Exploring the risks of a putative transmission of BSE to new species
Enric Vidal, 1 Natalia Fernández-Borges, 2 Belén Pintado, 3 Montserrat
Ordóñez, 1 Mercedes Márquez, 4 Dolors Fondevila, 4 Hasier Eraña, 2 Juan María
Torres, 5 Martí Pumarola, 4 Joaquín Castilla 2, 6, *
Abstract
The prion responsible for the Bovine Spongiform Encephalopathy (BSE) shows
unique features when compared with other prions. One of these features is its
ability to infect almost all experimentally tested animal models. In the paper
published in The Journal of Neuroscience1 we describe a series of experiments
directed toward elucidating which would be the in vivo behavior of BSE if it
would infect dogs and rabbits, two alleged prion resistant species. Protein
misfolding cyclic amplification (PMCA) was used to generate canidae and
leporidae in vitro adapted BSE prions. A characterization of their in vivo
pathobiological properties showed that BSE prions were capable not only of
adapting to new species but they maintained, in the case of rabbits, their
ability to infect transgenic mice expressing human PrP. The remarkable
adaptation ability of certain prions implies that any new host species could
lead to the emergence of new infectious agents with unpredictable transmission
potential. Our results suggest that caution must be taken when considering the
use of any mammal derived protein in feedstuffs.
Perspectives
Bovine Spongiform Encephalopathy (BSE) is one of the most well-known animal
prion diseases.2 The “mad cow disease” outbreak had unprecedented consequences
regarding worldwide public health and food safety policies. The reason for this
was the ability of the agent causing BSE to transmit to species other than
cattle, its original host, including human beings.3 Enormous economical efforts
were directed toward controlling the disease in cattle with exceptional results.
Indeed, policies such as the ban on using ruminant protein on feed drastically
reduced the reported BSE cases in cattle. The compulsory testing of a large
number of animals allowed to accurately monitoring the success of such measures.
In every country where these policies have been implemented, the BSE cases are
practically down to zero. Thus, updated risk analyses point to a relaxation of
the control measures. 2
Thanks to the research efforts directed toward this subject, many
previously unknown aspects of this prion disease have came to light during the
last decade, for instance, the existence of the so called atypical BSE cases.4,5
Two cattle prions strains have been identified in aged cattle and named BSE-L
and BSE-H after the different electrophoretic pattern of its proteinase-K
digested disease-associated BSE prion protein (PrPd) on western blotting.
Epidemiology and pathological features of the diagnosed cases suggest that those
are probably sporadic prion diseases and evidence suggests that they might have
had a crucial role in the origin of the BSE epizooty.6,7 If these atypical
presentations are indeed sporadic prion diseases, such as the ones known in
humans, it implies that current BSE control measures will not be effective to
eradicate them. In other words, even though passive surveillance and withdrawal
of specified risk material should prevent transmission to humans and the ban on
the use of ruminant meat and bone meal in feedstuffs should avoid horizontal
transmission, sporadic cases will still occur so we will have to coexist with
cattle prions and the risks associated to them. 4
With the exception of these atypical BSE strains, all BSE cases diagnosed
in cattle have been classified as classical BSE, and for many years BSE was
believed to be caused by a single stable agent.2 This observation was due to the
homogeneity of biological and laboratorial features of the PrPd, a pathological
isoform of the host encoded cellular prion protein (PrPC), which is believed to
be the ethiological agent of transmissible spongiform encephalopathies (TSEs).8
BSE associated PrPd is characterized in western blotting by a three band pattern
between 18 and 30 kDa, present after Proteinase-K digestion, with a predominance
of a diglycosylated moiety.9 Also, BSE showed stable pathobiological features
upon transmission to wild type inbred mouse lines which allowed precise
identification of the strain based on brain lesions and PrPd deposition profiles
when assessed by immunohistochemistry (IHC).10-12 These experiments suggested a
link between vCJD and BSE.3 6
Experiments using transgenic mice expressing bovine PrP (TgBov mice)
further supported the idea that the BSE epizootic was caused by a single agent
with no strain diversity.13-16 Additionally, after interspecies transmission
when sheep passaged BSE was inoculated back into TgBov mice, the disease
