Wednesday, January 28, 2015

BOVINE HEPARIN POSITION STATEMENT ON THE REINTRODUCTION and POTENTIAL BSE TSE PRION RISK FACTORS THEREFROM

BIOIBERICA
 
SCIENCE BOARD TO THE FDA June 4, 2014 FDA White Oak Campus Bldg 31 Rm 1503 10903 New Hampshire Ave Silver Spring, MD 20993 Barcelona, May 27th 2014
 
POSITION STATEMENT ON THE REINTRODUCTION OF BOVINE HEPARIN
 
Commercial heparin drug products were introduced into clinical use more than 70 years ago. Heparin sodium was first approved by the FDA on February 9th, 1939(1). The first commercial heparin preparations were derived from bovine tissues (lung or intestinal mucosa). Since most of unfractionated heparin applications were approved decades ago, there was little or no pharmaceutical development reported in the applications(2) . In fact, even today unfractionated heparin is defined as a "natural product that is poorly defined chemically"(2) or "a substance that is of biological origin and, due to its complexity, a combination of physico-chemical-biological testing together with testing and control of the manufacturing process is needed for its characterization and determination of quality"(3). For this reason, and due to the significant molecular differences between heparins of different origins that we have observed in our own studies or that are described in published literature, we consider that the benefit-risk assessment of the reintroduction of bovine heparin may be a risky challenge. Since the outbreak of bovine spongiform encephalopathy (BSE), only heparin derived from pig intestinal mucosa is found in Europe and USA, because the sourcing of heparin from bovine tissues could pose a risk to human health after description of the variant of Creutzfeld‐Jacob encephalopathy (vCJ) as a prion disease transmitted by cows suffering from BSE.
 
Though we are sure that the FDA has taken into consideration the scientific knowledge available on heparin sourced from different species/tissues, we would like to share our point of view with regards to the reintroduction of bovine heparin in commercial preparations. In particular, we believe there are two aspects of utmost importance:
 
1) the differences in the structural characteristics of heparin from different origins and
 
2) the increase of the BSE agent transmission risk via bovine heparin preparations.
 
1. Differences in the structural characteristics of heparin from different origins
 
Today there are analytical techniques that are able to discern relevant differences between complex products due to their molecular heterogeneity. Bioibérica has been studying the Heparin molecule and has found significant differences between heparins derived from different tissues.
 
Page 1 of 4
 
Oficina Comercial: Plaza Francesc Macià, 7, 8º-B. 08029 Barcelona - España. Tel. (34) 93 490 49 08. Fax (34) 93 490 97 11
 
Complejo Industrial Bioibérica: Ctra. Nacional II, Km. 680,6. 08389 Palafolls. Barcelona - España. Tel. (34) 93 765 03 90. Fax (34) 93 765 01 02
 
 
Our findings are aligned with the data published in the available literature, which also describes differences between heparins extracted from different tissues and species. E.g. "Heparins obtained from different tissues and different species also differ structurally. The most widely used tissue for the preparation of pharmaceutical grade heparin is porcine intestine. Heparin prepared from bovine lung differs substantially from porcine intestinal heparin. Bovine lung heparin has a higher sulfation level and slightly higher molecular weight than porcine intestinal heparin, increasing its affinity for thrombin (factor IIa). Porcine intestinal heparin contains an AT binding site primarily having N-acetyl group in residue A, while bovine lung heparin primarily has an N-sulfo group residue A, resulting in their slightly different affinities for AT" (4) .
 
Particularly important is the fact that these structural differences may lead to different efficacy or safety profiles: "Pharmaceutical grade heparins obtained from porcine and bovine intestinal mucosa differ significantly in their preponderant disaccharide compositions, anticoagulant activities, bleeding tendencies, doses required to inhibit experimental thrombosis and protamine neutralization curves. It is possible to obtain a heparin fraction from bovine mucosa with the typical disaccharide composition, but at a lower yield when compared with that from porcine source. Even possessing the typical disaccharide composition this bovine heparin fraction still shows a lower antithrombotic activity than porcine heparin"(5) . These observations may explain the increasing reports of bleeding and peri-or post-operative blood dyscrasias observed in Brazilian patients in 2008, "though it was not possible to correlate clinical events with specific heparin batches"(6). The heparin preparations from bovine and porcine origins were interchanged by health professionals in Brazil.
 
Also according to the regulatory authorities in Argentina (ANMAT), where bovine heparin is clinically in use, there were outstanding issues with specific activities of bovine heparin in the Inspection and Quality Control Program of 2012 (7).
 
2) Increase of the BSE agent transmission risk via bovine heparin preparations
 
The potential for contamination of heparin with the BSE agent has been a concern of the U.S. Food and Drug Administration (FDA): "FDA is also concerned about the potential for contamination of heparin with the bovine spongiform encephalopathy (BSE) agent derived from ruminant materials"(8). Therefore, FDA Guidance for Industry Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for Quality recommends testing and confirming the species origin of crude heparin in each lot of every shipment before use in the manufacture or preparation of a drug, to ensure the safety of drugs and devices that contain heparin and to protect public health.
 
Heparin sourced from bovine species is extracted either from the intestines or from the lungs. The intestines, from the duodenum to the rectum, of bovine animals of all ages are currently included in the list of Specified Risk Material (SRM) in the European Union (Regulation (EC) No 999/2001, as
 
Page 2 of 4
 
amended). The distal ileum of the small intestine is also considered as SRM in U.S.A (§310.22). As far as the lungs are concerned, they are classified in "Table IB lower-infectivity tissues" (peripheral tissues that have tested positive for infectivity and/or PrPTSE in at least one form of TSE) according to WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies (2010), though no detectable infectivity or PrPTSE is observed in cattle.
 
