Imagine a foreign disease making its way steadily across the country, killing horses one mosquito bite at a time. This disease isn’t easily spotted; after all, horses aren’t dropping as they’re bitten. Rather, development of the illness is an insidious, slow process that has you wondering what’s wrong with your horse for hours or maybe even days. The horse acts a little depressed, then eventually starts to tremble and twitch. Then he can’t get up. And, finally, with the help of your veterinarian, you’re forced to say goodbye.
The disease has no cure. No vaccine. No clear path of transmission.
West Nile Virus
A mosquito-borne zoonotic (affecting humans and specific animal species) arbovirus belonging to the genus Flavivirus in the family Flaviviridae. It’s commonly found in temperate and tropical regions of the world. Horses are highly susceptible to the virus, which causes the neurologic disease West Nile encephalitis.
AAEP Core Vaccines
Eastern/Western equine encephalitis, Rabies, Tetanus, and West Nile virus
Today, West Nile virus (WNV) might seem like just another preventable disease and a shot your horse gets once or twice a year—a single vaccine listed among several others in the American Association of Equine Practitioners’ (AAEP) core recommendations. But, a little more than 15 years ago, this virus and the severe neurologic disease it causes—which affects many species, including humans —posed the biggest health threat the horse industry had seen in the 20th century. This is the story of WNV in North America. It’s a story of a real risk to our country’s horses, as well as rapid spread of fear and irrational rumors. It’s also a story about how the veterinary community, the U.S. government, and animal health industry joined forces to find a way to protect our horses.
WNV Lands in the United States
Physicians first identified WNV in 1937 in a female resident of Uganda, Africa’s West Nile district. After that, the virus caused several outbreaks in the Eastern Hemisphere and was identified in horses in 1960. Today, WNV is the most widely distributed of the arboviruses (viruses spread by arthropods such as a ticks or mosquitoes), causing infections in Africa, the Middle East, South Asia, Australia, Southern Europe, and North and South America.
But until 1999, few American horse owners had heard of the virus.
That changed late in summer ’99, when authorities confirmed the first WNV case in the Western Hemisphere in Queens, New York. They first identified it in birds, and three months later confirmed the first human case. Doctors and veterinarians subsequently reported cases of WNV-related fever and encephalitis in humans, birds, and horses, and the virus started its march into New Jersey and Connecticut. The veterinary community and horse industry went on alert—the disease was aggressive in horses, and at the time we had no vaccine to protect them.
Luckily, experts already understood WNV’s basic life cycle from intelligence data collected by U.S. researchers stationed in Egypt during the 1950s. Specifically, they knew the cycle relied heavily on birds and mosquitoes.
But how did this virus get from Africa, the Middle East, and Europe to the United States in the first place? An airplane takes about 24 hours to travel the almost 7,900 miles from Uganda to New York. The trip requires Atlantic Ocean and Mediterranean Sea crossings and traversing three continents, with a layover in Europe.
Although we don’t know for certain how WNV got here, some epidemiologists theorize that pet smugglers inadvertently introduced WNV to North America by bringing infected birds to the continent from endemic areas.
Species at Risk for WNV
“There are actually about 13 viable theories of how the WNV got to New York City” says Nicholas Komar, SD, a biologist with the Centers for Disease Control (CDC), in Fort Collins, Colorado. “My favorite (theory) is that an infected mosquito came over in an airplane, deplaned in New York City, and fed on an urban bird like a house sparrow, initiating a local amplification among the large population of bird-feeding Culex pipiens (mosquito species), which thrived in New York City in 1999 due to local drought conditions and absence of mosquito control operations.”
Nicholas Komar, SD,
serves in the Arbovirus Diseases Branch of the Centers for Disease Control’s National Center for Emerging Zoonotic Infection Diseases Division of Vector-Borne Diseases. He’s a WNV expert who’s published numerous scientific papers on the disease.
