The role of mathematical modelling in understanding the epidemiology and control of sheep transmissible spongiform encephalopathies: A review

Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom.
Veterinary Research (Impact Factor: 2.82). 02/2010; 41(4):42. DOI: 10.1051/vetres/2010014
Source: PubMed


To deal with the incompleteness of observations and disentangle the complexities of transmission much use has been made of mathematical modelling when investigating the epidemiology of sheep transmissible spongiform encephalopathies (TSE) and, in particular, scrapie. Importantly, these modelling approaches allow the incidence of clinical disease to be related to the underlying prevalence of infection, thereby overcoming one of the major difficulties when studying these diseases. Models have been used to investigate the epidemiology of scrapie within individual flocks and at a regional level; to assess the efficacy of different control strategies, especially selective breeding programmes based on prion protein (PrP) genotype; to interpret the results of scrapie surveillance; and to inform the design of surveillance programmes. Furthermore, mathematical modelling has played an important role when assessing the risk to human health posed by the possible presence of bovine spongiform encephalopathy in sheep. Here, we review the various approaches that have been taken when developing and analysing mathematical models for the epidemiology and control of sheep TSE and assess their impact on our understanding of these diseases. We also identify areas that require further work, discuss future challenges and identify data gaps.

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    • "S3–S5). Despite this, most previous analyses have relied on data for a single outbreak (see Gubbins et al., 2010 for a review) and the present study represents the first attempt to link surveillance data and outbreak data in a rigorous manner. In addition, the present study analysed data fora large number of outbreaks, which allowed us to incorporate flockto-flock variation in epidemiological parameters when assessing the impact of control measures. "
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    ABSTRACT: Current strategies to control classical scrapie remove animals at risk of scrapie rather than those known to be infected with the scrapie agent. Advances in diagnostic tests, however, suggest that a more targeted approach involving the application of a rapid live test may be feasible in future. Here we consider the use of two diagnostic tests: recto-anal mucosa-associated lymphatic tissue (RAMALT) biopsies; and a blood-based assay. To assess their impact we developed a stochastic age- and prion protein (PrP) genotype-structured model for the dynamics of scrapie within a sheep flock. Parameters were estimated in a Bayesian framework to facilitate integration of a number of disparate datasets and to allow parameter uncertainty to be incorporated in model predictions. In small flocks a control strategy based on removal of clinical cases was sufficient to control disease and more stringent measures (including the use of a live diagnostic test) did not significantly reduce outbreak size or duration. In medium or large flocks strategies in which a large proportion of animals are tested with either live diagnostic test significantly reduced outbreak size, but not always duration, compared with removal of clinical cases. However, the current Compulsory Scrapie Flocks Scheme (CSFS) significantly reduced outbreak size and duration compared with both removal of clinical cases and all strategies using a live diagnostic test. Accordingly, under the assumptions made in the present study there is little benefit from implementing a control strategy which makes use of a live diagnostic test.
    Full-text · Article · Sep 2013
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    • "The risk of infection or clinical classical scrapie at population level has been studied much less frequently given the difficulties of selecting and following up scrapie-affected flocks over time. Some attempts have been made with differing levels of success, but most of them were subject to bias in the genotype data sources or in the selection of flocks for study, mainly managed by research institutes [7]. In some cases, it was unavoidable to prevent farmers from altering their breeding policy once the genotype of the animals had been revealed [8]. "
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    ABSTRACT: Total number and genotypes of animals in holdings selected for the genotype & cull option in the Compulsory Scrapie Flock Scheme (CSFS) in Great Britain were extracted from the National Scrapie Plan data warehouse. The association between various genotype-related measures and scrapie prevalence infection was tested using zero-inflated negative binomial models with the counts of positive cases as dependent variable, and country, number of flocks in the scheme, flock size, surveillance source and the following genotype-related measurements: the centered-log ratios (clr) oof the 15 genotypes, of the proportions of the 5 alleles at codons 136, 154 and 171, of the proportions of the 5 NSP types, and two flock-susceptibility risk indicators, as explanatory variables. A total of 319341 genotyped animals from 168 holdings were included in the analysis. An increased proportion of the ARR/ARR genotype corresponded to a decrease in the number of scrapie cases. ARR/AHQ, AHQ/VRQ, ARH/VRQ and ARQ/VRQ genotypes, NSP type V, ARH, ARQ, AHQ and VRQ alleles and the low and high-susceptibility risk indicators are all associated with an increase risk in the number of scrapie cases. Regardless the management practices; the increased susceptibility that the non-ARR alleles confer on an individual could be extrapolated at the population level. Increasing prevalence of ARR allele reduces the overall risk of scrapie at population level. At genotype level, the VRQ/VRQ genotype, present a very low frequency in the study population, seems to play a residual effect in the overall risk of scrapie in a flock.
    Full-text · Article · Feb 2011 · Veterinary Research
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    • "The appropriate measure of the transmission risk is the basic reproduction number R0. It is defined in our context as the expected number of secondary cases of infection produced by a single primary scrapie infection in a population in which all animals of susceptible genotype are still uninfected [24-26]. R0 = 1 is the threshold value of the reproduction number below which the within-flock infection can not sustain itself and only small outbreaks can be expected in the flock [27,28]. "
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    ABSTRACT: ABSTRACT: Susceptibility to scrapie, a transmissible spongiform encephalopathy in sheep, is modulated by the genetic make-up of the sheep. Scrapie control policies, based on selecting animals of resistant genotype for breeding, have recently been adopted by the Netherlands and other European countries. Here we assess the effectiveness of a breeding programme based on selecting rams of resistant genotype to obtain outbreak control in classical scrapie-affected sheep flocks under field conditions. In six commercially-run flocks following this breeding strategy, we used genotyping to monitor the genotype distribution, and tonsil biopsies and post-mortem analyses to monitor the occurrence of scrapie infection. The farmers were not informed about the monitoring results until the end of the study period of six years. We used a mathematical model of scrapie transmission to analyze the monitoring data and found that where the breeding scheme was consistently applied, outbreak control was obtained after at most four years. Our results also show that classical scrapie control can be obtained before the frequency of non-resistant animals is reduced to zero in the flock. This suggests that control at the national scale can be obtained without a loss of genetic polymorphisms from any of the sheep breeds.
    Full-text · Article · Jan 2011 · Veterinary Research
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