Borrelia recurrentis – Habitat, Morphology, Pathogenesis, Treatment

What is Borrelia recurrentis?

• Borrelia recurrentis is a species of spirochete bacteria that causes relapsing fever, a disease characterized by recurring episodes of fever separated by afebrile periods. This bacterium is unique among pathogens due to its ability to repeatedly alter the proteins on its surface, which allows it to evade the host’s immune response and causes the cyclical nature of the illness.
• The primary mode of transmission for B. recurrentis is through the human body louse (Pediculus humanus humanus). This relationship has been documented since the 19th century, and the body louse remains the only confirmed vector for transmitting this bacterium between humans. However, in some regions, such as Ethiopia, B. recurrentis DNA has been detected in head lice, raising questions about whether they can also serve as vectors. Further research is needed to confirm their role in disease transmission.
• Relapsing fever caused by B. recurrentis typically begins with an initial febrile episode, followed by a period of relief and subsequent relapses. This pattern is driven by the bacterium’s ability to undergo antigenic variation, a process where it changes the structure of its surface proteins to escape recognition by the immune system. This mechanism makes relapsing fever distinct from other febrile illnesses and presents a unique challenge in diagnosis and treatment.

Scientific classification of Borrelia recurrentis

Domain:	Bacteria
Phylum:	Spirochaetota
Class:	Spirochaetia
Order:	Spirochaetales
Family:	Borreliaceae
Genus:	Borrelia
Species:	B. recurrentis

Geographical Distribution and Habitat of Borrelia recurrentis

Borrelia recurrentis is the cause of relapsing fever, with distinct patterns of prevalence based on hygiene, environmental factors, and the vectors involved.

• Geographical Distribution
  • Epidemic louse-borne relapsing fever is now rare due to improvements in hygiene and insecticide use.
  • This form of the disease is still present in parts of northeastern Africa, particularly in Ethiopia.
  • Some occurrences have also been noted in regions of South America.
  • Endemic tick-borne relapsing fever has a global presence.
  • In the United States, it is particularly prevalent in the western states.
• Habitat
  • The bacteria primarily reside in the bloodstream during infection.
  • They are also found in various organs, including the spleen, liver, lungs, kidneys, and bone marrow of infected individuals.
  • These tissue reservoirs play a role in sustaining the infection and contributing to relapses.

Morphology of Borrelia recurrentis

Borrelia recurrentis is a unique spirochete bacterium with distinctive structural characteristics that differentiate it from other spirochetes like treponemes and leptospires. Below is a breakdown of its key morphological features:

• Shape and Size
  • Exhibits an uneven spiral shape with one or both ends pointed.
  • Measures between 8–20 micrometers in length and 0.2–0.4 micrometers in width.
• Spiral Coils
  • Possesses 5–10 loose, irregular spiral coils along its structure.
  • Coils are coarse and uneven compared to the smoother spirals of treponemes or leptospires.
• Endoflagella
  • Contains 15–20 endoflagella per cell.
  • These internal flagella contribute to its distinctive motility and structural integrity.
• Staining and Gram Reaction
  • Classified as Gram-negative.
  • Demonstrates well under Wright and Giemsa stains, making microscopic identification easier.
• Motility
  • Actively motile in fresh blood preparations.
  • Moves with a corkscrew-like motion and alternates between forward and backward waves.

Cultural Characteristics of Borrelia recurrentis

Borrelia recurrentis exhibits unique cultural characteristics that set it apart from many other bacteria. Its growth and isolation require specific environmental conditions and living hosts due to its intricate nutritional needs. Here’s a breakdown of the key points:

• Oxygen Requirements
  • Classified as microaerophilic, meaning it thrives in environments with low oxygen levels.
• Optimal Growth Temperature
  • Prefers a temperature range of 28–30°C for its growth.
• Nutritional Demands
  • Has complex nutritional requirements, making it challenging to grow on artificial culture media.
  • Reliance on specialized conditions limits its cultivation outside living systems.
• Growth in Embryos
  • Successfully cultured on the chorioallantoic membrane of chick embryos.
• Animal Models for Isolation
  • Mice and rats are highly susceptible to infection, making them ideal models for primary isolation.
  • Clinical specimens, such as blood or tissue, can be introduced into these animals via intraperitoneal inoculation to propagate the bacteria.
• Distribution in Host Systems
  • After inoculation, the bacteria appear rapidly in the blood.
  • They persist in the brain for an extended period, offering another site for recovery during experiments.

