Creutzfeldt-Jakob disease and other spongiform encephalopathies

Part of the Communicable Disease Control Manual

Chapter last reviewed and updated in July 2020. A description of changes can be found at Updates to the Communicable Disease Control Manual.

Contents


Epidemiology in New Zealand

Creutzfeldt-Jakob Disease (CJD) is one of the transmissible spongiform encephalopathies that affect humans. Sporadic CJD, accounting for 85–90% of CJD, occurs at an incidence of 1–2 per million per year.

Other transmissible spongiform encephalopathies include kuru (once common amongst the Fore people of Papua New Guinea), and hereditary forms such as Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia. CJD is subdivided into sporadic (previously known as classic), familial, iatrogenic and variant forms. The variant form of CJD (vCJD) is linked epidemiologically and through laboratory studies to bovine spongiform encephalopathy (BSE) in cattle.

All spongiform encephalopathies are caused by proteinaceous infectious particles (termed ‘prions’) that undergo conformational change, leading to cellular death and inducing a similar conformational change in other proteins around them.

Case definition

This is based on consensus criteria used internationally, which include case history and examination findings, cerebral magnetic resonance imaging (MRI), electroencephalogram (EEG), cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) or 14-3-3 protein and definitively brain histopathology.

Criteria of the National CJD Research & Surveillance Unit (UK) (PDF, 252 KB) are available from their website. 

Clinical description

Creutzfeldt-Jakob Disease is a rapidly progressive and universally fatal neurodegenerative disease. Subtypes of CJD are differentiated by causative mechanism and clinical picture, as summarised Immediately below. Clinical differentiators between these subtypes are not considered reliable; in other words genetic, iatrogenic and sporadic types for example can be clinically indistinguishable. 

Sporadic CJD (sCJD) is thought to arise spontaneously and accounts for around 85 percent of all cases of CJD globally. 

Familial CJD (fCJD) is a hereditary form that accounts for 10–15 percent of all cases of CJD, occurring in geographic clusters. It is an autosomal dominant inheritance. Close blood relatives of people with genetic CJD have a 1 in 2 chance of carrying the gene and developing the disease.

Variant CJD (vCJD) is suspected to occur from eating beef and beef products from cattle infected with BSE. It often starts with psychiatric symptoms, such as anxiety and depression.

Prions are found outside the nervous system as well as within it, especially in the lymphoid tissues throughout the body. No cases of vCJD have been reported in New Zealand to date.

Iatrogenic CJD (iCJD) is an infection passed on from treatment or procedures from any case (sporadic, familial, variant) and can be considered iatrogenic. It accounts for less than 1% of all cases of CJD.

Historically, it has been transmitted via pituitary hormones and dura mater grafts derived from human cadavers (treatments no longer in use), and more recently through corneal transplantation and contaminated neurosurgical instruments. Infection with variant CJD has been linked with blood transfusion in four patients in the United Kingdom.

Investigations for diagnosis

Cerebral spinal fluid real-time quaking-induced conversion (CSF RT-QuIC )[1] is the most specific non-histological diagnostic test for ante-mortem diagnosis of sCJD. When this test is positive, only ‘rapidly progressive cognitive impairment’ is required as a clinical feature to meet a surveillance classification as ‘probable sCJD’. As CSF RT-QuIC is not 100% sensitive, and as CSF analysis can be limited by the presence of blood, careful clinical assessment and other investigations remain relevant.

Cerebral spinal fluid real-time protein 14-3-3, the traditional CSF test, has inferior specificity and sensitivity compared to CSF RT-QuIC, but is still used as laboratories transition to RT-QuIC. CSF protein 14-3-3 is a supporting investigation and may be useful when CSF RT-QuIC is not available. CSF 14-3-3 utility can be improved by the addition of CSF total Tau. New Zealand CSF samples for CSF RT-QuIC, protein 14-3-3 and total Tau are analysed at the Florey Laboratory, University of Melbourne.[2]

Magnetic resonance imaging (MRI), particularly abnormal diffusion weighed imaging in the basal ganglia and/or multiple cortical regions, is a useful supporting investigation.

EEG can also be useful, although may show non-specific abnormalities earlier in the clinical course.

Note that, with the exception of CSF RT QuIC, clinical features on neurological examination must be present for cases to be classified as ‘possible’ or ‘probable’ sCJD (see Diagnostic criteria).

Case classification

  • See case definition above. 
  • The CJD Registry classifies cases notified according to the consensus diagnostic criteria. It may not be possible to classify some cases where information is limited. 

Spread of infection

Incubation period

Sporadic and familial cases

Arises spontaneously.

Variant cases

Based on the small number of vCJD cases, the incubation period for foodborne transmission is approximately 13 years.

Iatrogenic cases

  • Neurosurgical cases and EEG depth electrodes: 12–28 months
  • Dural grafts: 1.5–18 years
  • Growth hormone: 6–34+ years
  • Based on the small numbers of vCJD cases, the blood transfusion-related transmissions is around 5–9 years.

Mode of transmission

Sporadic and familial

Not applicable (arises spontaneously).

Variant CJD

Variant CJD is most likely to have been caused by consumption of food products contaminated by BSE-infected cattle.

Iatrogenic CJD

Infection is passed on as a result of medical treatment or invasive medical intervention through exposure to infectious material from a case. Most cases of iCJD have been transmitted through cadaveric dural grafts or treatment with human pituitary hormones; two cases have been transmitted through corneal transplantation, contaminated neurosurgical instruments or from EEG depth electrodes. Each acquired form involves the inoculation, implantation or transplantation of infectious material.

