Deadly Spring Syndromes
Good news travels fast in the horse business; bad news travels even faster. In the case of an outbreak of mysterious early fetal loss and late-gestation foal loss, cooperation and quick sharing of information served to help researchers investigate and track down a killer--maybe.
In several states this spring, including Ohio, West Virginia, and possibly some other states--but especially Kentucky where there is a concentration of Thoroughbred breeding farms--strange things started happening following an unusual weather pattern this spring of warm weather, frost, and then drought. It all began coming to light when one large breeding farm in Lexington, Ky., had several mares undergo ultrasound examinations in late April for fetal sexing at about 60-65 days of gestation.
That is the optimum time for determining the gender of the next generation. Normal ultrasound exams are done early (at about Day 14 of gestation) to determine pregnancy, and again at about 30 days to verify pregnancy. After that, mares are periodically checked by manual palpation. What was discovered during those fetal sexing ultrasounds was the tip of the iceberg. Mares were losing pregnancies at an astounding rate.
Tom Riddle, DVM, a founding partner of the Rood and Riddle Equine Hospital in Lexington, was performing the fetal sexing at Taylor Made Farm on April 26. On that day, he discovered two cases of unexpected early fetal loss on the farm in Jessamine County. On April 30, Riddle found a dead early-term fetus in a mare in Bourbon County. Riddle said conversations with another veterinarian revealed that more mares had been found either with dead early-term fetuses or with live fetuses surrounded by a cloudy fluid. (After going back and researching records, researchers now think the first case of early fetal loss began about April 23 in a mare which was 60 days in foal.)
On May 1, Riddle found three more cases, which prompted him to call Neil Williams, DVM, PhD, at the Kentucky Livestock Disease Diagnostic Center to alert him of incoming recovered fetuses and blood serums from the mares which had aborted. Riddle also contacted Roberta Dwyer, DVM, Dipl. ACVPM, of the University of Kentucky's Gluck Equine Research Center, a specialist in preventive medicine and epidemiology.
Dwyer and David Powell, BVSc, MRCVS, FRCVS, another experienced epidemiologist at the Gluck Center, visited two farms having problems with early fetal loss on May 2. At that time, late-gestation mares were starting to abort foals, and at-term mares were producing stillborn (dead) or very sick foals in numbers much higher than had ever been seen.
A meeting was called with veterinarians and researchers on May 3 to share information and to determine what samples needed to be taken to begin an investigation.
Horse owners should remember that this was the week before the Kentucky Derby, and the eyes of the Thoroughbred industry and the world were focused on Saturday, May 5, for the race termed the "Greatest Two Minutes In Sports." But down on the farm, the story was quite different.
On Derby Eve, May 4, Doug Byars, DVM, Dipl. ACVIM, head of the internal medicine facility at the veterinary firm of Hagyard-Davidson-McGee in Lexington, reported that 14 red-bag foals were brought to the clinic that day. The following day, when the rest of the country's attention was focused on the excitement of the Kentucky Derby, farm managers in Lexington were under siege. The highest number of aborted foals and fetuses taken to the Diagnostic Center in one day during the entire outbreak was Derby Day, May 5, with 73. One farm manager said there was a line of vehicles waiting to drop off dead foals for necropsy, which is offered as a free service in Kentucky as part of the University of Kentucky's extension program.
All Breeds Affected
What should be remembered in this tale of woe is that all types of mares and foals were affected. From April 28 through May 6, a total of 318 aborted/stillborn equine fetuses/foals were taken to the Diagnostic Center for testing and evaluation. For the same time period the previous year, only 46 aborted/stillborn fetuses/foals were seen at the Diagnostic Center, marking a 700% increase in the deaths for this year.
Lenn R. Harrison, VMD, Director of the Diagnostic Lab and one of the chief investigators in the losses, listed the breeds represented as affected at that time in the order of how many were seen (remember, Thoroughbreds are the most populous breed in the area). Following are the breeds seen with aborted foals/fetuses at the time of his report: Thoroughbred, Standardbred, Tennessee Walking Horse, American Saddle Horse, Quarter Horse, Appaloosa, Rocky Mountain Horse, Arabian, Paint, Morgan, Hanoverian, Paso Fino, Miniature, pony, crossbred (at least three), warmblood, and mule.
