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  • Review Article
  • Published:

The importance of ongoing international surveillance for Creutzfeldt–Jakob disease

Nature Reviews Neurology volume 17, pages 362–379 (2021)Cite this article

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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.

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 variant CJD (vCJD) epidemic was a devastating consequence of the bovine spongiform encephalopathy (BSE) epizootic.

  • Studies indicate the widespread prevalence of vCJD-associated prion protein in BSE-exposed populations.

  • Although new diagnoses of vCJD have declined in parallel with the suppression of BSE, lessons from other prion diseases indicate the potential for highly extensive incubation phases lasting decades.

  • Emerging animal prion diseases might harbour the potential for zoonotic transmission to humans.

  • Continued CJD surveillance is a necessity to meet the potential for further cases of vCJD or the emergence of novel prion diseases in humans.

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Fig. 1: The global burden of vCJD.
Fig. 2: Brain MRI in individuals with CJD.
Fig. 3: Histological features of sCJD.
Fig. 4: Western blot typing in CJD.
Fig. 5: Histological features of genetic forms of prion diseases.
Fig. 6: Histological features of vCJD.
Fig. 7: BSE and vCJD in the UK.
Fig. 8: A model CJD surveillance system.

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References

  1. National CJD Research & Surveillance Unit. 28th Annual Report 2019. Creutzfeldt-Jakob Disease Surveillance in the UK https://www.cjd.ed.ac.uk/sites/default/files/Report28.pdf (2020).

  2. Uttley, L., Carroll, C., Wong, R., Hilton, D. A. & Stevenson, M. Creutzfeldt-Jakob disease: a systematic review of global incidence, prevalence, infectivity, and incubation. Lancet Infect. Dis. 20, e2–e10 (2020).

    Article  PubMed  Google Scholar 

  3. Kovacs, G. G. et al. Genetic prion disease: the EUROCJD experience. Hum. Genet. 118, 166–174 (2005). An international study on the epidemiology of genetic prion diseases in the Euro-CJD network nations.

    Article  CAS  PubMed  Google Scholar 

  4. Masters, C. L. et al. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann. Neurol. 5, 177–188 (1979).

    Article  CAS  PubMed  Google Scholar 

  5. Brown, P. et al. Iatrogenic Creutzfeldt-Jakob disease, final assessment. Emerg. Infect. Dis. 18, 901–907 (2012). A detailed summary of the iCJD epidemic worldwide.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Prusiner, S. B. Prions. Proc. Natl Acad. Sci. USA 95, 13363–13383 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nobel Media. The Nobel Prize in Physiology or Medicine 1997 https://www.nobelprize.org/prizes/medicine/1997/summary (2020).

  8. Gajdusek, D. C. & Zigas, V. Kuru; clinical, pathological and epidemiological study of an acute progressive degenerative disease of the central nervous system among natives of the Eastern Highlands of New Guinea. Am. J. Med. 26, 442–469 (1959).

    Article  CAS  PubMed  Google Scholar 

  9. Collinge, J. et al. Kuru in the 21st century–an acquired human prion disease with very long incubation periods. Lancet 367, 2068–2074 (2006). A surveillance report on Kuru, a disease associated with endocannibalism in Papua New Guinea, demonstrating extensive incubation lasting several decades associated with prion protein codon 129 polymorphism status.

    Article  PubMed  Google Scholar 

  10. National CJD Research & Surveillance Unit. Variant CJD cases worldwide https://www.cjd.ed.ac.uk/surveillance/data-and-reports (2020).

  11. Smith, P. G. & Bradley, R. Bovine spongiform encephalopathy (BSE) and its epidemiology. Br. Med. Bull. 66, 185–198 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. World Organization for Animal Health. Number of cases of bovine spongiform encephalopathy (BSE) reported in the United Kingdom https://www.oie.int/en/animal-health-in-the-world/bse-specific-data/number-of-cases-in-the-united-kingdom/ (2020).

  13. World Organization for Animal Health. Number of reported cases of bovine spongiform encephalopathy (BSE) in farmed cattle worldwide (excluding the United Kingdom) https://www.oie.int/animal-health-in-the-world/bse-situation-in-the-world-and-annual-incidence-rate/number-of-reported-cases-worldwide-excluding-the-united-kingdom/ (2020).

  14. Centers for Disease Control and Prevention. Chronic Wasting Disease (CWD) https://www.cdc.gov/prions/cwd/occurrence.html (2020).

  15. Rudge, P. et al. Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years. Brain 138, 3386–3399 (2015). Case series demonstrating that human growth hormone-associated iCJD can incubate for several decades, influenced by prion protein gene codon 129 polymorphism status.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Brandel, J. P. et al. Variant Creutzfeldt-Jakob disease diagnosed 7.5 years after occupational exposure. N. Engl. J. Med. 383, 83–85 (2020).

    Article  PubMed  Google Scholar 

  17. Parchi, P. et al. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann. Neurol. 46, 224–233 (1999). A large clinicopathological series on sCJD demonstrating the relationship between clinical features and the underlying genetics and neuropathology.

    Article  CAS  PubMed  Google Scholar 

  18. Palmer, M. S., Dryden, A. J., Hughes, J. T. & Collinge, J. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 352, 340–342 (1991).

    Article  CAS  PubMed  Google Scholar 

  19. Collinge, J., Palmer, M. S. & Dryden, A. J. Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 337, 1441–1442 (1991).

    Article  CAS  PubMed  Google Scholar 

  20. Mok, T. et al. Variant Creutzfeldt-Jakob disease in a patient with heterozygosity at PRNP Codon 129. N. Engl. J. Med. 376, 292–294 (2017). The first confirmed case of vCJD with prion protein gene codon 129 heterozygosity, a factor associated with prolonged incubation in other forms of acquired prion disease.

    Article  PubMed  Google Scholar 

  21. Chen, C. & Dong, X. P. Epidemiological characteristics of human prion diseases. Infect. Dis. Poverty 5, 47 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Parchi, P. et al. Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann. Neurol. 39, 767–778 (1996).

    Article  CAS  PubMed  Google Scholar 

  23. Head, M. W. et al. Prion protein heterogeneity in sporadic but not variant Creutzfeldt-Jakob disease: UK cases 1991-2002. Ann. Neurol. 55, 851–859 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Tee, B. L., Longoria Ibarrola, E. M. & Geschwind, M. D. Prion diseases. Neurol. Clin. 36, 865–897 (2018).

    Article  PubMed  Google Scholar 

  25. Will, R. G. et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347, 921–925 (1996). The original case series demonstrating a new variant of CJD in the UK with atypical features, identifying the beginning of the vCJD epidemic.

    Article  CAS  PubMed  Google Scholar 

  26. Chazot, G. et al. New variant of Creutzfeldt-Jakob disease in a 26-year-old French man. Lancet 347, 1181 (1996). The first identified case of vCJD in France, following the recognition of vCJD in the UK the same year.

    Article  CAS  PubMed  Google Scholar 

  27. Maheshwari, A. et al. Recent US case of variant Creutzfeldt-Jakob disease — global implications. Emerg. Infect. Dis. 21, 750–759 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. European Centre for Disease Prevention and Control. Creutzfeldt-Jakob disease. Annual Epidemiological Report for 2017. (ECDC, 2020).

  29. Brandel, J. P., Peckeu, L. & Haïk, S. The French surveillance network of Creutzfeldt-Jakob disease. Epidemiological data in France and worldwide. Transfus. Clin. Biol. 20, 395–397 (2013).

