Borrelia

Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. The ability of Borrelia to express different repertoires of surface proteins allows for bacterial transmission and evasion of the host immune system. Borrelia utilizes Ixodes ticks, Ornithodoros ticks, and the human body louse as vectors, and the resulting diseases include Lyme disease and relapsing fever.

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General Characteristics of Borrelia

Basic features of Borrelia species

  • Gram-negative, corkscrew-shaped spirochetes
  • Larger than Treponema species
  • Visualization:
    • Dark-field microscopy
    • Wright or Giemsa stain
    • Difficult to visualize using Gram stain
  • Microaerophilic
  • Surrounded by an additional phospholipid-rich outer membrane and few exposed proteins
  • Difficult to culture on ordinary media; Barbour-Stoenner-Kelly (BSK) medium is commonly used.

Dark-field microscopy of Borrelia burgdorferi

Image: “Borrelia burgdorferi (CDC-PHIL-6631) lores” by CDC. License: Public Domain

Clinically relevant species

  • Lyme disease:
    • B. burgdorferi
    • B. afzelii
    • B. garinii
  • Relapsing fever:
    • Tick-borne disease is associated with multiple species and includes:
      • B. hermsii
      • B. turicatae
      • B. miyamotoi
      • B. hispanica
      • B. duttoni
      • B. persica
    • Louse-borne: B. recurrentis

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Pathogenesis

Reservoirs

  • Rodents
  • Birds
  • Bats
  • White-tailed deer
  • Humans (B. recurrentis)

Transmission

  • Ticks
    • Occurs through saliva injection during feeding
    • Ticks are usually very small and the bite is often unnoticed.
    • Longer attachment is associated with a higher risk of transmission.
    • Associated species
      • Ixodes scapularis (deer tick)
      • Ornithodoros
  • Louse
    • Species: Pediculus humanus corporis (human body louse)
      • Lives on clothing
      • Only feeds on humans
    • B. recurrentis is introduced when the louse is crushed by humans.
      • Can enter through breaks in the skin or conjunctivae (from rubbing eyes)
      • Not transmitted from louse saliva or feces

Virulence

  • Motility
    • Possess numerous axial filaments
      • Thin endoflagella in the periplasmic space
      • Allows them to move in a spinning fashion
    • Propels the organism through blood and extracellular matrix
    • Allows escape from phagocytosis
  • Outer surface proteins (Osps)
    • Surface lipoproteins can be up- or down-regulated to facilitate transmission.
    • OspA
      • Responsible for attachment to the midgut of ticks
      • Down-regulation results in detachment and transfer to the saliva of ticks.
    • OspC 
      • Allows invasion through the host skin
      • Important for the use of plasminogen
        • Digests fibrin and glycoproteins
        • Assists movement through extracellular matrix
  • Variable major proteins (VMPs) provide antigenic variation. 
    • Borrelia are able to change major antigens on their surface.
    • Allows the bacteria to evade the adaptive immune response of the host
  • Endo- and exotoxins are generally not produced; symptoms are due to the immune system of the host.

Axial filaments of Borrelia:
Axial filaments are made up of multiple periplasmic flagella (bottom picture). This allows the spirochete (top picture) to move in a spinning fashion.

Image by Lecturio.

At-risk populations

  • Tick-borne diseases:
    • Hikers
    • Campers
    • Woodworkers
  • Louse-borne diseases:
    • Refugees
    • Homeless

Diseases Caused by Borrelia

The following diseases are caused by Borrelia:

Table: Diseases caused by Borrelia
DiseaseLyme diseaseRelapsing fever
Associated species
  • B. burgdorferi (United States)
  • B. afzelii and B. garinii (Europe)
  • B. hermsii, B. turicatae, B. miyamotoi (TBRF)
  • B. recurrentis (LBRF)
Clinical manifestations
  • Fever, myalgias, lymphadenopathy
  • Skin: erythema chronicum migrans
  • Recurrent fever, myalgias, arthralgia, headache, delirium
  • Skin: macular or purpuric rash on trunk and extremities, erythema multiforme
Complications
  • Neurological: Bell’s palsy, meningitis, meningoradiculitis, encephalomyelitis
  • Cardiac: myocarditis, AV block
  • Musculoskeletal: migratory polyarthritis
  • Neurological: Bell’s palsy, meningitis, myelitis
  • Cardiac: myocarditis
  • Pulmonary: ARDS
  • Hematologic: thrombocytopenia, hemoptysis, epistaxis
DiagnosisClinical, supported using ELISA and Western blotClinical, dark-field microscopy, Giemsa stain, or Wright stain of blood smear
Management
  • Doxycycline
  • Ceftriaxone for severe disease
  • Doxycycline, penicillin G
  • Severe disease: penicillin G, ceftriaxone
Prevention
  • ↓ tick exposure → protective clothing, repellents, remove ticks
  • PEP: doxycycline for those in ↑ risk areas
  • TBRF: ↓ tick exposure → sealing floors in houses, avoid rodents, tick repellents
  • LBRF: ↓ louse exposure → improved hygiene, ↓ crowding, washing clothes
  • PEP: doxycycline for those in ↑ risk areas

