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From: TSS ()
In Reply to: Re: McDonald's Corp. seven scientists and experts and a pharmaceutical supplier Seriologicals Corp. U.S. NOT PROTECTED AGAINST MAD COW DISEASE posted by TSS on January 7, 2006 at 7:11 am:
December 19, 2005 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Dear Sir or Madame: The McDonalds Corporation buys more beef than any other restaurant in the United States. It is essential for our customers and our company that the beef has the highest level of safety. Concerning BSE, the most effective way to insure this is to create a system that processes cattle that are not exposed to the disease. As a company we take numerous precautions via our strict specifications to help and assure this, however we feel that the force of federal regulation is important to ensure that the risk of exposure in the entire production system is reduced to as close to zero as possible. 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. It is our opinion that the government can take further action to reduce this risk and 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 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 caution against using the 18 month enhanced surveillance as a justification to relax or impede further actions. While this surveillance indicates an epidemic is not underway, it does not clear the US cattle herd from infection. The positive cases indicate probable exposure prior to the 1997 feed ban, a time when BSE appears to have been circulating in animal feed. BSE cases are most likely clustered in time and location, so while enhanced surveillance provides an 18 month snapshot, it does not negate the fact that US and Canadian cattle were exposed to BSE and that the current feed controls contain “leaks”. 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 .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. The proposed rule still allows the possibility for cattle to be exposed to BSE through: Feeding of materials currently subject to legal exemptions from the ban (e.g., poultry litter, plate waste) We are most concerned that the FDA has chosen to include a provision that 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. Firstly, there are two issues regarding the complex logistics of this option. We do not feel that it is possible to have adequate removal especially during the warmer months. In addition, we do not feel that there are adequate means to enforce complete removal. Unlike slaughterhouses, there are no government inspectors at rendering plants or deadstock collection points. Most importantly, there is emerging information that at end stage disease (a natural BSE case); infectivity may also be included in additional tissues such as peripheral nerves (Buschmann and Groschup, 2005 – see attached). This published work supports publicly reported studies in Japan where by western blot testing, prions have been found in the peripheral nerves of a naturally infected 94-month-old cow. If this is the case, the amount of infectivity left in the system from an infected bovine would surpass 10% and the full extent is still unknown. McDonalds has convened it own International Scientific Advisory Committee (ISAC) as well as co-sponsored a symposium of TSE scientists on the issue of tissue distribution. The consensus of both groups was that the pathogenesis of BSE might not be entirely different from TSEs in other species at the point where the animal is showing signs of the disease. These scientists feel that the studies as reported above have merit. The current studies not only re-enforce the risk of down and deadstock but also appear to provide additional information that these animals may be a potential source of greater levels of infectivity into the feed system. Hence, we suggest that the FDA consult with TSE scientists as well. Leaving the tissues from the highest risk category of 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 that 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 cattle that die on the farm would also have a substantial influence on the spread of BSE if the disease were introduced.” The base case scenario showed that the mean total number of ID50s (i.e., dosage sufficient to infect 50 percent of exposed cattle) from healthy animals at slaughter presented to the food/feed system was 1500. The mean total number of ID50s from adult cattle deadstock presented to the feed system was 37,000. This illustrates the risk of “4D cattle” (i.e., deadstock). From the Harvard Risk Assessment, 2001, Appendix 3A Base Case and Harvard Risk Assessment, 2001 Executive Summary McDonalds also urges agencies of the US government to work with academia and industry on research in the following areas: · Methods to inactivate TSEs agents which then may allow a product to be used and even fed to animals without risk · Alternative uses for animal byproducts which would maintain some value In July 2004, McDonalds in cooperation with others sponsored a meeting at Penn State. The purpose of the meeting was to review work conducted by Dr. Bruce Miller looking at the feasibility of using carcasses and animal byproducts as renewable alternatives to fossil fuels in large energy generating boilers. A number of government representatives were also invited to this meeting. We are aware that Dr. Miller continues this work which shows great promise. We suggest that the FDA explore the possibility of this alternative use that may also have a positive impact on the environment. The McDonalds Corporation will continue to work with the FDA and other government agencies to implement a strong BSE risk control program. We 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, Dick Crawford Corporate Vice President, Government Relations xxxxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxx dick.crawford@mcd.com ============================================================================ ============================================================================ December 20, 2005 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Dear Sir or Madame: As scientists and recognized experts who have worked in the field of TSEs for decades, we are deeply concerned by the recent discoveries of indigenous BSE infected cattle in North America and appreciate the opportunity to submit comments to this very important proposed rule We strongly supported the measures that USDA and FDA implemented to protect public health after the discovery of the case of bovine spongiform encephalopathy (BSE) found in Washington State in 2003. We know of no event or discovery since then that could justify relaxing the existing specified risk material (SRM) and non-ambulatory bans and surveillance that were implemented at that time. Further, we strongly supported the codification of those changes, as well as additional measures to strengthen the entire feed and food system. The discovery of additional cases of indigenous BSE in North America since that time has validated our position and strengthened our convictions. We caution against using the 18 month enhanced surveillance as a justification to relax or impede further actions. While this surveillance has not uncovered an epidemic, it does not clear the US cattle herd from infection. While it is highly likely that US and Canadian cattle were exposed to BSE prior to the 1997 feed ban, we do not know how many cattle were infected or how widely the infection was dispersed. BSE cases are most likely clustered in time and location, so while enhanced surveillance provides an 18 month snapshot, it does not negate the fact that US and Canadian cattle were exposed to BSE. We also do not know in any quantitative or controlled way how effective the feed ban has been, especially at the farm level. At this point we cannot even make a thorough assessment of the USDA surveillance as details such as age, risk category and regional distribution have not been released. A number of countries initially attempted to take partial steps in regard to feed controls only to face repeated disappointments in predicted downturns of the epidemic course. We in North America could do this experiment all over again, waiting for each new warning before adding more stringency to our control measures, or we can benefit from the experience of others and take decisive measures now to arrest any further development of underlying cases that is implicit in those already discovered to date. The discovery of 5 indigenous North American cases, including one born after the implementation of the current feed ban, should provide the necessary incentive to implement, monitor and enforce a comprehensive and protective feed ban that is more congruent with the measures that have been proven to be effective throughout the world. In particular, we urge the FDA to act without further delay to strengthen the animal feed regulations by implementing the program proposed by the Canadian Food Inspection Agency (CFIA) in the December 11, 2004 Gazette. This includes removing all specified risk materials (SRMs) and deadstock from all animal feed. We also urge that the FDA discontinues the legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk). Many of these exemptions do not exist in other countries. Bovine products and byproducts are used for both food and pharmaceuticals. These human uses require the highest level of safety. Because of the hardy nature of the BSE agent and its high potential for cross contamination, the most effective way to protect bovine products and bovine derived materials from contamination by BSE is to ensure that infected animals or carcasses never enter processing plants. The goal would be to discover and remove infected animals from production as early as possible in the infection and long before they would be sent to slaughter. Until we have diagnostic tools powerful enough to allow us to discover the disease early in its prolonged pre-clinical incubation, we have to rely on the next best strategy which is to prevent any exposure through feed. The exemptions in the current ban as well as in the newly proposed rule make this difficult if not impossible, as they still provide legal avenues for ruminants to consume potentially contaminated ruminant protein. It is our opinion that the proposed rule falls woefully short in effective measures to minimize the potential