Control Guideline for Public Health Units

Public health priority:

  • Classical CJD – Routine for possible, probable and confirmed cases.
  • Variant CJD – High for possible, probable and confirmed cases.

PHU response time: Initiate response to classical CJD within 3 working days. Investigate variant CJD within 1 working day. Enter probable and confirmed cases on NDD within 3 working days.

Case management: Provide guidelines on infection control to treating clinicians. Alert the clinician of the need for him or her to notify the case to the Australian National CJD Registry.

Contact management: Requires liaison with Communicable Diseases Branch, NSW Department of Health (CDB).

Last updated: 06 September 2004
  1. Reason for surveillance
  2. Case definitions
  3. Notification criteria and procedure
  4. The disease
  5. Managing single notifications
  6. Managing special situations

1. Reason for surveillance

  • To monitor the epidemiology of CJD and facilitate the prompt recognition of any case of variant CJD in NSW
  • To facilitate collection of information on potential risk factors for infection and national notification to the Australian National CJD Registry
  • To ensure carers and clinicians are aware of the infection control guidelines to minimise further transmission.

2. Case definition

CJD - Classical

Possible case

  • Progressive dementia of less than 2 years duration, and
  • EEG atypical or not known, and
  • At least 2 of the following clinical features:
    • Myoclonus
    • Visual or cerebellar disturbance
    • Pyramidal / extrapyramidal dysfunction

Probable case

  • Progressive dementia of less than 2 years duration, and
  • a typical EEG (e.g. presence of periodic, 1-2 Hz sharp wave discharges), and/or positive 14-3-3 protein in CSF, and
  • at least 2 of the following clinical features:
    • Myoclonus
    • Visual or cerebellar signs
    • Pyramidal or extrapyramidal signs
    • Akinetic mutism.

Confirmed case

  • Progressive neurological disorder, and
  • neuropathological confirmation on examination of brain tissue supplemented by immunocytochemistry for protease-resistant PrP (Western Blot).

CJD - variant

Possible case

  • As for probable cases - except MRI signs not required, and EEG (if performed) should not show the typical appearance of classical CJD.

Probable case

  • Progressive neuro-psychiatric disorder, and
  • Duration of illness of greater than 6 months, and
  • Routine investigations do not suggest alternative diagnosis, and
  • No history of potential iatrogenic exposure, and
  • At least 4 of the following symptoms:
    • Early psychiatric symptoms
    • Persistent painful sensory symptoms
    • Ataxia
    • Myoclonus or chorea or dystonia
    • Dementia, and
      • Bilateral pulvinar high signals on MRI or
      • Progressive neuro-psychiatric disorder, and
      • Duration of illness of greater than 6 months, and
      • Routine investigations do not suggest alternative diagnosis, and
      • No history of potential iatrogenic exposure, and
      • Positive tonsil biopsy.

Confirmed case

  • Progressive neuro-psychiatric disorder, and
  • neuropathological confirmation of variant CJD on examination of brain tissue.

Factors to be considered in case identification

The above definitions are based on WHO definitions and definitions used by the Australian National CJD Registry (ANCJDR). National case definitions for CJD are still under development at July 2004.

The Australian Government funds the Australian National CJD Registry (ANCJDR) based at the University of Melbourne. The ANCJDR undertakes national surveillance for CJD. The ANCJDR also provides laboratory testing for 14-3-3 protein in CSF and advice to neurologists investigating potential cases of CJD.

Tests used in diagnosis of CJD include testing of CSF for markers of neuronal damage (14-3-3 protein and neuronspecific enolase protein) and EEG, in addition to other standard neurological tests to exclude alternative diagnoses. Note that a negative 14-3-3 protein result alone does not necessarily exclude the diagnosis, nor does absence of typical EEG (particularly if only one EEG performed) - the ANCJDR can provide advice in such situations.

Variant CJD does not show the typical EEG pattern seen in classical CJD. MRI often shows bilateral high pulvinar signals. In those with variant CJD the abnormal prion protein may be found in the tonsils on biopsy. Note however that positive tonsil biopsy does not allow a definitive diagnosis.

Definitive diagnosis for both classical and variant CJD requires examination of brain tissue, generally post-mortem. Although brain biopsy is usually diagnostic in CJD, due to its risks it is not recommended for routine use on living patients in the diagnosis of CJD (although may be used in the investigation of certain alternative diagnoses).

