A Response to the Media Release of CSIRO dated 19 February 1996 entitled THE LATEST ON RABBIT CALICIVIRUS
Niall Byrne or Nicholas Newland web@its.csiro.au 19 Jan 96 (Earlier press releases are available at CSIRO Rabbit News)
CSIRO states: Rabbit calicivirus has not spread to new areas of Australia since January 1996.
Dr. Smith: Is the sudden halt of RHD virus spread due to decreased surveillance and diagnostic effort or has the mechanism of spread mysteriously ceased to operate? What are the mechanisms of spread? Are any of these known for sure?
CSIRO states: It is continuing to infect rabbits in areas behind the front of its earlier spread.
Dr. Smith: If areas inside the red zone (behind the front) continue to spread, why are the perimeters not spreading? Shouldn't the spread extend outward as well as inward?
CSIRO states: "Rabbit numbers are low where the virus has spread on Wilpoorinna Station, but following rain in January, rabbits are breeding like rabbits in areas it has missed" reports Ron Sinclair of the Animal and Plant Control Commission, South Australia. "Reports from properties in the northern Flinders Ranges suggest that rabbit calicivirus has not spread through hilly areas, but has been very effective in controlling rabbits on the flats," he noted. Field studies on the impact on the virus are continuing by Australian and New Zealand scientists. This information will be made public once it has been analyzed.
Dr. Smith: What is the difference between the explosive spread with the virus spreading several kilometers per day in both north/northeast and north/northwest directions with leap frog breaks hundreds of kilometers from known suspected areas?
Regarding Mutation
CSIRO states: Rumours that rabbit calicivirus will mutate to infect humans and other animals are unfounded.
Dr. Smith: Where have the rumors that RHD virus will mutate to infect humans coming from? These statements have not come from U.S. scientists. These scientists persist in their assessment that the Caliciviridae are as a group unusually plastic in nature, 4 of the 5 commonly accepted groupings can cross specie barriers to infect multiple host species and these same 4 groups infect humans. RHD/RCD virus is the only one of the calicivirus groupings where cross species transmission including human infection is not yet reported, thus lessons learned from the more adequately studied caliciviruses suggest cross species infection should be expected and human infection should not be unexpected. To say that such concerns involving cross species transmission are unfounded is to ignore great quantities of published data on the Caliciviridae. With regard to mutation many of the species adaptations seen are mutation ( changes in base sequence from the parent virus) driven. Please note, the cause for calicivirus genomic instability can be found in the replicative nature of RNA viruses where copy errors for the RNA genome are estimated to be one per every 10,000 for each nucleotide base. This leads to the concept of quasi species where a replicating calicivirus population is made up of a collection of virions having different genomic sequence which leads to a shift in virus types, escape from immunity and, yes, adaptation to new host species.
CSIRO states: Scientists in the Rabbit Calicivirus Program have given seminars and briefed colleagues at most of the laboratories that have worked with rabbit calicivirus including: Tubingen in Germany, Plum Island in the USA, France, Spain, UK, Sweden, Switzerland and others. A full list is available.
Dr. Smith: Giving seminars and briefings to the biomedical community does not constitute soliciting and getting scientific approval to release rabbit calicivirus, a new disease, onto the Australian continent. The news release statement did not say that approval was given but the casual reader would easily assume that. Also, giving briefings and seminars does not constitute a leadership position for Australia in research areas. Indeed, rabbit calicivirus research has been ongoing in Europe for years before it began in Australia. The Europeans sequenced the virus and have developed the vaccines which are available and have now been provided to Australia. Is the list that is available a list of scientists that approve Australian activities, or a list of seminars given or a list of laboratories visited?
CSIRO states: Overseas, scientists have tested rabbit calicivirus in 15 different animal species - and none became infected or sick from it. Australians have done a much larger study.
Dr. Smith: Where is the report of the 15 species of animals tested? We know foxes and dogs developed antibodies and some naturally infected foxes in Sweden show possible evidence of caliciviruses in bile duct tissue. How much virus was given? What were the tests used to prove that infection did not occur?
CSIRO states: In this three year study, 28 different species of animals were inoculated with large doses of the virus. None of those animals became infected or sick from it. This is one of the largest studies even undertaken to determine the host range of an animal virus.
