Porcine Prion Protein Amyloid
DOI:
10.1080/19336896.2015.1065373
Received: 1 Jun 2015
Accepted: 17 Jun 2015
Accepted author version posted online: 28 Jul 2015
Abstract
Mammalian prions are composed of misfolded aggregated prion protein (PrP)
with amyloid-like features. Prions are zoonotic disease agents that infect a
wide variety of mammalian species including humans. Mammals and by-products
thereof which are frequently encountered in daily life are most important for
human health. It is established that bovine prions (BSE) can infect humans while
there is no such evidence for any other prion susceptible species in the human
food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or
susceptible and resistant pets (cat and dogs respectively). PrPs from these
species have been characterized using biochemistry, biophysics and neurobiology.
Recently we studied PrPs from several mammals in vitro and found evidence for
generic amyloidogenicity as well as cross-seeding fibril formation activity of
all PrPs on the human PrP sequence regardless if the original species was
resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was
among the studied. Experimentally inoculated pigs as well as transgenic mouse
lines overexpressing porcine PrP have, in the past, been used to investigate the
possibility of prion transmission in pigs. The pig is a species with
extraordinarily wide use within human daily life with over a billion pigs
harvested for human consumption each year. *** Here we discuss the possibility
that the largely prion disease resistant pig can be a clinically silent carrier
of replicating prions.
PORCINE SPONGIFORM ENCEPHALOPATHY PSE AND DEADSTOCK DOWNER PIGS
EXPERIMENTAL INTRACEREBRAL AND ORAL INOCULATION OF SCRAPIE TO SWINE:
PRELIMINARY REPORT
Date: February 6, 2006 at 12:33 pm PST
Title: EXPERIMENTAL INTRACEREBRAL AND ORAL INOCULATION OF SCRAPIE TO SWINE:
PRELIMINARY REPORT
SEE MORE HERE ;
PORCINE SPONGIFORM ENCEPHALOPATHY PSE
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral
Inoculation
snip...
In the US, feeding of ruminant by-products to ruminants is prohibited, but
feeding of ruminant materials to swine, mink and poultry still occurs. Although
unlikely, the potential for swine to have access to TSE-contaminated feedstuffs
exists.
snip...
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral
Inoculation
(see tonnage of mad cow feed in commerce USA...tss)
In an experimental study of the transmissibility of BSE to the pig, seven
of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral
inoculation with a homogenate of bovine brain from natural BSE cases developed
lesions typical of spongiform encephalopathy.
Title: Experimental Intracerebral and Oral Inoculation of Scrapie to Swine:
Preliminary Report
In the United States, feeding of ruminant by-products to ruminants is
prohibited, but feeding of ruminant materials to swine and poultry still occurs.
The potential for swine to have access to scrapie-contaminated feedstuffs
exists, but the potential for swine to serve as a host for
replication/accumulation of the agent of scrapie is unknown. The purpose of this
study was to perform oral and intracerebral inoculation of the U.S. scrapie
agent to determine the potential of swine as a host for the scrapie agent and
their clinical susceptibility.
snip...
IN CONFIDENCE
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
1. CMO should be aware that a pig inoculated experimentally (ic, iv, and
ip) with BSE brain suspension has after 15 months developed an illness, now
confirmed as a spongiform encephalopathy. This is the first ever description of
such a disease in a pig, although it seems there ar no previous attempts at
experimental inoculation with animal material. The Southwood group had thought
igs would not be susceptible. Most pigs are slaughtered when a few weeks old but
there have been no reports of relevant neurological illness in breeding sows or
other elderly pigs. ...see full text ;
IN CONFIDENCE
So it is plausible pigs could be preclinically affected with BSE but since
so few are allowed to reach adulthood this has not been recognised through
clinical disease. ...
snip...
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
While this clearly is a cause for concern we should not jump to the
conclusion that this means that pigs will necessarily be infected by bone and
meat meal fed by the oral route as is the case with cattle. ...
we cannot rule out the possibility that unrecognised subclinical spongiform
encephalopathy could be present in British pigs though there is no evidence for
this: only with parenteral/implantable pharmaceuticals/devices is the
theoretical risk to humans of sufficient concern to consider any action.
May I, at the outset, reiterate that we should avoid dissemination of
papers relating to this experimental finding to prevent premature release of the
information. ...
3. It is particularly important that this information is not passed outside
the Department, until Ministers have decided how they wish it to be handled.
...
But it would be easier for us if pharmaceuticals/devices are not directly
mentioned at all. ...