    Article  PubMed  Google Scholar 

  30. Heinemann, U. et al. Creutzfeldt-Jakob disease in Germany: a prospective 12-year surveillance. Brain 130, 1350–1359 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. Maddox, R. A. et al. Prion disease incidence in the United States: 2003-2015. Neurology 94, e153–e157 (2020).

    Article  PubMed  Google Scholar 

  32. Geschwind, M. D. Prion diseases. Continuum 21, 1612–1638 (2015).

    PubMed  Google Scholar 

  33. Ladogana, A. et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology 64, 1586–1591 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Horan, G. et al. Creutzfeldt-Jakob disease in Ireland: epidemiological aspects 1980-2002. Eur. Neurol. 51, 132–137 (2004).

    Article  PubMed  Google Scholar 

  35. Velásquez-Pérez, L., Rembao-Bojorquez, D., Guevara, J., Guadarrama-Torres, R. M. & Trejo-Contreras, A. Creutzfeldt-Jakob disease in Mexico. Neuropathology 27, 419–428 (2007).

    Article  PubMed  Google Scholar 

  36. Begue, C. et al. Creutzfeldt-Jakob disease surveillance in Argentina, 1997-2008. Neuroepidemiology 37, 193–202 (2011).

    Article  PubMed  Google Scholar 

  37. Martins, V. R., Gomes, H. R., Chimelli, L., Rosemberg, S. & Landemberger, M. C. Prion diseases are undercompulsory notification in Brazil: surveillance of cases evaluated by biochemicaland/or genetic markers from 2005 to 2007. Dement. Neuropsychol. 1, 347–355 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Adam, A. M. & Akuku, O. Creutzfeldt-Jakob disease in Kenya. Trop. Med. Int. Health 10, 710–712 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Hajjaj, I. & Kissani, N. First case of presumed sporadic Creutzfeldt-Jakob disease in Marrakech, Morocco [In French]. Med. Trop. 71, 289–291 (2011).

    CAS  Google Scholar 

  40. Negm, M. & Hashish, E. Probable Creutzfeldt-Jakob disease — a case report at Suez Canal University Hospital, Egypt. Egypt. J. Neurol. Psychiatry Neurosurg. 55, 36 (2019).

    Article  Google Scholar 

  41. Nozaki, I. et al. Prospective 10-year surveillance of human prion diseases in Japan. Brain 133, 3043–3057 (2010).

    Article  PubMed  Google Scholar 

  42. Shi, Q. et al. Analysis of the advantage features of Beijing surveillance network for Creutzfeldt-Jakob disease. Prion 9, 304–314 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lolekha, P., Rasheed, A. & Yotsarawat, C. Creutzfeldt-Jakob disease in a tertiary care hospital in Thailand: a case series and review of the literature. J. Mov. Disord. 8, 136–140 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Qi, C., Zhang, J. T., Zhao, W., Xing, X. W. & Yu, S. Y. Sporadic Creutzfeldt-Jakob disease: a retrospective analysis of 104 cases. Eur. Neurol. 83, 65–72 (2020).

    Article  PubMed  Google Scholar 

  45. Lim, J. S. et al. Characteristics of Korean patients with suspected Creutzfeldt-Jakob disease with 14-3-3 protein in cerebrospinal fluid: Preliminary study of the Korean Creutzfeldt-Jakob disease active surveillance program. Prion 9, 136–143 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Klug, G. M. et al. Intensity of human prion disease surveillance predicts observed disease incidence. J. Neurol. Neurosurg. Psychiatry 84, 1372–1377 (2013).

    Article  PubMed  Google Scholar 

  47. Stehmann, C. et al. Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2019. Commun. Dis. Intell. https://doi.org/10.33321/cdi.2019.43.35 (2020).

    Article  Google Scholar 

  48. Ahmad, A., Rao, F. & Aieshah, S. Two cases of Creutzfeldt-Jakob disease from an ongoing dementia registry in Pakistan. J. Pak. Med. Assoc. 64, 705–707 (2014).

    PubMed  Google Scholar 

  49. Kharel, H., Adhikari, P., Pokhrel, N. B., Kharel, Z. & Nepal, G. The first reported case of Creutzfeldt-Jakob disease from Nepal. Clin. Case Rep. 8, 198–202 (2020).

    Article  PubMed  Google Scholar 

  50. Safar, J. G. Molecular pathogenesis of sporadic prion diseases in man. Prion 6, 108–115 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Collins, S. et al. Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study. Lancet 353, 693–697 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Mahillo-Fernandez, I. et al. Surgery and risk of sporadic Creutzfeldt-Jakob disease in Denmark and Sweden: registry-based case-control studies. Neuroepidemiology 31, 229–240 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Puopolo, M., Ladogana, A., Vetrugno, V. & Pocchiari, M. Transmission of sporadic Creutzfeldt-Jakob disease by blood transfusion: risk factor or possible biases. Transfusion 51, 1556–1566 (2011).

    Article  PubMed  Google Scholar 

  54. de Pedro Cuesta, J. et al. Sensitivity to biases of case-control studies on medical procedures, particularly surgery and blood transfusion, and risk of Creutzfeldt-Jakob disease. Neuroepidemiology 39, 1–18 (2012). A review article evaluating 18 case–control studies in sCJD demonstrating the methodological challenges involved in working with CJD.

    Article  PubMed  Google Scholar 

  55. Alperovitch, A. et al. Codon 129 prion protein genotype and sporadic Creutzfeldt-Jakob disease. Lancet 353, 1673–1674 (1999).

    Article  CAS  PubMed  Google Scholar 

  56. Cooper, S. A., Murray, K. L., Heath, C. A., Will, R. G. & Knight, R. S. Isolated visual symptoms at onset in sporadic Creutzfeldt-Jakob disease: the clinical phenotype of the “Heidenhain variant”. Br. J. Ophthalmol. 89, 1341–1342 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hermann, P. et al. Validation and utilization of amended diagnostic criteria in Creutzfeldt-Jakob disease surveillance. Neurology 91, e331–e338 (2018). Prospective study validating the 2017 diagnostic criteria for sCJD demonstrating a sensitivity of 97% and a specificity of 99%.

    Article  PubMed  Google Scholar 

  58. Zerr, I. et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain 132, 2659–2668 (2009). International study demonstrating the utility of MRI for the diagnosis of sCJD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tschampa, H. J. et al. Pattern of cortical changes in sporadic Creutzfeldt-Jakob disease. Am. J. Neuroradiol. 28, 1114–1118 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Steinhoff, B. J. et al. Diagnostic value of periodic complexes in Creutzfeldt-Jakob disease. Ann. Neurol. 56, 702–708 (2004).

    Article  PubMed  Google Scholar 

  61. Schmitz, M. et al. Validation of 14-3-3 protein as a marker in sporadic Creutzfeldt-Jakob disease diagnostic. Mol. Neurobiol. 53, 2189–2199 (2016).

    Article  CAS  PubMed  Google Scholar 

  62. Chohan, G. et al. The role of cerebrospinal fluid 14-3-3 and other proteins in the diagnosis of sporadic Creutzfeldt-Jakob disease in the UK: a 10-year review. J. Neurol. Neurosurg. Psychiatry 81, 1243–1248 (2010).

    Article  CAS  PubMed  Google Scholar 

  63. Sanchez-Juan, P. et al. CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 67, 637–643 (2006).

    Article  CAS  PubMed  Google Scholar 

  64. Green, A. J. E. RT-QuIC: a new test for sporadic CJD. Pract. Neurol. 19, 49–55 (2019).

    Article  PubMed  Google Scholar 

  65. Cramm, M. et al. Stability and reproducibility underscore utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease. Mol. Neurobiol. 53, 1896–1904 (2016). International study demonstrating consistently high sensitivity of RT-QuIC and specificity of 99% for the diagnosis of CJD.

