Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 1
of 15
UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF FLORIDA Ft. Lauderdale
Division
CASE NO.
BIOAXONE BIOSCIENCES, INC., a Florida corporation, as successor in interest
to Bioaxone Therapeutic, Inc., a Canadian Business corporation, Plaintiff,
v.
NORDION (US), INC., a Delaware corporation, formerly known as MDS, INC.;
and RICERCA BIOSCIENCES, LLC., a Delaware Limited Liability Company, as
successor in interest to MDS PHARMA SERVICES, INC., a Nebraska corporation,
Defendants.
Plaintiff, BIOAXONE BIOSCIENCES, INC., a Florida corporation with its
principal place of business in Ft. Lauderdale, Florida ("Bioaxone" or
"Plaintiff")!, by and through its undersigned counsel, files this civil action
against Defendant, NORDION (US), INC., a lBioAxone acquired all of the assets,
including all rights to the drug Cethrin, from BioAxoneTherapeutique, Inc., a
Canadian business corporation (''Therapeutique''). Therapeutique conveyed all of
its intellectual property, as well as the name "Cethrin" to BioAxone.
Therapeutique also transferred all rights in the clinical trial of Cethrin,
including the Clinical Master Trial File, the investigation of a new drug (INO)
file with the FDA, and the Clinical Trial Application (CTA) with Health Canada.
Therefore, BioAxone is the successor in interest to all rights previously owned
by' Therapeutique.
Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 2
of 15
Delaware corporation ("Nordion"), formerly known as MDS, INC., with its
principal place of business in Ottawa, Ontario; and RICERCA BIOSCIENCES, LLC., a
Delaware limited liability company with its principal place of business in
Concord, Ohio ("Ricerca"), as the successor in interest of MDS PHARMA SERVICES,
INC., a Nebraska corporation, ("MDS"); collectively referred to as the
"Defendants." NORDION is a foreign corporation authorized to transact business
in the State of Florida. MDS PHARMA SERVICES, INC. was a wholly owned subsidiary
of MDS, INC., now known as NORDION (US), INC., and was a foreign corporation
authorized to do and doing business in the State of Florida. RICERCA is a
foreign limited liability company authorized to transact business in the State
of Florida which is the successor in interest to MDS PHARMA SERVICES, INC.,
through its purchase and acquisition of MDS PHARMA SERVICES, INC., on or about
March 2010.
1. This is an action for negligence against the Defendants arising from the
improper and negligent use of contaminated material in the preparation of the
Bacterial Master Cell Bank ("MCB") for a new breakthrough drug, Cethrin" (BA-21
0), researched and developed by BIOAXONE. Cethrin is a biologic drug that will
provide the most advanced treatment for patients who have suffered acute spinal
cord injury. Defendants negligently prepared the MCB using kanamycin they
purchased that was made in China and that contained beef broth and avian
products. The MCB is contaminated with beef broth and avian products that cause
human disease including bovine spongiform encephalopathy ("BSE"), commonly known
as mad cow disease, which created an unreasonably dangerous risk of the
development of BSE in patients to whom the Cethrin made from the contaminated
MCB would be administered.
Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 3
of 15
2. This Court has subject matter jurisdiction pursuant to 28 V.S.C. § 1332
because the matter in controversy exceeds the minimum jurisdictional
requirements of this Court and because the Plaintiff is a citizen of a state
different from the Defendants.
3. Venue for this action is proper in this Court because each Defendant
holds a certificate of authority to transact business in Florida. is registered
to transact business in Florida. and Plaintiff resides and transacts business in
this District. Many of the acts that are alleged in this Complaint occurred in
this District and at least one of the Defendants can be found, resides, or
transacts business in this District.
4. At all times material hereto, the parties hereto transacted business
related to Cethrin in Florida by and through their employees and/or agents
including but not limited to participating in telephonic and in person meetings,
correspondence, and making and/or accepting payments.
5. MDS PHARMA SERVICES, INC., was a wholly owned subsidiary of MDS, INC.,
now known as Defendant, NORDION. As its wholly owned subsidiary, NORDION,
exercised extensive control over MDS PHARMA SERVICES and, as such, MDS PHARMA
SERVICES, served as the agent or apparent agent of NORD ION. In addition,
NORDION sells its products in Florida and as such its products are in the stream
of commerce throughout the State of Florida. PARTIES
6. At all times material hereto, Plaintiff, BIOAXONE, was and is the owner
and developer of Cethrin, a new breakthrough biologic drug providing treatment
for patients who have suffered acute spinal cord injury. Defendant, MDS was
retained by BIOAXONE to create, prepare, and qualify a Bacterial Master Cell
Bank to be used in the development of Cethrin.
7. At all times material hereto, Defendant, MDS PHARMA SERVICES, INC.,
provided discovery, pre-clinical studies, and clinical trial services to
biopharmaceutical and biotechnology companies incorporated and doing business in
Florida. such as BIOAXONE.
SNIP...
27. On or about October 16, 2008, a formal status report was provided to
BIOAXONE during which BIOAXONE was informed, for the first time, that the MCB
was not GMP compliant.
28. At all times prior to October 16, 2008, MDS/RICERCA had actual or
constructive knowledge that the kanamycin it purchased and used in the
preparation of the MCB for BIOAXONE was contaminated and was not fit or intended
for use in humans.
29. At all times prior to October 16,2008, MDS/RICERCA had actual or
constructive knowledge that the purchase and use of contaminated kanamycin in
the preparation of the MCB for BIOAXONE created an unreasonably dangerous and
foreseeable risk of adventitious agents that cause human disease including the
development of BSE or mad cow disease in humans.
30. At all times material hereto, MDS/RICERCA knew that the preparation of
the MCB for
Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 9
of 15
BIOAXONE was for use in the development of a biologic drug, Cethrin, to be
administered to humans.
31. At all times prior to October 16, 2008, MDS/RICERCA had actual or
constructive knowledge that the purchase and use of contaminated kanamycin in
the preparation of the MCB for BIOAXONE created a foreseeable risk that the FDA
would deem Cethrin adulterated and cause the FDA and/or any other regulatory
agency to fail to approve its use as a drug product to be administered to human
patients.
32. At all times material hereto, MDS/RICERCA knew or should have known
that it had a continuing duty to follow and comply with the GMPs in the
preparation of the MCB. In addition to ensuring compliance with the GMPs,
MDS/RICERCA had a duty to follow its own standard operating procedures and
quality assurance standards in its purchase and use of animal-free raw materials
in the preparation and qualification of the MCB for BIOAXONE.
33. Despite its actual or constructive knowledge of its use of the
contaminated kanamycin in the preparation of the MCB, MDS/RICERCA failed to
diligently, timely, properly or otherwise inform BIOAXONE that the kanamycin
used in the preparation and qualification of the MCB was animal-derived, was not
fit or intended for human use, and, as a result, had contaminated the MCB.
The Clerk shall CLOSE this case. Any party may move to re-open the case if
there is a problem in reaching a final settlement agreement. Any pending motions
are DENIED as moot. DONE and ORDERED in chambers, at Miami, Florida on September
19,2013.
Case 0:12-cv-60739-RNS Document 115 Entered on FLSD Docket 09/20/2013 Page
1 of 1
Case No. 12-60739-Civ-SCOLA/ROSENBAUM
vs.
Nordion Inc. f/k/a/ MDS Inc.; Nordion (Canada) Inc. f/k/a/ MDS (Canada)
Inc.; and Nordion (US) Inc. f/k/a MDS Pharma Services (US) Inc., Defendants.
THIS MA TIER is before the Court upon Plaintiff notifying the Court that a
settlement had been reached with the remaining Defendants. The parties have
settled this matter, and it will be administratively closed pending the filing
of a stipulation of [mal dismissal, pursuant to Federal Rule of Civil Procedure
41 (a)(l )(A)(ii), or the Plaintiff moving for dismissal pursuant to Rule
41(a)(2). A stipulation of [mal dismissal, or a motion for dismissal, shall be
filed by October 18, 2013. If the parties file a stipulation of final dismissal
pursuant to Rule 41(a)(l)(A)(ii) and wish to have this Court retain jurisdiction
to enforce their settlement, the parties must include the following sentence in
their stipulation of dismissal: "The effectiveness of this stipulation of
dismissal is conditioned upon the Court's entry of an order retaining
jurisdiction to enforce the terms of the settlement agreement reached in this
case." See Anago Franchising, Inc. v. Shaz, LLC, 677 F.3d 1272, 1280 (11th Cir.
2012). This sentence is required because a joint stipulation of dismissal is
otherwise self-executing and deprives the Court of jurisdiction to do anything
further. See id.
