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In this VetGirl podcast, we discuss transmission, pathophysiology and testing for Lyme disease. Lyme disease is caused by the spirochete Borrelia burgdorferi (Bb). While Bb can be transmitted by urine, milk, and blood, the most common transmission is likely via tick infestation by hard-shell deer ticks (e.g., Ixodes scapularis or other related Ixodes species). Ixodes ticks have a 2-year life cycle and hatch in the spring (into larvae). A female tick lays approximately 2000 eggs. Larvae become infected with Bb when feeding on white-footed mice, which are persistently infected, but often remain unaffected or asymptomatic. The larvae molt into nymphs that feed on new hosts. While nymphs are less effective vectors than adult ticks, they can still infect their hosts within the four-day feeding period. Likewise, nymphs can become infected when feeding on an infected animal. In the fall, nymphs molt to adults, with 50% of adult ticks in the Northeast estimated to be carrying Bb. Once the tick attaches and feeds, the spirochetes (which live in the midgut of the tick) begin to migrate to the salivary gland and enter the host. Risk of infection is believed to be minimal during the first 12 hours of feeding. Typically, transmission of Bb occurs during prolonged feeding periods (typically > 48 hours).
While in the tick, Outer Surface Protein A (OspA) allows Bb to remain anchored in the midgut. During feeding, a trigger signals down-regulation of OspA protein and up-regulation of OspC expression (e.g., this may be due to a temperature increase by the host). OspC allows Bb to become established within the host and avoid detection by the immune system.
Following a tick bite, local skin infestation occurs, progressing to infection within the joint capsules, muscles, connective tissue, and lymph nodes. Experimentally, incubation of Bb takes anywhere between 2-5 months. Bb persists in the body for a long duration, and can be found in the joints, skin, connective tissue, muscle, lymph nodes, and kidneys. Less commonly, Bb can be found in the blood, synovial fluid, or CSF, but this is rare.
Historically, testing for Lyme was done based on antibodies against Bb via enzyme-linked immunosorbent assays (ELISA) and indirect fluorescent antibody (IFA) techniques. Culture and PCR can potentially be performed, but are typically very difficult (due to low number of organisms) or complicated. With certain tests, false positive results may be seen due to vaccination or cross-reaction to similar organisms. Positive tests can be confirmed with Western blot or ELISA looking specifically against certain proteins (recombinant Osp C or C6). Western blot can be used to differentiate seropositive dogs from vaccine. This technology is not commonly utilized as compared to a decade ago; this is typically only recommended if the vaccinal status is important to the veterinarian.
Currently, the most common commercially available tests for Lyme test for antibodies against Lyme C6 peptide. These include: SNAP 3Dx and 4Dx and the quantitative C6 antibody test (both available through Idexx Laboratories). As C6 is expressed only during infection, a positive result is consistent with nature exposure or ongoing infection. While quantitative C6 levels are beneficial, they are still unspecific. The elevation in C6 levels does appear to correlate with circulating anti-Lyme immune complexes, and quantitative C6 levels is thought to decrease with antibiotic therapy.
Newer serologic testing may become more utilized, including Cornell’s newest multiplex Multiplex assay (a quantitative serologic test which includes a Western blot and quantitation of antibodies directed against OspA, OspC, and OspF during acute or chronic infection), Antech’s newest serologic test AccuPlex4 (which identifies antibodies to 5 antigens) and Abaxis ELISA quantitative Lyme test. For further information on testing, the reader is referred to additional resources.
References available upon request.