Seven Things You Need To Know About Equine Influenza

Influenza epidemics in horses date as far back as 433 A.D. In more recent times, an 1872 outbreak in Canada and the northeastern United States brought all equine-based commerce, transportation, and services to a standstill—an estimated 80-99% of horses in the region were affected, with 1-2% dying. It only took 90 days for this epidemic to spread from Toronto, Canada, throughout the United States and as far south as Cuba. In an era when everything depended on transport via horse power, this had a staggering effect on daily life.

 

In 1987 in India, an outbreak involved the infection of 27,000 horses. In Australia in 2007, imported horses from Japan became the index cases of influenza that, due to biosecurity lapses, circulated from the quarantine station to infect 70,000 naive (never exposed or vaccinated) Australian horses, wreaking losses of a billion dollars in productivity and function.

 

You can see why researchers worldwide are so motivated to study this highly contagious disease and develop effective vaccines to protect the horse population.

 

“In recent times, flu tends not to be deadly in the USA,” says Wendy Vaala, VMD, Dipl. ACVIM, an equine technical services representative for Merck Animal Health. “This is because most horses will have received some colostral immunity from an immunized mare’s first milk and/or some immunization.” 

 

She says the virus’ high morbidity (sickness) rate especially impacts the racing industry and organized competitive events because of days of missed work. Although clinical signs typically abate relatively quickly, it takes two to three weeks for infected horses to recover fully. Veterinarians recommend horses get a week of rest for every day of fever. 

 

 

Because horses rarely die from equine influenza virus (EIV) and people generally are not aware of its economic consequences, there is less fiscal motivation for surveillance. The Australian outbreak did underline the economic impact but, as yet, there is no formal study on this aspect of influenza outbreaks. “In the United States, vaccine companies probably put more into surveillance than any group. By knowing how EIV changes, it is then possible to be pre-emptive,” says Gabriele Landolt, DVM, MS, PhD, Dipl. ACVIM, associate professor at Colorado State University’s College of Veterinary Medicine and Biomedical Sciences, in Fort Collins, who has a special interest in EIV. 

 

A wealth of research has been devoted to uncovering the details about EIV: what it is, how it mutates, how it spreads to other species, what vaccines are effective, and what preventive strategies are useful, to name a few. Based on the most recent research, here are the main things you need to understand about this disease to best protect your horse:

 

 

The culprit currently responsible for this viral infection is the equine H3N8 subtype of influenza A virus. Influenza A virus is subtyped according to the combination of hemagglutinin (HA, a protein that allows the virus to attach to and enter host cells) and neuraminidase (NA, one of the virus’ key enzymes) on its surface. These biochemical specifics are what allow the flu virus to target mammalian tissues, enter and infect tissue cells, reduce normal immune function, and create variations in susceptibility between species (why one subtype might fell a pig but barely affect a human, and vice versa). Subtypes are further categorized into strains, which change over time. As new strains emerge, vaccination against older strains might not adequately protect individuals.

 

 

Developing effective vaccines against EIV has always been challenging due to the pathogen’s ability to mutate. Equine influenza virus is an RNA virus, meaning its genetic material is encoded in RNA—a less stable nucleic acid than DNA—and it skips an important “proofreading” step, so to speak, when it replicates. Thus, it mutates more readily than a DNA virus. “As an RNA virus, its genetic diversity allows adaptation to a new environment or for escape from the host’s immune system,” Landolt explains. “This tendency is called antigenic drift, which modifies the virus enough to minimize the efficacy of targeted vaccines. (An antigen is a substance that causes the immune system to produce antibodies, or proteins that aim to eliminate the virus.) Drift occurs because the primary neutralizing antibodies against EIV are directed toward hemagglutinin proteins—these antigens mutate in response to immune pressure.”

 

Many current vaccines against influenza are prepared from inactivated (killed) virus, which Landolt says does not induce a broad immune response. “If there is any change in the influenza virus, as with antigenic drift, then the horse receives less than optimal protection from vaccines,” she says. “In addition, immunity from killed vaccines tends to be short-lasting.”

 

Vaccination timing also has a significant effect on protection against influenza. During a 2003 Newmarket, U.K., outbreak, researchers linked the length of time since a horse’s previous vaccination to his risk of becoming infected, with the level of protection peaking within the first three months following immunization. More than a decade later, however, this concept might be changing.

