What labs should be ordered for a patient suspected of having a tick-borne illness?

Laboratory Testing for Suspected Tick-Borne Illnesses

Order a complete blood count (CBC) immediately for any patient with suspected tick-borne illness, as thrombocytopenia and leukopenia are characteristic findings that can guide early diagnosis and treatment decisions. 1

Initial Laboratory Workup

Essential First-Line Tests

• CBC with differential is the most critical initial test, revealing characteristic findings including:

  • Leukopenia (WBC <4.5 x 10⁹ cells/L) 1
  • Thrombocytopenia (platelets <150 x 10⁹ cells/L) 1
  • These findings help distinguish tick-borne illness from viral gastroenteritis or other nonspecific febrile illnesses 1

• Comprehensive metabolic panel should be ordered to assess liver function, as hepatic abnormalities occur in 50-75% of ehrlichiosis and anaplasmosis cases 2

• Blood smear examination (Wright's, Giemsa, or Diff-Quik stain) can provide rapid presumptive diagnosis by identifying morulae in leukocytes for ehrlichiosis/anaplasmosis, though sensitivity is low (only 1-20% of cases) 1

Pathogen-Specific Molecular and Serologic Testing

Acute Phase Testing (First Week of Illness)

• PCR testing on EDTA-anticoagulated whole blood (3-5 mL preferred) for:

  • Anaplasma phagocytophilum 1
  • Ehrlichia chaffeensis 1
  • Spotted fever group rickettsiae 1
  • PCR is most sensitive during the first week of illness and before or within 48 hours of starting doxycycline 1

• Serologic testing (acute serum) for:

  • Borrelia burgdorferi (Lyme disease) 1
  • E. chaffeensis 1
  • A. phagocytophilum 1
  • Note: Serology is often negative during the first week, so negative results do not rule out disease 1

Convalescent Phase Testing (2-4 Weeks After Onset)

• Paired acute and convalescent sera for IFA (indirect immunofluorescence antibody) testing is the reference standard for serologic confirmation 1
  • A fourfold or greater increase in IgG antibody titer confirms diagnosis 1
  • Convalescent serum should be collected 2-4 weeks after acute specimen 1
  • Single elevated titers (≥1:64) support but do not confirm diagnosis 1

Lyme Disease-Specific Testing Algorithm

• Two-tier testing approach for early disseminated or late Lyme disease:

  • First: EIA (enzyme immunoassay) for IgG and IgM antibodies 1, 3
  • Second: Western blot confirmation only if EIA is positive or equivocal 1, 3
  • Never perform Western blot without positive or equivocal EIA screening 1

• For neuroborreliosis: obtain paired serum/CSF antibody levels to calculate CSF/serum antibody index 1, 3

Tissue-Based Testing (When Applicable)

For Spotted Fever Group Rickettsioses

• Eschar biopsy or swab (if eschar present):

  • Punch biopsy specimens (≥4 mm) are preferred over swabs 1
  • Eschars contain abundant rickettsiae and represent the best clinical sample for diagnosis 1
  • Submit for PCR and immunohistochemistry 1

• Skin biopsy of rash (≥4 mm punch biopsy):

  • Most sensitive during first week before doxycycline therapy 1
  • Submit for PCR, culture, and immunohistochemistry 1

Critical Timing Considerations

• Collect specimens before initiating doxycycline therapy whenever possible, as antibiotic treatment rapidly decreases PCR sensitivity within 24-48 hours 1

• Do not delay treatment while awaiting laboratory results when clinical suspicion is high, particularly for Rocky Mountain spotted fever which has high mortality 1, 4

• Early antibiotic treatment may blunt antibody response, potentially causing false-negative serology 3

Additional Supportive Tests

• Blood, urine, and stool cultures should be ordered to exclude other causes of sepsis and fever of unknown origin 1

• Liver function tests are valuable as transaminase elevations are common in ehrlichiosis and anaplasmosis 2

Common Pitfalls to Avoid

• Do not rely on negative acute-phase serology to exclude tick-borne disease, as antibodies are typically absent during the first 7 days of illness when patients present for care 1

• Do not test patient-retrieved ticks for infections, as this is not recommended and does not guide clinical management 4

• Do not order Western blot as a standalone test—it must be preceded by positive or equivocal EIA screening 1

• Do not interpret detectable antibodies as indication for treatment in asymptomatic patients, as antibodies can persist for months to years after resolved infection 1

• Consult your microbiology laboratory before ordering specialized tests to confirm specimen requirements, testing availability, and turnaround times, as many tests require referral to reference laboratories 1, 3

Geographic and Epidemiologic Context

• Patient travel history, recent outdoor activities in wooded areas, and geographic location are essential for determining which specific pathogens to test for 1, 3

• Testing should be targeted based on local epidemiology rather than ordering comprehensive panels for all patients 3