HAVE ANOTHER GLASS OF CWD PRIONS COURTESY Dane County Wisconsin Mike DiMaggio, solid waste manager
HAVE ANOTHER GLASS OF CWD PRIONS COURTESY Dane County Wisconsin Mike DiMaggio, solid waste manager
----- Original Message -----
From: TERRY SINGELTARY
To: bjohnston@madison.com
Cc: dunphy@co.dane.wi.us ; dimaggio.mike@co.dane.wi.us ; matzinger@co.dane.wi.us ; rasmussen.holly@co.dane.wi.us ; Regan@co.dane.wi.us ; younes@co.dane.wi.us ; welch@co.dane.wi.us ; fahey@co.dane.wi.us ; olson.shaun@co.dane.wi.us ; efoley@madison.com ; tkelley@madison.com ; jhuntley@madison.com ; stubbs@co.dane.wi.us ; desmidt@co.dane.wi.us ; bruskewitz@co.dane.wi.us ; vedder.barbara@co.dane.wi.us ; wheeler@co.dane.wi.us ; hesselbein@co.dane.wi.us
Sent: Saturday, August 23, 2008 9:52 PM
Subject: re-CWD... Not to worry, Have another glass of tap water ?
re-CWD... Not to worry, Have another glass of tap water ?
Greeting Dane County Wisconsin,
a kind greetings from Bacliff, Texas. I read this article and it disturbed me greatly. so I thought I would send you the latest science on TSE, and what Mr. DiMaggio thinks is so set in stone, may not be as so sound as he would think. please take this data with great concern, and study it carefully, and the sources these studies come from comes from. it helps sometimes with decisions like this that you have all the data. ...
thank you! and kindest regards...terry
IN REPLY to ;
'A real infringement on democracy' Local laws regulating campaign signs may be unconstitutional Bill Lueders on Thursday 08/07/2008
snip...
Not to worry
According to a new UW-Madison study, the prions that cause mad cow disease are not destroyed by conventional sewage treatment and could end up contaminating water and fertilizer. This may be of interest to folks 'round here, given that the state Department of Natural Resources has for the past few months been dumping the carcasses of deer with chronic wasting disease (CWD) in the county's Rodefeld landfill, from which leachate is pumped into the sewerage treatment plant.
But, it turns out, there's absolutely nothing to worry about!
"The study we did on prions shows we can contain them in the landfill," says Mike DiMaggio, the county's solid waste manager. The two-year study, also done by the UW, recommended that the county put soil above and below the dumped deer. That way, says DiMaggio, leaking prions "attach to the dirt [and] don't go anywhere."
The DNR began dumping carcasses in the landfill last Nov. 15, two weeks after getting County Board approval. The DNR's Gene Miller, who oversees the program, estimates that it's since dumped about 90 tons of deer, of which "3% or less" are believed to be contaminated with CWD.
DiMaggio isn't troubled by the new UW study because, he says, comparing mad cow disease to CWD is "like comparing polio to MS or heart disease."
But aren't both always-fatal brain gnawers variants of Creutzfeldt-Jakob disease, spread by prions? DiMaggio says he's not an expert; thankfully, there's one on hand.
Joel Pederson, the UW environmental chemist who did the latest study, says the only danger would be "if prions were able to escape a landfill." But the soil sandwich they are buried in makes that unlikely.
"If carcasses are properly placed within a landfill," says Pederson, "we expect that prions would not be released at a level of concern."
There you have it. Science has spoken. Have another glass of tap water.
http://www.thedailypage.com/isthmus/article.php?article=23414
Greetings again,
re-CWD... Not to worry, Have another glass of tap water.
"If carcasses are properly placed within a landfill," says Pederson, "we expect that prions would not be released at a level of concern."
stupid is, as stupid does. ...Forest Gump
please note recent paper on TSE, and CWD below and comments from Aguzzi, Sigurdson, Heikenwaelder et al. then further recent research to follow that as well. ...TSS
Molecular Mechanisms of Prion Pathogenesis
Adriano Aguzzi, Christina Sigurdson, and Mathias Heikenwaelder Institute of Neuropathology, University Hospital of Z¨ urich, CH-8091 Z¨ urich, Switzerland; email: adriano.aguzzi@usz.ch, mathias.heikenwaelder@usz.ch, christina.sigurdson@usz.ch Annu. Rev. Pathol. Mech. Dis. 2008. 3:11-40 First published online as a Review in Advance on August 8, 2007 The Annual Review of Pathology: Mechanisms of Disease is online at pathmechdis.annualreviews.org This article's doi: 10.1146/annurev.pathmechdis.3.121806.154326 Copyright c 2008 by Annual Reviews. All rights
Annu. Rev. Pathol. Mech. Dis. 2008. 3:11-40 First published online as a Review in Advance on August 8, 2007 The Annual Review of Pathology: Mechanisms of Disease is online at pathmechdis.annualreviews.org This article's doi: 10.1146/annurev.pathmechdis.3.121806.154326 Copyright c 2008 by Annual Reviews. All rights reserved 1553-4006/08/0228-0011$20.00
Abstract
Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrPC) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt- Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrPSc, a misfolded and aggregated â-sheet-rich isoform of PrPC. However, PrPSc may or may not be completely congruent with the infectious moiety. Here, we discuss the molecular mechanisms leading to neurodegeneration, the role of the immune system in prion pathogenesis, and the existence of prion strains that appear to have different tropisms and biochemical characteristics.
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As an example in the field of human medicine, four cases of vCJD have been reported to be caused by blood transfusion (9- 11). This indicates that BSE prions can be recycled among humans, which has caused considerable alarm that the supply of bloodderived pharmaceuticals may be threatened (12). In particular, the report of a subclinical blood-derived vCJD infection in an individual carrying a heterozygote methionine/ valine polymorphism at codon 129 of the human PRNP gene (10) suggests that transmission of BSE prions to humans enhances their virulence and broadens the spectrum of susceptible recipients. In this respect, it has been demonstrated that polymorphisms at codon 129 of the human PRNP gene control susceptibility and incubation time in human patients (e.g., 129MM versus 129MV or 129VV drastically increases the susceptibility of humans to BSE prions). It was reported only recently that most individuals who suffered from kuru and were polymorphic at codon 129 showed incubation times longer than 50 years (13). Moreover, recent reports indicate that there is still a lot to be learned about the mechanisms of prion transmission (e.g., human to human or within scrapie-affected animal flocks) and prion tropism underlining the complex alternating distribution patterns of PrPSc (e.g., PrPSc deposition in lymphoid tissue, the CNS) and prion infectivity under varying conditions (e.g., chronic inflammation) and hosts (e.g., sheep, elk and deer, human): Chronic inflammation can alter the tropism of prion infectivity or PrPSc to organs hitherto believed prion free (e.g., liver, pancreas, kidney of mice, mammary gland of sheep, muscle of humans) (14-16). Moreover, PrPSc was reported in spleen and muscle tissue of sporadic Creutzfeldt-Jakob disease (sCJD) patients (17), and prion infectivity was demonstrated in muscle, blood, and saliva of deer suffering from CWD (18, 189). Also, prion infectivity was shown to be excreted via urine of prion-infected nephritic mice, a process defined as prionuria (19). These results emphasize the need for further assessment of possible public health risks from TSE-affected extraneural organs. It is very well possible that preexisting pathophysiological conditions of the infected host additionally contributed to unexpected distribution patterns of prion infectivity. For example, the presence of prion infectivity in the blood of sheep or deer may influence the deposition of prion infectivity in various organs previously deemed prion free. Therefore, it should be carefully reconsidered whether only organs of the CNS and the lymphoreticular system should be included in the current risk classifications of biologicals in the future. It will be important to test altered prion tropism profiles in nonlymphoid organs and body fluids (e.g., blood, urine, milk, saliva) of ruminants (e.g., sheep, goat, cattle, elk, and deer) and human patients suffering from sCJD and vCJD.
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Recent in vivo evidence indicated that a similar phenomenon of conformational variants may occur in Alzheimer's disease (151). Here the existence of Aâ strains that can seed and accelerate aggregation and Aâ pathology was posited. These intriguing observations support the hypothesis that the pathogenetic mechanisms operating in Alzheimer's disease and in prion diseases have more in common than we often appreciate (152). Perhaps future studies will address whether different Aâ strains with distinct biochemical or neuropathological characteristics occur in humans. Can multiple prion strains coexist and effect prion replication? Two subtypes of sporadic CJD have recently been demonstrated to coexist in humans (62). Experimental studies have shown that when two strains infect the same host, one strain can impede the ability of the second strain to cause disease (153). Bartz and colleagues (154) recently suggested that this might be caused by the suppression of prion replication of the second strain. Strain features are useful for tracing prion infections between species. When transmitted to primates, BSE causes lesions strikingly similar to that of vCJD (155, 156). BSE is most likely transmissible to humans too, and strong circumstantial evidence (157-159) suggests that BSE is the cause of vCJD, which has claimed more than 200 lives in the United Kingdom (3, 160), as well as a much smaller number in some other countries (161).
NATURAL TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: WHAT IS NEW? Cattle Prions More than a few surprises have come from further investigations of prion strains in field cases of TSEs. Until recently, BSE was believed to be associated with one single prion strain, classified by an exclusive and remarkably stable biochemical profile of PrPSc. However, distinct molecular signatures have recently been discovered through the large-scale screening of cattle mandated by European authorities in the context of BSE surveillance. These atypical profiles fall into either of two groups: H-type cases of protease-resistant fragments with a molecular weight higher than BSE, and bovine amyloidotic spongiform encephalopathy, or L type (lower) (162). To test whether these different biochemical and histopathological properties correspond to distinct strains, the Laude laboratory transmitted H-type-PrPSc isolates from French cattle into transgenic mice expressing bovine or ovine PrP (163). The recipient mice developed neurological signs exhibiting strain-specific features clearly distinct from that of the classical BSE agent, providing pivotal evidence that the underlying strains are distinct.
Atypical Sheep Scrapie In 1998, aberrant cases of sheep scrapie were described in Norway and the strain was newly classified as Nor98 (164). Active European Union surveillance later revealed additional cases of atypical scrapie in several other countries (165, 166). Sheep infected with Nor98, or atypical scrapie, accumulated PrPSc primarily in the cerebellum and cerebral cortex rather than in the brainstem target in the classical strain (167). Additionally, on western blot analysis of atypical scrapie cases, an additional small-molecular-weight (10-12 kDa) PrP fragment appeared afterPKdigestion and was shown by epitope mapping to lack both N and C termini of PrP (167, 168). Furthermore, atypical scrapie cases occurred not only in the classical scrapie-susceptible genotypes (A136 R154 Q171), but also in genotypes associated with high resistance to classical scrapie (A136 R154 R171) (165, 166). Were these atypical scrapie cases also infectious? In 2001, atypical scrapie cases were shown to be transmissible prion diseases after inoculated ovine PrP-expressing transgenic mice developed disease and prion aggregates (169). In the meantime, several countries appear to be reporting extremely high incidences of atypical scrapie, and in fact atypical scrapie appears to be the rule rather than the exception in some geographical areas.
