Tuesday, July 18, 2017



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

From: Customer Service - NASS <nass@nass.usda.gov>

Sent: Mon, Jul 17, 2017 2:29 pm

Subject: re-mink

Good afternoon,
Please see the following email in response to your request for data.
Thank you,
April Quade
U.S. Department of Agriculture, National Agricultural Statistics Service
Agricultural Statistics Board, Public Affairs Section
Room 5038, South Building
1400 Independence Avenue, SW
Washington, DC 20250
T: 800-727-9540 F: 202-690-2090
From: Salmon, Miste - NASS
Sent: Monday, July 17, 2017 3:27 PM
To: Customer Service - NASS <nass@nass.usda.gov>
Cc: Quade, April - NASS <April.Quade@nass.usda.gov>
Subject: RE: re-mink
Hi April,
No, I am not able to any of the questions in the data request.  The Fur Commission, which represents US mink farmers, would be able to help him or refer him to someone that could address his questions.
Here is their information:

Miste Salmon

USDA, National Agricultural Statistics Service

Livestock Branch, Poultry & Specialty Commodities Section

Phone:  202-720-3244 |  Fax:  855-593-5474

From: Customer Service - NASS 

Sent: Monday, July 17, 2017 3:13 PM

To: Salmon, Miste - NASS <Miste.Salmon@nass.usda.gov>

Subject: FW: re-mink
Hi Miste,
I’m not sure if you can provide an answer for the following email or not.  If not, any suggestions?
Thank you,
April Quade
U.S. Department of Agriculture, National Agricultural Statistics Service
Agricultural Statistics Board, Public Affairs Section
Room 5038, South Building
1400 Independence Avenue, SW
Washington, DC 20250
T: 800-727-9540 F: 202-690-2090
 From: Terry Singeltary [mailto:flounder9@verizon.net
Sent: Friday, July 14, 2017 4:09 PM
To: Customer Service - NASS <nass@nass.usda.gov>
Cc: USDA_ESMIS@cornell.edu
Subject: re-mink
Greetings NASS et al, 
i have kept up with the mink population for years, but have never heard of any testing programs for mink, testing for the Transmissible Mink Encephalopathy TME TSE Prion disease. i was wondering if there is such a program to test mink for the TME TSE Prion disease? are mink used as a by-product for feed for any species? this recent study showing cwd transmission to pigs by the oral route is very troubling, considering the major loophole in the feed ban to date with cervid. i remember the work Marsh did with the Mink and feed, that turned out to be caused by 95%+ dead stock downer cow feed, that caused the TME. so i am very curious as to any such testing for mink, and are mink allowed in any type of feed?
hope you can help me out, many thanks!
kindest regards, terry

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3.3.5 Chronic Wasting Disease: Lateral Transmission 3049 3050 305 I 3052 3053 

Because the potential impact of this source is insignificant (see Section 2.3.5), we do not quantitatively model its impact on the prevalence of BSE in the U.S. cattle population or its contribution to contamination of the U.S. food supply. 

3053 3.3.6 Mink 3054 3055 3056 3057 3058 3059 3060 3061 3062 3063 3064 3065 3066 3067 3068 3069 3070 3071 3072 3073 3074 3075 3076 3077 

As is the case with cervids, FDA regulations prohibit the administration to cattle of feed fortified with protein derived from mink, although this ban may not completely prevent such exposures. 

This section describes our development of an upper bound estimate on this exposure, which we estimate to be on the order of 1 cattle oral IDso annually. 

The true value is likely to be substantially lower, and could be zero. 

Our methodology is similar to that used to evaluate the exposure risk associated with CWD. 

Annual cattle exposure to TME attributable to consumption of mink-derived protein is the product of the 

1) number of diseased animals harvested, 

2) the number of mink IDsl,s per animal slaughtered, 

3) the fraction of animals rendered, 

4) the inverse of the species barrier, and 

5) the proportion of infectivity surviving rendering and administered to cattle. 

Number of diseased animals harvested: A total of 2.6 million mink are harvested in the U.S. annually (U.S. Department of Agriculture 200 lb). The prevalence of disease is unknown. We assume that the prevalence of clinical and pre-clinical disease are both similar to the corresponding rates for scrapie, or approximately 0.1% and 10%, respectively. Hence, we estimate that there are 2,600 clinical animals and 260,000 pre-clinical animals slaughtered each year. 

Number of mink ID50s per case: As we estimated for scrapie, we assume that pre-clinical animals harbor an average of 600 mink ID50s, whereas clinical animals harbor 10,000 mink ID50s. 

Fraction of animals rendered We estimate that 60% of slaughtered mink are rendered (Platt 2001). 

- 89 - 

 Section 3 3078 3079 3080 308 1 3082 3083 3084 3085 3086 3087 3088 3089 3090 3091 3092 3093 3094 

The species barrier: Experimental transmission of TME from the Stetsonville outbreak to cattle via i.c. inoculation resulted in animals developing a fatal spongiform encephalopathy (Marsh 1991), although it appeared to be distinct from BSE. As with CWD, we assume that the species barrier for TME transmitted to cattle is 10(5).

Proportion of infectivity surviving rendering and administered to cattle: As in the case of CWD, we assume that this value is now 0.1%. 

Total infectivity reaching cattle: Total infectivity reaching cattle from clinical TME cases amounts to 0.2 cattle oral ID50s annually, while the corresponding value for pre-clinical animals is 0.9 cattle oral ID50s. 

The total amounts to 1 cattle oral ID50 per year, or approximately 0.1 cattle oral ID50s per month. 

Because this source exposes cattle to substantially less infectivity than does scrapie (as modeled in Section 3.3.3), we do not quantitatively model its impact on the prevalence of BSE in the U.S. cattle population or its contribution to contamination of the U.S. food supply.

3.3.7 Pigs 

3095 3096 3097

*** Because the potential impact of this source is insignificant (see Section 2.3.7), we do not quantitatively model its impact on the prevalence of BSE in the U.S. cattle population or its contribution to contamination of the U.S. food supply.

3099 3.3.8 Poultry

3100 Because the potential impact of this source is insignificant (see Section 2.3.8), we do not quantitatively model its impact on the prevalence of BSE in the U.S. cattle population or its contribution to contamination of the U.S. food supply.

3103 3104 3.3.9 

Recycled Waste


Because the potential impact of this source is insignificant (see Section 2.3.9), we do not quantitatively model its impact on the prevalence of BSE in the U.S. cattle population or its contribution to contamination of the U.S. food supply. 3108 

Journal of General Virology (1994), 75, 2151-2155. Printed in Great Britain 2151 

Experimental infection of mink with bovine spongiform encephalopathy

Mark M. Robinson, 1,2. William J. Hadlow, 3 Tami P. Huff, 1 Gerald A. H. Wells, 4 Michael Dawson, 4 Richard F. Marsh s and John R. Gorham L2

1 USDA-ARS Animal Disease Research Unit, Bustad 337, WSU, Pullman, Washington 99164-7030, 2 Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040, 3 908 South Third Street, Hamilton, Montana 59840-2924, U.S.A., 4 Central Veterinary Laboratory, New Haw, Addlestone, Surrey KT15 3NB, U.K. and 5 Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, Wisconsin 53706, U.S.A.

To determine whether the aetiological agent of bovine spongiform encephalopathy (BSE) is pathogenic for mink, standard dark mink were inoculated with coded homogenates of bovine brain from the U.K. Two homogenates were from cows affected with BSE. The third was from a cow that came from a farm with no history of having had BSE or having been fed ruminantderived, rendered by-products, the proposed vehicle for introduction of the BSE agent. Each homogenate was inoculated intracerebraUy into separate groups of mink and a pool of the three was fed to a fourth group. Signs of neurological disease appeared in mink an average of 12 months after intracerebral inoculation and 15 months after feeding. Decreased appetite, lethargy and mild to moderate pelvic limb ataxia were the predominant clinical signs, quite unlike the classic clinical picture of transmissible mink encephalopathy (TME). Microscopic changes in brain sections of most affected mink were those of a scrapie-like spongiform encephalopathy. Vacuolar change in grey matter neuropil was accompanied by prominent astrocytosis. Varying greatly in severity from one mink to another, the degenerative changes occurred in the cerebral cortex, dorsolateral gyri of the frontal lobe, corpus striatum, diencephalon and brainstem. 

Although resembling TME, the encephalopathy was distinguishable from it by less extensive changes in the cerebral cortex, by more severe changes in the caudal brainstem and by sparing of the hippocampus. 

***The results of this study extend the experimental host range of the BSE agent and demonstrate for the first time the experimental oral infection of mink with a transmissible spongiform encephalopathy agent from a naturally infected ruminant species. 


Author item Hamir, Amirali item Kunkle, Robert item Miller, Janice item Greenlee, Justin item Richt, Juergen Submitted to: International Veterinary Vaccines and Diagnostics Conference Publication Type: Abstract Only Publication Acceptance Date: 3/15/2006 Publication Date: 6/25/2006 Citation: Hamir, A.N., Kunkle, R.A., Miller, J.M., Greenlee, J.J., Richt, J.A. 2006. 

