Structural compatibility of infecting prion proteins with those of a new host determine whether they will be successfully transmitted. When the connection was made between bovine spongiform encephalopathy (BSE or “mad cow” disease) and human illnesses in the 1990s, it raised the public profile of the underlying prion diseases as the implications of animal and public health crises, and their economic impacts, became apparent. At the core of these concerns is how prions, the infectious agent, diversify and expand their host range. On page 1154 of this issue, Angers et al. ( 1) reveal how this occurs in chronic wasting disease (CWD), a contagious prion disease of wild deer and elk. Its prevalence in the United States raised fears that, like BSE, it might transmit to humans.
Prions cause fatal neurodegenerative diseases of humans and animals such as scrapie in sheep and goats, BSE in cattle, and Creutzfeldt-Jakob disease in humans ( 2). They consist of a rogue form of a protein produced by an infected animal, not by a foreign DNA or RNA genome, and pass from one species to another via dietary and other routes of transmission. Prions are thought to be composed principally or entirely of polymers of misfolded prion protein (known collectively as PrP scrapie or PrPSc). They propagate by recruiting the normal host prion protein (PrPC) via seeded protein fi brilization. In this process, fragmentation of elongating fi brils leads to an autocatalytic, exponential amplifi cation process that effectively mimics a conventional infectious agent in its ability to invade and colonize susceptible hosts. Despite the absence of a nucleic acid genome, prions exist as multiple strains that can be serially propagated in laboratory animals and differentiated by the patterns of disease they produce. Because multiple strains can be maintained in inbred mice with identical PrP genes, prions cannot be encoded by differences in PrP primary structure (its amino acid sequence). Rather, it is thought that they represent structurally different PrPSc seeds that recruit host PrPC into polymers of misfolded PrP. Thus, strains may be associated with biochemically distinct PrPSc types that can propagate on serial passage in susceptible hosts, including those from different species ( 3– 5) (see the figure).
PrPs have a highly conserved structure, which is presumably central to their ability to infect across species. Although differences in PrPC primary structure have been considered a barrier to cross-species infection, the “strain-ness” of a prion is fundamental to its ability to infect a new species. Thus, two prion types, or strains, that propagate in one species may have different abilities to cross a transmission barrier ( 6). Under the conformational selection model ( 7), of the possible PrPSc strains that can overcome natural clearance and propagate effectively in mammals, only a subset is compatible with a given host PrPC structure, and can thereby propagate in that host. Transmission barriers can be explained by the degree of overlap between strain types that are permissible in the two species concerned. Such effects may also be encountered within a species where there are PrP polymorphisms. A common human PrP polymorphism (at amino acid position 129) dramatically affects strain selection ( 4, 8) and has a powerful effect on human susceptibility to prion disease ( 9, 10). Important PrP polymorphisms are also seen in sheep and other species, and conformational selection occurs with yeast prions as well ( 11).
However, in some cases, prions do not maintain their identity in a new host but switch properties. Such strain “mutation” ( 12) may result from crossing between species, or intraspecies transmission due to PrP polymorphism or the effect of genetic background ( 13). The new strain generated may be more or less pathogenic in a second species than its progenitor, so mutation has potential public and animal health implications.
Although is has been argued that prion strains may be cloned ( 12), such material is heterogeneous when assessed by physical and biochemical methods. It may be that prion strains represent an ensemble of molecular species maintained under host selection ( 14). Such a quasispecies would have a dominant component with recognizable biochemical and biological properties, but also have lower-abundance subspecies. The preferential selection of the latter in an alternate host that is unable to propagate the dominant species could explain strain mutation ( 14), as observed in prion-infected cell cultures ( 15).
