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Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance

Posted May 28 2013 12:45pm

Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance

Mabel Cruz, Ignacio Mahillo-Fernandez, Alberto Rábano, Ake Siden, Miguel Calero, Henning Laursen, Kare Mølbak, Javier Almazán and Jesus de Pedro-Cuesta

Emerging Themes in Epidemiology 2013, 10:5 doi:10.1186/1742-7622-10-5

Published: 23 May 2013

Abstract (provisional)


There is increasing epidemiological evidence of etiological links between general surgery and sporadic Creutzfeldt-Jakob disease (sCJD) with long incubation periods. The purpose of this study was to identify specific surgical procedures potentially associated with sCJD to be targeted for preventive presurgical-intervention guidance.


We propose a three-step clinical guidance outline where surgical procedures associated with sCJD clinical onset -- potentially more contaminant - are taken into account. Data on hospital discharges and surgical procedures were obtained from Danish and Swedish national in-patient hospital registries for 167 sCJD cases, onset 1987--2003, and for 835 matched and 2,224 unmatched population controls. Surgery was allocated to different life-time periods as previously reported, and frequencies were compared using logistic regression analysis. In the year preceding clinical onset, persons with sCJD underwent a statistically significant higher number of minor surgical interventions (OR (95%CI): 17.50 (3.64-84.24)), transluminal endoscopies (OR: 2.73 (1.01--7.37)) and gastrointestinal operations (OR: 3.51 (1.21--10.19)) compared to matched controls. Surgical discharges clustered towards clinical onset. These differences increased during the clinical period, with statistically significant higher frequencies for both endoscopies and minor surgery (OR: 13.91 (5.87-32.95), and for main surgical procedures (OR: 2.10 (1.00-4.39)), particularly gastrointestinal surgery (OR: 6.00 (1.83-19.66)), and surgery contacting skeletal muscle. Comparisons with unmatched controls yielded similar results for neurosurgery in the clinical period (OR: 19.40 (2.22-168.34)).


These results suggest that some types of surgical procedures are associated with sCJD, after clinical onset or particularly just before onset. Selective planning of such surgery to minimize instrument/device contamination or quarantining might be feasible. Conditional to progress in sCJD etiological research, results are relevant for guidance development.

Guidance revision

The CJDIP will be dissolved as an expert panel on 31st March 2013. From 1st April 2013, the ACDP will advise government on all generic TSE risk management issues. 14 Responsibility for actions on individual CJD incidents will from 1st April 2013 be managed at the local level; however, local incident teams will be able, if necessary, to refer exceptional or novel issues, outside the scope of the guidance, to the TSE RM SG. Thus in light of these structural changes, the CJDIP and TSE RM SG Secretariats have been asked to review and revise their existing published guidance to ensure that it is coherent, practicable and meets the requirements of application by local teams. The revised guidance will be provided in a form that gives clarity on actions to be taken and on where responsibilities lie. The aim is to ensure that advice is understood and appropriately put into practice, and that risks are managed directly where and when they occur. This revised TSE guidance will sit within a wider review of ACDP guidance currently being undertaken by the Health and Safety Executive. The group advised on the broader issues relating to the guidance revision, including format, timing and process. The Secretariats are now in the process of undertaking the guidance revision.

• Breast milk The subgroup had been asked to consider a request to amend their infection control guidance (Part 4) with regard to eligibility to donate to breast milk banks. Although some concern was expressed regarding inconsistency between different guidance documents, there was general consensus that the TSE infection control guidance should remain as it stands and that those individuals who have received a single blood donation since 1980 should still be allowed to donate breast milk.

• IAH TSE Risk Assessment Following cessation of experimental TSE work at the Institute for Animal Health Compton, a risk assessment had been prepared as part of a land quality assessment for the farm estate. The TSE RM SG was asked review this risk assessment and comment on the residual risks from the TSE waste disposal activities and whether the mitigation measures to reduce the risks were appropriate.

• TSE agent decontamination Following revision of TSE infection control guidance, the Animal Health and Veterinary Laboratories Agency queried omission of the following sentence, “Paraffin sections from blocks of tissue not previously decontaminated should be immersed in 96% formic acid for 5 minutes after de-waxing.” It was suggested to introduce a sentence into Annex C:

1. recognising that not all tissues had been decontaminated before being cut,

2. if they had not been decontaminated, a risk assessment should be carried out, and

3. this might then involve treatment with formic acid.

