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)
******************************
[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
------------------------------------------------------------------
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]
******
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
--------------------------------------------------------------------------------
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...
==============================================
Saturday, August 4, 2012
Final Feed Investigation Summary - California BSE Case - July 2012
=============================================
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