exhibited typical features of BSE in this model, except for a reduced incubation
period when compared with cattle BSE.17 Surprisingly, inoculation with atypical
BSE isolates also showed features of classical BSE in this model, suggesting a
possible link between these strains.6,18,19 6
Interspecies transmission of prions is a phenomenon worth studying since
strain properties can be modified by new hosts. As an example, chronic wasting
disease (CWD) prions proved not to be transmissible to hamsters20 but, upon
transmission to ferrets, which were indeed susceptible, CWD prions could readily
infect hamsters.21 BSE has in fact been described to change, to a certain
extent, upon passage through species other than cattle, i.e., sheep. Passage
through sheep resulted in an increase of BSE virulence when inoculated into
TgBov mice.17 So, attention must be paid to the emergence of new prion strains
or the modifications that new hosts might pose to the pathobiological properties
of already known strains, particularly regarding the ability to transmit to
other species, including humans. 3
In vitro amplification of prions22 has proven to be an effective tool to
predict the in vivo behavior of certain prions.23,24 Not only does it accelerate
the transmission process but it also can be used to push the system, by
challenging healthy brain homogenates of different species with different prion
strains at high concentration and directly in a test tube, to find out what
would happen in case certain cross-species transmission of prions would occur in
nature. Several publications support protein misfolding cyclic amplification
(PMCA) ability to mimic potential in vivo scenarios. For instance, the
susceptibility of rabbits to prion diseases was predicted by PMCA and then
demonstrated in its natural host23 and, likewise, other species PrP could also
be misfolded in vitro including dogs and horses.25 4
In the paper published in The Journal of Neuroscience1 we describe a series
of experiments directed toward elucidating which would be the in vivo behavior
of BSE, one of the most relevant prions in Europe, in case it managed to cross
certain transmission barriers. The species chosen were dogs and rabbits for
several reasons, namely both are species in close contact with human beings and
no reports of prion susceptibility had been published at the time the
experiments were designed, thus they were species considered to be probably
prion resistant. 1
The experiments consisted in an initial in vitro phase in which dog and
rabbit normal brain homogenates were subjected to PMCA with a BSE seed. In a
second phase, the newly obtained prions were inoculated into TgBov mice and in a
transgenic model expressing human PrP (TgHum)26 to assess their in vivo behavior
in comparison to the original BSE seed. 1
Several interesting findings were obtained from that set of experiments. To
start with, BSE was the only prion strain that could be propagated in vitro in
both alleged resistant species, a capacity which lacked other prion strains
originated in other hosts, such as scrapie. The typical BSE biochemical
signature (western blotting) remained unchanged in both species even after
multiple in vitro amplification cycles.
Interestingly, the pathobiological features of these newly in vitro
obtained prions, such as their infectivity, incubation times, biochemical
profile, lesion profile, and etcetera were remarkably comparable to those of BSE
when bioassayed in transgenic mouse models overexpressing bovine and human PRNP.
Of particular interest were the bioassay results in tgHum mice which evidenced
the zoonotic potential of rabbit adapted BSE. Two out of nine inoculated TgHum
mice succumbed with a prion disease as confirmed by WB and immunohistochemical
techniques.
It is clear that the BSE strain has unique features when compared with
other prions, particularly in terms of disease phenotype stability and
permeability to different hosts. One can speculate that these differences must
reside in an also unique PrPSc structure; so unique that its conformation is
reproducible on a considerably wide range of amino acid sequences.11 This is not
the case for other prions, which upon interspecies transmission are not able to
maintain its strain characteristics. For instance, mouse adapted prions such as
139A and ME7 with a single species barrier crossing to the hamster model, a
rather similar species, undergo profound strain changes.27 2
To fully understand why certain prion conformations, such as that of the
BSE strain, remain unaltered in varying amino acid scenarios it is mandatory to
resolve its structure, probably with a resolution of a few nanometers, and
compare it to other prion strains. Only when this is achieved, a qualitative
leap will be attained to better comprehend the prion propagation mechanisms.
