Sunday, December 16, 2007

Risk factors for sporadic Creutzfeldt-Jakob disease

Sunday, December 16, 2007 Risk factors for sporadic Creutzfeldt-Jakob disease Published Online: 11 Dec 2007

Copyright © 2007 American Neurological Association

Original Article

Risk factors for sporadic Creutzfeldt-Jakob disease

Hester J. T. Ward, FFPH 1 *, Dawn Everington, MSc 1, Simon N. Cousens, MA 2, Blaire Smith-Bathgate, RGN 1, Michelle Gillies, MRCP 1, Katy Murray, MRCP 1, Richard S. G. Knight, FRCPE 1, Peter G. Smith, DSc 2, Robert G. Will, FRCP 1 1National Creutzfeldt-Jakob Disease Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom 2Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom

email: Hester J. T. Ward (

*Correspondence to Hester J. T. Ward, National CJD Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, United Kingdom

Funded by: Department of Health; Grant Number: 121/7400 Scottish Executive Health Department; Grant Number: R39924



Although surgical transmission of Creutzfeldt-Jakob disease (CJD) has been demonstrated, these iatrogenic cases account for only a small proportion of all CJD cases. The majority are sporadic CJD (sCJD) cases of unknown cause. This study investigated whether some cases classified as sCJD might have an unrecognized iatrogenic basis through surgical or other medical procedures


This study compared medical risk factors from 431 sCJD cases referred 1998 to 2006 with 454 population control subjects. Possible geographic and temporal links between neurological and gynecological operations in 857 sCJD cases referred from 1990 to 2006 were investigated


A reported history of ever having undergone surgery was associated with increased risk for sCJD (odds ratio, 2.0; 95% confidence interval, 1.3-2.1; p = 0.003). 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. No convincing evidence was found of links (same hospital, within 2 years) between cases undergoing neurosurgery or gynecological surgery


It is unlikely that a high proportion of UK sCJD cases are the result of transmission during surgery, but we cannot exclude the possibility that such transmission occurs occasionally. A study based on accurate surgical histories obtained from medical records is required to determine whether the increased risk associated with reported surgical history reflects a causal association or recall bias. Ann Neurol 2007

---------------------------------------------------------------------------- ---- Received: 24 May 2007; Revised: 5 September 2007; Accepted: 1 October 2007 Digital Object Identifier (DOI)

10.1002/ana.21294 About DOI

Additional Material


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 ;

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.


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

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 ;

Evidence For CJD/TSE Transmission Via Endoscopes From Terry S. Singletary, Sr


Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States





Transmissible Mink Encephalopathy TME



Economics, Statistics and Operational Research Department of Health Skipton House, 80 London Road, London SE1 6LW

March 2005

British Medical Bulletin 66:255-265 (2003) © 2003 The British Council

Acquired prion disease: iatrogenic CJD, variant CJD, kuru Robert G Will National CJD Surveillance Unit, Department of Clinical Neuroscience, Western General Hospital, Edinburgh, UK


Human prion diseases can be classified as sporadic, hereditary or acquired. The cause of sporadic Creutzfeldt-Jakob disease (CJD) is unknown, hereditary cases are associated with mutations of the prion protein gene (PRNP) and acquired forms are caused by the transmission of infection from human to human or, as a zoonosis, from cattle to human. Although acquired forms of human prion disease are rare, the transmission of a fatal and untreatable neurological disorder has had major implications for public health and public policy.

Iatrogenic CJD

Since the first evidence of iatrogenic transmission of CJD in 1974, via a corneal transplant, other mechanisms of iatrogenic transmission have been identified including neurosurgical instruments, depth electrodes, human pituitary hormones and human dura mater grafts. All these transmissions have involved cross-contamination with material in, or adjacent to, the brain where the expected levels of infectivity would be highest (Table 1). The route of inoculation has been parenteral, either by surgery or by intramuscular injection.

Corneal grafts and depth electrodes

Iatrogenic transmission of CJD was first suggested in 19741; CJD developed 18 months after transplantation of a cadaveric corneal graft, which had been obtained from a donor who had died of pathologically confirmed CJD. A second case was described in 19972 in which both donor and recipient died from pathologically confirmed CJD, although the delay between corneal transplant and the development of CJD was 30 years. These cases provide strong circumstantial evidence of transmission of CJD through cadaveric corneal grafts.

