Ehrlichiosis
2024 Case Definition

Background

Ehrlichiosis is the general name given to the diseases caused by obligate intracellular bacteria in the genus Ehrlichia within the family Anaplasmataceae. Ehrlichia species are tickborne pathogens and are the most commonly reported species transmitted by Amblyomma americanum, the lone star tick¹. The majority of reported human infections are caused by either Ehrlichia chaffeensis or Ehrlichia ewingii. Most cases of ehrlichiosis occur across the south-central, southeastern, and mid-Atlantic states, although Ehrlichia muris eauclairensis, which is transmitted by Ixodes scapularis, the blacklegged tick, has been reported from travelers to, or residents of, Minnesota and Wisconsin^2,3. Ehrlichiosis typically presents 5 to 14 days after a tick bite with a combination of nonspecific clinical symptoms, such as fever, fatigue, and headache. Illness is often accompanied by laboratory abnormalities including leukopenia, thrombocytopenia, and mildly elevated liver enzymes. Ehrlichiosis may result in severe illness or even death in older or immunocompromised individuals or if treatment is delayed. Serologic testing is commonly used to diagnosis ehrlichiosis, but antibodies to Anaplasma and Ehrlichia spp. can cross-react.

Clinical Criteria

• Objective clinical evidence: fever as reported by patient or healthcare provider, anemia, leukopenia, thrombocytopenia, or any hepatic transaminase elevation.
• Subjective clinical evidence: chills/sweats, headache, myalgia, nausea/vomiting, or fatigue/malaise.

Laboratory Criteria

Confirmatory laboratory evidence:

• Detection of E. chaffeensis*, E. ewingii*, E. muris eauclairensis*, unspeciated Ehrlichia spp., or other Ehrlichia spp. DNA in a clinical specimen via amplification of a specific target by polymerase chain reaction (PCR) assay, nucleic acid amplification tests (NAAT), or other molecular method, OR,
• Serological evidence of a fourfold change₁ in immunoglobulin G (IgG)-specific antibody titer to Ehrlichia spp. antigen by indirect immunofluorescence assay (IFA) in paired serum samples (one taken in first two weeks after illness onset and a second taken two to ten weeks after acute specimen collection)₂, OR
• Demonstration of ehrlichial antigen in a biopsy or autopsy sample by immunohistochemical methods OR
• Isolation of E. chaffeensis*, E. ewingii*, E. muris eauclairensis*, unspeciated Ehrlichia spp., or other Ehrlichia spp. from a clinical specimen in cell culture with molecular confirmation (e.g., PCR or sequence).

Presumptive laboratory evidence:

• Serological evidence of elevated IgG antibody reactive with Ehrlichia spp. antigen by IFA at a titer ≥1:128 in a sample taken within 60 days of illness onset, OR
• Microscopic identification of intracytoplasmic morulae in leukocytes in a sample taken within 60 days of illness onset.

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.
* Ehrlichia chaffeensis infection was formerly included in the category Human Monocytic Ehrlichiosis (HME); Ehrlichia ewingii infection was formerly included in the category Ehrlichiosis (unspecified, or other agent); Ehrlichia muris eauclairensis infection was formerly included in the category Undetermined Anaplasmosis/Ehrlichiosis.
¹A four-fold change in titer is equivalent to a change of two dilutions (e.g., 1:64 to 1:256).
² A four-fold rise in titer should not be excluded as confirmatory laboratory criteria if the acute and convalescent specimens are collected within two weeks of one another.

Criteria to Distinguish a New Case from an Existing Case

A person previously reported as a probable or confirmed case-patient may be counted as a new case-patient when there is an episode of new clinically compatible illness with confirmatory laboratory evidence.

Suspect

• Meets confirmatory or presumptive laboratory evidence with no or insufficient clinical information to classify as a confirmed or probable case (e.g., a laboratory report only).

Probable

• Meets presumptive laboratory evidence with fever as reported by patient or healthcare provider AND at least one other objective or subjective clinical evidence criterion (excluding chills/sweats), OR
• Meets presumptive laboratory evidence without a reported fever but with chills/sweats AND
  • at least one objective clinical evidence criterion, OR
  • two other subjective clinical evidence criteria.

Confirmed

• Meets confirmatory laboratory evidence AND at least one of the objective or subjective clinical evidence criteria.

Case Classification Comments

• Ehrlichiosis is reported at the species level only if molecular testing is performed, as antibodies to closely-related species of Ehrlichia can cross-react with multiple antigens; serologic assays cannot definitively distinguish between species. Therefore, E. chaffeensis, E. ewingii, and E. muris eauclairensis ehrlichiosis reported cases should only be classified as “Confirmed.” Cases reported within the “Ehrlichia, other spp. or unspeciated” can be classified as either “Probable” or “Confirmed”.
• Patients should not be classified as cases for both anaplasmosis and ehrlichiosis based on serologic evidence alone.
• Ehrlichia spp. bacteria are closely related to A. phagocytophilum, and many patients are tested using serologic panels that include targets for both species. As a result, it is not uncommon for jurisdictions to receive positive antibody results for both Ehrlichia spp. and Anaplasma with the same collection date for a single patient. Public health agencies should use a combination of titer levels, information about the location of possible exposures, clinical manifestations, and the incidence of a particular disease in the geographic areas of exposure to help determine the appropriate disease type for individual patients.

• Ehrlichiosis | 2000 Case Definition
• Ehrlichiosis | 1998 Case Definition
• Ehrlichiosis | 1996 Case Definition