If materials from bovine species are allowed to be used in the manufacture of Heparin, all the necessary complementary measures to minimize the risk of transmission of BSE should be considered. E.g.:
 
- the source animals and their geographical origin (animals should be sourced from countries with an active BSE surveillance and never from countries with undetermined BSE risk status),
 
- the nature of animal material and procedures in place to avoid cross-contamination with higher risk materials, and
 
- the production process validated for the clearance of BSE agents. To sum up, the reintroduction of bovine heparin in commercial heparin preparations would need to be thoroughly justified based on overwhelming evidences that the benefits outweigh the risks, in particular for:
 
- Differences in the structural characteristics may lead to different clinical efficacy and safety profile. Clinical and safety data of bovine heparin should be available according to current non-clinical and clinical guidelines. If different bovine tissues were used in addition to the current porcine material, the heterogeneity of the heparin preparations in the market would increase significantly, and health professionals would need to be warned about this.
 
- There should be a scientifically grounded evidence to justify that the benefits of having commercially available bovine heparin outweigh the increase of the risk of the BSE agent to be transmitted via bovine heparin. Stringent measures should be put in place for the sourcing and production of bovine heparin, which should require dedicated manufacturing facilities to avoid cross-contamination of the porcine heparin (that could be detected by the current FDA requirement to test porcine heparin for the absence of ruminant species contamination by PCR technique).
 
Sincerely yours, Irene Bartolí Regulatory Affairs BIOIBERICA, S.A.
 
Page 3 of 4
 
REFERENCES
 
(1) Center for Drug Evaluation and Research. Application Number 201370Orig1s000. Summary Review. Ann. T. Farrel, M.D. Acting Division Director. Heparin sodium, Vials for Injection.
 
(2) Regulatory Requirements and Recommendations for Heparin Application. Arthur B. Shaw, Ph.D. Product Quality Reviewer US Food and Drug Administration. 5th Workshop on the Characterization of Heparin Products August 14-15, 2012.
 
(3) EMA/CHMP/BWP/429241/2013, Guideline on the use of starting materials and intermediates collected from different sources in the manufacturing of non-recombinant biological medicinal products (June 2013).
 
(4) Production and Chemical Processing of Low Molecular Weight Heparins. Seminars in Thrombosis and Hemostasis, Vol. 25, Suppl. 3, 1999. Robert J. Linhard, Ph.D and Nur Sibel Gunay, M.S.
 
(5) Structural and functional differences between bovine and porcine mucosal heparins. Paulo A. S. Mourão, Laboratório de Tecido Conjuntivo Hospital Universitário Clementino Fraga Filho Universidade Federal do Rio de Janeiro. 4th Workshop on the characterization of heparin products 8-9 July, 2010 London.
 
(6) Heparin: shortage and high selling prices. Should beef mucosa heparin be reconsidered? Giuseppe Mascellani. 4th Workshop on the characterization of heparin products 8-9 July, 2010 London.
 
(7) Regulatory and Dossier Requirements for Heparin in Argentina. Biochemist M. Verónica López Cepero Division of Identification and Quantification Department of Biologic Products National Administration of Drugs, Food and Medical Devices. 5th Workshop on the Characterization of Heparin Products August 14-15, 2012.
 
(8) Federal Register Volume 77, Number 29 (Monday, February 13, 2012). Draft Guidance for Industry on Heparin for Drug and Medical Device Use; Monitoring Crude Heparin for Quality; Availability.
 
Page 4 of 4
 
 

snip...see full text ;
 
Monday, October 31, 2011
 
Getting the Farm Out of Pharma for Heparin Production
 
http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/getting-farm-out-of-pharma-for-heparin.html



Wednesday, July 06, 2011

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation

(see tonnage of mad cow feed in commerce USA...tss)

http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html

In an experimental study of the transmissibility of BSE to the pig, seven of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral inoculation with a homogenate of bovine brain from natural BSE cases developed lesions typical of spongiform encephalopathy.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=10684682&dopt=Abstract

PLEASE NOTE, these old BSE Inquiry links take a while to open with the wayback machine, so be patient. ...tss

Title: Experimental Intracerebral and Oral Inoculation of Scrapie to Swine: Preliminary Report

In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility.

snip...

IN CONFIDENCE

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

1. CMO should be aware that a pig inoculated experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months developed an illness, now confirmed as a spongiform encephalopathy. This is the first ever description of such a disease in a pig, although it seems there ar no previous attempts at experimental inoculation with animal material. The Southwood group had thought igs would not be susceptible. Most pigs are slaughtered when a few weeks old but there have been no reports of relevant neurological illness in breeding sows or other elderly pigs. ...see full text ;

http://web.archive.org/web/20040302031004/www.bseinquiry.gov.uk/files/yb/1990/08/23001001.pdf

IN CONFIDENCE

So it is plausible pigs could be preclinically affected with BSE but since so few are allowed to reach adulthood this has not been recognised through clinical disease. ...

http://web.archive.org/web/20040904150118/www.bseinquiry.gov.uk/files/yb/1990/08/23002001.pdf

snip...

CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

snip... see full text ;

Thursday, November 10, 2011

National Meat Association v. Harris Docket No., 10-224

DEADSTOCK DOWNER PIGS AND PORCINE SPONGIFORM ENCEPHALOPATHY PSE

Court Likely to Overturn Calif. Law on Livestock

http://transmissiblespongiformencephalopathy.blogspot.com/2011/11/national-meat-association-v-harris.html

 
Friday, April 20, 2012

Ultrastructural findings in pigs experimentally infected with bovine spongiform encephalopathy agent

http://madporcinedisease.blogspot.com/2012/04/ultrastructural-findings-in-pigs.html



"The fact that certain medicinal products could be injected directly into the body (most commonly intramuscularly) meant that in theory they would pose a greater risk than beef products in food."
 
