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Evidence of effective scrapie transmission via colostrum and milk in sheep.

Konold T, Moore SJ, Bellworthy SJ, Terry LA, Thorne L, Ramsay A, Salguero FJ, Simmons MM, Simmons HA - BMC Vet. Res. (2013)

Bottom Line: 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.By contrast, milk samples from five VRQ/VRQ and 11 ARQ/ARQ scrapie-free sheep did not have detectable scrapie PrP on repeated tests.Detection of scrapie prion protein in individual milk samples from scrapie-affected ewes confirms PMCA as a valuable in vitro test.

View Article: PubMed Central - HTML - PubMed

Affiliation: Specialist Scientific Support Department, Animal Health and Veterinary Laboratories Agency Weybridge, New Haw Addlestone, Surrey KT15 3NB, UK. Timm.Konold@ahvla.gsi.gov.uk

ABSTRACT

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.

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Incubation periods in days of scrapie milk donor, milk recipient sheep and lateral transmission controls. The median incubation periods for milk donors were 808.5 (range: 683–1436) days in Study 1, 657 (623–679) days in Study 2 and 666 (639–784) days in Study 3. The median incubation periods for milk recipients were 713 (588–816) days in Study 1, 729 (682–755) in Study 2 and 696.5 (694–738) days in Study 3. Lateral transmission controls in Study 1 had a median incubation period of 889 (range: 746–1095) days and colostrum recipients in Study 3 730 (693–749) days.
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Figure 1: Incubation periods in days of scrapie milk donor, milk recipient sheep and lateral transmission controls. The median incubation periods for milk donors were 808.5 (range: 683–1436) days in Study 1, 657 (623–679) days in Study 2 and 666 (639–784) days in Study 3. The median incubation periods for milk recipients were 713 (588–816) days in Study 1, 729 (682–755) in Study 2 and 696.5 (694–738) days in Study 3. Lateral transmission controls in Study 1 had a median incubation period of 889 (range: 746–1095) days and colostrum recipients in Study 3 730 (693–749) days.

Mentions: All of the 15 remaining scrapie milk recipients (out of a total of 18 sheep, see “Additional file 1: summary” for an overview and [2]) developed clinical signs of scrapie and were culled at 19–27 months of age (see “Additional file 2: 07-1092” showing a scrapie milk recipient at clinical end-point) 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 end-stage disease). Immunohistochemical and Western blot examination of the brains confirmed the clinical diagnosis in all sheep (presence of PrPd or its proteinase-resistant form, PrPres). All except for the last culled lateral transmission control, which displayed alopecia with skin lesions and a positive scratch test at the time of cull, presented with vacuolar changes in the obex. This sheep was also the only one that had no detectable PrPd in recto-anal mucosa-associated lymphoid tissue (RAMALT) at 14.5 months post exposure although it was present in a further biopsy at 34 months of age. The incubation periods of the scrapie-affected milk recipients (= time from birth to cull), lateral transmission controls (= time from exposure (mixing) to cull) and those of the milk donor sheep are shown in Figure 1.


Evidence of effective scrapie transmission via colostrum and milk in sheep.

Konold T, Moore SJ, Bellworthy SJ, Terry LA, Thorne L, Ramsay A, Salguero FJ, Simmons MM, Simmons HA - BMC Vet. Res. (2013)

Incubation periods in days of scrapie milk donor, milk recipient sheep and lateral transmission controls. The median incubation periods for milk donors were 808.5 (range: 683–1436) days in Study 1, 657 (623–679) days in Study 2 and 666 (639–784) days in Study 3. The median incubation periods for milk recipients were 713 (588–816) days in Study 1, 729 (682–755) in Study 2 and 696.5 (694–738) days in Study 3. Lateral transmission controls in Study 1 had a median incubation period of 889 (range: 746–1095) days and colostrum recipients in Study 3 730 (693–749) days.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750761&req=5

Figure 1: Incubation periods in days of scrapie milk donor, milk recipient sheep and lateral transmission controls. The median incubation periods for milk donors were 808.5 (range: 683–1436) days in Study 1, 657 (623–679) days in Study 2 and 666 (639–784) days in Study 3. The median incubation periods for milk recipients were 713 (588–816) days in Study 1, 729 (682–755) in Study 2 and 696.5 (694–738) days in Study 3. Lateral transmission controls in Study 1 had a median incubation period of 889 (range: 746–1095) days and colostrum recipients in Study 3 730 (693–749) days.
Mentions: All of the 15 remaining scrapie milk recipients (out of a total of 18 sheep, see “Additional file 1: summary” for an overview and [2]) developed clinical signs of scrapie and were culled at 19–27 months of age (see “Additional file 2: 07-1092” showing a scrapie milk recipient at clinical end-point) 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 end-stage disease). Immunohistochemical and Western blot examination of the brains confirmed the clinical diagnosis in all sheep (presence of PrPd or its proteinase-resistant form, PrPres). All except for the last culled lateral transmission control, which displayed alopecia with skin lesions and a positive scratch test at the time of cull, presented with vacuolar changes in the obex. This sheep was also the only one that had no detectable PrPd in recto-anal mucosa-associated lymphoid tissue (RAMALT) at 14.5 months post exposure although it was present in a further biopsy at 34 months of age. The incubation periods of the scrapie-affected milk recipients (= time from birth to cull), lateral transmission controls (= time from exposure (mixing) to cull) and those of the milk donor sheep are shown in Figure 1.

Bottom Line: 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.By contrast, milk samples from five VRQ/VRQ and 11 ARQ/ARQ scrapie-free sheep did not have detectable scrapie PrP on repeated tests.Detection of scrapie prion protein in individual milk samples from scrapie-affected ewes confirms PMCA as a valuable in vitro test.

View Article: PubMed Central - HTML - PubMed

Affiliation: Specialist Scientific Support Department, Animal Health and Veterinary Laboratories Agency Weybridge, New Haw Addlestone, Surrey KT15 3NB, UK. Timm.Konold@ahvla.gsi.gov.uk

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus