treatment not indicated for asymptomatic lyme postive dog

Issues involving physical examinations and testing. Questions, answers, theories, and evidence.
When are examinations and testing necessary?

treatment not indicated for asymptomatic lyme postive dog

Postby guest » Fri Oct 31, 2003 1:04 pm

of the American Veterinary Medical Association
© 2000-2003 American Veterinary Medical Association.
All rights reserved.
Journal Home | Table of Contents | Get Acrobat Reader | Logout
November 1, 2003 (Volume 223, No. 9)
Zoonosis Update
Lyme borreliosis
Curtis L. Fritz, DVM, MPVM, PhD, DACVPM, and Anne M. Kjemtrup, DVM, MPVM, PhD *


In 1976, public health officials investigated a cluster of suspected juvenile rheumatoid arthritis cases that occurred among residents of Lyme, Connecticut, and neighboring communities.1 More than 50 residents were evaluated for recurrent, usually short-lived (1 to 2 weeks’ duration) attacks of swelling and pain in a few large joints. Clinical, laboratory, and epidemiologic evidence failed to substantiate an immune-mediated pathogenesis. An arthropod-transmitted bacterium was suspected as the etiologic agent, as many patients also had an expanding, red, annular rash that resembled erythema chronicum migrans (a lesion identified in Europe in the early 20th century that was associated with tick bites and was responsive to penicillin).2,3 An infectious cause for the disease was confirmed when spirochetal bacteria isolated from Ixodes dammini (now considered I scapularis) ticks4 and blood, CSF, and other tissues of patients were shown to be identical.5-7 The bacterium was named Borrelia burgdorferi, and the multisystemic symptoms associated with infection were called Lyme disease or Lyme borreliosis (distinguishing it from other forms of borreliosis caused by other Borrelia spp). Subsequently, B burgdorferi was identified in ticks in numerous regions of the United States, and infection was associated with clinical illness in nonhuman animals, including dogs and horses.

Findings of experimental, ecologic, epidemiologic, and clinical research conducted in the last 2 decades have tremendously expanded our scientific understanding of Lyme borreliosis. The genome of the causative spirochete has been sequenced, ecologic dynamics of its maintenance in nature have been described, effective diagnostic and treatment protocols have been established, and vaccines have been developed. However, as coverage by the popular media of this complex disease is often a farrago of fact, fallacy, and opinion, familiarity with the current scientific body of knowledge on Lyme borreliosis is critical to enable practicing veterinarians to appropriately address concerns of their clients and to effectively manage animals with the disease.


The genus Borrelia is in the order Spirochetae, which contains genera that are pathogenic to humans and other animals, such as Leptospira and Treponema, to which belong the agents of leptospirosis and syphilis, respectively.8 Like other spirochetes, Borrelia spp are spiral shaped, gram-negative, and have an outer sheath encasing endofibrils.9 Unique to Borrelia spp are a singular linear chromosome (with additional linear and circular plasmids) and life cycles that require both arthropod vectors and mammalian hosts.10

Borrelia spp may be generally grouped into those that cause a relapsing fever-type illness (eg, B hermsii) and those that cause Lyme borreliosis.10 Spirochetes in the relapsing fever group typically utilize soft (ie, argasid) ticks as their vector. Some relapsing fever-type Borrelia spirochetes have recently been recovered from hard (ie, ixodid) ticks,11,12 but the pathogenic potential of these isolates remains unknown. The Lyme borreliosis Borrelia complex is often divided into B burgdorferi sensu stricto (B burgdorferi ss; those Borrelia genetically identical to the type-strain B31, recovered from an I scapularis tick from Long Island, NY13) and B burgdorferi sensu lato (B burgdorferi sl; all other closely related Borrelia). Borrelia burgdorferi ss, B afzelii, and B garinii cause Lyme borreliosis in humans and animals in Europe and Japan.14,15 Only B burgdorferi ss is recognized as a cause of Lyme borreliosis in the United States.16 Recently, B bissettii was recovered from a human patient in Slovenia17; although B bissettii has been identified in ticks in the United States,18 no infection of mammals with this bacterium has been documented.

A linear chromosome and 21 plasmids comprise the genome of the B burgdorferi B31 type strain.19 The genome codes for over 150 lipoproteins, some of which are key to the spirochete’s ability to transfer dbetween the tick vector and mammalian host. Several lipoproteins that localize to the outer surface of the spirochete (outer surface proteins [Osps]) are important in the transmission of Borrelia spirochetes to a vertebrate host and the host’s subsequent immune response. While in the gut of the tick, the spirochete expresses chiefly Osp A.20 The spirochete switches from Osp A to Osp C expression during a period of accelerated reproduction at the beginning of the tick’s blood meal.20 The variable major protein-like sequence expressed (VlsE) Osp has an invariable region conserved across many species of Borrelia and is highly immunogenic in mice, dogs, and primates.21-24 An understanding of the kinetics of these and other expressed proteins (eg, decorin binding proteins and flagellin) is important for diagnosis (measurement of mammalian antibody response to bacterial proteins) and prevention (identification of potential vaccine candidates) of Lyme borreliosis.

Ecology and Transmission

Borrelia burgdorferi is maintained in nature in a cycle that involves hard ticks of the Ixodes genus as vectors and small mammals or birds as reservoir hosts. Ixodes spp are 3-host ticks that attach to a host and take a blood meal at each life stage (larva, nymph, and adult), then drop off the host to molt in the environment.25 Larval and nymphal stages of Ixodes spp are found in moist, protected areas, such as under leaf litter in humid hardwood forests. The principal hosts of immature Ixodes ticks are small rodents, lizards, and ground-feeding birds. The immature ticks typically require 2 to 4 days of attachment to the host to complete a blood meal. At the adult stage, an Ixodes tick climbs to the tips of grasses, where it waits (or quests) for a large mammal host to brush against it. Adult ticks feed typically for 5 to 7 days. The abundance and activity of each life stage differ by season and are dependent on weather, sunlight, and host availability.26,27

In the northeastern and upper midwestern United States, I scapularis (commonly known as the deer tick or black-legged tick) is the principal vector of B burgdorferi. Larval and nymphal I scapularis acquire B burgdorferi primarily from infected white-footed mice (Peromyscus leucopus).5,28,29 Borrelia burgdorferi is transmitted transstadially from larva to nymph and from nymph to adult. Ixodes scapularis that become infected as larvae or nymphs can subsequently transmit the agent as nymphal and adult ticks when they feed in the summer and fall, respectively.30 Transovarial transmission (adult female to egg) is rare and inefficient.25,31,32 White-tailed deer (Odocoileus virginianus) are the preferred hosts of adult I scapularis; however, because they are poor reservoirs for B burgdorferi,33 they serve chiefly to maintain the population of ticks and not that of B burgdorferi. Furthermore, birds may introduce infected I scapularis into previously nonendemic areas or serve as reservoir hosts for B burgdorferi.34,35

The transmission cycle of B burgdorferi in the western United States is slightly more complicated. The western black-legged tick, I pacificus, is the tick vector, but it is not directly involved in the maintenance cycle. The spirochete is maintained in an independent enzootic cycle involving I spinipalpis as the arthropod vector36,37 and dusky-footed woodrats (Neotoma fuscipes) and kangaroo rats (Dipodomys californicus) as the rodent reservoirs.38 Larval and nymphal I pacificus can acquire B burgdorferi when they occasionally feed on these infected rodents. After molting to nymphs and adults, which feed in the spring and fall, respectively, infected ticks can transmit the bacteria to humans and domestic animals.39,40 Larval and nymphal I pacificus prefer to feed on lizards, particularly the western fence lizard (Sceloperus occidentalis). Lizards contain a borreliacidal factor in their blood that effectively purges B burgdorferi infections from feeding ticks.41 This is 1 explanation for the lower percentage of infected adult ticks among I pacificus in the western United States (typically 1 to 6%),42,43 compared with the percentage among I scapularis in the eastern United States (typically > 50%).44 Birds also may play a role in the transmission cycle of B burgdorferi in specific habitats in the western United States.45