    Article  CAS  PubMed  Google Scholar 

  66. Atarashi, R., Sano, K., Satoh, K. & Nishida, N. Real-time quaking-induced conversion: a highly sensitive assay for prion detection. Prion 5, 150–153 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ironside, J. W., Ritchie, D. L. & Head, M. W. Phenotypic variability in human prion diseases. Neuropathol. Appl. Neurobiol. 31, 565–579 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Wadsworth, J. D. & Collinge, J. Molecular pathology of human prion disease. Acta Neuropathol. 121, 69–77 (2011).

    Article  CAS  PubMed  Google Scholar 

  69. Mead, S., Lloyd, S. & Collinge, J. Genetic factors in mammalian prion diseases. Annu. Rev. Genet. 53, 117–147 (2019).

    Article  CAS  PubMed  Google Scholar 

  70. Mead, S. Prion disease genetics. Eur. J. Hum. Genet. 14, 273–281 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. Public Health England. Public health action following a report of a new case of CJD or a person at increased risk of CJD. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/474338/CJD_public_health_action_new_case_301015.pdf (2015).

  72. US Department of Health and Human Services, Food and Drug Administration. Recommendations to reduce the possible risk of transmission of Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease by blood and blood components. https://www.fda.gov/media/124156/download (2020).

  73. Mastrianni, J. A. The genetics of prion diseases. Genet. Med. 12, 187–195 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Bagyinszky, E. et al. Early-onset Alzheimer’s disease patient with prion (PRNP) p.Val180Ile mutation. Neuropsychiatr. Dis. Treat. 15, 2003–2013 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Moore, R. C. et al. Huntington disease phenocopy is a familial prion disease. Am. J. Hum. Genet. 69, 1385–1388 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Webb, T. E. et al. Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series. Brain 131, 2632–2646 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Paucar, M. et al. Genotype-phenotype analysis in inherited prion disease with eight octapeptide repeat insertional mutation. Prion 7, 501–510 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Oldoni, E. et al. PRNP P39L variant is a rare cause of frontotemporal dementia in Italian population. J. Alzheimers Dis. 50, 353–357 (2016).

    Article  CAS  PubMed  Google Scholar 

  79. Nitrini, R. et al. Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17. Arq. Neuropsiquiatr. 59, 161–164 (2001).

    Article  CAS  PubMed  Google Scholar 

  80. Cracco, L., Appleby, B. S. & Gambetti, P. Fatal familial insomnia and sporadic fatal insomnia. Handb. Clin. Neurol. 153, 271–299 (2018).

    Article  PubMed  Google Scholar 

  81. Goldfarb, L. G. et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. Science 258, 806–808 (1992).

    Article  CAS  PubMed  Google Scholar 

  82. Takada, L. T. et al. Genetic prion disease: experience of a rapidly progressive dementia center in the United States and a review of the literature. Am. J. Med. Genet. B Neuropsychiatr. Genet. 174, 36–69 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Shi, Q. et al. The features of genetic prion diseases based on Chinese surveillance program. PLoS One 10, e0139552 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Hsiao, K. et al. Mutation of the prion protein in Libyan Jews with Creutzfeldt-Jakob disease. N. Engl. J. Med. 324, 1091–1097 (1991).

    Article  CAS  PubMed  Google Scholar 

  85. Ladogana, A. et al. High incidence of genetic human transmissible spongiform encephalopathies in Italy. Neurology 64, 1592–1597 (2005).

    Article  CAS  PubMed  Google Scholar 

  86. Montagna, P., Gambetti, P., Cortelli, P. & Lugaresi, E. Familial and sporadic fatal insomnia. Lancet Neurol. 2, 167–176 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. Jeong, B. H. & Kim, Y. S. Genetic studies in human prion diseases. J. Korean Med. Sci. 29, 623–632 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Melis, M. et al. Genetic Creutzfeldt-Jakob disease in Sardinia: a case series linked to the PRNP R208H mutation due to a single founder effect. Neurogenetics 21, 251–257 (2020).

    Article  CAS  PubMed  Google Scholar 

  89. Beck, J., Collinge, J. & Mead, S. Prion protein gene M232R variation is probably an uncommon polymorphism rather than a pathogenic mutation. Brain 135, e209 (2012).

    Article  PubMed  Google Scholar 

  90. Rodriguez, M. M. et al. A novel mutation (G114V) in the prion protein gene in a family with inherited prion disease. Neurology 64, 1455–1457 (2005).

    Article  CAS  PubMed  Google Scholar 

  91. Katrak, S. M. et al. Familial Creutzfeldt-Jakob disease in an Indian kindred. Ann. Indian. Acad. Neurol. 22, 458–461 (2019).

    PubMed  PubMed Central  Google Scholar 

  92. Will, R. G. Acquired prion disease: iatrogenic CJD, variant CJD, kuru. Br. Med. Bull. 66, 255–265 (2003).

    Article  CAS  PubMed  Google Scholar 

  93. Collinge, J. et al. A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea. Philos. Trans. R. Soc. Lond. B Biol. Sci. 363, 3725–3739 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Alpers, M. P. Review. The epidemiology of kuru: monitoring the epidemic from its peak to its end. Philos. Trans. R. Soc. Lond. B Biol. Sci. 363, 3707–3713 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Duffy, P. et al. Letter: Possible person-to-person transmission of Creutzfeldt-Jakob disease. N. Engl. J. Med. 290, 692–693 (1974).

    Article  CAS  PubMed  Google Scholar 

  96. Koch, T. K., Berg, B. O., De Armond, S. J. & Gravina, R. F. Creutzfeldt-Jakob disease in a young adult with idiopathic hypopituitarism. Possible relation to the administration of cadaveric human growth hormone. N. Engl. J. Med. 313, 731–733 (1985).

    Article  CAS  PubMed  Google Scholar 

  97. Boyd, A. et al. Transmissible spongiform encephalopathies in Australia. Commun. Dis. Intell. Q. Rep. 25, 248–252 (2001).

    CAS  PubMed  Google Scholar 

  98. Croes, E. A., Roks, G., Jansen, G. H., Nijssen, P. C. & van Duijn, C. M. Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone. J. Neurol. Neurosurg. Psychiatry 72, 792–793 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Brown, P., Brandel, J.-P., Preese, M. & Sato, T. Iatrogenic Creutzfeldt–Jakob disease: the waning of an era. Neurology 67, 389–393 (2006).

    Article  PubMed  Google Scholar 

  100. Ae, R. et al. Update: dura mater graft-associated Creutzfeldt-Jakob disease - Japan, 1975-2017. MMWR Morb. Mortal Wkly Rep. 67, 274–278 (2018). Most recently published report on dura mater graft-associated iCJD in Japan, the centre of the global epidemic.

    Article  PubMed  PubMed Central  Google Scholar 

  101. US Department of Health and Human Services, Food and Drug Administration. Guidance for Industry and FDA Staff. Class II Special Controls Guidance Document: Human Dura Mater https://www.fda.gov/media/71309/download (2003).

  102. World Health Organization. WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies. Report of a WHO consultation Geneva, Switzerland, 23-26 March 1999. (WHO, 1999).

  103. Cali, I. et al. Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone. Acta Neuropathol. Commun. 3, 37 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Hamaguchi, T. et al. Insight into the frequent occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan. J. Neurol. Neurosurg. Psychiatry 84, 1171–1175 (2013).