The Clerk shall CLOSE this case. Any party may move to re-open the case if
there is a problem in reaching a final settlement agreement. Any pending motions
are DENIED as moot. DONE and ORDERED in chambers, at Miami, Florida on September
19,2013.
ROBERT N. SCOLA, JR.
Nordion Settles $90M Mad Cow Contamination Suit
By Juan Carlos Rodriguez 0 Comments Law360, New York (September 23, 2013,
1:52 PM ET) -- Nordion Inc. on Thursday settled a $90 million lawsuit filed by
Bioaxone Biosciences Inc. accusing it of contaminating the development of a
spinal cord injury drug with animal products that could cause mad cow disease,
leading federal regulators to deny the drug’s approval.
No details about the settlement in Florida federal court were available
Monday, but U.S. District Judge Robert N. Scola ordered the case closed based on
Bioaxone’s notice of settlement. He said if there was a problem finalizing the
settlement, either party could move...
Medical Co. Launches $90M Suit Over Mad Cow Contamination
By Juan Carlos Rodriguez
Law360, New York (April 26, 2012, 6:09 PM ET) -- Bioaxone Biosciences Inc.
on Thursday sued two partners for $90 million for allegedly contaminating the
development of a spinal cord injury drug with animal products that could cause
mad cow disease, leading the U.S. Food and Drug Administration to deny the
drug's approval.
Nordion and BioAxone BioSciences Reach an Agreement to Settle Claims by
Business Wire via The Motley Fool Sep 24th 2013 7:49AM
Updated Sep 24th 2013 7:50AM Nordion and BioAxone BioSciences Reach an
Agreement to Settle Claims
OTTAWA, Canada--(BUSINESS WIRE)-- Nordion Inc. (TSX:NDN) (NYS: NDZ) has
reached an agreement to settle claims filed against Nordion and its subsidiaries
by BioAxone BioSciences, Inc. ("BioAxone") for a nominal amount. The parties are
finalizing the settlement documents, which are expected to be
confidential.
During fiscal 2012, Nordion was served with a Complaint relating to the
Company's former MDS Pharma Services business. This legal action, commenced by
BioAxone in Florida, related to the preparation and qualification of a Bacterial
Master Cell Bank relating to the development of a biologic drug. BioAxone
further alleged that it had suffered damages in an amount greater than US$90
million.
The settlement is expected to have a non material impact on Nordion's
financial position, which the Company intends to report in its fourth quarter
fiscal 2013 results.
About Nordion Inc.
Nordion Inc. (TSX:NDN) (NYS: NDZ) is a global health science company that
provides market-leading products used for the prevention, diagnosis and
treatment of disease. We are a leading provider of medical isotopes and
sterilization technologies that benefit the lives of millions of people in more
than 40 countries around the world. Our products are used daily by
pharmaceutical and biotechnology companies, medical-device manufacturers,
hospitals, clinics and research laboratories. Nordion has approximately 450
highly skilled employees in three locations. Find out more at www.nordion.com
and follow us at
http://twitter.com/NordionInc.
Forward-Looking Statements
Certain statements contained in this news release constitute
"forward-looking statements" relating to an agreement to settle a claim against
Nordion and its subsidiaries and the settlement's impact on Nordion's financial
position. These statements are based on current beliefs and assumptions of
management, however are subject to known and unknown risks, uncertainties and
other factors that may cause actual results to differ materially from the
forward-looking statements in this news release as the settlement documents have
not yet been finalized and the Company is in the middle of its fourth quarter
and results are not yet available.
For additional information with respect to certain of these and other
beliefs, assumptions, risks and uncertainties, please refer to Nordion's Annual
Information Form for fiscal 2012 available on SEDAR at www.sedar.com and on
EDGAR on www.sec.gov. These documents are also available on Nordion's website at
www.nordion.com.
Nordion INVESTORS: Ana Raman, 613-595-4580 investor.relations@nordion.com
or MEDIA: Shelley Maclean, 613-592-3400 x 2414 shelley.maclean@nordion.com
KEYWORDS: North America Canada
INDUSTRY KEYWORDS:
The article Nordion and BioAxone BioSciences Reach an Agreement to Settle
Claims originally appeared on Fool.com.
BioAxone receives FDA approval for acute spinal cord injury trial MONTREAL,
Jan. 11 /CNW Telbec/ -
BioAxone Therapeutic Inc. has announced that the US Food and Drug
Administration (FDA) Centre for Drug Evaluation and Research has approved the
Company's investigational new drug (IND) application for Cethrin(R) (BA-210) in
acute spinal cord injury (SCI). The Company had previously received approval
from Health Canada for initiation of its clinical program with Cethrin(R) in
Canada. The approval of the IND submission paves the way for the initiation of
the human clinical trial program in the USA.
BioAxone will assess the safety and efficacy of several doses of BA-210 in
this clinical trial. The trial will enroll up to 48 patients with complete,
thoracic or cervical SCI who have no motor or sensory function in the sacral
segment of their spinal cord, and who are scheduled to undergo spinal
decompression surgery within 7 days of their injury.
"BA-210 is a recombinant protein which acts as a Rho antagonist to promote
neurogeneration and neuroprotection in the Central Nervous System (CNS). It has
been designed by BioAxone to penetrate CNS tissue and is being developed for
delivery at the site of spinal cord injury during surgical intervention," said
Dr. Henry E. Khouri, Vice-President of Clinical Development at BioAxone.
"We are excited about the potential of this treatment," said the study
Principal Investigator, Dr. Michael Fehlings, Neurosurgeon and Medical Director,
Krembil Neuroscience Center, Toronto Western Hospital and Professor of
Neurosurgery, University of Toronto.
"The delivery of Cethrin(R) represents a unique approach to this treatment
as it requires a single application, is non-invasive and will minimize risk to
patients," Dr. Fehlings added. "As the Company's first approved IND application,
this is a significant and exciting milestone for BioAxone. We are eager to start
the study in the US," Dr. Khouri added.
About BioAxone. BioAxone Therapeutic is a privately held neuroscience
Company based in Montreal, whose goal is to develop and commercialize products
which meet significant medical needs in spinal cord injury and retinal eye
diseases, such as macular degeneration. The Company specializes in the
development and commercialization of proprietary technologies that target Rho
signaling. Other products in the development stage are second-generation
recombinant protein compounds. The Company also has small molecule Rho kinase
inhibitors under preclinical investigation.
BioAxone Therapeutic Study Demonstrates Positive Interim Results for Spinal
Cord Injury Six-week Follow-up Results of Phase I/IIa Trial Show Safety,
Tolerability and Neurological Outcome of Cethrin(R)
MONTREAL, Nov. 27 /PRNewswire/ -
BioAxone Therapeutic announced today positive interim results on its Phase
I/IIa North American dose escalation clinical trial on Cethrin(R) for the
treatment of acute spinal cord injury (SCI). The Company reported that data on
safety, tolerability and neurological outcome from the six-week follow-up of the
trial of Cethrin(R) at four dose levels (0.3, 1, 3 and 6 mg) indicates that this
treatment is safe and well tolerated and that the functional benefit may be dose
dependent.
The twelve-month study is evaluating 37 patients from 9 centers in the U.S.
and Canada who suffered a complete thoracic or cervical injury (i.e. ASIA Grade
A, having no sensory or motor function below the level of the spinal cord
injury).
"We have now passed the most critical period of observation regarding the
safety of Cethrin(R) with more than half of the patients having completed their
six-month follow-up. None of the patients has shown any adverse events related
to the administration of this drug and the outcome continues to be encouraging
for patients who have completed the six-month follow-up," said Dr. Michael
Fehlings, the lead investigator for the study. Dr. Fehlings is a Professor of
Neurosurgery at the University of Toronto and holds the Krembil Chair in Neural
Repair and Regeneration at Toronto Western Hospital.
The trial is not placebo controlled but has an efficacy component based on
the American Spinal Injury Association's (ASIA) scale which is designed to
assess sensory and motor function in patients. In this trial, 31% of patients,
after six weeks, recovered some sensory and/or motor function below the level of
their injury and converted from a complete injury to an incomplete injury.
"We are excited about Cethrin(R)'s excellent safety profile and the
neurological outcomes observed to date," said Dr. Frank Bobe, President and CEO
of BioAxone. "BioAxone is at the frontier of this new science and we are
actively looking for commercial partners to join us in accelerating the
development of Cethrin(R)."
Cethrin(R) is a recombinant protein that is topically delivered onto the
spinal cord during decompression/stabilization surgery. "Cethrin(R) is the first
of a new class of drugs that is specifically designed to penetrate cells and
inhibit Rho, a signaling master switch whose activation triggers cell death and
exacerbates spinal cord damage following injury," said Dr. Patrick Tremblay,
Vice President of Research and Development at BioAxone.