for further transmissions of the disease. By the FDA’s own analysis, exempted tissues (such as distal ileum, DRGs, etc) contain approximately 10% of the infectivity in affected animals. Thus the proposed rule still allows the possibility for cattle to 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 has chosen to include a provision that would allow tissues from deadstock into the feed chain. We do not believe that down or dead stock should be allowed into the food or feed chain whatever the age of the animal and whether or not the CNS tissues are removed. We do not support the provision to allow removal of brain and spinal cord from deadstock over 30 months for a number of reasons. [RR1] This category of animals contains the highest level of infectivity and that infectivity is in other tissues besides just brain and spinal cord. Recent improvements in the BSE bioassay, have now made it possible to detect BSE infectivity 1000 time more efficiently than before. This assay has revealed the presence of BSE infectivity in some but not all peripheral nerves and in one muscle. (Buschmann and Groschup, 2005) This published and peer reviewed work is consistent with other publicly reported studies in Japan where, by western blot testing, prions were found in the peripheral nerves of a naturally infected 94-month-old cow. We feel that the studies as reported above have merit. The current studies not only re-enforce the risk of down and deadstock but also appear to provide additional information that these animals may be a potential source of greater levels of infectivity into the feed system. We also doubt that brain and spinal cord can be completely removed especially during warmer weather. Given the biological composition of these tissues, they are predisposed to rapid autolysis. As world wide surveillance for BSE increases, several atypical cases of bovine TSE have been discovered. These cases either show no clinical signs, or present as ‘downers’, and have an atypical neuropathology with respect to lesion morphology and distribution, causing problems in both clinical and post-mortem diagnosis. The origin of the cases are unclear but they suggest that even should typical BSE be eliminated, there may be other TSE diseases of cattle that could result by “mutation” and selection. Refeeding of contaminated protein could potentially perpetuate transmission much like typical BSE. An effective feed ban could prevent the expansion of such strains. We also note that there are other species which are susceptible to BSE and the current regulations allow for SRMs to be included in feed for these animals. For BSE to be perpetuated, the animal production system must have a source of agent and a means by which cattle or other susceptible species are exposed to this agent. We feel that in North America, the source and routes of exposure still exist, hence allowing for the continued recycling of BSE. We have detailed the scientific justifications for our position below. Source of the agent: SRMs (Specified Risk Materials) 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. For example, the skull and vertebral column which encase the brain and spinal cord, respectively, can be assumed to have gross 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 tissue distribution of infectivity in BSE infected cattle has primarily been determined by 3 studies conducted in the United Kingdom all of which had limitations. In two of the studies, bioassays were done in mice which are at least 1000 fold less sensitive to BSE infection than cattle themselves. Only higher titers of infectivity can be detected by this method. These investigations found infectivity in the brain, spinal cord, retina, trigeminal ganglia, dorsal root ganglia, distal ileum and bone marrow (the bone marrow finding was from one animal). Infectivity was found in distal ileum of experimentally infected calves beginning six months after challenge and continuing at other intervals throughout life. (Wells et. al., 1994; 1998). The bioassay study in calves has produced similar results and in addition infectivity has been found in tonsil. The study is still in progress. Another project has found infectivity in the lymphoid tissue of third eyelid from naturally infected animals. (Dr. Danny Matthews, UK DEFRA, personal communication). While bioassay in cattle is far preferable to mice in terms of sensitivity, cattle nevertheless present their own limitations in terms of the long incubation time and the limited number of animals that can be used for assay compared to rodents. As a consequence the significance of the negative finding for many tissues is questionable. In fact, by the end of 2004 there was increasing evidence in species other than cattle that peripheral nerves and muscle have infectivity. (Bosque et al., 2002; Glatzel et al., 2003;Bartz et al., 2002; Androletti et al., 2004; Mulcahy et al., 2004; Thomzig et al., 2003; Thomzig et al., 2004) In some of these species, studies indicate that the agent migrates to the brain and spinal cord, replicates to high levels in the CNS and then spreads centrifugally from the spinal cord back down through the spinal neurons to the junction of the nerves and muscle into the muscle cells themselves. A recent German study (Buschmann and Groschup, 2005) examined nerves and muscle from a cow naturally infected with BSE and found that infectivity was present in several peripheral nerves and one muscle. The method of detection was bioassay in bovinized transgenic mice that show the same or greater sensitivity to transmission of BSE as cattle. This research concurs with findings by Japanese scientists that BSE infectivity is present in peripheral nerves at least in the clinical stage of disease. It is our opinion that there is increasing evidence that the pathogenesis of BSE might not be entirely different from TSEs in other species at the point of clinical disease in that there is peripheral involvement. We feel that the studies as reported above have merit. The current studies not only re-enforce the risk of down and deadstock but also appear to provide additional information that these animals may be a potential source of greater levels of infectivity into the feed system. In the event that FDA may confer with USDA about the risks associated with peripheral nerves we want to point out one issue. In the recent publication of the final rule on the importation of whole cuts of boneless beef from Japan, 9 CFR Part 94 [Docket No. 05-004-2] RIN 0579-AB93, we disagree with the interpretation provided by USDA, APHIS. APHIS seems to discount the studies conducted by Groschup et al. 2005. on the basis that the transgenic mouse bioassay that they used may be too sensitive. In taking this position they have failed to realize that the point of an assay is to reveal in which tissues the infectivity resides and its relative concentration to brain or spinal cord. For this purpose, no assay can be too sensitive. Of course, the probability of an actual infection will be affected by the efficiency of infection which will be a function of dose, route of exposure and any host barrier effects that are present. We would also like to point out a factual error in the conclusion. APHIS states, “Given these factors, APHIS has determined that the finding of BSE infectivity in facial and sciatic nerves of the transgenic mice is not directly applicable to cattle naturally infected with BSE. Therefore, we do not consider it necessary to make any adjustments to the risk analysis for this rulemaking or to extend the comment period to solicit additional public comment on this issue.” It is incorrect that the infectivity was found in the peripheral nerves of transgenic mice. The peripheral nerves were harvested from a cow naturally infected with BSE. Transgenic mice were used as a bioassay model. “Peripheral Nerves Issue: Two commenters stated that the underlying assumption of the proposed rule, that whole cuts of boneless beef from Japan will not contain tissues that may carry the BSE agent, is no longer valid because researchers have found peripheral nervous system tissues, including facial and sciatic nerves, that contain BSE infectivity.\2\ One of these commenters requested APHIS to explain whether and what additional mitigation measures are needed to reduce the risks that \2\ Bushmann, A., and Groschup, M.; Highly Bovine Spongiform Response: APHIS is familiar with the results of the study mentioned by the commenters in which mice, genetically engineered to be highly susceptible to BSE and to overexpress the bovine prion protein, were inoculated with tissues from a BSE-infected cow. This study demonstrated low levels of infectivity in the mouse assay in the facial and sciatic nerves of the peripheral nervous system. APHIS has evaluated these findings in the context of the potential occurrence of Source of the agent: Deadstock The total amount of TSE infectivity in a TSE infected animal increases steadily throughout the infection and exponentially once the infectivity reaches the brain. Infected individuals only exhibit recognizable clinical signs once infectivity titers have reached high levels in the brain. Surveillance data collected throughout Europe indicates there is a much greater likelihood for BSE to be detected in dead or down cattle than from healthy normal animals. This has so far also been borne out by the experience in North America. Animals that die of BSE harbor the greatest amount of agent that can be produced by the disease. Leaving the tissues from the highest risk category of cattle in the animal feed chain will effectively nullify the purported intent of this regulation. This point is supported by the 2001 Harvard risk assessment model that 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 cattle that die on the farm would also have a substantial influence on the spread of BSE if the disease were introduced.” The base case scenario showed that the mean total number of ID50s (i.e., dosage sufficient to infect 50 percent of exposed cattle) from healthy animals at slaughter presented to the food/feed system was 1500. The mean total number of ID50s from adult cattle deadstock presented to the feed system was 37,000. This illustrates the risk of “4D cattle” (i.e., deadstock). From the Harvard Risk Assessment, 2001, Appendix 3A Base Case and Harvard Risk Assessment, 2001 Executive Summary It is likely that these numbers would have to be adjusted upwards, if the UK attack rate and Groschup data were considered. Inflammation and TSEs There have been 3 recent peer reviewed publications which indicate that chronic inflammatory conditions in a host with a TSE may induce prion replication in, or distribution to organs previously thought to be low or no risk. They are as follows: Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions (Heikenwalder et. al. 2005 www.sciencexpress.org/20 January 2005/ Page 1/ 10.1126/science.1106460) 2. Coincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion (Seeger et al., Science 14 October 2005:Vol. 310. no. 5746, pp. 324 – 326 DOI: 10.1126/science.1118829) 3. PrPsc in mammary glands of sheep affected by scrapie and mastitis (Ligios C., et al. Nature Medicine, 11. 