 Infectivity of bovine materials used in medicinal products and the importance of inoculation route
 
3.221 The risk from infectivity present in medicinal products was considered by the Southwood Working Party. They noted that ‘the greatest risk . . . would be from the parenteral injection of material derived from bovine brain or lymphoid tissue’.538 (As described previously, it was generally accepted that the oral route was considerably less efficient than the parenteral route.539)
 
3.222 In reality, different routes exist within the parenteral category – intracerebral, intraperitoneal, intramuscular, intravenous, intraspinal and subcutaneous. Experiments in 1978 looking at several of these routes found the efficiency between them to vary. Intracerebral and intraspinal were generally the most efficient, followed by intravenous, intraperitoneal and then subcutaneous.540 The fact that certain medicinal products could be injected directly into the body (most commonly intramuscularly) meant that in theory they would pose a greater risk than beef products in food.
 
3.223 Various cattle tissues were of relevance to medicinal products, including insulin, heparin, surgical catgut sutures and serum. The consideration given to these materials prior to March 1996 is addressed in vol. 7: Medicines and Cosmetics.
 
533 SEAC 22/5 534 Wells, G. (1998) Preliminary Observations on the Pathogenesis of Experimental Bovine Spongiform Encephalopathy (BSE): An Update, Veterinary Record, 142, 103 535 Wells, G., Hawkins, S., Green, P., Spencer, Y., Dexter, I. and Dawson, D. (1999) Limited Detection of Sternal Bone Marrow Infectivity in the Clinical Phase of Experimental Bovine Spongiform Encephalopathy (BSE), Veterinary Record, 144, 292–4 536 Scott, M.R., Will, R., Ironside, J., Nguyen, H.-O., Tremblay, P., DeArmond, S.J. and Prusiner, S.B. (1999) Compelling Transgenetic Evidence for Transmission of Bovine Spongiform Encephalopathy Prions to Humans, Proceedings of the National Academy of Sciences of the USA, 96, 15137–42 537 Scott, M.R., Safar, J., Telling, G., Nguyen, H.-O., Groth, D., Torchia, M., Kochler, R., Tremblay, P., Walther, D., Cohen, F., DeArmond, S. and Prusiner, S. (1997) Identification of a Prion Protein Epitope Modulating Transmission of Bovine Spongiform Encephalopathy Prions to Transgenic Mice, Proceedings of the National Academy of Sciences of the United States of America, 94, 14279–84 538 IBD1 tab 2 para. 5.3.3 539 Kimberlin, R. and Walker, C. (1989) Pathogenesis of Scrapie in Mice after Intragastric Infection, Virus Research, 12, 213–20; Diringer, H., Beekes, M. and Oberdieck, U. (1994) The Nature of the Scrapie Agent: The Virus Theory, Annals of The New York Academy of Science, 724, 246–58; Prusiner, S., Cochran, S. and Alpers, S. (1985) Transmission of Scrapie in Hamsters, Journal of Infectious Diseases, 152, 971–8 540 Kimberlin, R.H. and Walker, C.A. (1978) Pathogenesis of Mouse Scrapie: Effect of Route of Inoculation on Infectivity Titres and Dose-Response Curves, Journal of Comparative Pathology, 88, 39–47
 
 
COMMERCIAL IN CONFIDENCE
 
NOT FOR PUBLICATION
 
COMMITTEE ON SAFETY OF MEDICINES
 
WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY
 
3. Products for injection using bovine tissue
 
This category includes tissue derived products, other than from brain or lymphoid tissue and excludes bovine blood.
 
3.1 Bovine Pancreas
 
3.1.1 Insulin
 
The following companies hold licences for bovine insulin.
 
Source Country
 
Denmark
 
USA
 
USA
 
Denmark, Sweden, USA, Italy, Canada, Portugal, Netherlands
 
In 1988 a sample consignment from UK was used. UK source material is no longer used.
 
Comment
 
There are no bovine insulins manufctured from UK sourced material.
 
Bovine insulin is not widely prescribed, but has a niche in the market for diabetics unable to tolerate other products.
 
3.1.2 Glucagon
 
bovine pancreas from USA.
 
as for insulin - Scandinavia, USA, Italy, Canada, Portugal and Netherlands.
 
3.1.3
 
Miscellaneous products containing Bovine Pancreas
 
3.1.3.1 Zonulysin (Chymotrypsin) - sourced from Canada
 
3.1.3.2 Streptokinase - culture medium, containing bovine muscle and pancreas are used in process - all sourced from Germany
 
3.1.3.3 Fibrinogen + Desoxyribonuclease - bovine pancreas sourced from Canada and S Africa.
 
3.2. Vaccines using Bovine Products in process
 
snip...see full text ;
 
 
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 catastrope. 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 grannular 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 ben 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 labeled 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 use 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 inoculatted 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.
 
==================================================================
 
Greetings List Members,
 
pretty disturbing document. now, what would stop this from happening with the vaccineCJD in children???
 
kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA
 
 
2014
 
 
Evidence for zoonotic potential of ovine scrapie prions
 
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics
 
Abstract
 
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
 
Subject terms: Biological sciences• Medical research At a glance
 
 
Suspect symptoms
 
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
 
28 Mar 01 Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
 
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
 
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...
 
2001
 
Suspect symptoms
 
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
 
28 Mar 01
 
Like lambs to the slaughter
 
31 March 2001
 
by Debora MacKenzie Magazine issue 2284.
 
FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
 
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
 
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
 
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.
 
Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.
 
Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.
 
As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.
 
"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.
 
But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.
 
People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.
 
But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."
 
There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
 
Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.
 
 
why do we not want to do TSE transmission studies on chimpanzees $
 
5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
 
snip...
 
R. BRADLEY
 
 
1: J Infect Dis 1980 Aug;142(2):205-8
 
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
 
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
 
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
 
snip...
 
