Sunday, December 04, 2016

Heidenhain variant of Creutzfeldt–Jakob disease in a patient who had bovine bioprosthetic valve implantation

Year : 2016 | Volume : 64 | Issue : 10 | Page : 767-769

Heidenhain variant of Creutzfeldt–Jakob disease in a patient who had bovine bioprosthetic valve implantation

Jehard Hashoul1, Waleed Saliba2, Irina Bloch3, Haneen Jabaly-Habib1

1 Department of Ophthalmology, Baruch Padeh Medical Center, Poriya, Israel 2 Department of Internal Medicine, Emek Medical Center, Afula, Israel 3 Department of Neurology, Emek Medical Center, Afula, Israel

 Correspondence Address:

 Jehard Hashoul

P. O. Box: 3, Jish, Galilee 13872 Israel

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0301-4738.195003 Creutzfeldt–Jakob disease (CJD) is a rare neurodegenerative disorder characterized by rapidly progressing dementia, general neurologic deterioration, and death. When the leading symptoms are visual disturbances, it is termed as the Heidenhain variant of CJD (HvCJD). CJD was reported following prion-contaminated pericardium transplants but never after bovine bioprosthetic cardiac valve. In this case report, we describe HvCJD in a patient who had a bovine bioprosthetic cardiac valve implant. An 82-year-old-woman was referred to neuro-ophthalmology clinic for unexplained visual loss that started 1 month previously. Medical history included aortic valve replacement with bovine bioprosthetic valve. On examination, best-corrected visual acuity was 20/120 in the right eye and 20/200 in the left eye; otherwise, the eye examination was normal. Humphrey visual fields revealed complete right homonymous hemianopsia. Magnetic resonance imaging (MRI) demonstrated nonspecific white matter changes. A week later, she was hospitalized due to memory impairment; repeated MRI and total body computed tomography scan showed no significant findings. Electroencephalography recordings and extremely elevated cerebrospinal fluid tau protein were compatible with CJD. The patient died 3 weeks later; autopsy was not performed. The patient had HvCJD. Ophthalmologists being first to see these patients should be aware of this diagnosis. Contaminated bovine bioprosthetic valve might be another source for prion disease. Further research is required to establish this issue.



>>> The patient had HvCJD. Ophthalmologists being first to see these patients should be aware of this diagnosis.

>>> Contaminated bovine bioprosthetic valve might be another source for prion disease.


40,000 human heart valves a year from BSE herds

Sun, 3 Sep 2000.

Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary Sr. of Bacliff, Texas Opinion (webmaster):

Below are some shocking documents. Here is a British company preparing 40,000 heart valves a year from bovine pericardium, primarily for export, and they are not required to source this material from BSE-free herds even in peak epidemic years. It is amazing to watch health "authorities" grovelling on their bellies to wring petty concessions from middle management at obscure little companies. The main worry is not the practise of using 800 potentially infected cows a week for human heart transplant material but that the press or recipients will get wind of it, hurting business.

BSE wasn't the problem, it was awkward queries from importing countries like the US. The cows are stunned using brain penetration -- can't do anything about the chunks of bovine brain blasted into the circulatory system, it's the norm. Can't use younger lower-risk animals either, patch would not be big enough. It is fascinating to see the British government worrying about, but doing nothing, with pigs with BSE 10 years ago. While scrapie was long used as an excuse for continuing with human use of BSE-tainted material, little sheep material was used medically. Bovine transplants, vaccines, insulin doeses, etc. are far more dangerous than dietary material as injections, and are done on a very wide scale. So scrapie was never a valid analogy to BSE, as MAFF knew full well.

The British government deferred to the manufacturer's rep for an opinion on how contaminated pericardium might be, just as this appeared showing that this tissue is extremely dangerous: CJD in a patient who received homograft [was it really?] tissue for tympanic membrane closure. Eur Arch Otorhinolaryngol 1990;247(4):199-201 Tange RA, Troost D, Limburg M We report the case history of a 54-year-old man who developed a fatal neurological disorder 4 years after a successful tympanoplasty with homograft pericardium... COMMERCIAL IN CONFIDENCE

Miss M Duncan From: Dr E Hoxey Date: 29 January 1990 cc: Mr R Burton Dr N Richardson Ms K Turner Ms J Dhell Mr N Weatherhead

BOVINE SPONGIFORM ENCEPHALOPATHY

1. In your absence on sick leave, I chaired the STD BSE group meeting on 26th January 1990.

2. The minutes of the meeting will be circulated shortly but I was asked to bring to your attention the concerns of the group regarding the BMS heart valve.

3. This concern arose from a number of points on the agenda:-

i) the______________decision to source all raw material for sutures from Australasia from January 1990.

ii) the major cleandown and decontamination proposed for the factory and the possibility of press interest that this may generate.

iii) the indication in the Tyrell Report on Research that the infective agent may be induced to cross the species barrier by intracerebral, intraperitoneal or intravenous injection.

4. As you are aware, the____________situation has been a model which we have observed closely.

5. Reviewing the BMS situatien, we considered the incidence of BSE in the herds used for materials, the processing received by the material and the age of the cattle used. Given the number of uncertainties and lack of definitive information on BSE, the_______________model was still considered as a good one. The group were uncomfortable with the position of BMS as the only company using UK sourced material.

