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By Joseph Kays
Many University of Florida faculty watched with pride this spring as Ocala-bred Silver Charm raced into history by winning the Kentucky Derby and Preakness.
They've seen many horses like Silver Charm come through UF's College of Veterinary Medicine over the years. Home to the state's only veterinary college, and adjacent to the second-largest Thoroughbred horse-producing area in the United States, UF has a long history of research in equine health and performance.
Much of that research is funded by the very industry it benefits, through several large grants from the state Division of Pari-Mutuel Wagering. The agency oversees Florida's Thoroughbred and Greyhound racetracks and jai-alai frontons.
Louise H. Courtelis who with her late husband Alec have been long-time benefactors of UF, says the university's colleges of medicine and veterinary medicine "are blessed to work hand in hand for the benefit of all species."
Courtelis says the colleges exemplify her Town and Country Farms motto: "It's Performance That Counts."
UF's College of Veterinary Medicine administers a $250,000 annual research program financed through the Pari-Mutuel Trust Fund, which was established with proceeds from legal gambling activities in Florida. The college awards money to individual researchers throughout the State University System in an open grant competition. Since assuming responsibility for the competition in 1995, the college has awarded 12 grants totaling $475,000.
"The research funded through the pari-mutuel program has great potential to help the horse industry in Florida," says Dr. Charles Courtney, associate dean for research and graduate studies in the College of Veterinary Medicine. "Dollars for equine research from other sources are scarce and highly competed for nationwide. Equine research is expensive, and sustained funding, such as that provided by Florida's pari-mutuel program, is needed so meaningful, long-term studies can be conducted, the results of which can be applied to the benefit of the equine athlete."
In addition to the annual funding program, the veterinary college has separate grants from the Division of Pari-Mutuel Wagering to perform drug-elimination studies and to conduct necropsies on horses that die at racetracks.
Mystery Disease
About the only thing researchers know for sure about the deadly equine neurological disease called equine protozoal myeloencephalitis, or EPM, is that they don't know all that much.
It seems that for every advance in understanding EPM, there is a frustrating reversal. One thing is certain: The incidence and economic costs of EPM continue to mount.
Recent studies indicate that as many as half the horses in the United States have EPM antibodies in their blood. Fortunately, the vast majority of those horses never show any outward sign of the disease.
But for the ones that do, the results can be debilitating, or even deadly.
Veterinarians at UF's Veterinary Medical Teaching Hospital treat more than 60 horses a year for EPM-related disorders such as paralysis and incoordination, and half never improve.
"Roughly 20 percent of all horses with EPM die, and only about 10 percent totally recover," says Dr. Robert MacKay, a professor of large animal medicine and member of a UF research team studying the disease.
Drawing on $134,000 in support from the Pari-Mutuel Trust Fund, UF scientists are focusing their efforts on the Sarcocystis parasite believed to be the cause of EPM.
EPM seems to be particularly prevalent among young racehorses, possibly because training and travel weaken the horses' immune systems and their ability to fight the parasite.
Based on studies at UF and the University of Kentucky, it is now generally accepted that the opossum is one of the two hosts needed for the EPM-causing parasite known as Sarcocystis neurona to complete its life cycle.
Sarcocystis neurona requires at least one carnivorous host, the opossum, and one herbivorous host to complete its life cycle.
The parasites reproduce rapidly in the opossum's intestine, eventually entering the outside environment in its feces. Some herbivore ingests parasites from the opossum feces, dies and is eaten by another opossum and the cycle begins anew.
The horse is what pathobiologists call an aberrant or "dead-end" host. It contracts the parasite by eating or drinking from sources contaminated by opossum feces, but the parasite cannot mature inside the horse for transmission back to the opossum. In its attempt to mature, the parasite replicates in the horse and wreaks havoc with the animal's nervous system.
Identification of the opossum as the apparent carnivorous host is only one step in the effort to establish the entire life cycle of Sarcocystis neurona in the laboratory. Being able to reproduce the disease under laboratory conditions is vital to developing a cure or preventive measures.