Cell Wall Components and Antigenic Structure of Borrelia recurrentis

The cell wall and antigenic structure of Borrelia recurrentis play critical roles in its ability to evade the immune system and cause recurring infections. Below is a detailed exploration of its features:

• Antigenic Variation
  • A hallmark of B. recurrentis is its ability to undergo antigenic variation.
  • This property allows the bacterium to change its surface antigens, preventing effective recognition by the host immune system.
• Role of Linear Plasmids
  • Antigenic variation is driven by DNA rearrangements in the linear plasmids of the bacterium.
  • These genetic changes result in the expression of different surface proteins during the infection cycle.
• Impact on Relapsing Fever
  • The recurring episodes of fever characteristic of relapsing fever are directly linked to these antigenic shifts.
  • As the immune system begins to respond to one antigenic form, the bacterium switches to a new form, causing a relapse.

Virulence Factors of Borrelia recurrentis

The virulence of Borrelia recurrentis stems largely from its unique ability to evade the host immune response. This evasion mechanism directly influences the clinical manifestations of relapsing fever. Here’s a detailed breakdown:

• Antigenic Shift
  • The bacterium’s primary virulence factor is its capacity for antigenic shift, a process where surface antigens are altered.
  • This enables B. recurrentis to escape immune detection and clearance, allowing the infection to persist within the host.
• Immune Evasion
  • Antigenic variation disrupts the host immune system’s ability to maintain a consistent response.
  • As the host begins to recognize and respond to one antigenic form, the bacterium switches to another, rendering the immune response ineffective.
• Impact on Relapsing Fever
  • These antigenic changes are directly responsible for the alternating febrile and afebrile phases seen in relapsing fever.
  • During febrile periods, the immune system reacts to a specific antigenic variant, but once the bacteria shift antigens, a new cycle of infection begins.

Pathogenesis of Relapsing Fever

Relapsing fever caused by Borrelia recurrentis begins with the bacterium penetrating the skin and entering the bloodstream. From there, it spreads systemically, affecting multiple organs. Its ability to evade the host immune system drives the cyclic nature of the disease.

• Initial Bloodstream Invasion
  • The bacteria penetrate the skin, enter the circulation, and rapidly disseminate to internal tissues.
  • Once in the bloodstream, the host immune system initiates a response by producing Borrelia-specific IgM antibodies.
• Immune Response and Clearance
  • IgM antibodies bind to the bacteria, leading to their agglutination.
  • This triggers complement-mediated lysis, effectively clearing the bacteria from the bloodstream.
• Antigenic Variation
  • Some bacteria evade clearance by altering their outer surface proteins.
  • Gene rearrangement allows them to express new antigenic variants that are unrecognizable by existing IgM antibodies.
• Recurring Cycles of Fever
  • The immune system must start over, generating antibodies against the new antigens.
  • While the new immune response clears the altered bacteria, another antigenic shift occurs, causing a relapse.
• Development of Humoral Immunity
  • Over successive cycles of infection and immune response, humoral immunity develops.
  • This eventually leads to recovery as the immune system becomes more effective at recognizing and eliminating the pathogen.

Clinical Syndromes of Borrelia recurrentis

Borrelia recurrentis is responsible for relapsing fever, presenting in two forms: epidemic louse-borne and endemic tick-borne. Both share similar clinical features, but their mode of transmission differs.

• Incubation Period
  • Symptoms typically appear after an incubation period of about 7 days.
  • This phase is marked by the absence of visible signs as the bacteria establish themselves in the host.
• Hallmarks of the Disease
  • Repeated episodes of high fever are the defining feature.
  • Common symptoms during these episodes include headache and muscle pain (myalgia).
  • Enlargement of the spleen (splenomegaly) and liver (hepatomegaly) often occurs alongside the fever.
• Bacteremic Phase
  • During febrile episodes, the bacteria circulate in high numbers within the bloodstream.
  • This phase corresponds to the most symptomatic part of the disease.
• Afebrile Period and Relapses
  • Fever subsides after 3–7 days as the immune system temporarily clears the bacteria from circulation.
  • After an afebrile period lasting 4–7 days, the fever recurs.
  • Each recurrence coincides with the reappearance of Borrelia in the blood, resulting from antigenic variation that allows the bacteria to evade immune detection.
• Relapse Frequency
  • The number of relapses varies, typically ranging between 3 and 10 cycles before the disease resolves.
  • Each episode follows the same pattern of fever, clearance, and relapse.

Reservoir, Source, and Transmission of Infection of Borrelia recurrentis

Borrelia recurrentis, the pathogen behind relapsing fever, has distinct reservoirs and transmission mechanisms depending on whether it is the epidemic louse-borne or endemic tick-borne form.