    Article  PubMed  Google Scholar 

  105. Abrams, J. Y. et al. Lower risk of Creutzfeldt-Jakob disease in pituitary growth hormone recipients initiating treatment after 1977. J. Clin. Endocrinol. Metab. 96, E1666–E1669 (2011).

    Article  CAS  PubMed  Google Scholar 

  106. Brandel, J. P. et al. Distribution of codon 129 genotype in human growth hormone-treated CJD patients in France and the UK. Lancet 362, 128–130 (2003).

    Article  CAS  PubMed  Google Scholar 

  107. Zeidler, M. et al. New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests. Lancet 350, 903–907 (1997).

    Article  CAS  PubMed  Google Scholar 

  108. National CJD Research & Surveillance Unit. Creutzfeldt-Jakob Disease Surveillance in the UK. 27th Annual Report 2018. http://www.cjd.ed.ac.uk/sites/default/files/report27.pdf (2019).

  109. Spencer, M. D., Knight, R. S. & Will, R. G. First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features. BMJ 324, 1479–1482 (2002). Cohort study of 100 individuals with vCJD describing the clinical features important for diagnosis and surveillance.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Heath, C. A. et al. Validation of diagnostic criteria for variant Creutzfeldt-Jakob disease. Ann. Neurol. 67, 761–770 (2010).

    PubMed  Google Scholar 

  111. Collie, D. A. et al. Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathologically confirmed cases. Am. J. Neuroradiol. 24, 1560–1569 (2003). Large study characterizing the pulvinar thalamic abnormalities seen on MRI in vCJD.

    PubMed  PubMed Central  Google Scholar 

  112. Green, A. J. E. et al. Use of 14–3–3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease. J. Neurol. Neurosurg. Psychiatry 70, 744 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Ironside, J. W. Neuropathology of variant Creutzfeldt-Jakob disease. C. R. Biol. 325, 27–31 (2002).

    Article  CAS  PubMed  Google Scholar 

  114. Ward, H. J. et al. Risk factors for variant Creutzfeldt-Jakob disease: a case-control study. Ann. Neurol. 59, 111–120 (2006).

    Article  PubMed  Google Scholar 

  115. Ironside, J. W. Variant Creutzfeldt-Jakob disease. Haemophilia 16, 175–180 (2010).

    Article  CAS  PubMed  Google Scholar 

  116. Brown, P. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease. BMJ 322, 841–844 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Food Standards Agency. Bovine Spongiform Encephalopathy. Food Standards Agency https://www.food.gov.uk/safety-hygiene/bovine-spongiform-encephalopathy-bse (2017).

  118. World Organization for Animal Health. Bovine Spongiform Encephalopathy (BSE) https://www.oie.int/en/animal-health-in-the-world/animal-diseases/Bovine-spongiform-encephalopathy/ (2018).

  119. Centers for Disease Control and Prevention. Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease. Control Measures https://www.cdc.gov/prions/bse/control-measures.html (2018).

  120. The European Parliament. Regulation (EC) no 999/2001 of the European Parliament and of the Council as of 22 May 2001 laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies. Official Journal of the European Communities L147/1-40. https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:32001R0999&from=EN (2001).

  121. BBC News. Timeline: British Beef Ban http://news.bbc.co.uk/2/hi/uk_news/4785610.stm#:~:text=MARCH%201996,live%20cattle%2C%20meat%20and%20products (2006).

  122. Bradley, R. & Wilesmith, J. W. Epidemiology and control of bovine spongiform encephalopathy (BSE). Br. Med. Bull. 49, 932–959 (1993).

    Article  CAS  PubMed  Google Scholar 

  123. Collinge, J., Sidle, K. C., Meads, J., Ironside, J. & Hill, A. F. Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383, 685–690 (1996). Landmark study demonstrating molecular characteristics and transmission properties of vCJD-associated prion protein with similarity to that seen in BSE, suggesting BSE was the source of vCJD.

    Article  CAS  PubMed  Google Scholar 

  124. Palmer Clephan, M. A week that shook the meat industry: the effects on the UK beef industry of the BSE crisis. Br. Food J. 98, 17–25 (1996).

    Article  Google Scholar 

  125. Food Standards Agency. BSE and Beef. New Controls Explained. Advicsory Committee for Social Science https://acss.food.gov.uk/sites/default/files/multimedia/pdfs/publication/bsebooklet.pdf (2006).

  126. BBC News. UK Beef Export Ban Lifted by EU http://news.bbc.co.uk/1/hi/uk/4784810.stm (2006).

  127. European Commission. BSE: UK Embargo to be Lifted https://ec.europa.eu/commission/presscorner/detail/en/IP_06_278 (2006).

  128. BBC News. UK Beef Exports to US Resume after more than 20 years https://www.bbc.co.uk/news/business-54347426 (2020).

  129. Fickling, D. EU Lifts Ban on British Beef Exports https://www.theguardian.com/uk/2006/may/03/bse.eu (2006).

  130. BBC News. ‘Mad cow disease’: What is BSE? https://www.bbc.co.uk/news/uk-45906585 (2018).

  131. Cooper, J. D. & Bird, S. M. UK bovine carcass meat consumed as burgers, sausages and other meat products: by birth cohort and gender. J. Cancer Epidemiol. Prev. 7, 49–57 (2002).

    Article  CAS  PubMed  Google Scholar 

  132. Cooper, J. D. & Bird, S. M. UK dietary exposure to BSE in beef mechanically recovered meat: by birth cohort and gender. J. Cancer Epidemiol. Prev. 7, 59–70 (2002).

    Article  CAS  PubMed  Google Scholar 

  133. Cooper, J. D. & Bird, S. M. UK dietary exposure to BSE in head meat: by birth cohort and gender. J. Cancer Epidemiol. Prev. 7, 71–83 (2002).

    Article  CAS  PubMed  Google Scholar 

  134. Chen, C.-C. & Wang, Y.-H. Estimation of the exposure of the UK population to the bovine spongiform encephalopathy agent through dietary intake during the period 1980 to 1996. PLoS One 9, e94020 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. Chadeau-Hyam, M. et al. Estimation of the exposure of the French population to the BSE agent: comparison of the 1980-95 consumption of beef products containing mechanically recovered meat in France and the UK, by birth cohort and gender. Stat. Methods Med. Res. 12, 247–260 (2003).

    Article  PubMed  Google Scholar 

  136. Reuters. France confirms case of mad cow disease Reuters https://www.reuters.com/article/us-france-madcow-idUSKCN0WQ15S (2016).

  137. BBC News. ‘Mad cow disease’ at Aberdeenshire farm after BSE confirmed https://www.bbc.co.uk/news/uk-scotland-north-east-orkney-shetland-45901043 (2018).

  138. Bruce, M. E. et al. Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389, 498–501 (1997).

    Article  CAS  PubMed  Google Scholar 

  139. Lasmezas, C. I. et al. BSE transmission to macaques. Nature 381, 743–744 (1996).

    Article  CAS  PubMed  Google Scholar 

  140. Collinge, J. et al. Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378, 779–783 (1995).

    Article  CAS  PubMed  Google Scholar 

  141. Will, R. G., Matthews, W. B., Smith, P. G. & Hudson, C. A retrospective study of Creutzfeldt-Jakob disease in England and Wales 1970-1979. II: Epidemiology. J. Neurol. Neurosurg. Psychiatry 49, 749–755 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Will, R. G. et al. Descriptive epidemiology of Creutzfeldt-Jakob disease in six European countries, 1993–1995. Ann. Neurol. 43, 763–767 (1998).

