The Australian government soon will make a decision about the eligibility of the rabbit hemorrhagic disease virus,a.k.a.rabbit calicivirus, as a biological control agent. It is my understanding that in order for the virus to be approved as such an agent , it must be demonstrated to be species-specific.

My concern is that you and your office may believe CSIRO experiments with a number of species were a valid test of those species susceptibility to RHDV. I believe the following facts are relevant to this issue:

1. The species challenged received an inoculum known to infect rabbits, but there is no knowledge that the same dose is sufficient to infect other species.

As an example, the infecting dose for a human rotavirus in humans is about 10 infectious units. The infecting dose of a human rotavirus in mice is 10 log 5 to 10 log 8 infectious units, 4- to 8-fold log higher. Giving 10 infectious units of human rotavirus to mice results in no infection or illness. Giving the large dose may result in symptoms.

The point here is that the CSIRO experiments did not challenge the species with a range of doses, a routine standard in any laboratory attempting to achieve infection in an animal model.

2) The dose selected by CSIRO was intended to be "sub-immunogenic", not eliciting in the animal any antibody response.

Choice of such a dose puts the challenge at the low end of what might be expected to accomplish infection in another species. If I wanted to be sure a mouse had been adequately challenged with a human rotavirus, without being sick, I would be sure to use several logs more virus than that dose capable of inducing antibody.

3) The dose selected by the CSIRO is far less than would be expected in the natural situation for a released virus.

The point here is that in order to test the reasonable possibility of a virus' ability to infect a species in nature, one should test that species with the amount of virus it could be reasonably exposed to. The CSIRO dose is several thousand-fold less than would be expected for natural predators and scavengers of wild rabbits.

4) The proper procedure to test susceptibility in a species that shows an antibody response is to go back to the same species with higher challenge doses.

Animals can be infected with low challenge doses, showing no symptoms or signs of infection, yet mount antibody response. The proof that the species is truly resistant to illness with that virus is to challenge the animal with higher doses.

In my opinion, the CSIRO experiments provide no reasonable evidence to support the conclusion that RHDV is species-specific. Further, the experiments conducted to evaluate tissues and other animal samples for evidence of infection as a result of the RHDV challenges have not been published or undergone peer-review, as far as I can tell. The description of how and when such samples were evaluated (samples/tissues collected 6 weeks after challenge) raises grave doubts as to the credibility of that evaluation.