• Annex F – Endoscopy The Choice Framework for local Policy and Procedures (CFPP) 01-06 guidance on decontamination of flexible endoscopes was published in June 2012. This guidance differs from that currently in the ACDP TSE guidance Annex F. Alignment of the two sets of guidance was needed, and the group agreed to amend Annex F with regard to:

1. management of endoscopes following use on asymptomatic “at increased risk” from vCJD patients,

2. differential guidance for some asymptomatic “at increased risk” patients, and

3. considerations for nasendoscopy and non variant forms of CJD.

• Plasma products A re-assessment of the risks to plasma product recipients had been undertaken following the re-examination of the risk of blood-borne transmission of vCJD by the DH Health Protection Analytical Team. The group agreed with the conclusions that:

• For most recipients of “high risk” plasma products the maintenance of the ‘at increased risk’ of vCJD notified status should continue;

• A limited number of patients in receipt of “high risk” plasma products, e.g. some of those treated for Von Willebrand’s Disease or for clotting disorders should be identified, re-assessed and denotified;

• Denotification should also be considered for (two) individuals in receipt of “medium risk” plasma products who have been re-assessed as unlikely to have received enough product to cross the 1% at risk threshold.

6.2 Transmissible Spongiform Encephalopathy Risk Assessment Sub Group (TSE RA SG) The TSE RA SG met five times in 2012 on the 10th January, 30th April, 25th May, 12th July, and 25th October. The following key issues were considered by the TSE Risk Assessment Sub Group in 2012:

• Prevalence of vCJD – appendix study


The TSE RA SG reviewed the protocol design of vCJD prevalence appendix survey in detail to ensure that the results were robust and therefore reliable when used to inform risk management policy.

Results The most recent study of UK prevalence of abnormal prion protein tested 32,441 appendix samples, collected since 2000 during surgery on patients born between 1941 and 1985. Of these, 16 samples were judged to be “positive”. This indicates a central prevalence estimate very close to 1 in 2,000 in the age cohort covered, with a 95% confidence interval running from approximately 1 in 3,500 to 1 in 1,250. The group agreed that the recent appendix survey provides the most reliable available indication of the prevalence of asymptomatic vCJD infection within the UK population. The group reviewed and agreed a revised blood risk assessment prepared by the DH Health Protection Analytical Team in response to the increasing mis-match between the numbers of predicted and observed clinical cases of vCJD which suggested that the assumptions in the previous risk assessment may have been too precautionary. The agreed risk assessment included new assumptions pertaining to level of infectivity, the time-period during which blood is considered infective, and prevalence.


Despite the welcome fall in vCJD diagnoses, the group agreed that the indication of relatively widespread, albeit “silent”, vCJD infection necessitates continued attention to the risks of secondary, person-to-person transmission, and for applied research to support the development and implementation of risk management strategies. Gaining further information on prevalence of infection also remains a key area, especially through the investigation of tissues from groups presumed unexposed to BSE and of the feasibility of surveying the prevalence of abnormal prion protein in blood.

A position statement was prepared by the group and is available on the website at


The TSE RA SG supported the proposed commissioning by DH of two presumed negative control studies of the UK prevalence of human prion disease by IHC study of stored human appendix tissue. It is proposed that the first study should use material or to 1980. This will cover the UK population prior to the earliest presumed exposure to BSE via diet. A second presumed negative control study would use appendix tissue collected in the UK from patients born after 1 January 1996. This will cover the UK population after the introduction of presumed effective animal feed and meat controls, and cover a UK population with a presumed lower risk of exposure to food associated TSE than those born earlier.

• Assessment of vCJD risks associated with the consumption of desinewed meat Following a Food and Veterinary Organisation audit of mechanically separated meat desinewed meat (MSM/DSM) production in the UK in March 2012, the European Commission asked the UK to cease production of DSM from ruminant bones, on the grounds that they consider DSM to be MSM which must not be made from ruminant bones under TSE Regulations. The Food Standards Agency’s interpretation of the term MSM however, excludes DSM. The CMO sought the TSE RA SG’s view on the TSE risk to consumers from consumption of products containing DSM. Advice was provided and the TSE RA SG’s conclusions formed a component of the evidence presented to the Environment, Food and Rural Affairs

Select Committee in June 2012.

