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Creutzfeldt-Jakob disease--implications for anaesthetists in New Zealand.

Creutzfeldt-Jakob disease (CJD) is a progressive, fatal neurological disease. With the recognition of a variant form in 1996, CJD has become more prominent in the medical literature. The majority of cases have been reported in the United Kingdom. However, there has recently been a highly publicised case in New Zealand of a potential transmission of CJD between neurosurgical patients.

In this review, the presentation, pathology and incidence of CJD are examined, with particular reference to iatrogenic transmission.

METHODS

A search of electronic databases Medline (1950 to November 2008), Embase and Evidence Based Medicine Reviews using keywords "CJD", "anaesthesia" (MeSH terms) and "New Zealand" (key word) was performed to source relevant articles. The websites of the Australian and New Zealand College of Anaesthetists, New Zealand Society of Anaesthetists, Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Northern Ireland (AAGBI) were searched for reference to CJD. The publications recommended by the New Zealand Ministry of Health to reduce the risk of CJD transmission were also reviewed.

BACKGROUND

CJD belongs to the wider group of transmissible spongiform encephalopathies (TSE), also known as prion diseases, which may affect humans and animals. It came very much into the spotlight when a new aggressive human form, known now as variant CJD (vCJD), was described in 1996 (1). A link with bovine spongiform encephalopathy, or 'mad cow disease', was implied and subsequently confirmed. The bovine form presented in the mid 1980s, mostly within the UK. Thus, vCJD is the only TSE to have been transmitted between species (2).

More recently, in New Zealand, CJD has again come into the public eye with extensive media coverage (3). In early 2007, concerns were raised that neurosurgical patients had been exposed to CJD-contaminated instruments during their operative procedures. The specific case relates to a patient who had had a cadaveric dural graft in 1984 and following neurosurgery in 2007, developed signs of CJD. The patient subsequently died and the diagnosis of CJD was confirmed.

Human TSEs, including CJD, are rare but due to their unusual resistance to standard decontamination methods and consequent risk of patient-patient transmission, management of infected or possibly infected patients requires additional precautions. In most routine clinical contacts no additional precautions are required and isolation nursing is unnecessary. However, in the operating theatre, controls are required to prevent iatrogenic transmission (2).

It is now realised that in the past, anaesthetic equipment has been insufficiently decontaminated and sterilised and may act as a vector for disease transmission (4). Precautions against transmission of infection between patients, or between patient and anaesthetist should be a routine part of clinical anaesthetic practice.

Prion proteins are normal cellular proteins that have undergone a structural change rendering the abnormal protein resistant to degradation. The site and mechanism of this refolding change is unknown and prions are found only in TSEs (2). Prions accumulate in neurological tissue and pathological examination shows a classic sponge-like appearance created in the brain by microscopic vacuoles, deposition of amyloid plaques, neuronal loss and astrocytosis. In addition to the neuropathological changes, prion proteins gene analysis and immunocytochemistry are used to assist the diagnosis of CJD (5).

CJD remains a fatal condition as there are no proven treatments, although several drugs that may slow or halt the disease process have been studied in small numbers of patients. Four of the most studied drugs are the analgesic flupirtine, intraventricular pentosan polysulphate, amantadine (a dopaminergic drug with anti-influenza virostatic actions) and the anti-malarial, quinacrine. However, there is insufficient evidence to introduce any into clinical practice at present (6).

CLASSIFICATION

Human TSEs are very rare and include CJD, fatal familial insomnia, Gerstmann-Straussler-Scheinker Syndrome and Kuru. CJD is the most common of the human TSEs and can be divided into four types (5).

Sporadic CJD was first described in 1921. This is the most common form and has been found worldwide, with an incidence of about one per million population per year. Sporadic CJD comprises around 85% of cases and the average age of onset is 65 years. It presents as a rapidly fatal (four to six months) dementia with associated focal neurology, including ataxia, myoclonus, visual disturbances and rigidity (2). The aetiology is currently unclear but it is thought that a spontaneous change arises in normal prion proteins.

