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

Posted Jul 08 2010 8:10am
Public release date: 8-Jul-2010

Contact: SINC 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.

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; 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.



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. 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 (¼ope), 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


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


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.


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.


see full text 217 pages ;

Sunday, January 17, 2010

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

Sunday, January 17, 2010

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

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

Friday, November 20, 2009

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

Sunday, May 10, 2009

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




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;


Docket Management

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

Comment Number: EC -1

Accepted - Volume 1

Daily Dockets - 04/10/03

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

Monday, August 17, 2009

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

Tuesday, March 16, 2010

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

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

Tuesday, August 12, 2008

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

Tuesday, May 11, 2010

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

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

Wednesday, February 24, 2010

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

ICID International Scientific Exchange Brochure -

Tuesday, June 1, 2010

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

Wednesday, June 16, 2010

Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

Friday, November 30, 2007


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

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