Experimental transmission of transmissible mink encephalopathy (TME) to cattle by intracerebral inoculation [abstract]. 4th International Veterinary Vaccines and Diagnostics Conference. p. 89. Paper No. PO53.

Interpretive Summary: Technical Abstract: 

To compare clinicopathological findings of transmissible mink encephalopathy (TME) with other transmissible spongiform encephalopathies (TSE, prion diseases) that have been shown to be experimentally transmissible to cattle (sheep scrapie, and chronic wasting disease, CWD), 2 groups of calves (n = 4 each) were intracerebrally inoculated with TME agents from 2 different sources (mink with TME and a bovine with TME). 

Two uninoculated calves served as controls. 

*** Within 15.3 months post inoculation (PI), all animals from both inoculated groups developed clinical signs of central nervous system (CNS) abnormality; their CNS tissues had microscopic spongiform encephalopathy (SE); and PrP**res was detected in their CNS tissues by immunohistochemistry (IHC) and Western blot (WB) techniques. 

*** These findings demonstrate that intracerebrally inoculated cattle not only amplify TME PrP**res but also develop clinical CNS signs and extensive lesions of SE. 

*** The latter has not been shown with other TSE agents (scrapie and CWD) similarly inoculated into cattle. 

The findings also suggest that the diagnostic techniques currently used for confirmation of bovine spongiform encephalopathy (BSE) would detect TME in cattle should it occur naturally. 

However, it would be a diagnostic challenge to differentiate TME in cattle from BSE. 

Our recent preliminary results indicate that WB may be able to differentiate between bovine TME and BSE.


Title: Evaluation of the zoonotic potential of transmissible mink encephalopathy

Author item Comoy, Emmanuel item Mikol, Jacqueline item Ruchoux, Marie-madeleine item Durand, Valerie item Luccantoni-freire, Sophie item Dehen, Capucine item Correia, Evelyne item Casalone, Cristina item Richt, Juergen item Greenlee, Justin item Torres, Juan Maria item Brown, Paul item Deslys, Jean-philippe

Submitted to: Pathogens Publication Type: Peer Reviewed Journal Publication Acceptance Date: 7/30/2013 Publication Date: 7/30/2013 

Citation: Comoy, E.E., Mikol, J., Ruchoux, M., Durand, V., Luccantoni-Freire, S., Dehen, C., Correia, E., Casalone, C., Richt, J.A., Greenlee, J.J., Torres, J.M., Brown, P., Deslys, J. 2013. Evaluation of the zoonotic potential of transmissible mink encephalopathy. Pathogens. 2:(3)520-532.

Interpretive Summary: Cases of bovine spongiform encephalopathy (BSE) or mad cow disease can be subclassified into at least 3 distinct disease forms with the predominate form known as classical BSE and the others collectively referred to as atypical BSE. Atypical BSE can be further subdivided into H-type and L-type cases that are distinct from classical BSE and from each other. Both of the atypical BSE subtypes are believed to occur spontaneously, whereas classical BSE is spread through feeding contaminated meat and bone meal to cattle. Transmissible mink encephalopathy (TME) is another prion disease that transmits to cattle and show similarities to L-type BSE when subjected to laboratory testing. The purpose of this study was to use non-human primates (cynomologous macaque) and transgenic mice expressing the human prion protein to determine if TME could represent a potential risk to human health. TME from two sources (cattle and raccoons) was able to infect non-human primates and transgenic mice after exposure by the intracranial route. This result suggest that humans may be able to replicate TME prions after an exposure that allows infectious material access to brain tissue. At this time, it is unknown whether non-human primates or transgenic mice would be susceptible to TME prions after oral exposure. The results obtained in these animal models were similar to those obtained for L-type BSE. Although rare, the existence of TME and that it transmits to cattle, non-human primates, and transgenic mice suggest that feed bans preventing the feeding of mammalian tissues to cattle should stay in place and that regular prion surveillance during the slaughter should remain in place. Parties with interest in the cattle and beef industries and regulatory officials responsible for safe feeding practices of cattle will be interested in this work.

Technical Abstract: Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis to the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques assume a low cattle-to-primate species barrier: we therefore evaluated the zoonotic potential of cattle-adapted TME. In less than two years, this strain induced in cynomolgus macaques a neurological disease similar to L-BSE and distinct from c-BSE. TME derived from another donor species (raccoon) induced a similar disease with shorter incubation periods. 

***L-BSE and cattle-adapted TME were also transmissible to transgenic mice expressing human PrP. Interestingly, secondary transmissions to transgenic mice expressing bovine PrP showed the maintenance of prion strain features for the three tested bovine prion strains (cattle TME, c-BSE and L-BSE) regardless of intermediate host. 

***Thus, TME is the third animal prion strain transmissible to both macaques and humanized transgenic mice, suggesting zoonotic potentials that should be considered in the risk analysis of animal prion diseases for human health. Moreover, the similarities between TME and L-BSE are highly suggestive of a link between those strains, and of the presence of L-BSE decades prior to its identification in USA and Europe.

Rev. sci. tech. Off. int. Epiz., 1992, 11 (2), 539-550 Transmissible mink encephalopathy * R.F. MARSH ** and W.J. HADLOW *** 

Summary: Transmissible mink encephalopathy (TME) is a rare disease of ranch-raised mink caused by exposure to an as yet unidentified contaminated food ingredient in the ration. The clinical and pathological similarities between TME and scrapie, together with the indistinguishable physicochemical characteristics of their transmissible agents, suggest that sheep may be the source of infection. However, experimental testing of oral susceptibility of mink to several different sources of sheep scrapie have been unsuccessful. These results indicate that either the feeding of scrapie-infected sheep tissues to mink is not the cause of TME, or that there exists a strain of sheep scrapie having high mink pathogenicity that remains unknown. Additional sources of sheep scrapie need to be tested in mink, and epidemiological investigations of new incidents of TME need to emphasise obtaining a thorough history of past feeding practices. KEYWORDS: Cattle - Encephalopathies - Food-borne disease - Mink - Scrapie - Sheep - Unidentified feed ingredient. 


Experimental transmission to other species

TME has been experimentally transmitted to the European ferret (Mustela putorius furo) (8, 27), striped skunk (Mephitis mephitis) and raccoon (Procyon lotor) (8), American sable (pine marten) (Martes martes) and beech marten (Martes foina) (19), Syrian hamster (Mesocricetus auratus) (27) and Chinese hamster (Cricetus griseus) (22), rhesus monkey (Macaca mulatta) (7, 27), stumptail macaque (Macaca arctoides) (7), squirrel monkey (Saimiri sciureus) (7), sheep and goat (13), and cattle (31).

Attempts to transmit TME to mice have been unsuccessful (12, 27, 32). Interestingly, scrapie agent from naturally-infected Suffolk sheep which was passaged three times in mink became non-pathogenic for mice (unpublished data).

Experimental TME in these recipient species always produces long incubation periods (months to years) followed by a progressive course of neurological disease ending in death. Their pathological responses have also been similar, featuring microvacuolation of the grey matter (spongiform degeneration) and reactive 


astrocytosis. However, differences have been observed in the behaviour of the TME agent on backpassage to mink. TME produced in the skunk and raccoon (8), rhesus and squirrel monkey and stumptail macaque (6), sheep (13) and goat (13, 16), cattle (31), and early passages in Syrian hamsters (2, 16, 29) all backpassage relatively easily into mink. In contrast, high passage Syrian hamster TME (2, 29) and ferret TME (unpublished data) are not transmissible back to mink. 

Physicochemical properties of the transmissible agent

The original studies of Burger and Hartsough (3) demonstrated that the TME agent was filterable through 0.5 µm Seitz filtres, resistant to heating in a boiling water bath for 15 min., and resistant to treatment with 0.3% formalin for 12 h at 37°C. Further studies later showed that the transmissible agent is less than 50 nm minimum dimension, sensitive to diethylether, resistant to ultraviolet irradiation, relatively resistant to 10% formalin in minced brain tissue, and sensitive to proteolytic digestion (25).


Association with feed and estimation of the length of incubation in naturally-exposed mink

The numerous observations of the occurrence of TME on mink ranches sharing feed firmly establishes the infection as a food-borne disease. It is also possible to estimate minimal and maximal incubation periods based on the age of affected mink and the transfer of animals from one ranch to another. The observation that mink transferred seven months previously from the Wisconsin mink ranch in 1947 also developed TME indicates that this would be a minimum incubation period, a finding consistent with the seven month incubation of TME after experimental oral exposure of mink to infected brain tissue (3, 31). More importantly, a maximum incubation period of ten to twelve months is apparent in at least two incidents of TME (Hayward and Stetsonville, Wisconsin) since some animals less than twelve months of age were affected (3,31). Epidemiological studies on the Stetsonville incident of TME in 1985 further show that exposure must have occurred during a six to eight week period between the time when young kits began to consume the mink feed and when a group of 600 new animals were introduced to the herd and remained unaffected.

