Bovine Spongiform Encephalopathy BSE: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Scientists Comments December 20, 2005

Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Scientists Comments December 20, 2005

''It is our opinion that the proposed rule falls woefully short in effective measures to minimize the potential for further transmissions of the disease.''

Posted on Wed, Jan. 04, 2006

Group: U.S. not protected against mad cow

LIBBY QUAID

Associated Press

WASHINGTON - Researchers and the nation's No. 1 burger seller say the government is not fully protecting animals or people from mad cow disease. Stronger steps are needed to keep infection from entering the food chain for cattle, the critics wrote in comments to the Food and Drug Administration.

The group includes McDonald's Corp., seven scientists and experts and a pharmaceutical supplier, Serologicals Corp. The government proposed new safeguards two months ago, but researchers said that effort "falls woefully short" and would continue to let cattle eat potentially infected feed, the primary way mad cow disease is spread.

"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," the researchers wrote. McDonald's said the risk of exposure to the disease should be reduced to zero, or as close as possible. "It is our opinion that the government can take further action to reduce this risk," wrote company Vice President Dick Crawford.

In people, eating meat or cattle products contaminated with mad cow disease is linked to a rare but fatal nerve disorder, variant Creutzfeldt-Jakob Disease. No one is known to have contracted the disease in the United States. The disease has turned up in two people who lived in the U.S., but it's believed they were infected in the United Kingdom during an outbreak there in the 1980s and 1990s. The U.S. has found two cases of mad cow disease in cows. Since the first case, confirmed in December 2003 in a Canadian-born cow in Washington state, the government has tested more than half a million of the nation's 95 million cows. The second case was confirmed last June in a Texas-born cow.

"While this surveillance has not uncovered an epidemic, it does not clear the U.S. cattle herd from infection," the researchers said.

The primary firewall against mad cow disease is a ban on using cattle remains in cattle feed, which the U.S. put in place in 1997. However, the feed ban has loopholes that create potential pathways for mad cow disease. For example, using restaurant plate waste is allowed in cattle feed.

The Food and Drug Administration proposed in October to tighten the rules, but critics said glaring loopholes would remain. The FDA, which regulates animal feed, accepted public comments on the proposal through last month. An agency spokeswoman said Wednesday it would be inappropriate to respond to those comments. The critics said their biggest concern is that tissue from dead animals would be allowed in the feed chain if brains and spinal cords have been removed. Brains and spinal cords are tissues that can carry mad cow disease. In dead cattle that had the disease, infection had spread beyond brains and spinal cords. Leaving tissue from dead cattle in the feed chain would negate FDA's attempt to strengthen its safeguards, the critics said.

The most effective safeguards, they said, would be to: _Ban from animal feed all tissues considered "specified risk materials" by the Agriculture Department, which requires that such materials be removed from meat that people eat. This includes tissues beyond the brain and spinal cord, such as eyes or part of the small intestine. _Ban the use of dead cattle in animal feed. _Close loopholes allowing plate waste, poultry litter and blood to be fed back to cattle.

Within the meat industry, many say the FDA proposal is effective, although some companies contend new rules are unneeded. The American Meat Institute Foundation, which represents meat processing companies, backs the FDA proposal.

"To take out the most potentially infected material, and that would be brains and spinal cords, that removes about 90 percent of the potential infectivity that is in an animal - if it's infected," said Jim Hodges, AMI Foundation president.

Mad cow disease is the common name for bovine spongiform encephalopathy, or BSE, a degenerative nerve disease in cattle. ON THE NET

Food and Drug Administration: http://www.fda.gov

American Meat Institute: http://www.meatami.com/

http://www.duluthsuperior.com/mld/duluthsuperior/living/health/13549744.htm

BSE LIST SERVE ARCHIVE ON Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Scientists Comments December 20, 2005

https://lists.aegee.org/?A2=BSE-L;63705ec1.0601&S=

https://lists.aegee.org/?A2=BSE-L;ca270650.0601&S=

https://lists.aegee.org/?A2=BSE-L;fb548f88.0601&S=

https://lists.aegee.org/?A2=BSE-L;f5ab4b78.0601&S=

https://lists.aegee.org/?A2=BSE-L;a5235c32.0601&S=

https://lists.aegee.org/?A2=BSE-L;9d5cf22e.0601&S=

https://lists.aegee.org/?A2=BSE-L;da6fcf1f.0601&S=

https://lists.aegee.org/?A2=BSE-L;283f7694.0601&S=

Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed

December 20,2005

Division of Dockets Management (HFA-305)

Food and Drug Administration

5630 Fishers Lane

Room 1061

Rockville, MD 20852

Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed

Dear Sir or Madame:

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 OUT 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 fi-om 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. 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 tq 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- 004-21 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 he 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 l3SE infectivity in facial and sciatic nerves of the transgenic mice is nalt 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.

From [Docket No. 05-004-21 RIN 0579-AB93:

“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 these tissues may be present in Japanese beef. This commenter further requested an additional comment period to obtain public comments to treat this new scientific finding.

\2\ 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: 93442, September 1, 2005.

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 infectivity in the peripheral nerves of cattle and the corresponding risks of the presence of infectivity in such tissues resulting in cattle or human exposure to the BSE agent. The results from these experiments in genetically engineered mice should be interpreted with caution, as the findings may be influenced by the overexpression of prion proteins and may not accurately predict the natural distribution of BSE infectivity in cattle. Further, the overexpression of prion proteins in transgenic mice may not accurately mimic the natural disease process because the transgenic overexpressing mice have been shown to develop spontaneous lethal neurological disease involving spongiform changes in the brain and muscle degeneration.\3\ In addition, the route of administration to the mice was both intraperitoneal and intracerebral, which are two very efficient routes of infection as compared to oral consumption. 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.”

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 thot 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 ID50.s (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, 200 1, Appendix 3A Base Case and Harvard Risk Assessment, 200 1 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:

1 Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions (Heikenwalder et. al. 2005 >~xx .sci~:n~c\rpl-css.~~r~/~O .lunuarv 2005/ Parrc l/ &).I 1zois~icllcc.l lOh4hO)

2. Coincident Scrapie Infection and Nephritis Lead to Urinary Priori Excretion (Seeger et al., Science 14 October 2005:Vol. 310. no. 5746, pp. 324 - 326 DOI: lO.l126/science. 1118829)

3. PrPS” in mammary glands of sheep affected by scrapie and mastitis (Ligios C., et al. Nature Medicine, 11. 3 137 - 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 thai. 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 a 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, lo-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 bc 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 .001 gr 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, 2002% 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 RO 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). CIral 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 re-enforce 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:

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.

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, USPH[S, and Senior Investigator, NIH (retired) Consultant, TSE Risk Management 78 15 Exeter Rd. Bethesda, MD 208 14 Fax 301-652-43 12 Email: paLII\\ hr-c~~~rl~~/‘~c)m~as~.rlct -----

Neil R Cashman MD Professor, Department 0-C Medicine (Neurology) Diener Chair of Neurode:generaGve Diseases Centre for Research in Neurodegenerative Diseases 6 Queen’s Park Crescent West Toronto Ontario M5S3H2 Ph: 416-978-1875 Fax: 4 16-978- 1878 e-mail: neil.cashman@utoronto.ca

Linda A. Detwiler, DVM Consultant, TSE Risk Management 225 Hwy 35 Red Bank, NJ 07701 Ph 732-74 l-2290 Fax 732-741-775 1 Email: l.~\Vc~92’rr’ac,l.c0111.

Laura Manuelidis, MD Professor and Head of Neuropathology, Department of Surgery and Faculty of Neurosciences Yale Medical School 333 Cedar St. New Haven, CT 065 10 email: I~IL~ra.~~~ar~clclirli~~~~~~alc.cdi~ Tel: 203-785-4442

Jason C. Bar-k, Ph.D. Assistant Professor Department of Medical Microbiology and Immunology Creighton University 2500 California Plaza Omaha, NE 68178 (402) 280- 18 11 voice (402) 280-l 875 fax jbartz@creighton .edu

Robert B. Petersen, Ph.D. Associate Professor of Pathology and Neuroscience Case Western Reserve University 5- 123 Wolstein 13~1ilding 2 103 Cornell Road Cleveland, OH 44 106-26122 Phone 216-368-6709 FAX 360-838-9226 Email rhp~,-c\\~~.c~!t~ Robert G. Rohwer, Ph.D. Director, Molecular Neurovirology Laboratory Veterans Affairs Medicall Center Medical Research Service 151 Assoc. Professor of Neurology School of Medicine University of Maryland ;at Baltimore 10 N. Greene St. Baltimore, MD 21201 ph. 4 1 O-605-7000 x6462 Fax 4 1 o-605-7959 email: rrohwer@maryland.edu

REFERENCES

Signatories: ...snip...see full text with references and submitters names;

FDA PROPOSED RULE DECEMBER 20, 2005

http://web.archive.org/web/20091106182858/http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000490-vol40.pdf

December 20, 2005

Division of Dockets Management (HFA-305) Food and Drug Administration

5630 Fishers Lane

Room 1061

Rockville, MD 20852

Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273)

Substances Prohibited From Use in Animal Food and Feed

Dear Sir or Madame:

https://web.archive.org/web/20120121152959/http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf

9 December 2005

Division of Dockets Management (RFA-305)

Food and Drug Administration

5630 Fishers Lane

Room 1061

Rockville, MD 20852

Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273)

Substances Prohibited From Use in Animal Food and Feed

Dear Sir or Madame:

Serologicals Corporation is a global provider of biological products to life science companies. The Company’s products are essential for the research, development and manufacturing of biologically based diagnostic, pharmaceutical and biological products. customers include many of the leading research institutions, diagnostic and pharmaceutical companies throughout the world. The Company’s products and technologies are used in a wide variety of applications within the areas of neurobiology, cell signaling, oncology, angiogenesis, apoptosis, developmental biology, cellular physiology, hematology, immunology, cardiology, infectious diseases and molecular biology.

