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Disease control and eradication approaches using marker or DIVA vaccination have never been applied for the aquaculture industry. The challenges and successes experienced in agriculture can provide a guide to successful applications of DIVA strategies against notifiable diseases if this approach were to be adopted in aquaculture.

As well as reducing the impacts of disease, vaccination can also be used to manage or eradicate a disease from a region. It has previously been preferred to terminate vaccination, once a disease-free status had been achieved, as it is expensive for farmers to continue vaccinating (Bouma, 2005). Control of notifiable diseases by mass-culling is generally not acceptable to society (Pasick, 2004; Bouma, 2005), although this approach has been used extensively for both the livestock industry and aquaculture, e.g. for the control of ISA outbreaks in Scotland (Hastings et al., 1999). However, once a disease-free status has been obtained in consumer countries, trade may be adversely affected for vaccinating countries, as was observed with Aujeszky’s disease (AD) in the Netherlands in the 1980s. At this time, disease free-countries, such as the UK and Denmark, employed a sero-surveillance-identify-cull strategy for AD without vaccination in order to retain disease-free status. Therefore export of swine products, e.g. to Japan and USA, was possible, but no import was allowed from countries where the disease was endemic, or if animals were vaccinated, as this would hamper sero-surveillance strategies (Bouma, 2005). Ultimately Pseudorabies virus (PrV), the

causative agent of AD, became an expensive virus for Dutch farmers, not because of animal losses from AD, but losses from trade as their vaccinated stock could not be exported (Stegeman et al., 1997 cited in Bouma, 2005). This is a similar problem for countries where FMD is endemic, as significant constraints are imposed on international trade in live animals and animal products, resulting in high economic impacts associated with loss of export markets and consumer fears (Paarlberg et al., 2002; Clavijo et al., 2004).

The application of marker vaccines, in combination with additional management measures, such as reduced contacts between herds, can contribute to reducing the R value <1 thus improving the possibility of disease eradication, e.g. as seen for PrV (Pasick, 2004;

Bouma, 2005), while providing a means to identify uninfected vaccinated animals. The first successful application of a DIVA strategy was achieved for the control and subsequent eradication of PrV through use of a glycoprotein E (gE) negative vaccine and gE specific serological diagnostic test (Van Oirschot et al., 1990; 1996; Stegeman, 1995; Van Oirschot, 1999; Vannie et al., 2007). However, complications with using DIVA vaccination strategies for controlling notifiable disease also exist for the livestock industry (Bosman et al., 2012).

Obtaining AD-free status breaks the trading restrictions with countries of the same status, but in the event of new outbreaks, as seen for CSF and FMD, disease can spread quickly to naïve pig populations. The control of AD infected farms would involve emergency vaccination and isolation of the virus by movement restrictions. According to the contingency plans for DIVA vaccination of PrV, a 10 km zone around infected farms (i.e. ring vaccination) would be established and all pigs within this zone would be protectively vaccinated while movement restrictions are imposed. This avoids culling of infected, but apparently healthy animals thus preventing controversial mass culling used for control of FMD and CSF (Bosman et al., 2012). However, other animal welfare issues that must be considered during emergency

DIVA vaccination strategies, are the overcrowding and aging of animals that cannot be traded out-with the surveillance zone during the course of the outbreak (Bosman et al., 2012).

However, the benefits of DIVA strategies far outweigh any potential negative impacts. DIVA vaccination has been accepted for control of AI by some countries in the EU.

This has provided an opportunity for consistent monitoring of stocks, and assurance to trading partners on the infection-free status of vaccinated poultry during low pathogenic avian influenza (LPAI) (Capua et al., 2003; 2004; Avellaneda et al., 2010). Furthermore, prophylactic use of vaccines against exotic viral infections in production animals is now undertaken exclusively in regions where disease is endemic. For example, DIVA strategies have been used for many years in South America in order to satisfy their OIE status of

‘FMD-free with vaccination’ in support of exports, e.g. beef. Due to the extensive farming practiced in these countries, clinical surveillance is not easy and sero-surveillance using DIVA offers many advantages (Uttenthal et al., 2010). DIVA strategies have also enabled the eradication of FMD from vaccinated pig populations in the far-east and in countries after emergency vaccination, e.g. against FMD in Macedonia and Albania in 1996 (Uttenthal et al., 2010). Recently, a ‘genetic DIVA’ approach has also been applied to populations of wild boars against classical swine fever virus (CSFV) as transmission of the virus to domestic pigs caused outbreaks of CSF (Blome et al., 2011). Problems were encountered with diagnosis of dead pigs within the surveillance zones because of false positive PCR results to vaccine strain virus, thus a differential real-time RT-PCR (rRT-PCR) assay was developed in order to differentiate nucleic acid of wild-type virus from the vaccine strain (Blome et al., 2011).

Ultimately, implementing a combination of vaccination and eradication programmes through DIVA strategies could enable a ‘vaccinate-to-live’ policy for notifiable diseases. By emergency ‘ring vaccination’ with marker vaccines and DIVA sero-surveillance, it may be

possible to reduce transmission, clinical disease, and the presence of infectious virus within animal stocks, and perhaps fish farms, without jeopardising animal trade.