• Blood tests for vCJD

A joint meeting was held between the TSE RA SG and the Prion Working Group in October 2012 to discuss the development of a blood test for vCJD and its potential use for a blood prevalence study. Four tests were reviewed including the MRC Prion Unit assay, NHSBT QuIC assay, SNBTS PMCA assay, and the Prionics assay.

ACDP Secretariat

February 2013



Peter Bennett and Maren Daraktchiev

Health Protection Analytical Team

Department of Health

Wellington House

133155 Waterloo Road, London SE1 8UG


DRAFT (v.1.10) February 1st 2013










1. Total usage of components

2. Distribution of units by age of recipients

3. Posttransfusion survival

4. Transfusionrelated vCJD infections and followup of recipients






This paper considers the transmission of variant CreutzfeldtJakob Disease (vCJD) from person to person though receipt of donated blood components. It presents a mathematical model, primarily designed to examine how many future clinical cases might be caused in this way. Key inputs to the model include the number of donors that might be carrying vCJD infection without showing any symptoms, the infective dose in blood components sourced from such a donor, and the likelihood of recipients surviving long enough to develop symptoms of vCJD if infected. In addition, the results of the model need to be consistent with the number of cases seen to date. Much of the analysis concerns the potential transmission of vCJD though red cell transfusion: this is the component most commonly transfused, and the small number of known transmissions have all been associated with red cells. However, the analysis is also extended to consider the possibility of transmission via Fresh Frozen Plasma (FFP).

Any attempt to quantify the potential impact of transmission has to take account of many scientific uncertainties about vCJD. We therefore use a scenariobased approach. After reviewing some of the key evidence, the analysis uses a range of values for each of the key inputs, endorsed by the relevant expert scientific group. The model then generates a range of possible scenarios for the number of transfusionrelated cases that might appear in future and how many of these future cases would be caused by transfusions yet to happen. The analysis presented here is intended to be precautionary, and may be subject to substantial change as understanding of disease develops.

Despite the small number of clinical cases seen to date that might plausibly be associated with transfusion, current knowledge leaves open a substantial range of scenarios as regards future cases. Nevertheless, this range has narrowed with the passage of time, as compared with previous analyses. For red cell transmission, plausible numbers of future vCJD cases associated with red cell transfusion range from almost zero up to about 1,000 spread over the next 60 years. About half these cases would be caused by transfusions that have already taken place. The cental estimate for the number of clinical cases that might be caused by future red cell transfusions is roughly 160, with an upper limit of 460. For Fresh Frozen Plasma, the central estimate is roughly 45, and the upper limit 120. However, the number of “silent” vCJD infections associated with transfusion would be much higher than the number of clinical cases. It is therefore important to maintain, and if possible enhance, measures to prevent onward transmission of infection, notably the exclusion of recipients from donating blood.



A1: Total usage of components

Leaving aside a small historical use of whole blood, the annual provision of components by the four UK blood services is shown in the following Table, sourced from successive annual reports for Serious Hazards of Transfusion1:

Table A1: Summary of issues by UK Blood Services 1999–2011



• We suggest that calculations of exposures should count all transfusions from 1990 onward, and continue to treat historical risks per donor exposure as constant.

o it appears unlikely that more complex calculations dependent on the age distribution of the donor base are justified as there is now less support for a strong “cohort effect” for historical prevalence of infection – e.g. that it was largely confined to the 196185 “Hilton cohort”.

o other variations may have existed (e.g. delay in onset of infection making earlier donations less risky, while later donations would have been subject to leucodepletion and other precautionary measures) but these are insufficiently known and may tend to cancel each other out.

• Use of this method would produce a substantially smaller estimate of infection risk than that used to date. Nevertheless, the calculation remains precautionary, in assuming:

(a) that only a small minority (4%) of secondary vCJD infections amongst recipients surviving at least 10 years would have shown up as recognisable clinical cases, and

(b) that more vCJD cases may have been caused by bloodborne infection than the 3 identified so far.

• If accepted as “appropriately precautionary”, a historical risk of vCJD infection of 1 in 30,000 per donor exposure would retain a simple – but arguably more credible – rule of thumb for risk assessment and management purposes.

