Abstract
BackgroundMost previous analyses of scrapie outbreaks have focused on flocks run by research institutes, which may not reflect the field situation. Within this study, we attempt to rectify this deficit by describing the epidemiological characteristics of 30 sheep flocks naturally-infected with classical scrapie, and by exploring possible underlying causes of variation in the characteristics between flocks, including flock-level prion protein (PrP) genotype profile. In total, the study involved PrP genotype data for nearly 8600 animals and over 400 scrapie cases.Methodology/Principal FindingsWe found that most scrapie cases were restricted to just two PrP genotypes (ARQ/VRQ and VRQ/VRQ), though two flocks had markedly different affected genotypes, despite having similar underlying genotype profiles to other flocks of the same breed; we identified differences amongst flocks in the age of cases of certain PrP genotypes; we found that the age-at-onset of clinical signs depended on peak incidence and flock type; we found evidence that purchasing infected animals is an important means of introducing scrapie to a flock; we found some evidence that flock-level PrP genotype profile and flock size account for variation in outbreak characteristics; identified seasonality in cases associated with lambing time in certain flocks; and we identified one case that was homozygous for phenylalanine at codon 141, a polymorphism associated with a very high risk of atypical scrapie, and 28 cases that were heterozygous at this codon.Conclusions/SignificanceThis paper presents the largest study to date on commercially-run sheep flocks naturally-infected with classical scrapie, involving 30 study flocks, more than 400 scrapie cases and over 8500 PrP genotypes. We show that some of the observed variation in epidemiological characteristics between farms is related to differences in their PrP genotype profile; although much remains unexplained and may instead be attributed to the stochastic nature of scrapie dynamics.
Highlights
Scrapie is a fatal neurodegenerative disorder of sheep and goats within the transmissible spongiform encephalopathy (TSE) group of diseases, which includes variant Creutzfeldt-Jakob disease and kuru in humans, bovine spongiform encephalopathy (BSE) in cattle and chronic wasting disease (CWD) in mule deer and elk
In this paper we have described naturally-occurring outbreaks of classical scrapie in 30 UK sheep flocks, the largest number yet described in detail, and have illustrated the marked variability that exists in their epidemiological characteristics, such as outbreak duration, disease incidence and the prion protein (PrP) genotype and age-at-onset of cases
While scrapie strain and the stochastic nature of scrapie dynamics may play important roles in driving epidemiological variability between flocks, we have shown that at least some of this variability is accounted for by differences in the flocks’ PrP genotype profiles
Summary
Scrapie is a fatal neurodegenerative disorder of sheep and goats within the transmissible spongiform encephalopathy (TSE) group of diseases, which includes variant Creutzfeldt-Jakob disease (vCJD) and kuru in humans, bovine spongiform encephalopathy (BSE) in cattle and chronic wasting disease (CWD) in mule deer and elk. A host genetic component, the ovine prion protein (PrP) gene, strongly affects progression to clinical disease and the incubation period (IP), such that some sheep PrP alleles confer resistance or longer IPs, while others confer susceptibility or shorter IPs [5,6,7,8]. This discovery has allowed the possibility of genetic-based selective breeding programmes to control scrapie, and such programmes are implemented across the European Union (EU). The study involved PrP genotype data for nearly 8600 animals and over 400 scrapie cases
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