The multiple species of Borrelia that exist worldwide and the broad host range of their vector ticks contribute to complex life cycles for agents of Lyme borreliosis in other areas of the world.46 Each of the Borrelia genotypes in Europe is associated with a specific vertebrate host: B burgdorferi ss and B afzelii with small rodents47,48 and B garinii with birds.48,49 In Japan, I persulcatus is the primary vector tick that maintains B afzelii, B garinii, and B burgdorferi ss in enzootic cycles; this species of tick also transmits these agents to humans and domestic animals.50 All 3 genospecies of B burgdorferi sl have been documented in both rodents and birds.50-52

In all vector ticks, the Borrelia spirochetes undergo both quantitative and qualitative changes prior to and during an infected tick’s blood meal. When a larval or nymphal Ixodes tick ingests B burgdorferi from an infected host, the spirochetes localize to the gut and multiply until the tick molts, at which time the number of spirochetes decreases greatly, resulting in questing nymphs or adults with few spirochetes.53,54 Once the infected nymphal or adult tick attaches to a new host, spirochetes multiply rapidly in the lumen of the midgut, and there is a change in Osp expression from Osp A (hypothesized to be an adhesion for spirochete attachment to the midgut)55 to Osp C.56 The expression of Osp C is subsequently decreased in spirochetes that are in the salivary glands of ticks.20 Thus, Osp C is thought to facilitate the transmission step wherein the spirochetes migrate from the midgut to the hemocele and finally to the salivary glands, from which they can be transmitted to the host.20 The spirochetes’ development and migration take approximately 2 to 3 days; therefore, transmission to the mammalian or avian host is relatively inefficient until 48 hours after tick attachment.57 Feeding by ticks is a dynamic process involving the release of many immunologically active substances from the ticks’ salivary glands. The host’s initial immune response temporarily delays the spirochetes’ migration from the bite site,58 but subsequent downregulation of proinflammatory factors in the host’s skin permits the pathogen to disseminate to other organ systems.27


In 1982, the Centers for Disease Control and Prevention (CDC) initiated surveillance for Lyme borreliosis in humans in the United States. In 1991, the Council of State and Territorial Epidemiologists adopted a standardized surveillance case definition and added Lyme borreliosis to the list of nationally notifiable diseases. In 2000, 17,730 cases of Lyme borreliosis were reported nationwide.59

Although cases of Lyme borreliosis have been reported from 49 states, the multiple ecologic factors required to maintain an effective enzootic cycle translate to a regional geographic distribution of Lyme borreliosis. In 2000, reported incidence of human Lyme borreliosis ranged from 0 cases/100,000 persons in 6 states (eg, Montana) to 110 cases/100,000 persons in Connecticut. Between 1995 and 2000, reported incidence of Lyme borreliosis exceeded 10 cases/100,000 person-years in 7 states (Connecticut, Delaware, Maryland, New Jersey, New York, Pennsylvania, and Rhode Island). Each year, > 90% of reported cases occur among residents of the northeastern and upper-central states. In these same areas, serologic evidence of exposure to B burgdorferi has been observed in a high proportion of dogs (in some instances > 50%).60,61 In contrast, seroprevalence estimates among clinically normal dogs in the southern and western United States have been uniformly low (≤ 3.5%) and generally within the margin of error of false-positives for the assays used.62-64

Risk of infection with B burgdorferi is correlated with the opportunity of being bitten by an infected tick and dependent on the density of vector ticks in an endemic area, the proportion of ticks infected, and the duration and nature of the susceptible host’s activities in that area. Most cases of Lyme borreliosis are believed to be acquired from the bites of nymphal ticks, which are most abundant in the late spring and early summer. In 1 study,65 > 50% of humans reported to have Lyme borreliosis in an endemic county of New York experienced onset of illness in June or July. Residence in or near areas of relatively undisturbed and dense vegetation poses the greatest risk.65 Outdoor recreational activities in similar vegetated areas can also increase chance of infection.66 Persons whose occupation places them in wooded areas (eg, forestry or wildlife workers) may occasionally be exposed to infected ticks.67 Dogs and horses that have ongoing access to densely vegetated areas near their home (peridomestic exposure) or occasional recreational access to these same areas are at equal or greater risk of becoming infected, compared with humans.68

Signs and Symptoms

Humans—The signs and symptoms of Lyme borreliosis in humans are commonly categorized as early localized, early disseminated, or late disseminated manifestations.69,70 Early localized Lyme borreliosis is synonymous with erythema migrans, which is a red, expanding rash that occurs 1 to 36 days following a bite from an infected tick.71 Erythema migrans appears most often at the site of the tick bite, expands over the course of several days, often clears centrally, and resolves spontaneously without specific treatment. Nonspecific flu-like symptoms such as fever, headache, fatigue, and muscle and joint pain often accompany or follow erythema migrans. As the erythema migrans resolves, spirochetes complete their migration through the skin and enter other organ systems, where they cause symptoms referable to the tissues invaded. Objective manifestations associated with early disseminated Lyme borreliosis include meningitis and cranial nerve deficits (most commonly a unilateral facial nerve palsy)72 and atrioventricular conduction deficits.73 If not treated, the disease will progress in some patients to late disseminated symptoms, characterized by large joint oligoarthritis74 and central nervous dysfunction, commonly encephalopathy and radiculopathies.75

Dogs—Surveillance studies have detected serologic evidence of exposure to B burgdorferi in a variable but large percentage (25 to 90%) of dogs in endemic areas.76-80 However, not all infected dogs will develop clinical signs of Lyme borreliosis, and younger dogs are more likely to do so than older dogs.81 Furthermore, dogs appear to lack the spectrum of clinical signs reported in humans with Lyme borreliosis, despite occasionally extensive systemic dissemination of spirochetes.82 The clinical manifestations of Lyme borreliosis in dogs have been previously reviewed.83 Briefly, 2 to 5 months after being infected with B burgdorferi, dogs most commonly develop lameness, frequently with accompanying fever and anorexia.81 Arthritis is usually evident and confined to a single joint, most commonly the carpus or tarsus. In dogs experimentally infected by a single inoculation of B burgdorferi, arthritis was self-limited, although recurrent episodes of 3 to 6 days’ duration occurred for up to several weeks.81,84 The potential for progression and persistence of arthritis in naturally or repeatedly exposed dogs is not as well described. A distinctive renal syndrome attributed to B burgdorferi infection in dogs has been described.85,86 Renal manifestations of Lyme borreliosis are histologically characterized by glomerulonephritis, tubular necrosis, and interstitial lymphoplasmacytic inflammation that are associated with a rapidly progressive and frequently fatal glomerular disease. Although B burgdorferi spirochetes have been identified in renal tissue,86 the pathogenesis of B burgdorferi-associated renal disease is not well understood. In some dogs, CNS dysfunction87,88 and heart block secondary to myocarditis89 have been attributed to B burgdorferi infection.