CWD is prevalent in wild cervids (deer and elk) in several U.S. states and has been recognized in Canada and South Korea. It spreads readily between wild animals, and urine, feces, and saliva are infectious ( 16). The occurrence of multiple strains of CWD is likely, given that multiple cervid species and different PrPC structures (including within-species PrP polymorphism) are involved, and the existence of at least two CWD strains (CWD 1 and 2) has now been demonstrated by Angers et al. The authors show that CWD prion strain selection and mutation are influenced by the amino acid at position 226 in PrP ( 4, 8), which differs between deer and elk. Although CWD 1 and 2 can be distinguished by biological strain typing methods, their biochemical characteristics are similar by the molecular strain typing methods used. Assuming that the “proteinonly” model of replication is correct, such differences in disease-associated PrP must exist. However, these differences may reside in protease- sensitive forms of abnormal PrP, which are important components of prion isolates.
What is the importance of the findings of Angers et al. for public health? One method to model human susceptibility, as done with BSE in the 1990s ( 2), is to determine the susceptibility of transgenic mice expressing human PrPC to CWD prion infection in comparison to susceptibility in human and other animal strains. Studies so far show that such mice are resistant ( 17, 18). However, it is necessary to repeat these studies with all CWD strains identified and to take account of permutations of PrP polymorphisms in CWD affected animals and humans. This further evidence for the role of PrP polymorphism on strain selection and mutation should highlight the potential for a new zoonotic prion strain to emerge from prion evolution in animal reservoirs, notably in worldwide endemic scrapie of sheep and goats as well as CWD in deer and elk.
Prion-like mechanisms may be relevant in common human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Accumulation of misfolded host proteins occurs in these diseases, and seeded protein aggregation may be relevant to the etiology and spread of pathology ( 14). It will be of great interest to see if the phenomena of conformational and kinetic selection of strains and their mechanisms of neurotoxicity are also important in these and other diseases of protein misfolding.
Prion propagation. (A) A limited set of mammalian PrPSc conformations can propagate as prions using the PrPC present in susceptible host species. Prions transmit readily between hosts that express the same PrPC, and may do so in those with different PrPC if there is substantial overlap of permissible conformations (species I and II). If there is little or no overlap (species I and III), a major transmission barrier occurs. (B) A prion strain may be a molecular ensemble maintained under host selection. (a) A strain can propagate in the same species expressing identical PrPC; (b) strain mutation may occur when prions colonize the same species with a different PrPC, or (c) may propagate in a different species with compatible PrPC; (d) if not compatible in a new species, mutation may occur.
