I would like to address some of the issues that you raised in the message from September 25th, concerning RHDV. First of all, I would like to state that I am involved in research on Caliciviridae in humans in a public health setting, so my perspective on things is from that angle. I have no experience with rabbit caliciviruses, or any other animal caliciviruses. I express my own personal views on the problem as a virologist.

This being said, I would like to comment on the following:

1. Host specificity of RHDV. So far there is no clear evidence of interspecies transmission of rabbit caliciviridae to other animals or humans. In view of the knowledge of other caliciviruses - where interspecies transmission has occurred - this should be an area of constant alertness. It has been shown that some animals other than rabbits did seroconvert following ingestion of infected rabbits (fox) or following experimental infection (from memory, I think Kiwi was one of them). This does raise the question whether the antibodies in foxes result from infection or merely from exposure to bulk amounts of the viruses without replication (the latter being the current hypothesis). I have seen no experimental evidence proving either option. In my opinion this matter should be resolved as it is crucial...

2. I think that the use of viruses in general as biologic agents as a concept is very risky. It is not easy to control viruses that spread as rapidly as RCV. Case in point (for me anyway) is the unexpected high rate of spread of virus that was observed once it was introduced into Australia: from that incident, a novel feature of the epidemiology of these viruses became clear, namely that it can be spread by vectors (insects). This had not been predicted from earlier epidemiological studies in Europe.

3. Besides the associated uncontrollable risks, there are other arguments against the use of biological agents. Typically, introduction of a new virulent virus into a naive population will initially cause serious effects (high mortality in rabbits in this case) , but will eventually result in adaption of virus and host (balanced pathogenicity concept) so that the Australian rabbits would no longer die of RHDV. Therefore, one would predict that the effects of RHDV introduction is merely temporary.

4. The area that I would review very carefully prior to release of calicivirus as a control agent is that of vaccination (of pet rabbits eg.) Is there a protective vaccine that does not cause problems? My reason for this is that in human enteric caliciviruses there is some debate on the role of immunity following infection. In some studies it has been suggested that prior infection may actually cause more serious illness on subsequent exposure to viruses of the same family. As I mentioned, I am not familiar enough with rabbit caliciviruses to answer this question, but it certainly would have to be addressed.

Finally, in case of a release as has happened, I would want to know what the chances are that transmission of RHDV into other species (including humans) would be detected. Is there a sensitive surveillance system, can microbiological reference labs detect the viruses..etc. An epidemiologist might be able to tell you more about the sensitivity of monitoring, but one thing is clear: if interspecies transmission would appear on a low scale, it takes a substantial surveillance system to detect that.

I hope that this information is of use to you.