Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance
Methodology
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)
Background
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.
Results
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)).
Conclusions
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
Protocol
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.
Interpretation
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
Future
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
ACDP/100/P4e
vCJD AND TRANSFUSION OF BLOOD COMPONENTS: AN UPDATED RISK ASSESSMENT
Peter Bennett and Maren Daraktchiev
Health Protection Analytical Team
Department of Health
Wellington House
133155 Waterloo Road, London SE1 8UG
FINAL
DRAFT (v.1.10) February 1st 2013
CONTENTS SUMMARY 1
1. INTRODUCTION 2
2. CASE EVIDENCE, PREVIOUS SCENARIOS AND MODEL CALIBRATION 4
3. INPUTS AND ASSUMPTIONS REVISITED 9
4. MODELLING METHODS 17
5. RESULTS AND DISCUSSION 29
6. CONCLUDING COMMENTS AND CAVEATS 32
ANNEXES
A. BACKGROUND EVIDENCE AND DATA
1. Total usage of components
2. Distribution of units by age of recipients
3. Posttransfusion survival
4. Transfusionrelated vCJD infections and followup of recipients
B. ESTIMATING THE RISK OF vCJD INFECTION FROM PAST RECEIPT OF BLOOD
COMPONENTS
C. PAST AND FUTURE SECONDARY CASES: ILLUSTRATIVE SCENARIOS
D. SUMMARY OF “CALIBRATED” MODEL RUNS
FINAL DRAFT IN CONFIDENCE
SUMMARY
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.
1
ANNEX A: BACKGROUND EVIDENCE AND DATA
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
snip...
Conclusions
• 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
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/all-clinically-relevant-blood.html
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
Current limitations about the cleaning of luminal endoscopes and TSE prion risk factors there from
Article in Press
http://creutzfeldt-jakob-disease.blogspot.com/2012/10/current-limitations-about-cleaning-of.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
From Terry S. Singletary, Sr flounder@wt.net 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?
PRION www.landesbioscience.com
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,
UPDATE DECEMBER 2010
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
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 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.
TSS
posted by Terry S. Singeltary Sr. at
11:45 AM