Familial CJD accounts for 5 to 10% of CJD patients and occurs in those with a genetic disposition to the disease (7).

Iatrogenic CJD has most commonly been related to treatments using human cadaveric dura mater or pituitary hormones (8). Corneal grafts and neurosurgical instruments have also been associated with transmission. Incubation periods range from one to two years for the rare cases of transmission from neurosurgical instruments or intracerebral electrodes to over 30 years for pituitary hormone recipients (2). The use of cadaver-derived dura mater has been prohibited in New Zealand since 1987 (9). Patients with CJD from pituitary hormones display a progressive cerebellar syndrome (2). Internationally, there have been no reported cases of transmission of CJD by occupational exposure (2).

Variant CJD affects younger individuals with an average age of onset of 27 years. The clinical illness lasts longer, for 14 months on average, and initially presents with psychiatric and sensory disorders. Movement disorders and dementia then follow. Classification of definite vCJD requires a progressive neuropsychiatric disorder and tissue confirmation. A spongiform change and extensive prion protein deposition are demonstrated with florid plaques throughout the cerebrum and cerebellum. In vCJD the classic EEG changes associated with CJD are absent.

EPIDEMIOLOGY

In New Zealand, CJD became a notifiable disease in 1996 and between 1996 to 2007 there were 37 cases of CJD reported, 14 confirmed and 23 probable, equating to around one per million population per year. This was a similar rate to pre- 1996 and comparable with the worldwide incidence. According to Ministry of Health surveillance data there has been no case of vCJD identified in New Zealand (9,10).

In the UK, the total number of deaths from definite or probable vCJD was 164 to December 2008 and only three cases were still alive. The number of deaths has been declining since a peak in the year 2000 of 28 deaths and has reduced to five deaths per year in the past three years to 2007 (5). Thus, the anticipated epidemic has not materialised.

As of September 2008 there have been 42 deaths from vCJD reported outside the UK. Of these, 23 were in France, four in Ireland and the others were isolated cases throughout the world, though none in Australia or New Zealand. Six of the 42 patients had lived for a significant time in the UK (5).

In the UK there have been four probable transmissions of vCJD related to blood transfusion (11). There is no record of transmission of standard CJD by blood transfusion. The UK Blood Transfusion Service has introduced many precautionary measures including importation of plasma for fractionation, exclusion from donation the recipients of blood transfusion since 1980 and introduction of leucodepletion (11). However they suggest that leucodepletion, from animal data, is likely only to reduce prion infectivity by about 40%.

In New Zealand, since February 2000, blood donors who lived for six months or more in the UK between 1980 and 1996 have been excluded from blood donation (9). This period relates to the time during which eating beef in the UK may have led, through exposure to BSE, to a risk of developing vCJD. In New Zealand in 2002, those who had received a blood transfusion in the UK after 1980 were also excluded from blood donation. From 2006 these exclusions have been extended to include residence and transfusion in France and the Republic of Ireland. The New Zealand Ministry of Health also introduced universal leucodepletion in 2001 (9).

IATROGENIC TRANSMISSION

In all types of CJD, the highest prion concentration occurs in neurological tissue--spinal cord, brain and posterior eye. These tissues are therefore considered high risk. However, distribution of the abnormal prion protein is more widespread in Vcjd (2). vCJD prions have been detected at post-mortem in the lymphoreticular tissue of appendix, tonsillar and GI lymph node tissue. Consequently, infectivity of tonsil, appendix, spleen, thymus, adrenal gland and other lymphoid tissue in vCJD is considered medium risk, but low risk in all other CJD.

As prions are small enough to remain on instruments after standard washing and are resistant to traditional chemical and physical methods of decontamination, they have proven to be an infection risk (7). They are not significantly affected by formalin or ethyl oxide (disinfectants) and remain infective after standard autoclaving, for example 134[degrees]C for three minutes (2). Standard washing techniques reduce the concentration of prions in an exponential manner (12) and therefore effective cleaning is the most efficient method of eliminating the TSE agent (2). This will be more efficient if instruments are kept moist between exposure and decontamination (13). After about 10 decontamination cycles, infectivity becomes negligible (2).