6. The group considered that it may be worthwhile arranging a further meeting with___________to confidentially make them aware that they would now be the only company using UK sourced bovine material for products of this type.

7. Clearly, __________and__________ are now in an exposed position in this area and all the implications need te be considered. Could we have your news on this proposal please?

Dr E V Hoxey PD STD PG1A 716 RSQ Ext 3356

90/01.29/19.1

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B.S.E. GUIDELINES ON BOVINE IMPLANTS & BLOOD CONTACT DEVICES - MEETING WITH MANUFACTURERS

DATE: 8 DECEMBER 1989

DH REPRESENTATIVES Nigel Richardson Will Burton Eammon Hoxey Jeremy Tinkler Helen Campbell

 Carol Bleakley

 Bill Waine

The main purpose of the meeeting is to discuss the companies current manufacturing procedures, future plans and their compliance with the BSE guidelines. Their views were also sought as to the practical feasibility of the guidelines with respect to the manufacturing process, and any improvements that could be suggested.

The meetings were held separately with each company. Neither had received any queries concerning BSE from countries to which their products are exported.

CURRENT POSITION

1.__________ have brought in a microbiologist as a technical scientific adviser, initially to inform them of the current understanding of BSE. He is still available to them and keeps them up to date with new developments.

2. At present they produce bovine pericardial heart valves, & (a sister company) produces heparin coated products (from a porcine source). In the future it is possible that they will introduce a bovine patch produced from bovine pericardium from the same source. They will keep the Department informed of any progress in this area.

SOURCE MATERIAL

3. The source material for the manufacture of heart valves is bovine pericardial sacs. The cows used are 18-24 months old when slaughtered, the majority around 18 months. BMS have no knowledge of the actual age.

4. The cows are killed using brain penetration. Dr Bleakley made the point that as far as she was aware this was the only method used in this country. Meat inspectors are paid to obtain the bovine pericardium. They are paid a set rate but bonuses are given for increased yields. Mr Burton expressed concern as to the conflict of interests that may arise as a result of this. Dr Bleakley did not believe that this was the case because of the relationship BMS had developed with the inspectors.

89/12.12/8.1


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COMMENTS ON THE GUIDELINES

14. Dr. Bleakley believed that the pericardium would not allow the replication of the causative agent, and does not present a risk.

15. She suggested that the guidelines were impossible to implement from the point of view of the manufacturing process for the following reasons:-

-It is not possible to use closed herds simply because of the numbers of cattle involved. This is up to 800 each week.

-Calves under 6 months old cannot be used as the pericardium is too thin to be incorporated into a valve.

-For cows this in the age group used brain penetration is the only method of slaughtering used in this country.

PROPOSALS PUT FORWARD BY DR BLEAKLEY

16. The goverment should fund research in this area. For example, investigating the presence or absence of the infectious agent in other parts of the body, such as the pericardium. Also to look at how the slaughtering process affects the spread of the disease.

17. Ideally the answer would be to take random tissue samples in order to detect contaminated material. This is not currently feasible with the length of time required to conduct titre testing.

COMMENTS ON THE REVIEW ON METHODS OF STERILIZATION FOR BSE

18. Everything present reflected the published material, but the validity of some of this is questionable. It was pointed out that:-

-it was stated that different strains display different heat sensitivity, but this does not appear to be chemically related

-the claim to be "effective' would depend on the type of material that was being used and the time involved.

CURRENT POSITION

19.____________ manufacture porcine valves and bovine pericardial patches. The possibility of producing porcine conduits is currently being investigated. This has not yet progressed.

20. The material is obtained from 2 abattoires in this country:-

-Dorchester, where veal calves under 18 weeks are slaughtered for sourcing pericardium for ________________. These are used to produce small patches of less than 90mm diameter, this may be divided into 4 quadrants. This represents 80-90% of sales.

-Fairham where cows between 5 and 10 years old are slaughtered to produce larger patches and strips of 100mm by 45mm.

89/12.12/8.2

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32. As a result of the concern voiced of direct inoculation of BSE via sectioning instruments it was stated that it would be feasible to use new blades with each carcass.

COMMENTS ON THE GUIDELINES

33. Dr Waine was not convinced of the need for sterile sectioning equipment and separate packaging from the abattoire. He felt that this would merely have a cosmetic effect.

34. He suggested that the possibility of bovine-human cross-infection was very remote.

35. He did not believe that it was possible for manufacturers to follow the guidelines as they stand.

PROPOSALS

36. Dr Waine felt that the steps taken by the Government had been realistic to control the outbreak.

REVIEW

37. Dr Waine did not believe that any sterilization treatment proposed would retain the surgical usage of the pericardium.

VALVES

38. The response has been that this problem is restricted to the U.K. Thier material is obtained from the same Italian source as the patches. There is no age specification on the cows but the preference is for the larger valves which would therefore come from the older animals.

PORCINE VALVES

39. There was a small discussion as to whether these products do fall under the issued guidelines. The assumption had been made by the company that they are not included as pigs are not known to be susceptible to infection by a Scrapie-like agent. This was confirmed by Dr Hoxey.

