Variant Creutzfeldt-Jakob disease (vCJD)
The initial symptoms of variant Creutzfeldt-Jakob disease (vCJD) are usually psychiatric, most frequently depression, anxiety and withdrawal (Henry & Knight, 2002; Will & Ward, 2004). After a median of six months, neurological features develop, including cognitive impairment, ataxia and involuntary movements. The clinical course is progressive with the development of dementia and diffuse cortical deficits.
Death occurs after a median of 14 months from the onset of symptoms (range 6–39 months) and is often due to an intercurrent infection (Will & Ward, 2004). However, Henry and Knight stated that the disease is fatal after a median of 13 months and a range of 6–39 months (Henry & Knight, 2002).
In the study by Hilton (Hilton, 2006) the mean age at death for vCJD is 26 years and 29 years with a range of 12–74 years (Will & Ward, 2004; Smiths, 2004). This is in line with the overall median age of 28 at death for all vCJD diagnoses in the UK during the period January 1994–December 2009, with a range from 14 to 75 (Andrews, 2010). During the epidemic, the median age of onset did not change over time, suggesting an important age-related risk. This could be due to an age-dependent susceptibility, age-related exposure or both (Hilton, 2006). There is no significant difference in deaths between males and females (56% male, p=0.12).
Precise estimates of the length and variability of the incubation period for vCJD are difficult to obtain since they require knowledge of the time of infection, whereas exposure may have occurred over several years. Ghani assumes that the incubation period is approximately 15–18 years (Ghani, 2002), whereas Collinge concludes that the incubation period would be at least 11 years (Collinge, 1999).
Although a peak has passed, it is possible that there will be future peaks, possibly in other genetic groups. To date, all cases of vCJD have been genotyped as methionine homozygous at codon 129 of the PrP gene (about 40% of the population). If the other 60% of the population is not completely resistant to infection, the disease in these individuals is associated with a longer incubation period, therefore epidemics in this group may still occur (Smith, 2004). Kaski et al. reported the first suspected clinical case of vCJD in an individual heterozygous for methionine/valine (Kaski, 2009).
There is also the possibility of ongoing person-to-person transmission, as seen with three cases of vCJD infection following transfusion of packed red blood cells from asymptomatic donors who subsequently died from vCJD (Ironside, 2010). Furthermore, Peden et al. described a vCJD infection in the first known asymptomatic patient (Millar, 2010; Peden, 2010). The patient died from unrelated pathology with no evidence of neurological diseases. The infection was detected in a study of autopsy and biopsy materials from 17 neurologically asymptomatic patients with haemophilia, considered to be at increased risk of vCJD. The most likely route of infection was receipt of UK plasma products.
Finally, Smith assumes that the ascertainment of vCJD cases in young adults is nearly complete. In the absence of a reliable, minimally invasive, diagnostic test, the possibility remains that cases in the elderly are being missed due to the small proportion of those dying with dementia that are subject to post-mortem examination (Smiths, 2004).
Model input summary
Table 1. Transition probabilities and distributions used in the outcome tree
Health outcome |
Percent of health outcome in health state |
Transition probability |
Source/assumption |
Fatal cases following symptomatic infection |
|
100% |
|
Table 2. Disability weights and duration
Health
outcome |
Disability Weight (DW) (Haagsma, 2015) |
Duration |
||
DW |
Label |
In years |
Source |
|
Symptomatic infection |
0.407 (0.36–0.46) |
Motor plus cognitive impairments, severe.
|
1.151 (0.5–3.205) |
Will & Ward, 2004 |
References
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Andrews NJ. Incidence of variant Creutzfeldt-Jakob disease diagnoses and deaths in the UK, January 1994 - December 2009. 2010 [updated 22 June 2010]; Available from: http://www.cjd.ed.ac.uk/cjdq64jun10.pdf.
Collinge J. Variant Creutzfeldt-Jakob disease. Lancet. 1999 Jul 24;354(9175):317-23.
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Ironside JW. Variant Creutzfeldt-Jakob disease. Haemophilia. 2010 Jul;16 Suppl 5:175-80.
Kaski D, Mead S, Hyare H, Cooper S, Jampana R, Overell J, et al. Variant CJD in an individual heterozygous for PRNP codon 129. Lancet. 2009 Dec 19;374(9707):2128.
Millar CM, Connor N, Dolan G, Lee CA, Makris M, Wilde J, et al. Risk reduction strategies for variant Creutzfeldt-Jakob disease transmission by UK plasma products and their impact on patients with inherited bleeding disorders. Haemophilia. 2010 Mar;16(2):305-15.
Peden A, McCardle L, Head MW, Love S, Ward HJ, Cousens SN, et al. Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia. 2010 Mar;16(2):296-304.
Smith PG, Cousens SN, d' Huillard Aignaux JN, Ward HJ, Will RG. The epidemiology of variant Creutzfeldt-Jakob disease. Curr Top Microbiol Immunol. 2004;284:161-91.
Will RG, Ward HJ. Clinical features of variant Creutzfeldt-Jakob disease. Curr Top Microbiol Immunol. 2004;284:121-32.