A number of our products are derived from bovine blood or other bovine tissues sourced in the United States, hence the overall health of the national herd is extremely important to our company as well as to our customers and their patients. Some of our bovine based products are used in the manufacture of vaccines and drugs for humans, hence it is critical that all measures are taken to assure these are safe and free from disease especially Bovine Spongiform Encephalopathy (BSE). The most effective way to insure this is to create a system which processes cattle that are BSE free. As a company there are a number of precautions that we can take by our strict specifications but many of the needed precautions require the force of federal regulation, hence we appreciate the opportunity to submit comments to this very important proposed rule.

Division of Dockets Management (HFA-305) Page 2 9 December 2005

the FDA to act without further delay and implement additional measures which will reduce the risk of BSE recycling in the US cattle herd.

We feel that for the FDA to provide a more comprehensive and protective feed ban, specified risk materials (SRMs) and deadstock must be removed from all animal feed and that legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk) should be discontinued.

SRMs, as defined by the USDA, are tissues which, in a BSE infected animal, are known to either harbor BSE infectivity or to be closely associated with infectivity. If SRMs are not removed, they may introduce BSE infectivity and continue to provide a source of animal feed contamination. Rendering will reduce infectivity but it will not totally eliminate it. This is significant as research in the United Kingdom has shown that a calf may be infected with BSE by the ingestion of as little as .OOl gram of untreated brain.

The current proposed rule falls short of this and would still leave a potential source of infectivity in the system. In fact by the FDA’s own statement the exempted tissues which are known to have infectivity (such as distal ileum, DRGs, etc) would cumulatively amount to 10% of the infectivity in an infected animal, This proposed rule would still allow for the possibility that cattle could be exposed to BSE through:

1. Feeding of materials currently subject to legal exemptions from the ban (e.g., poultry litter, plate waste)

2. Cross feeding (the feeding of non-ruminant rations to ruminants) on farms; and

3. Cross contamination of ruminant and non-ruminant feed

We are most concerned that the FDA has chosen to include a provision which would allow tissues from deadstock into the feed chain. We do not support the provision to allow the removal of brain and spinal cord from down and deadstock over 30 months of age for several reasons. These are the animals with the highest level of infectivity in tissues which include more than brain and spinal cord. We do not feel that there can be adequate removal and enforcement of this regulation especially during warmer weather. In addition there is emerging information that at end stage disease, infectivity may also be included in additionai tissues such as peripheral nerves (Buschmann and Groschup, 2005).

Leaving the tissues from these cattle in the animal feed chain will effectively nullify the intent of this regulation. This point is illustrated by the 2001 Harvard risk assessment model which demonstrated that eliminating dead and downer, 4D cattle, from the feed stream was a disproportionately effective means of reducing the risk of re-infection “The disposition of c&e that die on the farm would also have a substantial influence on the spread of BSE if the disease were in traduced. ” The base case scenario showed that the mean total number ofID.50~ (i.e., dosage sufficient to infect SO percent of exposed cattte) from healthy animals at slaughter presented to the food/feed system was 1500, The mean total number of ID.50.s from adult cattle

Division of Dockets Management (HFA-305) Page 3 9 December 2005

deadstock presented to the feed system was 37,000. deadstock).

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

Serologicals and companies like ours which supply components of drugs and biologicals have a responsibility to the manufacturers of these products, the medical community and their patients as well as regulatory agencies throughout the world to provide the safest products as possible. Since there is no test for BSE in live cattle or for product, the regulatory agencies throughout the world expect us to reduce or eliminate risk via sourcing criteria, These parameters may include but not be limited to country of origin, herd of origin, age of the animal, etc. The United States is no longer a country with negligible risk, hence individual animal criteria has become more important. In fact other Centers of the FDA have stated that more attention should be given to sourcing from herds likely to be a source of BSE free animals. The exemptions in the current ban as well as in the newly proposed rule make this difficult if not impossible as there are still legal avenues for ruminants to consume potentially contaminated ruminant protein. In addition, the USDA still has not implemented a system of identification and traceability.

Serologicals urges agencies of the US government to work with academia and industry on research in the following areas:

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 value

Serologicals will continue to work with the FDA and other government agencies to implement a strong BSE risk control program, Serologicals would like to reiterate our opinion that for the FDA to provide a more comprehensive and protective feed ban, specified risk materials (SRMs) and deadstock must be removed from all animal feed and that legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk) should be discontinued. Thank you for the opportunity to submit these comments to the public record.

Respectfully, SEROLOGICALS CORPORATION James J. Kramer, Ph.D. Vice President, Corporate Operations

9 December 2005 Division of Dockets Management (RFA-305)

SEROLOGICALS CORPORATION James J. Kramer, Ph.D. Vice President, Corporate Operations

http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000383-01-vol35.pdf

http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000490-vol40.pdf

Subject: SV: McDonald's Corp. seven scientists and experts and a pharmaceutical supplier Seriologicals Corp. U.S. NOT PROTECTED AGAINST MAD COW DISEASE

From: Karin Irgens <Karin.Irgens@MATTILSYNET.NO>

Reply To: Bovine Spongiform Encephalopathy <BSE-L@LISTS.AEGEE.ORG>

Date: Thu, 12 Jan 2006 16:54:12 +0100 Content-Type: text/plain Parts/Attachments: text/plain (8651 lines)

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

Hello Terry

Do you have the link for this text from 7 scientists ?

Best regards, Karin

-----Opprinnelig melding-----

Fra: Bovine Spongiform Encephalopathy [mailto:BSE-L@aegee.org] På vegne av Terry S. Singeltary Sr.

Sendt: 11. januar 2006 19:31

Til: BSE-L@aegee.org

Emne: Re: McDonald's Corp. seven scientists and experts and a pharmaceutical supplier Seriologicals Corp. U.S. NOT PROTECTED AGAINST MAD COW DISEASE

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

Subject: Re: McDonald's Corp. seven scientists and experts and a pharmaceutical supplier Seriologicals Corp. U.S. NOT PROTECTED AGAINST MAD COW DISEASE

Date: January 11, 2006 at 9:27 am PST

December 19, 2005

Division of Dockets Management (HFA-305)

Food and Drug Administration

5630 Fishers Lane

Room 1061 Rockville, MD 20852

Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273)

Substances Prohibited From Use in Animal Food and Feed

Dear Sir or Madame:

The 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”.

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) Cross feeding (the feeding of non-ruminant rations to ruminants) on farms; and 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 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

Rockville, MD 20852

Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273)

Substances Prohibited From Use in Animal Food and Feed

Dear Sir or Madame:

The 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.

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.

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).

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.

From [Docket No. 05-004-2] RIN 0579-AB93[RR2] :

“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 these tissues may be present in Japanese beef. This commenter further requested an additional comment period to obtain public comments to treat this new scientific finding. ---------------------------------------------------------------------------

Source of the agent: 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

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)

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.

Certainly, blood and blood proteins should not be used as feed without conclusive evidence that they are safe.

Unfiltered Tallow

Plate Waste

Exposure: Cross Feeding and Cross Contamination

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.

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.)

Exposure: Susceptibility of other Species

Felines

Other species

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.

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)

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.

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 Professor, Department of Medicine (Neurology) Diener Chair of Neurodegenerative Diseases Centre for Research in Neurodegenerative Diseases 6 Queen's Park Crescent West Toronto Ontario M5S3H2 xxxxxxxxxxxxxxxxxx

xxxxxxxxxxxxxxxxx

e-mail: neil.cashman@utoronto.ca

Linda A. Detwiler, DVM Consultant, TSE Risk Management

xxxxxxxxxxxxxxxxxxxxxxx

xxxxxxxxxxxxxxxxxxxx

xxxxxxxxxxxxxxxxxx

Email: LAVet22@aol.com

Laura Manuelidis, MD

Professor and Head of Neuropathology, Department of Surgery and Faculty of Neurosciences Yale Medical School

xxxxxxxxxxxxxxxxxxxx email: laura.manuelidis@yale.edu xxxxxxxxxxxxxxxxxxxxxxxx

Jason C. Bartz, Ph.D. Assistant Professor Department of Medical Microbiology and Immunology Creighton University 2500 California Plaza Omaha, NE 68178 xxxxxxxxxxxxxxxxxxxxx

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. Director, Molecular Neurovirology Laboratory Veterans Affairs Medical Center Medical Research Service 151 Assoc. Professor of Neurology School of Medicine University of Maryland at Baltimore 10 N. Greene St. Baltimore, MD 21201 xxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxx

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. J Clin Invest. 2004 May;113(10):1465-72.

Thomzig A, Kratzel C, Lenz G, Kruger D, Beekes M. Widespread PrPSc accumulation in muscles of hamsters orally infected with scrapie. EMBO Rep. 2003 May;4(5):530-3.

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.

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

Dockets Entered on December 22, 2005 2005D-0330, Guidance for Industry and FDA Review Staff on Collection of Platelets by Automated ... EC 203, McDonald's Restaurants Corporation, Vol #:, 34 ...

http://www.fda.gov/ohrms/dockets/dailys/05/Dec05/122205/122205.htm

http://web.archive.org/web/20090711225814/http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC203.htm

[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 03-025IFA-2 Terry S. Singeltary

Page 1 of 17

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://web.archive.org/web/20060316114732/http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf

2002N-0273 Animal Proteins Prohibited in Ruminant Feed

FDA Comment Number : EC240

Submitter : Mr. Masahiro Mori Date & Time: 01/04/2006 05:01:26

Organization : Embassy of Japan

Category : International Government

Issue Areas/Comments

GENERAL

Comments of Japan on the United States? WTO/SPS Notification (G/ https://www.fsis.usda.gov/sites/default/files/media_file/2020-07/BSE_Risk_Assess_Response_Public_Comments.pdf SPS/N/USA/1141)

The Government of Japan welcomes the opportunity to comment on the United States? notification (G/SPS/N/USA/1141) on substances prohibited from use in Animal food or feed.

The Food safety risk assessment related to the import of beef and beef offal from the U.S.A. and Canada by the Food Safety Commission of Japan (FSC) was completed on December 8, 2005. Regarding the feed ban, the following was noted as an addendum to the conclusion on the risk assessment report of FSC:

To prevent BSE exposure and amplification in U.S.A and Canada, the use of SRM must be prohibited completely. The ban must be applied not only to cattle feed but also to all other animal food/feed that may cause cross-contamination.?