Association with specific feed ingredients

There is no definite association between the occurrence of TME and feeding sheep tissues to mink. Conversely, there are two incidents of TME which occurred in Ontario in 1963 (12) and Stetsonville (Wisconsin) in 1985 (31), where the mink rancher stated with a high degree of certainty that sheep had not been fed. The Stetsonville incident is especially interesting because this rancher was a "dead stock" feeder who used mostly dairy cows which he collected daily within a 50-mile radius of his mink ranch. Meat-and-bone meal is commonly used in mink feeds. In the 1940s and 1950s, individual ranchers blended their own cereal mixtures, often including meat-and-bone meal purchased from the local feed store. This practice was discontinued in the 1960s when commercial mink food cereals became available from suppliers like Kellogg and Purina. While these blends often contain meat-and-bone meal of unknown species 


composition, they are an unlikely source of TME since they are prepared in large batches and distributed to hundreds of mink ranches.

Experimental testing of mink susceptibility to sheep scrapie and bovine transmissible mink encephalopathy

To test the experimental susceptibility of mink to the scrapie agent, six sources of sheep brain from the United Kingdom, one drowsy goat brain, and fourteen mouseadapted "strains" (all gifts from Dr Alan G. Dickinson, former Director of the Neuropathogenesis Unit in Edinburgh) were injected intracerebrally into a total of 65 mink. Only one of these animals developed a TME-like disease after an incubation period of 22 months (29). Other experiments testing American sources of the sheep scrapie agent have resulted in all mink inoculated intracerebrally with either of two scrapie-infected Suffolk sheep brains developing TME-like disease in 11 to 12 months (15) and 16 to 24 months (29) post-infection. In these studies, a brain from an American Cheviot sheep with scrapie failed to produce disease in mink, and scrapieinfected sheep or goat brain was not pathogenic for mink by oral exposure. Although these findings do not seem to support the premise that TME results from feeding sheep tissues infected with the scrapie agent to mink, they clearly show that different sources of the agent can vary in their pathogenicity for mink. Therefore, it is possible a sheep scrapie agent may exist that is capable of producing disease in mink 7 to 12 months after oral exposure.

To investigate the possibility that the Stetsonville incident of TME may have been caused by feeding infected cattle tissues to mink, two Holstein steers were inoculated intracerebrally with mink brain. A fatal spongiform encephalopathy developed in both after 18 and 19 months (31). Backpassage of each bovine brain into mink by either intracerebral inoculation or oral exposure resulted in rapid transmission of TME with incubation periods of 4 and 7 months, respectively. These findings indicate little deadaptation of the TME agent for mink after one passage in cattle, and they are consistent with the Stetsonville incident of TME being caused by feeding tissues of infected cattle. The implications of this possibility for spreading an unrecognised BSElike disease in American cattle are discussed elsewhere (24, 33).


Onset of clinical disease is insidious and is often assessed most readily by an observer familiar with the normal behaviour of the particular mink. Usually, hyperexcitability, hyperesthesia, and increased aggressiveness are the first behavioural changes detected. The mink vigorously attacks, almost as though frenzied, an object moved along the sides of the cage. Its responses to touch and sound are exaggerated. Loud noises easily startle it. Early on, the mink becomes careless in defecating; it deposits feces randomly instead of at a single site as normal mink do. At this stage, the mink often consumes less feed. This seems more a reflection of its reluctance to climb the side of the cage to obtain feed placed on the top rather than of inability to do so or of diminished appetite. Within a few days to a week or so, unsteadiness of the hindquarters becomes evident, especially when the mink is forced to move rapidly or caused to turn sharply. It falls repeatedly to the side. 


As the initial hyperexcitability wanes, the mink acquires a fixed facial expression and is often found in a quiet state with its head down. When aroused, it becomes active but resumes the drowsy attitude once it is left undisturbed. In many mink, the tail becomes curled over the back much like that of a squirrel. Occasionally, tremor of the whole body, or shivering occurs. Some mink circle continually. Convulsions are rare. Impaired vision progressing to almost complete blindness often supervenes. As the disease progresses, incoordination of the hind limbs becomes increasingly worse. The mink then tends to slide along on its abdomen by propelling itself with its fore limbs. When they too become affected, forward locomotion is virtually impossible. True (flaccid) paralysis does not occur. The mink is able to move its hind limbs but they are typically held in a flexed position close to the body. Resistance to their passive movement is often increased. Response to pin-prick seems normal. Compulsive biting of self or objects characteristically dominates the behaviour of the mink in the advanced stage of the disease. Once a mink bites down on an object, it holds on tenaciously either because it refuses to let go or because it is unable to do so. Biting the flanks and tail is common and often causes severe mutilation, such as partial amputation of the tail, which usually proves fatal. Eventually, the mink becomes less aware of its surroundings. It spends much of the time in a deeply somnolent state from which it is not easily aroused. In the end, it becomes stuporous and is often found dead with its teeth firmly clamped onto the wire mesh of the cage. Typically, the disease evolves slowly and relentlessly over a period of weeks. In a few mink, however, it follows a rapidly-advancing downhill course to death in about a week. Mink kept in outside sheds during the winter may die after an unusually short course, perhaps because of some failure in thermoregulation. Exceptionally, the course is prolonged for several months. But most mink die in an unkempt, debilitated state two to seven weeks after onset of clinical signs. The disease is always fatal.


As in the related encephalopathies, the essential lesion of TME comprises spongiform change in the grey matter neuropil, neuronal degeneration and astrocytosis (9). Generally, the spongiform change is the most striking component. Composed of small, round, optically empty vacuoles, it varies in severity from scattered patches of holes to diffuse rarefaction of the grey matter. The most common expression of neuronal degeneration is shrinkage and increased basophilia of nerve cells. They become angular and stain uniformly dark, obscuring the nuclei. In areas of severe degeneration, neurons may disappear. Much less commonly, neurons have large vacuoles in their cytoplasm. Such cells are found mainly in the brain stem. Astrocytosis (hypertrophy and hyperplasia of fibrous astrocytes) is also a prominent component of the lesion the extent of which is best demonstrated by Cajal's gold sublimate technique. Its intensity tends to parallel that of the spongiform change. Usually it becomes apparent as an increased number of large pale, naked nuclei often disposed in clusters, but occasionally gemistocytic astrocytes are seen. Even when intense, the astrocytosis is not accompanied by any appreciable laying down of astroglial fibres. The topographical distribution of these neurohistological changes helps distinguish TME from other spongiform encephalopathies. Characteristically, the cerebral cortex (neocortex) is regularly the site of the spongiform change, neuronal degeneration, 


and diffuse astrocytosis. They are most severe in gyri of the frontal lobes, especially in the middle and deeper layers. The degenerative lesion becomes less severe in the more caudal lobes of the cerebral hemisphere. Changes in the hippocampus are moderate, whereas those in the central amygdaloid nucleus are regularly severe. The corpus striatum is also a regular site of spongiform change and astrocytosis, as is the diencephalon. Severe degeneration occurs in the thalamus, though not in all nuclei. Especially affected are those of the caudal dorsal portion of the thalamus and the medial geniculate nucleus. In general, the changes in the hypothalamus are more uniformly distributed.

Although the neurohistological changes also occur in the more caudal parts of the brain, they are generally less severe and more variable than those rostrally. Changes are found in most structures of the midbrain tectum and tegmentum, but especially in the caudal colliculus and periaqueductal grey matter. In the pons and medulla oblongata, the changes are even less severe and more limited in their distribution. Here, the astrocytosis is much less intense and the spongiform change more variable than in the more rostral structures. Affected nuclei include the vestibular, hypoglossal, lateral reticular and dorsal motor nucleus of the vagus. In contrast to what happens in some spongiform encephalopathies, the cerebellum is spared, as is the spinal cord. This description pertains to the disease as seen in North America. It varies somewhat from that given for TME occurring elsewhere (20).


Age, sex, and colour phase susceptibility

Studies have shown no appreciable difference in the susceptibility of mink to TME based on age, sex, or colour phase as measured by the length of incubation in animals inoculated by various routes and the endpoint titre of infectivity in brain tissue (26, 28). One difference has been observed in brain lesions produced in mink inoculated intracerebrally with TME; aged mink homozygous for the Aleutian gene and manifesting the Chediak-Higashi syndrome have reduced spongiform degeneration compared with mink without this genetic anomaly or young mink with the syndrome (28).

