Emerging Infections/CJD

CJD

• Creutzfeldt-Jakob disease (CJD) biannual update (2012/1)

 

 

Creutzfeldt-Jakob disease (CJD) biannual update (2012/1)

This six-monthly report provides an update on reports of incidents of potential iatrogenic (healthcare-acquired) exposure to CJD, and on the National Anonymous Tonsil Archive. The data are correct as of 3 February 2012.

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

Reports of incidents of potential iatrogenic exposure to CJD via surgery: 2000 to 31 December 2011.

A surgical incident occurs when a patient with or at increased risk of CJD has undergone surgery without the appropriate infection control guidance being followed [3]. This could happen if a patient undergoes surgery during the incubation period of CJD, or because information about CJD risk factors is not available at the time of surgery. If this happens, surgical instruments that may be contaminated with the infectious agent that causes CJD, could pose a transmission risk when they are re-used on other patients.

In June 2010 the CJD Incidents Panel changed its protocol for reporting surgical incidents, and a new reporting algorithm was published on the HPA CJD Section website. Under the new protocol only CJD cases (or patients at increased risk of CJD) who have undergone surgical procedures which are thought to pose a possible transmission risk (ie within the likely infectious incubation period, and involving medium or high risk procedures) are categorised as 'surgical incidents'. Other procedures, either earlier in the incubation period, or involving low infectivity tissues, are categorised as 'CJD reports'.

Table 1 shows the number of CJD surgical incidents reported to the CJD Incidents Panel from 2000 to 31 December 2011 by the diagnosis of the index patient. Advice has been issued for five surgical incidents and 37 CJD reports that were reported to the CJD Incidents Panel in 2011.

Information about the CJD Incidents Panel can be found on the HPA website [4].

Table 1: CJD surgical incidents (n=437) reported to the CJD Incidents Panel (which have been closed, or where advice has been issued) by diagnosis of index patient: 2000 to 30 June 2011

Index patient status	'00	'01	'02	'03	'04	'05	'06	'07	'08	'09	'10		'11		Total incidents (% of total)	Total CJD reports
											Incid'ts	Rep'ts	Incid'ts	Rep'ts
Sporadic (possible, probable or definite)	7	19	22	24	16	18	31	17	21	15	5	4	1	22	196 (44%)	26 (63%)
vCJD (possible, probable or definite)	6	14	22	5	4	1	2	–	1	1	–	–	–	1	56 (13%)	1 (2%)
Familial including 'at risk' familial	–	2	2	7	1	3	7	–	2	3	2	–	–	1	29 (7%)	1 (2%)
'At risk' vCJD blood component recipient	–	–	–	–	4	10	5	1	–	–	2	–	–	–	22 (5%)	–
'At risk' - vCJD plasma product recipient	–	1	2	–	10	18	9	8	6	9	3	–	4	2	70 (16%)	2 (5%)
'At risk' - other	–	–	2	2	1	2	5	–	–	1	7	–	-	9	20 (5%)	9 (22%)
CJD type unclear/ CJD unlikely	1	1	–	4	1	1	2	–	–	–	–	–	–	1	10 (2%)	1 (2%)
Not CJD	2	1	4	7	7	1	1	–	3	–	1	–	–	–	27 (6%)	–
Other	–	–	1	1	1	2	1	–	–	–	1	–	–	1	7 (2%)	1 (2%)
No longer considered 'at-risk'	–	–	1	–	–	–	–	1	–	–	2	–	–	–	4 (1%)	–
Total –	16	38	56	50	45	56	63	27	33	29	23	4	5	37	441	41

* Some percentages do not total 100 due to rounding. Prior to 2010, all reports were recorded as incidents.

If the investigation of a surgical incident identifies any instruments that are considered to be potentially contaminated with the infectious agent, and that could still pose an infection risk to other patients, the Panel advises that these instruments should be removed from general use or refurbished. These instruments may be quarantined, kept for exclusive use on the index patient, refurbished (endoscopes only) or destroyed.

Since 2000 there have been 86 incidents in which instruments have been permanently removed from general use or refurbished (endoscopes only).

