Monday, September 17, 2012

Rapid Transepithelial Transport of Prions Following Inhalation

Rapid Transepithelial Transport of Prions Following Inhalation



Anthony E. Kincaid1,2,3↴, Kathryn F. Hudson1, Matthew W. Richey1 and Jason C. Bartz3 + Author Affiliations



1Department of Physical Therapy 2Department of Biomedical Sciencesy 3Department of Medical Microbiology and Immunolog, Creighton University, Omaha, Nebraska 68178



ABSTRACT



Prion infection and pathogenesis is dependent upon 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 15-180 minutes following inoculation, but not in the adjacent nasal 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 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 Corresponding author E-mail: akincaid@creighton.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







Saturday, September 01, 2012


Resistance of Soil-Bound Prions to Rumen Digestion







Published Date: 2011-02-11 16:00:09


Subject: PRO/AH/EDR> Prion disease update 2011 (02)


Archive Number: 20110211.0473


PRION DISEASE UPDATE 2011 (02)




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[4]




Airborne transmission (mice) Date: 14 Jan 2011 Source: Science Daily [edited] <http://www.sciencedaily.com/releases/2011/01/110113213056.htm>




New findings suggest airborne pathogens can induce mad cow disease




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Airborne prions are also infectious and can induce mad cow disease or Creutzfeldt-Jakob disorder, new findings suggest. This is the surprising conclusion of researchers at the University of Zurich, the University Hospital Zurich, and the University of Tuebingen. They recommend precautionary measures for scientific labs, slaughterhouses, and animal feed plants. The prion is the infectious agent that caused the epidemic of mad cow disease, also termed bovine spongiform encephalopathy (BSE), and claimed the life of over 280 000 cows in the past decades. Transmission of BSE to humans, such as, by ingesting food derived from BSE-infected cows, causes variant Creutzfeldt-Jakob disease, which is characterized by a progressive and invariably lethal break-down of brain cells.




It is known that prions can be transmitted through contaminated surgical instruments and, more rarely, through blood transfusions. The consumption of food products made from BSE-infected cows can also induce the disease that is responsible for the death of almost 300 people. However, prions are not generally considered to be airborne -- in contrast to many viruses including influenza and chicken pox.




Prof Adriano Aguzzi's team of scientists at the universities of Zurich and Tuebingen and the University Hospital Zurich have now challenged the notion that airborne prions are innocuous. In a study, mice were housed in special inhalation chambers and exposed to aerosols containing prions. Unexpectedly, it was found that inhalation of prion-tainted aerosols induced disease with frightening efficiency. Just a single minute of exposure to the aerosols was sufficient to infect 100 per cent of the mice, according to Prof Aguzzi who published the findings in the Open-Access-Journal "PLoS Pathogens." The longer exposure lasted, the shorter the time of incubation in the recipient mice and the sooner clinical signs of a prion disease occurred. Prof Aguzzi says the findings are entirely unexpected and appear to contradict the widely held view that prions are not airborne. The prions appear to transfer from the airways and colonize the brain directly because immune system defects -- known to prevent the passage of prions from the digestive tract to the brain -- did not prevent infection.




Precautionary measures against prion infections in scientific laboratories, slaughterhouses, and animal feed plants do not typically include stringent protection against aerosols. The new findings suggest that it may be advisable to reconsider regulations in light of a possible airborne transmission of prions. Prof Aguzzi recommends precautionary measures to minimize the risk of a prion infection in humans and animals. He does, however, emphasize that the findings stem from the production of aerosols in laboratory conditions and that Creutzfeldt-Jakob patients do not exhale prions.




Reference --------- Haybaeck J, Heikenwalder M, Klevenz B, et al: Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice. PLoS Pathog. 2011; 7(1): e1001257. DOI:10.1371/journal.ppat.1001257;








Abstract:




Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild type mice, as well as tga20 transgenic mice overexpressing PrPC, efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrPC selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells, or complement components. Brains of diseased mice contained PrPSc and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.




Author summary: Prions, which are the cause of fatal neurodegenerative disorders termed transmissible spongiform encephalopathies (TSEs), can be experimentally or naturally transmitted via prion-contaminated food, blood, milk, saliva, feces, and urine. Here we demonstrate that prions can be transmitted through aerosols in mice. This also occurs in the absence of immune cells as demonstrated by experiments with mice lacking B-, T-, follicular dendritic cells (FDCs), lymphotoxin signaling, or with complement-deficient mice. Therefore, a functionally intact immune system is not strictly needed for aerogenic prion infection. These results suggest that current biosafety guidelines applied in diagnostic and scientific laboratories ought to include prion aerosols as a potential vector for prion infection.




