Wednesday, June 11, 2008

Transmission and Detection of Prions in Feces

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


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 (

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 (


>>>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.<<<

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.

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:

Science 14 October 2005:Vol. 310. no. 5746, pp. 324 - 326DOI: 10.1126/science.1118829

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.


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...


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:

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.



-------- 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."

Greetings FDA,

Thursday, April 03, 2008 A prion disease of cervids: Chronic wasting disease 2008

1: Vet Res. 2008 Apr 3;39(4):41

Saturday, May 17, 2008

Are cheetahs on the run from prion-like amyloidosis?


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