Ehrlichiosis: Reporting and Surveillance

DHS surveillance resources

• Ehrlichiosis Case Reporting and Investigation Protocol (previously called EpiNet)—Ehrlichiosis, P-02228 (PDF)
• Ehrlichiosis case report form for mail or fax—Tickborne Rickettsial Disease Case Report, F-00336 (PDF)
• Preparation and response—Vectorborne Disease Toolkit, P-01109 (PDF)

Provider resources

• Transmission, symptoms, diagnosis and treatment from the CDC (Centers of Disease Control and Prevention)—Ehrlichiosis
• Practical guide for health care and public health professionals from CDC—Morbidity and Mortality Weekly Report: Diagnosis and Management of Tickborne Rickettsial Diseases (PDF)
• Epidemiology, clinical presentation, diagnosis, treatment and prevention—Ehrlichiosis Caused by Ehrlichia Muris Eauclairensis, P-03243 (PDF)

Ehrlichia and Anaplasma infections can have similar signs and symptoms. In parts of Wisconsin, the two agents also can overlap geographically. Diagnostic tests are needed to identify the specific agent causing illness. Most patients who need testing for Ehrlichia also should be tested for Anaplasma. In Wisconsin, providers should order a panel that includes testing for both Ehrlichia and Anaplasma.

Several different lab tests are used to help diagnose ehrlichiosis.

Polymerase chain reaction (PCR)

PCR is the preferred diagnostic test for Ehrlichia. It’s highly sensitive and specific during the acute disease phase (the first week of illness). Perform PCR testing using whole blood collected upon the initial physician’s visit, before starting antibiotics. A positive PCR result is confirmation of Ehrlichia infection. A negative result doesn’t rule out infection. Treatment shouldn’t be withheld due to a negative result.

Testing for Ehrlichia muris eauclairensis species is available commercially only by PCR. It’s not available by serology. Therefore, it’s important for providers who routinely perform serologic testing to collect an additional sample for PCR testing of Ehrlichia muris eauclairensis species if you suspect this agent.

Serologic testing

Serologic testing is less specific than the PCR test and cross-reactivity often occurs among the Anaplasma and Ehrlichia agents. Serologic confirmation of Anaplasma phagocytophilum or Ehrlichia species infection requires demonstration of at least a fourfold change (e.g., 1:64 to 1:256, or 1:128 to 1:512) in immunoglobulin G (IgG) specific antibody titer between paired acute and convalescent sera tested by indirect immunofluorescence assay (IFA).

Collect the acute sample during the first week of illness. Collect the convalescent sample two to four weeks later.

A single positive IgG titer may indicate a current or past infection.

Immunoglobulin M (IgM) antibody tests aren’t as reliable as IgG antibody tests. IgM tests are less specific, and so they are more likely to produce false positive results. IgM antibodies can persist for a long period of time, so positive IgM titers may not indicate acute infection. Single IgM antibody tests shouldn’t be used for diagnosis.

Serologic tests based on enzyme immunoassay (EIA) only provide a positive or negative result. They can’t be used to measure changes in antibody titers between paired sera.

Cross-reactivity between Anaplasma phagocytophilum and Ehrlichia species often occurs with serologic testing. Therefore, the agent demonstrating at least a four-fold higher titer is most likely causing the illness. The agent is undermined if there’s less than a four-fold difference in titer.

Smear/morulae

During acute infection, observation of morulae in the cytoplasm of granulocytes can provide a preliminary diagnosis. Labs usually report where morulae are observed: monocytes or granulocytes. If the smear found morulae in monocytes, the agent is most likely Ehrlichia chaffeensis. If the smear found morulae in granulocytes, the agent is most likely Anaplasma phagocytophilum. Ehrlichia ewingii also most commonly infects granulocytes. The target cell for Ehrlichia muris eauclairensis isn’t known.

If a lab routinely performs only peripheral blood smears, the DHS Division of Public Health (DPH) recommends a PCR or an IFA test to accompany a blood smear for more definitive results.

Immunohistochemistry detection and cell culture

Immunohistochemistry (IHC) detection and cell culture are confirmatory tests. However, it’s rare to see these types of positive test results.

In addition to a positive lab result, a patient also should have a clinically compatible illness. Most patients with ehrlichiosis will exhibit fever, sweats, or chills and at least one of the following:

• Headache
• Body aches
• Anemia (low red blood cell count)
• Leukopenia (low white blood cell count)
• Thrombocytopenia (low platelet count)
• Elevated liver enzymes
• Eschar (dark scab around the site of tick bite)
• Rash (in up to 60% of children, less than 30% of adults with E. chaffeensis)

Providers should prescribe treatment right away whenever ehrlichiosis is clinically suspected. Treatment for ehrlichiosis should not be delayed while waiting for lab results. Treatment should not be withheld on the basis of an initial negative lab result. Treatment decisions should be based on clinically compatible signs and symptoms and an assessment of the patient’s likelihood of tick exposure. Delaying treatment can be dangerous.

Ehrlichiosis can be treated with antibiotics. Doxycycline is the antibiotic of choice for adults and children of all ages. Most people treated with oral antibiotics during the early stages of ehrlichiosis fully recover. Some patients may continue to have headache, weakness, and malaise for weeks after receiving treatment.

*Treat patients with suspected ehrlichiosis with doxycycline until at least three days after the fever is resolved and until you see evidence of clinical improvement. The minimum course of antibiotics is five days. Patients with suspected E. muris eauclairensis infection should be treated with doxycycline for 10–14 days to cover for possible co-infection with Borrelia burgdorferi (Lyme disease).

Antibiotic treatment following a tick bite isn’t recommended to prevent ehrlichiosis. There’s no evidence this practice is effective, and it may only delay onset of disease.