1. R. C. Angers et al., Science 328, 1154 (2010).
2. J. Collinge, Annu. Rev. Neurosci. 24, 519 (2001).
3. R. A. Bessen, R. F. Marsh, J. Virol. 68, 7859 (1994).
4. J. Collinge et al., Nature 383, 685 (1996).
5. G. C. Telling et al., Science 274, 2079 (1996).
6. A. F. Hill et al., Nature 389, 448, 526 (1997).
7. J. Collinge, Lancet 354, 317 (1999).
8. J. D. Wadsworth et al., Science 306, 1793 (2004).
9. M. S. Palmer et al., Nature 352, 340 (1991).
10. S. Mead et al., Science 300, 640 (2003).
11. R. B. Wickner et al., Annu. Rev. Genet. 38, 681 (2004).
12. M. E. Bruce, A. G. Dickinson, J. Gen. Virol. 68, 79 (1987).
13. S. E. Lloyd et al., J. Gen. Virol. 85, 2471 (2004).
14. J. Collinge, A. R. Clarke, Science 318, 930 (2007).
15. J. Li et al., Science 327, 869 (2010).
16. C. K. Mathiason et al., PLoS ONE 4, e5916 (2009).
17. G. Tamguney et al., J. Virol. 80, 9104 (2006).
18. Q. Kong et al., J. Neurosci. 25, 7944 (2005).www.sciencemag.org
SCIENCE VOL 328 28 MAY 2010
Friday, May 14, 2010
Prion Strain Mutation Determined by Prion Protein Conformational Compatibility and Primary Structure
Published Online May 13, 2010 Science DOI: 10.1126/science.1187107 Science Express Indexhttp://www.sciencemag.org/cgi/content/abstract/science.1187107
see full text and more here ;http://chronic-wasting-disease.blogspot.com/2010/05/prion-strain-mutation-determined-by.html
John Collinge wrote ;
>>> "They consist of a rogue form of a protein produced by an infected animal, not by a foreign DNA or RNA genome...Despite the absence of a nucleic acid genome, prions exist as multiple strains" <<<
SOME interesting findings and comments below ; Our laboratory continues to do fundamental research on infectious dementias and the causes of neurodegenerative disease. The transmission of variant Creutzfeldt-Jakob Disease (vCJD) to normal mice as well as to neuronal cultures here (PMID: 19097123) proves that the vCJD infectious agent is derived from epidemic “mad cow disease” (BSE) in the UK. This virus-like agent is a unique strain belonging to the group that causes Transmissible Spongiform Encephalopathies (TSEs). These agents affect many mammalian species. Our transmission of kuru, a human TSE in New Guinea, both to mice and to monotypic cultures (PMID: 19633190) shows kuru is another unique agent that is also geographically restricted. In addition, there are vast differences in the incubation time and regional brain lesions that distinguish the many distinct geographic human CJD and sheep scrapie isolates (dramatic brain differences in CJD strains isolated from the USA and Japan can be seen athttp://info.med.yale.edu/neurosci/faculty/manuelidis_main.htmlhttp://www.ncbi.nlm.nih.gov/sites/entrezhttp://www.pnas.org/content/106/32/13529.fullhttp://info.med.yale.edu/neurosci/faculty/manuelidis_files/tse/25_nm_virion.pdf
Our results emphasize an environmental origin of TSE infectious agents . Indeed, it is likely that environmental causes, infectious, toxic and traumatic, underlie more common dementias such as Alzheimer’s Disease. This line of approach deserves increased investigation, especially in view of major public health issues. Our stable tissue culture models of many different TSE strains, as well as the ability to rapidly assay infectivity in culture (PMID: 18989813; PMID: 18788938, and see below), offer exciting new avenues for direct molecular analysis of infectious TSE particles and rational approaches to prevent and cure these infections. We here point out some of the reasons why we think it likely that the infectious agent is a virus rather than a misfolded host protein.
The backwards evolution of the prion concept
Sometimes speculations leap so far ahead of evidence that they develop a detached life of their own. When popularized, unfounded beliefs can also be difficult to erase. Through much of the Middle Ages it was believed that plagues were a consequence of divine retribution. Yet most people in the USA today realize that plagues are caused by infectious organisms. Eradication of these organisms is both preventive and curative. Barrier experiments during the 1700s first proved that rats and other forms of visible life did not arise spontaneously. However, the idea of spontaneous generation of microscopic forms of life, such as bacteria and viruses, persisted until similar barrier and filtration experiments of Pasteur and others were undertaken. These showed a pre-existing “seed” or organism had to be present to generate new life. Furthermore, modern molecular genetics clearly shows infectious organisms all need nucleic acid for true replication (making many new copies), and viral and bacterial genomes can be propagated solely by using their nucleic acid (DNA or RNA) sequences. Moreover, simply modifying these sequences alters the strain-specific properties of infectious agents.