Horses—Antibodies against B burgdorferi have been detected in ≥ 20% of horses residing in endemic areas.90-92 However, clinical illness associated with B burgdorferi infection appears to be uncommon in horses. No histologic changes or clinical signs were observed in 7 ponies experimentally infected with B burgdorferi, although spirochetes were detected in tissues and specific antibody was detected in serum.93 Clinical signs attributed to infection with B burgdorferi in horses include lethargy, low-grade fever, and stiffness and swelling in distal appendicular joints.91 Borrelia burgdorferi spirochetes were detected in brain tissue from a horse with neurologic signs suggestive of encephalitis94 and in the anterior chamber of the eye in a pony with uveitis and carpal synovitis.95

Other domestic animals—Parasitism by infected Ixodes spp and detection of antibody against B burgdorferi have been reported in cats,96 but the clinical significance of exposure to B burgdorferi among cats is uncertain. In 1 study in a Lyme borreliosis-endemic area,96 high titers to B burgdorferi were detected in cats with joint lameness; however, the proportion of cats with antibodies against B burgdorferi did not differ between cats with lameness only and cats with non-specific febrile illness.

Serologic evidence of B burgdorferi infection has been detected in large and small domestic ruminants,97,98 but it remains undetermined whether the organism causes clinical disease in these species. Detection of antibody against B burgdorferi in serum or synovial fluid was associated with lameness and joint swelling among cattle in an endemic region.99,100 Attempts to experimentally infect cattle with B burgdorferi suggest they have a low susceptibility.101


Diagnosis of Lyme borreliosis can be made on the basis of history of exposure to Ixodes ticks in an endemic area, compatible clinical signs, laboratory evidence of infection, consideration and exclusion of other diseases, and, possibly, response to antimicrobial treatment.83,102 Laboratory results alone are not prima facie evidence of infection but must be interpreted with regard to the pretest probability of the disease existing in the patient.103,104 Establishing the prior probability of Lyme borreliosis is particularly important for species such as dogs that lack a pathognomonic sign of infection like the erythema migrans rash in humans.

Given the fastidious growth requirements of B burgdorferi, attempts to culture spirochetes from blood or other tissues are difficult and most often unrewarding. Thus, most commercially available clinical laboratory tests rely on detection of antibodies in serum. Serologic assays for IgM, IgG, or combined immunoglobulin against B burgdorferi are available through most commercial laboratories. The sensitivity of serologic assays is directly dependent on the kinetics of the immunologic response following infection. In humans, serum concentration of IgM against B burgdorferi increases within 2 to 3 weeks of infection, peaks around 3 to 6 weeks, and then gradually decreases.105 Changes in serum IgG concentration lag that of IgM; IgG concentration begins to increase 4 to 6 weeks after infection, peaks at 6 to 8 weeks or later, and remains high for months to years.6 In most or all dogs, IgG seroconversion occurs prior to onset of clinical signs, usually within 4 to 6 weeks after exposure.81,102

Enzyme immunoassays (EIAs) and immunofluorescent assays (IFAs) are the most commonly available serologic tests; however, despite their high sensitivity, these tests generally have poor specificity.104 Unstandardized and variable procedures for manufacture and validation of commercial test kits further reduce the reliability of these assays.106,107 In a laboratory proficiency study108 in which seroimmunologic tests for 14 different pathogens were evaluated, assays for B burgdorferi antibody had the poorest correlation between reference and nonreference laboratories. To improve test reliability for human patients, the CDC currently recommends a 2-step serodiagnostic strategy: an initial EIA or IFA, with specimens that yield positive or equivocal results for B burgdorferi further tested by western immunoblotting for IgM or IgG antibody, whichever is appropriate for the patient’s stage of illness.109

In dogs, the immunoblot band pattern does not merely enhance test reliability but provides indispensable information to differentiate serologic responses induced by natural infection with B burgdorferi from those produced by vaccination.77 Dogs that are vaccinated react most strongly to spirochetal proteins in the 31- to 34-kd range that correspond approximately to the Osp A , whereas naturally infected dogs show minimal reactivity to these proteins.110,111 Dogs and humans that are naturally exposed have a broad immunologic response to numerous B burgdorferi proteins between 15 and 100 kd; the number of immunoblot bands tends to increase with the progression of the disease.102,112-114 Although uniform interpretation criteria for immunoblots have been determined for diagnosis of Lyme borreliosis in humans,109,115 various strategies have been proposed for sera from dogs,102,110,116 but scientific consensus has not been reached.

Recently, an EIA test kit became commercially available for in-office diagnosis of Lyme borreliosis in dogs.a This assay uses a synthetic peptide, C6, as the antigen; this peptide is based on the sixth invariable region (IR6) in the VlsE Osp of B burgdorferi.117 The IR6 is greatly conserved among B burgdorferi strains and highly immunogenic in dogs.24 Although this assay shows promise,118,119 field studies that have validated its performance in large numbers of clinically well-characterized dogs have yet to be reported.

Detection of antibody against B burgdorferi is not definitive evidence of active or incipient Lyme borreliosis nor an indication of the need for treatment.78 Serologically detectable anti-B burgdorferi IgG may persist for months, years, or indefinitely following infection and resolution of clinical disease.79,120 For this reason, although serologic screening of scientifically selected populations may yield useful epidemiologic information, it is generally uninformative for clinically normal individuals (eg, those with a recognized tick bite that have no clinical signs of illness). In highly endemic areas where dogs may be regularly bitten by infected ticks, serologic testing cannot differentiate between dogs with active Lyme borreliosis and those with persistent antibodies from an earlier exposure. One study79 found that the prevalences of serum antibody against B burgdorferi did not differ between healthy dogs (89.6% seropositive) and those with joint or limb disorders compatible with Lyme borreliosis (92.9% seropositive). Serodiagnostic testing should be reserved for dogs with a history and clinical presentation that are highly suggestive of active Lyme borreliosis.


Although erythema migrans resolves spontaneously in most humans with Lyme borreliosis,121 the potential for symptoms to progress from mild flu-like illness to severe neurologic or arthritic disease underscores the need for prompt recognition and appropriate treatment. Even before the bacterial cause of Lyme borreliosis was confirmed, antimicrobials were observed to improve the outcome during all stages of disease.122 Numerous clinical trials and case series have demonstrated the efficacy of oral administration of doxycycline or amoxicillin for 14 to 21 days for the treatment of eyrthema migrans and other early symptoms.122-127 Uncomplicated arthritis associated with Lyme borreliosis can be successfully treated with oral or IV administration of doxycycline or amoxicillin for 28 days.128 Intravenous administration of ceftriaxone for 14 to 28 days is recommended for patients with any neurologic manifestations.129-131 Response to treatment may be slow and inversely correlated with duration and severity of symptoms.

As in humans with Lyme borreliosis, antimicrobial treatment in dogs can accelerate clinical resolution and reduce the chance of recrudescent Lyme borreliosis. Following experimental inoculation of dogs with B burgdorferi, spirochetes were repeatedly cultured from skin biopsy specimens prior to treatment; after 30 days of azithromycin (25 mg/kg [11.4 mg/lb], PO, q 24 h), ceftriaxone (25 mg/kg, IV, q 24 h), or doxycycline (10 mg/kg [4.5 mg/lb], PO, q 12 h), examination of biopsy specimens from multiple tissues failed to yield any viable spirochetes.84 In a similar study132 of experimentally infected dogs, administration of immunosuppresive dosages of corticosteroids led to a recurrence of severe lameness in 2 of 2 dogs that had not received antimicrobial treatment but in none of 12 that received antimicrobial treatment.

Treatment is rarely indicated for dogs with serologic evidence of B burgdorferi exposure in the absence of clinical disease. As stated previously, although the number of seropositive dogs in an endemic area can be high, the proportion of these that will develop clinical signs is low. Serologic status determined at a singular point in time is not predictive of future illness; a study78 of dogs without signs of illness in an endemic area of Connecticut showed that the incidence of signs of Lyme borreliosis over a 20-month observation period did not differ between dogs that were initially seropositive and those that were seronegative. A course of antimicrobials prescribed solely on the basis of arbitrarily timed serologic findings is unlikely to reduce morbidity or to be effective in preventing reexposure in an endemic area.