Chronic Wasting Disease Among all animal prion diseases, CWD of cervids is likely the most efficiently transmitted. CWD infections occur in mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), Rocky Mountain elk (Cervus elaphus nelsoni) (170), and moose (Alces alces shirasi) (171). Prevalence can reach as high as 30% in dense, free-ranging deer populations and nearly 100% in captive animals (171). Hypotheses for CWD transmission range from spread via direct contact to exposure through grazing in areas contaminated by prion-infected secretions, excretions (saliva, urine, feces), tissues (placenta), or decomposed carcasses. Insightful experimental studies have recently revealed two key findings: (a) Saliva from CWD-infected deer can transmit disease (18), and (b) CWD-infected carcasses allowed to decay naturally in confined pastures can lead to CWD infections in captive deer (172). Additionally, the abundant CWD-prion accumulation within lymphoid tissues may also lead to CWD prion buildup in nonlymphoid organs with lymphoid follicles, as was recently shown in kidney, potentially shifting shedding routes (173). It is unknown whether other types of inflammation, such as the granulomatous inflammation in the intestine seen in Johne's disease (Mycobacterium avium subsp. paratuberculosis; affects ruminants, including deer and elk) or parasitic inflammation, could lead to or perhaps increase prion excretion by fecal routes. The environmental prion contamination in CWD underscores the difficulties of CWD disease management.Within North America,CWDinfected deer and elk have been detected in 14 states and two Canadian provinces (170, 174, 175). CWD surveillance in Europe has been more limited. However, in Germany, a total of 7300 captive and free-ranging cervids were tested forCWDwith no sign of infection (176). Reindeer or caribou (Rangifer tarandus), from North America or Northern Europe respectively, have a highly homologous prion sequence compared with mule deer and thus are likely susceptible to CWD. Other European cervids such as moose and red deer (C. elaphus) are also expected to be CWD susceptible. The deer and elk primary protein structures are highly conserved, as seen in other mammals. Interestingly, a polymorphism at codon 225S/F may influence CWD susceptibility in mule deer. When comparing the frequency of genotypes among CWDnegative and -positive deer (n = 1482), the odds that a CWD-infected animal was 225SS was 30 times greater when compared with 225SF, whereas the frequency of 225SF/FF genotypes in CWD-negative deer was 9.3%, but only 0.3% in CWD-positive deer (177).
Additionally, elk have a polymorphism at codon 132 (M/L) of Prnp, corresponding to polymorphic codon 129 (M/V) in humans. Elk expressing 132ML and 132LL Prnp were reported to be overrepresented among elk with CWD when compared with uninfected controls (178), and 132LL elk experimentally infected with CWD have resisted infection for at least four years, whereas 132MM or 132ML elk (n = 2 each) developed terminal clinical prion disease by 23 or 40 months post inoculation, respectively, confirmed by immunohistochemistry and western blotting for PrPSc (179). White-tailed deer also have Prnp polymorphisms that may affect their CWD susceptibility. A reduced susceptibility to CWD was linked to a G96S and a Q95H polymorphism in a study comparing allelic frequencies from CWD-positive and CWDnegative free-rangingWisconsin white-tailed deer (180).
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http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.pathmechdis.3.121806.154326
Prion White Paper Issue: Can the potential presence of prions in land applied biosolids result in food chain contamination with the subsequent development of animal and human disease?
What are Prions and What are the Diseases Attributed to Exposure to Prions? “Prion” refers to a particular kind of protein found in animal tissue. Most prions occur in a normal, harmless form, but there are abnormal or infectious forms. The normal, harmless form has the same sequence of amino acids as the abnormal form, but the abnormal, or infectious, form takes a different folded shape. (Epstein, 2005)1. In their normal, non-infectious state, it is believed that prions are involved in cell-to-cell communications and other important functions. Unlike bacteria and viruses, prions do not contain genetic material. However, like viruses and bacteria, prions are infectious and replicate in host tissues. Throughout this white paper the word “Prion” is used to indicate the abnormal, infectious form of prions. Prions cause normal celluar proteins to convert to the abnormal or prion form. In animals affected with prion-caused diseases, prions have been found mainly in the brain, spinal cord, lymph nodes, spleen, tonsils, eyes, pancreas, adrenal gland, and blood. In studies with mice, prions have been observed in muscle tissue. Prions have not been observed in manure or biosolids.
It is now commonly accepted that prions are responsible for a number of previously known but little-understood animal (including human) diseases generally classified under transmissible spongiform encephalopathy diseases (TSEs) (Wikipedia, 2005)2. These diseases affect the structure of brain tissue and are all fatal and untreatable. The TSE diseases that have received the most attention recently include chronic wasting disease (CWD) that affects deer and elk, bovine spongiform encephalopathy (BSE) that affects cattle (“Mad Cow Disease”)(Collinge, 2001)3, and Creutzfeldt-Jacob Disease (CJ Disease) that affects humans.
What Are the Sources of Prions That May be Relevant to Wastewater Treatment and Biosolids Production?
• Abattatoirs, Animal Rendering, and Meat Processing Operations - These operations, if they process BSE-contaminated cattle, can serve as a potential source of prions in wastewater treatment plants. However, preliminary calculations on a worst case scenario in which the entire prion-infected brain of a slaughtered cattle were released into a wastewater treatment plant over the span of a day indicate that the resulting concentration of prions in the treatment plant’s effluent would be significantly less than the prion concentration necessary to infect an individual (assuming that the individual was directly consuming the treatment plant’s effluent (Pederson, 2005)4). A recent effluent guideline (USEPA, 2004a)5 and general pretreatment standards promulgated by the United States Environmental Protection Agency (USEPA) for the Meat and Poultry Products Point Source Category, and the ability of local wastewater treatment authorities to impose these guidelines and standards on these discharging operations make it extremely unlikely that this assumed mass of prion-infected tissue would ever enter the sewer.
• Landfill Leachates - Leachates from landfills can act as a potential source of prions to a wastewater treatment plant if the landfill accepts for disposal carcasses from BSE-contaminated cattle or CWD-contaminated deer or elk. However, in areas where CWD is being actively managed, the disposal of contaminated deer or elk carcasses in municipal solid waste landfills appears to be an uncommon practice. CWD management approaches in the United States in areas of known prion infectivity typically involve incineration of infected materials. For example, the State of Wisconsin’s policy is to test potentially prion- infected deer and elk and to subsequently incinerate all prion positive deer and elk carcasses and landfill all prion negative carcasses (Kester, 2005)6. Because prions are positively charged, and have been described as being “sticky”, they are likely to strongly sorb to solids and soils both in the landfill and to the landfill liner (Taylor, 2005)7. Therefore, even if BSE-contaminated (prion) material were disposed in a municipal solid waste landfill that sent leachate to a wastewater treatment plant, the potential that significant concentrations of prions would be contained in the leachate is very low. This should be confirmed once analytical methodologies are developed to determine prions in leachate.
• Urine, feces, and blood from CJ Disease patients - Several researchers (Gabizon, et. al. 20018; Reichl, et. al. 20029) have reported the presence of prions in the blood and urine of CJ Disease patients. Prions have not been reported in the feces of CJ Disease patients. It should be noted that the concentrations of prions in the blood and urine of CJ Disease patients would be relatively low and, after entry into the sewer with a vast amount of dilution available, even lower compared to the concentrations of prions in the neural tissue of these patients or in the neural tissue of BSE-infected meat that these patients may have consumed. This is important to consider since the risk assessment results presented below are based on these significantly higher prion contaminated materials than the levels of prion contamination in blood, urine, or untreated wastewaters.
Have Prions Been Detected in Wastewater or Biosolids? There are no reports in the scientific literature of the presence of prions in municipal wastewater or in biosolids. Currently, no validated analytical methodologies are available for the determination of prions in municipal wastewater influent, treated municipal wastewater effluent, or in biosolids. Once these analytical methods are developed, prions might be detected and quantified in these media. However, based on the discussion above, their concentrations would be expected to be extremely low and not capable of causing subsequent infection either through direct contact or indirectly through food chain contamination. Analytical methodologies exist for the detection of prions in brain and other neurological tissue, mammalian lymphoid tissue, blood, and urine. Prions have been detected in each of these biological materials (Pederson, 2005)4.
What are the Methods of Prion Destruction? Prions found in environmental media or in residuals such as biosolids appear to be extremely resistant to degradation and loss of infectivity. Current methods for denaturing prions and significantly reducing infectivity such as high temperatures and treatment with alkalis and bleach are applicable to prion-contaminated animal tissues but are not applicable to wastewater and biosolids treatment.
What Current Research and Measures Are Underway to Mitigate/Prevent Prion Entry Into Wastewater Treatment Plants?
• Abattatoirs, Animal Rendering, and Meat Processing Operations - The U.S. EPA in 2004 published an effluent guideline (regulatory standard) for the Meat and Poultry Products Point Source Category that will result in a dramatic reduction in the amount of animal tissue that can be discharged directly into the aquatic environment. (USEPA, 2004a)5. The technologies associated with this standard are designed to enhance ambient water quality by reducing the amount of solids such as animal tissues, biochemical oxygen demand (BOD), and ammonia that can be discharged into the aquatic environment. Although this regulation does not pertain nationally to operations that discharge into sanitary sewers (“indirect dischargers”), local wastewater treatment authorities are free to impose the standard’s technologies on these indirect dischargers through local pretreatment limits where the potential for the processing of infected animals exist. These operations are also subject to EPA’s General pretreatment regulations which will also reduce solids input to the sewer. The United Kingdom has promulgated guidance for their meat processing industry on practices that minimize the amount of neurological tissue lost to the sewer (Gale and Stanfield, 2001)10.
• Landfill Leachates - EPA has issued guidance on the operations of municipal solid waste landfills that accept prion-contaminated animal carcasses for disposal (USEPA, 2004b)11. This guidance discusses the importance of liners and leachate collection systems and recirculation of the leachate in the landfill rather than discharge of the leachate to the wastewater treatment plant for containment of prions at the landfill site.
• Urine, Feces, and Blood from CJ Disease Patients - There are no current regulations, at least at the Federal level, that prohibit pathology laboratories or mortuaries from disposing of prion-contaminated tissue and fluids of CJ Disease patients into the sanitary sewer. However, EPA has developed a draft strategy to reduce the prion contamination threat from the discharge of wastewater into the sanitary sewer from pathology/necropsy and research laboratories working with prion-contaminated tissues. (USEPA, 2005a)12.
• Research - Currently, there is at least one research effort (the University of Wisconsin/Madison funded by EPA) underway to characterize the potential presence and fate of prions in wastewater treatment plants. These studies will also determine the potential for prions to partition into and concentrate in biosolids (USEPA, 2005b)13.
What Are the Properties, Fate, and Transport of Prions in Wastewater Treatment and in the Land Application of Biosolids? Very little data in this area is available. Based on the properties of prions, it is expected that prions initially in wastewater (most likely at very small concentrations- see above discussion) will survive and most likely be attached to and be transported by solid particulates in the wastewater entering the wastewater treatment plant. Once in the wastewater treatment process, no significant decrease in prion infectivity or prion degradation is expected to occur because of prions’ resistance to physical and chemical conditions encountered in wastewater treatment plants.
Whatever little concentration of prions in the incoming wastewater, they are expected to strongly partition to and concentrate in biosolids during wastewater treatment. Research in progress will provide a quantitative estimate of this partitioning (USEPA, 2005b)13. Based on the physical and chemical stability of prions, it is expected that prions will persist in biosolids, albeit at expectedly very low levels with respect to potential infectivity and the very limited number of potential environmental transport pathways available to infect animals or humans.
Prions and their infectivity related to an animal TSE have been demonstrated to persist in soils for several years (Brown, 1991)14. Because of their strong affinity with solid particulates and, therefore, very low concentrations in the aqueous phase, prions are not expected to threaten human-consumed or animal feed crops through root uptake in biosolids land application. For the same reason, transport of prions to groundwater or surface waters from biosolids land application is not anticipated. Prions have no volatility so ambient air transport can be ruled out. The only potential significant environmental transport mechanism available for prions with subsequent exposure and potential infectivity to animals and humans is biosolids/soil ingestion by grazing ruminants and, theoretically, biosolids/soil ingestion by toddlers in a home garden scenario. However, for these potential pathways of exposure, it is highly unlikely that prion concentration in the biosolids could ever approach an infectious dose for either animals or humans based on the extremely high dilution that occurs in wastewater treatment plants if prion-contaminated tissue were discharged to these plants and the prions subsequently partitioned to the biosolids (see discussions in previous sections and the section below).
