Lethal biological control of rabbits – the most powerful tools for landscape-scale mitigation of rabbit impacts in Australia Tanja Strive1,2* and Tarnya E. Cox2,3 1Commonwealth Scientific and Industrial Research Organisation, Health & Biosecurity, Canberra, ACT, Australia 2Centre for Invasive Species Solutions, Canberra, Australia 3Vertebrate Pests Research Unit, New South Wales Department of Primary Industries, Orange, NSW, Australia Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021 *Author for correspondence

The viral biocontrol agents Myxoma virus (MYXV) and Rabbit Haemorrhagic Disease Virus (RHDV1), released in 1950 and 1996 respectively, are the only control tools to have resulted in significant and lasting landscape-scale suppression of rabbit populations in Australia. Multiple conservation benefits and significant economic savings have resulted from the long-term and widespread reductions in rabbit numbers and impacts. In an effort to ‘boost’ rabbit biocontrol, an additional variant of RHDV1 (’K5’) was recently released nationwide to counteract the decreasing effectiveness of both RHDV1 and MYXV that results from the evolutionary ‘arms race’ between viruses and their hosts. Two years prior to the K5 release, an exotic RHDV strain (RHDV2) appeared in Australia. The commercially available vaccine used to protect pet and farmed rabbits against the officially released K5 was ineffective against the exotic RHDV2, resulting in numerous deaths of domestic rabbits. This created substantial confusion about which strain was released as a biocontrol tool, as well as renewed concerns amongst pet rabbit owners and rabbit farmers about the use of viruses as lethal rabbit control tools in general. Ongoing effective control of wild rabbits in Australia is absolutely essential to protect the substantial conservation gains made by the long-term suppression of rabbit numbers over the past decades, and there is currently no alternative population control tool to achieve this at the required landscape scale. Vaccine formulations need updating to protect non-target farmed and pet rabbits from circulating field variants, including RHDV2, and to increase public acceptance for the ongoing use of viral biocontrol for feral rabbit populations. ABSTRACT

Key words: RHDV, pest, biocontrol, virus, rabbit, population, control, feral, impact, community, disease

DOI: https://doi.org/10.7882/AZ.2019.016

Introducing wild rabbits to ever recorded colonisations of a vertebrate invasive species Australia: a genuinely bad idea (Stodart and Parer 1988). Their reproductive prowess, combined with fewer predators and diseases than rabbits Amongst the many introduced vertebrates that have had faced in their country of origin, meant numbers soon built a lasting and devastating effect on Australia’s environment up and caused the historical rabbit plagues of the 1930s. and agriculture, the European rabbit (Oryctolagus cuniculus) Direct competition with native animals, overgrazing, and is perhaps the best known example, and Australia’s struggle soil disturbances leading to the loss of valuable topsoil, against rabbits has been the subject of many books (Fenner wreaked havoc with the Australian environment and and Ratcliffe 1965; Coman 2010; Munday 2017). European destroyed many livelihoods (Coman 2010; Munday 2017). rabbits were brought to Australia with the first fleet While the harvesting of rabbit meat and pelts created new (Peacock & Abbott, 2013) but the main introduction that livelihoods for some, the continental scale of the rabbit led to the continent being overrun by rabbits is believed to problem meant that all attempts at manual local control have been the introduction of a small number of wild type including trapping, fencing, poisoning and shooting, were rabbits from England into Geelong in 1859 (Coman 2010). insufficient to stem the tide (Coman 2010; Munday 2017). Introduced for sport by members of the Naturalisation Society, rabbits soon ran wild and spread across the habitable range. Approximately 70% of the continent, with Biological control of rabbits the exception of the wet tropics and extremely arid areas, Tools were needed that would work at a landscape scale, and were colonised by rabbits within 70 years, one of the fastest a self-disseminating lethal disease appeared to be the most

