title: Evidence of scrapie transmission to sheep via goat milk.
abstract: BACKGROUND
  Previous studies confirmed that classical scrapie can be transmitted via milk in sheep. The current study aimed to investigate whether scrapie can also be transmitted via goat milk using in vivo (new-born lambs fed milk from scrapie-affected goats due to the unavailability of goat kids from guaranteed scrapie-free herds) and in vitro methods (serial protein misfolding cyclic amplification [sPMCA] on milk samples).
  
  
  RESULTS
  In an initial pilot study, new-born lambs of two different prion protein gene (PRNP) genotypes (six VRQ/VRQ and five ARQ/ARQ) were orally challenged with 5 g brain homogenate from two scrapie-affected goats to determine susceptibility of sheep to goat scrapie. All sheep challenged with goat scrapie brain became infected based on the immunohistochemical detection of disease-associated PrP (PrP(sc)) in lymphoid tissue, with an ARQ/ARQ sheep being the first to succumb. Subsequent feeding of milk to eight pairs of new-born ARQ/ARQ lambs, with each pair receiving milk from a different scrapie-affected goat, resulted in scrapie in the six pairs that received the largest volume of milk (38-87 litres per lamb), whereas two pairs fed 8-9 litres per lamb, and an environmental control group raised on sheep milk from healthy ewes, did not show evidence of infection when culled at up to 1882 days of age. Infection in those 12 milk recipients occurred regardless of the clinical status, PrP(sc) distribution, caprine arthritis-encephalitis virus infection status and PRNP polymorphisms at codon 142 (II or IM) of the donor goats, but survival time was influenced by PRNP polymorphisms at codon 141. Serial PMCA applied to a total of 32 milk samples (four each from the eight donor goats collected throughout lactation) detected PrP(sc) in one sample each from two goats.
  
  
  CONCLUSIONS
  The scrapie agent was present in the milk from infected goats and was able to transmit to susceptible species even at early preclinical stage of infection, when PrP(sc) was undetectable in the brain of the donor goats. Serial PMCA as a PrP(sc) detection method to assess the risk of scrapie transmission via milk in goats proved inefficient compared to the bioassay.
authors.affiliation: Animal Sciences Unit, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. Timm.Konold@apha.gsi.gov.uk.
authors.forename: Timm
authors.initials: T
authors.lastname: Konold
authors.affiliation: Virology Department, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK.
authors.forename: Leigh
authors.initials: L
authors.lastname: Thorne
authors.affiliation: Animal Sciences Unit, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK.
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Simmons
authors.affiliation: Pathology Department, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK.
authors.forename: Steve A C
authors.initials: SA
authors.lastname: Hawkins
authors.affiliation: Pathology Department, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK.
authors.forename: Marion M
authors.initials: MM
authors.lastname: Simmons
authors.affiliation: Pathology Department, Animal and Plant Health Agency Lasswade, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, EH26 0PZ, UK.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: González
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005838:Genotype; D006041:Goats; D008892:Milk; D000072002:Prion Proteins / Q000235:genetics; D012608:Scrapie / Q000635:transmission*; D012756:Sheep; D016019:Survival Analysis
chemical_list: D000072002:Prion Proteins
keywords: Colostrum; Genotype; Goat; Milk; Prion protein; Protein misfolding cyclic amplification; Scrapie; Sheep; Transmissible spongiform encephalopathy; Transmission