Thursday, April 28, 2011

Chronic Wasting Disease Testing and Prevalence Wisconsin April 2011

Chronic Wasting Disease Testing and Prevalence

Contributed by Davin Lopez

Wisconsin has intensively monitored chronic wasting disease (CWD) for nine years. Between 2002 and March 2011, we have tested over 166,000 free-ranging deer, of which 1,570 have tested positive for CWD. All of the positive cases have been found within the current CWD Management Zone (CWD-MZ). Wisconsin has two separate cores of disease infection; one in the southwest part of the state and one in the southeast. The southeast CWD outbreak is contiguous with a CWD area in northern Illinois where 326 CWD positive deer have been found since 2002.

Since 2002, CWD prevalence within our western monitoring area has shown an overall increasing trend in all sex and age classes. During the past nine years, the trend in prevalence in adult males has risen from about 8 percent to over 16 percent and in adult females from about 3 percent to approximately 7 percent. During that same time, the prevalence trend in yearling males has increased from about 2 percent to about 6 percent and in yearling females from less than 2 percent to about 4 percent. We continue to see similar trends in the eastern monitoring area as well, albeit at lower prevalence levels.

We continue to find that disease prevalence is higher in males than females and higher in adults than yearlings. It is important to keep in mind that annual prevalence estimates are subject to sampling variation and that trends over time give us better information. These annual monitoring data are important for Wisconsin’s understanding of CWD distribution and prevalence.

We will continue to sample deer within the CWD-Management Zone (MZ), including both the southwestern and southeastern core infection areas, to track changes in both CWD prevalence and distribution. Currently, the exact locations of sampling within the CWD-MZ, as well as any possible locations outside of the CWD-MZ, are still being determined. This information will be available at registration and sampling stations, and on our website, prior to the opening of the 2011 archery season.

CWD in North America

As of 2011, 15 states and provinces have identified CWD within their free-ranging cervid (deer, elk, and moose) herds. In some of those 15, CWD has been detected in only a handful of deer, while in others, vast geographic areas and large numbers of animals are affected.

In Colorado and Wyoming, states where CWD has infected wild deer for several decades, recent studies have documented high prevalence rates (20-40%) and lower survival of CWD-infected deer when compared to uninfected deer. In Wyoming, high prevalence rates (~35%) have been identified across extensive geographic areas (>4,000 sq. mi.). Researchers suggest that CWD may be limiting deer numbers in these populations. Examining CWD in other states helps us anticipate the future impacts of CWD in Wisconsin. This knowledge will assist us in making the best management choices for our state.

CWD Management

Successfully managing CWD in Wisconsin will require a sustained effort over many years, necessitating cooperation and communication among the DNR, hunters, agricultural agencies, landowners, farmedcervid producers, and the many citizens of the state who benefit from a healthy deer herd. Although successful CWD management is very challenging for everyone involved, the alternative of letting the disease spread uncontrolled is much worse. Without a joint effort, I believe the long-term future of Wisconsin’s deer hunting could be in jeopardy. As we learn more about CWD, we will strive to make the best decisions for the current and future benefit of both Wisconsin’s deer and the people who value them. For information on our current plan for CWD in Wisconsin, please see our recently adopted Response Plan here:

http://new.dnr.wi.gov/DocumentLibrary/Repository/Lands/Wildlife%20Management/Wildlife_Health/CWD/CWD_15plan.pdf.



Buckhorn Flats Purchase

The State of Wisconsin has acquired the former Buckhorn Flats cervid farm near Almond, Wisconsin. Due to concerns about the presence of infectious CWD prions on the property, the DNR and Natural Resources Board believed that purchasing this property was essential for protecting the health of Wisconsin’s white-tailed deer. Thanks to the Stewardship Program, the State was able to make this important purchase. In keeping with the purchase objective of preventing spread of CWD, the property will be closed to public access to prevent spreading prion-contaminated soil or other materials beyond the property boundaries. Plans are in the works for using the property to further our knowledge of how long prions persist in the environment and what infection risk those prions present.

Thank you for your role in helping to manage CWD over the past nine years. Wisconsin is very fortunate to have a great conservation ethic and an appreciation for the natural world. Hunters are the cornerstone of conservation and wildlife management and your help and assistance is greatly appreciated.

Contributed by Tami Ryan and Wildlife Health Section Staff


http://dnr.wi.gov/org/land/wildlife/wildlife7.pdf




http://new.dnr.wi.gov/Default.aspx?Page=461ae2ef-2ed8-4ad8-bd46-d2463622de77





http://prodoasext.dnr.wi.gov/inter1/pk_cwd_zone_year$year.actionquery?p_cwd_year=2010&z_action=&z_chk=0




see maps ;


http://new.dnr.wi.gov/Default.aspx?Page=7194010f-50d2-4e46-8ed5-830cdf14a4f8




http://new.dnr.wi.gov/Default.aspx?Page=8ad0512c-a6f6-4a02-809b-e25bea53534e





Potential Human Health Risks from Chronic Wasting Disease There is no evidence that chronic wasting disease (CWD) can be passed to humans. However the World Health Organization (WHO) [exit DNR] and the Centers for Disease Control and Prevention (CDC) [exit DNR] recommond that people avoid eating venison from CWD positive deer or elk.


(PLEASE NOTE, THIS CLAIM IS FALSE. THERE IS MORE SCIENCE SHOWING THAT INDEED CWD WILL TRANSMIT TO MAN, THAN THERE IS EVIDENCE THAT IT WILL NOT. Einstein once said, 'The definition of insanity is doing the same thing over and over again and expecting different results.' re-transmission studies on TSE's...TSS)


http://new.dnr.wi.gov/Default.aspx?Page=7efb3a99-4a98-4598-9ded-3dcc13ca93aa






Wednesday, April 06, 2011

Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease


http://chronic-wasting-disease.blogspot.com/2011/04/presence-and-seeding-activity-of.html






Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions


Marcelo A. Barria1, Glenn C. Telling2, Pierluigi Gambetti3, James A. Mastrianni4 and Claudio Soto5,* + Author Affiliations

1 University of Texas Medical School at Houston, United States; 2 University of Kentucky, United States; 3 Case Western Reserve University, United States; 4 University of Chicago, United States; 5 University of Texas Medical School, United States * Corresponding author; email: claudio.soto@uth.tmc.edu

Received October 28, 2010. Accepted January 4, 2011. Copyright © 2011, The American Society for Biochemistry and Molecular Biology


http://www.jbc.org/content/early/2011/01/04/jbc.M110.198465.long




Our findings demonstrate that cervid PrPSc, upon strain adaptation by serial passages in vitro or in cervid transgenic mice, is capable of converting human PrPC to produce PrPSc with unique biochemical properties, likely representing a new human prion strain. The newly generated CWD-huPrPSc material has been inoculated into transgenic mice expressing human PrP to study infectivity and disease phenotype and this data will be published elsewhere. ...end


PLEASE SEE FULL TEXT ;


Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions

Marcelo A. Barria1, Glenn C. Telling2, Pierluigi Gambetti3, James A. Mastrianni4 and Claudio Soto5,* + Author Affiliations

1 University of Texas Medical School at Houston, United States; 2 University of Kentucky, United States; 3 Case Western Reserve University, United States; 4 University of Chicago, United States; 5 University of Texas Medical School, United States * Corresponding author; email: claudio.soto@uth.tmc.edu

Received October 28, 2010. Accepted January 4, 2011. Copyright © 2011, The American Society for Biochemistry and Molecular Biology eneration


http://www.jbc.org/content/early/2011/01/04/jbc.M110.198465.long




Tuesday, January 25, 2011


Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions


http://chronic-wasting-disease.blogspot.com/2011/01/generation-of-new-form-of-human-prpsc.html





PLEASE NOTE ;

there are now two documented strains of CWD, and science is showing that indeed CWD could transmit to humans via transmission studies ;


P35

ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A WISCONSIN STRAIN OF CWD

Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5

The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.


http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf




PPo3-7:

Prion Transmission from Cervids to Humans is Strain-dependent

Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi Gambetti and Liuting Qing Department of Pathology; Case western Reserve University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial Sloan-Kettering Cancer Center; New York, NY USA

Key words: CWD, strain, human transmission

Chronic wasting disease (CWD) is a widespread prion disease in cervids (deer and elk) in North America where significant human exposure to CWD is likely and zoonotic transmission of CWD is a concern. Current evidence indicates a strong barrier for transmission of the classical CWD strain to humans with the PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD strains. What remain unknown is whether individuals with the PrP-129VV/MV genotypes are also resistant to the classical CWD strain and whether humans are resistant to all natural or adapted cervid prion strains. Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP, indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains. Preliminary results on CWD transmission in transgenic mice expressing human PrP-129V will also be discussed.

Acknowledgement Supported by NINDS NS052319 and NIA AG14359.


PPo2-27:

Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A. Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer's disease and related Brain disorders; Dept of Neurology; University of Texas Houston Medical School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago; Chicago, IL USA

Prion diseases are infectious neurodegenerative disorders affecting humans and animals that result from the conversion of normal prion protein (PrPC) into the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of cervids is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. CWD is highly contagious and its origin, mechanism of transmission and exact prevalence are currently unclear. The risk of transmission of CWD to humans is unknown. Defining that risk is of utmost importance, considering that people have been infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the infectious form by CWD PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique, which mimic in vitro the process of prion replication. Our results show that cervid PrPSc can induce the pathological conversion of human PrPC, but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, this newly generated human PrPSc exhibits a distinct biochemical pattern that differs from any of the currently known forms of human PrPSc, indicating that it corresponds to a novel human prion strain. Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.


PPo2-7:

Biochemical and Biophysical Characterization of Different CWD Isolates

Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin, Germany

Key words: CWD, strains, FT-IR, AFM

Chronic wasting disease (CWD) is one of three naturally occurring forms of prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie in sheep. CWD is contagious and affects captive as well as free ranging cervids. As long as there is no definite answer of whether CWD can breach the species barrier to humans precautionary measures especially for the protection of consumers need to be considered. In principle, different strains of CWD may be associated with different risks of transmission to humans. Sophisticated strain differentiation as accomplished for other prion diseases has not yet been established for CWD. However, several different findings indicate that there exists more than one strain of CWD agent in cervids. We have analysed a set of CWD isolates from white-tailed deer and could detect at least two biochemically different forms of disease-associated prion protein PrPTSE. Limited proteolysis with different concentrations of proteinase K and/or after exposure of PrPTSE to different pH-values or concentrations of Guanidinium hydrochloride resulted in distinct isolate-specific digestion patterns. Our CWD isolates were also examined in protein misfolding cyclic amplification studies. This showed different conversion activities for those isolates that had displayed significantly different sensitivities to limited proteolysis by PK in the biochemical experiments described above. We further applied Fourier transform infrared spectroscopy in combination with atomic force microscopy. This confirmed structural differences in the PrPTSE of at least two disinct CWD isolates. The data presented here substantiate and expand previous reports on the existence of different CWD strains.


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




UPDATED DATA ON 2ND CWD STRAIN


Wednesday, September 08, 2010


CWD PRION CONGRESS SEPTEMBER 8-11 2010



http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html





CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.


http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf




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




snip...

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.

snip...

R. BRADLEY


http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf




Prions in Skeletal Muscles of Deer with Chronic Wasting Disease

Rachel C. Angers1,*, Shawn R. Browning1,*?, Tanya S. Seward2, Christina J. Sigurdson4,?, Michael W. Miller5, Edward A. Hoover4 and Glenn C. Telling1,2,3,§ + Author Affiliations

Abstract

The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.

Received for publication 21 November 2005. Accepted for publication 13 January 2006.


http://www.sciencemag.org/cgi/content/abstract/sci;311/5764/1117




Journal of Virology, September 2009, p. 9608-9610, Vol. 83, No. 18 0022-538X/09/$08.00+0 doi:10.1128/JVI.01127-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Prion Infectivity in Fat of Deer with Chronic Wasting Disease

Brent Race,# Kimberly Meade-White,# Richard Race, and Bruce Chesebro* Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, Montana 59840

Received 2 June 2009/ Accepted 24 June 2009

ABSTRACT Top ABSTRACT TEXT REFERENCES

Chronic wasting disease (CWD) is a neurodegenerative prion disease of cervids. Some animal prion diseases, such as bovine spongiform encephalopathy, can infect humans; however, human susceptibility to CWD is unknown. In ruminants, prion infectivity is found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle. In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.

snip...

The highest risk of human contact with CWD might be through exposure to high-titer CNS tissue through accidental skin cuts or corneal contact at the time of harvest and butchering. However, the likelihood of a human consuming fat infected with a low titer of the CWD agent is much higher. It is impossible to remove all the fat present within muscle tissue, and fat consumption is inevitable when eating meat. Of additional concern is the fact that meat from an individual deer harvested by a hunter is typically consumed over multiple meals by the same group of people. These individuals would thus have multiple exposures to the CWD agent over time, which might increase the chance for transfer of infection.

In the Rocky Mountain region of North America, wild deer are subject to predation by wolves, coyotes, bears, and mountain lions. Although canines such as wolves and coyotes are not known to be susceptible to prion diseases, felines definitely are susceptible to BSE (9) and might also be infected by the CWD agent. Deer infected with the CWD agent are more likely to be killed by predators such as mountain lions (11). Peripheral tissues, including lymph nodes, muscle, and fat, which harbor prion infectivity are more accessible for consumption than CNS tissue, which has the highest level of infectivity late in disease. Therefore, infectivity in these peripheral tissues may be important in potential cross-species CWD transmissions in the wild.

The present finding of CWD infectivity in deer fat tissue raises the possibility that prion infectivity might also be found in fat tissue of other infected ruminants, such as sheep and cattle, whose fat and muscle tissues are more widely distributed in both the human and domestic-animal food chains. Although the infectivity in fat tissues is low compared to that in the CNS, there may be significant differences among species and between prion strains. Two fat samples from BSE agent-infected cattle were reported to be negative by bioassay in nontransgenic RIII mice (3, 6). However, RIII mice are 10,000-fold-less sensitive to BSE agent infection than transgenic mice expressing bovine PrP (4). It would be prudent to carry out additional infectivity assays on fat from BSE agent-infected cattle and scrapie agent-infected sheep using appropriate transgenic mice or homologous species to determine the risk from these sources.


http://jvi.asm.org/cgi/content/full/83/18/9608





THE LATEST DATA ON TISSUE INFECTIVITY

WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010

MAJOR CATEGORIES OF INFECTIVITY: TABLES IA, IB, IC

The assignment of tissues to high, low, and undetected infectivity categories is based exclusively upon observations of naturally occurring disease, or primary experimental infection by the oral route (in ruminants). The Tables do not include results from disease models using strains of TSE that have been adapted to experimental animals, because passaged strain phenotypes can differ significantly and unpredictably from those of naturally occurring disease. However, for tissues and fluids of exceptional public health interest, such as muscle, intestine, skin, secretions and excretions, experimental results have been indicated in footnotes.

Because the detection of misfolded prion protein (PrPTSE) broadly parallels infectivity titers in various tissues [Beekes et al 1996; Andreoletti et al 2004], PrPTSE testing results are presented in parallel with bioassay data.

Although a given tissue may be positive or negative in different varieties of TSE, the expert group considered a tissue to be potentially infectious even if a positive result occurred in only a single disease. The categorical assignment of tissues will almost certainly undergo further revision as new data accumulate from increasingly sensitive tests.

IA: High-infectivity tissues: CNS tissues that attain a high titer of infectivity in the later stages of all TSEs, and certain tissues that are anatomically associated with the CNS.

IB: Lower-infectivity tissues: peripheral tissues that have tested positive for infectivity and/or PrPTSE in at least one form of TSE.

IC: Tissues with no detectable infectivity: tissues that have been examined for infectivity and/or PrPTSE with negative results.

Data entries are shown as follows:

+ Presence of infectivity or PrPTSE

- Absence of detectable infectivity or PrPTSE

NT Not tested

NA Not applicable ?

Uncertain interpretation

( ) Limited or preliminary data

[ ] Infectivity or PrPTSE data based exclusively on bioassays in transgenic

(Tg)mice over-expressing the PrP-encoding gene or PrPTSE amplification methods.

A word of caution is offered about tissues in Table IB for which positive results are so far limited to either detection of PrPTSE using amplification techniques (PMCA), or infectivity bioassays in Tg mice that over-express PrP. The amounts of pathological protein or infectious agent detected by these exquisitely sensitive assays may well fall below the threshold of transmissibility for normal animals and humans. WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies 5

A good example is illustrated in the studies of urine and feces from deer infected with CWD: bioassays using normal deer as recipient subjects were negative; subsequent bioassays performed in Tg mice were positive. A similar discordance was observed for BSE muscle inoculated into cattle and Tgmice. Until more evidence is compiled showing that positive results in experimental PMCA and Tg mouse assays equate to a risk of transmitting disease under natural conditions, it cannot be assumed that such results imply the existence of a substantial risk to the health of animals or humans.