The World Health Organisation produced a manual for surveillance of TSEs in 2003 and their previous advice has been updated to now include recommending single-use instruments or destruction of reusable instruments that have been in contact with high risk tissues (13). However, if this management is not possible or practical, the manual also gives extensive guidance on sterilisation procedures in Annex 4.1 (13).

Measures to reduce iatrogenic transmission in the operating environment have been divided into three main areas in a review by the National Institute for Health and Clinical Excellence (NICE) in the UK (14). First, more effective decontamination of instruments; second, prevention of migration of instruments between sets and finally, introduction of single-use instruments.

In high risk procedures (i.e. intradural neurosurgery, neuroendoscopy and posterior eye surgery), the NICE review (14) states there is a high risk of CJD transmission with migration of instruments between sets. They propose that systems should be set in place for tracking of instruments and ensuring no instruments are swapped. There was thought to be no significant risk from medium and low risk procedures with instrument swapping. Single-use instruments are the only reliable measure for preventing transmission of CJD between patients. However, they state this is not a cost-effective measure compared with taking additional sterilisation precautions. Their recommendation did not support change to single-use instruments except in neurosurgical endoscopy, as there was no cost-effectiveness demonstrated in the following procedures--neurosurgery, eye surgery, tonsillectomy, laryngoscopy and endoscopy. Rigid neuroendoscopes rather than flexible should be used as these can be cleaned and autoclaved. Decontamination of flexible endoscopes requires additional procedures (2,15). NICE conclude that it is likely that more effective agents to decontaminate prions will be developed in the next five years.

MANAGEMENT GUIDELINES

In New Zealand, the Ministry of Health have corresponded with all Health Boards since the 2007 Auckland incident and advocate that local policy should be based on the Australian infection control guidelines published by the Australian Government Department of Health and Ageing (15) and also on the UK Department of Health's Guidance from the Advisory Committee on Dangerous Pathogens' TSE working group (2). Thus each hospital should have an infection control policy on the management of patients with CJD based on the Australian and UK guidelines and the main points of these will be outlined below.

As there have been no reported cases of vCJD in Australia, the Australian guidelines consider only classical CJD rather than vCJD. They state that as the risk of transmission is remote, no extra precautions are required at this stage, though updated guidelines will be released if vCJD is reported in Australia (15). Looking more specifically for Australasian anaesthetists, the Australian and New Zealand College of Anaesthetists do not provide any specific information relating to CJD transmission in their Guidelines on Infection Control in Anaesthesia (16).

RISK ASSESSMENT

Definitive diagnosis of CJD requires pathological confirmation, either at autopsy or from brain biopsy. As tissue diagnosis is usually impractical, patients must have their risk of CJD diagnosis classified on a clinical basis when considering application of guidelines (15).

Classification should be made between symptomatic and asymptomatic patients. Symptomatic patients are then divided into those who have definite, probable or possible CJD or vCJD (2). The asymptomatic patients are those who have no clinical symptoms, but are at risk of disease development of the disease secondary to a family history or medical history (e.g. a history of previous dural graft).

The classification criteria (2) are presented in Table 1.

PERIOPERATIVE MANAGEMENT

There is much overlap between the Australian (15) and UK (2) Health Departments' theatre management guidelines. Both of these provide a general view of hospital and theatre care, but information directed to anaesthetists is brief. The AAGBI has recently published updated guidelines on infection control (4), which provide detail more specific to anaesthetists, though much of the information relates to vCJD.

In planning surgery for symptomatic patients, the operating theatre should be cleared of unnecessary equipment and staffing reduced to the minimum required (7,13). The patient should be scheduled last on the operating list where possible to allow extended cleaning of theatre surfaces prior to the next use (2,15). Included in the symptomatic patient group, in addition to the definite, probable and possible cases, are patients with neurological disease of unknown aetiology in whom the diagnosis of CJD is being actively considered, but do not fit the criteria for possible CJD or vCJD.

