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Rapid Transepithelial Transport of Prions following Inhalation

Posted Nov 26 2012 11:28am
Rapid Transepithelial Transport of Prions following Inhalation



Anthony E. Kincaida,b,c, Kathryn F. Hudsona,*, Matthew W. Richeya and Jason C. Bartzc



+ Author Affiliations



aDepartment of Physical Therapy



bDepartment of Biomedical Sciences



cDepartment of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska, USA



ABSTRACT



Prion infection and pathogenesis are dependent on the agent crossing an epithelial barrier to gain access to the recipient nervous system. Several routes of infection have been identified, but the mechanism(s) and timing of in vivo prion transport across an epithelium have not been determined. The hamster model of nasal cavity infection was used to determine the temporal and spatial parameters of prion-infected brain homogenate uptake following inhalation and to test the hypothesis that prions cross the nasal mucosa via M cells. A small drop of infected or uninfected brain homogenate was placed below each nostril, where it was immediately inhaled into the nasal cavity. Regularly spaced tissue sections through the entire extent of the nasal cavity were processed immunohistochemically to identify brain homogenate and the disease-associated isoform of the prion protein (PrPd). Infected or uninfected brain homogenate was identified adhering to M cells, passing between cells of the nasal mucosa, and within lymphatic vessels of the nasal cavity at all time points examined. PrPd was identified within a limited number of M cells 15 to 180 min following inoculation, but not in the adjacent nasal mucosa-associated lymphoid tissue (NALT). While these results support M cell transport of prions, larger amounts of infected brain homogenate were transported paracellularly across the respiratory, olfactory, and follicle-associated epithelia of the nasal cavity. These results indicate that prions can immediately cross the nasal mucosa via multiple routes and quickly enter lymphatics, where they can spread systemically via lymph draining the nasal cavity.



FOOTNOTES Received 24 July 2012. Accepted 5 September 2012. Address correspondence to Anthony E. Kincaid, akincaid@creighton.edu .



↵* Present address: Kathryn F. Hudson, Department of Pharmacology, Emory University, Atlanta, Georgia, USA.



Published ahead of print 12 September 2012



Copyright © 2012, American Society for Microbiology. All Rights Reserved.









Monday, November 26, 2012


Aerosol Transmission of Chronic Wasting Disease in White-tailed Deer


Nathaniel D. Denkers1, Jeanette Hayes-Klug1, Kelly R. Anderson1, Davis M. Seelig1, Nicholas J. Haley1, Sallie J. Dahmes2, David A. Osborn3, Karl V. Miller3, Robert J. Warren3, Candace K. Mathiason1 and Edward A. Hoover1,* + Author Affiliations 1 Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523-1619 2WASCO Inc., Monroe, Georgia 3Warnell School of Forestry and Natural Resources, University of Georgia, Athens, Georgia


ABSTRACT


While the facile transmission of chronic wasting disease (CWD) remains incompletely elucidated, studies in rodents suggest exposure of the respiratory mucosa may be an efficient pathway. The present study was designed to address this question in the native cervid host. Here we demonstrate aerosol transmission of CWD to deer with a prion dose >20-fold lower than that used in previous oral inoculations. Inhalation of prions may facilitate transmission of CWD and perhaps other prions infections.


FOOTNOTES ↵*Correspondence: Edward A. Hoover, Department of Microbiology, Immunology, and Pathology, Campus Delivery 1619, Colorado State University, Fort Collins, CO 80523-1619, Phone: 970-491-7587, Fax: 970-491-0523, edward.hoover@colostate.edu Copyright © 2012, American Society for Microbiology. All Rights Reserved.









Thursday, May 31, 2012


CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission, Scrapie, cats, species barrier, burial, and more






Thursday, December 29, 2011



Aerosols An underestimated vehicle for transmission of prion diseases?






please see more on Aerosols and TSE prion disease here ;







Elk and Deer Use of Mineral Licks: Implications for Disease Transmission Kurt C. VerCauteren1*, Michael J. Lavelle1, Gregory E. Phillips1, Justin W. Fischer1, and Randal S. Stahl1 1United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, National Wildlife Research Center, 4101 LaPorte Avenue, Fort Collins, CO 80521-2154, USA *Cooresponding author e-mail: kurt.c.vercauteren@aphis.usda.gov North American cervids require and actively seek out minerals to satisfy physiological requirements. Minerals required by free-ranging cervids exist within natural and artificial mineral licks that commonly serve as focal sites for cervids. Ingestion of soils contaminated with the agent that causes chronic wasting disease (CWD) may result in risk of contracting CWD. Our objective was to evaluate the extent and nature of use of mineral licks by CWD-susceptible cervid species. We used animal-activated cameras to monitor use of 18 mineral licks between 1 June and 16 October 2006 in Rocky Mountain National Park, north-central Colorado. We also assessed mineral concentrations at mineral licks to evaluate correlations between visitation rates and site-specific characteristics. We collected > 400,000 images of which 991 included elk, 293 included deer, and 6 included moose. We documented elk and deer participating in a variety of potentially risky behaviors (e.g., ingesting soil, ingesting water, defecating, urinating) while at mineral licks. Results from the mineral analyses combined with camera data revealed that visitation was highest at sodium-rich mineral licks. Mineral licks may play a role in disease transmission by acting as sites of increased interaction as well as reservoirs for deposition, accumulation, and ingestion of disease agents.










