Anaplasma Phagocytophilum Infection
2008 Case Definition

Clinical Description

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.

Exposure

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.

Comments

There are at least three species of bacteria, all intracellular, responsible for ehrlichiosis/anaplasmosis in the United States: E. chaffeensis, found primarily in monocytes, and A. phagocytophilum and E. 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 E. 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, immunohistochemistry, 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.

Laboratory Criteria For Diagnosis

Supportive:

• Serological evidence of elevated IgG or IgM antibody reactive with E. chaffeensis antigen by indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), dot-ELISA, or assays in other formats (CDC uses an IFA Immunoglobulin G [IgG] cutoff of ≥1:64 and does not use Immunoglobulin M [IgM] test results independently as diagnostic support criteria), OR
• Identification of morulae in the cytoplasm of monocytes or macrophages by microscopic examination

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 Criteria For Diagnosis

Confirmed:
Because the organism has never been cultured, antigens are not available. Thus, E. 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 PCR assay.

Laboratory Criteria For Diagnosis

See case classification