TBRF: tick-borne relapsing fever

LBRF: louse-borne relapsing fever

AV: atrioventricular

ARDS: acute respiratory distress syndrome

ELISA: enzyme-linked immunosorbent assay

PEP: post-exposure prophylaxis

Classic erythema migrans rash of Borrelia burgdorferi

Image: “Diagnostic challenges of early Lyme disease: lessons from a community case series” by Aucott J, Morrison C, Munoz B, Rowe PC, Schwarzwalder A, West SK. License: CC BY 2.0

Comparison of Spirochetes

Spirochetes are gram negative, spiral shaped, and motile. The following table briefly compares some clinically relevant spirochetes:

Table: Comparison of clinically relevant spirochetes
OrganismTreponema pallidum pallidumOther T. pallidum subspeciesTreponema carateumBorrelia burgdorfiBorrelia recurrentisLeptospira interrogans
Micro
  • Microaero
  • Not seen using Gram or Giemsa stain
  • Microaero
  • Not seen using Gram or Giemsa stain
  • Microaero
  • Not seen using Gram or Giemsa stain
  • Microaero
  • Seen using Giemsa and Wright stain
  • Microaero
  • Seen using Giemsa and Wright stain
  • Aerobic
  • Hooked ends
Virulence
  • Hyaluronidase
  • Fibronectin coating
  • Hyaluronidase
  • Fibronectin coating
  • Hyaluronidase
  • Fibronectin coating
  • Antigenic variation
  • Osp regulation
Antigenic variation
  • LPS
  • Hemolysins
  • Complement regulators and enzymes
ReservoirHumansHumansHumans
  • Rodents
  • Deer
Humans
  • Wild animals
  • Livestock
  • Domesticated animals
TransmissionSexual contactP2P contactP2P contactIxodes tickLouseDirect contact with animal tissue or fluids
ClinicalSyphilis
  • Yaws
  • Bejel
PintaLyme diseaseRelapsing fever
  • Leptospirosis
  • Weil’s disease
Diagnosis
  • VDRL
  • FTA-ABS
  • Direct visualization
  • Clinical
  • VDRL
  • FTA-ABS
  • Clinical
  • VDRL
  • FTA-ABS
  • Clinical
  • ELISA
  • Western blot
Blood-smear analysis
  • Blood culture
  • Urine culture
  • ELISA
  • PCR
Management
  • Penicillin G
  • Ceftriaxone
  • Doxycycline
  • Penicillin G
  • Azithromycin
  • Penicillin G
  • Azithromycin
  • Doxycycline
  • Amoxicillin
  • Ceftriaxone
  • Penicillin G
  • Doxycycline
  • Penicillin G
  • Doxycycline

Osp: outer surface protein

LPS: lipopolysaccharide

P2P: person-to-person

Microaero: microaerophilic

VDRL: Venereal Disease Research Laboratory test

FTA-ABS: fluorescent treponemal antibody absorption

ELISA: enzyme-linked immunosorbent assay

PCR: polymerase chain reaction

References

  1. Barbour, A.G. (2020). Clinical features, diagnosis, and management of relapsing fever. In Mitty, J. (Ed.), Uptodate. Retrieved December 21, 2020, from https://www.uptodate.com/contents/clinical-features-diagnosis-and-management-of-relapsing-fever
  2. Barbour, A.G.(2020). Microbiology, pathogenesis, and epidemiology of relapsing fever. In Mitty, J. (Ed.), Uptodate. Retrieved December 22, 2020, from https://www.uptodate.com/contents/microbiology-pathogenesis-and-epidemiology-of-relapsing-fever
  3. Barbour, A.G. (2020). Microbiology of Lyme disease. In Mitty, J. (Ed.), Uptodate. Retrieved December 22, 2020, from https://www.uptodate.com/contents/microbiology-of-lyme-disease
  4. Gladwin, M., & Trattler, B. (2008). Clinical microbiology made ridiculously simple (4th edition). Miami: MedMaster

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