Wednesday, February 3, 2010

Import Alert 62-07 Sygen Injectable (Bovine-Extracted GMI Monosialoganglioside) manufactured from bovine brain starting material

Import Alert 62-07 Import Program

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Import Alert

(Note: This import alert represents the Agency's current guidance to FDA field personnel regarding the manufacturer(s) and/or products(s) at issue. It does not create or confer any rights for or on any person, and does not operate to bind FDA or the public).

Import Alert # 62-07

Published Date: 10/02/2009

Type: DWPE Import Alert Name:

"Detention Without Physical Examination of Shipments of Sygen Injectable (Bovine-Extracted GMI Monosialoganglioside)"

Reason for Alert:

Sygen is an unapproved new drug manufactured by Fidia SpA, Italy, which is currently distributed under b(4) . The product presents BSE concerns because it is manufactured from bovine brain starting material. An inspection of Fidia conducted in February - March 2001, disclosed significant deficiencies regarding verification that the bovine brain source used in the manufacture of Sygen was obtained from a non-BSE country or that no commingling with any animal material from BSE risk countries had occurred. A Warning Letter was issued on June 28, 2001, to Fidia and CDER/OC is awaiting response.

The Office of Compliance has also learned that firms other than Fidia SpA are shipping Sygen to the U.S. Two such firms include TRB-Pharma of Brazil and its subsidiary, TransBussan of Switzerland. Neither of these firms has approved IND's for Sygen. Reportedly, the shipments are being offered for entry for personal treatment under FDA's procedures for Coverage of Personal Importations.


Districts may detain without physical examination all shipments of Sygen unless:

-they are coming directly from Fidia SpA, Padua, Italy;


-they are from finished product lot nos. b(4) and active pharmaceutical ingredient (API) lot no. 1(B)


-they are offered for entry under b(4) Districts encountering shipments of Sygen, which meet the listed criteria, contact for further instructions.

For questions concerning the new drug status of the product, please contact CDER.

Discretionary release of Sygen injectable under the Personal Importation guidance of Chapter 9 of the Regulatory Procedures Manual (RPM) is not appropriate. This drug poses an unreasonable health risk to the user due to possible exposure to Bovine Spongiform Encephalopathy (BSE) causative agents.

Product Description: Sygen, injectable

Charge: "The article is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears to be a new drug that is adulterated, misbranded, or without an effective new drug application (NDA) as required by Section 505. [Unapproved new drug, Section 505(a)]."

OASIS charge code - UNAPPROVED


"The article is subject to refusal of admission pursuant to Section 801(a)(1) in that it appears to be for use as a drug and may have been manufactured, processed, or packed under insanitary conditions, or the article appears to be prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health [Adulterated drug, Section 501 (a)(2)(a)]."

OASIS charge code - BSE DRUGS


"The article is subject to refusal of admission pursuant to Section 801(a)(1) in that it appears to be for use as a drug and may not have been manufactured, processed, packed, or held in conformity with current good manufacturing practices [Adulterated drug, Section 501 (a)(2)(B)]."

OASIS charge code - DRUG GMPS


(55 - - - --) Pharm Necess & Ctnr For Drug/Bio

(57 - - - --) Bio & Licensed In-Vivo & In-Vitro Diag

(60 - - - --) Human and Animal Drugs

(61 - - - --) Human and Animal Drugs

(62 - - - --) Human and Animal Drugs

(63 - - - --) Human and Animal Drugs

(64 - - - --) Human and Animal Drugs

(65 - - - --) Human and Animal Drugs

(66 U - - 01) Bone Parts (Natural Body Parts, Invivo Only)

(66 U - - 02) Cornea (Eye Parts) (Natural Body Parts, Invivo Only)

(66 U - - 03) Embryo (Natural Body Parts, Invivo Only)

(66 U - - 04) Hair (Natural Body Parts, Invivo Only)

(66 U - - 05) Heart (Natural Body Parts, Invivo Only)

(66 U - - 06) Kidney (Natural Body Parts, Invivo Only)

(66 U - - 07) Skin (Natural Body Parts, Invivo Only)

(66 U - - 08) Sperm (Natural Body Parts, Invivo Only)

(66 U - - 99) Natural Body Parts, Invivo Only, N.E.C.

