Ocular disease in horses with confirmed ocular or central nervous system Borrelia infection: Case series and review of literature.

OBJECTIVE: To describe the clinical presentation, treatment, and clinical outcome of horses with ocular disease and evidence of systemic or ocular Lyme disease. ANIMALS STUDIED: Five horses met the inclusion criteria of ocular disease with evidence of B burgdorferi present in ocular or CNS tissues. PROCEDURE: The goal of this study was to describe the clinical presentation and progression of ocular disease when associated with ocular or CNS B burgdorferi infection in horses. A retrospective review of medical records was performed on horses admitted for ocular disease with evidence of B burgdorferi infection between 1998 and 2015. The diagnosis of B burgdorferi-associated uveitis was based on histopathologic lesions of lymphohistiocytic and suppurative uveitis/endophthalmitis and intralesional argyrophilic spirochetes in either ocular or CNS tissue consistent with Borrelia. Leptospiral uveitis was ruled out by PCR. RESULTS: All five horses in the current study had intraocular inflammation at the time of presentation. Medical management with anti-inflammatories was successful in controlling uveitis in the two horses in which treatment of uveitis was attempted. Systemic treatment with oral tetracyclines was unsuccessful in a single case in which treatment of Borrelia was attempted. Four horses were euthanized due to progression of neurologic disease. The surviving horse had an enucleation performed and did not show systemic signs. CONCLUSIONS: Infection with Borrelia burgdorferi should be considered in endemic areas as a differential for horses with ocular disease, in particular, uveitis. The prognosis for uveitis and neurologic disease associated with Lyme disease was poor in the current study.

Lyme neuroborreliosis and bird populations in northern Europe.

Many vector-borne diseases are transmitted through complex pathogen-vector-host networks, which makes it challenging to identify the role of specific host groups in disease emergence. Lyme borreliosis in humans is now the most common vector-borne zoonosis in the Northern Hemisphere. The disease is caused by multiple genospecies of Borrelia burgdorferi sensu lato bacteria transmitted by ixodid (hard) ticks, and the major host groups transmit Borrelia genospecies with different pathogenicity, causing variable clinical symptoms in humans. The health impact of a given host group is a function of the number of ticks it infects as well as the pathogenicity of the genospecies it carries. Borrelia afzelii, with mainly small mammals as reservoirs, is the most common pathogen causing Lyme borreliosis, and it is often responsible for the largest proportion of infected host-seeking tick nymphs in Europe. The bird-borne Borrelia garinii, though less prevalent in nymphal ticks, is more likely to cause Lyme neuroborreliosis, but whether B. garinii causes disseminated disease more frequently has not been documented. Based on extensive data of annual disease incidence across Norway from 1995 to 2017, we show here that 69% of disseminated Lyme borreliosis cases were neuroborreliosis, which is three times higher than predicted from the infection prevalence of B. garinii in host-seeking ticks (21%). The population estimate of migratory birds, mainly of thrushes, explained part of the annual variation in cases of neuroborreliosis, with a one-year time lag. We highlight the important role of the genospecies' pathogenicity and the host associations for understanding the epidemiology of disseminated Lyme borreliosis.

Neuroborreliosis in a horse with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a rare condition in adult horses characterized by hypogammaglobulinemia and increased susceptibility to parasitic and bacterial infections, including recurrent respiratory diseases, septicemia, and meningitis. Lyme disease is often included as a differential diagnosis in CVID horses with signs of meningitis; however, the Borrelia burgdorferi organism has not been demonstrated previously within central nervous system tissues of CVID horses with neurologic disease, to our knowledge. We report herein a case of neuroborreliosis in a CVID horse, confirmed by combined immunologic testing, histopathology, real-time PCR assay, fluorescent in situ hybridization, and immunohistochemical staining. Implications of these findings include heightened monitoring of CVID horses for Lyme disease in endemic areas and appropriate therapy in the case of neurologic disease.

Cerebrospinal fluid Lyme multiplex assay results are not diagnostic in horses with neuroborreliosis.

BACKGROUND: The accuracy of the Lyme multiplex assay for the diagnosis of neuroborreliosis in horses is unknown. HYPOTHESIS/OBJECTIVES: To describe Lyme multiplex results in horses with a postmortem diagnosis of neuroborreliosis. The hypothesis was that paired serum and cerebrospinal fluid (CSF) results and a CSF : serum ratio would allow differentiation of horses with neuroborreliosis from those with other neurologic diseases. ANIMALS: Ninety horses that had neurologic examinations, serum and CSF Lyme multiplex analyses, and postmortem examination of the nervous system performed. METHODS: Retrospective study. Data collected included signalment, ante- and postmortem diagnoses, and serum and CSF Lyme multiplex results. The CSF : serum ratio was calculated by dividing CSF median fluorescent intensity (MFI) by serum MFI for each result. RESULTS: Ten horses had a final diagnosis of neuroborreliosis, 70 were diagnosed with other neurologic diseases, and 10 had no neurologic disease. Not all horses with neuroborreliosis had positive results: 4/10 had at least 1 positive serum result, 5/10 had at least 1 positive CSF result, and 3/10 had at least 1 CSF result 4-fold higher than the corresponding serum result. Results were similar for the 70 horses with other neurologic diseases: 53% had at least 1 positive serum result, 50% had at least 1 positive CSF result, and 16% had at least 1 CSF result 4-fold higher than the corresponding serum result. CONCLUSIONS AND CLINICAL IMPORTANCE: Positive Lyme multiplex results were common in horses with neurologic diseases and did not adequately differentiate horses with neuroborreliosis from horses with other disorders.

