CHRONIC WASTING DISEASE FOUND IN 24 MORE DEER IN ALBERTA

[flounder]

Wednesday, June 18, 2008

CHRONIC WASTING DISEASE FOUND IN 24 MORE DEER IN ALBERTA

http://chronic-wasting-disease.blogspot.com/2008/06/chronic-wasting-disease-found-in-24.html

Wasting disease found in 24 more deer

Erika Beauchesne Edmonton Journal

Wednesday, June 18, 2008

Twenty-four more cases of chronic wasting disease have been found in Alberta's wild deer, the Sustainable Resource Development of Alberta announced Tuesday.

The results, from a 2007-08 testing program, bring the province's count of the disease up to 53 cases.

CWD affects the central nervous system and causes infected animals to slowly waste away. Evidence suggests it does not affect humans. Darcy Whiteside, spokesperson for Sustainable Resource and Development, said the department has consulted with communities such as Provost, Oyen and Wainwright, where many of the diseased deer have been detected.

"The next step is really making hunters aware there are opportunities here," he said, referring to an ongoing hunting program the government implemented in 2005 when the first diseased deer was found 30 kilometers southeast of Oyen.

The program aims to reduce deer populations and track the disease.

"It's a contagious disease, so any animal we can take away from the population is a plus," he said, adding the province was seeing excessive growth in the number of wild deer even before CDW.

But Whiteside said the new numbers are not huge. "We're still seeing very low percentages," he said. "There were more deer tested this year."

http://www.canada.com/calgaryherald/news/story.html?id=182814b1-f9ac-4872-8860-a03d218ae460

CHRONIC WASTING DISEASE IN ALBERTA

Public Significance

This disease poses significant economic problems for farmers of elk and deer. CWD was unintentionally introduced into farmed elk populations from live wild elk and deer taken from affected areas in the U.S. It was then TRANSLOCATED to farms in various states as well as SASKATCHEWAN AND KOREA. The source of the infection on farms in Alberta is not known. The economics of trade in live elk and their products (primarily antler velvet) have been seriously affected. IN ADDITION, the association with BSE has let to possible PUBLIC HEALTH CONCERNS. ...

http://www.srd.gov.ab.ca/fishwildlife/livingwith/diseases/pdf/WDcwd.pdf

SEE CWD ALBERTA CASE BY CASE

http://www.srd.gov.ab.ca/fishwildlife/livingwith/diseases/chronicwastingdisease.aspx#CWD

http://www.srd.gov.ab.ca/fishwildlife/livingwith/diseases/chronicwastingdisease.aspx#CWD

SEE MAP UPDATE JANUARY 2008 UPDATE

http://www.srd.gov.ab.ca/fishwildlife/livingwith/diseases/pdf/Jan%202008%20fact%20sheet.pdf

http://www.srd.gov.ab.ca/fishwildlife/default.aspx

8. Human susceptibility to CWD

Millions of North Americans hunt deer and elk (U.S. Department of the Interior, Census Bureau), and there is no doubt that people have been exposed to CWD through venison consumption, particularly in light of recent data showing CWD prions in muscle [2]. Human susceptibility to CWD or to other newly emerging animal TSE [9, 14] is still unclear, although we can be somewhat reassured in that there have been no large scale outbreaks of human TSE cases in Colorado and Wyoming, where CWD has existed for decades [51]. Up until approximately 10 years ago, autopsies were not performed on suspect human TSE cases in many states due to biosafety concerns, therefore the diagnosis of potential new TSE strains has been hampered. This indicates that clinical TSE diagnoses in humans were not confirmed, nor was any strain typing done to look for the appearance of potentially subtle or unusual pathological or biochemical phenotypes of a new TSE strain. Fortunately, the autopsy rate for suspect cases is improving. At the National Prion Disease Pathology Surveillance Center at Case Western Reserve University (Cleveland, Ohio), Creutzfeldt-Jakob disease (CJD) suspect cases are studied and classified by CJD subtype. Thus far,

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*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,

however there have been no unusual or novel prion subtypes that might indicate the appearance of a new prion strain [7, 41]. Other indirect studies of human susceptibility to CWD also suggest that the risk is low. In biochemical conversion studies, Raymond et al. [68] showed that the efficiency of CWD to convert recombinant human PrP into amyloid fibrils was low, but similar to that of both BSE and scrapie fibrils to do the same. These results suggest that there is a molecular incompatibility in the conversion of human PrPC by CWD, sheep scrapie, or BSE, and that cross species infections in humans may be rare events. To determine whether common PrPSc strain features may link CWD and CJD, histopathology and the PrPSc biochemical characteristics from deer and elk were compared with that of humans with sporadic CJD (sCJD) cases that are methionine homozygous at codon 129 of the Prnp gene by Xie et al. [96], although strain features including histologic profile, target organs, and glycoform patterns will not necessarily remain the same upon crossing species barriers [6, 5, 8, 57]. The PrPSc form is cleaved by proteinase-K (PK) at different sites depending on the conformation of the protein and may aid determination of whether the PrPSc conformation is similar. By western blot (SDS-PAGE) of elk CWD, the unglycosylated PK-resistant PrPSc migrated at 21 kDa, similar to sCJD (MM1 subtype) and the PK cleavage site was the same, occurring at residues 78 and 82 as assessed by N-terminal sequencing. Conformational stability was evaluated by measuring the PrPSc stability under partially denaturing conditions and also showed no significant difference between elk CWD and sCJD MM1 PrPSc. However, elk CWD and human sCJD MM1 strains exhibited distinct glycoform patterns by two dimensional gel electrophoresis, suggesting that the strains differed. Future studies may utilize luminescent conjugated polymers, which were recently shown to distinguish naturally- and experimentally-derived prion strains [79]. To study elk-human prion species barriers, Kong et al. inoculated elk CWD into transgenic mice expressing either human PrP or elk PrP. Whereas the elk PrP expressing mice developed disease after only 118-142 days post-inoculation, human PrP expressing mice (129M) did not develop any features of TSE after more than 657 or more than 756 days [41]. In accordance with these results, Tamgüney et al. also reported that human PrP overexpressing mice were not susceptible to 9 CWD isolates from mule deer, white-tailed deer, and elk [84]. However, mice have a limited lifespan and further passages may be necessary to detect low levels of prion infectivity that may be present subclinically. Although indi rect evidence is accumulating that there may be a robust species barrier for CWD transmission to humans, one report indicates nonhuman primate susceptibility to CWD. Intracerebral inoculation of squirrel monkeys (Saimiri sciureus) demonstrated a positive CWD transmission [49]. Among non-human primates, however, the Prnp sequence of the new world monkeys are the most distant from humans [72], and therefore may not indicate that human prion conversion would occur by CWD.

snip...