Temporal and endstage distribution of the transmissible mink encephalopathy agent Extraneural tissues of mink have little TME infectivity. Animals inoculated subcutaneously have no extraneural infectivity until twenty weeks post-infection when the agent can also be first detected in the brain. After this time, the brain infectivity steadily increases to titres as high as 106LD5 0 per gram, while the infectivity in extraneural tissues (spleen, liver, kidney, intestine, mesenteric lymph node, and submandibular salivary gland) seldom exceed 103LD5 0 per gram (14). Other experiments measuring the distribution of infectivity in terminally affected mink inoculated either intramuscularly or intracerebrally have also shown low concentrations of the agent in extraneural tissues (26).

These findings, especially the limited extraneural replication of the TME agent, suggest that mink are not natural hosts of the agent (14). 



The diagnosis of TME is based on the appearance of progressive neurological disease in adult mink having neurohistological changes of spongiform degeneration of grey matter. These findings should be confirmed by experimental transmission to mink (3,4, 11, 17, 18,31) and by demonstration of the disease-specific prion protein ( PrP S c o r SAF protein) (1, 21, 31). PREVENTION, CONTROL AND ERADICATION Mink ranchers have been informed that feeding sheep (23) or downer cows (30) to their animals may result in TME. Because mink appear to be only an accidental host for this agent, however, the main impetus for eradication must be in identifying the source of infection. If the disease results from a rare "strain" of the scrapie agent in sheep, additional testing of scrapie-infected sheep brains in mink may determine the prevalence of such a pathogen. The successful control of scrapie would therefore eliminate the occurrence of TME.

If TME results from feeding infected cattle tissues to mink, there must be an unrecognised BSE-like infection in American cattle and in other countries where TME has been reported. This hypothetical agent need not have biological properties identical to those of the BSE agent because it is likely that cattle could be infected with several "strains" as are sheep. The significance of this scenario is not the importance this rare cattle disease may have for mink, but rather the impact it could have on cattle populations where changes in the feeding of animal protein increase the likelihood of cattle-to-cattle transmission.

Commercially-reared mink are a sentinel species trapped in an unnatural food chain. The identification of the feed ingredient causing TME may provide new insights into the epidemiological inter-relationships between the animal spongiform encephalopathies and, perhaps, into the properties of their transmissible agents that determine host specificity.

* * *


Résumé: L'encéphalopathie transmissible du vison (transmissible mink encephalopathy: TME), maladie rare du vison d'élevage, est provoquée par un constituant de la ration qui contamine celle-ci et qui n'a pas été identifié à ce jour. Ses caractéristiques cliniques et anatomo-pathologiques, semblables à celles de la tremblante, ainsi que les propriétés physico-chimiques non différenciables de leurs agents étiologiques, permettent de penser que le mouton est la source de l'infection. Cependant, les essais de contamination du vison par voie orale, avec du matériel infectieux provenant de cas de tremblante du mouton ont échoué. Ces résultats démontrent que la présence dans l'alimentation du vison, de tissus contaminés par l'agent de la tremblante, n'est pas responsable de la TME, ou qu'il existe une souche de tremblante inconnue très pathogène pour le vison. Il est nécessaire de faire appel à du matériel infectieux provenant 


d'autres cas de tremblante du mouton pour vérifier leur effet chez le vison. Il conviendra également, lors de nouveaux épisodes de TME, d'approfondir les recherches épidémiologiques pour avoir une connaissance complète des antécédents alimentaires.

MOTS-CLÉS : Bovins - Composantes non identifiées des aliments - Encéphalopathies - Ovins - Toxi-infections alimentaires - Tremblante - Vison.

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LA ENCEFALOPATÍA TRANSMISIBLE DEL VISÓN. - R.F. Marsh y W.J. Hadlow. Resumen: La encefalopatía transmisible del visón (transmissible mink encephalopathy: TME) es una enfermedad rara del visón de cría provocada por un ingrediente contaminado de la ración alimentaria que todavía no se ha identificado. Dadas las similitudes clínicas y patológicas entre la TME y el prurigo lumbar, así como la imposibilidad de diferenciar las características fisicoquímicas de sus agentes de transmisión, cabe pensar que la fuente de infección son los ovinos. Sin embargo, las pruebas de sensibilidad oral del visón a material infectado procedente de casos de prurigo lumbar ovino han fracasado. Estos resultados indican que, o bien la TME no se debe a la alimentación del visón con tejidos ovinos infectados por el agente del prurigo lumbar, o existe una cepa desconocida de prurigo lumbar muy patógena para el visón. Es preciso realizar nuevas pruebas exponiendo los visones a otras fuentes de prurigo lumbar, y profundizar las investigaciones epidemiológicas relativas a nuevos casos de TME a fin de obtener una relación completa de sus antecedentes alimentarios. PALABRAS CLAVE: Bovinos - Encefalopatías - Infección alimentaria - Ingrediente alimentario no identificado - Ovinos - Prurigo lumbar - Visón.

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1. BENNETT A.D., BIRKETT CR. & BOSTOCK C.J. (1992). - Molecular biology of scrapielike agents. In Transmissible Spongiform Encephalopathies of Animals (R. Bradley & D. Matthews, eds.). Rev. sci. tech. Off. int. Epiz., 11 (2) (in press).

2 . BESSEN R.A. & MARSH R.F. (1992). - Identification of two biologically distinct strains of transmissible mink encephalopathy in hamsters. J. gen. Virol., 73, 329-334.

3 . BURGER D. & HARTSOUGH G.R. (1965). - Encephalopathy of mink. II. Experimental and natural transmission. J. infect. Dis., 115, 393-399.

4 . DANILOV E.P., BUKINA N.S. & AKULOVA B.P. (1974). - Encephalopathy in mink (in Russian). Krolikovod. Zverovod., 17, 34.

5. DUKER I.I., GELLER V.I., CHIZHOV V.A., ROIKHEL V.M., POGODINA V.V., FOKINA G.I., SOBOLEV S.G. & KOROLEV M.B. (1986). - Clinical and morphological investigation of transmissible mink encephalopathy (in Russian). Vopr. Virusol., 31, 220-225 .

6. ECKROADE R.J. (1972). - Neuropathology and experimental transmission to other species of transmissible mink encephalopathy. PhD Thesis, University of Wisconsin-Madison. 549

7. ECKROADE R.J., Zu RHEIN G.M., MARSH R.F. & HANSON R.P. (1970). - Transmissible mink encephalopathy: experimental transmission to the squirrel monkey. Science, 169, 1088-1090.

8. ECKROADE R.J., Zu RHEIN G.M. & HANSON R.P. (1973). - Transmissible mink encephalopathy in carnivores: clinical, light and electron microscopic studies in raccoons, skunks and ferrets. J. infect. Dis., 9, 229-240 .

9. ECKROADE R. J., Zu RHEIN G.M. & HANSON R.P. (1979). - Experimental transmissible mink encephalopathy: brain lesions and their sequential development in mink. In Slow Transmissible Diseases of the Nervous System, Vol. 1 (S.B. Prusiner & W.J. Hadlow, eds.). Academic Press, New York, 409-449 .

10. GORHAM J. (1991). - Viral and bacterial diseases of mink raised in the Soviet Union. Fur Rancher, May/June, 3 .

11. HADLOW W.J. (1965). - Discussion of paper by D. Burger and G.R. Hartsough. In Slow, Latent, and Temperate Virus Infections (D.C. Gajdusek, C.J. Gibbs Jr & M. Alpers, eds.). NINDB Monograph 2 . U.S. Government Printing Office, Washington D.C, 303-305 .

12. HADLOW W.J. & KARSTAD L. (1968). - Transmissible encephalopathy of mink in Ontario. Can. vet. J., 9, 193-195.

13. HADLOW W.J., RACE R.E. & KENNEDY R.C. (1987). - Experimental infection of sheep and goats with transmissible mink encephalopathy virus. Can. J. vet. Res., 51 (1), 135-144.

14. HADLOW W.J., RACE R.E. & KENNEDY R.C. (1987). - Temporal distribution of transmissible mink encephalopathy virus in mink inoculated subcutaneously. J. Virol., 61 (10), 3235-3240.

15. HANSON R.P., ECKROADE R.J., MARSH R.F., Zu RHEIN G.M., KANITZ C.L. & GUSTAFSON D.P. (1971). — Susceptibility of mink to sheep scrapie. Science, 172, 859-861 .

16. HANSON R.P. & MARSH R.F. (1973). - Biology of transmissible mink encephalopathy and scrapie. In Slow Virus Diseases (W. Zeman & E.H. Lennette, eds.). Williams & Wilkins, Baltimore, 10-15.

17. HARTSOUGH G.R. & BURGER D. (1965). - Encephalopathy of mink. I. Epizootiologic and clinical observations. J. infect. Dis., 115, 387-392.

18. HARTUNG J., ZIMMERMANN H. & JOHANNSEN U. (1970). - Infectious encephalopathy in mink. I. Clinico-epidemiological and experimental studies (in German). Mh. VetMed., 25, 385-388 .

19. HARTUNG J., JOHANNSEN U. & ZIMMERMANN H. (1975). - Infectious encephalopathy in mink. III. Results of further field surveys and transmission experiments (in German). Mh. VetMed., 30, 23-27 .