Australian 118 Zoologist volume 40 (1) 2019 Theme Edition: Killing for Conservation Lethal biological control of rabbits promising method to achieve this (Fenner and Ratcliffe 1991 and subjected to extensive efficacy and species- 1965). Other forms of biocontrol were also contemplated specificity testing inside secure containment facilities (and some implemented) including the release of cats at the CSIRO Australian Animal Health Laboratory (successfully) and mongoose (unsuccessfully) into the bush (Lenghaus et al. 1994; Cooke and Fenner 2002; Cooke in Australia (Rolls 1969; Peacock and Abbott 2010), and 2014). Later, experimental assessments involved field the release of mustelids in New Zealand, which precipitated trials conducted on Wardang Island close to the South a suite of other problems (Dowding and Murphy 2001; Australian coast. From there, the virus infamously escaped Parkes and Murphy 2003). Various diseases and parasites in late 1995, likely aided by carrion feeding flies that were suggested and evaluated as control agents, but none can mechanically transmit the virus over great distances appeared suitable for the task until the appearance of by ingesting contaminated rabbit flesh (McColl et al. myxomatosis. The disease emerged when its causative 2002). Attempts to contain the outbreak failed, and the agent, the myxoma virus (MYXV), jumped from its natural virus was subsequently officially released in Australia in host Sylvilagus brasiliensis, a cottontail rabbit native to 1996 (Cooke 2014). A year later RHDV1 was illegally Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021 the Americas, to the European rabbit, causing severe introduced into New Zealand, where its release had not generalised disease and very high fatality rates in this new been approved by the government (O’Hara 2006). The host. Decades of research ultimately led to the release of the initial spread of RHDV1 across the Australian continent virus in 1950 at two sites near Lake Urana in 1950 (Kerr via insect vectors, and likely also aided by people, was swift 2012). MYXV is transmitted between rabbits via biting (Kovaliski 1998), and the impact substantial. Population insects such as mosquitoes and fleas, and following good declines of >90% were reported in some areas (Mutze et rainfall and resulting abundance in mosquito vectors, the al. 2008), although effectiveness in higher rainfall areas virus started to spread. The initial impact of myxomatosis was lower and in some cases negligible (Cooke et al. 2002; on Australian rabbit populations was substantial, with Richardson et al. 2007). This was later attributed to an case-fatality rates and population reductions of >99% endemic, non-virulent virus related to RHDV1, rabbit reported in some areas (Kerr and Best 1998). However, calicivirus Australia-1 (RCV-A1) that can cause partial within a few years, rabbits developed genetic resistance and transient immunity to lethal RHDV1 infections (Alves et al. 2019), and field strains of MYXV with more (Strive et al. 2010; Strive et al. 2013). moderate grades of virulence started to circulate. Work led by Professor Frank Fenner of the Australian National From an animal welfare perspective, RHDV1 was University discovered that MYXV and its host were considered a much more humane solution for rabbit control co-evolving to maximise transmission via biting insects compared to MYXV, as its extremely high virulence results (Fenner et al. 1994). This led to prolonged disease with high in a short course of disease. RHDV1 kills susceptible virus loads in the skin lesions that allowed a longer window rabbits between 36-72 hours after infection with clinical of time for insect vectors to transmit the disease, and also signs such as fever and lethargy observable for an average leading to increased survival rates of rabbits (Kerr et al. of 12 h prior to death. Sometimes no signs of disease are 2012). This ground breaking work later became the text observed and animals are found without any external signs book example for the evolution of virulence in an emerging of disease (reviewed in Abrantes et al., 2012) (Figure 1). In pathogen (Kerr 2012). Not only did this shift towards a less contrast to MYXV, which within a few years co-evolved virulent form of MYXV lead to rabbit numbers gradually with the host towards more moderate virulence grades, increasing again, it also had severe implications for animal RHDV1 has not been evolving towards an attenuated welfare. The prolonged disease led to the now well-known phenotype. It has been proposed that for RHDV1 the severe clinical signs of myxomatosis with abundant skin rabbit carcass, not the diseased animal, is the main source lesions and secondary bacterial infections often leading to of virus transmission via carrion-feeding flies, resulting blindness, and with a disease duration of several weeks in in selection for high levels of virulence associated with some cases (Kerr 2012) (Figure 1). Notably, in domestic a short duration of disease and high case-fatality levels rabbits not selected for MYXV resistance, field strains from (Elsworth et al. 2014; Schwensow et al. 2014). the 1990s (50 years after the initial release) now exhibit a hypervirulent phenotype, indicating that the arms race The massive decline in overall rabbit population densities remains ongoing (Kerr et al. 2017). across Australia following the arrival of RHDV1 led to substantial conservation benefits. For example, in arid As rabbit numbers increased again, the search began Australia the long-term reduction of rabbit populations for new and alternative means of biological control. In and associated decline of introduced predators such as 1984 a second highly lethal disease of European rabbits feral cats and foxes allowed for the recovery of three emerged (Liu et al. 1984), likened by some as lightning species of small native mammals to the extent that these striking twice in the same place. Rabbit haemorrhagic were removed from the IUCN red list (Pedler et al. 2016). disease (RHD) first became apparent in farmed rabbits Drastic reduction of the grazing pressure benefitted in China where it caused an infectious hepatitis with graziers (Figure 2) and facilitated the regeneration of case-fatality rates in excess of 90% (reviewed in Abrantes palatable tree and shrub species preferred by rabbits et al. 2012). The causative agent, rabbit haemorrhagic (Bird et al. 2012). This resulted in the recovery of semi- disease virus (RHDV1) was imported to Australia in arid woodland communities such as those in North Australian 2019 Zoologist volume 40 (1) 119 Theme Edition: Killing for Conservation Strive & Cox Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021

Figure 1: Cases of fatal myxomatosis (A) and RHD (B) in wild Australian rabbits. Showing (A) the typical cutaneous swelling and mucopurulent conjunctivitis caused by MYXV, and (B) the typical posture of a rabbit that died from acute RHD. RHDV casualties are often found above ground with no external signs of disease (Images: Tanja Strive).

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Figure 2: Native pasture regeneration during a period of drought on Thackaringa Station near Broken Hill between 2000 (A) and 2012 (B). Population knock down by RHDV1 was followed up with extensive warren ripping programs (Images: David Lord).

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West Victoria (Sandell 2002). RHDV1 substantially after the release of RHDV1, rabbit numbers gradually contributed to the economic benefits of viral biocontrol began to increase again (Saunders et al. 2010; Mutze et al. of rabbits; the combined economic impact of MYXV and 2015). It was apparent that a pipeline of additional tools RHDV1 between 1950 and 2011 was estimated to have was needed to maintain rabbit numbers and impacts at a resulted in more than $70 billion AUD in benefits to low level to protect the considerable environmental gains agricultural industries (Cooke et al. 2013). made in the past 70 years (Cox et al. 2013).

