Lyme Disease
Johanna L. Watson • Monica Aleman •
John E. Madigan
Lyme disease, also known as borreliosis, is one of the most important arthropod-borne bacterial infections in the United States.
It is caused by the spirochete Borrelia burgdorferi and affects humans, horses, dogs, and cats.1-4 Because Lyme borreliosis was first identified as the causative agent of an epidemic of juvenile inflammatory arthritis in children and adults in Old Lyme, Lyme, and East Haddam, Connecticut,5,6 medical references commonly cite “Lyme disease” when referring to B. burgdorferi infection.Epizootiology
B. burgdorferi is widely distributed in the northern hemisphere. Evidence of infection or exposure in horses has been reported in the United States in the Northeast, Midwest, Texas, and California.7 Lyme borreliosis has been extensively reported in England and other European countries, nations of the former Soviet Union, China, Japan, Southeast Asia, and South Africa.8 B. burgdorferi is transmitted to humans and animals by ticks belonging to the Ixodes ricinus complex.9 These ticks each feed three times during the larval, nymphal, and adult stages.5 The larvae and nymphs feed on wild animals, and adults are found most commonly on deer.9 On the East Coast, Ixodes scapularis ticks are the principle vector, whereas on the West Coast Ixodes pacificus, the western black-legged tick, is the main vector identified.10 I. scapularis is seen from the Atlantic coast to Oklahoma and Texas.11 A much higher percentage of I. scapularis ticks (12% to 99%) will carry the spirochete compared with I. pacificus, in which the maximum number of infected ticks is 4% to 5%.10,11 I. scapularis larval ticks principally acquire the spirochete from Peromycus leucopus, the white-footed mouse, and the nymphal stages are the major transmitters of disease to animals and humans.12 With I.
pacificus, the California kangaroo rat, Dipodomys californicus, and the dusky-footed wood rat, Neotoma fusicipes, are the likely enzootic reservoirs of B. burgdorferi.13Public Health Considerations
The CDC initiated surveillance for Lyme disease in 1982, and in January 1991 it became nationally reportable. Cases have been reported from 46 states, and the annual number of Lyme disease cases has increased 18-fold, from 497 to 8803. It is now the most common tick-transmitted disease in the United States.
B. burgdorferi organisms have been recovered from the urine of feral white-footed mice (P. leucopus).14 Contact transmission has been reported between white-footed mice,14 further complicating the understanding of transmission. Lacking any proof to the contrary, it is generally believed that any potential increased risk to humans from infected animals is due to animals bringing ticks into areas of human habitation, rather than any animal transmission.15
Molecular Biology
Immunochemical analysis of North American strains of B. burgdorferi reveal two abundant surface proteins termed outer surface protein A (OspA, 30 to 32 kD) and outer surface protein B (OspB, 34 to 36 kD).16 The 41-kD antigen is located on the flagellum and is similar to the flagellar antigens of other spirochetes.17 All isolates to date have four to nine pieces of extrachromosomal plasmid DNA. Plasmid may code for proteins that are important in pathogenicity, because the loss of infectivity of isolates that have been heavily passaged in the laboratory correlates with the loss of particular plasmids in culture.18 Recent work suggests that B. burgdorferi, like the relapsing fever-causing Borrelia (e.g., Borrelia hermsii), can vary its antigenicity, although by a different mechanism and using subtle alterations in the genome.19
Clinical Signs burgdorferi is sensitive to tetracycline and moderately sensitive to penicillin.
Amoxicillin, ceftriaxone, and imipenem are highly active against B. burgdorferi. Aminoglycosides, ciprofloxacin, and rifampin lack activity.38 Doxycycline twice daily in humans has been frequently used. Probenecid and ampicillin or amoxicillin also have been used.38 When CNS involvement is present, ceftriaxone or IV penicillin G has been used. The appropriate duration of therapy is unknown but is related to the stage of infection.Three different antimicrobials that included ceftiofur sodium (2.2 mg/kg/day IM), doxycycline (10 mg/kg/day PO), and tetracycline (5 mg/kg/day IV) were used for a 28-day period in experimentally infected ponies.39 High titers and B. burgdorferi isolation from skin biopsies confirmed infection. Antimicrobial therapy was initiated 3 months post exposure. Tetracycline was the most effective antimicrobial; it decreased antibody titers during and months after treatment, and bacterial isolation became negative in tissues. However, tissues were still positive for the spirochete on PCR.39 The efficacy on decreasing titers of tetracycline in the clinical setting has not been highly suc- cessful.40 Proposed treatment for Borrelia infection includes tetracycline (6.6 mg/kg IV q12h), doxycycline (10 mg/kg PO q12h), or ceftiofur (2.2 mg/kg IM q12h) for 3 to 4 weeks.35
A recombinant outer surface protein A (rOspA) subunit vaccine was shown to be effective in preventing infection in challenged horses with infected ticks.22,41 Specific recommendations for its use in the clinical setting are lacking.