Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions

Public release date: 8-Jul-2010

Contact: SINC info@plataformasinc.es 34-914-251-820 FECYT - Spanish Foundation for Science and Technology

Surgery linked to Creutzfeldt-Jakob disease

IMAGE: Surgery is linked to Creutzfeldt-Jakob disease.

"Based on the monitoring records of spongiform encephalopathy in two Nordic countries, we studied the possibility of transmission of the sporadic form of CJD through general surgery", explains Jesús de Pedro, main author of the study and head of prion monitoring in patients at the National Epidemiology Centre of the Carlos III Health Institute.

The finding, published recently in the Journal of Neurology, Neurosurgery & Psychiatry, reveals that, with a few exceptions, the risk of having contracted the sporadic form of CJD manifests itself at least 20 years after having undergone an operation.

"While we are not ruling out the idea that intraoperational transfusions may play a secondary part, the data suggest that the disease enters and spreads much more quickly within the central or peripheral nervous system", confirms De Pedro.

According to the authors, the fact that computer records of surgeries have been in place since the early seventies in hospitals in Sweden and Denmark enables operations on residents of those countries to be linked to cases of CJD, which "extends an extraordinary quality to the information and more credibility to the findings given the almost total absence of memory bias".

Why is the idea of transmission through surgery important?

The most interesting thing about this finding, which points to an external cause that could be prevented, is that "it may signify a shift in our understanding of the nature of neurodegenerative diseases, such as Alzheimer's or Parkinson's".

We might, therefore, ask ourselves if other types of motor neurone diseases can be transmitted through surgery and be latent for decades, such as those where risk factors, particularly physical professions and activities or certain sporting activities, for example, which are more likely to lead to surgery, have already been indicated.

"Suggesting that a disease could have been acquired during health care is a very delicate affirmation, as some relatives of patients with sporadic CJD may be tempted to seek compensation from health authorities for the alleged intraoperational transmission years previously, which would be impossible to prove in individual cases", he reasons.

Nonetheless, the most conclusive pattern that the study presents, albeit based on few cases and one that must be replicated in future studies, is that the onset of CJD occurs approximately 10 years after an operation on the retina with reused equipment.

###

References: Jesús de Pedro-Cuesta, Ignacio Mahillo-Fernández, Alberto Rábano, Miguel Calero, Mabel Cruz, Ake Siden, Henning Laursen, Gerhard Falkenhorst, Kare Mølbak y el Grupo de Investigación EUROSURGYCJD. "Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions". J Neurol Neurosurg Psychiatry (2010). doi:10.1136/jnnp.2009.188425.

http://www.eurekalert.org/pub_releases/2010-07/f-sf-slt070810.php


http://www.sciencedaily.com/releases/2010/07/100708071513.htm


J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2009.188425

Research paper

Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions

Jesús de Pedro-Cuesta1,2, Ignacio Mahillo-Fernández1,2, Alberto Rábano3, Miguel Calero2,4, Mabel Cruz5, Åke Siden5, Henning Laursen6, Gerhard Falkenhorst7, Kåre Mølbak7, EUROSURGYCJD Research Group + Author Affiliations

1Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain 2Consortium for Biomedical Research in Neurodegenerative Diseases (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas—CIBERNED),Madrid, Spain 3Pathology Unit, Fundación Alcorcón University Teaching Hospital, Alcorcon, Spain 4Department of Spongiform Encephalopathies, National Microbiology Center, Carlos III Institute of Health, Ctra. Majadahonda-Pozuelo, Majadahonda, Spain 5Department of Clinical Neurosciences, Neurology Division, Karolinska Institutet, Stockholm, Sweden 6Neuropathology Laboratory, Copenhagen, Denmark 7Department of Epidemiology, Statens Serum Institut, Copenhagen, Denmark Correspondence to Dr Jesús de Pedro Cuesta, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Calle Monforte de Lemos 5, Madrid 28029, Spain; jpedro@isciii.es Contributors JdP-C has full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Preliminary results were presented at the EUROCJD/NEUROCJD Public Health EU Meeting, held in Paris on 5 December 2006.

Received 9 July 2009 Revised 3 March 2010 Accepted 12 April 2010 Published Online First 14 June 2010 Abstract Objectives Evidence of surgical transmission of sporadic Creutzfeldt–Jakob disease (sCJD) remains debatable in part due to misclassification of exposure levels. In a registry-based case–control study, the authors applied a risk-based classification of surgical interventions to determine the association between a history of surgery and sCJD.

Design Case–control study, allowing for detailed analysis according to time since exposure.

Setting National populations of Denmark and Sweden.

Participants From national registries of Denmark and Sweden, the authors included 167 definite and probable sCJD cases with onset during the period 1987–2003, 835 age-, sex- and residence-matched controls and 2224 unmatched. Surgical procedures were categorised by anatomical structure and presumed risk of transmission level. The authors used logistic regression to determine the odds ratio (OR) for sCJD by surgical interventions in specified time-windows before disease-onset.

Results From comparisons with matched controls, procedures involving retina and optic nerve were associated with an increased risk at a latency of =1 year OR (95% CI) 5.53 (1.08 to 28.0). At latencies of 10 to 19 years, interventions on peripheral nerves 4.41 (1.17 to 16.6) and skeletal muscle 1.58 (1.01 to 2.48) were directly associated. Interventions on blood vessels 4.54 (1.01 to 20.0), peritoneum 2.38 (1.14 to 4.96) and skeletal muscle 2.04 (1.06 to 3.92), interventions conducted by vaginal approach 2.26 (1.14 to 4.47) and a pooled category of lower-risk procedures 2.81 (1.62 to 4.88) had an increased risk after =20 years. Similar results were found when comparing with unmatched controls.

Interpretation This observation is in concordance with animal models of prion neuroinvasion and is likely to represent a causal relation of surgery with a non-negligible proportion of sCJD cases.

snip...

DISCUSSION

The key features of the present study design enabled us to address novel aspects of the potential of surgical transmission of CJD.9 The additional introduction of an aetiological classification, that is unmasking associations hidden by the body-system approach,17 24 revealed a number of statistically significant associations, associations of higher magnitude and new effects with a particular pattern at 10e19 years’ latency. Limitations, which in part are discussed elsewhere,9 comprise: the low statistical power for some latencies and exposure categories; missing information on interventions undergone prior to registration or as outpatients; and lack of control of potential confounders such as blood transfusion, overlooked dura mater implants or hospital hygiene level.

The new SP classification system was built in a tissue/structure classification reported in 200522 combining features of the first WHO Classification on Tissue infectivity25 and of experimental efficiency of prion disease transmission to animals when using different routes of inocula administration.26e29 The plausibility of the risk excess of surgery of retina and peripheral nerves seen here might be supported by studies in experimental scrapie (Sc). PrPSc injected into the eye travelling via defined neuroanatomical connections has been demonstrated to be able to reach larger brain regions.30 31 In hamsters, PrPSc spreads along the vagus nerve to the medulla, pons, midbrain, cerebellum and thalamus via neuroanatomical pathways.32 The increasing risk found for SP involving veins, peritoneal cavity and lymph nodes at longer latencies fits proposals on prion neuroinvasion and transport, suggesting that prions first replicate and accumulate in the lymphoreticular system (LRS) (see Aguzzi and Calella33 for a recent review). In addition, it would appear that risk excess and latency are inversely correlated: for surgery of retina, OR 5.53, at mean 11 years; for surgery of peripheral nerves, OR 4.41, at 10e19 years; and for lower-risk SP OR 2.4, at $20 years. In summary, our findings might be consistent with proposed biological mechanisms potentially underlying the rapid access to the CNS by direct contact,34 prion uptake through the skin, neuroinvasion from the spleen and spread of prions along peripheral and CNS pathways.33 35

Compared with other studies, the main contribution of the new methodology may be credibility to consistently positive results from large recent studies covering lifetime surgery and pointing to likewise underlying diluting effects.7 8 In a study with negative results, retina surgery was unfortunately not investigated separately from other ophthalmological surgery.12 Findings for lower-risk procedures at >20 years would correspond to a similar risk excess before reclassification for main surgical procedures.9 However, the association with coronary surgery seen in TW-3 when using unmatched controls as well as the body system approach does not have a corresponding finding here. Since the association of coronary surgery with sCJD has been reported for Alzheimer’s disease at a similar latency, confounding from vascular risk factors generating both dementia and coronary disease followed by coronary surgery may be proposed as a potential explanation unrelated to prion transmission consistent with absence of findings after reclassification.36

Unrecorded information potentially determining our results might be the length of the pathway to the brain, short in the case of retina and acoustic nerve. An overlooked autologous dura mater graft, implanted during the above-mentioned acoustic neurinoma intervention, was excluded by direct perusal of the surgeon’s report, issued in 1977, by an author, HL, who excluded an accidentally transmitted CJD by dura mater implant. Improved cleaning of instruments in recent times may in part explain decreased excess risk with shorter latencies. Blood transfusion has not been identified as a risk factor for sCJD; however, Riggs et al warn about the weaknesses of caseecontrol studies frequently reporting protective effects.37 Inability to adjust for blood transfusion is a limitation of the study, since it has been estimated that blood transfusion is present in 50% of all major surgical interventions38; blood thus comprises a potential confounder.39 Since it would appear that the excess risk seen here for some tissues, for instance for retina surgery, is difficult to attribute to simultaneous blood transfusion, some of the present results might be consistent with confounded effects of surgical instruments and blood. This view contradicts observations on variant CJD, where transmission by blood has been demonstrated,40e43 but not risk excess for surgery.44 However, differences between sCJD and vCJD or Kuru are so large that inferences should perhaps be inappropriate. Furthermore, the exposures studied might not be independent phenomena representing either a potential entry site for prions or the above-mentioned uncontrolled confounding. For example, cohorting of surgical instruments occurs, and an instrument used once for retina surgery, for example, has in all likelihood been repeatedly used for retina surgery. It is therefore possible that our findings could in part be explained by infectivity determined by tissue remnants adhered to instruments (not controlled for here) rather than by the putative entry site (ie, tissue contacted). Consequently, the 18%9 to 35%7 proportion of sCJD which has been suggested might be causally related to surgery, while in theory consistent with observations from animal models, would be difficult to ascribe to a single biological mechanism based on these data.

The results might be surprising, since identified iatrogenic events related to surgery appear to be very rare. Surveillance since 1993 by 11 countries at the EUROCJD consortium includes data on more than 6000 sCJD cases (http://www. eurocjd.ed.ac.uk/genetic.htm). The number of iatrogenic cases related to surgery are 53 assigned to dura mater, two to corneal implants and nil to neurosurgery. However, routine surveillance data will usually not recognise surgical risk exposures for iatrogenic CJD other than grafts. Reasons to explain this might be: (1) the overwhelming difference in annual cohort size, that is 100 000 surgical in-patients per million in Sweden 2004 (http://192.137.163.40/epcfs/index.asp?modul¼ope), versus approximately 200 dura mater grafts per million in the 1990s in Japan45; (2) the comparatively large attrition by low survival of neurosurgical and dura mater grafted cohorts45e47; (3) surveillance encompasses the end of the iCJD epidemic48; (4) large differences in duration of incubation periods, mean 11 years for iCJD by dura mater reduce differences in cumulative risk48; (5) similar genetic susceptibility might be a strong determinant of surgical risk linked or not to grafts, and is shared by iCJD and sCJD as shown by homozygosity at codon 12948 49 but can be interpreted in different ways. CJD surveillance captures epidemiologically compelling evidences required for correct CJD diagnosis; the OR for exposure to cadaveric dura mater for CDJ in Japan50 was 32.5 95% CI (2.6 to infinity). Our three cases with history of retina surgery were first discharged with CJD diagnosis from three different hospitals, at different years, in two countries, and most probably diagnosed by different clinicians. Views for iCJD from surveillance and results of this study are perhaps not so difficult to reconcile when biology, diagnosis, epidemiology and public-health practice51 are simultaneously considered.

The potential applicability of results in prevention is complex. Cautiousness might be recommended for planning of surgical interventions for patients where CJD diagnosis has been considered, and for decontamination and quarantining of such surgical instruments, avoiding reuse during the interval CJD diagnosis has not been excluded. Established instrument-quarantining, -tracking, -cleaning and prion-disinfection policies, which generally target infrequent procedures, such as neurosurgery and ophthalmological, spine and ear surgery,38 52 are based on decontamination of remnants and applied to surgical activity defined by the type of surgeon, that is, by body-system group. Current sterilisation procedures undertaken in hospitals for delicate instrumentation are insufficient to ensure total removal of infectious prion protein, and carriers of infective prions are difficult to detect.52 53 Extension of such measures, after appropriate assessment, to instruments contacting or potentially contacting veins, female genital organs, peritoneal cavity, peripheral nerves and muscle could be a priority. In addition, new decontamination procedures54 may have a widerthan- expected field of application.

To sum up, these results suggest that surgery constitutes a risk factor for sCJD, acting with long incubation periods, and less frequently with shorter latencies when the central- or peripheral nervous system as well as skeletal muscle are implicated. In addition, results are in concordance with animal models of experimental prion transmission through various routes of inoculation that may mimic accidentally transmitted CJD, and might have implications for prevention of CJD spread in medical settings.

see full text with charts etc here, and thank you for free full text access. ...TSS


http://jnnp.bmj.com/content/early/2010/06/12/jnnp.2009.188425.abstract?sid=2b27497a-91ea-49db-93c9-860427bef10d


http://jnnp.bmj.com/content/early/2010/06/12/jnnp.2009.188425.full.pdf


FRIENDLY FIRE AND OR PASS IT FORWARD MODE OF TRANSMISSION


NY State Legislation Presentation New York State Association of Central Service Professionals

October 24, 2007

Meeting Objectives Introduce NYSACSP organization Describe the role of central service as it impacts patient safety and sterilization practices Discuss proposed changes in legislation Present rationale for changes in legislation New York State Central Service Professionals Delegation Mary Olivera, BA, MS, CRCST, President Marcia Hardick, RN,BS,CGRN, Education Director Anthony Monaco, Strategic Advisor Evelyn Baez, CRCST - President, LIACS Chapter, Representative to NYSACSP BOD Who are we? Central Service workers in healthcare ?? Managers, supervisors, technicians ?? Hospital, ambulatory care, private sector Supporting ?? Operating room - surgical staff; surgeons, nurses ?? Patient care units ?? Ambulatory care What We Do Responsibilities ?? Promote patient safety • Prevent cross contamination • Decrease incidence of nosocomial infections ?? Reprocess medical/surgical instrumentation and devices • Safe handling and decontamination • Inspection, preparation, package • Sterilization • Quality monitoring, documentation Our Challenges We are a “dumping ground” No standardization of performance Increasing technology Complex instrumentation Risk of exposure to pathogens Reduce nosocomial infections

snip...

Terry Singletary, whose mother died from a type of CJD called Heidenhain Variant, told UPI health officials were not doing enough to prevent people from being infected by contaminated medical equipment. "They've got to start taking this disease seriously and they simply aren't doing it," said Singletary, who is a member of CJD Watch and CJD Voice -- advocacy groups for CJD patients and their families.

snip...

