Overview of Lyme Borreliosis

On the basis of DNA analysis, 19 different genospecies fall within the Borrelia burgdorferi sensu lato complex. Within this complex, the most important spirochete species are B burgdorferi sensu stricto (North America, Europe), B afzelii (Europe, Asia), B bavariensis, and B garinii (Europe, Asia), all of which are pathogenic for people. Only B burgdorferi sensu stricto has been shown so far to be pathogenic for domestic animals under experimental conditions. Tick vectors of B burgdorferi sensu lato are hard-shelled Ixodes ticks. In the USA, these are primarily I scapularis in the northeast and Midwest and I pacificus on the Pacific coast. I ricinus and I persulcatus are the primary vectors in Europe and Asia. B miyamotoi is another member of the genus Borrelia. Although this spirochete is transmitted by ixodid ticks and may cause infections in mammals characterized by clinical signs such as fever, headache, fatigue, and muscle aches, the bacterium is a relapsing, fever-causing organism.

Ixodid ticks hatch from eggs as uninfected larvae. Both larvae and nymphs may acquire spirochetes from Borrelia-carrying hosts. Small mammals, especially rodents, play a major role as reservoir hosts. Birds and lizards may also harbor certain Borrelia species and serve as reservoir hosts. Infection rates of the vectors vary according to region and season and can be as high as 50% in adult ticks. After tick attachment, >24 hr elapse before the first B burgdorferi sensu lato organisms are transmitted into the host’s skin. Stable infection of the host occurs at >53 hr into the blood meal. Therefore, early removal of attached ticks reduces the potential for spirochete transmission. B burgdorferi sensu lato organisms are not transmitted by insects, body fluids (urine, saliva, semen), or bite wounds. Experimental studies have shown that dams infected before gestation may transmit spirochetes to their pups in utero.

Numerous clinical syndromes have been attributed to Lyme borreliosis in domestic animals, including limb and joint disease and renal, neurologic, and cardiac abnormalities. In dogs, intermittent, recurrent lameness; fever; anorexia; lethargy; and lymphadenopathy with or without swollen, painful joints are the most common clinical signs. The second most common syndrome associated with Lyme borreliosis is renal failure, which is generally fatal. It is characterized by uremia, hyperphosphatemia, and severe protein-losing nephropathy, often accompanied by peripheral edema. Bernese Mountain Dogs and Labrador Retrievers in particular often show high Borrelia-specific antibody levels; immune complexes in kidney tissues lead to severe inflammation. In human medicine, single case reports have described abnormalities with bradycardia with the cardiac form of Lyme borreliosis, whereas facial paralysis and seizure disorders are thought to be expressions of the neurologic form.

Diagnosis is based on history, clinical signs, elimination of other diagnoses, laboratory data, epidemiologic considerations, and response to antibiotic therapy. Autoimmune panels, CBC, blood chemistry, radiographs, and other laboratory data are generally normal, except for results pertaining directly to the affected system (eg, soft-tissue swelling in limbs, neutrophil accumulation in synovial fluids of affected joints, uremia in renal disease).

Serologic testing for antibodies specific for B burgdorferi sensu lato is an adjunct to clinical diagnosis. Antibodies can be detected with ELISA (including rapid test systems), Western blots, line immunoassays (LIA), and with fluorescent bead-based multiplex assays. Because of their low specificity, indirect immunofluorescent antibody assays are no longer recommended. The standard procedure for antibody detection is a two-tiered approach in which samples are screened with a sensitive ELISA, and only positively reacting samples are rechecked with specific confirmatory tests. Western blot or LIA testing helps to differentiate the immune response elicited by infection from that induced by vaccination.

Alternatively, blood or serum samples can be tested with peptide-based assays (C6 peptide), which is specific for infection-induced antibodies. However, demonstration of specific antibodies indicates exposure to bacterial antigen only and does not equate to clinical disease. Approximately 5%–10% of dogs in central Europe carry Borrelia-specific antibodies with no clinical signs. Additionally, false-negative results can occur with the C6 peptide assays shortly after infection. Long incubation periods, persistence of antibodies for months to years, and the disassociation of the antibody response from the clinical stage of disease make diagnosis by blood testing alone impossible.

