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Soil particles found to boost prion’s capacity to infect

flounder

Well-known member
Subject: Oral Transmissibility of Prion Disease Is Enhanced by Binding to
Soil Particles "We observed an almost 700-fold difference"
Date: July 7, 2007 at 10:09 am PST

Soil particles found to boost prion’s capacity to infect
July 6, 2007

by Terry Devitt

The rogue proteins that cause chronic wasting disease (CWD) exhibit a
dramatic increase in their infectious nature when bound to common soil
particles, according to a new study.

Writing in the journal Public Library of Science (PLoS) Pathogens, a group
led by University of Wisconsin-Madison prion expert Judd Aiken reports that
prions, the protein agents of a family of fatal brain disorders, bind
tightly to a common soil mineral and significantly increase the oral
transmissibility of the agent.

The finding is important because it may help explain how chronic wasting
disease and scrapie persist in the environment and spread efficiently in
animal populations.

"We found a huge difference between infectious agent alone and infectious
agent bound to these soil particles," says Aiken, the senior author of the
new study and a professor of comparative biosciences in the UW-Madison
School of Veterinary Medicine. "We observed an almost 700-fold difference"
in the rate of infection.

Prions are an abnormal form of a protein produced normally by the body.
Tough as nails, they can persist in the environment for long periods of time
and retain their infectious capabilities. It is believed that prions may
persist in the soil around the carcasses of dead animals and other locations
where infected animals shed the protein in body fluids.

"These disease agents can stay out there for years and stay infectious,"
Aiken explains.

And herbivores such as deer and sheep, which are susceptible to prion
infection, tend to consume a fair amount of dirt daily as they graze and
forage. They are also known to consume soil as a source of minerals. Mineral
licks are frequented by many animals, raising the prospect that the agents
may become concentrated in the soil.

Relatively little is known about the routes of prion transmission in
animals, but the new Wisconsin study may help to resolve one puzzle: Oral
transmission of prions, says Aiken, tends not to be very efficient.

"This is a dichotomy in our field, and maybe (the new research) is part of
the answer."

In their studies, the Wisconsin researchers looked at the ability of prions
to bind to different types of common soil minerals. One, known as
montmorillonite, is a type of clay and prions seem to have a special
affinity for latching onto the microscopic particles.

"We expected the binding of the montmorillonite to be the highest among the
minerals we examined. However, we were surprised by the strength of the
binding," notes Joel Pedersen, a UW-Madison professor of soil science who
helped direct the new study.

The Wisconsin team also looked at the ability of the prion to bind to two
other common soil minerals: quartz and kaolinite, another common clay
mineral.

"We found binding of the abnormal protein to all three," says Aiken, "but
the binding to montmorillonite was very avid, very tight. We found it very
difficult to remove the prions from the montmorillonite."

Feeding the prion-mineral mix to hamsters, a common animal model for prion
disease, Aiken's team expected to see a lower rate of infection than animals
dosed with pure agent. Surprisingly, prions bound to montmorillonite were
significantly more infectious than prions alone.

"We thought the binding might decrease infectivity," Aiken explains. "In
each case, you add montmorillonite and we get more animals sicker and
quicker than in the absence of montmorillonite clay."

What is occurring in soils in the woods and on the farm is unknown, says
Pedersen, but the new findings may help begin to answer some key questions
about how prions survive in the soil and retain their infectious nature,
sometimes for years.

In the case of scrapie, the prion disease of sheep, observations of sheep
pastures in the United Kingdom and Iceland have shown that animals
introduced into pastures that once held infected animals could become
infected. Infectivity of prions was also enhanced when they were bound to wh
ole soil.

"Since the 1940s it's been known that 'infected pastures' have the ability
to infect new animals," according to Aiken.

Pedersen notes that soils are a complex mixture of organic and inorganic
components that vary across the landscape and that scientists are just
beginning to tease out factors in soils that may contribute to
transmissibility. The new study implies, he says, "that some soils may
promote the transmission of the prion agent more readily than others."

Why that's the case is unknown, Pedersen explains, but the Wisconsin team is
exploring several hypotheses: that the soil particles might somehow protect
the prion from degradation in the digestive system, that prions bound to
clay might change the route or degree of uptake of the agent, or that the
mineral somehow alters the size of prion aggregates, which have been shown
to be more infectious than prions alone.