Our records show that while some use is made of porcine materials in
medicinal products, the only products which would appear to be in a
hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for
which the source material comes from outside the United Kingdom, namely America
China Sweden France and Germany. The products are manufactured by Ferring and
Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon,
makes use of porcine skin - which is not considered to be a ''high risk''
tissue, but one of its uses is described in the data sheet as ''in dural
replacement''. This product is sourced from the United Kingdom.....
snip...
It was not until . . . August 1990, that the result from the pig persuaded
both SEAC and us to change our view and to take out of pig rations any residual
infectivity that might have arisen from the SBOs.
4.303 The minutes of the meeting record that:
It was very difficult to draw conclusions from one experimental result for
what may happen in the field. However it would be prudent to exclude specified
bovine offals from the pig diet. Although any relationship between BSE and the
finding of a spongiform encephalopathy in cats had yet to be demonstrated, the
fact that this had occurred suggested that a cautious view should be taken of
those species which might be susceptible. The 'specified offals' of bovines
should therefore be excluded from the feed of all species. 17
http://web.archive.org/web/20031026084516/http://www.bseinquiry.gov.uk/files/yb/1990/09/07001001.pdf
IN CONFIENCE
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
1. CMO should be aware that a pig inoculated experimentally (ic, iv, and
ip) with BSE brain suspension has after 15 months developed an illness, now
confirmed as a spongiform encephalopathy. This is the first ever description of
such a disease in a pig, although it seems there ar no previous attempts at
experimental inoculation with animal material. The Southwood group had thought
igs would not be susceptible. Most pigs are slaughtered when a few weeks old but
there have been no reports of relevant neurological illness in breeding sows or
other elderly pigs. ...see full text ;
IN CONFIDENCE
So it is plausible pigs could be preclinically affected with BSE but since
so few are allowed to reach adulthood this has not been recognised through
clinical disease. ...
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
While this clearly is a cause for concern we should not jump to the
conclusion that this means that pigs will necessarily be infected by bone and
meat meal fed by the oral route as is the case with cattle. ...
we cannot rule out the possibility that unrecognised subclinical spongiform
encephalopathy could be present in British pigs though there is no evidence for
this: only with parenteral/implantable pharmaceuticals/devices is the
theoretical risk to humans of sufficient concern to consider any action.
May I, at the outset, reiterate that we should avoid dissemination of
papers relating to this experimental finding to prevent premature release of the
information. ...
3. It is particularly important that this information is not passed outside
the Department, until Ministers have decided how they wish it to be handled.
...
But it would be easier for us if pharmaceuticals/devices are not directly
mentioned at all. ...
Our records show that while some use is made of porcine materials in
medicinal products, the only products which would appear to be in a
hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for
which the source material comes from outside the United Kingdom, namely America
China Sweden France and Germany. The products are manufactured by Ferring and
Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon,
makes use of porcine skin - which is not considered to be a ''high risk''
tissue, but one of its uses is described in the data sheet as ''in dural
replacement''. This product is sourced from the United Kingdom.....
BSE TO PIGS NEWS RELEASE
CONFIDENTIAL
BSE: PRESS PRESENTATION
http://web.archive.org/web/20030820195733/http://www.bseinquiry.gov.uk/files/yb/1990/09/20010001.pdf
http://web.archive.org/web/20030820195733/http://www.bseinquiry.gov.uk/files/yb/1990/09/25013001.pdf
http://web.archive.org/web/20030820195733/http://www.bseinquiry.gov.uk/files/yb/1990/09/25015001.pdf
INDUSTRY RESPONSE TYPICAL
DEFENSIVE BRIEFING
http://web.archive.org/web/20030820195733/http://www.bseinquiry.gov.uk/files/yb/1990/09/25016001.pdf
CONFIDENTIAL
pigs & pharmaceuticals
COMMERCIAL IN CONFIDENCE COMMITTEE ON SAFETY OF MEDICINE NOT FOR
PUBLICATION BOVINE SPONGIFORM ENCEPHALOPATHY WORKING GROUP
There are only two products using porcine brain and these use
corticotrophin BP, made from porcine pituitary, source from outside the
UK.............
snip...
7 OF 10 LITTLE PIGGIES WENT ON TO DEVELOP BSE;
1: J Comp Pathol. 2000 Feb-Apr; 122(2-3): 131-43. Related Articles,
Links
Click here to read
The neuropathology of experimental bovine spongiform encephalopathy in the
pig.
