Creutzfeldt-Jakob disease

Notification requirement for Creutzfeldt-Jakob disease

Creutzfeldt–Jakob disease (CJD) is a ‘routine’ notifiable condition and must be notified by medical practitioners and pathology services in writing within 5 days of diagnosis.

This is a Victorian statutory requirement.

Primary school and children’s services centre exclusion for Creutzfeldt-Jakob disease

School exclusion is not applicable.

Infectious agent of Creutzfeldt-Jakob disease

The infectious agent is a unique abnormal prion protein, designated as PrP. This protein is an insoluble, protease-resistant amyloid form of a normal cellular protein designated as PrPc. PrP acts on normal prions, causing them to change into the abnormal infectious form in a cascade-like manner.

Identification of Creutzfeldt-Jakob disease

Clinical features

CJD belongs to a group of rare diseases known to affect humans and animals, called transmissible spongiform encephalopathies (TSE). CJD presents in humans in either a classical or a variant form.

Classical CJD

Classical CJD (cCJD) is one of four rare prion diseases that affect humans. The others are kuru, Gerstmann–Straussler–Scheinker disease and fatal familial insomnia.

Classical CJD occurs in sporadic, familial and iatrogenic forms. Sporadic cases account for 85–90 per cent of CJD cases and have an unknown cause. Familial cases make up 5–10 per cent and are associated with a genetic mutation. Less than 5 per cent are iatrogenic.

The symptoms of classical CJD usually begin at an average age of 65 years. Most cases occur between 45 and 75 years. The onset is commonly a rapidly progressive dementia, sometimes following a prodrome of psychiatric symptoms and sleep disturbance. One third of people, however, may present with cerebellar symptoms such as dysarthria, falls and truncal ataxia. With disease progression there may be pyramidal or spinal cord involvement, muscle atrophy or fasciculations and frequently myoclonus (involuntary muscle twitching), classically triggered by sudden stimulus such as loud noise (so-called ‘startle myoclonus’). Survival beyond 1 year is unusual; death ensues at a median of 4.5 months following diagnosis.

Variant CJD

Variant CJD (vCJD) was first described in the United Kingdom in 1996. The disease is strongly linked to the consumption of cattle products infected with the prion protein that causes bovine spongiform encephalopathy (BSE) or ‘mad cow’ disease. There are clinical differences between vCJD and cCJD. Variant CJD affects younger people (median age of 28 years) and the duration of illness is longer (median of 14 months). It more commonly begins with prominent psychiatric symptoms, such as depression and anxiety. Involuntary movements and sensory symptoms, such as pain, are usually present and the cerebellum is nearly universally affected. The peak of cases of vCJD in the United Kingdom was 28 in 2000; the current incidence is fewer than three cases per year.

Diagnosis

Diagnosis is by the clinical presentation, disease progression and exclusion of other causes. EEG and MRI scans yield distinct results between classical and variant CJD. CSF tests, including 14-3-3 protein, assist diagnosis. Definitive diagnosis is usually made at autopsy by detection of the PrP and demonstration of the typical pathological spongiform changes in the brain. Brain biopsy, while possible, is not recommended. The diagnosis can also be confirmed by the detection of PrP in other human tissue, such as tonsillar tissue, by biopsy where a strong clinical indication exists (such as strong evidence for vCJD, in which PrP is more frequently detectable in lymphoreticular tissue).

Incubation period of Creutzfeldt-Jakob disease prions

The incubation period is difficult to ascertain and varies from 15 months up to 40 years in iatrogenic cases.

Public health significance and occurrence of Creutzfeldt-Jakob disease

Iatrogenic forms of classical CJD have been associated with cadaver-derived human pituitary hormone and cadaver-derived dura mater grafts (Lyodura in Australia). There have been no cases in Australia associated with cadaver-derived corneal grafts or contaminated surgical instruments. Worldwide, the last known cases associated with contaminated surgical instruments occurred in the United States in the 1970s. Sporadic CJD continues to occur; about 20 cases are reported in Australia annually. Global annual incidence is approximately one per 1 million population.