Prevention and Control

The foundation for preventing Lyme borreliosis in domestic animals and humans is the reduction of the risk of tick bites at the environmental or individual level. Avoiding tick bites prevents not only Lyme borreliosis but also other tick-borne diseases, such as ehrlichiosis and babesiosis, in regions where these pathogens are present. A knowledge of the ecologic requirements for the tick-borne diseases that are present in a given area is critical toward selection and implementation of the most effective integrated prevention strategies.133 In areas where Lyme borreliosis is a peridomestic risk, tick density may be managed locally by targeting animal hosts or by modifying the environment to decrease the availability of tick habitat. Products that kill or repel ticks can reduce the likelihood that ticks will attach to pets. Induced immunity through vaccination may provide additional protection in some highly endemic areas.

Some of the most effective approaches to environmental control of ticks target the reservoir animals that sustain I scapularis populations. The use of permethrin-treated cotton balls as nesting material decreased the load of immature I scapularis on white-footed mice.134 Although the number of ticks that infested rodents appeared to decrease with this method over a 3-year period, the number of questing ticks did not differ between treated and untreated sites.135 The concept of targeting small mammals for tick control was developed commercially as rodent bait boxes that contain fipronil.b The success of this targeted approach depends on limiting access of alternative tick hosts to treated areas; therefore, large-scale implementation may be impractical. Bait boxes have not proven as effective in the reduction of tick numbers in the western United States, probably because I pacificus feeds on a wider range of vertebrate hosts, compared with I scapularis.136 White-tailed deer have also been effectively targeted in attempts to control adult I scapularis. Feeding stations were designed whereby deer that rub against 4 amitraz-impregnated posts transfer acaracide onto their heads and necks (regions of the body where I scapularis ticks most frequently attach on deer).137 In areas where these feeding stations were deployed, the number of adult I scapularis observed on deer carcasses was less than that observed on carcasses in areas without the feeding stations.

Environmental approaches to tick control (eg, pesticide application and landscape modification) are designed to decrease suitable habitat for ticks. Acaracides can be a useful adjunctive treatment on limited spatial scales, but applications must be targeted to specific areas and timed appropriately in order to maximize control and minimize excess pesticide residue in the environment.138,139 Fencing that excludes deer (ie, > 2 m in height) can be constructed around small areas such as a residential property to decrease the number of adult Ixodes ticks deposited and thus reduce the number of tick progeny in the environment.140 A swath of mulch or other inert material placed between wooded areas and lawns can provide an effective impediment to tick movement into areas where they are likely to encounter people and pets.

Control of ticks on dogs is facilitated by the availability of collars impregnated with permethrin or amitraz and topical solutions containing fipronil,c permethrin,d or selamectin.e The myriad of recently developed ectoparasiticides and their control efficacy have been reviewed.141 Amitraz-impregnated collars appear to be more effective at interrupting the tick life cycle and longer acting than topical applications of fipronil.142 The appropriate use of amitraz-impregnated collars on dogs can provide effective tick control and thereby prevent infection with B burdorferi.143 Amitraz is also available as a spray or dip for tick control on domestic livestock; its use is contraindicated in horses, pregnant or nursing bitches, and cats. Selamectin is effective in control of brown dog ticks (Rhipicephalus sanguineus) and American dog ticks (Dermacentor variabilis) on dogs and is safe to use on cats. However, in a study144 in Europe, topical application of permethrin was more effective at repelling European Ixodes spp, compared with topical application of selamectin. Topical administration of permethrin products is contraindicated for cats.141

Ideally, owners should examine their pets after visiting tick-infested areas. Although a thorough inspection may not reveal all ticks, prompt removal of those that are found can prevent most tick-borne diseases because there is often a lag period between the initiation of feeding by the tick and pathogen transmission. Borrelia burgdorferi spirochetes are not efficiently transmitted to the host until 24 to 48 hours after the tick begins to feed.145 Ticks should be removed with fine-pointed forceps by grasping the tick at the mouth-parts as close to the skin as possible and pulling gently, firmly, and perpendicularly away from the skin. A variety of commercial productsf-h are available that can be effective in removal of nymphal and adult ticks when used properly.146 Crushing the tick during the removal procedure does not appear to increase likelihood of transmission of Borrelia spirochetes.145 After the tick’s removal, the bite site should be washed with an antiseptic compound. The efficacy of antimicrobial prophylaxis for dogs after tick bites is unknown. When considering a prophylactic course of antimicrobials for a tick bite, veterinarians should carefully weigh the risk of tick-borne disease versus the risk of an adverse drug reaction.

Two whole-cell B burgdorferi bacterin vaccines are available for canids.i,j An initial efficacy study147 by 1 of the manufacturers indicated that the vaccine protected laboratory dogs against the development of lameness following syringe-delivered challenge with several different strains of B burgdorferi. Results of a large-scale field study61 indicated that the vaccine was safe and effective at preventing development of Lyme borreliosis in many breeds of dogs. A survey148 of dogs from a single practice in a Lyme borreliosis-endemic area showed a higher prevalence of seroreactivity to the B burgdorferi C6 antigen among unvaccinated dogs (64%), compared with the prevalence among dogs that had received annual vaccination with the whole-cell bacterin (5%). Results of a study149 involving a model of Lyme borreliosis in hamsters indicated that immunity that develops subsequent to administration of the bacterin is specific to B burgdorferi infections (ie, not protective against B afzelii or B garinii) and short-lived (< 1 year). Findings of a similar study150 suggested that immune-mediated arthritis was associated with the B burgdorferi bacterin; however, it remains uncertain whether there is an association between immune-mediated arthritis in dogs and use of this vaccine.

A recombinant subunit vaccine that contains the highly immunogenic Osp A is the next generation of vaccines available for prevention of Lyme borreliosis in dogs.k Because Osp A is expressed by B burgdorferi primarily in the gut of ticks prior to feeding, immunity against Osp A is thought to function through complement-mediated lysis of B burgdorferi in the tick’s gut soon after the tick begins its blood meal.151 In a study152 involving use of the subunit vaccine in dogs, protection against B burgdorferi transmission by naturally infected I scapularis was demonstrated. A recombinant B burgdorferi vaccine for horses, also based on the Osp A antigen, has been shown to be safe and protective but is not yet commercially available.153

Recommended schedules for both the bacterin and recombinant vaccines require administration of an initial dose, a booster vaccination 2 to 4 weeks later, and annual revaccination.147,152 The decision to vaccinate against B burgdorferi should be based on an assessment of each dog’s risk of exposure to B burgdorferi, including factors such as the regional endemicity of Lyme borreliosis and the dog’s likelihood of contact with Ixodes spp.154 Vaccination should target at-risk dogs prior to exposure to B burgdorferi, because limited information is available regarding the safety and efficacy of the vaccine after administration to previously exposed dogs.61 Clients who choose to have their dogs vaccinated against B burgdorferi should be cautioned that the vaccine confers no protection against other tick-borne diseases (eg, ehrlichiosis), and therefore acaracides or other measures for reducing tick bites should nonetheless be adopted. These same factors should be considered for vaccination of horses when a commercial product becomes available.

Public Health Considerations

Recognition of ixodid ticks on pets provides the veterinarian an opportunity to provide a public health service by alerting owners to their own potential exposure to tick-borne diseases. Clients should be assured that dogs with Lyme borreliosis do not serve as a direct or indirect source of infection for humans. Although ticks may rarely acquire B burgdorferi from infected dogs,155 dogs are not efficient maintenance reservoirs of these spirochetes and are only incidental hosts for larval and nymphal Ixodes spp that serve as vectors for Lyme borreliosis. However, pets may incidentally acquire ticks from outside and transport them to the peridomestic environment before the ticks have had an opportunity to attach. Detection of a tick on a client’s pet should motivate a discussion on appropriate acaracide use.

