Anaplasma phagocytophilum, Coltivirus (Colorado Tick Fever), and Ehrlichia Species

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Influenza-like illness after exposure to tick

Laboratory Testing

  • For laboratory testing suggestions, refer to the CDC's publication, Tickborne Diseases of the U.S.
  • Clinical laboratory testing offers little help in initial diagnosis when immediate therapeutic decisions are required
  • Initial testing
    • CBC with differential
      • Thrombocytopenia and leukopenia – suggest Anaplasma phagocytophilum infection (anaplasmosis), but consider Babesia microti and coltivirus (Colorado tick fever) testing, depending on exposure region
      • Peripheral smear (Wright or Giemsa stain)
        • Morulae presence (limited sensitivity for diagnosis)
          • In granulocytes – Anaplasma infection is more common, but Ehrlichia ewingii also infects granulocytes
          • In monocytes – E. chaffeensis most common
          • Peripheral smear most useful for Anaplasma because many patients can be positive; ≤10% for Ehrlichia spp
    • Liver function tests
      • Mild elevation is suggestive for Anaplasma or Ehrlichia spp, but normal results cannot rule out either
  • If rash is present in patient in endemic region, suggest co-testing for AnaplasmaEhrlichia spp, and Borrelia spp (see Tickborne Disease Testing algorithm)
  • PCR – most sensitive method to confirm Ehrlichia spp and Anaplasma infection (particularly during early phase of disease)
    • Preferred test option for
      • Timely and accurate diagnosis
      • Rapid turn-around time
  • Antibody testing (IFA)
    • Single acute phase testing usually inadequate (most testing in first week is negative)
    • Repeat IFA serologies in 10-14 days may be helpful  
      • Seroconversion is typically best demonstrated by testing of specimens spaced 3-6 weeks apart
    • Antibodies to Ehrlichia spp and Anaplasma are highly cross-reactive (limited specificity for diagnosis)
      • Both organisms should be tested for in all suspected cases
    • Patients treated with tetracycline-class antibiotics early in infection may not seroconvert
  • Culture
    • Difficult to perform
    • May require several weeks to isolate

Differential Diagnosis

Tickborne diseases in the U.S. include

  • Anaplasmosis (or human granulocytic anaplasmosis) (Anaplasma phagocytophilum)
  • Babesiosis (Babesia microti)
  • Colorado tick fever (coltivirus)
  • Ehrlichioses (or human monocytic ehrlichiosis) (Ehrlichia chaffeensis, E. ewingii, and E. muris-like [EML])
  • Lyme disease (Borrelia burgdorferi)
  • Rocky Mountain spotted fever (Rickettsia rickettsii)
  • Spotted fever rickettsioses (Rickettsii parkeri and Rickettsii species 364D)
  • Tickborne relapsing fever
  • Tularemia (Francisella tularensis)
  • Powassan virus (deer tick virus)
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Tick-Borne Disease Panel by PCR, Blood 2008670
Method: Qualitative Polymerase Chain Reaction

Ehrlichia and Anaplasma Species by Real-Time PCR 2007862
Method: Qualitative Polymerase Chain Reaction


Rare E. ewingii and E. canis infections cannot be differentiated by this test

Babesia Species by PCR 2008665
Method: Qualitative Polymerase Chain Reaction

Ehrlichia chaffeensis Antibodies, IgG & IgM by IFA 0051002
Method: Semi-Quantitative Indirect Fluorescent Antibody


May require acute and convalescent specimens to determine presence of disease

Anaplasma phagocytophilum (HGA) Antibodies, IgG and IgM 0097303
Method: Semi-Quantitative Indirect Fluorescent Antibody


May require acute and convalescent samples to determine presence of disease

Babesia microti Antibodies, IgG and IgM by IFA 0093048
Method: Semi-Quantitative Indirect Fluorescent Antibody


Will not detect B. duncani or strain MO-1


May require acute and convalescent specimens to determine presence of disease


Holly M. Biggs, Behravesh CB, Bradley KK, et al. Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis. 65(2);1–44. Centers for Disease Control and Prevention. Atlanta, GA [Last Updated May 2016; Accessed: May 2016]

General References

Bakken JS, Dumler S. Human granulocytic anaplasmosis. Infect Dis Clin North Am. 2008; 22(3): 433-48, viii. PubMed

Bakken JS, Dumler S. Human granulocytic anaplasmosis. Infect Dis Clin North Am. 2015; 29(2): 341-55. PubMed

Dana AN. Diagnosis and treatment of tick infestation and tick-borne diseases with cutaneous manifestations. Dermatol Ther. 2009; 22(4): 293-326. PubMed

Dumler S, Madigan JE, Pusterla N, Bakken JS. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2007; 45 Suppl 1: S45-51. PubMed

Harris RM, Couturier BA, Sample SC, Coulter KS, Casey KK, Schlaberg R. Expanded Geographic Distribution and Clinical Characteristics of Ehrlichia ewingii Infections, United States Emerg Infect Dis. 2016; 22(5): 862-5. PubMed

Ismail N, Bloch KC, McBride JW. Human ehrlichiosis and anaplasmosis. Clin Lab Med. 2010; 30(1): 261-92. PubMed

Romero JR, Simonsen KA. Powassan encephalitis and Colorado tick fever. Infect Dis Clin North Am. 2008; 22(3): 545-59, x. PubMed

Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review JAMA. 2016; 315(16): 1767-77. PubMed

St Clair K, Decker CF. Ehrlichioses: anaplasmosis and human ehrlichiosis. Dis Mon. 2012; 58(6): 346-54. PubMed

Walker DH, Paddock CD, Dumler S. Emerging and re-emerging tick-transmitted rickettsial and ehrlichial infections. Med Clin North Am. 2008; 92(6): 1345-61, x. PubMed

Medical Reviewers

Last Update: September 2016