 

For the past seven years, researchers at Merck Animal Health, in collaboration with Nicola Pusterla, DVM, PhD, Dipl. ACVIM, a professor of equine internal medicine at the University of California (UC), Davis, have been surveying equine upper respiratory infections. Veterinarians from more than 300 clinics throughout the United States have sent more than 4,600 samples to the UC Davis testing lab. Vaala reports some startling news: “In the past three years, we are seeing an increase in EIV cases. In 2013, EIV … almost surpassed the incidence of equine herpesvirus-4, which historically has been the most common upper respiratory tract infection. There are increasing numbers of EIV cases even in horses with a history of vaccination.” 

 

She notes another significant difference between EIV positives reported from March 2008 to Feb. 2010 and those reported from March 2010 to Nov. 2013: the age of infected horses. “In the initial two years of testing, 62% of EIV cases occurred in 1- to 5-year-olds, particularly those in stressful conditions like training,” Vaala says. “But, in samples from (March) 2010 to (Nov.) 2013, 30% of horses with EIV were in the 6- to 10-year-old range (compared to 18% from 2008-2010); 11- to 15-year-olds were infected as well. 

 

“Now there appears to be a shift from EIV being predominately a young horse disease,” she continues. “During the most recent three years, there have been more documented cases of EIV among vaccinated horses—some with a history of EIV vaccination within the previous two to four months. Therefore, it appears that we can no longer be complacent about EIV.”

 

Previous research results indicated that vaccination during an outbreak, even using inactivated vaccines, helps limit infection. Yet, researchers on the Merck/UC Davis project noted failures with every brand of killed EIV vaccine. 

 

 

“Studies that have delved into the reason behind viral shedding in vaccinated horses have identified a ‘mismatch’ between vaccine strains and active circulating influenza virus in the field,” explains Landolt. “Standardization of inactivated virus vaccines is important to improve potency and protection.” 

 

In contrast, an intranasal modified-live virus (MLV) vaccine might provide more complete protection. The intranasal vaccine is designed to stimulate an immune response in the respiratory tract that neutralizes the entire virus upon administration.

 

“The MLV vaccine is recommended during an outbreak because even a naive horse, one that has never received influenza vaccine, will develop protective immunity within a week of receiving the intranasal MLV vaccine,” says Vaala. 

 

“Any horse that is at high risk—based on age, training, travel, commingling—should be immunized (with any EIV vaccine) every six months,” says Landolt. 

 

 

The World Organization for Animal Health (known as OIE due to its former title, Office International des Epizooties) routinely studies which influenza strains are epidemiologically relevant. (Epidemiology is the study of the patterns, causes, and effects of health and disease conditions in defined populations and helps practitioners identify risk factors for disease and targets for preventive care.) For instance, the H3N8 virus that currently circulates in the United States is Clade 1 of the Florida sublineage (think of a Clade as a group of viruses that share a particular branch of a viral family tree). Currently, only the Clade 1 EIV strain circulates in the United States, but Europe, South Africa, Japan, and Australia have experienced both Clade 1 and 2 strains. As we’ve noted, influenza is highly variable and adaptive and changes frequently. 

 

“The USA Clade 1 strain has made a change from the isolates seen a decade ago,” Vaala says. “The OIE is using continual analysis of field surveillance data to recommend suitable vaccine strains for inclusion in commercial vaccines.” 

 

This assists vaccine manufacturers in planning product adjustments and helps guide veterinarians in selecting vaccines with the potential to be most protective.

 

 

Studies on the equine immune system indicate that the exercising horse’s respiratory tract might be more susceptible to viral infection than that of a rested horse. And, of course, any immune-suppressed individual is more susceptible to viral infection; this is well-known in people as well as in horses.

 

Scientists wondered if this exercise-induced immunosuppression would alter the safety of administering an MLV vaccine, so they monitored horses in a treadmill study. They concluded that the MLV intranasal vaccine is safe and still stimulates protection three months later.

 

 

Neurologic disease is not usually associated with an EIV outbreak. But in one recent study, researchers from the Animal Health Trust, in Newmarket, focused on influenza’s ability to cause it. They took a closer look at the 2003 Newmarket EIV outbreak, during which two unvaccinated horses developed neurologic signs.

 

“Equine influenza virus infection can result in encephalitis (inflammation of the brain),” the study authors determined. 

 

In this case, nonsuppurative (meaning it doesn’t produce pus) encephalitis was found on necropsy in the affected horses—this has been described in humans, and while not common, it is mostly found in children. Although veterinarians do not yet know how influenza virus induces encephalopathy (brain disease or damage), they suspect that the virus replicates in the central nervous system.