Released February 20, 2002
We received this last Friday from Dr. Alvin Smith. We were hoping to get a little more work done before announcing it. But it has reached the press and so we thought we?d better get it out. If you are wondering what it all as to do with RHD, please pay special attention to the last sentence in the second paragraphand the last half of the last paragraph. The proverbial will now start hitting the fan and something will get done.Old Virus With a New Face
The date was April 19, 1932 and the place Buena Park, California. An outbreak of Foot and Mouth Disease had just been reported in a large herd of swine being fed raw garbage from the port city of Los Angeles. Eradication involved slaughter and burial of over 19,000 head of livestock. This chronicles the arrival of Vesicular Exanthema of Swine, a new disease that was mistaken for Foot and Mouth Disease, but this case of mistaken identity would be just the first of a long series of serious errors occurring over the next 70 years as USDA Regulatory Officials struggled to make this Calicivirus fit inside the box.First, it was labeled "California Disease", but in 1952 it escaped California and spread throughout the U.S. triggering a Federal eradication program. Its? origins were said to be de novo but in 1976 its? primary reservoirs were shown to be ocean fish. The virus was also stated to be host specific with swine being the only naturally infected species, but by 1980 over 20 animal species as phylogenetically diverse as fish and apes were proven hosts. In 1959 Vesicular Exanthema of Swine was officially declared eradicated from the U. S. and was designated a Foreign Animal Disease even though all known outbreaks had either originated from or occurred inside the continental U.S. But, by 1985 irrefutable evidence demonstrated that the Vesicular Exanthema of Swine virus group was not eradicated but instead was endemic in U.S. herds. From 1933 to 1983 the official definitive diagnostic test for differentiating Vesicular Exanthema virus from Foot and Mouth Disease virus and Vesicular Stomatitis virus was to inoculate cattle, swine and horses. The Vesicular Exanthema Virus would infect only swine and occasionally horses but cattle would never be infected. Now after 50 years this "gold standard" test is no longer valid. The Vesicular Exanthema virus group can not only infect cattle, but can also cause the disease "Vesicular Exanthema" in cattle and spread by contact. For 65 years the "official" Public Health and textbook information being taught was that the Vesicular Exanthema group of viruses were not zoonotic. In 1998 this too was proven to be false. These viruses can cause a blistering disease in people and more recent reports provide compelling evidence of their causing human hepatitis and abortion.
In the February 15, 2002 issue of the JAVMA in the Public Veterinary Medicine: Regulatory section, faculty from the Oregon State University College of Veterinary Medicine, Laboratory for Calicivirus Studies (Dr. Al Smith and Douglas Skilling) and their colleagues from AVI BioPharma, a Portland/Corvallis based biotech firm and the Center for Pediatric Research in Norfolk, Virginia published on yet another new and important twist in the story of the Vesicular Exanthema group of Caliciviruses. Following is a summary of the article titled:
Detection of vesicular of swine-like Calicivirus in tissues from a naturally infected spontaneously aborted bovine fetus.
