Lyme Disease in Horses

Infection with Borrelia burgdorferi, a tick-borne spirochete and the causative agent of Lyme disease, has been increasingly recognized in equids in North America and other parts of the world. However, the true incidence of clinical Lyme disease is unknown. Signs and problems historically attributed to B burgdorferi infection in horses include chronic weight loss, sporadic lameness, stiffness, arthritis, swollen joints, muscle tenderness or wasting, hepatitis, laminitis, fever, abortion, hyperesthesia, behavior change, uveitis, and encephalitis. In all likelihood, many horses are infected and seroconvert but show minimal or no clinical signs. Some horses displaying clinical signs with a putative diagnosis of Lyme disease likely have been exposed to the organism but have another disease process, such as noninfective osteoarthritis, as the cause of the signs. The limitations of serologic testing, combined with the variable clinical manifestations of infection, make diagnosis of clinical disease challenging and frustrating for practitioners, some of whom believe the disease is underdiagnosed and some of whom believe it does not exist. A recent survey of equine veterinarians in the northeast United States revealed that approximately 45% of practitioners considered Borrelia infection to be absent or rare, whereas 28% considered it common. Only 8% considered clinical Lyme disease to be common, whereas 2% thought that it did not exist in horses. Similarly, in a survey of German veterinarians, 56% of practitioners believed that B burgdorferi infection causes Lyme disease in horses, whereas 18% believed that Lyme disease does not exist in horses. Experimental models of infection have confirmed that B burgdorferi will infect horses, migrate through many tissues and organs, and elicit a host immune response. However, the experimentally infected ponies in one study did not develop clinical signs of Lyme disease, and Koch’s postulates have yet to be fulfilled for this disease in horses.

Reported Cases and Signs of Lyme Neuroborreliosis

When B burgdorferi infects the peripheral or central nervous system, Lyme neuroborreliosis (LNB) may result. This syndrome has been documented in humans and horses and has been experimentally induced in rodents and primates. In humans, LNB most commonly causes one or more parts of a well-defined triad consisting of lymphocytic meningitis, cranial neuritis, and radiculoneuritis. Some people develop more disseminated neuropathies, and the rare patient develops myelitis or encephalitis. Although signs of LNB have been well defined in humans, this disease is known as the new “great imitator” because of its varying clinical presentations.

Limited but fairly convincing information supports the premise that B burgdorferi may cause LNB in horses. Although experimentally infected ponies did not show clinical signs of LNB, B burgdorferi was confirmed with polymerase chain reaction (PCR) to have infected the meninges of one of seven ponies in one trial and to have caused lymphocytic perineuritis and neuritis in one of four ponies in a second trial. Additionally, five naturally occurring cases of equine LNB have been well described in the literature. The first recognized case was reported more than 25 years ago in a horse from Wisconsin with signs of encephalitis, including head tilt, flaccid paralysis of the tail, dysphagia, and abnormal behavior, including aimless wandering. The horse was serologically positive for exposure to B burgdorferi, and the organism was isolated from the brain at postmortem using culture, with subsequent identification by direct immunofluorescence. Subsequently, a horse in the United Kingdom was reported to have clinical signs of lethargy, anorexia, pyrexia, ataxia, hyperesthesia, uveitis, and polysynovitis. The horse was positive for anti-Borrelia immunoglobulin G antibodies in serum and synovial fluid by enzyme-linked immunosorbent assay (ELISA) testing. Of note, cerebrospinal fluid (CSF) was negative for antibodies. Despite treatment with oxytetracycline, the horse dete­riorated, developing stupor, recumbency, and dangerous behavior, and was euthanatized. Necropsy revealed lymphohistiocytic leptomeningitis and vasculitis, and PCR performed after culture enrichment confirmed Borrelia in the brain and other tissue samples.

More recently, three additional cases of equine LNB from the United States have been described. A horse from the Mid-Atlantic region showed signs including behavior changes, neck stiffness, and poor performance. Cerebrospinal fluid analysis yielded a neutrophilic pleocytosis with increased total protein, and Western blot testing of serum samples obtained 3 days apart revealed conversion from equivocal to low or moderate positive results, although ELISA results remained equivocal. Polymerase chain reaction on CSF was positive for B burgdorferi. Despite an initial response to treatment with doxycycline and phenylbutazone, after treatment was discontinued the horse had a recurrence of neurologic signs, including neck stiffness, ataxia, tremors, unilateral vestibular disease, menace response deficits, and abnormal behavior. Rapid progression of signs necessitated euthanasia, and necropsy revealed lymphohistiocytic leptomeningitis and vasculitis as well as lymphocytic cranial neuritis and peripheral radiculoneuritis. Postmortem PCR testing of brain tissue for B burgdorferi was negative. In a separate report, LNB was diagnosed in two horses with progressive neurologic signs. One horse initially had neck and back pain, lumbar hyperesthesia, lethargy, inappetence, weight loss, and uveitis, and eventually developed ataxia, paresis, facial paralysis, abnormal behavior, head and neck tremor, and recumbency. That horse was consistently seronegative for Lyme disease despite being tested three times over 9 months at two laboratories. The other horse had a prolonged course of waxing and waning muscle atrophy, gait deficits, and hyperesthesia that progressed to facial nerve deficits, ataxia, and behavior changes. Necropsy results in both cases were consistent with lymphocytic meningitis, radiculoneuritis, and mild encephalitis, and LNB was confirmed by direct observation of spirochetes with silver staining, PCR (in only one case), and immunohistochemistry.

In summary, signs of equine LNB are variable and may mimic other diseases, including equine protozoal myeloencephalitis, viral encephalitides (West Nile virus, Eastern or Western equine encephalomyelitis, rabies, equine herpesvirus-1 myeloencephalopathy), or bacterial meningoencephalitis. Initial signs may be vague and nonspecific, including lethargy, neck or back pain, poor appetite, weight loss, and abnormal behavior. However, signs are likely to progress to more specific signs of nervous system disease, including hyperesthesia, more severe changes in mental status, cranial nerve deficits, ataxia, muscle tremors, and neurogenic muscle atrophy. Progression may be rapid or slow, and neurologic signs may be accompanied by additional problems, such as uveitis and polysynovitis. Because of the variability in reported clinical signs and the prevalence of equine exposure to Borrelia in certain areas of the world, practitioners should include equine LNB in the differential diagnosis of horses in Borrelia-endemic areas with signs of neurologic disease.