14. SEAC stated that, in the interests of public health, this case demonstrates the importance of both in life and in death surveillance of recipients of blood products derived from blood donations from individuals subsequently found to be infected with the vCJD agent. The committee also noted that this case highlighted the importance of obtaining autopsies in such patients and, more generally, the committee reiterated the concern that it had expressed previously, that a mechanism was needed to increase the autopsy rate amongst the UK population to reduce the possibility that cases of vCJD were being missed. 15. SEAC emphasised the importance of the DH-funded sheep transfusion study which is designed to investigate the infectivity of different blood fractions taken from sheep experimentally infected with BSE by transfusing them into ARQ homozygous sheep. The committee noted that the two presumed human cases of blood transfusion-associated vCJD infection indicated the potential infectivity of transfused blood. However, current technology is unable to quantify the levels of infectivity in blood and a rapid diagnostic test remained a key research priority. SEAC 2. Hilton DA, Ghani AC, Conyers L, Edwards P, McCardle L, Ritchie D, Penney M, Hegazy D, Ironside JW. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. Journal of Pathology: 203 (3).733-739. Published Online: 21 May 2004 http://www.seac.gov.uk/statements/state070804.htm no need to hurry now that every human on the planet has been needlessly exposed. we all can only hope we outlive the disease, and can remember to tell about it. seems the uk and the usa have been mirrored in this nightmare from day one; Also, because source material for gelatin and tallow was tightly controlled and subject to processing that would reduce any infectivity present, Members were also content for gelatin and tallow to remain exempt from the current feed ban. However, Members considered there was a theoretical possibility that if blood meal derived from a sheep infected with scrapie were included in a sheep ration, this could present a risk to animal health. If so, it may theoretically compromise current efforts to eradicate scrapie from the national flock. SEAC asked that this potential risk and its implications be considered within the context of the national scrapie eradication plan. http://www.seac.gov.uk/summaries/summ_0900.htm The exact same recipe for B.S.E. existed in the U.S. for years and years. In reading over the Qualitative Analysis of BSE Risk Factors-1, this is a 25 page report by the USDA:APHIS:VS. It could have been done in one page. The first page, fourth paragraph says it all; "Similarities exist in the two countries usage of continuous rendering technology and the lack of usage of solvents, however, large differences still remain with other risk factors which greatly reduce the potential risk at the national level." Then, the next 24 pages tries to down-play the high risks of B.S.E. in the U.S., with nothing more than the cattle to sheep ratio count, and the geographical locations of herds and flocks. That's all the evidence they can come up with, in the next 24 pages. Something else I find odd, page 16; "In the United Kingdom there is much concern for a specific continuous rendering technology which uses lower temperatures and accounts for 25 percent of total output. This technology was _originally_ designed and imported from the United States. However, the specific application in the production process is _believed_ to be different in the two countries." A few more factors to consider, page 15; "Figure 26 compares animal protein production for the two countries. The calculations are based on slaughter numbers, fallen stock estimates, and product yield coefficients. This approach is used due to variation of up to 80 percent from different reported sources. At 3.6 million tons, the United States produces 8 times more animal rendered product than the United Kingdom." "The risk of introducing the BSE agent through sheep meat and bone meal is more acute in both relative and absolute terms in the United Kingdom (Figures 27 and 28). Note that sheep meat and bone meal accounts for 14 percent, or 61 thousand tons, in the United Kingdom versus 0.6 percent or 22 thousand tons in the United States. For sheep greater than 1 year, this is less than one-tenth of one percent of the United States supply." "The potential risk of amplification of the BSE agent through cattle meat and bone meal is much greater in the United States where it accounts for 59 percent of total product or almost 5 times more than the total amount of rendered product in the United Kingdom." Considering, it would only take _one_ scrapie infected sheep to contaminate the feed. Considering Scrapie has run rampant in the U.S. for years, as of Aug. 1999, 950 scrapie infected flocks. Also, Considering only one quarter spoonful of scrapie infected material is lethal to a cow. Considering all this, the sheep to cow ration is meaningless. As I said, it's 24 pages of B.S.e. To be continued... Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA http://bmj.bmjjournals.com/cgi/eletters/320/7226/8/b#EL1 Race R, Raines A, Raymond GJ, Caughey B, Chesebro B. (2001) Long-term subclinical carrier state precedes scrapie replication and adaptation in a resistant species: analogies to bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease in humans. J Virol. 75(21):10106-12. Cattle infected with bovine spongiform encephalopathy (BSE) appear to be a reservoir for transmission of variant Creutzfeldt-Jakob disease (vCJD) to humans. Although just over 100 people have developed clinical vCJD, millions have probably been exposed to the infectivity by consumption of BSE-infected beef. It is currently not known whether some of these individuals will develop disease themselves or act as asymptomatic carriers of infectivity which might infect others in the future. We have studied agent persistence and adaptation after cross-species infection using a model of mice inoculated with hamster scrapie strain 263K. Although mice inoculated with hamster scrapie do not develop clinical disease after inoculation with 10 million hamster infectious doses, hamster scrapie infectivity persists in brain and spleen for the life span of the mice. In the present study, we were surprised to find a 1-year period postinfection with hamster scrapie where there was no evidence for replication of infectivity in mouse brain. In contrast, this period of inactive persistence was followed by a period of active replication of infectivity as well as adaptation of new strains of agent capable of causing disease in mice. In most mice, neither the early persistent phase nor the later replicative phase could be detected by immunoblot assay for protease-resistant prion protein (PrP). If similar asymptomatic carriers of infection arise after exposure of humans or animals to BSE, this could markedly increase the danger of additional spread of BSE or vCJD infection by contaminated blood, surgical instruments, or meat. If such subclinical carriers were negative for protease-resistant PrP, similar to our mice, then the recently proposed screening of brain, tonsils, or other tissues of animals and humans by present methods such as immunoblotting or immunohistochemistry might be too insensitive to identify these individuals. Ramasamy I, Law M, Collins S, Brooke F (2003). Organ distribution of prion proteins in variant Creutzfeldt-Jakob disease. Lancet Infect Dis. 3(4):214-22. In this article we give an overview of the transmissible spongiform encephalopathies, with emphasis on the evidence for the distribution of abnormal prions in tissues. The normal prion protein is distributed ubiquitously throughout human body tissues. Endogenous expression of the normal prion protein, as well as auxiliary proteins, plays a part in accumulation of the abnormal prion protein. As exemplified by variant Creutzfeldt-Jakob disease (vCJD) the abnormal prion protein can accumulate in the host lymphoid system, in particular the follicular dendritic cells. The route for the disease-related prion neuroinvasion is likely to involve the peripheral nervous system. An alternative route may involve blood constituents. Both animal studies and studies on vCJD patients suggest a potential for abnormal prion distribution in several peripheral tissues other than the lymphoreticular system. In human beings the abnormal prion has been reported in the brain, tonsils, spleen, lymph node, retina, and proximal optic nerve. Infectivity, although present in peripheral tissues, is at lower levels than in the central nervous system (CNS). Animal models suggest that the growth of infectivity in the CNS is likely to be gradual with maximum values during the clinical phase of disease. That tissues may harbour the abnormal prion, at different levels of infectivity, during the incubation period of the disease raises concerns of iatrogenic transmission of the disease either after surgery, blood transfusion, or accidental organ transplantation from donors in the preclinical phase of the disease. BACKGROUND: The disease-associated