1137 – 1138, 2005) These studies from the Aguzzi laboratory warn that concurrent chronic inflammatory disease could dramatically alter the distribution of BSE infectivity in infected cattle. Down and dead stock are at higher risk for both BSE and other systemic conditions. If the results reported above are also applicable to cattle, the carcasses of dead and down stock affected by BSE might contain even higher levels of infectivity, or contribute infectivity via tissues that are not ordinarily at risk in normal animals. Exposure: Industry Practices or Exemptions which may pose a risk Poultry Litter In the United States poultry litter can be fed to cattle. There are two potential sources of risk from poultry litter. Poultry litter not only consists of digested feed but also of feed which spills from the cages. As a consequence, the practice of feeding litter back to cattle is by its nature non-compliant with the current feed ban if the poultry themselves are being fed ruminant protein. Given that ruminant protein can no longer be fed to ruminants in the United States and that most, if not all, countries will no longer import North American ruminant MBM, an even larger part of poultry diets is now ruminant MBM. Spillage provides a direct link to back to cattle but feces are also likely to contain infectivity. There is no reason to expect that TSE infectivity would be inactivated by passage through the poultry gut, and only a slim possibility that composting would reduce infectivity at all. Thus poultry feces are another potential route of transmission back to cattle. Evidence for this comes from rodent experiments where infectivity was demonstrated in the feces after being fed: “Laboratory experiments show that mice orally challenged with scrapie have detectable infectivity that passes through the gut. Gut contents and fecal matter may therefore contain infectivity, and it is noted that in experimental oral challenges in cattle conducted in the UK, feces must be treated as medical waste for one month following the challenge. It is concluded that digestive contents and fecal material from livestock or poultry currently being fed with MBM potentially contaminated with BSE should not be used as a feed ingredient for animal feed.” [Proceedings: Joint WHO/FAO/OIE/ Technical Consultation on BSE: public health, animal health and trade. Paris, 10-14 June 2001; and Alan Dickinson, personal communication]. It may be possible to remove the risk from poultry litter by sterilization. However, unless or until a method can be developed and validated, poultry litter should be banned from ruminant feed. 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. Unfiltered Tallow Ruminant tallow is exempted from the current feed ban. Tallow contains protein impurities (i.e. MBM) that could be a source of TSE infectivity. There are no impurity level requirements for this tallow. It has been reported that it is standard practice to produce tallow which has an impurity level of .15% or below, but it is not clear that this is fully adequate to remove the risk of transmission and there is no requirement to meet even this standard. We urge that protein contaminants be excluded from tallow and that SRMs also be removed. Plate Waste Plate waste is not limited to meat (muscle tissue). For example, cuts that include a portion of the spinal cord or that are contaminated by cord or ganglia during preparation could contain high levels of infectivity if derived from a TSE infected animal late in the preclinical stage of infection. At best this material would only be exposed to normal cooking temperatures. USDA, APHIS experience with the Swine Health Protection Act has revealed that plate waste also includes uncooked trimmings and bones. Although the current FDA regulation requires the plate waste be treated again, there are no specifications which would render a TSE agent inactive. Of greatest risk would be any bovine source of infectivity but also sheep scrapie, although not known to be a risk for human consumption, is one of the possible origins of BSE. The sheep scrapie agent is known to be widely dispersed including relatively high titers in lymphoid as well as nervous tissue. We support the USDA’s opposition to the exemption of “plate waste” as stated in written comments since 1997. Exposure: Cross Feeding and Cross Contamination The UK epidemiology has clearly shown that BSE contaminated feed is the primary if not sole vehicle for the transmission of BSE between cattle. Moreover, results from the United Kingdom’s attack rate study indicate that it does not take much exposure to transmit BSE to cattle. Recent results from the attack rate study which is still in progress have found that .1 g of brain transmitted BSE by the oral route to 3 cows out of 15 thus far, and .01 and .001gr of brain have transmitted BSE (1 cow out of 15). (Danny Matthews, DEFRA presentation at TAFS meeting, Washington, DC April 2004). Rendering may reduce infectivity but it does not eliminate it. (Taylor et al, 1995; Taylor et al, 1997; Schreuder et al, 1998). Given that BSE can be transmitted to cattle via an oral route with just .001 gram of infected tissue, it may not take much infectivity to contaminate feed and keep the disease recycling. This is especially true in countries like the US and Canada which do not have dedicated lines and equipment to manufacture and process feed for ruminants and non-ruminants. In addition, epidemiological investigations in European countries have shown that cross feeding and cross contamination on farm can be a significant vehicle for continued BSE transmission even after feed bans are well established. Cross feeding is the practice of feeding meal for poultry or pigs or pet food (which can legally contain ruminant MBM) to cattle on the same farm. This is usually due to simple human error or negligence. (Hoinville, 1994; Hoinville et al, 1995; Doherr et al, 2002a; Stevenson et al, 2000) FDA, CVM reports that compliance with the existing feed ban is high. For the most part this does not include the compliance level on the farm. There are hundreds of thousands of farms in the US. Many of these have multiple species. That is, they raise cattle, pigs, chickens etc., on the same premises. The sheer numbers of farms make it very difficult to assure compliance on farm and to adequately cover all farms by inspection. Even if the rendering industry and feed industry can maintain 100% compliance at their facilities, if a producer inadvertently feeds chicken feed containing bovine MBM to their cattle, they negate a perfect compliance rate higher in the chain. Recent data from the Harvard BSE risk assessment suggest that the level of misfeeding on farms plays a significant role in the ability of the agent to recycle. In fact George Gray, principal investigator for the study, stated that if, in the United States, misfeeding were to occur at a level of 15%, the R0 would be over 1, indicating that the BSE level would not be declining. (George Gray presentation at the Meeting on BSE Prevention in North America: An Analysis of the Science and Risk; January 27, 2005, Washington, DC.) The May 2003 Canadian BSE case illustrates the difficulty of on farm enforcement and its serious ramifications. The BSE positive cow was rendered and the MBM distributed to various locations. Two of these locations were poultry farms which mixed their own feed. The farms also had cattle. The subsequent investigation could not eliminate the possibility that the cattle had been fed the same feed as the poultry. The cattle on these farms were completely depopulated. Human error is extremely difficult to prevent, and managing the risk through enforcement is problematical when confronted with the extreme logistical challenges of on farm monitoring. By eliminating the highest risk materials (SRMs and deadstock) which could introduce infectivity into the feed stream, the MBM resulting from processing becomes inherently safer. If mistakes are then made on farm, they no longer contribute to the recycling of BSE. Exposure: Susceptibility of other Species Felines A transmissible spongiform encephalopathy has been diagnosed in eight species of captive wild ruminants as well as exotic felines (cheetahs, pumas, a tiger and an ocelot) and domestic cats (Wyatt 1991). There have been over 80 domestic cat cases of Feline Spongiform Encephalopathy (FSE) in Great Britain, and cats in Norway, Northern Ireland, Lichtenstein and Switzerland. The agent isolated from several of these cases is indistinguishable from BSE in cattle using strain typing in mice, suggesting that FSE is actually BSE in exotic and domestic cats. Epidemiological evidence suggests BSE contaminated feed to be the probable source of infection in these species. (MAFF Progress Report, June 1997), thus providing additional supporting evidence for the dangers of BSE contaminated feed and reinforcing the necessity of removing all sources of potential contamination from the feed stream. Other species Studies conducted at the National Institutes of Health Rocky Mountain Laboratory caution against assuming that animals which do not become clinically ill are not infected. It is unknown if certain animals may become carriers, i.e., become infected, shed agent but do not progress to clinical disease. Infection of certain rodent species with different TSE strains suggests the possibility of a carrier state (Race and Chesebro, 1998; Race et. al, 2001, Race et al., 2002). In the more recent studies, mice were inoculated with 263K hamster