"Once demonstrating that we have the agent of EPM in the laboratory, it will be possible to study the pathology and treatment of this disease under controlled conditions for the first time," MacKay says.
The problem, says UF pathobiology Professor John Dame, is that Sarcocystis is a parasite of major importance and the most basic facts about its life cycle are unknown.
"No one can propagate the parasite under controlled conditions in a form infectious for horses," says Dame, a nucleic acid chemist. "We have a good deal more work to do yet to isolate it and propagate it."
Dame says there may be several species of Sarcocystis which parasitize the opossum and only one or a few of them may cause EPM. Having molecular tools to detect the Sarcocystis species which cause the disease also will help in identifying the parasite in its intermediate herbivorous host.
"Right now, we're trying to discriminate between the different genetic properties of the parasites we take from opossums," he says. "Once we've grouped them based on these properties, then we can test in horses to determine which ones cause the disease."
The UF team, which also includes pathobiology Professors Ellis Greiner and Pamela Ginn, already has eliminated a genetically similar Sarcocystis parasite called Sarcocystis falcatula, which is known to cycle between brown-headed cowbirds and opossums.
Sarcocystis falcatula and Sarcocystis neurona share an identical gene sequence, pointing to a very close relationship. But when the researchers administered falcatula parasite eggs to horses, the animals didn't get infected.
"What this tells us," Dame says, "is that two species of the Sarcocystis parasite can be very closely related and not be the cause of EPM.
"Knowing what doesn't cause the disease, however, can be important," Dame says, since like all science, this is hypothesis-driven trial by elimination.
While the researchers continue to refine their methods of isolating Sarcocystis parasites and administering them to horses, horse owners already are using the knowledge derived from these experiments to protect their animals from the disease. Many are securing their feed and water better, so opossums cannot get near them, and taking steps to reduce the opossum populations on their farms.
Flu Shot
UF pathology and pediatrics Professor Parker Small jokes that he and UF infectious diseases Professor Brad Bender began working on a vaccine for equine and human influenza because there was very little market for the mouse influenza vaccine they had developed.
"I'm not sure whether Dr. Bender or I was in charge of marketing, but we have not had a single mouse ask for a flu shot," Small jests.
But it's no joke that influenza kills more than 80,000 people a year in the United States and many times that number in other parts of the world.
So for years, Small and Bender have been working with Dr. Bernard Moss at the National Institutes of Health to develop an influenza vaccine that could be safely, efficiently and inexpensively administered. They hoped such a vaccine could be a model for a new approach to immunizing children in developing nations.
Existing flu vaccines are designed primarily to prevent pneumonia by activating serum antibodies that protect the lungs. Since the emphasis is on protecting the lungs, many people who receive the vaccine still get upper-respiratory flu symptoms, but don't die.
The ideal vaccine would prevent both pneumonia and nasal infection by inducing both serum and mucus antibodies. It also would be multi-valent, meaning it would protect against multiple strains of influenza, or even multiple viruses.
Until the advent of genetic engineering, vaccines for viral diseases were composed primarily of weakened or dead viruses. These vaccines triggered the body's immune response, protecting the person against being infected with the full-strength virus found in nature.
But with the ability to manipulate virus genes, scientists now can trigger human immune responses by inserting one or more genes that code for the protein-coating of several dangerous viruses, including influenza, into a harmless virus "vector," or vehicle.
Moss and his NIH colleagues have achieved this by inserting influenza genes into a modified version of the vaccinia virus that has been used for years as the smallpox vaccine. When the team administered the genetically engineered vaccinia virus to laboratory mice through the nose or gut, it "turned on" both serum and mucosal immune responses.
Through the kind of serendipity researchers say is common on a campus where the medical and veterinary colleges are in such proximity, Small and longtime friend Paul Gibbs, a professor of virology in the veterinary college's Department of Pathobiology, determined they could help each other advance influenza research.
"Paul sees this vaccine as an end to a veterinary problem, while we see it as the means to an end of a human problem," Small says. "That's the beauty of having a college of medicine and a college of veterinary medicine on the same campus. We often can multiply the value of our research by transferring it from humans to animals, or vice versa."
