Real and perceived issues involving animal proteins - C. R. Hamilton

May 3, 2002

FAO CORPORATE DOCUMENT REPOSITORY

Title: PROTEIN SOURCES FOR THE ANIMAL FEED INDUSTRY...

Real and perceived issues involving animal proteins - C. R. Hamilton

C. R. Hamilton
Director Research and Nutritional Services
Darling International Incorporated
U.S.A.

THE RENDERING INDUSTRY

The rendering industry has and continues to be closely integrated with animal and meat production in countries where these industries are well established. On a global perspective, rendering provides an important service to society and the animal feeding industries by processing approximately 60 million tonnes per year of animal by-products derived from the meat and animal production industries. During slaughter and processing, between 33 and 43 percent by weight of the live animal is removed and discarded as inedible waste. These materials, which include fat trim, meat, viscera, bone, blood and feathers are collected and processed by the rendering industry to produce high quality fats and proteins that have traditionally been used in the animal feed and oleochemical industries around the world. Without the rendering industry, the accumulation of unprocessed animal byproducts would impede the meat industries and pose a serious potential hazard to animal and human health.

One definition of rendering is to ‘clarify or purify by melting’ (heat processing). Unprocessed animal by-products may contain 60 percent or more water (Figure 1).

The primary reasons for using heat when processing these raw materials are to remove the moisture and facilitate fat separation. Desiccation significantly reduces the total volume from 60 million tonnes of raw material to about 8 million tonnes of animal proteins and 8.2 million tonnes of rendered fats. Stored properly, these finished products are stable for long periods of time. Heat processing also benefits the finished product customer. The temperatures used (115° to 145° C) are more than sufficient to kill bacteria, viruses and many other micro-organisms, to produce an aseptic protein product that is free of potential biohazards and environmental threats. Done correctly, heat processing also denatures the proteins slightly, which enhances their digestibility.

Figure 1. Raw material composition

Modern efficient rendering facilities are concentrated in countries and regions possessing strong and well-established animal production industries. Renderers in North America process nearly 25 million tonnes of animal byproducts per year, while those in the European Union process about 15 million tonnes. Argentina, Australia, Brazil and New Zealand collectively process another 10 million tonnes of animal byproducts per year. The total value of finished rendered products, worldwide is estimated to be between US$6 and US$8 billion per year.

RENDERED PRODUCTS - NUTRITIONAL VALUE

Animal products include meat and bone meal, blood meal, poultry by-product meal (poultry meal) and feather meal. These are all concentrated sources of protein and amino acids and some are also good sources of vitamins and essential minerals (Table 1).

This makes them important feed ingredients for livestock, poultry and companion animals in the United States and many other countries of the world. Meat and bone meal, blood meal, feather meal and poultry meal are suitable for use in feeds for a wide range of animal species, including fish and shrimp (Table 2).

As shown in Figure 2, more than two million tonnes of meat and bone meal and poultry meal combined are used annually by the United States feed industry alone. Animal proteins have traditionally been important sources of proteins and other nutrients for livestock and poultry in the United States and their acceptance in Latin America and Asia has grown substantially in the past five years. Animal proteins are also used extensively in pet foods. About 1.5 million tonnes of meat and bone meal and poultry meal is used by the United States pet food industry each year. The use of non-marine animal proteins in aquaculture feeds is a relatively new practice, but this application is expected to continue to grow, especially as competition and prices for fishmeal increase.

TABLE 1
Nutrient composition of animal proteins^a

Item	Meat & Bone Meal	Blood Meal^b	Feather Meal	Poultry Meal
Crude protein, %	50.4	88.9	81.0	60.0
Fat, %	10.0	1.0	7.0	13.0
Calcium, %	10.3	0.4	0.3	3.0
Phosphorus, %	5.1	0.3	0.5	1.7
TME_N, kcal/kg	2666^c	3625	3276	3120
Amino Acids
Methionine, %	0.7	0.6	0.6	1.0
Cystine, %	0.7	0.5	4.3	1.0
Lysine, %	2.6	7.1	2.3	3.1
Threonine, %	1.7	3.2	3.8	2.2
Isoleucine, %	1.5	1.0	3.9	2.2
Valine, %	2.4	7.3	5.9	2.9
Tryptophan, %	0.3	1.3	0.6	0.4
Arginine, %	3.3	3.6	5.6	3.9
Histidine, %	1.0	3.5	0.9	1.1
Leucine, %	3.3	10.5	6.9	4.0
Phenylalanine, %	1.8	5.7	3.9	2.3
Tyrosine, %	1.2	2.1	2.5	1.7
Glycine	6.7	4.6	6.1	6.2
Serine	2.2	4.3	8.5	2.7

^a NRC 1994; ^bRing or flash dried; ^c Dale, 1997

TABLE 2
Suitability of animal proteins to supply a portion of the protein in feeds for various animal species

	Meal
Specie	Meat & Bone	Blood	Feather	Poultry
Chickens	Yes	Yes	Yes	Yes
Turkeys	Yes	Yes	Yes	Yes
Cattle	No	Yes	Yes	Yes
Fish^b	Yes	Yes	Yes	Yes
Shrimp^b	Yes	?	Yes	Yes
Dogs^c	Yes	Yes	Yes	Yes

^a Guaranteed to be free of ruminant material. ^b As a partial replacement for fishmeal. ^c Approximately 25 to 40% of the dry matter in premium dog foods are animal by-products.

Some nutritionists underestimate the digestibility and the nutritional value of animal proteins. This misperception dates back many years to when poor processing techniques and equipment were used to render animal by-products. Since that time, new processes, improved equipment and greater understanding of the effects of time, temperature and processing methods on amino acid availability have resulted in significant improvements in the digestibility of animal proteins. Improved understanding as to how best to incorporate them into commercial formulas and improved formulation procedures also increased the nutritional value of animal proteins. Data published since 1984 demonstrate that the digestibility of essential amino acids, especially lysine, threonine, tryptophan and methionine, in meat and bone meal, has improved (Table 3).

BIOSECURITY AND FINISHED PRODUCT SAFETY

Biosecurity of food and food related products is largely perception based on trust and education. Food and feed are derived directly or indirectly from biological organisms. Natural variation, the environment, storage conditions, usage and the potential interaction with other biological organisms (such as micro-organisms) make it impractical to guarantee food safety in absolute terms. Despite the best efforts on the part of companies, farmers, regulatory agencies, politicians and others involved in the food chain, all of the potential risks cannot be alleviated 100 percent of the time. Therefore, it is necessary to manage these risks using sound scientific principles and facts. In some recent crisis situations, politics, fear and supposition have replaced logic and science in risk management decisions.

Figure 2. Animal protein usage by the United States' feed industry

TABLE 3
Digestibility of meat and bone meal since 1984

Amino Acid	1984^a	1989^b	1990^c	1992^d	1995^e	2001^f
Lysine, %	65	70	78	84	94	92
Threonine, %	62	64	72	83	92	89
Tryptophan, %	---	54	65	83	---	86
Methionine, %	82	---	86	85	96	92
Cystine, %	---	---	---	81	77	76

^a Jorgensen et al., 1984; ^b Knabe et al., 1996; ^c Batterham et al., 1990.^d Firman, 1992;^eParsons et al., 1997;^f Pearl, 2001b

During the past decade, a number of safety-related challenges have daunted the rendering industry. These challenges resulted from perceived rather than proven risks. Public and political perceptions were influenced by media sensationalism, a general movement of society away from its agrarian roots, lack of scientific knowledge concerning bovine spongiform encephalopathy (BSE) and other hazards, inadequate analytical procedures for routine detection of potential hazards such as dioxins, public expectations that government and industry assure a safe food supply, opportunistic marketing strategies and the political agendas of activist organizations. The Precautionary Principle adopted by the European Union has served to catalyze these perceptions because in its development and enforcement, perceived risks and political image frequently overruled science.

The World rendering industry recognizes its role in assuring food safety and in protecting human and animal health. The rendering process is an effective method for ensuring biosecurity because processing conditions and volumes, raw material characteristics and drying create an unfavorable environment for viruses, bacteria and other micro-organisms to survive and grow. Rendering is the most logical method for collecting and processing animal by-products because it possesses the infrastructure to safely and responsibly recycle these products, allow traceability and produce safe finished products.

The rendering industry is closely regulated by the appropriate agencies within the resident region, country or province. In the United States, State and Federal agencies each routinely inspect rendering facilities for compliance to applicable regulations and finished product safety tolerances. Rendering facilities are inspected by the United States Food and Drug Administration (FDA) for compliance to BSE related regulations. State Feed Control Officials inspect and test finished products as they enforce quality, adulteration and feed safety policies.

Rendering industry organizations provide technical support and education in quality assurance and feed safety. Using United States based organizations as examples, the Animal Protein Producers Industry (APPI) administers industry-wide programmes for biosecurity, pathogen reduction, continuing education and third-party certification for compliance to BSE related regulations. The Fats and Proteins Research Foundation (FPRF) solicits and funds industry and university research to address pertinent biosecurity and nutrient value issues.

Three primary food safety issues dominate discussions about the safety of feeding animal proteins to animals. These are Salmonella contamination (bacterial pathogens), BSE and dioxins. Each of these issues present legitimate concerns and all are known to threaten animal and human health. However, in each case, the risk of spreading these risks through finished rendered products is largely perceived rather than factual. The value of the rendering process as a mechanism to control risks of microbial pathogens as well as other hazards (with the possible exception of the agent causing BSE) is illustrated in Table 4, which is based on a report from the United Kingdom Department of Health (2001).

Salmonella

Salmonella are destroyed by heat when exposed to temperatures of 55° C for one hour or 60° C for 15 to 20 minutes (Franco, 1993). Processing temperatures of between 115° C and 145° C are used to render animal by-products. These temperatures are more than sufficient to kill Salmonella and other pathogenic bacteria present in raw animal by-products (Tables 4 and 5). However, Salmonella are opportunistic organisms and may re-contaminate products after cooking or processing and during storage, transport and handling. Post process contamination is of concern for all feed ingredients and not restricted only to animal proteins. Despite this fact, animal proteins continue to be more closely scrutinized for Salmonella contamination than other feed ingredients.

Davies and Funk (1999) completed an extensive review of Salmonella epidemiology and control. They summarized that while feeds of animal origin receive the most attention as sources of Salmonella, it is now recognized that feeds of plant origin, such as soybean meal, are often contaminated with Salmonella. Data showing the incidence of Salmonella contamination in various feed ingredients in North America, Europe and the United Kingdom are shown in Table 6. These data suggest that all feed ingredients may be contaminated with Salmonella. Brooks (1989) demonstrated that the relative risk of Salmonella contamination in complete feed is less for animal proteins than for soybean meal, fishmeal and grain. Even if the Salmonella prevalence in animal proteins is equal to or exceeds that of other ingredients, animal proteins pose two- to threefold less risk of contaminating complete feed, because animal proteins typically have much lower (2 to 5 percent) inclusion rates than other ingredients (Table 7).

More than 2 200 different serotypes of Salmonella have been identified and only a few of these cause disease in humans or animals. Almost all of the Salmonella serotypes that have been identified in animal proteins are innocuous and do not cause disease (Davies and Funk, 1999). Furthermore, dried animal proteins do not provide a favorable environment for Salmonella organisms to proliferate, primarily because the water activity is too low. Figure 3 illustrates this point. Salmonella choleraesuis (a human pathogen) remained viable in meat and bone meal for less than two days after inoculation. In order to limit Salmonella (or other pathogenic organisms) in meat and other animal products, it is necessary to control the most important sources of contamination first. Feed is not the most important contributor to Salmonella contamination of these products. Data collected from commercial swine production facilities in the United States suggest that employees, cats, rodents, insects and environmental factors are much more important Salmonella reservoirs than feed (Table 8). Drinking water had more than a five-fold greater incidence of Salmonella than feed.

TABLE 4
Summary of potential health risks for various methods of handling animal by-products

Disease/Hazardous Agent	Exposure of humans to hazards from each handling method
Disease/Hazardous Agent	Rendering	Incineration	Landfill	Pyre	Burial
Campylobacter, E. coli, Listeria, Salmonella, Bacillus anthacis, C. botulinum, Leptospira, Mycobacterium tuberculosis var bovis, Yersinia	Low	Low	Some	Low	High
Cryptosporidium, Giardia	Low	Low	Some	Low	High
Clostridium tetani	Low	Low	Some	Low	High
Prions for BSE, Scrapie	Some	Low	Some	Some	High
Methane, CO₂	Low	Low	Some	Low	High
Fuel-specific chemicals, Metal salts	Low	Low	Low	High	Low
Particulates, SO₂, NO_2,nitrous particles	Low	Some	Low	High	Low
PAHs, dioxins	Low	Some	Low	High	Low
Disinfectants, detergents	Low	Low	Some	Some	High
Hydrogen sulfide	Low	Low	Some	Low	High
Radiation	Low	Some	Low	Some	Some

^a Adapted from United Kingdom Department of Health, 2001.

