Biology and Cultural Properties
Morphologically, these pathogens are slender spirochetes measuring $0.3–0.6 \times 2–20\text{ }\mu\text{m}$. They possess 3 to 10 large, irregular coils, and motility is mediated by a specialized periplasmic flagellar apparatus (consisting of 15–20 axial filaments). When stained with Giemsa stain, the bacteria stain purple-blue and readily take up aniline dyes.
The genetic apparatus is unique among bacteria: it consists of a small linear chromosome and a large set of circular and linear plasmids. Cultivating these microorganisms is challenging due to strict nutritional requirements. Complex media supplemented with serum, ascitic fluid, or tissue extracts are needed. Optimal growth conditions include a temperature of 28–35 °C and an atmosphere enriched with 5–10% $CO_2$. Alternatively, they can be propagated in the yolk sac of embryonated chicken eggs.
Borrelia species are environmentally unstable. They are rapidly inactivated by heat (45–48 °C kills them in 30 minutes) and drying. However, they tolerate low temperatures and freezing very well.
Discovery and Etiology of Lyme Disease
The first clinical description of erythema migrans was made by Afzelius in 1909. Later, in 1975, an outbreak of specific arthritis among children in Lyme, Connecticut, drew researchers' attention. The causative agent was isolated from ticks in 1982 by W. Burgdorfer.
Depending on the geographic region, Lyme disease is caused by different species within the Borrelia burgdorferi sensu lato complex. In North America, the classic species B. burgdorferi sensu stricto predominates, whereas in Eurasia, B. garinii and B. afzelii play the primary role. These species differ noticeably in their antigenic structure.
The natural reservoir consists of small mammals, primarily white-footed mice and other rodents. Transmission is vector-borne via the bites of hard ticks (Ixodes spp.) during the warm months. Susceptibility to infection is high, but human-to-human transmission does not occur (patients are not epidemiologically contagious).
Antigenic Structure and Virulence Factors
The antigenic system is complex and highly variable, consisting of:
- Internal antigens: These include flagellar proteins (p41, flagellin) and cytoplasmic cylinder proteins (p93). Antibodies against these develop early in infection but do not confer protective immunity.
- Surface antigens (Osp): Lipid-modified outer surface proteins (types A, B, C, D, E, F) encoded by plasmids that help the pathogen evade host immunity.
A key feature is antigenic phase variation. The OspC protein is expressed within the tick vector and during early human infection. The OspA protein (which has multiple serovars) dominates during later stages of the disease and when B. burgdorferi is cultured in vitro.
The pathogenesis involves bacterial attachment to host cells via outer surface lipoproteins. The pathogen interacts with macrophages, stimulating the release of interleukin-1 and triggering systemic inflammation. Arthritis develops largely due to autoimmune mechanisms: at human body temperature (37 °C), the bacterium expresses heat shock proteins that share homology with human proteins (molecular mimicry).
Clinical Manifestations and Diagnostics
Lyme disease typically progresses through three sequential stages following an incubation period of 3–32 days (starting with an erythematous papule at the bite site):
- Localized stage: Characterized by erythema migrans (expanding annular red lesion), regional lymphadenopathy, and a flu-like syndrome.
- Disseminated stage: Develops around weeks 4–5. Borrelia spread hematogenously to target organs, leading to cardiac manifestations (myocarditis, AV block) and central nervous system involvement (aseptic meningitis).
- Late stage: Appears weeks to months later. The hallmark manifestation is chronic arthritis affecting large joints.
Isolating the organism from blood or CSF is difficult. Therefore, diagnosis relies on a staged algorithm. In the early localized stage, skin biopsies of the erythema can be evaluated via dark-field microscopy or PCR. From the disseminated stage onward, serological assays (ELISA, indirect immunofluorescence assay [IFA]) are used to detect IgM and IgG antibodies. PCR is valuable for cerebrospinal fluid and synovial fluid analysis.
Treatment relies on targeted antibiotic therapy, primarily tetracyclines. There is no widely available human vaccine; prevention centers on protective clothing and tick avoidance.