There are currently no effective therapies for spinal cord injury and the
nearly 12,000 new patients each year in North America alone. Despite significant
scientific breakthroughs existing clinical interventions remain limited to
reducing local inflammation of the spinal cord.
About Cethrin(R)
Cethrin(R)'s active ingredient, BA-210, is a recombinant protein which acts
as a Rho GTPase antagonist to promote neuroprotection and neuroregeneration in
the central nervous system (CNS). It was engineered by BioAxone to effectively
penetrate into CNS tissue, where it has been clearly shown to elicit the rescue
and repair of damaged neurons in preclinical animal models. To obtain
Cethrin(R), BA-210 is mixed with a commercially available fibrin sealant,
Tisseel(R), and is delivered in a single dose directly onto the dura mater of
the spinal cord during decompression/stabilization surgery. Cethrin(R) was
granted orphan drug status by the U.S. Food and Drug Administration (FDA) in
December 2005.
About BioAxone Therapeutic
BioAxone is a privately owned neuroscience company specializing in the
development and commercialization of proprietary technologies that target Rho
signaling. Established in April 2000 and headquartered in Montreal, Canada,
BioAxone has demonstrated expertise in recombinant protein product development
and has a focused small-molecule program. SOURCE BIOAXONE THERAPEUTIC INC.
Greetings,
JUST MAKES me mad as hell. all these damn tort laws to protect the
companies that expose you to this crap, to where if you are exposed and or even
if you go on later and have the disease and die, TORT laws again protect the
company that manufactures these products. but yet, the company or industry can
suit each other at will, win 90 MILLION dollar verdicts (or whatever they got in
this case) over potential mad cow tainted product, but yet, when the consumers
consume, and are then exposed, and or infected, you just have more TORT REFORM,
to these blatant acts of greed, and not much recourse. this is not right. ...
================================================
BioAxone Therapeutic Inc. has announced that the US Food and Drug
Administration (FDA) Centre for Drug Evaluation and Research has approved the
Company's investigational new drug (IND) application for Cethrin(R) (BA-210) in
acute spinal cord injury (SCI). The Company had previously received approval
from Health Canada for initiation of its clinical program with Cethrin(R) in
Canada. The approval of the IND submission paves the way for the initiation of
the human clinical trial program in the USA.
BioAxone will assess the safety and efficacy of several doses of BA-210 in
this clinical trial. The trial will enroll up to 48 patients with complete,
thoracic or cervical SCI who have no motor or sensory function in the sacral
segment of their spinal cord, and who are scheduled to undergo spinal
decompression surgery within 7 days of their injury.
"BA-210 is a recombinant protein which acts as a Rho antagonist to promote
neurogeneration and neuroprotection in the Central Nervous System (CNS). It has
been designed by BioAxone to penetrate CNS tissue and is being developed for
delivery at the site of spinal cord injury during surgical intervention," said
Dr. Henry E. Khouri, Vice-President of Clinical Development at BioAxone.
31. At all times prior to October 16, 2008, MDS/RICERCA had actual or
constructive knowledge that the purchase and use of contaminated kanamycin in
the preparation of the MCB for BIOAXONE created a foreseeable risk that the FDA
would deem Cethrin adulterated and cause the FDA and/or any other regulatory
agency to fail to approve its use as a drug product to be administered to human
patients.
================================================
JUST WHAT ABOUT USA TISSUE DONOR HERDS ???
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
Greetings List Members,
I was lucky enough to sit in on this BSE conference call today and even
managed to ask a question. that is when the trouble started.
I submitted a version of my notes to Sandra Blakeslee of the New York
Times, whom seemed very upset, and rightly so.
"They tell me it is a closed meeting and they will release whatever
information they deem fit. Rather infuriating."
and i would have been doing just fine, until i asked my question. i was
surprised my time to ask a question so quick.
(understand, these are taken from my notes for now. the spelling of names
and such could be off.)
[host Richard Barns] and now a question from Terry S. Singeltary of CJD
Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for
serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have
him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue
donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD
world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
from this point, i was still connected, got to listen and tape the whole
conference. at one point someone came on, a woman, and ask again;
SNIP...SEE FULL TEXT ;
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Monday, August 26, 2013
***The Presence of Disease-Associated Prion Protein in Skeletal Muscle of
Cattle Infected with Classical Bovine Spongiform Encephalopathy
Monday, March 19, 2012
***Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform
Encephalopathy PLoS One. 2012; 7(2): e31449.
***Infectivity in skeletal muscle of BASE-infected cattle
Wednesday, April 06, 2011
***Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in
Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease
Sunday, November 21, 2010
***Preclinical Deposition of Pathological Prion Protein in Muscle of
Experimentally Infected Primates and potential Iatrogenic TSE there from
Preclinical Deposition of Pathological Prion Protein in Muscle of Experimentally
Infected Primates
EMBO reports AOP Published online: 11 April 2003
***Widespread PrPSc accumulation in muscles of hamsters orally infected
with scrapie
Achim Thomzig, Christine Kratzel, Gudrun Lenz, Dominique KrÒ¼ger &
Michael Beekes Robert Koch-Institut, P26, Nordufer 20, D-13353 Berlin,
Germany
Received 13 February 2003; Accepted 13 March 2003; Published online 11
April 2003.
Abstract :
Scrapie, bovine spongiform encephalopathy and chronic wasting disease are
orally communicable, transmissible spongiform encephalopathies (TSEs). As
zoonotic transmissions of TSE agents may pose a risk to human health, the
identification of reservoirs for infectivity in animal tissues and their
exclusion from human consumption has become a matter of great importance for
consumer protection. In this study, a variety of muscles from hamsters that were
orally challenged with scrapie was screened for the presence of a molecular
marker for TSE infection, PrPSc (the pathological isoform of the prion protein
PrP). Sensitive western blotting revealed consistent PrPSc accumulation in
skeletal muscles from forelimb and hindlimb, head, back and shoulder, and in
tongue. Previously, our animal model has provided substantial baseline
information about the peripheral routing of infection in naturally occurring and
orally acquired ruminant TSEs. Therefore, the findings described here highlight
further the necessity to investigate thoroughly whether muscles of TSE-infected
sheep, cattle, elk and deer contain infectious agents.
snip...see;
Monday, June 22, 2009
***PrPTSE in muscle-associated lymphatic tissue during the preclinical
stage of mice orally-infected with BSE
Friday, December 05, 2008
***Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice
Sunday, August 26, 2012
Detection of PrPSc in peripheral tissues of clinically affected cattle
after oral challenge with BSE
more here;
Wednesday, April 24, 2013
Dissociation between Transmissible Spongiform Encephalopathy (TSE)
Infectivity and Proteinase K-Resistant PrPSc Levels in Peripheral Tissue from a
Murine Transgenic Model of TSE Disease
Therefore, the assumption that the levels of peripheral infectivity are
lower than those in the central nervous system is not always correct, and this
could have implications for current food safety regulations.
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
Sunday, June 9, 2013
TSEAC March 14, 2013: Transmissible Spongiform Encephalopathies Advisory
Committee Meeting Webcast
Monday, September 02, 2013
Atypical BSE: role of the E211K prion polymorphism
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research Unit
Sunday, September 1, 2013
Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy
We previously described the biochemical similarities between PrPres derived
from L-BSE infected macaque and cortical MM2 sporadic CJD: those observations
suggest a link between these two uncommon prion phenotypes in a primate model
(it is to note that such a link has not been observed in other models less
relevant from the human situation as hamsters or transgenic mice overexpressing
ovine PrP [28]). We speculate that a group of related animal prion strains
(L-BSE, c-BSE and TME) would have a zoonotic potential and lead to prion
diseases in humans with a type 2 PrPres molecular signature (and more
specifically type 2B for vCJD)
snip...
Together with previous experiments performed in ovinized and bovinized
transgenic mice and hamsters [8,9] indicating similarities between TME and
L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME
outbreaks in North America and Europe during the mid-1900s.
Volume 19, Number 4—April 2013
Letter
Iatrogenic Creutzfeldt-Jakob Disease from Commercial Cadaveric Human
Growth Hormone
To the Editor: Iatrogenic Creutzfeldt-Jakob disease (iCJD) is an acquired
form of prion disease that has been declining in incidence since the mid-1990s
(1). Worldwide, at least 226 cases of iCJD, including 29 US cases, have been
associated with administration of contaminated human growth hormone (hGH) from
cadavers. Reported incubation periods ranged from 5 to 42 years (mean 17 years)
(2). Commercially produced cadaveric hGH has been associated with only 1
previously reported case of iCJD: CJD developed in a 39-year-old Austrian man
≈22 years after he received commercial cadaveric hGH (Crescormon, Kabivitrum,
Stockholm, Sweden) during 1984–1985 (3). We report a second case of probable
iCJD acquired through treatment with commercial cadaveric hGH.