40. The pigs are electrocuted and the heart and pericardium obtained prior to inspection.

41. One abattoire supplies them with most of their porcine requirments.

H Campbell PG2C Room 312 RSQ Ext. 3212 12 December 1989

89/12.12/8.3


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TIP740203/3 0241

Bovine Spongiform Meeting Held On Friday 26th January 1990

Present Dr E Hoxey {chairman) Mr W Burton Dr N Richardson Mrs J Dhell Ms K Turner MS H Cambell Mr N Weatherhead (secretary)

 copies: Miss Duncan

1.Apologies

Apologies were received from Miss Duncan

2.Minutes of the last meeting.

The previous minutes were accepted.

3.Matters arising not on the agenda.

As agreed at the previous meeting the paper on "Inactivation of Scrapie-like Agents" was sent with a Covering letter drafted by Dr Hoxey to all companies that use Bovine or Porcine materiais.

4.Report on the STD meeting with ___________________

The minutes of the meeting were discussed by the committee it was noted that:-

a} _____________ now meet DH Guidelines as the devices produced from the calf material comply as that they are obtained from animals less than 6 months old.The company had written to confirm that they now source older animals from overseas.

b) _____________ are unable to meet the DH Guidelines. and will not be doing so in the foreseeable future. The panel showed concern over the stance that BMS are taking. The committee felt that it was important to arrange a further meeting to inform them that they are now the only company using UK sourced material. [see minutes of the meeting dated 8/12/89 attached). Dr Hoxey agreed to write separatey to Miss Duncan on this issue.

action: Dr Hoxey

5. Report on the CSM/MCA BSE working party meeting 10/1/90

Mr Burton had produced a note of the above meeting as the minutes had as yet not been distributed. The committee noted that:-

90/01.26/20.1


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TIP740203/3 0242

1) _______________ has exceeded all expectations tn complying with DH Guidelines. They will be sourcing all raw material from Australasia from January 1990.

2) _______________ are using an international expert _______________ to advise them on factory decontamination at the change over of source.

3) The use of Dr Taylor and the factory decontamination may qenerate press interest.

4) The offal ban has not yet been expanded to include Scotland.

5) The CSM/MCA BSE working group agrees with the approach that STD are taking to Tissue Harvesting and wished to be kept updated.

The note of the meeting is attached for reference.

6. STD Database updating

Mr Burton drafted a minute for signature by Mr Worroll.The object of the minute was to enable STD to keep a check on companies that use animal material in their products.

The control manual committee amended the minute and agreed that the audit report procedure should include (if it does not already) a statement to the effect that the company information section should include details of raw materials used.

The CMC suggested a sentence to the effect "Team leaders visiting Blue Guide companies should additionally take account of Mr Worroll's minute of Jan 1990." The committee agreed with this sentence and passed it back for inclusion in the Base-line Documents.

action N Weatherhead

7. Review of the 'Interim Report of the Consultative Committee on Research into BSE" (Tyrell committee report.)

Mrs Dhell presented a summarized Version of the above document to the committee. It was noted that only the research studies catorqorised high/medium priority would all somehow receive funding. The committee expressed a wish to find out:-

1) Areas which have not been prioritised which have relevance to STDS area of interest.

2) Has any party taken up the study "Investigation into the fate of bovine and ovine tissues and product that could lead to infection by as yet unrecognised routes."

90/01.26/20.2


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TIP740203/3 0243

3. The protocol of work being carried out by the Clinical Research Laboratory in Harrow add proposed by the Neuropathogenesis unit in Edinburgh:

a) Have they any plans to include pericardium. If not could PD suggest that they miqht include it.

b) What controls are they using.

c) Will it be possible to arrange a visit.

4) It was suggested that Dr Pickles be contacted as the DH representitive on the Tyrell committee, to enquire if comments on this document were being sought by the committee, as PD has a number of points it wishes to raise.

8. Incorporation of Guidance into Chemical Methods for the sterilization of animal tissue Used in medical Devices.

The draft paper on methods of validation in chemical sterilization was shown to the BGRP for comments, these were later received. A copy was also forwarded to MCA and despite numerous reminders no reply had as yet been received.

The committee recommended that the paper on "Chemical Methods for the Sterilization of Animal Tissue Used in Medical Devices" should be amended include Tissue Harvesting. The BGRP will be informed of this and a copy of tbe document will be presented to the next CMS/MCA BSE working group which is to be held on 4th July l99O.

Mrs Dhell to arrange a meeting to draft this ammendment.

Mrs Turner action:Hr Tinkler Mrs Dhell Dr Hoxey

9. Possibility of sending STD paper 'Inactivation of Scrapie-like Agents" to Dr Taylor and Dr Kimberlin for their comments.

The committee felt that the paper should be sent to Dr Taylor and Dr Klmberlin and that they should be invited to comment. If they subsequently required payment for this work the committee felt that the Department should finance it if necessary.

Mrs Dhell will draft a letter to accompany the report for Miss Duncan to sign.

action: Mrs Dhell

90/01.26/20.3


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TIP740203/3 0244

10. - presentation on current situation

Miss Duncan's report was passed over until the next meeting.

1l. Oral discussion on relevant media interest and media reports.

The discussion mainly revolved around _____________ and the exposed position PD would be in if the media became involved. The possible press coverage expected in relation to events at ___________ could also raise the profile of BSE in "medical" products.