Non-lethal biocontrol options Enter RHDV1 K5 Substantial effort went into investigating non-lethal In 2009 a project (the ‘Boost’ project) funded by the control options for rabbits. A process termed virally- Invasive Animals Cooperative Research Centre (IACRC) vectored-immunocontraception investigated the use of was undertaken to investigate the importation and genetically modified and attenuated MYXVs as vaccine release of additional variants of RHDV to improve rabbit Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021 vectors to deliver an anti-fertility antigen aimed at biocontrol. At that time Australia only had one variant of rendering female rabbits infertile. While proof of concept RHDV1, an isolate from Czechoslovakia (Czech variant), was achieved, the duration of infertility was insufficient released in 1995/6, and its descendants (Kovaliski et to achieve long term population reduction (van Leeuwen al. 2014; Eden et al. 2015). Throughout the rest of the and Kerr 2007). In addition, it was uncertain if the world where RHDV1 exists, there is a greater genetic vaccine virus would ever be able to spread amongst wild diversity of the virus, possibly giving the virus an increased populations in the presence of competing wild type MYXV capacity to outcompete any genetic resistance developing strains and achieve the required female sterilisation in rabbits. The ultimate aim of the Boost project was to rates of 60-80% (Twigg et al. 2000) and work on this identify a variant that could overcome genetic resistance approach was discontinued in 2005 (van Leeuwen and and immunity to the Czech variant, as well as the Kerr 2007). Recent rapid advances in gene technologies partial protection conveyed by the non-pathogenic has sparked considerable discussions about the potential calicivirus RCV-A1, (Strive et al. 2009). In addition, it to genetically modify entire populations for more humane was hypothesized that an increase in genetic diversity pest management (Esvelt et al. 2014, Moro et al. 2018), alone may increase viral fitness in the face of developing for example, by genetically altering populations to only genetic resistance of the host and provide some benefit to produce male offspring which could ultimately lead to a RHDV1-mediated biocontrol in Australia. population collapse. However, such technologies are still in the developmental stages for mammals, and in addition The Boost project imported 38 RHDV variants from to technical advances, extensive regulatory and risk around the world and evaluated them, along with one assessments and public consultations would be required Australian field variant (a descendant of the Czech before any such approach be considered. variant), for their genetic variance compared to the original Czech variant. Fifteen variants, including the Australian field variant, were identified as being sufficiently different MYXV and RHDV1: a hard act to genetically from the Czech variant to warrant further follow investigation and animal testing (PestSmart 2014). Six The success of viral biocontrol of rabbits is largely due to variants were then chosen for further experimental work the self-disseminating nature of both MYXV and RHDV1. and were evaluated against both vaccinated and RCV-A1 Following their initial introduction, both viruses became infected laboratory rabbits, as well as in descendants of endemic in Australia’s wild rabbit populations, causing known genetically-resistant wild rabbits (Elsworth et al. smaller but regular outbreaks at varying intervals with 2012). RHDV1 K5 was selected as the candidate variant no additional costs incurred. Insect-aided transmission for release due to its ability to overcome the transient continues to allow both viruses to travel great distances protective effects of the non-pathogenic calicivirus RCV- between rabbit populations that are not directly connected. A1 as well as its ability to infect genetically-resistant All this notwithstanding, it is important to note that viral rabbits at lower dose rates (PestSmart 2014). While one biocontrol of rabbits is not a silver bullet leading to rabbit other variant could overcome vaccination against RHDV1 eradication, neither in the short- nor the long-term (suggesting it could overcome acquired immunity), its (Morin et al. 2014). Even the most devastating outbreak case fatality rate was too low (14-28%) to consider it as will not eradicate 100% of animals, and it is necessary to an effective viral biocontrol agent. follow up with complementary, mechanical methods to prevent populations from rebounding. In addition, over Safety concerns are paramount for the approval of a viral time, some Australian rabbits appear to have evolved biocontrol agent and species-specificity is a prerequisite. some level of genetic resistance to RHDV1 (Nystrom et Prior to the approval of the original Czech variant, the first al. 2011; Elsworth et al. 2012), although in contrast to RHDV1 released in Australia, species-specificity testing MYXV resistance this took longer and did not lead to an carried out in 28 vertebrate species revealed no signs of attenuation of the disease (Elsworth et al. 2014). Long- productive infection in any animal other than the rabbit term trends have shown that approximately one decade (Lenghaus et al. 1994). Trace amounts of viral RNA have Australian 122 Zoologist volume 40 (1) 2019 Theme Edition: Killing for Conservation Lethal biological control of rabbits been found in rodents and small mammals co-habiting medical research were affected. The appearance and with rabbits (Merchan et al. 2011), and scavengers such spread of RHDV2 caused substantial confusion about the as foxes, that are exposed to large amounts of viral different biological properties of the two viruses in popular antigen when consuming carcasses after RHD outbreaks, and social media. For example, which strain was intended have detectable antibodies to RHDV1 (Leighton et al. to be registered as a biocontrol agent for deliberate release 1995; Philbey et al. 2005). However, in the absence of (K5) and which was an exotic incursion (RHDV2) and evidence for viral replication, these observations are which of the strains infected and killed young rabbits and merely indicative of the high environmental load and could overcome vaccine protection. With this complex stability of the virus. Since its emergence more than scenario, and fuelled by the distressing loss of domestic three decades ago, RHDV1 (including subtypes similar rabbits to RHDV2, the use of viral biocontrol for rabbits to K5) has been circulating in domestic and wild rabbit was again subject to considerable public debate, ranging populations worldwide. Despite the massive exposure, from concerns about welfare and species-specificity there has been no evidence of RHDV1 infecting and through to allegations that RHDV2 was deliberately Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021 causing disease in any species other than rabbits. released by the government. A pilot vaccine efficacy study demonstrated 100% protection against RHDV1 K5 Following approval as a biocontrol agent by the Australian by the vaccine commercially available in Australia (Read Pesticides and Veterinary Medicines Authority, RHDV1 and Kirkland 2017) but the study was heavily criticised K5 was released in a nation-wide coordinated program because it tested vaccine efficacy only to 30 days post at over 330 sites, with both community and agency- vaccination, not 12 months. Although RHDV variants run sites encompassing every State and Territory. The similar to K5 have been circulating outside Australia release occurred in March 2017 with participating sites since the mid-1990s and have been effectively managed in undertaking pre-release rabbit counts in Jan/Feb 2017 and Europe with existing vaccines (OIE 2016), and despite the post-release rabbit counts in April 2017. fact that K5 had also already been through a successful release assessment and approval process (which included assessment of vaccine efficacy), a campaign was launched RHDV2: an unexpected arrival is by a group of concerned rabbit owners to stop the impacting the K5 release K5 release based on concerns the vaccine would be In May 2015, routine testing of a dead wild rabbit ineffective. As with other contentious issues in invasive revealed infection with a European variant of RHDV species control, media updates on the release were not just not known to be present in Australia (Hall et al., 2015). actively debated but also attracted a substantial amount The virus had a high level of genetic similarity with of online trolling, including some serious threats to isolates described in the Iberian Peninsula in 2013/14 scientists and staff involved in the release. The campaign (Lopes et al., 2015); however, the route of entry into was unsuccessful, and, in the first week of March 2017, Australian wild rabbits remains unresolved. This virus, RHDV1 K5 was released in Australia. termed RHDV2, in contrast to the original RHDV1s and RHDV1 K5, can affect a very high proportion of Leading up to the nationwide release, an unexpectedly young rabbits. In addition, RHDV2 has been shown large number of rabbit owners vaccinated their animals, to overcome acquired immunity due to prior exposure leading to a temporary shortage of the commercial vaccine to RHDV1 (Peacock et al. 2017; Calvete et al, 2018) in Australia. This demonstrated that i) the number of and has been reported to infect and kill several hare domestic rabbits in Australia was underestimated, and ii) species including the European brown hare (Lepus a large number of rabbit owners had previously chosen europeaus), the only other lagomorph species present not to vaccinate their pets against RHDV1, which had in Australia (Hall et al. 2017; Velarde et al. 2017). been circulating in Australian wild rabbit populations and These traits are likely to confer a strong competitive posing a risk to domestic rabbits since 1995. The renewed advantage in the field, and indeed RHDV2 became public debate again raised many questions regarding the dominant strain in the Australian landscape the use of viruses as a control agent for vertebrates in within 18 months of its arrival (Mahar et al. 2018). As general and, in particular, the safety, necessity and ethical it is antigenically quite different, commercial vaccines justification of this approach. available in Australia are not sufficiently protective against this strain (Dalton et al. 2014; OIE 2016). Consequently, as RHDV2 spread westwards from Why is biological control for eastern Australia, reports of mortalities in domestic rabbits still considered in rabbits due to RHDV2 increased (Mahar et al. 2018). Australia?

