Equine Infectious Disease Research Studies

Ongoing research into equine infectious diseases will mean better ways to protect and treat the problems.

Equine influenza vaccines for horses come in a variety of forms and differ in the strains they contain. Arnd Bronkhorst Photography

There is always ongoing research on infectious diseases in horses. In this article we focus on three published research reports that might have implications for many of your equine patients.

Live-Attenuated Equine Influenza Vaccine

(Editor’s note: There has been ongoing research on this equine influenza vaccine since this information was reported in peer-reviewed literature. Expect more information to be published soon, so be on the lookout for that journal article. Also please note that this is about an experimental vaccine, not one that is commercially available.)

It has been several decades since a live-attenuated equine influenza vaccine (EIV-LAIV) has been updated. Most flu vaccine research has focused on inactivated (killed) virus in intramuscular and intranasal forms.

The H3N8 equine influenza virus has crossed beyond equines into dogs such as racing greyhounds sharing a track with horses, and also to pigs and camels; there is concern regarding its potential to threaten humans.

Researchers at the University of Rochester investigated an updated, intranasal, live-attenuated, cold-adapted flu vaccine administered first to mice and ferrets with following trials done in horses [Baz, M.; Paskel, M.; Matsuoka, Y.; et al. A Live Attenuated Equine H3N8 Influenza Vaccine Is Highly Immunogenic and Efficacious in Mice and Ferrets. Journal of Virology, Feb 2018, vol. 89. No. 3; pp. 1652-1659].

This influenza vaccine is being developed using reverse genetics—using recombinant DNA technology, it begins with a protein or DNA that contains no genetic information, then working backward, investigators produce a mutant gene phenotype with a specific function. A single dose of the vaccine significantly generated “robust neutralizing antibody titers” that provided full protection against viral challenge in mice and ferrets.

The vaccine was further tested on four yearling or 2-year old horses; two other similarly aged horses served as controls [Rodriguez, L.; Reedy, S.; Nogales, A.; et al. Development of a novel equine influenza virus live-attenuated vaccine. Virology 2018, vol. 516; pp. 76-85]. Control horses were separated so there would be no shedding of nasal vaccine to them from those immunized.

In the days immediately following intra-nasal administration of vaccine, none of the vaccinated horses developed fever; one horse coughed once; and three horses had a slight, bilateral serous nasal discharge on days 2 and 3 following challenge.

Virus shedding was identified with PCR of nasopharyngeal swabs on days 1-3, with its peak at day 2, indicative of viral replication. Viral challenge of H3N8 EIV was given via nebulizer at 27 days after the horses received a single dose of intranasal spray vaccine.

Despite viral exposure, none of the vaccinated horses developed flu-like signs such as fever, nasal discharge or cough, whereas both controls did. There was some swelling of the submandibular or parotid lymph nodes in all the horses, but the severity was greater and the duration longer in the controls.

An attenuated live vaccine is able to elicit greater immune responses that provide longer periods of protection than what is achieved with killed flu viral vaccines.

Administration through the nasal route simulates how a horse would acquire a natural infection and the subsequent mucosal immune responses. The study concluded that the horses vaccinated with this new EIV-LAIV are protected very quickly from EIV challenge with just a single dose.

Another key feature to this vaccine is the ability for the manufacturer to rapidly update it by introducing new influenza strains that develop through antigenic drift.

Lyme Disease

Lyme disease caused by Borrelia burgdorferi infection has become a more pressing problem in horses, people and dogs in endemic areas where Ixodes ticks (black-legged and deer ticks) abound, especially in the Northeast, Northwest and Midwestern parts of the United States.

Seroprevalence has been on the rise in all of these areas. The 2018 ACVIM Consensus Report provided a comprehensive description of all that is known about the disease in horses [Divers, T.J.; Gardner, R.B.; Madigan, J.E.; Witonsky, S.G.; Bertone, J.J.; Swinebroad, E.L.; Schutzer, S.E.; and Johnson, A.L. Borrelia burgdorferi Infection and Lyme Disease in North American Horses: A Consensus Statement. J Vet Intern Med 2018, vol. 32; pp. 617-632].

The bacterial reservoir occurs in white-footed mice and gray squirrels; the Ixodes tick reservoir includes large wild mammals. Several hours might be necessary to allow transfer of the bacteria to the mammalian host, following which Borrelia spreads through the connective tissue and into the blood for systemic dissemination.

It takes three to four weeks after exposure until testing methods can detect antibodies indicative of exposure. Exposure does not always mean a horse has developed active infection.