Previous studies had already reported that BSE is able to retain its
biochemical and biological properties upon interspecies passage through certain
species such as sheep,17,28 goats,29 felidae,30 mice11 or humans.3,31 Although
other authors have also reported that some biochemical features might change
after certain BSE interspecies transmissions such as in deer32 or when testing
certain transgenic mouse experimental models.33 9
Coexistence for centuries with animal prions, such as scrapie, without any
apparent risks to the human population was disturbed by the emergence of a
zoonotic prion disease in cattle: BSE. Of course, this new prion strain found
its way into the field leaded by mankind’s artificial husbandry practices. So at
this point any further intervention should be preceded by a meticulous
consideration of all the possible risks involved. Regulations regarding TSE
control and surveillance are being revised, predictably less surveillance will
be performed and the roadmap is leading toward a reintroduction of animal
derived protein in feedstuffs, provided that cannibalism does not happen, i.e.,
a determined species is not to be fed with formulas containing animal protein of
its own species. Thus, feeding any farmed animal with mammal derived protein is
to be banned yet, with the exception of pet-food [Regulation (EC) No 999/2001 in
the Official Journal of the European Communities]. Our results evidence that BSE
prions are capable not only of adapting to new species, even to those which
apparently are more resistant than others, but in doing so they maintain their
ability to infect human beings. And if, in an unlikely but yet possible case,
this should occur in the field, the resulting prion, as any other infectious
agent, might find its way to adapt and maybe evolve in a changing environment.
Eventually it might even lead to the emergence of new infectious agents with
unpredictable transmission potential. Given that spontaneous prions are out
there in the field, results such as the ones presented here suggest that caution
must be taken when considering the use of animal derived protein in feedstuffs.
A SPECIAL THANKS TO Joaquín Castilla ET AL, AND OF COURSE
www.landesbioscience.com et al. ...TSS
NOW, let us analyze some of these findings, from previous findings that
went ignored for all these years and decades, what I call ‘passing it around’.
...TSS
Subject: CANINE SPONGIFORM ENCEPHALOPATHY: A NEW FORM OF ANIMAL PRION
DISEASE
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.
***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.
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
Friday, March 8, 2013
Dogs may have been used to make Petfood and animal feed
SEE FULL TEXT ;
*** IN CONFIDENCE ***
*** SUSPECT BSE IN A HORSE ***
CYO BSE 1 9
IN CONFIDENCE
SUSPECT BSE IN A HORSE
The Parliamentary Secretary (Mr Maclean) will wish to be aware that, in
making his differential diagnosis, a veterinary surgeon in the Reading area has
included the possibility of BSE in a horse under his care. Although it is
unlikely to be BSE, because of the symptoms exhibited the veterinarian believes
that he cannot exclude the possibility. The case was brought to the notice of
one of the veterinary staff at the CVL by the owner's veterinary surgeon and
liaison is being maintained.
The horse in question is a five-year old eventing gelding which was
purchased by the present owner about four months ago. Approximately two months
after purchase the animal became a little apprehensive, developed mild nervous
symptoms and became over-sensitive to noise. The nervous symptoms have increased
and the horse is now practically impossible to ride. Investigations by the
owner's private veterinary surgeon are continuing but it is likely that the
animal will have to be destroyed.
If the horse should die or be destroyed, a full post-mortem examination
will be required for insurance purposes and will probably be carried out at a
non-Ministry laboratory. However, Mr Bradley of the Pathology Department, CVL,
has informed the private veterinary surgeon that he is willing to provide a
second opinion on the brain histology if requested.
I will keep the Parliamentary Secretary informed of any further
developments in the case.
I CRAWFORD
14 May 1990
Mr M P H Hill, PS/Parliamentary secretary (Mr Maclean) - by FAX
cc:
Private Offices
Mr K C Meldrum
Mrs E A J Attridge D J Evans Mr K C Taylor Mr R Lawson Mr R Bradley.