    Article  CAS  PubMed  Google Scholar 

  143. Puopolo, M. et al. Mortality trend from sporadic Creutzfeldt-Jakob disease (CJD) in Italy, 1993-2000. J. Clin. Epidemiol. 56, 494–499 (2003).

    Article  PubMed  Google Scholar 

  144. Nakamura, Y. et al. Incidence rate of Creutzfeldt-Jakob disease in Japan. Int. J. Epidemiol. 28, 130–134 (1999).

    Article  CAS  PubMed  Google Scholar 

  145. Case Western Reserve University. National Prion Disease Pathology Surveillance Center https://case.edu/medicine/pathology/divisions/prion-center (2021).

  146. Brandel, J. P. et al. Variant Creutzfeldt-Jakob disease in France and the United Kingdom: evidence for the same agent strain. Ann. Neurol. 65, 249–256 (2009).

    Article  CAS  PubMed  Google Scholar 

  147. Riverol, M. et al. Variant Creutzfeldt-Jakob disease occurring in mother and son. J. Neurol. Neurosurg. Psychiatry 83, 235–236 (2012).

    Article  PubMed  Google Scholar 

  148. Coulthart, M. B. et al. A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia. Brain 139, 2609–2616 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Kaski, D. et al. Variant CJD in an individual heterozygous for PRNP codon 129. Lancet 374, 2128 (2009).

    Article  PubMed  Google Scholar 

  150. Wells, G. A. et al. A novel progressive spongiform encephalopathy in cattle. Vet. Rec. 121, 419–420 (1987).

    Article  CAS  PubMed  Google Scholar 

  151. Appleby, B. S. et al. Characteristics of established and proposed sporadic Creutzfeldt-Jakob disease variants. Arch. Neurol. 66, 208–215 (2009).

    PubMed  Google Scholar 

  152. Hamaguchi, T. et al. Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease. Neurology 64, 643–648 (2005).

    Article  CAS  PubMed  Google Scholar 

  153. Krasnianski, A. et al. Clinical findings and diagnostic tests in the MV2 subtype of sporadic CJD. Brain 129, 2288–2296 (2006).

    Article  PubMed  Google Scholar 

  154. Meissner, B. et al. Sporadic Creutzfeldt-Jakob disease: clinical and diagnostic characteristics of the rare VV1 type. Neurology 65, 1544–1550 (2005).

    Article  CAS  PubMed  Google Scholar 

  155. National CJD Research and Surveillance Unit. Estimation of the incidence of variant Creutzfeldt-Jakob disease diagnoses and deaths in the UK January 1994-December 2011 https://www.cjd.ed.ac.uk/sites/default/files/cjdq72.pdf (2012).

  156. Klitzman, R. L. Incubation period of human prion disease. Lancet 368, 913 (2006).

    Article  PubMed  Google Scholar 

  157. Moore, R. A., Vorberg, I. & Priola, S. A. Species barriers in prion diseases–brief review. Arch. Virol. Suppl. 19, 187–202 (2005).

    Google Scholar 

  158. Hagiwara, K. I., Hara, H. & Hanada, K. Species-barrier phenomenon in prion transmissibility from a viewpoint of protein science. J. Biochem. 153, 139–145 (2013).

    Article  CAS  PubMed  Google Scholar 

  159. Hewitt, P. E., Llewelyn, C. A., Mackenzie, J. & Will, R. G. Creutzfeldt-Jakob disease and blood transfusion: results of the UK transfusion medicine epidemiological review study. Vox Sang. 91, 221–230 (2006). UK surveillance study demonstrating two cases of transfusion-transmitted vCJD and another case of pre-clinical vCJD.

    Article  CAS  PubMed  Google Scholar 

  160. Urwin, P. J., Mackenzie, J. M., Llewelyn, C. A., Will, R. G. & Hewitt, P. E. Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study. Vox Sang. 110, 310–316 (2016).

    Article  CAS  PubMed  Google Scholar 

  161. Wadsworth, J. D. et al. Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 358, 171–180 (2001). Autopsy study demonstrating peripheral presence of prion protein in the lymphoreticular system of individuals with vCJD.

    Article  CAS  PubMed  Google Scholar 

  162. Hilton, D. A. et al. Specificity of lymphoreticular accumulation of prion protein for variant Creutzfeldt-Jakob disease. J. Clin. Pathol. 57, 300–302 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Notari, S. et al. Multiorgan detection and characterization of protease-resistant prion protein in a case of variant CJD examined in the United States. PLoS One 5, e8765 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. Hilton, D. A. Pathogenesis and prevalence of variant Creutzfeldt-Jakob disease. J. Pathol. 208, 134–141 (2006).

    Article  CAS  PubMed  Google Scholar 

  165. Hilton, D. A. et al. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J. Pathol. 203, 733–739 (2004). The first in a trilogy of studies demonstrating prevalent abnormal prion protein in resected appendix tissues derived from UK individuals exposed to BSE.

    Article  CAS  PubMed  Google Scholar 

  166. Gill, O. N. et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ 347, f5675 (2013). The second in a trilogy of studies demonstrating prevalent abnormal prion protein in resected appendix tissues derived from UK individuals exposed to BSE.

    Article  PubMed  PubMed Central  Google Scholar 

  167. Gill, O. N. et al. Prevalence in Britain of abnormal prion protein in human appendices before and after exposure to the cattle BSE epizootic. Acta Neuropathol. 139, 965–976 (2020). The third in a trilogy of studies, demonstrating abnormal prion protein in appendices resected from UK individuals outside of the established window of exposure to BSE.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Clewley, J. P. et al. Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ 338, b1442 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Hill, A. F. et al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353, 183–189 (1999).

    Article  CAS  PubMed  Google Scholar 

  170. Wroe, S. J. et al. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 368, 2061–2067 (2006).

    Article  PubMed  Google Scholar 

  171. Llewelyn, C. A. et al. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 363, 417–421 (2004).

    Article  CAS  PubMed  Google Scholar 

  172. Peden, A. H., Head, M. W., Ritchie, D. L., Bell, J. E. & Ironside, J. W. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364, 527–529 (2004).

    Article  PubMed  Google Scholar 

  173. Davidson, L. R., Llewelyn, C. A., Mackenzie, J. M., Hewitt, P. E. & Will, R. G. Variant CJD and blood transfusion: are there additional cases? Vox Sang. 107, 220–225 (2014).

    Article  CAS  PubMed  Google Scholar 

  174. Peden, A. et al. Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia 16, 296–304 (2010).

    Article  CAS  PubMed  Google Scholar 

  175. Houston, F., Foster, J. D., Chong, A., Hunter, N. & Bostock, C. J. Transmission of BSE by blood transfusion in sheep. Lancet 356, 999–1000 (2000).

    Article  CAS  PubMed  Google Scholar 

  176. McCutcheon, S. et al. All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD. PLoS One 6, e23169 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Bishop, M. T. et al. Prion infectivity in the spleen of a PRNP heterozygous individual with subclinical variant Creutzfeldt-Jakob disease. Brain 136, 1139–1145 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  178. Clarke, P., Will, R. G. & Ghani, A. C. Is there the potential for an epidemic of variant Creutzfeldt-Jakob disease via blood transfusion in the UK? J. R. Soc. Interface 4, 675–684 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Garske, T. & Ghani, A. C. Uncertainty in the tail of the variant Creutzfeldt-Jakob disease epidemic in the UK. PLoS One 5, e15626 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Department of Health & Social Care. Risk assessment of the transmission of vCJD by blood components https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/843533/risk-assessment-of-the-transmission-of-vcjd-by-blood-components.pdf (2019).