Standard precautions are essential when dealing with blood and disposal of sharps. Staff carrying out invasive procedures should be aware of the hazards and single-use disposable equipment used wherever practical. There is no evidence of infectivity of saliva, body secretions or excreta. Specimens should be sent with a biohazard label, double-bagged and laboratories should be advised in advance (2).

In symptomatic patients, a liquid-repellent gown over a plastic apron, gloves, mask and goggles or full-face visor should be worn for procedures. These should be single-use only and, where possible, then destroyed by incineration. All surfaces that may be exposed to high-risk tissues should be covered in plastic, which can then be incinerated (2). In asymptomatic at risk patients (those patients with a genetic or familial risk or an iatrogenic exposure) the above precautions apply, but gowns may be reprocessed if not single-use (2).

Any needles or probes used near the high risk tissues of brain, spinal cord or posterior eye and medium risk tissues of anterior eye and olfactory epithelium must be disposable (4). As lymphoreticular tissues are classed as medium risk in vCJD then instruments such as laryngoscopes and bronchoscopes, which come into contact with postoperative tonsillar tissue, are potentially contaminated. These should be either destroyed or quarantined (4).

The anaesthetic component of the Australian government guidelines simply recommends "routine reprocessing" of anaesthetic equipment with no further explanation (12). In a UK publication, Farling et al7 recommend that any equipment that directly contacts mucosa, including tubing and masks, should be single-use or, if reusable, should be disposed of in any case (7). The same authors stated that ventilators were to be quarantined for use again only with the same patient, and not to be used again for any other patient except those with a definite diagnosis of CJD. However, this advice is not current (P Farling, personal communication) and the author now refers to the guidance of the CJD Incidents Panel that the anaesthetic circuit should be disposed of, single-use filters should always be used and there is no requirement to quarantine the anaesthesia machine (17).

There has been much debate in the UK about the safety of single-use equipment, particularly in relation to tonsillectomy, when its use was introduced as a requirement and was subsequently withdrawn after increasing adverse incidents (4,18). Concerns regarding complication rates due to the inadequate quality of single-use instruments arose. The withdrawal of advice, however, related to surgical equipment and has caused much confusion. The current AAGBI recommendations are that single-use laryngoscopes are not mandatory for tonsil and adenoid surgery (4). They maintain that the risk of the laryngoscope blade becoming contaminated is small when performing an emergency reintubation with exposed tonsillar tissue, compared with the risk of using a disposable laryngoscope in a potentially difficult intubation. Further, the AAGBI recommendations are that tracheal tubes, supraglottic airways and oral airways should be destroyed after adenoid or tonsil surgery. This advice relates to batch cleaning and the potential contamination and transfer of proteins between laryngeal mask airways (19).

A recent survey of UK practice suggests extensive non-compliance with the previous AAGBI guidance. The previous guidance advised anaesthetists that it was 'desirable' to protect anaesthetic equipment from tonsillar tissue (20). Particularly, this related to disposable laryngeal mask use, protection of the laryngoscope handle and blade and, less commonly, use of a disposable sheath or blade on the laryngoscope (21).

When instruments not designated single-use are used, they should be treated according to the patient's risk and the tissue risk (2). Instruments exposed to procedures involving high-risk tissue (brain, spinal cord and posterior eye) should be destroyed in cases of definite or probable CJD and vCJD. Instruments should also be destroyed in the genetic or iatrogenic at risk group. In procedures involving medium risk tissues (i.e. anterior eye, olfactory epithelium and in vCJD lymphoid tissue), the instruments used in the patients with definite or probable CJD or vCJD, should also be destroyed. In the remaining group of patients (those with possible infectivity), instruments exposed to procedures involving high and medium risk tissues should be quarantined until a definite diagnosis has been confirmed (2). Quarantined instruments may be used again for the same patient during the course of their treatment (15).

When being washed, instruments should remain underwater to reduce the likelihood of splashing. The use of instruments that cannot be cleaned and reprocessed because of design or technology (e.g. fibreoptic scopes, bronchoscopes, cystoscopes, laparoscopes) should be avoided (15). Some complex instruments may be shielded or guarded so that the entire item does not need to be destroyed. In the UK, the CJD surveillance unit, based in Edinburgh, has CJD exposed fibreoptic equipment that can be utilised for definite CJD and vCJD cases (5,22).

