Borrelia burgdorferi

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Lyme Disease Testing Algorithm

Clinical Background

Lyme disease is the most common vector-borne disease in the U.S.

Epidemiology

Incidence - increased 40% from 2001 to 2002
Age - bimodal peaks (pediatric 5-14 years; elderly >60 years)
Sex - M:F; 1:1 except for the presentation of acrodermatitis chronica atrophicans (M<F)
Transmission - infected Ixodes tick bite

Organism

Borrelia burgdorferi is a member of the Spirochaetales family which also includes Treponema and Leptospira

Risk Factors

Exposure in regions where deer population is high during the spring or summer
Northeast or Midwest geographic location
- 12 U.S. states account for 95% of reported cases

Clinical Presentation

Centers for Disease Control (CDC) clinical case epidemiologic surveillance criteria for defining Lyme disease
- Erythema migrans (EM) greater than or equal to 5 cm in diameter or
- Laboratory confirmation of infection and at least 1 late manifestation
  - Musculoskeletal manifestation - recurrent, brief attacks of objective joint swelling in 1 or more joints
  - Neurological manifestations
    - All or part of a triad
      - Lymphocytic meningitis - CSF pleocytosis with higher number of monocytes
      - Cranial neuritis
      - Radiculoneuritis - termed Garin-Bujadoux-Bannworth syndrome
      - Encephalomyelitis - requires demonstration of CSF antibody production
  - Cardiovascular manifestations - acute second or third degree arteriovenous (AV) heart block
Lyme disease stages
- Stage 1 early localized
  - Occurs within hours to several weeks after infection
  - Characterized by erythema migrans (EM) or lymphocytoma (rare in U.S.)
  - Manifestations
    - Regional adenopathy and/or minor constitutional symptoms
- Stage 2 early disseminated
  - Occurs weeks to months following the tick bite
  - Characterized by neurologic and cardiac involvement (manifested in 15% and 8% of patients, respectively)
  - Manifestations
    - Fever
    - Myalgias
    - Multiple EM lesions
    - Meningitis
    - Bells palsy
    - Guillain-Barré-like syndrome
    - Cardiac conduction abnormalities
    - Arthritis
- Stage 3 late disseminated
  - Occurs within a few weeks to 2 years following infection
  - Symptoms are more severe than early disseminated
  - Characterized by arthritis or central nervous system involvement
    - Occurs in 60% of individuals not effectively treated early in infection
    - Tends to be intermittent, lasting from several days to weeks
  - Manifestations
    - Memory loss
    - Fatigue
    - Polyneuropathy
Initial symptoms usually appear in late spring/early summer, when ticks are active
Late manifestations occur anytime

Treatment

Lyme disease, caught early, is easily treated
- Treatment prevents progression to chronic stage
- Severe, long-term effects occur in <10% of untreated patients
If known tick bite and erythema migrans present, proceed with treatment; testing is not necessary

Prevention

Avoid exposure to ticks
If exposure is unavoidable, use protective clothing and tick repellant; check for and remove ticks

See Also

Babesia microti

Dengue Fever Virus

Ehrlichia chaffeensis

Francisella tularensis

Meningitis, Acute

Parvovirus B 19 - Parvo

Rickettsia rickettsii - Rocky Mountain Spotted Fever

Tick-Borne Diseases

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Lyme Disease Testing Algorithm

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Borrelia burgdorferi Antibodies, Total by ELISA with Reflex to IgG & IgM by Western Blot (Early Disease)

ARUP #: 0050267

Methodology: Enzyme-Linked Immunosorbent Assay/Western Blot

Use:

Screen for Lyme disease <8 weeks after onset of disease

If known tick bite and erythema migrans present, proceed with treatment - no testing necessary

Limitations:

No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific

Diagnosis depends on clinical features, combined with available laboratory tests

Follow-up:

Test name: Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA with Reflex to IgG & IgM by Western Blot

ARUP #: 0051043

Methodology: Enzyme-Linked Immunosorbent Assay/Western Blot

Use:

Screen for Lyme disease <8 weeks after onset of disease

If known tick bite and erythema migrans present, proceed with treatment - no testing necessary

Limitations:

No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific

Diagnosis depends on clinical features, combined with available laboratory tests

Test name: Borrelia burgdorferi Antibodies, IgG & IgM by Western Blot

ARUP #: 0050254

Methodology: Western Blot

Use:

Confirm an equivocal or positive antibody test performed <8 weeks after appearance of erythema migrans

If known tick bite and erythema migrans present, proceed with treatment - no testing necessary

Limitations:

No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific

Diagnosis depends on clinical features, combined with available laboratory tests

Follow-up:

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

Test name: Borrelia burgdorferi Antibody, IgG by Western Blot

ARUP #: 0050255

Methodology: Western Blot

Use:

Confirm an equivocal or positive antibody test performed >8 weeks after appearance of erythema migrans

If known tick bite and erythema migrans present, proceed with treatment - no testing necessary