Similar to strategies for domestic pets, prevention of tick-borne diseases in humans relies on tick-bite avoidance behaviors and practices. Standard recommended precautions to take while in areas inhabited by ticks include the following:

Avoid areas where ticks are present.

Wear long pants and long-sleeved shirts when in tick habitats. Tuck pant legs into boots or socks and tuck shirt into pants.

Wear light-colored clothing so ticks can be easily seen.

Apply a repellent registered for use against ticks; always follow directions on the product label.

Inspect oneself and children frequently for ticks while in tick habitat.

Stay in the middle of the trail; avoid trail margins, brush, and grassy areas.

Once out of tick habitat, thoroughly check entire body for ticks. Parents should examine their children, especially on the scalp and hairline.

In endemic areas where exposure to ticks is peridomestic (eg, the eastern United States), tick-bite prevention measures must be part of a regular, daily routine. Techniques for removal of ticks are the same for humans and pets. In humans, prophylactic administration of antimicrobials after a tick bite is not warranted in most cases because the risk of adverse reaction to the antimicrobial agent is usually greater than the risk of disease. However, a single 200-mg dose of doxcycline within 72 hours after a documented I scapularis tick bite was shown to be effective in preventing Lyme borreliosis among persons in a hyperendemic area in New York.156 In endemic regions, a recombinant Osp A vaccine approved for use in humans was 76% effective in preventing development of Lyme borreliosis among study subjects who received the full 3-dose series.157 However, this vaccine is no longer commercially available.158


Despite more than 25 years’ experience with Lyme borreliosis, much remains to be learned about this complex zoonosis. Practicing veterinarians, particularly those in the northeastern and upper midwestern states, where Lyme borreliosis is highly endemic, should be familiar with the ecologic features and typical clinical signs of Lyme borreliosis. Interpretation of signs and serologic test results should be made with consideration of the regional prevalence of Lyme borreliosis and the animal’s opportunity for exposure to infected Ixodes spp. The availability of recently marketed topical acaracides is a valuable adjunctive measure in prevention of Lyme borreliosis. A maximally effective prevention strategy should include consideration of environmental modification, activity restrictions, routine examinations for ticks, prompt removal of attached ticks, and vaccination. Technologic advances, such as the C6 EIA and the Osp A recombinant vaccine, offer the promise of additional tools for the clinical management and prevention of this tick-borne zoonosis.

aSNAP 3Dx, IDEXX Laboratories, Westbrook, Me.
bMaxforce Tick Management System, Aventis Environmental Science, Montvale, NJ.
cFrontline, Merial, Duluth, Ga.
dBiospot, Farnam Pet Products, Phoenix, Ariz.
eRevolution, Pfizer Inc, New York, NY.
fTicked-Off, Ticked-Off Inc, Dover, NH.
gTick Plier, Sawyer Products, Safety Harbor, Fla.
hPro-Tick Remedy, SCS Ltd, Stony Point, NY.
iGalaxy Lyme, Schering-Plough Animal Health, Union, NJ.
jLymeVax, Fort Dodge Animal Health, Overland Park, Kan.
kRecombitek Lyme, Merial, Duluth, Ga.



1. Steere AC, Malawista SE, Snydman DR, et al. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three Connecticut communities. Arthritis Rheum 1977;20:7–17.

2. Thyresson N. Historical notes on skin manifestations of Lyme borreliosis. Scand J Infect Dis Suppl 1991;77:9–13.

3. Burgdorfer W. Discovery of the Lyme disease spirochete and its relation to tick vectors. Yale J Biol Med 1984;57:515–520.

4. Oliver JH Jr, Owsley MR, Hutcheson HJ, et al. Conspecificity of the ticks Ixodes scapularis and I. dammini (Acari: Ixodidae). J Med Entomol 1993;30:54–63.

5. Burgdorfer W, Barbour AG, Hayes SF, et al. Lyme disease—a tick-borne spirochetosis? Science 1982;216:1317–1319.

6. Steere AC, Grodzicki RL, Kornblatt AN, et al. The spirochetal etiology of Lyme disease. N Engl J Med 1983;308:733–740.

7. Benach JL, Bosler EM, Hanrahan JP, et al. Spirochetes isolated from the blood of two patients with Lyme disease. N Engl J Med 1983;308:740–742.

8. Paster BJ, Dewhirst FE. Phylogenetic foundation of spirochetes. J Mol Microbiol Biotechnol 2000;2:341–344.

9. Wang G, van Dam AP, Schwartz I, et al. Molecular typing of Borrelia burgdorferi sensu lato: taxonomic, epidemiological, and clinical implications. Clin Microbiol Rev 1999;12:633–653.

10. Roberts DM, Carlyon JA, Theisen M, et al. The bdr gene families of the Lyme disease and relapsing fever spirochetes: potential influence on biology, pathogenesis, and evolution. Emerg Infect Dis 2000;6:110–122.

11. Fukunaga M, Takahashi Y, Tsuruta Y, et al. Genetic and phenotypic analysis of Borrelia miyamotoi sp. nov., isolated from the ixodid tick Ixodes persulcatus, the vector for Lyme disease in Japan. Int J Syst Bacteriol 1995;45:804–810.

12. Scoles GA, Papero M, Beati L, et al. A relapsing fever group spirochete transmitted by Ixodes scapularis ticks. Vector Borne Zoonotic Dis 2001;1:21–34.

13. Hovind-Hougen K. Ultrastructure of spirochetes isolated from Ixodes ricinus and Ixodes dammini. Yale J Biol Med 1984;57:543–548.

14. Hashimoto Y, Kawagishi N, Sakai H, et al. Lyme disease in Japan. Analysis of Borrelia species using rRNA gene restriction fragment length polymorphism. Dermatology 1995;191:193–198.

15. van Dam AP, Kuiper H, Vos K, et al. Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. Clin Infect Dis 1993;17:708–717.

16. Mathiesen DA, Oliver JH Jr, Kolbert CP, et al. Genetic heterogeneity of Borrelia burgdorferi in the United States. J Infect Dis 1997;175:98–107.

17. Maraspin V, Cimperman J, Lotric-Furlan S, et al. Solitary borrelial lymphocytoma in adult patients. Wien Klin Wochenschr 2002;114:515–523.

18. Postic D, Marti Ras N, Lane RS, et al. Expanded diversity among Californian Borrelia isolates and description of Borrelia bissettii sp. nov. (formerly Borrelia group DN127). J Clin Microbiol 1998;36:3497–3504.

19. Fraser CM, Casjens S, Huang WM, et al. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 1997;390:580–586.

20. Ohnishi J, Piesman J, de Silva AM. Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks. Proc Natl Acad Sci U S A 2001;98:670–675.

21. Liang FT, Alvarez AL, Gu Y, et al. An immunodominant conserved region within the variable domain of VlsE, the variable surface antigen of Borrelia burgdorferi. J Immunol 1999;163:5566–5573.

22. Liang FT, Aberer E, Cinco M, et al. Antigenic conservation of an immunodominant invariable region of the VlsE lipoprotein among European pathogenic genospecies of Borrelia burgdorferi SL. J Infect Dis 2000;182:1455–1462.

23. Liang FT, Philipp MT. Analysis of antibody response to invariable regions of VlsE, the variable surface antigen of Borrelia burgdorferi. Infect Immun 1999;67:6702–6706.

