Borrelia Species

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

Lyme Disease Evaluation

Indications for Testing

  • Borrelia burgdorferi (Lyme disease)
    • Patient at risk for Lyme disease with clinical symptoms
      • Tick bite
      • Presence in area endemic for Lyme disease
    • No testing necessary if patient presents with tick bite and erythema migrans – proceed with treatment
  • Borrelia hermsii (tickborne relapsing fever [TBRF])
    • Patient with relapsing fever and exposure to tick bite in area endemic for TBRF

Laboratory Testing

  • B. burgdorferi
    • Current two-step testing CDC recommendations for serologic diagnosis of Lyme disease
    • B. burgdorferi or C6 peptide antibodies total by ELISA
      • Positive or indeterminate (if neurological symptoms present, see Neurologic Disease Evaluation below)
        • <4 weeks after disease onset
          • B. burgdorferi IgG and IgM antibodies by Western blot
            • Positive IgG and negative IgM – Lyme disease confirmed
            • Negative IgG and positive IgM – Lyme disease or false-positive IgM
              • Follow-up IgG Western blot (within 30 days) recommended to help confirm Lyme disease and rule out false-positive IgM Western blot
            • Negative IgG and IgM – consider other causes of false-positive ELISA result (syphilis, rheumatoid arthritis, acute EBV, HIV, subacute bacterial endocarditis, systemic lupus erythematosus, periodontitis)
              • If Lyme disease still suspected or patient immunocompromised – order Borrelia spp by PCR
        • ≥4 weeks after disease onset
          • B. burgdorferi IgG antibodies by Western blot
            • Positive – Lyme disease confirmed
            • Negative – see negative IgG and IgM above
        • Even if testing is positive for Lyme disease, consider coinfection with Borrelia miyamotoiBabesia microti, Anaplasma phagocytophilum, or Ehrlichia chaffeensis
      • Negative
        • No further testing on initial specimen; test convalescent specimen if suspicion for tickborne disease exists
        • Endemic regions –  consider coinfection with Borrelia miyamotoiB. microti, A. phagocytophilum, E. chaffeensis
    • ​​Lyme arthritis
      • Use Lyme disease serologies to establish diagnosis
        • Patients need positive serologies for B. burgdorferi to consider evaluation for arthritis because arthritis is a late manifestation
      • PCR – B. burgdorferi DNA is detectable in synovial fluid or synovium in most untreated patients
  • B. hermsii
    • Blood smear during acute episode – observation of spirochetes confirms diagnosis
    • Serology for antibodies – retrospective confirmation requires acute and convalescent specimens
  • B. miyamotoi – available only at single laboratory
    • Serology – retrospective confirmation

Neurologic Disease Evaluation

Indications for Testing

  • Meningoradiculitis, meningitis, cranial nerve deficits

Criteria for Diagnosis

Laboratory Testing

  • Acute neurological symptoms present
    • Full meningitis workup (CSF studies)
      • Lumbar fluid analysis; should also include testing for other bacterial and viral etiologies (eg, West Nile virus)
      • Cell count – lymphocytic pleocytosis is typical (>8 wbc/mm3)
      • Total protein, glucose, culture with gram stain
    • B. burgdorferi antibodies (total) by ELISA (CSF)
    • As an alternative, consider one of the following Borrelia tests instead of the total antibodies test
      • B. burgdorferi total C6 peptide antibodies by ELISA (CSF)
      • B. burgdorferi IgG and IgM antibodies by Western blot (CSF)
      • Consider Borrelia spp by PCR
    • If any of the Borrelia tests above are positive – CNS disease suggested
      • Full CSF antibody index must be performed to get more conclusive evidence of neurological disease
  • Chronic neurological symptoms present
    • Full meningitis workup (CSF studies; see above)
    • One of the following Borrelia tests
      • B. burgdorferi IgG antibodies by Western blot (CSF)
      • Borrelia spp by PCR
      • If either Borrelia test is positive – CNS disease suggested

Differential Diagnosis

Borrelia species cause tickborne diseases that may be difficult to diagnose because initial symptoms are similar to other more common illnesses (eg, influenza). Most laboratory testing is retrospective and used as confirmation that an individual was infected with a tickborne organism. Lyme disease caused by B. burgdorferi is the most common vector-borne disease in the U.S.