CVL
(hand written notes i cannot read all (cut short) as follows...tss)
The Parliamentary Secretary (Mr Maclean was grateful for this. He said that
we must keep very close to ...on it, and when the horse dies, or is put down we
must be told immediately. He also feels it is very important that our veterinary
staff be involved in the brain examination. .........(cannot read the rest
.............TSS)
90/05.14/10.1
Mr A Huws Principal WOAD2A CP2
SUSPECT BSE IN A HORSE
You will wish to be aware that on Thursday afternoon 25 June the T/DVO
Powys received a phone call from a veterinary Surgeon reporting his suspicion
that a horse had ___contracted BSE after having been fed cattle cake___.
The clinical symptoms described were similar to those shown by cattle there
___being a similar case some months ago on the same premises___.
The owner' s name and address is:
Irene Thomas J Thomas & Company Riding Stables Penybryn Llangorse
Brecon
The horse is a 12 year old gelding used for pony trekking.
By yesterday evening the horse was in a comatose state and on humane
grounds was destroyed by the veterinary Surgeon. At his request a full post
mortem and laboratory investigation will be carried out at the Carmarthen
Veterinary Investigation Centre this morning to ascertain the exact cause; I
have been told this will take at least two weeks. Charges to the veterinary
Surgeon have been waived in this instance.
I will inform you immediately I receive a diagnosis.
26 June 1990
D SUMMERS DRVO
cc
Mr D R Williams, RVO
Mr A R Hunter, SVIO
90/06.26/10.1
Mr A Huws Principal WOAD2A CP2
SUSPECT BSE IN A HORSE
You will wish to be aware that on Thursday afternoon 25 June the T/DVO
Powys received a phone call from a veterinary Surgeon reporting his suspicion
that a horse had contracted BSE after having been fed cattle cake. The clinical
symptoms described were similar to those shown by cattle there being a similar
case some months ago on the same premises.
The owner' s name and address is:
Irene Thomas J Thomas & Company Riding Stables Penybryn Llangorse
Brecon
The horse is a 12 year old gelding used for pony trekking.
By yesterday evening the horse was in a comatose state and on humane
grounds was destroyed by the veterinary Surgeon. At his request a full post
mortem and laboratory investigation will be carried out at the Carmarthen
Veterinary Investigation Centre this morning to ascertain the exact cause; I
have been told this will take at least two weeks. Charges to the veterinary
Surgeon have been waived in this instance.
I will inform you immediately I receive a diagnosis.
26 June 1990
D SUMMERS DRVO
cc
Mr D R Williams, RVO
Mr A R Hunter, SVIO
90/06.26/10.1
full text ;
we know that horses, especially quarter horses and show horses are fed feed
with high animal protein content, and it’s perfectly legal.
see ;
Nonprohibited Materials:
These feed materials CAN be fed to ruminants.
A. The following protein products derived from mammals, including
ruminants, are exempt from the Ruminant Feed Ban rule and CAN be fed to
ruminants:
Blood and blood products
Milk products (milk and milk protein)
Pure porcine (pork) protein
Pure equine (horse) protein
Gelatin Inspected meat products, such as plate waste, which have been
cooked and offered for human food and further heat processed for animal feed.
snip... see full text ;
From: TSS
Subject: MAD COW/HORSE FEED BAN VIOLATIONS WARNING LETTER July 20, 2001 USA
Date: August 14, 2001 at 11:36 am PST
DEPARTMENT OF HEALTH AND HUMAN SERVICE
July 20, 2001
CERTIFIED MAIL RETURN RECEIPT REQUESTED
WARNING LETTER Ref. KAN 2001-028
Mr. Eric N. Blomkuist, CEO Farnam Companies, Inc. 301 W. Osborn P.O. Box
34820 Phoenix, AZ 85013
Dear Mr. Blomkuist:
An inspection of your Council Bluffs, Iowa facility that serves as a
manufacturing/repackaging site for animal feed and as a distribution operation
for animal drugs and feeds conducted on June 13-20, 2001 by an Investigator
representing this office found significant deviations from the requirements set
forth in Title 21, Code of Federal Regulations, Part 589.2000 - Animal Proteins
Prohibited in Ruminant Feed. This regulation is intended to prevent the
establishment and amplification of Bovine Spongiform Encephalophathy (BSE)
within the borders of the United States. Such deviations cause products being
manufactured and/or distributed by your facility to be adulterated within the
meaning of Section 402(a)(4) and misbranded within the meaning of Section 403(F)
of the Federal Food, Drug, and Cosmetic Act (the Act).
