Downloaded from http://veterinaryrecord.bmj.com/ on May 14, 2015 - Published by group.bmj.com
Research
Research EDITORIAL
Control of scrapie by selective breeding: what are we getting for free? Thomas J. Hagenaars In 2001, Great Britain adopted the National Scrapie Plan (NSP), which aimed to control classical scrapie (and reduce the risk of bovine spongiform encephalopathy) in sheep. The NSP is a breeding programme that makes use of the strong influence of the prion protein (PRNP) genotype on the level of susceptibility to scrapie by selecting for certain genotypes with low susceptibility to scrapie. Together with programmes in the Netherlands and France, the NSP was among the first such programmes in the European Union (EU), initiated before the breeding programmes became obligatory according to European Commission regulation in 2004 (an obligation which was lifted again in 2007). In common with the French programme and those of other EU member states initiated since 2004, the NSP selects animals for breeding based on genotyping and is restricted to breeding flocks, despite the fact one would Thomas J. Hagenaars, MSc, PhD, Central Veterinary Institute, Wageningen University and Research Centre, Lelystad, The Netherlands e-mail: [email protected]
528 | Veterinary Record | May 24, 2014
seek to control scrapie at the national level (commercial as well as breeding flocks). The rationale is that if breeding flocks become less susceptible, in time this effect will be automatically disseminated to commercial flocks, leading to a lower scrapie susceptibility of the entire national flock. By virtue of this dissemination, the NSP breeding programme confers an indirect effect on flocks that do not participate in the programme and these flocks essentially gain some genetic protection ‘for free’. The time frame needed to observe substantial dissemination to non-participating flocks is not obvious and would be determined by the rate at which replacement breeding animals are recruited by commercial flocks. A paper by Ortiz-Pelaez and others (2014), summarised on p 530 of this issue of Veterinary Record, seeks to evaluate the effect of the NSP on genotype distribution within the British national flock. It does so by comparing genotype frequencies in a random sample of almost 10,000 brain samples collected for scrapie surveillance in 2012 and 2013 to the results of a previous random genotyping study conducted in 2002 (Tongue and others 2008). This
Downloaded from http://veterinaryrecord.bmj.com/ on May 14, 2015 - Published by group.bmj.com
Research
Direct protection effect only
Herd immunity effect Attack rate
comparison suggests that, over the course of 10 years, the NSP has led to an increased prevalence of the scrapie-resistant allele (ARR), from 43.3 per cent to 52.3 per cent. By comparing this to an estimated increase in ARR frequency from 50.4 per cent to 68.8 per cent in ram lamb birth cohorts in the NSP breeding flocks over the course of only four years between 2002 and 2006, Ortiz-Pelaez and others (2014) put the magnitude of the indirect effect of the breeding programme in perspective. For further comparison, in the Netherlands, where the breeding programme extends across all flocks (both breeding and commercial), random genotyping samples during the period 2005 to 2013 suggested an increase in ARR prevalence from 37.5 per cent in 2005 to 61.4 in 2009 (Melchior and others 2011), to 69.9 per cent in 2013. An important question is the extent to which the increase in resistance has led to a reduction in scrapie transmission. Has the prevalence of scrapie in Great Britain declined between 2002 and 2013? Although this question is beyond the scope of the work by Ortiz-Pelaez and colleagues, the evolution of the genotype distribution described in their paper is a crucial piece of information for interpreting any observed change in scrapie prevalence; if a decrease is observed, is it in proportion to the reduction in prevalence of susceptible genotypes, or is it more pronounced (as has been shown to be the case in the Netherlands [Hagenaars and others 2010]) due to a herd immunity effect? Arguably, after the genetic dissemination effect discussed above, this latter effect (shown in Fig 1) is a second benefit that one would expect to obtain ‘for free’. For a first indication, one may look at the scrapie surveillance results reported by the UK to the EU (European Commission 2013). These results show that scrapie prevalence in UK healthy slaughter sheep has declined from the order of 100 cases per 10,000 animals tested in the years 2002 to 2005 to frequencies lower than 10
Proportion of population protected by vaccine FIG 1: Illustration of the concept of herd immunity. The herd immunity effect expected to benefit the NSP is comparable to increasing population-level immunity against childhood diseases such as measles via vaccination. Vaccination not only benefits immunised individuals but also reduces the force of infection experienced by the remaining susceptible individuals, thereby providing indirect protection. As shown, this leads to full herd immunity occurring above a critical vaccination coverage
per 10,000 animals in all years from 2007 to 2012 (except 2011). This reduction in scrapie prevalence of more than 90 per cent compares to an estimated reduction of only 35 per cent in the prevalence of NSP types III-V (groups of susceptible genotypes) between 2002 and 2012 that can be extracted from the results reported in Ortiz-Pelaez and others (2014). The greater reduction in scrapie prevalence could be an effect of both herd immunity and culling under the Compulsory Scrapie Flocks Scheme, which has been in force since 2004. To monitor the effect of the NSP on the genotype profile of the British national flock, it is desirable to genotype far more samples than the limited yearly numbers set as minimum requirements by the European Commission. The study by Ortiz-Pelaez and others (2014) illustrates the valuable insight that can be gained by extensive genotyping efforts.
