Abstract
Objectives: To predict the size of the vCJD epidemic it is important to know whether the description of cases of vCJD in 1996 represent the first cases of a new disease entity or whether detection was due to increased surveillance of CJD in humans. Detection of earlier cases would suggest a shorter incubation period and might lead to predictions of epidemic size being revised.
Methods: All certified deaths (excluding external injury and poisoning) in residents of Wales aged 15–45, between 1985 and 1995, were reviewed to detect vCJD deaths that might have been overlooked. 12 091 deaths were reviewed. "Non-specific fatal disorders compatible with vCJD" were defined. Deaths recorded to diseases other than those defined were rejected from further analysis (8769). Remaining cases (3322) were subdivided. Group A comprised deaths recorded to suicide, transport accidents, and those that could not be ascertained (ICD9 rubrics E950–959, E800–848, and 7999), a total of 2698 cases. Group B comprised deaths due to neurological disease, psychiatric disease, or substance abuse (624).
Results: For group A, remaining brain material was identified (n=218, 8.1%) and examined by routine histology and immunocytochemistry for prion protein. No cases of vCJD were detected. For group B, review of remaining clinical information was undertaken. Of 624 cases, information was available on 447 (72%). Brain tissue was examined by routine histology and immunocytochemistry in 47 (7.5%) cases. Sufficient clinical and pathological information was available to exclude all these as potential cases of vCJD.
Conclusion: Variant CJD is a new disease entity and not simply the result of better case ascertainment.
Full Text
The Full Text of this article is available as a PDF (110.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bell J. E., Gentleman S. M., Ironside J. W., McCardle L., Lantos P. L., Doey L., Lowe J., Fergusson J., Luthert P., McQuaid S. Prion protein immunocytochemistry--UK five centre consensus report. Neuropathol Appl Neurobiol. 1997 Feb;23(1):26–35. [PubMed] [Google Scholar]
- Bruce M. E., Will R. G., Ironside J. W., McConnell I., Drummond D., Suttie A., McCardle L., Chree A., Hope J., Birkett C. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature. 1997 Oct 2;389(6650):498–501. doi: 10.1038/39057. [DOI] [PubMed] [Google Scholar]
- Budka H., Aguzzi A., Brown P., Brucher J. M., Bugiani O., Gullotta F., Haltia M., Hauw J. J., Ironside J. W., Jellinger K. Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol. 1995 Oct;5(4):459–466. doi: 10.1111/j.1750-3639.1995.tb00625.x. [DOI] [PubMed] [Google Scholar]
- Esiri M. M., Carter J., Ironside J. W. Prion protein immunoreactivity in brain samples from an unselected autopsy population: findings in 200 consecutive cases. Neuropathol Appl Neurobiol. 2000 Jun;26(3):273–284. doi: 10.1046/j.1365-2990.2000.00239.x. [DOI] [PubMed] [Google Scholar]
- Harries-Jones R., Knight R., Will R. G., Cousens S., Smith P. G., Matthews W. B. Creutzfeldt-Jakob disease in England and Wales, 1980-1984: a case-control study of potential risk factors. J Neurol Neurosurg Psychiatry. 1988 Sep;51(9):1113–1119. doi: 10.1136/jnnp.51.9.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill A. F., Desbruslais M., Joiner S., Sidle K. C., Gowland I., Collinge J., Doey L. J., Lantos P. The same prion strain causes vCJD and BSE. Nature. 1997 Oct 2;389(6650):448-50, 526. doi: 10.1038/38925. [DOI] [PubMed] [Google Scholar]
- Hilton D. A., Fathers E., Edwards P., Ironside J. W., Zajicek J. Prion immunoreactivity in appendix before clinical onset of variant Creutzfeldt-Jakob disease. Lancet. 1998 Aug 29;352(9129):703–704. doi: 10.1016/S0140-6736(98)24035-9. [DOI] [PubMed] [Google Scholar]
- Lasmézas C. I., Deslys J. P., Demaimay R., Adjou K. T., Lamoury F., Dormont D., Robain O., Ironside J., Hauw J. J. BSE transmission to macaques. Nature. 1996 Jun 27;381(6585):743–744. doi: 10.1038/381743a0. [DOI] [PubMed] [Google Scholar]
- Majeed A., Lehmann P., Kirby L., Knight R., Coleman M. Extent of misclassification of death from Creutzfeldt-Jakob disease in England 1979-96: retrospective examination of clinical records. BMJ. 2000 Jan 15;320(7228):145–147. doi: 10.1136/bmj.320.7228.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott M. R., Will R., Ironside J., Nguyen H. O., Tremblay P., DeArmond S. J., Prusiner S. B. Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15137–15142. doi: 10.1073/pnas.96.26.15137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wells G. A., Scott A. C., Johnson C. T., Gunning R. F., Hancock R. D., Jeffrey M., Dawson M., Bradley R. A novel progressive spongiform encephalopathy in cattle. Vet Rec. 1987 Oct 31;121(18):419–420. doi: 10.1136/vr.121.18.419. [DOI] [PubMed] [Google Scholar]
- Will R. G., Ironside J. W., Zeidler M., Cousens S. N., Estibeiro K., Alperovitch A., Poser S., Pocchiari M., Hofman A., Smith P. G. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996 Apr 6;347(9006):921–925. doi: 10.1016/s0140-6736(96)91412-9. [DOI] [PubMed] [Google Scholar]
- Will R. G., Zeidler M., Stewart G. E., Macleod M. A., Ironside J. W., Cousens S. N., Mackenzie J., Estibeiro K., Green A. J., Knight R. S. Diagnosis of new variant Creutzfeldt-Jakob disease. Ann Neurol. 2000 May;47(5):575–582. [PubMed] [Google Scholar]
- Zeidler M., Stewart G. E., Barraclough C. R., Bateman D. E., Bates D., Burn D. J., Colchester A. C., Durward W., Fletcher N. A., Hawkins S. A. New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests. Lancet. 1997 Sep 27;350(9082):903–907. doi: 10.1016/s0140-6736(97)07472-2. [DOI] [PubMed] [Google Scholar]