The inspection revealed the following:
There are no written procedures demonstrating the clean-out process used to
prevent the cross- contamination of product. Your firm uses common equipment for
product manufactured with prohibited material and for feed and/or drugs that are
not.
Your firm distributes products that may contain prohibited material,
specifically Flex Free, Equinyl, Generation and Max Flex, that are not labeled
with the required cautionary statement "Do Not Feed to Cattle or Other
Ruminants"
The above is not intended to be an all-inclusive list of violations. As a
manufacturer of products intended for animal feed use you are responsible for
assuring that your overall operation and the products you manufacture and
distribute are in compliance with the law. At the conclusion of the inspection
Form FDA483, List of Inspectional Observations was issued to Ronald G. Adler,
Plant Manager identifying these and other deviations. A copy is enclosed for
your information.
Our Investigator reported a telephone discussion with Mr. Barry G. Harrison
who identified himself as the Corporate Counsel of the Farnam Companies, Inc.
During this discussion Mr. Harrison, reportedly, claimed the products in
question are exempt from the cautionary statement requirement. This claimed
exemption is based on the fact the products are intended only for the equine
market and your firm defines horses as pets. We cannot accept this claimed
exemption because while some horses may be held as pets, horses are also working
animals and in some parts of North America, food animals.
Based on our knowledge of working ranches, horse feed is often stored in
the same general area as ruminant feed making a conspicuous cautionary statenmit
vital on feeds and supplements, containing prohibited materials.
You should take prompt action to correct the above violations and to
establish procedures whereby such violations do not recur. Failure to make
immediate and lasting corrections may result in regulatory actions without
further notice including but not limiting to product seizure and/or injunction.
You should respond, in writing, Within 15 working days of the steps you
have taken to bring your firm into compliance with the law. Please include all
the steps you plan to take, the timeframe for completing these actions and any
documentation demonstrating the action's completion.
Your response should be directed to Ralph J. Gray, Compliance Officer at
the above address.
Sincerely, Charles W. Sedgwick District Director Kansas City District
Office
Cc: Mr. John C. Williams CEO, Manufacturing and Distribution Farnam
Companies, Inc, 1302 Law Ross Road Council Bluffs, IA 51501
Subject: Re: MAD COW/HORSE FEED BAN VIOLATIONS WARNING LETTER July 20, 2001
Date: Tue, 14 Aug 2001 23:43:26 –0400
From: "Robert A. LaBudde"
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######## Bovine Spongiform Encephalopathy #########
At 01:41 PM 8/14/01 -0700, Terry wrote: >DEPARTMENT OF HEALTH AND HUMAN
SERVICE > >July 20, 2001 > >Our Investigator reported a telephone
discussion with Mr. Barry G. >Harrison who identified himself as the
Corporate Counsel of the Farnam >Companies, Inc. During this discussion Mr.
Harrison, reportedly, claimed >the products in question are exempt from the
cautionary statement >requirement. This claimed exemption is based on the
fact the products >are intended only for the equine market and your firm
defines horses as >pets. We cannot accept this claimed exemption because
while some horses >may be held as pets, horses are also working animals and
in some parts >of North America, food animals. > >Based on our
knowledge of working ranches, horse feed is often stored in >the same general
area as ruminant feed making a conspicuous cautionary >statenmit vital on
feeds and supplements, >containing prohibited materials.
Terry:
Perhaps you should pester FDA about this "loophole". Apparently, "pet food"
does not have to bear the warning labels specified for food animals.
I can't see any serious objection to expanding the label requirement to ALL
animal food, not just food animals.
Also, horses are "ruminants", so it's disturbing that they might escape the
feed ban by being classified as "pets". Another good reason to extend the
warning labels and regulation to all animal foods.
Perhaps you could submit a request for ruling to the FDA on this issue to
propose amending the regulation to include all animal foods, including pet
foods.