SUMMARY

Despite being a rare disease, CJD is of clinical importance to anaesthetists due to the resistance of prion proteins to standard sterilisation techniques. The implications for the anaesthetist are based on the risk of iatrogenic transmission during invasive procedures. A recent case in New Zealand of potential iatrogenic transfer of CJD following a neurosurgical procedure highlights the need for each hospital to ensure that it has a policy for the management and control of CJD infection in confirmed or suspected or cases.

The New Zealand Ministry of Health have cited reference to the Australian and UK Health Departments guidelines for management of CJD cases. These guidelines have been outlined and their clinical implications discussed. The Australian guidelines appropriately have not included vCJD management, though are prepared to adapt if required.

In the Australasian clinical context CJD is rare, but given the mobility of patient populations and possible, though unlikely, change in clinical incidence, the Australasian anaesthetist should be aware of the implications of CJD, particularly variant CJD.

ACKNOWLEDGEMENTS

The author thanks Dr Richard French for assistance with preparation of the manuscript and Dr Peter Farling and his medical technical officers for their correspondence.

Accepted for publication on December 8, 2008.

REFERENCES

(1.) Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347:921-925.

(2.) Ministry of Health. Guidance from the Advisory Committee on Dangerous Pathogens' Ministry of Health. Guidance from the Advisory Committee on Dangerous Pathogens' TSE working group Part 4. From http://www.advisorybodies.doh.gov.uk/ acdp/tseguidance/Index.htm Accessed November 2008.

(3.) New Zealand Herald (2007) Lifetime wait for disease's death sentence. From http://www.nzherald.co.nz/topic/story.cfm? c_id=149&objectid=10432278. Accessed November 2008.

(4.) Association of Anaesthetists of Great Britain and Ireland. Infection control in anaesthesia. Anaesthesia 2008; 63:1027-1036.

(5.) The University of Edinburgh. The National Creutzfeldt-Jakob Disease Surveillance Unit (NCJDSU). From http://www.cjd. ed.ac.uk Accessed November 2008.

(6.) Stewart LA, Rydzewska LHM, Keogh GF, Knight RSG. Systematic review of therapeutic interventions in human prion disease. Neurology 2008; 70:1272-1281.

(7.) Farling P, Smith G. Anaesthesia for patients with Creutzfeldt-Jakob disease. A practical guide. Anaesthesia 2003; 58:627-629.

(8.) Brown P, Preece M, Brandel JP, Sato T, McShane L, Zerr I et al. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000; 55:1075-1081.

(9.) Ministry of Health. Creutzfeldt Jakob Disease. From http:// www.moh.govt.nz/moh.nsf/indexmh/cjd Accessed November 2008.

(10.) Ministry of Health Public Health Surveillance. From http:// www.surv.esr.cri.nz/PDF_surveillance/AnnSurvRpt/2007 AnnualSurvRpt.pdf Accessed November 2008.

(11.) UK Blood Transfusion and Tissue Transplantation Services. Creutzfeldt Jakob disease. From http://www.transfusionguidelines. org.uk/index.asp?Publication=DL&Section=12&pagei d=794 Accessed November 2008.

(12.) Smith G. Variant CJD. What you need to know at present. Royal College of Anaesthetists Bulletin 2001; 7:302-304.

(13.) WHO manual for surveillance of human transmissible spongi-form encephalopathies. WHO manual for surveillance of human transmissible spongiform encephalopathies. From http://whqlibdoc.who.int/publications/2003/9241545887.pdf Accessed November 2008.

(14.) National Institute for Health and Clinical Excellence (2006). Patient safety and reduction of transmission of Creutzfeldt-Jakob disease (CJD) via interventional procedures. From http://www.nice.org.uk/nicemedia/pdf/ip/IPG196guidance.pdf Accessed November 2008.

