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1.  Evidence of effective scrapie transmission via colostrum and milk in sheep 
Background
Evidence for scrapie transmission from VRQ/VRQ ewes to lambs via milk was first reported in 2008 but in that study there were concerns that lateral transmission may have contributed to the high transmission rate observed since five control lambs housed with the milk recipients also became infected. This report provides further information obtained from two follow-up studies, one where milk recipients were housed separately after milk consumption to confirm the validity of the high scrapie transmission rate via milk and the second to assess any difference in infectivity from colostrum and subsequent milk. Protein misfolding cyclic amplification (PMCA) was also used to detect prion protein in milk samples as a comparison with the infectivity data and extended to milk samples from ewes without a VRQ allele.
Results
Seven pairs of lambs fed colostrum and milk individually from seven scrapie-affected sheep (pre-clinical or clinical) presented with disease-associated prion protein, PrPd, in rectal lymphoid tissue at 4–5 months of age. Five further pairs of lambs fed either colostrum or subsequent milk from five pre-clinical scrapie-affected sheep equally presented with PrPd in lymphoid tissue by 9 months of age. Nine sheep were lost due to intercurrent diseases but all remaining milk or colostrum recipients, including those in the original study with the lateral transmission controls, developed clinical signs of scrapie from 19 months of age and scrapie was confirmed by brain examination. Unexposed control sheep totalling 19 across all three studies showed no evidence of infection.
Scrapie PrP was amplified repeatedly by PMCA in all tested milk samples from scrapie-affected VRQ/VRQ sheep, and in one scrapie-affected ARQ/ARQ sheep. By contrast, milk samples from five VRQ/VRQ and 11 ARQ/ARQ scrapie-free sheep did not have detectable scrapie PrP on repeated tests.
Conclusions
Feeding of milk from scrapie-affected sheep results in a high transmission rate in VRQ/VRQ sheep and both colostrum and milk transmit scrapie. Detection of scrapie prion protein in individual milk samples from scrapie-affected ewes confirms PMCA as a valuable in vitro test.
doi:10.1186/1746-6148-9-99
PMCID: PMC3750761  PMID: 23651710
Transmissible spongiform encephalopathy; Scrapie; Sheep; Milk; Colostrum; Transmission; PMCA; Prion protein; RAMALT; Copper
2.  The natural atypical scrapie phenotype is preserved on experimental transmission and sub-passage in PRNP homologous sheep 
Background
Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries. Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease.
However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. The first successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.
Results
This study demonstrates that atypical scrapie has distinct clinical, pathological and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.
Conclusions
Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage.
doi:10.1186/1746-6148-6-14
PMCID: PMC2848638  PMID: 20219126
3.  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.
doi:10.1186/1746-6148-5-38
PMCID: PMC2768688  PMID: 19818127
4.  Pruritus is a common feature in sheep infected with the BSE agent 
Background
The variability in the clinical or pathological presentation of transmissible spongiform encephalopathies (TSEs) in sheep, such as scrapie and bovine spongiform encephalopathy (BSE), has been attributed to prion protein genotype, strain, breed, clinical duration, dose, route and type of inoculum and the age at infection. The study aimed to describe the clinical signs in sheep infected with the BSE agent throughout its clinical course to determine whether the clinical signs were as variable as described for classical scrapie in sheep. The clinical signs were compared to BSE-negative sheep to assess if disease-specific clinical markers exist.
Results
Forty-seven (34%) of 139 sheep, which comprised 123 challenged sheep and 16 undosed controls, were positive for BSE. Affected sheep belonged to five different breeds and three different genotypes (ARQ/ARQ, VRQ/VRQ and AHQ/AHQ). None of the controls or BSE exposed sheep with ARR alleles were positive. Pruritus was present in 41 (87%) BSE positive sheep; the remaining six were judged to be pre-clinically infected. Testing of the response to scratching along the dorsum of a sheep proved to be a good indicator of clinical disease with a test sensitivity of 85% and specificity of 98% and usually coincided with weight loss. Clinical signs that were displayed significantly earlier in BSE positive cases compared to negative cases were behavioural changes, pruritic behaviour, a positive scratch test, alopecia, skin lesions, teeth grinding, tremor, ataxia, loss of weight and loss of body condition. The frequency and severity of each specific clinical sign usually increased with the progression of disease over a period of 16–20 weeks.
Conclusion
Our results suggest that BSE in sheep presents with relatively uniform clinical signs, with pruritus of increased severity and abnormalities in behaviour or movement as the disease progressed. Based on the studied sheep, these clinical features appear to be independent of breed, affected genotype, dose, route of inoculation and whether BSE was passed into sheep from cattle or from other sheep, suggesting that the clinical phenotype of BSE is influenced by the TSE strain more than by other factors. The clinical phenotype of BSE in the genotypes and breed studied was indistinguishable from that described for classical scrapie cases.
doi:10.1186/1746-6148-4-16
PMCID: PMC2390527  PMID: 18445253
5.  Evidence of scrapie transmission via milk 
Background
The risk of scrapie infection increases with increased duration and proximity of contact between sheep at lambing. Scrapie infectivity has not been detected in milk but cellular prion protein, the precursor of disease-associated prion protein PrPd, has been found in milk from ruminants. To determine whether milk is able to transmit scrapie, 18 lambs with a prion protein genotype associated with high susceptibility to scrapie (VRQ/VRQ) were fed milk from twelve scrapie-affected ewes of the same genotype, and 15 VRQ/VRQ sheep reared on scrapie-free dams served as controls.
Results
Three lambs fed milk from scrapie-affected ewes were culled due to intercurrent diseases at 43, 44 and 105 days of age respectively, and PrPd was detected in the distal ileum of the first two lambs, whilst PrPd was not found in lymphoreticular tissues in the third lamb. A control lamb, housed in a separate pen and culled at 38 days of age, was also negative for PrPd in a range of tissues. Samples of recto-anal mucosa associated lymphoid tissue collected from the remaining 15 live lambs at seven months of age (between five to seven months after mixing) were positive for PrPd in the scrapie milk recipients, whereas PrPd was not detected in the remaining 14 controls at that time. A subsequent sample collected from control lambs revealed PrPd accumulation in two of five lambs eight months after mixing with scrapie milk recipients suggestive of an early stage of infection via lateral transmission. By contrast, the control sheep housed in the same building but not mixed with the scrapie milk recipients were still negative for PrPd.
Conclusion
The presence of PrPd in distal ileum and rectal mucosa indicates transmission of scrapie from ewe to lamb via milk (or colostrum) although it is not yet clear if such cases would go on to develop clinical disease. The high level of infection in scrapie-milk recipients revealed by rectal mucosal testing at approximately seven months of age may be enhanced or supplemented by intra-recipient infection as these lambs were mixed together after feeding with milk from scrapie-affected ewes and we also observed lateral transmission from these animals to lambs weaned from scrapie-free ewes.
doi:10.1186/1746-6148-4-14
PMCID: PMC2374774  PMID: 18397513

Results 1-5 (5)