Ryder SJ, Hawkins SA, Dawson M, Wells GA.
Veterinary Laboratories Agency Weybridge, Woodham Lane, New Haw,
Addlestone, Surrey, KT15 3NB, UK.
In an experimental study of the transmissibility of BSE to the pig, seven
of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral
inoculation with a homogenate of bovine brain from natural BSE cases developed
lesions typical of spongiform encephalopathy. The lesions consisted principally
of severe neuropil vacuolation affecting most areas of the brain, but mainly the
forebrain. In addition, some vacuolar change was identified in the rostral
colliculi and hypothalamic areas of normal control pigs. PrP accumulations were
detected immunocytochemically in the brains of BSE-infected animals. PrP
accumulation was sparse in many areas and its density was not obviously related
to the degree of vacuolation. The patterns of PrP immunolabelling in control
pigs differed strikingly from those in the infected animals.
PMID: 10684682 [PubMed - indexed for MEDLINE]
snip...
In the United States, feeding of ruminant by-products to ruminants is
prohibited, but feeding of ruminant materials to swine and poultry still occurs.
The potential for swine to have access to scrapie-contaminated feedstuffs
exists, but the potential for swine to serve as a host for
replication/accumulation of the agent of scrapie is unknown. The purpose of this
study was to perform oral and intracerebral inoculation of the U.S. scrapie
agent to determine the potential of swine as a host for the scrapie agent and
their clinical susceptibility.
see full text and more transmission studies here ;
Transgenic mice expressing porcine prion protein resistant to classical
scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical
scrapie.
Emerg Infect Dis. 2009 Aug; [Epub ahead of print]
The case for mad pigs in the US
From the Consumer Policy Institute and Consumers Union: March 24,
1997
Stephen F. Sundlof, D.V.M., Ph.D Center for Veterinary Medicine Food and
Drug Administration 7500 Standish Place, Room 482, HFV 1 RockvLIle, MD 20855
Dear Dr. Sundlof:
We are writing to you to submit information that has recently come to our
attention which suggests that a TSE like disease (transmissible spongiform
encephalopathy) might exist in pigs in the U.S. We believe this new informantion
calls for intensive research and makes it urgent to ban the use of all mammalian
proteins, including swine, in the feed of all food animals, until better answers
are found.
The evidence for the potential PSE (porcine spongiform encephalopathy ) is
as follows. In 1979, an FSQS veternarian, Dr. Masuo Doi, noticed some unusual
central nervous system (CNS) symptoms in young (about 6 months old) hogs coming
into a slaughter plant In Albany, New York. Since the plant received hogs from a
wide variety of sources (New York, Canada, Indiana, Illinois, Ohio, and other
Midwestern states) and was not a plant used to dealing with diseased animals,
Dr. Doi thought that the problem might be affecting hogs slaughtered nationwide.
So, he decided to conduct a detailed study on central nervous system (CNS)
symptoms/disease in young hogs coming into that slaughter plant. The study ran
for 15 months (January, 1979 to March, 1980) and consisted of extended
observations of the behavior of animals with suspected CNS symptoms at the
plant, followed by pathological, histopatholpgical, and microbiological work on
tissues from various organs of particular animals after slaughter.
For his behavioral observational work, Dr. Doi extended the usual two day
observation period to three to four days, during which he took careful notes on
the animals' behavior and other vital signs. During the 15 month period of the
study, some 106 animals exhibiting CNS symptoms were retained during antemortem
inspection.
A 1980 paper that summarized Dr. Doi's findings on the clinical symptoms
and incidence of the 'disease," contained descriptions of these symptoms that
sound remarkably similar to the symptoms noted for bovine spongiform
encephalopathy (BSE):
"Excitable or nervous temperament to external stimuli such as touch to the
skin, handling and menacing approach to the animals is a common characteristic
sign among swine affected with the disease.... In the advanced stage of the
disease, manifestation of neurological signs are evidenced in the form of
general ataxia . . . Many animals have been found to be "downers' at first
observation; if the hindquarters of these downers are raised they may be able to
walk one or two steps and then fall to the ground" (Doi et al., 1980: 2, 4).
Indeed, a table of symptoms includes, for the early stage: "excitability and
nervousness (squealing, smacking of lips, grinding of teath, chewing, gnawing
ant foaming at mouth); stiffness of limbs . . . 'tic'; weakness of hindquarters;
focal tremors of skeletal muscles"; and for the advanced stage: depression;
ataxia; crossing over of limbs . . . kneeling posture . . . crawling". In
addition to his clinical observations, Dr. Doi also made an 8 mm film of
thirteen of the affected animals; film of two of the pigs was shown at the MPI
National Pathology Meeting in Seattle, Washington on flay 20, 1979.
