A literature review was conducted in order to identify unique weaknesses in the physiology or metabolism of pigs that could be targeted with specific chemicals (i.e. an 'Achilles' heel' search). A promising weakness identified was the species' susceptibility to methaemoglobin-forming compounds, most likely related to their uniquely low levels of methaemoglobin reductase. Further examination revealed that sodium nitrite is a cost-effective, readily available methaemoglobin-forming compound that is highly toxic to domestic pigs, which has caused numerous accidental poisonings. Pen trials on pigs showed that sodium nitrite delivered by gavage (>90 mg kg À1 ) and freely consumed in bait (>400 mg kg À1 ) caused rapid and lethal rises in methaemoglobin. Sodium nitrite appeared to be more humane than currently used toxins, with deaths following bait consumption being considerably quicker and with fewer symptoms (within 80 min of clinical signs beginning; clinical signs including infrequent vomiting, lethargy, ataxia and dyspnoea). The review also identified a second deficiency in the metabolism of pigs, namely high sensitivity to selective inhibition of cytochrome P450 liver enzymes. This leads to potentially lethal interactions between various drugs, such as two antibiotics, monensin and tiamulin. A pen trial confirmed that the antibiotic combination in a single gavage dose was reliably and rapidly lethal to pigs. However, its utility as a pig toxin is low, because it was unpalatable to pigs when delivered in bait and appeared to cause pain and suffering (leading to the early termination of pen trials). The findings presented here demonstrate the potential of sodium nitrite as an additional feral pig toxin.1. High toxicity. 2. Acceptability to the target population. 3. Commercially and appropriately available. 4. Appropriate degradation. 5. The toxin must remain at the site of application. 6. Acceptable operator hazard.

The release of myxoma virus (MYXV) and Rabbit Haemorrhagic Disease Virus (RHDV) in Australia with the aim of controlling overabundant rabbits has provided a unique opportunity to study the initial spread and establishment of emerging pathogens, as well as their co-evolution with their mammalian hosts. In contrast to MYXV, which attenuated shortly after its introduction, rapid attenuation of RHDV has not been observed. By studying the change in virulence of recent field isolates at a single field site we show, for the first time, that RHDV virulence has increased through time, likely because of selection to overcome developing genetic resistance in Australian wild rabbits. High virulence also appears to be favoured as rabbit carcasses, rather than diseased animals, are the likely source of mechanical insect transmission. These findings not only help elucidate the co-evolutionary interaction between rabbits and RHDV, but reveal some of the key factors shaping virulence evolution.

The endemic non-pathogenic Australian rabbit calicivirus RCV-A1 is known to provide some cross protection to lethal infection with the closely related Rabbit Haemorrhagic Disease Virus (RHDV). Despite its obvious negative impacts on viral biocontrol of introduced European rabbits in Australia, little is known about the extent and mechanisms of this cross protection. In this study 46 rabbits from a colony naturally infected with RCV-A1 were exposed to RHDV. Survival rates and survival times did not correlate with titres of serum antibodies specific to RCV-A1 or cross reacting to RHDV, but were instead influenced by the time between infection with the two viruses, demonstrating for the first time that the cross protection to lethal RHDV infection is transient. These findings are an important step towards a better understanding of the complex interactions of co-occurring pathogenic and non-pathogenic lagoviruses.

Multi‐strain, host‐disease dynamics describe a system where multiple strains of a pathogen compete for susceptible individuals of a single host. The theoretical properties of these systems have been well studied, but there are few empirical studies in wildlife hosts. We examined the impacts of two novel strains of rabbit haemorrhagic disease virus (RHDV) recently introduced into Australia, one inadvertently (RHDV2) and one deliberately for rabbit biocontrol (RHDV‐K5), by analysing long‐term monitoring data for introduced European rabbits Oryctolagus cuniculus from 18 sites throughout Australia. We examined population‐level impacts using rabbit spotlight counts pre‐ and post‐arrival of the two strains. We also analysed serological data to determine potential interactions among the introduced and existing field strains of RHDV, as well as a pre‐existing benign strain of calicivirus (RCV‐A1). Serological analyses suggested that RHDV2 arrived in Australia during spring 2014 and spread rapidly through the Australian rabbit population within 2 years. Following the establishment of RHDV2, rabbit abundance was reduced by an average of 60%, with impacts most pronounced in South and Western Australia. In contrast, the deliberate release of RHDV‐K5 had little impact on rabbit populations. Although RHDV2 has spread rapidly throughout Australia, our serological analyses do not support the observation that RHDV2 is rapidly replacing existing field strains of RHDV, as was previously reported in Australia and Europe. Nevertheless, RHDV2 has negatively impacted the ability of RHDV and RCV‐A1 to spread within rabbit populations, most likely due to its ability to infect juvenile rabbits, thereby removing them from the pool of susceptible individuals available to be infected by competing strains. Synthesis and applications. The impact of the release of a novel strain of rabbit haemorrhagic disease virus (RHDV‐K5) for rabbit biocontrol in Australia has been suppressed by the emergence of a competing strain, RHDV2. Hence, the success of further releases of similar RHDV strains for rabbit biocontrol appears doubtful. Despite this, RHDV2 has suppressed rabbit abundances by an average of 60%, with impacts most pronounced in South and Western Australia. Whether the incursion of RHDV2 leads to the competitive exclusion of other endemic RHDV strains remains to be resolved. However, the existence of partial cross‐immunity could allow some level of coexistence between RHDV2 and RHDV strains, at least in the medium term.