11. Disease control challenges posed by CWD

Evidence is building that indicates efficient horizontal transmission occurs in CWD, indeed a complicating aspect in disease control [91]. Potential transmission mechanisms range from spread via direct contact among animals to environmental exposure through grazing in areas contaminated by prion-infected secretions, excretions (saliva, urine, feces), tissues (placenta), or decomposed carcasses. Recently, in a breakthrough finding, saliva from CWD infected deer was shown to transmit prion disease [50]. An additional experiment by Miller and colleagues showed that CWD-infected carcasses allowed to decay naturally in confined pastures can lead to CWD infections in captive deer, demonstrating the potential for environmental contamination to spread infection [55]. Modelling studies have provided further

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support that environmental contamination is likely playing a significant role in transmitting CWD [56, 53]. Additionally, infectious prions have been demonstrated to bind soil particles and remain infectious to animals by both intracerebral and oral exposure routes [38, 37]. Prion infectivity has been recovered from soil more than two years after experimental exposure to prions, suggesting the soil may serve as a reservoir for CWD prions [75]. Taken together, these results indicate that there may even be multiple sources for CWD exposure, perhaps through direct contact and environmental routes. Significant challenges to CWD eradication exist in free-ranging cervids. Infected deer and elk range over a broad geographic region, and even previously surmised geographic barriers such as the Continental Divide have proven passable by infected animals. Ridding the environment of CWD-contaminated soil or even CWD-infected carcasses is not possible. Moreover, the available ante-mortem diagnostic tests for surveillance are laborious and impractical for large numbers of free-ranging animals [74, 88, 95]. Therefore for a wildlife manager, this disease is costly to survey and difficult to control.

12. Conclusion

CWD in cervids is efficiently transmitted, likely more than any other TSE in animals or humans. Therefore, it is unlikely that this TSE can be eradicated, but perhaps through an improved understanding of transmission routes, biological factors influencing pathogenesis, and the molecular basis of CWD prion conversion, a targeted strategy for interrupting disease spread may be developed.

Acknowledgements

I thank Drs. Michael Miller, Jason Bartz and Mathias Heikenwalder for critical review of the manuscript.

snip...see full text 19 pages ;

http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v08092.pdf

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

Subject: Species barriers for chronic wasting disease by in vitro conversion of prion protein Date: November 3, 2007 at 10:57 am PST

Species barriers for chronic wasting disease by in vitro conversion of prion protein

Li Li a, Michael B. Coulthart b, Aru Balachandran c, Avi Chakrabartty d, Neil R. Cashman a,* a Brain Research Centre, Division of Neurology, Department of Medicine, University of British Columbia and Vancouver Coastal Health, UBC Hospital, 2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5 b Prion Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Man., Canada R3E 3R2 Q1 c National Reference Laboratory for Scrapie and CWD, Animal Diseases Research Institute, Canadian Food Inspection Agency, 3851 Fallowfield Road, Nepean, Ont., Canada K2H 8P9 d University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, Ont., Canada M5G 1L7 Received 6 October 2007

Abstract

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that can affect North American cervids (deer, elk, and moose). Using a novel in vitro conversion system based on incubation of prions with normal brain homogenates, we now report that PrPCWD of elk can readily induce the conversion of normal cervid PrP (PrPC) molecules to a protease-resistant form, but is less efficient in converting the PrPC of other species, such as human, bovine, hamster, and mouse. However, when substrate brain homogenates are partially denatured by acidic conditions (pH 3.5), PrPCWD-induced conversion can be greatly enhanced in all species. Our results dem- onstrate that PrPC from cervids (including moose) can be efficiently converted to a protease-resistant form by incubation with elk CWD prions, presumably due to sequence and structural similarities between these species. Moreover, partial denaturation of substrate PrPC can apparently overcome the structural barriers between more distant species.

snip...

Although Syrian hamsters were initially deemed resistant to CWD [19], a recent publication demonstrates that CWD can be transmitted and adapted to hamster [20].

snip...

Substrate denaturation and human health

We confirm with multiple species that acid/GdnHCl- treated brain PrPC is a superior substrate for in vitro con- version than untreated PrPC, possibly by overcoming con- formational barriers in partial denaturation of substrate PrPC. PrP conversion in scrapie-infected neuroblastoma cells is believed to occur in endosomes, a low-pH and reducing environment [26]. The non-ruminant stomach possesses a low pH lumen, and PrPC is expressed in this organ [27]. Such acidic (denaturing) organ or cellular organellar environments might also promote CWD trans- mission to non-cervid species, including humans.

Acknowledgments

This work was supported by the Canadian Institutes of Health Research (Institute of Infection and Immunity, Safe Food and Water program) and PrioNet Canada.

[20] G.J. Raymond, L.D. Raymond, K.D. Meade-White, A.G. Hughson, C. Favara, D. Gardner, E.S. Williams, M.W. Miller, R.E. Race, B. Caughey, Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains, J. Virol. 81 (2007) 4305–4314.

http://jvi.asm.org/cgi/content/abstract/81/8/4305

2007 Elsevier Inc. All rights reserved.

Please cite this article in press as: L. Li et al., Species barriers for chronic wasting disease by in vitro..., Biochem. Biophys. Res. Commun. (2007), doi:10.1016/j.bbrc.2007.10.087

http://www.sciencedirect.com/

Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains

Gregory J. Raymond1, Lynne D. Raymond1, Kimberly D. Meade-White1, Andrew G. Hughson1, Cynthia Favara1, Donald Gardner2, Elizabeth S. Williams3§, Michael W. Miller4, Richard E. Race1*, and Byron Caughey1*

Running title: CWD transmission to rodent species

Laboratory of Persistent Viral Diseases1, and Rocky Mountain Veterinary Branch2, NIAID, NIH, Rocky Mountain Laboratories, Hamilton, MT 59840; Department of Veterinary Sciences, University of Wyoming, Laramie, WY 820703; Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526-20974. §deceased *corresponding authors: Byron Caughey, Rocky Mountain Labs, 903 S. 4th St, Hamilton, MT 59840, USA; [email protected]; Tel: (406) 363-9264; FAX: (406) 363-9286 Richard Race, Rocky Mountain Labs, 903 S. 4th St, Hamilton, MT 59840, USA; [email protected]; Tel: (406) 363-9358; FAX: (406) 363-9286

In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer and elk were inoculated intracerebrally into various rodent species to assess their susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters; transgenic mice expressing the Syrian golden hamster prion protein; and, RML Swiss and C57 BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian and Armenian hamsters had limited susceptibility to certain of the CWD inocula as evidenced by incomplete attack rates and long incubation periods. With serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized as isolates with either short (85-89 days) or long (408-544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained, or diverged into, at least two distinct transmissible spongiform encephalopathy strains.

snip...

Differences in PrP-res glycoform patterns analyzed from several CWD- affected deer and elk have also suggested that CWD in mule deer may be more heterogeneous than in elk (19). Curiously, however, this apparent strain difference was not manifested when the identical mule deer CWD inoculum was serially passaged through only one recipient species. Serial passage in Sg hamsters yielded only the fast isolate (Table 1 and Figure 3), while passage first through the Tg (haPrP) mice then into Sg hamsters yielded only the slow isolate (Table 2 and Figure 3). With this in mind, it is important to consider other possible explanations for these results. One possibility is that CWD might be able to undergo a stochastic change into a more rapid and aggressive strain in Sg hamsters, and that this happened to occur after the mule deer CWD inoculations. A similar emergence of both fast and slow strains has been observed upon inoculation of TME into Sg hamsters (5). These strains developed even when a clonal isolate of the TME inoculum was used, suggesting that they arose in the recipient Sg hamsters rather than in the mink source (1). Finally, although extensive precautions were taken, we cannot formally prove that inadvertent contamination of the mule deer CWD inoculum with hamster-derived 263K strain did not occur which potentially could yield short- incubation-period passages in Sg hamsters (Table 1). However, the incubation period observed with the CWD passages (85-89 d) were significantly longer than 263K incubation periods observed in our lab (70-75 d) and no mock-infected

controls became sick during their lifespan. Also, we saw no 263K-like infectivity develop in the highly susceptible Tg (haPrP) mice even though we used the identical primary inoculum for both recipient species. Interestingly, the similarity of the Sg hamster-adapted CWD fast isolate and 263K might be due to a common origin since there is circumstantial evidence that CWD arose from cervid exposure to sheep scrapie, which was also the origin of the 263K strain in hamsters (14). Furthermore, the Hyper strain derived from TME inoculations has 263K-like strain characteristics in Sg hamsters (5). Thus, it would appear that both CWD and TME transmissions into Sg hamsters can result in divergent fast and slow strains.

