Epidemiological characteristics of classical scrapie outbreaks in 30 sheep flocks in the United Kingdom

Abstract

Background: Most 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 findings: We 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/significance: This 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.

Figure 1. Time-course of scrapie outbreaks in 30 sheep flocks in the UK.

(a) Occurrence and origin of cases within each outbreak. Time zero corresponds to the first case of scrapie in each flock. The origin of cases is that recorded in the Scrapie Notifications Database (SND). (b) Frequency of cases by birth cohort. Time zero corresponds to the first birth cohort for which the farmer had received genotype results from the IAH. The date that the farmer of flock 7 was informed of his genotypes was unknown and is not displayed. (c,d) Epidemic curves showing the cumulative number of cases in (c) outbreaks <50 months long; and (d) outbreaks >50 months long. Legends indicate flock identification number.

Figure 2. Epidemiological characteristics of scrapie outbreaks in 30 sheep flocks in the UK.

(a) Distribution of the number of cases. (b,c) PrP genotypes of cases in flocks with at least five cases of scrapie: (b) proportion (%) of cases by genotype; and (c) frequency of cases by genotype. Genotypes are indicated by the legend in figure (c). (d) Age-at-onset of scrapie cases: mean (black squares) and range (error bars) for age-at-onset, and age of first case (white circle). (e,f) Box and whisker plots for the age at onset in (e) ARQ/VRQ and (f) VRQ/VRQ animals in individual flocks. The boxes show the lower quartile, median and upper quartile; the whiskers represent 1.5 times the interquartile range; and the crosses indicate any outlying values.