TABLE 5
Efficacy of the United States’ rendering system in the destruction of pathogenic bacteria

Pathogen	Raw Tissue^b	Post Process^b
Clostridium perfringens	71.4 %	0 %
Listeria species	76.2 %	0 %
L. monocytogenes	8.3 %	0 %
Campylobacter species	29.8 %	0 %
C. jejuni	20.0 %	0 %
Salmonella species	84.5 %	0 %

^a Trout et al., 2001. Samples from 17 different rendering facilities taken during the winter and summer. ^b Percent of the number of samples found to be positive for pathogens out of the total samples collected.

TABLE 6
Incidence of Salmonella in feed ingredients

Ingredient	Item	Country
Ingredient	Item	Netherlands^a	Germany^b	USA^c	Canada^d	United Kingdom^e
Animal	Samples	2026	17	101	Not reported	120
Proteins	% Positive	6	6	56	20	3
Vegetable	Samples	1298	196	50	Not reported	2002
Proteins	% Positive	3	26	36	18	7
Grains	Samples		37		Not reported	1026
Grains	% Positive		3		5	1
Fish Meal	Samples				Not reported	1316
Fish Meal	% Positive				22	22

^a Beumer and Van der Poel, 1997; ^b Sreenivas, 1998; ^c McChesney et al., 1995; ^d Canadian Food Inspection Agency, 1999;^e Brooks, 1989

TABLE 7
Relative risk of Salmonella contamination in complete feed^a

Ingredient	Salmonella
Ingredient	Amount in formula (%)	Incidence (%)(+)	Risk Factor
Grain	66.9	0.9	0.602
Soybean meal	24.9	2.7	0.672
Fishmeal	2.2	13.2	0.290
Meat Meal	3.0	3.0	0.09
Fat	----	----	----
Vitamin mineral mix	----	----	----

^a Brooks, 1989

Figure3. Salmonella choleraesius viability in mammalian bone meal (MBM)^a(7 to 25 percent moisture) and stored at 28.8^OC. ^aSutton et al. 1992

TABLE 8
Reservoirs of Salmonella contamination on Illinois swine farms.^a

Reservoir	Number samples	Percent positive
Employee footwear	93	17.2 %
Cats	22	13.6 %
Drinking water	33	12.1 %
Mice/rodents	59	10.2 %
Floor material	471	7.9 %
Flies	95	7.4 %
Feed	100	2.0 %

^a Weigel et al. 1999.

These data all clearly demonstrate that animal proteins should not be the primary focus of concern in feeding programs designed to reduce the incidence of Salmonella. Why then, is Salmonella in feed ingredients, especially animal proteins, scrutinized so closely? - Because of perception - not fact. Requiring all animal proteins, or even all feed ingredients, to be Salmonella free has little impact on overall food safety without controlling the more important sources of contamination. Salmonella reduction/prevention is a farm - to - plate issue affecting all segments of the feed manufacturing, animal production, meat processing and retail meats industries.

Bovine spongiform encephalopathy (BSE)

What is BSE (‘Mad Cow Disease’)? ’Mad Cow Disease’ is an inaccurate term used to describe Bovine Spongiform Encephalopathy (BSE), because cows do not appear ’mad’ or ’crazy’ when they have the disease. This was a term coined by the news media in order to gain public attention and sensationalize the story. BSE is a more appropriate and accurate term to use when the disease is discussed. BSE is one of several related diseases that affect a number of different animal species and humans. These diseases are collectively called transmissible spongiform encephalopathies (TSEs).

BSE is a chronic degenerative disease that affects the central nervous system of cattle. The only positive cases detected outside of the United Kingdom and Mainland Europe were reported in Japan in late 2001. The incubation period is thought to be between two and eight years and it has been associated with a new form of Creutzfeldt-Jakob Disease (CJD) in humans. CJD has been recognized for many years as a sporadic disease that affects about 1 person per million. New variant Creutzfeldt-Jakob Disease (_vCJD) differs in etiology and it affects people at a younger age.

Fortunately, BSE is not easily passed from animal to animal, so it is not a contagious disease. It also affects specific tissues in cattle and is confined primarily to the brain, spinal cord and a few other tissues. Muscle and fat do not appear to be affected by the disease and are considered to be safe.

Why is BSE a growing concern? BSE is a complex disease that is poorly understood, even by the scientists who have worked in the field for many years. At least six different theories are used to explain its cause and transmission. A complete understanding of the disease is hampered by the long incubation period (up to 8 years for cattle). As a result, reporters, activists and some scientists and government officials consider theories and assumptions as fact. This combined with innuendo and the sensationalism associated with a possible link between BSE and human disease has created undue concern and panic among consumers. BSE is also compatible with the anti-meat and organic food agendas of certain activist groups in the United States and in Europe. These groups are organized and well funded and have developed focused media campaigns in order to advance their causes.

No single theory has been proven to explain the cause of BSE and/or _vCJD. Each theory can be supported by circumstantial, experimental or epidemiological evidence. However, until more is understood about the disease, theories will continue to be used to explain the cause. It is clear that abnormal prion proteins are involved in the disease. However, their role is not completely clear, so it is difficult to determine whether prion proteins cause disease or are an effect produced by some unidentified infectious agent or toxin.

Recognize regional differences. Efficient control and surveillance systems around the world make it possible to successfully manage the BSE issue. In general, BSE remains a regional disease and is largely confined to the United Kingdom and Mainland Europe. In the case of Japan, the cattle found to be positive for BSE were assumed to have contracted the disease through eating meat and bone meal that was exported from the United Kingdom or Mainland Europe where BSE had previously occurred. Therefore, animal proteins from the different countries where BSE has not existed represent a different risk than countries having the disease. The North American countries have implemented good BSE prevention efforts. Even though other transmissible spongiform encephalopathies (TSE), such as Scrapie in sheep and chronic wasting disease (CWD) in deer and elk exists in these countries, these diseases have been shown to differ in their etiology from BSE. Australia and New Zealand are free of these diseases.

Situation in the United States. The United States differs from Europe. A number of differences between the United States and Europe, in terms of livestock feeding and rearing practices, livestock demographics and governmental programmes, exist with respect to BSE risk assessment.

Sheep and cattle numbers in the United Kingdom are more concentrated than in the United States (Table 9). The United Kingdom is roughly the size of the State of Oregon and it has about four times more sheep than the entire United States. In addition to a dense sheep population, the United Kingdom also has more than 11 million cattle. As a result, there are almost 3 sheep for each bovine in the United Kingdom and 12 bovines for every sheep in the United States. The United Kingdom and the rest of the European Union have similar livestock demographics.

TABLE 9
Cattle and sheep demographics of United Kingdom, European Union and United States

Category	United Kingdom	United States	European Union
Cattle and calves (million head)	11.2	99.7	82.7
Cattle slaughter (million head)	2.3	35.6	27.9
All sheep (million head)	31.0	7.8	98.6
Sheep slaughter (million head)	18.7	3.9	78.3
Cattle to sheep ratio	1:2.8	12:1	1:1.2

Because vegetable protein sources are not as readily available in Europe as they are in the United States, ingredients used to provide supplemental protein in animal feeds have differed for many years. Compared to the United States, rendered animal proteins have historically been used at much higher concentrations in animal feeds in Europe. Further, animal proteins in Europe were commonly added to veal calf feeds and fed to cattle as young as two days old. Most United States’ beef production is concentrated in commercial feedlots where cattle are fed low forage rations consisting primarily of soy and corn. However, few feedlots exist in Europe and cattle are fed primarily on grass with protein supplements. Thus, the beef industry in Europe consists primarily of veal meat and older beef. Because, sheep are the most common ruminant animal in Europe, rendered animal proteins contained a higher proportion of sheep material than in the United States. Assuming that all rendered sheep protein was fed to dairy cows, those in the United Kingdom would consume 1.54 kg of sheep derived protein per day compared to only 79 grams in the United States. This comparison is even more dramatic because the US renderers voluntarily stopped processing sheep material prior to 1995.

Some scientists believe that BSE originated from Scrapie, a TSE that has been known to affect sheep for more than 300 years. Given the differences in sheep concentration and production statistics between the United States and Europe, the risk of BSE occurring in the United States is markedly lower than in Europe. When differences in feeding practices are also considered, the level of risk is further decreased.

The ’Triple Firewall’ strategy. The United States developed a series of ’firewalls’ to prevent BSE from occurring within its borders. The United States’ risk analysis approach was very different from that used in Europe, primarily because United States’ officials recognized from the beginning that zero risk was not attainable. The United States programme is a progressive and continuously evolving one designed to proactively prevent the introduction of BSE (import restrictions), prevent amplification, should the disease ever be introduced into the United States (ruminant feed ban) and implement an aggressive targeted detection system (surveillance). All steps were based on science and have been the result of joint efforts among governmental agencies and all segments of the beef, dairy, feed and rendering industries (Table 10).

Brain tissue from more than 22 900 cattle were tested and found to be negative for BSE between 1990 and February of 2002. This programme has primarily focused on the segment of the cattle population that represents the greatest risk for BSE. As scientists in Europe have learned more about the cattle most likely to test positive for the disease, surveillance in the United States has been adjusted accordingly. The most recent modification to include ’downer cows’ resulted in a substantial increase in sample submissions. Target sample numbers for the year 2002 are double the targets for the preceding year.

The record keeping requirements that rendering companies and the feed industry are required to comply with also require a high degree of traceability for animal proteins. Regulated by the FDA, it is possible to trace finished proteins and fats from collection to use.

Actions by the US rendering industry. The United States’ rendering industry fully supports BSE prevention programmes and efforts developed by the United States’ FDA, Animal and Plant Health Inspection Service (APHIS) and other federal and state governmental agencies. The rendering industry is committed to achieving 100 percent compliance to the FDA ban (No. 21 CFR 589.2000) which prohibits the feeding of mammalian proteins (with some specified exemptions) to cattle and other ruminant animals.

The rendering industry has been actively involved in programmes to prevent BSE in the United States since before 1995, when renderers voluntarily stopped rendering sheep material. This was to prevent any scrapie-infected material from entering the food chain, especially through feed for ruminant animals.

When the FDA first considered preventative measures in 1996, renderers and cattle producers voluntarily stopped using meat and bone meal derived from ruminant animals in cattle feed. This later became official when the FDA published the rule prohibiting the use of these materials in feeds intended for cattle and other ruminant animals. The rendering industry was actively involved in preparing this rule and fully supported it from its introduction in 1997. The only meat and bone meal permitted for use in ruminant animal feed in the United States is material that comes from processing plants that slaughter or process only non-ruminant animals. material is prohibited from use in feeds for cattle and other ruminant animals.

TABLE 10
Summary of United States BSE prevention efforts

Year	Prevention Programme
1985	Imports of British Beef halted
1986	BSE made a legally reportable disease
1989	Ruminant animals from countries with BSE banned
1990	BSE surveillance program initiated
1990	Veterinarian education efforts about BSE increased
1991	Risk assessment conducted (an on-going process)
1993	Surveillance programme expanded
1996	Voluntary ban on use of ruminant derived proteins in cattle feed initiated
1997	FDA ban on use of ruminant derived proteins in feed for cattle and other ruminants
1997	European ruminant animals and products banned
1998	Scrapie eradication program published
1999	Surveillance programme expanded to include “downer cows”
2000	All animal proteins from European Union banned
2001	Harvard Risk Assessment Study to be completed
2001	Risk potential and preventative measures reassessed - on-going process

If the raw material cannot be verified to be of 100 percent non-ruminant origin, then the resulting finished. While hazard analysis critical control point (HACCP) programmes target known hazards that can be eliminated or controlled through the rendering process, they also include in-plant enforcement of policies that apply to the acceptance or rejection of raw material. This provides further assurance that material from suspect cattle (such as those being tested for BSE through the APHIS surveillance programme), sheep, goats and other animals susceptible to TSEs are not received and processed.

The FDA feed ban includes requirements that finished products are clearly labeled and records of raw material receipts and finished product sales be kept and made available for inspection by the FDA. This allows the FDA to verify the source of raw materials and verify compliance to the feed ban among feed manufacturers, dealers, distributors and end users. For renderers who process proteins exempted under the feed ban, safeguards to prevent cross-contamination must be demonstrated in practice and in writing.

The American Protein Producers Industry (APPI) recently introduced a certification programme for rendering companies, to verify compliance to the feed ban, based on inspections by third-party auditors. The goal is to have 100 percent participation among all rendering companies in the United States and 100 percent compliance to the feed ban. This program does not replace FDA inspections, although results are available for FDA review. The American Feed Ingredient Association (AFIA) developed a similar programme for commercial feed manufacturers. The American Meat Industry (AMI) has also developed a programme for cattle producers to certify that the cattle they are offering for slaughter have been fed in accordance with FDA regulations.

