Ehrlichiosis, Anaplasmosis, and Colorado Tick Fever - Tick-Borne Diseases

  • 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, Tick-borne 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 human granulocytic anaplasmosis (HGA), but consider B. microti and Colorado tick fever screening
    • Liver function tests
      • Mild elevation in HGA, human monocytic ehrlichiosis (HME)
    • Peripheral smear (Wright or Giemsa stain)
      • Morulae present
        • HGA, HME
          • In neutrophils or bands – HGA
          • In monocytes – HME
          • Peripheral smear most useful in HGA because 25-75% of patients will be positive; ≤10% in HME
      • Immunofluorescence
        • Staining positive in Colorado tick fever
  • If rash cannot be identified as HME, suggest testing for Lyme disease (see Lyme Disease Testing algorithm)
  • PCR – most sensitive method to confirm Ehrlichia and Anaplasma infection (particularly during early phase)
    • Preferred test option for
      • Timely and accurate diagnosis
      • Rapid turn-around time
  • Serology – antibody testing by 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 with samples spaced 3-6 weeks apart
    • Antibodies to Ehrlichia and Anaplasma are highly cross-reactive
      • 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

Tick-borne diseases in the U.S. include

  • Lyme disease (Borrelia burgdorferi)
  • Human ehrlichiosis (human monocytic ehrlichiosis [HME], human granulocytic ehrlichiosis [HGE], and human granulocytic anaplasmosis [HGA])
  • Rocky Mountain spotted fever (Rickettsia rickettsii)
  • Babesiosis (Babesia microti)
  • Colorado tick fever (CTF)



  • Incidence – 1.7/1,000,000 in the U.S.
  • Age – more common in persons >60 years
  • Sex – M>F
  • Transmission
    • HGA – tick (Ixodes scapularis); reservoir species (white-footed mouse, white-tailed deer)
    • HGE – tick (Ixodes scapularis); reservoir species (white-footed mouse, white-tailed deer)
    • HME – tick (Amblyomma americanum and Dermacentor variabilis); reservoir species (white-tailed deer, red fox)
    • Peak infectious season – April-September
    • Infection rate – highest in Southeast and mid-Atlantic states


  • Obligate intracellular bacteria
  • Human ehrlichiosis is caused by at least 3 different ehrlichial species in the U.S. – E. chaffeenis, E. ewingii, and a thirdEhrlichia species provisionally called Ehrlichia muris-like (EML)
  • Human granulocytic anaplasmosis (HGA) – Anaplasma phagocytophilum
    • Infects neutrophils and granulocytes
  • Human granulocytic ehrlichiosis (HGE) – E. ewingii
    • Infects neutrophils and granulocytes
  • Human monocytic ehrlichiosis (HME) – E. chaffeensis
    • Infects monocytes and macrophages

Risk Factors

  • Exposure in regions where tick is endemic
    • HGA – upper Midwest and Northeast U.S.; May-August
    • HGE – upper Midwest and Northeast U.S.; May-August
    • HME – South Central and Southeast U.S.; May-August
  • Older age
  • Immunocompromised state
  • Asplenia

Clinical Presentation

  • Incubation – 1-2 weeks
  • HGA, HGE, and HME infections are clinically indistinguishable
    • Influenza-like – headache, myalgias, fever, chills, malaise, cough
    • Rash – macular, maculopapular or petechial
      • Rare in HGA
  • Elderly and immunocompromised patients are more prone to severe infections and death


  • Antibiotic therapy should begin as soon as possible after onset of symptoms
    • Because of nonspecific clinical presentation, HME is difficult to diagnose and can result in high fatality rate if untreated
    • Serological diagnosis confirmation may take several weeks because convalescent titers are required


  • Wear clothing for maximum skin coverage (long sleeves and pants)
    • White or light colors allow ticks to be more easily seen
  • Prompt removal of ticks

Colorado Tick Fever


  • Prevalence – 200-400 cases per year in the U.S.
  • Transmission – tick (Dermacentor andersoni); reservoir species (small rodents, including chipmunk, squirrel, rat)
  • Infection rate highest in Rocky Mountain region of North America at elevations above 4,000 feet


  • Coltivirus genus and Reoviridae family
  • Double-stranded RNA arbovirus

Clinical Presentation


  • Supportive care

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

Follow Up

May require acute and convalescent samples to determine presence of disease

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

Follow Up

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

Follow Up

May require acute and convalescent samples to determine presence of disease

Related Tests


Chapman AS, Bakken JS, Folk SM, Paddock CD, Bloch KC, Krusell A, Sexton DJ, Buckingham SC, Marshall GS, Storch GA, Dasch GA, McQuiston JH, Swerdlow DL, Dumler SJ, Nicholson WL, Walker DH, Eremeeva ME, Ohl CA, Tickborne Rickettsial Diseases Working Group, CDC. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep. 2006; 55(RR-4): 1-27. PubMed

General References

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

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

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: April 2016