Classical CJD can be further described as sporadic, familial or iatrogenic in origin. This determination at present is made by the ANCJDR after review of case history, investigations etc. Genetic testing can aid in the classification of familial forms.

3. Notification criteria and procedure

CJD is to be notified by:

  • Medical practitioners and hospital CEOs
  • Laboratories.

(Ideal reporting by telephone on same day of diagnosis for variant CJD, and by mail for classical CJD).

Enter probable and confirmed cases on NDD within 3 working days.

4. The disease

CJD is a fatal neurological disorder thought to be caused by the accumulation of abnormal proteins known as prions. Prions are transmissible under certain rare circumstances.

CJD is part of a group of diseases known as Transmissible Spongiform Encephalopathies (TSEs). CJD has two main forms - classical (which includes sporadic, familial and iatrogenic cases) and variant CJD.

Variant CJD was recognised in the UK in 1996 and is thought to be caused by consumption of beef infected with Bovine Spongiform Encephalopathy (BSE), which is an animal TSE.

Other human TSEs are Gerstmann-Sträussler-Scheinker disease (GSS), kuru and Fatal familial insomnia (FFI), and for the purposes of this protocol are also classed as CJD.

CJD is a rare disease, with average of 1.13 cases per million population per year reported in Australia between 1998-2000. Of the cases recorded on the Register (1970- 2001) 90.3 per cent were sporadic, 7.5 per cent were familial and 2.2 per cent of cases were of iatrogenic origin (recipients of human pituitary hormones or dura mater grafts from cadavers).

As of June 2004 no cases of variant CJD have been reported in Australia. From October 1996 to June 2004 approximately 141 cases of vCJD have been reported in the UK, six in France and one each in Canada, Ireland, Italy and the United States of America.

Infectious agent

The infectious agent is thought to be an abnormal form of the prion protein (PrP). Prion proteins have at least two forms - a normal, cellular version (PrPC) and a disease-causing version (PrPSc). Exposure to the PrPSc can cause PrPC to become PrPSc.

Mode of transmission

Classical CJD can arise due to an inherited mutation in the PrP gene (familial CJD, GSS, FFI), or arise seemingly spontaneously without any recognised exposure to the tissue of another case (sporadic).

All forms of CJD can be transmitted from person-to person under certain rare circumstances.

CJD is transmitted by inoculation of the infectious agent (prions) from the infectious tissues of a case. In persons with classical CJD, the tissues considered to have 'high-infectivity' are the central nervous system (CNS) tissues (i.e. brain and spinal cord) and the eye (particularly the optic nerve and retina). Some tissues (kidney, liver, lung, lymph nodes/spleen, maxillofacial neurovascular tissue, placenta, CSF) are considered to have 'low-infectivity' on the basis of animal studies, but the results are not conclusive (CDHA, 2004; WHO 2003). Classical CJD is not thought to be transmissible via blood and blood products.

In contrast, in those with variant CJD there is evidence of significant levels of the infectious agent in other tissues such as lymphatic tissues (eg tonsils, spleen, lymph nodes), as well as the CNS and eye. There is evidence to suggest that variant CJD may be transmissible through blood and blood products.

Documented modes of person-to-person transmission of classical CJD include:

  • Iatrogenic:
    • Injection of contaminated human pituitary hormones (114 cases worldwide at July 2000)
    • Receipt of contaminated human dura mater grafts (139 cases worldwide at July 2000)
    • Receipt of contaminated corneal transplants (3 cases reported worldwide)
    • Exposure to contaminated stereotactic intracerebral EEG needles or neuro-surgical instruments (2 and 5 cases respectively reported worldwide).
  • Ritual funerary practices involving consumption of human brain tissue from a deceased person with infection in the central Highlands of New Guinea (kuru).

CJD is not transmitted through household, social or sexual contact.

Timeline

Incubation period

For sporadic cases of CJD the incubation period is not known, but is probably similar to that of kuru (4 to more than 20 years).

For iatrogenic cases of classical CJD the incubation period depends on the amount of abnormal protein introduced and the site at which it is introduced. Incubation periods for various sites of inoculation are estimated as:

  • Direct intracerebral introduction (eg via neurosurgery, stereotactic EEG, or via optic nerve) - approximately 16-28 months
  • Contaminated dura mater grafts - from 18 months to 18 years (median 6 years)
  • Subcutaneous injections of contaminated pituitary hormones - 5 to 30 years.

It appears that variant CJD may have an average incubation period of around 12 years, on the basis of UK surveillance data and information on when BSE was present in the UK human food chain.

