Mother Nature's Toxic Spill: An Analysis of Mare Reproductive Loss Syndrome

A good mystery has many clues, some more obvious than others, and some more misleading. Researchers are scientific detectives, trying to piece together observations and facts that lead to a conclusion. But, while some cases are concluded with all the pieces fitting together perfectly, some mysteries are never solved. Either scenario could be the final chapter for the current Mare Reproductive Loss Syndrome faced by horse owners this spring in Kentucky and other states. The investigation continues. For now, here is what is known, observed, and postulated, with a few educated guesses thrown in, and others thrown out.

Fact: Many horse health problems occurred over a short period of time this spring, including (but possibly not limited to) late-gestation foal losses, early-term fetal losses, pericarditis (fluid in the sac around the heart), uveitis (eye problems), laminitis, oral ulcers, and reduced weight gain in growing horses.

Fact: There was a "bell curve" of incidence in early fetal loss and late-gestation foal loss that peaked on Derby Day, May 5.

Fact: The problems followed a strange weather pattern this spring of warm, wet weather followed by frost (April 17 and 18), and then followed by drought.

Fact: Horses in a wide area in Kentucky and southern Ohio (at least) were affected.

Fact: Not all farms were hit, and not all farms were affected to the same degree.

Fact: Tent caterpillars were extremely prolific this year.

Fact: Pastures are a common denominator with all the affected horses.

The scientists will continue listing facts as they gather more information. These epidemiological studies will help unravel what is common among the farms with problems, and different on farms with little or no problems.

One thing is certain: the researchers' credo is "keep an open mind."

Mycotoxins Out (Maybe)
Weather can damage grasses, and that damage can make forages vulnerable to attack by outside forces. It was postulated early on that mycotoxins, fungal endophytes, phyto-estrogens, or other "bad" compounds formed in the grasses because of the weather. There are many different mycotoxins, and they are known to negatively affect reproduction and growth rates in other species. Therefore, it was theorized that mycotoxins could be the cause of the mare reproduction losses.

Mares were put on mycotoxin binders, restricted from grazing, and treated medically to preserve pregnancy. Late-gestation mares were closely observed for foaling problems and weak foals. Fields were cut to reduce the chance of horses grazing on affected grasses.

Early ELISA tests showed positive for zearalenone, a type of mycotoxin, and it was found in samples of mare urine and caterpillar excrecia. However, more sensitive testing showed absolutely no positives for zearalenone, or a range of other mycotoxins, in pasture samples or hay, according to Dr. David Powell of the Gluck Equine Research Center, a leading investigator in the team searching for answers.

"We've gone back with more reliable assays (HPLC) and gotten completely negative results," Powell said. "We feel based on that information that mycotoxins are not a factor, but we're keeping an open mind."

Powell said he is not recommending that farm managers and horse owners stop feeding the mycotoxin binders. "Those binders could have roles beyond mycotoxins. They could have a beneficial effect, and there are no harmful effects."

Others in the Field?
The remaining three areas of pasture research center on fungal endophytes (which attack a plant and enter it), phyto-estrogens (plant-produced estrogens), and other compounds.

Testing for fungal endophytes at this stage does not indicate that they are a cause of the problems experienced this spring. But, Powell said, due to the widespread incidence of problems in Kentucky and other states, researchers have not completely ruled out fungal endophytes as perhaps contributing to the health crisis.

Laboratories are pursuing tests for ergot alkaloids, particularly in urine samples from affected mares. "There are a wide range of ergot alkaloids. We we're not eliminating them at this stage," said Powell.

Phyto-estrogens are often associated with clover. Powell said comments from the field this spring were that a great deal of clover could be found during the critical period before the foal losses started.

"The test for phyto-estrogens is exceedingly complicated, and it has been difficult to identify labs in the United States to run these tests to the standards we feel are necessary," said Powell. "This is one reason we didn't come out earlier with information on the results of the tests."

Tent Caterpillars Crawl Back Into Picture
It's difficult at this point to find a tent caterpillar, but a few weeks ago, you couldn't open a door, walk down a path, or look at a tree without seeing them swarming. Opening gates created an avalanche of the crawling invaders, who chewed some trees down to the nubs.

"We think there is an association with cherry trees and tent caterpillars and the problems we've seen, based on examinations of pastures of farms badly affected," said Powell. "We have noticed an association with the presence of cherry trees (the favored meal of tent caterpillars) in pastures where mares lost fetuses, and the presence of massive numbers of caterpillars.