  • New species – Borrelia mayonii
    • CDC information – currently located only in upper Midwest; 6 reported cases
    • Tick vector – same as Lyme disease, Ixodes scapularis (black-legged tick)
    • Clinical presentation – same as Lyme disease

Clinical Presentation

  • Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

    Borrelia burgdorferi Antibodies, Total by ELISA with Reflex to IgG and IgM by Western Blot (Early Disease) 0050267
    Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

    Limitations 

    Diagnosis of Lyme disease should not be made on the basis of positive IgM results alone in patients with symptoms <4 weeks' duration; antibodies are usually undetectable during early localized stage

    Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA with Reflex to IgG & IgM by Western Blot 0051043
    Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

    Borrelia burgdorferi Antibodies, IgG & IgM by Western Blot 0050254
    Method: Qualitative Western Blot

    Follow-up 

    Retesting in 10-14 days may be helpful when serology test results are equivocal

    Borrelia burgdorferi Antibody, IgG by Western Blot 0050255
    Method: Qualitative Western Blot

    Borrelia Species by PCR (Lyme Disease) 0055570
    Method: Qualitative Polymerase Chain Reaction

    Limitations 

    Negative result does not rule out presence of PCR inhibitors or B. burgdorferi DNA concentrations below detection level of assay

    Tick-Borne Disease Panel by PCR, Blood 2008670
    Method: Qualitative Polymerase Chain Reaction

    Ehrlichia and Anaplasma Species by Real-Time PCR 2007862
    Method: Qualitative Polymerase Chain Reaction

    Limitations 

    Rare E. ewingii and E. canis infections cannot be differentiated by this test

    Cell Count, CSF 0095018
    Method: Cell Count/Differential

    Protein, Total, CSF 0020514
    Method: Reflectance Spectrophotometry

    Glucose, CSF 0020515
    Method: Enzymatic

    Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106
    Method: Stain/Culture/Identification

    Borrelia burgdorferi (Lyme Disease) Reflexive Panel (CSF) 2007335
    Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

    Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA (CSF) 0051046
    Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

    Limitations 

    Blood contamination or transfer of serum antibodies across blood-brain barrier is possible

    Follow-up 

    Detection of antibodies of B. burgdorferi in CSF may indicate CNS infection; follow up with additional CSF studies

    Retesting in 10-14 days may be helpful when serology test results are equivocal

    Borrelia burgdorferi Antibodies, IgG & IgM by Western Blot (CSF) 0055260
    Method: Qualitative Western Blot

    Limitations 

    Blood contamination or transfer of serum antibodies across blood-brain barrier is possible

    Follow-up 

    Detection of antibodies to B. burgdorferi in CSF may indicate CNS infection; follow up with additional CSF studies

    Babesia microti Antibodies, IgG and IgM by IFA 0093048
    Method: Semi-Quantitative Indirect Fluorescent Antibody

    Limitations 

    Will not detect B. duncani or strain MO-1

    Anaplasma phagocytophilum (HGA) Antibodies, IgG and IgM 0097303
    Method: Semi-Quantitative Indirect Fluorescent Antibody

    CD57+ NK Cells, Peripheral Blood by Flow Cytometry 2008912
    Method: Flow Cytometry

    Limitations 

    Significance of low CD57+NK values in diagnosing and monitoring chronic Lyme disease is not well established; use only in conjunction with other diagnostic tests specified in CDC Lyme Disease case definition

    Guidelines

    Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, Krupp L, Gronseth G, Bever CT, Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2007; 69(1): 91-102. PubMed

    Mygland A, Ljøstad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I, European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010; 17(1): 8-16, e1-4. PubMed

    Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler S, Nadelman RB. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006; 43(9): 1089-134. PubMed

    General References

    Bratton RL, Whiteside JW, Hovan MJ, Engle RL, Edwards FD. Diagnosis and treatment of Lyme disease. Mayo Clin Proc. 2008; 83(5): 566-71. PubMed

    Forrester JD, Kjemtrup AM, Fritz CL, et al. Tickborne Relapsing Fever - United States, 1990–2011. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention. Atlanta, GA [Last updated Jan 2015; Accessed: Feb 2016]

    Halperin JJ. Nervous system Lyme disease Infect Dis Clin North Am. 2015; 29(2): 241-53. PubMed

    Hu LT, Tsibris AM, Branda JA. CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 24-2015. A 28-Year-Old Pregnant Woman with Fever, Chills, Headache, and Fatigue. N Engl J Med. 2015; 373(5): 468-75. PubMed

    Hu LT. In the clinic. Lyme disease. Ann Intern Med. 2012; 157(3): ITC2-2 - ITC2-16. PubMed

    Molloy PJ, Telford SR, Chowdri HR, Lepore TJ, Gugliotta JL, Weeks KE, Hewins ME, Goethert HK, Berardi VP. Borrelia miyamotoi Disease in the Northeastern United States: A Case Series. Ann Intern Med. 2015; 163(2): 91-8. PubMed

    Murray TS, Shapiro ED. Lyme disease. Clin Lab Med. 2010; 30(1): 311-28. PubMed

    Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review JAMA. 2016; 315(16): 1767-77. PubMed

    Sood SK. Lyme disease in children Infect Dis Clin North Am. 2015; 29(2): 281-94. PubMed

    Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet. 2012; 379(9814): 461-73. PubMed

    Tick-borne Relapsing Fever (TBRF) . Information for Clinicians. Centers for Disease Control and Prevention. Atlanta, GA [Last updated Jan 2016; Accessed: Feb 2016]

    Wright WF, Riedel DJ, Talwani R, Gilliam BL. Diagnosis and management of Lyme disease. Am Fam Physician. 2012; 85(11): 1086-93. PubMed

    Medical Reviewers

    Last Update: August 2016