scrapie. There was a prolonged period (approximately one year) where there was no evidence of replication of infectivity. Furthermore, there was no evidence of PrPres during this phase of inactive persistence, which was followed by a period of active replication of infectivity and agent adaptation. In most cases, PrPres was not detected in the active phase as well. It is important to determine if this persistence and adaptation occurs in other species exposed to TSEs as it may have significance in feeding programs which continually expose other species to BSE infectivity. For example, if BSE infected brain and spinal cord are continually fed to certain species, it may be possible for the agent to persist and adapt in these new species. Over time, the ‘resistant’ species may become a source of agent. The results of Race and colleagues, warns that an inactive persistent phase might not produce detectable PrPres, yet there would be infectivity (Race et. al., 2001). Pigs displayed evidence of TSE infection after exposure to BSE by 3 distinct parenteral routes. Evidence of infectivity was found in the CNS, stomach, intestine and pancreas (Dawson et. al., 1990). Oral transmission has also been attempted in swine, but after an observation period of 84 months there was neither clinical nor pathological evidence of infection (Dawson et. al., 1990). Parenteral and oral transmission has also been attempted in chickens with no evidence of disease. Tissues from the BSE-challenged pigs and chickens were inoculated into susceptible mice to look for residual infectivity, but to date none has been found. In both instances the detection sensitivity was limited by the use of mice for bioassay instead of same species transmissions into cattle (or pigs and chickens). If any of these scenarios played out and inapparent infections became established in commercial species, those species could become reservoirs for reinfection of cattle and perpetuation or reintroduction of the epidemic. We also do not know if atypical cases of BSE are more pathogenic for other species and if chronic inflammation may influence the susceptibility of other species. We offer these possibilities to reinforce the need to eliminate all possible sources of infectivity from the feed stream. In January 2005, the European Union announced that BSE had been confirmed in a goat in France illustrating that the disease can be naturally transmitted to one of the small ruminants. The potential ramifications of this and the logistical challenges associated with controlling BSE in sheep or goats also provides a justification for removing SRMs from all animal feed. Although these species are covered under the current regulations the cross contamination and cross feeding aspects stated for cattle are applicable. The need to remove high risk material from all animal feed is also supported by other bodies with expertise in the field of TSEs: Recommendations of the World Health Organization (WHO) The World Health Organization (WHO) has issued the following recommendations for countries with BSE or those where a known exposure exists: · No part or product of any animal which has shown signs of a TSE should enter any food chain (human or animal). In particular: o All countries must ensure the killing and safe disposal of all parts or products of such animals so that TSE infectivity cannot enter any food chain. o Countries should not permit tissues that are likely to contain the BSE agent to enter any food chain (human or animal). From the report of a WHO Consultation on Public Health Issues related to Human and Animal Transmissible Spongiform Encephalopathies WHO/EMC/DIS 96.147, Geneva, 2-3 April 1996. Office of International Epizooties (OIE) The OIE is recommending that a list of SRMs which include brain, spinal cord, eyes, skull and vertebral column be removed from preparations used for food, feed, fertilizer, etc. If these tissues should not be traded we feel that they should not be used in domestic products either. BSE Code Article 2.3.13.18 “From cattle, originating from a country or zone with a minimal BSE risk, that were at the time of slaughter over 30 months of age, the following commodities, and any commodity contaminated by them, should not be traded for the preparation of food, feed, fertilizers, cosmetics, pharmaceuticals including biologicals, or medical devices: brains, eyes and spinal cord, skull, vertebral column and derived protein products. Food, feed, fertilizers, cosmetics, pharmaceuticals or medical devices prepared using these commodities should also not be traded.” Conclusion In conclusion we urge the FDA to implement, monitor and enforce a comprehensive and protective feed ban that is more congruent with the measures that have been proven to be effective in other countries that have experienced BSE. We do not feel that we can overstate the dangers from the insidious threat from these diseases and the need to control and arrest them to prevent any possibility of spread. We also wish to emphasize that as scientists who have dedicated substantive portions of our careers to defining the risks from TSEs as well as developing strategies for managing those risks, we are confident that technical solutions will be found for many of the challenges posed by these diseases. Thus, we urge the FDA to frame its regulations in terms that allow for the future use of any banned material if it can be proven safe for a given application. Signatories: Paul W. Brown, M.D. Medical Director, USPHS, and Senior Investigator, NIH (retired) Consultant, TSE Risk Management xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx Email: paulwbrown@comcast.net Neil R. Cashman MD xxxxxxxxxxxxxxxxx e-mail: neil.cashman@utoronto.ca Linda A. Detwiler, DVM xxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx Email: LAVet22@aol.com Laura Manuelidis, MD Professor and Head of Neuropathology, xxxxxxxxxxxxxxxxxxxx Jason C. Bartz, Ph.D. xxxxxxxxxxxxxxxxxxxx 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 xxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx Email rbp@cwru.edu Robert G. Rohwer, Ph.D. email: rrohwer@umaryland.edu REFERENCES Andreoletti O, Simon S, Lacroux C, Morel N, Tabouret G, Chabert A, Lugan S, Corbiere F, Ferre P, Foucras G, Laude H, Eychenne F, Grassi J, Schelcher F. PrPSc accumulation in myocytes from sheep incubating natural scrapie. Nat Med. 2004 Jun;10(6):591-3. Epub 2004 May 23. Anil,M.H.; Love,S.; Helps,C.R.; McKinstry,J.L.; Brown,S.N.; Philips,A.; Williams,S.; Shand,A.; Bakirel,T.; Harbour,D.A. - Jugular venous emboli of brain tissue induced in sheep by the use of captive bolt guns - Veterinary Record 2001 May 19; 148: 619-20 Anil,M.H.; Harbour,D.A. - Current stunning and slaughter methods in cattle and sheep. Potential for carcass contamination with central nervous tissue and microorganisms - Fleischwirtschaft 2001; 11: 123 Anil,M.H.; Love,S.; Helps,C.R.; Harbour,D. - Potential for carcass contamination with brain tissue following stunning and slaughter in cattle and sheep - Food Control 2002; 13: 431-6 Bartz JC, Kincaid AE, Bessen RA. Retrograde transport of transmissible mink encephalopathy within descending motor tracts. J Virol. 2002 Jun;76(11):5759-68. Bosque PJ, Ryou C, Telling G, Peretz D, Legname G, DeArmond SJ, Prusiner SB. Prions in skeletal muscle. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3812-7. Bushmann, A., and Groschup, M.; Highly Bovine Spongiform Encephalopathy-Sensitive Transgenic Mice Confirm the Essential Restriction of Infectivity to the Nervous System in Clinically Diseased Cattle. The Journal of Infectious Diseases, 192: 934-42, September 1, 2005. Dawson,M.; Wells,G.A.H.; Parker,B.N.; Scott,A.C. - Primary parenteral transmission of bovine spongiform encephalopathy to the pig - Veterinary Record 1990 Sep 29; 127(13): 338 Doherr,M.G.; Hett,A.R.; Rufenacht,J.; Zurbriggen,A.; Heim,D. - Geographical clustering of cases of bovine spongiform encephalopathy (BSE) born in Switzerland after the feed ban - Veterinary Record 2002 Oct 19; 151(16): 467-72 Glatzel M, Abela E, Maissen M, Aguzzi A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med. 2003 Nov 6;349(19):1812-20. Hadlow W. J., Kennedy R. C. & Race R. E. (1982) Natural infection of Suffolk sheep with Scrapie virus. J. Infect. Dis., 146, 657-664 Hoinville,L.J. - Decline in the incidence of BSE in cattle born after the introduction of the 'feed ban' - Veterinary Record 1994 Mar 12; 134(11): 274-5 Hoinville,L.J.; Wilesmith,J.W.; Richards,M.S. - An investigation of risk factors for cases of bovine spongiform encephalopathy born after the introduction of the 'feed ban' - Veterinary Record 1995 Apr 1; 136(13): 312-8 Houston,E.F.; Foster,J.D.; Chong,A.; Hunter,N.; Bostock,C.J. – Transmission of BSE by blood transfusion in sheep – Lancet 2000 Sep 16; 356(9234); 999-1000 Hunter,N.; Foster,J; Chong,A.; McCutcheon,S.; Parnham,D.; Eaton,S.; MacKenzie,C.; Houston,E.F. – Transmission of prion diseases by blood transfusion – Journal of General Virology 2002 Nov, 83(Pt 11); 2897-905. Love,S.; Helps,C.R.; Williams,S.; Shand,A.; McKinstry,J.L.; Brown,S.N.; Harbour,D.A.; Anil,M.H. - Methods for detection of haematogenous dissemination of brain tissue after stunning of cattle with captive bolt guns - Journal of Neuroscience Methods 2000 Jun 30; 99(1-2): 53-8 Mulcahy ER, Bartz JC, Kincaid AE, Bessen RA. Prion infection of skeletal muscle cells and papillae in the tongue. J Virol. 2004 Jul;78(13):6792-8. Race, R.; Chesebro, B. – Scrapie infectivity found in resistant species. Nature -1998 Apr 23;392(6678):770. Aguzzi,A.; Weissmann,C. - Spongiform encephalopathies. The prion's perplexing persistence. - Nature. 