Neurologic Disease Discussed
Subclinical Exposure Rate to WNV
It's extremely important to vaccinate horses at least two months before the West Nile virus (WNV) season, according to Maureen Long, DVM, PhD, Dipl. ACVIM, assistant professor of large animal veterinary medicine at the University of Florida. She presented rough data regarding 2001 Florida WNV exposure rates.
"Little is known about the occurrence of subclinical exposure in horses (how many horses have been infected, but don't show clinical disease)," she and colleagues wrote in the study. "Without this data, little inference can be drawn regarding the asymptomatic to symptomatic ratio and the need for vaccination once disease has occurred in the herd."
Long wanted to determine the rate of subclinical exposure in horses in the face of the 2001 outbreak of WNV in Florida. That year, 492 cases of WNV clinical illness were confirmed, with a 33% mortality rate. Also, researchers wanted to measure the IgM response in horses receiving the killed virus vaccine. IgM is a protective protein manufactured by lymphocytes (types of white blood cells). This response can also be used to detect recent exposure to a disease.
In July and August 2001, Florida veterinarians received letters requesting serum samples from horses prior to their first WNV immunization. The research group chose four locales, and the animals were grouped based on the following criteria:
- Group 1: Vaccinated horses located in a county with a confirmed avian, human, or equine WNV case;
- Group 2: Vaccinated horses located in a county without a confirmed avian, human, or equine WNV case;
- Group 3: Unvaccinated horses located in a county with a confirmed avian, human, or equine WNV case; or
- Group 4: Unvaccinated horses located in a county without a confirmed avian, human, or equine WNV case.
Veterinarians took blood samples when they gave each horse his first and second WNV vaccine injections, and they took additional samples on a weekly basis for five to six consecutive weeks. Groups 1, 3, and 4 were tested in late August-October 2001, while Group 2 horses were vaccinated in January 2002 and 2003.
Seventeen of 38 vaccinated horses (44%) locate at a farm in a county with confirmed WNV (Group 1) were positive at the time of the first WNV vaccination injection, indicating significant subclinical exposure. By the end of the blood sampling period, 26 of those horses (68%) became positive. Three horses (8%) on that farm experienced clinical WNV, and two were euthanized. At another farm, three of 73 (4%) Group 1 animals were positive at the time of the initial vaccination, and over the course of the data-gathering, 11 of 73 (15%) became positive. One of those 73 was examined for a short duration of stumbling (suggesting neurologic signs of clinical disease). At the same premise, horses which weren't vaccinated (Group 3) were also tested, and 6 of 36 (16%) became positive and remained so for one to six weeks.
In vaccinated horses from a county with no WNV (Group 2), none showed positive tests over six weeks of testing. In unvaccinated horses in a county without confirmed WNV (Group 4), one of 50 horses tested positive on one sample from the fifth week of testing.
"In two locations where clinical WNV disease was identified locally (Group 1), exposure over the peak arboviral season (peak activity of diseases spread by mosquitoes) varied from 15-68%," noted the researchers in the paper.
A very crude asymptomatic/symptomatic ratio of 1:9 was found, which is consistent with what has been found in prior research. That means for every nine WNV-positive horses not showing clinical infection, there is one positive animal which will likely develop clinical signs. Additionally, horses didn't seem to develop an IgM response to the vaccine, which means that IgM testing of vaccinated animals will not result in false positives and is an appropriate tool to use in following disease seroprevalence. (See article #5002 online.)
Acyclovir for Treating EHV-1 Myeloencephalopathy
Equine herpesvirus type-1 (EHV-1) myeloencephalopathy (EHM) generated more interest on TheHorse.com in 2003 than any other infectious disease, due in part to several fatal outbreaks in the news. Many questions about treatment were raised during these outbreaks, so researchers stepped forward and looked into the efficacy of one prominent treatment that was described. At the convention, Pamela A. Wilkins, DVM, MS, PhD, Dipl. ACVIM, ACVECC, of the University of Pennsylvania's New Bolton Center, discussed the use of acyclovir in the treatment of EHM.
The EHV-1 organism can cause several forms of disease, including rhinopneumonitis (a respiratory disease found mostly in young horses), abortions in pregnant mares, and neurologic disease. "EHM is a virus-induced central nervous system (CNS) vascular necrosis (blood vessel tissue death) with associated thrombosis (blood clotting) and ischemia (oxygen deprivation in the tissues)," wrote Wilkins and other collaborators on the research project. Probably the most prominent EHM outbreak last year was one at the University of Findlay in Findlay, Ohio, and included respiratory signs as well as EHM.
In the past, EHM therapy has been limited to supportive treatment. Anti-inflammatory drugs have been used, mainly corticosteroids such as dexamethasone and prednisolone. However, those drugs might be associated with some risk, because corticosteroid administration has been shown to reactivate latent (dormant) infection in horses (and latency often occurs after infection). Judicious use of anti-inflammatories is reasonable.
Acyclovir is an anti-viral drug with a high activity and selectivity for herpesviruses. It has been used in equine outbreaks, even though past studies have not established a clear-cut benefit of using the drug. Acyclovir is of potential interest to equine practitioners since it recently came off patent and "is potentially an affordable directed therapy for EHM," wrote the researchers. It can be given orally or intravenously (IV), but is much more expensive to administer IV.
