What diagnostic studies are recommended for Lyme disease and anaplasmosis (Anaplasma phagocytophilum infection)?

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From the Guidelines

For suspected Lyme disease and anaplasmosis, order a two-tier testing approach for Lyme disease consisting of an enzyme immunoassay (EIA) or immunofluorescence assay (IFA) followed by a Western blot if the first test is positive or equivocal, as recommended by the Infectious Diseases Society of America (IDSA) in 2021 1.

Key Testing Recommendations

  • For anaplasmosis, order polymerase chain reaction (PCR) testing of whole blood during the first week of illness, as well as examination of peripheral blood smears for morulae in white blood cells.
  • Serologic testing for anaplasmosis using indirect immunofluorescence antibody (IFA) assays should include acute and convalescent samples taken 2-4 weeks apart, with a fourfold rise in titer indicating infection.
  • Complete blood count (CBC), comprehensive metabolic panel, and liver function tests are also recommended as anaplasmosis can cause thrombocytopenia, leukopenia, and elevated liver enzymes.

Clinical Considerations

  • These tests should be ordered promptly when either infection is suspected, as early diagnosis improves treatment outcomes.
  • Remember that in early Lyme disease, serologic tests may be negative, and empiric treatment might be warranted based on clinical presentation and exposure history in endemic areas, as suggested by the IDSA guidelines in 2021 1.
  • Coinfection with Anaplasma phagocytophilum or Babesia microti should be considered in patients with Lyme disease who have a high-grade fever or characteristic laboratory abnormalities, particularly in geographic regions where these infections are endemic 1.

From the Research

Diagnostic Tests for Lyme Disease and Anaplasmosis

  • The diagnosis of Lyme disease is based on clinical manifestations and adjunctive laboratory testing 2.
  • Serologic testing is the principal means of laboratory diagnosis for Lyme disease 3.
  • For Lyme disease, standard 2-tier testing (STTT) incorporating a screening enzyme immunoassay (EIA) or an immunofluorescence assay (IFA) that reflexes to IgM and IgG immunoblots has been the primary diagnostic test since 1995 4.
  • A modified 2-tier test strategy using 2 EIAs was approved by the Food and Drug Administration in 2019, offering a faster, less expensive, and more sensitive assay compared with STTT 4.

Comparison of Lyme Disease and Anaplasmosis

  • Human granulocytic anaplasmosis (HGA) is a more severe illness than early Lyme disease, with patients experiencing more symptoms and having a higher body temperature on presentation 5.
  • HGA patients are also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes compared to patients with early Lyme disease 5.

Guidelines for Diagnosis and Treatment

  • The Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) have developed evidence-based clinical practice guidelines for the prevention, diagnosis, and treatment of Lyme disease 6.
  • These guidelines include recommendations for the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, and Lyme disease complicated by coinfection with other tick-borne pathogens 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Lyme disease: diagnosis and treatment.

Current opinion in rheumatology, 2020

Research

Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease.

MMWR. Morbidity and mortality weekly report, 2019

Research

Diagnostic Testing for Lyme Disease.

Infectious disease clinics of North America, 2022

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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