Summary 1.Additional methods are needed in Australia to control the European rabbit Oryctolagus cuniculus , which continues to destroy valued native flora. A control option under development, immunocontraception, is intended to suppress the rabbit's high fertility. It would spread contagiously via genetically modified myxoma virus and European rabbit fleas Spilopsyllus cuniculi . An experiment with field populations of rabbits assessed whether suppressing fertility reduces their abundance. 2. In south-eastern Australia, four treatments in three replicates were applied to 12 subpopulations of rabbits. The treatments were surgical sterilization of 0%, 40%, 60% and 80% of the adult and juvenile females trapped before the annual breeding seasons of 1993-96. 3. The sterilized populations produced fewer young but the average adult population size remained unchanged in all treatments. Immigration was minimal in all treatments. 4. Sterilized adult female rabbits survived much better than fertile females, indicating a high cost of reproduction. Immature rabbits and unsterilized adults of both sexes also survived better in the sterilization treatments. The improved survival in all rabbit classes compensated for reduced reproductive output. 5. Fleas were fewer on both adult females and males in the sterilized populations but this did not impede transmission of myxomatosis. 6. Synthesis and applications . Imposing sterility on rabbit populations reduces breedingseason peaks of abundance. Improved survival compensates for the sterility of up to 80% of females and sustains populations, even in the presence of drought and myxomatosis. Immunocontraception alone has poor prospects for controlling rabbits. Cost-effective rabbit control requires multiple, integrated forms of attrition.

The pathogenesis of two Californian strains of myxoma virus (MSW and MSD) was examined in European rabbits (Oryctolagus cuniculus) that were either susceptible to myxomatosis (laboratory rabbits) or had undergone natural selection for genetic resistance to myxomatosis (Australian wild rabbits). MSW was highly lethal for both types of rabbits with average survival times of 7.3 and 9.4 days, respectively, and 100% mortality. Classical clinical signs of myxomatosis were not present except in one rabbit that survived for 13 days following infection. Previously described clinical signs of trembling and shaking were observed in laboratory but not wild rabbits. Despite the high resistance of wild rabbits to myxomatosis caused by South American strains of myxoma virus, the MSW strain was of such high virulence that it was able to overcome resistance. The acute nature of the infection, relatively low viral titers in the tissues and destruction of lymphoid tissues, suggested that death was probably due to an acute and overwhelming immunopathological response to the virus. No virus was found in the brain. The MSD strain was attenuated compared to previously published descriptions and therefore was only characterized in laboratory rabbits. It is concluded that Californian MSW strain of myxoma virus is at the extreme end of a continuum of myxoma virus virulence but that the basic pathophysiology of the disease induced is not broadly different to other strains of myxoma virus.

Development of immunocontraceptives for wild rabbit populations requires selection of both effective antigens and effective delivery systems. Recombinant rabbit zona pellucida glycoprotein B (ZPB) produced in eukaryotic cells in vitro was an effective antigen and induced sustained infertility in 70% of female rabbits. This required two boosts and serum antibody titers of 12 800 or greater. Antibody titers in females were low after the initial immunization, as might be expected with a self-antigen; however, male rabbits had a strong antibody response, indicating that the protein was immunologically foreign. To develop a delivery system, ZPB was delivered by infection with a recombinant myxoma virus. In contrast to the results with ZPB protein, infection of rabbits induced a similar serum antibody response to ZPB in both sexes. This indicated that presentation of ZPB in the context of a virus infection was able to overcome tolerance in females. However, the antibody titers were lower than 12 800, and only 25% of female rabbits were infertile. This antibody response was boosted by injections of recombinant ZPB protein, after which 80% of female rabbits were infertile. Infertility was associated with antibody binding to zonae and varying degrees of ovarian pathology characterized by follicular degeneration and substantial depletion of primordial follicles. Oocyte and follicular degeneration appeared to be the principal mechanism of infertility and may be primarily induced by antibodies to ZPB.

To be able to study the dynamics of myxoma virus spread following a release in the field, a strain of virus is required that is both highly transmissible and readily differentiated from other field strains. Eight strains of virus of known virulence for laboratory rabbits and with previously mapped and sequenced restriction fragment length polymorphisms, were used to infect groups of seronegative wild rabbits. Based on these trials, and on the nature of the DNA polymorphism, a virus designated Brooklands/2-93 was chosen as a strain suitable for experimental release. These trials confirmed that resistance to myxomatosis within wild rabbit populations continues to be substantial and that some rabbits are highly resistant. These rabbits probably have little role in transmission of virus. Most of the virus strains tested induced very small or invisible primary lesions at the inoculation site. Thus the secondary skin sites such as eyelids, face and ears may be critical for transmission.

The trend of decreasing numbers of deaths reported to VAERS since 1992-1993 follows that observed for SIDS overall for the US general population following implementation of the 'Back to Sleep' program. These data may support findings of past controlled studies showing that the association between infant vaccination and SIDS is coincidental and not causal. VAERS reports of death after vaccination may be stimulated by the temporal association, rather than by any causal relationship.

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The epidemiology of myxomatosis was investigated in 12 populations of wild European rabbits at Wellstead in southern Western Australia, which were part of a larger study of the effects of imposing different levels of female sterility on rabbit population dynamics. Using serology, the aims were firstly to monitor the epidemic pattern of myxomatosis on the study sites between 1993 and 1996, and then to determine whether imposed sterility had any influence on the prevalence of myxomatosis. Two patterns of epidemics were observed during the study. The predominant pattern was a spring–summer outbreak that left approximately 90% of rabbits seropositive for myxoma virus antibodies. The second pattern was a slowly spreading epidemic that lasted from autumn until the following spring. This second type of epidemic may be important in the persistence of myxoma virus. Imposed levels of female sterility as high as 80% for three years had no significant effect on the proportion of animals seropositive for myxoma virus antibodies.

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