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
 
PMID: 6997404
 
 
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
 
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
 
snip...
 
76/10.12/4.6
 
 
 
Sunday, May 18, 2008
 
MAD COW DISEASE BSE CJD CHILDREN VACCINES
 
 
 
Sunday, May 1, 2011
 
W.H.O. T.S.E. PRION Blood products and related biologicals May 2011
 
 
 
The pharmaceutical industry
 
146 Bovine materials were, and are, also used in pharmaceutical, medical and veterinary medical products (see Annex 1 to Chapter 2 in vol. 7: Medicines and Cosmetics). The UK pharmaceuticals industry is one of the largest in the world. In 1997, for example, UK exports were worth over £5 billion and accounted for around 12 per cent of the world market. There were over 400 pharmaceutical manufacturers and research organisations in the UK, although the market was dominated by multinationals such as Glaxo Wellcome, SmithKline Beecham and Zeneca.9
 
147 Bovine materials from the slaughterhouse are used directly in pharmaceuticals. Several injectable medicines are derived directly from bovine sources. Hormones such as insulin and glucagon may be derived from bovine pancreases, and protein products such as aprotonin and heparin are derived from bovine lungs and intestinal mucous respectively. Sutures and some medical devices such as heart valves and pericardium patches are also derived directly from bovine materials, in this case the intestines, heart and serous membranes.
 
148 Bovine materials are also used indirectly in the manufacture of certain types of vaccine. Cells which are used to grow these vaccines are nourished in nutrientrich cultures that contain serum from the blood of foetal or new-born calves, or bovine serum albumin, which derives from the blood of older cattle. Bacterial cells are grown in nutrient-rich broths containing peptone derived from bovine meat, and some allergens are produced in special culture media which contain digests of calf brain and ox liver. In all these cases the bovine materials are not a constituent of the final product, but they are used in an ancillary way in the manufacturing process.
 
149 Tallow and gelatine are also used in several pharmaceutical and medical products. Gelatine is widely used as a pill coating and tallow is a constituent of most creams and ointments. Other uses of bovine products
 
150 Bovine materials are used in a wide range of processes and products in many different industries. They are used in toothpaste, chewing gum and pet food; in fertilisers and cosmetics; and in such varied products as fire extinguisher foam, buttons, handles, lubricants and racquet strings. Bovine materials are used in the manufacture of paint. Cattle skins are used for hides, and other bovine materials are included in cleaning agents used in leather processing.
 
9 Britain 1999: The Official Yearbook of the United Kingdom, London, The Stationery Office, 1998, p. 475
 
 
 
Sunday, December 15, 2013
 
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2013 UPDATE
 
 
 
Thursday, July 24, 2014
 
Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA
 
 
 
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.
 
*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.
 
*** It also suggests a similar cause or source for atypical BSE in these countries. ***
 
see page 176 of 201 pages...tss
 
 
 
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;
 
 
 
2007
 
Date: March 21, 2007 at 2:27 pm PST
 
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II PRODUCT
 
Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007 CODE Cattle feed delivered between 01/12/2007 and 01/26/2007 RECALLING FIRM/MANUFACTURER Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
 
Firm initiated recall is ongoing.
 
REASON Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.
 
VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI
 
___________________________________
 
PRODUCT Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007 CODE The firm does not utilize a code - only shipping documentation with commodity and weights identified. RECALLING FIRM/MANUFACTURER Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007.
 
Firm initiated recall is complete. REASON Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.
 
VOLUME OF PRODUCT IN COMMERCE 9,997,976 lbs. DISTRIBUTION ID and NV
 
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
 
 
 
Newberry Feed & Farm, Inc. 2/14/14
 
Department of Health and Human Services logo Department of Health and Human Services Public Health Service Food and Drug Administration Atlanta District Office 60 8th St., NE Atlanta, GA 30309
 
February 14, 2014
 
VIA UPS
 
J. Clint Layne, President/Co-owner Rhett Baker, Secretary-Treasurer/Co-owner Newberry Feed & Farm Center, Inc. 131 Giff Street Newberry, SC 29108
 
WARNING LETTER (14-ATL-04)
 
Dear Messrs. Layne and Baker,
 
An inspection of your feed mill located at 2431 Vincent Street, Newberry, SC 29108 conducted by Investigators from the U.S. Food & Drug Administration (FDA) and South Carolina Department of Agriculture on September 5-9, 2013 revealed significant violations of Current Good Manufacturing Practice (CGMP) regulations for Medicated Feeds found in Title 21, Code of Federal Regulations, Part 225 (21 C.F.R. 225). Such violations cause the medicated feeds manufactured at your facility to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for the manufacture, processing, packing, or holding of the medicated feeds do not conform to or are not operated or administered in conformity with current good manufacturing practices.
 
The inspection also revealed significant violations of the requirements set forth in Title 21, Code of Federal Regulations, Section 589.2000 (21 C.F.R. 589.2000), Animal Proteins Prohibited in Ruminant Feed. This regulation is intended to prevent the establishment and amplification of Bovine Spongiform Encephalopathy (BSE). Animal feeds and feed ingredients containing prohibited mammalian proteins are considered potentially injurious to ruminant and public health. Because you failed to comply with the requirements set forth in 21 C.F.R. 589.2000, the feed products manufactured and distributed by your facility are adulterated within the meaning of Section 402(a)(4) of the Act [21 U.S.C. 342(a)(4)] in that they have been prepared, packed, or held under insanitary conditions whereby they may have become contaminated with filth or rendered injurious to health. The adulterated feed was subsequently misbranded within the meaning of Section 403(a)(1) of the Act [21 U.S.C. 343(a)(1)] because it was not properly labeled with the required BSE cautionary statement.
 