Other potential routes of introduction include sources of infected birds or mosquitoes, especially considering the close proximity of two international airports—JFK and LaGuardia— as well as the Bronx Zoo near the disease’s initial point of diagnosis, where several bird residents had died of WNV starting over Labor Day weekend. Those early avian deaths included a pheasant, bald eagle, cormorant, and flamingos. Experts ruled out foreign birds legally imported to the Bronx Zoo as a source of infection, and zoo birds were an unlikely source because wild birds, including crows, outside the zoo had died first.
While the details of the virus’ journey to New York remain a mystery, some evidence suggests it might have originated in Israel. Genetic analysis completed within four short weeks of the outbreak’s start revealed that the New York virus most closely matched the one responsible for a 1998 outbreak in Israeli birds, including geese. The virus identified in New York also was similar to WNV found in Israeli patients in 1999. This strain caused a higher rate of avian deaths than previously studied WNV strains.
Viremia
Viral load
“Because the virus was a more virulent avian strain, more birds had higher viremia, making them capable of infecting more mosquitoes,” Komar explains. “In turn, this would tangentially infect more susceptible dead-end hosts, such as humans and horses.”
This didn’t bode well for either species stateside.
By year’s end 1999 authorities had confirmed 25 equine WNV cases, all in New York. Once U.S. health authorities correctly identified WNV that year, some experts held out hope that the cold winter months would kill infected mosquitoes and, in turn, eliminate the virus. But, alas, the virus had already spread, with infected mosquitoes and birds quickly identified in several more temperate states.
Epidemiologists and health authorities believed that the New York subway system environment, as well as storm-water drainage systems and basements, allowed infected mosquitoes to overwinter and serve as a source of infection in 2000. They further speculated that adult mosquitoes could pass on the virus to their offspring, a process called “transovarial transmission.”
A Westward Expansion
Much to the chagrin of researchers and veterinarians, albeit not to their surprise, the virus re-emerged when the weather warmed in early 2000 and mosquitoes started breeding.
“I used to think all mosquitoes were created equal but I learned (from WNV) that they have a preference for breeding grounds and what animal they feed off,” says Dr. Josie Traub-Dargatz of Colorado State University. “It is the lack of focused feeding of certain types of mosquitoes that contributed to the spread of WNV.”
Josie Traub-Dargatz, DVM, MS, Dipl. ACVIM,
is a professor in the population health section of the Department of Clinical Sciences at Colorado State University’s College of Veterinary Medicine and Biomedical Sciences in Fort Collins. She also serves the equine community as a specialist for the USDA-APHIS Veterinary Service Centers for Epidemiology and Animal Health.
Despite the widespread implementation of mosquito-control strategies (e.g., spraying of pesticides, limiting breeding-ground-providing standing water) WNV continued to flourish, largely because it did not behave like other arboviruses already present in the United States, which have geographic niches they rarely stray from: Eastern equine encephalitis (EEE) virus generally stays in the East and Western equine encephalitis (WEE) virus in the West. WNV, however, spread all directions.
A steady climb in equine cases in the Northeast ensued.
In 2001, the virus moved rapidly north to south, which experts expected due to migration routes of birds carrying the virus. The virus’ rapid east-to-west progression, however, surprised researchers. The disease reached California by 2003, less than four years after its North American introduction.
U.S. Equine WNV Cases 1999-2014
Press the play button to automatically advance through the years. Click on a year in the bar graph to see the map for that year. Hover over a state to see the number of cases reported in that state. Data source: CDC
- 0 cases
- 1-24 cases
- 25-199 cases
- 200-399 cases
- 400-799 cases
- 800+ cases
Total U.S. WNV Cases
Experts suggested that the virus accomplished this by “hitching a ride” via another specific type of mosquito species to the western United States.
“Once the virus crossed the Mississippi in 2002, its westward spread was certainly aided by the abundant WNV vector, Culex tarsalis, however, significant jumps from the Mississippi to a region far enough west where C. tarsalis are located could have been aided by human-built transport vessels like cars, trucks, trains, and planes,” Komar explains. “C. tarsalis is only present in the West and they are not known to fly long distances.”