What is the Risk to Human Health From BSE in Wastewater Treatment? In 2001, Gale and Stanfield performed a quantitative risk assessment for BSE in biosolids for land application to cattle pasturing and vegetable crop production in the United Kingdom (UK)(Gale and Stanfield, 2001)10. Using a worse case set of scenarios, they concluded: The risks to humans through consumption of vegetable crops are extremely low (approaches zero). Although the risks to cattle are higher, because of their higher exposure to soil and greater susceptibility to prion infectivity, the risk assessment model demonstrates that biosolids containing trace quantities of prions alone cannot initiate or sustain a BSE epidemic in the UK cattle herd. The conclusions are consistent with the findings from epidemiological studies, which so far, have not detected horizontal transmission of BSE (including transmission from BSE-contaminated pastures) (Gale and Stanfield, 2001). The risk assessment demonstrates the importance of containment of neurological tissue from animal processing operations and absolutely minimizing or eliminating the amount of neurological tissue from BSE-infected animals that enter the sewer system.
Other “first order” risk assessments and estimates have demonstrated under worst-case scenarios extremely low risks to the theoretically highest exposed population, the farmer, from prions in land applied biosolids . It should be noted that these risk assessments are performed on subpopulations that are at “bounded” maximum exposures. In reality, compared to these subpopulations that are used for risk estimation purposes, almost all people living in countries with mature and regulated agricultural industries are exposed orders of magnitude less to prions or for that matter to any other chemical or biological agent that can be found in trace quantities in biosolids or in background soils. This in turn results in orders of magnitude less risk to the general population from theoretical or actual exposure to these substances.
Summary The information presented in this fact sheet strongly suggests that the risk of prion transmission directly to ruminants and indirectly to humans with subsequent infection from biosolids land application is extremely low and indeed is practically zero. Prion transmission via biosolids land application seems less likely than other potential food chain pathways such as the consumption of prion-contaminated feed in animal raising operations and prion transmission to or between humans via contaminated surgical instruments and blood products, all of which are relatively rare, and compared to which, biosolids transmission of prions is even rarer.
There is an ongoing need for additional research in the areas described in this fact sheet to better quantify the information presented herein. Results of this research should further expand the scientific knowledge based on the subject of prions.
-------------------------------------------------------------------------------- References 1. Epstein E. and N. Beecher. 2005. Mad Cow Disease, Creutzfeld-Jakob Disease, other TSEs and Biosolids. J. Residuals Science and Technology. 2(3): 181-187.
2. Wikipedia. 2005. The Free Encyclopedia. “Transmissible spongiform encephalopathy”. Available on the Internet.
3. Collinge J. 2001. Prion diseases of humans and animals: Their causes and molecular basis. Ann. Rev. Neurosci. 24: 519-550.
4. Pedersen J. 2005. Personal communication from Joel Pedersen, University of Wisconsin/Madison, to Alan B. Rubin.
5. USEPA. 2004a. Effluent Limitations Guidelines and New Source Performance Standards for the Meat and Poultry Products Point Source Category. 69 Federal Register (173):54475-54555. September 8, 2004.
6. Kester G. 2005. Personal communication from Greg Kester, Wisconsin Department of Natural Resources, to Alan B. Rubin.
7. Taylor D. 2005. Personal communication from David Taylor, Madison (WI) Metropolitan Sewerage District, to Alan B. Rubin.
8. Gabizon R., Shaked G.M., Shaked Y., Karn-Inbal Z., Halami M., and I. Avraham. 2001. A protease resistant prion protein isoform is present in urine of animals and humans affected with prion diseases. J. Biol. Chem. 276(34): 31479-31482.
9. Reichl H., Balen A., and C.A. Jansen. 2002. Prion transmission in blood and urine: What are the implications for recombinant and urinary-derived gonadotropins? Human Reprod. (10): 2501-2508.
10. Gale P. and G. Stanfield. 2001. Towards a quantitative risk assessment for BSE in sewage sludge. Journal of Applied Microbiology. 91:563-569.
11. USEPA. 2004b. Recommended Interim Practices for Disposal of Potentially Contaminated Chronic Wasting Disease Carcasses and Wastes. Memorandum from: Robert Springer, Director, Office of Solid Waste to: RCRA Division Directors (Regions I-X), Superfund Division Directors (Regions I-X), OSWER Office Director. April 6, 2004.
12. USEPA. 2005a. EPA Draft Strategy Addendum to the Region 8 Local Limits Strategy. Discharges of Wastewater to Publicly-Owned Treatment Works (POTWs) from Pathology/Necropsy and Research Laboratories Working with Prion-Contaminated Tissue. Industrial Pretreatment Program (8P-W-P). May 9, 2005.
13. USEPA. 2005b. Preliminary Results from the First Phase of a Two Phase Study Examining the Fate of Prions in Wastewater Treatment. Poster presentation. USEPA Science Forum, Washington, DC. May 17, 2005.
14. Brown P. and D.C. Gajdusek. 1991. Survival of scrapie virus after 3 years internment. The Lancet. 337:269-270.
http://www.wef.org/ScienceTechnologyResources/Biosolids/PrionWhitePaper.htm
Monday, June 23, 2008 Persistence of Pathogenic Prion Protein during Simulated Wastewater Treatment Processes ASAP Environ. Sci. Technol., ASAP Article, 10.1021/es703186e Web Release Date: June 10, 2008
Copyright © 2008 American Chemical Society
Persistence of Pathogenic Prion Protein during Simulated Wastewater Treatment Processes
Glen T. Hinckley,?? Christopher J. Johnson,?? Kurt H. Jacobson,? Christian Bartholomay,§? Katherine D. McMahon,? Debbie McKenzie,? Judd M. Aiken,? and Joel A. Pedersen*?#
Department of Civil and Environmental Engineering, Department of Comparative Biosciences, and Department of Soil Science, University of Wisconsin, Madison, Wisconsin 53706
Received for review December 19, 2007
Revised manuscript received April 4, 2008
Accepted April 9, 2008
Abstract:
Transmissible spongiform encephalopathies (TSEs, prion diseases) are a class of fatal neurodegenerative diseases affecting a variety of mammalian species including humans. A misfolded form of the prion protein (PrPTSE) is the major, if not sole, component of the infectious agent. Prions are highly resistant to degradation and to many disinfection procedures suggesting that, if prions enter wastewater treatment systems through sewers and/or septic systems (e.g., from slaughterhouses, necropsy laboratories, rural meat processors, private game dressing) or through leachate from landfills that have received TSE-contaminated material, prions could survive conventional wastewater treatment. Here, we report the results of experiments examining the partitioning and persistence of PrPTSE during simulated wastewater treatment processes including activated and mesophilic anaerobic sludge digestion. Incubation with activated sludge did not result in significant PrPTSE degradation. PrPTSE and prion infectivity partitioned strongly to activated sludge solids and are expected to enter biosolids treatment processes. A large fraction of PrPTSE survived simulated mesophilic anaerobic sludge digestion. The small reduction in recoverable PrPTSE after 20-d anaerobic sludge digestion appeared attributable to a combination of declining extractability with time and microbial degradation. Our results suggest that if prions were to enter municipal wastewater treatment systems, most would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids.
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Introduction... snip
Monday, June 23, 2008
Persistence of Pathogenic Prion Protein during Simulated Wastewater
Treatment Processes
http://chronic-wasting-disease.blogspot.com/2008/06/persistence-of-pathogenic-prion-protein.html
http://www.organicconsumers.org/forum/index.php?showtopic=1621
P04.61 Survival of PrPSc during Simulated Wastewater Treatment Processes
Pedersen, J1; Hinckley, G1; McMahon, K2; McKenzie, D3; Aiken, JM3 1University of Wisconsin, Soil Science/Civil and Environmental Engineering, USA; 2University of Wisconsin, Civil and Environmental Engineering, USA; 3University of Wisconsin, Comparative Biosciences, USA
Concern has been expressed that prions could enter wastewater treatment systems through sewer and/or septic systems (e.g., necropsy laboratories, rural meat processors, private game dressing) or through leachate from landfills that have received TSE-contaminated material. Prions are highly resistant to degradation and many disinfection procedures raising concern that they could survive conventional wastewater treatment. Here, we report the results of experiments examining the partitioning and survival of PrPSc during simulated wastewater treatment processes including activated and mesophilic anaerobic sludge digestion. We establish that PrPSc can be efficiently extracted from activated and anaerobic digester sludges with 1% sodium dodecyl sulfate, 10% sodium undecyl sulfate, and 1% sodium N-lauryl sarcosinate. Activated sludge digestion does not result in significant degradation of PrPSc. The protein partitions strongly to the activated sludge solids and is expected to enter biosolids treatment processes. A large fraction of PrPSc survived simulated mesophilic anaerobic sludge digestion. Our results suggest that if prions were to enter municipal waste water treatment systems, most of the agent would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids. Land application of biosolids containing prions could represent a route for their unintentional introduction into the environment. Our results argue for excluding inputs of prions to municipal wastewater treatment facilities that would result in unacceptable risk of prion disease transmission via contaminated biosolids.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles
Christopher J. Johnson1,2, Joel A. Pedersen3, Rick J. Chappell4, Debbie McKenzie2, Judd M. Aiken1,2*
Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. .
In conclusion, our results provide compelling support for the hypothesis that soil serves as a biologically relevant reservoir of TSE infectivity. Our data are intriguing in light of reports that naïve animals can contract TSEs following exposure to presumably low doses of agent in the environment [5,79]. We find that Mte enhances the likelihood of TSE manifestation in cases that would otherwise remain subclinical (Figure 3B and 3C), and that prions bound to soil are orally infectious (Figure 5). Our results demonstrate that adsorption of TSE agent to inorganic microparticles and certain soils alter transmission efficiency via the oral route of exposure. full text is here:
http://pathogens.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.ppat.0030093
http://pathogens.plosjournals.org/perlserv/?request=get-pdf&file=10.1371_journal.ppat.0030093-L.pdf
http://pathogens.plosjournals.org/perlserv/?request=get-pdf&file=10.1371_journal.ppat.0030093-S.pdf
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0611&L=sanet-mg&T=0&F=&S=&m=1742&P=7260
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production ***
Cathrin E. Bruederle1*, Robert M. Hnasko1, Thomas Kraemer2, Rafael A. Garcia3, Michael J. Haas3, William N. Marmer3, John Mark Carter1
1 USDA-ARS WRRC, Foodborne Contaminants Research Unit, Albany, California, United States of America2 Forensic Toxicology, Institute of Legal Medicine, Saarland University, Homburg/Saar, Germany3 USDA-ARS ERRC, Fats, Oils and Animal Coproducts Research Unit, Wyndmoor, Pennsylvania, United States of America
Abstract The epidemic of bovine spongiform encephalopathy (BSE) has led to a world-wide drop in the market for beef by-products, such as Meat-and-Bone Meal (MBM), a fat-containing but mainly proteinaceaous product traditionally used as an animal feed supplement. While normal rendering is insufficient, the production of biodiesel from MBM has been suggested to destroy infectivity from transmissible spongiform encephalopathies (TSEs). In addition to producing fuel, this method simultaneously generates a nutritious solid residue. In our study we produced biodiesel from MBM under defined conditions using a modified form of alkaline methanolysis. We evaluated the presence of prion in the three resulting phases of the biodiesel reaction (Biodiesel, Glycerol and Solid Residue) in vitro and in vivo. Analysis of the reaction products from 263K scrapie infected MBM led to no detectable immunoreactivity by Western Blot. Importantly, and in contrast to the biochemical results the solid MBM residue from the reaction retained infectivity when tested in an animal bioassay. Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process.
