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Lyme borreliosis is a bacterial, tick-transmitted disease of animals (dogs, horses, probably cats) and humans. Many additional mammalian and avian species become infected but do not develop overt clinical signs. Areas of greatest incidence in the USA are regions in the northeast (particularly the New England states), the upper Midwest, and the Pacific coast. Lyme borreliosis also occurs in moderate climatic regions of Europe and Asia. The importance of borreliosis as a zoonotic disease is increasing.
Etiology and Transmission
Currently, on the basis of DNA-DNA reassociation analysis, 12 different species 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), and B garinii (Europe, Asia), all of which are pathogenic for humans. 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 Ixodes pacificus on the Pacific coast and I scapularis in the Midwest and northeast. I ricinus and I persulcatus are primary vectors in Europe and Asia.
Ixodid ticks hatch from eggs as uninfected larvae. Both larvae and nymphs may acquire spirochetes from Borrelia-carrying hosts. Small mammals, especially rodents, often 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 prior to gestation may transmit spirochetes to their pups in utero.
Clinical Findings
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 commonly observed clinical signs. The second most common syndrome associated with Lyme borreliosis is renal failure and 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, while facial paralysis and seizure disorders are thought to be expressions of the neurologic form.
Diagnosis
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) and protein immunoelectrophoresis (Western blot). Due to 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 a specific Western blot assay. Western blot 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. About 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.
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 be helpful 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 for 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 ticks, 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.
Treatment
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. Doxycyline is preferred over penicillins because mixed infections with other tick-borne pathogens are often found in patients with clinical signs. Clinical and research data indicate that infection in animals, including humans, may persist in spite of antibiotic therapy. In dogs, standard antibiotic doses and treatment for 4 wk have been demonstrated to be effective. Due to the persistence of B burgdorferi sensu lato, relapses may be expected. In these cases, antibiotics mentioned above can be used again, as persistent infection is not the result of acquired antibiotic resistance. Prolonged antibiotic therapy (>4 wk) may be beneficial for patients 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 NSAID concurrent with antibiotic therapy may lead to confusion over the source of clinical improvement and make diagnosis based on therapeutic response difficult.
Control and Prevention
Tick avoidance plays an important role in disease control. While highly effective products (permethrin, amitraz, and fipronil) 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 for the prevention of Lyme borreliosis in dogs have been in use since the early 1990s. Vaccines that only contained recombinant outer surface protein A (rOspA) have since been licensed for use in dogs. Vaccines are available in Europe that contain 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). Antibodies against OspA prevent spirochete transmission from ticks to the host. It has been demonstrated that when a tick attaches to a warm-blooded animal, B burgdorferi sensu lato organisms in that tick stop producing OspA and begin producing new proteins, OspC and others, prior to transmission. Development of vaccines that contain multiple B burgdorferi antigens that may contribute to enhanced protection is being pursued.
In endemic areas, young 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 prior to 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 package directions. Because antibody levels often drop quickly after the initial 2 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.
Zoonotic Risk
Lyme borreliosis is classified as a zoonosis. 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 humans during close contact.
Last full review/revision March 2012 by Reinhard K. Straubinger, DrMedVetHabil, PhD
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