Borrrelia burgdorferi (Lyme disease): Clinical Features, Diagnosis

Last updated on June 11th, 2021

Lyme disease or Lyme borreliosis is a vector-borne zoonotic disease caused by three genomospecies of Borrelia, collectively referred to as Borrrelia burgdorferi and rarely by Borrelia mayonii.

Characteristics of Borrelia burgdorferi

Borrelia burgdorferi is a helical-shaped spirochete that is poorly gram-stained (other spirochetes do not take up Gram stain). It is better viewed under a dark ground microscope or by silver impregnation staining. The ultrastructure of Borrelia is similar to Treponema and Leptospira with minor differences.

  • Size: Larger, 10-30 μm in length and 0.2-0.5 μm in width.
  • Spirals: They are less in number (3-10 μm) with wider spirals (3 μm) and longer amplitude (2 μm)
  • Endoflagella: More in number (7-11), attached subterminally at the pole.

Transmission

Rodents and deer are the main reservoirs of Lyme disease. It is widespread in USA, but also reported from other parts of the world.

Lyme disease is transmitted by the bite of black-legged tick (Ixodes scapularis or Ixodes pacificus ). All three stages of tick, (i.e. larval, nymphal, and adult stages) can transmit the infection but It is thought that nymphs infect more humans than adult ticks because they are so hard to see (<2 mm).

4 distinct life stages of tick
Life stages of tick (Image source)

Borrrelia burgdorferi expresses outer-surface protein A (OspA) in the midgut of the tick which is required for its survival in tick. When the bacterium reaches the salivary gland of the tick, it expresses protein OspC that binds to a tick salivary gland protein (Salp15). This attachment is crucial for transmission.

There is no evidence of person-person transmission of Lyme disease. There is no credible evidence that Lyme disease can be transmitted through air, food, water, or from the bites of mosquitoes, flies, fleas, or lice.

The tick must attach at least for 24 hours for transmission. Removing a tick quickly (within 24 hours) can greatly reduce the chance of getting Lyme disease.

Clinical Manifestations

If left untreated Lyme disease can produce a wide range of symptoms, depending on the stage of infection. These include fever, rash, facial paralysis, and arthritis.

Stage 1: Early localized infection

After an incubation period of 3-32 days, an annular maculopapular lesion develops at the site of the tick bite called erythema migrans, commonly involving thigh, groin and axilla. It may be absent in 20% of cases. Classic erythema migrans rash appears as “bull’s-eye”.

Erythema migrans can present itself in many different forms.
Different types of rash seen in Lyme disease. Not everyone will have “bullseye”  rash.
(Image source)

Stage 2: Early disseminated infection

If untreated, B. burgdorferi spread hematogenously to many sites within days or weeks resulting wider range of symptoms. These symptoms usually appear weeks or months after infection and can include:

  • Secondary annular skin lesions (more or larger rashes covering more parts of the body)
  • Musculoskeletal pain (arthralgia)
  • Profound malaise and fatigue
  • Bell’s palsy (facial paralysis)

Neurological abnormalities occur in 15% of cases and include meningitis, encephalitis, and typical lymphocytic meningoradiculitis seen in cases from Europe and Asia; called Bannwarth syndrome. Cardiac involvement occurs in 8% of cases, including atrioventricular block.

Stage 3: Late persistent infection (lyme arthritis)

Symptoms of late disseminated Lyme disease can appear months or even years after infection. Symptoms in this later stage of infection are more severe and include:

  • Frank arthritis involving large joints (especially the knees), lasting for weeks or months in a given joint.
  • Inflammation of the heart
  • Inflammaton of the brain, etc.

Laboratory Diagnosis

Sample depends on the clinical presentations and may include blood, CSF, or scrapping from skin lesions.

Borrelia in dark-field microscopy
Borrelia in dark-field microscopy (Image source)

Culture

Isolation of B. burgdorferi can be done by culturing specimens like skin lesions, blood or CSF in special medium called BSK medium (Barbour-Stoenner-Kelly). Cultures are incubated at 34oC and examined under dark field microscope weekly for two months.

Serology

it is the principal method of diagnosis of Lyme disease. In the first month of infection, both IgM and IgG are detected. As disease proceeds, IgM disappears and IgG response predominates.

  • Four-fold rise in titre at 2-3 weeks interval is more significant.
  • ELISA and western blot formats are available for separate detection of IgG and IgM.

Earlier, CDC recommended performing an ELISA first and if found positive or equivocal, it has to be confirmed by IgM and/or IgG immunoblots. This standard two-tiered testing (STTT) algorithm for Lyme disease serology is replaced by a modified two-tiered testing (MTTT) algorithm that employs two enzyme immunoassays (EIAs)

Modified two tiered testing for lyme disease
Modified two tiered testing for Lyme disease (Image source)

Molecular methods

PCR detecting specific DNA is much superior to culture for the detection of B. burgdorferi in joint fluid but its sensitivity is poor for CSF, blood or urine samples. PCR-RFLP of the intergenic rrf-rrl region has been used for genomospecies detection.

References and further readings

  • Microbe Wiki, Borrelia burgdorferi
  • Performance of a Modified Two-Tiered Testing Enzyme Immunoassay Algorithm for Serologic Diagnosis of Lyme Disease in Nova ScotiaIan R. C. Davis, Shelly A. McNeil, Wanda Allen, Donna MacKinnon-Cameron, L. Robbin Lindsay, Katarina Bernat, Antonia Dibernardo, Jason J. LeBlanc, Todd F. HatchetteJournal of Clinical Microbiology Jun 2020, 58 (7) e01841-19; DOI: 10.1128/JCM.01841-19
  • Lyme disease. Center for Disease Control and Prevention.
  • Bay Area Lyme Foundation
About Acharya Tankeshwar 467 Articles
Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. I am working as an Asst. Professor and Microbiologist at Department of Microbiology and Immunology, Patan Academy of Health Sciences, Nepal. If you want me to write about any posts that you found confusing/difficult, please mention in the comments below.

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