(66 - - - --) Human and Animal Drugs

(73 - - - --) Anesthesiology

(74 - - - --) Cardiovascular

(75 - - - --) Chemistry

(76 - - - --) Dental

(77 - - - --) Ear,Nose And Throat

(78 - - - --) Gastroenterological & Urological

(79 - - - --) General & Plastic Surgery

(80 - - - --) General Hospital/Personal Use

(81 - - - --) Hematology

(82 - - - --) Immunology

(83 - - - --) Microbiology

(84 - - - --) Neurological

(85 - - - --) Obstetrical & Gynecological

(86 - - - --) Ophthalmic

(87 - - - --) Orthopedic

(88 - - - --) Pathology

(89 - - - --) Physical Medicine

(90 - - - --) Radiological

(91 - - - --) Toxicology

List of firms and their products that have met the criteria for exclusion from Detention without Physical Examination (DWPE) under this Import Alert (a.k.a. Green List)

(3002806986) Fidia S.p.A.Date Published : 09/10/2009 Via Ponte Della Fabbrica, 3/a , Abano Terme, Padova, IT


The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.



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.


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...

B.S.E. and Veterinary Medicines

Thank you very much indeed for your letter of the 26th of January outlining to me the various steps that are proposing to take in order to reduce the risk from B.S.E. in veterinary medicines. It is, as you say, and extremely difficult problem. ....

Draft cover letter to product licence holders (considered by Human and Vet Medicines including deer)

(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.)


This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease.


Considered to be of great risk.




7. Any Other Business


8 June 1988 Internal CVL meeting to discuss the implications of BSE to Biologicals Products containing bovine extracted material (Annex 6). (YB 88/06.08/11.1-11.2) Following a detailed review of situation the following recommendations were made:

1. Specific concern over use of pituitary gland products by veterinary surgeons and companies. Paper to be produced for Tolworth (Veterinary Medicines Division).

2. Urgent review of all products both immunological and pharmaceutical for possible inclusion of ingredients of bovine origin.

3. Draft guidelines to be presented in full to the National Office of Animal Health (NOAH), the trade body representing the Veterinary Medicines part of the pharmaceutical industry, at next meeting on 11 July 1988


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.


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



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


another 6 pages of blank space. ...TSS



Medicines Act - Veterinary Products Committee




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

[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 ;




another 6 pages or so that are blank. ...TSS





7.2.1. Products with bovine brain/lymphoid tissue as ingredients and administered by injection...[111]

7.2.2 Products with bovine ingredients (other than brain/lymphoid tissue) and administered by injection...[135]

7.2.3 Tissue implants, open wound dressings, surgical materials, dental and opthalmic products with bovine ingredients...[27]

7.2.4. Products with bovine ingredients and administered topically...[5]

7.2.5 Products with bovine ingredients and administered orally...[9]

7.2.6 Products with other animal/insect/bird ingredients and administered:

a. by injection a: 117

b. by topically b: 6

c. orally c: 8

7.2.7 Products with materials produced from animal material by chemical processes, eg stearic acid, gelatin and lanolin...[156]

With two exceptions, the replies to date have not given any immediate cause for concern, although 176 products do not conform to the CSM/VPC guidelines.