Gibbs and his colleagues in the College of Veterinary Medicine's pathobiology department have been working for years to develop vaccines for emerging viral diseases that threaten Florida animals.
Gibbs calls equine influenza "the most important disease relative to the performance horse" because it can quickly cause an epidemic at a racetrack stable.
As part of a study involving 28 horses, the researchers have inoculated 16 horse with a vaccinia vaccine coding for the protein of a human influenza virus. For comparison, control horses are receiving nothing or a conventional vaccine. So far, the horses have developed both serum and mucus antibodies against the human influenza virus. This indicates that the virus vaccine replicates in the horse.
"Now that we've proven this approach will work," Small says, "the next step is to make a horse vaccine with genes from the horse influenzas."
Veterinary faculty also are helping the influenza researchers determine whether the vaccinia vaccine can be administered orally, a necessity if it is to be practical for use in developing countries, Small says.
The researchers know any orally administered vaccine will have to be coated to protect it against stomach acids and bile, but they wanted to see if the vaccine worked before they spent time developing a protective coating.
So, they enlisted the help of veterinary college faculty members Al Merritt and Lucy Edens to put the vaccinia virus directly into a horse's bowel.
"It is only because of Al's and Lucy's knowledge of the horse's gut that we were able to test our vaccine this way," Small says. "We are still evaluating the data, but the early results look promising."
Drug Decisions
Thoroughbred racing is supposed to have an element of chance to it, but not when it comes to drug testing that can disqualify a horse and lead to fines for those involved.
As more medications become available to treat horses for ailments ranging from stomach aches to hoof infections, and as racetrack tests become more sensitive, so does the need for clearer medication standards.
"I would love to have a chart that tells me exactly how long before a race I can use a certain medication," says Dr. Thomas Brokken, an equine veterinarian who practices at the Hialeah, Gulfstream and Calder racetracks in south Florida.
Such a chart is exactly what a team of University of Florida veterinary researchers hope to develop. Through a program funded by a two contracts totaling $450,000 from the Pari-Mutuel Trust Fund, they are working to specify the length of time needed to clear various therapeutic drugs from a horse's system. The researchers also are trying to determine whether there are appropriate "decision levels" for drugs, below which they have no apparent effect on performance.
Just like human athletes, horses receive medications for a wide variety of maladies, from penicillin for infections to tranquilizers to ease anxiety during shipping. But in Florida, racehorses are allowed to have only three medications in their systems on race day: Furosemide, Prednisolone Sodium Succinate and Phenylbutazone.
"The intent is to ensure that what the bettor sees is an honest race," says Dr. Patrick Colahan, associate chief of staff of the large animal hospital and principal investigator for the project. Drugs could be used to enhance or detract from a horse's performance, or to enable an injured horse to compete.
Researchers are cycling 16 Thoroughbred horses through a four-part exercise-and-drug protocol in which four are exercising with medication and four without it, while one quarter rest with medication and one quarter rest without it.
Exercising horses participate in a vigorous daily "workout" on a state-of-the-art, high-speed treadmill designed to maintain racing condition. The treadmill also allows researchers to monitor heart rate, respiration and other functions during the workout.
"The treadmill allows us to more precisely control the environment and obtain the most accurate measurements," Colahan says.
In addition to providing veterinarians like Brokken clearer guidelines, the research could lead to amendments in Florida racing statutes that will set "decision levels" for certain medications.
Patrick A. Colahan
Associate Professor, Department of Large Animal Clinical Sciences,
(352) 392-4700, colahan.vetmed1@mail.health.ufl.edu
John Dame
Associate Professor, Department of Pathobiology, (352) 392-4700, dame@icbr.ifas.ufl.edu
Paul Gibbs
Professor, Department of Pathobiology, (352) 392-5443, pgibbs@nervm.nerdc.ufl.edu
Robert MacKay
Associate Professor, Department of Large Animal Clinical Sciences,
(352) 392-4700, mackay.vetmed3@mail.health.ufl.edu
Parker A. Small
Professor, Departments of Pathology and Pediatrics, (352) 392-0686,
pasmall@college.med.ufl.edu