Mr Burton to obtain copies of any defensive briefings drafted by MCA in responce to the ______________ situation.

N Weatherhead

90/01.26/20.4



BSE offals used in cosmetics, toiletry and perfume industry

Sun, 3 Sep 2000.

 Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary Sr. of Bacliff, Texas

Miss Marion Kelly Cosmetic, Toiletry and Perfumery Association 35 Dover Street London W1X3RA

Department of Trade and Industry 10-18 Victoria Street London SW1H ONN Enquiries 01-215 5000 Telex 8811074 DTHQ G 01 215 3324 1 February 1990 Dear Marion As you know there is no record of bovine spongiform encepalopathy crossing to humans, but we need to take precautions to avoid any risk. There a number of cosmetric products on sale in the United Kingdom such as anti-ageing creams that contain extracts of bovine offal, primarily from spleen and thymus. [Two of the highest risk tissues. Note the epidemic has been raging for 4 years by the time of the non-binding voluntary suggestions here. -- webmaster] The purpose of this letter is to ask you to ask your members to eliminate any risk by reformulating such products to eliminate these extracts, or alternatively to use material derived from cattle reared outside the UK, Eire or the Channel Islands. [Eire, Channel Islands, and many other countries were thoroughly infected by then -- webmaster] Please let me know if you have any trouble persuading your members to do so. Yours sincerely R J ROSCOE CONSUMER SAFETY UNIT ROOM 407

90/02.01/14.1


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BSE110/1 0080

DEPARTMENT OF HEALTH AND SOCIAL SECURITY HANNIBAL HOUSE Room No ELEPHANT AND CASTLE LONDON SE1 6TE

1 February 1990

Mr R Roscoe Consumer Affairs Department of Trade and Industry 10-18 Victoria Street London SW1

Dear Richard

USE OF BOVINE OFFAL IN COSMETICS I am replying to your request for advice on the safety of the use of extracts of bovine offal in certain cosmetics, such as skin products claimed to have 'anti-ageing' properties with respect to bovine spongiform encephalopathy (BSE). As you are aware there are a number of cosmetic products on sale in the UK that contain small amounts of such extracts, primarily from spleen and thymus. We accept that the risk of transmission is likely to be remote, but believe that it would be prudent to eliminate any risk by reformulating such products. Alternatively if the incorporation of bovine extracts is retained, material derived from cattle reared outside the UK, Eire or the Channel Islands should be used. We would be grateful if you would transmit these recommendations to industry via the Trade Association CTPA. I attach background briefing prepared by medical colleagues from those sections most involved with consideration of BSE in DH, together with a copy of the Southwood report. Please let me know if you need any further information. Yours sincerely DR R J FIELDER Enclosure 90/2.1/7.1


 ===========


BSE110/1 0081

BACKGROUND BRIEFING




• Serologicals Corporation is now comprised of 3 main businesses: Celliance™, Chemicon™ and Upstate™.

All 3 Companies provide animal derived products of different species in their product offerings.

• Animal Blood Proteins Celliance™ provides a wide range of approximately 90 distinct animal protein products. These products, such as BSA, are primarily supplied to life science companies for use in blood typing and other diagnostic reagents. One of the primary uses of bovine albumin is to enhance the detection of blood group antibodies, a characteristic essential for the safe transfusion of whole blood. The Company also provides a line of highly purified animal proteins known as tissue culture media components that are used by biotechnology and biopharmaceutical companies as nutrient additives in cell culture media. Examples of these media components are Bovine EX-CYTE®, produced through a patented manufacturing process, and transferrin.

• A British company preparing 40,000 heart valves a year from bovine pericardium, primarily for export, and they are not required to source this material from BSE-free herds even in peak epidemic years. It is amazing to watch health "authorities" groveling on their bellies to wring petty concessions from middle management at obscure little companies.

• The main worry is not the practice of using 800 potentially infected cows a week for human heart transplant material but that the press or recipients will get wind of it, hurting business. Sun, 3 Sep 2000. Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary Sr. of Bacliff, Texas







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.



Other US BSE risks: the imported products picture 24 Jul 00 Trade Statistics: UK to US Compiled by Terry S.Singeltary Sr of Bacliff, Texas

[Opinion (webmaster): The US has focused for years on tracing, containing, and eradicating live animal imports from the UK or other countries with acknowledged BSE like Belgium, including some 499 cattle and the Vermont sheep. This strategy does not acknowledge imports of rendered bovine products from England during the BSE period nor secondary products such as surgical catgut, which is to say surgical cowgut, or dairy cattle embryos, vaccines for veterinarian and human medicines. What has become of these? Mr. Singeltary, who lost his mother to CJD of unexplained origin a few years back and went on to became a well-known TSE activist, has tracked down voluminous pertinent import data through correspondence with UK officials and searches of government web sites. Imports of such products are frequently cited by Europeans in rating BSE risks in the US and in shutting out US exports.

Many people's eyes glaze over when reviewing reams of sometimes older trade statistics. There is no proof that any of the imported products was contaminated with BSE nor if so, any evidence that any BSE product lead to infection in US livestock, surgical patients, or what not. Nonetheless, the data obtained by Mr. Singeltary establish that an appalling variety and tonnage of products that were imported by the US from the UK and othr BSE-affected countries during the peak of the BSE epidemic years.]