Considering the succession of updated Tables of the past few years, and the fact that inflammation has been shown to result in PrPTSE deposition in tissues that are not normally involved in TSE pathogenesis, it is evident that as testing continues, more tissues will find their way from Table IC into Table IB (but probably not from either Table IC or IB into Table IA). It is also evident that the data generated to date are far from complete, and that a great deal more work needs to be done if conclusions about the tissue distribution and significance of infectivity in a given TSE are to be based on direct measurements rather than by analogy to other forms of the disease.

Finally, it is critically important to understand that categories of infectivity are not the same as categories of risk, which require consideration not only of the level of infectivity in tissue, but also of the amount of tissue to which a person or animal is exposed, and the route by which infection is transmitted. For example, although the level of tissue infectivity is the most important factor in estimating the risk of transmission by instrument crosscontamination during surgical procedures (e.g., neurosurgery versus general surgery), it will be only one determinant of the risk of transmission by blood transfusions, in which a large amount of low-infectivity blood is administered intravenously, or the risk of transmission by foodstuffs that, irrespective of high or low infectivity, involve a comparatively inefficient oral route of infection.

snip...

Table IC: Tissues with no detected infectivity or PrPTSE

snip...

Musculo-skeletal tissues

Bone NT - NT - - NT NT NT NT NT

Tendon NT - NT - - NT NT NT NT NT

snip...

please see full text with tables here ;

WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010

also in the references at bottom i saw ;

12. A single positive marrow in multiple transmission attempts from cattle orally dosed with BSE-infected brain [Wells et al., 1999; Wells et al., 2005; Sohn et al., 2009].


http://www.who.int/bloodproducts/tablestissueinfectivity.pdf





From: TSS (216-119-163-189.ipset45.wt.net)

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"

To:

Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

Sent: Monday, September 30, 2002 9:22 AM

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.

That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention



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



From:

Sent: Sunday, September 29, 2002 10:15 AM

To: [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask]

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

snip...

full text ;


http://chronic-wasting-disease.blogspot.com/2009/02/exotic-meats-usa-announces-urgent.html





FDA is not recalling this CWD positive elk meat for the well being of the dead elk ;



Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II


http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html




see full text ;


http://chronic-wasting-disease.blogspot.com/2009/04/cwd-update-infection-studies-in-two.html






2002



Subject: Re: CWD AMERICA ???

Date: Fri, 12 Jul 2002 19:10:18 +0200

From: "INFORMATION DEPT" Organization: O.I.E

To: "Terry S. Singeltary Sr."

References:

I agree with you Dr Terry. The OIE, namely the International Animal Health Code Commission is working on making proposals to Member Countries to change the OIE lists so to avoid some the problems mentioned in you e-mail. This will take at least two years before adoption by the International Committee. For BSE, countries asked the OIE to post information on BSE on the OIE web site.

Personally, I am interested in Chronic Wasting Disease and I follow what is distributed through ProMed. Delegates of OIE Member Countries can propose diseases to be added to the list.

Kind regards.

Karim Ben Jebara

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

From: "Terry S. Singeltary Sr."

To: "INFORMATION DEPT"

Sent: Friday, July 12, 2002 8:43 PM

Subject: Re: CWD AMERICA ???

hello Dr. Jebara,

many thanks for your swift and kind reply.

if i am not mistaken, it was the same email address. it was 3 or 4 weeks ago i wrote, as it is, i don't save 'sent' emails anymore, unless very important.

my main concern (besides the fact that a potential TSE has been in the USA cattle for some time, but the APHIS do not test to find), is that the CWD could very well be transmitting to humans, and i just did not see to much posted about it on OIE site.

Coming back to your question, Chronic Wasting Disease is not an OIE

listed disease. Please see OIE disease lists at


http://www.oie.int/eng/maladies/en_classification.htm#ListeA).




why is this TSE (CWD) not listed and followed as with BSE ?

Article 1.1.3.2. 1. Countries shall make available to other countries, through the OIE, whatever information is necessary to minimise the spread of important animal diseases and to assist in achieving better worldwide control of these diseases.


http://www.oie.int/eng/normes/MCode/A_00005.htm




The USA CWD is an important animal disease.

why is it not followed?

The decision to add or delete a disease from the OIE lists, come through proposals made by Member Countries and it has to be adopted by the International Committee.

i _urgently_ suggest a proposal to the OIE to follow this disease very closely, and to propose _more_ testing in the USA for TSEs in the USA cattle...

kindest regards, terry



INFORMATION DEPT wrote:

Dear Sir,

This is the first time that I receive your e-mail. To whom have you written in the OIE or to which address?

Coming back to your question, Chronic Wasting Disease is not an OIE listed disease. Please see OIE disease lists at


http://www.oie.int/eng/maladies/en_classification.htm#ListeA).




Countries should report to the OIE any disease even is not listed in the OIE's lists in some conditions (example: an exceptional epidemiological event). Please read Chapter 1.1.3 of the International animal health code to have more information on disease notification and epidemiological information agreed by OIE Member Countries at :


http://www.oie.int/eng/normes/MCode/A_00005.htm





The decision to add or delete a disease from the OIE lists, come through proposals made by Member Countries and it has to be adopted by the International Committee.

Hope that I answered to your question.


Best regards.

Dr Karim Ben Jebara Head Animal Health Information Department OIE



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

From: "Terry S. Singeltary Sr."

To:

Sent: Friday, July 12, 2002 6:18 PM

Subject: CWD AMERICA ???

I WROTE TO OIE RECENTLY ASKING 'WHY OIE DOES NOT FOLLOW CWD IN AMERICA' ? with no reply ? i am still seeking an answer ?

many thanks, and kind regards, terry


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


Title: Experimental Second Passage of Chronic Wasting Disease (Cwd(mule Deer)) Agent to Cattle

Authors

Hamir, Amirali Kunkle, Robert Miller, Janice - ARS RETIRED Greenlee, Justin Richt, Juergen

Submitted to: Journal of Comparative Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: July 25, 2005 Publication Date: January 1, 2006 Citation: Hamir, A.N., Kunkle, R.A., Miller, J.M., Greenlee, J.J., Richt, J.A. 2006. Experimental second passage of chronic wasting disease (CWD(mule deer)) agent to cattle. Journal of Comparative Pathology. 134(1):63-69.

Interpretive Summary: To compare the findings of experimental first and second passage of chronic wasting disease (CWD) in cattle, 6 calves were inoculated into the brain with CWD-mule deer agent previously (first) passaged in cattle. Two other uninoculated calves served as controls. Beginning 10-12 months post inoculation (PI), all inoculates lost appetite and weight. Five animals subsequently developed clinical signs of central nervous system (CNS) abnormality. By 16.5 months PI, all cattle had been euthanized because of poor prognosis. None of the animals showed microscopic lesions of spongiform encephalopathy (SE) but the CWD agent was detected in their CNS tissues by 2 laboratory techniques (IHC and WB). These findings demonstrate that inoculated cattle amplify CWD agent but also develop clinical CNS signs without manifestation of microscopic lesions of SE. This situation has also been shown to occur following inoculation of cattle with another TSE agent, namely, sheep scrapie. The current study confirms previous work that indicates that the diagnostic tests currently used for confirmation of bovine spongiform encephalopathy (BSE) in the U.S. would detect CWD in cattle, should it occur naturally. Furthermore, it raises the possibility of distinguishing CWD from BSE in cattle due to the absence of microscopic lesions and a unique multifocal distribution of PrPres, as demonstrated by IHC, which in this study, appears to be more sensitive than the WB. Technical Abstract: To compare clinicopathological findings of first and second passage of chronic wasting disease (CWD) in cattle, a group of calves (n=6) were intracerebrally inoculated with CWD-mule deer agent previously (first) passaged in cattle. Two other uninoculated calves served as controls. Beginning 10-12 months post inoculation (PI), all inoculates lost appetite and lost weight. Five animals subsequently developed clinical signs of central nervous system (CNS) abnormality. By 16.5 months PI, all cattle had been euthanized because of poor prognosis. None of the animals showed microscopic lesions of spongiform encephalopathy (SE) but PrPres was detected in their CNS tissues by immunohistochemistry (IHC) and Western blot (WB) techniques. These findings demonstrate that intracerebrally inoculated cattle not only amplify CWD PrPres but also develop clinical CNS signs without manifestation of morphologic lesions of SE. This situation has also been shown to occur following inoculation of cattle with another TSE agent, scrapie. The current study confirms previous work that indicates the diagnostic techniques currently used for confirmation of bovine spongiform encephalopathy (BSE) in the U.S. would detect CWD in cattle, should it occur naturally. Furthermore, it raises the possibility of distinguishing CWD from BSE in cattle due to the absence of neuropathologic lesions and a unique multifocal distribution of PrPres, as demonstrated by IHC, which in this study, appears to be more sensitive than the WB.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=178318





PLUS, oral transmission between cervids, either infected carcases AND ESPECIALLY FEED THAT HAS ANIMAL PROTEIN, PLEASE SEE ;


PRODUCT Custom deer feed made for a Wisconsin farm. The product was in bags holding about 40 pounds each. Recall # V-122-4. CODE 1-30-04 on the product invoice and mixing record. RECALLING FIRM/MANUFACTURER Crivitz Feed Mill, Crivitz, WI, by telephone on February 20, 2004. Wisconsin State initiated recall is complete. REASON The recalled deer feed contained steamed bone meal which is prohibited material in feed for ruminants.