1998 Apr 23;392(6678):763-4 Race,R.E.; Raines,A.; Raymond,G.J.; Caughey,B.W.; Chesebro,B. - 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. - Journal of Virology 2001 Nov; 75(21): 10106-12 Race,R.E.; Meade-White,K.; Raines,A.; Raymond,G.J.; Caughey,B.W.; Chesebro,B. - Subclinical Scrapie Infection in a Resistant Species: Persistence, Replication, and Adaptation of Infectivity during Four Passages. - Journal of Infectious Diseases 2002 Dec 1; 186 Suppl 2: S166-70 Schreuder, B.E.C., Geertsma, R.E., van Keulen, L.J.M., van Asten, J.A.A.M., Enthoven, P., Oberthür, R.C., de Koeijer, A.A., Osterhaus, A.D.M.E., 1998. Studies on the efficacy of hyperbaric rendering procedures in inactivating bovine spongiform encephalopathy (BSE) and scrapie agents. Veterinary Record 142, 474-480 Stevenson, M. A., Wilesmith, J. W., Ryan, J. B. M., Morris, R.S., Lockhart, J. W., Lin, D. & Jackson, R. (2000) Temporal aspects of bovine spongiform encepalopathy in Great Britain: individual animal-associated risk factors for the disease. Vet. Rec. 147, 349-354. Stevenson, M. A., Wilesmith, J. W., Ryan, J. B. M., Morris, R. S., Lawson, A.B., Pfeiffer, D. U. & Lin, D. (2000) Descriptive spatial analysis of the epidemic of bovine spongiform encephalopathy in Great Britain to June 1997. Vet. Rec. 147, 379-384. Taylor, D.M., Woodgate, S.L., Atkinson, M.J., 1995. Inactivation of the bovine spongiform encephalopathy agent by rendering procedures. Veterinary Record, Vol.137: pp.605-610. Taylor, D.M., Woodgate, S.L., Fleetwood, A.J., Cawthorne, R.J.G., 1997. The effect of rendering procedures on scrapie agent. Veterinary Record, Vol.141, pp 643-649. Thomzig A, Schulz-Schaeffer W, Kratzel C, Mai J, Beekes M. Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie. Wilesmith, J.W., Ryan, J. B. M., Hueston, W. D., & Hoinville, L. J. (1992) Bovine spongiform encephalopathy: epidemiological features 1985 to 1990. Vet. Rec., 130, 90-94. Wilesmith, J. W., Wells, G. A. H., Ryan, J. B. M., Gavier-Widen, D., & Simmons, M. M. (1997) A cohort study to examine maternally associated risk factors for bovine spongiform encephalopathy. Vet. Rec., 141, 239-243. Wells G.A.H., Dawson M., Hawkins, S.A.C., Green R. B., Dexter I., Francis 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. [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. ============================================================================================== ============================================================================================== [Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle 03-025IFA 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 Greetings FSIS, I would kindly like to submit the following to [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 THE BSE/TSE SUB CLINICAL Non-Ambulatory Disabled Cattle Broken bones and such may be the first signs of a sub clinical BSE/TSE Non-Ambulatory Disabled Cattle ; snip...FULL TEXT ; http://docket.epa.gov/edkfed/do/EDKStaffAttachDownloadPDF?objectId=090007d480993808 http://docket.epa.gov/edkfed/do/EDKStaffCollectionDetailView?objectId=0b0007d48096b40d EPA's EDOCKET has been migrated into a federal-wide system to better serve citizens As of Friday, November 25, 2005 at 8 am, EDOCKET became permanently unavailable. HERE is my submission in full ; I thought you should have this data. some important BSE transmission studies out of Japan on the #11 cow. again, many thanks for your courage. That Texas mad cow would never have been confirmed if not for your courage... with warmest regards, Terry S. Singeltary Sr. ----- Original Message ----- Thank you for taking this submission via email. i have had trouble submitting via the comment page due to the length of my submission. I was not sure that my file attachment that i submitted via the ; EDOCKET: Go to http://www.epa.gov/feddocket I submitted yesterday, just did not know if the file reached anyone. so to make sure, I am sending to you to submit for me. many thanks, Terry From: TSS () August 24, 2005 Importation of Whole Cuts of Boneless Beef from Japan [Docket No. 05-004-1] RIN 0579-AB93 TSS SUBMISSION My name is Terry S. Singeltary Sr. ======================================================================== This section of the FEDERAL REGISTER contains notices to the public of ======================================================================== Animal and Plant Health Inspection Service 9 CFR Part 94 [Docket No. 05-004-1] AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Proposed rule. ----------------------------------------------------------------------- SUMMARY: We are proposing to amend the regulations governing the DATES: We will consider all comments that we receive on or before ADDRESSES: You may submit comments by any of the following methods: snip... International guidelines for trade in animal and animal products Chapter 2.3.13 of the Code and supplemented by Appendix 3.8.4 of the Greetings again APHIS ET AL, Muscle tissue has recently been detected with PrPSc Yoshifumi Iwamaru, Yuka Okubo, Tamako Ikeda, Hiroko Hayashi, Mori- Priori Disease Research Center, National Institute of Animal Health, 3-1-5 Abstract Bovine spongiform encephalopathy (BSE) is a disease of cattle that causes The specified risk materials (SRM) are tissues potentially carrying BSE The 11th BSE case in Japan was detected in fallen stock surveillance. PrPSc was detected in brain, spinal cord, dorsal root ganglia, trigeminal Our results suggest that the currently accepted definitions of SRM in 179 T. Kitamoto (Ed.) International Symposium of Prion Diseases held in Sendai, October 31, to The hardback book title is 'PRIONS' Food and Drug Safety 107 Vet Pathol 42:107–108 (2005) Letters to the Editor Editor: Absence of evidence is not always evidence of absence. In the article ‘‘Failure to detect prion protein (PrPres) by immunohistochemistry in striated muscle tissues of animals experimentally inoculated with agents of transmissible spongiform encephalopathy,’’ recently published in Veterinary Pathology (41:78–81, 2004), PrPres was not detected in striated muscle of experimentally infected elk, cattle, sheep, and raccoons by immunohistochemistry (IHC). Negative IHC, however, does not exclude the presence of PrPSc. For example, PrPres was detected in skeletal muscle in 8 of 32 humans with the prion disease, sporadic Creutzfeldt-Jakob disease (CJD), using sodium phosphotungstic acid (NaPTA) precipitation and western blot.1 The NaPTA precipitation, described by Wadsworth et al.,3 concentrates the abnormal isoform of the prion, PrPres, from a large tissue homogenate volume before western blotting. This technique has increased the sensitivity of the western blot up to three orders of magnitude and could be included in assays to detect PrPres. Extremely conspicuous deposits of PrPres in muscle were detected by IHC in a recent case report of an individual with inclusion body myositis and CJD.2 Here, PrPres was detected in the muscle by immunoblotting, IHC, and paraf- fin-embedded tissue blot. We would therefore caution that, in addition to IHC, highly sensitive biochemical assays and bioassays of muscle are needed to assess the presence or absence of prions from muscle in experimental and natural TSE cases. Christina Sigurdson, Markus Glatzel, and Adriano Aguzzi Institute of Neuropathology University Hospital of Zurich Zurich, Switzerland References 1 Glatzel M, Abela E, et al: Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med 349(19):1812–1820, 2003 2 Kovacs GG, Lindeck-Pozza E, et al: Creutzfeldt-Jakob disease and inclusion body myositis: abundant diseaseassociated prion protein in muscle. Ann Neurol 55(1): 121–125, 2004 3 Wadsworth JDF, Joiner S, et al: Tissue distribution of protease resistant prion protein in variant CJD using a highly sensitive immuno-blotting assay. Lancet 358:171–180, 2001 Diagnosis of prions in patients should utilize novel strategy, team says A technique for detecting prions in tissue, developed in recent years by The finding indicates that the diagnostic technique, known as the The finding suggests that reliance on the current methods for detecting In the study, the team compared the ability of the CDI and the two "In about 80 percent of the different brain regions examined, prions "These findings indicate that histology and immunohistochemistry should "If the traditional techniques are used at autopsy, they must be applied Moreover, while the study examined the efficacy of the CDI in comparison "The studies reported here are likely to change profoundly the approach More broadly, the scientists say, the high sensitivity of the CDI "Whether immunohistochemistry underestimates the incidence of one or The finding will be printed on-line and in print on March 1, 2005 in The study brings into high relief the different detection strategies of Standard immunohistochemistry, developed in the DeArmond lab 20 years The limitation of this technique is that scientists have since learned The CDI addresses this limitation by revealing the region of PrPSc that Detractors would say that it is not necessary to detect the minute level Prusiner won the 1997 Nobel Prize in Physiology or Medicine for The CDI was developed by members of the Prusiner lab. The CDI Prusiner, Safar, DeArmond and other members of the Institute for Other co-authors of the study were Michael D. Geschwind, Camille The study was funded by the National Institutes of Health, the John The UCSF Institute for Neurodegenerative Diseases: FURTHER COMPARISON OF THE CDI TO THE STANDARD DIAGNOSTIC PROCEDURES, Explanation as to why the CDI is more sensitive than Western blot DeArmond cites additional evidence about Western blot analysis from a Explanation as to why IHC for prions is less sensitive than the CDI: IHC ### http://pub.ucsf.edu/newsservices/releases/200502147/ NEUROSCIENCE Diagnosis of human prion disease Jiri G. Safar *, , Michael D. Geschwind , , Camille Deering *Institute for Neurodegenerative Diseases, Memory and Aging Contributed by Stanley B. Prusiner, December 22, 2004 Abstract With the discovery of the prion protein (PrP), The clinical diagnosis of human prion disease is often Recently, the role of IHC in the diagnosis of scrapie in the The CDI was developed to quantify PrPSc in tissue samples The CDI detected HuPrPSc with a sensitivity comparable to Our studies show that only the CDI detected PrPSc in all Histologic changes in prion disease have been shown to Studies of the white matter in CJD brains were particularly Most immunoassays that detect HuPrPSc do so only after Gerstmann–Sträussler–Scheinker, an inherited human prion The studies reported here are likely to change profoundly Our results suggest that using the CDI to test large numbers Acknowledgements Methods We used a highly sensitive method of detection — involving the concentration of PrPSc by differential precipitation with sodium phosphotungstic acid, which increased the sensitivity of Western blot analysis by up to three orders of magnitude — to search for PrPSc in extraneural organs of 36 patients with sporadic Creutzfeldt–Jakob disease who died between 1996 and 