Medicated Feed CGMP violations observed during the inspection include, but are not limited to, the following:
 
1. You failed to ensure that all equipment that comes in contact with the active drug component, feeds in process or finished medicated feed is subject to reasonable and effective procedures to prevent unsafe contamination of feeds with drugs. [21 C.F.R. 225.65(b)]
 
Your written equipment cleaning procedure that requires flushing with a minimum of (b)(4) does not appear to be effective to prevent unsafe contamination of your manufactured feed. During the inspection, our Investigators observed a build-up of feed residue on surfaces inside the mixer that was approximately three inches thick in accumulation. This build-up was observed on the equipment throughout the inspection, including after flushing had been performed. In addition, the cleaning procedure does not include cleaning of the hand-add chute or scoops/buckets used to handle ingredients that are then used to manufacture medicated feed. During the inspection, our Investigators observed a build-up of feed residues approximately four inches thick on the inside of the chute used to add the drug ingredients and other “hand-adds”. Considering the extent of residue accumulation—some of which would include the drug sources used in your medicated feeds—on surfaces in the mixer and the hand-add chute, it is likely that chunks of this material break off periodically, and may sometimes end up in feeds not intended to contain that drug.
 
This is a repeat observation from the July 24-26, 2012 inspection. Your response to the Form FDA 483, Inspectional Observations, issued to you following the 2012 inspection stated the buckets and scoops would be replaced, and you would schedule a regular cleaning of the equipment every (b)(4). Based on the accumulation of residual feed observed on manufacturing equipment during the inspection and which remained following flushing, you have either failed to implement the promised corrective action or you have failed to ensure that the corrective action was lasting and effective in preventing the violation from recurring.
 
On October 3, 2013, we received your response to the Form FDA 483 issued to you following the September 2013 inspection. You state in your response that you have posted signs, added cleaning of the dump chute to the (b)(4) cleaning procedure, and increased the physical cleaning of the mixer to (b)(4). You also state that dedicated scoops will be used for each component or drug and have ordered disposable liners for the buckets that will be discarded following each dumping of product. However, you did not provide any documentation to demonstrate these changes have been made, such as photos of the new sign or newly cleaned equipment, or copies of the revised cleaning procedure.
 
2. You failed to investigate and implement corrective action where the results of assays indicated that the level of drug in medicated feed was not in accord with label specifications or not within permissible assay limits. An original or copy of the record of such action must be maintained on the premises. [21 C.F.R. 225.58(d)]
 
Your firm failed to adequately investigate and implement corrective action when you received an assay result on 6/21/13 for a Type C medicated feed containing Amprolium, showing the drug present at 73% of the concentration stated on the label. This assay result is outside of the assay limits of 80-120% established in 21 C.F.R. 558.4. The subsequent review of production and inventory records conducted by your firm revealed these records were “OK”, and it was determined the feed sample was taken incorrectly. Your firm’s “\investigation sheet” dated 6/21/13 states the corrective action as “[t]rying to make sure the samples are taken correctly.” No technique or procedural changes were made in response to the described corrective action, however. Thus, your firm failed to implement any corrective action in response to the out of specification assay result.
 
Your firm also received assay results for a Type C medicated broiler feed containing a Salinomycin concentration of 75% on 7/7/12 and 78% on 8/3/12. These assay results are outside the specification tolerance of 80-120% of the concentration stated on the label. [21 C.F.R. 558.4]. Your firm did not initiate any investigation or corrective action after receiving these results. Failure to investigate and implement corrective action following an out-of-limits assay is a repeat observation from the July 24-26, 2012 inspection.
 
In your response to the Form FDA 483 issued to you following the September 2013 inspection, you state that you have instructed personnel further on completing the investigation form and have also added sampling instructions to the procedures manual. However, you did not provide copies of the new/revised investigation form or the revisions to the procedures manual discussing sampling.
 
3. Your daily inventory records fail to record the batches or production runs (or lots) of medicated feed in which each drug was used. [21 C.F.R. 225.42(b)(6)(iii)] Although your daily inventory records appear to contain all of the other required information, due to the way the form is designed, there is only space to record one batch per day per drug and no space to record the name of the product, lot number, or other identifier for that batch. Your daily inventory record must reflect every batch or lot of medicated feed manufactured each day.
 
4. You failed to document in the daily inventory record actions taken to reconcile any discrepancies in the daily inventory record. [21 C.F.R. 225.42(b)(6)(v)] For example, the drug inventory conducted on 8/30/13 revealed a discrepancy with respect to one fifty pound bag of (b)(4)(a Type A medicated article). It does not appear that your firm took any action to reconcile this discrepancy.
 
You state in your response to both #3 and #4 above that you have added an area to the inventory control sheet to report any drugs that do not reconcile, and that there is a space to make notes and/or adjustments to inventory to ensure they reconcile. However, you did not indicate that the inventory control sheet had been adjusted to provide for the possibility that any single drug may be used more than once a day, and you did not provide any documentation—such as a copy of the revised form—to demonstrate that these changes have been made.
 
5. You have failed to properly identify, store, handle, and control drugs in your mixing areas to maintain their integrity and identity [21 C.F.R. 225.42(b)(4)]. Our inspection found that your firm was storing bags of Type A Medicated Articles in a manner and location that allowed them to be covered in bird droppings.
 
This finding also relates to your obligations under 21 C.F.R. 225.20(b)(2) and (3), which requires the facility to be maintained in a reasonably clean and orderly manner, and for access by birds and other pests to be minimized. During the September 5-6, 2013 inspection, our Investigators observed birds (greater than ten) nesting, flying, perched and foraging in the mill. Your response indicated that you are investigating ways to keep birds out of the mill, but that you did not yet have a plan at that time. You indicated that you would have a plan in place by November 1, 2013, but did not provide further information regarding any plan.
 