10 January 1990 COMMERCIAL IN CONFIDENCE

NOT FOR PUBLICATION

COMMITTEE ON SAFETY OF MEDICINES WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY



Monday, February 01, 2010

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







Thursday, December 24, 2015

Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence for Prion Type Variability Influencing Clinical Course and Laboratory Findings



Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'

DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785

FAX COVER SHEET

DATE: 4-23-98

TO: Mr. Terry Singeltary @ -------

FROM: Gerald Campbell

FAX: (409) 772-5315 PHONE: (409) 772-2881

Number of Pages (including cover sheet):

Message:

*CONFIDENTIALITY NOTICE*

Snip…

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.

***TYPE: Anatomic(A) or Clinical(C) Diagnosis. IMPORTANCE: 1-immediate cause of death (COD); 2.ureterlying COD; 3-contributory COD: 4.concomitant, significant; 5-incidental ***

Patient Name: POULTER, BARBARA Patient Location: AUTOPSY Room/Bed: Printed Date; Time: 01/30/98 - 0832

Page: 1 Continued .... --------------

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683

Pathology Report

Autopsy NO,: AU-97-00435

MICROSCOPIC DESCRIPTION: The spongiform change is evident in all areas of neocortex, varying from mild to moderate in severity with only very mild neuronal loss and gliosis. In the bilateral occipital lobes, there is severe loss cortical neurons and gliosis, with a corresponding pallor of the underlying white matter. There is only minimal, focal spongiform change in corpus striatum, lentiform nuclei, thalamus, hippocampus, brainstem and cerebellum. There is no significant loss of neurons from the lateral geniculate nucleus, and the optic chiasm and tracts are well-myelinated.

SECTIONS TAKEN: N-l) Pituitary, N-2) Right frontal, N-3) Right inferior frontal, N-4) Right caudate putamen. N-5) Right lentiform nuclei, N-6) Right hippocampus, N-7) optic chiasm. N-8) Left inferior temporal lobe, N-9) Right inferior occipital, N-10} Cerabellum. N-l1) Midbrain, N-12) Pons, N-13) Medulla.

FINAL DIAGNOSES: BRAIN: 1. Clinical history of rapidly progressive dementia, clinically consistent with Creutzfeldt-Jakob Disease.

a. spongiform encephalopathy, most Severe in occipital lobes, consistent with Heidenhain variant of Creutzfeldt-Jakob disease.

b. Ventriculer enlargement, moderate, consistent with atrophy. 1. Communicating spherical enlargement of occipital horn of left lateral ventricle (possible incidental congenital anomaly).

DURA; Left subdural hemorrhage, recent, minimal.

PITUITARY: Severe capillary congestion.

COMMENTS; See also western blot report from Dr. Gambetti's lab Amyloid stains are not completed for this case as of this date. The results, which are not essential for the diagnosis, will be reported separately in an addendum.

(this was hand written notes) no amyloid evident in the special stains. no evidence of plaques.GAE

Gerald A. Campbell, M.D., Pathologist Division of Neuropathology

(Electronic Signature}. (Gross: 01/16/98 Final: 02/08/98

Snip…

Page: 6 END OF REPORT --------------

The University of Texas Medical Branch at Galveston

Gerald A, Campbell, Ph.D., M.D, Associate Professor and Director Division of Neuropathology Department of Pathology

February 26, 1998

Pierluigi Gambetti, M.D. Professor Institute of Pathology Case Western Reserve University 2085 Adelbert Road Cleveland Ohio 44106

Dear Dr, Gambetti:

Enclosed please find the microscopic slides and autopsy report from our patient, Barbara Poulter (Hosp.# 11851lQ, Autopsy # AU97-435). These slides are being sent for consultation at the request of Mr. Singletary, Ms. Poulter's son and next of kin. We will also send frozen tissue from the brain on dry ice next week, and someone will call you on the day the tissue is shipped. Please return the slides when you have finished with your examination. If you need any further information, please do not hesitate to call me. Thanks for your assistance with this case.

Sincerely, Gerald A. Campbell ------------------ CASE WESTERN RESERVE UNIVERSITY

February 26, 1988

Gerald Campbell, M.D,, PhD. Division of Neuropathology, G85 University TX Medical Branch Galveston, TX 77555-0785

Dear Dr. Campbell,

As per our telephone conversation concerning a recent case of CJD, I Will be willing to examine slides and the frozen tissue on western blotting, I will issue a report to you about our conclusions. Below is my address, Our Fed Ex number is XXXXXXXXXXXXXXX.

Thank your for your assistance in this matter,

Best personal regards,

Pierluigi Gambetti, M.D.

PG:In

Division of Neuropathology Pierluigi Gambetti, M.D. Director Institute Of Neuropathology 2085 Adelbert Road Cleveland, Ohio 44106

Phone 216-368-0587 Fax 216-368-2546 ------------------ CASE WESTERN RESERVE UNIVERSITY

February 27, 1998

Dr. Gerald A. Campbell The University of Texas Medical Branch at Galveston Division of Neuropathology, G85 Galveston. TX 77555-0785

Dear Dr. Campbell,

We are in receipt of the slides you sent on Mrs. Barbara Poulter (your #: AU97-435;our#098-28).

