Borrelia burgdorferi (Bb) is a tickborne organism associated with illness in humans in Lyme, Connecticut in 1975 and the clinical syndrome was termed Lyme disease.
The organism is transmitted by Ixodes ticks, the life cycle of which has been reviewed extensively. These field ticks have a 2-year life cycle and mostly quest on vegetation in prime suburban real estate.
Although Bb infection of dogs occasionally can be transmitted transplacentally or by blood, urine or milk, tickborne transmission is considered most common. Clinical illness from Bb was first suggested in dogs in 1984 and 1985.
Most people exposed to Bb show clinical signs, including an acute illness (flulike signs, erythema migrans rash), subsequent arthritis and possibly cardiac, neurologic or chronic skin changes; only 10% are asymptomatic. In contrast, 95% of exposed dogs remain asymptomatic.
How is Canine Lyme Disease Diagnosed?
No individual test result documents clinical illness from Bb infection. So, the diagnosis of Lyme disease should include:
- Evidence of exposure to Bb,
- Clinical signs consistent with Lyme disease,
- Consideration of other differentials, and hopefully
- Response to treatment.
Evidence of exposure to Bb generally includes Ixodes tick exposure in an endemic area for Lyme or positive test results in tests for Bb. Endemic areas for Lyme disease in people have been mapped by the Centers for Disease Control.
In 2003, just 12 states (PA, NY, NJ, MA, CN, RI, WI, MD, MN, DE, VA, NH) accounted for 95% of cases, with 89% of the cases occurring in the Northeast and mid-Atlantic region and 6% in the upper Midwest. Presence of deer is not required for exposure; migratory birds such as robins can carry Ixodes ticks to previously unaffected areas.
Antibiotics Used to Treat Lyme Disease in Dogs
In humans, doxycycline, amoxicillin and ceftriaxone are considered drugs of choice. On the basis of extrapolation from results in humans and some research studies, tetracycline derivatives or amoxicillin are recommended most frequently by veterinarians for the treatment of Lyme disease.
Because differentstrains of Bb exist in the field and because it is difficult to diagnose Lyme disease in the field or induce clinical disease in experimentally infected dogs, the optimal drugs and duration of therapy are unknown. Most experts recommend administration of doxycycline at 10 mg / kg PO q24h for a minimum of 1 month.
Doxycycline was recommended most frequently because of the possibility of other coinfections (RMSF, anaplasmosis, ehrlichiosis, leptospirosis) that could respond to doxycycline and because it is inexpensive and has antiinflammatory properties.
In humans, the recommended treatment for acute Lyme disease is only 10 days of doxycycline. However, experimentally infected dogs do not develop clinical disease during the acute phase and the infection is likely to be more widespread than in humans that have acute Lyme disease with flulike signs or erythema migrans rash.
In humans, the entity known as “chronic Lyme disease” is debated and one study showed that long-term antibiotic treatment helped as much as placebo. Polyarthropathy could be immune-mediated and improve faster with added glucocorticoids.
Dogs with presumed Lyme nephropathy might require longer duration of doxycycline therapy and usually are treated with adjunctive therapies such as angiotensin-converting enzyme inhibitors, low-dose aspirin, Omega-3 fatty acids, dietary therapy and if indicated, additional antihypertensives, fluid therapy as needed and possible immunomodulating drug therapy.
Response to Treatment of Lyme Disease in Dogs
Response to treatment is expected within 1-2 days for acute Lyme arthropathy, although titers can remain positive for many months to years. The response could be the result of the self-limiting nature of the disease, inadvertent treatment of another doxycycline-responsive infection, reactive arthritis or the anti-inflammatory and antiarthritic properties of doxycycline.
However, PLN associated with Lyme disease tends to respond slowly, possibly because chronic disease changes exist before diagnosis and initiation of treatment.
Monitoring Dogs Treated for Lyme Disease
Clinical signs of disease should be monitored routinely. Most experts recommend following proteinuria in all dogs with Lyme disease (complete urinalysis, in-house E.R.D.-HealthScreen Urine Test or a urine protein / creatinine ratio).
However, the optimal recheck interval or duration is unknown. In a limited number of experimentally infected dogs, quantitative C6 antibody concentrations decreased after treatment, so evaluating pre- and 6-month post treatment quantitative C6 concentrations has been recommended by some.
However, information concerning quantitative C6 kinetics in untreated field cases has not been published and the predictive value of the test for subsequent illness is unknown. In addition, a low positive titer might not disappear with treatment, perhaps because of immune memory.
Vaccines Available for Bb Infections of Dogs
In the United States, four vaccines are currently available:
- Monovalent bacterin, available since 1990.
- Bivalent bacterin, available since 1994.
- Nonadjuvanted rOspA vaccine, available since 1996.
- Adjuvanted rOspA vaccine, available since 1999.
Response to Lyme vaccination can be measured by determining how many vaccinated dogs become ill (preventative fraction for disease) or by determining how many vaccinated dogs seroconvert (preventative fraction for seroconversion).
In one study, use of the monovalent bacterin resulted in an average preventive fraction for illness of 78% (58% in seropositive and 86% in seronegative dogs).