8. The first exception was from which gave very limited information about a very large number of homoepathic medicines with material obtained from cattle and a number with material from the brain. Of these, 53 were injectable products of which 20 were derived from cattle brain. A list of these products is attached as Appendix 1 to Annex D. The second exception relates to the product, 'Surgical Catgut', which is sourced from UK bovine intestines and will contain lymphoid material...

see full text ;

please see ;

Sunday, December 16, 2007

Risk factors for sporadic Creutzfeldt-Jakob disease

Increased risk was not associated with surgical categories chosen a priori but was confined to the residual category other surgery, in which the increase in risk appeared most marked for three subcategories: skin stitches, nose/throat operations, and removal of growths/cysts/moles.


which the increase in risk appeared most marked for three subcategories:

skin stitches, nose/throat operations, and removal of growths/cysts/moles.

10 January 1990

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





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 License Holders, indicating that the bovine small intestine source material was derived from UK cattle, unlike 8 other licensed 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.



U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date (Customs Value, in Thousands of Dollars) (Units of Quantity: Kilograms)

<--- Dec 1998 ---> <--- 1998 YTD --->

Country Quantity Value Quantity Value


WORLD TOTAL . . . . . . . 10,801 3,116 143,058 40,068

Belgium . . . . . . . . . --- --- 107 14

France . . . . . . . . . 81 49 2,727 1,132

Switzerland . . . . . . . --- --- 1,357 1,693

United Kingdom . . . . . 1,188 242 35,001 5,564

see url now available at ;

Part II

2.1 Bovine Small Intestine

This is the largest single category, comprising 9 product licenses for surgical catgut, held by 3 Companies ;

2.2 Skin

Bovine dermal collagen is present in 2 products for correction of tissue contour deformities by injection and 4 implantable haemostates.

Source USA, USA, W Germany, W. Germany, France. ...


MAY 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

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.



The responses by the companies were presented by Ms Turner and were categorised by MCA standards, the products that were discussed were all low volume usage products eg sutures, heart valves.

8. As the responses included some materials of human origin it was decided that more information should be sought about CJD. There had been 2 recent deaths reported associated with human growth hormone. These were being investigated.


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.

see all 76 pages ;


1. Please see the attached note of a recent meeting in Brussels. For Dr. Purford should read Dr. Purves (I think). If the Germans get their way, and it looks as if they might, because of worries about BSE we could end up with a ban on certain bovine materials being exported from the UK for pharmaceutical manufacture. Thse materials include cell cultures of bovine origin (? and also any cultures which have been fed bovine nutrient material), bovine serum, and fetal calf serum.

2. Whilst export of these raw materials may be very limited, it is only a small step to include in this export ban any finished product made from such materials. This would include virtually all biologicals and vaccines. This could have very serious effects on the export trade of British Manufacturers of biologicals because even where they source their bovine ingredients outside the UK it might be impossible or at least very difficult to bypass any export ban.

3. Our own line is that we have not used regulations to restrict the use of British bovine material for non-food use, although certain offals cannot be used for human consumption. ...

Export of British 'Biological' Pharmaceuticals

No papers were presented by our American guests and none covered the subject of pharmaceuticals. ...


Thanks for your note. I am disappointed not to have been informed about this meeting in advance and am surprised that Dr. Tyrrell was not involved either. I find it insulting to be told the proceedings were in confidence and find your excuse about only hosting the meeting unconvincing.

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.


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


89/06.19/8.1 BSE3/1 0191 Hr J Maslin (MAFF) Ref: Maslin3g

From: Dr H Pickles Med SEB/B Date: 3 July 1989


I was interested to see the list of by-products sent to the HSE. Those of particular concern included:

* small intestines: sutures (I thought the source was ovine but you are checking this)

* spinal cord: pharmaceuticals

* thymus: pharmaceuticals

Are you able to give me more information on which UK manufacturers use these materials? Our proposed ban on bovine offal for human consumption would not affect these uses, I assume.

snip...see full text ;

USDA allows diseased animals into human food supply

Mon, 14 Aug 2000. Information provided by Terry S. Singeltary Sr. Farm Sanctuary web site