In addition, the following violations of the Animal Proteins Prohibited in Ruminant Feed regulation [21 C.F.R. 589.2000] were observed during the inspection:
 
1. You failed to use clean out procedures or other means adequate to prevent carryover of protein derived from mammalian tissues to feeds that may be used for ruminants [21 C.F.R. 589.2000(e)(1)(iii)(B)]. Your feed is therefore adulterated under Section 402(a)(4) [21 U.S.C. 342(a)(4)] of the Act.
 
Because your firm uses animal proteins prohibited from use in ruminant feeds, and also makes feeds for ruminants, you are required to have a cleanout procedure adequate to prevent carryover into ruminant feeds. As noted above, our Investigators observed a significant build-up of feed residues inside the feed mixer and the hand-add chute, which remained following your cleanout procedure. This equipment is used for processing both proteins derived from mammalian tissues and feeds for ruminants. Since flushing was ineffective in removing the accumulated feed from the equipment, your clean out procedure was inadequate to prevent carryover of protein derived from mammalian tissues to feeds intended for ruminant animals.
 
Your response indicates that your corrective actions for this item are the same as for Item 1 above. However, as noted above, you did not provide any documentation to demonstrate that the changes you discussed have been made, or that they were adequate to address this issue.
 
2. You failed to label all products which contained or may have contained prohibited materials and that are intended for use in animal feed with the BSE cautionary statement, "Do not feed to cattle or other ruminants." [21 C.F.R. 589.2000(e)(1)(i).]
 
As discussed above, your clean out procedure is inadequate to prevent carryover of protein derived from mammalian tissues to feeds intended for ruminant animals. Thus, all feeds manufactured using your mixer and hand-add chute that did not contain the BSE cautionary statement “Do not feed to cattle or other ruminants,” are misbranded under Section 403(a)(1) [21 U.S.C. 343(a)(1)] of the Act. For example, a batch of Carolina Choice Beef Conditioner Custom Mix (b)(4), manufactured on September 6, 2013, while there was a significant build-up of feed residues in the feed mixer, was misbranded as its label did not contain the required BSE cautionary statement.
 
The above is not intended to be an all-inclusive list of violations at your facility. As a medicated and non-medicated feed manufacturer, you are responsible for assuring that your overall operation and the products you manufacture and distribute are in compliance with the law. You should take prompt action to correct these violations, and you should establish procedures whereby such violations do not recur. Failure to promptly correct these violations may result in regulatory and/or administrative sanctions. These sanctions include, but are not limited to, seizure, injunction, and/or notice of opportunity for a hearing on a proposal to withdraw approval of your Medicated Feed Mill License under Section 512(m)(4)(B)(ii) of the Act and 21 C.F.R. 515.22(c)(2).
 
Based on the results of the September 5-9, 2013 inspection, evaluated together with the evidence before FDA when the Medicated Feed Mill License was approved, the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of medicated feeds are inadequate to assure and preserve the identity, strength, quality, and purity of the new animal drugs therein. This letter constitutes official notification under the law and provides you an opportunity to correct the above described violations.
 
You should notify this office, in writing, within fifteen (15) working days of the receipt of this letter of the steps you have taken to bring your firm into compliance with the law. Your response should include an explanation of each step being taken to correct the violations and prevent their recurrence. In your response, please include the timeframe in which the corrections will be completed and provide any documentation that will effectively assist us in evaluating whether the corrective actions have been made and the adequacy of such. If you are unable to complete the corrective actions within fifteen (15) working days, identify the reason for the delay and the time within which you will complete the corrections. Include copies of any available documentation demonstrating that corrections have been made.
 
Your written response should be sent to the U.S. Food and Drug Administration, Attn: Janice L. King, Compliance Officer, at the address noted in the letterhead. If you have questions, please contact Mrs. King at 843-746-2990 or write her at the noted address.
 
Sincerely, /S/ Philip S. Campbell Acting District Director Atlanta District Office
 
cc: South Carolina Department of Agriculture, Phillip C. Trefsgar
 
 
Tuesday, December 23, 2014
 
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION
 
 
Sunday, December 15, 2013
 
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE
 
 
Friday, April 19, 2013
 
FDA BSE TSE PRION NEWS FEED AND ANNUAL INSPECTION OF FEED MILLS REPORTS HAS CEASED TO EXIST
 
 
American Association of Zoo Veterinarians Infectious Disease Committee Manual 2013
 
BOVINE SPONGIFORM ENCEPHALOPATHY (BSE)
 
Little is known about atypical BSE. The origin and natural routes of transmission, if any, have yet to be determined. Almost all cases have been in older cattle (usually > 8 years of age) that have shown little resemblance to the clinic-pathological picture seen in classical disease. It has been suggested that the disease may be sporadic or be caused by a genetic mutation, but no convincing evidence has been found to support either of these ideas. The correct answer will probably only come by study of the future annual incidence curves of both types of disease. Regardless of the origin of atypical BSE, the possibility of recycling the disease in cattle and other ruminants, as well as the potential for transmission to humans, mandate a continuation of feed and specified-risk materials (SRM) bans, together with diagnostic testing programs for some time to come.
 
snip...
 
Naturally occurring cases of BSE in species other than cattle have been very limited and have been linked to exposure to contaminated feed or infected carcasses. The majority of cases originated in the UK and like BSE in cattle, have declined with the implementation of feed controls. None of the exotic animals were infected in the wild.
 
Experts who may be consulted: Linda A. Detwiler, DVM Clinical Professor Department of Pathobiology and Population Medicine
 
College of Veterinary Medicine Mississippi State University 732-580-9391 Fax: 732-741-7751 ldetwiler@belle-terre.com
 
 
Atypical BSE: Transmissibility
 
 BASE (L) transmitted to:  cattle (IC) - inc < 20 mos and oral?)
 