A hypothetical new form of life called a “prion” (an acronym for a protein infectious particle, later identified as the host protein “PrP”) is claimed to have remarkable features that are most reminiscent of ancient beliefs. Yet there is no direct evidence for many prion claims. These include the spontaneous generation of infectivity by a normal mammalian protein. Spontaneous conversion was a convenient belief (and legal cover) for governments dealing with practices that led to the epidemic outbreak of mad cow disease. Unlike spontaneous events that should occur with some type of mathematical frequency, the characteristics of the specific mad cow infectious agent had never been seen before. Additionally, the disease occurred only in places exposed to contaminated products (i.e., not spontaneously made by the host). Removing infected materials dramatically and abruptly diminished the UK cow epidemic. Similarly, new kuru infections disappeared after the cessation of ritual cannibalism in New Guinea Perhaps more disingenuous, in view of the experimental data, are the statements that TSE infectious agents, “because they are prions”, contain no nucleic acids (DNA or RNA). The prion concept was introduced in 1982 (PMID: 6801762) despite the fact that the preparations treated to abolish nucleic acids had enough DNA to code for a million human beings (reviewed in PMID: 12828865). In fact, the only two subsequent “peer-reviewed” experimental papers (from 1993 and 2005) to conclude that there are no nucleic acids of >50 bases in TSE infectious fractions are written by S. Prusiner’s prion group. Neither of these reports used modern sensitive end labeling, or established RT-PCR methods for nucleic acid detection (PMID: 16051871). Nor were controls such as enteroviral particles added to monitor nucleic acid extraction. Moreover, detailed RT-PCR methods published in 1994 (PMID: 8152913) had already demonstrated endogenous virus with >5,000 bases co-migrates with infectious TSE particles during purification. These TSE and viral particles were resistant to exhaustive nuclease digestion. It is also notable that both the R. Marsh (PMID: 1972202) and C. Weissmann groups independently uncovered nucleic acids of >300 bases in Prusiner’s purified prion preparations that were presumably free of nucleic acids. Several groups in France have also independently reported nucleic acids in their own infectious preparations (PMID: 18422484, and cited inhttp://www.sciencemag.org/cgi/eletters/327/5967/869#12963
The belief that an infectious protein, rather than a covert nucleic acid, must code for the wellestablished different TSE agent strains (sporadic CJD, kuru, BSE and various scrapie isolates) excludes the objective evidence of nucleic acids in infectious preparations. Recent claims that prion protein mutates and evolves (PMID: 20044542), instead of a nucleic acid, also replays the discredited Tobacco Mosaic Virus story where a self-catalyzed crystalline protein was said to be the causal infectious agent. This Nobel Prize work simply ignored the viral nucleic acid present in the preparations that coded for the viral replication.
We continue to work on the more parsimonious concept that the fundamental infectious particle causing CJD, scrapie and other TSEs is a small virus of ~25nm, as determined experimentally by independent size, density and ultrastructural studies (PMID: 17044041; PMID: 17267596). PrP acts as a necessary host receptor or scaffold for this virus, and pathologic PrP amyloid is formed late in infection as a result of this interaction. Notably, microglia that have negligible PrP and no detectable PrP amyloid have shown very high levels of infectivity (PMID: 12368333). Thus we continue to do work on TSEs to understand this group of infectious agents and the ways they cause dementia. There are far more parts of this puzzle than the prion protein.
The following table lists essential prion claims that are contradicted by experimental data. The findings continue to implicate a 25nm diameter virus as the cause of TSEs.
CLAIM* Experiment COMMENT
1) “PrPSc (PrP amyloid, PrP-res) is proportional to titer” FALSE diverse data from many labs
2) “Procedures that modify or hydrolyze PrPSc inactivate prions” TRUE They also inactivate viruses
3) “No evidence exists for a virus-like particle” FALSE discrete ~25nm viral particle
4) “Transmissible particles are devoid of nucleic acid” FALSE all infectious preps contain long nucleic acids
5) “PrP gene mutations cause formation of PrPSc” FALSE toxic pathology, but no PrPSc
6) “PrP gene mutations cause transmissible disease” not reproducible Contamination with lab scrapie 263K
7) “Prion diversity is enciphered by PrPSc” conformation FALSE changing PrP-res folding has no effect on strain or titer
8) TSE “strains can be generated by passing through hosts with different PrP genes” rarely Strains typically keep their unique identity in different species (as BSE)
9) “No sign of an immune response to foreign agent” FALSE Early innate immune responses before detectable PrP-res
10) “Accumulation of PrPSc associated with pathology” TRUE PrPSc is a late response to infection
11) Protein X postulated to bind PrP for transmission X not found PrP itself not infectious; X is probably a virus
12) “Prions defy the rules of protein structure” TRUE possibly also of thermodynamics
13) CJD infectious agent arises spontaneously No evidence An idea predating evolution
TABLE I: Major arguments and the “wealth of data…for the fundamental principles of prion biology”. PrPsc the presumably “infectious scrapie or prion form” is revealed by limited protease digestion of tissue in a test tube and is equivalent to PrP amyloid, PrP-res, aggregated PrP.