  181. Bennett, P. & Daraktchiev, M. vCJD and transfusion of blood components: an updated risk assessment. (Department of Health, 2013).

  182. Crowder, L. A., Schonberger, L. B., Dodd, R. Y. & Steele, W. R. Creutzfeldt-Jakob disease lookback study: 21 years of surveillance for transfusion transmission risk. Transfusion 57, 1875–1878 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Holmqvist, J. et al. No evidence of transfusion transmitted sporadic Creutzfeldt-Jakob disease: results from a bi-national cohort study. Transfusion 60, 694–697 (2020).

    Article  PubMed  Google Scholar 

  184. Riggs, J. E., Moudgil, S. S. & Hobbs, G. R. Creutzfeldt-Jakob disease and blood transfusions: a meta-analysis of case-control studies. Mil. Med. 166, 1057–1058 (2001).

    Article  CAS  PubMed  Google Scholar 

  185. Wilson, K., Code, C. & Ricketts, M. N. Risk of acquiring Creutzfeldt-Jakob disease from blood transfusions: systematic review of case-control studies. BMJ 321, 17–19 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Urwin, P. et al. Sporadic Creutzfeldt-Jakob disease in 2 plasma product recipients, United Kingdom. Emerg. Infect. Dis. 23, 893–897 (2017).

    Article  PubMed Central  Google Scholar 

  187. UK Government. Advisory committee on the safety of blood, tissues and organs. paediatric components working group - report. importation of plasma and use of apheresis platelets as risk reduction measures for variant Creutzfeldt-Jakob Disease https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/829906/SaBTO_PC_report.pdf (2019).

  188. Concha-Marambio, L. et al. Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease. Sci. Transl. Med. 8, 370ra183 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  189. Bougard, D. et al. Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease. Sci. Transl. Med. 8, 370ra182 (2016).

    Article  PubMed  CAS  Google Scholar 

  190. Castilla, J., Saá, P., Hetz, C. & Soto, C. In vitro generation of infectious scrapie prions. Cell 121, 195–206 (2005).

    Article  CAS  PubMed  Google Scholar 

  191. Moudjou, M. et al. Highly infectious prions generated by a single round of microplate-based protein misfolding cyclic amplification. mBio 5, e00829–13 (2013).

    PubMed  PubMed Central  Google Scholar 

  192. Cali, I. et al. PMCA-replicated PrP(D) in urine of vCJD patients maintains infectivity and strain characteristics of brain PrP(D): transmission study. Sci. Rep. 9, 5191 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  193. Department of Health & Social Care. Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. part 3: laboratory containment and control measures https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/209757/Part_3_-_Laboratory_containment_and_control_measures.pdf (2003).

  194. Honda, H. et al. Abnormal prion protein deposits with high seeding activities in the skeletal muscle, femoral nerve, and scalp of an autopsied case of sporadic Creutzfeldt-Jakob disease. Neuropathology https://doi.org/10.1111/neup.12717 (2021).

    Article  PubMed  Google Scholar 

  195. Glatzel, M., Abela, E., Maissen, M. & Aguzzi, A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N. Engl. J. Med. 349, 1812–1820 (2003).

    Article  CAS  PubMed  Google Scholar 

  196. Takao, M., Kimura, H., Kitamoto, T. & Mihara, B. PrPres deposition in the retina is a common finding of sporadic, familial and iatrogenic Creutzfeldt-Jakob diseases (CJD). Acta Neuropathol. Commun. 6, 78 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  197. Head, M. W. et al. Prion protein accumulation in eyes of patients with sporadic and variant Creutzfeldt-Jakob disease. Invest. Ophthalmol. Vis. Sci. 44, 342–346 (2003).

    Article  PubMed  Google Scholar 

  198. Kresl, P. et al. Accumulation of prion protein in the vagus nerve in Creutzfeldt-Jakob disease. Ann. Neurol. 85, 782–787 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Orru, C. D. et al. Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease. Sci. Transl. Med. 9, eaam7785 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  200. Mammana, A. et al. Detection of prions in skin punch biopsies of Creutzfeldt-Jakob disease patients. Ann. Clin. Transl. Neurol. 7, 559–564 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Huor, A. et al. Infectivity in bone marrow from sporadic CJD patients. J. Pathol. 243, 273–278 (2017).

    Article  PubMed  Google Scholar 

  202. Ruegger, J. et al. A case-control study of sporadic Creutzfeldt-Jakob disease in Switzerland: analysis of potential risk factors with regard to an increased CJD incidence in the years 2001-2004. BMC Public Health 9, 18 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  203. Belondrade, M. et al. Correlation between bioassay and protein misfolding cyclic amplification for variant Creutzfeldt-Jakob disease decontamination studies. mSphere 5, e00649–19 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Notari, S. et al. Assessing prion infectivity of human urine in sporadic Creutzfeldt-Jakob disease. Emerg. Infect. Dis. 18, 21–28 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Moda, F. et al. Prions in the urine of patients with variant Creutzfeldt-Jakob disease. N. Engl. J. Med. 371, 530–539 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  206. Van Dorsselaer, A. et al. Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach. PLoS One 6, e17815 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  207. Wientjens, D. P. et al. Risk factors for Creutzfeldt-Jakob disease: a reanalysis of case-control studies. Neurology 46, 1287–1291 (1996).

    Article  CAS  PubMed  Google Scholar 

  208. Cocco, P. L., Caperna, A. & Vinci, F. Occupational risk factors for the sporadic form of Creutzfeldt-Jakob disease. Med. Lav. 94, 353–363 (2003).

    CAS  PubMed  Google Scholar 

  209. Alcalde-Cabero, E. et al. Health professions and risk of sporadic Creutzfeldt-Jakob disease, 1965 to 2010. Euro Surveill. 17, 20144 (2012).

    Article  PubMed  Google Scholar 

  210. Hermann, P. et al. Sporadic Creutzfeldt-Jakob disease among physicians, Germany, 1993-2018. Emerg. Infect. Dis. 26, 1710–1719 (2020).

    Article  CAS  PubMed Central  Google Scholar 

  211. Tenny, S., Kerndt, C. C. & Hoffman, M. R. in StatPearls (StatPearls Publishing LLC., 2021).

  212. Government of Canada. Creutzfeldt-Jakob Disease Surveillance System (CJDSS) Report https://www.canada.ca/en/public-health/services/surveillance/blood-safety-contribution-program/creutzfeldt-jakob-disease/cjd-surveillance-system.html (2021).

  213. Centers for Disease Control and Prevention. Creutzfeldt-Jakob Disease, Classic (CJD). Occurrence and Transmission https://www.cdc.gov/prions/cjd/occurrence-transmission.html (2019).

  214. Nishimura, Y. et al. A nationwide trend analysis in the incidence and mortality of Creutzfeldt–Jakob disease in Japan between 2005 and 2014. Sci. Rep. 10, 15509 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Rhoads, D. D. et al. Diagnosis of prion diseases by RT-QuIC results in improved surveillance. Neurology 95, e1017–e1026 (2020).

    Article  CAS  PubMed  Google Scholar 

  216. Murray, K. et al. Is there evidence of vertical transmission of variant Creutzfeldt-Jakob disease? J. Neurol. Neurosurg. Psychiatry 82, 729–731 (2011).

    Article  PubMed  Google Scholar 

  217. Puopolo, M. et al. Spatial epidemiology of sporadic Creutzfeldt-Jakob disease in Apulia, Italy. Neuroepidemiology 54, 83–90 (2020).