Singletary said CDC's assertion that no CJD cases from infected equipment or tissues have been detected since 1976 is misleading. "They have absolutely no idea" whether any cases have occurred in this manner, he said, because CJD cases often aren't investigated and the agency has not required physicians nationwide report all cases of CJD. "There's no national surveillance unit for CJD in the United States; people are dying who aren't autopsied, the CDC has no way of knowing" whether people have been infected via infected equipment or tissues, he said.

snip...


see full text 217 pages ;


http://www.iahcsmm.org/images/certification-map/NY/State_Presentation_Guide_2008.pdf


Sunday, January 17, 2010

CJD Following up: Patients never contracted brain disorder UW Hospital patients

http://creutzfeldt-jakob-disease.blogspot.com/2010/01/cjd-following-up-patients-never.html


Sunday, January 17, 2010

Human tissue, recovered from a donor history indicated increased risk factors for Creutzfeldt-Jacob disease Lions Eye Bank

http://creutzfeldt-jakob-disease.blogspot.com/2010/01/human-tissue-recovered-from-donor.html


Saturday, January 16, 2010 Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al

http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html


Friday, November 20, 2009

SaBTO Advisory Committee on the Safety of Blood, Tissues and Organs Summary of the Eighth Meeting, 27 October 2009

http://vcjdtransfusion.blogspot.com/2009/11/sabto-advisory-committee-on-safety-of.html


Sunday, May 10, 2009

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)


http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html


2006

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4271t1.pdf


2004

http://www.fda.gov/ohrms/dockets/ac/04/transcripts/2004-4075T1.DOC


2003


Asante/Collinge et al, that BSE transmission to the 129-methionine

genotype can lead to an alternate phenotype that is indistinguishable

from type 2 PrPSc, the commonest _sporadic_ CJD;


http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm


2001

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf


Docket Management

Docket: 02N-0370 - Neurological Devices; Classification of Human Dura Mater

Comment Number: EC -1

Accepted - Volume 1


http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be11.html


http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004bdfe.html


http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004bdfc.html


Daily Dockets - 04/10/03

00D-1662 Use of Xenotransplantation Products in Humans. EMC 98 Terry S. Singeltary Sr. Vol#: 3. 01F ...

www.fda.gov/ohrms/dockets/dailys/03/Apr03/041003/041003.htm - 05-20-2003 - Cached

# Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of 2002; [TSS SUBMISSION ON POTENTIAL FOR BSE/TSE & FMD 'SUITCASE BOMBS'] - TSS 1/27/03 (0)

Docket Management

Docket: 02N-0276 - Bioterrorism Preparedness; Registration of Food Facilities, Section 305 Comment Number: EC-254 [TSS SUBMISSION]

http://www.fda.gov/ohrms/dockets/dockets/02n0276/02N-0276-EC-254.htm


Monday, August 17, 2009

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex J,K, AND D Published: 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/transmissible-spongiform-encephalopathy.html


Tuesday, March 16, 2010

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Part 4 REVISED FEB. 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/03/transmissible-spongiform-encephalopathy.html


Friday, July 17, 2009

Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units Volume 3 No 28; 17 July 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/revision-to-pre-surgical-assessment-of.html


Tuesday, August 12, 2008

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html


Tuesday, May 11, 2010

Current risk of iatrogenic Creutzfeld-Jakob disease in the UK: efficacy of available cleaning chemistries and reusability of neurosurgical instruments

http://creutzfeldt-jakob-disease.blogspot.com/2010/05/current-risk-of-iatrogenic.html


Saturday, January 16, 2010 Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al Evidence For CJD/TSE Transmission Via Endoscopes

http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html


Wednesday, February 24, 2010

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th

ICID International Scientific Exchange Brochure -

http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html


Tuesday, June 1, 2010

USA cases of dpCJD rising with 24 cases so far in 2010

http://cjdtexas.blogspot.com/2010/06/usa-cases-of-dpcjd-rising-with-24-cases.html


Wednesday, June 16, 2010

Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

http://creutzfeldt-jakob-disease.blogspot.com/2010/06/defining-sporadic-creutzfeldt-jakob.html



Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION


http://cjdquestionnaire.blogspot.com/





tarball, aka flounder, alias TSS, and for those that remember, madcowdeadmommadson


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

Organ distribution of prion proteins in variant Creutzfeldt-Jakob disease

The Lancet Infectious Diseases, Volume 3, Issue 4, Pages 214 - 222, April 2003

doi:10.1016/S1473-3099(03)00578-4Cite or Link Using DOI

Organ distribution of prion proteins in variant Creutzfeldt-Jakob disease

Original Text

Dr I Ramasamy a , M Law b, S Collins c, F Brook a

Summary

In this article we give an overview of the transmissible spongiform encephalopathies, with emphasis on the evidence for the distribution of abnormal prions in tissues. The normal prion protein is distributed ubiquitously throughout human body tissues. Endogenous expression of the normal prion protein, as well as auxiliary proteins, plays a part in accumulation of the abnormal prion protein. As exemplified by variant Creutzfeldt-Jakob disease (vCJD) the abnormal prion protein can accumulate in the host lymphoid system, in particular the follicular dendritic cells. The route for the disease-related prion neuroinvasion is likely to involve the peripheral nervous system. An alternative route may involve blood constituents. Both animal studies and studies on vCJD patients suggest a potential for abnormal prion distribution in several peripheral tissues other than the lymphoreticular system. In human beings the abnormal prion has been reported in the brain, tonsils, spleen, lymph node, retina, and proximal optic nerve. Infectivity, although present in peripheral tissues, is at lower levels than in the central nervous system (CNS). Animal models suggest that the growth of infectivity in the CNS is likely to be gradual with maximum values during the clinical phase of disease. That tissues may harbour the abnormal prion, at different levels of infectivity, during the incubation period of the disease raises concerns of iatrogenic transmission of the disease either after surgery, blood transfusion, or accidental organ transplantation from donors in the preclinical phase of the disease.


http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(03)00578-4/fulltext#article_upsell


Cadaver corneal transplants -- without family permission

Houston, Texas channel 11 news 28 Nov 99

Reported by Terry S. Singeltary Sr. son of CJD victim

"It was a story about how the Lions eye bank were harvesting corneas from victims in the Morgue, without their consent. Under Texas law, this appears to be legal (remember Texas has the Veggie liable law). Even if Family says no, this appears to happen, from what the news story said. They said the only way to prevent this, is to fill out a form, stating not to have this done. So if you don't fill out the form, they can do this. How many people don't know about the form?

This is not only disgusting and appalling, it could be highly infectious. Without proper background checking of the donors, on their physical history, checking on past dementia, and/or family history, some of these unfortunate victims, could be passing a human TSE.

Response Jill Spitler Clevelland Eye Bank:

"No, we are not stealing.........Yes, you do have such a law in the state of Texas, but not all your state Eye Banks utilize the law. The Eye Bank that you're speaking of is only one of 43 certified Eye Bank throughout the USA.

And there are measure taken per the Medical Standards of the Eye Bank Association of America, the certifying body for eye banks and per FDA regulations to address those concerns that you speak of.

I would suggest that those interested/concern with transplant contact their local agencies. The Eye Bank Association of America has a web. site . Further if anyone has problems contacting or finding out about their local organization(s), call me or e-mail me I would be glad to help. My e-mail address is jill@clevelandeyebank.org"

Terry Singeltary responds:

"Explain this to the family in Houston who went to their loved ones funeral, only to find out that the loved one that was in the casket, had their corneas removed without their permission, without the consent of the victim or it's family. They would not have known it, only for the funny look the victim had. So, they questioned, only to find out, the corneas, had in fact, been removed without consent.

I call that stealing, regardless what the law states. This type of legal grave robbing is not a logical thing to do without knowing any type of background of the victims medical past, which really will not prove anything due to the incubation period. Eye tissue being potentially a highly infective source, there are risks here.

Should they not at least know of the potential ramifications of TSE's (the person receiving the corneas)?

Should there not be some sort of screening?

Should there be some sort of moral issue here? If this is the case, and in fact, they can come take your corneas, without your consent, then what will they start taking next, without your consent?

Lets look at a hypothetical situation: What would happen if my Mom (DOD 12-14-97 hvCJD) would have gotten into a car wreck and died, before the symptoms of CJD appeared. Not much money, so there was no autopsy. What would have happened to that recipient of those infecting corneas?"

Comment (webmaster): Actual transmission of CJD by means of corneal transplant may or may not be rare. The incidence of infectivity in older people could be fairly high; this is not to be confused with the lower incidence of symptomatic (clinical) CJD. It is very unlikely that familial CJD would have been diagnosed in earlier generations; however, without interviewing the family even known kindreds would not be excluded.

In blood donation, a much stricter policy is followed, even though corneal transplant may be far more dangerous (being a direct link to the brain and not going through purification steps).

Since highly sensitive tests for pre-clinical CJD are now available, it would make sense to screen corneas for CJD, just as they are screened for AIDS, hepatitus, and a host of other conditions.


http://mad-cow.org/~tom/dec99_news.html#bbb


please see full text here ;

Monday, August 31, 2009

HUMAN BODY PARTS FOR SALE TO THE HIGHEST BIDDER Inside a Creepy Global Body Parts Business


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/human-body-parts-for-sale-to-highest.html


THE LEGALITY OF STEALING ORGAN/TISSUE...

TEXAS STATUTES

Sec. 693.012. Removal of Corneal Tissue Permitted Under Certain Circumstances.

On a request from an authorized official of an eye bank for corneal tissue, a justice of the peace or medical examiner may permit the removal of corneal tissue if:

(1) the decedent from whom the tissue is to be removed died under circumstances requiring an inquest by the justice of the peace or medical examiner;

(2) no objection by a person listed in Section 693.013 is known by the justice of the peace or medical examiner; and

(3) the removal of the corneal tissue will not interfere with the subsequent course of an investigation or autopsy or alter the decedent's postmortem facial appearance.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.012

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TEXAS STATUTES Sec. 693.003. Consent Required in Certain Circumstances.

(a) A medical examiner or a person acting on the authority of a medical examiner may not remove a visceral organ unless the medical examiner or person obtains the consent of a person listed in Section 693.004.

(b) If a person listed in Section 693.004 is known and available within four hours after death is pronounced, a medical examiner or a person acting on the authority of a medical examiner may not remove a nonvisceral organ or tissue unless the medical examiner or person obtains that person's consent.

(c) If a person listed in Section 693.004 cannot be identified and contacted within four hours after death is pronounced and the medical examiner determines that no reasonable likelihood exists that a person can be identified and contacted during the four-hour period, the medical examiner may permit the removal of a nonvisceral organ or tissue.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.003

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PLEASE NOTE; the bottom would only pertain to those who know of the law. if you don't know about it, you cannot dispute, so in four hours, they can legally remove body organs, as long as they don't disfigure. and who is to know the difference? makes me wonder of some of my dead relatives, and if they were burried with their eye's and or any of their organs. This is very disturbing, if not for moral reasons, but for the risk of dangerous pathogens (human TSE's, etc.) to be transmitted. only time will tell, but i am very disturbed. these laws are not morally correct. They should be re-written as to they cannot so easily take your organs, with no one knowing. The Family or Victim, must consent. There should be some kind of research on donor/family medical history... TSS

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Sec. 693.013. Persons Who May Object to Removal.

The following persons may object to the removal of corneal tissue:

(1) the decedent's spouse;

(2) the decedent's adult children, if there is no spouse;

(3) the decedent's parents, if there is no spouse or adult child; or

(4) the decedent's brothers or sisters, if there is no spouse, adult child, or parent.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.013

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


to cover one's butt....



Sec. 693.014. Immunity From Damages in Civil Action.

(a) In a civil action brought by a person listed in Section 693.013 who did not object before the removal of corneal tissue, a medical examiner, justice of the peace, or eye bank official is not liable for damages on a theory of civil recovery based on a contention that the person's consent was required before the corneal tissue could be removed.

(b) Chapter 104, Civil Practice and Remedies Code, applies to a justice of the peace, medical examiner, and their personnel who remove, permit removal, or deny removal of corneal tissue under this subchapter as if the justice of the peace, medical examiner, and their personnel were state officers or employees.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.014

[[[as you can see, they knew it was wrong when they wrote the laws. or they would not have covered the rear-ends so well...TSS]]]

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

thanks again, kind regards, Terry S. Singeltary Sr.


############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############


full text ;

Saturday, January 26, 2008

CJD HGH BODY SNATCHERS


http://creutzfeldt-jakob-disease.blogspot.com/2008/01/cjd-hgh-body-snatchers.html



URGENT DATA ON ATYPICAL BSE RISK FACTORS TO HUMANS AND ANIMALS OIE REFUSE TO ACKNOWLEDGE $

position: Post Doctoral Fellow Atypical BSE in Cattle

Closing date: December 24, 2009

Anticipated start date: January/February 2010

Employer: Canadian and OIE Reference Laboratories for BSE CFIA Lethbridge Laboratory, Lethbridge/Alberta

snip...

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

snip...


http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2



please see full text ;

Wednesday, March 31, 2010

Atypical BSE in Cattle


http://bse-atypical.blogspot.com/2010/03/atypical-bse-in-cattle-position-post.html


Wednesday, February 24, 2010

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th

ICID International Scientific Exchange Brochure -


http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html



TSE


http://transmissiblespongiformencephalopathy.blogspot.com/



Monday, October 19, 2009

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

snip...

I ask Professor Kong ;

Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment

''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''

Professor Kong reply ;

.....snip

''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete.

Thanks for your interest.''

Best regards,

Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA

END...TSS

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



http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html



TSS

Creutzfeldt-Jakob disease (CJD) biannual update (2010/1)

Emerging infections/CJD

Creutzfeldt-Jakob disease (CJD) biannual update (2010/1)

This six-monthly report provides an update on reports of incidents of potential iatrogenic (healthcareacquired) exposure to CJD via surgery, and on the National Anonymous Tonsil Archive. Data are correct as of 26 January 2010.

For numbers of CJD case reports, readers should consult data provided by the national CJD Surveillance Unit (NCJDSU), Edinburgh [1]. The latest yearly analysis of vCJD reports (onsets and deaths) is also available from the NCJDSU website [2].

Reports of incidents of potential iatrogenic exposure to CJD via surgery:

2000 to 31 December 2009

Since the previous update report [3], 19 surgical incidents were reported – between 1 July and 31 December 2009 – bringing the total number reported since 2000 to 407 (table 1). A surgical incident occurs when a patient undergoes surgery but is only identified as having CJD or being at risk of CJD at a later date. This means that the ACDP TSE Working Group infection control guidelines would not have been followed. The surgery carried out on an index patient with, or at risk of CJD, may result in contamination of the instruments with abnormal prion protein. Table 1 shows the number of CJD surgical incidents reported to the CJD Incidents Panel from January 2000 to 31st December 2009 by the diagnosis of the index patient. Information about the CJD Incidents Panel can be found on the HPA website [4].

Table 1. Closed CJD Surgical Incidents (n=407) reported to the CJD Incidents Panel, by diagnosis of index patient: 1 January 2000 to 30 June 2009

Incident type 2000 2001 2002 2003 2004 2005 2006 2007 2008 First half 2009 Total

1. Sporadic (possible, probable or definite) 7 19 22 24 16 18 31 17 21 11 186(46%)

2. vCJD (possible, probable or definite) 6 14 22 5 4 1 2 – 1 1 56(14%)

3. Familial including 'at risk' familial – 2 2 7 1 3 7 – 2 2 26(6%)

4. 'At risk' vCJD blood component recipient – – – – 4 10 6 1 – – 21(5%)

5. 'At risk' - vCJD plasma product recipient – 1 2 – 10 18 9 8 6 8 62(15%)

6. 'At risk' - other – – 2 2 1 2 4 – – 1 12(3%)

7. CJD type unclear/ CJD unlikely 1 1 4 1 1 2 – – – 10(2%)

8. Not CJD 2 1 4 7 7 1 1 – 3 – 26(6%)

9.Other – – 1 1 1 2 1 – – – 6(1%)

10. No longer considered 'at-risk' – – 1 – – – – 1 – – 2(0%)

Total 16 38 56 50 45 56 63 27 33 23 407(100%)

Investigation of surgical incidents may result in advice to remove surgical instruments from clinical use (to quarantine, destroy, or donate for research). Such advice is generally only given for instruments considered to be potentially contaminated with the CJD agent that have not undergone a certain number of cycles of use and decontamination since their use on an index patient. Hospitals are asked to consider sending any instruments to be permanently removed from use to the Surgical Instrument Store (held by the Health Protection Agency, Porton Down) for research. Since 2000, there have been 46 incidents in which instruments were permanently removed from use.