24. Liang FT, Jacobson RH, Straubinger RK, et al. Characterization of a Borrelia burgdorferi VlsE invariable region useful in canine Lyme disease serodiagnosis by enzyme-linked immunosorbent assay. J Clin Microbiol 2000;38:4160–4166.

25. Patrican LA. Absence of Lyme disease spirochetes in larval progeny of naturally infected Ixodes scapularis (Acari:Ixodidae) fed on dogs. J Med Entomol 1997;34:52–55.

26. Randolph SE, Green RM, Hoodless AN, et al. An empirical quantitative framework for the seasonal population dynamics of the tick Ixodes ricinus. Int J Parasitol 2002;32:979–989.

27. Zeidner N, Mbow ML, Dolan M, et al. Effects of Ixodes scapularis and Borrelia burgdorferi on modulation of the host immune response: induction of a TH2 cytokine response in Lyme disease-susceptible (C3H/HeJ) mice but not in disease-resistant (BALB/c) mice. Infect Immun 1997;65:3100–3106.

28. Bosler EM, Coleman JL, Benach JL, et al. Natural distribution of the Ixodes dammini spirochete. Science 1983;220:321–322.

29. Levine JF, Wilson ML, Spielman A. Mice as reservoirs of the Lyme disease spirochete. Am J Trop Med Hyg 1985;34:355–360.

30. Stafford KC III, Cartter ML, Magnarelli LA, et al. Temporal correlations between tick abundance and prevalence of ticks infected with Borrelia burgdorferi and increasing incidence of Lyme disease. J Clin Microbiol 1998;36:1240–1244.

31. Lane RS, Burgdorfer W. Transovarial and transstadial passage of Borrelia burgdorferi in the western black-legged tick, Ixodes pacificus (Acari: Ixodidae). Am J Trop Med Hyg 1987;37:188–192.

32. Schoeler GB, Lane RS. Efficiency of transovarial transmission of the Lyme disease spirochete, Borrelia burgdorferi, in the western blacklegged tick, Ixodes pacificus (Acari: Ixodidae). J Med Entomol 1993;30:80–86.

33. Telford SR III, Mather TN, Moore SI, et al. Incompetence of deer as reservoirs of the Lyme disease spirochete. Am J Trop Med Hyg 1988;39:105–109.

34. Richter D, Spielman A, Komar N, et al. Competence of American robins as reservoir hosts for Lyme disease spirochetes. Emerg Infect Dis 2000;6:133–138.

35. Smith RP Jr, Rand PW, Lacombe EH, et al. Role of bird migration in the long-distance dispersal of Ixodes dammini, the vector of Lyme disease. J Infect Dis 1996;174:221–224.

36. Brown RN, Lane RS. Lyme disease in California: a novel enzootic transmission cycle of Borrelia burgdorferi. Science 1992;256:1439–1442.

37. Maupin GO, Gage KL, Piesman J, et al. Discovery of an enzootic cycle of Borrelia burgdorferi in Neotoma mexicana and Ixodes spinipalpis from northern Colorado, an area where Lyme disease is nonendemic. J Infect Dis 1994;170:636–643.

38. Lane RS, Brown RN. Wood rats and kangaroo rats: potential reservoirs of the Lyme disease spirochete in California. J Med Entomol 1991;28:299–302.

39. Burgdorfer W, Lane RS, Barbour AG, et al. The western black-legged tick, Ixodes pacificus: a vector of Borrelia burgdorferi. Am J Trop Med Hyg 1985;34:925–930.

40. Padgett KA, Lane RS. Life cycle of Ixodes pacificus (Acari: Ixodidae): timing of developmental processes under field and laboratory conditions. J Med Entomol 2001;38:684–693.

41. Lane RS, Quistad GB. Borreliacidal factor in the blood of the western fence lizard (Sceloporus occidentalis). J Parasitol 1998;84:29–34.

42. Lane RS, Foley JE, Eisen L, et al. Acaralogic risk of exposure to emerging tick-borne bacterial pathogens in a semirural community in Northern California. Vector Borne Zoonotic Dis 2001;1:197–210.

43. Li X, Peavey CA, Lane RS. Density and spatial distribution of Ixodes pacificus (Acari: Ixodidae) in two recreational areas in north coastal California. Am J Trop Med Hyg 2000;62:415–422.

44. Piesman J, Clark KL, Dolan MC, et al. Geographic survey of vector ticks (Ixodes scapularis and Ixodes pacificus) for infection with the Lyme disease spirochete, Borrelia burgdorferi. J Vector Ecol 1999;24:91–98.

45. Wright SA, Thompson MA, Miller MJ, et al. Ecology of Borrelia burgdorferi in ticks (Acari: Ixodidae), rodents, and birds in the Sierra Nevada foothills, Placer County, California. J Med Entomol 2000;37:909–918.

46. Randolph SE, Craine NG. General framework for comparative quantitative studies on transmission of tick-borne diseases using Lyme borreliosis in Europe as an example. J Med Entomol 1995;32:765–777.

47. Hu CM, Humair PF, Wallich R, et al. Apodemus sp. rodents, reservoir hosts for Borrelia afzelii in an endemic area in Switzerland. Zentralbl Bakteriol 1997;285:558–564.

48. Kurtenbach K, Peacey M, Rijpkema SG, et al. Differential transmission of the genospecies of Borrelia burgdorferi sensu lato by game birds and small rodents in England. Appl Environ Microbiol 1998;64:1169–1174.

49. Humair PF, Postic D, Wallich R, et al. An avian reservoir (Turdus merula) of the Lyme borreliosis spirochetes. Zentralbl Bakteriol 1998;287:521–538.

50. Nakao M, Uchikawa K, Dewa H. Distribution of Borrelia species associated with Lyme disease in the subalpine forests of Nagano prefecture, Japan. Microbiol Immunol 1996;40:307–311.

51. Miyamoto K, Sato Y, Okada K, et al. Competence of a migratory bird, red-bellied thrush (Turdus chrysolaus), as an avian reservoir for the Lyme disease spirochetes in Japan. Acta Trop 1997;65:43–51.

52. Nakao M, Miyamoto K. Mixed infection of different Borrelia species among Apodemus speciosus mice in Hokkaido, Japan. J Clin Microbiol 1995;33:490–492.

53. Burkot TR, Piesman J, Wirtz RA. Quantitation of the Borrelia burgdorferi outer surface protein A in Ixodes scapularis: fluctuations during the tick life cycle, doubling times, and loss while feeding. J Infect Dis 1994;170:883–889.

54. Hodzic E, Feng S, Freet KJ, et al. Borrelia burgdorferi population kinetics and selected gene expression at the host-vector interface. Infect Immun 2002;70:3382–3388.

55. Pal U, de Silva AM, Montgomery RR, et al. Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A. J Clin Invest 2000;106:561–569.

56. Piesman J, Schneider BS, Zeidner NS. Use of quantitative PCR to measure density of Borrelia burgdorferi in the midgut and salivary glands of feeding tick vectors. J Clin Microbiol 2001;39:4145–4148.

57. Piesman J, Dolan MC. Protection against Lyme disease spirochete transmission provided by prompt removal of nymphal Ixodes scapularis (Acari: Ixodidae). J Med Entomol 2002;39:509–512.

58. Shih CM, Pollack RJ, Telford SR III, et al. Delayed dissemination of Lyme disease spirochetes from the site of deposition in the skin of mice. J Infect Dis 1992;166:827–831.

59. Centers for Disease Control and Prevention. Lyme disease—United States, 2000. MMWR Morb Mortal Wkly Rep 2002;51:29–31.

60. Hinrichsen VL, Whitworth UG, Breitschwerdt EB, et al. Assessing the association between the geographic distribution of deer ticks and seropositivity rates to various tick-transmitted disease organisms in dogs. J Am Vet Med Assoc 2001;218:1092–1097.

