European Creutzfeldt-Jakob Disease surveillance
The European Creutzfeldt-Jakob disease Surveillance System (EUROCJD) has achieved all the objectives in the original grant application to DG SANCO (Directorate-General for Health and Consumers). The ability to continue to coordinate CJD surveillance in Europe has had major benefits and, in particular, the facility to provide real-time data on variant Creutzfeldt-Jakob disease (vCJD) internationally. Through the EUROCJD system, it has been possible to establish travel history in all cases of vCJD internationally, and to confirm in each case the country of likely human exposure to bovine spongiform encephalopathy (BSE). Cases of secondary iatrogenic transmission of vCJD through blood transfusion have been identified in the UK.
The primary objective of this project has been the identification and characterisation of all cases of vCJD in participating countries by establishing surveillance systems for all forms of human prion disease in these countries. Another objective of the system has been to identify novel forms of human prion disease that might be related to BSE infection and cases caused by secondary iatrogenic transmission. The project aimed to provide an early warning system for new cases of vCJD and to disseminate information via a website and through scientific publications.[+] Read More
During the period of the project, cases of variant CJD have been identified (see Table) in a number of regions with additional cases of vCJD having also been identified in Japan (1) and USA (2).
Some cases of vCJD, including cases in Ireland, Canada and the USA, had a history of extended residence in the UK during the period of maximal human exposure to the BSE agent and it is likely that the causal exposure to BSE took place in the UK rather than the country of residence. By using the known periods of residence of these cases in the UK, it is possible to estimate a mean incubation period and the figure compares this with incubation period estimates in iatrogenic CJD in kuru. It is apparent that the estimated incubation periods in relation to vCJD are consistent with both the minimum incubation period in iatrogenic CJD and kuru and the median incubation period in relation to human growth hormone-related CJD.
An important issue in relation to the non-UK cases of vCJD is whether they were exposed to BSE infection in exports from the UK or to indigenous BSE. This issue is discussed in a paper form the EUROCJD group1. The conclusion is that it is possible that non-UK variant cases were exposed to UK exports rather than to indigenous BSE and this may be consistent with the relative delay in the peak of onsets of vCJD cases in France in comparison to the UK. The temporal development of outbreaks of vCJD is an important issue in relation to predictions of the future course of any epidemic. In the UK, the data indicates that the numbers of deaths per annum from vCJD may have peaked in 2000 and there may also have been a peak in non-UK cases in 2005.
One important aspect of vCJD epidemiology is that there have been a number of cases of vCJD identified in recent years in France, although this is consistent with a previous mathematical prediction model2. One aspect of the French cases that differentiates them from the UK cases is that they are older on average, although this is of only borderline significance.
During the period of the project, four instances of presumed transmission of vCJD infection through blood transfusion were identified in the UK, including three clinical cases and one subclinical or preclinical infection3.
The third US patient with vCJD was born and raised in Saudi Arabia and has lived permanently in the United States since late 2005. According to the US case report, the patient was most likely infected as a child when living in Saudi Arabia.
*The case from Japan had resided in the UK for 24 days in the period 1980 to 1996.
1 Sanchez Juan P et al., Sources of Variant Creutzfeldt-Jakob Disease outside the United Kingdom, EID, 13, pp. 1166-1169
2 Chadeau-Hyam, M., Alperovitch, A., Risk of variant Creutzfeldt-Jakob disease in France, Int J Epidemiol, 2005, 34, pp. 46-52
3 Hewitt, P.E., Llewelyn, C.A., Mackenzie, J., Will, R.G., Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiology Review study, Vox Sanguinis, 2006, 91, pp. 221-230
Further analysis suggested that transfusion transmission of vCJD was relatively efficient and that infectivity was present in blood during the incubation period and prior to the onset of clinical disease. This is an important issue for public health and individuals with vCJD who had previously donated blood; they have also been identified in France, Spain, Ireland and Saudi Arabia.
In addition to the study of vCJD, other forms of human prion disease are also ascertained and annual mortality rates per million for sporadic CJD (definite and probable) in participating countries are listed online (see www.eurocjd.ed.ac.uk).
The major activity is achieving and sustaining systematic surveillance for human prion diseases in participating countries. This involves a regular review of methodologies, of diagnostic criteria and of available diagnostic investigations.
An important activity for the group has been the review and, if necessary, updating of diagnostic criteria for the various forms of human prion disease. A decision was made to revise the variant CJD diagnostic criteria to take account of two cases, in Italy and Japan, in which the EEG had shown an appearance that was consistent with sporadic CJD. The revised criteria have been adopted in an amended form as the case definition for the European Centre for Disease Prevention and Controls (ECDC) Designated Surveillance Networks.
The results of a questionnaire circulated to determine public health policies in participating countries in relation to the potential of secondary transmission of vCJD are being analysed.
An Early Warning System was provided by the EUROCJD system during the course of the project. Each new case of vCJD has been notified following identification through the Early Warning and Response System (EWRS).
The project has had important implications for public health policy in the EU and other countries.