================================================================
Robert A. LaBudde, PhD, PAS, Dpl. ACAFS e-mail: ral@lcfltd.com Least Cost
Formulations, Ltd. URL: http://lcfltd.com/ 824
Timberlake Drive Tel: 757-467-0954 Virginia Beach, VA 23464-3239 Fax:
757-467-2947
"Vere scire est per causas scire"
=========================end...tss=====================
It has become appallingly obvious that our technology has exceeded our
humanity.
Albert Einstein
Stupid is, as stupid does, and some times you just can’t fix stupid $$$
never say never with TSE Prions. ...TSS
Thursday, January 5, 2012 Horse Meat, slaughter for consumption USA
Horse slaughter in Texas and everywhere else should be against the law
http://equinespongiformencephalopathy.blogspot.com/2012/01/horse-meat-slaughter-for-consumption.html
FELINE SPONGIFORM ENCEPHALOPATHY FSE
From: Terry S. Singeltary Sr.
Sent: Friday, March 16, 2012 10:09 AM
Subject: [BSE-L] Rabbits are not resistant to prion infection
Rabbits are not resistant to prion infection
Francesca Chianinia,1, 1.. Natalia Fernández-Borgesb,c,1, 2.. Enric Vidald, 3.. Louise Gibbarda, 4.. Belén Pintadoe, 5.. Jorge de Castroc, 6.. Suzette A. Priolaf, 7.. Scott Hamiltona, 8.. Samantha L. Eatona, 9.. Jeanie Finlaysona, 10.. Yvonne Panga, 11.. Philip Steelea, 12.. Hugh W. Reida, 13.. Mark P. Dagleisha, and 14.. Joaquín Castillab,c,g,2
+ Author Affiliations
1.. aMoredun Research Institute, Penicuik, Near Edinburgh EH26 0PZ, Scotland, United Kingdom; 2.. bCIC bioGUNE, Derio 48160, Bizkaia, Spain; 3.. gIKERBASQUE, Basque Foundation for Science, Bilbao 48011, Bizkaia, Spain; 4.. cDepartment of Infectology, Scripps Florida, Jupiter, FL 33458; 5.. fLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; 6.. dCentre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; and 7.. eCentro Nacional de Biotecnología (CNB), 28049 Cantoblanco, Madrid, Spain 8.. Edited by Reed B. Wickner, National Institutes of Health, Bethesda, MD, and approved February 16, 2012 (received for review December 6, 2011)
Abstract
The ability of prions to infect some species and not others is determined by the transmission barrier. This unexplained phenomenon has led to the belief that certain species were not susceptible to transmissible spongiform encephalopathies (TSEs) and therefore represented negligible risk to human health if consumed. Using the protein misfolding cyclic amplification (PMCA) technique, we were able to overcome the species barrier in rabbits, which have been classified as TSE resistant for four decades. Rabbit brain homogenate, either unseeded or seeded in vitro with disease-related prions obtained from different species, was subjected to serial rounds of PMCA. De novo rabbit prions produced in vitro from unseeded material were tested for infectivity in rabbits, with one of three intracerebrally challenged animals succumbing to disease at 766 d and displaying all of the characteristics of a TSE, thereby demonstrating that leporids are not resistant to prion infection. Material from the brain of the clinically affected rabbit containing abnormal prion protein resulted in a 100% attack rate after its inoculation in transgenic mice overexpressing rabbit PrP. Transmissibility to rabbits (>470 d) has been confirmed in 2 of 10 rabbits after intracerebral challenge. Despite rabbits no longer being able to be classified as resistant to TSEs, an outbreak of “mad rabbit disease” is unlikely.
a.. in vitro replication b.. scrapie c.. transmissible spongiform encephalopathy
Footnotes
a.. ↵1F.C. and N.F.-B. contributed equally to this work.
b.. ↵2To whom correspondence should be addressed. E-mail: castilla@joaquincastilla.com a.. Author contributions: F.C., N.F.-B., S.A.P., and J.d.C. designed research; F.C., N.F.-B., E.V., L.G., B.P., J.d.C., S.A.P., S.H., S.L.E., J.F., Y.P., P.S., H.W.R., M.P.D., and J.C. performed research; F.C., N.F.-B., E.V., S.A.P., and J.C. contributed new reagents/analytic tools; F.C., N.F.-B., E.V., S.A.P., and J.C. analyzed data; and F.C., N.F.-B., S.A.P., H.W.R., M.P.D., and J.C. wrote the paper.
