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

Diagnosis

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

Clinical Background

Tick-borne diseases in the U.S. include

Ehrlichiosis

Epidemiology

  • 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

Organisms

  • Obligate intracellular bacteria
  • Human ehrlichiosis is caused by at least 3 different ehrlichial species in the U.S. – E. chaffeenis, E. ewingii, and a third Ehrlichia 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

Treatment

  • 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

Prevention

  • 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

Epidemiology

  • 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

Organism

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

Clinical Presentation

Treatment

  • Supportive care

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Tick-Borne Disease Panel by PCR, Blood 2008670
Method: Qualitative Polymerase Chain Reaction

Diagnose infection from Ehrlichia, Anaplasma, and  Babesia species infecting humans

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

Diagnose infection from Ehrlichia and Anaplasma species infecting humans

Detects and speciates Anaplasma phagocytophilum; Ehrlichia chaffeensis; E. ewingii/E. canis; E. muris-like

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

 
Babesia Species by PCR 2008665
Method: Qualitative Polymerase Chain Reaction

Detect presence of B. microti

Nucleic acid from B. duncani, B. divergens, strain MO-1, and strain EU-1 are detected but are not differentiated

   
Colorado Tick Fever Antibodies, IgG and IgM, IFA 0093167
Method: Immunofluorescence Assay
(Indirect Fluorescent Antibody)

Diagnose infection with Colorado tick fever

 

May require acute and convalescent samples to determine presence of disease

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

Diagnose infection with Ehrlichia chaffeensis

 

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

Diagnose infection with Anaplasma phagocytophilum

 

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

Diagnose Babesia microti infection

 

May require acute and convalescent samples to determine presence of disease

Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Initial testing for infectious process

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Use to screen for hepatic dysfunction

Wright Stain
Giemsa Stain
Ehrlichia chaffeensis Antibody, IgM by IFA 0051003
Method: Semi-Quantitative Indirect Fluorescent Antibody

IgM titers alone may not be sufficient to confirm disease

Ehrlichia chaffeensis Antibody, IgG by IFA 0051004
Method: Semi-Quantitative Indirect Fluorescent Antibody
Anaplasma phagocytophilum (HGA) Antibody, IgG 0097317
Method: Semi-Quantitative Indirect Fluorescent Antibody
Anaplasma phagocytophilum (HGA) Antibody, IgM 0097318
Method: Semi-Quantitative Indirect Fluorescent Antibody

IgM titers alone may not be sufficient to confirm disease

Borrelia burgdorferi Antibodies, Total by ELISA with Reflex to IgG and IgM by Western Blot (Early Disease) 0050267
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Screen for Lyme disease <4 weeks after onset of disease