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - Report of a visit to the USA - April-May 1989 - G A H Wells [head of England's main veterinary lab -- webmaster]

2. Meeting with USDA, BSE Task Force


Sunday, May 18, 2008



J Gen Virol 84 (2003), 1047-1052; DOI 10.1099/vir.0.18774-0

Molecular analysis of iatrogenic scrapie in Italy Gianluigi Zanusso1, Cristina Casalone2, Pierluigi Acutis2, Elena Bozzetta2, Alessia Farinazzo1, Matteo Gelati1, Michele Fiorini1, Gianluigi Forloni3, Man Sun Sy4, Salvatore Monaco1 and Maria Caramelli2

1 Department of Neurological and Visual Sciences, University of Verona, Piazzale L. A. Scuro, 10, 37134 Verona, Italy 2 CEA Istituto Zooprofilattico del Piemonte, Liguria e Valle d’Aosta, Via Bologna 148, 10154 Torino, Italy 3 Laboratorio di Biologia delle Malattie Neurodegenerative, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy 4 Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-1712, USA

Correspondence Maria Caramelli


An accidental intra- and interspecies transmission of scrapie occurred in Italy in 1997 and 1998 following exposure to a vaccine against Mycoplasma agalactiae. PrPSc in affected sheep and goats, collected from a single flock exposed to vaccination 2 years earlier, was molecularly typed. In five animals with iatrogenic scrapie, a PrPSc type with a 20 kDa core fragment was found in all areas of the brain investigated. In three sheep and one goat, this isoform co-occurred with a fully glycosylated isoform that had a protease-resistant backbone of 17 kDa, whereas in two sheep and four goats, the two PrPSc types were detected in different regions of the brain. In sheep with natural field scrapie, a PrPSc type with physico-chemical properties indistinguishable from the 20 kDa isoform was found. The present results suggest the co-presence of two prion strains in mammary gland and brain homogenates used for vaccination.

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

######### Bovine Spongiform Encephalopathy #########

THE VETERINARY RECORD 516 No 47. Vol. 58 November 23rd, 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


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 dramtic 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 neccessary 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 produceing 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 occuring 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 althought 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 throught 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 transmision 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 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

Sent: Friday, January 29, 2010 3:23 PM
Subject: 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 pathogenesis 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.

From: xxxx
To: Terry Singeltary
Sent: Saturday, December 05, 2009 9:09 AM
Subject: 14th ICID - abstract accepted for 'International Scientific Exchange'

Your preliminary abstract number: 670

Dear Mr. Singeltary,

On behalf of the Scientific Committee, I am pleased to inform you that your abstract

'Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009'

WAS accepted for inclusion in the INTERNATIONAL SCIENTIFIC EXCHANGE (ISE) section of the 14th International Congress on Infectious Diseases. Accordingly, your abstract will be included in the "Intl. Scientific Exchange abstract CD-rom" of the Congress which will be distributed to all participants.

Abstracts accepted for INTERNATIONAL SCIENTIFIC EXCHANGE are NOT PRESENTED in the oral OR poster sessions.

Your abstract below was accepted for: INTERNATIONAL SCIENTIFIC EXCHANGE

#0670: Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

Author: T. Singeltary; Bacliff, TX/US

Topic: Emerging Infectious Diseases Preferred type of presentation: International Scientific Exchange

This abstract has been ACCEPTED.

#0670: Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

Authors: T. Singeltary; Bacliff, TX/US

Title: Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

Body: 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 feed 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.


12 years independent research of available data


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.


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.