The patient was born at 32 weeks’ gestation with subsequent developmental
delay, agenesis of the corpus callosum, and panhypopituitarism. He demonstrated
clinical and laboratory signs of growth hormone deficiency but was denied
treatment with hGH through the US government–supported National Hormone and
Pituitary Program (NHPP) because he did not meet the height requirement.
Treatment with commercial cadaveric hGH began when he was 5.8 years of age and
continued for 23 months (1983–1985). He received 1.5 units intramuscularly 3×
per week and was primarily treated with Asellacrin (Ares-Serono, Geneva,
Switzerland). In early 1984, for an unspecified duration, he received Crescormon
(Kabivitrum) because of an Asellacrin shortage. Treatment was halted in 1985
because of iCJD concerns and resumed 2 years later with recombinant hGH.
Figure
Figure. . . Maps showing axial fluid attenuated inversion recovery (FLAIR),
diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) at
the level of the basal nuclei (top row) and dorsal frontoparietal cortex...
At age 33, 26.5 years (range 25.5–28 years) after the midpoint of
commercial cadaveric hGH treatment, dizziness and gait imbalance developed,
causing a fall. The patient’s mental status also began declining, and he never
returned to his baseline status. Six months after illness onset, he experienced
hallucinations, weakness of lower extremities, and limb ataxia. Seven months
after the fall, he entered a state of akinetic mutism; he died 9 months after
symptom onset. A lumbar puncture, performed 8 months after illness onset,
demonstrated 14-3-3 proteins and an elevated cerebrospinal fluid (CSF) τ level
of 14,111 pg/mL (decision point 1,150 pg/mL) (4), although the specimen was
contaminated with blood (39,375 erythrocytes/μL). Electroencephalogram
demonstrated severe diffuse encephalopathy. Two brain magnetic resonance imaging
studies performed 8 months after illness onset indicated probable CJD, given
lack of prior metabolic and anoxic insults (Figure). The patient was discharged
from a referral hospital with this diagnosis; no postmortem analysis was
conducted.
On the basis of World Health Organization criteria, we conclude that this
patient had probable iCJD as a result of hGH treatment (5). The patient’s
condition was treated with 2 different formulations of commercial cadaveric hGH,
including one of the same brands in the same year as that of the first reported
patient with iCJD associated with commercial cadaveric hGH (3). The patient’s
incubation period (25.5–28 years) is well within expectations (1).
Despite an ongoing active surveillance program that identified ≈3,500 of
≈4,500 post-1977 cadaveric hGH recipients in the US NHPP, all 29 CJD infections
in NHPP recipients occurred among the estimated ≈2,700 pre-1977 recipients
(1,2). This significant reduction in iCJD was attributed to the 1977
introduction of a highly selective, column chromatography step in the hormone
purification protocol that can markedly reduce prion infectivity (1,2). As shown
by the many iCJD cases linked to hGH in France, the efficacy of column
chromatography purification steps may vary (1). Commercially derived cadaveric
hGH was produced in different laboratories from those that produced
NHPP-distributed hGH, and sufficient details regarding sourcing and production
methods of the commercial products are lacking. Approximately 10,000 persons,
mostly outside the United States, received commercial cadaveric hGH produced by
Kabivitrum, and substantially fewer persons received product from Ares-Serono
(A.F. Parlow, pers. comm.). Identification through passive surveillance of 2 CJD
cases among recipients of such hGH further supports a causal, rather than
chance, association between commercial hormone and CJD. It also suggests a
difference in iCJD risk between post-1977 NHPP-distributed hGH and commercial
cadaveric hGH.
Limitations of this report include the lack of neuropathologic
confirmation and insufficient information to strongly implicate a single
commercial cadaveric hGH product as infection source. The report of another iCJD
case-patient who received Crescormon during the same period provides some
evidence that the product was the source of prion contamination. Although the
patient may have had sporadic CJD, his young age at disease onset (33 years)
makes this unlikely (6).
This report suggests that a potential risk for iCJD in persons who
received commercial cadaveric hGH should be considered. Also, clinicians should
not assume that all cadaveric hGH administered after 1977 carries the same risk
for infectivity. In addition, when CJD is being considered as a clinical
diagnosis, a history of exposure to cadaveric hGH should always be sought, even
when patients have normal or tall stature. Finally, we recommend that when a
clinical diagnosis of CJD is suspected, but before the patient’s death, the
local caregivers, with the family, should initiate arrangements for a postmortem
examination to confirm diagnosis (e.g., www.cjdsurveillance.com).
Brian S. Appleby , Mei Lu, Alberto Bizzi, Michael D. Phillips, Sally M.
Berri, Madeleine D. Harbison, and Lawrence B. Schonberger
Author affiliations: Cleveland Clinic Foundation, Cleveland, Ohio, USA
(B.S. Appleby, M. Lu, M.D. Phillips); Instituto Clinico Humanitas,Milan, Italy
(A. Bizzi); Case Western Reserve University, Cleveland (S.M. Berri); Mount Sinai
School of Medicine, New York, New York, USA (M.D. Harbison); Centers for Disease
Control and Prevention, Atlanta, Georgia, USA (L.B. Schonberger)
Sunday, February 10, 2013
Creutzfeldt-Jakob disease with unusually extensive neuropathology in a
child treated with native human growth hormone
Sunday, February 10, 2013
Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection
report/CJD
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
Sunday, September 08, 2013
Iatrogenic Creutzfeldt-Jakob disease via surgical instruments and
decontamination possibilities for the TSE prion
Saturday, July 6, 2013
Small Ruminant Nor98 Prions Share Biochemical Features with Human
Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive
Prionopathy
Research Article
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
Thursday, October 25, 2012
Current limitations about the cleaning of luminal endoscopes and TSE prion
risk factors there from
Article in Press
2011 TO 2012 UPDATE
Saturday, December 3, 2011
Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform
Encephalopathies
Volume 17, Number 12—December 2011
snip...
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
TIP740203/l 0424 CONFIDENTIAL
TWA LITTLE minute
2. We have identified one problem over where we are unable to act and this
is the use of gonadotrophins in embryo transfer work. Some veterinary surgeons
are quite legally using this exemption from the Medicines Act contained in
Section 9(2) to prepare gonadotrophins from pituitary glands from various
species, including cattle. These hormones are used to stimulate superovulation
in donor cows.
COMMERCIAL IN CONFIDENCE
3.2 Minute 5.3 - 5.4 Bovine Spongiform Encephalopathy
It was reported that some replies had been received from Companies using
pituitary glands in their products. Copies of the BSE document had also been
sent to DHSS and NIBSC.
and then another 3 + pages of blank space. ...TSS
COMMERCIAL IN CONFIDENCE
BSE - CURRENT POSITION WITH VETERINARY LICENCED PRODUCTS (MA.1968)
There are three areas of particular concern, vaccines (including emergency
vaccines), pharmaceuticals which are covered by MA licences and unlicenses
hormonal products produced under exemptions claimed under (Section 9(2)
Medicines Act).
1) Vaccines
NOT FOR PUBLICATION
another 6 pages of blank space. ...TSS
COMMERCIAL IN CONFIDENCE
COMMERCIAL IN CONFIDENCE
Medicines Act - Veterinary Products Committee
COMMERCIAL IN CONFIDENCE
MANAGEMENT IN CONFIDENCE
CERTIFIED BSE-FREE HERDS FOR SOURCE OF MATERIAL FOR BIOLOGICAL PRODUCTS
COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
snip...
I was quite prepared to believe in unofficial pituitary hormones, also in
the 1970's, whether as described by Dr. Little, or in other circumstances, for
animal use.
snip...
The fact that there were jars of pituitaries (or extract) around on
shelves is attested by the still potent 1943 pituitaries, described in Stockell
Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having
taken the trouble to collect them, they were not lightly thrown out...
more on the 1968 medicine act, they forgot to follow i.e. no Scrapie-like
disease. ...TSS
Draft cover letter to product licence holders (considered by Human and Vet
Medicines including deer)
CONCERN ABOUT BSE IN HUMAN MEDICINE
(It was noted with concern that hormone extracts could be manufactured by
a veterinary surgeon for administration to animals under his care without any
Medicines Act Control.)
COMMERCIAL IN CONFIDENCE
TWA LITTLE STATEMENT 331
snip...
8. The Secretary of State has a number of licences. We understand that the
inactivated polio vaccine is no longer being used. There is a stock of smallpox
vaccine. We have not been able to determine the source material. (Made in sheep
very unlikely to contain bovine ingredients).