Citation: Bruederle CE, Hnasko RM, Kraemer T, Garcia RA, Haas MJ, et al. (2008) Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production. PLoS ONE 3(8): e2969. doi:10.1371/journal.pone.0002969
Editor: Neil Mabbott, University of Edinburgh, United Kingdom
Received: April 21, 2008; Accepted: July 24, 2008; Published: August 13, 2008
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: CRIS 5325-32000-007-00D and CRIS 5325-32000-008-00D
Competing interests: The authors have declared that no competing interests exist.
* E-mail: cathrin.bruederle@gmail.com
snip...
Discussion Decontamination of pathogenic prions has turned out to be a challenging endeavor. Prions are known to be unusually resistant to common decontamination methods. BSE is believed to be a result of insufficient decontamination and rendering methods of ruminant coproducts that were used as animal feed. Although this led to a devastating feed-borne epidemic among cattle, a major concern here is the overwhelming evidence for the zoonotic transmission of bovine prions to humans [20]. Total elimination of TSEs requires methods that completely destroy any potential prion infectivity in a large scale format. Production of biodiesel from bovine fat and brain tissue has been proposed to be a useful tool for decontamination of prions resulting in safe biodiesel [21]. In our study we evaluated an inexpensive large scale method (in situ transesterification) for production of biodiesel for TSE decontamination potential. Furthermore we investigated potential infectivity present not only in the biodiesel but also in the two other phases developed from the process, a solid MBM residue and glycerol. The solid MBM residue is of particular interest for its potential as a nutritious feed additive for ruminants such as cattle. In our hands, under optimal conditions for transesterification, the solid MBM residue retained 7% of the initial triglyceride and 90% of the initial protein content [17]
The alkaline methanolysis method efficiently produced biodiesel from MBM spiked with hamster brain and the method eliminated PrPsc detection in all products as determined by Western blot. Our biochemical results are comparable to previous studies, at least with regards to the biodiesel and glycerol phase [15]. Biodiesel and glycerol products had no detectable infectivity in our long term animal assay (survival>200d). In contrast to the biodiesel and glycerol phase, we show that the remaining solid MBM residue that had been spiked with scrapie brain retained infectivity in our sensitive bioassay. All animals inoculated with the infected solid MBM residue developed scrapie. However, increased survival time suggests the reaction did reduce infectivity in solid MBM residue from 10-3 ID50 to 10-9 ID50 (a partial decontamination of ~6 logs), based on a standard hamster survival curve that we established in our laboratory according to previous reported results [18]. The broad distribution of time-to-death for these animals is likely due to uneven distribution of infectious material in the inoculum, as the residue produced a relatively coarse suspension in the syringe. We suggest that, in addition to disinfection by the alkaline methanolysis reaction, we observe significant partitioning of infectivity, from the liquid phases into the solid residue. Another possible explanation for increased survival of animals inoculated with the solid MBM residue could be a high binding affinity of the prion protein to MBM and thus a sustained release from MBM in the brain. A phenomenon like this was described previously for prion binding to soil minerals [22]. In our study, when spiked into MBM, PrPsc was only detectable by Western Blot after boiling of sample in detergent. On the other hand we could show that control animals that received infected MBM not subjected to the reaction (MBM sc) developed disease in a time frame comparable to a standard scrapie brain homogenate.
Our results clearly show that Western Blot detection alone is insufficient to conclude on the absence of infectious prion, particularly when assessing a grossly heterogeneous sample such as MBM. This study illustrates that lack of prion detection in vitro does not necessarily exclude infectivity as determined by bioassay.
Furthermore the residual scrapie infectivity detected in the solid MBM residue probably limits the use of ruminant MBM as a feed additive to only non-ruminants, such as fish and fowl, as they are not susceptible to TSEs. Relatively minor variations of this reaction (e.g., more heat and/or alkali) may prove fully effective for complete destruction of infectivity in the solid MBM residue, but must be cost-effective if suspect MBM is to be considered as a ruminant feed additive.
http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0002969
Monday, June 23, 2008
Persistence of Pathogenic Prion Protein during Simulated Wastewater Treatment Processes
http://chronic-wasting-disease.blogspot.com/2008/06/persistence-of-pathogenic-prion-protein.html
http://organicconsumers.org/forum/index.php?showtopic=1621
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Friday, August 15, 2008 Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
http://chronic-wasting-disease.blogspot.com/2008/08/prion-infected-meat-and-bone-meal-is.html
http://organicconsumers.org/forum/index.php?showtopic=1935
Science 14 October 2005:Vol. 310. no. 5746, pp. 324 - 326DOI: 10.1126/science.1118829 Reports
Coincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion
Harald Seeger,1* Mathias Heikenwalder,1* Nicolas Zeller,1 Jan Kranich,1 Petra Schwarz,1 Ariana Gaspert,2 Burkhardt Seifert,3 Gino Miele,1 Adriano Aguzzi1
Prion infectivity is typically restricted to the central nervous and lymphatic systems of infected hosts, but chronic inflammation can expand the distribution of prions. We tested whether chronic inflammatory kidney disorders would trigger excretion of prion infectivity into urine. Urinary proteins from scrapie-infected mice with lymphocytic nephritis induced scrapie upon inoculation into noninfected indicator mice. Prionuria was found in presymptomatic scrapie-infected and in sick mice, whereas neither prionuria nor urinary PrPSc was detectable in prion-infected wild-type or PrPC-overexpressing mice, or in nephritic mice inoculated with noninfectious brain. Thus, urine may provide a vector for horizontal prion transmission, and inflammation of excretory organs may influence prion spread.
snip...
SEE FULL TEXT ;
http://chronic-wasting-disease.blogspot.com/2008/06/transmission-and-detection-of-prions-in.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
Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip...
full text ;
http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
P01.47
Quantifying the Species Barrier in Chronic Wasting Disease by a Novel in vitro Conversion Assay
Li, L1; Coulthart, MB2; Balachandran, A3; Chakrabartty, A4; Cashman, NR1 1University of British Columbia, Brain Research Centre, Canada; 2Public Health Agency of Canada, National Microbiology Laboratory, Canada; 3Animal Diseases Research Institute, Canada Food Inspection Agency, National Reference Laboratory for Scrapie and CWD, Canada; 4Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Canada
Background: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that can affect North American cervids (deer, elk, and moose). Although the risk of CWD crossing the species barrier and causing human disease is still unknown, however, definite bovine spongiform encephalopathy (BSE) transmission to humans as variant CJD (vCJD), it would seem prudent to limit the exposure of humans to CWD.
Aim: In view of the fact that BSE can be readily transmitted to non-bovid species, it is important to establish the species susceptibility range of CWD.
Methods: In vitro conversion system was performed by incubation of prions with normal brain homogenates as described before, and protease K (PK) resistant PrP was determined by immunoblotting with 6H4 monoclonal prion antibody.
Results: Our results demonstrate that PrPC from cervids (including moose) can be efficiently converted to a protease-resistant form by incubation with elk CWD prions, presumably due to sequence and structural similarities between these species. Interestingly, hamster shows a high conversion ratio by PrPCWD. Moreover, partial denaturation of substrate PrPC can apparently overcome the structural barriers between more distant species.
Conclusions: Our work correctly predicted the transmission of CWD to a wild moose. We find a species barrier for prion protein conversion between cervids and other species, however, this barrier might be overcome if the PrPC substrate has been partially denatured in a cellular environment. Such an environment might also promote CWD transmission to non-cervid species, *** including humans. Acid/GdnHCl-treated brain PrPC was a superior substrate for the in vitro conversion than PrPC treated at physiological pH. This has implications for the process by which the prion protein is converted in disease.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
SEWING THE SEEDS OF MAD COW (CWD) THROUGH ANIMAL PROTEIN $
[PDF]
BSE INQUIRY Statement of behalf of the Environment Agency ... File Format: PDF/Adobe Acrobat - View as HTML ... his Statement of March 1998 to the BSE Inquiry ... systems subject to regular or intermittent contamination by rapid movement of recharge water
BSE INQUIRY
Statement of behalf of the Environment Agency Concerning Thruxted Mill By Mr C. P. Young Principal Hydrogeologist, Soil Waste and Groundwater Group WRc plc; Medmenham, Bucks
http://www.bse.org.uk/files/ws/s490.pdf
http://www.americansportsman.com/messageboard/hunting/smallgamehunting/deer/viewpost.asp?mb=deerhunting&post=642
http://www.biggamehunt.net/forums/viewtopic.php?t=14549&start=0
http://www.michigan-sportsman.com/forum/showthread.php?t=23313
Monday, June 30, 2008 Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease
http://chronic-wasting-disease.blogspot.com/2008/06/risk-behaviors-in-rural-community-with.html
10 people killed by new CJD-like disease
Public release date: 9-Jul-2008 [ Print Article E-mail Article Close Window ]
Contact: Claire Bowles claire.bowles@rbi.co.uk 44-207-611-1210 New Scientist
10 people killed by new CJD-like disease A NEW form of fatal dementia has been discovered in 16 Americans, 10 of whom have already died of the condition. It resembles Creutzfeldt-Jakob disease - with patients gradually losing their ability to think, speak and move - but has features that make it distinct from known forms of CJD.
No one yet knows how the disease originates, or under what conditions it might spread. Nor is it clear how many people have the condition. "I believe the disease has been around for many years, unnoticed," says Pierluigi Gambetti, director of the US National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, Ohio. Cases may previously have been mistaken for other forms of dementia.
Since Gambetti's team wrote a paper describing an initial 11 cases referred to his centre between 2002 and 2006 (Annals of Neurology, vol 63, p 697), another five have come to light. "So it is possible that it could be just the tip of the iceberg," Gambetti says.
http://www.eurekalert.org/pub_releases/2008-07/ns-tpk070908.php
Thursday, July 10, 2008 A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html
Thursday, July 10, 2008 A New Prionopathy update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html
Sunday, August 10, 2008
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
I hate to inform them, but sporadic CJD has increased. sporadic CJD in the USA went from 28 cases _documented_ in 1997, to 170 cases of sporadic CJD _documented_ in 2007. i'm not a math wiz, but looks like an increase to me. ...
6 Includes 55 cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
2008 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.
http://www.cjdfoundation.org/fact.html
"the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine."
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1, Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1, Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4, Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4, Jean-Philippe Deslys1
1 Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps Florida, Jupiter, Florida, United States of America, 5 Genetics Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
Abstract Background Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.
Methodology/Principal Findings Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.
Conclusion/Significance Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.
Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017
Editor: Neil Mabbott, University of Edinburgh, United Kingdom
Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20, 2008
Copyright: © 2008 Comoy 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: This work has been supported by the Network of Excellence NeuroPrion.
Competing interests: CEA owns a patent covering the BSE diagnostic tests commercialized by the company Bio-Rad.
* E-mail: emmanuel.comoy@cea.fr
Tuesday, August 19, 2008
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate
http://bse-atypical.blogspot.com/2008/08/atypical-bse-base-transmitted-from.html
Owner and Corporation Plead Guilty to Defrauding Bovine Spongiform Encephalopathy (BSE) Surveillance Program
PLEASE SEE FULL TEXT ;
Monday, June 16, 2008 Mad Cows and Computer Models: The U.S. Response to BSE
http://bse-atypical.blogspot.com/
Sunday, March 16, 2008 MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE March 16, 2008
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
Sunday, August 10, 2008
Thursday, July 10, 2008 A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html
Thursday, July 10, 2008 A New Prionopathy update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html
MY COMMENTS, for whatever they are worth ;
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
Communicated by: Terry S. Singeltary Sr.
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
http://pro-med.blogspot.com/2007/11/proahedr-prion-disease-update-2007-07.html
http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963
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.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
http://www.thepathologicalprotein.com/
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT
http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
http://www.bmj.com/cgi/eletters/320/7226/8/b#6117
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406
Wednesday, August 20, 2008
Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?