Wilkins and colleagues studied usefulness of the drug by looking at blood concentrations in five Findlay horses receiving it. The five sick horses were treated with 10 mg/kg of acyclovir orally twice a day for three to four days before blood sampling. The veterinarians took blood samples at specific times after administration, and they found that the drug was detected in all of the horses, confirming that the drug was reaching the circulatory system and thus the CNS. All horses were confirmed to have EHM and all survived.
There were no adverse reactions to administration of the drug, according to Wilkins, who in collaboration with Ray Sweeney VMD, Dipl. ACVIM, of New Bolton Center, and Mark Papich, DVM, MS, of North Carolina State University's College of Veterinary Medicine, has a classic pharmaceutical study of acyclovir underway to determine more specifics on the drug, such as what the optimum dose and dose interval should be.
"Preliminary data from one of our collaborators, Dr. Edward Dubovi, Cornell University College of Veterinary Medicine, shows that equine herpes myeloencephalitis is sensitive to acyclovir," said Wilkins. "It will not be an instant cure, nor will it fully prevent new cases, but at Findlay, there were no losses after acyclovir use," she said. (See article #4996 online.)
What is EPM?
In 1964, a condition was described as segmental myelitis, noted Kenton Morgan, DVM, Dipl. ACT, a Bayer Animal Health technical service veterinarian at the Horseman's Day seminar. He said necropsy exams showed sections of spinal cord affected, but at that time scientists didn't know the cause. In 1976, the problem was given its current name, equine protozoal myeloencephalitis (EPM). "Myelo" refers to spinal cord; "encephalo" refers to brain; "itis" refers to inflammation/infection.
EPM is a protozoal disease that causes inflammation in the brain and spinal cord of the horse. In the early 1990s, an organism was grown from affected equine spinal cord and given the name Sarcocystis neurona. (There is a Neospora organism that can cause EPM, but only in a very small number of cases.)
The Sarcocystis group of protozoa have a complex two-host life cycle, said Morgan. Much has been learned about the life cycle of S. neurona in the last eight years. It wasn't until 1995 that researchers learned the opossum was the definitive host.
A two-host life cycle means a definitive host sheds the infective parasite in its feces, and intermediate hosts complete the life cycle (for EPM it's the nine-banded armadillo, striped skunk, raccoon, sea otter, and cat). The intermediate host does not shed an infective form of the parasite. The life cycle is completed only if the intermediate host dies and is eaten by the opossum because the parasite is in muscle tissue of the intermediate host.
An opossum sheds sporocysts (the infective form) in its feces. An intermediate host picks up the parasite, which goes through a replication process while in the intermediate host. This results in sarcocysts in the muscle of the intermediate host, which can live for years with the parasite in its muscle tissue. When those intermediate hosts die and an opossum eats the infected muscle, the opossum ingests sarcocysts and the parasite undergoes additional replication and completes its life cycle.
Horses and EPM
The horse is thought to be a dead-end host. That means the parasite is not passed to other animals (there is debate on whether horse muscle contains a form of the parasite that could be passed to the definitive host). The horse picks up the parasite from grazing or drinking around infected opossum feces. Replication of the parasite occurs somewhere in the horse.
A case at Michigan State University indicates that the horse might be a true intermediate host, said Morgan. A four-month-old foal died after being admitted to the hospital and researchers found sarcocysts in the tongue of this foal. That was the first time the sarcocyst stage of the parasite had been found in a horse. However, this finding might have been because the foal was so sick. (See article #4545 online.)
In the horse, the parasite is ingested and somewhere in the horse goes through
replication and changes form from sporocyst to merozoite, Morgan explained. These are the infective forms that invade cells. This stage of parasite can cross the blood-brain barrier by gaining access into white blood cells. They invade a nerve cell and through asexual replication form a sack-like structure (schizont) that ruptures and kills the host cell and releases more parasites to infect other host cells.
Most horses which ingest sporocysts clear the infection, but they are positive for antibodies to the parasite in their blood. A small number of horses don't clear the parasite, and they are candidates to develop neurologic signs of EPM, he said.
Clinical signs include asymmetrical ataxia (incoordination) with or without atrophy (muscle wasting). Morgan explained that means one side is not affected the same as the other. Most other CNS problems in horses produce symmetrical clinical signs (which are the same on both sides of the horse).
Bayer Animal Health's Marquis was the first licensed treatment for EPM. The active ingredient is ponazuril. This product is a paste formulation that is given once daily for 28 consecutive days. The drug has demonstrated effectiveness in treating horses with EPM since its approval in 2001, and it has a favorable safety profile.
Another drug--Navigator, sold by IDEXX--had just received FDA approval for the treatment of EPM. The active ingredient is nitazoxanide. It is also a paste medication given for 28 days. (See article #2652 online.) Veterinarians occasionally might use other treatments. Supportive therapy can include anti-inflammatory products and vitamin E.
Morgan stressed that good management practices can reduce the risk factors that contribute to disease incidence. Keep feed sources clean and free of opossums and protect your hay from rodent infestation. Dispose of any animal carcasses on or near your property. Minimize stress, especially during transport. There is a licensed vaccine available; talk to your veterinarian about its use in your situation. (See article #4989 online.)
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