end...

http://jvi.asm.org/cgi/reprint/JVI.02474-06v1

http://jvi.asm.org/cgi/content/abstract/JVI.02474-06v1

Transmissible Mink Encephalopathy TME

http://transmissible-mink-encephalopathy.blogspot.com/

see full text ;

CWD

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

Wednesday, June 18, 2008

CHRONIC WASTING DISEASE FOUND IN 24 MORE DEER IN ALBERTA

http://chronic-wasting-disease.blogspot.com/2008/06/chronic-wasting-disease-found-in-24.html

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

 

[Kathy]

Check out the map indicating where these CWD positive animals were found. Once again, not far from CFB Suffield (actuall its a NATO base), and CFB Wainwright.

Time to find out how many of these animals were identified as being CWD positive from brain samples, tonsil samples, and/or both. Dr Pybus stated at the Feb 2008 CWD meeting in Nisku, AB that most of the CWD positives were only positive in the tonsils - and not positive in the brain tissue, yet many were also emaciated.

The animals from the hunters were likely all diagnosed based on brain samples, as they may or may not have had tonsil/lymph tissue with their head submittions.

Evidence of CWD in the brain indicates inhalation of the small metal nanoparticles that are responsible for the formation of prion fibrils. Time for the Alberta and Saskatchewan government to come clean on what metals are they identifying in these samples: tungsten, depleted uranium, strontium, barium, et al.

By identifying the metal nucleator that deforms the proteins and causes the formation of the protein fibrils, the SOURCE of the metals can then be isolated and stopped.

 

[bse-tester]

Kathy rote:

Evidence of CWD in the brain indicates inhalation of the small metal nanoparticles that are responsible for the formation of prion fibrils. Time for the Alberta and Saskatchewan government to come clean on what metals are they identifying in these samples: tungsten, depleted uranium, strontium, barium, et al.

A bold statement that may contain some truths Kathy but to pose the above as being the only implied cause would be a stretch. Otherwise a bold statement that has merit perhpas. But can we be sure those particles were in the general vicinity at the time and where did they originate and also, keep in mind that deer tend to live their entire lives within a few square mile of where they were born.

 

[Kathy]

Hey Ron how's it going? Haven't had alot of time for the boards, but here are some more thoughts.

It's 5 years since the first identified Canadian cases of BSE. Research in Edmonton, you'd think, has burned the prion material to temperatures that would eliminate all the protein material, and leave just the elements. I thought that was why they kept the labs in edmonton, not calgary, because that is where the research reactor is at.

We have a fairly large spread, and we see deer come and go. I noticed how researchers in Sask, tried tracking the herds, and they said that they stay close to home - so to speak. But, that is a big assumption to apply to ALL animals. The antelope in our area travel down to the Red Deer river for winter and come back here in the spring/summer. Thats quite a distance, compared to the tracking data presented in Nisku.

Another thing is that these insoluble fired metal nanoparticles are re-suspended in the atmosphere with daylight heating. They are then blown in the wind, and redeposited in fog, rain or snow. I'm sure during winter blizzards we are exchanging snow with regions far north and south from us. It will snow a few inches, then the winds pick up, and its gone. Where does it go? Where-ever the wind takes it.

I do believe that the main kahonas KNOW what the problem is, and they are keeping it from us - because they think they know best and they will fix it.

Don't worry though, once all the livestock producers have registered their premises, the authorities can track the problem and work on eliminating the producer - thus the diseased animals. "This premise off-limits" signs will be going up - maybe a sign business is a good 'exit strategy'.

I saw a TV report that showed how in situ uranium mining in Texas is drawing the metal from deep water wells. They said it was just ignorance and bad luck that the people using water wells from this area were unknowingly drinking "heavy water". Contamination is natural - has nothing to do with their leaching processes. [sound familiar, like the coal bed methane in Albertan's water wells].

Is it going to be Albertans' and Saskatchewans' bad luck, that the wells (water, oil, gas, mining) are contaminated with radio-active resources. It's natural, just because we brought it to the surface and spread the waste (drilling mud and mine tailings, for example) on your land and now your cows are sick.... don't blame us, its inevitable; it's business.

The NATO forces don't even have to be using DU arsenal, they just have to use our tungsten weapons to hit a DU plated (inactive) tank. Either way, the DU burns and the region is coated with the toxic metal nanoparticles.

I don't believe the military when they say they don't/haven't used DU weapons at Suffield. Its the largest military base in the Western Hemisphere, surrounded by sparsely populated communities. It's perfect for testing all kinds of nasty stuff.

The CWD east of CFB Wainwright could be related to the incinerator they have there also.

 

[Kathy]

RELATED ARTICLE from Not One More Acre - ranchers fighting against the expansion of the Pinon Canyon Military Maneuver Site:

Not 1 More Acre!
PO Box 773
Trinidad, Colorado 81082

[email protected]

Please phone your thanks to Wes McKinley for standing up with and for taxpayers everywhere: 303.866.2398.


Lawmaker: Uranium Found In Soil At Pinon Canyon Site
McKinley Also Wants To Know Why Army Didn't Ask For Help Fighting Wildfire

DENVER -- A Colorado lawmaker said high levels of uranium have been found in soil samples he took from Fort Caron's training site in southeastern Colorado.

Democratic state Rep. Wes McKinley said he collected the samples during a tour of the 238,000-acre Piñon Canyon Maneuver Site earlier this year and had them analyzed by a laboratory.

He didn't identify the lab.

The Army didn't immediately return phone messages.

McKinley said the samples showed uranium levels as high as 60 parts per million. State regulations require a cleanup if uranium levels are above 20 parts per million.

McKinley said Colorado's normal background radiation level is 5 to 6 parts per million.
He said he wants the state health department to investigate and to demand a federal cleanup.

Part of the Piñon Canyon Maneuver Site has been burning for more than week, after lighting started a wildfire. The 48,000-acre Bridger Fire was 85 percent contained on Wednesday. During the initial days of the wildfire, Fort Carson chose to fight the fight alone and didn't ask for help, McKinley said.

"How in the world can we be doing what we do all over the globe, and (the Army) can't even take care of a fire in their backyard," McKinley asked. "This proves that if they can't take care of 250,000 acres. If they had 700,000, we'd have three times the danger, three times the exposure we've got now. We want answers. We don't want this to happen again."

He also questioned how the fire started. Fort Carson said it started from the lightning strike, but McKinley said there are "persistent rumors" that the Army was conducting a controlled burn and it got out of hand.

McKinley said the burn would have been "illegal," since the area was under a fire ban at the time.

According to the lawmaker, Fort Carson said the fire started on Tuesday, but local residents reported seeing smoke early Monday.

 

[flounder]

CHRONIC WASTING DISEASE, CERVIDS - CANADA (02): (ALBERTA) ****************************************************
A ProMED-mail post <http://www.promedmail.org> ProMED-mail is a program of the International Society for Infectious Diseases <http://www.isid.org>

Date: Wed 18 Jun 2008 Source: The Calgary Herald, Edmonton Journal report [edited] <http://www.canada.com/calgaryherald/news/story.html?id=182814b1-f9ac-4872-8860-a03d218ae460>

Wasting disease found in 24 more deer

snip...