 Cynomolgus macaques (IC)
 
 Mouse lemurs (IC and oral)
 
 wild-type mice (IC)
 
 bovinized transgenic mice (IC and IP)
 
 humanized transgenic mice (IC)
 
 H cases transmitted to:
 
 cattle – IC incubations < 20 months
 
 bovinized transgenic mice (IC)
 
 ovinized transgenic mice (IC)
 
 C57BL mice (IC)
 
 One study did not transmit to humanized PrP Met 129 mice
 
Evaluation of Possibility of Atypical
 
BSE Transmitting to Humans
 
 Possble interpretation:
 
 L type seems to transmit to nonhuman primates with greater ease than classical BSE
 
 L type also transmitted to humanized transgenic mice with higher attack rate and shorter incubation period than classical?
 
 H type did not transmit to Tg Hu transgenic mice
 
Linda Detwiller, 5/10/2011
 
 
I ask Professor Kong ;
 
Thursday, December 04, 2008 3:37 PM
 
Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment
 
IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....
 
Professor Kong reply ;
 
.....snip
 
As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.
 
Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA
 
BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.
 
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
 
 
 
P.4.23 Transmission of atypical BSE in humanized mouse models
 
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA
 
Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were argely undefined.
 
Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice.
 
Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.
 
Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time. The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.
 
Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.
 
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
 
 
 
 
14th International Congress on Infectious Diseases H-type and L-type Atypical BSE January 2010 (special pre-congress edition)
 
18.173 page 189
 
Experimental Challenge of Cattle with H-type and L-type Atypical BSE
 
A. Buschmann1, U. Ziegler1, M. Keller1, R. Rogers2, B. Hills3, M.H. Groschup1. 1Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany, 2Health Canada, Bureau of Microbial Hazards, Health Products & Food Branch, Ottawa, Canada, 3Health Canada, Transmissible Spongiform Encephalopathy Secretariat, Ottawa, Canada
 
Background: After the detection of two novel BSE forms designated H-type and L-type atypical BSE the question of the pathogenesis and the agent distribution of these two types in cattle was fully open. From initial studies of the brain pathology, it was already known that the anatomical distribution of L-type BSE differs from that of the classical type where the obex region in the brainstem always displays the highest PrPSc concentrations. In contrast in L-type BSE cases, the thalamus and frontal cortex regions showed the highest levels of the pathological prion protein, while the obex region was only weakly involved.
 
Methods:We performed intracranial inoculations of cattle (five and six per group) using 10%brainstemhomogenates of the two German H- and L-type atypical BSE isolates. The animals were inoculated under narcosis and then kept in a free-ranging stable under appropriate biosafety conditions. At least one animal per group was killed and sectioned in the preclinical stage and the remaining animals were kept until they developed clinical symptoms. The animals were examined for behavioural changes every four weeks throughout the experiment following a protocol that had been established during earlier BSE pathogenesis studies with classical BSE.
 
Results and Discussion: All animals of both groups developed clinical symptoms and had to be euthanized within 16 months. The clinical picture differed from that of classical BSE, as the earliest signs of illness were loss of body weight and depression. However, the animals later developed hind limb ataxia and hyperesthesia predominantly and the head. Analysis of brain samples from these animals confirmed the BSE infection and the atypical Western blot profile was maintained in all animals. Samples from these animals are now being examined in order to be able to describe the pathoge esis and agent distribution for these novel BSE types.
 
Conclusions: A pilot study using a commercially avaialble BSE rapid test ELISA revealed an essential restriction of PrPSc to the central nervous system for both atypical BSE forms. A much more detailed analysis for PrPSc and infectivity is still ongoing.
 
 
14th ICID International Scientific Exchange Brochure - Final Abstract Number: ISE.114
 
Session: International Scientific Exchange
 
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009
 
T. Singeltary Bacliff, TX, USA
 
Background: An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
 
Methods: 12 years independent research of available data
 
Results: I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
 
Conclusion: I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
 
 
snip... see more breaches in the BSE aka mad cow Triple Firewall, that never was here ;
 
Friday, January 23, 2015
 
*** Replacement of soybean meal in compound feed by European protein sources and relaxing the mad cow ban $
 
 
 
To date, 27 cases of L-BSE and 24 cases of H-BSE have been report­ed worldwide (16), thus meaning that the prevalence of atypical BSE is considerably lower than that of C-BSE. However, recent studies showed that L-BSE is easily transmissible to transgenic mice expressing human (17,18) or bovine (19,20) prion protein, as well as to non-human primates (21), with shorter incubation periods than for the transmission of C-BSE to these animals.
 
***The virulent nature of L-BSE has stimulated new concern for human public health since the transmis­sion of C-BSE to humans resulted in variant Creutz­feldt-Jakob disease (vCJD) (4-7), a new emergent prion disease.
 
 
 
***Infectivity in skeletal muscle of BASE-infected cattle
 
***The present data offer novel information on the tropism of the BASE agent and highlight relevant public health issues. While the transmission barrier for classical BSE is high in most species, BASE prions are readily transmissible to a variety of mammals including non-human primates [11–13,35]. Accordingly, the possibility of spreading of BASE prions through skeletal muscle to other species should be taken into account and evaluated in risk analysis studies.
 
 
 
 
 
P.4.23
 
Transmission of atypical BSE in humanized mouse models
 
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA
 
Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.
 
Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.
 
Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time. The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.
 
Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.
 
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
 
 
 
SUMMARY REPORT CALIFORNIA ATYPICAL L-TYPE BOVINE SPONGIFORM ENCEPHALOPATHY CASE INVESTIGATION JULY 2012 CALIFORNIA
 
Summary Report BSE 2012
 
Executive Summary
 
 
 
Saturday, August 4, 2012
 
Final Feed Investigation Summary - California atypical L-type BSE Case - July 2012
 
 
Saturday, August 4, 2012
 
Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation
 
 
Wednesday, December 31, 2014
 
NASDA BSE, CWD, SCRAPIE, TSE, PRION, Policy Statements updated with amendments passed during the NASDA Annual Meeting Updated September 18, 2014
 
 
 
Sunday, January 11, 2015
 
Docket No. APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of Animals and Animal Products Singeltary Submission
 
 
 
2001
 
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
 
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
 
[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;
 
[unknown woman] what group are you with?
 
