Introduction to Borrelia afzelii
Borrelia afzelii is a Gram-negative, microaerophilic, spirochete bacterium primarily transmitted through the bite of infected Ixodes ticks. It is one of the main causative agents of Lyme borreliosis (LB) in Europe, where it is particularly prevalent. Lyme borreliosis is a tick-borne disease caused by a group of closely related Borrelia species, collectively known as the Borrelia burgdorferi sensu lato complex. Among the European species in this complex, B. afzelii stands out for its adaptation to rodent hosts and its association with specific clinical manifestations in humans, such as chronic skin conditions and arthritis.
Etiology and Morphology of Borrelia afzelii
Like other spirochetes, B. afzelii is a thin, elongated spiral-shaped bacterium measuring approximately 0.2 μm in diameter and up to 30 μm in length. Its structure consists of a protoplasmic cylinder surrounding an axial filament made up of multiple periplasmic endoflagella, which gives it a characteristic corkscrew motility. This motility is crucial for its invasive nature, allowing the bacterium to navigate through host tissues effectively. It shares many morphological traits with other Borrelia species, including the presence of 7 to 20 flagella encased within the periplasmic space, contributing to its movement.
B. afzelii has a segmented genome consisting of a linear chromosome and multiple plasmids, which play an essential role in its infectivity and adaptation to different environments. The genome includes several plasmids that encode outer surface lipoproteins (e.g., OspA, OspB, and OspC) and proteins involved in antigenic variation, such as VlsE. The ability of B. afzelii to adapt to various hosts is, in part, attributed to these genomic features, which facilitate evasion of the host immune system.
Epidemiology and Geographic Distribution
B. afzelii is predominantly found in Europe and Asia, where it is transmitted by Ixodes ricinus and Ixodes persulcatus ticks. It is highly adapted to rodent reservoir hosts, especially species like voles (Apodemus spp.), which maintain long-term systemic infections that facilitate transmission to ticks. Unlike other Borrelia species such as Borrelia garinii and Borrelia valaisiana, which are bird-adapted, B. afzelii primarily exploits rodents for its lifecycle, contributing to its persistence in forested and peri-urban areas where these small mammals thrive.
Although B. afzelii is less frequently found in bird hosts, some field studies have recovered B. afzelii-infected larvae from bird species such as the European robin (Erithacus rubecula) and the great tit (Parus major). However, the bacterium does not establish systemic infections in birds, which limits their role as effective reservoirs for the pathogen.
Transmission Dynamics
The principal mode of transmission for B. afzelii is via the bite of infected Ixodes ticks, which feed on infected rodents and then transmit the bacterium to new hosts, including humans. In its rodent hosts, B. afzelii establishes a long-term systemic infection, which is key to its successful transmission. Infected ticks maintain the pathogen through transstadial transmission, where larvae or nymphs become infected by feeding on an infected host and retain the bacterium as they molt into their next stage.
Co-feeding transmission, wherein infected and uninfected ticks feed in close proximity on the same host, has been documented as a significant transmission strategy for B. afzelii on rodent hosts. This allows the bacterium to evade the host immune system and infect ticks without the need for a systemic infection. However, this mechanism appears inefficient in avian hosts, as demonstrated in experimental studies with blackbirds (Turdus merula) and great tits (Parus major). In these birds, co-feeding transmission of B. afzelii was observed to be negligible, with only a small fraction of larval ticks (3.33% in great tits) acquiring the bacterium. Furthermore, spirochetes detected in these ticks were found to be non-viable, suggesting that the complement system of birds may play a role in killing the bacterium during blood feeding.
Host Specificity and Immune Evasion
B. afzelii exhibits a high degree of host specificity, being well-adapted to rodents but not avian hosts. This host specificity is thought to be mediated by the complement system of the host. In vitro studies have shown that B. afzelii is resistant to the complement system of rodents but is rapidly lysed by the complement of birds. Conversely, bird-adapted Borrelia species, such as B. garinii, are resistant to bird complement but are lysed by rodent complement. This complement-mediated specificity helps to explain why B. afzelii is primarily associated with rodent hosts and why it is rarely found in viable form in ticks feeding on birds.
