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Ehrlichia species are small, obligate intracellular bacteria, similar to rickettsia, that infect peripheral blood leukocytes. Organisms are transmitted to humans through tick bites, most commonly Amblyomma americanum (Lone Star tick) or Ixodes, which is also associated with Lyme disease. In the United States, three Ehrlichia species are known to cause symptomatic human infection; Ehrlichia chaffeensis, E. ewingii and Ehrlichia muris-Like Agent (EML). Ehrlichia chaffeensis is the most common cause of human ehrlichiosis and causes human monocytic ehrlichiosis (HME). E. ewingii is also transmitted to humans by the Lone Star tick. Dogs, cats and deer have also been infected with E. ewingii.  Ehrlichia muris-Like Agent (EML) is transmitted to humans by the blacklegged tick, Ixodes scapularis. So far, cases have only been identified in patients who were exposed to ticks in Minnesota and Wisconsin.

Ehrlichia multiply in cytoplasmic vacuoles, forming tightly packed clusters of bacteria called morulae. Symptoms typically appear a median of 9 days (range 5–14 days) after the bite of an infected tick. Common signs and symptoms include fever, headache, malaise, and myalgia. Nausea, vomiting and diarrhea may also occur, especially in children. Approximately one-third of patients develop a skin rash approximately 5 days after illness onset that varies from petechial to maculopapular or diffuse erythema. The rash typically involves the extremities and trunk but can affect the palms, soles, or face. Cough or respiratory symptoms develop in one third of. Meningitis or meningoencephalitis is present in approximately 20% of patients. Other severe manifestations include ARDS, toxic shock-like or septic shock-like syndromes, renal failure, hepatic failure, coagulopathies, and occasionally, hemorrhage. Mortality rate is approximately 3%.

Laboratory findings include leukopenia, thrombocytopenia, and mildly elevated hepatic transaminases. Anemia occurs later in approximately 50% of cases. In approximately 20% of patients, morulae can be observed in monocytes in peripheral blood. During the recovery phase, absolute lymphocytosis is seen in most patients. Mild-to-moderate hyponatremia might also be present.

When CSF is evaluated, a lymphocytic pleocytosis is most commonly observed, although neutrophilic pleocytosis also can occur. CSF protein is often elevated and glucose is normal.

Recommended testing for HME includes IgG antibody for Ehrlichia chaffeensis. An immunofluorescence assay titer of 1:64 or higher suggests current or previous infection. In general, the higher the titer, the more likely the patient has an active infection. Four-fold rises in titer with serial testing also indicate active infection. Diagnostic titers usually appear by the third week after symptom onset. Falsely negative results can occur if a specimen is collected too early in the course of illness. Ehrlichia ewingii antibodies cross-react with serologic assays for Ehrlichia chaffeensis. Specimen requirement for antibody testing is a red top tube of blood.

PCR techniques allow direct detection of pathogen-specific DNA from patients' whole blood during the acute phase of disease.Positive results indicate presence of specific DNA from Ehrlichia chaffeensis, Ehrlichia ewingii, or Ehrlichia muris-like organism and support the diagnosis of ehrlichiosis. Negative PCR results indicate the absence of ehrlichiosis agent at detectable levels in the sample tested and do not exclude the diagnosis. Specimen requirement is one lavender top tube of blood.

Ticks should not be submitted for identification or testing. Likewise, the examination of peripheral blood smears for ehrlichia morulae is very low yield (≤20%) and is unreliable as a diagnostic test.

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