VOLUME OF PRODUCT IN COMMERCE 515 pounds.

DISTRIBUTION WI.

END OF ENFORCEMENT REPORT FOR APRIL 7, 2004

###

http://www.fda.gov/bbs/topics/enforce/2004/ENF00842.html





Experimental oral transmission of chronic wasting disease to red deer (Cervus elaphus elaphus): Early detection and late stage distribution of protease-resistant prion protein

Aru Balachandran, Noel P. Harrington, James Algire, Andrei Soutyrine, Terry R. Spraker, Martin Jeffrey, Lorenzo González, Katherine I. O’Rourke

Abstract — Chronic wasting disease (CWD), an important emerging prion disease of cervids, is readily transmitted by intracerebral or oral inoculation from deer-to-deer and elk-to-elk, suggesting the latter is a natural route of exposure. Studies of host range susceptibility to oral infection, particularly of those species found in habitats where CWD currently exists are imperative. This report describes the experimental transmission of CWD to red deer following oral inoculation with infectious CWD material of elk origin. At 18 to 20 months post-inoculation, mild to moderate neurological signs and weight loss were observed and animals were euthanized and tested using 3 conventional immunological assays. The data indicate that red deer are susceptible to oral challenge and that tissues currently used for CWD diagnosis show strong abnormal prion (PrPCWD) accumulation. Widespread peripheral PrPCWD deposition involves lymphoreticular tissues, endocrine tissues, and cardiac muscle and suggests a potential source of prion infectivity, a means of horizontal transmission and carrier state.

Can Vet J 2010;51:169–178

http://canadianveterinarians.net/publications-journal-issue-abstracts.aspx





Journal of General Virology (1999), 80, 2757-2764. © 1999 Society for General Microbiology

--------------------------------------------------------------------------------

Other Agents

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 ehoover@lamar.colostate.edu

Abstract TOP Abstract Introduction Methods Results Discussion References

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.

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




Chronic wasting disease (CWD), an important emerging prion disease of cervids, is readily transmitted by intracerebral or oral inoculation from deer-to-deer and elk-to-elk, suggesting the latter is a natural route of exposure.

http://canadianveterinarians.net/publications-journal-issue-abstracts.aspx





Chronic Wasting Disease Susceptibility of Four North American Rodents

Chad J. Johnson1*, Jay R. Schneider2, Christopher J. Johnson2, Natalie A. Mickelsen2, Julia A. Langenberg3, Philip N. Bochsler4, Delwyn P. Keane4, Daniel J. Barr4, and Dennis M. Heisey2 1University of Wisconsin School of Veterinary Medicine, Department of Comparative Biosciences, 1656 Linden Drive, Madison WI 53706, USA 2US Geological Survey, National Wildlife Health Center, 6006 Schroeder Road, Madison WI 53711, USA 3Wisconsin Department of Natural Resources, 101 South Webster Street, Madison WI 53703, USA 4Wisconsin Veterinary Diagnostic Lab, 445 Easterday Lane, Madison WI 53706, USA *Corresponding author email: cjohnson@svm.vetmed.wisc.edu

We intracerebrally challenged four species of native North American rodents that inhabit locations undergoing cervid chronic wasting disease (CWD) epidemics. The species were: deer mice (Peromyscus maniculatus), white-footed mice (P. leucopus), meadow voles (Microtus pennsylvanicus), and red-backed voles (Myodes gapperi). The inocula were prepared from the brains of hunter-harvested white-tailed deer from Wisconsin that tested positive for CWD. Meadow voles proved to be most susceptible, with a median incubation period of 272 days. Immunoblotting and immunohistochemistry confirmed the presence of PrPd in the brains of all challenged meadow voles. Subsequent passages in meadow voles lead to a significant reduction in incubation period. The disease progression in red-backed voles, which are very closely related to the European bank vole (M. glareolus) which have been demonstrated to be sensitive to a number of TSEs, was slower than in meadow voles with a median incubation period of 351 days. We sequenced the meadow vole and red-backed vole Prnp genes and found three amino acid (AA) differences outside of the signal and GPI anchor sequences. Of these differences (T56-, G90S, S170N; read-backed vole:meadow vole), S170N is particularly intriguing due its postulated involvement in "rigid loop" structure and CWD susceptibility. Deer mice did not exhibit disease signs until nearly 1.5 years post-inoculation, but appear to be exhibiting a high degree of disease penetrance. White-footed mice have an even longer incubation period but are also showing high penetrance. Second passage experiments show significant shortening of incubation periods. Meadow voles in particular appear to be interesting lab models for CWD. These rodents scavenge carrion, and are an important food source for many predator species. Furthermore, these rodents enter human and domestic livestock food chains by accidental inclusion in grain and forage. Further investigation of these species as potential hosts, bridge species, and reservoirs of CWD is required.

Potential Venison Exposure Among FoodNet Population Survey Respondents, 2006-2007

Ryan A. Maddox1*, Joseph Y. Abrams1, Robert C. Holman1, Lawrence B. Schonberger1, Ermias D. Belay1 Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, GA *Corresponding author e-mail: rmaddox@cdc.gov

The foodborne transmission of bovine spongiform encephalopathy to humans, resulting in variant Creutzfeldt-Jakob disease, indicates that humans can be susceptible to animal prion diseases. However, it is not known whether foodborne exposure to the agent causing chronic wasting disease (CWD) in cervids can cause human disease. The United States Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance for foodborne diseases through an extensive survey administered to respondents in selected states. To describe the frequency of deer and elk hunting and venison consumption, five questions were included in the 2006-2007 FoodNet survey. This survey included 17,372 respondents in ten states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. Of these respondents, 3,220 (18.5%) reported ever hunting deer or elk, with 217 (1.3%) reporting hunting in a CWD-endemic area (northeastern Colorado, southeastern Wyoming, and southwestern Nebraska). Of the 217 CWD-endemic area hunters, 74 (34.1%) were residents of Colorado. Respondents reporting hunting were significantly more likely to be male than female (prevalence ratio: 3.3, 95% confidence interval: 3.1-3.6) and, in general, older respondents were significantly more likely to report hunting than younger respondents. Venison consumption was reported by more than half (67.4%) of the study population, and most venison consumers (94.1%) reported that at least half of their venison came from the wild. However, more than half (59.1%) of the consumers reported eating venison only one to five times in their life or only once or twice a year. These findings indicate that a high percentage of the United States population engages in hunting and/or venison consumption. If CWD continues to spread to more areas across the country, a substantial number of people could potentially be exposed to the infectious agent.


http://www.cwd-info.org/pdf/3rd_CWD_Symposium_utah.pdf





NOW FOR RISK FACTORS FOR CWD TRANSMISSION TO CATTLE ;


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

From: David Colby

To: flounder9@verizon.net

Cc: stanley@XXXXXXXX

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

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

Dear Terry Singeltary,

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

Warm Regards, David Colby

--

David Colby, PhDAssistant ProfessorDepartment of Chemical EngineeringUniversity of Delaware

PLEASE SEE FULL TEXT ;

Wednesday, January 5, 2011

ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011

Prions

David W. Colby1,* and Stanley B. Prusiner1,2

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




re-ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions

CWD to cattle figures CORRECTION

Greetings,

I believe the statement and quote below is incorrect ;

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

Please see ;

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

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



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


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




kindest regards,

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




Thank you!