61. Levy SA, Lissman BA, Ficke CM. Performance of a Borrelia burgdorferi bacterin in borreliosis-endemic areas. J Am Vet Med Assoc 1993;202:1834–1838.

62. Wright JC, Chambers M, Mullen GR, et al. Seroprevalence of Borrelia burgdorferi in dogs in Alabama, USA. Prev Vet Med 1997;31:127–131.

63. Greene RT, Levine JF, Breitschwerdt EB, et al. Antibodies to Borrelia burgdorferi in dogs in North Carolina. Am J Vet Res 1988;49:473–476.

64. Olson PE, Kallen AJ, Bjorneby JM, et al. Canines as sentinels for Lyme disease in San Diego County, California. J Vet Diagn Invest 2000;12:126–129.

65. Orloski KA, Campbell GL, Genese CA, et al. Emergence of Lyme disease in Hunterdon County, New Jersey, 1993: a case-control study of risk factors and evaluation of reporting patterns. Am J Epidemiol 1998;147:391–397.

66. Lane RS, Manweiler SA, Stubbs HA, et al. Risk factors for Lyme disease in a small rural community in northern California. Am J Epidemiol 1992;136:1358–1368.

67. Schwartz BS, Goldstein MD. Lyme disease in outdoor workers: risk factors, preventive measures, and tick removal methods. Am J Epidemiol 1990;131:877–885.

68. Eng TR, Wilson ML, Spielman A, et al. Greater risk of Borrelia burgdorferi infection in dogs than in people. J Infect Dis 1988;158:1410–1411.

69. Dattwyler RJ. Lyme borreliosis: an overview of the clinical manifestations. Lab Med 1990;21:290–292.

70. Kalish R. Lyme disease. Rheum Dis Clin North Am 1993;19:399–426.

71. Nadelman RB, Wormser GP. Erythema migrans and early Lyme disease. Am J Med 1995;98:15S–23S.

72. Pachner AR, Steere AC. The triad of neurologic manifestations of Lyme disease: meningitis, cranial neuritis, and radiculoneuritis. Neurology 1985;35:47–53.

73. Steere AC, Batsford WP, Weinberg M, et al. Lyme carditis: cardiac abnormalities of Lyme disease. Ann Intern Med 1980;93:8–16.

74. Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987;107:725–731.

75. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med 1990;323:1438–1444.

76. Burgess EC. Natural exposure of Wisconsin dogs to the Lyme disease spirochete (Borrelia burgdorferi). Lab Anim Sci 1986;36:288–290.

77. Guerra MA, Walker ED, Kitron U. Quantitative approach for the serodiagnosis of canine Lyme disease by the immunoblot procedure. J Clin Microbiol 2000;38:2628–2632.

78. Levy SA, Magnarelli LA. Relationship between development of antibodies to Borrelia burgdorferi in dogs and the subsequent development of limb/joint borreliosis. J Am Vet Med Assoc 1992;200:344–347.

79. Magnarelli LA, Anderson JF, Schreier AB. Persistence of antibodies to Borrelia burgdorferi in dogs of New York and Connecticut. J Am Vet Med Assoc 1990;196:1064–1068.

80. Magnarelli LA, Anderson JF, Kaufmann AF, et al. Borreliosis in dogs from southern Connecticut. J Am Vet Med Assoc 1985;186:955–959.

81. Appel MJ, Allan S, Jacobson RH, et al. Experimental Lyme disease in dogs produces arthritis and persistent infection. J Infect Dis 1993;167:651–664.

82. Callister SM, Jobe DA, Schell RF, et al. Detection of borreliacidal antibodies in dogs after challenge with Borrelia burgdorferi-infected Ixodes scapularis ticks. J Clin Microbiol 2000;38:3670–3674.

83. Levy SA, Barthold SW, Domback DM, et al. Canine Lyme borreliosis. Compend Contin Educ Pract Vet 1993;15:833–846.

84. Straubinger RK. PCR-Based quantification of Borrelia burgdorferi organisms in canine tissues over a 500-day postinfection period. J Clin Microbiol 2000;38:2191–2199.

85. Dambach DM, Smith CA, Lewis RM, et al. Morphologic, immunohistochemical, and ultrastructural characterization of a distinctive renal lesion in dogs putatively associated with Borrelia burgdorferi infection: 49 cases (1987–1992). Vet Pathol 1997;34:85–96.

86. Grauer GF, Burgess EC, Cooley AJ, et al. Renal lesions associated with Borrelia burgdorferi infection in a dog. J Am Vet Med Assoc 1988;193:237–239.

87. Azuma Y, Kawamura K, Isogai H, et al. Neurologic abnormalities in two dogs suspected Lyme disease. Microbiol Immunol 1993;37:325–329.

88. Mandel NS, Senker EG, Bosler EM, et al. Intrathecal production of Borrelia burgdorferi-specific antibodies in a dog with central nervous system Lyme borreliosis. Compend Contin Educ Pract Vet 1993;15:581–586.

89. Levy SA, Duray PH. Complete heart block in a dog seropositive for Borrelia burgdorferi. Similarity to human Lyme carditis. J Vet Intern Med 1988;2:138–144.

90. Marcus LC, Patterson MM, Gilfillan RE, et al. Antibodies to Borrelia burgdorferi in New England horses: serologic survey. Am J Vet Res 1985;46:2570–2571.

91. Magnarelli LA, Anderson JF, Shaw E, et al. Borreliosis in equids in northeastern United States. Am J Vet Res 1988;49:359–362.

92. Magnarelli LA, Anderson JF. Class-specific and polyvalent enzyme-linked immunosorbent assays for detection of antibodies to Borrelia burgdorferi in equids. J Am Vet Med Assoc 1989;195:1365–1368.

93. Chang YF, Novosol V, McDonough SP, et al. Experimental infection of ponies with Borrelia burgdorferi by exposure to Ixodid ticks. Vet Pathol 2000;37:68–76.

94. Burgess EC, Mattison M. Encephalitis associated with Borrelia burgdorferi infection in a horse. J Am Vet Med Assoc 1987;191:1457–1458.

95. Burgess EC, Gillette D, Pickett JP. Arthritis and panuveitis as manifestations of Borrelia burgdorferi infection in a Wisconsin pony. J Am Vet Med Assoc 1986;189:1340–1342.

96. Magnarelli LA, Anderson JF, Levine HR, et al. Tick parasitism and antibodies to Borrelia burgdorferi in cats. J Am Vet Med Assoc 1990;197:63–66.

97. Hovmark A, Asbrink E, Schwan O, et al. Antibodies to Borrelia spirochetes in sera from Swedish cattle and sheep. Acta Vet Scand 1986;27:479–485.

98. Ji B, Collins MT. Seroepidemiologic survey of Borrelia burgdorferi exposure of dairy cattle in Wisconsin. Am J Vet Res 1994;55:1228–1231.

99. Burgess EC. Borrelia burgdorferi infection in Wisconsin horses and cows. Ann N Y Acad Sci 1988;539:235–243.

100. Wells SJ, Trent AM, Robinson RA, et al. Association between clinical lameness and Borrelia burgdorferi antibody in dairy cows. Am J Vet Res 1993;54:398–405.

101. Tuomi J, Rantamäki LK, Tanskanen R. Experimental infection of cattle with several Borrelia burgdorferi sensu lato strains; immunological heterogeneity of strains as revealed in serological tests. Vet Microbiol 1998;60:27–43.

102. Jacobson RH, Chang YF, Shin SJ. Lyme disease: laboratory diagnosis of infected and vaccinated symptomatic dogs. Semin Vet Med Surg (Small Anim) 1996;11:172–182.

