Unconfirmed toxins color perspectives

Jul 01, 2001

Mare Reproductive Loss Syndrome (MRLS) has some equine veterinarians questioning the alleged cause of the affliction two months after it claimed the lives of more than 525 foals in Kentucky, West Virginia and Ohio.

Investigators at the University of Kentucky have linked a "cyanide theory" to the syndrome that was responsible for a surge in late-gestation foal losses and early-term fetal losses from late April to late May. (See "Gluck rules out Mycotoxins...", DVM July, 2001 p.1)

The theory asserts that Eastern tent caterpillars, which had been living in cyanide-tainted cherry trees, somehow transferred the cyanide to grazing horses. The trees' leaves wilted following a drought, causing caterpillars to fall into the pastures. The tree leaves are a likely source of the toxins, although officials are also looking at a hemlock link.

"I think everybody is very hopeful that (the cyanide theory) is the cause, because that is something we can deal with," says Dr. Tom Riddle, founding partner of Rood & Riddle Equine Hospital and the first veterinarian to focus on the early fetal loss problem. "(But) there is some skepticism that we may not be at the bottom of the cause yet."

He makes reference to a similar fetal loss incident that occurred on numerous farms in Central Kentucky in 1981. Large numbers of mares aborted in this case as well.

"No definite cause was ever found for that outbreak," Riddle adds.

Dr. Kim Sprayberry, an internist at Hagyard-Davidson-McGee, says blame may not end with the tent caterpillar.

"Some veterinarians do not think this is necessarily the end of the story or the whole story," Sprayberry says. "There is still other information that should be pursued, and the search for etiology should really not end here."

There has been little mention of how pericarditis, uveitis and the reproductive loss are all linked, she says.

"Could the cyanogenic compounds cause all these things?" Sprayberry asks. "There are as many questions raised by this theory as are answered by it.

"I think the tent caterpillar and cyanogenic theory may play a role," she says. "In many ways it fits the time course, and cyanogenic compounds have been found in the heart muscle of some aborted foals. But there are still enough unanswered questions that it would behoove us all to keep looking and leave no stone unturned in the search for other possible causes."

'No room for error'

If the cyanide theory is wrong, Dr. Doug Byars, director of internal medicine at Hagyard-Davidson-McGee, says there is "no room for error."

Even though he says he has a "tremendous amount of confidence" in the cyanide theory proposed by Dr. Lenn Harrison at the Kentucky Diagnostic Laboratory, he still strongly believes "this needs to be sorted out definitively so we can have restored confidence in the industry here in Kentucky." He cites the number of horse owners who already have transported their horses elsewhere because of the significant loss in the state.

At presstime, Byars had a more pressing concern, which was reported by the Associated Press. He says he still sees many cases of horses with inflamed hearts (pericarditis), while the loss of foals and fetuses has eased up.

Byars says he normally treats two or three pericarditis cases a year. But in early June five new cases were sent to the clinic, and in the last month, an increase of 10 times the number of pericarditis cases were brought in.

The illnesses leave some officials questioning whether an undiscovered toxin is also involved.

Don't expect an easy answer to the complex syndrome, says Dr. Roger Murphy, independent practitioner and president of the Kentucky Veterinary Medical Association and Kentucky Association of Equine Practitioners.

"Basically the general consent is that this was not a problem created by a single entity," he says. "This was a multi-faceted attack on the reproductive systems and other systems of the horses in this area through a combination of several different aspects - the mycotoxin, cyanide, fescue, endophyte problems."

Drought likely significantly affected the level of cyanide precursor in the cherry trees as well as the influx of the overwhelming number of caterpillars that developed in the face of the drought, Murphy says.

The "final straw," he says, was the cyanide.

Other surfacing theories

Prior to the cyanogenic compound theory, veterinarians learned that the destructive agent could be a mycotoxin, fungal endophyte, phyto-estrogen or other "bad compound" from the pastures. Mycotoxins are known to negatively impact reproduction and growth rates in species, according to University of Kentucky researchers.

Scientists examined the mycotoxin and other fungal possibilities closely after Kentucky endured an unusual weather pattern this spring consisting of warm, wet weather followed by frost (mid-April), then drought.

"The freak (ice) storm is the one reason why people initially focused on it being a plant-related toxin, because the climatic conditions fit that," says Sprayberry. "When you see epidemics of animal toxicity or animal poisoning, it's after a bout of severe drought or a freeze or something that damages the plants."

Mares were initially given mycotoxin binders, forbidden to graze and treated to preserve pregnancy. Early ELISA tests showed positive for zearalenone, a mycotoxin, but later extensive testing disproved the results.

Prepared for worst

Throughout the ongoing investigation, veterinarians across the state and in the Ohio Valley took charge of the situation.

"I think that this (incident) has made us even more aware of how an unknown problem can crop up seemingly from nowhere and have a devastating effect on our practices," says Riddle. "I'd like to think that the next time something like this happens, we'll all be a little better prepared to organize ourselves and search for an answer."

Nevertheless, he credits the University of Kentucky for its thoroughness in maintaining a Web site for the public and updating veterinarians on the latest information.

