Ehrlichiosis and Colorado Tick Fever

Tick-borne diseases in the United States include the following

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

HGA – Anaplasma phagocytophilum
- E. ewingii (human ewingii ehrlichiosis) – agent of the disease formerly known as human granulocytotropic ehrlichiosis (HGE) and now known as HGA
  - 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 diagnosis and can result in high fatality rate if untreated
- Serological diagnosis confirmation may take several weeks as 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 – asceptic meningitis, meningoencephalitis

Treatment

Supportive care

Indications for Testing

Flu-like illness after exposure to tick

Laboratory Testing

Clinical laboratory testing offers little help in initial diagnosis when immediate therapeutic decisions are required
Initial testing
- CBC with differential
  - Thrombocytopenia and leucopenia – suggest HGA but consider Babesia and Colorado tick fever screening
- Liver function tests
  - Mild elevation in HGA, 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 as 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 on all organisms in this group
- 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
T. pallidum (secondary)
Thrombotic thrombocytopenic purpura
Neisseria meningitidis

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Initial testing for infectious process

Test name: Hepatic Function Panel

ARUP #: 0020416

Methodology: Refer to individual components.

Use:

Testing for liver function

Mildly elevated in HGA, HME

Test name: Ehrlichia and Anaplasma species by Real-Time PCR

ARUP #: 2003078

Methodology: Real-Time Polymerase Chain Reaction /DNA Probe Hybridization

Use:

Diagnose infection from Ehrlichia or Anaplasma organisms

Test name: Colorado Tick Fever Antibodies, IgG & IgM, IFA

ARUP #: 0093167

Methodology: Immunofluorescence Assay

Use:

Diagnose infection with Colorado tick fever

Limitations:

IgM titers alone may not be sufficient to confirm disease

Follow-up:

May require acute and convalescent samples to determine presence of disease

Test name: Ehrlichia chaffeensis Antibodies, IgG & IgM by IFA

ARUP #: 0051002

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Use:

Diagnose infection with Ehrlichia chaffeensis

Limitations:

IgM titers alone may not be sufficient to confirm disease

Follow-up:

May require acute and convalescent samples to determine presence of disease

Test name: Anaplasma phagocytophilum (HGA) Antibodies, IgG & IgM

ARUP #: 0097303

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Use:

Diagnose infection with Anaplasma phagocytophilum

Limitations:

IgM titers alone may not be sufficient to confirm disease

Follow-up:

May require acute and convalescent samples to determine presence of disease

Test name: Babesia microti Antibodies, IgG & IgM by IFA

ARUP #: 0093048

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Use:

Diagnose Babesia microti infection

Limitations:

IgM titers alone may not be sufficient to confirm disease

Follow-up:

May require acute and convalescent samples to determine presence of disease

Additional Tests Available

Test name: Wright Stain

ARUP #:

Methodology:

Comments:

Test name: Giemsa Stain

ARUP #:

Methodology:

Comments:

Test name: Ehrlichia chaffeensis Antibody, IgM by IFA

ARUP #: 0051003

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Ehrlichia chaffeensis Antibody, IgG by IFA

ARUP #: 0051004

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Anaplasma phagocytophilum (HGA) Antibody, IgG

ARUP #: 0097317

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Anaplasma phagocytophilum (HGA) Antibody, IgM

ARUP #: 0097318

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Ehrlichia chaffeensis DNA, Real-Time PCR

ARUP #: 2002994

Methodology: Real-Time Polymerase Chain Reaction

Comments:

Useful for early diagnosis of ehrlichiosis infection

Guidelines

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. 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

Hill, Harry R., MD. Group Medical Director, Laboratory of Immunology, ARUP Laboratories, and Executive Director of the ARUP Institute for Clinical and Experimental Pathology; Professor and Division Head, Pathology (Clinical), University of Utah

Comprehensive Review: February 2011
Last Update: February 2011

Babesia microti

Borrelia burgdorferi

Dengue Fever Virus

Encephalitis, Infectious

Enterovirus

Francisella tularensis

Leptospira Species

Meningitis, Acute

Rickettsia rickettsii

Rickettsia typhi

Toxoplasma gondii