[TSS] CJD Watch and my Mom died from hvCJD we are trying to tract down CJD and other human TSE's world wide. i was invited to sit in on this from someone inside the USDA/APHIS and that is why i am here. do you intend on banning me from this conference now?
 
at this point the conference was turned back up, and i got to finish listening. They never answered or even addressed my one question, or even addressed the issue. BUT, i will try and give you a run-down for now, of the conference.
 
snip...full text ;
 
 
Thursday, January 15, 2015
 
41-year-old Navy Commander with sporadic Creutzfeldt–Jakob disease CJD TSE Prion: Case Report
 
 
 
Subject: *** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease aka mad cow type disease
 
what is CJD ? just ask USDA inc., and the OIE, they are still feeding the public and the media industry fed junk science that is 30 years old.
 
why doesn’t some of you try reading the facts, instead of rubber stamping everything the USDA inc says.
 
sporadic CJD has now been linked to BSE aka mad cow disease, Scrapie, and there is much concern now for CWD and risk factor for humans.
 
My sincere condolences to the family and friends of the House Speaker Becky Lockhart. I am deeply saddened hear this.
 
with that said, with great respect, I must ask each and every one of you Politicians that are so deeply saddened to hear of this needless death of the Honorable House Speaker Becky Lockhart, really, cry me a friggen river. I am seriously going to ask you all this...I have been diplomatic for about 17 years and it has got no where. people are still dying. so, are you all stupid or what??? how many more need to die ??? how much is global trade of beef and other meat products that are not tested for the TSE prion disease, how much and how many bodies is this market worth?
 
Saturday, January 17, 2015
 
*** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease
 
 
 
 who’s kidding whom $$$ i.e. USDA INC AND THE OIE
 
2014
 
***Moreover, L-BSE has been transmitted more easily to transgenic mice overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.
 
***It has been suggested that some sporadic CJD subtypes in humans may result from an exposure to the L-BSE agent.
 
*** Lending support to this hypothesis, pathological and biochemical similarities have been observed between L-BSE and an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and another sCJD subtype (MM genotype) [15].
 
snip...
 
 
Monday, October 10, 2011
 
EFSA Journal 2011 The European Response to BSE: A Success Story
 
snip...
 
EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far
 
*** but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded.
 
*** Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.
 
snip...
 
 
 
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...
 
 
*** HUMAN MAD COW DISEASE nvCJD TEXAS CASE NOT LINKED TO EUROPEAN TRAVEL CDC ***
 
Sunday, November 23, 2014
 
*** Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European ***
 
the patient had resided in Kuwait, Russia and Lebanon. The completed investigation did not support the patient's having had extended travel to European countries, including the United Kingdom, or travel to Saudi Arabia. The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.
 
 
Sunday, December 14, 2014
 
*** ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD strains, TSE prion aka Mad Cow Disease United States of America Update December 14, 2014 Report ***
 
http://transmissiblespongiformencephalopathy.blogspot.com/2014/12/alert-new-variant-creutzfeldt-jakob.html


J Neurol Neurosurg Psychiatry 2002;72:792-793 doi:10.1136/jnnp.72.6.792 Short report

 
Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

 
E A Croes1, G Roks1,*, G H Jansen3, P C G Nijssen2, C M van Duijn1

 
+ Author Affiliations 1Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands 2Department of Neurology, St Elisabeth Hospital, PO Box 90151, 5000 LC Tilburg, Netherlands 3Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands

 
Correspondence to: Professor C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands; vanduijn@epib.fgg.eur.nl Received 27 December 2001 Accepted 12 March 2002 Revised 1 March 2002

 
Abstract

 
A 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic CJD. This is the longest incubation period described so far for iatrogenic CJD. Furthermore, this is the first report of CJD after diagnostic use of hGH. Since the patient was one of the first in the world to receive hGH, other cases of iatrogenic CJD can be expected in the coming years.

 
snip...

 
An incubation period as long as 38 years had never been reported for iatrogenic CJD. Huillard d'Aignaux et al7 studied the incubation period in 55 patients with hGH related CJD in a cohort of 1361 French hGH recipients. The median incubation period was between 9 and 10 years. Under the most pessimistic model, the upper limit of the 95% confidence interval varied between 17 and 20 years. Although the infecting dose cannot be quantified, it can be speculated that the long incubation period in our patient is partly explained by the administration of a limited amount of hGH. This hypothesis is supported by experimental models, in which higher infecting doses usually produce shorter incubation periods.6 Since our patient was one of the first in the world to receive hGH, this case indicates that still more patients with iatrogenic CJD can be expected in the coming years. Another implication of our study is that CJD can develop even after a low dose of hGH. This case once more testifies that worldwide close monitoring of any form of iatrogenic CJD is mandatory.

 
http://jnnp.bmj.com/content/72/6/792.long


Saturday, December 13, 2014

 
*** Terry S. Singeltary Sr. Publications TSE prion disease Peer Review ***

 
Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 
snip...

 
http://transmissiblespongiformencephalopathy.blogspot.com/2014/12/terry-s-singeltary-sr-publications-tse.html
 


Thursday, January 22, 2015
 
Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?
 
 
 

Tuesday, December 30, 2014
 
TSEAC USA Reason For Recalls Blood products, collected from a donors considered to be at increased risk for Creutzfeldt-Jakob Disease (CJD), were distributed END OF YEAR REPORT 2014
 
 
 

TSS

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