Saturday, March 23, 2013

CJD Incidents Panel to be disbanded

Friday, May 10, 2013

Evidence of effective scrapie transmission via colostrum and milk in sheep

Tuesday, March 05, 2013

A closer look at prion strains Characterization and important implications Prion

7:2, 99–108; March/April 2013; © 2013 Landes Bioscience

Monday, April 15, 2013

Dr. Stephen B. Thacker Director Centers for Disease Control and Prevention′s Office of Science, Epidemiology and Laboratory Services (OSELS) dies from Creutzfeldt Jakob Disease CJD

Sunday, February 10, 2013

Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection report/CJD

Thursday, January 17, 2013

TSE guidance, surgical, dental, blood risk factors, Part 4 Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings (updated January 2013)

Friday, June 29, 2012

Highly Efficient Prion Transmission by Blood Transfusion

Monday, May 6, 2013

Warning of mad cow disease threat to blood transfusions

Tuesday, April 30, 2013

Mad cow infected blood 'to kill 1,000’

Wednesday, August 24, 2011

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011 (SEE VIDEO)

Saturday, May 25, 2013

Brain homogenates from human tauopathies induce tau inclusions in mouse brain

Tuesday, May 21, 2013

IS ALZHEIMER’S DISEASE A PRION DISEASE? the possible secondary transmission by blood transfusion are posed

Sunday, May 19, 2013

CJD BLOOD SCREENING, DONORS, AND SILENT CARRIERS House of Commons Written Answers 16 May 2013

Tuesday, May 7, 2013

Proteinopathies, a core concept for understanding and ultimately treating degenerative disorders?

Tuesday, May 21, 2013

CJD, TSE, PRION, BLOOD Abstracts of the 23rd Regional Congress of the International Society of Blood Transfusion, Amsterdam, The Netherlands, June 2-5, 2013

Tuesday, March 5, 2013

Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)

FDA believes current regulation protects the public from BSE but reopens comment period due to new studies

Thursday, October 25, 2012

Current limitations about the cleaning of luminal endoscopes and TSE prion risk factors there from

Article in Press

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

From Terry S. Singletary, Sr 1-24-3

Tuesday, July 31, 2012

11 patients may have been exposed to fatal disease Creutzfeldt-Jakob Disease CJD Greenville Memorial Hospital

Thursday, August 02, 2012

CJD case in Saint John prompts letter to patients Canada CJD case in Saint John prompts letter to patients

Friday, February 10, 2012

Creutzfeldt-Jakob disease (CJD) biannual update (2012/1) potential iatrogenic (healthcare-acquired) exposure to CJD, and on the National Anonymous Tonsil Archive

Monday, November 26, 2012

Aerosol Transmission of Chronic Wasting Disease in White-tailed Deer

Thursday, December 29, 2011

Aerosols An underestimated vehicle for transmission of prion diseases?


please see more on Aerosols and TSE prion disease here ;

Saturday, February 12, 2011

Another Pathologists dies from CJD, another potential occupational death ?

another happenstance of bad luck, a spontaneous event from nothing, or friendly fire ??

Tuesday, December 14, 2010

Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J,


Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

Thursday, September 02, 2010

NEUROSURGERY AND CREUTZFELDT-JAKOB DISEASE Health Law, Ethics, and Human Rights The Disclosure Dilemma

Thursday, August 12, 2010

USA Blood products, collected from a donor who was at risk for vCJD, were distributed July-August 2010

Sunday, August 01, 2010

Blood product, collected from a donors possibly at increased risk for vCJD only, was distributed USA JULY 2010

Thursday, July 08, 2010

Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010

Thursday, July 08, 2010


Wednesday, June 02, 2010

CJD Annex H UPDATE AFTER DEATH PRECAUTIONS Published: 2 June 2003 Updated: May 2010

Tuesday, May 11, 2010

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

Tuesday, May 04, 2010

Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010

Tuesday, March 16, 2010

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

Monday, August 17, 2009

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

Monday, July 20, 2009

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

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

Sunday, May 10, 2009

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

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

Wednesday, August 20, 2008

Tonometer disinfection practice in the United Kingdom: A national survey

Tuesday, August 12, 2008

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

Monday, December 31, 2007

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

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.

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

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