The Panel may advise contacting and informing some patients of their possible exposure to CJD in a surgical incident. Such advice is generally only given for patients who have definitely been exposed to potentially contaminated instruments which have been used on risk tissues in certain index patients. The Panel may advise that some of these patients should be considered „at-risk of CJD for public health purposes' and asked to take certain precautions (ie, not to donate blood or other tissues and to inform their medical and dental carers prior to any invasive procedures) in order to reduce the risk of transmitting the CJD agent further. Since 2000, 22 incidents have given rise to such advice. There are currently nine incidents in which 77 patients have been categorised as „at-risk' by the Panel, according to the current risk assessment. Seven of these patients died before notification. A total of 31 patients are currently notified of their „at-risk' status. Notifications are pending for another 31 patients. Three patients have not been notified due to local, clinical decisions.

The Panel has revised its advice on endoscopy and anterior eye patients. This has led to patients being denotified in 2006 and 2009. This resulted in reclassification of 38 patients from the „at-risk' category; 32 in anterior eye surgery, two in invasive endoscopy.

Table 2. Panel advice to inform patients that they are ‘at-risk' of CJD/vCJD: 1 January 2000 to 30 June 2009

Diagnosis of index patient Procedure on index patient Number of Incidents Alive 'at-risk' Died before notification Total Notified Not notified Total

Sporadic CJD Brain biopsy 2 20 1* 21 2 28

vCJD Appendectomy 1 – 2* 2 – 2

Endoscopy and GI surgery 2† 3 1 ** 4 1 5

'At risk' vCJD Endoscopy and GI surgery 4 8 30** 38 4 42

Total – 9 31 34 65 7 77

*Local decision not to notify.

† The index patient in one of these incidents was a haemophiliac plasma product recipient with evidence of vCJD infection.

** Notification pending.

National anonymous tonsil archive for studies of detectable abnormal prion protein

The National Anonymous Tonsil Archive (NATA) continues to receive approximately 250 tonsil pairs per week (figure 1). The archive had received a total of 81,604 tonsil pairs up to the end of December 2009 from hospitals in England and Scotland. A further 3,000 tonsil pairs have been received from the Medical Research Council Prion Unit at the Institute for Neurology, National Hospital for Neurology and Neurosurgery. Therefore the total number of tonsil pairs in the archive was 84,604. The number of collection forms that were completed but no tonsil tissue collected was 2,395 (1,565 due to patient objection and 830 due to clinical pathology being requested).

Out of the 100 NHS Hospital Trusts that perform over 200 tonsillectomies per year in England, 91 have been recruited and are currently sending tonsil pairs to NATA on a regular basis. There are 120 hospitals sites within these trusts taking part in NATA. At present, approximately 50,000 tonsillectomies are performed annually in England. Figure 2 shows the number of tonsil pairs received from each Strategic Health Authority.

Figure 1. Number of tonsil pairs collected for NATA quarterly: Q1 2004 – Q4 2009

Just over 5,000 tonsillectomies are performed in Scotland each year. The project in Scotland, where there are 14 hospitals that each carry out more than 200 tonsillectomies per year, is being coordinated by Health Protection Scotland. All fourteen of these hospitals have been recruited and are collecting tonsils for NATA. The tonsil tissue is being transported to the Health Protection Agency in Colindale for inclusion in the archive. Figure 3 shows all hospitals in England and Scotland currently recruited in the study.

Figure 2. Tonsils pairs collected by Strategic Health Authority, January 2004 - December 2009

Figure 3. NHS Trusts and Scottish Hospitals currently collecting and sending tonsil tissue to the archive December 2009

Testing of homogenates of the tonsil tissue from the archive began at the end of January 2007. Two enzyme immunoassays (EIAs) are being used for the initial screening of the homogenates for the presence of abnormal prion protein. These EIAs allow the identification of any tonsils that need to be investigated further by the more specific tests of Western blotting (WB) and immunohistochemistry (IHC) [5].

References

1. The National Creutzfeldt-Jakob Disease Surveillance Unit, The University of Edinburgh. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm.


2.The National Creutzfeldt-Jakob Disease Surveillance Unit, The University of Edinburgh. Incidence of variant Creutzfeldt-Jakob Disease Onsets and Deaths in the UK January 1994 - December 2006. Edinburgh: NCJDSU, 2 February 2007. Available at: http://www.cjd.ed.ac.uk/vcjdqdec06.htm.


3. HPA. Biannual CJD update (2009/1). Health Protection Report [serial online] 2009; 3(27): Emerging Infections/CJD. Available at: http://www.hpa.org.uk/hpr/archives/2009/hpr2709.pdf.


4. HPA. CJD Incidents Panel [online]. London: HPA, 2010. Available at: http://www.hpa.org.uk/web/HPAweb&Page&HPAwebAutoListName/Page/1204031511121.


5. Spongiform Encephalopathy Advisory Committee. Combining evidence from tissue surveys to estimate the prevalence of subclinical vCJD. London: SEAC, 2008. Available at: http://www.seac.gov.uk/papers/paper100-2.pdf.


Health Protection Report Vol 4 No. 7 - 19 February 2010


http://www.hpa.org.uk/hpr/archives/2010/hpr0710.pdf





Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible ...


http://bse-atypical.blogspot.com/2010/01/14th-international-congress-on.html




Saturday, January 16, 2010

Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al


http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html




Monday, July 20, 2009

Pre-surgical risk assessment for variant Creutzfeldt-Jakob disease (vCJD) risk in neurosurgery and eye surgery units


http://vcjdtransfusion.blogspot.com/2009/07/pre-surgical-risk-assessment-for.html




[2] UK: SEAC position statement on dentistry Date: Sat 30 Jun 2007 Source: Position Statement vCJD and Dentistry, Spongiform Encephalopathy Advisory Committee (SEAC) Update, June 2007 [edited]





Position Statement vCJD and Dentistry ------------------------------------- Issue ----- 1. The Department of Health (DH) asked SEAC to advise on the findings of preliminary research aimed at informing estimates of the risk of variant Creutzfeldt-Jakob Disease (vCJD) transmission via dentistry.

Background ---------- 2. Prions are more resistant than other types of infectious agents to the conventional cleaning and sterilization practices used to decontaminate dental instruments (1). Appreciable quantities of residual material may remain adherent to the surface after normal cleaning and sterilization (2). Therefore, if dental tissues are both infectious and susceptible to infection, the dental instruments are a potential mechanism for the secondary transmission of vCJD. Dentistry could be a particularly significant route of transmission for the population as a whole, due to the large number of routine procedures undertaken and also because dental patients have a normal life expectancy.

This is in contrast with other transmission routes, such as blood transfusion and neurosurgery, where procedures are often carried out in response to some life-threatening condition. Additionally, the ubiquity of dental procedures and the lack of central records on dental procedures means that should such transmission occur, then it would be difficult to detect and control.

3. No cases of vCJD transmission arising from dental procedures have been reported to date (3). Previous DH risk assessments (4,5) have focused on 2 possible mechanisms for the transfer of vCJD infectivity via dental instruments; accidental abrasion of the lingual tonsil and endodontic procedures that involve contact with dental pulp. In considering these assessments, SEAC agreed that the risk of transmission via accidental abrasion of the lingual tonsil appears very low. However, the risk of transmission via endodontic procedures may be higher and give rise to a self sustaining vCJD epidemic under circumstances where (i) dental pulp is infective, (ii) transmission via endodontic instruments is efficient and (iii) a large proportion of vCJD infections remain in a subclinical carrier state (SEAC 91, February 2006). In light of this, SEAC advised that restricting endodontic files and reamers to single use be considered (6). SEAC recommended reassessment of these issues as new data emerge.

New research ------------ 4. Preliminary, unpublished results of research from the Health Protection Agency, aimed at addressing some of the uncertainties in the risk assessments, were reviewed by SEAC (SEAC 97, May 2007). The prion agent used in these studies is closely related to the vCJD agent. This research, using a mouse model, shows that following inoculation of mouse-adapted bovine spongiform encephalopathy (BSE) directly into the gut, infectivity subsequently becomes widespread in tissues of the oral cavity, including dental pulp, salivary glands and gingiva, during the preclinical as well as clinical stage of disease.

5. It is not known how closely the level and distribution of infectivity in the oral cavity of infected mice reflects those of humans infected with vCJD, as there are no comparable data from oral tissues, in particular dental pulp and gingiva, from human subclinical or clinical vCJD cases (7). Although no abnormal prion protein was found in a study of human dental tissues, including dental pulp, salivary glands and gingiva from vCJD cases, the relationship between levels of infectivity and abnormal prion protein is unclear (8). Infectivity studies underway using the mouse model and oral tissues that are presently available from human vCJD cases will provide some comparable data. On the basis of what is currently known, there is no reason to suppose that the mouse is not a good model for humans in respect to the distribution of infectivity in oral tissues. Furthermore, the new data are consistent with published results from experiments using a hamster scrapie model (9).

6. A 2nd set of experiments using the same mouse model showed that non-invasive and transient contact between gingival tissue and fine dental files contaminated with mouse-adapted BSE brain homogenate transmits infection very efficiently. It is not known how efficient gingival transmission would be if dental files were contaminated with infectious oral tissues and then subsequently cleaned and sterilized, a situation which would more closely model human dental practice. Further studies using the mouse model that would be more representative of the human situation, comparing oral tissues with a range of doses of infectivity, cleaned and sterilized files and the kind of tissue contact with instruments that occurs during dentistry, should be considered.

7. SEAC considered that the experiments appear well designed and the conclusions justified and reliable, while recognizing that the research is incomplete and confirmatory experiments have yet to be completed. It is recommended that the research be completed, submitted for peer-review and widely disseminated as soon as possible so others can consider the implications. Nevertheless, these preliminary data increase the possibility that some oral tissues of humans infected with vCJD may potentially become infective during the preclinical stage of the disease. In addition, they increase the possibility that infection could potentially be transmitted not only via accidental abrasion of the lingual tonsil or endodontic procedures but a variety of routine dental procedures.

Implications for transmission risks ----------------------------------- 8. The new findings help refine assumptions made about the level of infectivity of dental pulp and the stage of incubation period when it becomes infective in the risk assessment of vCJD transmission from the reuse of endodontic files and reamers (10). For example, if one patient in 10 000 were to be carrying infection (equivalent to about 6000 people across the UK, the best current estimate (11), the data suggest that in the worst case scenario envisaged in the risk assessment, reuse of endodontic files and reamers might lead to up to 150 new infections per annum. It is not known how many of those infected would go on to develop clinical vCJD. In addition, transmission via the reuse of endodontic files and reamers could be sufficiently efficient to cause a self-sustaining vCJD epidemic arising via this route.

9. These results increase the importance of obtaining reliable estimates of vCJD infection prevalence. Data that will soon be available from the National Anonymous Tonsil Archive may help refine this assessment and provide evidence of the existence and extent of subclinical vCJD infection in tonsillectomy patients. Further data, such as from post mortem tissue or blood donations, will be required to assess prevalence in the general UK population (12).

10. Recent guidance issued by DH to dentists to ensure that endodontic files and reamers are treated as single use (13) is welcomed and should, as long as it is effectively and quickly implemented, prevent transmission and a self-sustaining epidemic arising via this route. However, the extent and monitoring of compliance with this guidance in private and National Health Service dental practice is unclear.

11. The new research also suggests that dental procedures involving contact with other oral tissues, including gingiva, may also be capable of transmitting vCJD. In the absence of a detailed risk assessment examining the potential for transmission via all dental procedures, it is not possible to come to firm conclusions about the implications of these findings for transmission of vCJD. However, given the potential for transmission by this route, serious consideration should be given to assessing the options for reducing transmission risks, such as improving decontamination procedures and practice or the implementation of single use instruments.

12. The size of the potential risk from interactions between the dental and other routes of secondary transmission, such as blood transfusion and hospital surgery, to increase the likelihood of a self-sustaining epidemic is unclear.

13. It is likely to be difficult to distinguish clinical vCJD cases arising from dietary exposure to BSE from secondary transmissions via dental procedures, should they arise, as a large proportion of the population is likely both to have consumed contaminated meat and undergone dentistry.

However, an analysis of dental procedures by patient age may provide an indication of the age group in which infections, if they occur, would be most likely to be observed. Should the incidence of clinical vCJD cases in this age group increase significantly, this may provide an indication that secondary transmission via dentistry is occurring. Investigation of the dental work for these cases may provide supporting data. There is no clear evidence, to date, based on surveillance or investigations of clinical vCJD cases, that any vCJD cases have been caused by dental procedures, but this possibility cannot be excluded.

Conclusions ----------- 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 [2007] recommending that endodontic files and reamers be treated as single use, which, provided this policy is adhered to, will remove any risk of a self-sustaining epidemic arising from reuse of these instruments. To minimize 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 proven robust and effective, could significantly reduce transmission risks.

References ---------- (1) Smith et al. (2003) Prions and the oral cavity. J. Dent. Res. 82, 769-775. (2) Smith et al. (2005) Residual protein levels on reprocessed dental instruments. J. Hosp. Infect. 61, 237-241. (3) Everington et al. (2007) Dental treatment and risk of variant CJD - a case control study. Brit. Den. J. 202, 1-3. (4) Department of Health. (2003) Risk assessment for vCJD and dentistry. (5) Department of Health (2006) Dentistry and vCJD: the implications of a carrier-state for a self-sustaining epidemic. Unpublished. (6) SEAC (2006) Position statement on vCJD and endodontic dentistry . (7) Head et al. (2003) Investigation of PrPres in dental tissues in variant CJD. Br. Dent. J. 195, 339-343. (8) SEAC 90 reserved business minutes. (9) Ingrosso et al. (1999) Transmission of the 263K scrapie strain by the dental route. J. Gen. Virol. 80, 3043-3047. (10) Department of Health (2006) Dentistry and vCJD: the implications of a carrier-state for a self-sustaining epidemic. Unpublished. (11) Clarke & Ghani (2005) Projections of future course of the primary vCJD epidemic in the UK: inclusion of subclinical infection and the possibility of wider genetic susceptibility R. J. Soc. Interface. 2, 19-31. (12) SEAC Epidemiology Subgroup (2006) position statement of the vCJD epidemic . (13) DH (2007) Precautionary advice given to dentists on re-use of instruments .

-- Communicated by Terry S. Singletary, Sr.

******


http://www.promedmail.org/pls/otn/f?p=2400:1001:19224::::F2400_P1001_BACK_PAGE,F2400_P1001_ARCHIVE_NUMBER,F2400_P1001_USE_ARCHIVE:1001,20070702.2112,Y




http://promedmail.oracle.com/pls/otn/f?p=2400:1001:1843502045853916::::F2400_P1001_BACK_PAGE,F2400_P1001_ARCHIVE_NUMBER,F2400_P1001_USE_ARCHIVE:1001,20070702.2112,Y






Monday, December 31, 2007

Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation


http://creutzfeldt-jakob-disease.blogspot.com/2007_12_01_archive.html





Subject: CJD: update for dental staff Date: November 12, 2006 at 3:25 pm PST

1: Dent Update. 2006 Oct;33(8):454-6, 458-60.

CJD: update for dental staff.



http://seac992007.blogspot.com/2008/06/seac-2008-one-hundredth-meeting-of.html






Friday, July 24, 2009

UW Hospital and Clinics Addresses Creutzfeldt-Jakob Disease Risk

PLEASE SEE ;

Pre-surgical risk assessment for variant Creutzfeldt-Jakob disease (vCJD) risk in neurosurgery and eye surgery units

Hospitals should already be using a questionnaire in Annex J of the ACDP TSE Working Group Infection Control guidance to find out whether any patients who are about to undergo any surgery or endoscopy may be at increased risk of being infected with CJD. If a patient is found to have an increased risk of CJD prior to their surgery or endoscopy then special infection control precautions may need to be taken.

