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A link between scrapie and Creutzfeldt-Jakob disease (CJD) is likely to exist. Based on old observations on scrapie, new experiments on bovine spongiform encephalopathy, and modern reviews on CJD, my proposal fits general rules of virus transmission.

The scrapie model in hamsters has been used to search for the agents that cause Creutzfeldt-Jakob disease in man and similar transmissible encephalopathies in animals. We found structures that are extraordinarily small for a virus, but exhibit viral structural properties in negatively stained samples, by electron microscopy in fractions containing scrapie-associated fibrils.

The report in March 1996 of 10 human cases of a novel from of Creutzfeldt-Jakob disease in the United Kingdom, and its possible link to the agent that causes bovine spongiform encephalopathy (BSE), raises many questions about the safety of animal-derived products and by-products entering the food chain or being used in medicine. This Memorandum updates the preventive measures put forward in 1991 to minimize the risks associated with the use of bovine-derived materials in medicinal products and medical devices.

We have previously observed small virus-like particles in the brain of hamsters with experimental scrapie. Here we report that small virus-like structures can be isolated from brains of patients with Creutzfeldt-Jakob disease and identified by electronmicroscopy.

Between 1969 and 30 September 1995, 79 Austrian patients had Creutzfeldt-Jakob disease (CJD) diagnosed neuropathologically by necropsy or biopsy. The annual incidence has significantly increased in recent years (average 0.18 per million in 1969-85, and 0.67 per million in 1986-94; estimate for 1995: 1.5 per million). Also, the percentage of patients with CJD over 70 years at death increased significantly until 1989 but is since in decline. There is no regional clustering, familial occurrence, or recognised iatrogenic risk. One patient had a 10 year history of intramuscular injection of purified bovine RNA preparation (Regeneresen) from various organs including the brian. The ages at death are symmetrically distributed around the median of 64 years. The median duration of disease is four months. Most patients (76%) died within six months of onset. Retrospectively, 86% of patients fulfilled clinical criteria of probable or possible CJD. Neuropathology showed the classic triad of spongiform change, astrogliosis, and neuronal loss in most cases. Two cases did not show unequivocal tissue alterations, but anti-PrP immunocytochemistry detected PrP deposits also in these cases. It is concluded that the recent rise in incidence of CJD in Austria most likely reflects increased awareness and diagnosis of CJD rather than a real increase. As bovine spongiform encephalopathy (BSE) has not been reported in Austria, the data do not support a link between a rise in incidence of sporadic CJD and BSE.

An efficient purification protocol for infectivity causing a transmissible spongiform encephalopathy (TSE) is described. From fractions purified by this protocol about 3 × 108 LD50 but only 3 ng of nucleic acids per gram of brain material can be isolated from all TSE-affected brains (hamster, human, sheep, cattle). By PAGE such fractions from brains of infected and control hamsters contained only one distinct nucleic acid band of 1.5 kb together with some broader smear of nucleic acid material. Although distilled water was used for such purifications, quite often a similar nucleic acid band was isolated from blanks containing no brain material. In all instances this material proved to be DNA. The result challenges the potentially important claim that purified infectious preparations of TSE-specific amyloid are free of nucleic acids of viral size. Nucleic acids isolated by other groups from diseased brain were not detected in preparations isolated by the new protocol. The application of this purification protocol in future studies will be helpful to decide whether TSEs are caused by agents containing nucleic acid or by protein only.