    Article  PubMed  Google Scholar 

  218. Klug, G. M. et al. Enhanced geographically restricted surveillance simulates sporadic Creutzfeldt-Jakob disease cluster. Brain 132, 493–501 (2009).

    Article  PubMed  Google Scholar 

  219. Hannaoui, S., Schatzl, H. M. & Gilch, S. Chronic wasting disease: Emerging prions and their potential risk. PLoS Pathog. 13, e1006619 (2017). Review article summarizing the chronic wasting disease epizootic in deer and elk.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  220. Osterholm, M. T. et al. Chronic wasting disease in cervids: implications for prion transmission to humans and other animal species. mBio 10, e01091–19 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  221. Våge, J. Chronic Wasting Disease (CWD) identified in a wild reindeer at Hardanger Plateau https://www.vetinst.no/en/news/chronic-wasting-disease-cwd-identified-in-a-wild-reindeer-at-hardanger-plateau (Norwegian Veterinary Institute, 2020).

  222. Mathiason, C. K. et al. Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314, 133–136 (2006).

    Article  CAS  PubMed  Google Scholar 

  223. Haley, N. J. et al. Detection of chronic wasting disease prions in salivary, urinary, and intestinal tissues of deer: potential mechanisms of prion shedding and transmission. J. Virol. 85, 6309–6318 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Tamguney, G. et al. Asymptomatic deer excrete infectious prions in faeces. Nature 461, 529–532 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Tennant, J. M. et al. Shedding and stability of CWD prion seeding activity in cervid feces. PLoS One 15, e0227094 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Miller, M. W., Williams, E. S., Hobbs, N. T. & Wolfe, L. L. Environmental sources of prion transmission in mule deer. Emerg. Infect. Dis. 10, 1003–1006 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  227. Mathiason, C. K. et al. Infectious prions in pre-clinical deer and transmission of chronic wasting disease solely by environmental exposure. PLoS One 4, e5916 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  228. Yuan, Q., Telling, G., Bartelt-Hunt, S. L. & Bartz, J. C. Dehydration of prions on environmentally relevant surfaces protects them from inactivation by freezing and thawing. J. Virol. 92, e02191–17 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  229. Angers, R. C. et al. Prions in skeletal muscles of deer with chronic wasting disease. Science 311, 1117 (2006).

    Article  CAS  PubMed  Google Scholar 

  230. Raymond, G. J. et al. Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. J. Virol. 81, 4305–4314 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Di Bari, M. A. et al. Chronic wasting disease in bank voles: characterisation of the shortest incubation time model for prion diseases. PLoS Pathog. 9, e1003219 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  232. Perrott, M. R., Sigurdson, C. J., Mason, G. L. & Hoover, E. A. Mucosal transmission and pathogenesis of chronic wasting disease in ferrets. J. Gen. Virol. 94, 432–442 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Mathiason, C. K. et al. Susceptibility of domestic cats to chronic wasting disease. J. Virol. 87, 1947–1956 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Hamir, A. N. et al. Transmission of chronic wasting disease of mule deer to Suffolk sheep following intracerebral inoculation. J. Vet. Diagn. Invest. 18, 558–565 (2006).

    Article  PubMed  Google Scholar 

  235. Hamir, A. N. et al. Experimental transmission of chronic wasting disease agent from mule deer to cattle by the intracerebral route. J. Vet. Diagn. Invest. 17, 276–281 (2005).

    Article  PubMed  Google Scholar 

  236. Marsh, R. F., Kincaid, A. E., Bessen, R. A. & Bartz, J. C. Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J. Virol. 79, 13794–13796 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Race, B. et al. Lack of transmission of chronic wasting disease to cynomolgus macaques. J. Virol. 92, e00550–18 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Kong, Q. et al. Chronic wasting disease of elk: transmissibility to humans examined by transgenic mouse models. J. Neurosci. 25, 7944–7949 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Barria, M. A. et al. Molecular barriers to zoonotic transmission of prions. Emerg. Infect. Dis. 20, 88–97 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Kurt, T. D. et al. Human prion protein sequence elements impede cross-species chronic wasting disease transmission. J. Clin. Invest. 125, 2548 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  241. Olszowy, K. M. et al. Six-year follow-up of a point-source exposure to CWD contaminated venison in an upstate New York community: risk behaviours and health outcomes 2005-2011. Public Health 128, 860–868 (2014).

    Article  CAS  PubMed  Google Scholar 

  242. Abrams, J. Y., Maddox, R. A., Harvey, A. R., Schonberger, L. B. & Belay, E. D. Travel history, hunting, and venison consumption related to prion disease exposure, 2006-2007 FoodNet Population Survey. J. Am. Diet. Assoc. 111, 858–863 (2011).

    Article  PubMed  Google Scholar 

  243. Williams, E. S. Chronic wasting disease. Vet. Pathol. 42, 530–549 (2005).

    Article  CAS  PubMed  Google Scholar 

  244. Miller, M. W. et al. Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming. J. Wildl. Dis. 36, 676–690 (2000).

    Article  CAS  PubMed  Google Scholar 

  245. Edmunds, D. R. et al. Chronic wasting disease drives population decline of white-tailed deer. PLoS One 11, e0161127 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  246. Zobeley, E., Flechsig, E., Cozzio, A., Enari, M. & Weissmann, C. Infectivity of scrapie prions bound to a stainless steel surface. Mol. Med. 5, 240–243 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Flechsig, E. et al. Transmission of scrapie by steel-surface-bound prions. Mol. Med. 7, 679–684 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Luhr, K. M., Löw, P., Taraboulos, A., Bergman, T. & Kristensson, K. Prion adsorption to stainless steel is promoted by nickel and molybdenum. J. Gen. Virol. 90, 2821–2828 (2009).

    Article  CAS  PubMed  Google Scholar 

  249. Bartz, J. C., Marsh, R. F., McKenzie, D. I. & Aiken, J. M. The host range of chronic wasting disease is altered on passage in ferrets. Virology 251, 297–301 (1998).

    Article  CAS  PubMed  Google Scholar 

  250. Padilla, D. et al. Sheep and goat BSE propagate more efficiently than cattle BSE in human PrP transgenic mice. PLoS Pathog. 7, e1001319 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. Espinosa, J. C. et al. Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie. Emerg. Infect. Dis. 15, 1214–1221 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  252. Babelhadj, B. et al. Prion disease in dromedary camels, Algeria. Emerg. Infect. Dis. 24, 1029–1036 (2018). First detection of a novel prion disease affecting camels in Algeria, not believed to be related to any known prion diseases.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. World Organization for Animal Health. Camel prion disease: a possible emerging disease in dromedary camel populations? https://oiebulletin.com/wp-content/uploads/2019/12/OIE-News-December-2019-Camel-prion-disease.pdf (2019).

  254. Horigan, V. et al. Assessing the aggregated probability of entry of a novel prion disease agent into the United Kingdom. Microb. Risk Anal. 16, 100134 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  255. Food and Agriculture Organization of the United Nations. Data: live animals http://www.fao.org/faostat/en/#data/QA (2020).

  256. Northern Territory Government. Environment: animals. Feral camel https://nt.gov.au/environment/animals/feral-animals/feral-camel (2015).

  257. Jaunmuktane, Z. et al. Evidence for human transmission of amyloid-beta pathology and cerebral amyloid angiopathy. Nature 525, 247–250 (2015). Autopsy study of eight individuals with iCJD demonstrating that amyloid-β may be transmissible via cadaveric hormone injection, analogous to prion protein.