To accomplish the effectively enforced feed ban requested in the OIE Terrestrial Animal Health Code (CHAPTER 2.3.13, Bovine Spongiform Encephalopathy), whole SRM should be excluded as high risk material from animal feed chain as the above-mentioned addendum points out. The U.S. Government should also carry out continuous BSE surveillance sufficient to verify the efficacy of U.S. feed ban and make necessary revision of its feed regulations on a basis of its results.

The Government of Japan would like to request that the U.S. Government take account of the above comments in implementing its animal food and feed regulations.

http://web.archive.org/web/20120128115225/http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC240.htm

Embassy of Japan

http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC240.

http://web.archive.org/web/20110827211303/http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000383-01-vol35.pdf

Singeltary Comment Docket No: 2002N-0273 (formerly Docket No. 02N-0273)

MY comments/questions are as follows ;

1. SINCE the first Harvard BSE Risk Assessment was so flawed and fraught with error after the PEER REVIEW assessment assessed this fact, how do you plan on stopping this from happening again, will there be another peer review with top TSE Scientist, an impartial jury so-to-speak, to assess this new and updated Harvard BSE/TSE risk assessment and will this assessment include the Atypical TSE and SRM issues ?

*** Suppressed peer review of Harvard study October 31, 2002 ***

http://web.archive.org/web/20050308184249/http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf

2. WITH A RECENT NATION WIDE MAD COW FEED BAN RECALL in the past few months that consisted of some 10,878.06 TONS, then another Mad Cow feed ban warning letter in May, IT should seem prudent to ask why our feed bans continue to fail in 2006, and continue to fail today ?

snip...see full text;

http://web.archive.org/web/20050308184249/http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf

Singeltary Full Comments Submissions;

http://web.archive.org/web/20090419033608/http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf

http://web.archive.org/web/20090424070455/http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf

Linda A. Detwiler, DVM

225 Hwy 35

Red Bank, New Jersey 07701 cf

Phone: 732-741-2290 LZ

Cell: 732-580-9391 l,

Fax: 732-741-7751

May 7, 2004

FSIS Docket Clerk 03-025IF

U.S. Department of Agriculture 03-025IF-634 Food Safety and Inspection Service Linda A. Detwiler

300 12th Street, SW. Room 102 Cotton Annex Washington, DC 20250

RE: DEPARTMENT OF AGRICULTURE Food Safety and Inspection Service

9 CFR Parts 301, 309, 310, 311, 313, 318, 319 and 320

Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle; Meat Produced by Advanced Meat/Bone Separation Machinery and Meat Recovery (AMR) Systems; Prohibition of the Use of Certain Stunning Devices Used To Immobilize Cattle During Slaughter; Bovine Spongiform Encephalopathy (BSE) Surveillance Program

The USDA is to be commended for taking the much needed actions outlined in the interim final rules. Current evidence indicates that the risk to humans from BSE is extremely low. However, these actions are essential for the further protection of public health in the United States as the detection of the Canadian case of BSE in May 2003, provided evidence that the BSE agent had indeed been introduced into the North American cattle production system. USDA must continue to monitor new scientific findings as well as other world events and adjust the regulations accordingly.

Docket Number 01-033IF: Prohibition of the Use of Certain Stunning Devices Used To Immobilize Cattle During Slaughter

I am in full support of the prohibition of all devices which may cause the release of brain macro- emboli into the circulatory system of stunned cattle. Given there has been consistent evidence that stunning methods utilizing air-injection have resulted in the circulation of macro-emboli from Central Nervous System (CNS) tissue, USDA should make this interim final rule permanent. (Garland, et al, 1996; personal observation) Docket Number 03-025IF: Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Nonambulatory Disabled Cattle

Specified Risk Materials (SRMs)

Lam in full support of the interim final rule which prohibits SRMs from being included in food for human consumption. In addition to the list of tissues published in this rule, I am requesting that additional tissues be added to the list. These would include the dura (“sheath”) covering the spinal cord and the entire intestine (from pylorus to rectum). The scientific justification is provided below. These SRMs should also be prohibited from ANY FDA regulated food or product intended for human consumption, including but not limited to flavorings, extracts, etc.

Evidence from the United Kingdom indicates that BSE is the most likely cause of the vCJD (Will et al., 1996). The UK’s Spongiform Encephalopathy Advisory Committee (SEAC) concluded that although there was no direct scientific evidence of a link between BSE and vCJD, based on current data and in the absence of any credible alternative, the most likely explanation at that time was that the cases were linked to exposure to BSE before the introduction of control measures, in particular, the specified bovine offal (SBO) ban in 1989. Given that it has been postulated that one of the most likely routes of exposure is through the consumption of meat contaminated with infected CNS tissue (Will, 1999), SRM bans are one of the most important measures for the protection of human health.

The list of tissues to be considered by USDA as SRM includes those bovine tissues where actual infectivity has been identified (based on the research outlined below) or tissues which have a close association to the infected tissues.

A study was conducted to examine the pathogenesis of BSE in cattle, i.e. the replication (tissue distribution) of the agent during the incubation period. This study first identified the agent via mouse bioassay in the distal ileum of the experimentally infected calves. It is thought that the agent may be associated with the lymphoid tissue of the intestines. The calves were four months of age at the time of oral dosing. First isolation of the agent in the distal ileum was made at six months after challenge. Subsequent isolations from the distal ileum were made at ten, 14 and 18 months after dosing. (Wells et. al., 1994) This study has also identified infectivity in spinal cord, brain, dorsal root ganglia, and trigeminal ganglia beginning at 32 months post challenge. (Wells, et. al. 1998). The study was repeated using calves as the bioassay model. Results of the calf bioassay study are very similar to the mouse bioassays. However, this study has also identified apparently low levels of infectivity in tonsil (Update of the Opinion on TSE Infectivity Distribution in Ruminant Tissues adopted by the EU Scientific Steering Committee on November 7-9, 2002). Lymphoid tissue of the 3" eyelid from naturally infected cattle has also demonstrated a low level of infectivity (Presentation by Danny Matthews, UK VLA at the TAFS Workshop, Washington, DC; April 6, 2004). The calf bioassay study is still in progress.

It should be pointed out that the data on the distribution of BSE infectivity in the bovine was derived primarily from 2 studies, one of which has not been completed. The studies conducted are very logistically challenging and expensive. Not every tissue could undergo bioassay. Some tissues were assumed to have a risk due to a close association or the identification of PrPres and are considered as SRM. Such is the case with dura and the remaining sections of intestine.

Dura

Dura was harvested but not tested in the pathogenesis study. Its close association with the brain and spinal cord and the documented evidence of its role in the human to human transmission of ' Creutzfeldt-Jakob Disease (CJD) has prompted scientists to designate bovine dura as a high risk tissue.

Dura may become separated from the vertebral column during the fabrication process allowing the possibility that it be included in ground beef products or contaminate surfaces where deboning occurs. | recommend that USDA amend the definition of SRM to include dura and that it be removed along with spinal cord on the kill floor.

Intestine

The scenario described above is essentially true for the intestine. Infectivity was readily detectable in the distal ileum of cattle infected with BSE. While certain additional sections of the intestine were tested with no infectivity identified, not every section of the intestine was included in the bioassays. Positive immunostaining for PrPres was identified along the length of the intestine providing evidence for the entire intestine to be considered as SRM per EU regulations. (personal communication Danny Matthews, UK, VLA). The International Advisory Committee appointed by Secretary Veneman also recommended that the SRM ban in the US be amended to the entire intestine from duodenum to rectum. I recommend that the USDA adjust the definition of SRM to include the entire intestine from duodenum to rectum.

The removal of SRMs to protect public health is also supported by the WHO and the Harvard Risk Assessment.

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:

- 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.

- Countries should not permit tissues that are likely to contain the BSE agent to enter any food chain (human or animal)

citation:

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

The Harvard Study also made recommendations similar to the WHO, “Our evaluation of potential risk mitigation actions highlights potential measures to further reduce the already low likelihood that BSE could spread to cattle or contaminate human food if it were to arise...... Implementation of a UK-style ban on specified risk material (e.g., spinal cords, brains, vertebral columns) from both human food and animal feed reduces the predicted number of BSE cases in cattle by 80% and the potential human exposure by 95%.”

Cross contamination between SRMs and edible tissue can add risk to products intended for human consumption. Therefore, USDA, FSIS is urged to assure that each slaughterplant which processes cattle have systems in place which prevent cross contamination between edible tissue and SRMs. This should include separate equipment, such as knives, blades, etc where appropriate and utilize effective (for TSE agents) disinfection procedures for equipment used to handle SRMs.

The Update of the Opinion on TSE Infectivity Distribution in Ruminant Tissues adopted by the EU Scientific Steering Committee on November 7-9, 2002 provides some guidelines to avoid cross contamination. Under separate cover I have submitted a CD of practices used throughout Europe and in some plants in the United States. The CD also includes effective disinfection methods that are recommended by the WHO. These practices assist in the reduction of cross contamination.

Nonambulatory Disabled Cattle

As appropriately described in the interim final rule, nonambulatory disabled cattle constitute the majority of the BSE high risk population. I agree that they should be prohibited from being included in the supply of food for human consumption. I also agree with the definition as written in the Interim Final Rule. I urge the USDA to not alter this definition and to continue to prohibit for human food any bovine which cannot walk to the “knock box” regardless of reason.

Downers accounted for over half of the detected BSE cases in both the EU and Switzerland in 2003. In Switzerland 21 cases of BSE were confirmed. Two were from normal slaughter, eleven were from the fallen stock and emergency slaughter (equivalent to US downers) and eight were clinical BSE suspects (ref . http://www.bvet.admin.ch/0_navigation-e/0_index-intern htm] ) In the European Union (January - September 2003) a total of 947 cases were confirmed. Of these confirmed cases 189 (20%) were from normal slaughter, 525 (55.4%) were from the fallen stock/emergency slaughter (US Downers) and 233 (24.6%) were clinical BSE suspects (ref http://europa.eu.int/comm/food/food/biosafety/bse/annual_reps_en.htm).