Annex J of the TSE Infection Control guidance has recently been revised, and now advises that patients who are due to have high risk surgery [1] or neuro-endoscopy should be asked an additional question: whether they have received transfusions of blood or blood components from 80 or more donors since 1980. This is because these patients may have an increased risk of being infected with variant CJD (vCJD).

On 16 July 2009 the HPA wrote to the chief executives of NHS trusts asking them to ensure that the guidance is implemented. Detailed information and tools for implementing the guidance can be downloaded from the links below.

If you have any queries about the implementation of the guidance, please contact the HPA Centre for Infections CJD Section at mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000260/!x-usc:mailto:cjd@hpa.org.uk or on 020 8327 6074/6411.

Background information on this new pre-surgical assessment is contained in this Letter to chief executives - July 2009 (PDF, 73 KB) written to all hospitals in England.

The new version of Annex J of the TSE Infection Control Guidance contains new question for patients undergoing high risk surgery and neuro-endoscopy. These questions should be used to assess patients' CJD risk factors.

Clinicians carrying out the new pre-surgical assessment should read Pre-surgical assessment Information for healthcare staff - July 2009 (PDF, 163 KB) This vCJD Algorithm for per-surgical roles - July 2009 (PDF, 28 KB) shows suggested roles and responsibilities for infection control teams, surgical teams and blood transfusion specialists.

Information on patients' transfusion histories should be collected using the Highly transfused vCJD risk assessment form - July 2009 (Word Document, 328 KB) This form is also available as a vCJD risk assessment spreadsheet - July 2009 (Excel Spreadsheet, 2.7 MB). This may help calculate the number of blood donors to a patient. The form may be posted or emailed to the HPA Centre for Infections CJD Section mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000260/!x-usc:mailto:cjd@hpa.org.uk.

Blood transfusion laboratories may wish to use this draft Letter to other blood laboratories - July 2009 (Word Document, 31 KB) when collecting transfusion information from other hospitals.

Pre-surgical assessment teams and patients may wish to read this vCJD Information for presurgical patients - July 2009 (PDF, 29 KB) about this new pre-surgical assessment.

[1] High risk surgery is defined as surgery involving any of the following organs or tissues (high risk tissues): brain, spinal cord, cranial nerves (specifically the entire optic nerve and only the intercranial components of the other cranial nerves), cranial nerve ganglia, posterior eye (specifically the posterior hyaloid face, retina, retinal pigment epithelium, choroid, subretinal fluid, optic nerve) and pituitary gland.

Letter to chief executives - July 2009 (PDF, 73 KB) Added/updated: 16 July 2009


http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469060207




Pre-surgical assessment Information for healthcare staff - July 2009 (PDF, 163 KB) Added/updated: 16 July 2009


http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469061870




vCJD Algorithm for per-surgical roles - July 2009 (PDF, 28 KB) Added/updated: 16 July 2009


http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469062057




Highly transfused vCJD risk assessment form - July 2009 (Word Document, 328 KB) Added/updated: 16 July 2009


http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469062225




Letter to other blood laboratories - July 2009 (Word Document, 31 KB) Added/updated: 16 July 2009


http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469062420




vCJD Information for presurgical patients - July 2009 (PDF, 29 KB) Added/updated: 16 July 2009


http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469062586




vCJD risk assessment spreadsheet - July 2009 (Excel Spreadsheet, 2.7 MB) Added/updated: 16 July 2009


http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247728926790




full text ;



http://www.hpa.org.uk/webw/HPAweb&Page&HPAwebAutoListName/Page/1247469069188




http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247728926790




see also ;

Friday, July 17, 2009

Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units Volume 3 No 28; 17 July 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/07/revision-to-pre-surgical-assessment-of.html




Tuesday, August 12, 2008

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)


http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html




Thursday, January 29, 2009

Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number 2-February 2009 Research


http://creutzfeldt-jakob-disease.blogspot.com/2009/01/medical-procedures-and-risk-for.html




SEE FULL TEXT ;


Friday, July 24, 2009

UW Hospital and Clinics Addresses Creutzfeldt-Jakob Disease Risk


http://creutzfeldt-jakob-disease.blogspot.com/2009/07/uw-hospital-and-clinics-addresses.html



http://creutzfeldt-jakob-disease.blogspot.com/2009/07/uw-hospital-warning-53-patients-about.html




Sunday, January 17, 2010

CJD Following up: Patients never contracted brain disorder UW Hospital patients


http://creutzfeldt-jakob-disease.blogspot.com/2010/01/cjd-following-up-patients-never.html




Friday, February 05, 2010


New Variant Creutzfelt Jakob Disease case reports United States 2010 A Review


http://vcjd.blogspot.com/2010/02/new-variant-creutzfelt-jakob-disease.html





CJD


http://creutzfeldt-jakob-disease.blogspot.com/





Sunday, February 14, 2010


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



http://bseusa.blogspot.com/2010/02/docket-no-fsis-2006-0011-fsis-harvard.html




Friday, January 29, 2010


14th International Congress on Infectious Diseases H-type and L-type Atypical BSE January 2010 (special pre-congress edition)


http://bse-atypical.blogspot.com/2010/01/14th-international-congress-on.html





TSS

CJD Following up: Patients never contracted brain disorder UW Hospital patients

Following up: Patients never contracted brain disorder Posted: Sunday, January 17, 2010 6:55 am

In July, 53 UW Hospital patients were notified that they faced a tiny risk of contracting a deadly brain disorder because they were operated on with potentially contaminated surgical instruments.

The patients were told to contact the hospital if they began experiencing any symptoms of Creutzfeldt-Jakob disease, including difficulty walking, vision problems and memory loss. As of mid-December, none had reported any of the warning signs, hospital spokeswoman Lisa Brunette said.

She’s not surprised. Brunette said the always-fatal disease can take up to 20 years to manifest, and the notified patients faced an “infinitesimal” chance of contracting it.

The hospital contacted the patients after a woman who had undergone brain surgery for a tumor was later discovered to have the disease after her condition continued to deteriorate. Before the diagnosis, the 53 patients were operated on using the instruments, which had been sterilized but hadn’t undergone the enhanced sterilization recommended by the Centers for Disease Control and Prevention for CJD-exposed instruments.

UW Hospital has offered free treatment if any of the patients contract the disease, although Brunette said chances of that happening are “very slim.”

— Dee J. Hall


http://host.madison.com/wsj/news/local/article_bae73894-9706-55b6-966d-e8e56a4f293a.html





> Brunette said the always-fatal disease can take up to 20 years to manifest,

> and the notified patients faced an “infinitesimal” chance of contracting it.



Greetings,


WHAT did anyone expect the spokesperson of the UW Hospital to say ?

ONE MUST REALIZE, all iatrogenic CJD is, is sporadic CJD, until a known route and source of the TSE agent is proven.

Considering the TSE prion agent can incubate up to 50+ YEARS, by the time one becomes clinical, and dies, the route and source is long forgotten.

It surely would have not been the complete truth, like, WE DONT KNOW, BUT, HERE ARE THE FACTS ;

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract


Sunday, January 17, 2010

Human tissue, recovered from a donor history indicated increased risk factors for Creutzfeldt-Jacob disease Lions Eye Bank

http://creutzfeldt-jakob-disease.blogspot.com/2010/01/human-tissue-recovered-from-donor.html


Saturday, January 16, 2010 Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al

http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html


Friday, November 20, 2009

SaBTO Advisory Committee on the Safety of Blood, Tissues and Organs Summary of the Eighth Meeting, 27 October 2009

http://vcjdtransfusion.blogspot.com/2009/11/sabto-advisory-committee-on-safety-of.html


Sunday, May 10, 2009

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)

http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html


Monday, August 17, 2009

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex J,K, AND D Published: 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/transmissible-spongiform-encephalopathy.html


Friday, July 17, 2009

Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units Volume 3 No 28; 17 July 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/revision-to-pre-surgical-assessment-of.html


Tuesday, August 12, 2008

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html


Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html


Tuesday, August 18,

2009 BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009

http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html


R.I.P. MOM hvCJD confirmed DECEMBER 14, 1997

Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html



Friday, January 15, 2010

New York Firm Recalls Beef Carcass That Contains Prohibited Materials (BSE)

http://bse-atypical.blogspot.com/2010/01/new-york-firm-recalls-beef-carcass-that.html



Saturday, January 2, 2010

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

http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html


my comments to PLosone here ;

http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd



TSS

Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al

Evidence For CJD/TSE Transmission Via Endoscopes

From Terry S. Singletary, Sr flounder@wt.net 1-24-3

I have researched human/animal TSEs now for over 5 years due to the death of my Mother from the Heidenhain Variant Creutzfeldt Jakob disease, one of six - known - variants of the infamous 'sporadic' CJD.

I did a little survey several years ago about CJD and ENDOSCOPY in 2001, and then went there again when another article was released recently. However, they seemed to only be concerned with the vCJD strain and risk from endoscopy equipment.

My concerns are if vCJD can be transmitted by blood, and there are now 6 variants of the infamous sporadic CJDs that they are documenting to date, how do they know that none of these 6 variants will not transmit the agent (prion) via blood?...especially since the sporadic CJDs are the only ones documented to date to transmit via the surgical arena and now that the CWD is spreading more and more, who knows about the cattle?

I would always read this study and it would bring me back to reality as to how serious/dangerous this agent is in the surgical/medical arena. You might want to read this short abstract from the late, great Dr. Gibbs twice, and let it really sink in. And please remember while reading some of these transmission studies, that most all, if not ALL these agents transmit freely to primates. Humans, of course, are primates.

Regarding claims that:

'Well, it has never been documented to transmit to humans."

There are two critical factors to think about:

A. CJD/TSEs in the USA are NOT reportable in most states and there is NO CJD/TSE questionnaire for most victims and their families, and the one they are now issuing asks absolutely nothing about route and source of the (prion) agent, only how the disease was diagnosed. Furthermore, the elderly are only very rarely autopsied, ie looking for Alzheimer's or 'FAST Alzheimer's' OR prion disease-related factors and phenomena, such as heart failure caused by disease.

B. It is unethical and against the law to do transmission studies of TSEs to humans, they are 100% FATAL.

I suggest you read these case studies about medical arena CJD transmission very carefully:

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract




Tissue Infectivity and TSEs (brain = high / rectum = medium)

[PDF]TSE infectivity distribution in ruminant tissues

... small intestine Distal small intestine Proximal colon Distal colon Rectum ... on the basis of the most recent scientific data, the sheep tissue infectivity ...

http://www.europa.eu.int/comm/food/fs/sc/ssc/out241_en.pdf




... entire bovine intestine from duodenum to rectum

... in any other extra neural tissue

... could promote the spread of infectivity

... Abnormal prion protein could also be


http://www.europa.eu.int/comm/food/fs/sc/ssc/out215_en.pdf





Transmission of prion diseases by blood transfusion

Nora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 David Parnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2

1 Journal of General Virology (2002), 83, 2897-2905. Printed in Great Britain Published ahead of print (16 July 2000) in JGV Direct as DOI 10.1099/vir.0.18580-0 Transmission of prion diseases by blood transfusion Nora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 David Parnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2 1 Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK 2 Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK Author for correspondence: Nora Hunter. Fax +44 131 668 3872. e-mail nora.hunter@bbsrc.ac.uk Received 16 May 2002; Accepted 9 July 2002 This article is now available in the November 2002 print issue of JGV (vol. 83, 2897-2905). The complete issue of the journal may be seen in electronic form on JGV Online (http://vir.sgmjournals.org). 0001-8580 © 2002 SGM

Abstract

Attempts to detect infectivity in the blood of humans and animals affected with transmissible spongiform encephalopathies (TSEs or prion diseases) have often been inconclusive because of the limitations of cross-species bioassays and the small volumes of blood that can be injected by the intracerebral route. A model has been developed for the experimental study of TSE transmission by blood transfusion using sheep experimentally infected with bovine spongiform encephalopathy (BSE) or natural scrapie as donors and susceptible scrapie-free sheep as recipients. Donors and recipients of the same species greatly increase the sensitivity of the bioassay and in sheep large volumes of blood can be injected by the intravenous (i.v.) route. Transmission of BSE to a single animal using this approach was reported recently. This study confirms this result with a second transmission of BSE and four new cases of transmission of natural scrapie. Positive transmissions occurred with blood taken2 at pre-clinical and clinical stages of infection. Initial studies indicate that following such infection by the i.v. route, deposition of the abnormal prion protein isoform, PrPSc, in peripheral tissues may be much more limited than is seen following oral infection. These results confirm the risks of TSE infection via blood products and suggest that the measures taken to restrict the use of blood in the UK have been fully justified.

Introduction

Creutzfeldt-Jakob disease (CJD) is one of a group of related diseases known as prion diseases or transmissible spongiform encephalopathies (TSEs), a group that also includes scrapie in sheep and bovine spongiform encephalopathy (BSE) in cattle. A new variant of CJD (vCJD) in human beings in the UK (Will et al., 1996) is thought to have been the result of infection with the same agent that causes BSE in cattle (Bruce et al., 1997). The numbers of vCJDinfected people remain unknown, although, to date, over 100 clinical cases have been recordedin the UK. Amongst many sources of concern, one major question relates to the safety of blood transfusions and blood products - especially when inadvertently sourced from individuals during the long pre-clinical phase of vCJD, a time at which these individuals may act as asymptomatic carriers of the infectious agent. There is no epidemiological evidence to indicate that iatrogenic CJD has ever occurred via blood or blood products but vCJD is a new disease with a different pathogenesis and may present different risks.

The TSE disease-associated form of the prion protein (PrPSc) of the neuronal glycoprotein PrPC is often used as a marker for infectivity. Using a sensitive Western blotting technique, no PrPSc was detected in the buffy coat from one vCJD patient (Wadsworth et al., 2001). Although a novel method for detection of PrPSc in scrapie sheep blood has been described (Schmerr et al., 1997), the study was limited by a low number of samples and the technique requires further validation. Other investigators using the more conventional method of immunocytochemistry failed to demonstrate PrPSc in peripheral blood leucocytes of scrapie-infected sheep (Herrmann et al., 2002).

An alternative to PrPSc detection is direct bioassay of infectivity by inoculation of material into hosts of the same or different species. In laboratory rodents experimentally infected with TSE, a number of investigators have demonstrated infectivity in blood and blood components during the pre-clinical and clinical phases of infection (Brown et al., 1998; Diringer, 1984; Manuelidis et al., 1978). However, infectivity has not been isolated, so far, from blood components of natural animal hosts of TSEs (Hadlow et al., 1982; Marsh et al., 1973). Isolated reports of transmission of CJD to laboratory rodents by whole blood or buffy coat from human3 patients have been questioned for a variety of reasons (Brown, 1995).

A large-scale study conducted by the National Institutes of Health failed to demonstrate infectivity in blood from 13 patients with CJD, using either highly susceptible primates or rodents as bioassay hosts (Brownet al., 1994). With vCJD, no infectivity was detected in blood from two patients using mouse bioassays (Bruce et al., 2001). Many of these studies could have failed to reveal low levels of infectivity in blood because of the use of rodents as bioassay hosts, thus limiting the sensitivity by crossing a species barrier. Also, in most cases, the intracerebral (i.c.) route of inoculation was used, because it is the most efficient, but this severely limits the volume of blood that can be assayed.