While preparations for the planned K5 release in March It was estimated that the release of the K5 variant 2017 were well-advanced, RHDV2 had reached Western would achieve a reduction in the rabbit population of Australia and Tasmania, and RHDV2 outbreaks were between 15 and 25%, depending on how far it would re-occurring in the eastern States. Wild rabbits as well spread beyond release sites as well as the overall level of as domestic rabbits kept as pets and bred for meat and immunity of local populations. As this was a low estimate Australian 2019 Zoologist volume 40 (1) 123 Theme Edition: Killing for Conservation Strive & Cox compared to the initial impacts of MYXV and RHDV1 is paramount (Cooke 2012). While rabbit populations Czech, and as rabbit numbers were not as high as they have not recovered to pre-MYXV or pre- RHDV1 levels, had been prior to the release of RHDV1 in the mid- numbers have been gradually increasing again over the 1990s, a frequently- asked question was ‘why bother’? past ten years (e.g. (Mutze et al. 2015). The sustained The aim of the K5 release was predominantly to slow reduction of rabbit numbers and their impacts remain down the recovery of rabbit populations, compensate for critically important on many levels. Rabbits are listed as the evolving genetic resistance in rabbits to circulating a Key Threatening Process through competition and land strains, reduce the additional damage caused by the degradation, and threaten 304 animal and plant species, presence of RCV-A1, and protect the benefits gained and nine ecological communities (Commonwealth 2016). by long-term reduction of rabbit numbers (Figure 3). In addition, there is a substantial amount of literature This emphasises that biocontrol is most effective as showing that the presence of rabbits, even at very low part of a larger, integrated control program (Figure 3); densities, can prevent the recruitment of certain palatable immediately after the initial population knock-down, tree and shrub species and increase the proportion Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021 follow-up using additional control methods are needed, of unpalatable species, particularly in arid Australian not only to sustainably reduce rabbit impacts on the environments (reviewed in Mutze 2016). For example, environment and agricultural productivity, but also to even at low densities <0.5 rabbits/ha, the selective grazing meet animal welfare demands by reducing the need to of rabbits prevented the regeneration of highly palatable repeatedly kill large numbers of animals. One of the species such as Allocasuarina (Bird et al. 2012), a key most effective means for long-term suppression of rabbit component of some semi-arid ecosystems. numbers is harbour destruction. A study investigating the effect of rabbit warren-ripping in the wake of the first The impacts of invasive species, in particular introduced spread of RHDV in the late 1990s demonstrated that cats and foxes, continue to be the main drivers for the loss reductions in rabbit populations persisted for at least a of mammalian biodiversity in Australia (Woinarski et al. decade (McPhee and Butler 2010). 2015). The sustained biocontrol of rabbits has been shown to cause both top-down and bottom-up biodiversity impacts, not only removing grazing pressure and direct Rabbits remain one of Australia’s competition with native mammals, but also leading to worst introduced vertebrate pests a long-term reduction of feral cat and fox populations. Despite the success of MYXV and RHDV, rabbits continue Due to these multiple effects, targeting rabbits has been to keep many Australian ecosystems in a degraded state, highlighted as an important strategy in an environment and active ongoing and effective rabbit control in Australia where smart investment decisions need to be made

Figure 3: General trends in rabbit numbers, estimated benefits of MYXV and RHDV1 (Czech strain), and predicted benefits of the RHDV1 K5 virus release with and without additional conventional control. The rabbit impact threshold shown is for illustration purposes only, impact thresholds vary in the context of different landscapes and/or ecological communities. Figure modified from (Saunders et al. 2010; Cox et al. 2013).

