Valacyclovir and Heparin May Improve Survival in Horses with EHM

B y M a r i e R o s e n t h a l , M S

In recent naturally occurring outbreaks in Virginia of equine herpesvirus myeloencephalopathy (EHM), all horses that received treatment with valacyclovir and heparin survived, while horses that did not receive this combination were euthanized.

Veterinarians from Marion duPont Scott Equine Medical Center, VA-MD Regional College of Veterinary Medicine at Virginia Tech, in Leesburg, performed a retrospective review of medical records collected from 3 EHM outbreaks in which this novel treatment combination was used. Megan Marchitello, DVM, a resident at the Marion duPont Scott Equine Medicine Center, described the case findings at the AAEP 65th Annual Convention in Denver.

The first outbreak occurred on a small residential farm that held 4 horses; 2 of the horses had a recent history of travel and 1 had been recently introduced without a quarantine period. The second farm held 41 horses with no history of travel, but the horses had multiple shared water sources. The third facility held 66 horses with a much higher incidence of travel than the other 2 farms, and had recently held a horse show on the premises.

“All 3 outbreaks occurred in a 6 month period between 2017 and 2018, and veterinarians from the Marion duPont Scott Equine Medical Center, 6 ambulatory practices and the Virginia Department of Agriculture and Consumer Services (VDACS), worked together to create a uniform quarantine and treatment protocol,” Dr. Marchitello said.

The horses were considered positive for equine herpesvirus-1 (EHV-1) if they had a positive PCR test result or developed acute neurologic deficits. During the outbreak period, horses were considered negative if they had a negative PCR, even if they developed a fever. A horse was considered exposed if it shared “airspace” or husbandry staff with a known infected horse.

Nasal secretions and blood were collected from all horses at facility 1 and only symptomatic horses at facilities 2 and 3. The samples were submitted to the VDACS to for testing.

The farms quarantined the horses for 21 days after the last fever, and daily temperature checks were recommended at least twice a day. Any horse with a fever of 101.5° F, nasal discharge, lymphedema or acute neurologic deficits, was isolated from the general population.

A standard treatment protocol was recommended at all facilities. After EHV-1 infection was confirmed, prophylactic valacyclovir was recommended for all exposed horses. “Metaphylactic” heparin was then recommended for all horses that displayed clinical signs of disease. Additional treatments were recommended by the supervising veterinarian on a case by case basis, including anti-inflammatories and anti-oxidants. All horses showing neurologic deficits were given corticosteroids, mostly dexamethasone.

Among all 3 outbreaks, 111 horses with a mean age of 11 were exposed to the virus; 23 horses developed clinical signs leading to a morbidity rate of 20%, according to Dr. Marchitello. “Four horses exhibited recurrent fever, however, repeatedly tested negative on PCR. So for the purpose of this study, they were considered unaffected. However, they were isolated from the general population and did receive our treatment protocol,” she said.

The sick horses displayed a variety of clinical signs, including fever, lymphedema and nasal discharge. Ten horses aged 5 to 22 were diagnosed with EHM after developing neurologic deficits, including ataxia (10 horses), asymmetric vestibular deficits (2) and encephalopathy (1).

“Heparin was administered at the onset of fever or other clinical signs of EHV-1 and always in conjunc- tion with valacyclovir,” she said. “Seventeen horses with clinical disease received heparin metaphyactically, 2 at the onset of neurologic disease and 15 at the onset of fever. Of these 15 horses, 4 went on to develop EHM.” Only 4 horses with clinical signs of EHM did not receive heparin and were euthanized for the development of 5/5 ataxia.

“When evaluating the population of horses that developed clinical signs, targeted treatment was significantly associated with a decreased incidence of EHM. The 4 horses that did not receive our targeted treatment did receive other treatments like anti-inflammatories and antioxidants. However, they did not receive valacyclovir and heparin, and they failed to survive,” Dr. Marchitello said.

“So overall, the take-home message is that all horses that received valacyclovir and heparin survived and all horses that did not receive this targeted treatment were euthanized,” she said.

Understanding how EHV-1 infection occurs can help explain how this combination could be effective for infected horses, according to Dr. Marchitello. The virus enters the respiratory tract, infects the lymph nodes and then moves to the bloodstream. In the case of EHM, the virus can then disseminate to the lining of the blood vessels of the central nervous system, causing damage to the spinal cord or brain.

Heparin blocks thrombin production, which can decrease the viral load; valacyclovir decreases viremia and nasal shedding, she explained.

The study had several limitations, Dr. Marchitello admitted. “Because of the retrospective nature of this study, our referral hospital was introduced to these outbreaks at different times of infection. And it was also difficult to enforce a standard treatment protocol due to varying client compliance,” she said.

In addition, financial constraints limited the number of horses that were tested, so they did not know the true prevalence of infection.

“Lastly, our reliance on qualitative rather than quantitative PCR may have decreased our sensitivity in detecting EHV, especially in the horses that experienced fevers and may have been low shedders,” she said.

She said a case-control study is needed to evaluate this treatment plan, as well as other therapeutics that could block viral fusion or endocytosis. These studies would be worthwhile, because EHV-1 is one of the most prevalent infections among U.S. horses. Equine herpesvirus is ubiquitous in horse populations with prevalence ranging from 60% to 80%.

“So, for practical purposes, the veterinarian should presume that most horses are latently infected,” Dr. Marchitello said.