Although surprised at the relentless spread of the virus, experts did not stand idly by waiting to see how much worse each year would get for horses and owners.
Protecting Horses with a Conditional Vaccine
As the virus spread in those early days, Fort Dodge (now Zoetis) researchers worked to concoct the first equine WNV vaccine. By 2001—within two years of identifying the first cases in New York—USDA’s Animal and Plant Health Inspection Service (APHIS) issued a “conditional license” for the vaccine, branded as “Innovator.”
“Data required for a conditional license are reduced from that needed for a full license in that the firm needs to demonstrate a ‘reasonable expectation of efficacy’ as defined by USDA,” explains Dr. Mary Beth Evans, an APHIS licensing reviewer. “Conditional products must meet the same safety and purity requirements as fully licensed products. That the vaccine was manufactured as an inactivated product (produced using killed virus) and the chemical components used had previously been shown to be safe, the risk of a catastrophic safety issue was a minuscule event.”
Mary Beth Evans, DVM, MS
is a senior staff veterinary medical officer with the USDA/APHIS.
The West Nile virus vaccine ultimately received a full license in 2003. Data collected on the efficacy of the vaccine showed that 95% of horses that received two doses and were experimentally challenged with the virus one year later didn’t exhibit viremia, while 82% of similarly challenged unvaccinated horses developed active WNV infection.
“That product became one of the most popular vaccines in the United States, and I think it is amazing that the industry accepted and implemented it so quickly, recognizing that the term ‘conditional’ (could have been viewed by the public as) synonymous with ‘not safe,’” Traub-Dargatz says. “There are few who would argue that the rapid development of the vaccine didn’t play a key role in the control of WNV in those early years.”
WNV: Where We Stand Today
Today, according to CDC data, 47 states and the District of Columbia have reported cases of WNV in humans, horses, mosquitoes, or other animals (all expect Hawaii, Maine, and Alaska). State veterinarians reported only 377 equine WNV cases in 2013, down from a high of more than 15,000 in 2002. However, experts agree that this statistic doesn’t accurately reflect the actual number of cases.
“West Nile virus in horses is largely under-reported,” explains Dr. Angela M. Pelzel-McCluskey of the USDA. “The cases reported through ArboNET (a CDC arbovirus surveillance site), and subsequently on the APHIS website, are confirmed at a laboratory by diagnostic testing and officially reported by a veterinarian to state authorities,” she said.
Angela Pelzel-McCluskey, DVM,
is an equine epidemiologist in Surveillance, Preparedness, and Response Services with USDA-APHIS.
This means that for cases to be included in the “official” number of infections, a horse owner has to pay for testing and veterinarian has to take a diagnostic sample, submit it to the laboratory, and report findings to the state if the test comes back positive.
“Not all owners can, will, or want to test their horses, and there are also many veterinarians who may not specifically recommend WNV testing to a horse owner to confirm a case,” Pelzel-McCluskey says. “For example, if the horse is not vaccinated and has clinical signs consistent with WNV infection, the veterinarian and/or owner may not think it necessary to get the diagnostics done to ‘prove’ it.”
Current Vaccine Options
Veterinarians agree that vaccination is the best way to protect your horse from WNV, which is why it is included in the AAEP’s core vaccination schedule.
Dr. Maureen Long of University of Florida has treated horses since WNV’s early introduction into the United States and is a strong advocate for vaccination.
Maureen Long, DVM, PhD, MS, Dipl. ACVIM,
is an associate professor of infectious disease and pathology at the University of Florida’s College of Veterinary Medicine, in Gainesville.
“One in 11 horses exposed to WNV via mosquito bite will develop neurological disease,” Long points out. “About two of every five horses that become neurological will die from the disease. One of the remaining three will not recover completely. Lower numbers of horses than humans become sick each year from WNV because of the success of vaccination. WNV is entirely preventable in the fully and repeatedly vaccinated horse.”