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

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



please see full text of my submission here ;


Wednesday, January 5, 2011

ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011

Prions

David W. Colby1,* and Stanley B. Prusiner1,2


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





Thursday, February 17, 2011

Environmental Sources of Scrapie Prions


http://scrapie-usa.blogspot.com/2011/02/environmental-sources-of-scrapie-prions.html



Monday, February 14, 2011

THE ROLE OF PREDATION IN DISEASE CONTROL: A COMPARISON OF SELECTIVE AND NONSELECTIVE REMOVAL ON PRION DISEASE DYNAMICS IN DEER

NO, NO, NOT NO, BUT HELL NO !

Journal of Wildlife Diseases, 47(1), 2011, pp. 78-93 © Wildlife Disease Association 2011


http://chronic-wasting-disease.blogspot.com/2011/02/role-of-predation-in-disease-control.html



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






Wednesday, February 16, 2011


IN CONFIDENCE


SCRAPIE TRANSMISSION TO CHIMPANZEES


IN CONFIDENCE


http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html




Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5–May 2011


http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html





Wednesday, March 9, 2011

27 U.S. Senators want to force feed Japan Highly Potential North America Mad Cow Beef TSE PRION CJD March 8, 2011

President Barack Obama The White House

1600 Pennsylvania Avenue, W Washington, DC 20500

Dear President Obama:


http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/27-us-senators-want-to-force-feed-japan.html





Monday, May 11, 2009

Rare BSE mutation raises concerns over risks to public health


http://bse-atypical.blogspot.com/2009/05/rare-bse-mutation-raises-concerns-over.html





Sunday, April 17, 2011

Transmission of Prion Strains in a Transgenic Mouse Model Overexpressing Human A53T Mutated [alpha]-Synuclein

Journal of Neuropathology & Experimental Neurology:

POST AUTHOR CORRECTIONS, 8 April 2011 doi: 10.1097/NEN.0b013e318217d95f

http://bse-atypical.blogspot.com/2011/04/transmission-of-prion-strains-in.html





Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html





Tuesday, April 26, 2011

sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)



http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html





Friday, April 15, 2011

PRION TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PROJECTS, RESEARCH FUNDING, BSE VOLUNTARY TESTING UPDATE IN NORTH AMERICA 2011



http://prionunitusaupdate2008.blogspot.com/2011/04/prion-transmissible-spongiform.html





PRION TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY RESEARCH FUNDING U.S.A.


COMPARE TO USA PRION FUNDING 2011


"which includes the ___elimination___ of Prion activities ($5,473,000),"


All Other Emerging and Zoonotic Infectious Diseases CDC‘s FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.


http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf






Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
flounder9@verizon.net

Labels:

Wednesday, April 06, 2011

Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease

Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease

Abstract Introduction Results Discussion Materials and Methods Acknowledgments Author Contributions References Martin L. Daus1, Johanna Breyer2, Katja Wagenfuehr1, Wiebke M. Wemheuer2, Achim Thomzig1, Walter J. Schulz-Schaeffer2, Michael Beekes1*

1 P24 - Transmissible Spongiform Encephalopathies, Robert Koch-Institut, Berlin, Germany, 2 Prion and Dementia Research Unit, Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany

Chronic wasting disease (CWD) is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE), or prion disease, occurring in cervids such as white tailed-deer (WTD), mule deer or elk in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report for the first time a direct biochemical demonstration of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity, the static and dynamic biochemical markers for biological prion infectivity, respectively, in skeletal muscles of CWD-infected cervids, i. e. WTD for which no clinical signs of CWD had been recognized. The presence of PrPTSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrPTSE was revealed by protein misfolding cyclic amplification (PMCA). Semi-quantitative Western blotting indicated that the concentration of PrPTSE in skeletal muscles of CWD-infected WTD was approximately 2000-10000 -fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE was located in muscle-associated nerve fascicles but not, in detectable amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.

snip...

Discussion

In the wake of the BSE epidemic, variant Creutzfeldt-Jakob disease has emerged as a previously unknown prion disease of humans. This has shown that significant risks for public health may potentially emanate from the presence of animal prions in human foodstuffs. When assessing such risks in the context of CWD, key factors that need to be considered are i) the distribution of CWD prions in infected animals and ii) the potential transmissibility of such prions to humans.

PMCA-based in vitro studies have indicated a rather high transmission barrier for CWD to macaques as well as to transgenic mice expressing the human prion protein, as no conversion of cellular prion proteins into PrPres could be induced by seeding PMCA reactions with CWD-infected brain tissue [22]. Consistent with these findings, transgenic mice overexpressing human prion protein with methionine or valine at polymorphic residue 129 were resistant to infection with CWD prions from mule deer [23]. Furthermore, recent in vivo studies revealed a robust barrier for the transmission of CWD to macaques which, again, is suggestive of a rather low risk for CWD transmission to humans [24]. However, squirrel monkeys could be infected with CWD [24], and increasing evidence points to the existence of different CWD isolates [25], [26]. Thus, it remains to be further clarified whether CWD may be caused by multiple prion strains with distinct transmission properties.

It has been shown previously that skeletal muscle tissue from CWD infected mule deer may contain prion infectivity [18]. Also, Western blot- and immunohistochemical analyses of heart muscles from CWD-infected Rocky mountain elk and white-tailed deer revealed the presence of pathological prion protein in cardiac myocytes. PrPTSE was found in the left ventricle of the heart at a 10- to 100- fold lower concentration as compared to the brain, but not in skeletal muscle [27].

Here we report the direct detection of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity in skeletal muscles from cervids, i. e. WTD for which no clinical signs of prion disease had been recognized, using Western blotting, tissue blotting and PMCA as analytical techniques. Kurt et al. [22] recently reported that normal brain homogenate (NBH) from Syrian hamsters effectively supports the amplification of PrPres from CWD seeds in serial PMCA. Building on similar findings previously made in our laboratory (not shown) we also used hamster NBH as substrate for our PMCA analyses. We found that PrPres generated by PMCA after seeding with CWD- or 263K scrapie agents did not exhibit significant differences in the glycosylation- or electrophoretic migration patterns (not shown). As a safeguard to PMCA specificity safety measures aimed at preventing inadvertent cross-contamination with both prions from cervids or hamsters were implemented. Specifically, we sealed our PMCA reaction tubes with parafilm and paraffin wax, performed all pipetting steps exclusively with plugged single-use pipette tips, and changed gloves each time before handling a new PMCA sample. With these safety measures in place unseeded controls in which PMCA was performed with normal hamster brain homogenate only did not produce any unspecific PrPres staining in our experimental setup.

Our findings were obtained by an alternative methodology to bioassays in animals (i. e. combined biochemical detection of PrPTSE and its proteinaceous seeding activity) but are consistent with the observations reported by Angers et al. [18]. They may also provide an explanation for the negative findings by Jewell et al. [27] in skeletal muscle, since our Western blot results indicate a substantially lower concentration of PrPTSE in such tissue than reported for heart muscle.

Yet, it has to be noted that our assessments of PrPTSE levels in skeletal muscles were based on findings in presumably pre- or subclinically infected animals. Therefore, the concentration of PrPTSE in skeletal muscles of WTD with clinically manifest CWD may possibly exceed our estimate which refers to clinically inconspicuous animals that are more likely to enter the human food chain. Our tissue blot findings in skeletal muscles from CWD-infected WTD would be consistent with an anterograde spread of CWD prions via motor nerve fibres to muscle tissue (figure 4A). Similar neural spreading pathways of muscle infection were previously found in hamsters orally challenged with scrapie [28] and suggested by the detection of PrPTSE in muscle fibres and muscle-associated nerve fascicles of clinically-ill non-human primates challenged with BSE prions [29]. Whether the absence of detectable PrPTSE in myofibers observed in our study is a specific feature of CWD in WTD, or was due to a pre- or subclinical stage of infection in the examined animals, remains to be established. In any case, our observations support previous findings suggesting the precautionary prevention of muscle tissue from CWD-infected WTD in the human diet, and highlight the need to comprehensively elucidate of whether CWD may be transmissible to humans. While the understanding of TSEs in cervids has made substantial progress during the past few years, the assessment and management of risks possibly emanating from prions in skeletal muscles of CWD-infected cervids requires further research.