Harvard Risk Analysis. The United States Department of Agriculture commissioned the Harvard Center for Risk Analysis at the Harvard University School of Medicine to evaluate the potential for BSE to occur in the United States. The ’Harvard Risk Analysis’ was made public in November 2001 (Cohen et al., 2001). The study concluded that the United States is highly resistant to any introduction of BSE or similar disease. Further, BSE is extremely unlikely to become established in this country because measures taken by agencies of the United States’ government were and continue to be effective at reducing the spread of BSE. The feed ban introduced by the FDA in 1997 to prevent amplification of the disease should it ever occur in the United States, was considered to be one of the most important safeguards. The full report is available on the USDA web site located at http://www.aphis.usda.gov/oa/bse/.

Species that animal proteins are derived from differ in risk. Specie and type of tissue used to produce animal protein affects the risk from BSE. Neither pork nor poultry derived proteins have been implicated as potential sources of the BSE agent. Europe is in the process of classifying its animal by-products in case its total ban on feeding animal proteins is lifted. Materials derived from non-ruminant animals approved for human consumption may eventually be available for use in animal feeds. Other countries are not presently classifying animal by-products, although some additional actions may occur in the United States as the various regulatory agencies work to further strengthen BSE prevention efforts, even though additional regulations are not scientifically warranted.

A number of governmental agencies around the world are working to develop testing methodologies to assist them in identifying the type of material from which animal proteins were derived. For example, it is possible to identify species-specific DNA using polymerase chain reaction (PCR). Species-specific DNA can be identified even if the DNA is partially degraded. It is also possible to differentiate skeletal muscle in protein meals, using ELISA. Detection limits and validation procedures are being completed for these technologies. As these issues are resolved, acceptable thresholds will be established by the appropriate regulatory agencies. At present the unit sample cost is projected to be moderately high. However, as the technology is adopted, the costs are expected to decrease.

Acceptable testing methodologies to identify restricted use proteins in feed for cattle and other ruminant animals will make it simpler to verify compliance to feed bans and restrictions. These regulatory tools will make it possible to validate that animal proteins are used safely in feeds, even in countries known to have BSE present. The greatest challenge will be in establishing uniform threshold limits for the presence of prohibited materials in these feeds.

Transmission studies. The majority of experiments designed to study transmission of BSE and other TSEs among animals of the same species or from specie to specie, used the intra-cranial route to introduce raw nervous tissue directly into the brain of the test animals. Oral transmission is assumed to be much less effective because intestinal absorption followed by transport and concentration of the infectious agent in the target tissues must occur. Therefore, oral exposure (i.e. via contaminated feed) is generally assumed to be one hundred thousand-fold less effective than direct exposure by the intra-cranial route (Schreuder et al., 1998). Given the potential losses that may occur via oral exposure, a large number of infectious units must be consumed in order for the disease to develop. For humans, the oral infectious dose (ID₅₀) is estimated to be 10¹³ BSE prion molecules, which is a very large dose compared to known bacterial and viral pathogens (Gunn, 2001). While heat processing does not destroy the infectious agent, processing at 134° C for 3 minutes caused a 2.5 log reduction in infectivity (Schreuder et al., 1998). Therefore, the risk of spreading BSE by feeding fully processed animal proteins is extremely low.

Pearl (2001a) summarized several oral challenge studies that are in progress in the United States and in the United Kingdom. Because BSE has not been found in the United States, BSE challenge studies can only be conducted in Europe. Scientists in the United States use scrapie and CWD infected material in their challenge studies.

Chickens orally challenged with BSE. A 57- month study to determine the susceptibility of chickens to BSE was conducted in the United Kingdom. Chickens were challenged with BSE infected brain tissue by intra-cranial, intra-peritoneal and oral (esophageal tube) routes. No infectivity was found in any of the chicken tissue assayed upon completion of the study, regardless of the route used to introduce infective material. These results suggest that BSE is not transmitted to chickens.

Cattle orally challenged with Scrapie. An 8-year study conducted in the United States determined the effects of orally or intra-cranially challenging 34 calves with rendered proteins and fats from scrapie infected sheep. There was no evidence of oral transmission at any time during the course of the study. A second experiment, also in the United States, orally challenged 17 calves with rendered scrapie positive brain tissue from sheep. All animals were negative for BSE (and scrapie) after 8 years. However, 9 calves challenged with intra-cerebral inoculations were positive for a scrapie-like infection.

Cattle orally challenged with chronic wasting disease. A total of 26 calves were inoculated (oral or intra-cranial) with brain tissue from CWD infected mule deer in 1997. Three calves from each challenge group (oral or intra-cranial) were sacrificed in 1999 and found to be negative for disease. The remaining animals are still alive and all appear healthy.

HAZARD ANALYSIS CRITICAL CONTROL POINT

Rendering companies in the United States, Europe and other countries have adopted HACCP programmes as an important component of their biosecurity and food safety programmes. HACCP programmes require an evaluation of the entire rendering process, identification of potential hazards (such as Salmonella), identification of critical points in the process where the hazard(s) can be controlled and development of procedures to control these processes and ensure destruction or removal of the hazard. Additional controls may also be included at various points in the process to assure quality (QA) of the finished product(s). A generalized HACCP - QA programme for a typical rendering facility is shown in Figure 4. It is anticipated that the FDA will require that the US rendering industry use HACCP programmes within the next two years.

Dioxins

Concern with dioxin increased because of a clearly criminal act that occurred in Belgium. Prior to this event, most rendering companies developed and implemented sampling and testing protocols to ensure that finished fat and animal proteins were not contaminated with potentially hazardous compounds, such as pesticides and PCB’s. The rendering process does not produce dioxins, as shown in Table 4. Because of the extremely expensive nature of analyzing production samples for dioxins, testing protocols test for PCB’s which are recognized by regulatory agencies all over the world as indicators of dioxins.

Figure 4. Basic production flow-chart with HACCP and quality control points

Dioxins can enter rendered products by one of two methods: (1) the most likely is by accidental or intentional contamination and (2) the presence of dioxins in animal tissues. Maximum tolerances for PCB’s already exist. The European Union and the United States FDA are both considering adoption of maximum tolerance levels for all dioxins. As sensitive and inexpensive analytical procedures to test for dioxin in the parts per trillion range are developed, rendering companies will readily adopt the technology to ensure that finished rendered products are safe from dioxins.

SUMMARY

Animal proteins are an important class of ingredients for animal nutritionists to use in feed formulas. The United States’ rendering industry produces nutrient rich products that are highly digestible, do not contain anti-growth factors and are safe to use in livestock, poultry, pet and aquaculture feeds.

The rendering process kills Salmonella and other food pathogens, although post process contamination can still occur. All feed ingredients may be contaminated with Salmonella.

However, reservoirs of Salmonella present in animal production facilities are a much greater hazard to food safety than feed ingredients. Until these sources of contamination are controlled, little benefit to controlling Salmonella prevalence in feed ingredients will be realized.

Bovine spongiform encephalopathy continues to be surrounded by myth and misperceptions. If feed-contaminated animal proteins spread this disease, countries that have never reported an incidence of BSE represent a much lower risk than those where the disease has occurred. BSE has never been reported in the United States, despite the presence of a progressive surveillance programme that began in 1990. The United States complimented surveillance with import bans and restrictions to prevent introduction of BSE into the United States. In the event that BSE was ever found in the United States, the FDA preemptively instituted a ban on the feeding of meat and bone meal from ruminant animals to cattle and other ruminants to prevent amplification and spread of the disease. Additionally, the rendering industry voluntarily stopped processing sheep and goat material and recently introduced an industry wide programme to verify compliance with the FDA feed ban using third-party auditors.

Differences between the United States and Europe in livestock demographics, feeding practices and governmental policies pertaining to BSE make the occurrence of BSE in the United States unlikely. Oral transmission via infected feed has not been proven and would require exposure to an extraordinarily large number of infectious molecules. The sum of all of these efforts and statistics make it highly unlikely that BSE will occur in the United States. To date, BSE remains a European phenomenon, with 99 percent of all cases in the world occurring in the United Kingdom.

Based on current accepted theories, the specific tissues and animal specie from which the tissues were derived as well as the country or regions of the world all interact to influence the risk of BSE. As methodologies are developed that allow identification of the specie and type of tissue that animal proteins are derived from, it will be much simpler for governments to regulate the feeding of animal proteins.

The World Rendering Industry supports programmes to prevent and control BSE. The US Rendering Industry fully complies with the United States Food and Drug Administration’s ban on feeding certain mammalian animal proteins to cattle and other ruminants. Rendering companies also support industry programmes developed to certify compliance with this rule and participate in the APPI compliance certification programme, using third-party auditors.

REFERENCES

Batterham, E. S., et al. 1990. British Journal of Nutrition, 64: 679.

Beumer, H. & Van der Poel, A. F. B. 1997. Feedstuffs, Dec. 29.

Brooks, P. 1989. Technical Service Publication, National Renderers Association, Inc. Canadian Food Inspection Agency, 1999.

Cohen, et al. 2001. Report from the Harvard Center for Risk Analysis, Harvard School of Public Health.

Dale, N. 1997. Journal of Applied Poultry Research, 6: 169.

Davies, P. R. & Funk, J. A. 1999. Proc. 3^rd International Symposium on the Epidemiology and Control of Salmonella in Pork, August 5-7. p. 1-11.

Firman, J. D. 1992. Journal of Applied Poultry Research, 1: 350.

Franco, D. A. 1993. Proceedings of the 54^th Minnesota Nutrition Conference. p. 21-35.

Gunn, M. 2001. Irish Vetinerary Record, 54(4): 192.

Jorgensen, H., Sauer, W. C. &. Thacker, P. A. 1984. Journal of Animal Science, 58: 926.

Knabe, D. A. 1996. In: The Original Recyclers. p. 176-202. APPI, FPRF and NRA.

McChesney, D. G., Kaplan G. & Gardner, P. 1995. Feedstuffs, Feb. 13. p. 20 & 23.

NRC. 1994. Nutrient Requirements of Poultry (9^th Rev. Ed.). Washington D. C, National Academy Press.

Parsons, C. M., Castanon, F. & Han, Y. 1997. Poultry Science, 76: 361.

Pearl, G. G. 2001a. Directors Digest # 308. Fats and Proteins Research Foundation.

Pearl, G. G. 2001b. Proceedings Mid-West Swine Nutrition Conference. Sept. 5. Indianapolis, IN, USA.

Schreuder, B. E. C., et al. 1998. Veterinary Record, 142: 474.

Sreenivas., P. T. 1998. Feed Mixing, 6(5): 8.

Sutton, A. L., Scheidt, A. B. & Patterson, J. A. 1992. Final Research Report. Fats and Protein Research Foundation.

Trout, H. F., Schaeffer, D., Kakoma, I. & Pearl, G. 2001. Directors Digest #312. Fats and Proteins Research Foundation.

United Kingdom Department of Health. 2001. A rapid qualitative assessment of possible risks to public health from current foot and mouth disposal options - Main Report. June.

Weigel, R., Barber, D., Isaacson, R. E., Bahnson P. B.& Jones, C. J. 1999. Proceedings 3^rd International Symposium on the Epidemiology and Control of Salmonella in Pork. August 5-7 p. 180-183.

http://www.fao.org/docrep/007/y5019e/y5019e0g.htm

ftp://ftp.fao.org/docrep/fao/007/y5019e/y5019e00.pdf

Real and perceived issues involving animal proteins C. R. Hamilton May 3, 2002, a review of USDA MAD COW DISEASE BSE FEED

FIRST, please see the drastic decrease of mad cow disease in the UK after the mad cow feed ban went into force ;

SUMMARY OF PASSIVE SURVEILLANCE REPORTS IN GREAT BRITAIN

PASSIVE SURVEILLANCE

SUSPECTS RESTRICTIONS LIFTED DUE TO ALTERNATIVE SLAUGHTER NOT YET SUSPECTS KNOWN TO HAVE BEEN SLAUGHTERED SUSPECTS WITH OUTCOME SLAUGHTERED SUSPECTS IN WHICH BSE NOT SLAUGHTERED SUSPECTS IN WHICH BSE PRIVATE SUBMISSIONS IN WHICH

YEAR RESTRICTED DIAGNOSIS NOTIFIED SLAUGHTERED PENDING CONFIRMED CONFIRMED BSE CONFIRMED

Pre 18.07.88 1142 1 0 980 0 414 727 0

1988 2512 140 0 2372 0 192 2180 4

1989 8443 386 0 8057 0 924 7133 4

1990 17323 682 0 16641 0 2460 14181 0

1991 30003 982 0 29021 0 3995 25026 6

1992 44844 1690 0 43154 0 6474 36680 2

1993 42931 1847 0 41084 0 6714 34370 0

1994 30259 1551 0 28708 0 4765 23943 2

1995 17945 789 0 17156 0 2855 14301 1

1996 10697 547 0 10150 0 2137 8013 3

1997 5604 302 0 5302 0 992 4310 3

1998 4291 260 0 4031 0 852 3179 1

1999 2984 146 0 2838 0 582 2256 2

2000 1870 117 0 1753 0 442 1311 0

2001 1218 66 0 1152 0 371 781 0

2002 877 68 0 809 0 364 445 0

2003 456 43 0 413 0 240 173 0

2004 351 41 0 310 0 228 82 0

2005 186 30 0 156 0 117 39 0

2006 144 26 0 118 0 103 15 0

2007 69 11 0 58 0 51 7 0

2008 39 7 0 32 0 30 2 0

2009 22 7 0 15 0 14 1 0

2010 19 7 0 12 0 12 0 0

2011 11 2 0 9 0 9 0 0

2012 5 2 0 3 0 3 0 0

2013 2 0 0 2 0 2 0 0

2014 2 0 0 2 0 2 0 0

2015 0 0 0 0 0 0 0 0

2016 0 0 0 0 0 0 0 0

Total 223107 9749 0 213358 0 34930 178428 28

Data valid to 31 January 2016

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/499418/pub-tse-stats-gboverview.pdf

SECOND, what has MAFF...now DEFRA, what have they said about the mad cow feed ban in the USA in 2012?