The previous system of clinical examination of the nonambulatory bovine was not adequate for determining a disposition regarding BSE. This was clearly illustrated by the two native cases of BSE in North America. Both cases of BSE (May and December) were observed by veterinarians prior to slaughter. Neither was specifically set aside as a BSE clinical suspect. The Washington State case was passed for human consumption because she was determined to have a calving injury (which apparently masked signs of BSE or other neurological disease) and the May 2003 case detected in Canada was slaughtered in January and went to rendering. The testing of this cow was completed in May.

Neurological, metabolic or other diseases which affect coordination and other aspects of gait often predispose an animal to injuries such as broken limbs or soft tissue damage. If the animal is then down because of a broken leg, or torn ligament, the injury may be the prominent or sole presenting sign. Without a complete diagnostic work up and history of disease progression the true underlying cause of the nonambulatory condition may be impossible to ascertain.

I have listed the clinical signs of BSE below. This is the list provided on the UK’s DEFRA website. In reviewing the list, the vast majority of signs would be difficult if not impossible to observe once an anima! is down.

http://www.defra.gov.uk/animalh/bse/bse-science/level-4-bse.html#symptoms

The clinical symptoms of BSE are varied. Most cattle with BSE show a gradual development of symptoms over a period of several weeks or even months, although some can deteriorate very rapidly. Only a small proportion of affected cattle show what would be considered typical "mad cow" signs. Most suspects show several (but not all) of the following symptoms if they are observed closely enough:

apprehensiveness

nervousness

reluctance to cross concrete, turn corners, enter yards, go through doorways or permit milking

occasional aggression directed at other cattle or humans manic kicking when milked

head shyness, with head held low

high stepping gait, particularly hind legs

difficulties in rising

tremors

loss of condition, weight or milk yield

In addition, per the list, difficulty in rising is a clinical sign of BSE. Eventually cattle with BSE progress and become recumbent. Per the interim rule testing is not absolute and cannot

guarantee absence of infectivity. In fact in at most countries beef from tested animals cannot be labeled as BSE free.

I do suggest that this regulation not prohibit any individual or family from using one of their own nonambulatory animals for personal consumption. This can be done at their risk through custom slaughter.

Docket Number 03-0381F: Meat Produced by Advanced Meat/Bone Separation Machinery and Meat Recovery (AMR) Systems and Docket Number 03-025IF: Prohibition of the Use of Specified Risk Materials for Human Food

The restrictions on AMR are the most important regulations put into place by the USDA. I fully support all of the prohibitions placed on the production of meat from AMR systems. J also urge that for the reasons outlined in the SRM section above, dura be prohibited from being included in AMR product.

In the original Harvard risk assessment completed in 2001 as well as the update in 2003, in the US system it was illustrated that AMR could deliver more 1D50s for potential human consumption than the direct consumption of brain and spinal cord together.

The 2001 Harvard risk assessment’s base case scenario found that out of 1000 simulation runs the mean number of 1D50s (infectious doses) available for human consumption would be 35. Almost 11 1D50s (10.9) would be derived from brain and spinal cord. Twenty (more than half) are derived from AMR products. (Harvard Risk Assessment, 2001 Section 3.1.2.7 - 3.1.2.9; Appendix 3A Base Case).

Statistics from the Harvard Risk Assessment (2003) showing ID50s from brain and spinal cord vs. AMR product:

Worse case scenario

Mean 5% percentile 95" percentile

Total 1D50s available for humans - 6000 2000 12,000

*[D50s from brain - 770 5.2 2000

1D50s from spinal cord - 280 2 760

ID50s from AMR - 2900 960 5600

Best case scenario

Total IDS0s available for humans - 10 0 36

*1D50s from brain - 1.6 0 0

1DSQs from spinal cord - 69 0 0

1D50s from AMR - 3.7 0 10

* Additional tissues included but not listed here.

Lalso agree that Mechanically Separated Product should be completely prohibited for human consumption.

Surveillance

The proposed increased surveillance program announced by USDA APHIS is essential. In order to estimate the amount of BSE in the US national herd it is imperative that as many of the high risk population be tested as possible. This is also true for Canada. Without this surveillance the US will not be able to monitor the effects of past and present control efforts. It is important for the industry, academia and government to work together to achieve this goal. We need to know if there is any regionality to cases, what ages are affected and if the current feed ban has failed.

Animal Feed

Epidemiological evidence in Europe and results from the 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, has found that .001 gr of raw infected brain can transmit BSE (1 cow out of 15) through the oral route. The role of cross contamination was under estimated throughout Europe. Experience in other countries has also shown that human error especially at the farm level is difficult to control. It is imperative that the feed ban be effective. There are a number of actions which still need to be taken by the FDA to prevent any potential recycling of the BSE agent in the US cattle population. The FDA is urged to act immediately and put these measures in place.

Per the 2001 Harvard risk assessment, “Our evaluation of potential risk mitigation actions highlights potential measures to further reduce the already low likelihood that BSE could spread to cattle or contaminate human food if it were to arise. Prohibiting the rendering of animals that die on the farm, possibly of BSE, removes a great deal of potential contamination in the animal feed chain and reduces average predicted cases of BSE following introduction of ten infected cattle by 77%. Implementation of a UK-style ban on specified risk material (¢.g., spinal cords, brains, vertebral columns) from both human food and animal feed reduces the predicted number of BSE cases in cattle by 80% and the potential human exposure by 95%.”

Thank you for the opportunity to comment on these rules.

Linda A. Detwiler, DVM

Drlucele Detus | OP vee REFERENCES

Garland, T., Bauer, N., Bailey, M. (1996) Brain emboli in the lung of cattle after stunning. The Lancet, 348: 610.

Wells G.A.H., Hawkins, $.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. Will, R. (1999) New variant Creutzfeldt-Jakob Disease. Biomed & Pharmacother, 53, 9-13.

Will, R. G., Ironside, J. W., Zeidler, M., Cousens, S. N., Estibeiro, K., Alperovitch, A., Poser, S., Pocchiari, M., Hofman, A. & Smith, P. G. (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet., 347, 921-925,

http://web.archive.org/web/20090424070445/http://www.fsis.usda.gov/OPPDE/Comments/03-025IF/03-025IF-634.pdf

Linda A. Detwiler, DVM 225 Hwy 35 Red Bank, New Jersey 07701 L Phone: 732-741-2290 lj Cell: 732-580-9391

Fax: 732-741-7751

May 6, 2004

03-025IF 03-025IF-631 Linda A. Detwiler

FSIS Docket Clerk

U.S. Department of Agriculture Food Safety and Inspection Service 300 12th Street, SW.

Room 102 Cotton Annex Washington, DC 20250

RE: DEPARTMENT OF AGRICULTURE Food Safety and Inspection Service

[Docket No. 03-025N] 9 CFR Parts 301, 309, 310, 311, 313, 318, 319 and 320

The USDA’s Food Safety Inspection Service requested any additional comments or information on practices which would reduce or eliminate cross contamination between

I am submitting a CD with a presentation;

snip...see full submission with presentation from Dr. Detwiler;

http://web.archive.org/web/20090418170519/http://www.fsis.usda.gov/OPPDE/Comments/03-025IF/03-025IF-631.pdf

Public Comments on Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle:========

Title: Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle FR Document Number: 05-17683 Legacy Document ID: RIN:

Publish Date: 09/07/2005 00:00:00 Submitter Info:

First Name: Jason Last Name: Frost Mailing Address: 37 Observatory Circle, NW City: Washington Country: United States State or Province: DC Postal Code: 20008

Organization Name: New Zealand Embassy

COMMENTS ON FEDERAL REGISTER 9 CFR Parts 309 et al [Docket No. 03- 025IF] Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle: Interim final rule and request for comments

On 12 January 2004, the Food Safety Inspection Service (FSIS) published an Interim Final Rule titled Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle: Interim final rule and request for comments.

This rule prohibited the use of certain cattle material, to address the potential risk of bovine spongiform encephalopathy (BSE), in human food, including dietary supplements, and cosmetics. On 7 September 2005 FSIS issued an amendment to this interim final rule to permit collection of the small intestine excluding the distal ileum and sought further comments.

New Zealand welcomes the opportunity to comment on the amendment to FSIS Docket No.03-0251FA. This submission, while supporting and commending FSIS on the amendment, reiterates the position presented in New Zealand’s original comments on the interim final rule when first issued, that there is no scientific justification for applying the interim rule to New Zealand given its widely acknowledged BSE-free risk status.

New Zealand has closely followed the events in the United States and around the world since the United States announced its first case of BSE late in 2003. New Zealand continues to strongly advocate that the world take a more rational risk-based approach to dealing with this disease of cattle, noting that it has only infected consumers in countries where the epidemic resulted in thousands of cattle cases and precautions to protect the human population had not yet been implemented effectively. Regulatory reactions and decisions around the world need to be commensurate with the real risk selected hazards pose to our consumers relative to the other diseases with which we are battling. This is a position New Zealand has firmly supported. There is a continued need for such a principled approach to ensure we can more appropriately focus and apportion resources on those areas most likely to significantly improve and protect the health of our populations.

A science and risk-based response from the United States in respect of domestic BSE measures is also crucial in underpinning appropriate international standards. It is unlikely that the international community will be prepared to adopt risk-based standards if the United States itself does not demonstrate this approach. Accordingly, New Zealand remains concerned that the measures introduced by the interim final rule, which are directly in response to the discovery of BSE in North America, continue to be applied to New Zealand bovine products. New Zealand is not aware of any risk assessment of our BSE status being conducted by the United States. The measures applied by FSIS are in excess of the relevant international standard (OIE). Most of our trading partners acceptance of New Zealand’s BSEfree status has meant that there are no SRMs associated with cattle born, raised and slaughtered in New Zealand.