August 20, 2008
http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html
with kindest regards,
I am sincerely,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
----- Original Message -----
From: TERRY SINGELTARY
To: bjohnston@madison.com
Cc: dunphy@co.dane.wi.us ; dimaggio.mike@co.dane.wi.us ; matzinger@co.dane.wi.us ; rasmussen.holly@co.dane.wi.us ; Regan@co.dane.wi.us ; younes@co.dane.wi.us ; welch@co.dane.wi.us ; fahey@co.dane.wi.us ; olson.shaun@co.dane.wi.us ; efoley@madison.com ; tkelley@madison.com ; jhuntley@madison.com ; stubbs@co.dane.wi.us ; desmidt@co.dane.wi.us ; bruskewitz@co.dane.wi.us ; vedder.barbara@co.dane.wi.us ; wheeler@co.dane.wi.us ; hesselbein@co.dane.wi.us
Sent: Saturday, August 23, 2008 9:52 PM
Subject: re-CWD... Not to worry, Have another glass of tap water ?
re-CWD... Not to worry, Have another glass of tap water ?
Greeting Dane County Wisconsin,
a kind greetings from Bacliff, Texas. I read this article and it disturbed me greatly. so I thought I would send you the latest science on TSE, and what Mr. DiMaggio thinks is so set in stone, may not be as so sound as he would think. please take this data with great concern, and study it carefully, and the sources these studies come from comes from. it helps sometimes with decisions like this that you have all the data. ...
thank you! and kindest regards...terry
IN REPLY to ;
'A real infringement on democracy' Local laws regulating campaign signs may be unconstitutional Bill Lueders on Thursday 08/07/2008
snip...
Not to worry
According to a new UW-Madison study, the prions that cause mad cow disease are not destroyed by conventional sewage treatment and could end up contaminating water and fertilizer. This may be of interest to folks 'round here, given that the state Department of Natural Resources has for the past few months been dumping the carcasses of deer with chronic wasting disease (CWD) in the county's Rodefeld landfill, from which leachate is pumped into the sewerage treatment plant.
But, it turns out, there's absolutely nothing to worry about!
"The study we did on prions shows we can contain them in the landfill," says Mike DiMaggio, the county's solid waste manager. The two-year study, also done by the UW, recommended that the county put soil above and below the dumped deer. That way, says DiMaggio, leaking prions "attach to the dirt [and] don't go anywhere."
The DNR began dumping carcasses in the landfill last Nov. 15, two weeks after getting County Board approval. The DNR's Gene Miller, who oversees the program, estimates that it's since dumped about 90 tons of deer, of which "3% or less" are believed to be contaminated with CWD.
DiMaggio isn't troubled by the new UW study because, he says, comparing mad cow disease to CWD is "like comparing polio to MS or heart disease."
But aren't both always-fatal brain gnawers variants of Creutzfeldt-Jakob disease, spread by prions? DiMaggio says he's not an expert; thankfully, there's one on hand.
Joel Pederson, the UW environmental chemist who did the latest study, says the only danger would be "if prions were able to escape a landfill." But the soil sandwich they are buried in makes that unlikely.
"If carcasses are properly placed within a landfill," says Pederson, "we expect that prions would not be released at a level of concern."
There you have it. Science has spoken. Have another glass of tap water.
http://www.thedailypage.com/isthmus/article.php?article=23414
Greetings again,
re-CWD... Not to worry, Have another glass of tap water.
"If carcasses are properly placed within a landfill," says Pederson, "we expect that prions would not be released at a level of concern."
stupid is, as stupid does. ...Forest Gump
please note recent paper on TSE, and CWD below and comments from Aguzzi, Sigurdson, Heikenwaelder et al. then further recent research to follow that as well. ...TSS
Molecular Mechanisms of Prion Pathogenesis
Adriano Aguzzi, Christina Sigurdson, and Mathias Heikenwaelder Institute of Neuropathology, University Hospital of Z¨ urich, CH-8091 Z¨ urich, Switzerland; email: adriano.aguzzi@usz.ch, mathias.heikenwaelder@usz.ch, christina.sigurdson@usz.ch Annu. Rev. Pathol. Mech. Dis. 2008. 3:11-40 First published online as a Review in Advance on August 8, 2007 The Annual Review of Pathology: Mechanisms of Disease is online at pathmechdis.annualreviews.org This article's doi: 10.1146/annurev.pathmechdis.3.121806.154326 Copyright c 2008 by Annual Reviews. All rights
Annu. Rev. Pathol. Mech. Dis. 2008. 3:11-40 First published online as a Review in Advance on August 8, 2007 The Annual Review of Pathology: Mechanisms of Disease is online at pathmechdis.annualreviews.org This article's doi: 10.1146/annurev.pathmechdis.3.121806.154326 Copyright c 2008 by Annual Reviews. All rights reserved 1553-4006/08/0228-0011$20.00
Abstract
Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrPC) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt- Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrPSc, a misfolded and aggregated â-sheet-rich isoform of PrPC. However, PrPSc may or may not be completely congruent with the infectious moiety. Here, we discuss the molecular mechanisms leading to neurodegeneration, the role of the immune system in prion pathogenesis, and the existence of prion strains that appear to have different tropisms and biochemical characteristics.
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As an example in the field of human medicine, four cases of vCJD have been reported to be caused by blood transfusion (9- 11). This indicates that BSE prions can be recycled among humans, which has caused considerable alarm that the supply of bloodderived pharmaceuticals may be threatened (12). In particular, the report of a subclinical blood-derived vCJD infection in an individual carrying a heterozygote methionine/ valine polymorphism at codon 129 of the human PRNP gene (10) suggests that transmission of BSE prions to humans enhances their virulence and broadens the spectrum of susceptible recipients. In this respect, it has been demonstrated that polymorphisms at codon 129 of the human PRNP gene control susceptibility and incubation time in human patients (e.g., 129MM versus 129MV or 129VV drastically increases the susceptibility of humans to BSE prions). It was reported only recently that most individuals who suffered from kuru and were polymorphic at codon 129 showed incubation times longer than 50 years (13). Moreover, recent reports indicate that there is still a lot to be learned about the mechanisms of prion transmission (e.g., human to human or within scrapie-affected animal flocks) and prion tropism underlining the complex alternating distribution patterns of PrPSc (e.g., PrPSc deposition in lymphoid tissue, the CNS) and prion infectivity under varying conditions (e.g., chronic inflammation) and hosts (e.g., sheep, elk and deer, human): Chronic inflammation can alter the tropism of prion infectivity or PrPSc to organs hitherto believed prion free (e.g., liver, pancreas, kidney of mice, mammary gland of sheep, muscle of humans) (14-16). Moreover, PrPSc was reported in spleen and muscle tissue of sporadic Creutzfeldt-Jakob disease (sCJD) patients (17), and prion infectivity was demonstrated in muscle, blood, and saliva of deer suffering from CWD (18, 189). Also, prion infectivity was shown to be excreted via urine of prion-infected nephritic mice, a process defined as prionuria (19). These results emphasize the need for further assessment of possible public health risks from TSE-affected extraneural organs. It is very well possible that preexisting pathophysiological conditions of the infected host additionally contributed to unexpected distribution patterns of prion infectivity. For example, the presence of prion infectivity in the blood of sheep or deer may influence the deposition of prion infectivity in various organs previously deemed prion free. Therefore, it should be carefully reconsidered whether only organs of the CNS and the lymphoreticular system should be included in the current risk classifications of biologicals in the future. It will be important to test altered prion tropism profiles in nonlymphoid organs and body fluids (e.g., blood, urine, milk, saliva) of ruminants (e.g., sheep, goat, cattle, elk, and deer) and human patients suffering from sCJD and vCJD.
snip...
Recent in vivo evidence indicated that a similar phenomenon of conformational variants may occur in Alzheimer's disease (151). Here the existence of Aâ strains that can seed and accelerate aggregation and Aâ pathology was posited. These intriguing observations support the hypothesis that the pathogenetic mechanisms operating in Alzheimer's disease and in prion diseases have more in common than we often appreciate (152). Perhaps future studies will address whether different Aâ strains with distinct biochemical or neuropathological characteristics occur in humans. Can multiple prion strains coexist and effect prion replication? Two subtypes of sporadic CJD have recently been demonstrated to coexist in humans (62). Experimental studies have shown that when two strains infect the same host, one strain can impede the ability of the second strain to cause disease (153). Bartz and colleagues (154) recently suggested that this might be caused by the suppression of prion replication of the second strain. Strain features are useful for tracing prion infections between species. When transmitted to primates, BSE causes lesions strikingly similar to that of vCJD (155, 156). BSE is most likely transmissible to humans too, and strong circumstantial evidence (157-159) suggests that BSE is the cause of vCJD, which has claimed more than 200 lives in the United Kingdom (3, 160), as well as a much smaller number in some other countries (161).
NATURAL TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: WHAT IS NEW? Cattle Prions More than a few surprises have come from further investigations of prion strains in field cases of TSEs. Until recently, BSE was believed to be associated with one single prion strain, classified by an exclusive and remarkably stable biochemical profile of PrPSc. However, distinct molecular signatures have recently been discovered through the large-scale screening of cattle mandated by European authorities in the context of BSE surveillance. These atypical profiles fall into either of two groups: H-type cases of protease-resistant fragments with a molecular weight higher than BSE, and bovine amyloidotic spongiform encephalopathy, or L type (lower) (162). To test whether these different biochemical and histopathological properties correspond to distinct strains, the Laude laboratory transmitted H-type-PrPSc isolates from French cattle into transgenic mice expressing bovine or ovine PrP (163). The recipient mice developed neurological signs exhibiting strain-specific features clearly distinct from that of the classical BSE agent, providing pivotal evidence that the underlying strains are distinct.
Atypical Sheep Scrapie In 1998, aberrant cases of sheep scrapie were described in Norway and the strain was newly classified as Nor98 (164). Active European Union surveillance later revealed additional cases of atypical scrapie in several other countries (165, 166). Sheep infected with Nor98, or atypical scrapie, accumulated PrPSc primarily in the cerebellum and cerebral cortex rather than in the brainstem target in the classical strain (167). Additionally, on western blot analysis of atypical scrapie cases, an additional small-molecular-weight (10-12 kDa) PrP fragment appeared afterPKdigestion and was shown by epitope mapping to lack both N and C termini of PrP (167, 168). Furthermore, atypical scrapie cases occurred not only in the classical scrapie-susceptible genotypes (A136 R154 Q171), but also in genotypes associated with high resistance to classical scrapie (A136 R154 R171) (165, 166). Were these atypical scrapie cases also infectious? In 2001, atypical scrapie cases were shown to be transmissible prion diseases after inoculated ovine PrP-expressing transgenic mice developed disease and prion aggregates (169). In the meantime, several countries appear to be reporting extremely high incidences of atypical scrapie, and in fact atypical scrapie appears to be the rule rather than the exception in some geographical areas.