-- Communicated by: Terry S Singeltary Sr <[email protected]>

[If one looks for a disease then it is entirely likely one will be found. Indeed CWD is a contagious disease but the mechanism is not completely determined. However, there is mounting evidence that hunters may be propagating the disease. When an animal is field dressed and the gut pile is left in the field (hence field dressed) then other deer come and consume the gut piles. We know that prions seem to be presented to the central nervous system through the gastro intestinal tract. So leaving the GI and the associated lymph nodes is like leaving the disease out. The animal may not appear ill because the disease has not progressed to the point of being visible. Some may say that deer are not carnivorous, but indeed, given the opportunity to eat gut piles, birds, eggs, etc, they clearly avail themselves of these opportunities. - Mod.TG

Alberta, in western Canada, can be located on the HealthMap/ProMED-mail interactive map at <http://healthmap.org/promed?v=55.4,-101.9,4>. - CopyEd.MJ]

[see also: Chronic wasting disease, cervids - Canada (SK): elk 20080517.1647 2007 ---- Chronic wasting disease, cervids - Canada (04): (SK, NS) 20071027.3497 Chronic wasting disease, cervids - Canada (03): (AB, SK) 20070117.0227 Chronic wasting disease, cervids - Canada (02): (SK) 20070112.0139 Chronic wasting disease, cervids - Canada: (AB) 20070105.0051 2006 ---- Chronic wasting disease, cervids - Canada (AB) 20060224.06042006 2005 ---- Chronic wasting disease, cervids - Canada (AB) (02) 20051213.3585 Chronic wasting disease, cervids - Canada (AB) 20050907.2650] ...................................tg/mj/dk

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

Subject: DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability Date: Fri, 16 May 2003 11:47:37 -0500 From: "Terry S. Singeltary Sr." <[email protected]> To: [email protected]

Greetings FDA,

i would kindly like to comment on; Docket 03D-0186FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability Several factors on this apparent voluntary proposal disturbs me greatly, please allow me to point them out;

1. MY first point is the failure of the partial ruminant-to-ruminant feed ban of 8/4/97. this partial and voluntary feed ban of some ruminant materials being fed back to cattle is terribly flawed. without the_total_ and _mandatory_ ban of all ruminant materials being fed back to ruminants including cattle, sheep, goat, deer, elk and mink, chickens, fish (all farmed animals for human/animal consumption), this half ass measure will fail terribly, as in the past decades...

2. WHAT about sub-clinical TSE in deer and elk? with the recent findings of deer fawns being infected with CWD, how many could possibly be sub-clinically infected. until we have a rapid TSE test toassure us that all deer/elk are free of disease (clinical and sub-clinical), we must ban not only documented CWD infected deer/elk, but healthyones as well. it this is not done, they system will fail...

3. WE must ban not only CNS (SRMs specified risk materials), but ALL tissues. recent new and old findings support infectivity in the rump or ass muscle. wether it be low or high, accumulation will play a crucial role in TSEs.

4. THERE are and have been for some time many TSEs in theUSA. TME in mink, Scrapie in Sheep and Goats, and unidentified TSE in USA cattle. all this has been proven, but the TSE in USA cattle has been totally ignored for decades. i will document this data below in my references.

5. UNTIL we ban all ruminant by-products from being fed back to ALL ruminants, until we rapid TSE test (not only deer/elk) but cattle in sufficient numbers to find (1 million rapid TSE test in USA cattle annually for 5 years), any partial measures such as the ones proposed while ignoring sub-clinical TSEs and not rapid TSE testing cattle, not closing down feed mills that continue to violate the FDA's BSE feed regulation (21 CFR 589.2000) and not making freely available those violations, will only continue to spread theseTSE mad cow agents in the USA.

I am curious what we will call a phenotype in a species that is mixed with who knows how many strains of scrapie, who knows what strain or how many strains of TSE in USA cattle, and the CWD in deer and elk (no telling how many strains there), but all of this has been rendered for animal feeds in the USA for decades. it will get interesting once someone starts looking in all species, including humans here in theUSA, but this has yet to happen...

6. IT is paramount that CJD be made reportable in every state (especially ''sporadic'' cjd), and that a CJD Questionnaire must be issued to every family of a victim of TSE. only checking death certificates will not be sufficient. this has been proven as well (see below HISTORY OF CJD -- CJD QUESTIONNAIRE)

7. WE must learn from our past mistakes, not continue to make the same mistakes...

references

snip...

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

Christina J. Sigurdson1, Elizabeth S. Williams2, Michael W. Miller3,Terry R. Spraker1,4, Katherine I. O'Rourke5 and Edward A. Hoover1Department of Pathology, College of Veterinary Medicine and BiomedicalSciences, Colorado State University, Fort Collins, CO 80523- 1671, USA1Department of Veterinary Sciences, University of Wyoming, 1174 SnowyRange Road, University of Wyoming, Laramie, WY 82070, USA 2Colorado Division of Wildlife, Wildlife Research Center, 317 WestProspect Road, Fort Collins, CO 80526-2097, USA3Colorado State University Veterinary Diagnostic Laboratory, 300 WestDrake Road, Fort Collins, CO 80523-1671, USA4Animal Disease Research Unit, Agricultural Research Service, USDepartment of Agriculture, 337 Bustad Hall, Washington State University,Pullman, WA 99164-7030, USA5Author for correspondence: Edward Hoover.Fax +1 970 491 0523. [email protected]

deer fawns (Odocoileus hemionus) were inoculated orally with abrain homogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Fawns were necropsied and examined for PrP res, the abnormal prion protein isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an immunohistochemistry assay modified to enhance sensitivity. PrPres was detected in alimentary-tract-associatedl ymphoid tissues (one or more of the following: retropharyngeal lymphnode, tonsil, Peyer's patch and ileocaecal lymph node) as early as 42days p.i. and in all fawns examined thereafter (53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of three control fawns receiving a control brain inoculum, nor was PrPres detectable in neural tissue of any fawn. PrPres-specific staining was markedly enhanced by sequential tissue treatment with formic acid, proteinase K and hydrated autoclaving prior to immunohistochemical staining with monoclonalantibody F89/160.1.5. These results indicate that CWD PrP res can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.

snip...

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

snip...

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

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

now, just what is in that deer feed? _ANIMAL PROTEIN_

Subject: MAD DEER/ELK DISEASE AND POTENTIAL SOURCES

Date: Sat, 25 May 2002 18:41:46 -0700 From: "Terry S. Singeltary Sr." Reply-To: BSE-LTo: BSE-L

8420-20.5% Antler DeveloperFor Deer and Game in the wildGuaranteed Analysis Ingredients / Products Feeding Directions

snip...

_animal protein_

http://www.surefed.com/deer.htm

BODE'S GAME FEED SUPPLEMENT #400A RATION FOR DEERNET WEIGHT 50 POUNDS22.6 KG.

snip...