Dr. Doi sent tissue samples from suspect cases to the USDA's Eastern
Laboratory in Athens, GA for pathological, histopathogical and microbiological
work. Known infectious diseases were ruled out. As Dr. Doi points out,
"Histopathological studies of tissue collected from the brain and spinal cord of
these animals in the early stage of the disease show congestion, hemorrhage and
neuronal degeneration. All animals in the advanced stage of the disease have
been confined to have Encephalitis or Meningitis by MPI laboratory" (Doi et al.,
1980: 5). Eventually some 60 animals were confirmed by the MPI Laboratory to
have encephalitis or meningitis, with no ldentifiable cause. As pointed out in a
paper presented at the 1979 MPI National Pathology Meetings,
"Since January, a number of hogs in this establishment have been found, in
antemortem, to show what appears to be CNS. Sets of tissue samples were sent to
the laboratory for examination, various tests were done which include
histological study (E H stain), fluorescence antibody technique, virus
neutralization and viral and bacteriological isolation. Differential diagnosis
was also done to exclude vitamin B deficiency, post vaccination reaction,
chlorinated hydrocarbon, arthritis, and transport stress" (Doi et al., 1979).
The brains of the 60 animals were examined. The brain of one of these pigs, on
histopathological analysis, exhibited signs reminiscent of a TSE. This
histopathological work was performed by Dr. Karl Langheinrich,
Pathologist-In-Charge at USDA's Eastern Laboratory in Athens, Georgia. According
to the USDA FSQS laboratory report, dated early November, 1979, Dr. Langheinrich
noted:
"Microscopic examination of the barrow tissues revealed a encephalopathy
and diffuse gliosis characterized by vacuolated neurons, loss of neurons and
gliosis in a confined region (nucleus) of the brain stem (anterior ventral
midbrain). Only an empty sometimes divided vacuole was present instead of the
normal morphology of a nerve cell. Occasionally a shriveled neuron was seen.
According to . . . Pathology of Domestic Animals, . . . 'The degeneration of
neurons, the reactivity of the glia .... are the classical hallmarks of viral
infection of the central nervous system' .... Scrapie of sheep, and
encephalopathy of mink, according to the literature, all produce focal
vacuolation of the neurons similar to the kind as described for this pig. I was
unable to locate any lead as to the cause of this interesting phenomenon in
other species including swine'' (Langheinrich, 1979). Indeed, Dr. Langheinrich's
main diagnosis was, " Encephalopathy and diffuse gliosis of undetermined
etiology." Portions of the brain were sent for microbiological testing to a
neurologist at the University of Georgia, where they came up negative for
pseudo-rabies. The brain was unique enough that USDA scientists, such as Dr.
Langheinrich and Or. Dot, mentioned it to student and scientific colleagues over
the years.
In 1979-1980, BSE was completely unknown. However, both the behavior of the
pigs, as well as the histopathology on at least one pig, both showed sign
consistent with a porcine TSE. This raises particular concern became the
affected animal was only 6 months old; in an animal this young, one would rust
expect to see any physical signs of TSE in the brain. Histopathology of TSEs can
be very variable, so that spongiform appearance (i.e. vacuolated neurons) are
not always present. Behavioral changes can be seen in TSE-infected animals
before any changes in brain morphology are visible. Dr. Clarence Gibbs, in
testimony before a Congressional hearing on the TSE issue on January 29, 1997
made just this point:
''In the mid-1960s, we demonstrated with our French and English
collaborators that during the early incubation of the TSEs, when the virus titer
in the brain was very low, there were already marked functional changes, even
though no pathology was yet detectable, even ultrastructurally. A month or hero
later, polynucleation of neurons appeared in spider monkeys, incubating kuru,
and somewhat later, microvacuolation and membrane changes visible only by
electron microscopy. This preceded the pest appearance of astrogliosis and
spongiform change. It was only much later that the classical scrapie TSE
pathology appeared with virus titers in brain of 10 -5 or higher" (Gibbs, 1997;
pg. 4). Given that TSEs can cause behavioral changes in infected animals before
any physical changes in the brain can be seen, that the manifestation of TSE in
the brain can be quite variable, and that changes in brain morphology are not
usually seen in 6 month old animals, we are concerned that the brain of one pig
actually showed physical evidence consistent with a TSE.