Most of those were late-gestation losses--foals nearly ready to be born. Only 25 of the 318 were early gestations (60-90 days). However, we should remember that many early gestation losses were not submitted for testing, so this figure doesn't indicate how many early fetal losses actually were happening.
A Team Effort
On May 6, a fax was sent to area veterinarians with what limited information was available. The following day, Monday May 7, a survey was distributed by the Kentucky Thoroughbred Farm Managers' Club and the University of Kentucky to be returned by the morning of May 9 to try and estimate the span of the problems, and to get a handle on any potential causes.
By the Monday after Derby Day, numbers were starting to emerge. Some farms already had lost 25-80% of the 2002 foals to early fetal loss. Losses of foals and fetuses ranged from zero on some farms to everything on others. And there was no evidence that the problem was decreasing. Of the late-term foals which were making it to intensive care clinics, only about 50% were surviving even with the most sophisticated care available for horses anywhere.
The first nationally published information on these spring syndromes appeared online at www.bloodhorse.com, owned by the weekly Thoroughbred magazine The Blood-Horse, a sister publication to The Horse. This magazine's web site, www.thehorse. com, also included daily updates on the situation, sometimes changing hourly.
Byars noted on May 6 that there were two distinct and unexplained syndromes--early fetal losses and what mare owners call "red bag" deliveries, or premature separation of the placenta, where the placenta comes out with or before the foal. This often causes the foal to suffocate if the birth is unattended. Some mares began to foal standing up, and some were agalactic (didn't develop an udder or produce milk normally).
"The foals don't want to breathe," said Byars. "There are a lot of stillbirths. Many of the foals that make it to the hospital have low white counts (the blood cells that fight infection), are septic (system-wide infections), and are dehydrated."
At that point, "no bugs"--contagious or infectious organisms--had been cultured either at private hospitals or at the Diagnostic Center. The syndrome didn't look like a "classical" fescue toxicosis, but veterinarians thought it could be something similar. Theories at that point ranged from this year's extreme Eastern tent caterpillar crop to mycotoxins in the grass. (Mycotoxins are produced by molds that grow in pastures and on feeds.)
Early recommendations were to treat every foaling mare as a high-risk foaling situation, administer domperidone to pregnant mares near term (a medication used to offset the problems associated with fescue toxicosis) and other medications (such as antibiotics) that your veterinarian might recommend, and take other medical steps to counter some of the problems seen in early-gestation mares.
For early pregnancies, it was suggested to ultrasound mares as recommended by your veterinarian. If mares were turned out, owners were to make sure there was hay available or limit grazing. It also was recommended that managers mow pastures in spite of the drought conditions experienced in Kentucky and other states. Byars recommended mowing at that point, "even though the damage may already be done.
"The statistics of losses are beyond what I've ever recognized in my 18 years in Kentucky," Byars said. "A few mares have normal foals. When I went to one farm Sunday (May 6) and checked one late-gestation mare, she was okay and so was the fetus. But that farm lost two foals that morning to stillbirths."
The Search For Answers Intensifies
The researchers and veterinarians all were looking toward an environmental cause for these syndromes, since none of the signs pointed toward an infectious or contagious disease process. Managers were being asked to ship mares out of state in record numbers. Veterinarians, vet techs, researchers, farm managers, and farm workers were stressed to the breaking point by long hours and frustration.
On May 7, a meeting was held at the Gluck Center with a wide array of specialists--such as pasture management consultants--to help identify areas of pasture chemistry and possible toxic agents for investigation. Throughout the research process, negative tests were more numerous than positive tests. Fetuses tested negative for nitrates/nitrites. Copper, iron, zinc, and selenium levels in mare sera were normal. Fluorescent antibody tests were negative for leptospirosis, and samples showed no signs of equine arteritis virus, adenovirus, or equine herpesviruses 1 and 4. Caterpillars tested negative for cyanide (more on this later).
What was seen at that point were indications of a mild pneumonia in fetuses, and higher than expected findings of two bacteria--Actinobacillus equuli and Streptococcus species, both of which grow best in low-oxygen situations.
It came to light that in 1980 and 1981, there were similar problems with early fetal loss in Kentucky. At that time, there was no ultrasound to check mares, just the indication that some mares were empty that should have been pregnant. No answer was found for those losses; fescue toxicosis was thought to have played a role at the time. In looking back, it was discovered that the weather patterns were nearly identical in those years--especially 1980--to 2001, with early hot weather followed by a frost and drought conditions.
