Creutzfeldt‐Jakob disease and blood transfusion safety

Abstract

Transmissible spongiform encephalopathies (TSEs) are untreatable, fatal neurologic diseases affecting mammals. Human disease forms include sporadic, familial and acquired Creutzfeldt-Jakob disease (CJD). While sporadic CJD (sCJD) has been recognized for near on 100 years, variant CJD (vCJD) was first reported in 1996 and is the result of food-borne transmission of the prion of bovine spongiform encephalopathy (BSE, 'mad cow disease'). Currently, 230 vCJD cases have been reported in 12 countries, the majority in the UK (178) and France (27). Animal studies demonstrated highly efficient transmission of natural scrapie and experimental BSE by blood transfusion and fuelled concern that sCJD was potentially transfusion transmissible. No such case has been recorded and case-control evaluations and lookback studies indicate that, if transfusion transmission occurs at all, it is very rare. In contrast, four cases of apparent transfusion transmission of vCJD infectivity have been identified in the UK. Risk minimization strategies in response to the threat of vCJD include leucodepletion, geographically based donor deferrals and deferral of transfusion recipients. A sensitive and specific, high-throughput screening test would provide a potential path to mitigation but despite substantial effort no such test has yet appeared. The initial outbreak of vCJD appears to be over, but concern remains about subsequent waves of disease among those already infected. There is considerable uncertainty about the size of the infected population, and there will be at least a perception of some continuing risk to blood safety. Accordingly, at least some precautionary measures will remain in place and continued surveillance is necessary.

Prevalence in Britain of abnormal prion protein in human appendices before and after exposure to the cattle BSE epizootic

“…A variety of risk management measures remain in place to limit the risks of person-to-person transmission of prions by blood transfusion or by re-use of surgical instruments in the general population. Whichever way the Appendix-3 Study is interpreted, the prevalence range of prion infection remains a concern, and maintenance of the full range of precautionary measures is a judgement that would need to be balanced against the costs and benefits of these risk reduction measures [1,37,42]. More specifically, it is reasonable to assume that the highest prevalence of asymptomatic infection is in the cohort that had greatest exposure to BSE and which contains all known clinical cases of vCJD, the 1961 to 1985 birth cohort [36].…”

“…This could lead to a self-sustaining secondary epidemic of vCJD in the population [16]. Several expensive and ongoing measures are in place to mitigate these risks [1,37,42]. A number of studies have been conducted to improve the accuracy of vCJD abnormal PrP prevalence estimates [7,11,15].…”

International haemovigilance: what have we learned and what do we need to do next?

“…Haemovigilance data have also been very useful for monitoring agents of great concern for the safety of blood supplies, such as variant Creutzfeldt–Jakob disease (vCJD). The threat of transfusion‐transmitted vCJD drove major policy and practice changes in the UK and internationally, but fortunately the feared ‘epidemic’ has not materialised (Bolton‐Maggs and Poles, ; Seed et al, ).…”

Review: Fluid biomarkers in the human prion diseases

“…These concerns were realised as iatrogenic vCJD was diagnosed in three recipients of blood from donors who themselves went on to die from vCJD, and asymptomatic infection was seen in a fourth transfusion recipient at post-mortem (89-91). These circumstances have been extensively reviewed elsewhere (92). This transmission of vCJD from human to human through transfusion of blood that was donated during the asymptomatic incubation phase of the disease,…”