The importance of ongoing international surveillance for Creutzfeldt-Jakob disease.

Neil Watson,Maurizio Pocchiari,Terri Lindsay,Alison Green,Janet Mackenzie,Suvankar Pal,Anna Ladogana,Jean-Philippe Brandel,Colin Smith,Peter Hermann,Inga Zerr

doi:10.1038/s41582-021-00488-7

Abstract

Creutzfeldt–Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disease associated with the accumulation of misfolded prion protein in the CNS. International CJD surveillance programmes have been active since the emergence, in the mid-1990s, of variant CJD (vCJD), a disease linked to bovine spongiform encephalopathy. Control measures have now successfully contained bovine spongiform encephalopathy and the incidence of vCJD has declined, leading to questions about the requirement for ongoing surveillance. However, several lines of evidence have raised concerns that further cases of vCJD could emerge as a result of prolonged incubation and/or secondary transmission. Emerging evidence from peripheral tissue distribution studies employing high-sensitivity assays suggests that all forms of human prion disease carry a theoretical risk of iatrogenic transmission. Finally, emerging diseases, such as chronic wasting disease and camel prion disease, pose further risks to public health. In this Review, we provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance remains vital both from a public health perspective and to support essential research into disease pathophysiology, enhanced diagnostic tests and much-needed treatments.

Highlights

Abstract | Creutzfeldt–Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disease associated with the accumulation of misfolded prion protein in the CNS
International CJD surveillance programmes have been active since the emergence, in the mid-1990s, of variant CJD, a disease linked to bovine spongiform encephalopathy
Emerging diseases, such as chronic wasting disease and camel prion disease, pose further risks to public health. In this Review, we provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance remains vital both from a public health perspective and to support essential research into disease pathophysiology, enhanced diagnostic tests and much-needed treatments

Summary

Key points

Creutzfeldt–Jakob disease (CJD) is a transmissible and universally fatal human prion disease; surveillance programmes exist globally to monitor trends in CJD epidemiology and mitigate public health risks. The Mok et al case study[20] added to growing concerns extrapolated from findings in iCJD5 and Kuru[9] that prion disease transmission might be associated with extensive incubation (multiple decades) in individuals with non-MM c129 genotypes, adding weight to ongoing concerns of a ‘second wave’ of individuals developing vCJD. Prion diseases transmit more readily between individuals of the same species than between individuals of different species[157,158] This characteristic is reflected in the significantly lower attack rate seen in primary vCJD secondary to BSE exposure (232 cases of vCJD worldwide[10] despite widespread exposure in BSE-affected regions11,135) than in iCJD5,104 and Kuru[9,94] (transmitted from human to human) and in the detection of several transfusion-mediated vCJD transmission events[159,160].

Bilateral pulvinar high signal on MRI scan

30 Cases of BSE Deaths from vCJD

Findings

Conclusions