Additionally, veterinarians recommend that owners waffling about vaccinating their horses against WNV should consider that:
- The WNV vaccine, depending on the chosen product, can cost as little as $25;
- 10-39% of unvaccinated horses inoculated with WNV via a mosquito show signs of infection;
- Vaccination provides horses nearly 100% protection against WNV;
- Most pharmaceutical companies guarantee their WNV vaccines’ efficacy, if administered by a licensed veterinarian, and will pay up to a certain amount to cover diagnostics and treatment; and
- The cost of supportive care for an infected horse can exceed $10,000 (cost varies based on location or clinic).
Traub-Dargatz suggests that when it comes to not vaccinating for WNV—or any of the diseases AAEP core vaccines protect against—owners fall into one of four groups.
- The uninformed, such as new horse owners;
- The informed owner who assumes the risk;
- An owner with hundreds of horses (making vaccination time-consuming and expensive); and
- Owners that truly just forget.
“Veterinarians play an important role in helping the first and last groups to get as many horses properly vaccinated as possible,” she says.
Killed-virus
An inactivated vaccine (or killed vaccine) consisting of virus particles grown in culture and then killed. These viruses are grown under controlled conditions and are rendered noninfectious.
Recombinant Vaccine
A recombinant vaccine is a vaccine produced through recombinant DNA technology, which involves inserting the DNA encoding an antigen that stimulates an immune response.
Chimera Vaccine
A chimera vaccine is created by genetically splicing two viruses together, producing a “chimeric” structure.
The U.S. market currently offers four WNV vaccines: two killed-virus, one canarypox recombinant, and one chimera.
Long and colleagues at University of Florida conducted one head-to-head trial using three of the four (one each of killed virus, canarypox recombinant, and chimera). They administered one of the three vaccines according to the manufacturer’s directions, with the exception of control horses that received only a diluent.
The researchers “challenged” the horses with WNV using an intrathecal method (i.e., directly into the cerebrospinal fluid) 28 days later. All six unvaccinated horses developed WNV, demonstrating the severity of the challenge method.
Of the vaccinated horses, “Regardless of what vaccine was administered, survivorship was 100%,” Long says.
Another study’s results agree that all available vaccines for WNV are effective; however, horses can and do respond differently to different commercially available vaccines.
At the 2013 AAEP annual convention, Dr. Kevin Hankins, a senior veterinarian in Zoetis’ equine veterinary operations, presented data resulting from comparing 240 horses’ immune responses to vaccination using a monovalent WNV vaccine (i.e., one that only protects against WNV) and vaccination with a multivalent (combination) vaccine against a combination of WNV, Eastern and Western equine encephalitis viruses, and tetanus.
Kevin Hankins, DVM, MBA,
is a senior veterinarian with Zoetis’ equine veterinary operations.
“All vaccinated horses showed evidence of responding to their respective vaccine protocols,” Hankins says.
In fact, the monovalent vaccine, when administered at the same time as EEE, WEE, and tetanus, rather than a vaccine that contains a combination of all four, caused a three- to fourfold increase in antibody titers, a measure of infection-fighting antibody levels in blood.
“This study shows that some horses might benefit from using a monovalent vaccine to protect them against WNV instead of a single vaccine against WNV, EEE, WEE, and tetanus,” Hankins says.
Such horses could include those that live in wet areas where it can be more challenging to control mosquitoes.
Hankins says that even if horses received a combination vaccine in the past, they can be boostered in the future with a monovalent vaccine for WNV and one or more separate vaccines protecting against other avoidable infectious diseases. Discuss such options with your veterinarian to customize your horse’s vaccination protocol for optimal protection, he advises.
Why Some Horses Might Get WNV, and Some Don’t
In North America researchers have identified equine risk factors for developing WNV encephalitis, but the overall significance of those remains unclear. Dr. Hugh Townsend and Dr. Tasha Epp of The University of Saskatchewan’s College of Veterinary Medicine published risk factor data from their research.