    Article  CAS  PubMed  Google Scholar 

  258. Jaunmuktane, Z. et al. Evidence of amyloid-beta cerebral amyloid angiopathy transmission through neurosurgery. Acta Neuropathol. 135, 671–679 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. Banerjee, G. et al. Early onset cerebral amyloid angiopathy following childhood exposure to cadaveric dura. Ann. Neurol. 85, 284–290 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  260. Purro, S. A. et al. Transmission of amyloid-beta protein pathology from cadaveric pituitary growth hormone. Nature 564, 415–419 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  261. Eisele, Y. S. et al. Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science 330, 980–982 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. Olanow, C. W. & Brundin, P. Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov. Disord. 28, 31–40 (2013).

    Article  CAS  PubMed  Google Scholar 

  263. Ayers, J. I., Fromholt, S. E., O’Neal, V. M., Diamond, J. H. & Borchelt, D. R. Prion-like propagation of mutant SOD1 misfolding and motor neuron disease spread along neuroanatomical pathways. Acta Neuropathol. 131, 103–114 (2016).

    Article  CAS  PubMed  Google Scholar 

  264. Clavaguera, F. et al. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc. Natl Acad. Sci. USA 110, 9535–9540 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  265. Hamaguchi, T. et al. Significant association of cadaveric dura mater grafting with subpial Abeta deposition and meningeal amyloid angiopathy. Acta Neuropathol. 132, 313–315 (2016).

    Article  PubMed  Google Scholar 

  266. Muayqil, T., Gronseth, G. & Camicioli, R. Evidence-based guideline: diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology 79, 1499–1506 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  267. National CJD Research & Surveillance Unit. Diagnostic criteria for Creutzfeldt-Jakob disease https://www.cjd.ed.ac.uk/sites/default/files/criteria.pdf (2017).

  268. National CJD Research & Surveillance Unit. Protocol. Surveillance of CJD in the UK https://www.cjd.ed.ac.uk/sites/default/files/NCJDRSU%20surveillance%20protocol-april%202017%20rev2.pdf (2017).

  269. European Centre for Disease Prevention and Control. EU case definition https://www.ecdc.europa.eu/en/infectious-diseases-public-health/variant-creutzfeldt-jakob-disease/eu-case-definition (2017).

  270. McNiven, K. et al. Enteral feeding is associated with longer survival in the advanced stages of prion disease. Brain Commun. 1, fcz012 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  271. Mead, S. & Rudge, P. CJD mimics and chameleons. Pract. Neurol. 17, 113–121 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  272. Otto, M. et al. Efficacy of flupirtine on cognitive function in patients with CJD: a double-blind study. Neurology 62, 714–718 (2004).

    Article  CAS  PubMed  Google Scholar 

  273. Haik, S. et al. Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 13, 150–158 (2014).

    Article  CAS  PubMed  Google Scholar 

  274. Tsuboi, Y., Doh-Ura, K. & Yamada, T. Continuous intraventricular infusion of pentosan polysulfate: clinical trial against prion diseases. Neuropathology 29, 632–636 (2009).

    Article  PubMed  Google Scholar 

  275. Stewart, L. A., Rydzewska, L. H., Keogh, G. F. & Knight, R. S. Systematic review of therapeutic interventions in human prion disease. Neurology 70, 1272–1281 (2008).

    Article  PubMed  Google Scholar 

  276. Collinge, J. et al. Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial. Lancet Neurol. 8, 334–344 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  277. Geschwind, M. D. et al. Quinacrine treatment trial for sporadic Creutzfeldt-Jakob disease. Neurology 81, 2015–2023 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  278. Varges, D. et al. Doxycycline in early CJD: a double-blinded randomised phase II and observational study. J. Neurol. Neurosurg. Psychiatry 88, 119–125 (2017).

    Article  PubMed  Google Scholar 

  279. Barbosa, B. et al. Second-Generation RT-QuIC Assay for the diagnosis of Creutzfeldt-Jakob disease patients in Brazil. Front. Bioeng. Biotechnol. 8, 929 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  280. Watson, N. et al. Application of telehealth for comprehensive Creutzfeldt-Jakob disease surveillance in the United Kingdom. J. Neurol. Sci. 420, 117221 (2020).

    Article  PubMed  CAS  Google Scholar 

  281. Appleby, B. S. et al. Feasibility of remote assessment of human prion diseases for research and surveillance. Dement. Geriatr. Cogn. Disord. 47, 79–90 (2019).

    Article  PubMed  Google Scholar 

  282. Klein, B. C. & Busis, N. A. COVID-19 is catalyzing the adoption of teleneurology. Neurology 94, 903–904 (2020).

    Article  CAS  PubMed  Google Scholar 

  283. Abu-Rumeileh, S. et al. Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease. J. Neurol. Neurosurg. Psychiatry 91, 1181–1188 (2020).

    Article  PubMed  Google Scholar 

  284. Cooper, S. K. et al. Detection of CWD in cervids by RT-QuIC assay of third eyelids. PLoS One 14, e0221654 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  285. John, T. R., Schatzl, H. M. & Gilch, S. Early detection of chronic wasting disease prions in urine of pre-symptomatic deer by real-time quaking-induced conversion assay. Prion 7, 253–258 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  286. Renard, D., Castelnovo, G., Collombier, L., Thouvenot, E. & Boudousq, V. FDG-PET in Creutzfeldt-Jakob disease: analysis of clinical-PET correlation. Prion 11, 440–453 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  287. Vallabh, S. M., Minikel, E. V., Schreiber, S. L. & Lander, E. S. Towards a treatment for genetic prion disease: trials and biomarkers. Lancet Neurol. 19, 361–368 (2020).

    Article  CAS  PubMed  Google Scholar 

  288. National CJD Research and Surveillance Unit. Creutzfeldt–Jakob disease in the UK (by calendar year) https://www.cjd.ed.ac.uk/sites/default/files/figs.pdf (2021).

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Acknowledgements

This work was carried out on behalf of the European Creutzfeldt–Jakob Disease Surveillance Network, which is funded by European Centre for Disease Prevention and Control.

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Authors and Affiliations

  1. National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK

    Neil Watson, Alison Green, Terri Lindsay, Janet Mackenzie, Colin Smith & Suvankar Pal

  2. Cellule Nationale de référence des MCJ, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

    Jean-Philippe Brandel

  3. National Reference Centre for TSE, Department of Neurology, University Medical Centre Göttingen, Göttingen, Germany

    Peter Hermann & Inga Zerr

  4. Registry of Creutzfeldt-Jakob Disease, Department of Neuroscience, Istituto Superiore di Sanità, Rome, Italy

    Anna Ladogana & Maurizio Pocchiari

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Contributions

S.P. and N.W. researched data for the article, made a substantial contribution to discussion of content, wrote the article, and reviewed and edited the manuscript before submission. J.-P.B., P.H., A.L. and J.M. made a substantial contribution to discussion of content and reviewed and edited the manuscript before submission. A.G., M.P. C.S. and I.Z. reviewed and edited the manuscript before submission. T.L. researched data for the article.

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Correspondence to Suvankar Pal.

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Nature Reviews Neurology thanks B. Appleby, E. Belay and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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European Creutzfeldt–Jakob Disease Surveillance Network (EuroCJD): https://www.eurocjd.ed.ac.uk

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Watson, N., Brandel, JP., Green, A. et al. The importance of ongoing international surveillance for Creutzfeldt–Jakob disease. Nat Rev Neurol 17, 362–379 (2021). https://doi.org/10.1038/s41582-021-00488-7

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