Story3LymeD

	Many horses whose blood tests positive for exposure to the Borrelia burgdorferi bacteria do not have lyme disease. Compatible clinical signs must also be present for a diagnosis to be definitive.
Lyme disease is a bacterial illness caused by the corkscrew-shaped (spirochetal) bacteria Borrelia burgdorferi. It is the most prevalent tick-associated illness in horses, humans, dogs, and cats in the northeastern United States, causing such nonspecific signs as fever, stiffness, muscle pain, and swollen joints. The so-called “deer ticks” or “black-legged ticks” are the most common carriers of the bacteria. The disease is endemic in the northeastern and mid-Atlantic states, Minnesota, Wisconsin, and northern California. Four to five years ago, equine clinician Thomas Divers, DVM, Dipl ACVIM, and Yung-Fu Chang, DVM, PhD, Dipl ACVM, a professor of population medicine and diagnostic sciences, were swamped with questions about Lyme disease in horses. They began testing the blood of horses to determine how widespread equine exposure to the bacteria was found. “It became clear that huge numbers of horses in the Northeast had produced antibodies, but no one knew what it meant because no one had done research on Lyme disease in horses before,” says Divers. He points out that in areas where humans are being infected at high rates, more than 50 percent of the horses had been exposed. In Connecticut, more than 70 percent of the horses have been exposed based on seroconversion, that is, the development of antibodies against a microorganism. Despite evidence of high exposure, only a small percentage of horses show obvious symptoms. Lyme disease is of particular concern to owners and trainers of performance horses, says Divers, because the stiffness and lameness that the disease produces can take a serious toll on performance. Such problems have been observed in Connecticut and eastern New York where many elite show and performance horses are trained. Since Chang had published a number of papers on Lyme disease in dogs, Divers teamed up with him and pathologist Sean McDonough, DVM, PhD, for a series of studies funded jointly by the Zweig Memorial Fund and the Dr. John Lowe Endowment. In the first phase, the researchers produced Lyme disease experimentally in ponies to study the response to the infection. They found microscopic evidence of the disease in the layer of skin just underneath the epidermis (dermis), lymph nodes, peripheral nerves, and around blood vessels near the joints. Clinical signs of the disease were not obvious in the experimental ponies, although subtle signs might have gone undetected. Some clinical signs previously attributed to Borrealia, in fact, were caused by infection by another organism, Anaplasma phagocytophila (also known as Ehrlichia equi). They also discovered which antibodies were important in diagnosing Borrealia and the temporal antibody response to infection, both of which have permitted improvements in diagnostic testing and/or interpretation. “We also found that horses stayed infected for months after the infected ticks were removed, suggesting that the infection is persistent, perhaps lifelong in some horses,” Divers points out. “All three antibiotics reduced the level of the ponies' antibody response, indicating that the organisms were suppressed somewhat, but only tetracycline completely cleared all four ponies of the infection. - Thomas Divers In the second phase of the studies, the researchers used an experimental vaccine based on an outer surface protein (OspA) that others had determined was important for immunity in other species. They vaccinated eight ponies on days 1, 20, and 82, which proved protective for an experimental challenge. “Although the vaccine is very similar to a vaccine available for dogs and to the vaccine for humans—which was taken off the market for possible side effects—we don't know if the dog vaccine would work in horses and we don't know how often the horse needs boosters,” Divers says. “What we do know is that the experimental vaccine provided protection in our experimental model and side effects were not noted. It is unlikely, however, to be effective after an infection has already occurred.” In the third phase of the study, the researchers analyzed antibiotic treatments. Because the infection did not trigger obvious clinical signs, the success of treatment was based on lab tests to determine if the organism was cleared from the ponies. The researchers infected 16 ponies and then tested three antibiotics: tetracycline administered intravenously, doxycycline administered orally, and ceftiofur administered with an intramuscular injection for three weeks in four ponies each. Four ponies were in a control group. After four months, the ponies were euthanized and evaluated. “All three antibiotics reduced the level of the ponies' antibody response, indicating that the organisms were suppressed somewhat, but only tetracycline completely cleared all four ponies of the infection. In the other two groups, the antibiotics cleared one of the four ponies but left three still infected,” Divers said. Tetracycline was likely the most effective because it was administered intravenously, which permitted very high levels of the antibiotic in the tissues. “With what we've learned so far about treatment, the reasonable recommendation would be to treat an infected horse with intravenous tetracycline initially, and if long-term treatment were desired, switch to the oral administration of docycycline, which is much more convenient and practical,” Divers concludes. Drs. Divers and Chang wish to further test the dog vaccine in horses, advance challenge studies following vaccination to determine how often boosters are needed, and change the doses of the various antibiotics to determine if that would make them more effective.