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...

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

THIRD, THE USDA FDA TRIPLE MAD COW DISEASE FIREWALL, WAS NOTHING MORE THAN INK ON PAPER !

now, let’s just for a moment put away the corporate junk science, and let’s look at recent updated BSE, CWD, Scrapie, TSE Prion sound science, could not hurt...

Saturday, January 31, 2015

European red deer (Cervus elaphus elaphus) are susceptible to Bovine Spongiform Encephalopathy BSE by Oral Alimentary route

http://transmissiblespongiformencephalopathy.blogspot.com/2015/01/european-red-deer-cervus-elaphus.html

I strenuously once again urge the FDA and its industry constituents, to make it MANDATORY that all ruminant feed be banned to all ruminants, and this should include all cervids as soon as possible for the following reasons...

======

In the USA, under the Food and Drug Administrations 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.

======

31 Jan 2015 at 20:14 GMT

*** Ruminant feed ban for cervids in the United States? ***

31 Jan 2015 at 20:14 GMT

see Singeltary comment ;

http://www.plosone.org/annotation/listThread.action?root=85351

Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus )

These results indicate that CWD PrP res can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.

snip...

These results indicate that mule deer fawns develop detectable PrP res after oral exposure to an inoculum containing CWD prions. In the earliest post-exposure period, CWD PrPres was traced to the lymphoid tissues draining the oral and intestinal mucosa (i.e. the retropharyngeal lymph nodes, tonsil, ileal Peyer's patches and ileocaecal lymph nodes), which probably received the highest initial exposure to the inoculum. Hadlow et al. (1982) demonstrated scrapie agent in the tonsil, retropharyngeal and mesenteric lymph nodes, ileum and spleen in a 10-month-old naturally infected lamb by mouse bioassay. Eight of nine sheep had infectivity in the retropharyngeal lymph node. He concluded that the tissue distribution suggested primary infection via the gastrointestinal tract. The tissue distribution of PrPres in the early stages of infection in the fawns is strikingly similar to that seen in naturally infected sheep with scrapie. These findings support oral exposure as a natural route of CWD infection in deer and support oral inoculation as a reasonable exposure route for experimental studies of CWD.

snip...

http://vir.sgmjournals.org/cgi/content/full/80/10/2757

Title: Experimental oral transmission of chronic wasting disease (CWD) to red deer (Cervus elaphus elaphus): early detection and late stage distribution of protease-resistant protein (PrP-res)

In this study, red deer (Cervus elaphus elaphus) were exposed to the prion agent by oral administration of brain homogenates from infected Rocky Mountain elk. Antemortem testing was performed at 7 months post infection and the deer were euthanized when clinical disease was observed at approximately 18 months after infection. The abnormal prion protein was assayed by immunohistochemistry, enzyme linked immunosorbent assay and western blot. Abnormal prion protein was found in the spinal cord, brainstem, cerebellum, midbrain, thalamus, and cerebrum in all 4 infected red deer. Most of the lymph nodes throughout the body were positive for abnormal prion proteins. Abnromal prion protein was observed in some additional peripheral tissues in some but not all of the deer. In particular, most areas of the gastrointestinal tract were positive for abnormal prions, although the salivary glands were rarely positive. This study demonstrates the potential for oral transmission of chronic wasting disease to red deer and confirms the usefulness of the current testing methods for post mortem diagnosis of the disease in this species.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=228787

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

http://www.plosone.org/annotation/listThread.action;jsessionid=635CE9094E0EA15D5362B7D7B809448C?root=7143

*** It also suggests a similar cause or source for atypical BSE in these countries. ***

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.

*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

*** It also suggests a similar cause or source for atypical BSE in these countries. ***

see page 176 of 201 pages...tss

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2009/prion2009_bookofabstracts.pdf

***atypical spontaneous BSE in France LOL***

FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many spontaneous events of mad cow disease $$$

***so 20 cases of atypical BSE in France, compared to the remaining 40 cases in the remaining 12 Countries, divided by the remaining 12 Countries, about 3+ cases per country, besides Frances 20 cases. you cannot explain this away with any spontaneous BSe. ...TSS

Sunday, October 5, 2014

France stops BSE testing for Mad Cow Disease

http://transmissiblespongiformencephalopathy.blogspot.com/2014/10/france-stops-bse-testing-for-mad-cow.html

10 years post mad cow feed ban August 1997

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

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

17 years post mad cow feed ban August 1997

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

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

Sunday, April 5, 2015

*** Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180 ***

http://madcowfeed.blogspot.com/2015/04/guidance-for-industry-ensuring-safety.html

P04.27

Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route

Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique, France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August University, Germany; 6German Primate Center, Germany

Background:

In 2001, a study was initiated in primates to assess the risk for humans to contract BSE through contaminated food. For this purpose, BSE brain was titrated in cynomolgus monkeys.

Aims:

The primary objective is the determination of the minimal infectious dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for humans. Secondly, we aimed at examining the course of the disease to identify possible biomarkers.

Methods:

Groups with six monkeys each were orally dosed with lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).

Results:

In an ongoing study, a considerable number of high-dosed macaques already developed simian vCJD upon oral or intracerebral exposure or are at the onset of the clinical phase. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of biomarkers.

Conclusions:

Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate. The difference in the incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However, there are rapid progressors among orally dosed monkeys that develop simian v CJD as fast as intracerebrally inoculated animals.

The work referenced was performed in partial fulfillment of the study “BSE in primates“ supported by the EU (QLK1-2002-01096).

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

Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate.

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

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

Calves were challenged by mouth with homogenised brain from confirmed cases of BSE. Some received 300g (3 doses of 100g), some 100g, 10g or 1g. They were then left to develop BSE, but were not subjected to the normal stresses that they might have encountered in a dairy herd. Animals in all four groups developed BSE. There has been a considerable spread of incubation period in some of the groups, but it appears as if those in the 1 and 10g challenge groups most closely fit the picture of incubation periods seen in the epidemic. Experiments in progress indicate that oral infection can occur in some animals with doses as low as 0.01g and 0.001g. .........

http://www.defra.gov.uk/animalh/bse/science-research/pathog.html#dose

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/20061003022720/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/20061003022724/http://www.bseinquiry.gov.uk/files/ws/s147f.pdf

Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle

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

snip...

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

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/mb/m09/tab05.pdf

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/mb/m09a/tab01.pdf

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf

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

Title: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease

Authors

item Greenlee, Justin item Moore, S - item Smith, Jodi - item Kunkle, Robert item West Greenlee, M -

Submitted to: American College of Veterinary Pathologists Meeting Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015 Publication Date: N/A Technical Abstract: The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy. In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=317901

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=260467

White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection

Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS

Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. Previous experiments demonstrated that white-tailed deer are susceptible to sheep-derived scrapie by intracranial inoculation. The purpose of this study was to determine susceptibility of white-tailed deer to scrapie after a natural route of exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal (1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with scrapie. Non-inoculated deer were maintained as negative controls. All deer were observed daily for clinical signs. Deer were euthanized and necropsied when neurologic disease was evident, and tissues were examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and western blot (WB). One animal was euthanized 15 months post-inoculation (MPI) due to an injury. At that time, examination of obex and lymphoid tissues by IHC was positive, but WB of obex and colliculus were negative. Remaining deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by potential natural routes of inoculation. In-depth analysis of tissues will be done to determine similarities between scrapie in deer after intracranial and oral/intranasal inoculation and chronic wasting disease resulting from similar routes of inoculation.

see full text ;

http://www.usaha.org/Portals/6/Reports/2010/report-cwal-2010.pdf

PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer

Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA

http://www.landesbioscience.com/journals/prion/03-Prion6-2-Transmission-and-strains.pdf

White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation

snip...

It is unlikely that CWD will be eradicated from free-ranging cervids, and the disease is likely to continue to spread geographically [10]. However, the potential that white-tailed deer may be susceptible to sheep scrapie by a natural route presents an additional confounding factor to halting the spread of CWD. This leads to the additional speculations that

1) infected deer could serve as a reservoir to infect sheep with scrapie offering challenges to scrapie eradication efforts and

2) CWD spread need not remain geographically confined to current endemic areas, but could occur anywhere that sheep with scrapie and susceptible cervids cohabitate.

This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation with a high attack rate and that the disease that results has similarities to CWD. These experiments will be repeated with a more natural route of inoculation to determine the likelihood of the potential transmission of sheep scrapie to white-tailed deer. If scrapie were to occur in white-tailed deer, results of this study indicate that it would be detected as a TSE, but may be difficult to differentiate from CWD without in-depth biochemical analysis.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199251/?tool=pubmed

http://chronic-wasting-disease.blogspot.com/2011/10/white-tailed-deer-are-susceptible-to.html

2012

PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer

Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA

snip...

The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like.

*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.

Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.

http://www.landesbioscience.com/journals/prion/03-Prion6-2-Transmission-and-strains.pdf

2011

*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie.

http://www.usaha.org/Portals/6/Reports/2011/report-cwal-2011.pdf

White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection

Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS

see full text ;

http://www.usaha.org/Portals/6/Reports/2010/report-cwal-2010.pdf

I urge everyone to watch this video closely...terry

*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***

http://zoomify.uzh.ch:8080/zoomify/videos/video-004/video-004.html

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249

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

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

Authors

item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -

Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.

Interpretive Summary:

The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans.

Technical Abstract:

Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health. 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

*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr. Submission ***

Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats

SUMMARY: We are reopening the comment period for our proposed rule that would revise completely the scrapie regulations, which concern the risk groups and categories established for individual animals and for flocks, the use of genetic testing as a means of assigning risk levels to animals, movement restrictions for animals found to be genetically less susceptible or resistant to scrapie, and recordkeeping requirements. This action will allow interested persons additional time to prepare and submit comments.

DATES: The comment period for the proposed rule published on September 10, 2015 (80 FR 54660-54692) is reopened. We will consider all comments that we receive on or before December 9, 2015. ...

http://www.regulations.gov/#!documentDetail;D=APHIS-2007-0127-0001

http://www.gpo.gov/fdsys/pkg/FR-2015-11-16/html/2015-29179.htm

http://www.regulations.gov/#!docketDetail;D=APHIS-2007-0127

COMMENT SUBMISSION TERRY S. SINGELTARY SR.

WITH regards to Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats, I kindly submit the following ;

>>>The last major revision of the scrapie regulations occurred on August 21, 2001, when we published in theFederal Register(66 FR 43964, Docket No. 97-093-5) a final rule amending part 79 by imposing additional restrictions on the interstate movement of sheep and goats.<<<

Indeed, much science has changed about the Scrapie TSE prion, including more science linking Scrapie to humans. sadly, politics, industry, and trade, have not changed, and those usually trump sound science, as is the case with all Transmissible Spongiform Encephalopathy TSE Prion disease in livestock producing animals and the OIE. we can look no further at the legal trading of the Scrapie TSE prion both typical and atypical of all strains, and CWD all stains. With as much science of old, and now more new science to back this up, Scrapie of all types i.e. atypical and typical, BSE all strains, and CWD all strains, should be regulated in trade as BSE TSE PRION. In fact, I urge APHIS et al and the OIE, and all trading partners to take heed to the latest science on the TSE prion disease, all of them, and seriously reconsider the blatant disregards for human and animal health, all in the name of trade, with the continued relaxing of TSE Prion trade regulations through the ‘NEGLIGIBLE BSE RISK’ PROGRAM, which was set up to fail in the first place. If the world does not go back to the ‘BSE RISK ASSESSMENTS’, enhance, and or change that assessment process to include all TSE prion disease, i.e. ‘TSE RISK ASSESSMENT’, if we do not do this and if we continue this farce with OIE and the USDA et al, and the ‘NEGLIGIBLE BSE RISK’ PROGRAM, we will never eradicate the TSE prion aka mad cow type disease, they will continue to mutate and spread among species of human and animal origin, and they will continue to kill. ...

please see ;

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 longe 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***

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

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

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

***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.

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

.108: Successful oral challenge of adult cattle with classical BSE

Sandor Dudas1,*, Kristina Santiago-Mateo1, Tammy Pickles1, Catherine Graham2, and Stefanie Czub1 1Canadian Food Inspection Agency; NCAD Lethbridge; Lethbridge, Alberta, Canada; 2Nova Scotia Department of Agriculture; Pathology Laboratory; Truro, Nova Scotia, Canada

Classical Bovine spongiform encephalopathy (C-type BSE) is a feed- and food-borne fatal neurological disease which can be orally transmitted to cattle and humans. Due to the presence of contaminated milk replacer, it is generally assumed that cattle become infected early in life as calves and then succumb to disease as adults. Here we challenged three 14 months old cattle per-orally with 100 grams of C-type BSE brain to investigate age-related susceptibility or resistance. During incubation, the animals were sampled monthly for blood and feces and subjected to standardized testing to identify changes related to neurological disease. At 53 months post exposure, progressive signs of central nervous system disease were observed in these 3 animals, and they were euthanized. Two of the C-BSE animals tested strongly positive using standard BSE rapid tests, 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. Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. We are further examining explanations for the unusual disease presentation in the third challenged animal.

