Abstract
BackgroundEvidence 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.ResultsSeven 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.ConclusionsFeeding 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.
Highlights
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 became infected
The present work was undertaken following the results from the initial study (Study 1), updated here, to further study scrapie transmission via milk by using the natural host, namely to confirm the high scrapie transmission rate via milk whilst lateral transmission was prevented by housing lambs separately after milk consumption (Study 2) and to investigate whether colostrum or subsequent milk in a lactation are effective in the transmission of scrapie in sheep (Study 3)
All of the 15 remaining scrapie milk recipients developed clinical signs of scrapie and were culled at 19–27 months of age whereas the five lateral transmission controls were culled with signs of scrapie at 27–40 months of age (25–36 months post exposure, see “Additional file 3: 07-1246” showing a lateral transmission control at endstage disease)
Summary
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 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. In a separate experiment it was shown that milk from ARQ/ARQ sheep orally inoculated with scrapie brain homogenate transmits scrapie to lambs [6] Both studies used milk from sheep co-infected with the maedi-visna virus (MVV), which can cause lymphofollicular mastitis that may contribute to prion secretion into milk [7] compared to a healthy udder. Milk samples from sheep, which included milk from some sheep used for the transmission study, were examined for presence of PrPsc using PMCA to allow comparison with the in vivo studies
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