Despite this, B. afzelii-infected larval ticks are frequently recovered from bird species in the wild. Several explanations have been proposed for this phenomenon, including the possibility of vertical transmission (though rare in Borrelia burgdorferi s.l.), partial blood meals from multiple hosts, or variation in the efficiency of co-feeding transmission between different strains of B. afzelii. Field studies have shown that some B. afzelii strains are more efficient at co-feeding transmission than others, which could explain the occasional presence of B. afzelii in bird-feeding ticks.
Clinical Manifestations in Humans
B. afzelii is strongly associated with distinct clinical manifestations in human Lyme borreliosis. Infected individuals commonly present with chronic skin conditions such as acrodermatitis chronica atrophicans (ACA) and erythema migrans, as well as arthritis, which can develop into a chronic condition if left untreated. Erythema migrans, a hallmark of early Lyme disease, is often the initial sign of infection, while ACA, a more advanced skin condition, is seen in late-stage infections and can cause significant tissue damage and skin atrophy.
Arthritis due to B. afzelii is typically oligoarticular, affecting large joints such as the knees. Chronic arthritis, which persists despite antibiotic treatment, has been linked to immune mechanisms and antigenic variation in the bacterium. The VlsE (Variable major protein-like sequence, expressed) antigenic variation system allows B. afzelii to change its surface proteins during infection, helping it evade the host's immune response and persist within tissues.
Molecular Characteristics and Genetic Diversity
B. afzelii exhibits genetic diversity across different strains, with considerable variation in plasmid content and outer surface protein (Osp) gene expression. The segmented genome of B. afzelii includes a linear chromosome of approximately 911 kb and multiple plasmids that encode genes important for survival, transmission, and immune evasion. These plasmids contain genes for several surface lipoproteins, including OspA, OspB, and OspC, which play roles in tick attachment and early infection in mammalian hosts.
Studies using pulsed-field gel electrophoresis and multilocus sequence typing (MLST) have shown that B. afzelii strains can be divided into subtypes based on genetic differences. Notably, subtypes Mla2 and Mla3 have been identified using MluI large restriction fragment patterns (LRFPs). These subtypes may differ in their host specificity or transmission efficiency, further contributing to the ecological diversity of B. afzelii.
Genetic exchange between B. afzelii strains in nature appears to be rare, and the bacterium has a low rate of horizontal gene transfer compared to other bacterial species. This low rate of recombination is likely due to the presence of restriction-modification systems encoded on its plasmids, which limit the uptake of foreign DNA. However, some genetic transfer may occur through cp32 prophages, which are thought to facilitate genetic exchange in the form of bacteriophages.
Transmission Dynamics and Reservoir Hosts
Rodents serve as the primary reservoir hosts for B. afzelii, maintaining the bacterium in the environment and allowing for its continued transmission to ticks. The life cycle of Ixodes ticks plays a crucial role in the ecology of B. afzelii, with immature ticks (larvae and nymphs) acquiring the bacterium from infected rodents. The infected nymphs then transmit the bacterium to new hosts, including humans, during their next blood meal. Importantly, transovarial transmission (from adult tick to eggs) is rare for B. afzelii, making host-to-tick transmission the primary mode of perpetuation.
The geographic distribution of B. afzelii is closely tied to the distribution of its tick vectors, particularly Ixodes ricinus and Ixodes persulcatus. These ticks are widely distributed across Europe and parts of Asia, with prevalence highest in regions where their rodent hosts are abundant. Migratory birds, although not competent hosts for B. afzelii, play an indirect role by dispersing ticks over large distances, potentially introducing the bacterium to new areas.