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. ***

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. ***

P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification

Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal Health; Tsukuba, Japan

To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).

Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.

Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, ***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.

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

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf

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

***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 FT. COLLINS CWD RISK FACTORS TO HUMANS

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

O18

Zoonotic Potential of CWD Prions

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.

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

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

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

P.105: RT-QuIC models trans-species prion transmission

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.

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

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

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

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf

HD.13: CWD infection in the spleen of humanized transgenic mice

Liuting Qing and Qingzhong Kong Case Western Reserve University; Cleveland, OH USA

Chronic wasting disease (CWD) is a widespread prion disease in free-ranging and captive cervid species in North America, and there is evidence suggesting the existence of multiple CWD strains. The susceptibility of human CNS and peripheral organs to the various CWD prion strains remains largely unclear. Current literature suggests that the classical CWD strain is unlikely to infect human brain, but the potential for peripheral infection by CWD in humans is unknown. We detected protease-resistant PrPSc in the spleens of a few humanized transgenic mice that were intracerebrally inoculated with natural CWD isolates, but PrPSc was not detected in the brains of any of the CWD-inoculated mice. Our ongoing bioassays in humanized Tg mice indicate that intracerebral challenge with such PrPSc-positive humanized mouse spleen already led to prion disease in most animals. These results indicate that the CWD prion may have the potential to infect human peripheral lymphoid tissues.

http://www.tandfonline.com/doi/pdf/10.4161/pri.24865

From: Terry S. Singeltary Sr.

Sent: Saturday, November 15, 2014 9:29 PM

To: Terry S. Singeltary Sr.

Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984

THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE

R. G. WILL

1984

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;

snip...

http://web.archive.org/web/20050425210551/http://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf

85%+ of all human tse prion disease is sporadic CJD.

see what the NIH prion Gods say themselves ;

‘’In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD. That assumption would be wrong.’’

‘’Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.’’

https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf

ARS VIRUS AND PRION RESEARCH / Research / Publication #277212

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

Title: Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation

Authors

item Greenlee, Justin item Nicholson, Eric item Smith, Jodi item Kunkle, Robert item Hamir, Amirali

Submitted to: Journal of Veterinary Diagnostic Investigation Publication

Type: Peer Reviewed Journal Publication Acceptance

Date: July 12, 2012

Publication Date: November 1, 2012

Citation: Greenlee, J.J., Nicholson, E.M., Smith, J.D., Kunkle, R.A., Hamir, A.N. 2012.

Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation.

Journal of Veterinary Diagnostic Investigation. 24(6):1087-1093.

Interpretive Summary: Chronic Wasting Disease (CWD), a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America, is a transmissible spongiform encephalopathy (TSE). TSEs are caused by infectious proteins called prions that are resistant to various methods of decontamination and environmental degradation. Cattle could be exposed to chronic wasting disease (CWD) by contact with infected farmed or free-ranging cervids. The purpose of this study was to assess the potential transmission of CWD from elk to cattle after intracranial inoculation, the most direct route to test the potential of a host to replicate an isolate of the prion agent. This study reports that only 2 of 14 calves inoculated with CWD from elk had clinical signs or evidence of abnormal prion protein accumulation. These results suggest that cattle are unlikely to be susceptible to CWD if inoculated by a more natural route. This information could have an impact on regulatory officials developing plans to reduce or eliminate TSEs and farmers with concerns about ranging cattle on areas where CWD may be present.

Technical Abstract:

***Cattle could be exposed to the agent of chronic wasting disease (CWD) through contact with infected farmed or free-ranging cervids or exposure to contaminated premises. The purpose of this study was to assess the potential for CWD derived from elk to transmit to cattle after intracranial inoculation. Calves (n=14) were inoculated with brain homogenate derived from elk with CWD to determine the potential for transmission and define the clinicopathologic features of disease.

Cattle were necropsied if clinical signs occurred or at the termination of experiment (49 months post-inoculation (MPI)).

Clinical signs of poor appetite, weight loss, circling, and bruxism occurred in two cattle (14%) at 16 and 17 MPI, respectively.

Accumulation of abnormal prion protein (PrP**Sc) in these cattle was confined to the central nervous system with the most prominent immunoreactivity in midbrain, brainstem, and hippocampus with lesser immunoreactivity in the cervical spinal cord.

*** The rate of transmission was lower than in cattle inoculated with CWD derived from mule deer (38%) or white-tailed deer (86%).

Additional studies are required to fully assess the potential for cattle to develop CWD through a more natural route of exposure, but a low rate of transmission after intracranial inoculation suggests that risk of transmission through other routes is low.

***A critical finding here is that if CWD did transmit to exposed cattle, currently used diagnostic techniques would detect and differentiate it from other prion diseases in cattle based on absence of spongiform change, distinct pattern of PrP**Sc deposition, and unique molecular profile.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=277212

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

Project Number: 5030-32000-103-00 Project Type: Appropriated

Start Date: Oct 01, 2011 End Date: Sep 30, 2016

Objective: 1. Investigate the pathobiology of atypical transmissible spongiform encephalopathies (TSEs) in natural hosts. A. Investigate the pathobiology of atypical scrapie. B. Investigate the pathobiology of atypical bovine spongiform encephalopathy (BSE). 2. Investigate the horizontal transmission of TSEs. A. Assess the horizontal transmission of sheep scrapie in the absence of lambing. B. Determine routes of transmission in chronic wasting disease (CWD) infected premises. C. Assess oral transmission of CWD in reindeer. 3. Investigate determinants of CWD persistence. A. Determine CWD host range using natural routes of transmission. B. Investigate the pathobiology of CWD.

Approach: The studies will focus on three animal transmissible spongiform encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease (CWD) of deer, elk, and moose. The research will address sites of accumulation, routes of infection, environmental persistence, and ante mortem diagnostics with an emphasis on controlled conditions and natural routes of infection. Techniques used will include clinical exams, histopathology, immunohistochemistry and biochemical analysis of proteins. The enhanced knowledge gained from this work will help mitigate the potential for unrecognized epidemic expansions of these diseases in populations of animals that could either directly or indirectly affect food animals.

http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=421870

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2014 Annual Report

1a.Objectives (from AD-416): 1. Investigate the pathobiology of atypical transmissible spongiform encephalopathies (TSEs) in natural hosts. A. Investigate the pathobiology of atypical scrapie. B. Investigate the pathobiology of atypical bovine spongiform encephalopathy (BSE). 2. Investigate the horizontal transmission of TSEs. A. Assess the horizontal transmission of sheep scrapie in the absence of lambing. B. Determine routes of transmission in chronic wasting disease (CWD) infected premises. C. Assess oral transmission of CWD in reindeer. 3. Investigate determinants of CWD persistence. A. Determine CWD host range using natural routes of transmission. B. Investigate the pathobiology of CWD.

1b.Approach (from AD-416): The studies will focus on three animal transmissible spongiform encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease (CWD) of deer, elk, and moose. The research will address sites of accumulation, routes of infection, environmental persistence, and ante mortem diagnostics with an emphasis on controlled conditions and natural routes of infection. Techniques used will include clinical exams, histopathology, immunohistochemistry and biochemical analysis of proteins. The enhanced knowledge gained from this work will help mitigate the potential for unrecognized epidemic expansions of these diseases in populations of animals that could either directly or indirectly affect food animals.

3.Progress Report: Research efforts directed toward meeting objective 1 of our project plan, Investigate the pathobiology of atypical transmissible spongiform encephalopathies (TSEs) in natural hosts, include work in previous years starting with the inoculation of animals for studies designed to address the pathobiology of atypical scrapie, atypical bovine spongiform encephalopathy (BSE), as well as a genetic version of BSE. Animals inoculated with atypical scrapie have not yet developed disease. Atypical BSE animals have developed disease and evaluation of the samples is currently underway. Animals inoculated with a genetic version of BSE have developed disease and the manuscript has been published (2012). In addition, we have investigated the possibility that atypical scrapie was present earlier than previously detected in the national flock by analyzing archived field isolates using methods that were unavailable at the time of original diagnosis. Sample quality was sufficiently degraded that modern methods were not suitable for evaluation. In research pertaining to objective 2, Investigate the horizontal transmission of TSEs, we have initiated a study to determine if cohousing non-lambing scrapie inoculated sheep is sufficient to transmit scrapie to neonatal lambs. At this time, scrapie free ewes have lambed in the presence of scrapie inoculated animals and the lambs are cohoused with these inoculated animals.

4.Accomplishments 1. Evaluated enzyme immunoassay for rapid identification of prion disease in livestock. Scrapie of sheep and bovine spongiform encephalopathy of cattle are diseases that cause damage to the central nervous system including the retina in the eye. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state and is resistant to breakdown by the host cells. Current diagnostic methods require the testing of brain material, which can be difficult to collect and may lead to contamination of the environment and exposure of personnel to the infectious agent. Eyes can be readily collected without opening the skull. ARS researchers at Ames, Iowa demonstrated that the enzyme immunoassay results using eyes of negative controls or samples collected from sheep or cattle with clinical signs were in agreement with approved confirmatory assays (western blot or immunohistochemistry). These results indicate the retina is a useful tissue for rapid diagnosis of prion disease in clinically ill sheep and cattle and could be considered to greatly increase the number of samples submitted for prion disease diagnosis with a minimal investment of time and limited exposure of personnel to prion agents.

2. Evaluated E211K cattle as a model for inherited human prion disease. Prion diseases cause damage to the central nervous system of animals and humans. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state and is resistant to breakdown by the host cells and thus accumulates and damages those cells. Some forms of prion disease are genetic and can be inherited. Current models of genetic prion disease in humans rely on mouse models expressing either the human prion protein (E200K) or a combination of both mouse and human sequences. In addition to being an entirely artificial system these mouse models have a short lifespan making them a less than ideal system to study a naturally occurring genetic disorder with a long incubation time and late onset of disease. Cattle, however, exhibit a number of similarities to humans with regard to prion disease and perhaps most notable is the late onset of genetic prion disease. ARS researchers at Ames, Iowa have produced cattle containing both 1 and 2 chromosome copies of the cattle prion gene (E211K) and evaluated many aspects of this prion protein from cattle including protein stability, protein expression levels and ratios, as well as evidence of oxidative stress. Taken together, these results highlight the differences between mouse models of genetic prion disease and a naturally occurring prion disease system in cattle and suggest that cattle will provide a more relevant understanding of genetic prion disease in humans than do current rodent models.

Review Publications Smith, J.D., Greenlee, J.J. 2014. Detection of misfolded prion protein in retina samples of sheep and cattle by use of a commercially available enzyme immunoassay. American Journal of Veterinary Research. 75(3):268-272.

Haldar, S., Beveridge, A.J., Wong, J., Singh, A.J., Galimberti, D., Borroni, D., Zhu, X., Blevins, J., Greenlee, J., Perry, G., Mukhopadhyay, C.K., Schmotzer, C., Singh, N. 2014. A low-molecular-weight ferroxidase is increased in the CSF of sCJD Cases: CSF ferroxidase and transferrin as diagnostic biomarkers for sCJD. Antioxidants & Redox Signaling. 19(14):1662-1675.

http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=421870&fy=2014

*** P.126: Successful transmission of chronic wasting disease (CWD) into mice over-expressing bovine prion protein (TgSB3985) ***

Larisa Cervenakova,1 Christina J Sigurdson,2 Pedro Piccardo,3 Oksana Yakovleva,1 Irina Vasilyeva,1 Jorge de Castro,1 Paula Saá,1 and Anton Cervenak1 1American Red Cross, Holland Laboratory; Rockville, MD USA; 2University of California; San Diego, CA USA; 3Lab TSE/OBRR /CBER/FDA; Rockville, MD USA

Keywords: chronic wasting disease, transmission, transgenic mouse, bovine prion protein

Background. CWD is a disease affecting wild and farmraised cervids in North America. Epidemiological studies provide no evidence of CWD transmission to humans. Multiple attempts have failed to infect transgenic mice expressing human PRNP gene with CWD. The extremely low efficiency of PrPCWD to convert normal human PrPC in vitro provides additional evidence that transmission of CWD to humans cannot be easily achieved. However, a concern about the risk of CWD transmission to humans still exists. This study aimed to establish and characterize an experimental model of CWD in TgSB3985 mice with the following attempt of transmission to TgHu mice.