CONFIDENTIAL
snip...
Subject: Re: VACCINES/CHILDREN/TSE'S -- 'CONFIDENTIAL'
Date: Wed, 6 Sep 2000 18:20:09 -0800
From: tom
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de References: 1
######### Bovine Spongiform Encephalopathy #########
Just when I was thinking the Internet had reached a terminal condition of
shallow pages and broken links, some young people come along and invent a really
effective Internet search engine:
http://www.google.com/ This works quite well
to search the entire
http://www.mad-cow.org
site (or find 393 web sites such as GenBank that link to it, or 936 sites that
cite it in text) back to 1996 as well as the BSE Inquiry
http://www.bse.org.uk/
Thus for louping ill (unnecessary cites suppressed):
Witness Statements 537 - Coulthard
29.Pituitary FSH from pigs has been used in the USA prior to its use in
the UK and much more extensively there and Canada.... 30.Thousands of embryos
were exported from this country to the USA prior to the ban being imposed... 42.
No cow pituitaries were used in the preparation of FSH [follicular stimulating
hormone] products compared with the case of louping ill vaccine for
scrapie.
In the 1930's: 18,000 UK sheep were inoculated against louping ill, a
brain inflammatory illness spread by ticks. Despite formalin-treatment of the
inoculated agent, the procedure gave rise to 1,500 cases of scrapie. Louping is
a Scottish word for fleeing or leaping, related to loping. In humans, louping
ill is called Russian spring-summer encephalitis, a meningo-encephalitis with
muscular tremors and spasms followed by varying degrees of paralysis.... [John
Lanchester 2 Dec 96 New Yorker]
In what the story calls a grand historical irony, this landmark series of
experiments was being confirmed at the same time in England as a result of an
outbreak of scrapie in several hundred sheep that had been immunized against
louping ill with a vaccine prepared from tissue from the brain, spinal cord, and
spleen of sheep that were belatedly discovered to have been exposed to natural
scrapie infection.[6.Gordon WS. Advances in veterinary research. Vet Rec 1946;
58: 516-520] The transmissible nature of the scrapie agent was thus established
beyond any doubt. [P Brown, 1755 and All That: A Historical Primer of TSE.
We need to look at the full text of the article and its cites to see how
they actually made the vaccine, whether they exported vaccine-infected sheep to
Canada and the US, and what became of the vaccinated flocks. Perhaps there is
still sample available, Moredun Institute is still around.
Gordon WS. Advances in veterinary research. Vet Rec 1946; 58: 516-520 (not
covered by Medline) Gordon, Bronlee and Wilson 1939 [full cite is available only
in a letter we don't have)
Terry was reading Draft Factual Account 17
236. Mrs Alderman replied on 3 June 1988, listing products containing
bovine insulin and noting there were two rabies vaccines listed but the species
used in manufacture was not shown.[282] 237. On 6 June 1988 Mr Lawrence wrote to
Sir Richard Southwood and enclosed some brief answers to the questions that had
been tabled at the meeting on 19 May.[283] In relation to Q6, which asked OWhat
is meat and other material from scrapie infected sheep used for - does it
include pet food and material for biological products?¹ Part of the answer
stated: ...
There has been one instance of inadvertant [sic] transmission of the
scrapie agent to sheep through louping ill vaccine (Gordon, Bronlee and Wilson
1939). One of the three batches of vaccine made in 1935 at the Moredun Institute
contained the scrapie agent resulting in 7% of the recipients of the 18, 000
doses in the batch developing scrapie. This vaccine was made from
formalin-inactivated sheep brain, and brought to the attention of research
workers that formalin, at a concentration of 0.35% for at least 3 months, which
inactivated conventional viruses, did not totally inactivate the scrapie agent.
----------------------------
4. Questions we might want to have answered are: the highest risk would be
from parenterals prepared from brain (eg rabies vaccine). Any species in which
transmissible spongiform encephalopathies have been described would be suspect
("natural" infections in sheep, goats, cattle, deer, mink, but can be
transmitted to hamster, mouse, guinea-pig etc). Are sterilisation processes
adequate for the most resistant strain of scrapie agent or for CJD agent? Should
companies be asked to include investigation for inclusion of scrapie agent (eg
mouse innoculation [sic]) in at least some batches? If BSE behaves like scrapie,
then we might expect other nervous tissue, spleen, lymph nodes and placenta to
be contaminated. Infection has been described in other tissues too, eg gut wall,
and we can not [sic] be sure blood is free. Do we know what bovine materials are
used in which products, both as the active ingredient and in production? Bovine
active ingredients in human products include insulin, vasopressin, bone, immune
globulins, fibrin, dermal collagen, albumin. Bovine serum albumin and fetal calf
serum must be used in preparation of very many products. For each of these
products would any "BSE agent" be destroyed or eliminated in processing? If not,
and the product is administered parenterally or topically into an open wound,
might there be a risk? [For oral products, there would only be a trivially
increased load on top of that taken in food in omnivores/carnivores including
man. But for some herbivores, this might allow the agent to be introduced into
yet another species].
--------------------------
Medicines and medical devises;
Subject: 2 known incidents of iatrogenic scrapie
Date: Thu, 7 Sep 2000 09:51:14 -0800
From: tom
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de References: 1
######### Bovine Spongiform Encephalopathy #########
One really has to wonder what went on in veterinary products produced
during the peak BSE years. At this point, there are only 2 known incidents, both
involving sheep brain vaccines.
I found a better source for needed references for iatrogenic scrapie in a
nice review by Ray Bradley at
http://www.iica.org.ar/Bse/6-%20Bradley.html.
Disclosure has been meagre on the 1998 vaccine incident in Italy. Note 3 of the
5 references are totally off Medline and the other 2 fail to have abstracts or
links, due to journal ineptness, burial in conference proceedings, and age of
article.
If anyone has the first 3, I would appreciate a fax 542-484-0669 US.
tom
GORDON , W.S., 1959. Scrapie panel. In: Proceedings of 63rd Annual Meeting
of the US Livestock Sanitary Association, 63, 286-294. [no medline record]
GORDON, W.S., 1946. Advances in Veterinary Research: Louping ill,
tick-borne fever and scrapie. Veterinary Record, 58, 516-525. [no medline
record]
GORDON , W.S., BROWNLEE, A.& WILSON, D.R., 1939. Studies in
louping-ill, tick-borne fever and scrapie. 3rd International Congress for
microbiology, 362-363. [no medline record]
-=-=--=
CAPUCCHIO, M.T., GUARDA,F., ISAIA,M.C., CARACAPPÀ, S. & DiMARCO,V.,
1998. Natural occurrence of scrapie in goats in Italy. Veterinary Record, 143,
452-453. [title only]
AGRIMI, U., GLUSOPPE, R.U., CARDONE, F., POCCHIARI, M. & CARAMELLI,
M., 1999. Epidemic transmissible spongiform encephalopathy in sheep and goats in
Italy. Lancet, 353, 560-561. [title only]
IATROGENIC DISEASE IN ANIMALS
Ray Bradley Private BSE Consultant Veterinary Laboratories Agency, United
Kingdom
There have been two reported incidents of iatrogenic disease in animals,
both involving scrapie. One was in Great Britain (Gordon, Brownlee and Wilson,
1939, Gordon 1946, 1959) the other in Italy (Capucchio et al, 1998, Agrimi et
al, 1999). Both resulted from infection being introduced into vaccines, louping
ill vaccine in Great Britain, Mycoplasma agalactiae vaccine in Italy. Each of
these vaccines was prepared from tissues that included sheep brain. In both
episodes it seems most likely that natural scrapie infection was present
unknowingly in some brains used for the purpose. Once prepared and having passed
all the conventional vaccine tests large numbers of sheep in Great Britain, and
goats and some sheep in Italy were inoculated. After the necessary incubation
period large numbers (> 1,000 in each case) of inoculated animals came down
with scrapie. In the meantime some inoculated clinically healthy goats and sheep
may have entered food and feed chains or have been used for other purposes. In
the British outbreak there appears to have been no consequence for humans who
may have consumed infected sheep. It is too early to say what may be the
consequences in Italy but measures have been taken to reduce any risk there may
have been. .........end
Louping-ill vaccine documents from November 23rd, 1946 FULL TEXT
THE VETERINARY RECORD 516 No 47. Vol. 58 November 23rd, 1946
NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND
ANNUAL CONGRESS, 1946
The annual Congress, 1946, was held at the Royal Veterinary College, Royal
College Street, London, N.W.I. from September 22nd to September 27th.