Tissue culture studies have shown that altering the PrP profile does not change the strain properties. The bands are tissue and cell-type specific, and unlike the infectious agent do not breed true (e.g., PMID: 15161970). Below is a picture of infected neuronal cultures and they can also show the pathological prion protein (in red) unlike mock-infected cultures (inset). Notably, despite the high level of pathological PrP in these cells they show no toxic response. Thus PrP itself may not be the ultimate or sole cause of neurodegeneration. These cells give reliable, rapid assays of the agent.
The ultrastructural 25nm particles have been found in more purified infectious TSE preparations. They do not bind PrP antibodies, unlike isolated amyloid fibrils (PMID: 17044041). These virus-like particles can also be identified in intact cells with high levels of infectivity (PMID: 17267596), and can be seen in compact arrays, like many conventional virions. An array is depicted here inside the cell and shown in a corresponding 3-D projection from different angles. These particle arrays are unrelated to the PrP amyloid fibrils in the cytoplasm identified structurally and by PrP antibodies.http://medicine.yale.edu/surgery/neuropathology/research/index.aspxhttp://medicine.yale.edu/surgery/neuropathology/Images/lmwebresearch_tcm313-46643.pdf
I will quote what one of the leading scientist in the world on prion disease once said about CWD, and then post some data on this topic. Good question, one that should be addressed. I will attempt to address it. I am a meat eater, and I don't care what you and others eat, but on the topic of human and animal Transmissible Spongiform Encephalopathy, I can assure you that you have not been told the complete truth. This is a long post, take the information, and please look at the source of the data. I post this data on blogs, no advertisements, not making money doing this. The information is for your benefit, please use as you wish. ...kind regards, terry
A. Aguzzi - Chronic Wasting Disease (CWD) also needs to be addressed.
Most serious because of rapid horizontal spread and higher prevalence than BSE in UK, up to 15% in some populations.
Also may be a risk to humans - evidence that it is not dangerous to humans is thin. ...end
REMEMBER, there are over twenty strains of typical scrapie, and the atypical scrapie cases (Nor-98) are mounting, two documented strains of Transmissible Mink Encephalopathy, and 3 strains of BSE in cattle, all of which have been documented in North America, all have been shown to transmit to man via lab studies in mice, with the L-type atypical BSE being much more virulent. Also, now there are two strains of CWD. all these TSE in different animals have been rendered and put into feed for livestock producing animals for human and animal in the USA. This is fact.
can humans get a prion disease from deer or elk that have CWD ?
as someone else stated here, no one knows for sure to date, but the likelyhood of being exposed to CWD from eating a CWD deer or elk is high, and then years on down the road, regardless whether or not this person ever goes clinical, due to any medical surgical, or dental procedures, blood donations, the agent will continue to spread, more humans exposed. the fact that some of these atypical TSE are mutating and becoming more virulent is very troublesome. the incubation time is shortened.