• Reservoir and Source of Infection (Epidemic Louse-Borne)
  • Humans are the only reservoir for the epidemic louse-borne form of Borrelia recurrentis.
  • The infection is transmitted only from person to person.
  • Individuals infected with relapsing fever serve as the source of the disease.
  • The human body louse (Pediculus humanus corporis) is the vector of the infection.
  • The Borrelia organisms are found in the hemolymph (blood) of the lice but are not excreted in saliva or excreta.
  • Transmission occurs when lice are crushed and the infected blood is rubbed into the skin, not through the louse’s bite.
• Reservoir and Source of Infection (Endemic Tick-Borne)
  • Endemic tick-borne relapsing fever is a zoonotic disease, transmitted from animals to humans.
  • Rodents and small mammals are the primary animal reservoirs of the disease.
  • The main vectors are soft ticks of the genus Ornithodoros.
  • These ticks can harbor the infection in their body tissues, with Borrelia being present in all parts of the tick’s body.
  • Unlike lice, the Borrelia organisms are secreted in saliva and excreta of the tick.
  • Transmission to humans occurs through the bite of infected ticks.
  • Ticks like Ornithodoros tholozani, Ornithodoros crossi, and Ornithodoros lahorensis serve as the primary vectors in India.
• Transmission Mechanism
  • Soft ticks are nocturnal feeders, usually feeding while their hosts are asleep.
  • They attach briefly for feeding, often unnoticed by the host.
  • The tick’s bite goes largely unfelt since they stay attached for only a few minutes.
  • Through this process, Borrelia is transferred from the tick’s saliva into the human bloodstream.

Laboratory Diagnosis of Borrelia recurrentis

Diagnosing Borrelia recurrentis, the cause of relapsing fever, relies on a variety of laboratory techniques. Each method provides distinct advantages depending on the stage of the disease and the availability of resources.

• Specimen Collection
  • Blood collected from a patient during a fever is essential for diagnosis.
  • Afebrile patients are less likely to yield useful specimens, as the bacteria are not present in the bloodstream during this phase.
• Microscopy
  • A wet mount preparation of the blood is examined using dark-field or phase contrast microscopy.
  • The Borrelia organisms can be identified by their characteristic dashing movements, which is a hallmark of their motility.
  • Alternatively, peripheral blood smears can be stained with Giemsa or Wright stains.
  • This staining method is highly sensitive and can detect Borrelia in 70% or more of louse-borne relapsing fever cases.
• Culture
  • Culturing Borrelia from clinical specimens is not routinely done.
  • This is because Borrelia has complex nutritional requirements and grows very slowly, making it impractical for typical diagnostic labs.
• Animal Inoculation
  • Animal inoculation offers a more sensitive method for detecting the pathogen.
  • The test involves injecting 1-2 mL of blood from the infected patient into a mouse intraperitoneally.
  • After 1–10 days, blood is collected from the mouse and examined daily for the presence of Borrelia over a 2-week period.
  • This method, while more effective, is time-consuming and less commonly used in routine practice.
• Serodiagnosis
  • Serological tests are generally not useful for diagnosing Borrelia recurrentis due to the organism’s antigenic phase variation.
  • This variation means that the immune system’s response changes over time, leading to unreliable serological results.

Treatment of Borrelia recurrentis Infection

Treating Borrelia recurrentis infections requires the use of antibiotics, with the choice depending on patient age and condition.

• Preferred Antibiotics
  • Tetracycline or erythromycin are the most effective options for treating relapsing fever caused by Borrelia recurrentis.
  • These antibiotics target the bacteria and help control the infection during its active phase.
• Considerations for Special Groups
  • Doxycycline is often recommended for children and pregnant women due to its safety profile.
  • This ensures that vulnerable populations receive effective treatment while minimizing risks.

Prevention and Control of Borrelia recurrentis Infection

Preventing Borrelia recurrentis infection involves several practical steps to reduce exposure to the vectors and manage the environment where the bacteria thrive.

• Louse-borne Relapsing Fever Prevention
  • Preventing louse infiltration is crucial. Lice are the primary vectors for the transmission of the infection from person to person.
  • The use of insecticides on clothing and bedding helps to control lice populations and minimize the risk of infection.
• Tick-borne Relapsing Fever Prevention
  • Protective clothing acts as a barrier against tick bites, which are the main means of transmitting the infection in tick-borne cases.
  • Insect repellents can be applied to skin and clothing to repel ticks and reduce the likelihood of them attaching to the body.
  • It’s important to avoid ticks and their habitats, such as areas with tall grass or brush, where ticks are most active.
• Lack of Vaccine
  • There is no vaccine available for either louse-borne or tick-borne relapsing fever.
  • Preventative measures focus solely on vector control and reducing exposure.