Natural transmission of BSE between sheep within an experimental flock.
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Biomedical subjects
Publications and source records attributed to G Dexter.
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Sixty Romney sheep of three prion protein genotypes were dosed orally at six months of age with an inoculum prepared from the brains of cattle clinically affected with BSE, and 15 sheep were left undosed as controls. They were randomly assigned within genotype to groups and were sequentially euthanased and examined postmortem at intervals of six or 12 months, depending on their predicted susceptibility. Tissue pools prepared from the three, four or five dosed animals in each group were inoculated into groups of 20 RIII mice as a bioassay for infectivity. Separate inocula were prepared from the matched control sheep killed at each time. In the ARQ/ARQ sheep killed four months after inoculation, infectivity was detected in the Peyer's patch tissue pool, and at 10 months it was detected in the spleen pool; from 16 months, infectivity was detected in a range of nervous and lymphoreticular tissues, including the spinal cord pool, distal ileum excluding Peyer's patches, liver, Peyer's patches, mesenteric and prescapular lymph nodes, spleen, tonsil and cervical thymus. No infectivity was detected in the tissue pools from the ARQ/ARR and ARR/ARR sheep killed 10 months or 22 months after infection.
Histopathological and bacteriological examinations were performed on 178 brains from Sardinian sheep which were showing neurological signs. The sheep represented the total number of sheep with neurological syndromes submitted for diagnostic investigations over a three-year period in Sardinia. Scrapie was detected in 57 cases, cerebrocortical necrosis in 25, intoxication by a typical Mediterranean plant (Cistus species) was suspected in 25, coenurosis was detected in 11 cases, Listeria monocytogenes in eight cases and focal symmetrical encephalomalacia in six cases. Non-suppurative inflammatory changes were observed in three of the brains and suppurative changes were noted in two. Lesions restricted to the spinal cord were found in three cases. In the remaining 38 cases there were no significant neuropathological changes.
Vascular amyloidosis in the brain is a pathological feature of ovine scrapie. Its occurrence varies between sheep, but whether this variation reflects differences in the host or the infecting scrapie strain (or both) is not clear. To investigate whether amyloidosis, like vacuolation and PrPsc distribution, is associated with genotype, the brains from 131 sheep representing a range of genotypes commonly associated with scrapie were examined histologically and immunohistochemically. Vascular amyloidosis was absent in 66 sheep, 59 of which were of the ARQ/ARQ genotype and seven the ARQ/AHQ genotype. In contrast, it was found in four of 39 ARQ/VRQ sheep (10.2%) and in 10 of 26 VRQ/VRQ sheep (38.4%). The distribution of amyloid was highly variable, but the most severely affected areas were the lateral geniculate nuclei (five cases) and the ventral thalamic nuclei (four cases). No amyloidosis was found in the medulla or in the basal nuclei. From this preliminary study it was concluded that amyloidosis is relatively rare in sheep with scrapie. Moreover, its occurrence appeared to depend on the presence of at least one valine at codon 136.
Scrapie free adult sheep were introduced to a sheep flock specifically maintained to maximise scrapie infection. Native born sheep of the highly susceptible VRQ/VRQ genotype in this flock show highly efficient transmission, evidenced by 100% infection, with an age at death of less than 2 years. Infection in introduced sheep was identified by biopsy of tonsilar and nictitating membrane lymphoid tissue. Progeny of these sheep were monitored and clinical disease confirmed by examination of the brain using routine diagnostic methods. Naïve sheep of New Zealand origin introduced to the flock in adulthood became infected, demonstrating that lateral transmission had occurred. Lambs born to introduced ewes became infected and died at the same age as lambs born to native ewes, consistent with lateral transmission of scrapie to lambs. Although maternal transmission cannot be totally excluded for the lambs in this study, the data are consistent with lateral transmission being the most important means of spread leading to the high incidence of scrapie observed in this flock.