Confirmed cases of West Nile virus plummet due to vaccination and rise in natural immunity

WEST NILE VIRUS, the devastating invader from the Middle East that killed one-third of horses that contracted it, is losing its grip on America's equine population. Confirmed cases of West Nile virus, which peaked at 15,257 in 2002, are down to just 423 in 2005 as of September 1, largely due to the efforts of horse owners to vaccinate against the deadly disease and to implement mosquito-control programs.

Besides California (277), Utah (19), Arizona (16), Idaho (14), and Nevada (13), 23 states reported single-digit numbers of confirmed cases, and 22 states remained free of equine cases of West Nile virus as of September 1. Texas, the hardest-hit state with 2,531 cases from 1999-2004, reported just seven equine cases as of September 1.

Avian cases of West Nile virus also have decreased. Maine, the only one of the 48 contiguous states that has never had a confirmed equine case of West Nile virus, has reported just four avian cases this year, which leads Maine State Veterinarian Donald Hoenig, V.M.D., and others to speculate that birds and other animals whose immune systems could not fight off the foreign flavivirus earlier in the decade are now developing natural immunity against it.

"We haven't had a horse with West Nile virus in our clinic for about 22 months," said Bonnie Rush, D.V.M., M.S., head of equine medicine and surgery at Kansas State University. West Nile virus was confirmed in 883 Kansas horses from 1999-2004, but as of September 1 the state has reported only one confirmed equine case.

"Most of them are treated in the field at this stage," Rush said, "and I think we have good population immunity, we have good vaccine compliance, and we have not had a case in a long time."

"The problem is that you can't rely on that to decrease your vaccinations because you really don't know which horses in your backyard have natural immunity and which ones don't," said Maureen Long, D.V.M., Ph.D., assistant professor of large animal medicine at the University of Florida, who has treated many of the 1,112 equine cases of West Nile virus reported in that state since 1999.

"Probably what we are going to start having are flavivirus outbreak cycles," she said. "St. Louis encephalitis [similar to West Nile virus] cycles through humans about every ten years. So I think we're still going to have outbreaks, but they are going to be separated by several years. And we may be able to avoid that altogether in the horse if we just keep vaccinating, because there is still going to be a sector of the population that is susceptible."

Vaccines

In 2001, Fort Dodge Animal Health released the first equine vaccine against West Nile virus, West Nile-Innovator, a killed-virus vaccine that has been proven to protect 94% of horses inoculated properly with a two-dose initial series.

Rumors abounded via the Internet that the product caused deformities in fetuses of broodmares vaccinated during pregnancy, but a study by Texas A&M University disproved these rumors. "We have found that there was no evidence [that the vaccine causes] adverse effects in pregnant mares," lead researcher Noah Cohen, V.M.D., Ph.D., said.

In 2004, Merial released a recombinant vaccine, RecombiTEK, which has been proven to be 100% effective two weeks after the initial two-dose vaccination. One year after their initial two-dose series, ten horses in Merial's study group were exposed to mosquitoes infected with West Nile virus, and only one horse contracted the disease.

This recombinant vaccine uses a genetically altered live virus, canarypox, to carry West Nile virus genes into the vaccinated animal, then the horse's immune system produces antibodies to protect against West Nile virus. Even though this is a live-virus vaccine, there is no danger the horse will acquire canarypox or West Nile virus from its use.

"The vector--canarypox virus--absolutely cannot replicate in a horse," Merial reported. "Neither can the West Nile virus fraction [of the vaccine] because the entire virus is not present."

On July 18, Fort Dodge announced that it was granted a license by the United States Department of Agriculture for a new vaccine, West Nile-Innovator DNA, which was developed through collaboration with the Centers for Disease Control and Prevention. The vaccine will be added to Fort Dodge's line of equine products early in 2006.

All three vaccines are available only through licensed veterinarians.

Even though the killed-virus West Nile-Innovator and the recombinant RecombiTEK vaccines are vastly different in how they are made, a study by Merial published in the winter 2004 edition of Veterinary Therapeutics found that RecombiTEK could be used as a booster for horses that previously had been vaccinated with West Nile-Innovator.

Both Fort Dodge and Merial recommend that after a two-dose series of vaccine administered four to five weeks apart (with the first dose given at least six weeks before the beginning of mosquito season), the horse should receive an annual booster. However, many researchers, clinicians, and state veterinarians believe this may not be often enough, especially in regions where mosquito season lasts longer than six months each year.

Long recommended booster shots every three to four months during mosquito season for optimum protection. In moderate climates, this would be in March or April and again in August or September.

Treatment

Researchers still have not found an antiviral drug effective in the treatment of horses showing clinical signs of West Nile virus: lack of coordination of the hindquarters, weakness, lethargy or depression, and muscle twitching, especially in the face and forequarters. So clinicians continue to rely on nonsteroidal anti-inflammatory drugs (phenylbutazone, Banamine) and supportive care, such as keeping the horse well-hydrated, providing intravenous nutrition, if necessary, and protecting a wobbly horse from injuring himself.

Long said she also administers plasma by manufacturers Novartis Animal Health and Lake Immunogenics Inc. with a high antibody count against West Nile virus to stimulate the horse's immune system to fight the disease.

During the initial West Nile virus outbreak in Kansas, Rush began treating horses with interferon-a, a naturally occurring protein that in low doses enhances the immune system's ability to fight disease. In high doses, it acts as an antiviral medication. Interferon-a also has anti-inflammatory properties.

Looking back, Rush said she is pleased with the results she achieved with the novel treatment.

"Interferon-a is still the treatment I would recommend," Rush said. "And the other thing I want to stress is that lots of people were using corticosteroids routinely early on, and clearly I think this is not a good idea."

According to Rush, in investigative studies of West Nile virus using mice, corticosteroids were administered to the mice to suppress their immune systems so they were sure to contract the virus.

"I don't say I would never do it, because if I needed to bring the swelling down in the [central nervous system] to get the horse up on its feet, I would give a single dose, but I would not routinely administer corticosteroids as part of my treatment for West Nile virus today," Rush said. "So I'm relying on [nonsteroidal anti-inflammatory drugs], intravenous DMSO, and supportive care."

Richard Bowen, D.V.M., Ph.D., professor of biomedical sciences at Colorado State University, has drawn the same conclusion from studies of West Nile virus in dogs.

"We treated these dogs with corticosteroids for a month, a fairly heavy dose but not something that would be out of the realm of possibility in treating an inflammatory condition, and, of course, horses get that kind of treatment, too," Bowen said. "And we found [the dogs] had relatively huge amounts of virus circulating in their bodies."

Bowen said he hoped someone would fund a study to see what effects corticosteroids would have on horses exposed to West Nile virus. He also offered words of encouragement in the battle against this deadly disease.

"I don't think anybody has done a study, but I think there's very good reason to believe that if a horse actually had West Nile virus, he'd be protected for many years to come," Bowen said. "All the similar viruses show that kind of pattern."