One of the most probable causes of the fetal/foal losses was put forth to be mycotoxins created when the lush early grass growth promoted mold growth on grasses in pastures. The grasses were damaged by frost and drought, making them ideal homes for the fungi that produce the harmful mycotoxins. It was known that in other livestock, mycotoxins can cause abortions. It was suggested that a mycotoxin binder be used as a supplement or increased in feeds already containing the binder to keep any mycotoxins from being absorbed from the horse's gut. These binders had been used at farms where fescue toxicosis was a problem in the past.
On May 10, an industry-wide meeting was held at the Keeneland sales pavilion, and it was standing room only with more than a thousand interested spectators in attendance. The story and its impact on the Thoroughbred industry had made national headlines with all the major television networks, and was carried on the major newswires around the world. Only days after the Kentucky Derby had made headlines, the world again was looking at Kentucky, this time at tragedy.
But, as was being discovered, other states were affected, too. One veterinarian from Ohio drove seven hours to attend the meeting because he was noticing problems with foaling mares in his area. That followed on the heels that day of reports of problems in two Ohio counties by Grant Frazer, BVSc, MS, of The Ohio State University.
Researchers announced that the number of cases of early fetal loss and late-gestation loss were continuing to grow, with numbers approaching 400 foals/fetuses submitted to the Diagnostic Center. One early test result came back positive for a mycotoxin called zearalenone, which is known to cause reproductive problems in other livestock. Zearalenone also was found in caterpillars and in the urine of a couple of mares affected by the syndrome. Also, it was suggested that Kentucky hay baled early in the year might contain whatever was causing the problems in horses, and should be tested or fed to other species of livestock.
While the meaning of finding zearalenone wasn't known at the time, veterinarians and researchers were leaving no stone unturned while looking for answers, or trying to protect horses.
Another development revealed that night was that whatever was causing the reproductive loss syndrome was beginning to affect horses of all sexes and ages. One serious syndrome was pericarditis. At least 20 pericarditis cases had been seen at area clinics in the days preceding the May 10 meeting, according to Byars. (Usually only two or three are seen per season.)
Pericarditis is a scary-sounding word that means fluid in the pericardial membrane surrounding the heart. Byars explained that the sac can only stretch so much, and when there is too much fluid, it compresses and compromises the heart. Byars said he took six to eight liters of fluid from around the hearts of adult horses, and a couple of liters of fluid from around the hearts of babies. Unfortunately, even in horses which survive there can be irreversible scarring around the heart that can compress the heart and compromise normal function.
"We may get out of the broodmare problem and be left with other clinical problems," said Byars that night.
He turned out to be right. In the next few days, cases of uveitis (serious eye problems) began to appear in newborn foals and in older horses. In the older horses, it was causing blindness. Also, some performance horses were developing laminitis with colitis, and some young horses weren't growing and putting on weight as usual. Veterinarians were seeing oral ulcers on some horses. There were more than 50 researchers tackling the problem, and while they found clues in successes and failures, no direct route of cause had been found.
Re-Enter the Caterpillar
While losses slowed over the next week to 10 days, the foaling season also was winding down, meaning there were fewer late-gestation foals to lose and fewer mares in the critical 40-days-and-up gestation period. The number of pericarditis cases and other problems also seemed to be abating. There is some lingering concern that the fetuses that were saved might not result in the healthiest of foals next year.
By May 22, it was shown with more sophisticated testing that the mycotoxin theory was out, probably. Also on the back burner were other pasture-related toxins such as fungal endophytes, phyto-estrogens (plant-produced estrogens), and ergot alkaloids. The researchers' credo of keeping an open mind was in full force.
What was back in the picture was the Eastern tent caterpillar and its favorite food, the black cherry tree. Caterpillars were tested early and not found to have cyanide in their systems, but it later was found that these caterpillars digest their food within six hours of eating, so they needed to be tested immediately upon receipt at the lab. The first caterpillars were delayed in testing, therefore giving the false negative test for cyanide.
It was difficult at that point to find a tent caterpillar, but a few weeks ago, horse owners in many states 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--especially black cherry 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."
