Title: Review on patient safety and reduction of risk of transmission of Creutzfeldt-Jakob disease (CJD)
Funder: Department of Health and Social Care

Abstract: The objective of the proposed work is to review the evidence base for the current risk of CJD transmission related to surgery in order to provide up-to-date relevant evidence to NICE about the cost-effectiveness of potential management strategies.

Lay abstract: Creutzfeldt-Jakob disease (CJD) is a progressive, fatal disease affecting the brain. CJD is caused by an abnormal infectious protein called a prion. Once infected, the concentration of CJD prions varies throughout the body, but reaches high levels in the brain and posterior eye, resulting in symptoms such as rapidly progressive dementia, personality changes, and hallucinations. Most people with CJD will die within a year of the symptoms, usually from infection, as the condition also causes physical symptoms that leave the body vulnerable to infection. Four classifications of CJD exist: sporadic CJD, variant CJD, familial CJD and iatrogenic CJD. Referrals of suspected CJD, and values for definitely-related CJD death (with neuropathological confirmation) or probably-related deaths (without neuropathological confirmation) are recorded by the CJD Research and Surveillance Unit in Edinburgh. 1 This source estimated that since 1990 there have been 3640 referrals and 2284 deaths of definite and probable CJD (data as at 2nd May 2017). Sporadic CJD has historically been the most common type of CJD, and has accounted for around 100 deaths per year in the UK since 2010. The cause of sporadic CJD is uncertain. Variant CJD (vCJD) was observed following the exposure of the UK population during the late 1980s and early 1990s to bovine spongiform encephalopathy that was transmitted to humans by eating food contaminated with the brain, spinal cord, or digestive tract of infected carcasses. This epidemic was first described in 19962 with the number of definitely or probably related deaths peaking at 28 in 2000. Since 2000, this value has diminished with only two definitely or probably related deaths reported since 2012. All people who have contracted vCJD have died. Familial (or genetic CJD) accounts for approximately 10 definite or probably related deaths per year. The number of definite or probably related iatrogenic deaths, which are caused by medical or surgical treatment, are fewer still, with none believed to have been through a surgical route, with the majority associated with blood transfusion. Prions are unlikely to be completely deactivated by conventional hospital cleansing and sterilisation techniques. Patients may therefore be infected iatrogenically with CJD by surgical instruments, endoscopes or laryngoscopes used previously in patients who have asymptomatic CJD but who are infectious. Immediately following the outbreak, the potential scale of the vCJD infection remained uncertain and estimations varied.3-5 Surgical transmission of CJD was considered to pose a potential risk to public health. Therefore, in 2005 the National Institute for Health and Care Excellence (NICE) commissioned ScHARR, at the University of Sheffield to conduct a systematic review and cost-effectiveness model of evidence on patient safety and reduction of risks of transmission of CJD.6 This evidence, together with data collected from elicitation experts were used to populate a model assessing the cost-effectiveness of single-use surgical instruments.7, 8 The outputs from the model were used to inform the guidance produced by the NICE IP Programme “Patient safety and reduction of risks of transmission of Creutzfeldt-Jakob Disease (CJD) and vCJD” (IPG196). While the cost-effectiveness analysis indicated that the introduction of single-use instruments was not cost-effective, there was great uncertainty in these results and a recommendation was made by the study authors that policy might need to be revised if pertinent data become available. An epidemic of CJD has not occurred since the original guidance and there is no evidence of transmission by surgery to date. However, a number of developments are believed to have occurred since 2006, which may be relevant to the research update. These include: • the finding of abnormal prion accumulation in the appendices of low-risk cohorts [e.g. born after 1996], • continued evolution of high quality and less expensive single-use instruments, • the failure of new decontamination methods effective against human prions to appear; the experts consulted for IPG196 believed these would emerge within five years, • difficulties implementing the recommendations in IPG196 across a number of units. The Medical Director of NHS England, the Chief Medical Officer and the chair of the DH Advisory Committee on Dangerous Pathogens (ACDP) have indicated that a full update of IPG196 is needed to have a system in place that is fit for purpose and to reduce the risks of horizontal transmission of CJD. In 2017, the NICE Interventional Procedures Programme commissioned ScHARR to update the clinical and cost-effectiveness evidence from 2005 (project no. IP1553). References 1. Edinburgh TUo. THE NATIONAL CJD RESEARCH & SURVEILLANCE UNIT (NCJDRSU). 2017. http://www.cjd.ed.ac.uk/ (Accessed 11.07.2017). 2. Will RG, Ironside J, Zeidler M, Estibeiro K, Cousens S, Smith P, et al. A new variant of Creutzfeldt-Jakob disease in the UK. The Lancet 1996;347:921-5. 3. Hilton DA, Ghani AC, Conyers L, Edwards P, McCardle L, Ritchie D, et al. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. The Journal of pathology 2004;203:733-9. 4. Ghani AC, Ferguson NM, Donnelly CA, Anderson RM. Factors determining the pattern of the variant Creutzfeldt-Jakob disease (vCJD) epidemic in the UK. Proceedings of the Royal Society of London B: Biological Sciences 2003;270:689-98. 5. Clarke P, Ghani AC. Projections of the future course of the primary vCJD epidemic in the UK: inclusion of subclinical infection and the possibility of wider genetic susceptibility. Journal of the Royal Society Interface 2005;2:19-31. 6. Lloyd Jones M, Stevenson M, Sutton A. Patient safety and reduction of risk of transmission of Creutzfeldt– Jakob disease (CJD) via interventional procedures. Systematic literature reviews final report. National Institute for Health and Care Excellence: School of Health and Related Research, University of Sheffield; 2006. 7. Stevenson M, Oakley JE, Chick SE, Chalkidou K. The cost-effectiveness of surgical instrument management policies to reduce the risk of vCJD transmission to humans. Journal of the Operational Research Society 2009;60:506-18. 8. Stevenson M, Oakley J, Chick SE. Patient safety and reduction of risk of transmission of Creutzfeldt–Jakob disease (CJD) via interventional procedures—final report: School of Health and Related Research, University of Sheffield; 2006.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: NEUROLOGICAL