Following the announcement In March, 1996 of ten cases of new variant CJD
(Creutzfeldt-Jakob Disease) in the United Kingdom and their possible connection
to BSE, Drs. Doi, Langheinrich and others urged reinvestigation of this
case.
In August, 1996, the USDA sent five slides, one of which was a
histopathology slide, to Dr. Janice Miller of USDA's Agricultural Research
Servicer . Dr. Miller stained four of the slides for prion protein (she didn't
stain the H&E slide). Dr. Miller told Consumers Union that Dr. Patrick
McCaskey, USDA/FSIS, in charge of the Research Center at Athens, GA, called her,
told her that he had five slides that all showed "problems" and asked her to
stain four of them. The H&E slide, which clearly show vacuoles in the
neurons (one sign of TSE), wasn't stained because to stain for PrP entails
removing the slide cover, baking the slide to destain it and then restaining it
for PrP; they didn't want to risk destroying the H&E slide.
Dr. Doi had kept frozen samples of the brain and spinal chord of the
suspect PSE pig in case the Eastern lab wanted more material for analysis.
Unfortunately, these samples were discarded when the packing plant in Albany, NY
closed in 1991. It appears that the brain material sent to the Univcrsity of
Georgia may have been discarded. [pers com.. Dr. Doi 3/13/97]
Dr. Miller found that the PrP stained in the four pig slides was found only
on the inside of neurons, while a positive control slide from a scrapie sheep
showed massive amounts of extraneuronal staining. In a letter summarizing her
results (copy attached), she concludes that the PrP stained in this pig was
normal: "In the pig sections you will see a small particulate type of staining
that is confined to neurons and as I indicated on the phone, I would interpret
as normal PrP. It is in marked contrast to the massive amount of extraneuronal
staining seen in the scrapie section" (Miller, 1996).
Unfortunately, Dr. Miller's finding toes not conclusively rule out a TSE.
We are concerned that while British BSE and serapie create a massive amount of
extraneuronal staining, there are TSEs where this isn't the case. Three
experiments were done in He U.S. -- in Mission, TX (APHIS work), Pullman,
Washington (ARS work), and Ames, Iowa (ARS work) -- to see whether sheep scrapie
can possibly infect cows. In all the experiments, cattle were inoculated with
tissue from scrapie -infected sheep primarily by intra-cranial injection, but in
the case of the Texas and Iowa studies also by oral feeding -- to see if cattle
were susceptible to scrapie at all. In all three experiments, the majority of
cows injected in the brain with scrapie-infected sheep material (usually brains)
also developed a fatal spongiform encephalopathy.
However, in all three examples, the symptoms of the spongifonn
encephalopathy differed from "mad cow" disease ~ England, as did the appearances
of slides from their brains. The brain lesions seen in all these animals were
more variable than those seen in England. When Dr. Miller did similar staining
for PrP from these brains (what she called "bovine scrapie") she only found PrP
stains on the inside of the neurons, not the massive extraneuronal staining seen
in BSE (Miller, pers. comm., March 7, 1997). Thus, Dr. Miller's finding of PrP
stains only inside the neurons in the suspect pigs is not particularly
reassuring.
In November 1996, USDA sent the single histopathology slide to Dr. William
Hadlow, one of the foremost spongiform encephalopathy pathologists in the world.
(For unknown reasons, Dr. Hadlow was only sent the one slide; he was not told of
the existence of the other slides, nor of Dr. Miller's findings, nor was he told
or given the behavioral report from Dr. Doi or the morphology work by Dr.
Langheinrich, or shown film of the affected pigs [Dr. Hadlow, pers. com.,
3/13/97] From this single slide, Dr. Hadlow found some evidence consistent with
TSEs but not enough for a conclusive diagnosis. He noted that the slide
contained vacuoles inside neurons, one of the signs of a TSE (Dr. Langheinrich
had noted this as well).