Australian 124 Zoologist volume 40 (1) 2019 Theme Edition: Killing for Conservation Lethal biological control of rabbits with the often scant resources available for biodiversity numbers as low as possible, while at the same time conservation (Pedler et al. 2016). reducing the potential disease reservoir for domestic rabbits. Ultimately, circulating field strains of RHDV and MYXV can only be eradicated in Australia by Wild rabbits are a disease eradicating the wild rabbit reservoir, and until this reservoir for domestic rabbits aspirational goal is achieved, the only way to effectively Effective control of wild rabbit populations is also in the protect non-target domestic rabbits is by vaccination interests of rabbit farmers and pet rabbit owners. While and biosecurity measures where no vaccine is available. RHDVs can be transmitted via contact, both RHDVs and MYXV are transmitted by insects; therefore containment through biosecurity measures alone is extremely Conclusions: challenging, if not impossible, for domestic rabbits that Maintaining wild rabbit numbers at low levels is have access to the outdoors. Since their introduction, key to protecting the significant conservation gains Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021 both MYXV and RHDV1 have been circulating in wild made by the long-term impact of the initial MYXV rabbits causing repeated outbreaks of disease at varying and RHDV releases. This may be achieved through intervals, affecting almost every wild rabbit population a combination of management tools, follow-up and in Australia investigated so far (e.g. McPhee et al. 2002; long-term management strategies resulting in sustained Mutze et al. 2010; Cox et al. 2017). Good biosecurity can benefits to biodiversity and agriculture as well as better protect domestic rabbits from the viruses to some degree overall outcomes for animal welfare. and domestic rabbit owners can currently vaccinate their animals against RHDV1 variants. However, higher Non-lethal control tools that are self-disseminating and densities and wider dispersions of wild rabbits increases effective at a landscape-scale clearly are the holy grail of the chance of biosecurity breeches and exposure of vertebrate pest management, and while no such tool has yet vaccinated rabbits to RHDV2 and MYXV, for which there been successfully developed for rabbits despite considerable are currently no effective vaccines available in Australia. efforts; ongoing research into this area is clearly warranted.

Since its confirmed arrival in 2015, RHDV2 has been In the meantime, it is essential that we continue to use, reported to cause several outbreaks in a year in some refine and integrate the control tools available for rabbit wild rabbit populations, although ongoing studies are control in order to maximise their impact. In the absence needed to allow the epidemiological patterns for this of other effective broad-scale, self-disseminating non- new virus to be determined. The originally released lethal tools such as fertility or genetic controls, we believe RHDV1 Czech has been re-released many times since that the net benefit justifies the continued application and the 1990s, and although it acted locally, it was not support of viral rabbit biocontrol. shown to enter the population of naturally-circulating field virus variants (Kovaliski et al.,2014). K5 is now The first national release of a viral biocontrol agent since available as a product for biological control. It is 1996 has highlighted that one of the biggest non-technical important to note that the alternative to a virus release challenges today is to gain public support, and to convey is not the absence of any virus, but rather a circulating complex and often counter-intuitive information in an field strain affecting wild populations at regular era where scientifically unsound technical information is intervals. Increasingly, any circulating field strain in readily available on-line and used to feed confirmation bias. Australia is likely to be the exotic RHDV2 (Mahar et al. 2018). However, used strategically in conjunction with Although RHDV2 was not deliberately released as a other control methods and in synergy with naturally- biocontrol tool, it is critical that effective vaccines are made occurring outbreaks, planned K5 virus releases could available to protect non-target domestic rabbits from this potentially reduce wild rabbit populations above and virus. This would likely increase the social acceptance of beyond that achieved by naturally-circulating viruses rabbit viral biocontrol, which remains an essential tool to and conventional control methods combined. K5 can manage rabbits at a landscape-scale on a continent that therefore play an important role in keeping wild rabbit faces the world’s worst ongoing mammal extinction rates.

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References: Abrantes, J., van der Loo, W., Le Pendu, J. and Esteves, Cox, T. E., Liu, J., de Ven, R. v. and Strive, T. 2017. P. J. 2012. Rabbit haemorrhagic disease (RHD) and rabbit Different Serological Profiles Two Co-Occurring Pathogenic haemorrhagic disease virus (RHDV): a review. Veterinary And Nonpathogenic Caliciviruses In Wild European Rabbits Research 43: 12. (Oryctolagus Cuniculus) Across Australia. Journal of Wildlife Diseases 53: 472-481. Alves J.M., Carneiro M., Cheng J.Y., de Matos A.L., Rahman M.M., Loog L., Campos P.F., Wales N., Eriksson A., Manica Dalton, K. P., Nicieza, I., Abrantes, J., Esteves, P. J. and Parra, A., Strive T., Graham S.C., Afonso S., Bell D.J., Belmont L., F. 2014. Spread of new variant RHDV in domestic rabbits on Day J.P., Fuller S.J., Marcheandeau S., Palmer W.J., Queney the Iberian Peninsula. Veterinary Microbiology 169: 67-73. G., Surridge A.K., Vieira F.G., McFadden G., Nielsen R., Thomas M., Gilbert P., Esteves P.J., Ferrand N. and Jiggins Dowding, J. E. and Murphy, E. C. 2001. The impact of