The ACVIM Consensus Statement noted that “Positive serology confirms past exposure or present infection but does not confirm clinical disease. Regardless of test methodology, a positive result does not prove causation of current clinical signs (clinical infection), nor does a positive result predict whether infection is likely to cause clinical signs in the future. There is no known correlation between magnitude of titer and likelihood of disease.”

Clinical syndromes associated with Lyme disease infection include: 1) neuroborreliosis; 2) uveitis; and c) cutaneous pseudolymphoma.

Lyme disease signs are highly varied, including:

  • atrophy of spinous muscles
  • dysphagia
  • facial paresis
  • laryngeal dysfunction and respiratory distress
  • spinal cord ataxia and paresis
  • behavioral changes
  • hyperesthesia
  • fasciculations
  • neck and back stiffness with pain
  • uveitis
  • joint effusion
  • cardiac arrhythmias
  • cranial nerves dysfunction
  • radiculoneuritis
  • meningitis

Practitioners have noted that horses presumptively infected with Borreliosis often have shifting limb or intermittent lameness; however, the association of B. burgdorferi infection with stiffness and lameness is not well documented, according to the Consensus Statement. Many other equine diseases cause development of clinical signs similar to those of Lyme disease, so diagnostic testing needs to rule possibilities in or out. Co-infection with other disease should also be considered.

Treatment protocols have been extrapolated from human treatment guidelines, B. burgdorferi antibiotic susceptibility and anecdotal reports. In general, tetracycline and derivatives (doxycycline and minocycline) and beta-lactam medications (penicillin and cephalosporins) are used.

To date, clinical trials are lacking for evaluation of which drugs best treat the myriad of overt and obscure clinical signs associated with Lyme disease. Bioavailability of oral medications is significantly different between humans and horses, so human information is not reliable for horses.

Duration of treatment is also not defined, but the report suggested basing it primarily on the horse’s clinical response and to a lesser extent on decline in serum antibody levels. Horses might remain serologically positive for months, or even years, following antibiotic treatment.

There is a low positive predictive value for serological testing for clinical signs of Lyme disease. With that in mind, the disease might be over-diagnosed in endemic areas. For horses that are seropositive, the Consensus Report recommended the importance of excluding other potential causes before initiating antimicrobial therapy. T

Tick control is essential to prevention. Horse owners should check their horses often and remove ticks as soon as possible. The report also recommended “tick-scaping” practices for environmental control: Dry, sunlit, regularly disturbed and clean areas that are well-maintained have fewer ticks. Keep horses away from wooded areas and transition zones into wooded areas. Mow pastures and clear away leaves and debris. Exclude deer as best as possible from proximity to horses. That said, the report emphasized that ticks survive fine in stalls and pastures even through winter.

Insect repellants might deter tick attachment for a few hours, but most products need frequent re-application. Off-label use of canine Lyme disease vaccines has been attempted in horses, but protective antibody levels drop significantly by four months.

Antimicrobial Resistance

A review of recent infectious disease research studies would be incomplete without broaching the topic of antimicrobial resistance (AMR).

An editorial column in an equine veterinary journal stressed how important it is for veterinary practitioners to embrace antimicrobial stewardship [Rendle, D.I., and Page, S.W. Antimicrobial resistance in companion animals. Equine Veterinary Journal 2018, vol. 50; pp. 147-152]. The authors stated, “We must assume responsibility for the most efficient and parsimonious use of antimicrobials.”

Part of the recipe for minimizing reliance on antimicrobial agents is to implement preventive and control measures to prevent disease in the first place, along with strategies and diagnostic tools (bacterial culture and sensitivity testing, for example) for early recognition of illness.

Another principal element to consider with use of antimicrobials is their effect on the intestinal microbiome. Lately, much light has been shed on the importance of the microbiome to general health and to the immune system of all species.

Rendle and Page further stressed, “The use of critically important antimicrobials in the absence of sound clinical justification in equine practice remains common and is inexcusable when there is clear evidence that their use promotes the development of resistance that presents a significant threat to human and animal health.”

Part of the reasons for using critically important antimicrobials such as fluoroquinolones and cephalosporins is based on convenience along with client demand. Equine practitioners can play an important role in educating clients and not succumbing to the ease of convenience.

Multiple drug resistant (MDR) pathogens and their genetic determinants of resistance are able to cross between animals and humans through close contact, through the food chain and through the environment. This possibility amplifies the adverse consequences of casual use of antimicrobial drugs without evidence-based science to justify their use. 

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