Thus, where transmission from blood has been successful, infectivity was usually concentrated in some way, for example, by the use of buffy coat fractions. Transmission by the intravenous (i.v.) route has been shown to be up to seven times less efficient than following i.c. infection (Brown et al., 1999), but there have been very few attempts to transmit TSEs by whole blood transfusion. Units of whole blood from three CJD cases were transfused into chimpanzees with negative results (Brown et al., 1994) and pooled blood from three terminally ill TSEinfected mice produced disease in 1 of 20 transfusion recipients (Brown et al., 1999). Sheep infected orally with BSE show widespread deposition of PrPSc in the lymphoreticular system (LRS) (Foster et al., 1996a, 2001b), similar to that seen in human vCJD patients.

In contrast, in cases of sporadic human CJD and cattle BSE, peripheral pathogenesis does not appear to involve the LRS (Hill et al., 1999; Wells et al., 1998). Sheep were chosen as a model in which to study transmission of TSEs by blood transfusion because of the similarity of the pathogenesis with vCJD and because large volumes of blood can be transferred in the absence of a species barrier. We have transfused whole blood and buffy coat from BSE-infected sheep and natural scrapie-infected sheep into susceptible but scrapie-free recipient animals. In the first report on these experiments (Houston et al., 2000), we described a single case of BSE infection via blood transfusion.

The significance of this finding in a single animal has been questioned. However, the present report gives details of further successful transmissions from BSE and natural scrapie cases, the latter being the first conclusive demonstration of infectivity in blood of naturally infected individuals. Although still incomplete, our study indicates a frequency of transmission of TSEs in at least 10 % of the transfusion recipients. We have decided to provide an update of our results because of the potential importance of the study for human health. In addition, in the two BSE transfusion cases examined so far, deposition of PrPSc in peripheral tissues appears rather limited when compared with sheep infected by the oral route. The potential implications of this observation for pre-clinical diagnosis and screening are discussed.

SNIP...

14 Discussion

With this report we have confirmed and extended our initial observation of a single case of BSE following transfusion of blood from a BSE-infected sheep and have provided the first conclusive evidence of significant levels of infectivity in blood in a naturally occurring TSE (scrapie). The experiment may take up to 5 years to complete; however, so far we have clear evidence of disease transmission by the blood transfusion route in 2 of 24 sheep (8 %) with BSE and 4 of 21 sheep (19 %) with scrapie, with two additional animals showing clinical signs in the BSE group. If the clinically suspect BSE-transfused sheep progress as expected, this would bring the transmission rate for BSE up to 17 %, comparable with the scrapie rate.

Positive transmissions have occurred not only with samples taken from sheep at the clinical phase of disease but also with those from apparently healthy donors as early as halfway through the incubation period (Fig. 1, lane 9; no PrPSc detection in the brain of donor J2746). Each TSE is transmitting to its appropriate susceptible genotype (AXQ/AXQ for BSE and VRQ/VRQ for scrapie) and Western blot/glycoform analyses support the conclusion that donors and recipients are infected with the same strains of BSE and scrapie. Our negative controls remain healthy, although still at relatively early stages post-transfusion and our positive controls are developing clinical signs at around, or greater than, 600 days post-challenge, showing incubation periods very similar to the transfusion cases. Whole blood transfusion (400-450 ml) cases are presenting incubation periods of around 600 days, which is very similar to those resulting from i.v. injection of 0.2 g BSE cattle brain homogenate. The transfusions might be expected to be more efficient because they are a sheepto-sheep transmission with no species barrier, which contrasts with the i.v. brain infections, which is a cattle-to-sheep transmission.

A full titration of the inoculum used in the cattle BSE brain i.v. controls is under way in mice but is incomplete at the time of writing. Accurate estimation of the levels of infectivity in blood will require i.v. titration in sheep; however, the results presented here suggest that they are significantly higher than suspected previously. Another important consideration is the distribution of infectivity among different blood components. Perhaps surprisingly, most positive transmissions so far have followed transfusion of whole blood rather than buffy coat, whereas previous studies have tended to find infectivity concentrated in the buffy coat fraction. As we now have a clinical case of scrapie resulting from transfusion of buffy coat, it is clear that, in our model, infectivity is also carried by the cells in this fraction. However, these preliminary results suggest that infectivity is not confined to the buffy coat fraction and that there may also be significant levels of infectivity in the plasma and/or red cell fractions. 15

The presence of infectivity in blood suggests that it should be possible to detect PrPSc or other surrogates of infectivity by alternative methods, with obvious benefits for development of ante-mortem diagnostic tests. Early reports of the use of capillary electrophoresis to detect PrPSc in the blood of scrapie-infected sheep showed some promise (Schmerr et al., 1997); however, a recent study could not detect PrPSc in peripheral blood leucocytes of scrapie-infected sheep using immunocytochemistry (Herrmann et al., 2002). PrPC is known to be expressed only on peripheral blood mononuclear cells in sheep, in contrast to humans where it is also found on platelets and, at low levels, on erythrocytes (Barclay et al., 2002; Herrmann et al., 2001; Holada et al., 1998). Since tissues that express PrPC do not always equate with areas that accumulate PrPSc and infectivity during disease, the distribution of infectivity in blood fractions of different species clearly merits more detailed analysis.

Immunocytochemical detection of PrPSc in peripheral tissues of two of the BSE transfusion cases has shown a greatly reduced involvement of lymphoid tissues, including tonsil, in the peripheral pathogenesis compared with NPU Cheviot sheep orally infected with BSE or natural scrapie (Foster et al., 2001a). A recent report has shown that a proportion of Romney sheep in the late pre-clinical stages of infection with BSE following oral dosing (22 months post-infection) have PrPSc deposits in the CNS in the absence of any detectable involvement of peripheral lymphoid tissues (Jeffrey et al., 2001). This study also noted the relatively late and variable onset of PrPSc accumulation in the lymphoid tissues of BSE-infected sheep.

A more detailed study of BSE and scrapie transfusion cases, and positive controls, will be undertaken to determine whether lack of involvement of the LRS is a consistent feature in animals infected by the i.v. route; the results will be published at a later date. If our preliminary observations are confirmed, there may be implications for human patients with the misfortune to have received blood products from vCJD cases, because a negative tonsil biopsy as a means of reassurance might very well be unreliable. On the other hand, it also may mean that if a human patient became infected with vCJD by the i.v. route, then the peripheral tissues and blood of this secondary case may not themselves be highly infectious. In conclusion, our results so far indicate that, with more than 10 % of transfusions resulting in disease in the recipients, blood transfusion represents an appreciable risk for transmission of TSEs in sheep and, by extension, of vCJD in human beings. The relatively short and consistent incubation periods seen in positive cases suggests that levels of infectivity in the blood may be higher than suspected previously, even in the pre-clinical stages of infection, and/or that transmission by the i.v. route is highly efficient. From these preliminary results, it would appear that measures taken to safeguard the blood supply in the UK are fully justified. 16

However, further work, in particular a thorough investigation of the distribution of infectivity in different blood fractions, is required before a reliable estimate of the risks associated with contaminated blood products can be made.

Acknowledgements The authors are indebted to the UK Department of Health, European Union and DEFRA for their financial contribution to this study.

see full text:

http://www.socgenmicrobiol.org.uk/JGVDirect/18580/18580ft.pdf



also, older data pertaining to CJD/TSEs/BLOOD...TSS

Sir, -- Professor Manuelidis and his colleagues (Oct 19, p896) report transmission to animals of Creutzfeldt-Jakob disease (CJD) from the buffy coat from two patients. We also transmitted the disease from whole blood samples of a patient (and of mice) infected with CJD.1 Brain, Cornea, and urine from this patient were also infectious, and the clinicopathological findings2 are summarised as follows.

A 70-year-old man was noted to have a slowing of speech and writing and some disorientation, all of which progressed rapidly. Decorticate rigidity, forced grasping, positive snout reflex, and myoclonus appeared within 2 months. Electroencephalogram revealed typical periodic synchronous discharge, and he died of pneumonia and upper gastrointestinal haemorrhage, about 3 months after onset of the symptoms. The Brain weighed 1290g and showed severe histological changes diagnostic of CJD, including spongiform change, loss of nerve cells, and diffuse proliferation of astrocytes. There were no inflammatory cells, microglia, neurofibrillary tangles, and amyloid plaques, although virus-like particles were detected by electron microscopy.

Results of innoculation in Mice

Inocula NO* Incubation period (days)+ Brain 7/10 (4) 789 (+ or - 112) Cornea 1/6 (0) 1037 Blood 2/13 (0) 1080 (+ or - 69) Urine 5/10 (1) 880 (+ or - 55) CSF 0/10

* Number of mice with CJD change/number examined histologically. Number with amyloid plaques shown in parentheses.

+ means + or - SD

Samples were taken aseptically at necropsy. 10% crude homogenates of brain and cornea in saline, whole blood (after crushing a clot), and untreated CSF and urine were innoculated intracerebrally into CF1 strain mice (20 ul per animal). Some mice showed emaciation, bradykinesia, rigidity of the body and tail, and sometimes tremor after long incubation periods. Tissues obtained after the animal died (or was killed) were studied histologically (table). Animals infected by various inocula showed common pathological changes, consisting of severe spongiform changes, glial proliferation, and a moderate loss of nerve cells. A few mice inoculated with brain tissue or urine had the same amyloid plaques found in patients and animals with CJD.3

In our long-term experiments, inoculating materials taken from twenty patients with CJD or Gerstmann-Straussler-Scheinker's disease (GSS) into rodents, positive results were obtained in seventeen cases, including this patient. Brain tissue transmitted the disease most frequently within the shortes incubation period, except for one case where the lymph node was the most infectious. Transmission through the cornea has been noted in man4 and in guineapigs.5 Whole blood samples taken from three patients were inoculated and a positive transmission occured only in the case recorded here. Mouse-to-mouse transmission through blood inoculation was successful after a mean incubation period of 365 days.1 Transmission through urine was positive in this patient only, and negative in one other patient and in many infected animals. Transmission through the CSF from eight patients was negative, yet transmission via the CSF of infected rats was positive.1

As viraemia has been proved in guineapigs,6 mice,1,7 and lately in patients with CJD, blood for transfusion or blood products for medical use must be tested for unconventional pathogens. For this purpose, we inoculated blood products inot rodents.8 The CJD pathogen was not found in the products examined. However, this approach takes too long to be of practical value. More efficient methods must be developed to detect pathogens and to eliminate them from blood. One proposal9 is to apply membrane filtration to the pruification protocol of human growth hormone suspected of being contaminated with CJD. Similar methods are needed for blood contamination.

Department of Neuropathology, Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka812, Japan

JUN TATEISHI

1. Tateishi J, Sato Y, Kaga M. Don H, Ohta M. Experimental transmission of (bum??cannot read) subacute spongiform encephalopathy to small rodents I: Clinical and histological observations. Acta Neuropathol (Berl) 1980; 51: 127.

2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakob disease with demonstration of virus-like particles. Acta pathol Jpn 1982;32: 695.

3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in the brains of mice with Creutzfeldt-Jakob disease. A?? Neurol 1984; 15: 278.

4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D. Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974; 290?: 692.

5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L. Experimental Creutzfeldt-Jakob disease transmitted via the eye with infected cornea. N Engl J Med 1977; 296: 1334.

6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimental Creutzfeldt-Jakob disease. Science 1978: 209?: 1069.

7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC. Creutzfeldt-Jakob disease in mice. Persistent viremiam and preferential replication of virus in low-density lymphocytes. Infect Immun 1983; 41: 154.

8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiform encephalopathis absent in blood products. J Med Virol 1985; 15: 11.

9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob disease pathogen in growth hormone preparations is eliminatable. Lancet (in press).


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


Something I submitted to GUT previously;

Subject: Re: gutjnl_el;21 Terry S. Singeltary Sr. (3 Jun 2002) "CJDs (all human TSEs) and Endoscopy Equipment"
Date: Thu, 20 Jun 2002 16:19:51 -0700
From: "Terry S. Singeltary Sr."
To: Professor Michael Farthing
CC: lcamp@BMJgroup.com
References: <001501c21099$5c8bc620$7c58d182@mfacdean1.cent.gla.ac.uk>

Greetings again Professor Farthing and BMJ,

I was curious why my small rebuttal of the article described below was not listed in this month's journal of GUT? I had thought it was going to be published, but I do not have full text access. Will it be published in the future? Regardless, I thought would pass on a more lengthy rebuttal of mine on this topic, vCJD vs sCJDs and endoscopy equipment. I don't expect it to be published, but thought you might find it interesting, i hope you don't mind and hope to hear back from someone on the questions I posed...

Here is my short submission I speak of, lengthy one to follow below that:

Date submitted: 3 Jun 2002

>> eLetter ID: gutjnl_el;21
>> >> Gut eLetter for Bramble and Ironside 50 (6): 888
>> >>Name: Terry S. Singeltary Sr. >>Email: flounder@wt.net
>>Title/position: disabled {neck injury}
>>Place of work: CJD WATCH
>>IP address: 216.119.162.85
>>Hostname: 216-119-162-85.ipset44.wt.net
>>Browser: Mozilla/5.0 (Windows; U; Win98; en-US; rv:0.9.4)
>>Gecko/20011019 Netscape6/6.2
>> >>Parent ID: 50/6/888
>>Citation:
>> Creutzfeldt-Jakob disease: implications for gastroenterology
>> M G Bramble and J W Ironside
>> Gut 2002; 50: 888-890 (Occasional viewpoint)
>> http://www.gutjnl.com/cgi/content/abstract/50/6/888
>> http://www.gutjnl.com/cgi/content/full/50/6/888
>>-----------------------------------------------------------------
>>"CJDs (all human TSEs) and Endoscopy Equipment"
>>----------------------------------------------------------------- >> >> >>
>>

regarding your article; >>
>>

Creutzfeldt-Jakob disease: implications for gastroenterology >>

>>

I belong to several support groups for victims and relatives
>>of CJDs. Several years ago, I did a survey regarding
>>endoscopy equipment and how many victims of CJDs have
>>had any type of this procedure done. To my surprise, many
>>victims had some kind of endoscopy work done on them.
>>As this may not be a smoking gun, I think it should
>>warrant a 'red flag' of sorts, especially since data now
>>suggests a substantial TSE infectivity in the gut wall
>>of species infected with TSEs. If such transmissions
>>occur, the ramifications of spreading TSEs from
>>endoscopy equipment to the general public would be
>>horrible, and could potential amplify the transmission
>>of TSEs through other surgical procedures in that
>>persons life, due to long incubation and sub-clinical
>>infection. Science to date, has well established
>>transmission of sporadic CJDs with medical/surgical
>>procedures.

Terry S. Singeltary Sr. >>CJD WATCH

Again, many thanks, Kindest regards,

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 flounder@wt.net CJD WATCH

[scroll down past article for my comments]

Subject: Creutzfeldt-Jakob disease: implications for gastroenterology & CJD 38 years after _diagnostic_ use of hGH (Iatrogenic CJDs & sporadic CJDs)
Date: Mon, 17 Jun 2002 16:46:46 -0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de

Bovine Spongiform Encephalopathy

OCCASIONAL VIEWPOINTS

Creutzfeldt-Jakob disease' implications for gastroenterology

M G Bramble, J W Ironside

Gut 2002;50:888-890

The current clinical views regarding variant Creutzfeldt-Jakob disease, and in particular transmission via endoscopy, of those representing both gastroenterology and the Spongiform Encephalopathy Advisory Committee are presented in an attempt to guide clinicians as to "best practice" given the current state of our knowledge.

