Approach Considerations
Lumbar puncture may be necessary in patients with fever and severe headache to rule out meningitis.
Buffy coat examination may reveal morulae, which are diagnostic characteristics of HME/HGA. Morulae are observed in the cytoplasm of neutrophils in patients with HGA and in monocytes in patients with HME. Only a minority of patients with HME have detectable morulae.
Diagnostic Workup
The diagnosis of human monocytic ehrlichiosis (HME) or human granulocytic anaplasmosis (HGA) rests on several testing methods:
Serology (2 types): (1) indirect fluorescent antibody and (2) enzyme-linked immunosorbent assays.
A single elevated immunoglobulin G (IgG) immunofluorescent antibody (IFA) Ehrlichia titer or (2) demonstration of a 4-fold or greater increase between acute and convalescent IFA Ehrlichia titers. [1]
Buffy coat examination: Ehrlichiosis may also be diagnosed by demonstrating characteristic morulae in the cytoplasm of leukocytes. Morulae are diagnostic of ehrlichiosis and occur more frequently in HGA than in HME. The microbiology laboratory should be alerted to look carefully in the blood smear for them.
Polymerase chain reaction: Detection of the organism with polymerase chain reaction (PCR) assay is now becoing widely available. Sensitivity and specificity of assays may vary but has been reported as high as 95-100 percent by some laboratories. [15]
Immunohistochemical stains: Although not a preferred method, immunohistochemical stains have been used to make the diagnosis of ehrlichiosis and anaplasmosis in a few patients through bone marrow staining tissue or autopsy tissue such as spleen, lymph nodes, liver, or lung. [16]
Culture: The infecting organism is extremely difficult to culture from blood and therefore is not recommended.
Laboratory Studies
A complete blood cell (CBC) count should be obtained for possible neutropenia, relative lymphopenia, and/or thrombocytopenia. Anemia is not a feature of ehrlichiosis and, if present, is not a hemolytic anemia, as in babesiosis.
Atypical lymphocytes have been reported in patients with ehrlichiosis. The erythrocyte sedimentation rate (ESR) is minimally/moderately elevated in ehrlichiosis.
Elevated C-reactive protein (CRP) levels are common in the first week of illness and typically resolve by the end of the second week.
Serum transaminases are frequently mildly elevated in ehrlichiosis, as well as in other tick-borne infectious diseases. Abnormal liver enzymes are found in 86% of patients.
If other infectious diseases are suspected, appropriate tests should be obtained to rule out these diagnoses. If coinfection with RMSF or babesiosis is suspected, appropriate serology should be obtained to diagnose each of these infectious diseases.
Microscopic examination (by an experienced microbiologist) of blood smears stained with eosin-azure type dyes, such as Wright-Giemsa stain, may reveal morulae in the cytoplasm of leukocytes. As many as 20% of patients with HME and 20-80% of patients with HGA may have morulae in the first week of infection. A negative result should not be taken as proof of no infection.
Hyponatremia (< 130 mEq/L) is found in 40% of patients.
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Female Lone Star tick, Amblyomma americanum, found in the southeastern and Midatlantic United States. It is a vector of several zoonotic diseases, including human monocytic ehrlichiosis and Rocky Mountain spotted fever. Courtesy of the CDC/Michael L. Levin, PhD.
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Map of the United States showing the distribution of the Lone Star Tick, which is the principle vector for ehrlichiosis.
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Established and reported distribution of anaplasmosis vectors Ixodes scapularis and Ixodes pacificus, by county, in the United States from 1907-1996. Courtesy of the Division of Vector-Borne Infectious Diseases at the Centers for Disease Control and Prevention.
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Anaplasmosis incidence by age. Courtesy of the Centers for Disease Control and Prevention.
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Ehrlichiosis incidence by age. Courtesy of the Centers for Disease Control and Prevention.
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This graph displays the number of human cases of ehrlichiosis caused by Ehrlichia chaffeensis reported to the Centers for Disease Control and Prevention (CDC) annually from 2000 through 2016. *From 2000 to 2008, ehrlichiosis was included in the reporting category “human monocytic ehrlichiosis” in reports to the National Notifiable Diseases Surveillance System (NNDSS). **Since 2008, ehrlichiosis has been reported to the NNDSS under the categories “Ehrlichia chaffeensis infections,” “Ehrlichia ewingii infections,” and “Undetermined ehrlichiosis/anaplasmosis infections”, which include infections caused by Ehrlichia muris eauclairensis. Only E chaffeensis infections are shown above. Courtesy of the CDC (https://www.cdc.gov/ehrlichiosis/stats/index.html).
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This graph shows the number of ehrlichiosis cases caused by Ehrlichia chaffeensis reported from 2000 through 2016 by month of onset to illustrate the seasonal trends. Cases are reported in each month of the year, although most are reported in June and July. Courtesy of the CDC (https://www.cdc.gov/ehrlichiosis/stats/index.html).
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This graph shows the number of US ehrlichiosis cases caused by Ehrlichia chaffeensis and reported to the CDC from 2000 to 2018. Courtesy of the CDC (https://www.cdc.gov/ehrlichiosis/stats/).
Tables
|
Human monocytic ehrlichiosis (HME) |
Human granulocytic anaplasmosis (HGA) |
Cell type Affected |
Monocytes |
Granulocytes |
Organism |
E chaffeensis |
A phagocytophilum |
Vector |
Amblyomma americanum (Lone Star tick) |
Ixodes scapularis (black-legged tick), Ixodes pacificus (Western black-legged tick) in California, Ixodes ricinus in Europe, and probably Ixodes persulcatus in parts of Asia |
Location |
Southeastern and south-central United States |
Wisconsin and Minnesota, less active in New York and Connecticut, also California |
Rash |
30% of adults, 60% of children |
Rare |
Prognosis |
~3% mortality |
< 1% mortality |