Materials and Methods. TgSB3985 mice and wild-type FVB/ NCrl mice were intracranially injected with 1% brain homogenate from a CWD-infected Tga20 mouse (CWD/Tga20). TgSB3985 and TgRM (over-expressing human PrP) were similarly injected with 5% brain homogenates from CWD-infected white-tailed deer (CWD/WTD) or elk (CWD/Elk). Animals were observed for clinical signs of neurological disease and were euthanized when moribund. Brains and spleens were removed from all mice for PrPCWD detection by Western blotting (WB). A histological analysis of brains from selected animals was performed: brains were scored for the severity of spongiform change, astrogliosis, and PrPCWD deposition in ten brain regions.

Results. Clinical presentation was consistent with TSE. More than 90% of TgSB3985 and wild-type mice infected with CWD/Tga20, tested positive for PrPres in the brain but only mice in the latter group carried PrPCWD in their spleens. We found evidence for co-existence or divergence of two CWD/ Tga20 strains based on biochemical and histological profiles. In TgSB3985 mice infected with CWD-elk or CWD-WTD, no animals tested positive for PrPCWD in the brain or in the spleen by WB. However, on neuropathological examination we found presence of amyloid plaques that stained positive for PrPCWD in three CWD/WTD- and two CWD/Elk-infected TgSB3985 mice. The neuropathologic profiles in CWD/WTD- and CWD/Elkinfected mice were similar but unique as compared to profiles of BSE, BSE-H or CWD/Tg20 agents propagated in TgSB3985 mice. None of CWD-infected TgRM mice tested positive for PrPCWD by WB or by immunohistochemical detection.

Conclusions. To our knowledge, this is the first established experimental model of CWD in TgSB3985. We found evidence for co-existence or divergence of two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice. Finally, we observed phenotypic differences between cervid-derived CWD and CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway to characterize these strains.

TSS

UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF THE STUDIES ON CWD TRANSMISSION TO CATTLE ;

CWD to cattle figures CORRECTION

Greetings,

I believe the statement and quote below is incorrect ;

"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."

Please see ;

Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=194089

" although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). "

shouldn't this be corrected, 86% is NOT a low rate. ...

kindest regards,

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

Thank you!

Thanks so much for your updates/comments. We intend to publish as rapidly as possible all updates/comments that contribute substantially to the topic under discussion.

http://cshperspectives.cshlp.org/letters/submit

re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations

1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu

http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html

Mule deer, white-tailed deer, and elk have been reported to develop CWD. As the only prion disease identified in free-ranging animals, CWD appears to be far more communicable than other forms of prion disease. CWD was first described in 1967 and was reported to be a spongiform encephalopathy in 1978 on the basis of histopathology of the brain. Originally detected in the American West, CWD has spread across much of North America and has been reported also in South Korea. In captive populations, up to 90% of mule deer have been reported to be positive for prions (Williams and Young 1980). The incidence of CWD in cervids living in the wild has been estimated to be as high as 15% (Miller et al. 2000). The development of transgenic (Tg) mice expressing cervid PrP, and thus susceptible to CWD, has enhanced detection of CWD and the estimation of prion titers (Browning et al. 2004; Tamgüney et al. 2006). Shedding of prions in the feces, even in presymptomatic deer, has been identified as a likely source of infection for these grazing animals (Williams and Miller 2002; Tamgüney et al. 2009b). CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures.

snip...

http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html

----- Original Message -----

From: David Colby To: flounder9@verizon.net

Cc: stanley@XXXXXXXX

Sent: Tuesday, March 01, 2011 8:25 AM

Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations

Dear Terry Singeltary,

Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter. Warm Regards, David Colby -- David Colby, PhDAssistant Professor Department of Chemical Engineering University of Delaware

===========END...TSS==============

SNIP...SEE FULL TEXT ;

http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html

Friday, August 14, 2015

*** Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation ***

http://chronic-wasting-disease.blogspot.com/2015/08/susceptibility-of-cattle-to-agent-of.html

*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***

Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3

http://jgv.sgmjournals.org/content/87/12/3737.full

*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.

http://collections.europarchive.org/tna/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

PL1

Using in vitro prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission.

Claudio Soto

Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston.

Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.

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

***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.

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

Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf

see ;

http://www.tandfonline.com/doi/pdf/10.4161/pri.28467

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058630

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567181/pdf/ppat.1003113.pdf

http://www.nature.com/srep/2015/150210/srep08358/full/srep08358.html?WT.ec_id=SREP-639-20150217

http://www.cell.com/cell-reports/pdfExtended/S2211-1247(15)00437-4

Wednesday, December 16, 2015

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4, Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1

1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK

Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.

snip...

Discussion

Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20). Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22). Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23).

Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing. Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building. Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9). The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture. When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier.

This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep. Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease. It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled. Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases. Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA. Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions.

PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice. In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals. In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay. False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28). This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm. This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc. In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc. Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing. The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material. In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12). A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30). This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model. Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions.

In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination. These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes.

Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification

http://journal.frontiersin.org/article/10.3389/fvets.2015.00032/full

Wednesday, December 16, 2015

*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission ***

http://scrapie-usa.blogspot.com/2015/12/objects-in-contact-with-classical.html

Circulation of prions within dust on a scrapie affected farm

Kevin C Gough1, Claire A Baker2, Hugh A Simmons3, Steve A Hawkins3 and Ben C Maddison2*

Abstract

Prion diseases are fatal neurological disorders that affect humans and animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk are contagious prion diseases where environmental reservoirs have a direct link to the transmission of disease. Using protein misfolding cyclic amplification we demonstrate that scrapie PrPSc can be detected within circulating dusts that are present on a farm that is naturally contaminated with sheep scrapie. The presence of infectious scrapie within airborne dusts may represent a possible route of infection and illustrates the difficulties that may be associated with the effective decontamination of such scrapie affected premises.

snip...

Discussion

We present biochemical data illustrating the airborne movement of scrapie containing material within a contaminated farm environment. We were able to detect scrapie PrPSc within extracts from dusts collected over a 70 day period, in the absence of any sheep activity. We were also able to detect scrapie PrPSc within dusts collected within pasture at 30 m but not at 60 m distance away from the scrapie contaminated buildings, suggesting that the chance of contamination of pasture by scrapie contaminated dusts decreases with distance from contaminated farm buildings. PrPSc amplification by sPMCA has been shown to correlate with infectivity and amplified products have been shown to be infectious [14,15]. These experiments illustrate the potential for low dose scrapie infectivity to be present within such samples. We estimate low ng levels of scrapie positive brain equivalent were deposited per m2 over 70 days, in a barn previously occupied by sheep affected with scrapie. This movement of dusts and the accumulation of low levels of scrapie infectivity within this environment may in part explain previous observations where despite stringent pen decontamination regimens healthy lambs still became scrapie infected after apparent exposure from their environment alone [16]. The presence of sPMCA seeding activity and by inference, infectious prions within dusts, and their potential for airborne dissemination is highly novel and may have implications for the spread of scrapie within infected premises. The low level circulation and accumulation of scrapie prion containing dust material within the farm environment will likely impede the efficient decontamination of such scrapie contaminated buildings unless all possible reservoirs of dust are removed. Scrapie containing dusts could possibly infect animals during feeding and drinking, and respiratory and conjunctival routes may also be involved. It has been demonstrated that scrapie can be efficiently transmitted via the nasal route in sheep [17], as is also the case for CWD in both murine models and in white tailed deer [18-20].

The sources of dust borne prions are unknown but it seems reasonable to assume that faecal, urine, skin, parturient material and saliva-derived prions may contribute to this mobile environmental reservoir of infectivity. This work highlights a possible transmission route for scrapie within the farm environment, and this is likely to be paralleled in CWD which shows strong similarities with scrapie in terms of prion dissemination and disease transmission. The data indicate that the presence of scrapie prions in dust is likely to make the control of these diseases a considerable challenge.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397813/pdf/13567_2015_Article_176.pdf

Monday, November 3, 2014

Persistence of ovine scrapie infectivity in a farm environment following cleaning and decontamination

http://transmissiblespongiformencephalopathy.blogspot.com/2014/11/persistence-of-ovine-scrapie.html

PPo3-22:

Detection of Environmentally Associated PrPSc on a Farm with Endemic Scrapie

Ben C. Maddison,1 Claire A. Baker,1 Helen C. Rees,1 Linda A. Terry,2 Leigh Thorne,2 Susan J. Belworthy2 and Kevin C. Gough3 1ADAS-UK LTD; Department of Biology; University of Leicester; Leicester, UK; 2Veterinary Laboratories Agency; Surry, KT UK; 3Department of Veterinary Medicine and Science; University of Nottingham; Sutton Bonington, Loughborough UK

Key words: scrapie, evironmental persistence, sPMCA

Ovine scrapie shows considerable horizontal transmission, yet the routes of transmission and specifically the role of fomites in transmission remain poorly defined. Here we present biochemical data demonstrating that on a scrapie-affected sheep farm, scrapie prion contamination is widespread. It was anticipated at the outset that if prions contaminate the environment that they would be there at extremely low levels, as such the most sensitive method available for the detection of PrPSc, serial Protein Misfolding Cyclic Amplification (sPMCA), was used in this study. We investigated the distribution of environmental scrapie prions by applying ovine sPMCA to samples taken from a range of surfaces that were accessible to animals and could be collected by use of a wetted foam swab. Prion was amplified by sPMCA from a number of these environmental swab samples including those taken from metal, plastic and wooden surfaces, both in the indoor and outdoor environment. At the time of sampling there had been no sheep contact with these areas for at least 20 days prior to sampling indicating that prions persist for at least this duration in the environment. These data implicate inanimate objects as environmental reservoirs of prion infectivity which are likely to contribute to disease transmission.

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

A CONTRIBUTION TO THE NEUROPATHOLOGY OF THE RED-NECKED OSTRICH (STRUTHIO CAMELUS) - SPONGIFORM ENCEPHALOPATHY

http://collections.europarchive.org/tna/20081105185647/http://www.bseinquiry.gov.uk/files/sc/Seac10/tab06.pdf

4.21 Three cases of SE’s with an unknown infectious agent have been reported in ostriches (Struthio Camellus) in two zoos in north west Germany (Schoon @ Brunckhorst, 1999, Verh ber Erkeg Zootiere 33:309-314). These birds showed protracted central nervous symptoms with ataxia, disturbances of balance and uncoordinated feeding behaviour. The diet of these birds had included poultry meat meal, some of which came from cattle emergency slaughter cases.

http://web.archive.org/web/20030331182151/http://www.bseinquiry.gov.uk/files/ws/s113.pdf

SE1806

TRANSMISSION STUDIES OF BSE TO DOMESTIC FOWL BY ORAL EXPOSURE TO BRAIN HOMOGENATE

1 challenged cock bird was necropsied (41 months p.i.) following a period of ataxia, tremor, limb abduction and other neurological signs. Histopathological examination failed to reveal any significant lesions of the central or peripheral nervous systems...

1 other challenged cock bird is also showing ataxia (43 months p.i.).

snip...

94/01.19/7.1

http://collections.europarchive.org/tna/20020525205812/http://bseinquiry.gov.uk/files/yb/1994/01/19007001.pdf

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/01/19007001.pdf

A notification of Spongiform Encephalopathy was introduced in October 1996 in respect of ungulates, poultry and any other animal.

4.23 MAFF have carried out their own transmission experiments with hens. In these experiments, some of the chickens exposed to the BSE agent showed neurological symptoms. However MAFF have not so far published details of the symptoms seen in chickens. Examination of brains from these chickens did not show the typical pathology seen in other SE’s. 4.24 A farmer in Kent in November 1996 noticed that one of his 20 free range hens, the oldest, aged about 30 months was having difficulty entering its den and appeared frightened and tended to lose its balance when excited. Having previously experienced BSE cattle on his farm, he took particular notice of the bird and continued to observe it over the following weeks. It lost weight, its balance deteriorated and characteristic tremors developed which were closely associated with the muscles required for standing. In its attempts to maintain its balance it would claw the ground more than usual and the ataxia progressively developed in the wings and legs, later taking a typical form of paralysis with a clumsy involuntary jerky motion. Violent tremors of the entire body, particularly the legs, became common, sparked off by the slightest provocation. This is similar to that seen in many BSE cases where any excitement may result in posterior ataxia, often with dropping of the pelvis, kicking and a general nervousness. Three other farmers and a bird breeder from the UK are known to have reported having hens with similar symptoms. The bird breeder who has been exhibiting his birds for show purposes for 20 years noticed birds having difficulty getting on to their perch and holding there for any length of time without falling. Even though the bird was eating normally, he noticed a weight loss of more than a pound in a bird the original weight of which was 5 pounds. 4.25 Histological examination of the brain revealed degenerative pathological changes in hens with a minimal vacuolation. The presence of PrP immunostaining of the brain sections revealed PrP-sc positive plaques and this must be regarded as very strong evidence to demonstrate that the hens had been incubating Spongiform Encephalopathy.

http://web.archive.org/web/20030331182151/http://www.bseinquiry.gov.uk/files/ws/s113.pdf

OPINION on : NECROPHAGOUS BIRDS AS POSSIBLE TRANSMITTERS OF TSE/BSE ADOPTED BY THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 7-8 NOVEMBER 2002

OPINION

1. Necrophagous birds as possible transmitters of BSE. The SSC considers that the evaluation of necrophagous birds as possible transmitters of BSE, should theoretically be approached from a broader perspective of mammals and birds which prey on, or are carrion eaters (scavengers) of mammalian species. Thus, carnivorous and omnivorous mammals, birds of prey (vultures, falcons, eagles, hawks etc.), carrion eating birds (crows, magpies etc.) in general could be considered possible vectors of transmission and/or spread of TSE infectivity in the environment. In view also of the occurrence of Chronic Wasting Disease (CWD) in various deer species it should not be accepted that domestic cattle and sheep are necessarily the only source of TSE agent exposure for carnivorous species. While some information is available on the susceptibility of wild/exotic/zoo animals to natural or experimental infection with certain TSE agents, nothing is known of the possibility of occurrence of TSE in wild animal populations, other than among the species of deer affected by CWD in the USA.