103. Porwancher R. A reanalysis of IgM Western blot criteria for the diagnosis of early Lyme disease. J Infect Dis 1999;179:1021–1024.

104. Tugwell P, Dennis DT, Weinstein A, et al. Laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med 1997;127:1109–1123.

105. Craft JE, Grodzicki RL, Shrestha M, et al. The antibody response in Lyme disease. Yale J Biol Med 1984;57:561–565.

106. Craven RB, Quan TJ, Bailey RE, et al. Improved serodiagnostic testing for Lyme disease: results of a multicenter serologic evaluation. Emerg Infect Dis 1996;2:136–140.

107. Schwartz BS, Goldstein MD, Ribeiro JM, et al. Antibody testing in Lyme disease. A comparison of results in four laboratories. JAMA 1989;262:3431–3434.

108. Troy GC, Becker MJ, Greene RT. Proficiency testing of selected antigen and antibody tests for use in dogs and cats. J Am Vet Med Assoc 1996;209:914–917.

109. Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 1995;44:590–591.

110. Gauthier DT, Mansfield LS. Western immunoblot analysis for distinguishing vaccination and infection status with Borrelia burgdorferi (Lyme disease) in dogs. J Vet Diagn Invest 1999;11:259–265.

111. Greene RT, Walker RL, Nicholson WL, et al. Immunoblot analysis of immunoglobulin G response to the Lyme disease agent (Borrelia burgdorferi) in experimentally and naturally exposed dogs. J Clin Microbiol 1988;26:648–653.

112. Sheets JT, Rossi CA, Kearney BJ, et al. Evaluation of a commercial enzyme-linked immunosorbent assay for detection of Borrelia burgdorferi exposure in dogs. J Am Vet Med Assoc 2000;216:1418–1422.

113. Barthold SW, Levy SA, Fikrig E, et al. Serologic responses of dogs naturally exposed to or vaccinated against Borrelia burgdorferi infection. J Am Vet Med Assoc 1995;207:1435–1440.

114. Hovius JW, Hovius KE, Oei A, et al. Antibodies against specific proteins of and immobilizing activity against three strains of Borrelia burgdorferi sensu lato can be found in symptomatic but not in infected asymptomatic dogs. J Clin Microbiol 2000;38:2611–2621.

115. Dressler F, Whalen JA, Reinhardt BN, et al. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis 1993;167:392–400.

116. Wieler LH, Szattelberger C, Weiss R, et al. Serum antibodies against particular antigens of Borrelia burgdorferi sensu stricto and their potential in the diagnosis of canine Lyme borreliosis. Berl Munch Tierarztl Wochenschr 1999;112:465–471.

117. Liang FT, Alvarez AL, Gu Y, et al. An immunodominant conserved region within the variable domain of VlsE, the variable surface antigen of Borrelia burgdorferi. J Immunol 1999;163:5566–5573.

118. Levy S, O’Connor TP, Hanscom JL, et al. Utility of an in-office C6 ELISA test kit for determination of infection status of dogs naturally exposed to Borrelia burgdorferi. Vet Ther 2002;3:308–315.

119. Liang FT, Steere AC, Marques AR, et al. Sensitive and specific serodiagnosis of Lyme disease by enzyme-linked immunosorbent assay with a peptide based on an immunodominant conserved region of Borrelia burgdorferi vlsE. J Clin Microbiol 1999;37:3990–3996.

120. Kalish RA, McHugh G, Granquist J, et al. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10–20 years after active Lyme disease. Clin Infect Dis 2001;33:780–785.

121. Steere AC, Bartenhagen NH, Craft JE, et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983;99:76–82.

122. Steere AC, Hutchinson GJ, Rahn DW, et al. Treatment of the early manifestations of Lyme disease. Ann Intern Med 1983;99:22–26.

123. Dattwyler RJ, Volkman DJ, Conaty SM, et al. Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. Lancet 1990;336:1404–1406.

124. Luger SW, Paparone P, Wormser GP, et al. Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. Antimicrob Agents Chemother 1995;39:661–667.

125. Dattwyler RJ, Luft BJ, Kunkel MJ, et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med 1997;337:289–294.

126. Luft BJ, Dattwyler RJ, Johnson RC, et al. Azithromycin compared with amoxicillin in the treatment of erythema migrans. A double-blind, randomized, controlled trial. Ann Intern Med 1996;124:785–791.

127. Massarotti EM, Luger SW, Rahn DW, et al. Treatment of early Lyme disease. Am J Med 1992;92:396–403.

128. Steere AC, Levin RE, Molloy PJ, et al. Treatment of Lyme arthritis. Arthritis Rheum 1994;37:878–888.

129. Dattwyler RJ, Halperin JJ, Volkman DJ, et al. Treatment of late Lyme borreliosis—randomised comparison of ceftriaxone and penicillin. Lancet 1988;1:1191–1194.

130. Logigian EL. Neurologic manifestations of Lyme disease. In: Rahn DW, Evans J, eds. Lyme disease. 5th ed. Philadelphia: American College of Physicians, 1998;89–106.

131. Wormser GP, Nadelman RB, Dattwyler RJ, et al. Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Clin Infect Dis 2000;31(suppl 1):1–14.

132. Straubinger RK, Straubinger AF, Summers BA, et al. Status of Borrelia burgdorferi infection after antibiotic treatment and the effects of corticosteroids: an experimental study. J Infect Dis 2000;181:1069–1081.

133. Dykstra EA, Slater MR, Teel PD, et al. Perceptions of veterinary clinics and pest control companies regarding tick-related problems in dogs residing in Texas cities. J Am Vet Med Assoc 1997;210:360–365.

134. Mather TN, Ribeiro JM, Spielman A. Lyme disease and babesiosis: acaricide focused on potentially infected ticks. Am J Trop Med Hyg 1987;36:609–614.

135. Stafford KC III. Third-year evaluation of host-targeted permethrin for the control of Ixodes dammini (Acari: Ixodidae) in southeastern Connecticut. J Med Entomol 1992;29:717–720.

136. Slowik TJ, Lane RS, Davis RM. Field trial of systemically delivered arthropod development-inhibitor (fluazuron) used to control woodrat fleas (Siphonaptera: Ceratophyllidae) and ticks (Acari: Ixodidae). J Med Entomol 2001;38:75–84.

137. Sonenshine DE, Allan SA, Norval RA, et al. A self-medicating applicator for control of ticks on deer. Med Vet Entomol 1996;10:149–154.

138. Mejlon HA, Jaenson TG, Mather TN. Evaluation of host-targeted applications of permethrin for control of Borrelia-infected Ixodes ricinus (Acari: Ixodidae). Med Vet Entomol 1995;9:207–210.

139. Monsen SE, Bronson LR, Tucker JR, et al. Experimental and field evaluations of two acaracides for control of I. pacificus (Acari: Ixodidae) in northern California. J Med Entomol 1999;36:660–665.

140. Daniels TJ, Fish D, Schwartz I. Reduced abundance of Ixodes scapularis (Acari: Ixodidae) and Lyme disease risk by deer exclusion. J Med Entomol 1993;30:1043–1049.

141. Taylor MA. Recent developments in ectoparasiticides. Vet J 2001;161:253–268.

142. Estrada-Peña A, Ascher F. Comparison of an amitraz-impregnated collar with topical administration of fipronil for prevention of experimental and natural infestations by the brown dog tick (Rhipicephalus sanguineus). J Am Vet Med Assoc 1999;214:1799–1803.

143. Elfassy OJ, Goodman FW, Levy

Return to Physical Examinations and Testing

Who is online

Users browsing this forum: No registered users and 1 guest