F.M.. 2019 Parallel adaptation of rabbit populations to myxoma predation by introduced mammals on endemic shorebirds in Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021 virus. Science. Feb 14:eaau7285. New Zealand: a conservation perspective. Biological Conservation 99: 47-64. Bird, P., Mutze, G., Peacock, D. and Jennings, S. 2012. Damage caused by low-density exotic herbivore populations: the Eden, J.-S., Kovaliski, J., Duckworth, J. A., Swain, G., Mahar, impact of introduced European rabbits on marsupial herbivores J. E., Strive, T. and Holmes, E. C. 2015. and Allocasuarina and Bursaria seedling survival in Australian coastal shrubland. Biological Invasions 14: 743-755. Comparative Phylodynamics of Rabbit Hemorrhagic Disease Virus in Australia and New Zealand. Journal of Virology 89: Calvete C., Mendoza M., Alcaraz A, Sarto M.P., Jiménez-de- 9548-9558. Bagüéss M.P., Calvo A.J., Monroy F. and Calvo J.H. 2018. Rabbit haemorrhagic disease: Cross-protection and comparative Elsworth, P., Cooke, B. D., Kovaliski, J., Sinclair, R., pathogenicity of GI. 2/RHDV2/b and GI. 1b/RHDV lagoviruses Holmes, E. C. and Strive, T. 2014. Increased virulence of in a challenge trial. Veterinary Microbiology 219: 87-95. rabbit haemorrhagic disease virus associated with genetic resistance in wild Australian rabbits (Oryctolagus cuniculus). Coman, B. 2010. Tooth and Nail: The Story of the Rabbit in Virology 464: 415-423. Australia: Text publishing, Melbourne, Australia. Elsworth, P. G., Kovaliski, J. and Cooke, B. D. 2012. Commonwealth 2016. Threat abatement plan for competition and Rabbit haemorrhagic disease: are Australian rabbits (Oryctolagus land degradation by rabbits, Commonwealth of Australia. http:// cuniculus) evolving resistance to infection with Czech CAPM www.environment.gov.au/biodiversity/threatened/publications/ 351 RHDV? Epidemiology and Infection 140: 1972-1981. tap/competition- and-land-degradation-rabbits-2016. Esvelt, K. M., Smidler, A. L., Catteruccia, F. and Church, Cooke, B., Chudleigh, P., S., S. and Saunders, G. 2013. The G. M. 2014. Concerning RNA-guided gene drives for the economic benefits of the biological control of rabbits in Australia, alteration of wild populations. eLife e03401. 1950 - 2011. Australian Economic History Review 53: 91-107. Fenner, F. and Ratcliffe, F. N. 1965. Myxomatosis. Cambridge Cooke, B. D. 2012. Rabbits: manageable environmental pests University Press, Cambridge, UK. or participants in new Australian ecosystems? Wildlife Research 39: 279-289. Fenner, F. and Ross, J. 1994. Myxomatosis. Pp 205-240 in The European rabbit: the history and biology of a successful colonizer, Cooke, B. D. 2014. Australia’s war against rabbits: the story of edited by H.V. Thompson and C.M. King. Oxford University rabbit haemorrhagic disease: CSIRO Publishing, Collingwood, Press, Oxford, UK. Victoria, Australia. Hall, R. N., Mahar, J. E., Haboury, S., Stevens, V., Holmes, E. Cooke, B. D. and Fenner, F. 2002. Rabbit haemorrhagic disease C. and Strive, T. 2015. Emerging Rabbit Hemorrhagic Disease and the biological control of wild rabbits, Oryctolagus cuniculus, Virus 2 (RHDVb), Australia. Emerging Infectious Diseases 21: in Australia and New Zealand. Wildlife Research 29: 689-706. 2276-2278.

Cooke, B. D., McPhee, S., Robinson, A. J. and Capucci, L. Hall, R. N., Peacock, D. E., Kovaliski, J., Mahar, J. E., 2002. Rabbit haemorrhagic disease: does a pre-existing RHDV- Mourant, R., Piper, M. and Strive, T. 2017. Detection like virus reduce the effectiveness of RHD as a biological control of RHDV2 in European brown hares (Lepus europaeus) in in Australia? Wildlife Research 29: 673-682. Australia. Veterinary Record 180: 121

Cox, T., Strive, T., Mutze, G., West, P. and Saunders, G. Kerr, P. J. 2012. Myxomatosis in Australia and Europe: a model 2013. Benefits of Rabbit Control in Australia: Report. Invasive for emerging infectious diseases. Antiviral Research 93: 387-415. Animals Cooperative Research Centre. Australian 126 Zoologist volume 40 (1) 2019 Theme Edition: Killing for Conservation Lethal biological control of rabbits

Kerr, P. J. and Best, S. M. 1998. Myxoma virus in rabbits. McPhee, S., Berman, D., Gonzales, A., Butler, K., Humphrey, Revue scientifique et technique-Office international des épizooties J., Muller, J., Waddington, J., Daniels, P., Koch, S. and 17: 256-268. Marks, C. 2002. Efficacy of a competitive enzyme-linked immunosorbent assay (cELISA) for estimating prevalence of Kerr, P. J., Cattadori, I. M., Liu, J., Sim, D. G., Dodds, J. W., immunity to rabbit haemorrhagic disease virus (RHDV) in Brooks, J. W., Kennett, M. J., Holmes, E. populations of Australian wild rabbits (Oryctolagus cuniculus). Wildlife Research 29: 635-647. C. and Read, A. F. 2017. Next step in the ongoing arms race between myxoma virus and wild rabbits in Australia is a novel McPhee, S. and Butler, K. 2010. Long-term impact of disease phenotype. Proceedings of the National Academy of Science coordinated warren ripping programmes on rabbit populations. 114: 9397-9402. Wildlife Research 37: 68-75.

