Public health priority:
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).
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 neuron-specific 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). The RPA Hospital’s Department of Neuropathology provides specialised CJD diagnostic services in NSW - further information for clinicians on testing for CJD is available from the Department's
CJD testing information.
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.
CJD is to be notified by:
(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.
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.
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.
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:
CJD is not transmitted through household, social or sexual contact.
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:
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.
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.
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 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.
Begin follow-up investigation within 3 working days for cases of classical CJD, and within 1 working day for cases of variant CJD.
Within 3 working day of notification enter cases on NDD.
The response to a notification will normally be carried out in collaboration with the patient's health carers and the ANCJDR.
PHU staff should:
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 is the responsibility of the treating doctor.
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:
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).
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.
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.
Education above for further restrictions.
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 RPA Hospital’s Department of Neuropathology - further information for clinicians on testing for CJD is available from the Department's
CJD testing information.
Defining and identifying "contacts" is not straightforward for CJD. Advice may be sought via CDB.
Only in unusual circumstances would there be contacts at risk of disease. Potential contacts include:
Potential contacts include:
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.
Nil available at present.
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.
As discussed in
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.
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.