1 The carrion birds are animals whose diet regularly or occasionally includes the consumption of carcasses, including possibly TSE infected ruminant carcasses.

http://ec.europa.eu/food/fs/sc/ssc/out295_en.pdf

snip... skroll down to the bottom ;

http://transmissiblespongiformencephalopathy.blogspot.com/2010/07/tse-road-map-2-strategy-paper-on-tse.html

Date: Mon, 11 Jun 2001 16:24:51 –0700

Reply-To: Bovine Spongiform Encephalopathy

Sender: Bovine Spongiform Encephalopathy

From: "Terry S. Singeltary Sr." Subject: The Red-Neck Ostrich & TSEs 'THE AUTOPSY'

http://chronic-wasting-disease.blogspot.com/2009/11/american-crows-corvus-brachyrhynchos.html

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

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

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

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

snip...

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

soundness of BSE maintenance sampling (APHIS),

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

snip...

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

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

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

-MORE Office of the United States Attorney District of Arizona FOR IMMEDIATE RELEASE For Information Contact Public Affairs February 16, 2007 WYN HORNBUCKLE Telephone: (602) 514-7625 Cell: (602) 525-2681

CORPORATION AND ITS PRESIDENT PLEAD GUILTY TO DEFRAUDING GOVERNMENT’S MAD COW DISEASE SURVEILLANCE PROGRAM

PHOENIX -- Farm Fresh Meats, Inc. and Roland Emerson Farabee, 55, of Maricopa, Arizona, pleaded guilty to stealing $390,000 in government funds, mail fraud and wire fraud, in federal district court in Phoenix. U.S. Attorney Daniel Knauss stated, “The integrity of the system that tests for mad cow disease relies upon the honest cooperation of enterprises like Farm Fresh Meats. Without that honest cooperation, consumers both in the U.S. and internationally are at risk. We want to thank the USDA’s Office of Inspector General for their continuing efforts to safeguard the public health and enforce the law.” Farm Fresh Meats and Farabee were charged by Information with theft of government funds, mail fraud and wire fraud. According to the Information, on June 7, 2004, Farabee, on behalf of Farm Fresh Meats, signed a contract with the U.S. Department of Agriculture (the “USDA Agreement”) to collect obex samples from cattle at high risk of mad cow disease (the “Targeted Cattle Population”). The Targeted Cattle Population consisted of the following cattle: cattle over thirty months of age; nonambulatory cattle; cattle exhibiting signs of central nervous system disorders; cattle exhibiting signs of mad cow disease; and dead cattle. Pursuant to the USDA Agreement, the USDA agreed to pay Farm Fresh Meats $150 per obex sample for collecting obex samples from cattle within the Targeted Cattle Population, and submitting the obex samples to a USDA laboratory for mad cow disease testing. Farm Fresh Meats further agreed to maintain in cold storage the sampled cattle carcasses and heads until the test results were received by Farm Fresh Meats.

Evidence uncovered during the government’s investigation established that Farm Fresh Meats and Farabee submitted samples from cattle outside the Targeted Cattle Population. Specifically, Farm Fresh Meats and Farabee submitted, or caused to be submitted, obex samples from healthy, USDA inspected cattle, in order to steal government moneys.

Evidence collected also demonstrated that Farm Fresh Meats and Farabee failed to maintain cattle carcasses and heads pending test results and falsified corporate books and records to conceal their malfeasance. Such actions, to the extent an obex sample tested positive (fortunately, none did), could have jeopardized the USDA’s ability to identify the diseased animal and pinpoint its place of origin. On Wednesday, February 14, 2007, Farm Fresh Meats and Farabee pleaded guilty to stealing government funds and using the mails and wires to effect the scheme. According to their guilty pleas:

(a) Farm Fresh Meats collected, and Farabee directed others to collect, obex samples from cattle outside the Targeted Cattle Population, which were not subject to payment by the USDA;

(b) Farm Fresh Meats 2 and Farabee caused to be submitted payment requests to the USDA knowing that the requests were based on obex samples that were not subject to payment under the USDA Agreement;

(c) Farm Fresh Meats completed and submitted, and Farabee directed others to complete and submit, BSE Surveillance Data Collection Forms to the USDA’s testing laboratory that were false and misleading;

(d) Farm Fresh Meats completed and submitted, and Farabee directed others to complete and submit, BSE Surveillance Submission Forms filed with the USDA that were false and misleading;

(e) Farm Fresh Meats falsified, and Farabee directed others to falsify, internal Farm Fresh Meats documents to conceal the fact that Farm Fresh Meats was seeking and obtaining payment from the USDA for obex samples obtained from cattle outside the Targeted Cattle Population; and

(f) Farm Fresh Meats failed to comply with, and Farabee directed others to fail to comply with, the USDA Agreement by discarding cattle carcasses and heads prior to receiving BSE test results. A conviction for theft of government funds carries a maximum penalty of 10 years imprisonment. Mail fraud and wire fraud convictions carry a maximum penalty of 20 years imprisonment. Convictions for the above referenced violations also carry a maximum fine of $250,000 for individuals and $500,000 for organizations. In determining an actual sentence, Judge Earl H. Carroll will consult the U.S. Sentencing Guidelines, which provide appropriate sentencing ranges. The judge, however, is not bound by those guidelines in determining a sentence.

Sentencing is set before Judge Earl H. Carroll on May 14, 2007. The investigation in this case was conducted by Assistant Special Agent in Charge Alejandro Quintero, United States Department of Agriculture, Office of Inspector General. The prosecution is being handled by Robert Long, Assistant U.S. Attorney, District of Arizona, Phoenix. CASE NUMBER: CR-07-00160-PHX-EHC RELEASE NUMBER: 2007-051(Farabee) # # #

http://www.usdoj.gov/usao/az/press_releases/2007/2007-051(Farabee).pdf

WE can only hope that this is a single incident. BUT i have my doubts. I remember when the infamous TOKEN Purina Feed Mill in Texas was feeding up to 5.5 grams of potentially and probably tainted BANNED RUMINANT feed to cattle, and the FDA was bragging at the time that the amount of potentially BANNED product was so little and the cattle were so big ;

"It is important to note that the prohibited material was domestic in origin (therefore not likely to contain infected material because there is no evidence of BSE in U.S. cattle), fed at a very low level, and fed only once. The potential risk of BSE to such cattle is therefore exceedingly low, even if the feed were contaminated."

http://www.fda.gov/bbs/topics/NEWS/2001/NEW00752.html

On Friday, April 30 th , the Food and Drug Administration learned that a cow with central nervous system symptoms had been killed and shipped to a processor for rendering into animal protein for use in animal feed. ... FDA's investigation showed that the animal in question had already been rendered into "meat and bone meal" (a type of protein animal feed). Over the weekend FDA was able to track down all the implicated material. That material is being held by the firm, which is cooperating fully with FDA.

http://www.fda.gov/bbs/topics/news/2004/NEW01061.html

WE now know all that was a lie. WE know that literally Thousands of TONS of BANNED and most likely tainted product is still going out to commerce. WE know now and we knew then that .005 to a gram was lethal. WE know that CWD infected deer and elk, scrapie infected sheep, BSE and BASE infected cattle have all been rendered and fed back to livestock (including cattle) for human and animal consumption.

Paul Brown, known and respected TSE scientist, former TSE expert for the CDC said he had ''absolutely no confidence in USDA tests before one year ago'', and this was on March 15, 2006 ;

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

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

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

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

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

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

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

PAUL BROWN COMMENT TO ME ON THIS ISSUE

Tuesday, September 12, 2006 11:10 AM

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

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

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

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

Table 1. Animal feed ingredients that are legally used in U.S. animal feeds

Animal

Rendered animal protein from Meat meal, meat meal tankage, meat and bone meal, poultry meal, animal the slaughter of food by-product meal, dried animal blood, blood meal, feather meal, egg-shell production animals and other meal, hydrolyzed whole poultry, hydrolyzed hair, bone marrow, and animal animals digest from dead, dying, diseased, or disabled animals including deer and elk Animal waste Dried ruminant waste, dried swine waste, dried poultry litter, and undried processed animal waste products

snip...

Conclusions

Food-animal production in the United States has changed markedly in the past century, and these changes have paralleled major changes in animal feed formulations. While this industrialized system of food-animal production may result in increased production efficiencies, some of the changes in animal feeding practices may result in unintended adverse health consequences for consumers of animal-based food products. Currently, the use of animal feed ingredients, including rendered animal products, animal waste, antibiotics, metals, and fats, could result in higher levels of bacteria, antibioticresistant bacteria, prions, arsenic, and dioxinlike compounds in animals and resulting animal-based food products intended for human consumption. Subsequent human health effects among consumers could include increases in bacterial infections (antibioticresistant and nonresistant) and increases in the risk of developing chronic (often fatal) diseases such as vCJD. Nevertheless, in spite of the wide range of potential human health impacts that could result from animal feeding practices, there are little data collected at the federal or state level concerning the amounts of specific ingredients that are intentionally included in U.S. animal feed. In addition, almost no biological or chemical testing is conducted on complete U.S. animal feeds; insufficient testing is performed on retail meat products; and human health effects data are not appropriately linked to this information. These surveillance inadequacies make it difficult to conduct rigorous epidemiologic studies and risk assessments that could identify the extent to which specific human health risks are ultimately associated with animal feeding practices. For example, as noted above, there are insufficient data to determine whether other human foodborne bacterial illnesses besides those caused by S. enterica serotype Agona are associated with animal feeding practices. Likewise, there are insufficient data to determine the percentage of antibiotic-resistant human bacterial infections that are attributed to the nontherapeutic use of antibiotics in animal feed. Moreover, little research has been conducted to determine whether the use of organoarsenicals in animal feed, which can lead to elevated levels of arsenic in meat products (Lasky et al. 2004), contributes to increases in cancer risk. In order to address these research gaps, the following principal actions are necessary within the United States: a) implementation of a nationwide reporting system of the specific amounts and types of feed ingredients of concern to public health that are incorporated into animal feed, including antibiotics, arsenicals, rendered animal products, fats, and animal waste; b) funding and development of robust surveillance systems that monitor biological, chemical, and other etiologic agents throughout the animal-based food-production chain “from farm to fork” to human health outcomes; and c) increased communication and collaboration among feed professionals, food-animal producers, and veterinary and public health officials.

REFERENCES...snip...end

Sapkota et al. 668 VOLUME 115 | NUMBER 5 | May 2007 • Environmental Health Perspectives

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1867957&blobtype=pdf

NOW, what about the product that is not reported ?

HOW many more Farm Fresh Meats, Inc. and Roland Emerson Farabee's are out there that submitted bogus samples for the infamous June 2004 ENHANCED BSE MAD COW COVER-UP, but did not get caught ?

IT was not bad enough to have the USDA et al bungle there own BSE Testing Protocols up so bad, it took Weybridge and a year of hounding by s o m e, and finally an act of Congress to finally get that cow confirmed, but once caught there, i guess the next best thing would be to have bogus BSE testing samples submitted for testing from healthy USDA cattle, what next ? not to forget about the other stumbling and staggering Tejas mad cow they rendered without any test at all, and the other Tejas mad cow that took 7+ months and an act of Congress to finally get confirmed from Weybridge. my God, even the three stooges, laural and hardy put all together could have thought up all this. $$$

The beef import forecast for the second quarter was unchanged from last month’s, despite pressure from higher-than-expected domestic cow slaughter that has remained high through most of this period. Beef imports into the United States from Australia, New Zealand, and Uruguay provide additional processing beef that, along with domestic cow and bull beef, is mixed with 50-percent trim from fed cattle to make ground beef. Forecast beef exports were raised slightly, mainly on continued (though gradual) improvements in sales to major Asian markets. In late May the World Animal Health Organization – known by its French acronym, OIE – designated the United States as having “controlled risk status” for bovine spongiform encephalopathy, or BSE. This designation reflects the OIE’s view that beef produced in the United States is safe for export, since BSE control measures such as feed bans and removal of specified risk materials result in negligible risk to consumers. However, the OIE standards are only guidelines. Individual countries may adopt differing standards, and those countries that do accept OIE standards must still undertake the bureaucratic processes to revise their rules and procedures.

http://www.ers.usda.gov/publications/ldp/2007/06Jun/ldpm156.pdf

(Adopted by the International Committee of the OIE on 23 May 2006)

11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to then Central Bureau............

http://www.oie.int/eng/Session2007/RF2006.pdf

daaa. ...

