Craig E. Greene
Lyme borreliosis is a commonly diagnosed vector-borne disease in people, most commonly in North America, Europe, and Asia. Unconfirmed accounts of the disease have been from other continents. Revelation of this disease in the last 20 years has had a major influence on research and interest in vector borne diseases. The news media has helped to focus public interest and concern about tick transmitted disease. A number of other vector-borne illnesses have been discovered in the pursuit of diagnostic therapeutic and preventative measures for borreliosis. Recognition of the importance of these illnesses has led to many improvements in our understanding and control of the insect vectors.
Borrelia are small spirochetes of a genus, which contains more than 20 species. Some have been isolated from diseased people and animals, while others have been found in asymptomatic reservoir hosts or ticks. The clinically important species are usually categorized into the relapsing-fever and Lyme borreliosis borreliae. The Lyme type borreliae have been divided into at least four genomic species groups. In North America, B. burgdorferi sensu stricto) is the primary isolate while in Europe, B. garinii and B. afzelii predominate. Other yet unidentified pathogenic and nonpathogenic strains of Borrelia exist, or await discovery. The differences in strains or species may account for the regional differences in clinical findings that have been reported.
Borrelia do not survive free living in the environment but are transmitted between vertebrate reservoir hosts via tick vectors. The ticks inhabit areas in temperate latitudes with cooler climatic conditions. In the United States, most cases occur in foci along the Northeastern seaboard, the upper Midwest, and the north pacific coast. Within Canada, Lyme borreliosis is endemic in southeastern Ontario. In Europe, most cases have been in the Scandinavian and Alpine countries.
The principal vectors of B. burgdorferi sensu lato are various species of Ixodes ticks. I. ricinus and I. persulcatus are the primary vectors in Europe and Eurasia, respectively. In the United States closely related black-legged ticks, I. scapularis (Northeast, Midwest, and Southeast) and I. pacificus (West) appear to be involved. In addition to B. burgdorferi, Ixodes species ticks are intermediate hosts for Anaplasma phagocytophila.
Lyme borreliosis is not spreading in epidemic proportions; rather it has been recently recognized, and as a novelty is being overdiagnosed by those using serologic testing. It is a real disease in certain restricted geographic locations has allowed for a proliferation of ticks and their deer hosts. Ixodes ticks do not survive long indoors and there is no evidence that infected pet dogs or cats pose a direct risk to humans. Spread of infection from dogs and cats to people is unlikely, and pets merely serve as sentinels for human infection. Dogs do not shed organisms in their urine.
Organisms multiply in the tick, eventually entering the host through tick saliva. A greater number of inoculated spirochetes increases the likelihood of infection. The number of attached ticks and correspondingly the number of inoculated spirochetes is more likely to produce clinical illness. Borrelia proliferate locally in skin at the site of tick inoculation for the duration of infection. From there they replicate and migrate through tissues. Only certain animals develop infection after tick bites. develop clinical illness, partly related to host immunity and virulence of the infecting strain of Borrelia. B. burgdorferi can persist and invade many host connective tissues. Clinical illness results from the host's own immune response. In some cases, responses to residual nucleic acid or plasmid nucleic acid may be responsible for the immunologic consequences.
Clinical illness occurs 2 to 6 months after tick exposure in experimentally infected dogs. The onset of clinical illness usually correlates with the initial increase in serum antibody titer. Acute signs are fever, shifting leg lameness, regional lymphadenomegaly and malaise. Polyarthritis is the predominant documented syndrome in dogs. Chronic nonerosive polyarthritis ensues in prolonged infections. Protein-losing glomerulopathy has been described in a few naturally infected dogs. Neurologic manifestations occur in infected people often as a later manifestation. Other syndromes reported in a few spontaneously diseased dogs have been circumstantial based on serologic data or microscopic evidence without organism isolation.
There are no specific hematologic or biochemical changes pathognomonic of borreliosis. Synovial fluid changes in dogs with borreliosis have been best substantiated with increased cell counts. Serologic reactivity to B. burgdorferi signifies exposure to the spirochete but does not prove that current clinical illness. In addition to seropositive results the animal should have a history of tick exposure with compatible clinical signs and a rapid response to antimicrobial therapy. Most commercially available assays detect antibodies to antigens of the whole organism, and as a result, can be nonspecific. For more specific analysis serial quantitative assays, or immunoblotting, or both can help determine the timing and specificity of the infection.
Various problems have been noted with serologic testing. First, there is no standardization among antigen preparations, techniques, and interpretations by different laboratories. Screening procedures are ELISA and indirect FA techniques. Cross reactions can occur with proteins from other spirochetes. False-negative antibody tests results are rare. Using immunoblotting is a supplemental measure to eliminate crossreactivity with antigens from vaccination or exposure to other closely related bacteria. In addition, a number of newly recognized novel protein antigens may also eventually serve as markers of natural infection because they are not expressed by in vitro derived organisms. Protein C6 is just such a novel antigen, that indicates reactivity to a Borrelia spp rather than another spirochete or bacterial infection. A commercially available test is available using this protein.
Culture of spirochetes from specimens of a diseased patient is the most definitive means of diagnosis but in most cases is difficult due to the low numbers of organisms present and the insensitivity of isolation methods. Special media and handling is required. PCR has been used to detect spirochete or plasmid nucleic acid in body fluids and tissue specimens. PCR results can vary according to primer selection. Nucleic acid fragments may persist in the synovial membranes after treatment, where they may perpetuate a persistent inflammatory process and make PCR results positive.
A specific diagnosis is difficult, therefore antibiotics are often given empirically in an attempt to make a therapeutic diagnosis. Clinical improvement may occur incidentally or as a nonspecific result of doxycycline. Early treatment of borreliosis may cause a reduction in antibody titers and organisms in tissues and prevention or cure of clinical lameness and joint lesions.
Most treatment is instituted for a minimum of 30 days and amoxicillin, azithromycin, ceftriaxone, and doxycycline have all been used. Unfortunately, relapse and recrudescence of infection can occur after the antimicrobial is discontinued. The persistence may stimulate chronic immune and inflammatory processes.
Nonsteroidal compounds offer relief for many of the painful arthritic complications, but judicious use is warranted because of their tendency to produce GI irritation. Glucocorticoids have also been hesitantly provided at very low anti-inflammatory dosages in the management of persistent pain and swelling from chronic arthritis that cannot be completely controlled with one or more courses of antibiotics, however, these may cause a further recrudescence because of infection exacerbation.
Whole cell and recombinant vaccines are being marketed for dogs to prevent borreliosis. The vaccines are recommended for use beginning at 9 to 12 weeks of age. Primary vaccination schedules consist of two inoculations 3 weeks apart. Vaccines given early in life, before potential exposure, offer the best means of protection. The practical and economic justification should be for dogs with the highest probability of contracting the disease, based on their geographic location, breed, and utility.
Vaccination should not be universally recommended or provided as a replacement for adequate tick control measures. Dogs should be selected for vaccination based on the geographic area in which they reside or travel and by their habits. The vaccines generate an immune response to OspA, a protein that is expressed in ticks. Therefore the vaccine should be administered prior to any exposure. One disadvantage is that vaccination produces a false-positive antibody response, which can only be resolved by immunoblotting or specific protein ELISA tests.
Supportive measures are needed to reduce the prevalence of infection in people and pets. Environmental insecticides and personal protection methods have received the most attention. Application of insecticides to relatively large environmental areas makes this control both expensive and difficult. Since tick control is so difficult in the environment, protection measures should involve use of topically applied residual adulticides and growth regulators on pets.