Best personal regards, Pierluigi Gambetti, M.D.

PG:sb

Division of Neuropathology Pierluigi Gambetti, M.D., Director

-----------------------------------

CASE WESTERN RESERVE UNIVERSITY

March 30, 1998

Dr. Gerald A, Campbell The University of Texas Medical Branch at Galveston Division of Neuropathology Department of Pathology Galveston, Texas

Dear Dr Campbell,

We performed Western immunoblot analysis on the frozen tissue from your case #AU97-435 (our #098-28). The Immunoblot reveals the presence of protease-resistant prion protein (PrPres) confirming the diagnosis of prion disease. The immunoblot pattern of PrPres is consistent with the diagnosis of Creutzfeldt-Jakob disease.

Thank you for referring to us this interesting case.

Sincerely,

Piero Parchi, M.D.

Pierluigi Gambetti, M.D.

PP:sb

Division of Neuropathology Pierluigi Gambetti, M.D., Director Case Western Reserve University

This Autopsy report is for the use of anyone, who is trying to understand this hideous disease CJD. I hope it can be beneficial for some in researching human TSE. Please remember, this was my Mom, and to use this with great respect.

thank you, kind regards,

Terry S. Singeltary Sr., Bacliff, Texas USA

-------------------------------

BARBARA FREDERICK POULTER

DIED 12-14-97

If I had one last thing I could tell you, it would be, I love you. I'm sorry for the stupid argument we had the last few months, BEFORE this hideous disease ROARED through your body. BUT, I PROMISE MOM, YOUR DEATH WILL NOT GO UNANSWERED!

HEIDENHAN VARIANT CREUTZFELDT JAKOB DISEASE

We got a call from my Mother around the end of Oct. saying "the damn'est thing has happened, I can't see, and if I'm talking to you and I don't make sense, bare with me, I'll come back". It was a shock to all of us. It seems that a few days before, she was crossing the ferry and became frightened because she was having problems seeing. She explained it as looking down a tunnel or not being able to see from the sides, and seeing brown spots.

We had NOT been talking, over something, we had NO control of, for a few months. So I did not know she had been having these visual problems, until she was blind. These were her first symptoms. From that point on, I was with her most everyday. I had to cross the Galveston/Bolivar ferry, and its about 30 minutes each way, so as the disease progressed, it gave me a great deal of time to think. When the visual problems started, it was about 2 weeks later, and she was blind. That led to coordination, and balance problems starting. But as this hideous disease progresses, it just GOES. You don't seem to catch up with it. It was like a fire in a hurricane. We would go out and get her things she needed one day, and the next day it would be obsolete, because the disease had gone to another stage. So you started over. Her coordination and balancing led to being in a wheel-chair. She was starting to get these trembles. I also noticed how her hands and feet started to go inward. Her speech was nothing more than jerble at this time, and this was probably about the 6th week, (at this point we had to tie her to the wheel chair, to keep her from falling out). The trembles had turned into SEVERE JERKS, that at times would take 3 of us to hold her down. I will never forget that....About her 8th week she became comatose....She died around the 10th week. I had spent the night, she had problems through the night, so the nurse came. She checked her out and comforted us, (HOSPICE IS A WONDERFUL ORGANIZATION). The nurse said she seemed to be alright and that it would probably be alright to go home for a few hours. I was on the Ferry, going back to Galveston, when I got the call, she was gone. What can you do, Mom was gone, and I was stuck on the Damn Ferry, going the wrong direction.

She knew what she had. I remember, before she had lost her speech completely. After a doctors conference, and CJD had come up. She heard us say CJD, and she screamed, SHE knew! At that point, I didn't know what was, much less, CREUTZFELDT JAKOB DISEASE.....I have learned a lot since. I have learned I truly miss my Mom and I am MAD as hell that she is gone!

Terry/MADSON!!!

SYMPTOMS:

VISION - BLIND IN ABOUT 10 TO 14 DAYS

COORDINATION AND MUSCLE CONTROL SWALLOWING DIFFICULTY CONFUSION AND DEMENTIA SPEECH PROBLEMS HALLUCINATIONS TREMBLES TOO SEVERE JERKING LOSS OF WEIGHT HANDS AND FEET GREW INWARD UPPER TRUNK STIFFNESS, SHOULDER, UPPER ARM





Sunday, January 17, 2016

Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease



Bovine Spongiform Encephalopathy BSE aka mad cow disease, CHRONIC WASTING DISEASE CWD AND SCRAPIE TSE PRION ZOONOSIS UPDATE


*** WDA 2016 NEW YORK ***

 We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions.

 Student Presentations Session 2

 The species barriers and public health threat of CWD and BSE prions

 Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University

 Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD.

Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders

http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf


PRION 2016 TOKYO

Zoonotic Potential of CWD Prions: An Update

Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3, Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6, Pierluigi Gambetti1, Qingzhong Kong1,5,6 1Department of Pathology, 3National Prion Disease Pathology Surveillance Center, 5Department of Neurology, 6National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. 4Department of Biological Sciences and Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada, 2Encore Health Resources, 1331 Lamar St, Houston, TX 77010

Chronic wasting disease (CWD) is a widespread and highly transmissible prion disease in free-ranging and captive cervid species in North America. The zoonotic potential of CWD prions is a serious public health concern, but the susceptibility of human CNS and peripheral organs to CWD prions remains largely unresolved. We reported earlier that peripheral and CNS infections were detected in transgenic mice expressing human PrP129M or PrP129V. Here we will present an update on this project, including evidence for strain dependence and influence of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of experimental human CWD prions.