While the FSIS advised that the interim final rule was in response “to the finding of an adult cow that tested positive for BSE in the State of Washington”, it is important to note that New Zealand’s disease status has not changed. Nor does our cattle population share a common risk profile with that of the United States. With the exception of very small volumes from Australia, which is also widely recognised as being BSE free, New Zealand has not imported meat and bone meal from any country since the early part of the last century. Nor have we imported animal feeds containing such ruminant protein from any BSE affected country (including the United States and Canada). New Zealand has imported very few live cattle from the US and Canada, all of which are identified and officially monitored and controlled. As a consequence of the integrated nature of international trade the continuing application of the FSIS’s interim final rule (specifically the declaring of certain bovine tissues from any country as adulterants regardless of whether they are truly SRMs), to demonstrably BSE free countries such as New Zealand, is having substantial adverse economic effects on New Zealand industries. These inappropriate negative impacts could easily be avoided.

Background

While the interim final rule’s stated intent was to protect the food supply from materials that may carry the risk of transmitting BSE, New Zealand remains concerned that the burden of many of the measures imposed are disproportionate to the actual risks involved. The US has only detected one indigenous case of BSE to date, hence there is an extremely low risk posed to US consumers by this disease. This raises the question of the extent of the measures introduced within the United States in response to such an extremely low risk. We acknowledge the linkage between BSE of cattle and vCJD of humans, but note that evidence that has accumulated since 1996, when vCJD was first reported, strongly indicates that it is not easy for humans to become infected with vCJD. At the peak of the British BSE epidemic well over 700 clinical cases of the disease were being reported each week. Since 1986, nearly 200,000 British cows have been confirmed with BSE and epidemiological modeling suggests that perhaps 1 to 2 million additional BSE-infected animals may have entered the human food supply in the United Kingdom. Despite that level of exposure, fewer than 160 cases of vCJD have been recorded in that country. That is, fewer than 18 cases per year, on average, and the evidence continues to suggest that the vCJD epidemic has peaked and is in decline.

The United States has applied substantial BSE-measures. It is extremely unlikely that a country such as the United States, which has applied anti-BSE measures with increasing stringency for several years, could experience a BSE epidemic as seen in the United Kingdom. In addition any possible exposure of the United States cattle population would at least be two or three orders of magnitude less than in the United Kingdom. The results to date of the United States Department of Agriculture surveillance and testing regimes support the fact that the United States is highly resistant to any proliferation of BSE and confirm the position formerly acknowledged by the Harvard-Tuskegee study of BSE.

Specific risk materials

New Zealand continues to support the United States decision to classify as SRMs brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column and dorsal root ganglia from animals of age 30 months and over, and the tonsils and distal ileum of all cattle in populations where a case of BSE has been reported. This response fully reflects the SPS principle that measures put in place to mitigate a food-borne risk should be proportionate to the risks involved. Current scientific knowledge indicates that exclusion of these tissues from animals of younger age would provide very little further mitigation of what is already an extremely low level of risk. New Zealand again urges the United States to take a scientific approach in recognizing that the exclusion of these tissues, from cattle of any age, is completely unwarranted in a country, such as New Zealand, demonstrated to be free from BSE.

Conclusion

It is essential that the United States takes a science and risk-based response in respect of domestic BSE measures as this is going to be crucial in securing appropriate international standards. It is unlikely that the international community will be prepared to adopt risk-based standards if the United States itself does not demonstrate this approach. Accordingly, New Zealand is concerned to see that the measures, which are directly in response to the discovery of BSE in North America, continue to be applied to New Zealand origin bovine products some 21 months after the interim final rule was issued. There is a continuing failure to apply the international standard (OIE) for BSE to exporting countries.

New Zealand requests that any subsequent measures adopted by the United States recognise the different BSE status or risk profile of bovine products from exporting countries. In doing so the United States would be giving appropriate regard to its obligations under the WTO Agreement on the Application of Sanitary and Phytosanitary Measures (the SPS Agreement).

New Zealand has a well established and widely acknowledged freedom from BSE and other TSEs. The existing measures achieve the same level of human and/or animal health protection anticipated by this interim final rule. The imposition of unnecessarily prescriptive trade requirements are impediments to legitimate trade and create unnecessary and burdensome compliance costs.

http://web.archive.org/web/20090801232201/http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-6.pdf

USDA, FSIS, APHIS, BSE, Harvard Study Reply to Singeltary et al

FDA PROPOSED RULE DECEMBER 20, 2005

https://www.fsis.usda.gov/sites/default/files/media_file/2020-07/BSE_Risk_Assess_Response_Public_Comments.pdf

''It is our opinion that the proposed rule falls woefully short in effective measures to minimize the potential for further transmissions of the disease.''

Subject: SEAC Draft minutes of the open session of the 93rd meeting held on 6th July 2006 (atypical BSE USA)

Date: August 22, 2006 at 3:03 pm PST SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE

Draft minutes of the open session of the 93rd meeting held on 6th July 2006

snip...

The Chair noted that recent reports described two cases of BSE in cattle in the United States of America (USA) as being similar to atypical cases of BSE found in a number of European countries. The Chair suggested that the term "atypical BSE", used in the USA report, is potentially confusing and that this would be discussed under any other business. Dr Danny Matthews (Veterinary Laboratories Agency [VLA]) explained that data from western blots of the USA cases resembled that of a small number of atypical cases of BSE in France. A study of the French cases had shown the condition to be transmissible to mice by intracerebral (ic) inoculation with the neuropathological phenotype maintained on transmission3. Claims have been made about the existence of atypical cases of BSE in other countries but these have yet to be confirmed. No study has yet examined the tissue distribution of abnormal prion protein (PrPSc) or infectivity in such atypical cases of BSE.

3 Baron et al. (2006) Transmission of new bovine prion to mice. Emerging. Infect. Diseases. 12, 1125-1128.

snip...

http://www.seac.gov.uk/minutes/draft93.pdf

https://discovery.nationalarchives.gov.uk/results/r?_q=bovine+spongiform+encephalopathy

However, based on analysis of molecular features of prion

diseases in cattle, this situation is similar to that in humans

(5), in which different subtypes of sporadic Creutzfeldt-

Jakob disease agents are found.

DISPATCHES

1126 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 12, No. 7, July 2006

http://www.cdc.gov/ncidod/EID/vol12no07/pdfs/vol12no07.pdf

Medical Sciences Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease

Snip...end

http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html

2022

Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation

Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation

Author item Greenlee, Justin item Cassmann, Eric item MOORE, SARA JO - Oak Ridge Institute For Science And Education (ORISE) item WEST GREENLEE, HEATHER - Iowa State University

Submitted to: Meeting Abstract

Publication Type: Abstract Only

Publication Acceptance Date: 6/24/2022

Publication Date: 9/16/2022

Citation: Greenlee, J.J., Cassmann, E.D., Moore, S., West Greenlee, H.M. 2022.

Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation.

Prion 2022 Conference abstracts: pushing the boundaries. 16(1):150. https://doi.org/10.1080/19336896.2022.2091286.

DOI: https://doi.org/10.1080/19336896.2022.2091286

Interpretive Summary:

Technical Abstract:

In 2006, a case of H-type bovine spongiform encephalopathy (H-BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent PRNP mutation associated with familial Creutzfeldt-Jakob disease. Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure. Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with the H-BSE agent from either the US 2004 case (wild type donor; n=3) or from the US 2006 case with the E211K polymorphism (n=4). Cattle were observed daily throughout the course of the experiment for the development of clinical signs. When signs were noted, animals were euthanized and necropsied. Cattle were confirmed positive for abnormal BSE prions by enzyme immunoassay (EIA; Idexx HerdChek BSE Ag Test), anti-PrP immunohistochemistry (IHC) on brainstem, and microscopic examination for vacuolation. Three-out-of-four (75%) calves with the EK211 genotype developed clinical signs of H-BSE including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and were euthanized. Two of the positive EK211 steers received H-BSE US 2004 inoculum (Incubation Period (IP): 59.3 and 72.3 months) while the other positive steer received the E211K H-BSE inoculum (IP: 49.7 months). EIA confirmed that abundant misfolded protein (O.D. 2.57-4.0) in the brainstem, and IHC demonstrated PrPSc throughout the brain. All cattle in the EE211 recipient group remain asymptomatic for the duration of the experiment (approximately 7 years post-inoculation). This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.

https://www.ars.usda.gov/research/publications/publication/?seqNo115=395351

''This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.''

Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation

Justin J. Greenleea, Eric D. Cassmanna, S. Jo Moorea,b, and M. Heather West Greenleec

aVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA; bOak Ridge Institute for Science and Education (ORISE), U.S. Department of Energy, Oak Ridge, TN, US; cDepartment of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, US

Aims: In 2006, a case of H-type bovine spongiform encephalopathy (H-BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent PRNP mutation associated with familial Creutzfeldt-Jakob disease. Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure.

Material and Methods: Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with the H-BSE agent from either the US 2004 case (wild type donor; n = 3) or from the US 2006 case with the E211K polymorphism (n = 4). Cattle were observed daily throughout the course of the experiment for the development of clinical signs. When signs were noted, animals were euthanized and necropsied. Cattle were confirmed positive for abnormal BSE prions by enzyme immunoassay (EIA; Idexx HerdChek BSE Ag Test), anti-PrP immunohistochemistry (IHC) on brainstem, and microscopic examination for vacuolation.

Results: Three-out-of-four (75%) calves with the EK211 genotype developed clinical signs of H-BSE including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and were euthanized. Two of the positive EK211 steers received H-BSE US 2004 inoculum (Incubation Period (IP): 59.3 and 72.3 months) while the other positive steer received the E211K H-BSE inoculum (IP: 49.7 months). EIA confirmed that abundant misfolded protein (O.D. 2.57–4.0) in the brainstem, and IHC demonstrated PrPScthroughout the brain. All wild type recipient cattle and a single EK211 steer remained asymptomatic for the duration of the experiment (approximately 7 years post-inoculation) and no abnormal prion protein was detected in these cattle by EIA.

Conclusions: This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1 g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.