Kerr, P. J., Ghedin, E., Depasse, J. V., Fitch, A., Cattadori, I. Merchan, T., Rocha, G., Alda, F., Silva, E., Thompson, G., Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021 M., Hudson, P. J., Tscharke, D. C., Read, A. F. and Holmes, de Trucios, S. H. and Pages, A. 2011. Detection of rabbit E. C. 2012. Evolutionary history and attenuation of myxoma haemorrhagic disease virus (RHDV) in nonspecific vertebrate virus on two continents. PLoS Pathogens 8: e1002950. hosts sympatric to the European wild rabbit (Oryctolagus cuniculus). Infection Genetics and Evolution 11: 1469-1474. Kovaliski, J. 1998. Monitoring the spread of rabbit hemorrhagic disease virus as a new biological agent for control of wild Morin, L., Sheppard, A. and Strive, T. 2014. Explainer: European rabbits in Australia. Journal of Wildlife Diseases 34: how ‘biocontrol’ fights invasive species. Pp 31298 in The 421- 428. Conversation. http://theconversation.com/explainer-how- biocontrol-fights-invasive-species- Kovaliski, J., Sinclair, R., Mutze, G., Peacock, D., Strive, T., Abrantes, J., Esteves, P. J. and Holmes, E. C. 2014. Molecular Moro D., Byrne M., Kennedy M., Campbell S. and Tizard epidemiology of Rabbit Haemorrhagic Disease Virus in Australia: M. 2018 Identifying knowledge gaps for gene drive research to when one became many. Molecular Ecology 23: 408-420. control invasive animal species: The next CRISPR step. Global Ecology and Conservation. Jan 1;13:e00363. Leighton, F. A., Artois, M., Capucci, L., Gavier-Widén, D. and Morisse, J.-P. 1995. Antibody response to rabbit viral Munday, B. 2017. Those wild rabbits: How they shaped Australia. hemorrhagic disease virus in red foxes (Vulpes vulpes) consuming Wakefield Press, Kent Town, Australia livers of infected rabbits (Oryctolagus cuniculus). Journal of Wildlife Diseases 31: 541-544. Mutze, G. 2016. Barking up the wrong tree? Are livestock or rabbits the greater threat to rangeland biodiversity in southern Lenghaus, C., Westbury, H., Collins, B., Ratnamohan, N. and Australia? Rangeland Journal 38: 523-531. Morrissy, C. 1994. Overview of the RHD project in Australia. Pp 104-129 in Rabbit haemorrhagic disease: issues in assessment Mutze, G., Bird, P., Jennings, S., Peacock, D., de Preu, N., for biological control, edited by R.K. Munro and R.T. Williams. Kovaliski, J., Cooke, B. and Capucci, L. 2015. Recovery of Bureau of Resource Sciences, Canberra. South Australian rabbit populations from the impact of rabbit haemorrhagic disease. Wildlife Research 41: 552-559. Liu, SJ, Xue, HP, Pu, BQ and Qian, NH 1984. A new viral disease in rabbits. Animal Husbandry and Veterinary Medicine Mutze, G., Bird, P., Cooke, B.D. and Henzell, R. 2008. 16(6): 253-255. Geographic and seasonal variation in the impact of rabbit haemorrhagic disease on European rabbits, Oryctolagus cuniculus, Lopes, A. M., Dalton, K. P., Magalhaes, M. J., Parra, F., and rabbit damage in Australia. Pp 279-293 in Lagomorph Esteves, P. J., Holmes, E. C. and Abrantes, J. 2015. Full Biology: Evolution, Ecology and Conservation, Edited by P. C. F. genomic analysis of new variant rabbit hemorrhagic disease Alves, K. Hackländer. Springer, Berlin-Heidelberg. virus revealed multiple recombination events. Journal of General Virology 96: 1309-1319. Mutze, G., Kovaliski, J., Butler, K., Capucci, L. and McPhee, S. 2010. The effect of rabbit population control programmes Mahar, J. E., Read, A. J., Gu, X., Urakova, N., Mourant, on the impact of rabbit haemorrhagic disease in south-eastern R., Piper, M., Haboury, S., Holmes, E. C., Strive, T. and Australia. Journal of Applied Ecology 47: 1137-1146. Hall, R. N. 2018. Detection and Circulation of a Novel Rabbit Hemorrhagic Disease Virus in Australia. Emerging Infectious Nystroem, K., G. Le Gall-Recule, P. Grassi, J. Abrantes, N. Diseases 24: 22-31. Ruvoen-Clouet, B. Le Moullac-Vaidye, A. M. Lopes, P. J. Esteves, T. Strive, S. Marchandeau, A. Dell, S. M. Haslam McColl, K. A., Merchant, J. C., Hardy, J., Cooke, B. D., and J. Le Pendu (2011). Histo-Blood Group Antigens Robinson, A. and Westbury, H. A. 2002. Evidence for insect Act as Attachment Factors of Rabbit Hemorrhagic Disease transmission of rabbit haemorrhagic disease virus. Epidemiology Virus Infection in a Virus Strain-Dependent Manner. PLoS and Infection 129: 655-663. Pathogens 7(8). Australian 2019 Zoologist volume 40 (1) 127 Theme Edition: Killing for Conservation Strive & Cox