_animal protein_

http://www.bodefeed.com/prod7.htm

IngredientsGrain Products, Plant Protein Products, Processed Grain By-Products,Forage Products, Roughage Products 15%, Molasses Products,

__Animal Protein Products__,

Monocalcium Phosphate, Dicalcium Pyosphate, Salt,Calcium Carbonate, Vitamin A Acetate with D-activated Animal Sterol(source of Vitamin D3), Vitamin E Supplement, Vitamin B12 Supplement,Riboflavin Supplement, Niacin Supplement, Calcium Panothenate, CholineChloride, Folic Acid, Menadione Soduim Bisulfite Complex, PyridoxineHydorchloride, Thiamine Mononitrate, d-Biotin, Manganous Oxide, ZincOxide, Ferrous Carbonate, Calcium Iodate, Cobalt Carbonate, DriedSacchoromyces Berevisiae Fermentation Solubles, Cellulose gum,Artificial Flavors added.http://www.bodefeed.com/prod6.htm

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

MORE ANIMAL PROTEIN PRODUCTS FOR DEER

Bode's #1 Game PelletsA RATION FOR DEERF3153GUARANTEED ANALYSISCrude Protein (Min) 16%Crude Fat (Min) 2.0%Crude Fiber (Max) 19%Calcium (Ca) (Min) 1.25%Calcium (Ca) (Max) 1.75%Phosphorus (P) (Min) 1.0%Salt (Min) .30%Salt (Max) .70%IngredientsGrain Products, Plant Protein Products, Processed Grain By-Products,Forage Products, Roughage Products, 15% Molasses Products,

__Animal Protein Products__,

Monocalcium Phosphate, Dicalcium Phosphate, Salt,Calcium Carbonate, Vitamin A Acetate with D-activated Animal Sterol(source of Vitamin D3) Vitamin E Supplement, Vitamin B12 Supplement,Roboflavin Supplement, Niacin Supplement, Calcium Pantothenate, CholineChloride, Folic Acid, Menadione Sodium Bisulfite Complex, PyridoxineHydrochloride, Thiamine Mononitrate, e - Biotin, Manganous Oxide, ZincOxide, Ferrous Carbonate, Calcium Iodate, Cobalt Carbonate, DriedSaccharyomyces Cerevisiae Fermentation Solubles, Cellulose gum,Artificial Flavors added.FEEDING DIRECTIONSFeed as Creep Feed with Normal Diet

http://www.bodefeed.com/prod8.htm

INGREDIENTS

Grain Products, Roughage Products (not more than 35%), Processed GrainBy-Products, Plant Protein Products, Forage Products,

__Animal Protein Products__,

L-Lysine, Calcium Carbonate, Salt, Monocalcium/DicalciumPhosphate, Yeast Culture, Magnesium Oxide, Cobalt Carbonate, BasicCopper Chloride, Manganese Sulfate, Manganous Oxide, Sodium Selenite,Zinc Sulfate, Zinc Oxide, Sodium Selenite, Potassium Iodide,Ethylenediamine Dihydriodide, Vitamin E Supplement, Vitamin ASupplement, Vitamin D3 Supplement, Mineral Oil, Mold Inhibitor, CalciumLignin Sulfonate, Vitamin B12 Supplement, Menadione Sodium BisulfiteComplex, Calcium Pantothenate, Riboflavin, Niacin, Biotin, Folic Acid,Pyridoxine Hydrochloride, Mineral Oil, Chromium Tripicolinate

DIRECTIONS FOR USE

Deer Builder Pellets is designed to be fed to deer under rangeconditions or deer that require higher levels of protein. Feed to deerduring gestation, fawning, lactation, antler growth and pre-rut, allphases which require a higher level of nutrition. Provide adequateamounts of good quality roughage and fresh water at all times.

http://www.profilenutrition.com/Products/Specialty/deer_builder_pellets.html

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

DEPARTMENT OF HEALTH & HUMAN SERVICESPUBLIC HEALTH SERVICEFOOD AND DRUG ADMINISTRATIONApril 9, 2001 WARNING LETTER01-PHI-12CERTIFIED MAILRETURN RECEIPT REQUESTED

Brian J. Raymond, Owner Sandy Lake Mills 26 Mill Street P.O. Box 117 Sandy Lake, PA 16145

PHILADELPHIA DISTRICT

Tel: 215-597-4390

Dear Mr. Raymond:Food and Drug Administration Investigator Gregory E. Beichner conducted an inspection of your animal feed manufacturing operation, located in Sandy Lake, Pennsylvania, on March 23,2001, and determined that your firm manufactures animal feeds including feeds containing prohibited materials. The inspection found significant deviations from the requirements set forth in Title 21, code of Federal Regulations, part 589.2000 - Animal Proteins Prohibited in Ruminant Feed. The regulation is intended to prevent the establishment and amplification of Bovine Spongiform Encephalopathy (BSE) . Such deviations cause products being manufactured at this facility to be misbranded within the meaning of Section 403(f), of the Federal Food, Drug, and Cosmetic Act (the Act).Our investigation found failure to label your swine feed with the required cautionary statement "Do Not Feed to cattleor other Ruminants" The FDA suggests that the statement be distinguished by different type-size or color or other means of highlighting the statement so that it is easily noticed by a purchaser.

In addition, we note that you are using approximately 140 pounds of cracked corn to flush your mixer used in the manufacture of animal feeds containing prohibited material. This flushed material is fed to wild game including deer, a ruminant animal.Feed material which may potentially contain prohibited material should not be fed to ruminant animals which may become part of the food chain.The above is not intended to be an all-inclusive list of deviations fromthe regulations. As a manufacturer of materials intended for animalfeed use, you are responsible for assuring that your overall operation and the products you manufacture and distribute are in compliance withthe law. We have enclosed a copy of FDA's Small Entity Compliance Guideto assist you with complying with the regulation... blah, blah, blah...

http://www.fda.gov/foi/warning_letters/g1115d.pdf

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

snip...end...full text ;

2003D-0186 Guidance for Industry: Use of Material From Deer and Elk In Animal Feed

EMC 1 Terry S. Singeltary Sr. Vol #: 1

http://www.fda.gov/ohrms/dockets/dailys/03/Jun03/060903/060903.htm

2003D-0186 Guidance for Industry: Use of Material From Deer and Elk In Animal Feed

EMC 7 Terry S. Singeltary Sr. Vol #: 1

2003D-0186 Guidance for Industry: Use of Material From Deer and Elk In Animal Feed

EMC 7 Terry S. Singeltary Sr. Vol #: 1

http://www.fda.gov/ohrms/dockets/dailys/03/oct03/100203/100203.htm

01N-0423 Substances Prohibited from use in animal food/Feed Ruminant

APE 5 National Renderers Association, Inc. Vol#: 2

APE 6 Animal Protein Producers Industry Vol#: 2

APE 7 Darling International Inc. Vol#: 2

EMC 1 Terry S. Singeltary Sr. Vol#: 3

http://www.fda.gov/ohrms/dockets/dailys/01/Oct01/101501/101501.htm

TSS

 

[Yanuck]

Communicated by: Terry S Singeltary Sr <[email protected]>

[If one looks for a disease then it is entirely likely one will be found. Indeed CWD is a contagious disease but the mechanism is not completely determined. However, there is mounting evidence that hunters may be propagating the disease. When an animal is field dressed and the gut pile is left in the field (hence field dressed) then other deer come and consume the gut piles. We know that prions seem to be presented to the central nervous system through the gastro intestinal tract. So leaving the GI and the associated lymph nodes is like leaving the disease out. The animal may not appear ill because the disease has not progressed to the point of being visible. Some may say that deer are not carnivorous, but indeed, given the opportunity to eat gut piles, birds, eggs, etc, they clearly avail themselves of these opportunities.

:shock: :shock: :shock: :shock: Seriously?!!!! come on, has anyone on here ever seen this happen?