Surgical incidents resulting in ‘at risk’ patients

The Panel may advise contacting and informing patients of their possible exposure to CJD following a surgical incident. These patients should be considered 'at-risk of CJD for public health purposes' and are asked to take certain precautions (ie not to donate blood, other tissues or organs, and to inform their medical and dental carers prior to any invasive procedures) in order to reduce the risk of transmitting the CJD agent.

The diagnosis of the index patient; the timing of the procedure relative to the development of clinical CJD; the tissue that instruments were in contact with during the procedure on the index patient; and the number of cycles of re-use and decontamination the instruments have been through following the procedure on the index case – all influence the possible risk to subsequent patients.

The threshold level of risk at which patients are considered to be ‘at increased risk’ of CJD is 1%, in addition to the background risk in the UK population. This risk threshold is based on risk assessment models, using precautionary assumptions. The 1% threshold level is used as a cut off for implementing public health precautions and is not intended to be a precise measure of an individual patient's risk. A similar threshold is used for identifying other patients who have been exposed to possible CJD risks following surgical, blood, plasma and tissue incidents.

From 2000 to 31 December 2011, there have been 26 surgical incidents in which the Panel has advised that 190 patients should be considered to have an increased risk of CJD.

Patient denotifications

Following changes in the assessment of tissue infectivity, the Panel has advised that 38 patients in 14 surgical incidents who were originally considered (and notified) as being ‘at risk' of CJD should no longer be considered ‘at risk', and should be denotified. In November 2005, gastrointestinal endoscopies without invasive procedures were reclassified as low risk procedures, and advice was issued to denotify two patients in one surgical incident. In 2006, anterior eye was reclassified as a ‘medium low' infectivity tissue. This led to a change in advice as only the first patient on whom instruments were used following an anterior eye procedure was to be considered as having an increased risk of CJD. Previously this had applied to the first two patients exposed to such instruments. This resulted in the Panel advising that 16 patients in seven incidents should be denotified. In 2009, the anterior eye was further reclassified as a low infectivity tissue. Following this change, the Panel advised that 20 patients should be denotified.

As of 31 December 2011, the Panel has received confirmation that of the 33 patients originally notified of their exposure (out of the 38 originally considered to be ‘at risk'), 25 patients have been informed that they are no longer considered ‘at risk' and eight patients died before they could be denotified.

Current 'at risk' patients resulting from surgical instruments

There are 13 surgical incidents in which 152 patients are still considered to be at increased risk of CJD. Currently, 119 of these 'at risk' patients have been notified that they are at increased risk of CJD. Local decisions have been taken not to notify four patients in these incidents.

Table 2: Surgical ‘at risk’ patients still identified as being ‘at increased risk of CJD’ by the Panel by procedure on the index patient

Diagnosis of index patient	Procedure on index patient	Number of incidents	Patients identified as 'at risk'	Patients who died before being notified	Local decision not to notify patient	Notified patients
Sporadic	Brain biopsy	2	28	2	1	25
Variant	Appendectomy	1	2	–	2	–
Variant	Endoscopy	1	1	–	1	–
Asymptomatic infected vCJD	Endoscopy	1	4	1	–	3
At risk variant	Endoscopy	5	36	4	–	32
At risk familial	Neurosurgery	1	31	10	–	21
At risk familial	Ophthalmic surgery	1	39	1	–	38
At risk sporadic	Ophthalmic surgery	1	11*	2	–	–
Total		13	152	20	4	119

* Notification of nine patients was pending at the time of this reporting period.

 

Monitoring of patients 'at increased risk' of CJD

The CJD Incidents Panel and the Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy Risk Management Subgroup (formerly the ACDP TSE Working Group) have identified a range of individuals and groups who may have been exposed to an increased risk of CJD as a consequence of their medical care (see table 3 below). The risks of iatrogenic CJD transmission to these different individuals are very uncertain, but potentially devastating. The CJD Incidents Panel has advised that these individuals should be informed of their risk and asked to follow public health precautions to avoid transmitting the infection to others.

It is important to follow up these individuals to help determine the risks of CJD spreading to patients through different routes. Follow up involves a range of activities and is carried out by different organisations. At core, follow up aims to ascertain whether any people who may have been exposed to increased CJD risks go on to develop CJD.