Citation: Daus ML, Breyer J, Wagenfuehr K, Wemheuer WM, Thomzig A, et al. (2011) Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease. PLoS ONE 6(4): e18345. doi:10.1371/journal.pone.0018345

Editor: Jason Bartz, Creighton University, United States of America

Received: December 17, 2010; Accepted: March 1, 2011; Published: April 1, 2011

Copyright: © 2011 Daus et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The study was sponsored by the Alberta Prion Research Institute (APRI, www.prioninstitute.ca), and the study was carried out within the APRI-sponsored research project “Comprehensive risk assessment of Chronic Wasting Disease (CWD) transmission to humans using non-human primates”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: BeekesM@rki.de

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018345


Thank you Professor Beekes et al, and again to PLos for open access !


This is another important study showing risk factors that should be taken seriously for human health via CWD, and risk factors there from iatrogenically i.e. via friendly fire or the pass it forward mode of human and animal Transmissible Spongiform Encephalopathy. in my opinion, we have floundered too long. IN 2001 i brought this up to the O.I.E., and they said they too were concerned, but yet a decade later, they too are still floundering, thus, humans and animals are still being exposed, and more and more science shows that CWD can transmit to humans. ...

kind regards, terry


Sent: Saturday, April 02, 2011 11:02 AM

Subject: [BSE-L] CWD Canada, 19 new cases

Current as of: 2011-02-29

Date confirmed Location Animal type infected January

January 19 Saskatchewan Deer January

January 4 Saskatchewan Deer

http://inspection.gc.ca/english/anima/disemala/rep/2011cwdmdce.shtml


CWD spreading in USA too ;

CWD Canada, 19 new cases 2011

TEN KANSAS DEER CONFIRMED POSITIVE IN CWD TESTS

CWD IN NEBRASKA IS INCREASING WITH 51 POSITIVE CAS...

South Dakota finds 25 more cases of Chronic Wastin...

Soil clay content underlies prion infection odds

Chronic wasting disease spreads farther west in Al...

THE ROLE OF PREDATION IN DISEASE CONTROL: A COMPAR...

Chronic Wasting Disease Found In A White-Tailed De...

CWD ILLINOIS UPDATE FEBRUARY 2011

CWD Minnesota deer feeding ban covering Dodge, Goo...

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



CANADA CJD UPDATE 2011


CJD Deaths Reported by CJDSS1, 1994-20112 As of January 31, 2011

3. Final classification of 49 cases from 2009, 2010, 2011 is pending.

snip...

http://www.phac-aspc.gc.ca/hcai-iamss/cjd-mcj/cjdss-ssmcj/pdf/stats_0111-eng.pdf


USA 2011

USA

National Prion Disease Pathology Surveillance Center

Cases Examined1

(November 1, 2010)

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 51 33 28 5 0 0

1997 114 68 59 9 0 0

1998 87 51 43 7 1 0

1999 121 73 65 8 0 0

2000 146 103 89 14 0 0

2001 209 119 109 10 0 0

2002 248 149 125 22 2 0

2003 274 176 137 39 0 0

2004 325 186 164 21 0 13

2005 344 194 157 36 1 0

2006 383 197 166 29 0 24

2007 377 214 187 27 0 0

2008 394 231 205 25 0 0

2009 425 258 215 43 0 0

2010 333 213 158 33 0 0

TOTAL 38315 22656 1907 328 4 3

1 Listed based on the year of death or, if not available, on year of referral;

2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;

3 Disease acquired in the United Kingdom;

4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;

5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

http://www.cjdsurveillance.com/pdf/case-table.pdf


Please notice where sporadic CJD cases in 1996 went from 28 cases, to 215 cases in 2009, the highest recorded year to date. sporadic CJD is on a steady rise, and has been since 1996.

I also urge you to again notice these disturbing factors in lines 5 and 6 ;

5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.


========end=====tss=====2011


Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)

(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)

http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html



Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html




THE steady rise of sporadic CJD cases in Canada AND USA, with many unusual cases of ''PENDING CLASSIFICATIONS" which have been pending now FOR 3 YEARS ???



Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions


Marcelo A. Barria1, Glenn C. Telling2, Pierluigi Gambetti3, James A. Mastrianni4 and Claudio Soto5,* + Author Affiliations

1 University of Texas Medical School at Houston, United States; 2 University of Kentucky, United States; 3 Case Western Reserve University, United States; 4 University of Chicago, United States; 5 University of Texas Medical School, United States * Corresponding author; email: claudio.soto@uth.tmc.edu

Received October 28, 2010. Accepted January 4, 2011. Copyright © 2011, The American Society for Biochemistry and Molecular Biology

http://www.jbc.org/content/early/2011/01/04/jbc.M110.198465.long


Our findings demonstrate that cervid PrPSc, upon strain adaptation by serial passages in vitro or in cervid transgenic mice, is capable of converting human PrPC to produce PrPSc with unique biochemical properties, likely representing a new human prion strain. The newly generated CWD-huPrPSc material has been inoculated into transgenic mice expressing human PrP to study infectivity and disease phenotype and this data will be published elsewhere. ...end


PLEASE SEE FULL TEXT ;

Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions

Marcelo A. Barria1, Glenn C. Telling2, Pierluigi Gambetti3, James A. Mastrianni4 and Claudio Soto5,* + Author Affiliations

1 University of Texas Medical School at Houston, United States; 2 University of Kentucky, United States; 3 Case Western Reserve University, United States; 4 University of Chicago, United States; 5 University of Texas Medical School, United States * Corresponding author; email: claudio.soto@uth.tmc.edu

Received October 28, 2010. Accepted January 4, 2011. Copyright © 2011, The American Society for Biochemistry and Molecular Biology eneration

http://www.jbc.org/content/early/2011/01/04/jbc.M110.198465.long


Tuesday, January 25, 2011

Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions

http://chronic-wasting-disease.blogspot.com/2011/01/generation-of-new-form-of-human-prpsc.html


PLEASE NOTE ;

there are now two documented strains of CWD, and science is showing that indeed CWD could transmit to humans via transmission studies ;


P35

ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A WISCONSIN STRAIN OF CWD

Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5

The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.

http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf


PPo3-7:

Prion Transmission from Cervids to Humans is Strain-dependent

Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi Gambetti and Liuting Qing Department of Pathology; Case western Reserve University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial Sloan-Kettering Cancer Center; New York, NY USA

Key words: CWD, strain, human transmission

Chronic wasting disease (CWD) is a widespread prion disease in cervids (deer and elk) in North America where significant human exposure to CWD is likely and zoonotic transmission of CWD is a concern. Current evidence indicates a strong barrier for transmission of the classical CWD strain to humans with the PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD strains. What remain unknown is whether individuals with the PrP-129VV/MV genotypes are also resistant to the classical CWD strain and whether humans are resistant to all natural or adapted cervid prion strains. Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP, indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains. Preliminary results on CWD transmission in transgenic mice expressing human PrP-129V will also be discussed.

Acknowledgement Supported by NINDS NS052319 and NIA AG14359.

PPo2-27:

Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A. Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer's disease and related Brain disorders; Dept of Neurology; University of Texas Houston Medical School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago; Chicago, IL USA

Prion diseases are infectious neurodegenerative disorders affecting humans and animals that result from the conversion of normal prion protein (PrPC) into the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of cervids is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. CWD is highly contagious and its origin, mechanism of transmission and exact prevalence are currently unclear. The risk of transmission of CWD to humans is unknown. Defining that risk is of utmost importance, considering that people have been infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the infectious form by CWD PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique, which mimic in vitro the process of prion replication. Our results show that cervid PrPSc can induce the pathological conversion of human PrPC, but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, this newly generated human PrPSc exhibits a distinct biochemical pattern that differs from any of the currently known forms of human PrPSc, indicating that it corresponds to a novel human prion strain. Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.

PPo2-7:

Biochemical and Biophysical Characterization of Different CWD Isolates

Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin, Germany

Key words: CWD, strains, FT-IR, AFM

Chronic wasting disease (CWD) is one of three naturally occurring forms of prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie in sheep. CWD is contagious and affects captive as well as free ranging cervids. As long as there is no definite answer of whether CWD can breach the species barrier to humans precautionary measures especially for the protection of consumers need to be considered. In principle, different strains of CWD may be associated with different risks of transmission to humans. Sophisticated strain differentiation as accomplished for other prion diseases has not yet been established for CWD. However, several different findings indicate that there exists more than one strain of CWD agent in cervids. We have analysed a set of CWD isolates from white-tailed deer and could detect at least two biochemically different forms of disease-associated prion protein PrPTSE. Limited proteolysis with different concentrations of proteinase K and/or after exposure of PrPTSE to different pH-values or concentrations of Guanidinium hydrochloride resulted in distinct isolate-specific digestion patterns. Our CWD isolates were also examined in protein misfolding cyclic amplification studies. This showed different conversion activities for those isolates that had displayed significantly different sensitivities to limited proteolysis by PK in the biochemical experiments described above. We further applied Fourier transform infrared spectroscopy in combination with atomic force microscopy. This confirmed structural differences in the PrPTSE of at least two disinct CWD isolates. The data presented here substantiate and expand previous reports on the existence of different CWD strains.