See end of article for authors' affiliations

Correspondence to: Professor MG Bramble, Endoscopy Centre, James Cook University Hospital, Marton Rd, Middlesbrough TS4 3BN, UK;

Most gastroenterologists working in the UK have been aware for some time that endoscopy may be a vector for the transmission of prions from a patient incubating, but not clinically manifesting, variant Creutzfeldt-Jakob disease (vCJD) to the next individuals undergoing the same procedure on the same list. To date there are no recorded cases of iatrogenic transmission of vCJD via endoscopy but it remains a risk which will be present for many years to come. Advice to health authorities on individual cases is through the CJD Incidents Panel. However, we are aware that advice to health professionals performing endoscopy needs to be as comprehensive as current evidence will allow, without making it impossible to perform endoscopic procedures on patients who will clearly derive long term health benefits from an accurate endoscopic diagnosis and/or treatment. This article represents the current clinical views of those representing both gastroenterology and the Spongiform Encephalopathy Advisory Com-mittee (SEAC). Both authors sit on the CJD Inci-dents Panel and have been advising the Depart-ment of Health on individual cases during the last year. It is important to note that the advice given in this article may be superseded if additional information or evidence becomes available.

CJD is a member of a group of neurological disorders known as the transmissible spongilorm encephalopathies or prion diseases, which affect both animals (such as scrapie in sheep or bovine spongiform encephalopathy (BSE) in cows) and humans. The precise nature of the transmissible agents responsible for these disorders is unknown but there is increasing evidence to support the prion hypothesis, which states that the agent is composed of an abnormally folded form of a host encoded protein, prion protein. The normal prion protein (PrPc) is expressed in many tissues but occurs at the highest levels in neurones in the central nervous system (CNS) where it may act as a copper binding protein, although its precise physiological role is unknown. The abnormal form of the protein (PrPSc) accumulates in the CNS in prion diseases; the infectious agent is remarkably resistant to most forms of degradation. The association between PrPSc and the gut has been eloquently described in a previous lead-ing article1 and gastroenterologists need to understand where we are in terms of our present day knowledge of this entity.

In humans, prion diseases occur in three major categories: sporadic, acquired, and familial. All are currently untreatable and universally fatal although recent studies have indicated that a combination of drugs may be effective in experimental prion diseases2: this approach is under consideration as a clinical trial. The sporadic form of CJD affects approximately one person per mil-lion per annum in the population on a worldwide basis. CJD has also occurred as an acquired iatrogenic disorder, transmitted to other humans through direct (inadvertent) inoculation of the brain via contaminated neurosurgical instruments, via corneal and dura mater grafts, or through administration of human pituitary ex-tracts used to treat growth hormone or gonadotrophin deficiency. Variant CJD (vCJD) is a new acquired form of CJD which was first reported in 1996 affecting mainly young adults and with a unique neuropathological phenotype.3 It is now widely accepted that bovine prions passed into the human population through consumption of BSE infected bovine tissues; the transmissible agent responsible for vCJD is identical to the BSE agent (but different from the agent in sporadic CJD). The incubation period for vCJD is likely to be lengthy and may have a mean value of 10-30 years. During this time the affected person has the potential to transmit the disease to others via surgical procedures which might result in the transfer of infected tissue into the next person operated on with the same surgical instruments.

The distribution of PrPSc in the body is different in sporadic and variant CJD, reflecting the differ-ent pathogenesis of the two forms. In the case ot sporadic CJD, prion infectivity is largely limited to the CNS (including the retina) and only opera-tions involving the brain and eye have resulted in iatrogenic transmission of the disease. Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4

"Endoscopy on patients who are incubating vCJD may result in exposure of the instrument (and particularly the biopsy forceps) to PrPsc''

In contrast, in vCJD the lymphoreticular system throughout the body contains PrPSc at the time of death, and experimental evidence suggests that the lymphoreticular system may contain significant levels of infectivity for most of the incuba-tion period.5 To support this, in vCJD abnormal prion protein was found in the germinal centres in the wall of an appendix from a vCJD patient that was removed eight months before the onset of neurological disease.6 As lymphoid follicles and germinal centres are widely distributed in the gastrointestinal tract (and are often biopsied), it is possible that endoscopy on patients who are incubating vCJD may result in exposure of the instrument (and particularly the biopsy forceps) to PrPsc. Consequently, the question now arises, how great is the risk of secondary (person to person) transmission in endoscoping a patient incubating vCJD? There are three scenarios which gastroenterologists are likely to encounter and this editorial will attempt to guide clinicians as to "best practice" given the current state of our knowledge.

UPPER GASTROINTESTINAL ENDOSCOPY

Scenario No 1

Occasionally gastroenterologists may be requested to endo-scope a patient with known or probable sporadic CJD (usually to site a PEG feeding tube). This can be carried out in the rou-tine way provided vCJD is not suspected. If inadvertently a patient with suspected vCJD is endoscoped, the instrument used should be quarantined until the postmortem diagnosis is known. If sporadic CJD is diagnosed, the endoscope can be returned to use following thorough cleaning and decontami-nation, as is normal practice. If vCJD is diagnosed the endoscope cannot be used again and should be quarantined or sent to the National CJD Surveillance Unit in Edinburgh for research purposes. The previous advice to destroy such instru-ments represents a lost opportunity to study the risks involved in more detail. It would also be good practice to inform colleagues locally that a quarantined instrument was available for use in other endoscopy units if they too had a patient with suspected vCJD requiring endoscopy.

Scenario No 2

For patients with known or probable vCJD,7 endoscopy should only be a last resort. Ultrasound guided insertion of a gastrostomy feeding tube would be preferable to a PEG feeding tube if local expertise is available. If not, endoscopy should be per-formed using an instrument already set aside for such patients. If no such instrument is available locally, one can be loaned to any hospital by the National CJD Surveillance Unit in Edinburgh (contact telephone number 0131 537 1980). If scenario No 2 becomes more common, endoscopes may need to be held regionally for this purpose.

Scenario No 3

This scenario covers patients who have been endoscoped by an instrument previously used on a patient who was not known to be incubating vCJD at the time of endoscopy but who sub-sequently went on to develop the disease. This could become the commonest scenario and it must be assumed that the patient who went on to develop vCJD was incubating the dis-ease at the time of the original endoscopy. This also means that infectious material may not have been removed completely by current methods of decontaminating endoscopes, and that subsequent patients have been exposed to the prion agent. The instrument used should therefore be quaran-tined until advice has been sought from the CJD Incidents Panel (Department of Health, Skipton House, London; contact telephone 0207 972 1761) as to the management of the situa-tion. Local infection control teams will need to be involved with contact tracing and information handling.

LOWER GASTROINTESTINAL ENDOSCOPY

It is unlikely that colonoscopy would be clinically justifiable in a patient known or strongly suspected as suffering from vCJD. However, it is quite possible that an asymptomatic patient incubating vCJD may undergo colonoscopy prior to diagnosis and this situation is essentially the same as in scenario 3. The risks of transmitting prion protein to the next patient are much greater however, due to a number of factors which relate to the amount of lymphatic tissue encountered during endos-copy and the number, site, and size of mucosal biopsies obtained by this method.

In general the risks of transmitting vCJD from one patient to another are dependent on the infectivity of the tissues involved, the amount of tissue contaminating the instrument, the effectiveness of the decontamination processes, and the susceptibility of subsequently exposed patients. Experimental studies suggest that levels of infectivity in prion diseases are highest in the CNS and retina, which are approximately two logs higher than in the tonsils and other lymphoreticular tis-sue. A recent study has also detected the abnormal form of the prion protein in rectal tissue from a patient with vCJD by western blot examination of autopsy tissues.8 The risk of transmitting vCJD through the endoscopy procedure itself is likely to be small, but contamination of the endoscope and forceps as a result of biopsy of lymphoid tissues may represent a larger (but currently unquantifiable) risk, even though only small amounts of tissue are involved.

"The risks of transmitting vCJD from one patient to another are dependent on the infectivity of the tissues involved, the amount of tissue contaminating the instrument, the effectiveness of the decontamination processes, and the susceptibility of subsequently exposed patients"

The greatest risk is undoubtedly that which ensues from biopsy of the terminal ileum where Peyer's patches may con-tain significant levels of prion protein for a patient incubating vCJD. The biopsy forceps and the colonoscope become poten-tial vectors for disease transmission under these circum-stances. Meticulous manual cleaning of the colonoscope is probably the best defence against person to person transmis-sion. The same is true of the biopsy forceps, but as disposable forceps are now available there is a strong argument for mov-ing towards the universal use of disposable biopsy forceps for mucosal samples taken at colonoscopy. Endoscopy units should now work towards a policy of using disposable biopsy forceps as the only practical way of minimising the risk which results from ileal biopsy. In addition, "random" biopsies should be kept to a minimum as lymphoid tissue is distributed widely throughout the gastrointestinal tract. Although thor-ough cleaning of flexible endoscopes ensures patient safety for "normal" pathogens, the same process may not be adequate for the PrPsc. The main benefit of the decontamination process under these circumstances is undoubtedly effective manual cleaning, as glutaraldehyde may stabilise PrPSc on the metal surface of the endoscope, with potentially adverse conse-quences. It follows that brushes used to clean the channels of the endoscope are used only once to ensure maximum efficiency and biopsy forceps should also be functioning opti-mally and discarded as soon as they appear to be under performing (tearing tissue rather than cutting it). The rubber valve protecting the biopsy channel is another item which is potentially disposable and serious consideration should be given to single use valves. Again, more research is required to determine "best practice". For rigid endoscopes, autoclaving at the recommended conditions for CJD9 is the best way of attempting decontamination.

What should endoscopists do in the short term? The answer to this question must be to ensure as far as possible that manual cleaning of endoscopes and reuseable accessories is of the highest standard. Endoscopy has a major role in patient care, and this should not be compromised unless it is absolutely unavoidable in the public interest. It is also essen-tial that endoscopes should be individually identifiable and their use traceable in any given patient population. Random biopsies should be kept to an absolute minimum (particularly of the ileum in colonoscopy) and endoscopy itself should be as atraumatic as possible, especially gastroscopy where the instrument is in contact with the mucosa covering the tonsils. Biopsy forceps should be treated as "high risk" and undergo thorough ultrasonic cleaning followed by autoclaving. As research in the UK progresses, it is likely that other procedures will be developed to inactivate prion infectivity and to remove proteins from instrument surfaces. The development of such techniques (along with more sensitive tests for prion detection) may well have an impact on future advice concern-ing endoscopy and CJD.

Depending on the final numbers of people infected with vCJD, we must assume that a significant number may undergo endoscopy before neurological symptoms appear10. It is there-fore up to every endoscopist to be aware of the dangers and follow the advice set out here. Further advice on specific cases and possible exposure incidents can be obtained from the CJD Incidents Panel (Department of Health, Skipton House, London; contact telephone 0207 972 1761).

Authors' affiliations M G Bramble, Endoscopy Centre, James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, UK J W Ironside, CJD Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

mike.bramble@stees.nhs.uk

Accepted for publication 19 November 2001

REFERENCES

1 Shmakov AN, Ghosh S. Prion proteins and the gut: une liaison dangereuse? Gut 2001;48:443-7.

2 Korth C, May BCH, Cohen FE, et al. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc Nail Acad Sci USA 2001;98:9836-41.

3 Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347:921-5.

4 Report of a Working Party of the British Society of Gastroenterology Endoscopy Committee. Cleaning and disinfection of equipment for gastrointestinal endoscopy. Gut 1998;42:585-93.

5 Hill AF, Butterworth R J, Joiner S, et al. Investigation of variant Creutzfeldt-Jacob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999;353:183-9.

6 Hilton DA, Fathers E, Edwards P, et al. Prion immunoreactivity in the appendix before the clinical onset of new variant Creutzfeldt-Jacob disease. Lancet 1998;352:703-4.

7 Will RG, Zeidler M, Stewart GE, et al. Diagnosis of new variant Creutzfeldt-Jakob disease. Ann Neuro12000;47:575-82.

8 Wadsworth JD, Joiner S, Hill AF, et al. Tissue distribution of protease resistant prion protein in variant Creutxfleldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 2001 ;358:171-80.

9 Dangerous Pathogens Spongiform Encephalopathy Advisory Committee. Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. London: The Stationary Office, 1998.

10 Ironside JW, Hilton DA, Ghani A, et al. Retrospective study of prion protein accumulation in tonsil and appendix tissue. Lancet 2000;355:1693-94.

http://www.gutjnl.com/cgi/content/abstract/50/6/888

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

Greetings List Members,

This is _very_ disturbing to me:

snip...

The distribution of PrPSc in the body is different in sporadic and variant CJD, reflecting the different pathogenesis of the two forms. In the case ot sporadic CJD, prion infectivity is largely limited to the CNS (including the retina) and only operations involving the brain and eye have resulted in iatrogenic transmission of the disease. Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4

snip...

i personally believe it is irresponsible for anyone to state in this day and time, that sporadic CJDs (now at 6 variants) will not transmit the disease by this route. considering infective dose cannot be quantified, only speculated, such a statement is thus, irresponsible. to hypothosize that sporadic CJD just happens spontaneously (with no scientific proof), that the PrPSc distribution in tissues of all sporadic CJDs is entirely different than that of vCJD, without being able to quantify the titre of infection, or even confirm all the different variants yet, again is _not_ based on all scientific data, then it's only a hypothosis. who is to say that some of these variants of sporadic CJD were not obtained _orally_?

also stated:

snip...

Although thorough cleaning of flexible endoscopes ensures patient safety for ''normal'' pathogens, the same process may not be adequate for the PrPSc.

snip...

The sporadic form of CJD affects approximately one person per mil-lion per annum in the population on a worldwide basis.

who is to say how much infectivity are in some of these variants of sporadic CJDs, without confirming this? if we look at the 6 different variants of sporadic CJDs, has the infective dose for all 6 _documented_ variants been quantified, and documented as being 'measurable'?

will there be more variants of sporadic CJDs, and what of the ramifications from them?

what of other strains/variants of TSE in cattle, BSE in sheep, CWD in cattle, or any of the 20+ strains of Scrapies in deer/elk? i get dizzy thinking of the different scenerio's. what would the human TSEs from these species look like and how can anyone quantify any tissue infectivity from these potential TSE transmissions to humans, and the risk scenerio described here from this potential route? could not some of these sporadic CJDs have derived directly or indirectly from one of these species, and if so, pose a risk by the route described here?

something else to consider, in the recent finding of the incubation period of 38 years from a _small_ dose of human growth hormone;

snip...

We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogentic CJD. Furthermore, our patient was _not_ treated with hGH, but only received a _low_ dose as part of a diagnostic procedure. (see full text below).

snip...

so my quesion is, how low is 'low' in quantifing the infectious dose in vCJD, comparing to _all_ sporadic CJDs, from the different potential routes, sources, and infectivity dose?

will the titre of infectivity in every tissue and organ of all sporadic CJDs stay exact or constant, no matter what the infective dose, route and species may be? this is considering you don't buy the fact that sporadic CJDs 85%+ of _all_ CJDs, are a happen stance of bad luck, happen spontaneously without cause, and are one-in-a-million world wide, with no substantial surveillance to confirm this.

Diagnosis and Reporting of Creutzfeldt-Jakob Disease T. S. Singeltary, Sr; D. E. Kraemer; R. V. Gibbons, R. C. Holman, E. D. Belay, L. B. Schonberger

http://jama.ama-assn.org/issues/v285n6/ffull/jlt0214-2.html

and what of Dr. Prusiner et al recent work about tissue infectivity;

Prions in skeletal muscle

snip...