Chronic Wasting Disease Among all animal prion diseases, CWD of cervids is likely the most efficiently transmitted. CWD infections occur in mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), Rocky Mountain elk (Cervus elaphus nelsoni) (170), and moose (Alces alces shirasi) (171). Prevalence can reach as high as 30% in dense, free-ranging deer populations and nearly 100% in captive animals (171). Hypotheses for CWD transmission range from spread via direct contact to exposure through grazing in areas contaminated by prion-infected secretions, excretions (saliva, urine, feces), tissues (placenta), or decomposed carcasses. Insightful experimental studies have recently revealed two key findings: (a) Saliva from CWD-infected deer can transmit disease (18), and (b) CWD-infected carcasses allowed to decay naturally in confined pastures can lead to CWD infections in captive deer (172). Additionally, the abundant CWD-prion accumulation within lymphoid tissues may also lead to CWD prion buildup in nonlymphoid organs with lymphoid follicles, as was recently shown in kidney, potentially shifting shedding routes (173). It is unknown whether other types of inflammation, such as the granulomatous inflammation in the intestine seen in Johne's disease (Mycobacterium avium subsp. paratuberculosis; affects ruminants, including deer and elk) or parasitic inflammation, could lead to or perhaps increase prion excretion by fecal routes. The environmental prion contamination in CWD underscores the difficulties of CWD disease management.Within North America,CWDinfected deer and elk have been detected in 14 states and two Canadian provinces (170, 174, 175). CWD surveillance in Europe has been more limited. However, in Germany, a total of 7300 captive and free-ranging cervids were tested forCWDwith no sign of infection (176). Reindeer or caribou (Rangifer tarandus), from North America or Northern Europe respectively, have a highly homologous prion sequence compared with mule deer and thus are likely susceptible to CWD. Other European cervids such as moose and red deer (C. elaphus) are also expected to be CWD susceptible. The deer and elk primary protein structures are highly conserved, as seen in other mammals. Interestingly, a polymorphism at codon 225S/F may influence CWD susceptibility in mule deer. When comparing the frequency of genotypes among CWDnegative and -positive deer (n = 1482), the odds that a CWD-infected animal was 225SS was 30 times greater when compared with 225SF, whereas the frequency of 225SF/FF genotypes in CWD-negative deer was 9.3%, but only 0.3% in CWD-positive deer (177).
Additionally, elk have a polymorphism at codon 132 (M/L) of Prnp, corresponding to polymorphic codon 129 (M/V) in humans. Elk expressing 132ML and 132LL Prnp were reported to be overrepresented among elk with CWD when compared with uninfected controls (178), and 132LL elk experimentally infected with CWD have resisted infection for at least four years, whereas 132MM or 132ML elk (n = 2 each) developed terminal clinical prion disease by 23 or 40 months post inoculation, respectively, confirmed by immunohistochemistry and western blotting for PrPSc (179). White-tailed deer also have Prnp polymorphisms that may affect their CWD susceptibility. A reduced susceptibility to CWD was linked to a G96S and a Q95H polymorphism in a study comparing allelic frequencies from CWD-positive and CWDnegative free-rangingWisconsin white-tailed deer (180).
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http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.pathmechdis.3.121806.154326
Prion White Paper Issue: Can the potential presence of prions in land applied biosolids result in food chain contamination with the subsequent development of animal and human disease?
What are Prions and What are the Diseases Attributed to Exposure to Prions? “Prion” refers to a particular kind of protein found in animal tissue. Most prions occur in a normal, harmless form, but there are abnormal or infectious forms. The normal, harmless form has the same sequence of amino acids as the abnormal form, but the abnormal, or infectious, form takes a different folded shape. (Epstein, 2005)1. In their normal, non-infectious state, it is believed that prions are involved in cell-to-cell communications and other important functions. Unlike bacteria and viruses, prions do not contain genetic material. However, like viruses and bacteria, prions are infectious and replicate in host tissues. Throughout this white paper the word “Prion” is used to indicate the abnormal, infectious form of prions. Prions cause normal celluar proteins to convert to the abnormal or prion form. In animals affected with prion-caused diseases, prions have been found mainly in the brain, spinal cord, lymph nodes, spleen, tonsils, eyes, pancreas, adrenal gland, and blood. In studies with mice, prions have been observed in muscle tissue. Prions have not been observed in manure or biosolids.
It is now commonly accepted that prions are responsible for a number of previously known but little-understood animal (including human) diseases generally classified under transmissible spongiform encephalopathy diseases (TSEs) (Wikipedia, 2005)2. These diseases affect the structure of brain tissue and are all fatal and untreatable. The TSE diseases that have received the most attention recently include chronic wasting disease (CWD) that affects deer and elk, bovine spongiform encephalopathy (BSE) that affects cattle (“Mad Cow Disease”)(Collinge, 2001)3, and Creutzfeldt-Jacob Disease (CJ Disease) that affects humans.
What Are the Sources of Prions That May be Relevant to Wastewater Treatment and Biosolids Production?
• Abattatoirs, Animal Rendering, and Meat Processing Operations - These operations, if they process BSE-contaminated cattle, can serve as a potential source of prions in wastewater treatment plants. However, preliminary calculations on a worst case scenario in which the entire prion-infected brain of a slaughtered cattle were released into a wastewater treatment plant over the span of a day indicate that the resulting concentration of prions in the treatment plant’s effluent would be significantly less than the prion concentration necessary to infect an individual (assuming that the individual was directly consuming the treatment plant’s effluent (Pederson, 2005)4). A recent effluent guideline (USEPA, 2004a)5 and general pretreatment standards promulgated by the United States Environmental Protection Agency (USEPA) for the Meat and Poultry Products Point Source Category, and the ability of local wastewater treatment authorities to impose these guidelines and standards on these discharging operations make it extremely unlikely that this assumed mass of prion-infected tissue would ever enter the sewer.
• Landfill Leachates - Leachates from landfills can act as a potential source of prions to a wastewater treatment plant if the landfill accepts for disposal carcasses from BSE-contaminated cattle or CWD-contaminated deer or elk. However, in areas where CWD is being actively managed, the disposal of contaminated deer or elk carcasses in municipal solid waste landfills appears to be an uncommon practice. CWD management approaches in the United States in areas of known prion infectivity typically involve incineration of infected materials. For example, the State of Wisconsin’s policy is to test potentially prion- infected deer and elk and to subsequently incinerate all prion positive deer and elk carcasses and landfill all prion negative carcasses (Kester, 2005)6. Because prions are positively charged, and have been described as being “sticky”, they are likely to strongly sorb to solids and soils both in the landfill and to the landfill liner (Taylor, 2005)7. Therefore, even if BSE-contaminated (prion) material were disposed in a municipal solid waste landfill that sent leachate to a wastewater treatment plant, the potential that significant concentrations of prions would be contained in the leachate is very low. This should be confirmed once analytical methodologies are developed to determine prions in leachate.
• Urine, feces, and blood from CJ Disease patients - Several researchers (Gabizon, et. al. 20018; Reichl, et. al. 20029) have reported the presence of prions in the blood and urine of CJ Disease patients. Prions have not been reported in the feces of CJ Disease patients. It should be noted that the concentrations of prions in the blood and urine of CJ Disease patients would be relatively low and, after entry into the sewer with a vast amount of dilution available, even lower compared to the concentrations of prions in the neural tissue of these patients or in the neural tissue of BSE-infected meat that these patients may have consumed. This is important to consider since the risk assessment results presented below are based on these significantly higher prion contaminated materials than the levels of prion contamination in blood, urine, or untreated wastewaters.
Have Prions Been Detected in Wastewater or Biosolids? There are no reports in the scientific literature of the presence of prions in municipal wastewater or in biosolids. Currently, no validated analytical methodologies are available for the determination of prions in municipal wastewater influent, treated municipal wastewater effluent, or in biosolids. Once these analytical methods are developed, prions might be detected and quantified in these media. However, based on the discussion above, their concentrations would be expected to be extremely low and not capable of causing subsequent infection either through direct contact or indirectly through food chain contamination. Analytical methodologies exist for the detection of prions in brain and other neurological tissue, mammalian lymphoid tissue, blood, and urine. Prions have been detected in each of these biological materials (Pederson, 2005)4.
What are the Methods of Prion Destruction? Prions found in environmental media or in residuals such as biosolids appear to be extremely resistant to degradation and loss of infectivity. Current methods for denaturing prions and significantly reducing infectivity such as high temperatures and treatment with alkalis and bleach are applicable to prion-contaminated animal tissues but are not applicable to wastewater and biosolids treatment.
What Current Research and Measures Are Underway to Mitigate/Prevent Prion Entry Into Wastewater Treatment Plants?
• Abattatoirs, Animal Rendering, and Meat Processing Operations - The U.S. EPA in 2004 published an effluent guideline (regulatory standard) for the Meat and Poultry Products Point Source Category that will result in a dramatic reduction in the amount of animal tissue that can be discharged directly into the aquatic environment. (USEPA, 2004a)5. The technologies associated with this standard are designed to enhance ambient water quality by reducing the amount of solids such as animal tissues, biochemical oxygen demand (BOD), and ammonia that can be discharged into the aquatic environment. Although this regulation does not pertain nationally to operations that discharge into sanitary sewers (“indirect dischargers”), local wastewater treatment authorities are free to impose the standard’s technologies on these indirect dischargers through local pretreatment limits where the potential for the processing of infected animals exist. These operations are also subject to EPA’s General pretreatment regulations which will also reduce solids input to the sewer. The United Kingdom has promulgated guidance for their meat processing industry on practices that minimize the amount of neurological tissue lost to the sewer (Gale and Stanfield, 2001)10.
• Landfill Leachates - EPA has issued guidance on the operations of municipal solid waste landfills that accept prion-contaminated animal carcasses for disposal (USEPA, 2004b)11. This guidance discusses the importance of liners and leachate collection systems and recirculation of the leachate in the landfill rather than discharge of the leachate to the wastewater treatment plant for containment of prions at the landfill site.
• Urine, Feces, and Blood from CJ Disease Patients - There are no current regulations, at least at the Federal level, that prohibit pathology laboratories or mortuaries from disposing of prion-contaminated tissue and fluids of CJ Disease patients into the sanitary sewer. However, EPA has developed a draft strategy to reduce the prion contamination threat from the discharge of wastewater into the sanitary sewer from pathology/necropsy and research laboratories working with prion-contaminated tissues. (USEPA, 2005a)12.
• Research - Currently, there is at least one research effort (the University of Wisconsin/Madison funded by EPA) underway to characterize the potential presence and fate of prions in wastewater treatment plants. These studies will also determine the potential for prions to partition into and concentrate in biosolids (USEPA, 2005b)13.
What Are the Properties, Fate, and Transport of Prions in Wastewater Treatment and in the Land Application of Biosolids? Very little data in this area is available. Based on the properties of prions, it is expected that prions initially in wastewater (most likely at very small concentrations- see above discussion) will survive and most likely be attached to and be transported by solid particulates in the wastewater entering the wastewater treatment plant. Once in the wastewater treatment process, no significant decrease in prion infectivity or prion degradation is expected to occur because of prions’ resistance to physical and chemical conditions encountered in wastewater treatment plants.
Whatever little concentration of prions in the incoming wastewater, they are expected to strongly partition to and concentrate in biosolids during wastewater treatment. Research in progress will provide a quantitative estimate of this partitioning (USEPA, 2005b)13. Based on the physical and chemical stability of prions, it is expected that prions will persist in biosolids, albeit at expectedly very low levels with respect to potential infectivity and the very limited number of potential environmental transport pathways available to infect animals or humans.
Prions and their infectivity related to an animal TSE have been demonstrated to persist in soils for several years (Brown, 1991)14. Because of their strong affinity with solid particulates and, therefore, very low concentrations in the aqueous phase, prions are not expected to threaten human-consumed or animal feed crops through root uptake in biosolids land application. For the same reason, transport of prions to groundwater or surface waters from biosolids land application is not anticipated. Prions have no volatility so ambient air transport can be ruled out. The only potential significant environmental transport mechanism available for prions with subsequent exposure and potential infectivity to animals and humans is biosolids/soil ingestion by grazing ruminants and, theoretically, biosolids/soil ingestion by toddlers in a home garden scenario. However, for these potential pathways of exposure, it is highly unlikely that prion concentration in the biosolids could ever approach an infectious dose for either animals or humans based on the extremely high dilution that occurs in wastewater treatment plants if prion-contaminated tissue were discharged to these plants and the prions subsequently partitioned to the biosolids (see discussions in previous sections and the section below).