PRION 2016 TOKYO In Conjunction with Asia Pacific Prion Symposium 2016 PRION 2016 Tokyo Prion 2016

http://prion2016.org/dl/newsletter_03.pdf


Cervid to human prion transmission

Kong, Qingzhong

Case Western Reserve University, Cleveland, OH, United States

Abstract

Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans. We hypothesize that:

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;

(3) Reliable essays can be established to detect CWD infection in humans;and

(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.

Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of "humanized" Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental "human CWD" samples will also be generated for Aim 3.

Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1.

Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental "human CWD" samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.

Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.

Public Health Relevance There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.

Funding Agency Agency National Institute of Health (NIH)

Institute National Institute of Neurological Disorders and Stroke (NINDS)

Type Research Project (R01)

Project # 1R01NS088604-01A1

Application # 9037884

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May

Project Start 2015-09-30

Project End 2019-07-31

Budget Start 2015-09-30

Budget End 2016-07-31

Support Year 1

Fiscal Year 2015

Total Cost $337,507

Indirect Cost $118,756

Institution

Name Case Western Reserve University

Department Pathology

Type Schools of Medicine

DUNS # 077758407

City Cleveland

State OH

Country United States

Zip Code 44106

http://grantome.com/grant/NIH/R01-NS088604-01A1


===========================================================

We hypothesize that:

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;

(3) Reliable essays can be established to detect CWD infection in humans;and

(4) *** CWD transmission to humans has already occurred. *** We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.

============================================================

Key Molecular Mechanisms of TSEs

Zabel, Mark D.

Colorado State University-Fort Collins, Fort Collins, CO, United States Abstract Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative diseases affecting humans, cervids, bovids, and ovids. The absolute requirement of PrPC expression to generate prion diseases and the lack of instructional nucleic acid define prions as unique infectious agents. Prions exhibit species-specific tropism, inferring that unique prion strains exist that preferentially infct certain host species and confront transmission barriers to heterologous host species. However, transmission barriers are not absolute. Scientific consensus agrees that the sheep TSE scrapie probably breached the transmission barrier to cattle causing bovine spongiform encephalopathy that subsequently breached the human transmission barrier and likely caused several hundred deaths by a new-variant form of the human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease of cervids, overcoming similar human transmission barriers. A groundbreaking discovery made last year revealed that mice infected with heterologous prion strains facing significant transmission barriers replicated prions far more readily in spleens than brains6. Furthermore, these splenic prions exhibited weakened transmission barriers and expanded host ranges compared to neurogenic prions. These data question conventional wisdom of avoiding neural tissue to avoid prion xenotransmission, when more promiscuous prions may lurk in extraneural tissues. Data derived from work previously funded by NIH demonstrate that Complement receptors CD21/35 bind prions and high density PrPC and differentially impact prion disease depending on the prion isolate or strain used. Recent advances in live animal and whole organ imaging have led us to generate preliminary data to support novel, innovative approaches to assessing prion capture and transport. We plan to test our unifying hypothesis for this proposal that CD21/35 control the processes of peripheral prion capture, transport, strain selection and xenotransmission in the following specific aims. 1. Assess the role of CD21/35 in splenic prion strain selection and host range expansion. 2. Determine whether CD21/35 and C1q differentially bind distinct prion strains 3. Monitor the effects of CD21/35 on prion trafficking in real time and space 4. Assess the role of CD21/35 in incunabular prion trafficking

Public Health Relevance Transmissible spongiform encephalopathies, or prion diseases, are devastating illnesses that greatly impact public health, agriculture and wildlife in North America and around the world. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease (CWD) of cervids, overcoming similar human transmission barriers. Early this year Canada reported its first case of BSE in over a decade audits first case of CWD in farmed elk in three years, underscoring the need for continued vigilance and research. Identifying mechanisms of transmission and zoonoses remains an extremely important and intense area of research that will benefit human and other animal populations.

Funding Agency Agency National Institute of Health (NIH)

Institute National Institute of Allergy and Infectious Diseases (NIAID)

Type High Priority, Short Term Project Award (R56)