Two cases were reported in 1977 in which CJD developed 2 years after stereotactic EEG recordings3. The instruments had previously been used in a patient with rapidly progressive dementia and myoclonus, who was later confirmed as having died of CJD. The electrodes had been disinfected with ethanol and formaldehyde vapour. The possibility that CJD had been transmitted via the electrodes was subsequently supported by transmission of CJD to a chimpanzee 18 months after intradural implantation of the suspect electrodes4.

Neurosurgical transmission

The original publication by Nevin and co-workers5 suggested that CJD was transmitted via contaminated neurosurgical instruments in the 1950s. A small number of patients with CJD underwent invasive procedures, including brain biopsy, and concurrent in-patients underwent neurosurgery for other conditions (e.g. removal of meningioma or cortical undercut). The re-admission of three of these cases 18–24 months later to the same hospitals with CJD provides strong circumstantial evidence of transmission through contaminated neurosurgical instruments. A similar case has been described in France6, but there have subsequently been no further published cases implicating neurosurgical instruments. The clinical features in these cases were very similar to sporadic CJD.

Dura mater grafts

The transmission of CJD from patient to patient by cadaveric dura mater grafts was first recognised in 1987 and there have now been at least 136 cases world-wide, including 88 cases identified in Japan7. Almost all of these cases have involved the insertion of Lyodura grafts produced by B. Braun Melsungen AG and processed before May 1987. Exceptions to the use of Lyodura grafts include one case in which the source was unknown, one case in which locally produced dura was implanted and one case associated with Tutoplast dura. The risk of transmission of CJD through dura mater grafts had been thought to be low because only a small number of recipients would receive contaminated material from any individual infected donor. The large number of Lyodura-associated cases of CJD suggests that there may have been cross-contamination during the production process.

For dura mater-associated cases of CJD in Japan, the mean latency period from receipt of the graft to the onset of CJD was 8.2 years (range, 1.3–16.1 years)8 and for the 114 reported cases world-wide by the millennium, the interval from the implantation of the graft to the development of clinical disease ranged from 1.5–18 years with a mean of about 6 years9. The risk of developing CJD after exposure to a dura mater graft is difficult to estimate because of limited information on the number of recipients. The major risk, however, appears to be in those individuals who received grafts between 1981 and 1987 (Fig. 1) and in Japan the minimum risk has been estimated at approximately one case of CJD per 3000 Lyodura graft recipients.

The majority of patients with dura mater-related CJD present with symptoms and signs consistent with sporadic CJD, but in some cases the presentation is less typical. A cerebellar syndrome has been described occasionally, but this does not necessarily correlate with the anatomical site of the original graft.

Human pituitary hormones

The treatment of short stature in children with human pituitary-derived growth hormone (hGH) was initiated in the late 1950s, and about 30,000 children had been treated with hGH world-wide by 1985. Small numbers of women were treated for infertility with human pituitary gonadotrophin over a similar period. In 1985, the occurrence of CJD in two hGH recipients in the US10,11 and one case in the UK12 provided strong circumstantial evidence of transmission of CJD via hGH, not least because the young age of the patients contrasted with that usually observed in CJD. Since then, CJD has developed in over 160 hGH recipients in a number of countries including the US, UK, France, New Zealand, and The Netherlands (Table 2). The overall proportion of CJD cases in the recipient population is about 1 in 100, but this proportion varies between countries, with the highest rate in France. The contrasting inter-country incidence may relate to differences in the methods of sourcing of pituitary glands or variations in hormone production. hGH was withdrawn in most countries in 1985 and human pituitary gonadotrophin has also been withdrawn in many countries following the occurrence of CJD in four recipients in Australia13.

hGH production required the pooling of many thousands of glands and it is presumed that contamination of the hormone preparation occurred when pituitary glands derived from patients who died from or were incubating CJD were included in the production process. The circumstantial evidence suggesting a causal link between hGH and CJD has been supported by transmission studies in which a squirrel monkey developed prion disease following inoculation with 1 of 76 potentially contaminated lots of hGH14. The incubation period in hGH-related CJD is impossible to estimate precisely because the timing of infection is not known. However, the estimated mean incubation period is 12 years with a range of 4.5 to over 25 years, based on the latency from the mid-point of treatment to the onset of clinical illness. The clinical features of human pituitary hormone-related CJD are distinct from sporadic CJD. In the great majority of cases, the initial presentation involves a progressive cerebellar syndrome, and other features including dementia develop late, if at all. It is possible that the route of inoculation of the infectious agent may be an important determinant to clinical expression of disease. In kuru, presumed to be due to a peripheral route of infection, cerebellar signs predominate in the early stages as in human pituitary hormone recipients, whereas in iatrogenic CJD, due to central inoculation, the clinical features are similar to sCJD.