Hugh Townsend, DVM, MSc,
is a professor of large animal medicine at the University of Saskatchewan’s Western College of Veterinary Medicine. He teaches veterinary internal medicine, is a Department of Community Health and Epidemiology adjunct professor at the Royal University Hospital, and is a research scientist at the University of Saskatchewan’s Vaccine and Infectious Disease Organization.
Tasha Epp, DVM, PhD,
is an associate professor of zoonosis in large animal clinical sciences at the University of Saskatchewan’s Western College of Veterinary Medicine.
“We assessed factors that contributed to death in 133 clinical cases; namely, week of onset of symptoms, gender, and coat color after accounting for regional differences,” says Epp. “The survival rate of horses with clinical signs presenting earlier in the season (i.e., Weeks 31-33 of the calendar year) was higher compared to horses with signs that developed later in the season (i.e., Weeks 36-38). Stallions were more at risk of death than either mares or geldings, and light-colored horses were more at risk of death, which was something we could not explain.”
Other studies conducted in the United States yielded different results regarding risk factors. In one 2004 study researchers found that factors associated with mortality from clinical disease included lack of vaccination, advanced age, inability to rise as a clinical sign, early season onset of clinical disease (the timing differs, depending on when the WNV season starts in different areas of North America), gender, and breed.
“We did not find any of the same factors in our study,” reports Epp.
However, in people and in other equine studies, older age does appear to result in more severe neurologic disease and mortality, says Long.
“At this time age should not be discounted,” she says. “Although the Townsend study is one of the best controlled studies performed, Canada has a shorter mosquito season and overall lower numbers of cases (than in the United States).”
In the southern states, such as Florida, mosquitoes and the possibility of them carrying WNV is a year-round challenge. No matter the location, using barn-safe electric fans, housing horses in barns, and blanketing reportedly decrease the risk of WNV infection, presumably because those strategies decrease possible exposure to infected mosquitoes.
WNV’s Future
West Nile virus is in North America to stay. And despite many scientists initially attempting to determine where the virus would go and how it would behave in North America, they almost unanimously agree that it was, and continues to be, impossible to predict.
In fact, the AAEP notes on its website: “The (West Nile) virus and mosquito host interactions result in regional change in virulence of the virus and no prediction can be made regarding future trends in local activity of the viruses.”
One question that plagues the equine industry is what will happen if the virus changes or mutates? Examples of other organisms that have changed include methicillin-resistant Staphylococcus aureus and equine herpesvirus-1. In the latter case, one single change of the virus at the DNA level, called a point mutation, resulted in a virus that caused neurologic disease rather than the more typical respiratory disease.
If the virus “evolves” or mutates, will our vaccines still be effective? Will we start to see a “super” WNV that causes even more severe disease?
Komar says vector-borne viruses undergo evolutionary change slower than other viruses, because they replicate in both vertebrate and invertebrate hosts. This means that a mutation that provides an evolutionary advantage for virus replication in mosquitoes might be disadvantageous for replication in vertebrate hosts.
“It is unlikely that the changing genotype of WNV in the U.S. will impact horse or human illness patterns,” Komar says. “However, it is not impossible, and another virus with a similar ecology has done just that. The WEE virus rarely causes disease in either people or horses in the 21st century, but it was a major cause of equine disease in the last century.”
What Did WNV Teach Us?
Just over 15 years ago, WNV caught human and horse health authorities by surprise when it entered the United States. Representatives from all corners of the industry rallied, educating horse owners on mosquito reduction techniques and creating an equine vaccine to save horses’ lives. Today, even more than then, the world is one community due to growing international equine movement and competition, and horses in North America simply make up a herd on a global scale, says Traub-Dargatz. “There will be another (new disease outbreak), it’s just a matter of time.” But, due in part to lessons learned during WNV’s emergence, we are better prepared for the “next West Nile virus,” whatever it may be. In the meantime, veterinarians agree, protect your horses from the real and known threat of WNV: vaccinate.