Project # 1R56AI122273-01A1

Application # 9211114

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Beisel, Christopher E

Project Start 2016-02-16

Project End 2017-01-31

Budget Start 2016-02-16

Budget End 2017-01-31

Support Year 1

Fiscal Year 2016

Total Cost

Indirect Cost Institution Name Colorado State University-Fort Collins

Department Microbiology/Immun/Virology

Type Schools of Veterinary Medicine

DUNS # 785979618 City Fort Collins

State CO

Country United States

Zip Code 80523

http://grantome.com/grant/NIH/R56-AI122273-01A1


PMCA Detection of CWD Infection in Cervid and Non-Cervid Species

Hoover, Edward Arthur

Colorado State University-Fort Collins, Fort Collins, CO, United States

Abstract Chronic wasting disease (CWD) of deer and elk is an emerging highly transmissible prion disease now recognized in 18 States, 2 Canadian provinces, and Korea. We have shown that Infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces, and in the tissues generating those body fluids and excreta, thereby leading to facile transmission by direct contact and environmental contamination. We have also shown that CWD can infect some non-cervid species, thus the potential risk CWD represents to domestic animal species and to humans remains unknown. Whether prions borne in blood, saliva, nasal fluids, milk, or excreta are generated or modified in the proximate peripheral tissue sites, may differ in subtle ways from those generated in brain, or may be adapted for mucosal infection remain open questions. The increasing parallels in the pathogenesis between prion diseases and human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, add relevance to CWD as a transmissible protein misfolding disease. The overall goal of this work is to elucidate the process of CWD prion transmission from mucosal secretory and excretory tissue sites by addressing these questions: (a) What are the kinetics and magnitude of CWD prion shedding post-exposure? (b) Are excreted prions biochemically distinct, or not, from those in the CNS? (c) Are peripheral epithelial or CNS tissues, or both, the source of excreted prions? and (d) Are excreted prions adapted for horizontal transmission via natural/trans-mucosal routes? The specific aims of this proposal are: (1) To determine the onset and consistency of CWD prion shedding in deer and cervidized mice; (2); To compare the biochemical and biophysical properties of excretory vs. CNS prions; (3) To determine the capacity of peripheral tissues to support replication of CWD prions; (4) To determine the protease- sensitive infectious fraction of excreted vs. CNS prions; and (5) To compare the mucosal infectivity of excretory vs. CNS prions. Understanding the mechanisms that enable efficient prion dissemination and shedding will help elucidate how horizontally transmissible prions evolve and succeed, and is the basis of this proposal. Understanding how infectious misfolded proteins (prions) are generated, trafficked, shed, and transmitted will aid in preventing, treating, and managing the risks associated with these agents and the diseases they cause.

Public Health Relevance Chronic wasting disease (CWD) of deer and elk is an emergent highly transmissible prion disease now recognized throughout the USA as well as in Canada and Korea. We have shown that infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces thereby leading to transmission by direct contact and environmental contamination. In that our studies have also shown that CWD can infect some non-cervid species, the potential risk CWD may represents to domestic animal species and humans remains unknown. The increasing parallels in the development of major human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, and prion diseases add relevance to CWD as a model of a transmissible protein misfolding disease. Understanding how infectious misfolded proteins (prions) are generated and transmitted will aid in interrupting, treating, and managing the risks associated with these agents and the diseases they cause.

Funding Agency Agency National Institute of Health (NIH)

Institute National Institute of Neurological Disorders and Stroke (NINDS)

Type Research Project (R01)

Project # 4R01NS061902-07

Application # 9010980

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May Project Start 2009-09-30

Project End 2018-02-28

Budget Start 2016-03-01

Budget End 2017-02-28

Support Year 7

Fiscal Year 2016

Total Cost $409,868

Indirect Cost $134,234 Institution Name Colorado State University-Fort Collins

Department Microbiology/Immun/Virology

Type Schools of Veterinary Medicine

DUNS # 785979618 City Fort Collins

State CO

Country United States

Zip Code 80523

http://grantome.com/grant/NIH/R01-NS061902-07


LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249
 

PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

O18

Zoonotic Potential of CWD Prions

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.

==================

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

==================

P.105: RT-QuIC models trans-species prion transmission

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.

================

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

================

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf


*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***

Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

http://wwwnc.cdc.gov/eid/article/20/1/13-0858_article.htm


http://chronic-wasting-disease.blogspot.com/2014/01/molecular-barriers-to-zoonotic.html


*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249


*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf


***********CJD REPORT 1994 increased risk for consumption of veal and venison and lamb***********

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994

Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss)

These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...

Table 9 presents the results of an analysis of these data.

There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).

Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.

There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).

The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

snip...see full report ;

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf


CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf


Monday, May 02, 2016

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html


*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD


http://chronic-wasting-disease.blogspot.com/2014/06/prion-2014-chronic-wasting-disease-cwd.html


http://chronic-wasting-disease.blogspot.com/2016/07/colorado-chronic-wasting-disease-cwd.html


http://chronic-wasting-disease.blogspot.com/


Monday, May 02, 2016

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html


 Saturday, April 23, 2016

PRION 2016 TOKYO

Saturday, April 23, 2016

 SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

 Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

 Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

 To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

 Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with ef?ciency comparable to that of cattle BSE. While the ef?ciency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20


 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

http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf


 *** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

 *** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

 *** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

 http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160


 O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

 Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

 Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.


 *** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,

 ***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),

 ***is the third potentially zoonotic PD (with BSE and L-type BSE),

 ***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.


 ===============


***thus questioning the origin of human sporadic cases***

 ***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
 
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
 

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html


Saturday, July 23, 2016

BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016

http://bovineprp.blogspot.com/2016/07/bovine-spongiform-encephalopathy-bse.html
 

Tuesday, July 26, 2016

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

http://bse-atypical.blogspot.com/2016/07/atypical-bovine-spongiform.html
 

Tuesday, November 29, 2016

Transmissibility of Gerstmann–Sträussler–Scheinker syndrome in rodent models: new insights into the molecular underpinnings of prion infectivity




kind regards, terry

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