The black cherry tree is one of the most widespread and common hardwood species in the Eastern United States. It is a well-known fact that the leaves of cherry trees--along with at least 60 families of flowering plants--can poison living creatures with cyanide. Healthy black cherry tree leaves contain prunasin, a cyanide precursor that is non-toxic. However, when leaves are damaged by drought, frost, wilting, being blown from trees during storms, etc., the prunasin molecule is split, allowing cyanide to be released.
Tom Tobin, MVB, MSc, PhD, MRCVS, Dipl. ABVT, a toxicologist with the Gluck Center, explained that cyanide causes tissue anoxia. This means cyanide keeps the body from being able to use oxygen at the cellular level, basically suffocating tissues. Harrison of the Diagnostic Center said low levels of cyanide or a cyanide-containing compound were found in the heart muscles of three fetuses sent to the University of Illinois for sampling. Samples of many different tissues were sent to the toxicology lab at the University of Illinois and other laboratories, and Harrison said testing will continue to validate the initial findings. "That is an observation that must be confirmed," he said.
However, he added, many foals which were compromised or stillborn had fluid and material in their lungs that suggested they were "gasping or struggling in utero," said Harrison.
Terry Fitzgerald, PhD, a professor of Biological Sciences at the State University of New York College at Cortland, literally wrote the book The Tent Caterpillars, and has studied these crawling creatures since 1976. Fitzgerald, who is working with the Gluck Center researchers, said that while the Eastern tent caterpillars have a cyanide poisoning potential, there have been no reported cases of it happening in mammals before.
"The pathway is not known (from the cherry tree to the caterpillar to the horses)," said Fitzgerald. "There is no precedent in the literature."
Fitzgerald, who has been working with researchers at the Gluck Center, said his original thinking was that the horses had browsed small, sprouting cherry trees. Birds eat the fruit from the black cherry tree and pass the seed in their feces, often while sitting on fences or electric wires over fields. "The young leaves are very toxic with cyanide," said Fitzgerald. He suggested that if people weren't mowing during the drought, there could have been an abundant crop of young cherry trees that the horses grazed because of the drought's reduction of normal pasture grass growth. Since pastures now have been mowed, it is unlikely, he said, that any of the young plants would still be there.
Fitzgerald also noted that Eastern tent caterpillars "regurgitate defensively" when attacked by predators or parasitoids. "Regurgitated juices collected from caterpillars that have just eaten contain both benzaldehyde and cyanide at the same concentration in which they occur in the leaves. It has been suggested that the Eastern tent caterpillar may arm itself intentionally by feeding preferentially on the youngest host leaves," which have the highest toxic potential. It isn't known if caterpillars could contaminate water supplies. It is known that cyanide breaks down quickly, so it isn't believed to still be in mowed fields.
Whatever the final test results conclude, researchers agree that the incident that caused the foal losses and other syndromes occurred during a short time period, affected horses, then was gone, leaving residual problems from the initial insult. They also agree that the unusual environmental conditions this spring created a scenario that is associated with the losses. What researchers hope is that a definite cause will be found, but what they know now is that in the future, the weather conditions will be monitored to give alerts to horse farm owners and managers should those conditions reappear at any time in the future.
A Final Word
The cooperation and openness of the veterinarians, researchers, farm managers, horse owners, and the industry at large was incredibly satisfying. The next few weeks will bring more information, and hopefully more solid answers to the problems that struck the horse industry this spring.
For continuing updates, check www.thehorse.com/mrls. Any information pertaining to early fetal loss, foal loss, and other syndromes experienced this spring in any state can be sent to us via this web site, or you can contact your state veterinarian's office for details on problems in your state.
Weather’s Contribution to the Spring Loss Syndromes
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 David Powell, BVSc, MRCVS, FRCVS, of the Gluck Equine Research Center in Kentucky. “In 1981, there was a similar syndrome that in every sense is what we’re seeing now, but not to the same extent…It's difficult to know if it was widespread and not reported. Also, the veterinary technology was 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, mares were only palpated at 42 days; ultrasound was not available. In looking to the future, Powell thinks that by working with the climate and weather researchers, we will be able to identify weather risks for these syndromes. In other words, if similar weather patterns occur in the future, scientists will alert the horse industry to take precautions.
About the Author
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.
POLL: University Equine Hospitals