Case Definitions: Ehrlichiosis

Ehrlichiosis

2023 Case Definition

CSTE Position Statement Number: 23-ID-04

Clinical Presentation

Ehrlichiosis typically presents 5 to14 days after a tick bite with a combination of nonspecific clinical symptoms such as fever, fatigue, headache. Illness is often accompanied by laboratory abnormalities including leukopenia, thrombocytopenia, and mildly elevated liver enzymes

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 change ¹ in immunoglobulin G (IgG)-specific antibody titer to Ehrlichia 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

** 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.

1 A 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.

Case classification

Confirmed*** :

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

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 reported fever but with chills/sweats AND

at least one objective clinical evidence criterion, OR

two other subjective clinical evidence criteria.

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).

*** Patients should not be classified as cases for both anaplasmosis and ehrlichiosis based on serologic evidence alone.

Criteria to Distinguish a New Case of Ehrlichiosis from Reports or Notifications which Should Not be Enumerated as a New Case for Surveillance

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.

Table VII.A. Classification Table: Criteria for Defining a Case of Ehrlichiosis

Criterion	Confirmed	Probable			Suspect
Clinical Evidence
Objective Clinical Evidence
Fever as reported by patient or healthcare provider	O	N
Anemia	O	O	O
Leukopenia	O	O	O
Thrombocytopenia	O	O	O
Hepatic transaminase elevation	O	O	O
Subjective Clinical Evidence
Chills/sweats	O		N	N
Headache	O	O
Myalgia	O	O
Nausea or vomiting	O	O
Fatigue or malaise	O	O
At least two of the following Subjective Clinical Evidence criteria: Headache Myalgia Nausea or vomiting Fatigue or malaise				N
No or insufficient clinical information to classify as a confirmed or probable case					N
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 test (NAAT), or other molecular method	O				O
Serological evidence of a fourfold change1 in immunoglobulin G (IgG)- specific antibody titer to Ehrlichia 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	O				O
Demonstration of ehrlichial antigen in a biopsy or autopsy sample by immunohistochemical method	O				O
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)	O				O
Serological evidence of elevated IgG antibody reactive with Ehrlichia spp. antigen by IFA ≥1:128 in a sample taken within 60 days of illness onset		O	O	O	O
Microscopic identification of intracytoplasmic morulae in leukocytes in a sample taken within 60 days of illness onset		O	O	O	O
Epidemiologic Linkage Evidence
N/A

Notes:

N = All “N” criteria in the same column are NECESSARY to classify a case.

O = At least one of these “O” (ONE OR MORE) criteria in each category (categories=clinical evidence, laboratory evidence, and epidemiologic evidence) in the same column—in conjunction with all “N” criteria in the same column—is required to classify a case.

* = Patients should not be classified as cases for both anaplasmosis and ehrlichiosis based on serologic evidence alone.

1 = A 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.