Murphy of the KVMA and KAEP believes if the incident was going to happen, only one place housed all the resources.

"If it (MRLS) had to occur in the industry, (Kentucky) is the best place for it to occur. Here we are able to investigate it, control it and eliminate it in the future," he says. "We have every international or renowned internal medicine person in the equine industry located here in three or four of the facilities.

"The research done at the (University of Kentucky) diagnostic lab and Gluck Center as well as the level of practice in this area is actually what brought this to the attention of the necessary people to find out what is going on. If this had happened anywhere else in the world, it would have had a heck of a lot more impact on the industry than it has here," he says.

But Sprayberry has some bones to pick with the investigational process. "What does not exist right now is a prompt conduit of information from the Gluck Center investigators to the practitioners who are seeing the cases in the field and in the hospitals."

Sprayberry faults officials from the University of Kentucky Gluck Center for delaying the release of information to the large veterinary practices in Kentucky responsible for treating the stricken mares.

Instead, Sprayberry recognizes the veterinarians in the field and especially the two large veterinary referral clinics - Hagyard-Davidson-McGee and Rood and Riddle as "sentinels" for the syndromes. "We see more of it than anyone, and have maybe a better appreciation for the scope of the problem than anyone, but there is still ineffective communication between practitioners and investigators."

Dean M. Scott Smith of the College of Agriculture at the University of Kentucky addresses her concerns: "The constant dialogue and sharing of information between equine practitioners, the scientific investigating team and farm owners and managers has been crucial in allowing the investigation to move forward at a rapid pace.

"During the initial rush and urgency associated with the first several days of MRLS, some communications may have missed connecting with veterinarians who needed it," he says. "Since then, several measures have been taken to give practitioners more timely and direct information."


When cases of MRLS started cropping up, the Kentucky Association of Equine Practitioners re-activated a group - the Emerging Disease Committee - to meet and advise fellow veterinarians what to do, what samples to submit and how to report losses. Members of the diagnostic facilities, field veterinarians, internal medicine specialists and the KVMA and KAEP represent the committee.

The meetings of various groups have resulted in immediate action, reports Dr. Bill Bernard of Rood & Riddle.

"We have had meetings on recommendations of the best therapy, how to approach it, and how to proceed with ongoing investigations."

However, he says all the various meetings have posed their own set of problems. "Part of the problem is that different groups are having meetings and sometimes information needs to be shared a little better than it is, but we are working on it."

Aside from meetings, the KVMA and KAEP have jointly coordinated the dissemination of data from the research diagnostic facilities, such as the Gluck Center and the Diagnostic Lab, and field service veterinarians, to the farm managers.

"We are the liaison for the different factions to try to draw everything together for collection and dissemination of information to the veterinary community," says Murphy, president of both associations. "Our purpose is not to keep the public informedit's to keep the membership informed of the status of the latest testing and how things are going among different field veterinarians to see the infant rate (increase or decrease). We are mainly a coordinating reference."

Most recently, the associations disseminated the latest results of the diagnostic lab testing of tissue and blood samples and conducted a joint meeting of the public, farm managers and veterinarians. Information from those entities was faxed to KAEP membership 24 hours in advance of the rest of the world.

"We are networking fairly closely with the membership to try and keep all the information fed into the machine so we can draw a correlation on the epidemiology of what is going on."

Murphy and others in the industry now await the results of an epidemiological survey, headed by Dr. Roberta Dwyer of the University of Kentucky, who is coordinating with the USDA. On May 31, the team traveled to 150 farms, including those farms that experienced significant foal/fetus losses and those that did not. Surveys were conducted by more than 20 veterinarians, state and federal animal health employees and other volunteers. The plan was to collect all data by June 6. At presstime, results were not available.

In the field

In addition to association meetings and search committee investigations, veterinarians have been toiling in the field working "ungodly hours under emotionally difficult circumstances" says Sprayberry.

And Riddle says one of the greatest obstacles to addressing the syndrome thus far is lack of conclusive facts.

"It is very difficult to make recommendations for practical management of our mares, which are pregnant from this year's breedings because we do not know the (definitive) cause of the abortions."

Even though veterinarians are assisting in every way they can, the emotional loss can be tremendous and overwhelming for the clients.

To assist clients in this time of grief, veterinarians from Rood and Riddle Equine Hospital and several other community groups sponsored a prayer service for the horse industry in early June. The goal of the event, according to organizers, was to "simply reach out and try to comfort and encourage the owners and caregivers of these horses."

Under all the pressure, Byars of Hagyard-Davidson-McGee tips his hat to the behind-the-scenes individuals.

"Support staff, people at farms, veterinarians, have all hunkered down and worked their hearts and souls behind these horses. A lot of the grassroots people have been wonderful," he says.

All these individuals have maintained a somewhat optimistic approach in the face of grave statistics.

"We may face as high as one-third of our population (foals) not being present (next year)," says Byars. "When you hear of 500 foals that may not sound like many, but (it's a different story) when you attach that to thousands of foals that will not be born next year."