Retrospective Evaluation of Horses Diagnosed with Neuroborreliosis on Postmortem Examination: 16 Cases (2004-2015).

BACKGROUND: Equine neuroborreliosis (NB), Lyme disease, is difficult to diagnose and has limited description in the literature. OBJECTIVE: Provide a detailed description of clinical signs, diagnostic, and pathologic findings of horses with NB. ANIMALS: Sixteen horses with histologically confirmed NB. METHODS: Retrospective review of medical records at the University of Pennsylvania and via an ACVIM listserv query with inclusion criteria requiring possible exposure to Borrelia burgdorferi and histologic findings consistent with previous reports of NB without evidence of other disease. RESULTS: Sixteen horses were identified, 12 of which had additional evidence of NB. Clinical signs were variable including muscle atrophy or weight loss (12), cranial nerve deficits (11), ataxia (10), changes in behavior (9), dysphagia (7), fasciculations (6), neck stiffness (6), episodic respiratory distress (5), uveitis (5), fever (2), joint effusion (2), and cardiac arrhythmias (1). Serologic analysis was positive for B. burgdorferi infection in 6/13 cases tested. CSF abnormalities were present in 8/13 cases tested, including xanthochromia (4/13), increased total protein (5/13; median: 91 mg/dL, range: 25-219 mg/dL), and a neutrophilic (6/13) or lymphocytic (2/13) pleocytosis (median: 25 nucleated cells/µL, range: 0-922 nucleated cells/µL). PCR on CSF for B. burgdorferi was negative in the 7 cases that were tested. CONCLUSION AND CLINICAL IMPORTANCE: Diagnosis of equine NB is challenging due to variable clinical presentation and lack of sensitive and specific diagnostic tests. Negative serology and normal CSF analysis do not exclude the diagnosis of NB.

Trends in surveillance data of human Lyme borreliosis from six federal states in eastern Germany, 2009-2012.

Lyme borreliosis (LB) is the most frequent vector-borne disease in Germany. For more than 10 years, data from mandatory notifications have been available from 6 federal states in the eastern part of Germany. A common case definition was applied. Clinical manifestations of erythema migrans, neuroborreliosis (radiculoneuritis, cranial neuritis, meningitis), and Lyme arthritis were notifiable. From 2009 to 2012, altogether 18,894 cases were notified. The overall incidence varied between 34.9 cases/100,000 inhabitants in 2009 and 19.54 cases/100,000 persons in 2012. LB in eastern Germany showed a pronounced seasonality with a peak in August. Decreasing as well as increasing trends were observed in different federal states. Females predominated among all cases (55.3%). The age distribution was bimodal with incidence peaks in children 5-9 years old (32.4 cases/100,000 persons in 2011) and in adults aged 60-69 years (56.7 cases/100,000 persons in 2011). Erythema migrans affected 95.4% of the patients and acute neuroborreliosis 3.3%. Among the latter, the most common manifestation was radiculoneuritis (n=316). Neuritis cranialis was more common in children than in adults (p<0.01). The same was true for meningitis (p<0.01). Altogether 2.0% of the LB cases developed Lyme arthritis. LB has a significant disease burden in the study area. Different levels of under-ascertainment in the surveillance system could explain parts of the differences in the incidence. Furthermore, there may be discrepancies in disease awareness among patients and physicians. Changes in time and differences among geographical regions could result from variations in risk factors related to human behaviour (e.g., outdoor activity). Additionally, vector-related risk factors may have varied (e.g., landscape, climate). Public health strategies with a particular focus on the high-incidence age groups should promote daily checks for ticks and prompt removal of ticks after exposure to avoid infection. Physicians should be able to recognize LB patients with early manifestations and promptly treat those appropriately.

Lyme neuroborreliosis in 2 horses.

Lyme neuroborreliosis--characterized as chronic, necrosuppurative to nonsuppurative, perivascular to diffuse meningoradiculoneuritis--was diagnosed in 2 horses with progressive neurologic disease. In 1 horse, Borrelia burgdorferi sensu stricto was identified by polymerase chain reaction amplification of B burgdorferi sensu stricto-specific gene targets (ospA, ospC, flaB, dbpA, arp). Highest spirochetal burdens were in tissues with inflammation, including spinal cord, muscle, and joint capsule. Sequence analysis of ospA, ospC, and flaB revealed 99.9% sequence identity to the respective genes in B burgdorferi strain 297, an isolate from a human case of neuroborreliosis. In both horses, spirochetes were visualized in affected tissues with Steiner silver impregnation and by immunohistochemistry, predominantly within the dense collagenous tissue of the dura mater and leptomeninges.

Protection against tick-transmitted Lyme disease in dogs vaccinated with a multiantigenic vaccine.

In an effort to develop a safe and effective vaccine for the prevention of Lyme borreliosis that addresses concerns raised over currently available vaccines, dogs were vaccinated twice with a multiantigenic preparation of Borrelia burgdorferi, strain N40, on days 0 and 20 of the experiment. About 70 and 154 days after the first immunization, dogs were challenged by exposing them to field-collected Ixodes scapularis ticks harboring B. burgdorferi. Vaccinated dogs were completely protected from infection by all criteria utilized to assess infection, developed high-titer anti-B. burgdorferi serum antibodies and growth inhibitory activity which persisted for over 200 days, and did not demonstrate any untoward consequence of vaccination. Serum absorption experiments revealed that borreliacidal and most likely protective antibodies in dogs receiving the multiantigenic preparation were not only elicited against the OspA antigen, but were also produced against additional yet to be determined targets on B. burgdorferi organisms. These data demonstrate that a multiantigenic vaccine is effective in preventing Lyme disease transmitted via the natural vector.