Aiken emphasizes there's still much to learn about routes of prion
transmission, and the role of soil is just beginning to be explored.

"Soil is a very complex medium and we don't know what the agent is binding
to" in natural or agricultural settings, Aiken says. "We do know that soil
is not the only way it transmits. Animal-to-animal transmission is
important, too."

In addition to Aiken and Pedersen, authors of the PLoS Pathogens paper
include Christopher J. Johnson, Rick J. Chappell and Debbie McKenzie. The
work was supported by a grant from the U.S. Department of Defense.

http://www.news.wisc.edu/13918


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*

1 Program in Cellular and Molecular Biology, University of
Wisconsin-Madison, Madison, Wisconsin, United States of America, 2
Department of Comparative Biosciences, School of Veterinary Medicine,
University of Wisconsin-Madison, Madison, Wisconsin, United States of
America, 3 Department of Soil Science and Molecular and Environmental
Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin,
United States of America, 4 Biostatistics and Medical Informatics,
University of Wisconsin Medical School, Madison, Wisconsin, United States of
America

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. Here, we assess the oral
infectivity of Mte- and soil-bound prions. We establish that prions bound to
Mte are orally bioavailable, and that, unexpectedly, binding to Mte
significantly enhances disease penetrance and reduces the incubation period
relative to unbound agent. Cox proportional hazards modeling revealed that
across the doses of TSE agent tested, Mte increased the effective infectious
titer by a factor of 680 relative to unbound agent. Oral exposure to
Mte-associated prions led to TSE development in experimental animals even at
doses too low to produce clinical symptoms in the absence of the mineral. We
tested the oral infectivity of prions bound to three whole soils differing
in texture, mineralogy, and organic carbon content and found soil-bound
prions to be orally infectious. Two of the three soils increased oral
transmission of disease, and the infectivity of agent bound to the third
organic carbon-rich soil was equivalent to that of unbound agent. Enhanced
transmissibility of soil-bound prions may explain the environmental spread
of some TSEs despite the presumably low levels shed into the environment.
Association of prions with inorganic microparticles represents a novel means
by which their oral transmission is enhanced relative to unbound agent.


snip...


Discussion
These experiments address the critical question of whether soil
particle–bound prions are infectious by an environmentally relevant exposure
route, namely, oral ingestion. Oral infectivity of soil particle–bound
prions is a conditio sine qua non for soil to serve as an environmental
reservoir for TSE agent. The maintenance of infectivity and enhanced
transmissibility when TSE agent is bound to the common soil mineral Mte is
remarkable given the avidity of the PrPTSE–Mte interaction [22]. One might
expect the avid interaction of PrPTSE with Mte to result in the mineral
serving as a sink, rather than a reservoir, for TSE infectivity. Our results
demonstrate this may not be the case. Furthermore, sorption of prions to
complex whole soils did not diminish bioavailability, and in two of three
cases promoted disease transmission by the oral route of exposure. While
extrapolation of these results to environmental conditions must be made with
care, prion sorption to soil particles clearly has the potential to increase
disease transmission via the oral route and contribute to the maintenance of
TSE epizootics.

Two of three tested soils potentiated oral prion disease transmission. The
reason for increased oral transmissibility associated with some, but not
all, of the soils remains to be elucidated. One possibility is that
components responsible for enhancing oral transmissibility were present at
higher levels in the Elliot and Bluestem soils than in the Dodge soil. The
major difference between the Dodge soil and the other two soils was the
extremely high natural organic matter content of the former (34%, [22]). The
Dodge and Elliot soils contained similar levels of mixed-layer
illite/smectite, although the contribution of smectite layers was higher in
the Dodge soil (14%–16%, [22]). The organic matter present in the Dodge soil
may have obstructed access of PrPTSE to sorption sites on smectite (or other
mineral) surfaces.

