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

Diagnosis

Indications for Testing

• Influenza-like illness after exposure to tick

Laboratory Testing

• Ehrlichia laboratory detections (CDC)
• 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)
• Serology (PCR or IFA) – antibody testing; PCR most sensitive method for confirmation
  • Single acute phase testing usually inadequate – most testing in first week is negative
    • Repeat PCR or IFA serologies in 10-14 days
  • High seroprevalence rates may be found in endemic areas
• Culture 
  • Difficult to perform
  • May require several weeks to isolate

Differential Diagnosis

• Babesia microti
• Borrelia burgdorferi
• Francisella tularensis
• Rocky Mountain spotted fever (Rickettsia rickettsii)
• Enterovirus (including coxsackievirus)
• Erythema infectiosum
• Human herpesvirus 6 (HHV6)
• Epstein-Barr virus
• Disseminated gonococcus (Neisseria gonorrhoea)
• Kawasaki disease
• Leptospira spp
• Treponema pallidum (secondary)
• Thrombotic thrombocytopenic purpura
• Neisseria meningitidis

Clinical Background

Tick-borne diseases in the U.S. include

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

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)
  • 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
• HGA – Anaplasma phagocytophilum
  • Ehrlichia ewingii (human ewingii ehrlichiosis) – agent of the disease known as HGA, formerly known as human granulocytotropic ehrlichiosis (HGE)
    • Infects monocular phagocytic cells
• HME – E. chaffeensis

Risk Factors

• Exposure in regions where tick is endemic
  • HGA – 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 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

• Identical to ehrlichiosis – macular rash in 5-15% of patients
• Complications – aseptic meningitis, meningoencephalitis

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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
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 & 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

Diagnostic Algorithm

  Lyme Disease Testing Algorithm