flatfish
06-13-2008, 05:05 PM
The Journal of Infectious Diseases 2008;198:81–89 © 2008 by the Infectious
Diseases Society of America. All rights reserved.
0022-1899/2008/19801-0015$15.00 DOI: 10.1086/588193
MAJOR ARTICLE
Transmission and Detection of Prions in Feces
Jiri G. Safar,1,2 Pierre Lessard,1 Gültekin Tamgüney,1,2 Yevgeniy Freyman,1
Camille Deering,1 Frederic Letessier,1 Stephen J. DeArmond,1,3 and Stanley
B. Prusiner1,2,4
1Institute for Neurodegenerative Diseases, Departments of 2Neurology,
3Pathology, and 4Biochemistry and Biophysics, University of California, San
Francisco, San Francisco
In chronic wasting disease (CWD) in cervids and in scrapie in sheep, prions
appear to be transmitted horizontally. Oral exposure to prion-tainted blood,
urine, saliva, and feces has been suggested as the mode of transmission of
CWD and scrapie among herbivores susceptible to these prion diseases. To
explore the transmission of prions through feces, uninoculated Syrian
hamsters (SHas) were cohabitated with or exposed to the bedding of SHas
orally infected with Sc237 prions. Incubation times of 140 days and a rate
of prion infection of 80%-100% among exposed animals suggested transmission
by feces, probably via coprophagy. We measured the disease-causing isoform
of the prion protein (PrPSc) in feces by use of the conformation-dependent
immunoassay, and we titrated the irradiated feces intracerebrally in
transgenic mice that overexpressed SHa prion protein (SHaPrP). Fecal samples
collected from infected SHas in the first 7 days after oral challenge
harbored 60 ng/g PrPSc and prion titers of 106.6 ID50/g. Excretion of
infectious prions continued at lower levels throughout the asymptomatic
phase of the incubation period, most likely by the shedding of prions from
infected Peyer patches. Our findings suggest that horizontal transmission of
disease among herbivores may occur through the consumption of feces or
foodstuff tainted with prions from feces of CWD-infected cervids and
scrapie-infected sheep.
Received 9 October 2007; accepted 15 November 2007; electronically published
27 May 2008.
(See the editorial commentary by Bosque and Tyler, on pages 8-9.)
Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grants AG02132, AG010770,
NS22786, and NS14069); G. Harold and Leila Y. Mathers Foundation; Sherman
Fairchild Foundation.
Reprints or correspondence: Dr. Stanley B. Prusiner, 513 Parnassus Ave.,
HSE-774, San Francisco, CA 94143-0518 (stanley@ind.ucsf.edu).
http://www.journals.uchicago.edu/doi/abs/10.1086/588193
The Journal of Infectious Diseases 2008;198:8–9 © 2008 by the Infectious
Diseases Society of America. All rights reserved.
0022-1899/2008/19801-0004$15.00 DOI: 10.1086/588194 EDITORIAL COMMENTARY
Prions' Travels-Feces and Transmission of Prion Diseases P. J. Bosque1,4 and
K. L. Tyler1,2,3,5
Departments of 1Neurology, 2Medicine, and 3Microbiology, University of
Colorado Health Sciences Center, 4Department of Medicine (Neurology), Denver
Health Medical Center, and 5Neurology Service, Denver Veterans Affairs
Medical Center, Denver, Colorado
Received 9 January 2008; accepted 9 January 2008; electronically published
27 May 2008.
(See the article by Safar et al., on pages 81-9.)
Potential conflicts of interest: The authors report that they have no
conflicts of interest regarding prions and prion disease.
Reprints or correspondence: Dr. K. L. Tyler, Neurology B-182, University of
Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262
(ken.tyler@uchsc.edu).
http://www.journals.uchicago.edu/doi/abs/10.1086/588194
PLEASE SEE 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.<<<
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
P04.61 Survival of PrPSc Submitted by flounder on Mon, 2007-10-01 14:27.
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
[5,7*9]. 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
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...
How do prions enter the urine? Upon extrarenalreplication, blood-borne
prions may beexcreted by a defective filtration apparatus.Alternatively,
prions may be produced locallyand excreted during leukocyturia.
Althoughprionemia occurs in many paradigms ofperipheral prion pathogenesis
(15, 16), thelatter hypothesis appears more likely, becauseprionuria was
invariably associated with localprion replication within kidneys.Urine from
one CJD patient was reported toelicit prion disease in mice (17, 18), but
not inprimates (19). Perhaps unrecognized nephriticconditions may underlie
these discrepantobservations. Inflammation-associated prionuriamay also
contribute to horizontal transmissionamong sheep, deer, and elk, whose high
efficiencyof lateral transmission is not understood.References and
Notes...snip...end
1 Institute of Neuropathology, University Hospital of Zürich,
Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.2 Institute of Clinical
Pathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091
Zürich, Switzerland.3 Institute of Biostatistics, University of Zürich,
Sumatrastrasse 30, CH-8006 Zürich, Switzerland. * These authors contributed
equally to this work. To whom correspondence should be addressed. E-mail:
adriano@pathol.unizh.ch
http://www.sciencemag.org/cgi/content/abstract/310/5746/324
The ability of the CWD agent to persist in contaminated environments for >2
years may further increase the probability of transmission and protract
epidemic dynamics (8). Because infectivity in contaminated paddocks could
not be measured, neither the initial levels nor degradation rate of the CWD
agent in the environment was estimable. However, the observed persistence of
the CWD agent was comparable to that of the scrapie agent, which persisted
in paddocks for ˜1 to 3 years after removal of naturally infected sheep (7).