"Initially, until we got the negative results in other areas, we were not focused extensively on caterpillars," he added. "Now we are focusing more detail on the cherry tree/caterpillar link."

Black cherry trees are one of the most widespread and common hardwood species in the Eastern United States. When cherry tree leaves are damaged (frost, trampling, drought, wilting, blown out of the tree during high winds), they contain cyanogenic precursors that release cyanide, according to information from Purdue University. Healthy leaves of cherry trees contain prunasin, a cyanide precursor that is non-toxic. But when the leaves are damaged, the prunasin molecule is split and free cyanide (also called prussic acid or hydrocyanic acid) is liberated.

"Cyanide prevents the body from being able to utilize oxygen at the cellular level, so although the animals physically can breathe, their tissues and cells suffocate," noted the Purdue University information.

Therefore, researchers are trying to determine if they can find some derivative of cyanide possibly carried by the caterpillars onto fields, or found in the caterpillars themselves. While caterpillars were found to have zearalenone in their excreta, they were not found to have cyanide in initial testing.

Climate 'Intimately Related'
Kentucky is known for wide fluctuations in weather, and researchers seem certain that this spring's weather patterns are related to the health problems in horses.

"It's interesting that when we compared the climate data with 1981 (a year of similar, though less widespread, foal/fetal loss), it was a mirror image," said Powell. "In 1981, there was a similar syndrome that in every sense is what we're seeing now, but not to the same extent. The population of horses is now greater, and the survey in 1981 was only locally. It's difficult to know if it was widespread and not reported.

"Also, the veterinary technology was much different in 2001 from 1981 because this year they (vets) picked it up earlier because of 60-65 day ultrasound exams," added Powell. "In 1981, they did exams at 42 days, and not again until much later. And it was all done with palpation, they didn't have ultrasound."

And the Tests Go On
Agronomists and nutritionists Dr. Jimmy Henning (of the University of Kentucky), Roger Allman (The Farm Clinic), and Dr. Steve Jackson (Bluegrass Equine Nutrition) have taken a multitude of samples of pastures and hay for testing. Grasses such as orchard grass, bluegrass, fescue, and clover (a legume) have been individually harvested for testing. Powell said there are pasture samples from prior to May 5 that are very important to the investigation. "We can't take pasture samples now that reflect what was going on over that relatively short period of time," he explained.

Hay samples might contain the best clues as to what was growing, or not growing, among the pastures early this spring.

Tissue and biologic samples also have been taken and are being studied and tested. One very useful group of samples are the 130 bloods taken at the beginning of the outbreak (May 3). Results of preliminary testing on those samples should be completed in a few days.

One hormone that researchers are interested in monitoring is prolactin. Fungal endophytes and ergot alkaloids depress prolactin production in mares. This is why pregnant mares exposed to endophyte-infested tall fescue respond to domperidone.

While recommendations have been made by veterinarians in the field to use domperidone to prevent pregnancy loss, Powell said farms with late-term pregnancies using the drug didn't see much help in saving foals.

Other samples being studied include tissue samples from foals and fetuses taken to the Kentucky Livestock Disease Diagnostic Center, urine from affected mares, and colostrum collected at the time of the worst losses.

"The pathology of fetuses, particularly the lung, is providing interesting pathways to study," said Powell. But at this point, he added, "from a biochemical point of view, there are no significant changes."

Tent caterpillars were collected and frozen for future study. Teams also have been sent north to collect caterpillars because they are still active in those regions. Powell said those samples will be important to look for potential toxins.


And the Killer Is...
Powell said historically when these syndromes have happened, scientists weren't able to come up with an answer. However, he said the big difference this time is that everyone was made aware of the problem much closer to when the event occurred.

"We could organize resources locally and nationally to identify the problem," said Powell.

"I can't say categorically we'll come up with an answer. My philosophy all along is to be focused and objective. I do feel we are utilizing all resources available to us locally, nationally, and internationally to come up with an answer."

In looking to the future, Powell thinks that by working with the climate and weather researchers, "we can come up with a climatic predictor that even without the knowledge of what the cause is, we can develop useful recommendations."

In other words, if certain weather patterns occur in the future, scientists will alert the horse industry to take precautions.

The search goes on, with cooperation, caution, and continued good science the guideposts. Other trails might turn up cold in the search for an answer, but like any good mystery, one "break" in the case is all that might be needed.

About the Author

Kimberly S. Brown

Kimberly S. Brown was the Publisher/Editor of The Horse: Your Guide To Equine Health Care from June 2008 to March 2010, and she served in various positions at Blood-Horse Publications since 1980.

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