O’Hara, P. 2006. The illegal introduction of rabbit haemorrhagic Saunders, G., Cooke, B., McColl, K., Shine, R. and Peacock, disease virus in New Zealand. Revue scientifique et technique- T. 2010. Modern approaches for the biological control of Office international des épizooties 25: 119. vertebrate pests: An Australian perspective. Biological Control 52: 288-295. OIE 2016. Manual of diagnostic tests and vaccines for terrestrial animals, Chapter 2.6.2 Rabbit haemorrhagic disease. In Office Schwensow, N. I., Cooke, B., Kovaliski, J., Sinclair, R., international des epizooties, Paris, France, pp. 1092-1106. Peacock, D., Fickel, J. and Sommer, S. 2014. Rabbit haemorrhagic disease: virus persistence and adaptation in Parkes, J. and Murphy, E. 2003. Management of introduced Australia. Evolutionary Applications 7: 1056-1067. mammals in New Zealand. New Zealand Journal of Zoology 30: 335-359. Stodart, E. and Parer, I. 1988. Colonisation of Australia by the rabbit Oryctolagus cuniculus (L.): Canberra, Commonwealth

Peacock, D. and Abbott, I. 2010. The mongoose in Australia: Scientific and industrial Research Organisation. Downloaded from http://meridian.allenpress.com/australian-zoologist/article-pdf/40/1/118/2617920/az_2019_016.pdf by guest on 24 September 2021 failed introduction of a biological control agent. Australian Journal of Zoology 58: 205-227. Strive, T., Wright, J. D. and Robinson, A. J. 2009. Identification and partial characterisation of a new lagovirus in Australian wild Peacock, D. and Abbott, I. 2013. The role of quoll (Dasyurus) rabbits. Virology 384: 97-105. predation in the outcome of pre-1900 introductions of rabbits (Oryctolagus cuniculus) to the mainland and islands of Australia Strive, T., Wright, J., Kovaliski, J., Botti, G., and Capucci, Australian Journal of Zoology 61: 206-280. L. 2010. The non-pathogenic Australian lagovirus RCV-A1 causes a prolonged infection and elicits partial cross-protection Peacock, D., Kovaliski, J., Sinclair, R., Mutze, G., Iannella, A. to rabbit haemorrhagic disease virus. Virology 398(1): 125-134. and Capucci, L., 2017. RHDV2 overcoming RHDV immunity in wild rabbits (Oryctolagus cuniculus) in Australia. Veterinary Strive, T., Elsworth, P., Liu, J., Wright, J. D., Kovaliski, Record 180(11): 280-280. J. and Capucci, L. 2013. The non-pathogenic Australian rabbit calicivirus RCV-A1 provides temporal and partial Pedler, R. D., Brandle, R., Read, J. L., Southgate, R., Bird, cross protection to lethal Rabbit Haemorrhagic Disease Virus P. and Moseby, K. E. 2016. Rabbit biocontrol and landscape- infection which is not dependent on antibody titres. Veterinary scale recovery of threatened desert mammals. Conservation Research 44:51. Biology 30: 774-782. Twigg, L. E., Lowe, T. J., Martin, G. R., Wheeler, A. G., PestSmart 2014. RHD-Boost. Import and evaluate new rabbit Gray, G. S., Griffin, S. L., O’Reilly, C. M., Robinson, D. J. haemorrhagic disease virus (RHDV) variants to strengthen and Hubach, P. H. 2000. Effects of surgically imposed sterility rabbit biocontrol. Report to the Vertebrate Pests Committee. on free-ranging rabbit populations. Journal of Applied Ecology PestSmart Toolkit publication, Invasive Animals Cooperative 37: 16-39. Research Centre, Canberra, Australia. van Leeuwen, B. H. and Kerr, P. J. 2007. Prospects for fertility Philbey, A., Kirkland, P. and Saunders, G. 2005. Assessment control in the European rabbit (Oryctolagus cuniculus) using of antibodies to rabbit haemorrhagic disease virus in fox serum myxoma virus-vectored immunocontraception. Wildlife Research as an indicator of infection in sympatric rabbit populations. 34: 511-522. Australian Veterinary Journal 83: 97-100. Velarde, R., Cavadini, P., Neimanis, A., Cabezón, O., Chiari, Read, A. and Kirkland, P. 2017. Efficacy of a commercial M., Gaffuri, A., Lavin, S., Grilli, G., Gavier-Widén, D., vaccine against different strains of rabbit haemorrhagic disease Lavazza, A. and Capucci, L. 2017. Spillover Events of Infection virus. Australian Veterinary Journal 95: 223-226. of Brown Hares (Lepus europaeus) with Rabbit Haemorrhagic Disease Type 2 Virus (RHDV 2) Caused Sporadic Cases of an Richardson, B. J., Phillips, S., Hayes, R. A., Sindhe, European Brown Hare Syndrome-Like Disease in Italy and S. and Cooke, B. D. 2007. Aspects of the biology of Spain. Transboundary and Emerging Diseases 64(6): 1750-1761. the European rabbit (Oryctolagus cuniculus) and rabbit haemorrhagic disease virus (RHDV) in coastal eastern Woinarski, J.C., Burbidge, A.A. & Harrison, P.L. 2015. Australia. Wildlife Research 34: 398-407. Ongoing unravelling of a continental fauna: decline and extinction of Australian mammals since European settlement. Proceedings of Rolls, E. C. 1969. They all ran wild: The Story of Pests on the Land the National Academy of Sciences 112(15): 4531-4540. in Australia. Angus and Robertson, Australia.

Sandell, P. 2002. Implications of rabbit haemorrhagic disease for the short-term recovery of semi-arid woodland communities in north-west Victoria. Wildlife Research 29: 591-598.

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