I assure you that the FDA did not recall this CWD postive elk meat in commerce, for the well being of the dead CWD postive 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
please see ;
RECALLS AND FIELD CORRECTIONS: FOODS CLASS II
PRODUCT a) Elk Meat, Elk Tenderloin, Frozen in plastic vacuum packaging. Each package is approximately 2 lbs., and each case is approximately 16 lbs.; Item number 755125, Recall # F-129-9;
b) Elk Meat, Elk Trim, Frozen; Item number 755155, Recall # F-130-9;
c) Elk Meat, French Rack, Chilled. Item number 755132, Recall # F-131-9;
d) Elk Meat, Nude Denver Leg. Item number 755122, Recall # F-132-9;
e) Elk Meat, New York Strip Steak, Chilled. Item number 755128, Recall # F-133-9;
f) Elk Meat, Flank Steak Frozen. Item number 755131, Recall # F-134-9; CODE Elk Meats with production dates of December 29, 30, and 31 RECALLING FIRM/MANUFACTURER Recalling Firm: Sierra Meats, Reno, NV, by telephone on January 29, 2009 and press release on February 9, 2009. Manufacturer: Noah’s Ark Holding, LLC, Dawson, MN. Firm initiated recall is ongoing. REASON Elk products contain meat derived from an elk confirmed to have Chronic Wasting Disease (CWD). VOLUME OF PRODUCT IN COMMERCE Unknown DISTRIBUTION NV, CA, TX, CO, NY, UT, FL, OK
END OF ENFORCEMENT REPORT FOR March 18, 2009
Sunday, April 12, 2009
CWD UPDATE Infection Studies in Two Species of Non-Human Primates and one Environmental reservoir infectivity study and evidence of two strainshttp://chronic-wasting-disease.blogspot.com/2009/04/cwd-update-infection-studies-in-two.html
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease
2008 1: Vet Res. 2008 Apr 3;39(4):41
A prion disease of cervids: Chronic wasting disease
*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
full text ;http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
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"
Cc: "Race, Richard (NIH)" ; ; "Belay,
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
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
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
Ermias Belay, M.D.
Centers for Disease Control and Prevention
Sent: Sunday, September 29, 2002 10:15 AM
To: email@example.com; firstname.lastname@example.org; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG
Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS
SEE also ;
A. Aguzzi - Chronic Wasting Disease (CWD) also needs to be addressed. Most
serious because of rapid horizontal spread and higher prevalence than BSE in
UK, up to 15% in some populations. Also may be a risk to humans - evidence
that it is not dangerous to humans is thin.http://www.tseandfoodsafety.org/activities/bse_conference_basel_april_02/2summar
Chronic Wasting Disease and Potential Transmission to Humans
Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,? Michael W. Miller,? Pierluigi Gambetti,§ and Lawrence B. Schonberger*
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ?University of Wyoming, Laramie, Wyoming, USA; ?Colorado Division of Wildlife, Fort Collins, Colorado, USA; and §Case Western Reserve University, Cleveland, Ohio, USA
Suggested citation for this article: Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from:http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm
Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions.
snip...full text ;http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm
Volume 12, Number 10-October 2006
Human Prion Disease and Relative Risk Associated with Chronic Wasting Disease
Samantha MaWhinney,* W. John Pape,? Jeri E. Forster,* C. Alan Anderson,?§ Patrick Bosque,?¶ and Michael W. Miller#
*University of Colorado at Denver and Health Sciences Center, Denver, Colorado, USA; ?Colorado Department of Public Health and Environment, Denver, Colorado, USA; ?University of Colorado School of Medicine, Denver, Colorado, USA; §Denver Veteran's Affairs Medical Center, Denver, Colorado, USA; ¶Denver Health Medical Center, Denver, Colorado, USA; and #Colorado Division of Wildlife, Fort Collins, Colorado, USA
Suggested citation for this article
The transmission of the prion disease bovine spongiform encephalopathy (BSE) to humans raises concern about chronic wasting disease (CWD), a prion disease of deer and elk. In 7 Colorado counties with high CWD prevalence, 75% of state hunting licenses are issued locally, which suggests that residents consume most regionally harvested game. We used Colorado death certificate data from 1979 through 2001 to evaluate rates of death from the human prion disease Creutzfeldt-Jakob disease (CJD). The relative risk (RR) of CJD for CWD-endemic county residents was not significantly increased (RR 0.81, 95% confidence interval [CI] 0.40-1.63), and the rate of CJD did not increase over time (5-year RR 0.92, 95% CI 0.73-1.16). In Colorado, human prion disease resulting from CWD exposure is rare or nonexistent. However, given uncertainties about the incubation period, exposure, and clinical presentation, the possibility that the CWD agent might cause human disease cannot be eliminated.