(15.) Australian Government Department of Health and Ageing. Infection Control Guidelines. Part 4-31. From http://www. health.gov.au/internet/main/publishing.nsf/Content/icg-guidelines-index. htm Accessed November 2008.

(16.) Australian and New Zealand College of Anaesthetists. Guidelines on Infection Control in Anaesthesia. From http:// www.anzca.edu.au/resources/professional-documents/professional-standards/ ps28.html Accessed November 2008.

(17.) CJD Incidents Panel. Annual Report of the CJD Incidents Panel 2001-2002 (Jan 2003). From http://www.hpa.org.uk/web/ HPAwebFile/HPAweb_C/1194947310873 Accessed November 2008.

(18.) Rowley E, Dingwall R. The use of single-use devices in anaesthesia: balancing the risks to patient safety. Anaesthesia 2007; 62:569-574.

(19.) Richards E, Brimacombe J, laupau W, Keller C. Protein cross-contamination during batch cleaning and autoclaving of the ProSealTM laryngeal mask airway. Anaesthesia 2006; 61:431-433.

(20.) Association of Anaesthetists of Great Britain and Ireland. Infection control in Anaesthesia (2002). From www.aagbi.org/ publications/guidelines/docs/infection02.pdf#search=%22 CJD%22 Accessed November 2008.

(21.) Clarke MB, Forster P, Cook TM. Airway management for tonsillectomy: a national survey of UK practice. Br J Anaesth 2007; 99:425-428.

(22.) Farling P, Popat M, Cooper S. Fibreoptic equipment and variant Creutzfeldt-Jakob disease. Anaesthesia 2003; 58:716-717.

J. M. TELFER *

Department of Anaesthesia, Christchurch Hospital, Christchurch, New Zealand

* M.B., Ch.B., F.R.C.A., F.A.N.Z.C.A., Fellow in Anaesthesia.

Address for reprints: Dr J. M. Telfer, 5 Sydenham Road, Glasgow G12 9NT, UK.
TABLE 1
Creutzfeldt-Jakob disease classification criteria

 Definite Probable

Sporadic CJD Requires tissue diagnosis Requires a rapidly
 progressive dementia and
 at least two of the
 following four--myo-
 clonus, visual or
 cerebellar problems,
 pyramidal or extra-
 pyramidal features and
 akinetic mutism. Also
 required are a typical
 EEG pattern or a
 positive assay for
 14-3-3 protein from
 cerebrospinal
 fluid.

Iatrogenic CJD Requires neuropathological examination. Patients will
 display progressive cerebellar syndrome in a pituitary
 hormone recipient or classical sporadic CJD signs in a
 patient with other exposure risks, for example dura
 transplant.

Familial CJD As for sporadic above, plus definite or probable CJD
 in a first-degree relative, OR a patient with a
 neuropsychiatric disorder and a disease-specific
 mutation in the prion protein gene.

vCJD Requires a tissue Presents with a
 diagnosis of spongiform progressive neuropsycho-
 change, extensive PrPc logical disorder for
 deposition and florid greater than 6 months
 plaques throughout the with no alternative
 cerebrum and diagnosis and either at
 cerebellum. The patient least four early
 must also have a psychiatric symptoms -
 progressive persistent painful
 neuropsychological sensory symptoms,
 disorder. ataxia, myoclonus/
 chorea/dystonia or
 dementia, or a positive
 tonsillar biopsy. Also
 the EEG will not show
 changes of CJD but there
 are classic MRI
 findings in the
 posterior thalamus.

 Possible

Sporadic CJD Will have rapidly
 progressive
 dementia, two of the
 previous symptoms
 and duration of less
 than 2 years.

Iatrogenic CJD

Familial CJD

vCJD As for probable but
 no positive MRI
 or tonsillar biopsy
 findings.

CJD=Creutzfeldt-Jakob disease, vCJD=variant Creutzfeldt-Jakob disease,
EEG=electroencephalogram, PrPc=prion protein cellular,
MRI=magnetic resonance imaging.
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Author:Telfer, J.M.
Publication:Anaesthesia and Intensive Care
Article Type:Report
Geographic Code:8NEWZ
Date:May 1, 2009
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