What serologies can I order for a patient with suspected recovery from a tickborne illness who is still experiencing fatigue?

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Serological Testing for Patients with Suspected Recovery from Tickborne Illness with Persistent Fatigue

For patients with suspected recovery from tickborne illness who are still experiencing fatigue, serological testing should include IgM and IgG antibody titers for Rocky Mountain spotted fever (RMSF), Ehrlichia chaffeensis, and Anaplasma phagocytophilum, with paired early and late convalescent samples to confirm diagnosis and monitor resolution. 1

Recommended Serological Tests

Primary Tests

  • IgM and IgG antibodies for:
    • Rocky Mountain spotted fever (RMSF)
    • Ehrlichia chaffeensis (HME)
    • Anaplasma phagocytophilum (HGA)
    • Borrelia burgdorferi (Lyme disease)

Supporting Laboratory Tests

  • Complete blood count (CBC) with differential
  • Liver function tests (particularly ALT and AST)
  • C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) 2

Timing of Serological Testing

  • Early convalescent phase: Around 2-3 weeks after symptom onset
  • Late convalescent phase: 8-12 weeks after symptom onset 1

Paired serum samples showing a decline in antibody titers (as demonstrated in Case 4 where RMSF IgM/IgG titers declined from 1,024/512 to 256/256 over time) can confirm recovery from the acute infection while helping to determine if persistent symptoms are related to ongoing infection or post-infectious syndrome 1.

Interpretation of Results

  • Positive serology with declining titers: Suggests recovery from acute infection with possible post-infectious syndrome
  • Persistently elevated or rising titers: May indicate ongoing or inadequate treatment of the infection
  • Negative serology: Consider alternative diagnoses or the possibility that initial infection was treated early before seroconversion occurred

Clinical Considerations

Post-Tickborne Illness Fatigue

Studies have shown that chronic fatigue syndrome (CFS) occurs in up to 71% of patients with a history of borreliosis (Lyme disease) 3. This suggests that persistent fatigue following tickborne illness is a common clinical entity that warrants appropriate evaluation.

Treatment Implications

If serological testing confirms inadequately treated tickborne illness, treatment with doxycycline may resolve persistent symptoms, as demonstrated in Case 4 where the patient's persistent fatigue and headache resolved within one week of doxycycline treatment 1.

Common Pitfalls to Avoid

  • Relying solely on initial negative serology: Antibody development may take several weeks; paired samples are more informative 1
  • Overlooking non-Lyme tickborne diseases: RMSF, ehrlichiosis, and anaplasmosis can all cause persistent symptoms 4
  • Assuming all post-infection fatigue is psychosomatic: Studies show a biological basis for post-tickborne illness fatigue 3, 5
  • Testing ticks rather than patients: Testing patient-retrieved ticks for infections is not recommended 4

Special Considerations

  • For patients with suspected Borrelia miyamotoi infection (a cause of hard tick relapsing fever), specific serological testing may be required as this pathogen may not be detected by standard Lyme disease serology 6, 7
  • Consider PCR testing for tickborne illnesses in patients with recent onset of symptoms (within 1 week) as PCR may detect infection before antibody development 2

By following this testing approach, you can better determine if persistent fatigue is related to inadequately treated tickborne illness that might benefit from additional antimicrobial therapy, or if it represents a post-infectious syndrome requiring symptomatic management.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Evaluation and Management of Fever and Neck Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

[Chronic fatigue syndrome following tick-borne diseases].

Neurologia i neurochirurgia polska, 2003

Research

Tickborne Diseases: Diagnosis and Management.

American family physician, 2020

Research

Hard Tick Relapsing Fever Caused by Borrelia miyamotoi in a Child.

The Pediatric infectious disease journal, 2016

Research

Surveillance for and Discovery of Borrelia Species in US Patients Suspected of Tickborne Illness.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018

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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