Further preliminary observations are reported of an experiment to examine the spread of infectivity and the occurrence of pathological changes in cattle exposed orally to infection with bovine spongiform encephalopathy. Calves were dosed at four months of age and clinically monitored groups were killed sequentially from two to 40 months after inoculation. Tissues were collected for bioassay, for histopathological examinations and for the detection of PrP. Previous reported observations have included the presence of infectivity in the distal ileum of cattle killed after six to 18 months, the earliest onset of clinical signs in an exposed animal after 35 months, and diagnostic histopathological changes in the brain, in association with clinical disease, after 36, 38 and 40 months. In spite of the relative inefficiency of the bioassay of scrapie-like agents across a species barrier the new observations confirm that the onset of clinical signs and pathological changes in the central nervous system (CNS) occur at approximately the same time. The earliest pathological change, the presence of abnormal PrP 32 months after inoculation, coincided with the earliest detected infectivity in the CNS and occurred shortly before there was evidence of typical spongiform changes in the brain 36 months after inoculation. Infectivity has now been demonstrated in the peripheral nervous system, in the cervical and thoracic dorsal root ganglia 32 to 40 months after inoculation and in the trigeminal ganglion 36 and 38 months after inoculation. At the time of writing evidence of infectivity in other tissues is confined to the distal ileum, not only after six to 18 months but also after 38 and 40 months, but these findings may be supplemented by the results of further mouse assays. Nevertheless, they are in general agreement with current knowledge of the pathogenesis of scrapie.

A RECENTLY published report (Wells and others 1998) updated interim findings in a sequential time point study which is examining the spread of infectivity and development of pathological changes in cattle exposed orally to infection with the agent of bovine spongiform encephalopathy (BSE) others 1994, 1996).These previous results described the schedule of examination of cattle, killed from two to 40 months after oral exposure, and the development of clinical signs in cattle 35 to 37 months after the exposure. They also demonstrated infectivity by mouse bioassay in: distal ileum (sampled from cattle six to 18 months, 38 months and 40 months after exposure); central nervous system -brain and spinal cord (sampled from cattle 32 to 40 months after exposure); and sensory ganglia -dorsal root ganglia (sampled from cattle 32 to 40 months after exposure) and trigeminal ganglion (sampled from cattle 36 months and 38 months after exposure). No infectivity had been detected in any of the 35 remaining tissues for which assays were complete at June 1997 (that is, those sampled from cattle two to 22 months after exposure).Mouse bioassays of a large range of tissues from all sequential kill time points of the study have now been completed (at December 1998) and will be reported in full elsewhere. This short communication reports additional data on the bioassay in C57B1-J6 mice of bone marrow, completing results for this tissue from all cattle in the study (Wells and others 1998).Details of the experimental design of the study have been described previously others 1996,1998). Bone marrow from the sternum (cancellous bone from the centre of the third or fourth sternebra) was sampled, as for each of the tissues taken, using new sterile disposable instruments or instruments sterilised by porous load autoclaving at a holding temperature of 136°C for 18 minutes at 30 lb/in2. The sternum was sawn sagitally and then transversely to isolate a portion of sternebra. With a new disposable scalpel and forceps a portion of cancellous bone containing marrow was removed from the sternebra. A weighed amount of the tissue was ground in a Griffiths tube and diluted with sterile saline to give a 10 per cent suspension. The suspension was filtered through sterile gauze before final aliquoting and freezing at -70°C. An aliquot was thawed just before inoculation. The samples were taken from BSE-exposed and control cattle at each sequential time point of the study. Pooled bone marrow from the BSE-exposed cattle was assayed in parallel with bone marrow from a clinically normal animal from undosed control groups. Mice were inoculated by intracerebral and intraperitoneal routes.Bioassays of tissues from cattle killed earlier than 22 months after exposure were conducted in RIII mice, whereas assays from 22 months and later times after exposure have been conducted in C57B1-J6 mice. Surviving mice were killed at an experimental end point of 650 days (RIII) or 950 days (C57B1-J6) after inoculation (Wells and others 1996). Postmortem confirmation of disease...

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