World-Wide Strangles Research

"Strangles is probably the most important bacterial disease of the horse," explained John Timoney, MVB, PhD, DSc, MRCVS, of the University of Kentucky's Gluck Equine Research Center, "and one for which a safe and effective vaccine is so very badly needed. There are four or five good laboratories in the world that are desperately trying to improve existing vaccines, or develop a novel vaccine."

In 1999, a leading United Kingdom horse charity teamed up with genome researchers to decode all of the genes in Streptococcus equi, the bacterium that causes strangles. The Home of Rest for Horses funded the project, carried out by members of the U.K. Streptococcal Interest group--including Neil Chanter, BSc, PhD, head of bacteriology at the Animal Health Trust; Julian Parkhill, BSc, PhD, leader of the sequencing team at the Sanger Centre; Duncan Maskell, MA, PhD, of Cambridge University; and Mike Kehoe, BSc, PhD, of Newcastle University.

The S. equi genome was decoded in 2000. All DNA segments were identified and decoded in overlapping segments. The job now is to determine where segments overlap. Chanter explained that since information on the genome sequence is openly available on the Internet, researchers worldwide are piecing together the puzzle.

Timoney expressed how grateful the research community is to the U.K. group, as the genome "allows us to very quickly sequence and express proteins that may be of value for inclusion in a more effective vaccine." All previous vaccine research relied on limited information as to how S. equi caused disease. The genome sequence will allow the researchers to identify for the first time all of the genes that S. equi needs to cause strangles. Researchers in Timoney's lab and U.K. researchers will mutate any gene likely to be expressed at the cell surface, where S. equi interacts with the immune cells and tissues of the horse.

"Using laboratory-based models, we will be able to assess the importance of each gene so that we will be able to see if horse antibodies can contribute to killing the bacterium or interfere with the colonization of cells," said Chanter.

Timoney explained that the synergistic effect of several different antibodies is needed to fight strangles. The variation in immunity from horse to horse will play a role in finding a vaccine that will suit every animal.

What's the time frame on availability of a new strangles vaccine? Chanter doesn't believe the best possible vaccine that makes optimal use of the sequence data will be available within 10 years, but Timoney thinks we might see it sooner. The Streptococcus family is a large one that affects many species. S. equi is a close relative to S. zooepidemicus, a frequent cause of respiratory infections and the most common cause of equine wound infections. Timoney hopes to use what he has learned about S. zooepidemicus to target the disease-causing proteins of S. equi.

Why A Better Vaccine?

There are injectable vaccines available that reduce the severity of the disease and result in fewer cases, but there are still outbreaks in vaccinated herds. In the spring of 1999, the Pinnacle IN intranasal vaccine became available in the United States. "Strangles is essentially a disease of the nasopharynx and associated lymph nodes, and doesn't penetrate very far. If you can stop it at the mucosa, there will be far less disease," explained Timoney.

"All horses have been thought to be resistant directly following a natural case of strangles. But we now know 30% become susceptible soon after recovery and can be re-infected if they are exposed," he said. This creates a problem when the antibodies are introduced in the intranasal vaccine.

Timoney hopes that after discovering new vaccine components from the sequence over the next year or two, the final stage of testing will be to find a delivery system that produces persistent, high-level immunity.

In the meantime, reactions to strangles vaccines of all types are not uncommon, and the benefits of protection must be weighed against the chance of reaction. Pinnacle IN can be inadvertantly introduced by way of other vaccines if a vet's hands are contaminated, which can cause a deep-seated abscess. For this reason, Timoney suggests that practitioners schedule intranasal vaccine clients on days other than when intramuscular vaccines will be administered, or use a hand disinfectant in between procedures.

Other problems associated with strangles include purpura hemorrhagica. Timoney explained that in purpura cases, walls of blood vessels are severely damaged--they become leaky and fluid and red blood cells seep through, resulting in edema or swelling of the limbs. The condition can range from mild to fatal, but can be thwarted with therapy if caught in time. Since the condition occurs so rapidly, researchers rarely get to study cases.

"(A purpura case) is a hyper-responder, meaning it already has a strong antibody response when the vaccination is given. Horses that develop purpura didn't need vaccination," Timoney explained. "That's the irony of it."

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