References
EUROPEAN COMMISSION (2013) Report on the monitoring of ruminants for the presence of transmissible spongiform encephalopathies (TSEs) in the EU in 2012. Safety of the Food Chain; Food Hygiene, Alert System and Training October 9, 2013 HAGENAARS, T. J., MELCHIOR, M. B., BOSSERS, A., DAVIDSE, A., ENGEL, B. & VAN ZIJDERVELD, F. G. (2010) Scrapie prevalence in sheep of susceptible genotype is declining in a population subject to breeding for resistance. Veterinary Research 6, 25 MELCHIOR, M. B., HAGENAARS, T. J., DAVIDSE, A., VAN KEULEN, L. J. M., BOSSERS, A. & VAN ZIJDERVELD, F. G. (2011) Active surveillance for scrapie in the Netherlands: effect of a breeding programme on the prevalence of scrapie in sheep (2002-2010)? Tijdschrift Voor Diergeneeskunde 136, 84-93 ORTIZ-PELAEZ, A., THOMPSON, C. E. & DAWSON, M. (2014) Impact of the National Scrapie Plan on the PRNP genotype distribution of the British national flock, 2002-2012. Veterinary Record doi:10.1136/ vr.102255 TONGUE, S. C., WILESMITH, J. W., NASH, J., KOSSAIBATI, M. & RYAN, J. (2008) The importance of the PrP genotype in active surveillance for ovine scrapie. Epidemiology and Infection 136, 703-712
doi: 10.1136/vr.g3392
May 24, 2014 | Veterinary Record | 529
Downloaded from http://veterinaryrecord.bmj.com/ on May 14, 2015 - Published by group.bmj.com
Control of scrapie by selective breeding: what are we getting for free? Thomas J. Hagenaars Veterinary Record 2014 174: 528-529
doi: 10.1136/vr.g3392 Updated information and services can be found at: http://veterinaryrecord.bmj.com/content/174/21/528
These include:
References Email alerting service
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Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Research
Research EDITORIAL
Control of scrapie by selective breeding: what are we getting for free? Thomas J. Hagenaars In 2001, Great Britain adopted the National Scrapie Plan (NSP), which aimed to control classical scrapie (and reduce the risk of bovine spongiform encephalopathy) in sheep. The NSP is a breeding programme that makes use of the strong influence of the prion protein (PRNP) genotype on the level of susceptibility to scrapie by selecting for certain genotypes with low susceptibility to scrapie. Together with programmes in the Netherlands and France, the NSP was among the first such programmes in the European Union (EU), initiated before the breeding programmes became obligatory according to European Commission regulation in 2004 (an obligation which was lifted again in 2007). In common with the French programme and those of other EU member states initiated since 2004, the NSP selects animals for breeding based on genotyping and is restricted to breeding flocks, despite the fact one would Thomas J. Hagenaars, MSc, PhD, Central Veterinary Institute, Wageningen University and Research Centre, Lelystad, The Netherlands e-mail: [email protected]
528 | Veterinary Record | May 24, 2014
seek to control scrapie at the national level (commercial as well as breeding flocks). The rationale is that if breeding flocks become less susceptible, in time this effect will be automatically disseminated to commercial flocks, leading to a lower scrapie susceptibility of the entire national flock. By virtue of this dissemination, the NSP breeding programme confers an indirect effect on flocks that do not participate in the programme and these flocks essentially gain some genetic protection ‘for free’. The time frame needed to observe substantial dissemination to non-participating flocks is not obvious and would be determined by the rate at which replacement breeding animals are recruited by commercial flocks. A paper by Ortiz-Pelaez and others (2014), summarised on p 530 of this issue of Veterinary Record, seeks to evaluate the effect of the NSP on genotype distribution within the British national flock. It does so by comparing genotype frequencies in a random sample of almost 10,000 brain samples collected for scrapie surveillance in 2012 and 2013 to the results of a previous random genotyping study conducted in 2002 (Tongue and others 2008). This
Downloaded from http://veterinaryrecord.bmj.com/ on May 14, 2015 - Published by group.bmj.com
Research
Direct protection effect only
Herd immunity effect Attack rate