What is the Risk to Human Health From BSE in Wastewater Treatment? In 2001, Gale and Stanfield performed a quantitative risk assessment for BSE in biosolids for land application to cattle pasturing and vegetable crop production in the United Kingdom (UK)(Gale and Stanfield, 2001)10. Using a worse case set of scenarios, they concluded: The risks to humans through consumption of vegetable crops are extremely low (approaches zero). Although the risks to cattle are higher, because of their higher exposure to soil and greater susceptibility to prion infectivity, the risk assessment model demonstrates that biosolids containing trace quantities of prions alone cannot initiate or sustain a BSE epidemic in the UK cattle herd. The conclusions are consistent with the findings from epidemiological studies, which so far, have not detected horizontal transmission of BSE (including transmission from BSE-contaminated pastures) (Gale and Stanfield, 2001). The risk assessment demonstrates the importance of containment of neurological tissue from animal processing operations and absolutely minimizing or eliminating the amount of neurological tissue from BSE-infected animals that enter the sewer system.
Other “first order” risk assessments and estimates have demonstrated under worst-case scenarios extremely low risks to the theoretically highest exposed population, the farmer, from prions in land applied biosolids . It should be noted that these risk assessments are performed on subpopulations that are at “bounded” maximum exposures. In reality, compared to these subpopulations that are used for risk estimation purposes, almost all people living in countries with mature and regulated agricultural industries are exposed orders of magnitude less to prions or for that matter to any other chemical or biological agent that can be found in trace quantities in biosolids or in background soils. This in turn results in orders of magnitude less risk to the general population from theoretical or actual exposure to these substances.
Summary The information presented in this fact sheet strongly suggests that the risk of prion transmission directly to ruminants and indirectly to humans with subsequent infection from biosolids land application is extremely low and indeed is practically zero. Prion transmission via biosolids land application seems less likely than other potential food chain pathways such as the consumption of prion-contaminated feed in animal raising operations and prion transmission to or between humans via contaminated surgical instruments and blood products, all of which are relatively rare, and compared to which, biosolids transmission of prions is even rarer.
There is an ongoing need for additional research in the areas described in this fact sheet to better quantify the information presented herein. Results of this research should further expand the scientific knowledge based on the subject of prions.
-------------------------------------------------------------------------------- References 1. Epstein E. and N. Beecher. 2005. Mad Cow Disease, Creutzfeld-Jakob Disease, other TSEs and Biosolids. J. Residuals Science and Technology. 2(3): 181-187.
2. Wikipedia. 2005. The Free Encyclopedia. “Transmissible spongiform encephalopathy”. Available on the Internet.
3. Collinge J. 2001. Prion diseases of humans and animals: Their causes and molecular basis. Ann. Rev. Neurosci. 24: 519-550.
4. Pedersen J. 2005. Personal communication from Joel Pedersen, University of Wisconsin/Madison, to Alan B. Rubin.
5. USEPA. 2004a. Effluent Limitations Guidelines and New Source Performance Standards for the Meat and Poultry Products Point Source Category. 69 Federal Register (173):54475-54555. September 8, 2004.
6. Kester G. 2005. Personal communication from Greg Kester, Wisconsin Department of Natural Resources, to Alan B. Rubin.
7. Taylor D. 2005. Personal communication from David Taylor, Madison (WI) Metropolitan Sewerage District, to Alan B. Rubin.
8. Gabizon R., Shaked G.M., Shaked Y., Karn-Inbal Z., Halami M., and I. Avraham. 2001. A protease resistant prion protein isoform is present in urine of animals and humans affected with prion diseases. J. Biol. Chem. 276(34): 31479-31482.
9. Reichl H., Balen A., and C.A. Jansen. 2002. Prion transmission in blood and urine: What are the implications for recombinant and urinary-derived gonadotropins? Human Reprod. (10): 2501-2508.
10. Gale P. and G. Stanfield. 2001. Towards a quantitative risk assessment for BSE in sewage sludge. Journal of Applied Microbiology. 91:563-569.
11. USEPA. 2004b. Recommended Interim Practices for Disposal of Potentially Contaminated Chronic Wasting Disease Carcasses and Wastes. Memorandum from: Robert Springer, Director, Office of Solid Waste to: RCRA Division Directors (Regions I-X), Superfund Division Directors (Regions I-X), OSWER Office Director. April 6, 2004.
12. USEPA. 2005a. EPA Draft Strategy Addendum to the Region 8 Local Limits Strategy. Discharges of Wastewater to Publicly-Owned Treatment Works (POTWs) from Pathology/Necropsy and Research Laboratories Working with Prion-Contaminated Tissue. Industrial Pretreatment Program (8P-W-P). May 9, 2005.
13. USEPA. 2005b. Preliminary Results from the First Phase of a Two Phase Study Examining the Fate of Prions in Wastewater Treatment. Poster presentation. USEPA Science Forum, Washington, DC. May 17, 2005.
14. Brown P. and D.C. Gajdusek. 1991. Survival of scrapie virus after 3 years internment. The Lancet. 337:269-270.
http://www.wef.org/ScienceTechnologyResources/Biosolids/PrionWhitePaper.htm
Monday, June 23, 2008 Persistence of Pathogenic Prion Protein during Simulated Wastewater Treatment Processes ASAP Environ. Sci. Technol., ASAP Article, 10.1021/es703186e Web Release Date: June 10, 2008
Copyright © 2008 American Chemical Society
Persistence of Pathogenic Prion Protein during Simulated Wastewater Treatment Processes
Glen T. Hinckley,?? Christopher J. Johnson,?? Kurt H. Jacobson,? Christian Bartholomay,§? Katherine D. McMahon,? Debbie McKenzie,? Judd M. Aiken,? and Joel A. Pedersen*?#
Department of Civil and Environmental Engineering, Department of Comparative Biosciences, and Department of Soil Science, University of Wisconsin, Madison, Wisconsin 53706
Received for review December 19, 2007
Revised manuscript received April 4, 2008
Accepted April 9, 2008
Abstract:
Transmissible spongiform encephalopathies (TSEs, prion diseases) are a class of fatal neurodegenerative diseases affecting a variety of mammalian species including humans. A misfolded form of the prion protein (PrPTSE) is the major, if not sole, component of the infectious agent. Prions are highly resistant to degradation and to many disinfection procedures suggesting that, if prions enter wastewater treatment systems through sewers and/or septic systems (e.g., from slaughterhouses, necropsy laboratories, rural meat processors, private game dressing) or through leachate from landfills that have received TSE-contaminated material, prions could survive conventional wastewater treatment. Here, we report the results of experiments examining the partitioning and persistence of PrPTSE during simulated wastewater treatment processes including activated and mesophilic anaerobic sludge digestion. Incubation with activated sludge did not result in significant PrPTSE degradation. PrPTSE and prion infectivity partitioned strongly to activated sludge solids and are expected to enter biosolids treatment processes. A large fraction of PrPTSE survived simulated mesophilic anaerobic sludge digestion. The small reduction in recoverable PrPTSE after 20-d anaerobic sludge digestion appeared attributable to a combination of declining extractability with time and microbial degradation. Our results suggest that if prions were to enter municipal wastewater treatment systems, most would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids.
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Introduction... snip
Monday, June 23, 2008
Persistence of Pathogenic Prion Protein during Simulated Wastewater
Treatment Processes
http://chronic-wasting-disease.blogspot.com/2008/06/persistence-of-pathogenic-prion-protein.html
http://www.organicconsumers.org/forum/index.php?showtopic=1621
P04.61 Survival of PrPSc during Simulated Wastewater Treatment Processes
Pedersen, J1; Hinckley, G1; McMahon, K2; McKenzie, D3; Aiken, JM3 1University of Wisconsin, Soil Science/Civil and Environmental Engineering, USA; 2University of Wisconsin, Civil and Environmental Engineering, USA; 3University of Wisconsin, Comparative Biosciences, USA
Concern has been expressed that prions could enter wastewater treatment systems through sewer and/or septic systems (e.g., necropsy laboratories, rural meat processors, private game dressing) or through leachate from landfills that have received TSE-contaminated material. Prions are highly resistant to degradation and many disinfection procedures raising concern that they could survive conventional wastewater treatment. Here, we report the results of experiments examining the partitioning and survival of PrPSc during simulated wastewater treatment processes including activated and mesophilic anaerobic sludge digestion. We establish that PrPSc can be efficiently extracted from activated and anaerobic digester sludges with 1% sodium dodecyl sulfate, 10% sodium undecyl sulfate, and 1% sodium N-lauryl sarcosinate. Activated sludge digestion does not result in significant degradation of PrPSc. The protein partitions strongly to the activated sludge solids and is expected to enter biosolids treatment processes. A large fraction of PrPSc survived simulated mesophilic anaerobic sludge digestion. Our results suggest that if prions were to enter municipal waste water treatment systems, most of the agent would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids. Land application of biosolids containing prions could represent a route for their unintentional introduction into the environment. Our results argue for excluding inputs of prions to municipal wastewater treatment facilities that would result in unacceptable risk of prion disease transmission via contaminated biosolids.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles
Christopher J. Johnson1,2, Joel A. Pedersen3, Rick J. Chappell4, Debbie McKenzie2, Judd M. Aiken1,2*
Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. .
In conclusion, our results provide compelling support for the hypothesis that soil serves as a biologically relevant reservoir of TSE infectivity. Our data are intriguing in light of reports that naïve animals can contract TSEs following exposure to presumably low doses of agent in the environment [5,79]. We find that Mte enhances the likelihood of TSE manifestation in cases that would otherwise remain subclinical (Figure 3B and 3C), and that prions bound to soil are orally infectious (Figure 5). Our results demonstrate that adsorption of TSE agent to inorganic microparticles and certain soils alter transmission efficiency via the oral route of exposure. full text is here:
http://pathogens.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.ppat.0030093
http://pathogens.plosjournals.org/perlserv/?request=get-pdf&file=10.1371_journal.ppat.0030093-L.pdf
http://pathogens.plosjournals.org/perlserv/?request=get-pdf&file=10.1371_journal.ppat.0030093-S.pdf
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0611&L=sanet-mg&T=0&F=&S=&m=1742&P=7260
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production ***
Cathrin E. Bruederle1*, Robert M. Hnasko1, Thomas Kraemer2, Rafael A. Garcia3, Michael J. Haas3, William N. Marmer3, John Mark Carter1
1 USDA-ARS WRRC, Foodborne Contaminants Research Unit, Albany, California, United States of America2 Forensic Toxicology, Institute of Legal Medicine, Saarland University, Homburg/Saar, Germany3 USDA-ARS ERRC, Fats, Oils and Animal Coproducts Research Unit, Wyndmoor, Pennsylvania, United States of America
Abstract The epidemic of bovine spongiform encephalopathy (BSE) has led to a world-wide drop in the market for beef by-products, such as Meat-and-Bone Meal (MBM), a fat-containing but mainly proteinaceaous product traditionally used as an animal feed supplement. While normal rendering is insufficient, the production of biodiesel from MBM has been suggested to destroy infectivity from transmissible spongiform encephalopathies (TSEs). In addition to producing fuel, this method simultaneously generates a nutritious solid residue. In our study we produced biodiesel from MBM under defined conditions using a modified form of alkaline methanolysis. We evaluated the presence of prion in the three resulting phases of the biodiesel reaction (Biodiesel, Glycerol and Solid Residue) in vitro and in vivo. Analysis of the reaction products from 263K scrapie infected MBM led to no detectable immunoreactivity by Western Blot. Importantly, and in contrast to the biochemical results the solid MBM residue from the reaction retained infectivity when tested in an animal bioassay. Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process.
Citation: Bruederle CE, Hnasko RM, Kraemer T, Garcia RA, Haas MJ, et al. (2008) Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production. PLoS ONE 3(8): e2969. doi:10.1371/journal.pone.0002969
Editor: Neil Mabbott, University of Edinburgh, United Kingdom
Received: April 21, 2008; Accepted: July 24, 2008; Published: August 13, 2008
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: CRIS 5325-32000-007-00D and CRIS 5325-32000-008-00D
Competing interests: The authors have declared that no competing interests exist.