20. JOHANNSEN H. & HARTUNG J. (1970). - Infectious encephalopathy in mink. II. Pathological studies (in German). Mh. VetMed., 25, 389-395 .

2 1 . KIMBERLIN R.H. (1992). - Bovine spongiform encephalopathy. In Transmissible Spongiform Encephalopathies of Animals (R. Bradley & D. Matthews, eds.). Rev. sci. tech. Off. int. Epiz., 11 (2) (in press).

22. KIMBERLIN R.H., COLE S. & WALKER C.A. (1986). - Transmissible mink encephalopathy (TME) in Chinese hamsters: identification of two strains of TME and comparisons with scrapie. Neuropathol. appl. Neurobiol., 12 (2), 197-206.

2 3. MARSH R.F. (1966). - Transmissible mink encephalopathy. Can sheep by-products transmit it to mink? Am. Fur Breeder, June, 19.

24. MARSH R.F. (1991). - Risk assessment on the possible occurrence of bovine spongiform encephalopathy in the United States. In Sub-Acute Spongiform Encephalopathies. Proceedings of a Seminar in the CEC Agricultural Research Programme, Brussels, 12-1 4 November 1990 (R. Bradley, M. Savey & B.A. Marchant, eds.). Kluwer Academic Publishers, Dordrecht, Boston & London, 41-46 . 550

2 5 . MARSH R.F. & HANSON R.P . (1969). - Physical and chemical properties of the transmissible mink encephalopathy agent. J. Virol., 3, 176-181 .

2 6 . MARSH R.F. , BURGER D. & HANSON R.P . (1969). - Transmissible mink encephalopathy: behaviour of the disease agent in mink. Am. J. vet. Res., 30, 1637-1642.

2 7 . MARSH R.F. , BURGER D., ECKROADE R. , ZU RHEIN G.M. & HANSON R.P . (1969). - A preliminary report on the experimental host range of the transmissible mink encephalopathy agent. J. infect. Dis., 120, 713-719.

2 8 . MARSH R.F. , SIPE J.C., MORSE S.S. & HANSON R.P . (1976). - Transmissible mink encephalopathy: reduced spongiform degeneration in aged mink of the Chediak-Higashi genotype. Lab. Invest., 34 (4), 381-386.

2 9 . MARSH R.F. & HANSON R.P . (1979). - On the origin of transmissible mink encephalopathy. In Slow Transmissible Diseases of the Nervous System, Vol. 1 (S.B. Prusiner & W.J. Hadlow, eds.). Academic Press, New York, 451-460 .

3 0 . MARSH R.F . & HARTSOUGH G.R. (1988). - Evidence that transmissible mink encephalopathy results from feeding infected cattle. In Proceedings of the IVth International Congress on Fur Animal Production (B.D. Murphy & D.B. Hunter, eds.). Canadian Mink Breeders Association, Toronto, 204-207.

3 1 . MARSH R.F., BESSEN R.A., LEHMANN S. & HARTSOUGH G.R. (1991). - Epidemiological and experimental studies on a new incident of transmissible mink encephalopathy. J. gen. Virol., 72 (3), 589-594.

3 2 . TAYLOR D.M., DICKINSON A.G., FRASER H. & MARSH R.F. (1986). - Evidence that transmissible mink encephalopathy agent is biologically inactive in mice. Neuropathol. appl. Neurobiol, 12 (2), 207-215 .

3 3 . WUSTENBERG W . & MARSH R. (1990). - Is it safe to feed meat and bone meal? Hoard's Dairyman, December, 944 . 

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.


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

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. 


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

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells 3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ... 

The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province! ...page 26. 

*** 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. 

1283 2.3.5 Chronic Wasting Disease: Lateral Transmission 

1284 Direct contact between cattle and cervids in regions where CWD is prevalent may provide another pathway by which cattle may become infected. Epidemiologic modeling suggests that among cervids, environmental contact provides a pathway for the spread of CWD (Miller 2000). Moreover, the prevalence of the disease under experimental conditions appears to be extraordinarily high. For instance, when deer within the endemic research facilities have been introduced into CWD negative deer herds, the disease quickly reaches a prevalence of 50% to 60% (U.S. Food and Drug Administration 2001 a). Nonetheless, there is no evidence that CWD can cause TSEs in cattle. 

As noted in Section 2.3.4, any such transmission would be limited by what appears to be a substantial species barrier. Moreover, cattle cohabiting with CWD infected deer and elk in a research facility in the endemic area have shown no evidence of infection (Williams 2001). 

Finally, targeted surveillance of cattle brains (by immunohistochemistry and histopathology) from endemic areas have failed to reveal the presence of CWD or any other TSEs (Gould 2000). 

2.3.6 Mink 1300 Transmissible Mink Encephalopathy (TME) is a rare disease known to occur only in 1301 farm-raised mink.

Epidemiological studies have suggested that TME is a foodbome disease with an incubation period of between seven months and a year (Hartsough 1965). The disease is characterized by a long incubation period, a clinical course of several weeks, and neurological changes.
Mink experience increased aggressiveness, hyperexitability, ataxia, and hyperaesthesia. Cases in Wisconsin and Minnesota were recognized on mink ranches as eariy as 1947. Outbreaks have been reported in Ohio, Canada, Finland, Germany, and Russia. Five outbreaks have been recorded in the U.S., affecting a total of 23 mink ranches (Hartsough 1965; Hadlow 1987; Marsh

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Section 2

1991). Three of the outbreaks in Wisconsin were associated with the use of fallen or sick cattle in mink feed (Hartsough 1965; Marsh 1991). However, there is no consensus over the source of disease initiating these outbreaks. The rancher involved in the Stetsonville, Wisconsin outbreak claimed that his mink were fed only dead stock and that they were never fed sheep. In theory, transmission of TME to a bovine could cause BSE. Inoculation of cattle with TME via i.c. administration resulted in spongiform encephalopathy a short time later (Marsh 1991; Robinson 1995). 

***In addition, cattle passage of TME remains pathogenic to mink when administered either orally or via i.c. (Marsh 1991). 

***According to Marsh, these results suggest that the species barrier between mink and cattle may not be substantial. 

To protect against the possibility that TME might be transmitted to cattle, the FDA prohibits use of mink protein in ruminant feed. Mink are considered prohibited materials. The relatively small number of farmed mink, their small size, and recycling prohibitions make transmission of a prion disease from mink to cattle extremely unlikely.

2.3.7 Pigs

There is a theoretical risk that cattle could be exposed to a TSE as the result of consuming feed supplemented with porcine-derived protein. Moreover, the fact that federal regulations classify protein from pigs as non-prohibited increases the potential for cattle to be exposed to any infectivity they may harbor.

There are two potential sources of this exposure: a natural TSE that infects pigs (Section, and BSE-contaminated feed in the gut at the time the pig is slaughtered (Section In practice, neither infectivity source will make a substantial contribution to cattle exposure because only a small portion of porcine-derived MBM is used as cattle feed. One reason for the limited use of porcine-derived protein in cattle feed derives in part from its price. For example, in May, 2001, the price of porcine-derived protein was $238/ton, compared to $177/ton for soy protein (Southern States Cooperative 2001). 

***In addition, much rendered porcine protein is used in feed for pigs The remainder of this section outlines additional factors that influence the importance of this potential source of TSE exposure among cattle. Because this source is unlikely to be significant, we do not address it quantitatively in our risk assessment (Section 3). 

Section 2

1342 Potential Infectivity in Pigs due to TSE Infection

Pigs might become infected with a TSE as the result of any of the following possibilities: 

The existence of a porcine-specific TSE agent; 

A nonspecific TSE agent not yet adapted to pigs that has an incubation period that is longer than the life of the pig; or 

The spontaneous misfolding of the prion protein leading to a spontaneous TSE case in porcine.

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Consumer groups in the U.S. have expressed concern that it may be possible for a pig to become infected with a TSE. This concern stems from a 1979 incident in which one of 60 pigs presented with clinical neurologic signs, neurological degeneration, and gliosis on histopatological examination (Hansen 1999). However, further testing showed that the lesions were not patognomonic of spongiform encephalopathy (Detwiler 2000). Moreover, the animal in question was young, a factor that is inconsistent with the TSE diagnosis. 

SSC (Section 4.1 a in (European Union Scientific Steering Committee 1999b)) concluded that these factors argue against the presence of an unrecognized spongiform encephalopathy in pigs in the U.S. Other evidence also suggests that the existence of a porcine-specific TSE agent is unlikely. No naturally occurring TSE has ever been reported in pigs (European Union Scientific Steering Committee 1999b). 

Moreover, pigs inoculated orally with BSE have not developed disease (European Union Scientific Steering Committee 1999b). 

