Case Definitions for Public Health Surveillance Purposes:
As of January 1, 2008, E. chaffeensis and E. ewingii infections are reported under distinct reporting categories.
This surveillance case definition was developed for national reporting of Human Ehrlichiosis; it is not intended to be used in clinical diagnosis.
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.
Clinical evidence: Any reported fever and one or more of the following: headache, myalgia, anemia, leukopenia, thrombocytopenia, or any hepatic transaminase elevation.
Ehrlichia chaffeensis infection (formerly Human Monocytic Ehrlichiosis [HME])
Laboratory criteria for diagnosis
- 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
- 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
Ehrlichia ewingii infection (formerly Ehrlichiosis [unspecified, or other agent])
Laboratory criteria for diagnosis
- 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.
Ehrlichiosis/Anaplasmosis, human, undetermined
- See case classification
History of having been in potential tick habitat in the 14 days prior to the onset of illness or history of tick bite or history of tick bite.
Suspected: A case with laboratory evidence of past or present infection but no clinical information available (e.g. a laboratory report).
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.
Confirmed: A clinically compatible case (meets clinical evidence criteria) that is laboratory confirmed.
Case Report Forms
For confirmed and probable cases of ehrlichiosis that have been identified and reported through the National Notifiable Disease Surveillance System, states are also encouraged to submit additional information using the CDC Case Report Form (CRF). This form collects additional important information that routine electronic reporting does not, such as information on how the diagnosis was made, and whether the patient was hospitalized or died. If a different state-specific form is already used to collect this information, this information may be submitted to CDC in lieu of a CRF.
2010 CDC Case Report Form: Tickborne Rickettsial Diseases (2010 version) (PDF – 982kb; 3 pages)
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.
The 2008 case definition appearing on this page was re-published in the 2009 CSTE position statement 09-ID-15. Thus, the 2008 and 2010 versions of the case definition are identical.