Borrelia afzelii is a rodent-adapted spirochete that plays a significant role in the epidemiology of Lyme borreliosis in Europe and Asia. Its transmission dynamics, host specificity, and genetic diversity make it a fascinating subject of study in the context of vector-borne diseases. While primarily associated with rodent hosts, its occasional presence in bird-feeding ticks has raised important questions about its transmission ecology. Understanding the molecular mechanisms of its immune evasion, particularly through antigenic variation and complement resistance, is essential for developing strategies to control Lyme disease and prevent its chronic manifestations in human populations.
Neurological Manifestations of Borrelia afzelii: Emerging Evidence
Traditionally, Borrelia afzelii has been associated with skin conditions such as acrodermatitis chronica atrophicans (ACA) and musculoskeletal manifestations like arthritis. However, emerging research suggests that B. afzelii may also contribute to neurological symptoms, challenging the long-standing belief that it does not cause significant neurological complications.
Pathophysiology of B. afzelii in Neurological Involvement
The pathogenesis of neurological symptoms in B. afzelii infections is still being explored. Like other Borrelia species, B. afzelii possesses the ability to evade the host immune system and persist in tissues, which may contribute to its capacity to cause neurological complications. The bacterium’s corkscrew motility and its ability to vary surface proteins, particularly through the VlsE antigenic variation system, are critical for evading immune responses. This mechanism may allow the bacterium to persist in tissues and cause prolonged or chronic infections, which could result in neurological symptoms.
While B. afzelii is not as frequently associated with neurological complications as Borrelia garinii, which is known for its neurotropism, cases involving B. afzelii have been documented. In these cases, the bacterium may induce inflammation in the peripheral nervous system, leading to conditions such as radiculopathy and facial nerve palsy, which are hallmarks of Lyme neuroborreliosis.
Clinical Evidence of Neurological Involvement
Clinical reports indicate that some patients infected with B. afzelii exhibit neurological symptoms. These cases have included peripheral nervous system complications, such as facial nerve palsy and radicular pain. While B. afzelii is not the primary Borrelia species linked to neuroborreliosis, these findings suggest that its role in neurological manifestations may have been previously underestimated.
For example, certain case studies have demonstrated neurological involvement in patients where B. afzelii was identified as the causative agent. Patients have reported symptoms such as headache, radicular pain, and facial nerve involvement. Although the bacterium’s involvement in these cases does not appear to be as aggressive or frequent as that of B. garinii, the presence of neurological symptoms linked to B. afzelii is nonetheless significant.
Implications for Diagnosis and Treatment
The recognition that B. afzelii may contribute to neurological symptoms has important implications for the diagnosis and treatment of Lyme borreliosis. Clinicians should consider the possibility of B. afzelii in patients presenting with neurological symptoms, particularly in regions where this species is prevalent. While B. garinii remains the primary suspect in cases of neuroborreliosis, B. afzelii should not be overlooked as a potential cause.
In terms of treatment, the antibiotic regimens used for neuroborreliosis are effective across the different Borrelia species. However, identifying the specific species involved may help guide clinicians in anticipating the course and potential complications of the disease, as B. afzelii-related neurological symptoms may present differently or progress at a different rate compared to infections caused by other species.
Serological Findings in Patients with Severe Neurological Complications
In several European countries, including Bulgaria, Romania, and Bosnia, there have been cases where patients with severe neurological complications were found to have serological evidence of Borrelia afzelii infection. These findings are significant, as B. afzelii has not historically been associated with prominent neurological involvement. However, it is important to note that the presence of antibodies specific to B. afzelii in these patients does not necessarily rule out the involvement of other Borrelia species.
Current diagnostic methods in many of these regions rely on standard serological tests, which may not have the precision to accurately distinguish between different Borrelia species. These limitations leave open the possibility that other Borrelia species, such as Borrelia garinii—a known cause of neuroborreliosis—could be involved in these cases, but remain undetected due to the constraints of existing testing techniques. This highlights the need for more advanced molecular diagnostics to better understand the role of various Borrelia species in neurological Lyme borreliosis across Europe.