Experimental inoculation of pigs with different strains of Kuru via parenteral administration did not lead to spongiform encephalopathy 52 to 76 months post inoculation (Gibbs 1979). A similar result was reported for pigs challenged with scrapie (European Union Scientific Steering Committee 1999b) up to 63 months after inoculation. Pigs have also been challenged with brain material from cattle naturally infected with BSE by combined i.c., i.p., and i.v. routes (Dawson 1990). This experiment is still ongoing but preliminary results show that seven of ten pigs developed spongiform encephalopathy (Ryder 2000). Experience in the UK during the BSE outbreak, when swine had significant exposure to BSE contaminated feed, suggests that the disease did not cross the species barrier to infect pigs (MAFF (Ministry of Agriculture Fisheries and Food - now Dept for Environment Food and Rural Affairs) 2001 b).

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Section 2

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In an ongoing experiment in which ten pigs were subject to oral challenge with large amounts of brain from cattle naturally infected with BSE, none of the animals have developed clinical disease or neuropathologic changes. The oral challenge consisted of homogenized brain from confirmed cases of BSE. Each pig received 1.2 kg of brain divided into three doses administered at intervals of one week. Mouse bioassays of neural and non-neural tissues from pigs killed at 84 months post inoculation were initiated in October and November, 1997 and were completed in May, 2000. As of the drafting of this report, there is no evidence of residual infectivity in any of the tissues. These findings may indicate that the species barrier between pigs and cattle is higher than the species barrier between cattle and humans or between cattle and other animals that have developed spongiform encephalopathy after exposure to BSE-contaminated MBM.

The fact that a naturally occurring spongiform encephalopathy has never been reported in pigs may indicate that pigs are particularly resistant to this type of disease. That is, the species barrier between pigs and other species may have prevented the transmission of natural disease to pigs. For example, it is very likely that pigs in the UK were exposed to substantial doses of contaminated MBM before the implementation of the UK feed ban. Although most pigs are slaughtered at a very young age, there are a significant number of sows and boars that usually live until age four. The fact that parenterally challenged animals developed disease 17 months post inoculation suggests that these four year old animals were sufficiently old to develop disease.

Other species serve as examples. Marsh et al. (1969) noted the recovery of TME from the spleen of one chicken, and from spleen, caecom, tonsils, and bursa of Fabricius after i.v. inoculation. Race and Chesebro (1998a), have shown that after inoculation of mice that either did or did not express the prion protein (PrP) gene with the hamster scrapie strain 263K, no clinical disease was produced in mice. However, infectivity found in the brain and spleen of mice expressing the priori protein was capable of causing disease in hamsters but not in mice. Hill et al. (ZOOO), have shown the possible presence of subclinical TSE in certain animals by demonstrating that a strain of hamster prions thought to be nonpathogenic for conventional mice leads to high levels of prion replication in such mice without causing clinical disease. Alternatively, it is possible that cases in pigs in the UK have gone unnoticed. Finally, even if pigs could become infected with a TSE, most are slaughtered at a young age, making it unlikely that the disease would have time to generate more than a small amount of


Section 2

infectivity. For example, in 1998, more than 95% of the pigs slaughtered in the U.S. were no older than six months (U.S. Department of Agriculture 1998). Potential Infectivity in Materials Consumed by Pigs

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Even if pigs do not become infected with a TSE, contaminated material may be present in their digestive tract when they die. In particular, if feed administered to pigs contains cattle derived MBM that is contaminated with BSE, pigs could harbor BSE in their alimentary tract. The following discussion outlines several factors suggesting that the potential is limited for BSE to be recycled through the guts of pigs. First, most pigs are not exposed to cattle-derived MBM because there are many other economical sources of protein. For example, in the U.S., soybean meal is usually the most economical source of high quality protein available for porcine diets. It is comparable to animal proteins in terms of the quality of its amino acid components and can be used as the only protein source in most swine diets. Other sources of proteins fed to pigs include porcine MBM, peanut meal, fish meal, cottonseed meal, canola meal, sunflower meal, and raw soy beans. The amount of protein added to feed varies based on the specific needs of the animal as it grows. MBM, blood meal, and plasma can comprise between 2.5 and 5 percent of feed for pigs’between weaning and 60 days of age and during the animal’s growing and finishing stages. Because it is not uniformly used, it is likely that approximately 80% of the pigs grown in the United States never receive MBM.

Second, even among pigs that do receive cattle-derived MBM, it is likely that little if any feed would remain in the GI system at the time of processing because pigs are usually sent to slaughter after restricting feed intake for 14 to 16 hours. Third, due to the high water content of the GI tract, its contents are unlikely to be rendered.

Finally, if the gut contents are rendered, any BSE-contaminated material that does make its way back to cattle will have gone through rendering twice, thus providing an additional opportunity for infectivity to be destroyed by this treatment.


Section 2

1441 2.3.8 Poultry

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Many of the same factors that make pigs an unlikely source of infectivity for cattle also make chickens an unlikely source. As a result, we do not quantitatively address this source in our risk assessment (Section 3). 


seems if my primitive education does not fail me, intracranial means inside the skull, and peroral means by the mouth. seems the price of tse prion poker just keeps going up...terry

Location: Virus and Prion Research
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin
Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:
Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent. Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 challenge="" groups="" month="" pigs="" remaining="" the="">6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC. Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" oral="">6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). 
This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. 
CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. 
This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. 
Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...
 we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.
May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. 
3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. 
But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. 
Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....
 snip...see much more here ; 
Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease

Porcine prion protein amyloid 

Per Hammarstr€om and Sofie Nystr€om* IFM-Department of Chemistry; Link€oping University; Link€oping, Sweden 

ABSTRACT. Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. 

Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions. 

KEYWORDS. prion, pig, amyloid fibril, misfolding, transmissibility, seeding, TSE, prion strain, strain adaptation


What about pigs? 

 In several recent papers which in our view have not received sufficient attention the notion of prion resistant pigs was challenged by generation of transgenic mice with knocked out endogenous PrP and overexpressed PoPrP. Different lines of tgPoPrP mouse were proven to be susceptible to clinical disease triggered by a variety of prion strains, suggesting that the surrogate host species (mouse) and prion strain are more important than what PrP sequence it expresses for neurotoxicity to commence. In more detail, Torres and colleagues experimentally subjected transgenic mouse lines expressing porcine PrP to a number of different TSE isolates.24-26 Their studies demonstrate that prion infection is strain specific when porcine PrP is overexpressed (4x) and used as in vivo substrate. PoTg001 mice inoculated with classical scrapie, regardless of donor genotype, resisted prion disease both at first and second passage (Fig. 3b). On the other hand, Nor98 scrapie (Atypical scrapie) as well as BSE from both cattle and BoTg mouse model resulted in clinical disease in the PoTg001 mice. However, in the first generation, disease progression was slow. Incubation time until death was as long as 600 d and the hit rate was low. This indicates that disease has barely developed by the time the mice reach their natural life span limit which in this study was set to 650 d Already in the second passage the hit rate was 100 % and the incubation time was cut in half (Fig. 3b). No further shortening of incubation time was observed upon third passage. This shows that PoPrP is capable of forming infectious and neurotoxic prions in vivo if triggered by a compatible prion strain and if given enough time to develop. Both BSE and Nor98 rapidly adapts to the PoPrP host sequence, resulting in higher penetrance as well as in markedly shorter life span already in the second passage, well within the limits of normal life span for a mouse.

There are several crucial variables which impact the susceptibility of prion diseases and transmission studies.27 PrP sequence of host, PrP sequence of prion, prion strain, prion dosage, PrP expression level of host, host genetic background, route of transmission and neuroinvasiveness if peripherally infected.28 Importantly the PrP expression level corresponds to the rate of prion disease onset.1 This likely reflects 2 converging variables: a) PrP as a substrate to the prion misfolding reaction i.e. selfcatalyzed conversion and b) PrP as a mediator of neurotoxicity through interactions with misfolded PrP within prions.

The non-homologous recPrPs presented here and in,12 easily adapt to each other and form amyloid fibrils in accordance with what is seen in vivo when inoculum composed of BoPrP used to challenge mice expressing PoPrP (Fig. 3b).24-26 A review of the literature showed that BSE strains have a high degree of penetrance in both experimental and accidental transmission. Over 50% of the species reported to be susceptible to prion disease were infected by a BSE strain.19 Recent data form our lab shows that the promiscuity of BoPrP fibrils holds true also in the case of recombinant in vitro experiments. When cross-seeding human, bovine, porcine, feline and canine PrPs with any of the other, the recBoPrP seed outcompetes the other seeds in all instances except when the HuPrP acted as substrate (Data not shown). In this case recPoPrP fibrils have the highest seeding efficiency (Fig. 1). These findings in combination with the Torres experiments,24-26 implicate that a PoPrP substrate in vivo (in pigs) could adapt to an amyloidogenic prion strain of bovine or ovine prion disease and hence replicate in the new host.