No case of variant CJD has been reported in Australia. Since 1986, more than 180,000 cases of BSE in cattle have been reported in the United Kingdom. The epizootic was linked to cattle being fed meat and bone meal containing the remains of other cattle; sheep suffering from scrapie in the same slaughterhouses were potentially a source. A feed ban on meat and bone meal was introduced in July 1988. Other countries have reported BSE in cattle imported from the United Kingdom. The rates of BSE are now decreasing. BSE has not been reported in Australian cattle. More than 175 cases of human vCJD have now been reported in Britain.

Reservoir of Creutzfeldt-Jakob disease prions

Prion disease is present in cattle (BSE), sheep, goats, mink, mule deer, elk, cats and exotic zoo animals. Transmission of vCJD in humans has been linked only to the consumption of meat and meat products from cattle with BSE.

Humans infected with vCJD and cCJD are potential sources of infection for other humans by iatrogenic means.

Mode of transmission of Creutzfeldt-Jakob disease prions

The majority of cases of classical CJD appear to occur spontaneously, with no source identified. In very rare cases, transmission of cCJD has occurred through iatrogenic means. This has included direct or indirect contact with brain tissue and cerebrospinal fluid; for example, corneal or dural grafts, injections of contaminated pituitary hormone obtained from cadavers, or contaminated surgical instruments (high-risk neural tissue surgery). Growth hormone is now made artificially. There is no evidence of risk to people in close casual contact with a person infected with CJD.

Variant CJD is believed to be transmitted to humans through the consumption of cattle infected with BSE.

There have been no cases of vCJD linked to the receipt of infected blood products in Australia. Three secondary cases are thought to have occurred by this route in the United Kingdom. As there is a theoretical risk of infection from blood products, blood donors are screened for possible exposure in areas affected by vCJD, particularly the United Kingdom.

Period of communicability of Creutzfeldt-Jakob disease

The central nervous system tissues are infectious during symptomatic illness of CJD. Animal studies suggest that lymphoid tissues and other organs are probably infectious before symptoms develop.

Susceptibility and resistance to Creutzfeldt-Jakob disease

Genetic mutations have been found in familial CJD. Genetic susceptibility also occurs for vCJD for humans who are homozygous for methionine at codon 129 of the prion gene.

Control measures for Creutzfeldt-Jakob disease

Preventive measures

Precautionary measures instituted in Australia to reduce the risk of vCJD importation include the following:

• Australia suspended the importation of cattle from the United Kingdom in 1988, from other European countries in 1991, and from other BSE-affected countries from the date the disease was first reported in those countries.
• The Therapeutic Goods Administration monitors the source of materials of animal origin used in the manufacture of medicines and medical devices.
• Since 2000, there has been a ban on blood products from people who lived in the United Kingdom for six months or more from 1980 until 1996.
• The Australian National CJD Registry based at the University of Melbourne conducts surveillance for vCJD.
• Since 1990, the Australian Department of Agriculture and its predecessors have conducted active surveillance for BSE in cattle.

Control of case

There is no specific treatment except for supportive care.

Hospitalised patients should be managed using standard precautions. Tissues, surgical instruments and all wound drainage should be considered contaminated and must be inactivated. The PrP is very resistant to destruction by normal methods, including standard sterilisation, and because of this instruments used on CJD patients, particularly in surgery involving the brain, spine or eye, may need to be destroyed.

Doctors making a diagnosis of CJD are asked to report their findings to the Australian National CJD Registry based at the University of Melbourne.

It is important to obtain an accurate history of travel, any previous surgical or dental procedures, and any history of exposure to cadaver-derived human growth hormone or transplanted tissue.

If there is no travel history, obtain details of any past procedure or surgery.

Inform the Australian Department of Agriculture of the need to monitor Australian cattle if de novo vCJD occurs.

Control of contacts

Individuals who have may have shared a common exposure with a case or who may have been exposed to infected material from a case, such as transplanted tissue, should be counselled by a specialist infectious diseases physician.

Control of environment

All wound drainage, tissues and surgical equipment should be considered to be contaminated (see also ‘Control of case’). They should be terminally disposed of or inactivated.

The World Health Organization has advised that no part or product of any animal that has shown signs of a TSE should enter a human or animal food chain.

Outbreak measures for Creutzfeldt-Jakob disease

In the event of cases of vCJD being detected in Australia, the Australian Government Department of Health and the Chief Medical Officer will coordinate the national response in consultation with the state and territory health departments and animal health authorities.

International measures

International advisories and human and animal quarantine issues are the responsibility of various Australian and state government departments.