Our data demonstrate that factors in addition to the amount of PrP expressed determine the tropism of prions for certain tissues. That some muscles are intrinsically capable of accumulating substantial titers of prions is of particular concern. Because significant dietary exposure to prions might occur through the consumption of meat, even if it is largely free of neural and lymphatic tissue, a comprehensive effort to map the distribution of prions in the muscle of infected livestock is needed. Furthermore, muscle may provide a readily biopsied tissue from which to diagnose prion disease in asymptomatic animals and even humans.

snip...

http://www.pnas.org/cgi/content/abstract/99/6/3812?maxtoshow=&HITS=10&hits= 10&RESULTFORMAT=&author1=prusiner&author2=prusiner&titleabstract=prions+meat+ tissue+mice&fulltext=prions+meat+tissue+mice&searchid=1024346978866_6016&stored_ search=&FIRSTINDEX=0&fdate=1/1/2002

can the science/diagnostic measures used to date, measure this, and at the same time guarantee that no titre of infectivity exists from sporadic CJDs (all of the variants), from this potential mode and route of transmission?

i don't think so, this is just my opinion. this is why i get paid nothing, and these scientists get the big bucks. i just hope i am wrong and the big bucks are correct in their _hypothisis_ of this potential mode/route of transmission with endoscopy equipment, from _all_ human TSEs.

i understand we have to weigh the risks of what we know to what we don't know, to the disease we _may_ catch to what we are having the procedure for, but to categorically state at this present time of scientific knowledge;

snip...

"Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4"

snip...

but, to categorically state this, in my opinion, is not only wrong, but potentially very dangerous to the future of human health...TSS

SHORT REPORT

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

E A Croes, G Roks, G H Jansen, P C G Nijssen, C M van Duijn ...............................................................

J Neurol Neurosurg Psychiatry 2002;72:792-793

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

Prion diseases are potentially transmissible. Human to human transmission was first reported in 1974, when a 55 year old woman was described who developed symptoms of Creutzfeldt-Jakob disease (CJD) 18 months after a corneal transplant.1 Since then, transmission has been reported after stereotactic electroencephalographic (EEG) depth recording, human growth hormone (hGH) and gonadotrophin treatment, and dura mater transplantation.2-5 More than 267 patients with iatrogenic CJD are known today and their number is growing.6 The most important iatrogenic cause of CJD is still contaminated cadaveric hGH. Exposure to contaminated hGH occurred before 1985, when recombinant growth hormone became available. In a recent study, incubation periods in 139 patients with hGH associated CJD were found to range from 5-30 years, with a median of 12 years.6 One of the factors influencing incubation time is genotype on polymorphic codon 129 of the prion protein gene.7 The incubation time is significantly shorter in people who are homozygous for either methionine or valine on this polymorphism.7

We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogenic CJD. Further-more, our patient was not treated with hGH but only received a low dose as part of a diagnostic procedure.

CASE REPORT

This patient presented at the age of 47 years with paraesthesia in both arms for six months, difficulty with walking for four weeks, and involuntary movements of mainly the upper extremities of two weeks' duration. He did not notice any change in cognitive function, although his twin sister had noticed minor memory disturbances. There was no family history of neurological disease. During childhood the patient had experienced a growth delay compared with his twin sister and with the average in the Netherlands. When he was 9 years old, a nitrogen retention test with 6 IU hGH over five days was performed to exclude growth hormone deficiency. Since the result was not decisive, a quantitative amino acid test was performed, which measures 30 amino acids during fasting and one, two, and three hours after growth hormone injection. No abnormal amino acid concentrations were found making the diagnosis of primordial dwarfism most likely. Therefore, no treatment with hGH was given.

On neurological examination we found a slight dysarthria without aphasia. Cranial nerve function was normal. Walking was unstable and wide based. During movements of the upper extremities myoclonic jerks were present. Sensation, muscle tone, and strength were normal. Co-ordination was impaired in all four limbs with a disturbed balance. Tendon reflexes were brisk at the arms and increased at the legs with a clonus in the ankle reflex. Plantar responses were both normal. On the mini mental state examination, the patient scored 30/30. Routine laboratory investigation, thyroid function, vitamin concentrations (B-1, B-6, B-12, and E), and copper metabolism were normal. Admission EEG examination showed generalised arrhythmic slow activity with diffuse spikes and spike waves. EEG examination two months later showed a further slowing of the rhythm with bilateral diphasic sharp waves but was not typical for CJD. Cerebral magnetic resonance imaging was normal. Cerebrospinal fluid examination showed 1 cell/3 µl, normal glucose and protein concentrations, and a strongly positive 14-3-3 protein test. The patient was homozygous for methionine on the PRNP codon 129 polymorphism. On clinical grounds, CJD was diagnosed. Within one month the patient's condition deteriorated rapidly and because of severe disturbances in coordination and progressive myoclonus he became bedridden. An eye movement disorder developed with slow saccadic and dysmetric eye movements. Temperature became unstable with peaks of 39°C without an infectious focus, for which a disorder of autoregulation was presumed. Until a very advanced stage, cognitive function was intact. The patient died five months after admission. The diagnosis of CJD was confirmed at necropsy. The brain weighed 990 g and showed clear cortical and cerebellar atrophy. Spongiosis, neuronal loss, and gliosis were found predominantly in the putamen, caudate nucleus, and basotemporal and cerebellar cortex; the cerebellum was the most severely affected of these. Vacuoles ranged from 2-12 µm. No amyloid or Kuru plaques were found. Immunohistochemical staining (3F4 antibody 1:1000, Senetek, USA) was clearly positive for prion protein accumulation in a "synaptic" distribution. Most deposition was found in the stratum moleculare of the cerebellum.

DISCUSSION

We describe a 47 year old patient who developed pathology proven CJD 38 years after hGH injections. The patient was never treated with hGH but received a small dose as part of a diagnostic procedure. The onset of CJD was signalled by prodromal symptoms of paraesthesia followed by a rapidly progressive ataxia. The disease presentation and course with predominantly cerebellar and eye movement disorders are compatible with iatrogenic CJD caused by hGH treatment.6 8

Growth hormone treatment was first described in 1958 but hGH was not produced on a larger scale from human pituitary glands until the beginning of the 1960s. In the Netherlands growth hormone extraction started in 1963 and was soon centrally coordinated. Until 1979 growth hormone was extracted non-commercially from pituitaries by a pharmaceutical company. In 1971 commercial products also became available. Our patient was one of the first to receive hGH in the Netherlands but the origin of this product was not recorded. A causal relation can therefore not be established with full certainty, but coincidentally receiving growth hormone and developing this very rare disease is unlikely. Since the clinical course in this relatively young patient is in accordance with an iatrogenic cause, we think the probability is high that the hGH injections explain the development of CJD in this patient.

The first Dutch patient with hGH related CJD died in 1990. 9 During several periods from 1963 to 1969 she received intramuscular injections of hGH. During an unknown period the hGH was derived from South America. At age 39, 27 years after starting the treatment, she developed an ataxic gait, slurred speech, sensory disorders, and myoclonus, but her cognitive function remained normal. Postmortem examination of the brain confirmed the diagnosis of CJD.9 Following the identification of this patient, a retrospective study was started to trace all 564 registered hGH recipients who were treated before May 1985. Until January 1995, none of these was suspected of having CJD.10 Since 1993 prospective surveillance for all forms of human prion disease has been carried out in the Netherlands and, apart from the patient described above, a further two patients with iatrogenic CJD have been identified, who developed the disease after dura mater transplantation.11

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

ACKNOWLEDGEMENTS

We are grateful to M Jansen PhD MD for his search for the origin of the growth hormone and P P Taminiau MD. CJD surveillance in the Netherlands is carried out as part of the EU Concerted Action on the Epidemiology of CJD and the the EU Concerted Action on Neuropathology of CJD, both funded through the BIOMED II programme, and is supported by the Dutch Ministry of Health. This surveillance would not have been possible without the cooperation of all Dutch neurologists and geriatricians. ........................................

Authors' affiliations

E A Croes, G Roks*, C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands

P C G Nijssen, Department of Neurology, St Elisabeth Hospital, PO Box 90151, 5000 LC Tilburg, Netherlands

G H Jansen, Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands

*Also the Department of Neurology, St Elisabeth Hospital

Correspondence to: Professor C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands; vanduijn@epib.fgg.eur.nl

Received 27 December 2001 In revised form 1 March 2002 Accepted 12 March 2002

Competing interests: none declared

REFERENCES

1 Duffy P, Wolf J, Collins G, et al. Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974;290:692-3.

2 Bernoulli C, Siegfried J, Baumgartner G, et al. Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1977;i:478-9.

3 Koch TK, Berg BO, De Armond SJ, et al. Creutzfeldt-Jakob disease in a young adult with idiopathic hypopituitarism: possible relation to the administration of cadaveric human growth hormone. N Engl J Med 1985;313:731-3.

4 Cochius JI, Burns RJ, Blumbergs PC, et al. Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin. Aust NZ J Med 1990;20:592-3.

5 Thadani V, Penar PL, Partington J, et al. Creutzfeldt-Jakob disease probably acquired from a cadaveric dura mater graft: case report. J Neurosurg 1988;69:766-9.

6 Brown P, Preece M, Brandel JP, et al. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000;55:1075-81.

7 Huillard d'Aignaux J, Costagliola D, Maccario J, et al. Incubation period of Creutzfeldt-Jakob disease in human growth hormone recipients in France. Neurology 1999;53:1197-201.

8 Billette de Villemeur T, Deslys JP, Pradel A, et al. Creutzfeldt-Jakob disease from contaminated growth hormone extracts in France. Neurology 1996;47:690-5.

9 Roos RA, Wintzen AR, Will RG, et al. Een patiënt met de ziekte van Creutzfeldt-Jakob na behandeling met humaan groeihormoon. Ned Tijdschr Geneeskd 1996;140:1190-3.

10 Wientjens DP, Rikken B, Wit JM, et al. A nationwide cohort study on Creutzfeldt-Jakob disease among human growth hormone recipients. Neuroepidemiology 2000;19:201-5.

11 Croes EA, Jansen GH, Lemstra AF, et al. The first two patients with dura mater associated Creutzfeldt-Jakob disease in the Netherlands. J Neurol 2001;248:877-81.

re-CJD after diagnostic use of human growth hormone

from a donor sourcing aspect, seems the record keeping here has a lot to be desired for, let us hope it has improved for recipients sake.

also, they speak of 'low dose fitting long incubation'. what about KURU still existing after some 40 years exposure had ceased. i don't believe in most instances the dose with kuru is low. just something else to ponder?

TSS

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12023427&dopt=Abstract

1: Ann Neurol 1999 Aug;46(2):224-33

Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.

Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.

snip...

The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.

snip...

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10443888&dopt=Abstract

were not all CJDs, even nvCJD, just sporadic, until proven otherwise?

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

http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html

Professor Michael Farthing wrote:

Louise Send this to Bramble (author) for a comment before we post. Michael

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

Subj: Reprocessing of Flexible Endoscopes and Endoscopic Accessories - an International Comparison of Guidelines Date: 9/17/02 3:28:43 AM Eastern Daylight Time
From: flounder@WT.NET (Terry S. Singeltary Sr.)
Sender: BSE-L@UNI-KARLSRUHE.DE (Bovine Spongiform Encephalopathy)
Reply-to: BSE-L@UNI-KARLSRUHE.DE (Bovine Spongiform Encephalopathy)
To: BSE-L@UNI-KARLSRUHE.DE

Bovine Spongiform Encephalopathy

Reprocessing of Flexible Endoscopes and Endoscopic Accessories - an International Comparison of Guidelines

Zeitschrift für Gastroenterologie

© Georg Thieme Verlag Stuttgart New York More about this journal

Endoscopic examinations and procedures are essential for diagnosis and treatment of gastrointestinal diseases. As a result of poor reprocessing practice microorganisms can be transmitted via endoscope. The majority of infection transmissions is due to insufficient performance of cleaning and disinfection disregarding guidelines of societies of gastrointestinal endoscopy.

A review of the literature and a comparison of European and American guidelines for reprocessing flexible endoscopes are given. Differences in the classification of endoscopic devices, on the possibility of prion transmission, recommendations on staff training and protection, quality assurance of reprocessing and evidence-based graduation of guidelines are stressed and discussed. With respect to the procedure of endoscope reprocessing, differences concerning the cleaning solution to choose, necessity of thoroughly manual cleaning and brushing of the accessible endoscope channels (even in the case of subsequent automatic reprocessing endoscopes in washers-disinfectors), disinfection solution, microbiological quality of water for final rinsing and rationale for alcohol flush of endoscope channels for better drying are mentioned.

The need for experimental investigations of the cleaning and disinfection process is stressed. In contrast to recent guidelines of European and American societies of gastrointestinal endoscopy, the now updated recommendations of the Robert Koch-Institute for reprocessing flexible endoscopes and endoscopic accessories are evidence-based and graduated.

Original Article Z Gastroenterol 2002; 40: 531-542 DOI: 10.1055/s-2002-32807 Table of Contents Leitlinien zur Aufbereitung flexibler Endoskope und endoskopischen Zusatzinstrumentariums im internationalen Vergleich Reprocessing of Flexible Endoscopes and Endoscopic Accessories - an International Comparison of Guidelines O. Leiß1, U. Beilenhoff2, L. Bader3, M. Jung2, M. Exner4 1Fachbereich Gastroenterologie, Deutsche Klinik für Diagnostik, Wiesbaden 2St. Hildegardis-Krankenhaus, Mainz 3Max von Pettenkofer-Institut der LMU München, München 4Hygiene-Institut der Universität Bonn, Bonn

Zusammenfassung

Endoskopische Untersuchungen und Eingriffe sind für Diagnostik und Therapie gastrointestinaler Erkrankungen unverzichtbar. Durch mangelhaft aufbereitete Endoskope können Mikroorganismen übertragen werden. Die Mehrzahl der Infektionsübertragungen bei Endoskopie ist auf unzureichende Reinigungs- und Desinfektionsmaßnahmen unter Missachtung aktueller Aufbereitungsrichtlinien der Fachgesellschaften zurückzuführen.

In einer Literaturübersicht werden die Leitlinien europäischer und amerikanischer Fachgesellschaften zur Aufbereitung flexibler Endoskope verglichen. Es werden Unterschiede in der Klassifikation des endoskopischen Instrumentariums, in der Bewertung der Prionenproblematik, in den Anforderungen an Personalschulung und Personalschutz, in der Betonung qualitätssichernder Maßnahmen und in der wissenschaftlichen Untermauerung und Graduierung der ausgesprochenen Empfehlungen dargestellt und diskutiert. Zu Einzelschritten der Aufbereitung werden Unterschiede hinsichtlich der einzusetzenden Reinigungslösung, der Notwendigkeit einer manuellen Bürstenreinigung der Endoskopkanäle (auch bei nachfolgender maschineller Aufbereitung), der Wahl des Desinfektionsmittels, der mikrobiologischen Qualität des zur Schlussspülung verwendeten Wassers und der Empfehlung einer Spülung der Endoskopkanäle mit Alkohol für eine verbesserte Trocknung herausgestellt und kritisch bewertet.

Es wird offensichtlich, dass experimentelle Untersuchungen zu Einzelaspekten der Endoskop-Aufbereitung weitgehend fehlen bzw. erst in jüngster Zeit bearbeitet wurden. Im Gegensatz zu bisherigen Leitlinien europäischer und amerikanischer Fachgesellschaften zur Endoskop-Aufbereitung sind die aktualisierten Empfehlungen des Robert Koch-Instituts zur Aufbereitung flexibler Endoskope und endoskopischen Zusatzinstrumentariums mit der verfügbaren Evidenz verknüpft und graduiert. Schlüsselwörter

Flexible Endoskope - Aufbereitung - Reinigung - Desinfektion - Personalschulung - Qualitätssicherung - Mikrobiologische Prüfungen - Hygiene Abstract

http://www.thieme-connect.com/DOI/DOI?10.1055/s-2002-32807

TSS

http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html

2009


Pre-surgical risk assessment for variant Creutzfeldt-Jakob disease (vCJD) risk in neurosurgery and eye surgery unitsHospitals should already be using a questionnaire in Annex J of the ACDP TSE Working Group Infection Control guidance to find out whether any patients who are about to undergo any surgery or endoscopy may be at increased risk of being infected with CJD. If a patient is found to have an increased risk of CJD prior to their surgery or endoscopy then special infection control precautions may need to be taken. The Department of Health has carried out an analysis [1] which explores the effect of receiving a large number of blood transfusions on a patient's risk of vCJD infection. The CJD Incidents Panel reviewed this analysis and advises that patients who have received blood components from 80 or more donors may have an increased risk of variant CJD (vCJD).