Transmission from cases

For sporadic, familial and iatrogenic cases of CJD, only the tissues of the central nervous system, including the brain, dura mater, spinal cord ganglia, CSF (low risk), posterior eye and the olfactory tract, appear to be infective. Blood transmission has not been demonstrated for sporadic CJD, but has been implicated in several cases of variant CJD. 

For variant CJD, abnormal prion protein has also been detected in various lymphoid tissues, including tonsils, spleen, gastrointestinal lymphoid tissues (for example, Peyers patches of the appendix and rectum), lymph nodes, thymus and adrenal gland. Some vCJD cases have been linked to blood transfusions, and it is thought that vCJD can be transmitted by blood components from people who are asymptomatic but later develop the disease.

There have been no isolations of infective material from human faeces, saliva, tears, vaginal secretions, semen or milk.

Period of communicability

Cases are increasingly likely to be infective during the last 40 percent of the incubation period or longer (that is, approximately eight years before the onset of symptoms for sporadic CJD). Central nervous system tissue is infective throughout symptomatic illness.

Notification procedure

‘Suspected CJD’ is notifiable, and attending medical practitioners must immediately report suspected cases directly to the New Zealand CJD register, at cjd.registry@otago.ac.nz, at the Department of Medicine, University of Otago, Dunedin School of Medicine.  

Notification to the CJD register requires completion of a questionnaire to allow case classification and assessment of risk factors for transmissible disease. 

Medical practitioners must also inform their local medical officer of health. Any cases suspected of being iatrogenic or variant CJD must also be notified to the director of public health. 

Management of case

Restriction

There is no reason to defer, deny or in any way discourage the admission of a person with CJD into any health care setting. Based on current knowledge, isolation of patients is not necessary; they can be nursed in the open ward system using standard precautions. Private room nursing care is not required for infection control, but may be appropriate for compassionate reasons.

In regard to invasive medical interventions, people with confirmed or suspected CJD are the highest-risk patients. They must be managed according to infection control policies using specific precautions (see documents referred to in ‘other control measures’, below). Cases must not donate blood or organs.

Treatment

Supportive.

Counselling

Provided by the clinician or by a psychologist. Referral to the Genetic Health Service may be made to counsel regarding familial risk. 

Management of others at risk

For infection control purposes, individuals with confirmed or suspected CJD are the highest-risk patients. Intermediate precautionary measures and counselling are also important for people who are identified as having been exposed to CJD or as being at risk of CJD (for example, have a family history).

Table 1: Categorisation of individuals at risk of CJD
Symptomatic cases As per case classification.
Asymptomatic individuals at risk from familial forms of CJD linked to genetic mutations

Individuals who have been shown by specific genetic testing to be at significant risk of developing CJD or other prion disease.

Individuals who have a blood relative known to have a genetic mutation indicative of familial CJD.

Individuals who currently have, or have had two or more blood relatives affected by CJD or other prion disease.

Asymptomatic individuals identified as potentially at risk due to iatrogenic exposures

Recipients of hormone derived from human pituitary glands, for example, growth hormone, gonadotrophin. (In New Zealand, the human pituitary hormone programme ceased in 1985.)

Individuals who have received a graft of dura mater. (In October 1988 the New Zealand Department of Health, now Ministry of Health, recommended that commercially produced dura mater not be used.)

Cases who have been contacted as potentially at risk, including individuals considered to be:

  • at risk of CJD/vCJD due to exposure to certain instruments used on a case who went on to develop CJD/vCJD or was at risk of vCJD
  • at risk of vCJD due to receipt of blood components or plasma derivatives
  • at risk of CJD/vCJD due to receipt of tissues/organs
  • at risk of vCJD due to the probability they could have been the source of infection for a case transfused with their blood who was later found to have vCJD.

Source: Adapted from UK Advisory Committee on Dangerous Pathogens (ACDP) 2007.

Note:

  • Categorisation of individuals by risk is in descending order.
  • This table does not include people who may theoretically be at increased risk because of food-related exposures (eg, eating beef from areas with previous BSE). This risk is thought to be extremely low.

Restrictions

Individuals at risk of disease must not donate blood or organs. They must notify their health care providers of their risk of developing prion disease as this has implications for lumbar puncture, endoscopy and surgical procedures and for transport and laboratory processing of samples.

Individuals who have spent six months or more in the United Kingdom, France or the Republic of Ireland between January 1980 and December 1996 must not donate blood; however, organ donation is allowed with informed consent.

Individuals who have a history of blood or blood product transfusion in the United Kingdom, France or the Republic of Ireland since 1980 must not donate blood. In addition, the New Zealand Blood Service does not accept tissues from individuals with the above blood transfusion history.

Other control measures

Identification of source

The CJD registry and local medical officers of health will liaise regarding any potential case clusters.

Disinfection and decontamination

Comprehensive advice on case care, occupational exposure, laboratory safety, decontamination of instruments and surfaces, waste disposal and post-mortem care can be found in control guidance documents published by both the Australian Department of Health and Ageing and the United Kingdom’s Department of Health. These documents are the basis of New Zealand’s national policy approach recommended by the Ministry of Health. They can be located at the following websites.

Reporting

See above, under Notification procedure.

References and further information

CJD registries


[1] For description see Alison Green. ‘RT-QuIC: a new test for sporadic CJD [PDF, 429].’ Practical Neurology, Volume 19 (2019), pp.49-55.

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