Anaplasma phagocytophilum and Ehrlichia Species - Anaplasmosis and Ehrlichiosis

In North America, ticks are primary vectors of infectious diseases. Some of the most common tickborne diseases in the U.S. include Lyme disease, babesiosis, ehrlichiosis, Rocky Mountain spotted fever, Anaplasmosis, tickborne relapsing fever, and tularemia. Other tickborne diseases include Colorado tick fever, Powassan virus, and spotted fever rickettsioses. Because many tickborne illnesses have similar clinical presentation, laboratory testing can aid in determining the proper course of treatment that can best minimize risk of severe disease.

Quick Answers for Clinicians

Which testing algorithms are related to this topic?

Diagnosis

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
        • Coltivirus testing not available at ARUP Laboratories; contact state health laboratories or the CDC for testing
      • 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

Background

Comparison of Tickborne Diseases

Tickborne Diseases, Organisms, Risk Factors, and Epidemiology (CDC, 2016)

 

Anaplasmosis

Colorado tick fever

Ehrlichiosis

Species

Anaplasma phagocytophilum

Coltivirus

Ehrlichia chaffeensis

E. ewingii

E. muris-like (EML)

Vector ticks

Ixodes scapularis (black-legged tick)

I. pacificus (western black-legged tick)

Dermacentor andersoni (Rocky Mountain wood tick)

Amblyomma americanum (lone star tick)

  • E. chaffeensis
  • E. ewingii

I. scapularis (suspected)

  • EML

Reservoir species

Deer, elk, rodents

Rodents

White-tailed deer, coyotes, dogs, goats

Incidence

1,761 cases (CDC, 2010)

83 cases (CDC, 2002-2012)

1,518 cases of E. chaffeensis and E. ewingii infections (CDC, 2013)

69 cases of EML infections (CDC, 2007–2013)

Season

Any month; highest during summer months; peaks in June and July

April-August

Any month; highest during summer months; peaks in June and July

Endemic area

I. scapularis – upper midwestern and northeastern U.S.

I. pacificus – West Coast

Rocky Mountains at 4,000-10,000 feet of altitude

E. chaffeensis, E. ewingii – southeastern, south central, and mid-Atlantic states

EML – Wisconsin and Minnesota

Clinical presentation

Influenza-like illness

Rash – uncommon (can be macular, maculopapular, or petechial)

In rare cases, life-threatening illnesses (difficulty breathing, hemorrhage, renal failure, neurological problems) or death

Influenza-like illness, with frequent biphasic fever

Rash – uncommon and short-lived (can be macular, maculopapular, or petechial)

Central nervous system diseases (stiff neck, confusion, meningitis, meningoencephalitis) (rare), life-threatening illnesses or death (rare)

E. chaffeensis, E. ewingii, and EML

  • Influenza-like illness
  • Life-threatening illnesses (eg, bleeding disorders, difficulty breathing, central nervous system diseases) or death (rare)

E. chaffeensis

  • Rash common in children; may be present in adults (macular, maculopapular, petechial, or erythrodermic); usually spares the face and may occur on palms and soles; rarely pruritic

E. ewingii and EML

  • Rash – uncommon

Age

>40 years

15-45 years

≥50 years

Sex

M>F

M>F

M>F

Coinfection

Babesia

Bartonella

Ehrlichia

Anaplasma

Same vector as tularemia; however, tularemia is not commonly transmitted by ticks in regions where Colorado tick fever is endemic

Babesia

Bartonella

Ehrlichia

Anaplasma

 

ARUP Lab Tests

Primary Tests

Preferred panel for diagnosing possible tickborne disease (ie, anaplasmosis, ehrlichiosis, or babesiosis) during the acute phase of the disease

Panel includes Anaplasma phagocytophilum, E. chaffeensis, E. ewingii/canis, E. muris-like (EML), Babesia species, B. microti

Preferred panel for diagnosing possible tick-borne disease (ie, Anaplasmosis or Ehrlichiosis) during the acute phase of the disease

Detects and differentiates Anaplasma phagocytophilum, Ehrlichia chaffeensis, E. ewingii, E. canis, EML

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

First-line test for diagnosing acute babesiosis

This PCR test detects nucleic acid from B. microti and detects but does not differentiate between B. duncani, B. divergens, strain MO-1, and strain EU-1

Blood smears are also appropriate for diagnosing and monitoring babesiosis disease; refer to parasites smear (Giemsa stain), blood

Diagnose infection with Ehrlichia chaffeensis

May require acute and convalescent specimens to determine presence of disease

Acceptable test for acute or convalescent phase of infection from Anaplasma phagocytophilum

May be useful when PCR testing is not an option (eg, outside the 2-week window for acute phase); however, PCR testing is generally preferred; refer to tickborne disease panel or Ehrlichia and Anaplasma spp tests

May require acute and convalescent samples to determine presence of disease

Useful if Giemsa stain is negative but high suspicion of babesiosis exists

Will not detect B. duncani or strain MO-1

May require acute and convalescent specimens to determine presence of disease

Related Tests

Initial testing for infectious process

Initial screening for hepatobiliary inflammation

Panel includes albumin; ALP; AST; ALT; bilirubin, direct; protein, total; and bilirubin, total

Wright Stain

Time sensitive

Screen for and detect spirochetes and blood parasites, including microfilaria, Babesia, Trypanosoma, and Plasmodiumspecies

Patient's travel history is necessary to aid in test interpretation

Most useful to detect antibodies during acute phase of disease; recommend concurrent testing with IgG E. chaffeensis

PCR testing is preferred; refer to tickborne disease panel or Ehrlichia and Anaplasma spp tests

Most useful to detect antibodies during convalescent phase of disease

PCR testing is preferred; refer to tickborne disease panel or Ehrlichia and Anaplasma spp tests

Most useful to detect antibodies during convalescent phase of disease

PCR testing is preferred; refer to tickborne disease panel or Ehrlichia and Anaplasma spp tests

Most useful to detect antibodies during acute phase of disease; recommend concurrent testing with IgG A. phagocytophilum

PCR testing is preferred; refer to tickborne disease panel or Ehrlichia and Anaplasma spp tests

IgM titers alone may not be sufficient to confirm disease

Preferred reflex test to detect Lyme disease in individuals with ≤4 weeks of clinical symptoms or exposure to tick

Positive/equivocal screen confirmed by immunoblot

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories
Contributor

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®