Limitations:

No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific

Diagnosis depends on clinical features, combined with available laboratory tests

Follow-up:

Test name: Borrelia species DNA Detection by PCR (Lyme Disease)

ARUP #: 0055570

Methodology: Polymerase Chain Reaction

Use:

Diagnose Lyme disease in patient with negative serologic results but disease still strongly suspected, or with immune deficiency

If known tick bite and erythema migrans present, proceed with treatment - no testing necessary

Limitations:

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

No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific

Diagnosis depends on clinical features, combined with available laboratory tests

Follow-up:

Test name: Borrelia burgdorferi Antibody, IgG by Western Blot (CSF)

ARUP #: 0055259

Methodology: Western Blot

Use:

Adjunct test for neuroborreliosis in patient with neurological symptoms >8 weeks after onset of disease

Limitations:

No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific

Diagnosis depends on clinical features, combined with available laboratory tests

Follow-up:

Detection of antibodies to B. burgdorferi in cerebrospinal fluid may indicate central nervous system infection

Consider possible contamination by blood or transfer of serum antibodies across blood-brain barrier

Test name: Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA (CSF)

ARUP #: 0051046

Methodology: Enzyme-Linked Immunosorbent Assay

Use:

Adjunct test for neuroborreliosis in patient with neurologic symptoms <8 weeks from onset of disease

Limitations:

No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific

Diagnosis depends on clinical features, combined with available laboratory tests

Follow-up:

Detection of antibodies of B. burgdorferi in CSF may indicate central nervous system infection

Consider possible contamination by blood or transfer of serum antibodies across blood-brain barrier

For equivocal test results, repeat testing in 10-14 days may be helpful

Test name: Borrelia burgdorferi Antibodies, Total by ELISA (CSF)

ARUP #: 0099483

Methodology: Enzyme-Linked Immunosorbent Assay

Use:

Screening test (confirmed by Western Blot) for neuroborreliosis in patient with neurologic symptoms <8 weeks from onset of disease

Limitations:

No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific
Diagnosis depends on clinical features, combined with available laboratory tests

Follow-up:

Detection of antibodies to B. burgdorferi in cerebrospinal fluid may indicate central nervous system infection

Consider possible contamination by blood or transfer of serum antibodies across blood-brain barrier

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

Test name: Borrelia burgdorferi Antibodies, IgG & IgM by Western Blot (CSF)

ARUP #: 0055260

Methodology: Western Blot

Use:

Confirm positive test for CSF antibodies

Limitations:

No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific

Diagnosis depends on clinical features, combined with available laboratory tests

Follow-up:

Detection of antibodies to B. burgdorferi in cerebrospinal fluid may indicate central nervous system infection

Consider possible contamination by blood or transfer of serum antibodies across the blood-brain barrier

Additional Tests Available

Test name: Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA

ARUP #: 0051044

Methodology: Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Borrelia burgdorferi Antibody, IgM by Western Blot

ARUP #: 0050253

Methodology: Western Blot

Comments:

Test name: Borrelia burgdorferi Total Antibodies, IgG and/or IgM by ELISA with Reflex to IgG by Western Blot (Late Disease)

ARUP #: 0050268

Methodology: Enzyme-Linked Immunosorbent Assay/Western Blot

Comments:

Test name: Borrelia burgdorferi Antibody, IgM by Western Blot (CSF)

ARUP #: 0055258

Methodology: Western Blot

Comments:

Test name: Borrelia hermsii Antibody Panel, IFA

ARUP #: 0093170

Methodology: Immunofluorescence Assay

Comments:

Test name: Lyme Antigen, Urine

ARUP #: 0050219

Methodology: Lyme Dot-Blot Assay

Comments:

Test name: Borrelia burgdorferi Antibodies, Total by ELISA

ARUP #: 0050216

Methodology: Enzyme-Linked Immunosorbent Assay

Comments: Alternative first line screening test for Lyme diseaseIf known tick bite and erythema migrans present, proceed with treatment - no testing necessaryUp to 40% of patients with early disease are seronegative by ELISA at time they present with erythema migransSerologic diagnosis often not established until advanced stage of diseaseNo objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specificDiagnosis depends on clinical features, combined with available laboratory testsRetesting in 10-14 days may be helpful when serology test results are equivocal

Test name: Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA with Reflex to IgG by Western Blot

ARUP #: 0051045

Methodology: Enzyme-Linked Immunosorbent Assay/Western Blot

Comments: Screen for Lyme disease >8 weeks after onset of diseaseIf known tick bite and erythema migrans present, proceed with treatment - no testing necessaryNo objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specificDiagnosis depends on clinical features, combined with available laboratory tests

Additional Information

Serological testing
- False-positive results from serologic tests may result from:
  - Other spirochetal disease (syphilis, periodontitis)
  - Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis)
  - Other infections (subacute bacterial endocarditis, HIV, Acute EBV)