2002. Results PrPSc was present in the brain tissue of all patients. In addition, we found PrPSc in 10 of 28 spleen specimens and in 8 of 32 skeletal-muscle samples. Three patients had PrPSc in both spleen and muscle specimens. Patients with extraneural PrPSc had a significantly longer duration of disease and were more likely to have uncommon molecular variants of sporadic Creutzfeldt–Jakob disease than were patients without extraneural PrPSc. Conclusions Using sensitive techniques, we identified extraneural deposition of PrPSc in spleen and muscle samples from approximately one third of patients who died with sporadic Creutzfeldt–Jakob disease. Extraneural PrPSc appears to correlate with a long duration of disease. From the Institute of Neuropathology and National Reference Center for Prion Diseases, University Hospital of Zurich, Zurich, Switzerland. Dr. Glatzel and Mr. Abela contributed equally to the article. Address reprint requests to Dr. Aguzzi at the Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstr. 12, CH-8091 Zurich, Switzerland, or at adriano@pathol.unizh.ch . Gabor G. Kovacs, MD PhD 1 2, Elisabeth Lindeck-Pozza, MD 1, Leila Chimelli, MD, PhD 3, Abelardo Q. C. Araújo, MD, PhD 4, Alberto A. Gabbai, MD, PhD 5, Thomas Ströbel, PhD 1, Markus Glatzel, MD 6, Adriano Aguzzi, MD, PhD 6, Herbert Budka, MD 1 * *Correspondence to Herbert Budka, Institute of Neurology, AKH 4J, Wühringer Gürtel 18-20, POB 48, A-1097 Vienna, Austria Funded by: Abstract Pathologicalprion protein (PrPSc) is the hallmark of prion diseases affecting primarily the central nervous system. Using immunohistochemistry, paraffin-embedded tissue blot, and Western blot, we demonstrated abundant PrPSc in the muscle of a patient with sporadic Creutzfeldt-Jakob disease and inclusion body myositis. Extraneural PrPC-PrPSc conversion in Creutzfeldt-Jakob disease appears to become prominent when PrPC is abundantly available as substrate, as in inclusion body myositis muscle. -------------- Received: 16 June 2003; Revised: 11 September 2003; Accepted: 11 September 2003 http://www3.interscience.wiley.com/ AS Professor Aguzzi kindly put it most recently ; 107 Christina Sigurdson, Markus Glatzel, and Adriano Aguzzi http://www.emboreports.org/ http://www.bseinquiry.gov.uk/files/yb/1990/01/19009001.pdf Recall Release CLASS II RECALL Congressional and Public Affairs WASHINGTON, Aug. 19, 2005 - Green Bay Dressed Beef, a Green Bay, Wis., establishment, is voluntarily recalling approximately 1,856 pounds of beef products that may contain portions of the backbone from a cow just over 30 months old, the U.S. Department of Agriculture's Food Safety and Inspection Service announced today. The product was from a cow imported directly for slaughter from Canada. Based on information provided by Canada, the products subject to this Class II recall are from a cow that is approximately one month older than the 30-month age limit. Both ante-mortem and post-mortem inspection were done on the cow in question. FSIS inspection program personnel determined the cow to be healthy and fit for human food. FSIS' designation of this recall as Class II is because it is a situation where there is a remote probability of adverse health consequences from the use of the product. FSIS learned about this as a result of a Canadian audit of their health certificate that accompanied the imported cow. Prior to slaughter, the health certificate accompanying the cow was presented to the establishment, and it appeared complete and accurate. However, a subsequent audit of information related to the health certificate by Canadian officials found that it was not accurate. Action has been taken by Canadian Food Inspection Agency officials in response to findings from the audit. The products subject to recall are: Each box bears the establishment number "410" inside the USDA seal of inspection. The products were produced on August 4, and were distributed to wholesale distributors in Pennsylvania, Florida, Illinois, Maryland, Minnesota and Wisconsin. Under the interim final rules FSIS implemented on January 12, 2004, certain specified risk materials must be removed from all cattle depending on the age of the animal. On this animal all specified risk materials for cattle 30 months and over were removed, with the exception of the vertebral column. At the time of slaughter, the animal was certified to be under 30 months of age and removal of the vertebral column was not required. A subsequent audit determined the animal was just over 30 months of age; therefore, the vertebral column is required to be removed. This is the reason for the recall of the selected products. Consumers with questions about the recall may contact Sally VandeHei, Executive Assistant at 1-877-894-3927. National media with questions may contact Jim Mulhern at (202) 496-2468. Local media with questions may contact Susan Finco at (920) 965-7750 ext.158. Consumers with other food safety questions can phone the toll-free USDA Meat and Poultry Hotline at 1-888-MPHotline (1-888-674-6854). The hotline is available in English and Spanish and can be reached from 10 a.m. to 4 p.m. (Eastern Time), Monday through Friday. Recorded food safety messages are available 24 hours a day. # : Docket No. 03-080-1 -- USDA ISSUES PROPOSED RULE TO ALLOW LIVE ANIMAL IMPORTS FROM CANADA EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA) Report Summary The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003. The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties. A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90’s when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries. EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases. From: Terry S. Singeltary Sr. [flounder@wt.net] Greetings FDA, snip... PLUS, if the USA continues to flagrantly ignore the _documented_ science to date about the known TSEs in the USA (let alone the undocumented TSEs in cattle), it is my opinion, every other Country that is dealing with BSE/TSE should boycott the USA and demand that the SSC reclassify the USA BSE GBR II risk assessment to BSE/TSE GBR III 'IMMEDIATELY'. for the SSC to _flounder_ any longer on this issue, should also be regarded with great suspicion as well. NOT to leave out the OIE and it's terribly flawed system of disease surveillance. the OIE should make a move on CWD in the USA, and make a risk assessment on this as a threat to human health. the OIE should also change the mathematical formula for testing of disease. this (in my opinion and others) is terribly flawed as well. to think that a sample survey of 400 or so cattle in a population of 100 million, to think this will find anything, especially after seeing how many TSE tests it took Italy and other Countries to find 1 case of BSE (1 million rapid TSE test in less than 2 years, to find 102 BSE cases), should be proof enough to make drastic changes of this system. the OIE criteria for BSE Country classification and it's interpretation is very problematic. a text that is suppose to give guidelines, but is not understandable, cannot be considered satisfactory. the OIE told me 2 years ago that they were concerned with CWD, but said any changes might take years. well, two years have come and gone, and no change in relations with CWD as a human health risk. if we wait for politics and science to finally make this connection, we very well may die before any decisions Development on Human and Animal Health Aspects of Transmissible Spongiform Encephalopathies 2005-2008 3.2.1 The species barrier and the carrier state 3.2.1.1 The possibility of ‘carrier’ states in animals and humans, and our present inability to identify them, pose a potential threat to public and animal health. The susceptibility of humans to BSE infection, and the ability of the disease to remain clinically silent for many years, is of major concern to DH. Although the death of a UK blood donor from vCJD in 1999 three years after making the donation and the subsequent death from vCJD of the recipient in 2003 have not been causally linked, transmission of infection through blood transfusion is the most likely explanation327. The case heightens concerns that ‘carriers’ could be transmitting the disease through blood, tissue and organ donation or by contaminating surgical instruments when undergoing surgery. DH will continue to support research to detect infectious prions in human tissue, to investigate the decontamination of surgical instruments and to develop measures to protect blood supplies. 3.2.1.2 Animal models of some TSEs have detected infectivity in blood. Experiments, which have involved transfusing large volumes of blood from infected sheep to healthy recipient sheep, have demonstrated that infectivity can be transmitted by blood transfusion. A central part of DH policy in this area has been the leucodepletion of blood donations and the efficacy of this technology can now be tested in sheep. probable means by which the disease was being spread. In an attempt to prevent further infections a ban on incorporating ruminant protein in ruminant feed was introduced in July 1988. Due to the long incubation period associated with this disease the efficacy of this control measure was not immediately apparent. As time passed it became clear from the number of cases born after the ban that it was not wholly effective. 4.5.5 Epidemiological analysis of these cases showed that a high proportion of them occurred in areas where the pig population was high. This observation, coupled with research data that showed that only a very small dose of the infective material was needed to cause disease in cattle, led to the conclusion that cross-contamination of feed was occurring. 4.5.6 Since 1988, increasingly stringent feed controls have been put in place. Key amongst these have been: • the ban on the use of specified bovine offal in all animal feed (September 1990); • the ban on feeding any farmed animal, including horses and fish, with mammalian meat and bone meal. (This began in March 1996 but following this ban there was a recall scheme and the date from which the ban was considered to be fully effective is regarded as being 1 August 1996); 62 v6.1 • EU-wide controls on feed which extended the ban to include all processed animal protein, including that derived from birds and fish (implemented in the UK from 1 August 2001). 