Variant CJD

snip... full text ;


----- Original Message -----

From: Terry S. Singeltary Sr.


Sent: Wednesday, November 29, 2006 1:24 PM

Subject: TSE advisory committee for the meeting December 15, 2006 [TSSSUBMISSION] November 29, 2006

Greetings FDA, DHH, Dr. Freas, and Dr. Harvey et al,

a kind and warm Holiday Greetings to you all. i kindly wish to submit the following to the TSE advisory committee for the meeting December 15, 2006, about the assessment for potential exposure to vCJD in human plasma-derived antihemophilic factor (FVIII) products manufactured from U.S. plasma donors and related communication material ;

i see the media picked up on this as a 'low risk', from what the gov. agency perceived to be to them;,0,7955259.story?coll=ny-leadhealthnews-headlines

however, i seem to disagree. from my primitive ciphering, i see it anotherway. this is a huge catastrophic risk. 3 in 160 is 1.9%. so call that 2% which is 1 in 50 or twenty per thousand or 20,000 per million. also, what about the mixed genotypes/mixed susceptibility? what about the silent carriers that donated tainted blood? what about the sporadic CJDs of UNKNOWN strain or phenotype? this risk assessment is just more BSe to me. just another in a long line of ...

Greetings again Dr. Freas et al at FDA,

THIS was like closing the barn door after the mad cows got loose. not only the red cross, but the FDA has failed the public in protecting them from the TSE aka madcow agent. TSE agent i.e. bse, base, cwd, scrapie, tme, and any sub strains thereof. we do not know if these strains will or have transmitted to humans as subclinical TSE or clinical disease, and we do not know if they have or will transmit second, third, forth passage via friendly fire i.e. multiple potential routes via medical, surgical, pharmaceutical etc. IF you remember correctly Dr. Freas et al, i called this long ago, almost 6 years ago ;


Terry S. Singeltary Sr. [] Monday, January 08, 200l 3:03 PM freas ...Freas, William From: Terry S. Singeltary Sr. [] Sent: Monday, January 08,200l 3:03 PM

To: freas@CBS5055530.CBER.FDA.GOV

Subject: CJD/BSE (aka madcow) Human/Animal TSE?s--U.S.--Submission

To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)

Greetings again Dr. Freas and Committee Members,

I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version). I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products.


I am beginning to think that the endless attempt to track down and ban, potential victims from known BSE Countries from giving blood will be futile. You would have to ban everyone on the Globe eventually? AS well, I think we MUST ACT SWIFTLY to find blood test for TSE's, whether it be blood test, urine test, eyelid test, anything at whatever cost, we need a test FAST. DO NOT let the incubation time period of these TSEs fool you. To think of Scrapie as the prime agent to compare CJD, but yet overlook the Louping-ill vaccine event in 1930's of which 1000's of sheep where infected by scrapie from a vaccine made of scrapie infected sheep brains, would be foolish. I acquired this full text version of the event which was recorded in the Annual Congress of 1946 National Vet. Med. Ass. of Great Britain and Ireland. From the BVA and the URL is posted in my (long version). ...

see full text ;

vCJD case study highlights blood transfusion risk

Wednesday, October 24, 2007

MADCOW USDA the untold story



[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle


[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

SEAC 99 DECEMBER 14, 2007


14. Preliminary research findings suggest that the potential risk of transmission of vCJD via dental procedures may be greater than previously anticipated. Although this research is incomplete, uses an animal model exposed to relatively high doses of infectivity, and there are no data from infectivity studies on human oral tissues, these findings suggest an increased possibility that vCJD may be relatively efficiently transmitted via a range of dental procedures. Ongoing infectivity studies using human oral tissues and the other studies suggested here will enable more precise assessment of the risks of vCJD transmission through dental procedures.

15. Guidance was issued to dentists earlier this year recommending that endodontic files and reamers be treated as single use which, provided it is adhered to, will remove any risk of a self-sustaining epidemic arising from re-use of these instruments. To minimise risk it is critical that appropriate management and audit is in place, both for NHS and private dentistry.