The mechanism by which Mte or other soil components enhances the oral
transmissibility of particle-bound prions remains to be clarified.
Aluminosilicate minerals such as Mte do not provoke inflammation of the
intestinal lining [39]. Although such an effect is conceivable for whole
soils, soil ingestion is common in ruminants and other mammals [25]. Prion
binding to Mte or other soil components may partially protect PrPTSE from
denaturation or proteolysis in the digestive tract [22,40] allowing more
disease agent to be taken up from the gut than would otherwise be the case.
Adsorption of PrPTSE to soil or soil minerals may alter the aggregation
state of the protein, shifting the size distribution toward more infectious
prion protein particles, thereby increasing the specific titer (i.e.,
infectious units per mass of protein) [41]. In the intestine, PrPTSE
complexed with soil particles may be more readily sampled, endocytosed
(e.g., at Peyer's patches), or persorbed than unbound prions.
Aluminosilicate (as well as titanium dioxide, starch, and silica)
microparticles, similar in size to the Mte used in our experiments, readily
undergo endocytotic and persorptive uptake in the small intestine [42–44].
Enhanced translocation of the infectious agent from the gut lumen into the
body may be responsible for the observed increase in transmission
efficiency.

Survival analysis indicated that when bound to Mte, prions from both BH and
purified PrPTSE preparations were more orally infectious than unbound agent.
Mte addition influenced the effective titer of infected BH to a lesser
extent than purified PrPTSE. Several nonmutually exclusive factors may
explain this result: (1) other macromolecules present in BH (e.g., lipids,
nucleic acids, other proteins) compete with PrPTSE for Mte binding sites;
(2) prion protein is more aggregated in the purified PrPTSE preparation than
in BH [45], and sorption to Mte reduces PrPTSE aggregate size, increasing
specific titer [41]; and (3) sorption of macromolecules present in BH to Mte
influences mineral particle uptake in the gut by altering surface charge or
size, whereas the approximately 1,000-fold lower total protein concentration
in purified PrPTSE preparations did not produce this effect.

We previously showed that other inorganic microparticles (kaolinite and
silicon dioxide) also bind PrPTSE [22]. All three types of microparticles
are widely used food additives and are typically listed as bentonite (Mte),
kaolin (kaolinite), and silica (silicon dioxide). Microparticles are
increasingly included in Western diets. Dietary microparticles are typically
inert and considered safe for consumption by themselves, do not cause
inflammatory responses or other pathologies, even with chronic consumption,
and are often sampled in the gut and transferred from the intestinal lumen
to lymphoid tissue [39,46,47]. Our data suggest that the binding of PrPTSE
to dietary microparticles has the potential to enhance oral prion disease
transmission and warrants further investigation.

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.


snip...full text ;


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


THANK YOU PLOS FOR OPEN ACCESS!!!...


TSS
 

Kathy

Well-known member
quote:

Aiken's team expected to see a lower rate of infection than animals dosed with pure agent.

This study jumps from assumtion to fact.

There has never been full characterization of the so-called infectious prion protein, therefore, there is no researcher that has been able to have a pure specimen of prion protein, or the agent causing the disease.

Researchers need to examine the contents of the soil extremely closely. There are elemtents that will bind with protein fragments, and cause their misfolding, polymerization and aggregation. These elements are the agent of disease, not the protein.

Many types of proteins with similar ligand binding sites are capable of binding with these elements (whether the binding causes disease or not, is dependent on many factors). Where these elemental particles lodge in the body is determined by their size and the filtering capabilities of the tissue/organ. Once these elemental particles (usually nanoparticles) are lodged in the brain, kidney, heart, etc.... they start to misfold, polymerize and aggregate protein fragments (of various types).

The agent causing the disease is the element - not the protein. The proteins fragments are scavenged by these elements and some elements cause irreversible binding, eg. Tungsten has a major affinity to proteins. Breakdown in the enzyme system that would normally reverse this binding, if capable, is an important factor in the disease progression.

Med Hypotheses. 2005;65(3):448-77.

Metal microcrystal pollutants: the heat resistant, transmissible nucleating agents that initiate the pathogenesis of TSEs?