Keywords: Transmissible Spongiform Encephalopathy Creutzfeldt Jakob Disease Prion

Monday, October 19, 2009

Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009


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 ;


''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


I look forward to further transmission studies, and a true ENHANCED BSE/atypical BSE surveillance program put forth testing all cattle for human and animal consumption for 5 years. a surveillance program that uses the most sensitive TSE testing, and has the personnel that knows how to use them, and can be trusted. I look forward to a stringent mad cow feed ban being put forth, and then strictly enforced. we need a forced, not voluntary feed ban, an enhanced feed ban at that, especially excluding blood. we need some sort of animal traceability. no more excuses about privacy. if somebody is putting out a product that is killing folks and or has the potential to kill you, then everybody needs to know who they are, and where that product came from. same with hospitals, i think medical incidents in all states should be recorded, and made public, when it comes to something like a potential accidental transmission exposure event. so if someone is out there looking at a place to go have surgery done, if you have several hospitals having these type 'accidental exposure events', than you can go some place else. it only makes sense. somewhere along the road, the consumer lost control, and just had to take whatever they were given, and then charged these astronomical prices. some where along the line the consumer just lost interest, especially on a long incubating disease such as mad cow disease i.e. Transmissible Spongiform Encephalopathy. like i said before, there is much more to the mad cow story than bovines and eating a hamburger, we must start focusing on all TSE in all species. ...TSS

please see full text ;

The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.


5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases; 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.

Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010 ***FINAL***

my comments to PLosone here ;

WHAT in the world would these folks want USA bovine brains for ??? They were not tested for BSE or any TSE. just look at the USA cow brains that were exported ;

U.S. Trade Quick-Reference Tables: August 2001 Exports




U.S. Domestic Exports: August 2001 and 2001 Year-to-Date, not Seasonally Adjusted

(FAS Value, in Thousands of Dollars) (Units of Quantity: Kilograms)

August 2001 2001, through August Quantity Value Quantity

Value WORLD TOTAL 23,052 35


192 Federal Rep. of Germany 0


4 Mexico 15,147 28


170 Norway 7,905 8


8 Singapore 0



US Dept of Commerce Economics and Statistics Administration US Census Bureau Washington, DC 20233

US Exports of Merchandise - V1-F02-ER12-09-US1 for Dec/02 and end of year (YTD) - Issued on Feb/03 and US Exports of Merchandise -V1-F03-ER12-09-US1 for Dec/03 and end of year (YTD) - Issued on Feb/04,

BRAINS OF BOVINE ANIMALS, EDIBLE, FROZEN (0206290030) Exports To Mexico Unit of Quantity-Kilograms

U.S. Exports Of Merchandise For December, 2003 Domestic Exports Foreign Exports Exports by 1st Unit of Quantity 57,279 N/A Exports by 2nd Unit of Quantity 0 N/A F.A.S. Export

Value 56,132 N/A

SHIPMENTS BY VESSEL F.A.S. Export Value 0 N/A Shipping Weight 0 N/A

SHIPMENTS BY AIR F.A.S. Export Value 0 N/A Shipping Weight 0 N/A

U.S. Exports Of Merchandise For The Year Through December, 2003 Domestic Exports Foreign Exports Exports by 1st Unit of Quantity 161,158 N/A Exports by 2nd Unit of Quantity 0

N/A F.A.S. Export Value 210,728 N/A

SHIPMENTS BY VESSEL F.A.S. Export Value 0 N/A Shipping Weight 0 N/A

SHIPMENTS BY AIR F.A.S. Export Value 0 N/A Shipping Weight 0 N/A



U.S. Domestic Exports: December 2004 and 2004 Year-to-Date, not Seasonally Adjusted

(FAS Value, in Thousands of Dollars) (Units of Quantity: Kilogram) December 2004 2004, through December Quantity Value Quantity Value .

World 37,727 33 363,222 344

Mexico 37,727 33 338,475 326

Romania 0 0 24,747 19

Monday, February 01, 2010

Import Alert 17-04 BSE CJD HIGH RISK TISSUES, Nutritional Supplements and Cosmetics

Monday, February 01, 2010

Import Alert 57-20 and 84-03 Human Dura Mater and risk factors there from due to Creutzfeldt Jakob Disease (CJD)


Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

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