snip... full text ;http://0-www.cdc.gov.mill1.sjlibrary.org/ncidod/EID/vol12no10/06-0019.htm
full text ;http://chronic-wasting-disease.blogspot.com/2006_12_01_archive.html
(10) Transmission of Elk and Deer Prions to Transgenic Micehttp://jvi.asm.org/cgi/content/abstract/80/18/9104
(30) Neurobiology of Disease Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Modelshttp://www.jneurosci.org/cgi/content/short/25/35/7944
(13) Prions in Skeletal Muscles of Deer with Chronic Wasting Diseasehttp://www.sciencemag.org/cgi/content/abstract/sci;311/5764/1117
(14) Volume 15, Number 5–May 2009 Research Chronic Wasting Disease Prions in Elk Antler Velvethttp://www.cdc.gov/eid/content/15/5/696.htm
Friday, May 14, 2010
Prion Strain Mutation Determined by Prion Protein Conformational Compatibility and Primary Structure
Published Online May 13, 2010 Science DOI: 10.1126/science.1187107 Science Express Indexhttp://chronic-wasting-disease.blogspot.com/2010/05/prion-strain-mutation-determined-by.html
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
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: email@example.com
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
Sunday, April 12, 2009
CWD UPDATE Infection Studies in Two Species of Non-Human Primates and one Environmental reservoir infectivity study and evidence of two strainshttp://chronic-wasting-disease.blogspot.com/2009/04/cwd-update-infection-studies-in-two.html
In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. BSE was not reported in the USA.
CWD occurred principally in two locations, this one at Sybille and in a similar faccility at Fort Collins, Colorado, some 120 miles southwest. It was estimated that in total probably 60-70 cases of CWD have occurred.
It was difficult to gain a clear account of incidence and temporal sequence of events (-this presumably is data awaiting publication - see below) but during the period 1981-1984, 10-15 cases occurred at the Sybille facility.
The moribidity amongst mule deer in the facilities ie. those of the natural potentially exposed group has been about 90% with 100% mortality.
Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.
see full text 33 pages ;http://collections.europarchive.org/tna/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
CHRONIC WASTING DISEASE BLOGhttp://chronic-wasting-disease.blogspot.com/
*****URGENT NOTE HERE ABOUT OIE AND THEIR JUNK SCIENCE ABOUT ATYPICAL BSE*****
Wednesday, March 31, 2010
Atypical BSE in Cattlehttp://bse-atypical.blogspot.com/2010/03/atypical-bse-in-cattle-position-post.html
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
Archive Number 20100405.1091 Published Date 05-APR-2010
Subject PRO/AH/EDR> Prion disease update 1010 (04)
[Terry S. Singeltary Sr. has added the following comment:
"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.
The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"
> Up until about 6 years ago, the pt worked at Tyson foods where she
> worked on the assembly line, slaughtering cattle and preparing them for
> packaging. She was exposed to brain and spinal cord matter when she
> would euthanize the cattle.
please see full text ;
Monday, March 29, 2010
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas
14th International Congress on Infectious Diseases H-type and L-type Atypical BSE January 2010 (special pre-congress edition)
18.173 page 189
Experimental Challenge of Cattle with H-type and L-type Atypical BSE
A. Buschmann1, U. Ziegler1, M. Keller1, R. Rogers2, B. Hills3, M.H. Groschup1. 1Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany, 2Health Canada, Bureau of Microbial Hazards, Health Products & Food Branch, Ottawa, Canada, 3Health Canada, Transmissible Spongiform Encephalopathy Secretariat, Ottawa, Canada
Background: After the detection of two novel BSE forms designated H-type and L-type atypical BSE the question of the pathogenesis and the agent distribution of these two types in cattle was fully open. From initial studies of the brain pathology, it was already known that the anatomical distribution of L-type BSE differs from that of the classical type where the obex region in the brainstem always displays the highest PrPSc concentrations. In contrast in L-type BSE cases, the thalamus and frontal cortex regions showed the highest levels of the pathological prion protein, while the obex region was only weakly involved.
