Researchers Contemplate Role of Vesiviruses in MRLS

Oregon State University (OSU) researchers announced last month that they linked vesiviruses to abortions seen during Central Kentucky's bout with mare reproductive loss syndrome in 2001 and concluded that vesivirus-specific reagents should be included in the diagnostic panel for aborting mares. A University of Kentucky researcher disagrees with the findings of the study, cautioning that a more causative relationship needs to be established before laboratories put tests in place.

Vesiviruses are a genus within the family Caliciviridae, and historically they are best known for causing a clinical disease in pigs, called vesicular exanthema of swine. These viruses were important when they were detected in the United States in the mid-1900s because clinical signs of vesiviral disease can mimic foot and mouth disease, which is a serious threat to the agriculture industry. The OSU researchers said in their study that they wanted to examine possible vesiviral involvement because these agents have been shown to cause abortion not only in swine, but in a variety of mammals including cats, and probably cattle and humans.

Alvin W. Smith, DVM, PhD, Dipl. ACALM, a professor in OSU's College of Veterinary Medicine, said, "It was an instance of undiagnosed abortion and of some considerable importance. Everyone was trying to figure out what was going on with these mares. I had been working with this agent for 30 years, and it had never been described as a natural infection in horses (although Smith found evidence of naturally occurring vesivirus infection in donkeys that were euthanatized on San Miguel Island, Calif., in the 1970s), so I thought, 'Why not just check it out and see if my virus is kicking around in these mares?' I have curiosity, I have a program (to test for vesiviruses at OSU's Laboratory for Calicivirus Studies), I have an abortogenic virus I know something about, these mares are in trouble...and the two might meet."

The Study
In two experiments described in the study published in the American Journal of Veterinary Research, Smith and his colleagues reported "significant association" between seropositive status for vesivirus and abortion in mares. The first experiment examined serum from three groups of horses: one group of Central Kentucky mares with a history of abortion problems, another group of "breeding-age control mares," and a group of mixed-age males and yearling fillies (negative control population). In that experiment, nearly 64% of mares from farms with abortion problems were seropositive for vesivirus antibodies. Forty percent of the breeding-age control mares were seropositive, and all of the horses in the negative control population were seronegative for vesivirus antibodies.

Smith said if he lowered the cut-off point for what was considered seropositive, up to 12% of the negative control population would have been considered seropositive. "I think some younger animals including males had antibody, although at a lower level," Smith said.

In the second experiment, researchers looked at seroprevalence of vesivirus antibodies in blood samples from horses taken before and after exposure to Eastern tent caterpillars (ETC) and their frass (excrement). There was also a negative control group. Mares that aborted during the experiment had an increase in seropositive status for vesivirus antibodies from 47.1% to 88.2%. Smith said he and his colleagues were unable to establish an association between the caterpillars and the vesiviruses.

Aside from the abortions, the horses that were seropositive for vesivirus appeared clinically normal. Smith said studies at the USDA's Plum Island Animal Disease Center have shown that about half of horses inoculated with vesivirus will develop blisters at the injection sites. He added that if you extrapolate from other research, vesiviruses could conceivably cause abortion, myocarditis, pneumonia, encephalitis, or a hemorrhagic disease. The assumption is that if a horse is seropositive and healthy, it has recovered from a vesivirus infection.

"The regulatory folks say that it's been eradicated," but Smith described vesivirus seroprevalence studies that showed up to 12% of livestock in a variety of areas in the country were positive for vesivirus. "The virus is endemic in cattle and swine, and it looks very much like it is endemic in horses, with as much antibody as we saw."

Smith said one of his studies showed humans have been widely exposed (5-10%), and that he has published serologic evidence of vesivirus association with transfusion transmitted hepatitis. "It would appear that people have acquired hepatitis from blood that could have this agent in it," he said.

"What I would hesitate to do is say this is associated with MRLS," said Smith, although OSU's press release distributed on June 23 said the viruses were linked to the abortion storms in 2001. "We were careful to say abortion. I think it (the vesivirus) is an agent that's active in the equine populations and can be another additional cause of abortion--not a specific type of abortion, just abortion. It's not at all unusual to not be able to identify the etiology of the abortion when these mares abort. I think this is just another one of those agents that causes abortion in horses, and is probably active at lower levels. I do not want to come off saying that we discovered the cause of MRLS...I think we are pointing out what appears to be a heretofore unrecognized cause of abortions in mares, and any time they (diagnostic labs) want to screen mares for reproductive loss, if they think it could be some kind of infectious agent, they should test for this as well."

If given the opportunity, Smith would like to more conclusively link the abortions to vesivirus. "When I get the opportunity to check fetal material, I'll try to isolate the virus. If I have the opportunity to look at the females that aborted...I will try to check for evidence of Calicivirus shifts that would suggest any relationship to that virus.

Smith would like to see horse owners and veterinarians test for vesivirus when mares abort. "Vesivirus...should become a standard diagnostic screen in these mares," he said. "OSU could make these tests available, or diagnostic laboratories could develop their own." He said if cases were detected, potential disease could be controlled by using infectious disease control measures such as quarantine and separate equipment for affected and unaffected animals.

"Over time, as people can start looking for this virus and looking for it in the diseased animal and insisting that the test be run, some will be negative, some will be positive, and the picture will begin to emerge," said Smith. "I find (diagnostic testing) more useful than setting up 'spendy' experimental infectivity experiments fraught with problems. (Testing) of samples from animals and areas where the diseases are occurring naturally is far easier, far more productive, and it will give you a much cleaner answer in the long run."

Bruce Webb, PhD, a University of Kentucky entomologist and MRLS researcher, provided many of the samples used in the Oregon study. "By its nature, this type of screening (serological) is useful to, one, detect agents that are known to cause a disease or, two, investigate whether a disease may be associated with a known agent." He explained the current study is of the second type in which researchers screened for an agent known to be abortigenic in other situations and correlated this agent with abortion in mares.

According to Webb, if data shows vesivirus is a potential cause of MRLS, it would be used as a basis for other experiments to test whether vesivirus can cause abortions in mares. Such studies would include experimental infection, which OSU researchers are not planning. Webb added, "The next step would be to try to isolate virus from archived tissue samples and set up an experiment in which infection was manipulated before drawing any conclusion as to the role, or lack of a role, of vesivirus infection in MRLS.

"The Oregon State report is an indication that there is some evidence of exposure to a virus group that is known to cause abortions in some other instances," added Webb. "These types of agents are, and should be, on our list of concerns and subjects of research as resources may permit."

University of Kentucky MRLS studies have shown little evidence of a virus being the cause of MRLS, such as a fever in affected mares or evidence of direct transmission of the disease between mares. "There is no direct evidence that vesivirus has caused a single case of MRLS," Webb said.

"In my view, the weight of the evidence, both experimental and practical, argue against vesivirus having any role in MRLS, and the recommendations that the author presents with regard to industry-wide monitoring are premature," Webb added.


About the Author

Stephanie L. Church, Editor-in-Chief

Stephanie L. Church, Editor-in-Chief, received a B.A. in Journalism and Equestrian Studies from Averett College in Danville, Virginia. A Pony Club and 4-H graduate, her background is in eventing, and she is schooling her recently retired Thoroughbred racehorse, Happy, toward a career in that discipline. She also enjoys traveling, photography, cycling, and cooking in her free time.

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