Infectivity period

Certain tissues (as described above) are infectious throughout clinical illness. It is not known if tissues are infectious before symptom onset, but there is some evidence to suggest certain tissues may be.

Clinical presentation

Classical CJD

The usual clinical presentation is characterised by progressive dementia. Cerebellar ataxia and myoclonus are common. CJD is always fatal and 90% of patients die within 12 months of onset. The mean age at onset for sporadic cases of CJD is 60 years.

Variant CJD

Variant CJD has a clinical pattern different to that of classical CJD. Variant CJD has affected younger people, with a median age of 29 years at death. The first symptoms of variant CJD are often psychiatric symptoms e.g. anxiety, insomnia, withdrawal. Neurological symptoms developed later in the course of illness than in classical CJD, and often painful sensory symptoms are the first neurological symptom. The duration of illness is longer for those with variant CJD, with an average of 14 months to death.

5. Managing single notifications

Response times

Investigation

Begin follow-up investigation within 3 working days for cases of classical CJD, and within 1 working day for cases of variant CJD.

Data entry

Within 3 working day of notification enter cases on NDD.

Response procedure

The response to a notification will normally be carried out in collaboration with the patient's health carers and the ANCJDR.

PHU staff should:

  • Confirm the onset date and symptoms of the illness, and the results of relevant diagnostic tests
  • Confirm the treating doctor has informed the ANCJDR; if not, PHU staff should request the doctor to promptly inform the ANCJDR (advise the doctor they should seek verbal family consent). The ANCJDR will undertake exposure investigation and final classification of the case. If a situation arises in which there is reluctance to contact the ANCJDR the PHU should commence the exposure investigation as detailed below and liaise with CDB
  • Ensure appropriate infection control guidelines are provided
  • Ensure CDB is urgently informed of possible variant CJD
  • Liaise with the ANCJDR and CDB to ensure investigation of relevant exposures in situations that may require public health action.

The ANCJDR follows-up each case referred to the Registry, gathering detailed information and investigating potential causes. Early involvement of the ANCJDR allows liaison with the clinical team to encourage appropriate investigations.

Case management

Case management is the responsibility of the treating doctor.

Exposure investigation

Due to the long incubation period for CJD information regarding exposures many years prior to illness may be relevant and should be sought. Currently the ANCJDR gathers this information using a standard questionnaire. Relevant information includes:

  • History of surgery, particularly neurosurgery or ophthalmic surgery or invasive neurological testing (including stereotactic EEG)
  • History of receipt of corneal transplant, or of receipt of human dura mater graft (particularly 'Lyodura', used in Australia between 1972 and 1987)
  • History of treatment with cadaver-derived human pituitary hormones (used for treatment of short stature or infertility - in Australia between the years 1967 and 1985)
  • History of receiving blood transfusions or other blood products, dental or surgical care, renal dialysis or other medical procedures
  • Family history of similar illness
  • Travel history, particularly for any case of variant CJD
  • History of consumption of food containing beef or bovine products for any case of variant CJD.

A history of donation of blood or other body tissues should also be sought from cases of variant CJD (by interview and review of relevant records of donors).

Education

PHU staff should ensure that health-care workers caring for the case are aware of the relevant infection control guidelines - at the time of writing (June 2004) these are the Australian Government Infection control guidelines for the prevention of transmission of infectious diseases in the health care setting and the NSW Health Infection Control Policy. Where contradictory, the Australian Government guidelines take precedence regarding CJD. Specific chapters in the former provide detailed guidelines regarding infection control measures, including equipment re-processing, for patients with CJD or at risk of CJD. These guidelines also include information for laboratory workers, those performing post-mortems and those in the funeral industry (Note that these persons should be informed of the possible diagnosis of CJD when requested to provide services for a person with suspected CJD, in order to allow these precautions to be implemented).

The case or relevant care-giver should be informed about the nature of the infection and the mode of transmission, and informed that cases should not donate blood or body parts. When persons with CJD seek medical or dental care they or their carers should notify involved personnel of their CJD status.

Isolation and restriction

Prions are resistant to standard procedures for decontaminating surgical and other instruments. During routine care for cases standard precautions are generally sufficient, however special precautions are required for certain medical, dental, laboratory procedures and post-mortem examinations (particularly in regards to managing instruments and equipment in contact with infectious tissues). For example, it is recommended that instruments that contact high-infectivity tissue during surgery or invasive diagnostic procedures on those with possible, probable or definite CJD be destroyed after use (or quarantined for future use on the same patient and then destroyed). Refer to the Australian Government Infection Control Guidelines for full details, including reprocessing for equipment used in other procedures. Health Care Associated Infections Prevention and Control Unit, NSW Health can be contacted for further advice.