comparison suggests that, over the course of 10 years, the NSP has led to an increased prevalence of the scrapie-resistant allele (ARR), from 43.3 per cent to 52.3 per cent. By comparing this to an estimated increase in ARR frequency from 50.4 per cent to 68.8 per cent in ram lamb birth cohorts in the NSP breeding flocks over the course of only four years between 2002 and 2006, Ortiz-Pelaez and others (2014) put the magnitude of the indirect effect of the breeding programme in perspective. For further comparison, in the Netherlands, where the breeding programme extends across all flocks (both breeding and commercial), random genotyping samples during the period 2005 to 2013 suggested an increase in ARR prevalence from 37.5 per cent in 2005 to 61.4 in 2009 (Melchior and others 2011), to 69.9 per cent in 2013. An important question is the extent to which the increase in resistance has led to a reduction in scrapie transmission. Has the prevalence of scrapie in Great Britain declined between 2002 and 2013? Although this question is beyond the scope of the work by Ortiz-Pelaez and colleagues, the evolution of the genotype distribution described in their paper is a crucial piece of information for interpreting any observed change in scrapie prevalence; if a decrease is observed, is it in proportion to the reduction in prevalence of susceptible genotypes, or is it more pronounced (as has been shown to be the case in the Netherlands [Hagenaars and others 2010]) due to a herd immunity effect? Arguably, after the genetic dissemination effect discussed above, this latter effect (shown in Fig 1) is a second benefit that one would expect to obtain ‘for free’. For a first indication, one may look at the scrapie surveillance results reported by the UK to the EU (European Commission 2013). These results show that scrapie prevalence in UK healthy slaughter sheep has declined from the order of 100 cases per 10,000 animals tested in the years 2002 to 2005 to frequencies lower than 10
Proportion of population protected by vaccine FIG 1: Illustration of the concept of herd immunity. The herd immunity effect expected to benefit the NSP is comparable to increasing population-level immunity against childhood diseases such as measles via vaccination. Vaccination not only benefits immunised individuals but also reduces the force of infection experienced by the remaining susceptible individuals, thereby providing indirect protection. As shown, this leads to full herd immunity occurring above a critical vaccination coverage
per 10,000 animals in all years from 2007 to 2012 (except 2011). This reduction in scrapie prevalence of more than 90 per cent compares to an estimated reduction of only 35 per cent in the prevalence of NSP types III-V (groups of susceptible genotypes) between 2002 and 2012 that can be extracted from the results reported in Ortiz-Pelaez and others (2014). The greater reduction in scrapie prevalence could be an effect of both herd immunity and culling under the Compulsory Scrapie Flocks Scheme, which has been in force since 2004. To monitor the effect of the NSP on the genotype profile of the British national flock, it is desirable to genotype far more samples than the limited yearly numbers set as minimum requirements by the European Commission. The study by Ortiz-Pelaez and others (2014) illustrates the valuable insight that can be gained by extensive genotyping efforts.
References
EUROPEAN COMMISSION (2013) Report on the monitoring of ruminants for the presence of transmissible spongiform encephalopathies (TSEs) in the EU in 2012. Safety of the Food Chain; Food Hygiene, Alert System and Training October 9, 2013 HAGENAARS, T. J., MELCHIOR, M. B., BOSSERS, A., DAVIDSE, A., ENGEL, B. & VAN ZIJDERVELD, F. G. (2010) Scrapie prevalence in sheep of susceptible genotype is declining in a population subject to breeding for resistance. Veterinary Research 6, 25 MELCHIOR, M. B., HAGENAARS, T. J., DAVIDSE, A., VAN KEULEN, L. J. M., BOSSERS, A. & VAN ZIJDERVELD, F. G. (2011) Active surveillance for scrapie in the Netherlands: effect of a breeding programme on the prevalence of scrapie in sheep (2002-2010)? Tijdschrift Voor Diergeneeskunde 136, 84-93 ORTIZ-PELAEZ, A., THOMPSON, C. E. & DAWSON, M. (2014) Impact of the National Scrapie Plan on the PRNP genotype distribution of the British national flock, 2002-2012. Veterinary Record doi:10.1136/ vr.102255 TONGUE, S. C., WILESMITH, J. W., NASH, J., KOSSAIBATI, M. & RYAN, J. (2008) The importance of the PrP genotype in active surveillance for ovine scrapie. Epidemiology and Infection 136, 703-712
doi: 10.1136/vr.g3392
May 24, 2014 | Veterinary Record | 529
Downloaded from http://veterinaryrecord.bmj.com/ on May 14, 2015 - Published by group.bmj.com
Control of scrapie by selective breeding: what are we getting for free? Thomas J. Hagenaars Veterinary Record 2014 174: 528-529
doi: 10.1136/vr.g3392 Updated information and services can be found at: http://veterinaryrecord.bmj.com/content/174/21/528
These include:
References Email alerting service
This article cites 3 articles, 0 of which you can access for free at: http://veterinaryrecord.bmj.com/content/174/21/528#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