For adaptation of experimental strains through multiple passages, donors are selected based on neurotoxicity (that is on TSE disease phenotype) not on basis of amyloid fibril formation. Hence the traits of transmissible amyloidotypic prion strains may be largely unexplored if these strains require more time to transform to neurotoxic strains e.g. as proposed by Baskakov’s model of deformed templating.8 There is experimental evidence for BSE transmission into pig via parenteral routes.16 with an incubation period of 2–3 years, well within what is to be considered normal lifespan. For a breeding sow in industrial scale pig farming that is 3–5 y (Bojne Andersson, personal communication).29,30 In small scale and hobby farming both sows and boars may be kept significantly longer. Collinge and Clarke.31 describe how prion titers reach transmissibility levels well before the prion burden is high enough to be neurotoxic and cause clinical disease. It is known that prion strains need time and serial passages to adapt. Knowing that pigs in modern farming are rarely kept for enough time for clinical signs to emerge in prion infected pigs it is important to be vigilant if there is a sporadic porcine spongiform encephalopathy (PSE) as has been seen in cattle (BASE) and sheep (Nor98). Hypothetically such a sporadic and then infectious event could further adapt and over a few generations have reached the point where clinical PSE is established within the time frame where pigs are being slaughtered for human consumption (Fig. 4).

FIGURE 4. Potential prion strain adaptation in pig. The red horizontal gradient indicates the hietherto unkown prion toxicity tolerance threshold for pigs, the blue vertical line indicates normal slaughter age for industrial pig farming, the green vertical line indicates the normal lifespan of a breeding sow in industrial scale pig farming, orange areas indicate window of neurotoxic prions before onset of clinical disease (dark orange indicates subclinical BSE as reported by Wells et al,16 pale orange indicate hypothetic outcome of PSE and strain adaptation. On the outmost right a potential subclinical sporadic PSE.


The pig is the most versatile species used by humans for food and other applications. Over 1,5 billion pigs are slaughtered each year worldwide for human use.32 Besides juicy pork sirloin other parts from pig are used for making remarkably diverse things such as musical instruments, china, leather, explosives, lubricants etc. Pig offal is used for human medicine, e.g., hormone preparations such as insulin and cerebrolysin, in xenographs, sutures, heparin and in gelatin for drug capsules.33,34

And that means not only pork, it means your pigskin wallet, catgut surgical suture...in tallow, in butter. It is undoubtedly in the blood supply. DC Gajdusek (From R. Rhodes ''Deadly Feast'' 35)

While the late Carleton Gajdusek had strong views in diverse areas of prion biology, according to journalist Richard Rhodes,35 he was correct on his prediction on BSE prions (vCJD) in the blood supply18 (see text box above). An opinionated scientist can sometimes be ignored due to a judgment of character and Gajdusek was certainly provocative. Notwithstanding society should remain vigilant on the possibility that Gajdusek was also prophetic on porcine prions given the exceptionally wide spread use of pigs in everyday human life and medicine. As discussed previously it is currently not established what relations transmissible neurotoxic prion strains and amyloid morphotypic mature APrP strains have. Given the hypotheses that amyloidotypic PrP conformations can transmit with low neurotoxicity.7,36 it is interesting to reflect on possible implications. Pigs are slaughtered at 6–8 months of age. Because amyloid deposition is associated with old age, this is likely far too young for spontaneous development of APrP amyloid from PoPrP as well as other amyloidogenic proteins. From the perspective of seeded amyloidogenesis it is however a potential ideal case for highly transmissible titers of APrP (Fig. 4). In such a scenario the potential of porcine prions constitutes the perfect storm, clinically silent due to neurotoxic resistance and with high titers of transmissibility. When it comes to prions CNS material is most heavily infected. In addition, however, fat tissue (to make lard and tallow) is known to harbor extraordinary amounts of amyloid in systemic amyloidoses.37 Amyloid fibrils of misfolded large proteins (AA, AL, ATTR) are notoriously hydrophobic due to the abnormal exposure of hydrophobic residues which normally in the folded structure being hidden in the protein core. The amyloid accumulation in fat tissue is likely a phase-separation from a rather hydrophilic environment in circulation toward the hydrophobic environment provided by adipocytes. Adipose tissue could in addition represent an in vivo environment well suitable for fibril formation. What about APrP?

In analysis of mice expressing Glycophosphatidylinositol, (GPI)-anchorless PrP, abdominal fat contains appreciable amounts of infectious prions in APrP isoform stained with ThS.38 Notably mice overexpressing anchorless PrP provides a silent carrier status for a long time prior to presenting symptoms and is severely afflicted by amyloid fibril formation following scrapie (RML) infection.39 Recall that this study showed that GPI-anchored PrP is needed to present clinical neurotoxicity. Evidently circulating anchorless-PrP (analogous to recPrP) is more amyloidogenic compared to GPI-anchored PrP and is poorly neuroinvasive.28 Amyloidosis is systemic in anchorless-PrP mice and is not limited to fat but is also found as extensive cardiac amyloid deposits.39 Interestingly cardiac APrP was recently reported in one BSE inoculated rhesus macaque which showed symptoms of cardiac distress prior to death from prion neurotoxicity.40 It is noteworthy that transgenic mice expressing PoPrP appear sensitive to strains with biochemical features of amyloidogenic prion strains i.e., BSE and Nor98.25,26,36 (Fig. 3b). We recently adopted the parallel inregister intermolecular b-sheet structural model of the APrP fibril from the Caughey lab to rationalize cross-seeding between various PrP sequences.12,41 It is tempting to use this structural model to speculate on the adaptation of mono-N-glycolsylated PoPrP at the expense of double-N-glycolylated PrP in the original BSE inoculum reported in the Torres experiments.25,26 In this APrP model monoglycosylated PrP at N197 is structurally compatible while N181 is not, due to burial in the in-register intermolecular cross-beta sheet (Fig. 5).

It appears that amyloidotypic prion strains, APrP, are transmissible but associated with lower neurotoxicity compared to diffuse aggregated PrP associated with synaptic PrP accumulations. It is possible that the amino acid substitutions in PoPrP compared to HuPrP and BoPrP are important for neurotoxic signal transmission (Fig. 2b, 5). The main issue hereby is that transmissibility of APrP will remain undetected unless used for surveillance. AA amyloidosis is frequent in many animals (e.g. cattle and birds) but is exceptionally rare in pigs.42 suggesting that APrP should it reside in pig fat would be traceable using newly developed screening methods.37


Should the topic of porcine PrP amyloid be more of a worry than of mere academic interest? Well perhaps. Prions are particularly insidious pathogens. A recent outbreak of peripheral neuropathy in human, suggests that exposure to aerosolized porcine brain is deleterious for human health.43,44 Aerosolization is a known vector for prions at least under experimental conditions.45-47 where a mere single exposure was enough for transmission in transgenic mice. HuPrP is seedable with BoPrP seeds and even more so with PoPrP seed (Fig. 1), indicating that humans could be infected by porcine APrP prions while neurotoxicity associated with spongiform encephalopathy if such a disease existed is even less clear. Importantly transgenic mice over-expressing PoPrP are susceptible to BSE and BSE passaged through domestic pigs implicating that efficient downstream neurotoxicity pathways in the mouse, a susceptible host for prion disease neurotoxicity is augmenting the TSE phenotype.25,26 Prions in silent carrier hosts can be infectious to a third species. Data from Collinge and coworkers.21 propose that species considered to be prion free may be carriers of replicating prions. Especially this may be of concern for promiscuous prion strains such as BSE.19,48 It is rather established that prions can exist in both replicating and neurotoxic conformations.49,50 and this can alter the way in which new host organisms can react upon cross-species transmission.51 The na€ıve host can either be totally resistant to prion infection as well as remain non-infectious, become a silent non-symptomatic but infectious carrier of disease or be afflicted by disease with short or long incubation time. The host can harbor and/or propagate the donor strain or convert the strain conformation to adapt it to the na€ıve host species. The latter would facilitate infection and shorten the incubation time in a consecutive event of intra-species transmission. It may be advisable to avoid procedures and exposure without proper biosafety precautions as the knowledge of silence carrier species is poor. One case of iatrogenic CJD in recipient of porcine dura mater graft has been reported in the literature.52 The significance of this finding is still unknown. The low public awareness in this matter is exemplified by the practice of using proteolytic peptide mixtures prepared from porcine brains (Cerebrolysin) as a nootropic drug. While Cerebrolysin may be beneficial for treatment of severe diseases such as vascular dementia,53 a long term follow-up of such a product for recreational use is recommended.


No potential conflicts of interest were disclosed


This work was supported by G€oran Gustafsson foundation, the Swedish research council Grant #2011-5804 (PH) and the Swedish Alzheimer association (SN).



***In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research, however, suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008). It is apparent, though, that CWD is affecting wild and farmed cervid populations in endemic areas with some deer populations decreasing as a result.

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.

Monday, April 04, 2016

*** Limited amplification of chronic wasting disease prions in the peripheral tissues of intracerebrally inoculated cattle ***



TUESDAY, APRIL 18, 2017 


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


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.