-- communicated by: Terry S Singeltary Sr flounder9@verizon.net




[Despite the perceived risk revealed by these experiments with laboratory mice there has been no evidence to date linking prion disease to employees in slaughterhouses, animal feed plants, or research laboratories. - Mod.CP]




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snip...end















Eurosurveillance, Volume 17, Issue 15, 12 April 2012




Research articles




Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to 2010




E Alcalde-Cabero1, J Almazán-Isla1, J P Brandel2, M Breithaupt3, J Catarino4, S Collins5, J Haybäck6, R Höftberger7, E Kahana8, G G Kovacs7,9, A Ladogana10, E Mitrova11, A Molesworth12, Y Nakamura13, M Pocchiari10, M Popovic14, M Ruiz-Tovar1, A L Taratuto15, C van Duijn16, M Yamada17, R G Will12, I Zerr3, J de Pedro Cuesta ()1




Date of submission: 04 November 2011




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In 2009, a pathologist with sporadic Creutzfeldt–Jakob Disease (sCJD) was reported to the Spanish registry. This case prompted a request for information on health-related occupation in sCJD cases from countries participating in the European Creutzfeldt Jakob Disease Surveillance network (EuroCJD). Responses from registries in 21 countries revealed that of 8,321 registered cases, 65 physicians or dentists, two of whom were pathologists, and another 137 healthcare workers had been identified with sCJD. Five countries reported 15 physicians and 68 other health professionals among 2,968 controls or non-cases, suggesting no relative excess of sCJD among healthcare professionals. A literature review revealed: (i) 12 case or small case-series reports of 66 health professionals with sCJD, and (ii) five analytical studies on health-related occupation and sCJD, where statistically significant findings were solely observed for persons working at physicians' offices (odds ratio: 4.6 (95 CI: 1.2–17.6)). We conclude that a wide spectrum of medical specialities and health professions are represented in sCJD cases and that the data analysed do not support any overall increased occupational risk for health professionals. Nevertheless, there may be a specific risk in some professions associated with direct contact with high human-infectivity tissue.




snip...




15. Terry S. Singeltary Sr. Doctor Antonio Ruiz Villaespesa, pathologist and CJD researcher deceased because of Creutzfeldt-Jakob Disease SPAIN. 21 Apr 2009. [Accessed 11 Apr 2012]. In: Monitoring the occurrence of emerging forms of CJD [blog]. Available from: http://cjdusa.blogspot.com.es/2009/04/doctor-antonio-ruiz-villaespesa.html




see full text ;



















Saturday, February 12, 2011



Another Pathologists dies from CJD, another potential occupational death ?



another happenstance of bad luck, a spontaneous event from nothing, or friendly fire ???











Friday, August 10, 2012


Incidents of Potential iatrogenic Creutzfeldt-Jakob disease (CJD) biannual update (July 2012)







Friday, August 10, 2012


Incidents of Potential iatrogenic Creutzfeldt-Jakob disease (CJD) biannual update (July 2012)







Friday, August 24, 2012


Iatrogenic prion diseases in humans: an update







please note, all Iatrogenic Creutzfedlt Jakob Disease CJD is, is sporadic CJD, until a route and source is confirmed. ...TSS





Sunday, February 12, 2012



National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas



snip...




CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER




Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas




Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas. She left 6 Kids and a Husband. The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community

who want's information about this terrible disease.-



Physician Discharge Summary, Parkland Hospital, Dallas Texas



Admit Date: 12/29/2009 Discharge Date: 1/20/2010 Attending Provider: Greenberg, Benjamin Morris; General Neurology Team: General Neurology Team



snip...



The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically. Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.



snip...






>>> Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. <<<




SEE MORE HERE ;




CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER









Thursday, August 16, 2012


Blood products, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease ( vCJD) USA JUNE, JULY, AUGUST 2012







Thursday, September 06, 2012


HANSARD, vCJD, blood, FFP, 5 Sep 2012 : Column 353W SaBTO








Saturday, May 26, 2012


Are USDA assurances on mad cow case 'gross oversimplification'?


SNIP...


What irks many scientists is the USDA’s April 25 statement that the rare disease is “not generally associated with an animal consuming infected feed.”


The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown, one of the world’s experts on this type of disease who retired recently from the National Institutes of Health. "(The agency) has no foundation on which to base that statement.”


“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an official with the USDA during the Clinton Administration now at Mississippi State.


In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the origins of atypical cases of BSE,” she said


The argument about feed is critical because if feed is the cause, not a spontaneous mutation, the California cow could be part of a larger outbreak.


SNIP...







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Saturday, August 4, 2012


Final Feed Investigation Summary - California BSE Case - July 2012






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SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE INVESTIGATION JULY 2012


Summary Report BSE 2012


Executive Summary







Saturday, August 4, 2012


Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation







in the url that follows, I have posted




SRM breaches first, as late as 2011.


then


MAD COW FEED BAN BREACHES AND TONNAGES OF MAD COW FEED IN COMMERCE up until 2007, when they ceased posting them.


then,


MAD COW SURVEILLANCE BREACHES.


Friday, May 18, 2012


Update from APHIS Regarding a Detection of Bovine Spongiform Encephalopathy (BSE) in the United States Friday May 18, 2012







Monday, August 6, 2012


TAFS BSE in USA August 6, 2012


BSE in USA







Sunday, August 26, 2012


Detection of PrPSc in peripheral tissues of clinically affected cattle after oral challenge with BSE


























Monday, July 23, 2012



The National Prion Disease Pathology Surveillance Center July 2012








Monday, August 13, 2012



Summary results of the second national survey of abnormal prion prevalence in archived appendix specimens August 2012







Monday, August 20, 2012



CASE REPORTS CREUTZFELDT-JAKOB DISEASE: AN UNDER-RECOGNIZED CAUSE OF DEMENTIA








TSS

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