 

[Mike]

A deer eat a gut pile? C'mon!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! :lol:

 

[Yanuck]

Well what I really wanted to say is I call BullShit! but am trying to be PC!!! 8)

 

[Big Muddy rancher]

I wouldn't say that deer eat "GUT PILES". But that does act as a fertilizer that could produce green tasty grass the next year. If these prions are as indestructible as they say, they could persist in the soil to be consumed again.

 

[Kathy]

The prion protein crystals are called 'protease resistant" because the digestive enzymes do not break them down to their constituents, amino acids, minerals....

For this reason, they are not causing disease via consumption. Inhalation of the metal particles would result in the translocation to the brain. If the prion fibrils are ingested, or even inhaled, they will be unavailable for further distribution because the body doesn't break it apart.

If consumption of meat/meat products caused the disease then in animals found with BSE - naturally occurring (NOT transmission experiments), these animals would have evidence of prions in the gut... and they did NOT.

None experimental BSE cattle had no evidence of prions anywhere except their brain, spinal cord and eyes.

During the experimental transmission procedures in labs, these prion fibrils are being destroyed and broken apart, into the components of the fibrils (nucleating metals and protein fragments).

In all the feeding trials (feeding the contaminated MBM) none of these animals developed BSE. In order to accomplish this task, the researchers had to homogenate brain tissue, sonicate it and directly inject the constituents into the empty stomachs of young calves. Even then the results were skewed by pooling brain samples in order to get a positive reading.

It is disturbing that the researchers have not CHARACTERIZED what constituents they are injecting into these animals (mostly intracranial injections). We are dealing with a toxin, not an infectious, agent. Just like lead - do we say eating lead causes infectious disease? No, but we know that Dr. A. Hamir found that lead exposure in dogs (especially those fed a low calcium diet/high fat) resulted in spongiform of the brain.

Dr. John Collinge and Dr. Weissman in usa patent application 20080108085 state that the prion will degrade in 24 hours unless it is attached to a metal. Copper would allow for the proper, reversible attachment onto the prion protein allowing it to function normally. These other metals like lead, cadmium, DU, barium, strontium... lead to misfolding that is irreversible. The metal/protein crystal then scavenges the metal-free prions onto the shell of the crystal.

Collinge et al. are considering metal surgical instruments... they failed to clearly show that their control animals with just the stainless steel wire implanted in their head - all died right away.

New research is attempting to coat the surgical instruments with silicon to prevent the metal ions from chelating off of them, thus contaminating the brain or other tissues directly in contact with them.

Just as with diabetics having dialysis, they have shown that metals such as aluminium are chelating from the instruments/tools used to perform the therapy and contaminating their blood. Many people on dialysis die from renal failure due to the plugging of their kidneys with these metals.

Eating the prion crystals only results in their being pooped out the back end, because they are not bioavailable to our systems (without medical intervention as with growth hormone implants taken from pituitary glands).

 

[flounder]

The prion protein crystals are called 'protease resistant" because the digestive enzymes do not break them down to their constituents, amino acids, minerals....
For this reason, they are not causing disease via consumption. Inhalation of the metal particles would result in the translocation to the brain. If the prion fibrils are ingested, or even inhaled, they will be unavailable for further distribution because the body doesn't break it apart. SNIP...END...TSS

A deer eat a gut pile? C'mon!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! :lol:

Communicated by: Terry S Singeltary Sr <[email protected]>

[If one looks for a disease then it is entirely likely one will be found. Indeed CWD is a contagious disease but the mechanism is not completely determined. However, there is mounting evidence that hunters may be propagating the disease. When an animal is field dressed and the gut pile is left in the field (hence field dressed) then other deer come and consume the gut piles. We know that prions seem to be presented to the central nervous system through the gastro intestinal tract. So leaving the GI and the associated lymph nodes is like leaving the disease out. The animal may not appear ill because the disease has not progressed to the point of being visible. Some may say that deer are not carnivorous, but indeed, given the opportunity to eat gut piles, birds, eggs, etc, they clearly avail themselves of these opportunities.

:shock: :shock: :shock: :shock: Seriously?!!!! come on, has anyone on here ever seen this happen?

THE fear is that CWD is a more virulent TSE, thus poses more risk to your precious commodities i.e. cattle futures $$$
via natural field conditions, plus, the real possibility of environmental exposure from gut pile to all animals. you think you have problems with atypical BSE in cattle, you wait until CWD has transmitted to cattle in the field, before doing anything about it, then you will find out what real trouble is about $$$


Samples from U.S. cattle experimentally exposed to CWD and other TSEs and showing variation in incubation time, lesion profile and susceptibility will be analyzed. ...


Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Diseases of Livestock

2007 Annual Report

1a.Objectives (from AD-416)


http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=408808&showpars=true&fy=2007


The white-tailed deer in Michigan is recognized as the primary reservoir host of bovine TB. Once the disease is eliminated from the deer, the disease should die out in the non-cervid species. As long as bovine TB exists in the wild, free-ranging deer population, there will be some risk to local wildlife species that feed on bovine TB-infected deer carcasses or gut piles.

http://www.michigan.gov/emergingdiseases/0,1607,7-186-25804_25811-75908--,00.html


For this reason, when I asked the DEC medical folks why they didn't require hunters to remove the gut-pile from the woods in the special CWD management ...

http://www.nysrpa.org/encon/CWD.html


Friday, August 8, 2008 PS 76-59: White-tailed deer carcass decomposition and risk of chronic wasting disease exposure to scavenger communities in Wisconsin Chris S. Jennelle, Michael D. Samuel, Cherrie A. Nolden, and Elizabeth A. Berkley. University of Wisconsin

Background/Question/Methods

Chronic wasting disease (CWD) is an infectious transmissible spongiform encephalopathy (TSE) afflicting members of the family Cervidae, and causes neurodegeneration and ultimately death. While there have been no reports of natural cross-species transmission of CWD outside this group, we addressed the role of white-tailed deer (Odocoileus virginianus) carcasses as environmental sources of CWD in Wisconsin. Our objectives were to estimate rates of deer carcass and gut pile decomposition in the environment, characterize vertebrate scavenger communities, and quantify the relative activity of scavengers to determine CWD exposure risk. We placed 40 disease-free deer carcasses and nine gut piles in the CWD-affected area of Wisconsin from September to April in 2003 through 2005. We used photos from remotely operated cameras to characterize scavenger communities and relative activity. We used Kaplan-Meier survival analysis and a generalized linear mixed model to quantify the driving factors and rate of carcass removal (decomposition) from the environment.

Results/Conclusions

We recorded 14 species of scavenging mammals (six visiting species), and eight species of scavenging birds (14 visiting species). Prominent scavengers included American crows (Corvus brachyrhynchos), raccoons (Procyon lotor), and Virginia opossums (Didelphis virginiana). We found no evidence that deer directly consumed conspecific remains, although they visited them frequently. Domestic dogs (Canis familiaris), cats (Felis catus), and cows (Bos spp.) either scavenged or visited carcass sites, which could increase exposure risk of CWD to humans and human food supplies. Deer carcasses persisted for a median of 18 to 101 days, while gut piles lasted for a median of three days. Habitat did not influence carcass decomposition, but mammalian and avian scavenger activity and higher temperatures (proxy for microbial and arthropod activity) were associated with greater rates of carcass removal. Infected deer carcasses serve as environmental sources of CWD prions to a wide variety of mammalian and avian scavengers. Such sources of infectious material likely influence the maintenance and spread of CWD (in particular), and should be considered in the dynamics of other disease systems as well. Prudence would dictate the use of preemptive management strategies, and we highlight strategies for carcass disposal to mitigate the influence of carcasses as environmental sources of infectious diseases.