Table 3. Individuals at increased risk of CJD up to 31 December 2011

'At risk' Group	Identified as 'at risk'	Ever notified as being 'at risk'	Alive and Notified	Cases	Asymptomatic infections
Recipients of blood from vCJD cases	67	27	18	3	1
Blood donors to vCJD cases	112	107	104	–	–
Other recipients from blood donors to vCJD cases	34	32	23	–	–
Plasma product recipients (all except one have non-bleeding disorders)	11	10	4	–	–
Surgical contacts of all CJD cases	141	119	110	–	–
Highly transfused patients (recipients of blood from ≥80 donors identified at pre-surgical assessment)	9	7	6	–	–
Total for at risk groups where HPA holds data	374	302	265	3	1
Patients with bleeding disorders who received UK sourced plasma products [a]	3,868	n/k	n/k	–	1
Recipients of human derived growth hormone [b]	1,883	1,883	1,521	67	–
Total for all 'at risk' groups [c]	6,125	At least 2,184	At least 1,786	70	2

a. Data provided by the UK Haemophilia Centre Doctors' Organisation (UKHCDO). These are minimum figures. Central reporting for bleeding disorder patients is incomplete, and some patients have opted out of the central UKHCDO database. Individual haemophilia centres were asked to send out standardised letters of notification to all their ‘at risk’ patients, but the exact number of patients who received these letters and are therefore aware of their risk is not known.
b. Data provided by the Institute for Child Health. A small number of ‘at risk' growth hormone recipients are not included in the Institute of Child Health study so the true number ‘at risk’ will be greater. The exact number of growth hormone recipients in the ICH study currently aware of their risk is not known, as given their age at the original notification many were informed indirectly, by their parents.
c. These are minimum figures given the comments made above.

Update on summary of abnormal prion prevalence

The National Anonymous Tonsil Archive (NATA) was set up in 2004 to prospectively collect 100,000 tonsils pairs obtained after routine tonsillectomies in England and Scotland and to test these samples for abnormal prion protein. Only tissues not required for patient care, which would normally be discarded, were collected. 

The NATA work is now finished with recruitment and testing of specimens stopped. Up to the end of September 2011, NATA received a total of 95,672 tonsil pairs from hospitals in England and Scotland, about 18,003 of which are from the birth cohort in which most vCJD cases have arisen (1961-1985) (figure 1). A further 3,010 tonsil pairs were received from the Medical Research Council Prion Unit at the UCL Institute for Neurology, National Hospital for Neurology and Neurosurgery. Therefore the total number of tonsil pairs in the archive is 98,682. The number of collection forms that were completed but where no tonsil tissue was collected was 2,557 (1,671 due to patient objection and 886 due to clinical pathology being requested for the sample).

Figure 1. Number of tonsil pairs collected by birth cohort: January 2004 to September 2011

Of the 100 NHS Hospital Trusts that perform over 200 tonsillectomies per year in England, 91 were recruited into the study and sent tonsil pairs to NATA on a regular basis. There were 120 hospital sites within these trusts taking part in NATA. During the seven year period, approximately 50,000 tonsillectomies were performed annually in England. Figure 2 shows the number of tonsil pairs received from each Strategic Health Authority area.

Figure 2. Tonsil pairs collected by Strategic Health Authority: January 2004 to September 2011 3. NHS Trusts and Scottish hospitals currently collecting and sending tonsil tissue to the archive July 2011

 

The tonsils have been screened for abnormal prion protein by two enzyme immunoassays (EIAs) and a small proportion selected for additional investigative analytical tests such as immunohistochemical testing (IHC) and Western blot tests. No positives were found.

An earlier study of appendix and some tonsil tissue, from operations conducted between 1995 and 1999, found three positive samples out of 12,674 screened for abnormal prion protein using the IHC method [5]. The prevalence estimate calculated from this study was 237 per million overall (95% CI: 49-692 per million) – or 380 per million (95% CI=80-1120 per million) in those born between 1961 and 1985. This prevalence estimate equals to one infection per 4,000 of the population in the 1961 to 1985 birth cohort, the cohort in which most vCJD cases have arisen.