Similarities between the CWD and scrapie agents suggest that environmental
persistence may be a common trait of prions. Whether persistence of the BSE
prion in contaminated feed production facilities or in environments where
cattle reside contributed to BSE cases in the United Kingdom after feed bans
were enacted (27) remains uncertain but merits further consideration.
Indirect transmission and environmental persistence of prions will
complicate efforts to control CWD and perhaps other animal prion diseases.
Historically, control strategies for animal prion diseases have focused on
infected live animals as the primary source of infection. Although live deer
and elk represent the most plausible mechanism for geographic spread of CWD,
our data show that environmental sources could contribute to maintaining and
prolonging local epidemics, even when all infected animals are eliminated.
Moreover, the efficacy of various culling strategies as control measures
depends in part on the rates at which the CWD agent is added to and lost
from the environment. Consequently, these dynamics and their implications
for disease management need to be more completely understood.
Acknowledgments
snip...
http://www.cdc.gov/ncidod/EID/vol10no6/04-0010.htm
-------- Original Message -------- Subject: DOCKET-- 03D-0186 -- FDA Issues
Draft Guidance on Use of Material From Deer and Elk in Animal Feed;
Availability Date: Fri, 16 May 2003 11:47:37 -0500 From: "Terry S.
Singeltary Sr." <flounder@wt.net> To: fdadockets@oc.fda.gov
Greetings FDA,
http://www.pabucks.com/deer-hunting-forum/viewtopic.php?t=1078&start=15
Thursday, April 03, 2008 A prion disease of cervids: Chronic wasting disease
2008
1: Vet Res. 2008 Apr 3;39(4):41
http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
Saturday, May 17, 2008
Are cheetahs on the run from prion-like amyloidosis?
http://betaamyloidcjd.blogspot.com/2008/05/are-cheetahs-on-run-from-prion-like.html
Chronic Wasting Disease CWD
http://chronic-wasting-disease.blogspot.com/
TSS
Diseases Society of America. All rights reserved.
0022-1899/2008/19801-0015$15.00 DOI: 10.1086/588193
MAJOR ARTICLE
Transmission and Detection of Prions in Feces
Jiri G. Safar,1,2 Pierre Lessard,1 Gültekin Tamgüney,1,2 Yevgeniy Freyman,1
Camille Deering,1 Frederic Letessier,1 Stephen J. DeArmond,1,3 and Stanley
B. Prusiner1,2,4
1Institute for Neurodegenerative Diseases, Departments of 2Neurology,
3Pathology, and 4Biochemistry and Biophysics, University of California, San
Francisco, San Francisco
In chronic wasting disease (CWD) in cervids and in scrapie in sheep, prions
appear to be transmitted horizontally. Oral exposure to prion-tainted blood,
urine, saliva, and feces has been suggested as the mode of transmission of
CWD and scrapie among herbivores susceptible to these prion diseases. To
explore the transmission of prions through feces, uninoculated Syrian
hamsters (SHas) were cohabitated with or exposed to the bedding of SHas
orally infected with Sc237 prions. Incubation times of 140 days and a rate
of prion infection of 80%-100% among exposed animals suggested transmission
by feces, probably via coprophagy. We measured the disease-causing isoform
of the prion protein (PrPSc) in feces by use of the conformation-dependent
immunoassay, and we titrated the irradiated feces intracerebrally in
transgenic mice that overexpressed SHa prion protein (SHaPrP). Fecal samples
collected from infected SHas in the first 7 days after oral challenge
harbored 60 ng/g PrPSc and prion titers of 106.6 ID50/g. Excretion of
infectious prions continued at lower levels throughout the asymptomatic
phase of the incubation period, most likely by the shedding of prions from
infected Peyer patches. Our findings suggest that horizontal transmission of
disease among herbivores may occur through the consumption of feces or
foodstuff tainted with prions from feces of CWD-infected cervids and
scrapie-infected sheep.
Received 9 October 2007; accepted 15 November 2007; electronically published
27 May 2008.
(See the editorial commentary by Bosque and Tyler, on pages 8-9.)
Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grants AG02132, AG010770,
NS22786, and NS14069); G. Harold and Leila Y. Mathers Foundation; Sherman
Fairchild Foundation.