See more of PS 76 - Latebreaking: Disease and Epidemiology See more of Latebreakers

See more of The 93rd ESA Annual Meeting (August 3 -- August 8, 2008)

http://eco.confex.com/eco/2008/techprogram/P14681.HTM


11. Disease control challenges posed by CWD

Evidence is building that indicates efficient horizontal transmission occurs
in CWD, indeed a complicating aspect in disease control [91]. Potential
transmission mechanisms range from spread via direct contact among animals
to environmental exposure through grazing in areas contaminated by
prion-infected secretions, excretions (saliva, urine, feces), tissues
(placenta), or decomposed carcasses.

snip...see full text 19 pages ;

http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v08092.pdf


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




Title: Susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from white-tailed deer

Authors

Hamir, Amirali Miller, Janice - ARS RETIRED Kunkle, Robert Hall, S - USDA, APHIS, NVSL, PL Richt, Juergen

Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: February 20, 2007 Publication Date: July 1, 2007 Citation: Hamir, A.N., Miller, J.M., Kunkle, R.A., Hall, S.M., Richt, J.A. 2007. Susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from white-tailed deer. Veterinary Pathology. 44:487-493.

Interpretive Summary: This study reports findings assessing susceptibility of cattle to infection following direct surgical inoculation of the transmissible spongiform encephalopathy (TSE), chronic wasting disease (CWD, from white tailed deer) into the brain of 14 cattle. Three-month-old calves were inoculated with the CWD agent from white tailed deer. Two non-inoculated calves served as controls. Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease. The findings also indicate that diagnostic techniques currently used for detection of bovine spongiform encephalopathy (BSE) would detect CWD in cattle should it ever cross the species barrier. Moreover, these findings confirm our earlier findings with CWD from mule deer, thus demonstrating a unique pattern of the CWD disease agent from deer when experimentally inoculated into cattle, further validating our ability to distinguish this form of cross-species TSE transmission from BSE in cattle. Technical Abstract: To compare clinicopathological findings of chronic wasting disease (CWD) from white-tailed deer (CWD**wtd) with other transmissible spongiform encephalopathies [transmissible spongiform encephalopathy (TSE), prion diseases) that have been shown to be experimentally transmissible to cattle [sheep scrapie, CWD of mule deer (CWD**md) and transmissible mink encephalopathy (TME)], 14 three-month-old calves were intracerebrally inoculated with the CWD**wtd agent. Two uninoculated calves served as controls. Within 26 months post inoculation (MPI), 12 inoculated animals had lost considerable weight and eventually became recumbent. Eleven of these had clinical signs of central nervous system (CNS) abnormality and all 12 were euthanized. Although microscopic lesions of spongiform encephalopathy (SE) were not seen in CNS tissues, PrP**res was detected by immunohistochemistry (IHC) and Western blot (WB). These findings demonstrate that when CWD**wtd is intracerebrally inoculated in cattle, 86% of inoculated cattle develop abnormal clinical signs and amplify PrP**res in their CNS tissues without evidence of morphologic lesions of SE. The latter has also been shown with other TSE agents (scrapie and CWD**md) similarly inoculated into cattle. These findings suggest that the diagnostic techniques currently used for confirmation of bovine spongiform encephalopathy (BSE) would detect CWD**wtd in cattle should it occur naturally. The absence of microscopic morphologic lesions and a unique IHC pattern of CWD**wtd in cattle, suggests that it should be possible to distinguish this form of cross-species transmission from BSE in cattle.

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

P04.27

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

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

Background:

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

Aims:

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

Methods:

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

Results:

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

Conclusions:

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

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

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

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

Risk of oral infection with bovine spongiform encephalopathy agent in primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys Summary The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is compounded by incomplete knowledge about the efficiency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these findings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man.

snip...

BSE bovine brain inoculum

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

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

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

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

PrPres biochemical detection

The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was

inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the first positive animal (%). The accuracy of

bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.

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

Published online January 27, 2005

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

It is clear that the designing scientists must

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

levels right down to 1 gram triggered infection.

http://www.bseinquiry.gov.uk/files/ws/s145d.pdf

2

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

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

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

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

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

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

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

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

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

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

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

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

dose levels right down to 1 gram triggered infection.

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

2003D-0186 Guidance for Industry: Use of Material From Deer and Elk In Animal Feed

EMC 7 Terry S. Singeltary Sr. Vol #: 1

Subject: DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability Date: Fri, 16 May 2003 11:47:37 -0500 From: "Terry S. Singeltary Sr." To: [email protected]

snip...

Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus ) Christina J. Sigurdson1, Elizabeth S. Williams2, Michael W. Miller3, Terry R. Spraker1,4, Katherine I. O'Rourke5 and Edward A. Hoover1

Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523- 1671, USA1 Department of Veterinary Sciences, University of Wyoming, 1174 Snowy Range Road, University of Wyoming, Laramie, WY 82070, USA 2 Colorado Division of Wildlife, Wildlife Research Center, 317 West Prospect Road, Fort Collins, CO 80526-2097, USA3 Colorado State University Veterinary Diagnostic Laboratory, 300 West Drake Road, Fort Collins, CO 80523-1671, USA4 Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, 337 Bustad Hall, Washington State University, Pullman, WA 99164-7030, USA5

Author for correspondence: Edward Hoover.Fax +1 970 491 0523. e-mail [email protected]

Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain homogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Fawns were necropsied and examined for PrP res, the abnormal prion protein isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an immunohistochemistry assay modified to enhance sensitivity. PrPres was detected in alimentary-tract-associated lymphoid tissues (one or more of the following: retropharyngeal lymph node, tonsil, Peyer's patch and ileocaecal lymph node) as early as 42 days p.i. and in all fawns examined thereafter (53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of three control fawns receiving a control brain inoculum, nor was PrPres detectable in neural tissue of any fawn. PrPres-specific staining was markedly enhanced by sequential tissue treatment with formic acid, proteinase K and hydrated autoclaving prior to immunohistochemical staining with monoclonal antibody F89/160.1.5. These results indicate that CWD PrP res can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.

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

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

Subject: MAD DEER/ELK DISEASE AND POTENTIAL SOURCES Date: Sat, 25 May 2002 18:41:46 -0700 From: "Terry S. Singeltary Sr." Reply-To: BSE-L To: BSE-L

8420-20.5% Antler Developer For Deer and Game in the wild Guaranteed Analysis Ingredients / Products Feeding Directions

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_animal protein_

http://www.surefed.com/deer.htm

BODE'S GAME FEED SUPPLEMENT #400 A RATION FOR DEER NET WEIGHT 50 POUNDS 22.6 KG.

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_animal protein_

http://www.bodefeed.com/prod7.htm

J Infect Dis. 2004 Aug 1;190(3):653-60.

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC. Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

http://www.ncbi.nlm.nih.gov/


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

Date: March 21, 2007 at 2:27 pm PST RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II ___________________________________ PRODUCT Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007 CODE Cattle feed delivered between 01/12/2007 and 01/26/2007 RECALLING FIRM/MANUFACTURER Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007. Firm initiated recall is ongoing. REASON Blood meal used to make cattle feed was recalled because it was cross-contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI

___________________________________ PRODUCT Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot-Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI – 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J – PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A-BYPASS ML W/SMARTA, Recall # V-025-2007 CODE The firm does not utilize a code - only shipping documentation with commodity and weights identified. RECALLING FIRM/MANUFACTURER Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete. REASON Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 9,997,976 lbs. DISTRIBUTION ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

http://www.fda.gov/bbs/topics/enforce/2007/ENF00996.html

Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE Risk (GBR) of the United States of America (USA) Question number: EFSA-Q-2003-083

http://www.efsa.europa.eu/EFSA/Scientific_Document/sr03_biohaz02_usa_report_v2_en1,0.pdf

Subject: FATEPriDE Environmental Factors that Affect the Development of Prion Diseases Date: February 18, 2006 at 9:24 am PST

FATEPriDE

Environmental Factors that Affect the Development of Prion Diseases.

