Tests

1st tests to order

CBC

Test
Result
Test

Leukopenia with absolute and relative lymphopenia is common during first week of the disease; usually associated with thrombocytopenia.

Marked absolute and relative rebound lymphocytoses are seen during second week of illness.[68]

Leukopenia or thrombocytopenia is present in up to two-thirds of patients at time of presentation.

Normal counts do not rule out diagnosis.

Anemia is less frequent.

Result

leukopenia; thrombocytopenia

LFTs

Test
Result
Test

Usually shows mildly to moderately elevated aminotransferases.

Bilirubin and alkaline phosphatase are usually within normal limits unless patient is already in critical condition (e.g., septic shock).

Result

elevated

peripheral blood smear

Test
Result
Test

Careful evaluation of peripheral blood smear is recommended to detect cytoplasmic morulae (Ehrlichia/Anaplasma inclusions) in leukocytes. [Figure caption and citation for the preceding image starts]: Peripheral blood smear showing intracytoplasmic morulae (arrow) of Anaplasma phagocytophilum in a polymorphonuclear neutrophil (Giemsa stain, 1000x)Courtesy of J. Stephen Dumler, MD [Citation ends].com.bmj.content.model.Caption@78320362

Although this is a recommended investigation, detection of morulae is considered insensitive as a diagnostic test in immunocompetent patients. However, in clinical experience, in immunocompromised patients a peripheral blood smear examination performed by an experienced hematologist may confirm the diagnosis more quickly.[67]

Present in <10% of human monocytotropic/monocytic ehrlichiosis (HME) cases and 25% to 75% of human granulocytotropic/granulocytic anaplasmosis (HGA) cases.​[17][48][62][63][66][69][70][99]

Result

cytoplasmic morulae in infected leukocytes

Tests to consider

immunofluorescence antibody assay

Test
Result
Test

Diagnostic for human monocytotropic/monocytic ehrlichiosis (HME) and human granulocytotropic/granulocytic anaplasmosis (HGA).[71][76][77][101]​​

Paired samples should be obtained during the acute and convalescent phases (i.e., 2-4 weeks later) to demonstrate rising antibody titers. A fourfold or greater increase in antibody titer is diagnostic.[68]

Sensitivity in paired samples approaches 100% with some false-negatives documented in patients who receive very early antibiotic treatment based on high clinical suspicion or in patients with AIDS.

Specificity varies greatly depending on timing of testing and serologic cross-reactions between Ehrlichia and Anaplasma species.

Cannot be used for diagnosis of human ewingii ehrlichiosis (HEE) due to extensive cross-reactive antibodies with E chaffeensis.

Result

antibodies against Ehrlichia chaffeensis or Anaplasma phagocytophilum

polymerase chain reaction

Test
Result
Test

Detects ehrlichial nucleic acids (DNA/RNA) from peripheral blood/tissue specimen using primers targeting a particular ehrlichial gene.[4][48][73]​​[76][77]

Available at specialized centers only (e.g., CDC, large reference laboratories and academic research laboratories).

Initial blood sample should be collected in a red-top tube for baseline serologic assays and ethylenediamine tetraacetic acid (EDTA)- or citrate-containing tubes.

Sensitivity and specificity depend on reaction conditions and protocol (e.g., DNA primers), and whether treatment has been administered prior to collection of sample to be processed by polymerase chain reaction (PCR).

PCR using primers specific for E ewingii is the only diagnostic method available for human ewingii ehrlichiosis (HEE);​E ewingii is not culturable.[4][88]

Result

Ehrlichia or Anaplasma DNA/RNA

Emerging tests

Western immunoblotting

Test
Result
Test

Useful to confirm immunofluorescence antibody assay (IFA) or differentiate between E chaffeensis and A phagocytophilum infections in areas where the 2 bacteria are endemic (e.g., mid-Atlantic and Northeastern states).[63][102]​​[103][104]​​[105]​​[106]​​[107]​​[108]​​[109]

Analytical sensitivity is theoretically higher than with IFA, although it has not been evaluated systematically.

Available only in highly specialized research laboratories.

Result

antibodies against Ehrlichia chaffeensis or Anaplasma phagocytophilum in serum

culture

Test
Result
Test

Requires cell monolayers for isolation and is cumbersome, time consuming, and costly. Growth takes several days to weeks.

Highly dependent on rapid inoculation after obtaining sample from patient.

Isolated more frequently in patients with HIV/AIDS.

Sample should be obtained at initial presentation before starting antibiotic treatment.

Available only in highly specialized research laboratories.

Result

Ehrlichia chaffeensis or Anaplasma phagocytophilum isolated from blood sample

immunohistochemistry

Test
Result
Test

Monoclonal or polyclonal antibodies used for antigen detection in tissue sections are obtained by biopsy or at autopsy.[46][110][111]​​

Result

Ehrlichia chaffeensis or Anaplasma phagocytophilum antigen

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