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.


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).


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.


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.


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.


What is the risk of chronic wasting disease being introduced into Great Britain? A Qualitative Risk Assessment October 2012

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 well as non-ruminants such as cats and dogs as well, as soon as possible for the following reasons...

31 Jan 2015 at 20:14 GMT

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

31 Jan 2015 at 20:14 GMT

Terry Singeltary Sr. comment ;




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

Greetings again FDA and Mr. Pritchett et al,

I would kindly like to comment on ;

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


Guidance for Industry

Use of Material from Deer and Elk in Animal Feed

This version of the guidance replaces the version made available September15, 2003.

This document has been revised to update the docket number, contact information, and standard disclosures. Submit comments on this guidance at any time.

Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified with the Docket No. FDA-2003-D-0432 (formerly 03D-0186).

For further information regarding this guidance, contact Burt Pritchett, Center for Veterinary Medicine (HFV-222), Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, 240-402-6276, E-mail: burt.pritchett@fda.hhs.gov.

Additional copies of this guidance document may be requested from the Policy and Regulations Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, and may be viewed on the Internet at either http://www.fda.gov/AnimalVeterinary/default.htm or http://www.regulations.gov.

U.S. Department of Health and Human Services Food and Drug Administration Center for Veterinary Medicine March 2016

Contains Nonbinding Recommendations


Guidance for Industry Use of Material from Deer and Elk in Animal Feed

This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title page.

I. Introduction

Under FDA’s BSE feed regulation (21 CFR 589.2000) most material from deer and elk is prohibited for use in feed for ruminant animals. This guidance document describes FDA’s recommendations regarding the use in all animal feed of all material from deer and elk that are positive for Chronic Wasting Disease (CWD) or are considered at high risk for CWD. The potential risks from CWD to humans or non-cervid animals such as poultry and swine are not well understood. However, because of recent recognition that CWD is spreading rapidly in white-tailed deer, and because CWD’s route of transmission is poorly understood, FDA is making recommendations regarding the use in animal feed of rendered materials from deer and elk that are CWD-positive or that are at high risk for CWD.

In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

II. Background

CWD is a neurological (brain) disease of farmed and wild deer and elk that belong in the animal family cervidae (cervids). Only deer and elk are known to be susceptible to CWD by natural transmission. The disease has been found in farmed and wild mule deer, white-tailed deer, North American elk, and in farmed black-tailed deer. CWD belongs to a family of animal and human diseases called transmissible spongiform encephalopathies (TSEs). These include bovine spongiform encephalopathy (BSE or “mad cow” disease) in cattle; scrapie in sheep and goats; and classical and variant Creutzfeldt-Jakob diseases (CJD and vCJD) in humans. There is no known treatment for these diseases, and there is no vaccine to prevent them. In addition, although validated postmortem diagnostic tests are available, there are no validated diagnostic tests for CWD that can be used to test for the disease in live animals.

Contains Nonbinding Recommendations

III. Use in animal feed of material from CWD-positive deer and elk

Material from CWD-positive animals may not be used in any animal feed or feed ingredients. Pursuant to Sec. 402(a)(5) of the Federal Food, Drug, and Cosmetic Act, animal feed and feed ingredients containing material from a CWD-positive animal would be considered adulterated. FDA recommends that any such adulterated feed or feed ingredients be recalled or otherwise removed from the marketplace.

IV. Use in animal feed of material from deer and elk considered at high risk for CWD Deer and elk considered at high risk for CWD include: (1) animals from areas declared by State officials 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 immediately before the time of slaughter were in a captive herd that contained a CWD-positive animal.

FDA recommends that materials from deer and elk considered at high risk for CWD no longer be entered into the animal feed system. Under present circumstances, FDA is not recommending that feed made from deer and elk from a non-endemic area be recalled if a State later declares the area endemic for CWD or a CWD eradication zone. In addition, at this time, FDA is not recommending that feed made from deer and elk believed to be from a captive herd that contained no CWD-positive animals be recalled if that herd is subsequently found to contain a CWD-positive animal.

V. Use in animal feed of material from deer and elk NOT considered at high risk for CWD FDA continues to consider materials from deer and elk NOT considered at high risk for CWD to be acceptable for use in NON-RUMINANT animal feeds in accordance with current agency regulations, 21 CFR 589.2000. Deer and elk not considered at high risk include: (1) deer and elk from areas not declared by State officials to be endemic for CWD and/or to be CWD eradication zones; and (2) deer and elk that were not at some time during the 60-month period immediately before the time of slaughter in a captive herd that contained a CWD-positive animal.


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

Greetings again FDA and Mr. Pritchett et al,

MY comments and source reference of sound science on this very important issue are as follows ;

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

I kindly wish to once again submit to Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed.

Thank you kindly for allowing me to comment again, ...and again...and again, on a topic so important, why it is ‘NON-BINDING’ is beyond me.

this should have been finalized and made ‘BINDING’ or MANDATORY OVER A DECADE AGO.

but here lay the problem, once made ‘BINDING’ or ‘MANDATORY’, it is still nothing but ink on paper.

we have had a mad cow feed ban in place since August 1997, and since then, literally 100s of millions of pounds BANNED MAD COW FEED has been sent out to commerce and fed out (see reference materials).


so, in my opinion, any non-binding or voluntary regulations will not work, and to state further, ‘BINDING’ or MANDATORY regulations will not work unless enforced.

with that said, we know that Chronic Wasting Disease CWD TSE Prion easily transmits to other cervid through the oral route.

the old transmission studies of BSE TSE floored scientist once they figured out what they had, and please don’t forget about those mink that were fed 95%+ dead stock downer cow, that all came down with TME. please see ;

It is clear that the designing scientists must also have shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection.

it is clear that the designing scientists must have also shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection.

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.


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


Sunday, March 20, 2016

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


Tuesday, April 19, 2016

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

10 years post mad cow feed ban August 1997 


Date: March 21, 2007 at 2:27 pm PST 


Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007 CODE Cattle feed delivered between 01/12/2007 and 01/26/2007 RECALLING FIRM/MANUFACTURER Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007. 

Firm initiated recall is ongoing. 

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

VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI ___________________________________ 


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. 


16 years post mad cow feed ban August 1997 2013 

Sunday, December 15, 2013 


Tuesday, December 23, 2014 


17 years post mad cow feed ban August 1997 

Monday, October 26, 2015 





Bovine Spongiform Encephalopathy BSE TSE Prion disease, aka mad cow disease. 


In vitro amplification of H-type atypical bovine spongiform encephalopathy by protein misfolding cyclic amplification 

"When considering the atypical L-BSE and H-BSE diseases of cattle, they have been assessed in both non-human primate and transgenic mouse bioassays (with mice transgenic for human PRNP) and both model systems indicate that H-BSE and L-BSE may have increased zoonotic potential compare with C-BSE. The detection of all types of BSE is therefore of significant importance." 

Monday, January 09, 2017 

Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle CDC Volume 23, Number 2—February 2017 

Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle. 


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

Wednesday, December 21, 2016 


Tuesday, September 06, 2016

A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation

Saturday, July 23, 2016


Tuesday, July 26, 2016

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

Monday, June 20, 2016

Specified Risk Materials SRMs BSE TSE Prion Program

Thursday, December 08, 2016 

USDA APHIS National Scrapie Eradication Program October 2016 Monthly Report Fiscal Year 2017 atypical NOR-98 Scrapie 

Saturday, December 01, 2007

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

Sunday, December 10, 2006

Transmissible Mink Encephalopathy TME

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

Wednesday, April 25, 2012


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

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

Wednesday, July 15, 2015

Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed?

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

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

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

Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT

First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 

Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 

University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 

This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 

Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 

At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 





Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened?

TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress

TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD

TUESDAY, JULY 04, 2017


MONDAY, JULY 17, 2017 

National Scrapie Eradication Program May 2017 Monthly Report Fiscal Year 2017

TUESDAY, MARCH 28, 2017 

*** Passage of scrapie to deer results in a new phenotype upon return passage to sheep ***

SUNDAY, JULY 16, 2017

*** Temporal patterns of chronic wasting disease prion excretion in three cervid species ***

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

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

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.

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

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

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

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


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

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

Saturday, April 23, 2016


Saturday, April 23, 2016

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 

why do we not want to do TSE transmission studies on chimpanzees $

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.



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

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

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

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

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

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



THURSDAY, JUNE 22, 2017 

World Organisation for Animal Health (OIE) to establish liaison office in College Station, Texas

THURSDAY, JULY 13, 2017 

EFSA BSE Sixty cases of mad cow disease since 2001 breached feed ban likely the cause 

Scientists investigate origin of isolated BSE cases

National Prion Center could lose all funding just as concern about CWD jumping to humans rises

SATURDAY, JULY 15, 2017 

National Prion Center could lose all funding just as concern about CWD jumping to humans rises

Terry S. Singeltary Sr.


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