Purdey M.
High Barn Farm, Elworthy, Taunton, Somerset TA4 3PX, UK. [email protected]

This paper exposes the flaws in the conventional consensus on the origins of transmissible spongiform encephalopathies (TSEs) which decrees that the protein-only misfolded 'prion' represents the primary aetiological transmissible agent, and then reviews/presents the emerging data which indicates that environmental exposure to metal microcrystal pollutants (sourced from munitions, etc.) represents the heat resistant, transmissible nucleating agents which seed the metal-prion protein (PrP)-ferritin fibril crystals that cause TSE. Fresh analytical data is presented on the levels of metals in ecosystems which support populations affected by clusters of variant Creutzfeldt-Jacob disease (vCJD), sporadic/familial CJD, and the scrapie types of TSE that have emerged in the UK, Sicily, Sardinia, Calabria and Japan. This data further substantiates the abnormal geochemical template (e.g., elevated strontium (Sr), barium (Ba) and silver (Ag)) which was observed as a common hallmark of the TSE cluster ecosystems across North America, thereby supporting the hypothesis that these microcrystals serve as the piezoelectrion nucleators which seed the growth/multireplication of the aberrant metal-PrP-ferritin fibril features which characterise the neuropathology of the TSE diseased brain. A secondary pathogenic mechanism entails the inactivation of the sulphated proteoglycans which normally regulate the mineralisation process. This can be induced by a rogue metal mediated chelation of free sulphur, or by contamination with organo-sulphur pollutants that substitute at natural sulphur bonds, or via a mutation to the S-proteoglycan cell line; thereby enabling the aberrant overgrowth of rogue fibril crystal formations that possess a piezoelectric capacity which compromises the ability of the contaminated individual to process incoming acoustic/tactile pressure waves in the normal way. The crystals transduce incoming sonic energy into electrical energy, which, in turn, generates magnetic fields on the crystal surfaces that initiate chain reactions of free radical mediated spongiform neurodegeneration. Metal microcrystal nucleating agents provide a group of plausible aetiological candidates that explain the unique properties of the TSE causal agent - such as heat resistance, transmissibility, etc. - which the protein-only prion model fails to fulfill. This paper also discusses the possible nutritional measures that could best be adopted by populations living in high risk TSE ecosystems; as a means of preventing the successful implantation of these rogue microcrystals and their consequent hypermineralisation of the soft tissues within the CNS.

PMID: 15908137
 

Kathy

Well-known member
Check out this website with pictures of the microcrystals of melamine which nucleated the protein found in cat urine which lead to renal disease and blockage, and death of many pets eating the contaminated pet food.

quote:
Microscopy
The following shows crystals (agglomeration of melamine and cyanuric acid) formed in the lab in cat urine by the addition of melamine and cyanuric acid. The composition of these crystals matches those found in the urine of affected pets when compared by infrared spectroscopy (FTIR).

link:
http://www.labservices.uoguelph.ca/urgent.cfm
 

Kathy

Well-known member
Here is an example of how metals like mercury, silver, uranium and gold inhibit enzyme activity in a dose dependent manner:

J Toxicol Environ Health. 1981 Jun;7(6):901-8.

Inhibition by metals of a canine renal calcium, magnesium-activated adenosinetriphosphatase.

Thompson JD, Nechay BR.

A number of metals were examined for inhibition of a canine renal calcium, magnesium-activated adenosinetriphosphatase (Ca2+, Mg2+-ATPase). Of the 27 metals investigated, only compounds of mercury, silver, gold, and uranium demonstrated 50% inhibition of the enzyme at concentrations lower than 10(-4) M. The order of inhibitory potency was Hg greater than Ag greater than U greater than Au. Organic mercury (chlormerodrin, mersalyl, p-chloromercuribenzoate) was less potent than inorganic mercuric chloride, but organic gold sodium thiomalate was equipotent with inorganic gold chloride. The inhibition produced by each metal decreased parallel to the decrease in enzyme activity, seen as the source of enzyme moved from the outer cortex inward to the papilla of the kidney. The regions of highest activity showed the greatest inhibition by each metal, and inhibition decreased as the control activity of the tissue decreased. This variability of inhibition was not related to the protein content of the enzyme preparation. As the ATP concentration increased, the inhibition produced by U was reduced; if the Mg (but not the Ca concentration) was increased while the ATP concentration remained constant, the inhibition increased. Changes in the Ca, Mg, and ATP concentrations did not alter the inhibition produced by Hg, Ag, and Au.

PMID: 6115068
 

flounder

Well-known member
1: J Infect Dis 1980 Aug;142(2):205-8



Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep
and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were
exposed to the infectious agents only by their nonforced consumption of
known infectious tissues. The asymptomatic incubation period in the one
monkey exposed to the virus of kuru was 36 months; that in the two monkeys
exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months,
respectively; and that in the two monkeys exposed to the virus of scrapie
was 25 and 32 months, respectively. Careful physical examination of the
buccal cavities of all of the monkeys failed to reveal signs or oral
lesions. One additional monkey similarly exposed to kuru has remained
asymptomatic during the 39 months that it has been under observation.

PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract



1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8



Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes
contaminated during neurosurgery.

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health, Bethesda,
MD 20892.

Stereotactic multicontact electrodes used to probe the cerebral cortex of a
middle aged woman with progressive dementia were previously implicated in
the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two
younger patients. The diagnoses of CJD have been confirmed for all three
cases. More than two years after their last use in humans, after three
cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the
electrodes were implanted in the cortex of a chimpanzee. Eighteen months
later the animal became ill with CJD. This finding serves to re-emphasise
the potential danger posed by reuse of instruments contaminated with the
agents of spongiform encephalopathies, even after scrupulous attempts to
clean them.

PMID: 8006664 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract


look at the table and you'll see that as little as 1 mg (or 0.001 gm) caused
7% (1 of 14) of the cows to come down with BSE;


Risk of oral infection with bovine spongiform encephalopathy agent in
primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog,
Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie
Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe
Deslys
Summary The uncertain extent of human exposure to bovine spongiform
encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease
(vCJD)--is compounded by incomplete knowledge about the efficiency of oral
infection and the magnitude of any bovine-to-human biological barrier to
transmission. We therefore investigated oral transmission of BSE to
non-human primates. We gave two macaques a 5 g oral dose of brain homogenate
from a BSE-infected cow. One macaque developed vCJD-like neurological
disease 60 months after exposure, whereas the other remained free of disease
at 76 months. On the basis of these findings and data from other studies, we
made a preliminary estimate of the food exposure risk for man, which
provides additional assurance that existing public health measures can
prevent transmission of BSE to man.


snip...


BSE bovine brain inoculum

100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg

Primate (oral route)* 1/2 (50%)

Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%)
1/15 (7%)

RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)

PrPres biochemical detection

The comparison is made on the basis of calibration of the bovine inoculum
used in our study with primates against a bovine brain inoculum with a
similar PrPres concentration that was

inoculated into mice and cattle.8 *Data are number of animals
positive/number of animals surviving at the time of clinical onset of
disease in the first positive animal (%). The accuracy of

bioassays is generally judged to be about plus or minus 1 log. ic
ip=intracerebral and intraperitoneal.

Table 1: Comparison of transmission rates in primates and cattle infected
orally with similar BSE brain inocula


Published online January 27, 2005

http://www.thelancet.com/journal/journal.isa


It is clear that the designing scientists must

also have shared Mr Bradley’s surprise at the results because all the dose

levels right down to 1 gram triggered infection.


http://www.bseinquiry.gov.uk/files/ws/s145d.pdf



2

6. It also appears to me that Mr Bradley’s answer (that it would take less
than say 100

grams) was probably given with the benefit of hindsight; particularly if one

considers that later in the same answer Mr Bradley expresses his surprise
that it

could take as little of 1 gram of brain to cause BSE by the oral route
within the

same species. This information did not become available until the "attack
rate"

experiment had been completed in 1995/96. This was a titration experiment

designed to ascertain the infective dose. A range of dosages was used to
ensure

that the actual result was within both a lower and an upper limit within the
study

and the designing scientists would not have expected all the dose levels to
trigger

infection. The dose ranges chosen by the most informed scientists at that
time

ranged from 1 gram to three times one hundred grams. It is clear that the
designing

scientists must have also shared Mr Bradley’s surprise at the results
because all the

dose levels right down to 1 gram triggered infection.


http://www.bseinquiry.gov.uk/files/ws/s147f.pdf




Oral Transmission of Chronic Wasting Disease in Captive Shira’s Moose

Terry J. Kreeger1,3, D. L. Montgomery2, Jean E. Jewell2, Will Schultz1 and
Elizabeth S. Williams2

1 Wyoming Game and Fish Department, 2362 Highway 34, Wheatland, Wyoming
82201, USA;
2 Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming
82071, USA
3 Corresponding author (email: [email protected]dblue.net )