4.5.7 As illustrated in fig. [ ] these later measures have reduced the spread of BSE. However, they have not been one hundred per cent effective. As at 31st December 2003 there had been 81 cases of BSE in animals born since 1 August 1996 in the UK. full text 33 PAGES ; http://www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf http://www.bseinquiry.gov.uk/ Cutlip RC, Miller JM, Race RE, Jenny AL, Katz JB, Lehmkuhl HD, DeBey BM, USDA, Agriculture Research Service, National Animal Disease Center, Ames, IA To determine if sheep scrapie agent(s) in the United States would induce a MeSH Terms: Substances: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8133096&dopt=Citation http://www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf COMMENTING ON THE SRMs AND THE REMOVAL OF SRMs. I FIND IT DISTURBING THAT RECENTLY, WOULD it not be likely that from some of these noncompliance reports that ALL we have heard about in the last 7 years or better, well, since the SINCE some 460 of these occurred because slaughter plants did not have an WHAT about the SRM violations? Violations of rules about the removal and In 10 percent of the NRs analyzed, plants incorrectly identified the age of IN my opinion, this could have led to many feed discrepancies and should WASHINGTON - August 18 - In stark contrast to the public relations message More than half the violations (460) occurred because slaughter plants did "The fact that 60 percent of the violations were due to a failure to even The analysis also found that: The violations described in the NRs occurred from January 2004 through March In 10 percent of the NRs analyzed, plants incorrectly identified the age of Public Citizen sent the FOIA request to the USDA in December 2004 after the ### On August 19, 2005, no inconclusive test results were reported. National Veterinary Services Laboratory (NVSL) Immunohistochemistry (IHC) Testing Summary The BSE enhanced surveillance program involves the use of a rapid screening test, followed by confirmatory testing for any samples that come back "inconclusive." The weekly summary below captures all rapid tests conducted as part of the enhanced surveillance effort. It should be noted that since the enhanced surveillance program began, USDA has also conducted approximately 9,200 routine IHC tests on samples that did not first undergo rapid testing. This was done to ensure that samples inappropriate for the rapid screen test were still tested, and also to monitor and improve upon IHC testing protocols. Of those 9,200 routine tests, one test returned a non-definitive result on July 27, 2005. That sample underwent additional testing at NVSL, as well as at the Veterinary Laboratories Agency in Weybridge, England, and results were negative. We have to be careful that we don't get so set in the way we do things that Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't Dr. Keller: Tissues are routinely tested, based on which tissue provides an Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't THE International guidelines for trade in animal and animal products which are developed by the World Organization for Animal Health (formerly known as the Office International des Epizooties (OIE)), is and has been terrible flawed. ALL one has to do is to look at the countries that have gone by there very minimal guidelines, most all went on to develop BSE. IT would be nice if the OIE et al would define “controlled BSE-risk country” or “effectively enforced ban”. The USA and North America have neither. THIS has been proven time and time again via the GAO, OIG and the European EFSA BSE-risk assessments of North American countries. Many Countries have not even reported there first case of BSE yet, and many countries have not even produced a risk analysis for BSE. A fine example is Mexico and Canada. I pointed out about Canada above, but now lets look at Mexico, which is also a BSE GBR III country. IN Mexico, they are NOT even required to remove SRM; the Assessment of the Geographical BSE-Risk (GBR) of MEXICO 2004 There is no SRM-ban. SRM is normally destined for human consumption. According to the CD, fallen stock from pasture and diseased animals are incinerated and not rendered. Conclusion on the ability to avoid recycling In light of the above information, it has to be assumed that the BSE agent, should it have entered Mexico, could have been recycled and potentially amplified. high external challenges with a very unstable system makes the occurrence of an internal challenge likely in Mexico from approximately 1993 onwards. 4.2 Risk that BSE infectivity entered processing It is likely that BSE infectivity entered processing at the time of imported ‘at - risk’ MBM (1993) and at the time of slaughter of imported live ‘at - risk’ cattle (mid to late 1990’s). The high level of external challenge is maintained throughout the reference period, and the system has not been made stable, leading to increased internal 4.3 Risk that BSE infectivity was recycled and propagated It is likely that BSE infectivity was recycled and propagated from approximately 1993. The risk has since grown consistently due to a maintained internal and external challenge and lack of a stable system. 5. CONCLUSION ON THE GEOGRAPHICAL BSE - RISK 5.1 The current GBR as function of the past stability and challenge The current geographical BSE risk (GBR) level is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. snip...end The action means that cattle sold by the companies to Texas ranchers after Friday's announcement are subject to seizure by the federal government, said a high-ranking Treasury official who asked not to be named. "Cattle already purchased and owned before the companies were identified as tied to the drug cartels are not going to suddenly be blocked," the official said. The Treasury Department plans to inform cattle associations and other groups later this week of the action taken against the Mexican companies, officials said. The Treasury also will provide other information, such as the brands used by the cattle companies linked to the drug cartels. For now, buyers are expected to practice due diligence when purchasing cattle. Two Mexican drug cartels were named in the Treasury Department's statement, the Arriola Marquez organization and the Arellano Felix cartel based in Tijuana. The Arriola Marquez group, based in Mexico's Chihuahua state, is linked to Mexican drug kingpin Joaquin "El Chapo" Guzman, the department said. Guzman leads one of the factions fighting for control of Nuevo Laredo and its smuggling routes into Texas, officials have said. snip... It is not clear how many Mexican cattle owned by companies linked to drug cartels had been sold in Texas, said government officials and Texas cattle raisers. snip...end http://www.chron.com/cs/CDA/ssistory.mpl/topstory/3319609 TRIPLE firewalls and SEALED borders, I dont think so. MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK Distinct prion strains can be distinguished by differences in incubation period, neuropathology and biochemical properties of disease-associated prion protein (PrPSc) in inoculated mice. Reliable comparisons of mouse prion strain properties can only be achieved after passage in genetically identical mice, as host prion protein sequence and genetic background are known to modulate prion disease phenotypes. While multiple prion strains have been identified in sheep scrapie and Creutzfeldt-Jakob disease, bovine spongiform encephalopathy (BSE) is thought to be caused by a single prion strain. Primary passage of BSE prions to different lines of inbred mice resulted in the propagation of two distinct PrPSc types, suggesting that two prion strains may have been isolated. To investigate this further, these isolates were subpassaged in a single line of inbred mice (SJL) and it was confirmed that two distinct prion strains had been identified. MRC1 was characterized by a short incubation time (110±3 days), a mono-glycosylated-dominant PrPSc type and a generalized diffuse pattern of PrP-immunoreactive deposits, while MRC2 displayed a much longer incubation time (155±1 days), a di-glycosylated-dominant PrPSc type and a distinct pattern of PrP-immunoreactive deposits and neuronal loss. These data indicate a crucial involvement of the host genome in modulating prion strain selection and propagation in mice. It is possible that multiple disease phenotypes may also be possible in BSE prion infection in humans and other animals. ======================= Cristina Casalone *, Gianluigi Zanusso , Pierluigi Acutis *, Sergio Ferrari , Lorenzo Capucci , Fabrizio Tagliavini ¶, Salvatore Monaco ||, and Maria Caramelli * *Centro di Referenza Nazionale per le Encefalopatie Animali, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna, 148, 10195 Turin, Italy; Department of Neurological and Visual Science, Section of Clinical Neurology, Policlinico G.B. Rossi, Piazzale L.A. Scuro, 10, 37134 Verona, Italy; Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Via Bianchi, 9, 25124 Brescia, Italy; and ¶Istituto Nazionale Neurologico "Carlo Besta," Via Celoria 11, 20133 Milan, Italy Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrPSc fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called "species barrier" between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrPSc accumulation. In addition, Western blot analysis showed a PrPSc type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrPSc. Strikingly, the molecular signature of this previously undescribed bovine PrPSc was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease. -------------------------------------------------------------------------------- C.C. and G.Z. contributed equally to this work. ||To whom correspondence should be addressed. E-mail: salvatore.monaco@mail.univr.it. www.pnas.org/cgi/doi/10.1073/pnas.0305777101 * Commissariat à l'Energie Atomique, Service de Neurovirologie, Direction des Sciences du Vivant/Département de Recherche Medicale, Centre de Recherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc, BP 6, 92 265 Fontenay-aux-Roses Cedex, France; Hôpital Neurologique Pierre Wertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, United Kingdom Edited by D. Carleton Gajdusek, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, and approved December 7, 2000 (received for review October 16, 2000) There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment. Introduction