Lyme disease is a bacterial illness caused by the corkscrew-shaped (spirochetal) bacteria Borrelia burgdorferi. It is the most prevalent tick-associated illness in horses, humans, dogs, and cats in the northeastern United States, causing such nonspecific signs as fever, stiffness, muscle pain, and swollen joints. The so-called “deer ticks” or “black-legged ticks” are the most common carriers of the bacteria. The disease is endemic in the northeastern and mid-Atlantic states, Minnesota, Wisconsin, and northern California.

Four to five years ago, equine clinician Thomas Divers, DVM, Dipl ACVIM, and Yung-Fu Chang, DVM, PhD, Dipl ACVM, a professor of population medicine and diagnostic sciences, were swamped with questions about Lyme disease in horses. They began testing the blood of horses to determine how widespread equine exposure to the bacteria was found.

“It became clear that huge numbers of horses in the Northeast had produced antibodies, but no one knew what it meant because no one had done research on Lyme disease in horses before,” says Divers. He points out that in areas where humans are being infected at high rates, more than 50 percent of the horses had been exposed. In Connecticut, more than 70 percent of the horses have been exposed based on seroconversion, that is, the development of antibodies against a microorganism. Despite evidence of high exposure, only a small percentage of horses show obvious symptoms.

Lyme disease is of particular concern to owners and trainers of performance horses, says Divers, because the stiffness and lameness that the disease produces can take a serious toll on performance. Such problems have been observed in Connecticut and eastern New York where many elite show and performance horses are trained.

Since Chang had published a number of papers on Lyme disease in dogs, Divers teamed up with him and pathologist Sean McDonough, DVM, PhD, for a series of studies funded jointly by the Zweig Memorial Fund and the Dr. John Lowe Endowment.

In the first phase, the researchers produced Lyme disease experimentally in ponies to study the response to the infection. They found microscopic evidence of the disease in the layer of skin just underneath the epidermis (dermis), lymph nodes, peripheral nerves, and around blood vessels near the joints. Clinical signs of the disease were not obvious in the experimental ponies, although subtle signs might have gone undetected. Some clinical signs previously attributed to Borrealia, in fact, were caused by infection by another organism, Anaplasma phagocytophila (also known as Ehrlichia equi). They also discovered which antibodies were important in diagnosing Borrealia and the temporal antibody response to infection, both of which have permitted improvements in diagnostic testing and/or interpretation.

“We also found that horses stayed infected for months after the infected ticks were removed, suggesting that the infection is persistent, perhaps lifelong in some horses,” Divers points out.

In the second phase of the studies, the researchers used an experimental vaccine based on an outer surface protein (OspA) that others had determined was important for immunity in other species. They vaccinated eight ponies on days 1, 20, and 82, which proved protective for an experimental challenge.

“Although the vaccine is very similar to a vaccine available for dogs and to the vaccine for humans—which was taken off the market for possible side effects—we don't know if the dog vaccine would work in horses and we don't know how often the horse needs boosters,” Divers says. “What we do know is that the experimental vaccine provided protection in our experimental model and side effects were not noted. It is unlikely, however, to be effective after an infection has already occurred.”

In the third phase of the study, the researchers analyzed antibiotic treatments. Because the infection did not trigger obvious clinical signs, the success of treatment was based on lab tests to determine if the organism was cleared from the ponies. The researchers infected 16 ponies and then tested three antibiotics: tetracycline administered intravenously, doxycycline administered orally, and ceftiofur administered with an intramuscular injection for three weeks in four ponies each. Four ponies were in a control group. After four months, the ponies were euthanized and evaluated.

“All three antibiotics reduced the level of the ponies' antibody response, indicating that the organisms were suppressed somewhat, but only tetracycline completely cleared all four ponies of the infection. In the other two groups, the antibiotics cleared one of the four ponies but left three still infected,” Divers said. Tetracycline was likely the most effective because it was administered intravenously, which permitted very high levels of the antibiotic in the tissues.

“With what we've learned so far about treatment, the reasonable recommendation would be to treat an infected horse with intravenous tetracycline initially, and if long-term treatment were desired, switch to the oral administration of docycycline, which is much more convenient and practical,” Divers concludes.

Drs. Divers and Chang wish to further test the dog vaccine in horses, advance challenge studies following vaccination to determine how often boosters are needed, and change the doses of the various antibiotics to determine if that would make them more effective.