Opening Meeting
[skip to scrapie vaccine issue...tss]
Papers Presented to Congress
SNIP...FULL TEXT ;
although 176 products do _not_ conform to the CSM/VPC guidelines.
COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
8. The Secretary of State has a number of licences. We understand that the
inactivated polio vaccine is no longer being used. There is a stock of smallpox
vaccine. We have not been able to determine the source material. (Made in sheep
very unlikely to contain bovine ingredients).
CONFIDENTIAL
CONFIDENTIAL
more on the 1968 medicine act, they forgot to follow
Draft cover letter to product licence holders (considered by Human and Vet
Medicines including deer)
2.3.Iatrogenic exposure
Iatrogenic exposure of scrapie has probably occurred twice. The first
report determined that the vehicle was a louping ill vaccine prepared from sheep
tissues and this infected a large number of sheep sheep (Gordon, 1946, Greig,
1950). The second was more recent and in this case a vaccine against Mycoplasma
agalactiae prepared from sheep tissues was incriminated (Agrimi et al 1999,
Capucchio, 1998) but not all outbreaks could be linked to the use of the
vaccine. In this episode goats were predominantly affected10.
*** 5.3.3 The greatest risk, in theory, would be from parenteral injection
of material derived from bovine brain or lymphoid tissue. Medicinal products for
injection or surgical implantation which are prepared from bovine tissues, or
which utilise bovine serum albumin or similar agents in their manufacture, might
also be capable of transmitting infectious agents. All medicinal products are
licensed under the Medicines Act by the Licensing Authority following guidance,
for example from the Committee on Safety of Medicines (CSM), the Committee on
Dental and Surgical Materials (CDSM) and their subcommittees. The Licensing
Authority have been alerted to potential concern about BSE in medicinal products
and will ensure that scrutiny of source materials and manufacturing processes
now takes account of BSE agent.
BEFORE the BSE Inquiry went online, i was requesting the daily hearings
and submissions, and they were sending them to me via air mail. then, when the
BSE Inquiry finally went online, i was then able to go back and match up some of
what i had with the YB numbers (above), with the official documents.
...TSS
BSE offals used in cosmetics, toiletry and perfume industry Sun, 3 Sep
2000. Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary
Sr. of Bacliff, Texas Miss Marion Kelly Cosmetic, Toiletry and Perfumery
Association 35 Dover Street London W1X3RA
Department of Trade and Industry 10-18 Victoria Street London SW1H ONN
Enquiries 01-215 5000 Telex 8811074 DTHQ G 01 215 3324 1 February 1990
40,000 human heart valves a year from BSE herds Sun, 3 Sep 2000.
Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary Sr.
of Bacliff, Texas
Opinion (webmaster): Below are some shocking documents. Here is a British
company preparing 40,000 heart valves a year from bovine pericardium, primarily
for export, and they are not required to source this material from BSE-free
herds even in peak epidemic years. It is amazing to watch health "authorities"
grovelling on their bellies to wring petty concessions from middle management at
obscure little companies. The main worry is not the practise of using 800
potentially infected cows a week for human heart transplant material but that
the press or recipients will get wind of it, hurting business.
BSE wasn't the problem, it was awkward queries from importing countries
like the US. The cows are stunned using brain penetration -- can't do anything
about the chunks of bovine brain blasted into the circulatory system, it's the
norm. Can't use younger lower-risk animals either, patch would not be big
enough. It is fascinating to see the British government worrying about, but
doing nothing, with pigs with BSE 10 years ago.
While scrapie was long used as an excuse for continuing with human use of
BSE-tainted material, little sheep material was used medically. Bovine
transplants, vaccines, insulin doeses, etc. are far more dangerous than dietary
material as injections, and are done on a very wide scale. So scrapie was never
a valid analogy to BSE, as MAFF knew full well.
The British government deferred to the manufacturer's rep for an opinion
on how contaminated pericardium might be, just as this appeared showing that
this tissue is extremely dangerous:
England worried briefly about infecting other countries 27 Aug 00
confidential correspondence obtained by Terry S. Singeltary Sr.
BSE11/2 020;
SC1337p
DEPARTMENT OF HEALTH AND SOCIAL SECURITY Richmond House, 79 Whitehall,
London SWIA 2NS Telephone 01-210 3000 From the Chief Medical Officer Sir Donald
Achson KBE DM DSc FRCP FFCM FFOM
Mr K C Meldrum Chief Veterinary Officer Ministry of Agriculture, Fisheries
and Food Government Buildings Hook Rise South Tolworth Surbiton Surrey KT6 7NG 3
January 1990
Dear Mr Meldrum
BOVINE SPONGIFORM ENCEPHALOPATHY
You will recall that we have previously discussed the potential risks of
BSE occurring in other countries as a result of the continuing export from the
UK of meat and bone that may be contaminated by scrapie or possibly BSE.
I remain concerned that we are not being consistent in our attempts to
contain the risks of BSE. Having banned the feeding of meat and bone meal to
ruminamts in 1988, we should take steps to prevent these UK products being fed
to ruminants in other countries. This could be achieved either through a ban on
the export of meat and bone meal, or at least by the proper labelling of these
products to make it absolutely clear they should not be fed to ruminants [or zoo
animals, including rare and endangered primates -- webmaster]. Unless some such
action is taken the difficult problems we have faced with BSE may well occur in
other countries who import UK meat and bone meal. Surely it is short sighted for
us to risk being seen in future as having been responsible for the introduction
of BSE to the food chain in other countries.
The documents below were provided by Terry S. Singeltary Sr on 8 May 2000.
They are optically character read (scanned into computer) and so may contain
typos and unreadable parts.
TIP740203/l 0424 CONFIDENTIAL
Mr Cunningham CMP3 From: D O Hagger MBI Dr Salisbury MED/IMCD3 Mr Burton
PD/STB/PG1B B/17/2 Date: 15.02.1989 Mr Dudley PD/AD4
BOVINE SPONGIFORM ENCEPHALOPATHY
Other US BSE risks: the imported products picture 24 Jul 00 Trade
Statistics: UK to US Compiled by Terry S. Singeltary Sr of Bacliff, Texas
[Opinion (webmaster): The US has focused for years on tracing, containing,
and eradicating live animal imports from the UK or other countries with
acknowledged BSE like Belgium, including some 499 cattle and the Vermont sheep.
This strategy does not acknowledge imports of rendered bovine products from
England during the BSE period nor secondary products such as surgical catgut,
which is to say surgical cowgut, or dairy cattle embryos, vaccines for
veterinarian and human medicines. What has become of these?
Mr. Singeltary, who lost his mother to CJD of unexplained origin a few
years back and went on to became a well-known TSE activist, has tracked down
voluminous pertinent import data through correspondence with UK officials and
searches of government web sites. Imports of such products are frequently cited
by Europeans in rating BSE risks in the US and in shutting out US exports.
Many people's eyes glaze over when reviewing reams of sometimes older
trade statistics. There is no proof that any of the imported products was
contaminated with BSE nor if so, any evidence that any BSE product lead to
infection in US livestock, surgical patients, or what not. Nonetheless, the data
obtained by Mr. Singeltary establish that an appalling variety and tonnage of
products that were imported by the US from the UK and othr BSE-affected
countries during the peak of the BSE epidemic years.]
10 January 1990 COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
COMMITTEE ON SAFETY OF MEDICINES WORKING PARTY ON BOVINE SPONGIFORM
ENCEPHALOPATHY
SURGICAL CATGUT SUTURES 2.1 At the first meeting of the Working Party on
Bovine Spongiform Encephalopathy on 6 September 1989, detailed consideration was
given to XXXXX Surgical Catgut. This arose from the Company's response to the
Letter to Licence Holders, indicating that the bovine small intestine source
material was derived from UK cattle, unlike 8 other licenced catgut sutures. In
contrast XXXXX Surgical Catgut was stated to hold over 90% share of the market
for catgut sutures, and to constitute approximately 83% of all sutures used in
U.K. IMPORTS OF SUTURES FROM THE KNOWN BSE COUNTRY;
Procedures Manual
Bovine Spongiform Encephalopathy (BSE)
Ongoing Surveillance Plan
Ongoing Surveillance Plan Implementation July 20, 2006
snip...
Personal Safety
If BSE is transmissible to humans in the occupational setting, the most
likely routes would be through contact with infective tissues through wounds or
open lesions on the skin, contact with mucous membranes (eyes and mouth), or
exceptionally, by swallowing. .....snip...end
SO, looks like to me the most likely route of transmission of BSE to
humans would be through inoculation i.e., the most likely routes would be
through contact with infective tissues through wounds or open lesions on the
skin, IF you look at all the successful transmission studies in the lab with
TSE, inoculations was the most successful route.
