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Research paper
Intensity of human prion disease surveillance predicts observed disease incidence
  1. Genevieve M J A Klug1,2,
  2. Handan Wand3,
  3. Marion Simpson1,
  4. Alison Boyd1,2,
  5. Matthew Law3,
  6. Colin L Masters1,2,
  7. Radoslav Matěj4,
  8. Rachel Howley5,
  9. Michael Farrell5,
  10. Maren Breithaupt6,
  11. Inga Zerr6,
  12. Cornelia van Duijn7,
  13. Carla Ibrahim-Verbaas7,8,
  14. Jan Mackenzie9,
  15. Robert G Will9,
  16. Jean-Philippe Brandel10,
  17. Annick Alperovitch10,
  18. Herbert Budka11,
  19. Gabor G Kovacs11,12,
  20. Gerard H Jansen13,
  21. Michael Coulthard14,
  22. Steven J Collins1,2
  1. 1Australian National Creuztfeldt-Jakob Disease Registry, Department of Pathology, The University of Melbourne, Parkville, Australia
  2. 2The Mental Health Research Institute of Victoria, The University of Melbourne, Parkville, Australia
  3. 3The Kirby Institute (formerly National Centre in HIV Epidemiology and Clinical Research), University of New South Wales, Coogee, Australia
  4. 4National Reference Laboratory for Diagnostics of Human Prion Diseases, Thomayer Teaching Hospital, Prague, Czech Republic
  5. 5CJD Surveillance Unit, Department of Neuropathology, Beaumont Hospital, Dublin, Ireland
  6. 6Dementia Research Unit, Department of Neurology, National Reference Center for TSE, Georg-August University, Göttingen, Germany
  7. 7Dutch National Prion Disease Registry, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
  8. 8Department of Neurology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
  9. 9National Creutzfeldt-Jakob Disease Research and Surveillance Unit, Western General Hospital, The University of Edinburgh, Edinburgh, UK
  10. 10Cellule Nationale de référence des maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, Paris, Cedex, France
  11. 11Institute of Neurology, Medical University of Vienna and Austrian Reference Center for Human Prion diseases, Vienna, Austria
  12. 12Semmelweis University Neuropathology and Prion Disease Reference Center, Budapest, Hungary
  13. 13Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada
  14. 14Canadian CJD Surveillance System and Prion Diseases Program, Public Health Agency of Canada, Winnipeg, Canada
  1. Correspondence to Genevieve M Klug or Professor Steven J Collins, Australian National Creuztfeldt-Jakob Disease Registry, Department of Pathology, The University of Melbourne, Parkville 3010, Australia; gmjak{at} or stevenjc{at}


Background Prospective national screening and surveillance programmes serve a range of public health functions. Objectively determining their adequacy and impact on disease may be problematic for rare disorders. We undertook to assess whether objective measures of disease surveillance intensity could be developed for the rare disorder sporadic Creutzfeldt–Jakob disease (CJD) and whether such measures correlate with disease incidence.

Method From 10 countries with national human prion disease surveillance centres, the annual number of suspected prion disease cases notified to each national unit (n=17 610), referrals for cerebrospinal fluid (CSF) 14-3-3 protein diagnostic testing (n=28 780) and the number of suspect cases undergoing diagnostic neuropathological examination (n=4885) from 1993 to 2006 were collected. Age and survey year adjusted incidence rate ratios with 95% CIs were estimated using Poisson regression models to assess risk factors for sporadic, non-sporadic and all prion disease cases.

Results Age and survey year adjusted analysis showed all three surveillance intensity measures (suspected human prion disease notifications, 14-3-3 protein diagnostic test referrals and neuropathological examinations of suspect cases) significantly predicted the incidence of sporadic CJD, non-sporadic CJD and all prion disease.

Conclusions Routine national surveillance methods adjusted as population rates allow objective determination of surveillance intensity, which correlates positively with reported incidence for human prion disease, especially sporadic CJD, largely independent of national context. The predictive relationship between surveillance intensity and disease incidence should facilitate more rapid delineation of aberrations in disease occurrence and assessment of the adequacy of disease monitoring by national registries.

  • Creutzfeldt-Jakob Disease
  • Prion
  • Epidemiology
  • Statistics

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