What laboratory tests should be ordered to check for tickborne illnesses?

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Laboratory Testing for Tickborne Illnesses

For suspected tickborne illnesses, laboratory testing should include specific tests based on geographic location, tick species, and clinical presentation rather than routine testing of all patients with tick bites. 1

Initial Testing Approach

  • Complete blood count with differential should be included in the initial laboratory workup 2
  • Consultation with the microbiology laboratory is essential to determine specimen requirements, testing availability, and turnaround times 3
  • Patient travel history, recent locations, and potential tick bite duration are critical factors in determining appropriate testing 1

Recommended Laboratory Tests by Pathogen

Rickettsial Diseases (Rocky Mountain Spotted Fever and other Spotted Fever Group Rickettsioses)

  • Serology: Acute and convalescent IFA for R. rickettsii IgM and IgG antibodies 3
  • PCR of whole blood (note: has low sensitivity except in severe disease) 3
  • Skin biopsy (preferably from a maculopapule containing petechiae or the margin of an eschar) for immunohistochemical staining 3
  • Rash biopsy for PCR testing 3

Ehrlichiosis (E. chaffeensis, E. ewingii, E. muris-like agent)

  • Wright or Giemsa stain of peripheral blood or buffy coat leukocytes smear during first week of infection to detect morulae 3
  • Serology: Acute and convalescent IFA titers for Ehrlichia antibodies 3
  • PCR of whole blood 3
  • Microscopy for morulae detection in white blood cells 3

Anaplasmosis (Human Granulocytic Anaplasmosis)

  • Wright or Giemsa stain of peripheral blood or buffy coat for morulae detection 3
  • Serology: Acute and convalescent IFA titers for Anaplasma antibodies 3
  • PCR of whole blood 3

Babesiosis

  • Primary test: Giemsa, Wright's, or Wright-Giemsa stains of peripheral thin and thick blood smears (Giemsa preferred) 3
  • Serology: Acute and convalescent IFA titers for Babesia antibodies (IgM and IgG) 3
  • PCR of whole blood 3

Lyme Disease

  • Early Lyme disease with erythema migrans: Serologic testing is insensitive in the first 2 weeks of infection 3
  • Early/disseminated or late/persistent Lyme disease: Two-tier testing = EIA IgG and IgM antibody screening followed by IgG and IgM Western blot if EIA is positive or equivocal 3
  • Neuroborreliosis: Paired serum/CSF antibody levels (CSF/serum antibody index) 3
  • PCR of blood, skin biopsy specimens, synovial fluid or tissue, CSF 3

Relapsing Fever Borreliae

  • Primary test: Darkfield microscopy or Wright's, Giemsa or Diff-Quik stains of peripheral thin or thick blood smears 3
  • PCR of blood, serum, or body fluids 3
  • Serologic testing 3

Colorado Tick Fever Virus

  • Virus-specific IFA-stained blood smears 3
  • Serology: IFA titers or complement fixation 3

Timing of Laboratory Testing

  • For serologic confirmation of tickborne diseases, IgG IFA testing of at least two serum samples collected 2-4 weeks apart (acute and convalescent phases) is recommended 3
  • A diagnosis is confirmed with a fourfold or greater increase in antibody titer in samples collected at appropriate intervals 3
  • A single elevated antibody titer is never sufficient to confirm acute infection with a rickettsial pathogen 3

Important Considerations and Pitfalls

  • Early antibiotic treatment can blunt the antibody response, potentially leading to false-negative results 3
  • A negative peripheral blood smear does not rule out tickborne disease due to often low and variable sensitivity 3
  • For Lyme disease, a Western blot should NOT be performed unless an initial EIA is reported as positive or equivocal 3
  • The majority of persons have increased IgG titers by the second week of illness, but some infections may have delayed development of significant antibody titers 3
  • The duration that antibodies persist after recovery varies depending on the pathogen and host factors 3

Geographic Considerations

  • Different tickborne pathogens have specific geographic distributions that should guide testing 1
  • Travel history should be carefully evaluated as some tickborne diseases may be acquired outside a patient's home region 3
  • Consider international travel history when evaluating for tickborne diseases not endemic to the United States 3

References

Guideline

Laboratory Tests for Tick Bite Evaluation

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Fever of Unknown Origin

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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