form of prion protein (PrP(res)) has been noted in lymphoreticular tissues in patients with variant Creutzfeldt-Jakob disease (vCJD). Thus, the disease could be transmitted iatrogenically by surgery or use of blood products. We aimed to assess transmissibility of the bovine spongiform encephalopathy (BSE) agent to primates by the intravenous route and study its tissue distribution compared with infection by the oral route. METHODS: Cynomolgus macaques were infected either intravenously or orally with brain homogenates from first-passage animals with BSE. They were clinically monitored for occurrence of neurological signs and killed humanely at the terminal stage of the disease. Brain, lymphoreticular tissues, digestive tract, and peripheral nerves were obtained and analysed by sandwich ELISA and immunohistochemistry for quantitative and qualitative assessment of their PrP(res) content. FINDINGS: Incubation periods after intravenous transmission of BSE were much shorter than after oral infection. We noted that PrP(res) was present in lymphoreticular tissues such as spleen and tonsils and in the entire gut from the duodenum to the rectum. In the gut, PrP(res) was present in Peyer's patches and in the enteric nervous system and nerve fibres of intestinal mucosa. Furthermore, PrP(res) was found in locomotor peripheral nerves and the autonomic nervous system. Amount of PrP(res) ranged from 0.02% to more than 10% of that recorded in brain. Distribution of PrP(res) was similar in animals infected by the intravenous or oral route. INTERPRETATION: Our findings suggest that the possible risk of vCJD linked to endoscopic procedures might be currently underestimated. Human iatrogenic vCJD cases infected intravenously raise the same public-health concerns as primary cases and need the same precautionary measures with respect to blood and tissue donations and surgical procedures. nope, the fda/usda et al have floundered too long now. they had there chance, but fumbled the mad cow ball again... still disgusted in Bacliff, Texas...TSS Importation of Whole Cuts of Boneless Beef from Japan [Docket No. 05-004-1] RIN 0579-AB93 TSS SUBMISSION http://docket.epa.gov/edkfed/do/EDKStaffAttachDownloadPDF?objectId=090007d480993808 http://docket.epa.gov/edkfed/do/EDKStaffCollectionDetailView?objectId=0b0007d48096b40d Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW BSE SAFEGUARDS (comment submission) https://web01.aphis.usda.gov/regpublic.nsf/0/eff9eff1f7c5cf2b87256ecf000df08d?OpenDocument http://www.fda.gov/ohrms/dockets/dockets/03n0312/03N-0312_emc-000001.txt Docket Management Docket: 02N-0273 - Substances Prohibited From Use in Animal Food or Feed; Animal Proteins Prohibited in Ruminant Feed Comment Number: EC -10 Accepted - Volume 2 PART 2 PDF]Freas, William TSS SUBMISSION File Format: PDF/Adobe Acrobat - Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary Sr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ... http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf Asante/Collinge et al, that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest _sporadic_ CJD; http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm Docket Management Docket: 96N-0417 - Current Good Manufacturing Practice http://www.fda.gov/ohrms/dockets/dailys/03/Mar03/031403/96N-0417-EC-2.htm Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION http://www.fda.gov/ohrms/dockets/dockets/03n0312/03N-0312_emc-000001.txt # Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of Docket Management Docket: 02N-0276 - Bioterrorism Preparedness; Registration of Food Facilities, Section 305 http://www.fda.gov/ohrms/dockets/dockets/02n0276/02N-0276-EC-254.htm OTC External Analgesic Drug Products, ... EMC 7, Terry S. Singeltary Sr. http://www.fda.gov/ohrms/dockets/dailys/03/oct03/100203/100203.htm DOCKETS ENTERED on 2/5/03. ... EMC 4 Terry S. Singeltary Sr. Vol#: 2. 03N-0009 Federal Preemption of State & Local Medical Device Requireme. ... Docket: 02N-0370 - Neurological Devices; Classification of Human Dura Mater Comment Number: EC -1 Accepted - Volume 1 ... 00D-1662 Use of Xenotransplantation Products in Humans. http://www.fda.gov/ohrms/dockets/dailys/03/Jun03/060903/060903.htm 2003D-0186 01N-0423 Substances Prohibited from use in animal food/Feed Ruminant APE 5 National Renderers Association, Inc. Vol#: 2 APE 6 Animal Protein Producers Industry Vol#: 2 APE 7 Darling International Inc. Vol#: 2 EMC 1 Terry S. Singeltary Sr. Vol#: 3 http://www.fda.gov/ohrms/dockets/dailys/01/Oct01/101501/101501.htm TSS
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