Project funded by the European Commission under the Quality of Life Programme.

Contract No: QLK4-CT-2002-02723

Project No: QLRT-2001-02723

Start Date

1st January 2003

Duration

36 months plus 6 month extension

Partners

1. The University of Bristol, UK (Co-ordinator) 2. National Environment Research Council-The British Geological Society, UK 3. University of Bath, UK 4. Free University of Berlin, Germany 5. University of Iceland, Iceland 6. Universita degli studi di Perugia, Italy 7. Universite Joseph Fourier Grenoble, France 8. Alpine Institute of Environmental Dynamics, France

Introduction

The work proposed here brings together top EU geo and biochemists focusing on determining the environmental factors that affect the development of prion diseases such as scrapie, bovine spongiform enchpalitis (BSE), chronic wasting disease (CWD) and Creutzfeld-Jacobs disease (CJD). First the geographical distribution of manganese and copper in soils will be investigated as risk factors. This will be undertaken due to the fact that prion diseases often are found in clusters. It now has been established that the normal metal for prion protein is copper but if that metal is replaced with manganese, the structure of the prion protein is altered. The role of organophosphate pesticides will also be investigated because it has been suggested that copper is complexed with organophosphate, preventing copper absorption.

Objectives

There is clear evidence that the occurrence of prion diseases often has a non-random distribution, suggesting a link to some environmental factors. The work proposed here will investigate risk factors, including the role of trace elements and organophosphates. Analysis of regional variation in local manganese/copper levels will be determined and compared to the incidence of the diseases. The ability of manganese and/or organophosphates in influencing conversion of the prion protein to an abnormal and/or infectious protein will be determined. In combination with geographical occurrence and geo-chemical considerations this program will identify whether these environmental considerations should be acted upon to bring about effective prevention or at least risk minimalisation of prion diseases in the EU and further afield.

Description of the Work

Recently it has been suggested that disbalance in dietary trace-elements and/or exposure to organophosphates might either cause or be a risk factor for prion disease development. In particular, high incidence of scrapie (e.g. in Iceland), chronic wasting disease, and in Slovakia and Italy CJD are associated with regions where soil and foliage are reported to be low in copper and high in manganese. This proposal will address whether exposure to a diet that has a high manganese/copper ratio can influence prion disease will also be addressed. In particular, we shall investigate this theory at the level of protein, cells, animals as well as geographical and geo-chemical associations with prion diseases. Animal models of prion disease and sheep from farms in regions of high scrapie will be investigated for a possible influence of level of manganese and copper on incidence or onset of these diseases. Bio-chemical and biophysical techniques will be used to investigate interaction of the prion protein with copper and manganese to determine the mechanism by which Mn substitution for Cu influences conversion to the abnormal isoform of the protein and whether such conversion results in protein that is infectious in mouse bioassay for infectivity. Additionally, a cell culture model will be used to generate abnormal prion protein by exposure to manganese. Cell culture model of infection will be used to assay whether prion disease alters manganese metabolism and transport of manganese into cells. The level of expression of the prion protein is in itself a risk factor for prion disease as it shortens the incubation time for the disease. This research will result in understanding of the role of disbalance in the trace elements Cu and Mn on the onset and mechanisms behind the occurrence of prion diseases and will for the first time define whether there are environmental risk factors for prion diseases.

Milestones and Expected Results

The study proposed here will produce a geo-chemical map of Europe for manganese and copper. These maps will be used to target field areas where prion diseases have occurred as clusters. The bio-chemical studies will establish whether the replacement of manganese for copper in prion protein is a risk factor for the disease _development_. Organophosphate will also be investigated as a risk factor. The study aims at minimising the risk of prion diseases for humans and animals in the EU.

http://www.arp-manchester.org.uk/FatePride.htm

SINCE THEN ;

Subject: FATEPriDE KEY FINDINGS ORGANOPHOSPHATE NO RELATIONSHIP TO CAUSE TSE Date: May 3, 2007 at 8:41 am PST

KEY FINDINGS

Organophosphate Studies

6. Studies using phosmet (an organophosphate pesticide) were carried out throughout the project. No relationship between this compound and the potential to cause a TSE were identified. In studies with oral dosing of rats, it was shown that PrP expression levels increased in the brain but there was no association between this and formation of proteinase K (PK) resistant PrP.

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12. A model of seed protein aggregation and fibril formation was established using PrP charged with Mn2+. PrP-Mn2+ was found to form small circular aggregates able to catalyse further protein aggregation and fibrilisation of PrP. This model unlike other published models (for example those of Baskakov et al.1) does not require the presence of denaturants and is not an autocatalytic process (i.e. the substrate of the reaction did not aggregate). The results suggest that Mn2+ may play a role in the formation of prion seeds

__although further studies showed that this material was not infectious in mouse bioassay.__

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24. The project also generated information concerning the relation of TSEs to environmental factors: • __Potentially no role for organophosphates in TSEs.__ • Increased Mn in the diet results in higher PrP levels in the brain. • No conclusion is yet possible in terms of the relationship between environmental trace element concentrations and the geographical occurrence of TSEs (classical scrapie or BSE). • Some confirmation was provided that in some specific farms occurrence of classical scrapie correlates with high Mn levels.

http://www.seac.gov.uk/papers/97-4.pdf

a) As regards the involvement of organophosphates in the origin of BSE, no new scientific information providing evidence or supporting the hypothesis by valid data became available after the adoption of the last opinion of the SSC on this issue. Consequently there is no reason for modifying the existing opinions.

b) Regarding the possibility of OP poisoning, the European legislation for registration of plant protection products and veterinary medicines – addressed in the enquiries – provide the basis for safe use of registered compounds and their formulations. Regarding the alleged intoxication cases reported and OP exposure it must be concluded that safety measures may not have been strictly followed.

References

Brown, D.R., Qin, K., Herms, J.W., Madlung, A., Manson, J., Strome, R., Fraser, P.E., Kruck, T., von Bohlen, A., Schulz- Schaeffer, W., Giese, A., Westaway, D. and Kretzschmar, H. (1997) The Cellular Prion Protein Binds Copper In Vivo, Nature, 390, 684-7. Purdey, M. (2000) Ecosystems Supporting Clusters of Sporadic TSEs Demonstrate Excesses of the Radical- Generating Divalent Cation Manganese and Deficiencies of Antioxidant Co-Factors Cu, Se, Fe, Zn Medical Hypotheses, 54, 278-306. Scientific Steering Committee, 1998. Opinion on possible links between BSE and Organophosphates. Adopted on 25-26 June 1998 Scientific Steering Committee, 2001. Opinion on Hypotheses on the origin and transmission of BSE. Adopted on 29-30 November 2001.

http://europa.eu.int/comm/food/fs/sc/ssc/out356_en.pdf

OP'S MEETING WITH PURDEY

http://www.bseinquiry.gov.uk/files/yb/1994/02/09001001.pdf

TSS