ABSTRACT: Three captive Shira’s moose (Alces alces shirasi) were orally
inoculated with a single dose (5 g) of whole-brain homogenate prepared from
chronic wasting disease (CWD)–affected mule deer (Odocoileus hemionus). All
moose died of causes thought to be other than CWD. Histologic examination of
one female moose dying 465 days postinoculation revealed spongiform change
in the neuropil, typical of transmissible spongiform encephalopathy.
Immunohistochemistry staining for the proteinase-resistant isoform of the
prion protein was observed in multiple lymphoid and nervous tissues. Western
blot and enzyme-linked immunosorbent assays provided additional confirmation
of CWD. These results represent the first report of experimental CWD in
moose.
Key words: Alces alces shirasi, chronic wasting disease, enzyme-linked
immunosorbent assay, immunohistochemistry, moose, oral inoculation, prion,
PrPCWD.


http://www.jwildlifedis.org/cgi/content/abstract/42/3/640


http://www.usaha.org/committees/reports/2005/report-wd-2005.pdf


Oral transmission and early lymphoid tropism of chronic wasting disease
PrPres in mule deer fawns (Odocoileus hemionus )
Christina J. Sigurdson1, Elizabeth S. Williams2, Michael W. Miller3, Terry
R. Spraker1,4, Katherine I. O'Rourke5 and Edward A. Hoover1

Department of Pathology, College of Veterinary Medicine and Biomedical
Sciences, Colorado State University, Fort Collins, CO 80523- 1671, USA1
Department of Veterinary Sciences, University of Wyoming, 1174 Snowy Range
Road, University of Wyoming, Laramie, WY 82070, USA 2
Colorado Division of Wildlife, Wildlife Research Center, 317 West Prospect
Road, Fort Collins, CO 80526-2097, USA3
Colorado State University Veterinary Diagnostic Laboratory, 300 West Drake
Road, Fort Collins, CO 80523-1671, USA4
Animal Disease Research Unit, Agricultural Research Service, US Department
of Agriculture, 337 Bustad Hall, Washington State University, Pullman, WA
99164-7030, USA5

Author for correspondence: Edward Hoover.Fax +1 970 491 0523. e-mail [log in
to unmask]


Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References

Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain
homogenate prepared from mule deer with naturally occurring chronic wasting
disease (CWD), a prion-induced transmissible spongiform encephalopathy.
Fawns were necropsied and examined for PrP res, the abnormal prion protein
isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an
immunohistochemistry assay modified to enhance sensitivity. PrPres was
detected in alimentary-tract-associated lymphoid tissues (one or more of the
following: retropharyngeal lymph node, tonsil, Peyer's patch and ileocaecal
lymph node) as early as 42 days p.i. and in all fawns examined thereafter
(53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of
three control fawns receiving a control brain inoculum, nor was PrPres
detectable in neural tissue of any fawn. PrPres-specific staining was
markedly enhanced by sequential tissue treatment with formic acid,
proteinase K and hydrated autoclaving prior to immunohistochemical staining
with monoclonal antibody F89/160.1.5. These results indicate that CWD PrP
res can be detected in lymphoid tissues draining the alimentary tract within
a few weeks after oral exposure to infectious prions and may reflect the
initial pathway of CWD infection in deer. The rapid infection of deer fawns
following exposure by the most plausible natural route is consistent with
the efficient horizontal transmission of CWD in nature and enables
accelerated studies of transmission and pathogenesis in the native species.


snip...

These results indicate that mule deer fawns develop detectable PrP res after
oral exposure to an inoculum containing CWD prions. In the earliest
post-exposure period, CWD PrPres was traced to the lymphoid tissues draining
the oral and intestinal mucosa (i.e. the retropharyngeal lymph nodes,
tonsil, ileal Peyer's patches and ileocaecal lymph nodes), which probably
received the highest initial exposure to the inoculum. Hadlow et al. (1982)
demonstrated scrapie agent in the tonsil, retropharyngeal and mesenteric
lymph nodes, ileum and spleen in a 10-month-old naturally infected lamb by
mouse bioassay. Eight of nine sheep had infectivity in the retropharyngeal
lymph node. He concluded that the tissue distribution suggested primary
infection via the gastrointestinal tract. The tissue distribution of PrPres
in the early stages of infection in the fawns is strikingly similar to that
seen in naturally infected sheep with scrapie. These findings support oral
exposure as a natural route of CWD infection in deer and support oral
inoculation as a reasonable exposure route for experimental studies of CWD.

snip...

http://vir.sgmjournals.org/cgi/content/full/80/10/2757




QUESTION, IS U.S.A. FOOD PRODUCTION SYSTEM POISONING US ?