Globally there has been a surge in Foot and Mouth Disease outbreaks and their devastating effect has been especially apparent in Britain. A rapid accurate differential diagnosis of Foot and Mouth Disease virus and other vesicular disease viruses is more critical now than ever before. Yet, that task has just become much more difficult and complex. A spontaneously aborted bovine fetus was necropsied, examined histologically and given a morphologic diagnosis of fetal stress syndrome. Laboratory tests using a bovine abortion screen protocol did not establish a definitive etiology. Additional immunohistochemical testing of lung tissue with a fluorescein labeled Calicivirus specific monoclonal antibody gave positive fluorescence. RT-PCR on the same tissue produced a 448 base pair amplicon having 99% sequence identity with a pathogenic Calicivirus known to have produced naturally occurring vesicular disease in bottle nosed dolphins and vesicular exanthema in experimentally exposed swine. There was 91% sequence identity to virus A48 the prototype Calicivirus strain for the Foreign Animal Disease, Vesicular Exanthema of Swine. Direct electron microscopy on fetal lung tissue confirmed the Calicivirus infection. This is the first study demonstrating the presence of a Calicivirus indistinguishable from the Foreign Animal Disease agent, Vesicular exanthema of Swine Virus in the diseased tissues of a naturally infected spontaneously aborted bovine fetus. Here we see an agent, which can mimic Foot and Mouth Disease hiding-out in the tissues of an aborted bovine fetus, a species that historically was considered refractory to infection with viruses of this class. Although this report is a "high Alert" for Regulatory Veterinary Medicine and for the differential diagnosis of Foot and Mouth Disease, from a simple herd health and production standpoint it is the discovery of a new zoonotic agent of viral abortion in cattle. Diagnostic reagents for detecting such Caliciviruses have been developed and can now be made available for testing diagnostic samples during routine abortion screening.
Calicivirus abortion has been seen in pigs, cats, four species of marine mammals and using serologic data has been associated with abortion in humans (general population 5% positive, aborting women 15-40% positive). Studies of equine abortion using single serum samples from over 100 animals and comparing a normal population (auction sales) to mares that either aborted or were in contact with aborting mares gave positive percentages of 39.9% and 80% respectively. In cattle where these same Vesicular Exanthema of Swine-like Caliciviruses have been known to be endemic for over 15 years, one paired sera study of aborting cows (250 sera, 125 pairs) gave the following result using the same ELISA test as reported above. Total positive out of 250 sera, 74.5% and of these 125 cows 11% developed a shift in serum antibody titer of 4 to >6 standard deviations (change in optical density values) between their acute and convalescent serum pairs. These data would of course be interpreted as a diagnostic positive for any established serologic test.
All of the above suggests that the Veterinary Practitioners should expect complete abortion screens provided by their Veterinary Diagnostic Laboratories to include tests for abortogenic Caliciviruses. Reagents for Calicivirus testing can be made available to these laboratories on a research basis through the Laboratory for Calicivirus Studies and or their University partner, AVI BioPharma. To assist the diagnostic laboratories and conscientious diagnosticians in justifying gearing-up to including Calicivirus testing, Practitioners should consider asking for these tests in instances where abortions of unknown etiology are occurring. Currently, many diagnostic laboratories are unable to provide definitive etiologic diagnosis on 50% or more of the abortion cases submitted and in some species the data given above suggests that perhaps 10% or more of these may be Calicivirus associated. So what can be done? Traditional vaccines are not be expected to be reliable because of the tremendous antigenic variability of these viruses and their rapid mutation rates. However, there are suggestions that highly conserved neutralizing epitopes could be developed into peptide vaccines. Perhaps more exciting, AVI BioPharma has shown that Antisense Platform technology will block caliciviruses growth in living cell culture systems and to date a live animal pilot study gave the same result. This provides hope that not only could virus infections be prevented but also treated by blocking virus growth with antisense compounds. For further reading the following general references are suggested:
Smith AW, Boyt PM. Caliciviruses of Ocean Origin: A Review.
J Zoo and Wildlife Med.
(1990) 21: 3-23
Smith AW. Virus cycles in Aquatic Mammals, Poikilotherms and Invertebrates.
In: Hurst CJ ed, Viral Ecology.
San Diego, Academic Press (2000); 447-491
Smith AW, Skilling DE, Cherry N et al. Calicivirus Emergence from Ocean
Reservoirs: Zoonotic and Interspecies Movements.
Emerging Inf. Dis. (1998); 4: 13-20
Stein DA, Skilling DE, Iversen PL et al. Inhibition of Infection in Mammalian
Tissue Culture with Antisense Morpholino Oligomers.
Antisense and Nucleic Acid Drug Development. (2001) 11: 317-325
--Hazel Rah To The Black Rabbit From Watership Down, by Richard Adams ©1972
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