IN light of Asante/Collinge et al findings that BSE transmission to the -------- Original Message -------- Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD Date: Thu, 28 Nov 2002 10:23:43 -0000 From: "Asante, Emmanuel A" To: Dear Terry, I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention. Thank you for your interest in the paper. In respect of your first question, the simple answer is, yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc. can be of any further assistance please to not hesitate to ask. Best wishes. <> ____________________________________ Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now) ____________________________________ snip... full text ; http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm SCRAPIE USA MONTHLY REPORT 2005 AS of March 31, 2005, there were 70 scrapie infected source flocks (Figure 3). There were 11 new infected and source flocks reported in March (Figure 4) with a total of 51 flocks reported for FY 2005 (Figure 5). The total infected and source flocks that have been released in FY 2005 are 39 (Figure 6), with 1 flock released in March. The ratio of infected and source flocks released to newly infected and source flocks for FY 2005 = 0.76 : 1. IN addition, as of March 31, 2005, 225 scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL), of which 53 were RSSS cases (Figure 7). This includes 57 newly confirmed cases in March 2005 (Figure 8). Fourteen cases of scrapie in goats have been reported since 1990 (Figure 9). The last goat cases was reported in January 2005. New infected flocks, source flocks, and flocks released or put on clean-up plans for FY 2005 are depicted in Figure 10. ... FULL TEXT ; http://www.aphis.usda.gov/vs/nahps/scrapie/monthly_report/monthly-report.html http://www.aphis.usda.gov/vs/nahps/cwd/labmap.html Chronic Wasting Disease and Potential Transmission to Humans Suggested citation for this article: Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions. Conclusions Environmental Sources of Prion Transmission in Mule Deer Suggested citation for this article: Miller MW, Williams ES, Hobbs NT, Wolfe LL. Environmental sources of prion transmission in mule deer. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no6/04-0010.htm Whether transmission of the chronic wasting disease (CWD) prion among cervids requires direct interaction with infected animals has been unclear. We report that CWD can be transmitted to susceptible animals indirectly, from environments contaminated by excreta or decomposed carcasses. Under experimental conditions, mule deer (Odocoileus hemionus) became infected in two of three paddocks containing naturally infected deer, in two of three paddocks where infected deer carcasses had decomposed in situ ≈1.8 years earlier, and in one of three paddocks where infected deer had last resided 2.2 years earlier. Indirect transmission and environmental persistence of infectious prions will complicate efforts to control CWD and perhaps other animal prion diseases. Prions cannot be directly demonstrated in excreta or soil. However, CWD infection–specific protease-resistant prion protein (PrPCWD) accumulates in gut-associated lymphoid tissues (e.g., tonsils, Peyer patches, and mesenteric lymph nodes) of infected mule deer (11,17,22), which implicates alimentary shedding of the CWD agent in both feces and saliva (10,11,17). Because PrPCWD becomes progressively abundant in nervous system and lymphoid tissues through the disease course (11), carcasses of deer succumbing to CWD also likely harbor considerable infectivity and thus serve as foci of infection. We could not determine the precise mechanism for CWD transmission in excreta-contaminated paddocks, but foraging and soil consumption seemed most plausible. Deer did not actively consume decomposed carcass remains, but they did forage in the immediate vicinity of carcass sites where a likely nutrient flush (23) produced lush vegetation (Figure). Our findings show that environmental sources of infectivity may contribute to CWD epidemics and illustrate the potential complexity of such epidemics in natural populations. The relative importance of different routes of infection from the environment cannot be discerned from our experiment, but each could play a role in sustaining natural epidemics. Although confinement likely exaggerated transmission probabilities, conditions simulated by this experiment do arise in the wild. Mule deer live in established home ranges and show strong fidelity to historic home ranges (24-26). As a result of such behavior, encounters with contaminated environments will occur more frequently than if deer movements were random. Feces and carcass remains are routinely encountered on native ranges, thus representing natural opportunities for exposure. Social behavior of deer, particularly their tendency to concentrate and become sedentary on their winter range, also may increase the probability of coming into contact with sources of infection in their environment. The ability of the CWD agent to persist in contaminated environments for >2 years may further increase the probability of transmission and protract epidemic dynamics (8). Because infectivity in contaminated paddocks could not be measured, neither the initial levels nor degradation rate of the CWD agent in the environment was estimable. However, the observed persistence of the CWD agent was comparable to that of the scrapie agent, which persisted in paddocks for ≈1 to 3 years after removal of naturally infected sheep (7). Similarities between the CWD and scrapie agents suggest that environmental persistence may be a common trait of prions. Whether persistence of the BSE prion in contaminated feed production facilities or in environments where cattle reside contributed to BSE cases in the United Kingdom after feed bans were enacted (27) remains uncertain but merits further consideration. Indirect transmission and environmental persistence of prions will complicate efforts to control CWD and perhaps other animal prion diseases. Historically, control strategies for animal prion diseases have focused on infected live animals as the primary source of infection. Although live deer and elk represent the most plausible mechanism for geographic spread of CWD, our data show that environmental sources could contribute to maintaining and prolonging local epidemics, even when all infected animals are eliminated. Moreover, the efficacy of various culling strategies as control measures depends in part on the rates at which the CWD agent is added to and lost from the environment. Consequently, these dynamics and their implications for disease management need to be more completely understood. The first positive result in a wild deer was announced on April 27, 2005 and came from a yearling white-tailed deer sampled from the Town of Verona, Oneida County. The second positive result is from a 3-year-old doe, located within a mile of the location where the initial positive result was detected. The sample tissues were tested at the State's Veterinary Diagnostic Laboratory at Cornell University. These are the first known occurrences of CWD in wild deer in New York State. DEC implemented intensive monitoring efforts after CWD was found in two captive white-tailed deer herds in Oneida County – the first incidents of CWD in New York State. On April 8, 2005, the State Department of Agriculture and Markets (DAM) completed testing of the captive deer and found a total of five positive results for CWD in the two captive herds. DEC, along with the U.S. Department of Agriculture's Wildlife Services program, completed intensive monitoring on April 30, 2005. The effort resulted in 290 samples of wild deer from Oneida County, two from neighboring Madison County, and 25 wild deer from the Town of Arietta, Hamilton County. Since 2002, DEC has conducted statewide sampling of wild deer for CWD. When combined with sampling efforts in Oneida and Hamilton Counties, DEC has collected more than 3,700 samples from wild white-tailed deer. DEC and DAM will continue public outreach to interested parties in central New York to help educate citizens on CWD and to discuss next steps to be taken. The agencies will hold a public meeting on Thursday, May 12, 2005, at 7 p.m. in the Vernon-Verona-Sherrill High School Auditorium, located on State Highway 31 in the Town of Verona. In addition, DEC and DAM will conduct additional outreach and continue to aggressively pursue inspection and enforcement across the State. DAM continues to investigate, sample and test white-tailed deer from two captive herds directly associated with the two herds that were confirmed positive for CWD in Oneida County. Results for these sampling efforts will be announced when available. Statewide sampling for CWD - which has resulted in more than 1,000 tests each year - will be increased to closely monitor the distribution and prevalence of CWD in wild deer. In addition, DEC has implemented emergency regulations regarding the handling, transport and management of deer in the State. The emergency regulations are currently in effect and represent an aggressive response to the recent discovery of chronic wasting disease (CWD) in Oneida County. DEC's emergency regulations are designed to ensure the proper handling of deer and prevent further spread of CWD in the wild herd. The emergency regulations are effective for 90 days. In addition, DEC will begin the process of developing permanent regulations, which will appear in the State Register and include a 45-day public comment period. CWD is a transmissible disease that affects the brain and central nervous system of certain deer and elk. There is no evidence that CWD is linked to disease in humans or domestic livestock other than deer and elk. More information on CWD can be found at DEC's website at www.dec.state.ny.us/website/dfwmr/wildlife/deer/currentcwd.html 05-48 P.O. Box 42 Bacliff, Texas USA 77518 Please note that it may take between 24 and 72 hours for the EDOCKET staff to process your comment before it is available publicly through EDOCKET. You can use the identifier noted above to find your comment through the Quick or Advanced Search pages when it is available. ======================================================== OLD TSS SUBMISSIONS; 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
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