In a separate study, preventive fraction for seroconversion was roughly 90% for the monovalent bacterin and 60% for the rOspA vaccine. Unfortunately, in these studies, dogs were not evaluated for Bb exposure before vaccination, complicating the interpretation of the data presented.
Studies evaluating preventative fraction for disease are probably of most value but are marred by the difficulties associated with making an accurate diagnosis of Lyme disease. OspA antigen is present in both bacterins and the rOspA vaccine.
The anti-OspA antibodies generated by vaccination kill Bb within the tick. Bacterins have been purported to stimulate anti-OspC antibodies as well as anti-OspA antibody titers. So, the preventive efficacy of a bacterin might be greater than for the subunit vaccine.
However, anti-OspC antibody bands are rarely seen on Western blot tests from dogs vaccinated with bacterins. Because bacterin contains more types of antigens, there might be more risk for immune-mediated reactions and adverse effects.
Adverse Effects Associated with Administration of Lyme Vaccines?
It has been estimated that administration of Lyme vaccine is associated with <2% adverse effects. Because Lyme arthropathy and Lyme nephropathy arise at least in part from immune responses against the organism, there are concerns that vaccination might contribute to the immunopathogenesis of disease in some dogs.
This sensitization has been demonstrated for other organisms, including feline infectious peritonitis virus, caprine encephalitis virus, and ovine visna-maedi virus. In humans, antibodies against several Bb antigens react with several autoantigens (i.e., molecular mimicry), including lymphocyte function-associated antigen 1 (LFA-1), myelin, myosin, cardiolipin and thyroid, which has complicated the use of Lyme vaccines in people.
The development of a Lyme bacterin for humans was considered too risky and was discontinued. The human subunit OspA vaccine was launched in December 1998 but was taken off the market in February 2002 because of poor sales.
There were concerns about possible immune-mediated sequelae in people with HLA-DR4 haplotype, who are predisposed to chronic nonresponsive Lyme disease, which might be triggered by OspA mimicry of LFA-1. A potentially safer second-generation vaccine for humans that excludes the cross-reactive epitope is being studied.
OspA has been shown to be proinflammatory and sensitizing in rat and hamster models of Lyme arthritis, causing them to have more severe signs upon challenge or re-exposure. Nonviable spirochetes trigger the production of inflammatory cytokines in dogs.
Almost 30% of dogs with putative Lyme nephropathy had been vaccinated. OspA was found in the renal cortex of dogs with Lyme nephropathy with the use of a mouse monoclonal anti-OspA stain. OspA is not yet proven to be the antigen involved in immune complex deposition in glomeruli but Lyme-associated nephropathy is an immune complex disease.
A dog with Lyme nephropathy who became very ill a few days after its second rOspA vaccine was described. The Western blot and SNAP tests showed no evidence of natural exposure, but a very high anti-OspA antibody concentration was detected.
Because OspA is in both bacterins and rOspA vaccines, there is concern about whether it could trigger, sensitize or add antigens to antigen-antibody immune complex deposition in target tissues such as synovia or glomeruli in genetically predisposed individuals.
Should Tick Control be Maintained?
Tick control in Lyme endemic areas is not only important to prevent Lyme disease but also to prevent RMSF, ehrlichiosis, anaplasmosis, babesiosis, bartonellosis and other infections. Tick control begins with avoidance of tick habitats, careful landscaping and daily checking for ticks.
Ixodes ticks are field ticks that quest for hosts, especially from leaf litter, lowlying vegetation, overhanging branches and wooded, brushy or overgrown lawns. State and other public health websites help owners analyze their property and create relatively safe “tick-free” zones.
Tick control products often recommended include fipronil, amitraz collar, permethrin / imidacloprid and other permethrin-containing products. In some situations, combinations of products might be beneficial (e.g. the amitraz collar is frequently combined with fipronil by ACVIM diplomates).
Any of these products can be effective in reducing transmission of Bb to dogs. However, products that prevent tick attachment (e.g. amitraz collar) or repel ticks (e.g. those containing permethrin) are needed to decrease transmission of other tickborne infections.
For example, although Bb and B microti require 2-3 days of tick attachment for effective transmission, R rickettsii and A phagocytophilum potentially can be transmitted during the first day of attachment.
Theoretically, transmission times might be shorter if a tick is detached and refeeds on another host, but after a tick cements itself to begin feeding, it is unlikely to become detached with intact mouthparts.
The amitraz collar works very well to help prevent transmission of Bb. It needs to be applied tightly enough to have skin contact (not just hair), it is only active against ticks (not fleas), the chemical is washed away from the skin if swimming or bathing occurs and it should not be used on dogs receiving tricyclic antidepressant medications for behavioral disorders. It is very toxic if eaten and the veterinarian should have the antidote yohimbine in the office.
Fipronil has been shown to decrease transmission of Bb and E canis. It is not washed away by swimming or bathing, kills fleas as well as ticks (but not until the second day of attachment) and can be used safely on cats.
Permethrin / imidacloprid has been proven to help prevent transmission of A phagocytophilum and Bb. It is not washed away by swimming or bathing with mild shampoo, repels and kills ticks as well as fleas and mosquitoes, but is toxic to cats.
Image credit: Wikimedia.