2 Indication

The condition

2.1 Creutzfeldt–Jakob disease (CJD) is a progressive, fatal neurological disease affecting the brain. It is caused by pathological accumulation of a transmissible form of protein called a prion. CJD belongs to a wider group of neurodegenerative disorders known as transmissible spongiform encephalopathies (TSEs) that affect both humans and animals. People with CJD typically present with rapidly progressive dementia, usually accompanied by myoclonus and cerebellar ataxia. Most people die within 4 months of disease onset, in a mute and immobile state.

Epidemiology of CJD

2.2 The incidence of any type of CJD (based on published surveillance studies) is 1 to 2 cases per million of the population worldwide. There are 4 aetiological CJD categories:

  • Sporadic CJD (sCJD) accounts for 85% to 90% of cases worldwide. The aetiology is not known. It has an annual incidence of 1 to 2 deaths per million of population per year. The general rate of age-adjusted detection of sCJD is increasing in the UK. Reasons for this include improved case ascertainment and an ageing population (in which there is a higher incidence).

  • Inherited (genetic or familial) CJD accounts for 5% to 15% of cases or about 10 deaths in the UK per year. It is associated with pathogenic mutations in the prion protein gene.

  • Variant CJD (vCJD) is a novel form of human prion disease, first recognised in the UK in 1996. It is believed to result from consumption of food derived from cattle infected with bovine spongiform encephalopathy (BSE), a fatal neurodegenerative disease that causes sponge-like changes in the brain. vCJD is characterised by extensive lymphoreticular tissue involvement and a young age at onset (the mean age at death is 28 years, compared with 66 years for sCJD). The clinical course of vCJD is distinct from that of sCJD. People with vCJD frequently present with sensory and psychiatric symptoms that are uncommon in people with sCJD. They develop progressive neurological signs such as gait disturbance, ataxia and tremor. The median duration of illness is longer than for sCJD (14 months compared with 4 months). By 2016 there had been 178 cases of vCJD in the UK. Three cases are considered to have occurred through blood transfusion and 175 cases were related to dietary exposure to BSE. The prevalence of non-clinical vCJD (abnormal prion accumulation in tissues without clinical symptoms) in the general UK population is estimated to be 240 per million, based on retrospective analyses of appendix specimens. In the UK, between 1988 and 1996, a series of measures were put in place to reduce the risk of people being exposed to BSE. Over the past 8 years there have been 0 or 1 deaths per year in the UK attributed to vCJD.

  • Iatrogenic CJD (iCJD) accounts for less than 1% of cases each year. It is the transmission of prions through surgical or medical procedures (especially from tissues with the highest concentration of prions, such as brain and posterior eye tissue) or human-derived products (growth hormone, gonadotropin, dura mater grafts and packed red blood cells). Surgically transmitted CJD (stCJD) is theoretically possible through prion-contaminated instruments that have been previously used on patients with CJD. This includes patients who are asymptomatic but infectious because neural tissue has a high infectious load, and there are difficulties in eradicating prions from surgical instruments. The most common causes of iCJD are historic use of human growth hormone and dura mater grafts, according to a review of worldwide iCJD cases published in 2012. In the UK, 85 iCJD cases were identified between 1970 and 2016. Eight were from dura mater grafts, 1 was from human gonadotrophin and 76 were from human growth hormone. There were 4 cases of possible stCJD through contaminated neurosurgical instruments between 1952 and 1974; 3 in the UK and 1 in France. The University of Sheffield's School of Health and Related Research (ScHARR) report indicates that the risk of stCJD is currently low and no cases were reported between 2005 and 2018. However, there is uncertainty about the future risk of stCJD because of the potentially long incubation period of CJD, difficulties in eradicating prions from surgical instruments, the presumed subclinical prevalence in the general population, and high levels of infectivity in the brain. Neurosurgical instruments used on people who are possibly carriers of CJD are handled in accordance with the Advisory Committee on Dangerous Pathogens' Transmissible Spongiform Encephalopathies risk management subgroup's guidance on safe working and the prevention of infection.

  • The number of deaths per year in the UK attributed to the 4 categories of CJD is reported by the National CJD Research and Surveillance Unit.

Incubation periods

2.3 Evidence from retrospective data in the ScHARR report shows that the incubation period of iatrogenic CJD ranges from 1 to 42 years with durations towards the shorter end of the range reported in cases of stCJD. Incubation times might be affected by the recipient's genotype and the infecting prion strain or subtype of CJD.

Infectivity

2.4 The infectivity of CJD is likely to be moderated by a number of factors including the recipient's genotype, the infecting prion strain, and the route of transmission. There are limited data about infectious dose or infectious titre in humans. The ID50 is the dose that would give the person receiving it a 50% chance of becoming infected. High values are expressed in log or factor-of-10 terms. For example, 1 g of brain tissue can have an ID50 of 108 (8 log). This means it carries a dose of 100,000,000 ID50. The model assumes that intracranial transfer of 0.01 micrograms of such brain tissue would result in the recipient having a 50% chance of becoming infected with CJD.

  • National Institute for Health and Care Excellence (NICE)