In conclusion, aerosols can infect mice with a surprisingly high efficiency. Just how important a role is played by this newly recognized pathway of spread in natural transmission is, as of now, unclear and in need of further studies. Although it was not identified as a route of infection in epidemiological studies thus far, the worryingly high attack rate suggests that we would be well-advised to carefully avoid the inhalation of aerosols from prion-containing materials. Key words: prion, prion transmission, scrapie, chronic wasting diseases, CWD, Creutzfeldt-Jacob-disease, CJD, TSE, aerosol, pathogens, allergens Submitted: 05/19/11 Accepted: 06/09/11 DOI: 10.4161/pri.5.3.16851 *Correspondence to: Lothar Stitz or Adriano Aguzzi; Email: lothar.stitz@fli.bund.de or adriano.aguzzi@usz.ch



PLEASE SEE FULL TEXT, AND AGAIN, many thanks to PLOS for open access !!!







Monday, September 17, 2012


Rapid Transepithelial Transport of Prions Following Inhalation







CWD has been identified in free-ranging cervids in 15 US states and 2 Canadian provinces and in ≈ 100 captive herds in 15 states and provinces and in South Korea (Figure 1, panel B). SNIP... Long-term effects of CWD on cervid populations and ecosystems remain unclear as the disease continues to spread and prevalence increases. In captive herds, CWD might persist at high levels and lead to complete herd destruction in the absence of human culling. Epidemiologic modeling suggests the disease could have severe effects on free-ranging deer populations, depending on hunting policies and environmental persistence (8,9). CWD has been associated with large decreases in free-ranging mule deer populations in an area of high CWD prevalence (Boulder, Colorado, USA) (5).



PLEASE STUDY THIS MAP, COMPARE FARMED CWD TO WILD CWD...TSS








Saturday, February 18, 2012


Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting Disease


CDC Volume 18, Number 3—March 2012


CWD has been identified in free-ranging cervids in 15 US states and 2 Canadian provinces and in ≈100 captive herds in 15 states and provinces and in South Korea (Figure 1, panel B).








Subject: CWD TSE PRION, AND SCRAPIE ?



*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.








White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection



Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS



Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. Previous experiments demonstrated that white-tailed deer are susceptible to sheep-derived scrapie by intracranial inoculation. The purpose of this study was to determine susceptibility of white-tailed deer to scrapie after a natural route of exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal (1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with scrapie. Non-inoculated deer were maintained as negative controls. All deer were observed daily for clinical signs. Deer were euthanized and necropsied when neurologic disease was evident, and tissues were examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and western blot (WB). One animal was euthanized 15 months post-inoculation (MPI) due to an injury. At that time, examination of obex and lymphoid tissues by IHC was positive, but WB of obex and colliculus were negative. Remaining deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by potential natural routes of inoculation. In-depth analysis of tissues will be done to determine similarities between scrapie in deer after intracranial and oral/intranasal inoculation and chronic wasting disease resulting from similar routes of inoculation.



see full text ;








PO-039:


A comparison of scrapie and chronic wasting disease in white-tailed deer


Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA






White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation snip... It is unlikely that CWD will be eradicated from free-ranging cervids, and the disease is likely to continue to spread geographically [10]. However, the potential that white-tailed deer may be susceptible to sheep scrapie by a natural route presents an additional confounding factor to halting the spread of CWD. This leads to the additional speculations that 1) infected deer could serve as a reservoir to infect sheep with scrapie offering challenges to scrapie eradication efforts and 2) CWD spread need not remain geographically confined to current endemic areas, but could occur anywhere that sheep with scrapie and susceptible cervids cohabitate. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation with a high attack rate and that the disease that results has similarities to CWD. These experiments will be repeated with a more natural route of inoculation to determine the likelihood of the potential transmission of sheep scrapie to white-tailed deer. If scrapie were to occur in white-tailed deer, results of this study indicate that it would be detected as a TSE, but may be difficult to differentiate from CWD without in-depth biochemical analysis.











Wednesday, February 16, 2011


IN CONFIDENCE SCRAPIE TRANSMISSION TO CHIMPANZEES IN CONFIDENCE






THE states are going to have to regulate how many farms that are allowed, or every state in the USA will wind up being just one big private fenced in game farm.


kind of like they did with the shrimping industry in the bays, when there got to be too many shrimp boats, you stop issuing permits, and then lower the exist number of permits, by not renewing them, due to reduced permits issued.


how many states have $465,000., and can quarantine and purchase there from, each cwd said infected farm, but how many states can afford this for all the cwd infected cervid game ranch type farms ??


11,000 game farms X $465,000., do all these game farms have insurance to pay for this risk of infected the wild cervid herds, in each state ??




Tuesday, December 20, 2011


CHRONIC WASTING DISEASE CWD WISCONSIN Almond Deer (Buckhorn Flats) Farm Update DECEMBER 2011



The CWD infection rate was nearly 80%, the highest ever in a North American captive herd.


RECOMMENDATION: That the Board approve the purchase of 80 acres of land for $465,000 for the Statewide Wildlife Habitat Program in Portage County and approve the restrictions on public use of the site.


Form 1100-001


(R 2/11)


NATURAL RESOURCES BOARD AGENDA ITEM


SUBJECT: Information Item: Almond Deer Farm Update


FOR: DECEMBER 2011 BOARD MEETING


TUESDAY


TO BE PRESENTED BY TITLE: Tami Ryan, Wildlife Health Section Chief



SUMMARY:












Wednesday, November 14, 2012


PENNSYLVANIA 2012 THE GREAT ESCAPE OF CWD INVESTIGATION MOVES INTO LOUISIANA and INDIANA






Monday, November 26, 2012


Aerosol Transmission of Chronic Wasting Disease in White-tailed Deer







TSS
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