Methods:We performed intracranial inoculations of cattle (five and six per group) using 10%brainstemhomogenates of the two German H- and L-type atypical BSE isolates. The animals were inoculated under narcosis and then kept in a free-ranging stable under appropriate biosafety conditions.At least one animal per group was killed and sectioned in the preclinical stage and the remaining animals were kept until they developed clinical symptoms. The animals were examined for behavioural changes every four weeks throughout the experiment following a protocol that had been established during earlier BSE pathogenesis studies with classical BSE.
Results and Discussion: All animals of both groups developed clinical symptoms and had to be euthanized within 16 months. The clinical picture differed from that of classical BSE, as the earliest signs of illness were loss of body weight and depression. However, the animals later developed hind limb ataxia and hyperesthesia predominantly and the head. Analysis of brain samples from these animals confirmed the BSE infection and the atypical Western blot profile was maintained in all animals. Samples from these animals are now being examined in order to be able to describe the pathogenesis and agent distribution for these novel BSE types. Conclusions: A pilot study using a commercially avaialble BSE rapid test ELISA revealed an essential restriction of PrPSc to the central nervous system for both atypical BSE forms. A much more detailed analysis for PrPSc and infectivity is still ongoing.
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
update October 2009
Bacliff, TX, USA
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
12 years independent research of available data
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
International Society for Infectious Diseases Web: http://www.isid.org
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''
Professor Kong reply ;
''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete.
Thanks for your interest.''
Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA
Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK–resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
Sunday, February 14, 2010
[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
Senate 'Down Under' link at bottom of the following url, my submission read out in the Hansard Senate recently by the ABA Chairman Brad Bellinger ;
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM 1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype of 'UNKNOWN' strain growing. ...
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
2008 - 2010
The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.
Wednesday, June 02, 2010
CJD Annex H UPDATE AFTER DEATH PRECAUTIONS Published: 2 June 2003 Updated: May 2010
Tuesday, June 1, 2010
USA cases of dpCJD rising with 24 cases so far in 2010
Friday, November 30, 2007
CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION
Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (TRANSCRIPT)
Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)
Saturday, June 13, 2009
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009
Friday, February 05, 2010
New Variant Creutzfelt Jakob Disease case reports United States 2010 A Review
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
my comments to PLosone here ;
Sunday, August 10, 2008
A New Prionopathy OR more of the same old BSe and sporadic CJD
USA DEAD STOCK DOWNER COWS
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
PLEASE be aware, for 4 years, the USDA fed our children all across the Nation dead stock downer cows, the most high risk cattle for BSE aka mad cow disease and other dangerous pathogens. who will watch our children for CJD for the next 5+ decades ???
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
NOW, for the ones that think the Government will not lie to you, just to save the industry at all cost, I have two words for you.
Tobacco and Asbestos. how many thousands and thousands of humans died for decades, and are still dying today from these two products, and how many decades did the industry and government lie about this ? just something to ponder, then ponder this ;
Wednesday, April 14, 2010
Food Combination and Alzheimer Disease Risk A Protective Diet
Saturday, March 22, 2008
10 Million Baby Boomers to have Alzheimer's in the coming decades 2008 Alzheimer's disease facts and figures
Monday, January 4, 2010
Rising Tide: The Impact of Dementia in Canada Huge wave of dementia cases coming, warns report
Alzheimer's and CJD
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
Labels: BSE, CJD, CWD, mutation, novel prion strains, SCRAPIE