What Do We Feed to Food-Production Animals? A Review of Animal Feed
Ingredients and Their Potential Impacts on Human Health


Amy R. Sapkota,1,2 Lisa Y. Lefferts,1,3 Shawn McKenzie,1 and Polly Walker1
1Johns Hopkins Center for a Livable Future, Bloomberg School of Public
Health, Baltimore, Maryland, USA; 2Maryland Institute for
Applied Environmental Health, College of Health and Human Performance,
University of Maryland, College Park, Maryland, USA;
3Lisa Y. Lefferts Consulting, Nellysford, Virginia, USA


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Table 1. Animal feed ingredients that are legally used in U.S. animal feeds



Animal


Rendered animal protein from Meat meal, meat meal tankage, meat and bone
meal, poultry meal, animal the slaughter of food by-product meal, dried
animal blood, blood meal, feather meal, egg-shell production animals and
other meal, hydrolyzed whole poultry, hydrolyzed hair, bone marrow, and
animal animals digest from dead, dying, diseased, or disabled animals
including deer and elk Animal waste Dried ruminant waste, dried swine waste,
dried poultry litter, and undried processed animal waste products


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Conclusions


Food-animal production in the United States has changed markedly in the past
century, and these changes have paralleled major changes in animal feed
formulations. While this industrialized system of food-animal production may
result in increased production efficiencies, some of the changes in animal
feeding practices may result in unintended adverse health consequences for
consumers of animal-based food products. Currently, the use of animal feed
ingredients,
including rendered animal products, animal waste, antibiotics, metals, and
fats, could result in higher levels of bacteria, antibioticresistant
bacteria, prions, arsenic, and dioxinlike compounds in animals and resulting
animal-based food products intended for human consumption. Subsequent human
health effects among consumers could include increases in bacterial
infections (antibioticresistant and nonresistant) and increases in the risk
of developing chronic (often fatal) diseases
such as vCJD. Nevertheless, in spite of the wide range of potential human
health impacts that could result from animal feeding practices, there are
little data collected at the federal or state level concerning the amounts
of specific ingredients that are intentionally included in U.S. animal feed.
In addition, almost no biological or chemical testing is conducted on
complete U.S. animal feeds; insufficient testing is performed on retail meat
products; and human health effects data are not appropriately linked to this
information. These surveillance inadequacies make it difficult to conduct
rigorous epidemiologic studies and risk assessments
that could identify the extent to which specific human health risks are
ultimately associated with animal feeding practices. For example, as noted
above, there are insufficient data to determine whether other human
foodborne bacterial illnesses besides those caused by S. enterica serotype
Agona are associated with animal feeding practices. Likewise, there are
insufficient data to determine the percentage of antibiotic-resistant human
bacterial infections that are attributed to the nontherapeutic use of
antibiotics in animal feed. Moreover, little research has been conducted to
determine whether the use of organoarsenicals in animal feed, which can lead
to elevated levels of arsenic in meat products (Lasky et al. 2004),
contributes to increases in cancer risk. In order to address these research
gaps, the following principal actions are necessary within the United
States: a) implementation of a nationwide reporting system of the specific
amounts and types of feed ingredients of concern to public health that are
incorporated into animal feed, including antibiotics, arsenicals, rendered
animal products, fats, and animal waste; b) funding and development of
robust surveillance systems that monitor biological, chemical, and other
etiologic agents throughout the animal-based food-production chain “from
farm to fork” to human health outcomes; and c) increased communication and
collaboration among feed professionals, food-animal producers, and
veterinary and public health officials.


REFERENCES...snip...end


Sapkota et al.
668 VOLUME 115 | NUMBER 5 | May 2007 • Environmental Health Perspectives


http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1867957&blobtype=pdf


look at the decline in BSE cases in reference to feed ban of tainted
materials ;

http://www.defra.gov.uk/animalh/bse/statistics/bse/overview.html

http://www.defra.gov.uk/animalh/bse/controls-eradication/feedban-bornafterban.html


The measures taken by the UK Government, in particular the feed ban, have
already resulted in a sharp decline in the incidence of BSE. ...

http://www.defra.gov.uk/animalh/bse/controls-eradication/index.html


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