* E-mail: cathrin.bruederle@gmail.com
snip...
Discussion Decontamination of pathogenic prions has turned out to be a challenging endeavor. Prions are known to be unusually resistant to common decontamination methods. BSE is believed to be a result of insufficient decontamination and rendering methods of ruminant coproducts that were used as animal feed. Although this led to a devastating feed-borne epidemic among cattle, a major concern here is the overwhelming evidence for the zoonotic transmission of bovine prions to humans [20]. Total elimination of TSEs requires methods that completely destroy any potential prion infectivity in a large scale format. Production of biodiesel from bovine fat and brain tissue has been proposed to be a useful tool for decontamination of prions resulting in safe biodiesel [21]. In our study we evaluated an inexpensive large scale method (in situ transesterification) for production of biodiesel for TSE decontamination potential. Furthermore we investigated potential infectivity present not only in the biodiesel but also in the two other phases developed from the process, a solid MBM residue and glycerol. The solid MBM residue is of particular interest for its potential as a nutritious feed additive for ruminants such as cattle. In our hands, under optimal conditions for transesterification, the solid MBM residue retained 7% of the initial triglyceride and 90% of the initial protein content [17]
The alkaline methanolysis method efficiently produced biodiesel from MBM spiked with hamster brain and the method eliminated PrPsc detection in all products as determined by Western blot. Our biochemical results are comparable to previous studies, at least with regards to the biodiesel and glycerol phase [15]. Biodiesel and glycerol products had no detectable infectivity in our long term animal assay (survival>200d). In contrast to the biodiesel and glycerol phase, we show that the remaining solid MBM residue that had been spiked with scrapie brain retained infectivity in our sensitive bioassay. All animals inoculated with the infected solid MBM residue developed scrapie. However, increased survival time suggests the reaction did reduce infectivity in solid MBM residue from 10-3 ID50 to 10-9 ID50 (a partial decontamination of ~6 logs), based on a standard hamster survival curve that we established in our laboratory according to previous reported results [18]. The broad distribution of time-to-death for these animals is likely due to uneven distribution of infectious material in the inoculum, as the residue produced a relatively coarse suspension in the syringe. We suggest that, in addition to disinfection by the alkaline methanolysis reaction, we observe significant partitioning of infectivity, from the liquid phases into the solid residue. Another possible explanation for increased survival of animals inoculated with the solid MBM residue could be a high binding affinity of the prion protein to MBM and thus a sustained release from MBM in the brain. A phenomenon like this was described previously for prion binding to soil minerals [22]. In our study, when spiked into MBM, PrPsc was only detectable by Western Blot after boiling of sample in detergent. On the other hand we could show that control animals that received infected MBM not subjected to the reaction (MBM sc) developed disease in a time frame comparable to a standard scrapie brain homogenate.
Our results clearly show that Western Blot detection alone is insufficient to conclude on the absence of infectious prion, particularly when assessing a grossly heterogeneous sample such as MBM. This study illustrates that lack of prion detection in vitro does not necessarily exclude infectivity as determined by bioassay.
Furthermore the residual scrapie infectivity detected in the solid MBM residue probably limits the use of ruminant MBM as a feed additive to only non-ruminants, such as fish and fowl, as they are not susceptible to TSEs. Relatively minor variations of this reaction (e.g., more heat and/or alkali) may prove fully effective for complete destruction of infectivity in the solid MBM residue, but must be cost-effective if suspect MBM is to be considered as a ruminant feed additive.
http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0002969
Monday, June 23, 2008
Persistence of Pathogenic Prion Protein during Simulated Wastewater Treatment Processes
http://chronic-wasting-disease.blogspot.com/2008/06/persistence-of-pathogenic-prion-protein.html
http://organicconsumers.org/forum/index.php?showtopic=1621
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Friday, August 15, 2008 Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
http://chronic-wasting-disease.blogspot.com/2008/08/prion-infected-meat-and-bone-meal-is.html
http://organicconsumers.org/forum/index.php?showtopic=1935
Science 14 October 2005:Vol. 310. no. 5746, pp. 324 - 326DOI: 10.1126/science.1118829 Reports
Coincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion
Harald Seeger,1* Mathias Heikenwalder,1* Nicolas Zeller,1 Jan Kranich,1 Petra Schwarz,1 Ariana Gaspert,2 Burkhardt Seifert,3 Gino Miele,1 Adriano Aguzzi1
Prion infectivity is typically restricted to the central nervous and lymphatic systems of infected hosts, but chronic inflammation can expand the distribution of prions. We tested whether chronic inflammatory kidney disorders would trigger excretion of prion infectivity into urine. Urinary proteins from scrapie-infected mice with lymphocytic nephritis induced scrapie upon inoculation into noninfected indicator mice. Prionuria was found in presymptomatic scrapie-infected and in sick mice, whereas neither prionuria nor urinary PrPSc was detectable in prion-infected wild-type or PrPC-overexpressing mice, or in nephritic mice inoculated with noninfectious brain. Thus, urine may provide a vector for horizontal prion transmission, and inflammation of excretory organs may influence prion spread.
snip...
SEE FULL TEXT ;
http://chronic-wasting-disease.blogspot.com/2008/06/transmission-and-detection-of-prions-in.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
Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip...
full text ;
http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
P01.47
Quantifying the Species Barrier in Chronic Wasting Disease by a Novel in vitro Conversion Assay
Li, L1; Coulthart, MB2; Balachandran, A3; Chakrabartty, A4; Cashman, NR1 1University of British Columbia, Brain Research Centre, Canada; 2Public Health Agency of Canada, National Microbiology Laboratory, Canada; 3Animal Diseases Research Institute, Canada Food Inspection Agency, National Reference Laboratory for Scrapie and CWD, Canada; 4Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Canada
Background: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that can affect North American cervids (deer, elk, and moose). Although the risk of CWD crossing the species barrier and causing human disease is still unknown, however, definite bovine spongiform encephalopathy (BSE) transmission to humans as variant CJD (vCJD), it would seem prudent to limit the exposure of humans to CWD.
Aim: In view of the fact that BSE can be readily transmitted to non-bovid species, it is important to establish the species susceptibility range of CWD.
Methods: In vitro conversion system was performed by incubation of prions with normal brain homogenates as described before, and protease K (PK) resistant PrP was determined by immunoblotting with 6H4 monoclonal prion antibody.
Results: Our results demonstrate that PrPC from cervids (including moose) can be efficiently converted to a protease-resistant form by incubation with elk CWD prions, presumably due to sequence and structural similarities between these species. Interestingly, hamster shows a high conversion ratio by PrPCWD. Moreover, partial denaturation of substrate PrPC can apparently overcome the structural barriers between more distant species.
Conclusions: Our work correctly predicted the transmission of CWD to a wild moose. We find a species barrier for prion protein conversion between cervids and other species, however, this barrier might be overcome if the PrPC substrate has been partially denatured in a cellular environment. Such an environment might also promote CWD transmission to non-cervid species, *** including humans. Acid/GdnHCl-treated brain PrPC was a superior substrate for the in vitro conversion than PrPC treated at physiological pH. This has implications for the process by which the prion protein is converted in disease.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
SEWING THE SEEDS OF MAD COW (CWD) THROUGH ANIMAL PROTEIN $
[PDF]
BSE INQUIRY Statement of behalf of the Environment Agency ... File Format: PDF/Adobe Acrobat - View as HTML ... his Statement of March 1998 to the BSE Inquiry ... systems subject to regular or intermittent contamination by rapid movement of recharge water
BSE INQUIRY
Statement of behalf of the Environment Agency Concerning Thruxted Mill By Mr C. P. Young Principal Hydrogeologist, Soil Waste and Groundwater Group WRc plc; Medmenham, Bucks
http://www.bse.org.uk/files/ws/s490.pdf
http://www.americansportsman.com/messageboard/hunting/smallgamehunting/deer/viewpost.asp?mb=deerhunting&post=642
http://www.biggamehunt.net/forums/viewtopic.php?t=14549&start=0
http://www.michigan-sportsman.com/forum/showthread.php?t=23313
Monday, June 30, 2008 Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease
http://chronic-wasting-disease.blogspot.com/2008/06/risk-behaviors-in-rural-community-with.html
10 people killed by new CJD-like disease
Public release date: 9-Jul-2008 [ Print Article E-mail Article Close Window ]
Contact: Claire Bowles claire.bowles@rbi.co.uk 44-207-611-1210 New Scientist
10 people killed by new CJD-like disease A NEW form of fatal dementia has been discovered in 16 Americans, 10 of whom have already died of the condition. It resembles Creutzfeldt-Jakob disease - with patients gradually losing their ability to think, speak and move - but has features that make it distinct from known forms of CJD.
No one yet knows how the disease originates, or under what conditions it might spread. Nor is it clear how many people have the condition. "I believe the disease has been around for many years, unnoticed," says Pierluigi Gambetti, director of the US National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, Ohio. Cases may previously have been mistaken for other forms of dementia.
Since Gambetti's team wrote a paper describing an initial 11 cases referred to his centre between 2002 and 2006 (Annals of Neurology, vol 63, p 697), another five have come to light. "So it is possible that it could be just the tip of the iceberg," Gambetti says.
http://www.eurekalert.org/pub_releases/2008-07/ns-tpk070908.php
Thursday, July 10, 2008 A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html
Thursday, July 10, 2008 A New Prionopathy update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html
Sunday, August 10, 2008
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
I hate to inform them, but sporadic CJD has increased. sporadic CJD in the USA went from 28 cases _documented_ in 1997, to 170 cases of sporadic CJD _documented_ in 2007. i'm not a math wiz, but looks like an increase to me. ...
6 Includes 55 cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
2008 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.
http://www.cjdfoundation.org/fact.html
"the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine."
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1, Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1, Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4, Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4, Jean-Philippe Deslys1
1 Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps Florida, Jupiter, Florida, United States of America, 5 Genetics Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
Abstract Background Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.
Methodology/Principal Findings Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.
Conclusion/Significance Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.
Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017
Editor: Neil Mabbott, University of Edinburgh, United Kingdom
Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20, 2008
Copyright: © 2008 Comoy 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: This work has been supported by the Network of Excellence NeuroPrion.
Competing interests: CEA owns a patent covering the BSE diagnostic tests commercialized by the company Bio-Rad.
* E-mail: emmanuel.comoy@cea.fr
Tuesday, August 19, 2008
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate
http://bse-atypical.blogspot.com/2008/08/atypical-bse-base-transmitted-from.html
Owner and Corporation Plead Guilty to Defrauding Bovine Spongiform Encephalopathy (BSE) Surveillance Program
PLEASE SEE FULL TEXT ;
Monday, June 16, 2008 Mad Cows and Computer Models: The U.S. Response to BSE
http://bse-atypical.blogspot.com/
Sunday, March 16, 2008 MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE March 16, 2008
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
Sunday, August 10, 2008
Thursday, July 10, 2008 A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html
Thursday, July 10, 2008 A New Prionopathy update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html
MY COMMENTS, for whatever they are worth ;
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
Communicated by: Terry S. Singeltary Sr.
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
http://pro-med.blogspot.com/2007/11/proahedr-prion-disease-update-2007-07.html
http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963
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.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
http://www.thepathologicalprotein.com/
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT
http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
http://www.bmj.com/cgi/eletters/320/7226/8/b#6117
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406
Wednesday, August 20, 2008
Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?
August 20, 2008
http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html
with kindest regards,
I am sincerely,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Labels: CWD, GROUND WATER, LEACHATE, prions, SEWAGE TREATMENT
posted by Terry S. Singeltary Sr. at
10:33 AM
2 Comments