Lymphocyte stimulation tests are available that measure the cellular immune response to Borrelia. In culture, Borrelia antigens are processed by antigen-presenting cells with which specific lymphocytes interact. Released cytokines (eg, interleukin-1 beta) in the culture supernatant are correlates for preceding Borrelia infections of the host. Scant information is available in terms of the test's sensitivity and specificity.

Isolation of B burgdorferi sensu lato by culture or detection of specific DNA by PCR from joints, skin tissue samples, or other sources may also help in diagnosis. However, direct detection of the organism is difficult, time consuming (up to 6 wk for culture), and in most cases produces negative results. Only a positive result is meaningful. Blood samples are generally negative, because the organism resides in tissue and not in the circulation.

Clinical signs of Lyme borreliosis are nonspecific. In addition to other orthopedic disorders (eg, trauma, osteochondritis dissecans, immune-mediated diseases), other infections should be considered. Anaplasma phagocytophilum can also induce intermittent, recurrent lameness. A phagocytophilum is transmitted by the same tick genus, and epidemiologic studies have revealed that up to 30% of all dogs in central Europe carry antibodies specific for this agent. Mixed infections should be considered when clinical signs are apparent.

Antibiotic therapy is indicated in all cases with clinical signs attributed to Lyme borreliosis. Antimicrobials in the tetracycline (eg, doxycycline 10 mg/kg, PO, bid) and penicillin (eg, amoxicillin 20 mg/kg, PO, tid) groups are effective, and rapid response is seen in limb and joint disease in most cases, although incomplete or transient resolution of signs occurs in a significant number of affected animals. Doxycycline is preferred over penicillins, because mixed infections with other tickborne pathogens are often found in animals with clinical signs. Clinical and research data indicate that low-level infection in animals, including people, may persist despite antibiotic therapy. In dogs, standard antibiotic doses and treatment for 4 wk have been demonstrated to be effective. If clinical signs recur, the antibiotics mentioned above can be used again, because persistent infection is not the result of acquired antibiotic resistance. Prolonged antibiotic therapy (>4 wk) may be beneficial for animals with continuing disease signs.

Symptomatic therapy directed toward the affected organ system and clinicopathologic abnormalities is also important, especially in renal disease. In limb and joint disease, the use of NSAIDs concurrent with antibiotic therapy may lead to confusion over the source of clinical improvement and make diagnosis based on therapeutic response difficult.

Tick avoidance plays an important role in disease control. Although highly effective repellents and acaricides in collars, sprays, and spot-ons are available for use on dogs, lack of owner compliance in application may often be a barrier to effective, longterm tick avoidance.

Killed, whole-cell bacterins to prevent Lyme borreliosis in dogs have been in use since the early 1990s. Vaccines that contain only recombinant outer surface protein A (rOspA) have since been licensed for use in dogs. Vaccines are available in Europe that contain antigens from different species of the B burgdorferi sensu lato complex. All current vaccines induce a strong antibody response predominately to OspA (lysate vaccines) or only against OspA (recombinant vaccines). During the tick's blood meal, antibodies against OspA bind to Borrelia organisms residing in the tick. Bound antibodies prevent spirochete migration within the tick and consequently Borrelia transmission from ticks to hosts. Later, during the blood meal, B burgdorferi sensu lato organisms in the engorging tick stop producing OspA and begin expressing new proteins, OspC and others, before transmission. Development of vaccines that contain multiple B burgdorferi antigens that may contribute to enhanced protection is being pursued.

In endemic areas, dogs should be vaccinated before natural exposure to ticks to attain the highest degree of protection. Dogs that have been exposed to ticks should be tested serologically for established infection before vaccination. Postinfection vaccination has little to no therapeutic effect on established infections. Two doses of vaccine should be administered SC to dogs ≥9–12 wk old at 3-wk intervals, or according to label directions. Because antibody levels often drop quickly after the initial two immunizations, additional booster vaccinations should be administered twice within the next year, preferably at 6-mo intervals (suggested schedule: spring, fall, spring) with annual vaccinations thereafter.

Lyme borreliosis is an important zoonotic disease. Animals and people are infected during the blood meal of hard-shelled ticks (Ixodes spp). Companion and farm animals are not the source of infection in people. Pets may bring unattached infected ticks into the household and subsequently the vectors may be passed on to other animals or people during close contact.