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


UPDATED DATA ON 2ND CWD STRAIN

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html


CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf


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


snip...

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.

snip...

R. BRADLEY

http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf



Prions in Skeletal Muscles of Deer with Chronic Wasting Disease

Rachel C. Angers1,*, Shawn R. Browning1,*?, Tanya S. Seward2, Christina J. Sigurdson4,?, Michael W. Miller5, Edward A. Hoover4 and Glenn C. Telling1,2,3,§ + Author Affiliations

Abstract

The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.

Received for publication 21 November 2005. Accepted for publication 13 January 2006.

http://www.sciencemag.org/cgi/content/abstract/sci;311/5764/1117


Journal of Virology, September 2009, p. 9608-9610, Vol. 83, No. 18 0022-538X/09/$08.00+0 doi:10.1128/JVI.01127-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Prion Infectivity in Fat of Deer with Chronic Wasting Disease

Brent Race,# Kimberly Meade-White,# Richard Race, and Bruce Chesebro* Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, Montana 59840

Received 2 June 2009/ Accepted 24 June 2009

ABSTRACT Top ABSTRACT TEXT REFERENCES

Chronic wasting disease (CWD) is a neurodegenerative prion disease of cervids. Some animal prion diseases, such as bovine spongiform encephalopathy, can infect humans; however, human susceptibility to CWD is unknown. In ruminants, prion infectivity is found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle. In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.

snip...

The highest risk of human contact with CWD might be through exposure to high-titer CNS tissue through accidental skin cuts or corneal contact at the time of harvest and butchering. However, the likelihood of a human consuming fat infected with a low titer of the CWD agent is much higher. It is impossible to remove all the fat present within muscle tissue, and fat consumption is inevitable when eating meat. Of additional concern is the fact that meat from an individual deer harvested by a hunter is typically consumed over multiple meals by the same group of people. These individuals would thus have multiple exposures to the CWD agent over time, which might increase the chance for transfer of infection.

In the Rocky Mountain region of North America, wild deer are subject to predation by wolves, coyotes, bears, and mountain lions. Although canines such as wolves and coyotes are not known to be susceptible to prion diseases, felines definitely are susceptible to BSE (9) and might also be infected by the CWD agent. Deer infected with the CWD agent are more likely to be killed by predators such as mountain lions (11). Peripheral tissues, including lymph nodes, muscle, and fat, which harbor prion infectivity are more accessible for consumption than CNS tissue, which has the highest level of infectivity late in disease. Therefore, infectivity in these peripheral tissues may be important in potential cross-species CWD transmissions in the wild.

The present finding of CWD infectivity in deer fat tissue raises the possibility that prion infectivity might also be found in fat tissue of other infected ruminants, such as sheep and cattle, whose fat and muscle tissues are more widely distributed in both the human and domestic-animal food chains. Although the infectivity in fat tissues is low compared to that in the CNS, there may be significant differences among species and between prion strains. Two fat samples from BSE agent-infected cattle were reported to be negative by bioassay in nontransgenic RIII mice (3, 6). However, RIII mice are 10,000-fold-less sensitive to BSE agent infection than transgenic mice expressing bovine PrP (4). It would be prudent to carry out additional infectivity assays on fat from BSE agent-infected cattle and scrapie agent-infected sheep using appropriate transgenic mice or homologous species to determine the risk from these sources.

http://jvi.asm.org/cgi/content/full/83/18/9608



THE LATEST DATA ON TISSUE INFECTIVITY

WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010

MAJOR CATEGORIES OF INFECTIVITY: TABLES IA, IB, IC

The assignment of tissues to high, low, and undetected infectivity categories is based exclusively upon observations of naturally occurring disease, or primary experimental infection by the oral route (in ruminants). The Tables do not include results from disease models using strains of TSE that have been adapted to experimental animals, because passaged strain phenotypes can differ significantly and unpredictably from those of naturally occurring disease. However, for tissues and fluids of exceptional public health interest, such as muscle, intestine, skin, secretions and excretions, experimental results have been indicated in footnotes.

Because the detection of misfolded prion protein (PrPTSE) broadly parallels infectivity titers in various tissues [Beekes et al 1996; Andreoletti et al 2004], PrPTSE testing results are presented in parallel with bioassay data.

Although a given tissue may be positive or negative in different varieties of TSE, the expert group considered a tissue to be potentially infectious even if a positive result occurred in only a single disease. The categorical assignment of tissues will almost certainly undergo further revision as new data accumulate from increasingly sensitive tests.

IA: High-infectivity tissues: CNS tissues that attain a high titer of infectivity in the later stages of all TSEs, and certain tissues that are anatomically associated with the CNS.

IB: Lower-infectivity tissues: peripheral tissues that have tested positive for infectivity and/or PrPTSE in at least one form of TSE.

IC: Tissues with no detectable infectivity: tissues that have been examined for infectivity and/or PrPTSE with negative results.

Data entries are shown as follows:

+ Presence of infectivity or PrPTSE

- Absence of detectable infectivity or PrPTSE

NT Not tested

NA Not applicable ?

Uncertain interpretation

( ) Limited or preliminary data

[ ] Infectivity or PrPTSE data based exclusively on bioassays in transgenic

(Tg)mice over-expressing the PrP-encoding gene or PrPTSE amplification methods.

A word of caution is offered about tissues in Table IB for which positive results are so far limited to either detection of PrPTSE using amplification techniques (PMCA), or infectivity bioassays in Tg mice that over-express PrP. The amounts of pathological protein or infectious agent detected by these exquisitely sensitive assays may well fall below the threshold of transmissibility for normal animals and humans. WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies 5

A good example is illustrated in the studies of urine and feces from deer infected with CWD: bioassays using normal deer as recipient subjects were negative; subsequent bioassays performed in Tg mice were positive. A similar discordance was observed for BSE muscle inoculated into cattle and Tgmice. Until more evidence is compiled showing that positive results in experimental PMCA and Tg mouse assays equate to a risk of transmitting disease under natural conditions, it cannot be assumed that such results imply the existence of a substantial risk to the health of animals or humans.

Considering the succession of updated Tables of the past few years, and the fact that inflammation has been shown to result in PrPTSE deposition in tissues that are not normally involved in TSE pathogenesis, it is evident that as testing continues, more tissues will find their way from Table IC into Table IB (but probably not from either Table IC or IB into Table IA). It is also evident that the data generated to date are far from complete, and that a great deal more work needs to be done if conclusions about the tissue distribution and significance of infectivity in a given TSE are to be based on direct measurements rather than by analogy to other forms of the disease.

Finally, it is critically important to understand that categories of infectivity are not the same as categories of risk, which require consideration not only of the level of infectivity in tissue, but also of the amount of tissue to which a person or animal is exposed, and the route by which infection is transmitted. For example, although the level of tissue infectivity is the most important factor in estimating the risk of transmission by instrument crosscontamination during surgical procedures (e.g., neurosurgery versus general surgery), it will be only one determinant of the risk of transmission by blood transfusions, in which a large amount of low-infectivity blood is administered intravenously, or the risk of transmission by foodstuffs that, irrespective of high or low infectivity, involve a comparatively inefficient oral route of infection.

snip...

Table IC: Tissues with no detected infectivity or PrPTSE

snip...

Musculo-skeletal tissues

Bone NT - NT - - NT NT NT NT NT

Tendon NT - NT - - NT NT NT NT NT

snip...

please see full text with tables here ;

WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010

also in the references at bottom i saw ;

12. A single positive marrow in multiple transmission attempts from cattle orally dosed with BSE-infected brain [Wells et al., 1999; Wells et al., 2005; Sohn et al., 2009].

http://www.who.int/bloodproducts/tablestissueinfectivity.pdf


From: TSS (216-119-163-189.ipset45.wt.net)

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"

To:

Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

Sent: Monday, September 30, 2002 9:22 AM

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.