See Education above for further restrictions.

Environmental evaluation

Nil

Investigation and treatment

There is no specific treatment for CJD, clinical management consists of supportive care.

The ANCJDR can provide expert advice on appropriate investigations in cases of suspected CJD.

Post-mortem examination of the brain is required for confirmation of CJD; consent from patient's next-of-kin is required. Discussing the sensitive issue of post-mortem with families would ideally be undertaken by the specialist clinical team caring for the patient, and begun early enough to allow the patient's family sufficient time to consider the issues prior to the patient's death.

Post-mortem examinations for persons with suspected CJD require special procedures and in NSW are performed at the Department of Forensic Medicine, Glebe.

Contact management

Identification of contacts

Defining and identifying "contacts" is not straightforward for CJD. Advice may be sought via CDB.

Classical CJD

Only in unusual circumstances would there be contacts at risk of disease. Potential contacts include:

  • Recipients of corneal transplants from an infectious case
  • Recipients of dura-mater grafts or pituitary hormones from an infectious case
  • Those exposed to instruments/equipment potentially contaminated during invasive neurological investigations, neurosurgery, or ophthalmic surgery on a case and not subjected to sufficient cleaning and re-processing for the inactivation of the infectious agent for CJD, such as described in the Australian Government Infection Control Guidelines. Contact Health Care Associated Infections Prevention and Control Unit, NSW Health for further advice as needed
  • Occupational exposure is also theoretically possible e.g. inoculation of infectious tissue via an injury from a contaminated instrument, however no such cases have been conclusively documented.
Variant CJD

Potential contacts include:

  • Recipients of blood product or other tissue donated by an infectious case
  • Those exposed to instruments/equipment potentially contaminated following surgery/invasive procedures on a case and not subjected to sufficient cleaning and re-processing for the inactivation of the infectious agent for CJD, such as described in the Australian Government Infection Control Guidelines. Contact Health Care Associated Infections Prevention and Control Unit, NSW Health for further advice as needed
  • Occupational exposure is also theoretically possible e.g. inoculation of infectious tissue via an injury from a contaminated instrument, however no such cases have been conclusively documented.

Any decision to trace and disclose potential exposure to the people in the above groups should be made in consultation with Communicable Diseases Branch and after a careful risk assessment and consultation with an expert panel. The risk of psychiatric injury due to the disclosure of a possible risk of contracting a fatal disease with a long incubation period and no cure must be considered, along with other issues.

Treatment

Nil available at present.

Passive Immunisation

Nil.

Active Immunisation

Nil

Antibiotic prophylaxis

None.

Education

As discussed above, any decision to trace and disclose potential exposure to the people in the above groups should be made in consultation with Communicable Diseases Branch and after a careful risk assessment and consultation with an expert panel.

Contacts should not donate blood or body parts.

Contacts should alert health care workers to their increased risk of CJD and health care workers should refer to the Commonwealth Infection control guidelines.

Appropriate counselling should be offered, and the person informed of relevant support groups.

Isolation and restriction

As discussed in Education above.

6. Managing special situations

Suspected health-care associated infection

If circumstances suggest the possibility of iatrogenic infection, notify CDB immediately.

Due to the complexity of risk assessment and legal and ethical issues involved in such a situation, investigation should be co-ordinated by CDB and any decision regarding a look-back investigation, where potentially exposed people are traced, should be made in consultation with CDB who may convene an expert panel.

In the event of possible contamination of an instrument, that instrument must not be used again until expert advice has been sought regarding its capacity to be safely reprocessed.

Variant CJD

A case of variant CJD in Australia would be a highly significant public health event, and the Commonwealth Government has developed guidelines for managing this event: How Australia will Respond to our First Case of vCJD: A Guide for the Public.

As at July 2004 Commonwealth Infection control guidelines for variant CJD are still in development. Infection control issues can be addressed in liaison with the Health Care Associated Infections Prevention and Control Unit, NSW Health.

If a case with variant CJD has donated blood or plasma while potentially infectious, or if transfused blood or blood products are suspected as the possible source of infection of vCJD, the CDB and the blood bank should be notified immediately.