b.. The authors declare no conflict of interest.
c.. This article is a PNAS Direct Submission.
a.. This article contains supporting information online at
Wednesday, October 30, 2013
SPECIFIED RISK MATERIAL (SRM) CONTROL VERIFICATION TASK FSIS NOTICE 70-13
10/30/13
Saturday, November 2, 2013
APHIS Finalizes Bovine Import Regulations in Line with International Animal
Health Standards while enhancing the spread of BSE TSE prion mad cow type
disease around the Globe
Friday, October 25, 2013
UK FSA TSE BSE Board meeting agenda: 5 November 2013
Thursday, June 6, 2013
FSA MORE BSE MAD COW CONTROL BREACHES JUNE 2013
Wednesday, September 25, 2013
Inspections, Compliance, Enforcement, and Criminal Investigations BSE TSE
PRION 2013
Sunday, September 25, 2011
Clinical Heidenhain Variant Of Sporadic Creutzfeldt-Jakob Disease (CJD)
With Co-occurrence Of Prion Protein Types 1 and 2
COEXISTENCE OF TSE PRION DISEASE
greetings cjd world,
I find this very interesting, this coesistence of different TSE prion
strains from different TSE sources. this new/old study out reminds me of way
back ;
According to Professor James Ironside of the National CJD Surveillance
Unit, Miss Rimmer's case was "unique" and tests showed signs of both vCJD and
new variant CJD.
"Our understanding of the case is not complete. It is one of the most
unusual and difficult cases I have ever come across," he explained.
"The characteristics of the disease suffered by Miss Rimmer do not fall
neatly into any category.
"The investigations that we have performed so far would indicate that this
case, unique as it is, has more similarities to sporadic CJD than to new
variant."
snip...
Mr Hughes returned a verdict of death by natural causes and concluded that
Miss Rimmer died of bronchial pneumonia caused by CJD. ...
SEE ;
Wednesday, October 09, 2013
WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281
in compensation REVISED
Thursday, October 10, 2013
CJD REPORT 1994 increased risk for consumption of veal and venison and lamb
Monday, October 14, 2013
Researchers estimate one in 2,000 people in the UK carry variant CJD
proteins
Friday, August 16, 2013
*** Creutzfeldt-Jakob disease (CJD) biannual update August 2013 U.K. and
Contaminated blood products induce a highly atypical prion disease devoid of
PrPres in primates
WHAT about the sporadic CJD TSE proteins ?
WE now know that some cases of sporadic CJD are linked to atypical BSE and
atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all
it’s sub-types $$$
Sunday, August 11, 2013
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing
an extreme increase of 48% between 2008 and 2010
Sunday, October 13, 2013
CJD TSE Prion Disease Cases in Texas by Year, 2003-2012
Tuesday, September 24, 2013
NORDION (US), INC., AND BIOAXONE BIOSCIENCES, INC., Settles $90M Mad Cow
TSE prion Contamination Suit Cethrin(R)
Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 1
of 15
with great sadness and disgust, I must inform you that our federal
government has failed us again, and chose the industry over sound science, with
regards to TSE prion disease, aka mad cow type disease...tss
Saturday, November 2, 2013
APHIS Finalizes Bovine Import Regulations in Line with International Animal
Health Standards while enhancing the spread of BSE TSE prion mad cow type
disease around the Globe
our society has failed terribly, to a point of being sick...very
sick.
thanks to our fine friends at the CDC and there attempt at a sick Halloween
prank with comparing this ever sickening movie world of the zombies, to our
loved ones that did die from a prion disease, we have to now put up with crap
like this zombie prion every year now. I think the CDC et al that came up with
this should be fired. ...
Tuesday, October 29, 2013
CDC keeps eye on zombie disease
Dr. Christopher Ziebell, director of the Emergency Medical Department at
University Medical Center Brackenridge says there are several diseases that
cause patients to exhibit zombie-like behavior.
One is the human equivalent of mad cow disease called Creutzfeldt-Jakob
disease.
kind regards, terry
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