Funded by: US Department of Agriculture

Acknowledgement: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was supported in part by an appointment to the Agricultural Research Service (ARS) Research Participation Program administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Department of Agriculture (USDA). ORISE is managed by ORAU under DOE contract number DE-SC0014664. All opinions expressed in this paper are the author’s and do not necessarily reflect the policies and views of USDA, ARS, DOE, or ORAU/ORISE.

https://www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286

WEDNESDAY, AUGUST 15, 2018

The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge

http://bovineprp.blogspot.com/2018/08/the-agent-of-h-type-bovine-spongiform.html

PRION 2018 CONFERENCE

P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge

Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2) (1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.

reading up on this study from Prion 2018 Conference, very important findings ;

***> This study demonstrates that the H-type BSE agent is transmissible by the oronasal route.

***> These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.

PRION 2018 CONFERENCE ABSTRACT

https://www.ars.usda.gov/research/publications/publication/?seqNo115=353094

https://downloads.regulations.gov/APHIS-2018-0087-0002/attachment_1.pdf

WEDNESDAY, OCTOBER 24, 2018

Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy

https://bse-atypical.blogspot.com/2018/10/experimental-infection-of-cattle-with.html

WEDNESDAY, OCTOBER 24, 2018

Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy

https://bse-atypical.blogspot.com/2018/10/experimental-infection-of-cattle-with.html

let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.

This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$

ALABAMA MAD COW g-h-BSEalabama

In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.

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

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

her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).

This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine–human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.

Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA

NATURE|Vol 457|26 February 2009

https://www.nature.com/articles/4571079b.pdf

https://www.nature.com/articles/4571079b

> Epidemiological investigations conducted by USDA personnel failed to reveal any evidence of a feed source contaminated with TSE material fed to this animal

http://www.aphis.usda.gov/newsroom/hot_issues/bse/downloads/EPI_Final5-2-06.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525843/

LMAO!

BANNED MAD COW FEED IN COMMERCE IN ALABAMA

Date: September 6, 2006 at 7:58 am PST PRODUCT

a) EVSRC Custom dairy feed, Recall # V-130-6;

b) Performance Chick Starter, Recall # V-131-6;

c) Performance Quail Grower, Recall # V-132-6;

d) Performance Pheasant Finisher, Recall # V-133-6.

CODE None RECALLING FIRM/MANUFACTURER Donaldson & Hasenbein/dba J&R Feed Service, Inc., Cullman, AL, by telephone on June 23, 2006 and by letter dated July 19, 2006. Firm initiated recall is complete.

REASON

Dairy and poultry feeds were possibly contaminated with ruminant based protein.

VOLUME OF PRODUCT IN COMMERCE 477.72 tons

DISTRIBUTION AL

______________________________

http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html

http://web.archive.org/web/20080229052729/http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html

PRODUCT Bulk custom dairy pre-mixes,

Recall # V-120-6 CODE None RECALLING FIRM/MANUFACTURER Ware Milling Inc., Houston, MS, by telephone on June 23, 2006. Firm initiated recall is complete. REASON Possible contamination of dairy animal feeds with ruminant derived meat and bone meal.

VOLUME OF PRODUCT IN COMMERCE 350 tons

DISTRIBUTION AL and MS

______________________________

PRODUCT

a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet, 50 lb. bags, Recall # V-121-6;

b) Tucker Milling, LLC #31120, Game Bird Breeder Pellet, 50 lb. bags, Recall # V-122-6;

c) Tucker Milling, LLC #31232 Game Bird Grower, 50 lb. bags, Recall # V-123-6;

d) Tucker Milling, LLC 31227-Crumble, Game Bird Starter, BMD Medicated, 50 lb bags, Recall # V-124-6;

e) Tucker Milling, LLC #31120, Game Bird Breeder, 50 lb bags, Recall # V-125-6;

f) Tucker Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags, Recall # V-126-6;

g) Tucker Milling, LLC #30116, TM Broiler Finisher, 50 lb bags, Recall # V-127-6

CODE All products manufactured from 02/01/2005 until 06/20/2006 RECALLING FIRM/MANUFACTURER Recalling Firm: Tucker Milling LLC, Guntersville, AL, by telephone and visit on June 20, 2006, and by letter on June 23, 2006. Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated recall is ongoing.

REASON Poultry and fish feeds which were possibly contaminated with ruminant based protein were not labeled as "Do not feed to ruminants".

VOLUME OF PRODUCT IN COMMERCE 7,541-50 lb bags

DISTRIBUTION AL, GA, MS, and TN

END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006

###

http://www.fda.gov/bbs/topics/ENFORCE/2006/ENF00964.html

http://web.archive.org/web/20070223174152/http://www.fda.gov/bbs/topics/ENFORCE/2006/ENF00964.html

Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125 TONS Products manufactured from 02/01/2005 until 06/06/2006

Date: August 6, 2006 at 6:16 pm PST PRODUCT

a) CO-OP 32% Sinking Catfish, Recall # V-100-6;

b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6;

c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;

d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6;

e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6;

f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6;

g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%, Recall # V-106-6;

h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to 20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6;

i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6;

j) CO-OP LAYING CRUMBLES, Recall # V-109-6;

k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall # V-110-6;

l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6;

m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 CODE

Product manufactured from 02/01/2005 until 06/06/2006

RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is complete.

REASON Animal and fish feeds which were possibly contaminated with ruminant based protein not labeled as "Do not feed to ruminants".

VOLUME OF PRODUCT IN COMMERCE 125 tons

DISTRIBUTION AL and FL

END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006

###

http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html

http://web.archive.org/web/20060821195949/http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html

MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE Sun Jul 16, 2006 09:22 71.248.128.67

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II

______________________________

PRODUCT

a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy Animals, Recall # V-079-6;

b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net weight 50lb (22.6 kg), Recall # V-080-6;

c) PRO-PAK, MARINE & ANIMAL PROTEIN CONCENTRATE FOR USE IN ANIMAL FEED, Recall # V-081-6;

d) Feather Meal, Recall # V-082-6 CODE

a) Bulk

b) None

c) Bulk

d) Bulk

RECALLING FIRM/MANUFACTURER H. J. Baker & Bro., Inc., Albertville, AL, by telephone on June 15, 2006 and by press release on June 16, 2006. Firm initiated recall is ongoing.

REASON

Possible contamination of animal feeds with ruminent derived meat and bone meal.

VOLUME OF PRODUCT IN COMMERCE 10,878.06 tons

DISTRIBUTION Nationwide

END OF ENFORCEMENT REPORT FOR July 12, 2006

###

http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html

http://web.archive.org/web/20070223180551/http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html

10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

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

http://web.archive.org/web/20091104111717/http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

***> The U.S. cases were animals born and raised in the U.S. (Texas, Alabama).

SEE HISTORY AT THE BOTTOM...TSS

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html

THURSDAY, OCTOBER 18, 2007

BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA, A REVIEW OF SORTS

http://madcowtesting.blogspot.com/2007/10/bse-base-mad-cow-testing-texas-usa-and.html

Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY

(see mad cow feed in COMMERCE IN ALABAMA...TSS)

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

Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY, what if?

BSE Case Associated with Prion Protein Gene Mutation

http://bovineprp.blogspot.com/2015/05/bse-case-associated-with-prion-protein.html

WEDNESDAY, AUGUST 15, 2018

***> The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge

http://bovineprp.blogspot.com/2018/08/the-agent-of-h-type-bovine-spongiform.html

THURSDAY, JUNE 25, 2020

First Report of the Potential Bovine Spongiform Encephalopathy (BSE)-Related Somatic Mutation E211K of the Prion Protein Gene (PRNP) in Cattle

https://bovineprp.blogspot.com/2020/06/first-report-of-potential-bovine.html

-------- 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" e.asante@ic.ac.uk

To: "'flounder@wt.net'" flounder@wt.net

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.

I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.

Emmanuel Asante

<<Asante et al 2002.pdf>>

____________________________________

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)

____________________________________

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.

https://www.nature.com/articles/srep11573

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),

***is the third potentially zoonotic PD (with BSE and L-type BSE),

***thus questioning the origin of human sporadic cases.

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

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

***thus questioning the origin of human sporadic cases***

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

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

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

PRION 2015 CONFERENCE

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019500/

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efﬁciency comparable to that of cattle BSE. While the efﬁciency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

Title: Transmission of scrapie prions to primate after an extended silent incubation period)

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

Sunday, January 10, 2021

APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission June 17, 2019

APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission

Greetings APHIS et al,

I would kindly like to comment on APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], and my comments are as follows, with the latest peer review and transmission studies as references of evidence.

THE OIE/USDA BSE Minimal Risk Region MRR is nothing more than free pass to import and export the Transmissible Spongiform Encephalopathy TSE Prion disease. December 2003, when the USDA et al lost it's supposedly 'GOLD CARD' ie BSE FREE STATUS (that was based on nothing more than not looking and not finding BSE), once the USA lost it's gold card BSE Free status, the USDA OIE et al worked hard and fast to change the BSE Geographical Risk Statuses i.e. the BSE GBR's, and replaced it with the BSE MRR policy, the legal tool to trade mad cow type disease TSE Prion Globally. The USA is doing just what the UK did, when they shipped mad cow disease around the world, except with the BSE MRR policy, it's now legal.

Also, the whole concept of the BSE MRR policy is based on a false pretense, that atypical BSE is not transmissible, and that only typical c-BSE is transmissible via feed. This notion that atypical BSE TSE Prion is an old age cow disease that is not infectious is absolutely false, there is NO science to show this, and on the contrary, we now know that atypical BSE will transmit by ORAL ROUTES, but even much more concerning now, recent science has shown that Chronic Wasting Disease CWD TSE Prion in deer and elk which is rampant with no stopping is sight in the USA, and Scrapie TSE Prion in sheep and goat, will transmit to PIGS by oral routes, this is our worst nightmare, showing even more risk factors for the USA FDA PART 589 TSE PRION FEED ban.

