The evaluation of exposure risks for natural transmission of scrapie within an infected flock.

BACKGROUND: Although the epidemiology of scrapie has been broadly understood for many years, attempts to introduce voluntary or compulsory controls to eradicate the disease have frequently failed. Lack of precision in defining the risk factors on farm has been one of the challenges to designing control strategies. This study attempted to define which parts of the annual flock management cycle represented the greatest risk of infection to naive lambs exposed to the farm environment at different times. RESULTS: In VRQ/VRQ lambs exposed to infected sheep at pasture or during lambing, and exposed to the buildings in which lambing took place, the attack rate was high and survival times were short. Where exposure was to pasture alone the number of sheep affected in each experimental group was reduced, and survival times were longer and related to length of exposure. CONCLUSION: At the flock level, eradication and control strategies for scrapie must take into account the need to decontaminate buildings used for lambing, and to reduce (or prevent) the exposure of lambs to infected sheep, especially in the later stages of incubation, and at lambing. The potential for environmental contamination from pasture should also be considered. Genotype selection may still prove to be the only viable tool to prevent infection from contaminated pasture, reduce environmental contamination and limit direct transmission from sheep to sheep.

Atypical scrapie in sheep from a UK research flock which is free from classical scrapie.

BACKGROUND: In the wake of the epidemic of bovine spongiform encephalopathy the British government established a flock of sheep from which scrapie-free animals are supplied to laboratories for research. Three breeds of sheep carrying a variety of different genotypes associated with scrapie susceptibility/resistance were imported in 1998 and 2001 from New Zealand, a country regarded as free from scrapie. They are kept in a purpose-built Sheep Unit under strict disease security and are monitored clinically and post mortem for evidence of scrapie. It is emphasised that atypical scrapie, as distinct from classical scrapie, has been recognised only relatively recently and differs from classical scrapie in its clinical, neuropathological and biochemical features. Most cases are detected in apparently healthy sheep by post mortem examination. RESULTS: The occurrence of atypical scrapie in three sheep in (or derived from) the Sheep Unit is reported. Significant features of the affected sheep included their relatively high ages (6 y 1 mo, 7 y 9 mo, 9 y 7 mo respectively), their breed (all Cheviots) and their similar PRNP genotypes (AFRQ/AFRQ, AFRQ/ALRQ, and AFRQ/AFRQ, respectively). Two of the three sheep showed no clinical signs prior to death but all were confirmed as having atypical scrapie by immunohistochemistry and Western immunoblotting. Results of epidemiological investigations are presented and possible aetiologies of the cases are discussed. CONCLUSION: By process of exclusion, a likely explanation for the three cases of atypical scrapie is that they arose spontaneously and were not infected from an exterior source. If correct, this raises challenging issues for countries which are currently regarded as free from scrapie. It would mean that atypical scrapie is liable to occur in flocks worldwide, especially in older sheep of susceptible genotypes. To state confidently that both the classical and atypical forms of scrapie are absent from a population it is necessary for active surveillance to have taken place.

Prions in the peripheral nerves of bovine spongiform encephalopathy-affected cattle.

With the use of increasingly sensitive methods for detection of the abnormal isoform of prion protein (PrP(Sc)) and infectivity in prion diseases, it has recently been shown that parts of the peripheral nervous system (PNS) of bovine spongiform encephalopathy (BSE)-affected cattle may become infected. It has been reported that prions spread to the central nervous system (CNS) via the PNS in sheep scrapie, but the pathogenesis of BSE in cattle is less well understood. To determine whether parts of the PNS other than those implicated directly in the hypothetical pathogenetic spread of agent from the intestine to the CNS become involved before or after the CNS is affected, PrP(Sc) distribution was investigated by a highly sensitive Western blotting technique in dorsal root ganglia, stellate ganglion, phrenic, radial and sciatic nerves, adrenal gland and CNS of cattle that were inoculated orally with BSE-affected brain and culled sequentially. In experimentally BSE-affected cattle, PrP(Sc) was first detected in the CNS and dorsal root ganglia; subsequently, PrP(Sc) accumulation was detected in the peripheral nerve trunks. PrP(Sc) was also detected in the adrenal glands of cattle that showed clinical signs. No PrP(Sc) was detected in the PNS of BSE-negative cattle. This study shows that, with respect to dorsal root ganglia, a paravertebral sympathetic ganglion and the somatic nerves examined, PrP(Sc) is detected in the PNS during the disease course at the same time as, or after, it accumulates in the CNS.

Monitoring for bovine spongiform encephalopathy in sheep in Great Britain, 1998-2004.

Bovine spongiform encephalopathy (BSE) may have been transmitted to British sheep via contaminated feed in the 1980s. Strain-typing techniques based on immunohistochemical (IHC) detection of abnormal protein (PrP(d)) and the molecular analysis of proteinase-resistant protein (PrP(res)) by Western blotting (WB) can discriminate between natural or experimental scrapie and experimental BSE in sheep. Between 1 January 1998 and 31 October 2001, 1247 sheep, clinically suspected of scrapie, were found to be positive by statutory tests in Great Britain. Archived brain tissue from these cases was retested by using these discriminatory methods. Twelve brain samples showed PrP(res) WB patterns that were unlike those found in natural or experimental scrapie. Prospective screening of fresh tissue from a further 1121 scrapie cases was also carried out between 1 November 2001 and 31 May 2004. Two samples gave WB results with similarities to the results found for experimental BSE in sheep. When all 14 unusual cases were tested by IHC, no match to experimental BSE in sheep was found. There were uncertainties within the retrospective study, where some equivocal results were obtained due to poor tissue quality or the unavailability of the optimum brain region. However, for the samples where tissue condition was optimum, our results provide no evidence for the presence of BSE in sheep. Epidemiological interpretation of the 450 flocks sampled indicates that the maximum proportion of sheep transmissible spongiform encephalopathy cases that could be BSE is 0.66%. This estimate is lower than calculated previously (5%), when the analysis was based on the results of strain typing in mice.