BSE-L@LISTS.AEGEE.ORG
Bovine Spongiform Encephalopathy
BSE-L is a discussion forum for scientists who are interested in Bovine
Spongiform Encephalopathy (BSE). BSE-L has been created on 20th July, 1994 by
Siegfried Schmitt. Impressum:
http://www.kaliv.de/impressum.html
LISTS.AEGEE.ORG ( BSE-L: 484 matches (only the first 50 will be shown).. )
From: TSS (216-119-138-163.ipset18.wt.net)
Subject: Louping-ill vaccine documents from November 23rd, 1946 Date:
September 10, 2000 at 8:57 am PST
Subject: Louping-ill vaccine documents from November 23rd, 1946
Date: Sat, 9 Sep 2000 17:44:57 -0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
THE VETERINARY RECORD 516 No 47. Vol. 58 November 23rd, 1946
NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND
ANNUAL CONGRESS, 1946
The annual Congress, 1946, was held at the Royal Veterinary College, Royal
College Street, London, N.W.I. from September 22nd to September 27th.
Opening Meeting
[skip to scrapie vaccine issue...tss]
Papers Presented to Congress
The papers presented to this year's Congress had as their general theme
the progressive work of the profession during the war years. Their appeal was
clearly demonstrated by the large and remarkably uniform attendance in the Grand
Hall of the Royal Veterinary College throughout the series; between 200 and 250
members were present and they showed a keen interest in every paper, which was
reflected in the expression of some disappointment that the time available for
discussion did not permit of the participation of more than a small proportion
of would-be contributors.
In this issue we publish (below) the first to be read and discussed, that
by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E., "Advances in Veterinary Research."
Next week's issue will contain the paper on "Some Recent Advances in Veterinary
Medicine and Surgery in Large-Animal Practice" by Mr. T. Norman Gold, M.R.C.V.S.
In succeeding numbers of the Record will be reproduced, also with reports of
discussions, that by Mr. W. L. Weipers, M.R.C.V.S., D.V.S.M., on the same
subject as relating to small-animal practice, and the papers by Mr. J. N.
Ritchie, B.SC., M.R.C.V.S., D.V.S.M., and Mr. H.W. Steele-Bodger, M.R.C.V.S., on
"War-time Achievements of the British Home Veterinary Services."
The first scientific paper of Congress was read by Dr. W. S. Gordon,
M.R.C.V.S., F.R.S.E. on Monday, September 23rd, 1946, when Professor J. Basil
Buxton, M.A., F.R.C.V.S, D.V.H., Prinicipal of the Royal Veterinary College,
presided.
Advances in Veterinary Research
by
W.S. GORDON, PH.D., M.R.C.V.S., F.R.S.E.
Agriculteral Research Council, Field Station, Compton, Berks.
Louping-ill, Tick-borne Fever and Scrapie
In 1930 Pool, Browniee; Wilson recorded that louping-ill was a
transmissible disease. Greig et al, (1931) showed that the infective agent was a
filter-passing virus with neurotropic characters and Browniee & Wilson
(1932) that the essential pathology was that of an encephalomyelitis. Gordon,
Browniee, Wilson & MacLeod (1932) and MacLeod & Gordon (1932) confirmed
and extended this work. It was shown that on louping-ill farms the virus was
present in the blood of many sheep which did not show clinical symptoms
indicating involvement of the central nervous system and that for the
perpetuation and spread of the disease these subclinical cases were probably of
greater importance that the frank clinical cases because, in Nature, the disease
was spread by the tick, lxodes ricinus L. More recently Wilson (1945, 1946) has
described the cultivation of the virus in a chick embryo medium, the pathogenic
properties of this culture virus and the preparation of louping-ill
antiserum.
Between 1931 and 1934 I carried out experiments which resulted in the
development of an effective vaccine for the prevention of louping-ill.* This
vaccine has been in general use since 1935 and in his annual report to the
Animal Diseases Research Association this year, Dr. Greig stated that about
227,000 doses of vaccine had been issued from Moredun alone.
Dr. Gordon illustrated this portion of his paper by means of graphs and
diagrams projected by the epidiascope.
This investigation, however, did not begin and end with the study of
louping-ill; it had, by good fortune, a more romantic turn and less fortunately
a final dramatic twist which led almost to catastrophe. After it had been
established that a solid immunity to louping-ill could be induced in sheep, a
group of immunized and a group of susceptible animals were placed together on
the tick-infected pasture of a louping-ill farm. Each day all the animals were
gathered and their temperatures were recorded. It was anticipated that febrile
reactions with some fatalities would develop in the controls while the
louping-ill immunes would remain normal. Contrary to expectation, however, every
sheep, both immune and control, developed a febrile reaction. This unexpected
result made necessary further investigation which showed that the febrile
reaction in the louping-ill immunes was due to a hitherto undescribed infective
agent, a Rickettsia-like organism which could be observed in the cytoplasm of
the granular leucocytes, especially the neutrophil polymorphs (MacLeod (1932),
Gordon, Browniee, Wilson & MacLeod. MacLeod & Gordon (1933). MacLeod
(1936). MacLeod collected ticks over many widely separated parts of Scotland and
all were found to harbour the infective agent of tick-borne fever, and it is
probable that all sheep on tick-infested farms develop this disease, at least on
the first occasion that they become infested with ticks. When the infection is
passed in series through susceptible adult sheep it causes a sever, febrile
reaction, dullness and loss of bodily condition but it rarely, if ever, proves
fatal. It is clear, however, that it aggravates the harmful effects of a
louping-ill infection and it is a serious additional complication to such
infections as pyaemia and the anacrobic infections which beset lambs on the hill
farms of Northern Britain.
Studying the epidemiology of louping-ill on hill farms it became obvious
that the pyaemic condition of lambs described by M'Fadyean (1894) was very
prevalent on tick infested farms Pyaemia is a crippling condition of lambs
associated with tick-bite and is often confused with louping-ill. It is caused
by infection with Staphylococcus aureus and affected animals may show abscess
formation on the skin, in the joints, viscera, meninges and elsewhere in the
body. It was thought that tick-borne fever might have been a predisposing factor
in this disease and unsuccessful attempts were made by Taylor, Holman &
Gordon (1941) to reproduce the condition by infecting lambs subcutaneously with
the staphylococcus and concurrently producing infections with tickborne fever
and louping-ill in the same lambs. Work on pyaemia was then continued by
McDiarmid (1946a, 1946b, 1946c), who succeeded in reproducing a pyaemic disease
in mice, guinea-pigs and lambs similar to the naturally occurring condition by
intravenous inoculation of Staphylococcus aureus. He also found a bacteraemic
form of the disease in which no gross pyaemic lesions were observed. The
prevention or treatment of this condition presents a formidable problem. It is
unlikely that staphylococcal ???oid will provide an effective immunity and even
if penicillin proved to be a successful treatment, the difficulty of applying it
in adequate and sustained dosage to young lambs on hill farms would be almost
insurmountable.
From 1931 to 1934 field trials to test the immunizing value and
harmlessness of the loup-ill vaccine were carried out on a gradually increasing
scale. Many thousands of sheep were vaccinated and similar numbers, living under
identical conditions were left as controls. The end result showed that an
average mortability of about 9 percent in the controls was reduced to less than
1 percent in the vaccinated animals. While the efficiency of the vaccine was
obvious after the second year of work, previous bitter experience had shown the
wisdom of withholding a biological product from widespread use until it had been
successfully produced in bulk, as opposed to small-scale experimental production
and until it had been thoroughly tested for immunizing efficiency and freedom
from harmful effects. It was thought that after four years testing this stage
had been reached in 1935, and in the spring of that year the vaccine was issued
for general use. It comprised a 10 percent saline suspension of brain, spinal
cord and spleen tissues taken from sheep five days after infection with
louping-ill virus by intracerebral inoculation. To this suspension 0-35 percent
of formalin was added to inactivate the virus and its safety for use as a
vaccine was checked by intracerbral inoculation of mice and sheep and by the
inoculation of culture medium. Its protective power was proved by vaccination
sheep and later subjecting them, along with controls, to a test dose of living
virus.