Reprints or correspondence: Dr. Stanley B. Prusiner, 513 Parnassus Ave.,
HSE-774, San Francisco, CA 94143-0518 (stanley@ind.ucsf.edu).
http://www.journals.uchicago.edu/doi/abs/10.1086/588193
The Journal of Infectious Diseases 2008;198:8–9 © 2008 by the Infectious
Diseases Society of America. All rights reserved.
0022-1899/2008/19801-0004$15.00 DOI: 10.1086/588194 EDITORIAL COMMENTARY
Prions' Travels-Feces and Transmission of Prion Diseases P. J. Bosque1,4 and
K. L. Tyler1,2,3,5
Departments of 1Neurology, 2Medicine, and 3Microbiology, University of
Colorado Health Sciences Center, 4Department of Medicine (Neurology), Denver
Health Medical Center, and 5Neurology Service, Denver Veterans Affairs
Medical Center, Denver, Colorado
Received 9 January 2008; accepted 9 January 2008; electronically published
27 May 2008.
(See the article by Safar et al., on pages 81-9.)
Potential conflicts of interest: The authors report that they have no
conflicts of interest regarding prions and prion disease.
Reprints or correspondence: Dr. K. L. Tyler, Neurology B-182, University of
Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262
(ken.tyler@uchsc.edu).
http://www.journals.uchicago.edu/doi/abs/10.1086/588194
PLEASE SEE 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.<<<
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
P04.61 Survival of PrPSc Submitted by flounder on Mon, 2007-10-01 14:27.
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
[5,7*9]. 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
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...
How do prions enter the urine? Upon extrarenalreplication, blood-borne
prions may beexcreted by a defective filtration apparatus.Alternatively,
prions may be produced locallyand excreted during leukocyturia.
Althoughprionemia occurs in many paradigms ofperipheral prion pathogenesis
(15, 16), thelatter hypothesis appears more likely, becauseprionuria was
invariably associated with localprion replication within kidneys.Urine from
one CJD patient was reported toelicit prion disease in mice (17, 18), but
not inprimates (19). Perhaps unrecognized nephriticconditions may underlie
these discrepantobservations. Inflammation-associated prionuriamay also
contribute to horizontal transmissionamong sheep, deer, and elk, whose high
efficiencyof lateral transmission is not understood.References and
Notes...snip...end
1 Institute of Neuropathology, University Hospital of Zürich,
Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.2 Institute of Clinical
Pathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091
Zürich, Switzerland.3 Institute of Biostatistics, University of Zürich,
Sumatrastrasse 30, CH-8006 Zürich, Switzerland. * These authors contributed
equally to this work. To whom correspondence should be addressed. E-mail:
adriano@pathol.unizh.ch
http://www.sciencemag.org/cgi/content/abstract/310/5746/324
The ability of the CWD agent to persist in contaminated environments for >2
years may further increase the probability of transmission and protract
epidemic dynamics (8). Because infectivity in contaminated paddocks could
not be measured, neither the initial levels nor degradation rate of the CWD
agent in the environment was estimable. However, the observed persistence of
the CWD agent was comparable to that of the scrapie agent, which persisted
in paddocks for ˜1 to 3 years after removal of naturally infected sheep (7).
Similarities between the CWD and scrapie agents suggest that environmental
persistence may be a common trait of prions. Whether persistence of the BSE
prion in contaminated feed production facilities or in environments where
cattle reside contributed to BSE cases in the United Kingdom after feed bans
were enacted (27) remains uncertain but merits further consideration.
Indirect transmission and environmental persistence of prions will
complicate efforts to control CWD and perhaps other animal prion diseases.
Historically, control strategies for animal prion diseases have focused on
infected live animals as the primary source of infection. Although live deer
and elk represent the most plausible mechanism for geographic spread of CWD,
our data show that environmental sources could contribute to maintaining and
prolonging local epidemics, even when all infected animals are eliminated.
Moreover, the efficacy of various culling strategies as control measures
depends in part on the rates at which the CWD agent is added to and lost
from the environment. Consequently, these dynamics and their implications
for disease management need to be more completely understood.
Acknowledgments
snip...
http://www.cdc.gov/ncidod/EID/vol10no6/04-0010.htm
-------- Original Message -------- Subject: DOCKET-- 03D-0186 -- FDA Issues
Draft Guidance on Use of Material From Deer and Elk in Animal Feed;
Availability Date: Fri, 16 May 2003 11:47:37 -0500 From: "Terry S.
Singeltary Sr." <flounder@wt.net> To: fdadockets@oc.fda.gov
Greetings FDA,
http://www.pabucks.com/deer-hunting-forum/viewtopic.php?t=1078&start=15
Thursday, April 03, 2008 A prion disease of cervids: Chronic wasting disease
2008
1: Vet Res. 2008 Apr 3;39(4):41
http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
Saturday, May 17, 2008
Are cheetahs on the run from prion-like amyloidosis?
http://betaamyloidcjd.blogspot.com/2008/05/are-cheetahs-on-run-from-prion-like.html
Chronic Wasting Disease CWD
http://chronic-wasting-disease.blogspot.com/
TSS