Dr. Smith: The Australian tests of 28 species can be criticized in that pure (cell culture derived) virus was not used. The 1000 rabbit infective dose is very small. So small in fact that it was below the immunogenic threshold of all 28 species with the possible exception of mice which were said to have detectable antibodies. This may have been a large study but it was a very weak study in terms of actually challenging the host non specificity of the virus. Tenuous evidence suggests the virus originated in rabbits. More conventional treatment of the epidemiologic data starting with the China outbreaks suggest a non European rabbit origin and a non rabbit origin. Time would be well spent in attempts to identify one or more reservoir species for the RHD virus.
CSIRO states: There are no guarantees in biology. All viruses mutate, that is normal, but mutations rarely have any effect on the way the virus behaves.
Dr. Smith: To state that mutations rarely have an effect on the way viruses behave is a totally invalid statement. Mutation (genomic change) has everything to do with the way viruses behave over time, survuve in the new hosts, change tissue trophisms and generally do what viruses do. New serotypes emerge, new host species become infected, new tissue tropisms form. RNA viruses are especially mutagenic and versatile.
CSIRO states: Throughout all RCD Program scientist's interactions with international virology experts, no-one in the world has presented any evidence to show that rabbit calicivirus poses any greater risk than the ubiquitous viruses in the environment that we come in contact with everyday.
Dr. Smith: The evidence of risk which RCD program scientists have been exposed to comes from understanding the broad base of knowledge concerning other caliciviruses and an almost non existent data bank regarding RCD involving actual research where screening for antibody or disease involving large numbers of various species of animals and people who have been exposed by natural contact with infected rabbits simply has not been carried out. Would one have to witness hemorrhagic deaths in non target species to perceive this Foreign Animal Disease agent as a threat to livestock, wildlife, pets and people. Are other disease manifestations of calicivirus infection , i.e., diarrhea, pneumonia, abortion, myocarditis, encephalitis, blistering and hepatitis of no concern or consequence? Please remember that it is the everyday contact with those so called "ubiquitous" viruses in our environment that result in virtually all viral diseases. The international perspective
CSIRO states: As part of the international search for any new information, the Office International des Epizooties (OIE), the world authority on animal health, was asked for all available information on safety aspects of rabbit calicivirus. The OIE has coordinated the pooling of international knowledge about this virus through a series of workshops and publications. The contributions from more than thirty eminent specialists, from eight countries and three regions of the world, are published in an issue of the Scientific and Technical Review (Vol 10 No.2) The possibility of transmission of rabbit calicivirus to humans was not raised then or subsequently, even though the virus was circulating in many countries. None of these countries has placed a ban or any restrictions on the consumption of rabbit meat, either at that period or since.
Dr. Smith: The OIE information was assembled several years ago 1990 (Is this an example of what we call new information?) and was not intended to present overall calicivirus data or concerns, but instead, it was a report on a new emerging international epizootic. Have other countries informed their citizens as Australia has done that infected (i.e., rabbits in contact with RHD virus) are safe for both humans and pets to eat? In those countries that are attempting to eradicate RHD are the control measures used which could include killing infected rabbits carried out with a recommendation that the carcasses are safe for the fresh rabbit meat trade and human consumption? Aren't we trying to present the non reporting of certain data by OIE as evidence that OIE has placed their stamp of approval on questionable activities for addressing RHD infection? Incidentally, does the OIE report even address RCD? They have compiled data on Rabbit Hemorrhagic Disease virus.
Kiwis
CSIRO states: The following information has been provided by the N.Z. government. Just before Christmas, four kiwi and six native bats were inoculated with rabbit calicivirus to determine whether or not they were susceptible to it. Neither species showed any clinical signs of the disease; and tissue samples from the bats produced negative results. However, analysis of blood samples from the kiwi did show low levels of antibodies. While it is very unlikely that this indicates they are susceptible to infection from the virus, further tests are necessary to eliminate that possibility. A more likely explanation for the presence of antibodies in the kiwi is that their immune systems reacted to the presence of viral material in the inoculation as a foreign body, but that no multiplication of virus occurred in the kiwi's tissues.
Dr. Smith: Of course the most likely explanation for the kiwis is that they did become infected especially in light of the reports that 28 of the other 29 species tested did not develop antibodies when given an identical dose (1000 rabbit infective doses) of virus.
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