The FDA PART 589 TSE PRION FEED ban has failed terribly bad, and is still failing, since August 1997. there is tonnage and tonnage of banned potential mad cow feed that went into commerce, and still is, with one decade, 10 YEARS, post August 1997 FDA PART 589 TSE PRION FEED ban, 2007, with 10,000,000 POUNDS, with REASON, Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. you can see all these feed ban warning letters and tonnage of mad cow feed in commerce, year after year, that is not accessible on the internet anymore like it use to be, you can see history of the FDA failure August 1997 FDA PART 589 TSE PRION FEED ban here, but remember this, we have a new outbreak of TSE Prion disease in a new livestock species, the camel, and this too is very worrisome.

WITH the OIE and the USDA et al weakening the global TSE prion surveillance, by not classifying the atypical Scrapie as TSE Prion disease, and the notion that they want to do the same thing with typical scrapie and atypical BSE, it's just not scientific.

WE MUST abolish the BSE MRR policy, go back to the BSE GBR risk assessments by country, and enhance them to include all strains of TSE Prion disease in all species. With Chronic Wasting CWD TSE Prion disease spreading in Europe, now including, Norway, Finland, Sweden, also in Korea, Canada and the USA, and the TSE Prion in Camels, the fact the the USA is feeding potentially CWD, Scrapie, BSE, typical and atypical, to other animals, and shipping both this feed and or live animals or even grains around the globe, potentially exposed or infected with the TSE Prion. this APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], under it's present definition, does NOT show the true risk of the TSE Prion in any country. as i said, it's nothing more than a legal tool to trade the TSE Prion around the globe, nothing but ink on paper.

AS long as the BSE MRR policy stays in effect, TSE Prion disease will continued to be bought and sold as food for both humans and animals around the globe, and the future ramifications from friendly fire there from, i.e. iatrogenic exposure and transmission there from from all of the above, should not be underestimated. ...

https://www.regulations.gov/comment/APHIS-2018-0087-0002

https://downloads.regulations.gov/APHIS-2018-0087-0002/attachment_1.pdf

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.230.8886&rep=rep1&type=pdf

https://bovineprp.blogspot.com/2020/12/bse-research-project-final-report-2005.html

http://bovineprp.blogspot.com/2020/12/

Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission

https://www.regulations.gov/comment/APHIS-2021-0004-0002

https://downloads.regulations.gov/APHIS-2021-0004-0002/attachment_1.pdf

Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification

https://www.regulations.gov/document/APHIS-2018-0011-0003

https://downloads.regulations.gov/APHIS-2018-0011-0003/attachment_1.pdf

RE-Inactivation of porcine endogenous retrovirus in pigs using CPISPR-Cas9

TERRY S. SINGELTARY SR.
retired

Mr.

seems that the USA feed ban for ruminant protein is still a serious problem, so there seems to still be a risk factor for pigs and Transmissible Spongiform Encephalopathy TSE prion disease. now with the updated science showing that pigs are susceptible to the Chronic Wasting Disease TSE Prion ORALLY, and cwd running rampant in the USA, any use of porcine organs should be tested for the CWD TSE Prion...

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Location: Virus and Prion Research

Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease

Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin

Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017

Publication Date: N/A Citation: N/A Interpretive Summary:

Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.

Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 month challenge groups). The remaining pigs (>6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.

Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). Conclusions:

This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge.

CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.

Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.

https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105

CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...

http://web.archive.org/web/20031026000118/www.bseinquiry.gov.uk/files/yb/1990/08/23004001.pdf

we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.

http://web.archive.org/web/20030822031154/www.bseinquiry.gov.uk/files/yb/1990/09/10007001.pdf

Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....

http://web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf

snip...see much more here ;

https://www.science.org/do/10.1126/comment.697946/full/

OIE Bulletin

Camel prion disease: a possible emerging disease in dromedary camel populations?

The identification of a new prion disease in dromedary camels in Algeria and Tunisia, called camel prion disease (CPD), extends the spectrum of animal species naturally susceptible to prion diseases and opens up new research areas for investigation.

Camel prion disease was identified in 2018 in adult camels showing clinical signs at the ante mortem inspection at slaughterhouses in the region of Ouargla (Algeria), and in 2019 in the region of Tataouine (Tunisia). It adds to the group of existing animal prion diseases, including scrapie in sheep and goats, chronic wasting disease (CWD) in cervids and BSE (mainly in bovines). The detection of a new prion disease in the dromedary population requires attention and investigation needs to be carried out to assess the risks of this disease to animal and public health. As of today, very limited epidemiological information is available to assess the prevalence, geographical distribution and dynamic of the transmission of the disease.

Based on the clinical signs suggesting prion disease, CPD seems to have occurred in 3.1% of the dromedaries brought to the abattoir in Ouargla. Pathognomonic neurodegeneration and disease specific prion protein (PrPSc) were detected in brain tissue from three symptomatic animals (source:

CDC article https://wwwnc.cdc.gov/eid/article/24/6/17-2007_article

In May 2019, the OIE received a report from Tunisia on a single case of a 12-year-old slaughtered dromedary camel showing neurological signs confirmed as CPD by the Istituto Superiore di Sanità (ISS) based in Italy.

www.oiebulletin.com

Is camel prion disease transmissible in natural conditions?

The involvement of lymphoid tissue in prion replication, observed both in the Algeria and Tunisia cases, is suggestive of a peripheral pathogenesis, which is thought to be a prerequisite for prion shedding into the environment. As with other animal prion diseases, such as scrapie and CWD, in which lymphoid tissues are extensively involved and horizontal transmission occurs efficiently under natural conditions, the detection of prion proteins in lymph nodes is suggestive of the infectious nature of CPD and concurs to hypothesise the potential impact of CPD on animal health. No evidence is currently available with which to argue for the relevance of CPD for human health. However, no absolute species barrier exists in prion diseases and minimising the exposure of humans to prion-infected animal products is an essential aspect of public health protection. As for the relationship between CPD and other animal prion diseases, preliminary analyses suggest that CPD prions have a different molecular signature from scrapie and BSE.

Actions on the follow up of CPD

Since the first description of CPD, the OIE promoted discussions on the impact of this new disease through the OIE Scientific Commission for Animal Diseases (Scientific Commission). The Scientific Commission consulted two OIE ad hoc Groups, one on BSE risk status evaluation of Members and the other on camelids. It analysed the information available from the Algeria and Tunisia cases to evaluate if CPD should be considered an ‘emerging disease’ based on the criteria listed in the Terrestrial Animal Health Code1 .

The OIE Scientific Commission noted that limited surveillance data were available on the prevalence of CPD and that the evidence was not sufficient to measure, at that time, the impact of the disease on animal or public health. Therefore, it was concluded that, with the current knowledge, CPD did not currently meet the criteria to be considered an emerging disease. Nonetheless, it was emphasised that CPD should be considered as a new disease not to be overlooked and called for the collection of further scientific evidence through research and surveillance in the affected countries and in countries with dromedary camel populations to measure the impact of the disease. As new scientific evidence becomes available, the OIE Scientific Commission will reassess whether this disease should be considered as an emerging disease.

The worldwide camel population is ~35 million head (FAO, 2019), 88% of which is found in Africa. The camel farming system is evolving rapidly, and these animals represent vital sources of meat, milk and transportation for millions of people living in the most arid regions of the world. This makes it necessary to assess the risk for animal and human health and to develop evidence-based policies to control and limit the spread of the disease in animals, and to minimise human exposure. As a first step, the awareness of Veterinary Services about CPD and its diagnostic capacity needs to be improved in all countries where dromedaries are part of the domestic livestock.

At the regional level, CPD was first discussed in the 18th Joint Permanent Committee of the Mediterranean Animal Health Network (REMESA) held in Cairo, Egypt, in June 2019 where an expert 1 a new occurrence in an animal of a disease, infection or infestation, causing a significant impact on animal or public health resulting from a) a change of a known pathogenic agent or its spread to a new geographic area or species, or b) a previously unrecognised pathogenic agent or disease diagnosed for the first time www.oiebulletin.com

from ISS, Italy, shared the knowledge available on the new disease with the 15 REMESA Member Countries. The discussion highlighted the need to strengthen surveillance systems in order to collect epidemiological data to inform the risk assessments. The results of these risk assessments will support the implementation of evidence-based policies to manage the risks in both animals and humans.

CPD was recently discussed atthe 15thConference of the OIE Regional Commission for the Middle East in November. During this conference, the CAMENET (Camel Middle East Network) launched a wide ranging proposal for training, coordinated surveillance and research on CPD. In addition, the ERFAN (Enhancing Research for Africa Network), a platform aimed at enhancing scientific cooperation between Africa and Italy, during its 2nd ERFAN meeting for North Africa, presented a project on CPD with the objective of increasing CPD coordinated surveillance in North Africa.

The OIE, through its Reference Laboratories for prion diseases, and by involving the above scientific initiatives, is keeping a close watch on the evolution of the disease to gather scientific evidence and to allow a proper and more thorough assessment of the risk associated with this novel disease.

◼ December 2019

http://web.archive.org/web/20210711171316/https://oiebulletin.com/wp-content/uploads/2019/12/OIE-News-December-2019-Camel-prion-disease.pdf

Tuesday, April 27, 2021

Working Document on Camel Prion Disease (CPrD) 14/09/2020

https://camelusprp.blogspot.com/2021/04/working-document-on-camel-prion-disease.html

Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease

Nathaniel D. Denkers ,Clare E. Hoover ,Kristen A. Davenport,Davin M. Henderson,Erin E. McNulty,Amy V. Nalls,Candace K. Mathiason,Edward A. Hoover

Published: August 20, 2020

https://doi.org/10.1371/journal.pone.0237410

We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237410

WE know now, and we knew decades ago, that 5.5 grams of suspect feed in TEXAS was enough to kill 100 cows.

look at the table and you'll see that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE;

Risk of oral infection with bovine spongiform encephalopathy agent in primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys

Summary The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is compounded by incomplete knowledge about the efficiency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these findings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man.

snip...

BSE bovine brain inoculum

100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg

Primate (oral route)* 1/2 (50%)

Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%)

RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)

PrPres biochemical detection

The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the first positive animal (%). The accuracy of bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.

Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula

Published online January 27, 2005

http://www.thelancet.com/journal/journal.isa

It is clear that the designing scientists must

also have shared Mr Bradley’s surprise at the results because all the dose

levels right down to 1 gram triggered infection.

http://web.archive.org/web/20090506002904/http://www.bseinquiry.gov.uk/files/ws/s145d.pdf

6. It also appears to me that Mr Bradley’s answer (that it would take less than say 100

grams) was probably given with the benefit of hindsight; particularly if one

considers that later in the same answer Mr Bradley expresses his surprise that it

could take as little of 1 gram of brain to cause BSE by the oral route within the

same species. This information did not become available until the "attack rate"

experiment had been completed in 1995/96. This was a titration experiment

designed to ascertain the infective dose. A range of dosages was used to ensure

that the actual result was within both a lower and an upper limit within the study

and the designing scientists would not have expected all the dose levels to trigger

infection. The dose ranges chosen by the most informed scientists at that time

ranged from 1 gram to three times one hundred grams. It is clear that the designing

scientists must have also shared Mr Bradley’s surprise at the results because all the

dose levels right down to 1 gram triggered infection.

http://web.archive.org/web/20090506004507/http://www.bseinquiry.gov.uk/files/ws/s147f.pdf

***> cattle, pigs, sheep, cwd, tse, prion, oh my!

***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).

Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/733407/DEFRA_QRA_TSE_in_cervids_June2018_v1.pdf

https://pubmed.ncbi.nlm.nih.gov/16423572/

http://chronic-wasting-disease.blogspot.com/2012/08/susceptibility-of-cattle-to-agent-of.html

DEFRA

Friday, December 14, 2012

DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012

snip.....

In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law. Animals considered at high risk for CWD include:

1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and

2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.

Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.

The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES.

It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.

Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.

There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.

snip.....

36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. snip..... The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).

snip.....

In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion. snip..... In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.

snip.....

Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.

snip.....

https://web.archive.org/web/20170404125557/http://webarchive.nationalarchives.gov.uk/20130822084033/http://www.defra.gov.uk/animal-diseases/files/qra_chronic-wasting-disease-121029.pdf

http://chronic-wasting-disease.blogspot.com/2021/03/

TUESDAY, MAY 31, 2022

USA Bovine Spongiform Encephalopathy BSE: description of typical and atypical cases

https://bovineprp.blogspot.com/2022/05/usa-bovine-spongiform-encephalopathy.html

TUESDAY, SEPTEMBER 13, 2022

BSE pathogenesis in the ileal Peyer’s patches and the central and peripheral nervous system of young cattle 8 months post oral BSE challenge

https://bovineprp.blogspot.com/2022/09/bse-pathogenesis-in-ileal-peyers.html

TUESDAY, SEPTEMBER 07, 2021

Atypical Bovine Spongiform Encephalopathy BSE OIE, FDA 589.2001 FEED REGULATIONS, and Ingestion Therefrom

https://bse-atypical.blogspot.com/2021/09/atypical-bovine-spongiform.html

Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA

https://bovineprp.blogspot.com/2021/10/bovine-spongiform-encephalopathy-bse.html

WEDNESDAY, JANUARY 12, 2022

Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA, what if?

https://bovineprp.blogspot.com/2022/01/bovine-spongiform-encephalopathy-bse.html

PLOS ONE Journal

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;

https://journals.plos.org/plosone/article/comment?id=10.1371/annotation/4f9be886-69fe-4c7c-922b-85b0ecbe6d53

IBNC Tauopathy or TSE Prion disease, it appears, no one is sure

Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT

***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.

***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***

http://www.plosone.org/annotation/listThread.action?root=86610

MONDAY, SEPTEMBER 19, 2022

589.2001 BSE TSE regulations which prohibits the use of high-risk cattle material in feed for all animal species 2022

https://animalhealthreportpriontse.blogspot.com/2022/09/5892001-bse-tse-regulations-which.html

SATURDAY, SEPTEMBER 24, 2022

Transmission of CH1641 in cattle

https://transmissiblespongiformencephalopathy.blogspot.com/2022/09/transmission-of-ch1641-in-cattle.html

FRIDAY, APRIL 1, 2022

USDA TAKES THE C OUT OF COOL, what's up with that?

https://naiscoolyes.blogspot.com/2022/04/usda-takes-c-out-of-cool-whats-up-with.html

MONDAY, JUNE 6, 2022

APHIS USDA History Highlight: APHIS Combats Bovine Spongiform Encephalopathy Published Jun 1, 2022

https://bovineprp.blogspot.com/2022/06/aphis-usda-history-highlight-aphis.html

MONDAY, NOVEMBER 30, 2020

***> REPORT OF THE MEETING OF THE OIE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES Paris, 9–13 September 2019 BSE, TSE, PRION

see updated concerns with atypical BSE from feed and zoonosis...terry

https://animalhealthreportpriontse.blogspot.com/2020/11/report-of-meeting-of-oie-scientific.html

WEDNESDAY, DECEMBER 8, 2021

Importation of Sheep, Goats, and Certain Other Ruminants AGENCY: Animal APHIA, USDA, FINAL RULE [Docket No. APHIS–2009–0095] RIN 0579–AD10

https://animalhealthreportpriontse.blogspot.com/2021/12/importation-of-sheep-goats-and-certain.html

WEDNESDAY, MARCH 24, 2021

USDA Animal and Plant Health Inspection Service 2020 IMPACT REPORT BSE TSE Prion Testing and Surveillance MIA

https://animalhealthreportpriontse.blogspot.com/2021/03/usda-animal-and-plant-health-inspection.html

SUNDAY, MARCH 21, 2021

Investigation Results of Texas Cow That Tested Positive for Bovine Spongiform Encephalopathy (BSE) Aug. 30, 2005 Singeltary's Regiew 2021

https://animalhealthreportpriontse.blogspot.com/2021/03/investigation-results-of-texas-cow-that.html

THURSDAY, AUGUST 20, 2020

Why is USDA "only" BSE TSE Prion testing 25,000 samples a year?

https://animalhealthreportpriontse.blogspot.com/2020/08/why-is-usda-only-bse-tse-prion-testing.html

THURSDAY, JANUARY 23, 2020

USDA Consolidates Regulations for NAHLN Laboratory Testing USDA Animal and Plant Health Inspection Service

sent this bulletin at 01/23/2020 02:15 PM EST

http://madcowusda.blogspot.com/2020/01/usda-consolidates-regulations-for-nahln.html

WEDNESDAY, APRIL 24, 2019

USDA Announces Atypical Bovine Spongiform Encephalopathy Detection Aug 29, 2018 A Review of Science 2019

https://bse-atypical.blogspot.com/2019/04/usda-announces-atypical-bovine.html

Saturday, July 23, 2016

BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016

http://bovineprp.blogspot.com/2016/07/bovine-spongiform-encephalopathy-bse.html

Tuesday, July 26, 2016

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

http://bse-atypical.blogspot.com/2016/07/atypical-bovine-spongiform.html

Monday, June 20, 2016

Specified Risk Materials SRMs BSE TSE Prion Program

http://specifiedriskmaterial.blogspot.com/2016/06/specified-risk-materials-srms-bse-tse.html

*** PLEASE SEE THIS URGENT UPDATE ON CWD AND FEED ANIMAL PROTEIN ***

Sunday, March 20, 2016

Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed ***UPDATED MARCH 2016*** Singeltary Submission

http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM052506.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery

SEE MAD COW FEED VIOLATIONS AFER MAD COW FEED VIOLATIONS ;

http://chronic-wasting-disease.blogspot.com/2016/03/docket-no-fda-2003-d-0432-formerly-03d.html

Tuesday, April 19, 2016

Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission

https://www.regulations.gov/#!documentDetail;D=FDA-2003-D-0432-0011

17 years post mad cow feed ban August 1997

Monday, October 26, 2015

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE October 2015

http://madcowusda.blogspot.com/2015/10/fda-part-589-substances-prohibited-from.html

Tuesday, December 23, 2014

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION

http://madcowusda.blogspot.com/2014/12/fda-part-589-substances-prohibited-from.html

16 years post mad cow feed ban August 1997 2013

Sunday, December 15, 2013

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE

http://madcowusda.blogspot.com/2013/12/fda-part-589-substances-prohibited-from.html

Saturday, August 29, 2009

FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009

http://madcowfeed.blogspot.com/2009/08/foia-request-feed-recall-2009-product.html

Friday, September 4, 2009

FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009

http://madcowfeed.blogspot.com/2009/09/foia-request-on-feed-recall-product.html

Thursday, March 19, 2009

MILLIONS AND MILLIONS OF POUNDS OF MAD COW FEED IN COMMERCE USA WITH ONGOING 12 YEARS OF DENIAL NOW, WHY IN THE WORLD DO WE TO TALK ABOUT THIS ANYMORE $$$

http://madcowfeed.blogspot.com/2009/03/millions-and-millions-of-pounds-of-mad.html

http://madcowusda.blogspot.com/2009/10/cvm-annual-report-fiscal-year-2008.html

MONDAY, FEBRUARY 25, 2019

***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019

https://bseinquiry.blogspot.com/2019/02/mad-dogs-and-englishmen-bse-scrapie-cwd.html

TUESDAY, APRIL 05, 2022

2022 American Academy of Neurology Emerging Sciences Abstract Website Incidence of Creutzfeldt-Jakob Disease in the United States 1993-2014

https://creutzfeldt-jakob-disease.blogspot.com/2022/04/incidence-of-creutzfeldt-jakob-disease_5.html

SATURDAY, OCTOBER 8, 2022

Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation

https://bovineprp.blogspot.com/2022/10/cattle-with-ek211-prnp-polymorphism-are.html

Terry S. Singeltary Sr.

Bovine Spongiform Encephalopathy BSE

Monday, October 10, 2022

Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Scientists Comments December 20, 2005

TERRY S. SINGELTARY SR.
retired

Mr.

No comments:

Post a Comment

Monday, October 10, 2022

Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Scientists Comments December 20, 2005

TERRY S. SINGELTARY SR. retired Mr.

No comments:

Post a Comment

TERRY S. SINGELTARY SR.
retired

Mr.