However, since such vacuoles occasionally occur normally in pigs, he
thought that was not something special: "About twelve (12) neurons in the
parasympathetic nucleus have unilocular optically empty vacuoles in the
perikaryon. This is the site where such vacuolated neurons have been seen in the
swine (as well as in cats and sheep) as an incidental finding. So I do not think
such cells have any significance in this pig" (Hadlow, 1996). However, he did
see evidence, Including changes in astrocytes, that suggested a TSE, but without
examining other parts of the brain to look for other evidence of TSE, he
couldn't be sure:
"I am impressed, though, with what seems to be an increase in the number of
astrocytes in the section. Some astrocytes are in clusters, some are enlarged
and vesicular. Where they are most numerous, a few rod cells (activated
microglia) are seen. These findings suggest some perturbation of the nervous
tissue. Although such a global response occurs in the transmissible spongifonn
encephalopathies, I do no! know its significance in this case without examining
other parts of the brain for changes characteristic of these diseases. Thus,
from looking; at this one (1) section of brain, I cannot conclude that the pig
was affected with a scrapie-like spongiform encephalopathy" (Hadlow, 1996). In
sum, Dr. Hadlow~s letter does not rule out the possibility of a TSE. He says
that there is suggestive evidence, but that he would need to look at other
slides/sections of the brain, to make a conclusive diagnosis.
In our view, the implications of this data are extremely serious.
Experiments in the United Kingdom have shown that pigs are susceptible to BSE.
Pigs inoculated with BSE develop a TSE (Dawson et al., 1990). Feeding
experiments are underway in the UK to see if BSE can be orally transmitted to
pigs; as of March, 1997, some 6 years after the start of the experiment, none of
the pigs fed BSE brain have come down with a TSE. Unfortunately the design of
this experiment severely limits what we will learn from it, and will most likely
not tell us conclusively if pigs can get BSE from feed. It turns out that the
pigs were not fed BSE brain continuously. Rather, the pigs were only fed BSE
brain material on three days, over a three week period (i.e.. one day each
week). Following these three doses, the pigs were never fed contaminated
material again. The total amount of infective material given to the pigs was
therefore quite small. Thus, a negative finding would be hard to interpret and
would not mean that BSE is not orally active in pigs.
We believe that as a top priority USDA should conduct follow-up studies to
look for potential CNS/PSE cases in pigs (we plan to communicate about this to
USDA separately). In brief, we feel that the following kinds of studies need to
be done:
i) TSE pathology experts should examine all the slides from the suspect pig
(2709). To our knowledge, at least 12 separate slides exist.
ii) Determine if any brain material from the suspect pig (2709) still
exists at the Unlverslty of Georgia. If so, this material should be retrieved
and used for transmission studies. In particular, suckling pigs should be
inoculated with the material and then permitted to live unto they die of a
disease or old age, at which point their brains should be examined for physical
signs of a TSE as well as for immunchistochemical evidence (i.e. staining
looking for the abnormal PrP).
iii) Increase antemortem inspection for CNS symptoms at hog facilities.
Inspectors should be trained to detect the subtle CNS symptoms seen in the Doi
et al. study. At a select number of slaughter facilities, animals exhibiting CNS
symptoms should be removed and held for observation until they die, at which
time their brains should be examined for evidence of a TSE.
iv) Research on CNS symptoms among Me 6,000 or so breeding sows which are
permitted to live for 3+ years. Sows exhibiting CNS symptoms should be removed
and held for observation until they die, at which time then brains should be
exernined for evidence of a TSE.
While such work is underway, given the above inforrnabon, we believe that
as a precutionary measure the FDA must expand the proposed ruminant plus
mink-to-ruminnant feed ban to prevent protein from any material, including hogs,
being fed to any food animal.
Sincerely,
Michael Hansen, Ph.D Research Associate
Jean Halloran Director
References
Dawson, M., Wells, G.A.H., Parker, B.N;J. and A.C Scott. 1990. Primary
parental transmission of bovine spongiform encephalopathy to the pig. Veternary
Record, pg. 338.
Doi, M., Matzner, N.D. and C. Rothaug. 1979. Observation of CNS disease in
market hogs at Est. 893 Tobin Packing Co., Inc. Albany, New York. United States
Department of Agriculture, Food Safety and Quality.Service, Meat and Poultry
Inspection Service. 7pp.
Doi, M, Langheinrich, K. and F. Rellosa. 1980. Observations of CNS signs in
hogs at Est. 893 Tobin Packing C:o., Inc. Presented by Dr. Lngheinrich at the
MPI National Pathology Meeting in Seattle, Washington on July 20, 1979.
Gibbs, C. 1997. Statement to the Committee on Governnent Reform and
Oversight, Subcommittee on Human Resources and Intergovernmental Relations, U.S.
House of Representatives. January 29,1997.
Hadlow, WJ. 1996. Letter to Patrick McCaskey, USDA/FSIS/Eastem Lab, dated
November 13, 1996.
