DISSS Home | Contact Us


•	8-City Enhanced Terrorism Surveillance Project: Resource Materials
•	Downloads
•	Epi Info™
•	National Notifiable Diseases Surveillance System

•	Data Systems
•	Public Health Surveillance

Ehrlichiosis/Anaplasmosis

Contents
•	Home - National Notifiable Diseases Surveillance System
•	Overview
•	Introduction
•	List of Nationally Notifiable Diseases
•	Alphabetical List of Case Definitions
•	Definition of Terms
•	Related Links
•	References
	Site Search

2008 Case Definition

Clinical presentation

A tick-borne illness characterized by acute onset of fever and one or more of the following symptoms or signs: headache, myalgia, malaise, anemia, leukopenia, thrombocytopenia, or elevated hepatic transaminases. Nausea, vomiting, or rash may be present in some cases. Intracytoplasmic bacterial aggregates (morulae) may be visible in the leukocytes of some patients.

Clinical evidence

Any reported fever and one or more of the following: headache, myalgia, anemia, leukopenia, thrombocytopenia, or any hepatic transaminase elevation.

Laboratory evidence

For the purposes of surveillance,

Ehrlichia chaffeensis infection (formerly included in the category Human Monocytic Ehrlichiosis [HME]):

Laboratory confirmed:
- Serological evidence of a fourfold change in immunoglobulin G (IgG)-specific antibody titer to E. chaffeensis antigen by indirect immunofluorescence assay (IFA) between paired serum samples (one taken in first week of illness and a second 2-4 weeks later), or
- Detection of E. chaffeensis DNA in a clinical specimen via amplification of a specific target by polymerase chain reaction (PCR) assay, or
- Demonstration of ehrlichial antigen in a biopsy or autopsy sample by immunohistochemical methods, or
- Isolation of E. chaffeensis from a clinical specimen in cell culture.
Laboratory supportive:
- Serological evidence of elevated IgG or IgM antibody reactive with E. chaffeensis antigen by IFA, enzyme-linked immunosorbent assay (ELISA), dot-ELISA, or assays in other formats (CDC uses an IFA IgG cutoff of ≥1:64 and does not use IgM test results independently as diagnostic support criteria.), or
- Identification of morulae in the cytoplasm of monocytes or macrophages by microscopic examination.

Ehrlichia ewingii infection (formerly included in the category Ehrlichiosis [unspecified, or other agent]):

Laboratory confirmed:
- Because the organism has never been cultured, antigens are not available. Thus, Ehrlichia ewingii infections may only be diagnosed by molecular detection methods: E. ewingii DNA detected in a clinical specimen via amplification of a specific target by polymerase chain reaction (PCR) assay.
Anaplasma phagocytophilum infection (formerly included in the category Human Granulocytic Ehrlichiosis [HGE]):

Serological evidence of a fourfold change in IgG-specific antibody titer to A. phagocytophilum antigen by indirect immunofluorescence assay (IFA) in paired serum samples (one taken in first week of illness and a second 2-4 weeks later), or
Detection of A. phagocytophilum DNA in a clinical specimen via amplification of a specific target by polymerase chain reaction (PCR) assay, or
Demonstration of anaplasmal antigen in a biopsy/autopsy sample by immunohistochemical methods, or
Isolation of A. phagocytophilum from a clinical specimen in cell culture.

Serological evidence of elevated IgG or IgM antibody reactive with A. phagocytophilum antigen by IFA, enzyme-linked immunosorbent Assay (ELISA), dot-ELISA, or assays in other formats (CDC uses an IFA IgG cutoff of ≥1:64 and does not use IgM test results independently as diagnostic support criteria.), or
Identification of morulae in the cytoplasm of neutrophils or eosinophils by microscopic examination.

Human ehrlichiosis/anaplasmosis – undetermined:
- See case classification

Exposure

Exposure is defined as having been in potential tick habitats within the past 14 days before onset of symptoms. A history of a tick bite is not required.

Case Classification

Confirmed: A clinically compatible case (meets clinical evidence criteria) that is laboratory confirmed.

Probable: A clinically compatible case (meets clinical evidence criteria) that has supportive laboratory results. For ehrlichiosis/anaplasmosis – an undetermined case can only be classified as probable. This occurs when a case has compatible clinical criteria with laboratory evidence to support ehrlichia/anaplasma infection, but not with sufficient clarity to definitively place it in one of the categories previously described. This may include the identification of morulae in white cells by microscopic examination in the absence of other supportive laboratory results.

Suspect: A case with laboratory evidence of past or present infection but no clinical information available (e.g. a laboratory report).

Comment

There are at least three species of bacteria, all intracellular, responsible for ehrlichiosis/ anaplasmosis in the United States: Ehrlichia chaffeensis, found primarily in monocytes, and Anaplasma phagocytophilum and Ehrlichia ewingii, found primarily in granulocytes. The clinical signs of disease that result from infection with these agents are similar, and the range distributions of the agents overlap, so testing for one or more species may be indicated. Serologic cross-reactions may occur among tests for these etiologic agents.

Four sub-categories of confirmed or probable ehrlichiosis/anaplasmosis should be reported: 1) human ehrlichiosis caused by Ehrlichia chaffeensis, 2) human ehrlichiosis caused by E. ewingii, 3) human anaplasmosis caused by Anaplasma phagocytophilum, or 4) human ehrlichiosis/anaplasmosis - undetermined. Cases reported in the fourth sub-category can only be reported as “probable” because the cases are only weakly supported by ambiguous laboratory test results.

Problem cases for which sera demonstrate elevated antibody IFA responses to more than a single infectious agent are usually resolvable by comparing the levels of the antibody responses, the greater antibody response generally being that directed at the actual agent involved. Tests of additional sera and further evaluation via the use of PCR, IHC, and isolation via cell culture may be needed for further clarification. Cases involving persons infected with more than a single etiologic agent, while possible, are extremely rare and every effort should be undertaken to resolve cases that appear as such (equivalent IFA antibody titers) via other explanations.

Current commercially available ELISA tests are not quantitative, cannot be used to evaluate changes in antibody titer, and hence are not useful for serological confirmation. Furthermore, IgM tests are not always specific and the IgM response may be persistent. Therefore, IgM tests are not strongly supported for use in serodiagnosis of acute disease.

References

Dumler JS. Barbet AF. Bekker CP. Dasch GA. Palmer GH. Ray SC. Rikihisa Y. Rurangirwa FR. 2001. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and 'HGE agent' as subjective synonyms of Ehrlichia phagocytophila. International Journal of Systematic & Evolutionary Microbiology. 51(Pt 6):2145-2165. Medline UI: 11760958