In 2008, the Spongiform Encephalopathy Advisory Committee (SEAC) considered the available NATA data [6]. At that time no abnormal prion protein positive samples had been found in nearly 55,000 samples, analysed by the high throughput dual EIA screening technique, including about 11,000 samples from the 1961 to 1985 birth cohort [7]. This translated to a prevalence estimate of zero per million (95% CI=0-324 per million) in this birth cohort. Statistical analysis of the data from the previous appendix survey and NATA showed the prevalence rates were consistent with each other.

To further investigate the prevalence of abnormal prion protein in the NATA samples from patients in the 1961 to 1985 birth cohort, the IHC technique was applied to screen 9,160 samples within that cohort; these samples which had already been shown to be negative when screened by the dual EIA technique [8]. One specimen showed a single strongly positive follicle. The specimen was negative when further investigated by EIA, IHC, and immunoblotting. This finding of 1 in 9,160 gives a prevalence estimate of 109 infections per million (95% CI: 3-608 per million) in those born between 1961 and 1985 which is not statistically different from the prevalence estimate based on the previous appendix study (exact p =0.64).

The results of NATA and the “IHC screening” sub-study were considered by SEAC in 2010 [9]. The committee agreed that “even though the positive sample suggested a possible prevalence of 1:10,000, the result from the Hilton data of 1:4,000 would still remain the most precautionary figure for risk management purposes”.

The Health Protection Agency is also coordinating a second Appendix Survey in order to test for abnormal prion protein in archived appendix tissues in two birth cohorts of individuals[10]. The study is an unlinked anonymous survey testing approximately 20,000 samples from individuals born between 1961 and 1985 and 10,000 from those born between 1941 and 1960. The study is continuing but the interim data shows that four out of 13,878 suitable samples across both birth cohorts have tested positive for disease associated prion protein (PrP CJD ). This translates to a prevalence estimate of 288 per million (95% CI=79-738 per million). Two of the four positive samples were from the 1941-1960 birth cohort resulting in a prevalence estimate of 641 per million (95% CI=78-2314 per million) compared to 186 per million (95% CI=23-671 per million) in the younger cohort of individuals. The interim data has been reviewed by the ACDP TSE Risk Assessment Sub-Group [11].

References

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

2. The National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh. Incidence of variant Creutzfeldt-Jakob disease onsets and deaths in the UK January 1994 - May 2011. Edinburgh: NCJDSU, 18 May 2011. Available at: http://www.cjd.ed.ac.uk/cjdq68.pdf.

3. Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. The ACDP TSE Risk Management Subgroup. http://www.dh.gov.uk/ab/ACDP/TSEguidance/index.htm.

4. HPA CJD Incidents Panel [online]. Available at: http://www.hpa.org.uk/web/ CJDIncidentsPanel.

5. Hilton DA, Ghani AC, Conyers L, Edwards P, McCardle L, Ritchie D, et al. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 2004; 203: 733-9.

6. Spongiform Encephalopathy Advisory Committee (SEAC). Prevalence of subclinical variant Creutzfeldt-Jakob Disease infections. August 2008, SEAC position statement; de Marco MF, Linehan J, Gill ON, Clewley JP, Brander S.  Large Scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain. J Pathol 2010; 222: 380-7.

7. Clewley J, Kelly CM, Andrews N, Vogliqi K, Mallinson G, Kaisar M, et al. Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ 2009; 338: b1442.

8. de Marco MF, Linehan J, Gill ON, Clewley JP, Brander S.  Large Scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain. J Pathol 2010; 222: 380-7.

9. Spongiform Encephalopathy Advisory Committee (SEAC). Minutes of the 104th Meeting held on 5 March 2010.

10. HPA Health Protection Report. Interim data from the current national survey of abnormal prion prevalence in archived appendix specimens. September 2011. Volume 5 No 36. Available at: http://www.hpa.org.uk/hpr/archives/2011/news3611.htm#cjd.

11. Advisory Committee on Dangerous Pathogens TSE Risk Assessment SubGroup. Minutes 14 July 2011. ACDP TSE RA Minutes.