Langheinrich, KA. 1979. USDA/FSQS Laboratory report on specimen 2709. Dated
November 8, 1979
Miller, J. 1996. Letter to Patrick McCaskey, USDA/ESIS/Eastern Lab, dated
September 6, 1996.
Dr. Janice Miller, ARS
HOUND STUDY
*** AS implied in the Inset 25 we must not _ASSUME_ that transmission of
BSE to other species will invariably present pathology typical of a scrapie-like
disease. ***
snip...
========================
2005
DEFRA Department for Environment, Food & Rural Affairs
Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904
6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
GTN: FAX:
Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518
21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS
Thank you for e-mail regarding the hounds survey. I am sorry for the long
delay in responding.
As you note, the hound survey remains unpublished. However the Spongiform
Encephalopathy Advisory Committee (SEAC), the UK Government's independent
Advisory Committee on all aspects related to BSE-like disease, gave the hound
study detailed consideration at their meeting in January 1994. As a summary of
this meeting published in the BSE inquiry noted, the Committee were clearly
concerned about the work that had been carried out, concluding that there had
clearly been problems with it, particularly the control on the histology, and
that it was more or less inconclusive. However was agreed that there should be a
re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound
study to see if any useful results could be gained from it. The Chairman
concluded that there were varying opinions within the Committee on further work.
It did not suggest any further transmission studies and thought that the lack of
clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as
conducted. As a result it is likely that the authors felt that it would not
stand up to r~eer review and hence it was never published. As noted above, and
in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether
additional work should be performed to examine dogs for evidence of TSE
infection. Although the Committee had mixed views about the merits of conducting
further work, the Chairman noted that when the Southwood Committee made their
recommendation to complete an assessment of possible spongiform disease in dogs,
no TSEs had been identified in other species and hence dogs were perceived as a
high risk population and worthy of study. However subsequent to the original
recommendation, made in 1990, a number of other species had been identified with
TSE ( e.g. cats) so a study in hounds was less
critical. For more details see- http://www.bseinquiry,
gov.uk/files/yb/1995/06/21005001 .pdf
As this study remains unpublished, my understanding is that the ownership
of the data essentially remains with the original researchers. Thus
unfortunately, I am unable to help with your request to supply information on
the hound survey directly. My only suggestion is that you contact one of the
researchers originally involved in the project, such as Gerald Wells. He can be
contacted at the following address.
Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone,
Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases
of spongiform encephalopathy in animals and poultry were made notifiable. Hence
since that date there has been a requirement for vets to report any suspect SE
in dogs for further investigation. To date there has never been positive
identification of a TSE in a dog.
I hope this is helpful
Yours sincerely 4
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
======================================
HOUND SURVEY
I am sorry, but I really could have been a co-signatory of Gerald's
minute.
I do NOT think that we can justify devoting any resources to this study,
especially as larger and more important projects such as the pathogenesis study
will be quite demanding.
If there is a POLITICAL need to continue with the examination of hound
brains then it should be passed entirely to the VI Service.
J W WILESMITH Epidemiology Unit 18 October 1991
Mr. R Bradley
cc: Mr. G A H Wells
3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would
by the end of the year, indentify the three brains that were from the
''POSITIVE'' end of the lesion spectrum.
*** OR-09: Canine spongiform encephalopathy—A new form of animal prion
disease ***
Monique David, Mourad Tayebi UT Health; Houston, TX USA
It was also hypothesized that BSE might have originated from an
unrecognized sporadic or genetic case of bovine prion disease incorporated into
cattle feed or even cattle feed contaminated with prion-infected human remains.1
However, strong support for a genetic origin of BSE has recently been
demonstrated in an H-type BSE case exhibiting the novel mutation E211K.2
Furthermore, a specific prion protein strain causing BSE in cattle is believed
to be the etiological agent responsible for the novel human prion disease,
variant Creutzfeldt-Jakob disease (vCJD).3 Cases of vCJD have been identified in
a number countries, including France, Italy, Ireland, the Netherlands, Canada,
Japan, US and the UK with the largest number of cases. Naturally occurring
feline spongiform encephalopathy of domestic cats4 and spongiform
encephalopathies of a number of zoo animals so-called exotic ungulate
encephalopathies5,6 are also recognized as animal prion diseases, and are
thought to have resulted from the same BSE-contaminated food given to cattle and
humans, although and at least in some of these cases, a sporadic and/or genetic
etiology cannot be ruled out. The canine species seems to display resistance to
prion disease and no single case has so far been reported.7,8 Here, we describe
a case of a 9 week old male Rottweiler puppy presenting neurological deficits;
and histological examination revealed spongiform vacuolation characteristic of
those associated with prion diseases.9 Initial biochemical studies using
anti-PrP antibodies revealed the presence of partially proteinase K-resistant
fragment by western blotting. Furthermore, immunohistochemistry revealed
spongiform degeneration consistent with those found in prion disease and
displayed staining for PrPSc in the cortex.
