Dynamics of a scrapie outbreak in a flock of Romanov sheep – estimation of transmission parameters

Hagenaars, T.H.J.; Donnelly, Christl A.; Ferguson, Neil M.; Anderson, Roy M.

doi:10.1017/s0950268803001055

Cited by 13 publications

(11 citation statements)

References 26 publications

(43 reference statements)

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“…SI animals either died from clinical scrapie (uncensored records) or were eliminated from the flock before clinical onset (right-censored). Simulations were performed using (i) genetic and biological parameters (infection rates, ages at clinical death and flock demography) described in scrapie outbreaks or already used in mathematical modelling (simulation design 1) (Matthews et al, 2001;Hagenaars et al, 2003;Hopp et al, 2003;Baylis et al, 2004;Eglin et al, 2005;Touzeau et al, 2005) and (ii) ages at death from scrapie reflecting observations made in our dataset (simulation design 2).…”

Section: Methodsmentioning

confidence: 99%

Advanced survival models for risk-factor analysis in scrapie

Corbière

Barillet

Andréoletti

et al. 2007

Journal of General Virology

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Because of the confounding effects of long incubation duration and flock management, accurate epidemiological studies of scrapie outbreaks are difficult to carry out. In this study, 641 Manech red-faced sheep from six scrapie-affected field flocks in Pyré né es Atlantiques, France, were monitored for clinical scrapie over a 6-9 year period. Over this period, 170 scrapie clinical cases were recorded and half of the culled animals were submitted for post-mortem transmissible spongiform encephalopathy diagnosis to assess their infectious status. Collected data were analysed using a 'mixture cure model' approach, which allowed for the discriminating effect of PrP genotype and flock origin on incidence and incubation period. Simulations were performed to evaluate the applicability of such a statistical model to the collected data. As expected, ARR heterozygote sheep were less at risk of becoming infected than ARQ/ARQ individuals and had a greater age at clinical onset. Conversely, when compared with ARQ/ARQ, the VRQ haplotype was associated with an increased infection risk, but not a shorter incubation period. Considering the flock effect, we observed that a high incidence rate was not associated with shorter incubation periods and that the incubation period could be significantly different in flocks harbouring similar infection risks. These results strongly support the conclusion that other parameters, such as the nature of the agent or flock management, could interfere with epidemiological dynamics of the infection in scrapie-affected flocks.

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Section: Methodsmentioning

confidence: 99%

Advanced survival models for risk-factor analysis in scrapie

Corbière

Barillet

Andréoletti

et al. 2007

Journal of General Virology

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“…One area in which mathematical modelling has been less successful, however, is in helping to elucidate routes of transmission. Although some studies have given attention to the interplay between horizontal and vertical transmission [ 37 , 39 , 57 ] or the role of an environmental reservoir for infectivity [ 38 , 39 ], models cannot easily be used to identify separate transmission routes. This is essentially because a decrease in transmission via one route can be compensated for by a corresponding increase in transmission via a different route without greatly affecting the predicted course of an epidemic.…”

Section: Discussionmentioning

confidence: 99%

“…We thus have the paradoxical effect (from a statistical viewpoint) that a “higher” incidence of cases may render it more difficult to quantify certain transmission parameters. This paradox is also apparent from a stochastic modelling analysis of a high-incidence scrapie outbreak in a flock of Romanov sheep [ 39 ]. One of the parameters studied in this analysis was the basic reproduction number, R 0 , an important summary parameter that quantifies the overall transmission potential of an infection in a population of given composition (in the case of scrapie this will be the PrP genotype composition of a flock) [ 37 , 57 ].…”

Section: Transmission Of Scrapie Within Flocksmentioning

confidence: 99%

“…Much of the work is exploratory in nature, for example, no detailed transmission parameter estimates have been attempted other than for a small number of outbreaks in specific flocks. The modelling analyses of the severe outbreak in the French flock of Romanov sheep [ 39 , 74 ] show that although some parameters remain highly uncertain, some of them can be meaningfully quantified: seasonality, onset of infectiousness and mean incubation period.…”

Section: Transmission Of Scrapie Within Flocksmentioning

confidence: 99%

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

2010

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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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“…Genotype age Incubation stage Figure 4 Proposed within-flock scrapie transmission model [189] http://www.cababstractsplus.org/cabreviews state (e.g. milk ewes cannot support milk sleeves and fall) [4,88].…”

Section: Infectedsmentioning

confidence: 99%

Current status of scrapie.

Saegerman

Vanopdenbosch²,

Berkvens³

2007

CABI Reviews

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Despite being controlled in many developed countries, scrapie remains endemic in many parts of the world. Economic losses result from mortality and culling of small ruminants and from market restrictions. Moreover, it is difficult to develop all-inclusive guidelines that could establish a scrapie-free status for a country. Unfortunately, the global picture remains incomplete because in many countries confusion still remains regarding the clinical picture of scrapie and information is not available owing to the absence of adequate epidemiosurveillance networks. Currently, the predominant theory is that PrP Sc is the infectious agent where host genetic factors play a central role. The precise transmission routes of scrapie and their relative contributions to the overall transmission intensity remain poorly documented and the physiopathology is not fully understood. However, it is evident that the purchase of female sheep from scrapie flocks, sharing pastures with scrapie flocks, sharing breeding rams and genetic host susceptibility are the main risk factors for the spread of the disease. A better understanding of the epidemiology of scrapie would greatly aid the development and evaluation of control and eradication strategies that were mainly based on selective depopulation of infected animals and genetically susceptible and/or related animals and also on the biosecurity and the use of selective genetic breeding programmes in healthy flocks. Some numbers of a new transmissible spongiform encephalopathy (TSE) form in small ruminants (atypical scrapie) have meanwhile been identified by TSE rapid testing using an assay, which also recognizes comparatively less proteinase K-resistant PrP Sc . Uncertainties remain regarding the pathogenesis of this new TSE form, as well as regarding their potential transmissibility within the affected species and to other species. Thus far, no borine spongiform encephalopathy (BSE) cases have been confirmed in sheep under natural conditions (a report of vertical transmission after experimental infection merits attention), but two historical cases of BSE in goats born in the 1990s have been identified. Currently BSE must also be considered in the differential diagnosis of scrapie. The development of prevention and control programmes should be assisted by new scientific findings.

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Dynamics of a scrapie outbreak in a flock of Romanov sheep – estimation of transmission parameters

Cited by 13 publications

References 26 publications

Advanced survival models for risk-factor analysis in scrapie

Advanced survival models for risk-factor analysis in scrapie

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

Current status of scrapie.

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