P.S. Thank You Honorable Phyllis Fong for trying to keep them straight anyway. ...TSS

Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html

Tuesday, August 18, 2009

BSE-The Untold Story - joe gibbs and singeltary 1999 – 2009

http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html

Saturday, December 12, 2015

BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION REPORT DECEMBER 14, 2015

http://bovineprp.blogspot.com/2015/12/bovine-spongiform-encephalopathy-bse.html

Saturday, December 12, 2015

CHRONIC WASTING DISEASE CWD TSE PRION REPORT DECEMBER 14, 2015

http://chronic-wasting-disease.blogspot.com/2015/12/chronic-wasting-disease-cwd-tse-prion.html

Saturday, December 12, 2015

CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015

http://creutzfeldt-jakob-disease.blogspot.com/2015/12/creutzfeldt-jakob-disease-cjd-tse-prion.html

Saturday, February 6, 2016

*** Secretary's Advisory Committee on Animal Health; Meeting [Docket No. APHIS-2016-0007] Singeltary Submission ***

http://animalhealthreportpriontse.blogspot.com/2016/02/secretarys-advisory-committee-on-animal.html

Friday, February 05, 2016

*** Report of the Committee on Wildlife Diseases FY2015 CWD TSE PRION Detections in Farmed Cervids and Wild ***

http://chronic-wasting-disease.blogspot.com/2016/02/report-of-committee-on-wildlife.html

Wednesday, January 20, 2016

Exportation of Live Animals, Hatching Eggs, and Animal Germplasm From the United States [Docket No. APHIS-2012-0049] RIN 0579-AE00 2016-00962

http://animalhealthreportpriontse.blogspot.com/2016/01/exportation-of-live-animals-hatching.html

Thursday, January 14, 2016

*** EMERGING ANIMAL DISEASES Actions Needed to Better Position USDA to Address Future Risks Report to the Chairman, Committee on Energy and Commerce, House of Representatives December 2015 GAO-16-132

GAO

http://animalhealthreportpriontse.blogspot.com/2016/01/emerging-animal-diseases-actions-needed_14.html

Friday, January 1, 2016

South Korea Lifts Ban on Beef, Veal Imports From Canada

http://usdavskorea.blogspot.com/2016/01/south-korea-lifts-ban-on-beef-veal.html

US CONGRESS, another failed entity...tss

Tuesday, December 29, 2015

*** Congress repeals country-of-origin labeling rule for beef and pork

http://naiscoolyes.blogspot.com/2015/12/congress-repeals-country-of-origin.html

December 28, 2015 at 2:21am

*** Australian government assessing risk of importing beef from US, Japan and the Netherlands

http://justgroundsonline.com/profiles/blogs/australian-government-assessing-risk-of-importing-beef-from-us?xg_source=msg_appr_blogpost

Thursday, December 24, 2015

Infectious disease spread is fueled by international trade

http://transmissiblespongiformencephalopathy.blogspot.com/2015/12/infectious-disease-spread-is-fueled-by.html

Saturday, December 12, 2015

NOTICE: Environmental Impact Statement on Large Livestock Carcasses TSE Prion REPORT December 14, 2015

http://transmissiblespongiformencephalopathy.blogspot.com/2015/12/notice-environmental-impact-statement.html

Thursday, December 17, 2015

Annual report of the Scientific Network on BSE-TSE 2015 EFSA-Q-2015-00738 10 December 2015

http://efsaopinionbseanimalprotein.blogspot.com/2015/12/annual-report-of-scientific-network-on.html

Sunday, October 18, 2015

World Organisation for Animal Health (OIE) and the Institut Pasteur Cooperating on animal disease and zoonosis research

http://bovineprp.blogspot.com/2015/10/world-organisation-for-animal-health.html

SSS SHOOT SHOVEL AND SHUT UP !

*** you can find some history of the BSE cases in Canada and Klein’s BSE SSS policy comment here ;

http://usdavskorea.blogspot.com/2016/01/south-korea-lifts-ban-on-beef-veal.html

Tuesday, August 12, 2014

MAD COW USDA TSE PRION COVER UP or JUST IGNORANCE, for the record AUGUST 2014

http://madcowusda.blogspot.com/2014/08/mad-cow-usda-tse-prion-cover-up-or-just.html

Saturday, December 12, 2015

*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION REPORT DECEMBER 14, 2015

http://bovineprp.blogspot.com/2015/12/bovine-spongiform-encephalopathy-bse.html

Thursday, October 22, 2015

*** Former Ag Secretary Ann Veneman talks women in agriculture and we talk mad cow disease USDA and what really happened ***

http://madcowusda.blogspot.com/2015/10/former-ag-secretary-ann-veneman-talks.html

*** Needless conflict ***

Nature 485, 279–280 (17 May 2012) doi:10.1038/485279b

Published online 16 May 2012

Terry S. Singeltary Sr. said:

I kindly wish to submit the following please ;

http://www.nature.com/nature/journal/v485/n7398/full/485279b.html

Comments on technical aspects of the risk assessment were then submitted to FSIS.

Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary.

This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

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

Owens, Julie

From: Terry S. Singeltary Sr. [flounder9@verizon.net]

Sent: Monday, July 24, 2006 1:09 PM

To: FSIS RegulationsComments

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

Page 1 of 98

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

FSIS, USDA, REPLY TO SINGELTARY

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

Singeltary to APHIS FDA USDA et al ;

http://www.regulations.gov/#!documentDetail;D=APHIS-2006-0026-0012;oldLink=false

http://www.regulations.gov/#!documentDetail;D=FDA-2014-D-1180-0003

Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

07 02:27 AM

Terry S. Singeltary Sr. said:

re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

2015-12-07 02:27 AM

Terry S. Singeltary Sr. said: re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)

http://www.nature.com/nature/journal/v525/n7568/full/nature15369.html

I would kindly like to comment on the Nature Paper, the Lancet reply, and the newspaper articles.

First, I applaud Nature, the Scientist and Authors of the Nature paper, for bringing this important finding to the attention of the public domain, and the media for printing said findings.

Secondly, it seems once again, politics is getting in the way possibly of more important Transmissible Spongiform Encephalopathy TSE Prion scientific findings. findings that could have great implications for human health, and great implications for the medical surgical arena. but apparently, the government peer review process, of the peer review science, tries to intervene again to water down said disturbing findings.

where have we all heard this before? it’s been well documented via the BSE Inquiry. have they not learned a lesson from the last time?

we have seen this time and time again in England (and other Country’s) with the BSE mad cow TSE Prion debacle.

snip...see full Singeltary Nature comment here;

http://www.nature.com/nature/journal/v525/n7568/full/nature15369.html#/comments

see Singeltary comments to Plos ;

Subject: 1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN

BSE101/1 0136

IN CONFIDENCE

CMO

From: . Dr J S Metiers DCMO

4 November 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. 'This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.

2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed". As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.

what are the implications for public health?

3. The route 'of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.

92/11.4/1.1

BSE101/1 0137

4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required’’ before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.

J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832 llllYc!eS 2 92/11.4/1.2

http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf

>>> The only tenable public line will be that "more research is required’’ <<<

>>> possibility on a transmissible prion remains open<<<

O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

*** Singeltary comment PLoS ***

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?

Posted by flounder on 05 Nov 2014 at 21:27 GMT

http://www.plosone.org/annotation/listThread.action?root=82860

Sunday, November 22, 2015

*** Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis Abstract

Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.

Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD 54.00

http://www.tandfonline.com/doi/abs/10.3109/13506129.2015.1095735?journalCode=iamy20

http://betaamyloidcjd.blogspot.com/2015/11/effect-of-heating-on-stability-of.html

*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract

the warning shots fired over the bow of the boat that were never heard ;

PITUITARY EXTRACT

This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease...

http://collections.europarchive.org/tna/20090114081754/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf

NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE

snip...

I was quite prepared to believe in unofficial pituitary hormones, also in the 1970's, whether as described by Dr. Little, or in other circumstances, for animal use.

snip...

The fact that there were jars of pituitaries (or extract) around on shelves is attested by the still potent 1943 pituitaries, described in Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the trouble to collect them, they were not lightly thrown out...

http://collections.europarchive.org/tna/20080102174454/http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf

3. The extraction is from a pool of pituitary glands collected from abbatoirs and the process used is unlikely to have any effect on the BSE agent. Hormones extracted from human pituitary glands have been responsible for a small number of Creutzfeldt Jacob disease in man.

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf

SEE LOOPHOLE ;

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/13008001.pdf

SEE LOOPHOLE SHOULD BE CLOSED ;

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/14006001.pdf

snip...see at bottom ;

Friday, January 10, 2014

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/vpspr-sgss-sffi-tse-iatrogenic-by.html

Tuesday, August 4, 2015

*** FDA U.S. Measures to Protect Against BSE ***

http://bseusa.blogspot.com/2015/08/fda-us-measures-to-protect-against-bse.html

*** now, from all the consumption and exposure above, now think iatrogenic cjd tse prion at a hospital near you, what if?

Thursday, August 13, 2015

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

http://creutzfeldt-jakob-disease.blogspot.com/2015/08/iatrogenic-cjd-due-to-pituitary-derived.html

Monday, August 17, 2015

*** FDA Says Endoscope Makers Failed to Report Superbug Problems OLYMPUS

*** I told Olympus 15 years ago about these risk factors from endoscopy equipment, disinfection, even spoke with the Doctor at Olympus, this was back in 1999. I tried to tell them that they were exposing patients to dangerous pathogens such as the CJD TSE prion, because they could not properly clean them. even presented my concern to a peer review journal GUT, that was going to publish, but then it was pulled by Professor Michael Farthing et al... see ;

http://transmissiblespongiformencephalopathy.blogspot.com/2015/08/fda-says-endoscope-makers-failed-to.html

Thursday, September 10, 2015

25th Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015

http://tseac.blogspot.com/2015/09/25th-meeting-of-transmissible.html

Thursday, January 14, 2016

Preventable Tragedies: Superbugs and How Ineffective Monitoring of Medical Device Safety Fails Patients REPORT

how can it be, HOW CAN IT BE $$$ not a word about CJD GSS FFI VPSPR TSE Prions that I saw...absolutely crazy, WE ARE MISSING THE BIGGER PICTURE!

how many victims that will never be reported ???

http://transmissiblespongiformencephalopathy.blogspot.com/2016/01/preventable-tragedies-superbugs-and-how.html

Saturday, January 16, 2016

Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Products Guidance for Industry

http://creutzfeldt-jakob-disease.blogspot.com/2016/01/revised-preventive-measures-to-reduce.html

Saturday, February 13, 2016

The Risk of Prion Infection through Bovine Grafting Materials in dentistry

http://bovineprp.blogspot.com/2016/02/the-risk-of-prion-infection-through.html

Monday, February 15, 2016

Distinctive properties of plaque-type dura mater graft-associated Creutzfeldt–Jakob disease in cell-protein misfolding cyclic amplification

http://creutzfeldt-jakob-disease.blogspot.com/2016/02/distinctive-properties-of-plaque-type.html

The Pathological Protein:

Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases

Philip Yam

''Answering critics like Terry Singeltary, who feels that the US undercounts CJD, Schonberger _conceded_ that the current surveillance system has errors but stated that most of the errors will be confined to the older population''....end

http://www.amazon.com/The-Pathological-Protein-Chronic-Diseases/dp/0387955089

http://transmissiblespongiformencephalopathy.blogspot.com/2014/12/terry-s-singeltary-sr-publications-tse.html

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

http://jama.jamanetwork.com/article.aspx?articleid=1031186

26 March 2003

Terry S. Singeltary, retired (medically) CJD WATCH

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?

http://www.neurology.org/content/60/2/176/reply#neurology_el_535

The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI

Tracking spongiform encephalopathies in North America

Original

Xavier Bosch

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt—Jakob ...

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(03)00715-1/abstract

Suspect symptoms

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

28 Mar 01

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America. Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html

2 January 2000

British Medical Journal

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

http://www.bmj.com/rapid-response/2011/10/28/us-scientist-should-be-concerned-cjd-epidemic-us-well

15 November 1999

British Medical Journal

vCJD in the USA * BSE in U.S.

http://www.bmj.com/rapid-response/2011/10/28/re-vcjd-usa-bse-us

Terry S. Singeltary Sr.

FDA Strengthens BSE Safeguards Animal Feed

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