Of major importance, PrPSc isolated from the Rottweiler was able to cross
the species barrier transmitted to hamster in vitro with PMCA and in vivo (one
hamster out of 5). Futhermore, second in vivo passage to hamsters, led to 100%
attack rate (n = 4) and animals displayed untypical lesional profile and shorter
incubation period.
In this study, we show that the canine species might be sensitive to prion
disease and that PrPSc isolated from a dog can be transmitted to dogs and
hamsters in vitro using PMCA and in vivo to hamsters.
If our preliminary results are confirmed, the proposal will have a major
impact on animal and public health and would certainly lead to implementing new
control measures for ‘canine spongiform encephalopathy’ (CSE).
References 1. Colchester AC, Colchester NT. The origin of bovine spongiform
encephalopathy: the human prion disease hypothesis. Lancet 2005; 366:856-61;
PMID:16139661; http://
dx.doi.org/10.1016/S0140-6736(05)67218-2.
2. Richt JA, Hall SM. BSE case associated with prion protein gene mutation.
PLoS Pathog 2008; 4:e1000156; PMID:18787697; http://dx.doi.org/10.1371/journal.
ppat.1000156.
3. Collinge J. Human prion diseases and bovine spongiform encephalopathy
(BSE). Hum Mol Genet 1997; 6:1699-705; PMID:9300662; http://dx.doi.org/10.1093/
hmg/6.10.1699.
4. Wyatt JM, Pearson GR, Smerdon TN, Gruffydd-Jones TJ, Wells GA, Wilesmith
JW. Naturally occurring scrapie-like spongiform encephalopathy in five domestic
cats. Vet Rec 1991; 129:233-6; PMID:1957458; http://dx.doi.org/10.1136/vr.129.11.233.
5. Jeffrey M, Wells GA. Spongiform encephalopathy in a nyala (Tragelaphus
angasi). Vet Pathol 1988; 25:398-9; PMID:3232315; http://dx.doi.org/10.1177/030098588802500514.
6. Kirkwood JK, Wells GA, Wilesmith JW, Cunningham AA, Jackson SI.
Spongiform encephalopathy in an arabian oryx (Oryx leucoryx) and a greater kudu
(Tragelaphus strepsiceros). Vet Rec 1990; 127:418-20; PMID:2264242.
7. Bartz JC, McKenzie DI, Bessen RA, Marsh RF, Aiken JM. Transmissible mink
encephalopathy species barrier effect between ferret and mink: PrP gene and
protein analysis. J Gen Virol 1994; 75:2947-53; PMID:7964604; http://dx.doi.org/10.1099/0022-1317-
75-11-2947.
8. Lysek DA, Schorn C, Nivon LG, Esteve-Moya V, Christen B, Calzolai L, et
al. Prion protein NMR structures of cats, dogs, pigs, and sheep. Proc Natl Acad
Sci U S A 2005; 102:640-5; PMID:15647367; http://dx.doi.org/10.1073/pnas.0408937102.
9. Budka H. Neuropathology of prion diseases. Br Med Bull 2003; 66:121-30;
PMID:14522854; http://dx.doi.org/10.1093/bmb/66.1.121.
Monday, March 26, 2012
CANINE SPONGIFORM ENCEPHALOPATHY: A NEW FORM OF ANIMAL PRION DISEASE
http://caninespongiformencephalopathy.blogspot.com/2012/03/canine-spongiform-encephalopathy-new.html
Monday, March 8, 2010
Canine Spongiform Encephalopathy aka MAD DOG DISEASE
Wednesday, July 29, 2015
Acquired transmissibility of sheep-passaged L-type bovine spongiform
encephalopathy prion to wild-type mice
Wednesday, July 15, 2015
*** Additional BSE TSE prion testing detects pathologic lesion in unusual
brain location and PrPsc by PMCA only, how many cases have we missed?
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Posted by flounder on 03 Jul 2015 at 16:53 GMT
SEE FULL TEXT ;
Terry S. Singeltary Sr. Bacliff, Texas USA 77518
flounder9@verizon.net