Vaccine for issue had to be free from detectable, living virus and capable
of protecting sheep against a test dose of virus applied subcutaneously. The
1935 vaccine conformed to these standards and was issued for inoculation in
March as three separate batches labelled 1, 2, and 3. The tissues of 140 sheep
were employed to make batch 1 of which 22,270 doses were used; 114 to make batch
2 of which 18,000 doses were used and 44 to make batch 3 of which 4,360 doses
were used. All the sheep tissues incorporated in the vaccine were obtained from
yearling sheep. During 1935 and 1936 the vaccine proved highly efficient in the
prevention of loup-ill and no user observed an ill-effect in the inoculated
animals. In September, 1937, two and a half years after vaccinating the sheep,
two owners complained that scrapie, a disease which had not before been observed
in the Blackface breed, was appearing in their stock of Blackface sheep and
further that it was confined to animals vaccinated with louping-ill vaccine in
1935. At that stage it was difficult to conceive that the occurrence could be
associated with the injection of the vaccine but in view of the implications, I
visited most of the farms on which sheep had been vaccinated in 1935. It was at
this point that the investigation reached its dramatic phase; I shall not forget
the profound effect on my emotions when I visited these farms and was warmly
welcomed because of the great benefits resulting from the application of
louping-ill vaccine, wheras the chief purpose of my visit was to determine if
scrapie was appearing in the inoculated sheep. The enquiry made the position
clear. Scrapie was developing in the sheep vaccinated in 1935 and it was only in
a few instances that the owner was associating the occurrence with louping-ill
vaccination. The disease was affecting all breeds and it was confined to the
animals vaccinated with batch 2. This was clearly demonstrated on a number of
farms on which batch 1 had been used to inoculate the hoggs in 1935 and batch 2
to inoculate the ewes. None of the hoggs, which at this time were three-
year-old ewes. At this time it was difficult to forecast whether all of the
18,000 sheep which had received batch 2 vaccine would develop scrapie. It was
fortunate, however, that the majority of the sheep vaccinated with batch 2 were
ewes and therfore all that were four years old and upwards at the time of
vaccination had already been disposed of and there only remained the ewes which
had been two to three years old at the time of vaccination, consequently no
accurate assessment of the incidence of scrapie could be made. On a few farms,
however, where vaccination was confined to hoggs, the incidence ranged from 1
percent, to 35 percent, with an average of about 5 percent. Since batch 2
vaccine had been incriminated as a probable source of scrapie infection, an
attempt was made to trace the origin of the 112 sheep whose tissues had been
included in the vaccine. It was found that they had been supplied by three
owners and that all were of the Blackface or Greyface breed with the exception
of eight which were Cheviot lambs born in 1935 from ewes which had been in
contact with scrapie infection. Some of these contact ewes developed scrapie in
1936-37 and three surviving fellow lambs to the eight included in the batch 2
vaccine of 1935 developed scrapie, one in September, 1936, one in February,
1937, and one in November, 1937. There was, therefore, strong presumptive
evidence that the eight Cheviot lambs included in the vaccine although
apparently healthy were, in fact, in the incubative stage of a scrapie infection
and that in their tissues there was an infective agent which had contaminated
the batch 2 vaccine, rendering it liable to set up scrapie. If that assumption
was correct then the evidence indicated that:-
(1) the infective agent of scrapie was present in the brain, spinal cord
and or spleen of infected sheep: (2) it could withstand a concentration of
formalin of 0-35 percent, which inactivated the virus of louping-ill: (3) it
could be transmitted by subcutaneous inoculation; (4) it had an incubative
period of two years and longer.
Two Frenchmen, Cuille & Chelle (1939) as the result of experiments
commenced in 1932, reported the successful infection of sheep by inoculation of
emulsions of spinal cord or brain material by the intracerebral, epidural,
intraocular and subcutaneous routes The incubation period varied according to
the route employed, being one year intracerebrally, 15 months intraocularly and
20 months subcutaneously. They failed to infect rabbits but succeeded in
infecting goats. Another important part of their work showed that the infective
agent could pass through a chamberland 1.3 filter, thus demonstrating that the
infective agent was a filtrable virus. It was a curious coincidence that while
they were doing their transmission experiments their work was being confirmed by
the unforeseeable infectivity of a formalinized tissue vaccine.
As a result of this experience a large-scale transmission experiment
involving the ue of 788 sheep was commenced in 1938 on a farm specially taken
for the purpose by the Animal Diseases Research Association with funds provided
by the Agricultural Research Council. The experiment was designed to determine
the nature of the infective agent and the pathogenesis of the disease. It is
only possible here to give a summary of the result which showed that (1) saline
suspensions of brain and spinal cord tissue of sheep affected with scrapie were
infective to normal sheep when inoculated intracerebrally or subcutaneously; (2)
the incubation period after intracerebral inoculation was seven months and
upwards and only 60 percent of the inoculated sheep developed scrapie during a
period of four and a half years; (3) the incubation period after subcutaneous
inoculation was 15 months and upwards and only about 30 percent of the
inoculated sheep developed the disease during the four and a half years: (4) the
infective agent was of small size and probably a filtrable virus.
The prolonged incubative period of the disease and the remarkable
resistance of the causal agent to formalin are features of distinct interest. It
still remains to determine if a biological test can be devised to detect
infected animals so that they can be killed for food before they develop
clinical symptoms and to explore the possibilities of producing an immunity to
the disease.
==================================================================
Scrapie Louping-ill Vaccine
‘There has been one instance of inadvertant [sic] transmission of the
scrapie agent to sheep through louping ill vaccine (Gordon, Bronlee and Wilson
1939). One of the three batches of vaccine made in 1935 at the Moredun Institute
contained the scrapie agent resulting in 7% of the recipients of the 18, 000
doses in the batch developing scrapie. This vaccine was made from
formalin-inactivated sheep brain, and brought to the attention of research
workers that formalin, at a concentration of 0.35% for at least 3 months, which
inactivated conventional viruses, did not totally inactivate the scrapie agent.
----------------------------
4. Questions we might want to have answered are:
the highest risk would be from parenterals prepared from brain (eg rabies
vaccine). Any species in which transmissible spongiform encephalopathies have
been described would be suspect (“natural” infections in sheep, goats, cattle,
deer, mink, but can be transmitted to hamster, mouse, guinea-pig etc). Are
sterilisation processes adequate for the most resistant strain of scrapie agent
or for CJD agent? Should companies be asked to include investigation for
inclusion of scrapie agent (eg mouse innoculation [sic]) in at least some
batches? If BSE behaves like scrapie, then we might expect other nervous tissue,
spleen, lymph nodes and placenta to be contaminated. Infection has been
described in other tissues too, eg gut wall, and we can not [sic] be sure blood
is free. Do we know what bovine materials are used in which products, both as
the active ingredient and in production? Bovine active ingredients in human
products include insulin, vasopressin, bone, immune globulins, fibrin, dermal
collagen, albumin. Bovine serum albumin and fetal calf serum must be used in
preparation of very many products. For each of these products would any “BSE
agent” be destroyed or eliminated in processing? If not, and the product is
administered parenterally or topically into an open wound, might there be a
risk? [For oral products, there would only be a trivially increased load on top
of that taken in food in omnivores/carnivores including man. But for some
herbivores, this might allow the agent to be introduced into yet another
species].
--------------------------
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
snip...see full text ;
Saturday, December 3, 2011
Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform
Encephalopathies
Volume 17, Number 12—December 2011
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to
Bramble et al
Evidence For CJD/TSE Transmission Via Endoscopes
From Terry S. Singletary, Sr flounder@wt.net 1-24-3
To date the OIE/WAHO assumes that the human and animal health standards set
out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE
which include the H-type and L-type atypical forms. This assumption is
scientifically not completely justified and accumulating evidence suggests that
this may in fact not be the case. Molecular characterization and the spatial
distribution pattern of histopathologic lesions and immunohistochemistry (IHC)
signals are used to identify and characterize atypical BSE. Both the L-type and
H-type atypical cases display significant differences in the conformation and
spatial accumulation of the disease associated prion protein (PrPSc) in brains
of afflicted cattle. Transmission studies in bovine transgenic and wild type
mouse models support that the atypical BSE types might be unique strains because
they have different incubation times and lesion profiles when compared to C-type
BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian
hamster the resulting molecular fingerprint had changed, either in the first or
a subsequent passage, from L-type into C-type BSE. In addition, non-human
primates are specifically susceptible for atypical BSE as demonstrated by an
approximately 50% shortened incubation time for L-type BSE as compared to
C-type. Considering the current scientific information available, it cannot be
assumed that these different BSE types pose the same human health risks as
C-type BSE or that these risks are mitigated by the same protective measures.
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection
against prion diseases is based on a certain numbers of hypotheses some of which
may turn out to be erroneous. In particular, a form of BSE (called atypical
Bovine Spongiform Encephalopathy), recently identified by systematic testing in
aged cattle without clinical signs, may be the origin of classical BSE and thus
potentially constitute a reservoir, which may be impossible to eradicate if a
sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases
constitute an unforeseen first threat that could sharply modify the European
approach to prion diseases.
Second threat
snip...
TSS