That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention

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

From:

Sent: Sunday, September 29, 2002 10:15 AM

To: [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask]

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

snip...

full text ;

http://chronic-wasting-disease.blogspot.com/2009/02/exotic-meats-usa-announces-urgent.html



FDA is not recalling this CWD positive elk meat for the well being of the dead elk ;



Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html


see full text ;

http://chronic-wasting-disease.blogspot.com/2009/04/cwd-update-infection-studies-in-two.html



Subject: Re: CWD AMERICA ???

Date: Fri, 12 Jul 2002 19:10:18 +0200

From: "INFORMATION DEPT" Organization: O.I.E

To: "Terry S. Singeltary Sr."

References: <3D2F0169.3@wt.net> <012901c229b2$ad43bb90$7f00000a@HPKB> <3D2F2358.5010700@wt.net>

I agree with you Dr Terry. The OIE, namely the International Animal Health Code Commission is working on making proposals to Member Countries to change the OIE lists so to avoid some the problems mentioned in you e-mail. This will take at least two years before adoption by the International Committee. For BSE, countries asked the OIE to post information on BSE on the OIE web site.

Personally, I am interested in Chronic Wasting Disease and I follow what is distributed through ProMed. Delegates of OIE Member Countries can propose diseases to be added to the list.

Kind regards.

Karim Ben Jebara

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

From: "Terry S. Singeltary Sr."

To: "INFORMATION DEPT"

Sent: Friday, July 12, 2002 8:43 PM

Subject: Re: CWD AMERICA ???

hello Dr. Jebara,

many thanks for your swift and kind reply.

if i am not mistaken, it was the same email address. it was 3 or 4 weeks ago i wrote, as it is, i don't save 'sent' emails anymore, unless very important.

my main concern (besides the fact that a potential TSE has been in the USA cattle for some time, but the APHIS do not test to find), is that the CWD could very well be transmitting to humans, and i just did not see to much posted about it on OIE site.

Coming back to your question, Chronic Wasting Disease is not an OIE

listed disease. Please see OIE disease lists at

http://www.oie.int/eng/maladies/en_classification.htm#ListeA).


why is this TSE (CWD) not listed and followed as with BSE ?

Article 1.1.3.2. 1. Countries shall make available to other countries, through the OIE, whatever information is necessary to minimise the spread of important animal diseases and to assist in achieving better worldwide control of these diseases.

http://www.oie.int/eng/normes/MCode/A_00005.htm


The USA CWD is an important animal disease.

why is it not followed?

The decision to add or delete a disease from the OIE lists, come

through proposals made by Member Countries and it has to be adopted by

the International Committee.

i _urgently_ suggest a proposal to the OIE to follow this disease very closely, and to propose _more_ testing in the USA for TSEs in the USA cattle...

kindest regards, terry



INFORMATION DEPT wrote:

Dear Sir,

This is the first time that I receive your e-mail. To whom have you written in the OIE or to which address?

Coming back to your question, Chronic Wasting Disease is not an OIE listed disease. Please see OIE disease lists at http://www.oie.int/eng/maladies/en_classification.htm#ListeA).

Countries should report to the OIE any disease even is not listed in the OIE's lists in some conditions (example: an exceptional epidemiological event). Please read Chapter 1.1.3 of the International animal health code to have more information on disease notification and epidemiological information agreed by OIE Member Countries at : http://www.oie.int/eng/normes/MCode/A_00005.htm


The decision to add or delete a disease from the OIE lists, come through proposals made by Member Countries and it has to be adopted by the International Committee.

Hope that I answered to your question.

Best regards.

Dr Karim Ben Jebara Head Animal Health Information Department OIE


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

From: "Terry S. Singeltary Sr."

To:

Sent: Friday, July 12, 2002 6:18 PM

Subject: CWD AMERICA ???

I WROTE TO OIE RECENTLY ASKING 'WHY OIE DOES NOT FOLLOW CWD IN AMERICA' ? with no reply ? i am still seeking an answer ?

many thanks, and kind regards, terry



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


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

Subject: OIE Scientific and Technical Review, Vol 11 (2) June 1992 Sub Acute Spongiform Encephalopathies in Animals (CWD???)

Date: Thu, 29 Jan 2004 14:49:03 -0600

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de

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

Richard Kimberlin has obviously declined and suggested to OIE that Ray Bradley takes on the role of both author of the introductory chapter and coordinator...

http://www.bseinquiry.gov.uk/files/yb/1991/03/04002001.pdf




http://collections.europarchive.org/tna/20081106101342/http://www.bseinquiry.gov.uk/files/yb/1991/03/04002001.pdf



OIE Scientifoc and Technical Review, Vol 11 (2) June 1992 Sub Acute Spongiform Encephalopathies in Animals

91\02.20\1.1-1.2 20/02/91 Minute S C Hutchins I Crawford

snip...

a) I think it would be advisable to include scrapie, BSE and transmissible mink encephalopathy (hence the proposed title)...

snip...



http://www.bseinquiry.gov.uk/files/yb/1991/02/19004001.pdf


http://collections.europarchive.org/tna/20080103024333/http://www.bseinquiry.gov.uk/files/yb/1991/02/19004001.pdf




and i proposed to OIE years ago to include CWD. but with these new atypical case of TSE showing up in cattle and sheep, it will be interesting to see how the OIE handles the USA demands on weakening the BSE/TSE regs for exporting countries;

Date: Fri, 12 Jul 2002 16:11:42 -0700

Reply-To: B S E-l

Sender: Bovine Spongiform Encephalopathy

From: TSS Subject: CWD/USA -- CWD/OIE?

snip...

Greetings List Members,

speaking with someone at the OIE about my concerns with CWD and the non-testing for TSEs in USA cattle, i find it very sad that the OIE does not follow CWD related issues. BUT, they voice my same concerns and said changes are in the makings. sadly, the changes will take about 2 years?

snip...

''I agree with you Dr Terry. The OIE, namely the International Animal Health Code Commission is working on making proposals to Member Countries to change the OIE lists so to avoid some the problems mentioned in you e-mail. This will take at least two years before adoption by the International Committee.''

snip...

two years is a very long time, on an issue of such importance to both humans and animals...

kind regards, terry

snip...


PAGE 25 Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculam (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in _all_ of these species with the shortest incubation period in the ferret...



http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf


http://collections.europarchive.org/tna/20090506002237/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf



Clearly, it is premature to draw firm conclusions about CWD passing naturally into humans, cattle and sheep, but the present results suggest that CWD transmissions to humans would be as limited by PrP incompatibility as transmissions of BSE or sheep scrapie to humans. Although there is no evidence that sheep scrapie has affected humans, it is likely that BSE has caused variant CJD in 74 people (definite and probable variant CJD cases to date according to the UK CJD Surveillance Unit). Given the presumably large number of people exposed to BSE infectivity, the susceptibility of humans may still be very low compared with cattle, which would be consistent with the relatively inefficient conversion of human PrP-sen by PrPBSE. Nonetheless, since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure of humans (as well as sheep and cattle) to CWD infectivity as has been recommended for other animal TSEs.

snip...

http://www.emboj.org/current.shtml


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


IN CONFIDENCE

TRANSMISSION TO CHIMPANZEES

snip...

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.

snip...

R. BRADLEY

http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf


http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf



http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf



same reason CJD/TSE is not reportable Nationally in the USA. same reason no CJD questionnaire exists in the USA that is issued to all victims and families of victims asking real questions pertaining to route and source of agent. no autopies for all demented of young AND OLD! same reason the USA is steadfast refusing to this day to rapid TSE test all cattle for human/animal consumption. the USA simply does not want to know$



hell, we should just retain it all, and just play like it has not happened for the next 40 years as well. hmm, something else to ponder ;


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


so, when/where is our first case transmission study of TSE on man going to be? i wish to witness this and have a few suggestions for our first human guinea-pigs ;-)


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


########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############


Saturday, December 18, 2010

OIE Global Conference on Wildlife Animal Health and Biodiversity - Preparing for the Future (TSE AND PRIONS) Paris (France), 23-25 February 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/oie-global-conference-on-wildlife.html



FRIENDLY FIRE AND OR THE PASS IF FORWARD MODE OF TSE IATROGENIC


Monday, February 7, 2011

FDA's Currently-Recommended Policies to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products 2011 ???

http://tseac.blogspot.com/2011/02/fdas-currently-recommended-policies-to.html


Thursday, August 12, 2010

USA Blood products, collected from a donor who was at risk for vCJD, were distributed July-August 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/usa-blood-products-collected-from-donor.html


Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html


Tuesday, March 29, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html


TSS

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