Theories Pursued on Causes of MRLS, Other Syndromes

A meeting of the Kentucky Association of Equine Practitioners on March 7 brought together six of the leading researchers/ investigators dealing with Mare Reproductive Loss and other syndromes seen in the spring of 2001. Each presenter had only 12 minutes to distill his/her ideas to the audience of mostly veterinarians. Each sounded reasonable as presented, although some sparked more controversy than others among the audience. The only clear-cut opinion after the meeting was a new optimism that, yes, this mystery could be solved with the clues that have been and will be put together by these researchers and through the input of clinicians.

One thing that was noted was the overlap in clinical signs from the various theories. Several things can cause the same physiologic results, such as fetal death, pericarditis (heart problems), and uveitis (eye problems). The spike in incidence of physical and reproductive problems indicated that whatever the cause, it came and went quickly and is no longer present in the environment. The timeframe surrounding the problems seems to point toward to a strange weather pattern being an inciter, whatever the cause. There also was consensus that whatever caused the heart, eye, and reproductive problems probably was dose-related or immune-status related since some horses were affected in a field where their pasturemates were not affected in any way.

The reports from the researchers also were varied enough to make everyone consider that there might have been more than one "cause."

It was emphasized that there is a variation in how species react to outside influences, whether they be molds, mycotoxins, or other toxins (whether from trees or grasses). Unfortunately, much of the research in textbooks on potential causes--such as mycotoxins--was done in other species, and those results might not be the same in horses as in cattle, sheep, and swine.

Heart Problems
Last year, Dr. Johanna Reimer, the only board certified veterinary cardiologist in Central Kentucky, was perplexed by the pericarditis cases she and her colleagues were seeing. Working with Dr. Claire Latimer, a specialist in veterinary ophthalmology who worked on the eye problems that occurred in some horses, Reimer looked for a reasonable cause that could affect so many horses in such different ways.

"We figured it was something that incited an immune response," said Reimer, of Rood and Riddle Equine Hospital in Lexington, Ky. "A literature search for pericarditis in healthy people pointed toward several things, including histoplasmosis (a fungal infection). But samples showed no evidence of histoplasmosis infection in these horses. One must consider the possibility that exposure to another fungal organism could cause pericarditis in a similar manner in horses."

Reimer believes that mare reproductive loss syndrome (MRLS) was due to mycotoxins produced by a fungus rather than by the fungus itself.

One point that Reimer noted was that if horses were immunosuppressed, then her treatment with steroids in the pericarditis cases would have been disastrous to the patients; yet steroid treatments gave relief to those horses. (Steroids are known to depress the immune system and delay healing.)
One clinical sign that Reimer noted that was news to several other researchers was the evidence of inflammation in the lungs of some of the pericarditis horses. "Some showed pneumonia on ultrasound, and the tracheal washes showed inflammatory processes, but no (causative) bacteria," noted Reimer.

Mycotoxins and Molds
Kyle Newman, PhD, a nutritional microbiologist with Venture Laboratories in Kentucky, is an expert on molds and mycotoxins. He started his talk by explaining what is known -- and not known -- about molds and mycotoxins in general. He also stressed that much of the research on mycotoxins has been done in other species and extrapolated to horses, which might or might not be correct given the different digestive systems of the species.

He also stated that in 2001, a unique mold might have produced a unique mycotoxin that has never been described before. Newman mentioned the possibility that caterpillar frass (manure) has the ability to support fungal growth, and researchers are looking at possible strains of fungi that might have grown in the frass and be a cause of the problems.

After discussing many types of toxins that can be found in the environment and how they didn't fit with the physical and clinical signs seen in 2001, Newman mentioned T-2, deoxynivalenol (DON), DAS, fusarenon-X, and fumonisin as ones which were known to be fetotoxic (kills the fetus before abortion) and can cause abortion. He said research at North Carolina and Guelph in Canada indicated that the forages found in Kentucky can support growth of some mycotoxins, and that fuserium and aflatoxins have been found in grass forages of the types growing in Kentucky.

"Fumonasin was not present, that is the good news," Newman said of his research.

He also reported that in a research project on a few pregnant mares, zearalenone, which is known to be abortogenic but not fetotoxic, did not have any effect on the mares, although it can cause abortion in other species.

He said lesions of the mouth and/or intestinal tract have been observed with DAS and T-2 toxins. This, he said, might explain the presence of high levels of secondary bacteria (Streptocci and Actinobacilli) found in adult and fetal tissues. The T-2 toxin is more toxic than DON, which inhibits protein synthesis and is immunosuppressive. However, research in a few horses seems to show that horses are resistant to DON toxins.

There is a debate whether fumonisins can caused unilateral blindness. Fusarenon-X was found to cause abortions with a single dose, and the response was dose-related. This toxin is also immunosuppressive and fetotoxic.

But for all the research ruling out--and possible ruling in -- various toxins, Newman warns that there are problems with analyzing mycotoxins in forages. He also noted that it is important to realize that most mycotoxins in nature do not exist alone, and synergism exists between many toxic compounds.

Dr. Dee Cross, a specialist in fungal endophytes from Clemson University, said that, "Horses will browse different plants during drought, frost, or other unusual weather conditions. My hypothesis is that the unusual weather caused mares to graze poison hemlock."

The coniine and gamma coniceine toxins found in hemlock are known to be abortogenic in some species. The signs that go along with this type of toxicity include muscular weakness, incoordination, trembling, cold limbs, cyanotic membranes, fast/shallow breathing, and death caused by paralysis of the diaphram. These toxins also are known to produce teratogenic effects (birth defects) including cleft palate and limb contractures.

A few mares last spring were noted to have muscle trembling prior to abortion, but this was only seen in a small portion (about 5%) of mares which aborted.

"Fescue didn't cause this problem, I'm convinced of that," said Cross. He also noted that hemlock is known to be very unpalatable to horses.

He said in his studies of pastures, that there was a high correlation between the presence of hemlock and reproductive losses. He also noted that the hemlock had been grazed on.

There was a question about why no problems were seen in cattle, which are less selective grazers and are more sensitive to the toxins in hemlock. Cross said there have been problems with cattle in experimental conditions, but there are no comparative data under field conditions. Cross also indicated that the rapid degradation of the compounds in the hemlock had made it difficult to assay for these toxins.

Cross said studies will be done with hemlock and pregnant mares this year.