16. It is also critical that a detailed and comprehensive assessment of the risks of all dental procedures be conducted as a matter of urgency. While taking into account the continuing scientific uncertainties, this will allow a more thorough consideration of the possible public health implications of vCJD transmission via dentistry and the identification of possible additional precautionary risk reduction measures. The assessment will require continued updating as more evidence becomes available on the transmissibility of vCJD by dental routes, and on the prevalence of infection within the population. A DH proposal to convene an expert group that includes dental professionals to expedite such an assessment is welcomed. Given the potential for transmission via dentistry, consideration should be given to the urgent assessment of new decontamination technologies which, if proved robust and effective, could significantly reduce transmission risks.

SEAC June 2007

27 SEAC Epidemiology Subgroup (2006) position statement of the vCJD epidemic.

28 DH (2007) Precautionary advice given to dentists on re-use of instruments

see full text 17 pages ;

SEAC 99th meeting on Friday 14th December 2007

DECEMBER 14, 2007, 10 year Anniversary of my Moms death 'confirmed' from Heidenhain Variant Creutzfeldt Jakob Disease


AS one of them _lay_ folks, one must only ponder ;

"WITH the Nor-98 now documented in five different states so far in the USA in 2007, and with the TWO atypical BSE H-BASE cases in Texas and Alabama, with both scrapie and CWD running rampant in the USA, IS there any concern from SEAC with the rise of sporadic CJD in the USA from ''UNKNOWN PHENOTYPE'', and what concerns if any, in relations to blood donations, surgery, optical, and dental, do you have with these unknown atypical phenotypes in both humans and animals in the USA ???"

"Does it concern SEAC, or is it of no concern to SEAC?"

"Should it concern USA animal and human health officials?"


----- Original Message ----- From: xxxxxxxxxx To: Sent: Thursday, November 22, 2007 5:39 AM Subject: QUESTION FOR SEAC

Mr Terry S Singeltary Sr., Bacliff, Texas 77518 USA.

Dear Mr Singeltary,

"Thank you for your e-mail of yesterday with the question for SEAC. I can confirm that this will be asked at the meeting on your behalf and the question and answer will appear in the minutes of the meeting which will be published on the SEAC Internet site."


Archive Number 20071105.3602 Published Date 05-NOV-2007 Subject PRO/AH/EDR> Prion disease update 2007 (07)

PRION DISEASE UPDATE 2007 (07) ****************************** A ProMED-mail post


[2] USA: National Prion Disease Pathology Surveillance Center Date: June 2007 Source: National Prion Disease Pathology Surveillance Center (USA) [edited]

CJD Cases examined ---------------------- Year / Referrals / Prion disease / Sporadic / Familial / Iatrogenic / vCJD

1996 / 42 / 32 / 26 / 4 / 0 / 0 1997 / 115 / 68 / 57 / 9 / 0 / 0 1998 / 93 / 53 / 45 / 7 / 1 / 0 1999 / 114 / 69 / 61 / 8 / 0 / 0 2000 / 151 / 103 / 89 / 14 / 0 / 0 2001 / 208 / 116 / 106 / 9 / 0 / 0 2002 / 255 / 143 / 118 / 23 / 2 / 0 2003 / 272 / 174 / 132 / 41 / 0 / 0 2004 / 334 / 183 / 157 / 21 / 0 / 1* 2005 / 352 / 195 / 152 / 37 / 1 / 0 2006 / 372 / 186 / 143 / 30 / 0 / 1** 2007 / 120 / 68 / 35 / 7 / 0 / 0 TOTAL / 2428*** / 1390**** / 1121 / 210 / 4 / 2

*Acquired in UK ** Acquired in Saudi Arabia *** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007. **** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007).


-- Cases are listed based on the year of death when available. If the year of death is not available, the year of sample receipt is used.

-- Referrals: Cases with possible or probable prion disease from which brain tissue or blood in the case of familial disease were submitted.

-- Inconclusive: Cases in which the samples were not sufficient to make a diagnosis.

-- Non-vCJD type unknown are cases in which the tissue submitted was adequate to establish the presence but not the type; in all cases, vCJD could be excluded.

-- Communicated by: Terry S. Singeltary Sr.

[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP],F2400_P1001_PUB_MAIL_ID:1010,39963

There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.

He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.

snip...full text ;


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