This report summarises the final results of this pilot and the subsequent milk transmission study, preliminary results of which were reported previously. Therefore, a pilot study was initiated to determine whether sheep were susceptible to goat scrapie following oral challenge with brain homogenate, which would mimic the route for a further milk transmission experiment, and to assess which genotype, VRQ/VRQ or ARQ/ARQ, was more susceptible.
However, previous transmission studies had only confirmed the susceptibility of goats to sheep scrapie by natural or oral infection but not vice-versa. Lambs were used as milk recipients because they could be sourced from a closed flock of known classical scrapie-free status. įollowing our infectivity studies in sheep milk, the study reported here aimed to investigate whether scrapie from goats can be transmitted to sheep via milk by the oral route. More recent research has suggested that PRNP genetics in goats may also play a role on susceptibility to scrapie, with polymorphisms at codons 127 (serine instead of glycine ), 142 (methionine instead of isoleucine ), 146 (S 146 and aspartic acid instead of asparagine ), 154 (H 154 instead of R 154), 211 (Q 211 instead of R 211) and 222 (lysine instead of Q 222) giving some protective effect against classical scrapie in goats. It has now been established that susceptibility to scrapie in sheep is predominantly influenced by PRNP polymorphisms at codons 136 (alanine or valine ), 154 (arginine or histidine ) and 171 (glutamine or R 171), with ARQ/ARR and ARR/ARR being highly resistant against classical scrapie and VRQ/VRQ, ARQ/ARQ and VRQ/ARQ being highly susceptible. At the time of that experiment, the influence of the prion protein genotype ( PRNP) on scrapie susceptibility was unknown.
The only previous infectivity study, in which two 3 month-old goats were intracerebrally inoculated with 1 ml of milk from an experimentally infected goat, failed to demonstrate transmission up to 29 months post inoculation. Studies on the infectivity of milk from small ruminants, which is used for human consumption, have become more relevant since the demonstration of the zoonotic potential of bovine spongiform encephalopathy (BSE) and the identification of naturally occurring BSE in goats. Disease transmission has been demonstrated in lambs fed milk from scrapie-affected ewes. Although the ability of the scrapie agent to transmit vertically and horizontally in small ruminants has been known for years, the sources or vehicles of infection were poorly understood and only recently has progress been made to establish which secretions and excretions are infectious. Scrapie is a transmissible spongiform encephalopathy (TSE) of sheep and goats, characterised by accumulation of disease-associated prion protein (PrP sc) in brain and lymphoid tissues.
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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.
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. 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. 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. 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.
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