Annex J of the TSE Infection Control guidance has recently been revised, and now advises that patients who are due to have high risk surgery [2 ] or neuro-endoscopy should be asked an additional question: whether they have received transfusions of blood or blood components from 80 or more donors since 1980.

On 16 July 2009 the HPA wrote to the chief executives of NHS trusts asking them to ensure that the guidance is implemented. Detailed information and tools for implementing the guidance can be downloaded from the links below.

If you have any queries about the implementation of the guidance, please contact the HPA Centre for Infections CJD Section at cjd@hpa.org.uk or on 020 8327 6074/6411.

Background information on this new pre-surgical assessment is contained in this Letter to chief executives - July 2009 (PDF, 73 KB) written to all hospitals in England.

The new version of Annex J of the TSE Infection Control Guidance contains a new question for patients undergoing high risk surgery and neuro-endoscopy. The questionnaire in Annex J should be used to assess patients' CJD risk factors.

Clinicians carrying out the new pre-surgical assessment should read Information for healthcare staff - November 2009 (PDF, 164 KB) This vCJD Algorithm for per-surgical roles - July 2009 (PDF, 28 KB) shows suggested roles and responsibilities for infection control teams, surgical teams and blood transfusion specialists.

Information on patients' transfusion histories should be collected using the Highly transfused vCJD risk assessment form - July 2009 (Word Document, 328 KB) This form is also available as a Highly transfused vCJD risk assessment form and tool - July 2009 (Excel Spreadsheet, 2.7 MB). This may help calculate the number of blood donors to a patient. The form may be posted or emailed to the HPA Centre for Infections CJD Section cjd@hpa.org.uk.

Blood transfusion laboratories may wish to use this draft Letter to other blood laboratories - July 2009 (Word Document, 31 KB) when collecting transfusion information from other hospitals.

Pre-surgical assessment teams and patients may wish to read vCJD Information for presurgical patients - July 2009 (PDF, 29 KB) about this new pre-surgical assessment.

[1] The risk of secondary vCJD infection of patients receiving a high number of blood transfusions. Department of Health, July 2009.

[2] High risk surgery is defined as surgery involving any of the following organs or tissues (high risk tissues): brain, spinal cord, cranial nerves (specifically the entire optic nerve and only the intercranial components of the other cranial nerves), cranial nerve ganglia, posterior eye (specifically the posterior hyaloid face, retina, retinal pigment epithelium, choroid, subretinal fluid, optic nerve) and pituitary gland.

•Letter to chief executives - July 2009 (PDF, 73 KB) Added/updated: 16 July 2009

•Pre-surgical assessment Information for healthcare staff - November 2009 (Word Document, 252 KB) Added/updated: 27 November 2009

•vCJD Algorithm for per-surgical roles - July 2009 (PDF, 28 KB) Added/updated: 16 July 2009

•Highly transfused vCJD risk assessment form - July 2009 (Word Document, 328 KB) Added/updated: 16 July 2009

•Letter to other blood laboratories - July 2009 (Word Document, 31 KB) Added/updated: 16 July 2009

•vCJD Information for presurgical patients - July 2009 (PDF, 29 KB) Added/updated: 16 July 2009

•Highly transfused vCJD risk assessment form and tool - July 2009 (Excel Spreadsheet, 2.7 MB) Added/updated: 8 December 2009


http://www.hpa.org.uk/webw/HPAweb&Page&HPAwebAutoListName/Page/1247469069188

Pre-surgical assessment for vCJD risk in neurosurgery and eye surgery units. Information for clinicians

1. Introduction. 2

Box 1 High risk tissues for patients with vCJD and at risk of vCJD. 2

2. Preparation and planning. 2

Box 2. Who may be involved in assessing patients’ vCJD risks 2

3. Proposed roles and responsibilities. 3

a. Pre-surgical assessment staff 3

Box 3: Questions for patients undergoing procedures involving high risk tissues 3

b. Lead consultant for blood transfusion/consultant for the hospital blood bank. 4

c. Infection Control Doctor 5

Box 4 Infection control actions for patients with an increased risk of vCJD. 6

d. Lead consultant for vCJD risk assessment 6

e. The CJD Section at the HPA Centre for Infections 7

f. General Practitioners (or other clinician) - Informing patients 8

Box 5 Public health advice for patients 9

g. General Practitioners – action. 9

h. Health Protection Units 10

Box 6 Tissue infectivity levels for patients with, or at increased risk of, vCJD. 10

4. Evaluation. 10

5. Frequently Asked Questions. 11

a.. Which patients should be asked for their transfusion history to assess their vCJD risk? 11

b. Why not assess all patients attending for any operation? 11

c.. Should patients attending for anterior eye surgery be asked for their blood transfusion history to assess their vCJD risk? 11

d.. What should happen if a patient who has, or might have, received blood from 80 or more donors needs surgery on medium risk tissues (e.g. cataract procedure or tonsillectomy)? 11

e. What happens if a patient identified as highly transfused when assessed prior to surgery on high risk tissues or neuro-endoscopy, has an operation involving medium risk tissues at a later date? 12

f.. Should doctors try to identify prospectively all their patients who may have received blood from 80 or more donors? 12

g.. What if patients ask their doctors whether they are at increased risk because of their blood transfusion history? 12

h. How should patients who have received large numbers of transfusions, but fewer than 80, be managed? 12

i... What information should be given to patients who may receive 80 or more transfusions as part of their treatment? 13

j. Might the 80 donor exposure cut off level for highly transfused patients change? 13

k. What is the CJD Incidents Panel? 13

l... What does the CJD Incidents Panel recommend? 13

1. Introduction

This information leaflet accompanies Annex J of the ACDP TSE Working Group infection control guidance[1]. This leaflet,and related documents are available on the HPA website[2].

Annex J describes how to assess pre-surgical patients for their risk of variant Creutzfeldt-Jakob disease (vCJD) and other transmissible spongiform encephalopathies (TSE). It includes new guidance on assessing patients undergoing surgery or neuro-endoscopy on high risk tissues. This includes identifying patients who have received blood from 80 or more donors, and may have an increased risk of vCJD. This leaflet aims to give practical information on how to assess these patients, and how to manage those who have an increased vCJD risk because of their transfusion history, or have an incomplete or uncertain transfusion history.

Box 1 High risk tissues for patients with vCJD and at risk of vCJD

brain

spinal cord

dura mater

cranial nerve ganglia

cranial nerves,

specifically: the entire optic nerve

only the intracranial components of other cranial nerves

posterior eye,

specifically:

posterior hyaloid face

retina

retinal pigment epithelium

choroid

subretinal fluid

optic nerve

pituitary gland

2. Preparation and planning

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

[1] http://www.dh.gov.uk/ab/ACDP/TSEguidance/index.htm

[2] http://www.hpa.org.uk/vCJDpresurgicalassessment

SEE FULL TEXT ;

http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469061870

Latest news 16 November 2009: Annex C: General principles of decontamination and waste disposal

Download

General principles of decontamination and waste disposal: ACDP TSE Working Group Annex C (PDF, 201K)

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_108602.pdf

12 October 2009:

Alert to urological surgeons – transrectal prostatic biopsy in men at risk of variant CJD Download alert to urological surgeons regarding the equipment used for patients at risk of vCJD requiring transrectal prostatic biopsy (PDF, 28K)

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_106909.pdf

Annex D - Transport of TSE-infected material Published: December 2003, updated: 23 January 2009

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_087484.pdf

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex J

ANNEX J

Assessment to be carried out before surgery and/or endoscopy to identify patients with, or at increased risk of, CJD or vCJD

Summary of advice (revised July 2009)

Annex J provides a clear and pragmatic way of assessing CJD and vCJD risk prior to surgery or endoscopy. Growing numbers of patients have been informed that they are at increased risk of CJD or vCJD. Therefore it is recommended that all patients about to undergo any surgery or endoscopy should be asked if they have ever been notified as at increased risk of CJD or vCJD. This recommendation is outlined in paragraphs J1 and J2. In addition, patients undergoing surgery or neuro-endoscopy which may involve contact with tissues of potentially high level TSE infectivity (“high risk tissues”) should, through a set of detailed questions, be assessed for their possible CJD/vCJD risk exposure. These questions are outlined in Table J1 and paragraphs J3 to J6.

Annex J has been revised (July 2009) to include a new question to be asked of all patients about to undergo surgery or neuro-endoscopy on high risk tissues. This new question (question 4 in Table J1) has been added to identify those patients who have received blood or blood components from 80 or more blood donors. These patients are now designated as at increased risk of vCJD by the CJD Incidents Panel. Table J1 and paragraph J6 provide guidance on how to identify those patients who have received multiple blood transfusions. An algorithm, included as Appendix A, guides health professionals through the process.

Recommendation for all surgical and endoscopy patients

J1. The CJD Incidents Panel has identified a number of individuals or groups who are at increased risk of CJD or vCJD (see paragraphs J14 – J18). At a local level arrangements should be put in place to ensure that patients who have been notified they are at increased risk of CJD/vCJD are identified before surgery or endoscopy, to allow appropriate infection control procedures to be followed.

All patients about to undergo any elective or emergency surgical or endoscopic procedure should be asked the question: “Have you ever been notified that you are at increased risk of CJD or vCJD for public health purposes?”

J2. The actions to take following the patient’s response to the above question are:

SEE FULL TEXT ;

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_102856.pdf

Update: Creutzfeldt-Jakob Disease Associated with Cadaveric Dura Mater Grafts --- Japan, 1979--2003 MMWR Weekly December 5, 2003 / 52(48);1179-1181

http://www2.niddk.nih.gov/AboutNIDDK/CommitteesAndWorkingGroups/HGH_CJD_Dec_11_2003_TAB_A.htm

Thursday, October 23, 2008

Creutzfeldt-Jakob Disease Associated with Cadaveric Dura Mater Grafts - Japan, 1979-2008 : UPDATE

http://creutzfeldt-jakob-disease.blogspot.com/2008/10/creutzfeldt-jakob-disease-associated.html

http://www.wellsphere.com/cjd-article/medical-procedures-and-risk-for-sporadic-creutzfeldt-jakob-disease-japan-1999-2008-warning-to-neurosurgeons-and-ophthalmologi/641229

Thursday, January 29, 2009

Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number 2-February 2009 Research

http://creutzfeldt-jakob-disease.blogspot.com/2009/01/medical-procedures-and-risk-for.html

Sunday, May 10, 2009

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)

http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html

Monday, August 17, 2009

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex J,K, AND D Published: 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/transmissible-spongiform-encephalopathy.html

Friday, July 17, 2009

Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units Volume 3 No 28; 17 July 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/revision-to-pre-surgical-assessment-of.html

Tuesday, August 12, 2008

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html

Thursday, July 23, 2009

UW Hospital warning 53 patients about possible exposure to rare brain disease

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/uw-hospital-warning-53-patients-about.html

Tuesday, April 21, 2009

Doctor Antonio Ruiz Villaespesa, pathologist and CJD researcher deceased because of Creutzfeldt-Jakob Disease SPAIN

http://cjdusa.blogspot.com/2009/04/doctor-antonio-ruiz-villaespesa.html

Br J Ophthalmol 2005;89:1131-1138 doi:10.1136/bjo.2004.063495 Clinical science Scientific reports Abnormal prion protein in the retina of the most commonly occurring subtype of sporadic Creutzfeldt-Jakob disease M W Head1, A H Peden1, H M Yull1, D L Ritchie1, R E Bonshek2, A B Tullo2 and J W Ironside1 + Author Affiliations

1National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK 2Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester M13 9WH, UK Correspondence to: Dr M W Head National CJD Surveillance Unit, Bryan Matthews Building, Western General Hospital, Edinburgh EH4 2XU, UK; m.w.head@ed.ac.uk Accepted 7 March 2005 Abstract Background: Involvement of the eye has been reported in patients with variant Creutzfeldt-Jakob disease (vCJD), but there is disagreement on whether retinal involvement occurs in sporadic Creutzfeldt-Jakob disease (sCJD).

Methods: Western blotting, paraffin embedded tissue blotting, and immunohistochemistry were used to test whether the abnormal form of the prion protein (PrPSc) accumulates to detectable levels in the eye in a case of the most common subtype of sCJD (MM1).

Results: Low levels of PrPSc were detectable in the retina, localised to the plexiform layers of the central retina. PrPSc was not detectable in other ocular tissues.

Conclusions: The abnormal form of the prion protein is present in the retina in the most common sCJD subtype (MM1), albeit at levels lower than those found previously in vCJD and in sCJD of the VV2 subtype.

http://bjo.bmj.com/content/89/9/1131.abstract

Friday, August 07, 2009

CJD Human Cornea Tissue, Recall END OF ENFORCEMENT REPORT FOR AUGUST 5, 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjd-human-cornea-tissue-recall-end-of.html

Wednesday, August 12, 2009

Unique clinicopathological features and PrP profiles in the first autopsied case of dura mater graft-associated Creutzfeldt-Jakob disease

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/unique-clinicopathological-features-and.html

Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html

Monday, July 27, 2009

U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?

WHY DID THIS VIDEO NOT SHOW ON EVERY NEWS CHANNEL IN THE U.S.A. $$$

IT IS A DAMNING VIDEO !!!

I WATCHED THIS RECENTLY, and had never seen it. i was so mad, i was spitting nails out faster than a framing gun.

WHY DID THE CANADIAN MEDIA ONLY PRESENT THIS TO THE U.S.A. PUBLIC (thank you very much though), and why has the U.S.A. MEDIA FAILED US ???

SNIP...

SEE DAMNING VIDEO AT BOTTOM OF BLOG HERE ;

Monday, July 27, 2009

U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html

NOW, AFTER SEEING THAT VIDEO, (first watch the video) lets go back in mad cow time here in the USA, shall we.

THERE must be an independent review of this cover-up, and the infamous ENHANCED BSE SURVEILLANCE AND TESTING OF 2004, that was nothing but a cover-up, and blundered at that, and plus a REDO of the testing of no less than 1 million head of cattle tested each year, for five years, with scientist from the EU overseeing the testing protocols, surveillance, and confirmation of all cases.

this video states the 'USA had to _admit_ a home grown case of mad cow in TEXAS." fact was, they did not finally admit anything, IT TOOK AN ACT OF CONGRESS, THE HONORABLE PHYLISS FONG AND THE O.I.G., TO MAKE THEM RETEST AND CONFIRM! that my friend is fact. and only after Prof. Aguzzi, Dr. Jean-Philippe Deslys, Dr. Collinge et al slammed them over the testing of that animal. and then we had the mad cow in Texas that they just refused to test, and was sent to a pet food rendering plant. NO TEST AT ALL. you must realize, when other officials, doctors, and such from other country's confront issues about things in the USA, they must walk on ice when doing so. read inbetween the lines here ;

i wrote all these scientist and doctors and the OIG about that damn texas cow, gave them the evidence i had from TAHC. so did others, but finally fong et al did something.

a bit of history for you mel. file this away. ...

Tuesday, July 28, 2009

MAD COW COVER-UP USA MASKED AS SPORADIC CJD

http://madcowtesting.blogspot.com/2009/07/mad-cow-cover-up-usa-masked-as-sporadic.html

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

http://www.oie.int/boutique/extrait/06heim937950.pdf

Tuesday, July 14, 2009

U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST

WHERE did we go wrong $$$

http://madcowtesting.blogspot.com/2009/07/us-emergency-bovine-spongiform.html

Saturday, January 2, 2010

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

http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html

my comments to PLosone here ;

http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd

TSS