Ehrlichiosis Epidemiology

A. Agent: Ehrlichiosis was not recognized in the U.S. until the late 1980’s and became a reportable disease in 19991,2. Ehrlichiosis is a general name used to describe several bacterial diseases in humans and animals. In the United States, ehrlichiosis can be caused by three different species of gram negative bacteria: Ehrlichia chaffeensis, Ehrlichia ewingii, and Ehrlichia muris-like (EML)1,2.

B. Clinical Description: Ehrlichiosis usually presents with non-specific symptoms, including fever, headache, fatigue, and muscle aches1,2. Chills, malaise, nausea, vomiting, diarrhea, confusion, and conjunctival infections can also occur1,2. Development of a skin rash is not a common feature of ehrlichiosis. About 60% of children and less than 30% of adults develop a rash1,2. The rash associated with Ehrlichia chaffeensis infection may range from maculopapular to petechial in nature, and is usually not itchy1,2. The combination of symptoms varies from person to person1,2. Severe illness can occur, including difficulty breathing or bleeding disorders1,2. Ehrlichiosis can be fatal if left untreated, and has a 1.8% case fatality rate. Immunocompromised individuals may experience a more severe clinical illness1,2.

C. Vectors: The Ehrlichia bacteria are spread to humans by the bite of an infected tick. In the United States, Amblyomma americanum (lone star tick) is the primary vector of Ehrlichia chaffeensis and Ehrlichia ewingii1,2. The long star tick is often found in the southeastern and south central United States. Three states (Oklahoma, Missouri, and Arkansas) account for 30% of all reported E. chaffeensis infections1,2. A vector has not been established yet for Ehrlichia muris-like (EML), but human travel-associated cases have been identified in Minnesota and Wisconsin1,2.

D. Mode of Transmission: Ehrlichiosis is spread by the bite of an infected Amblyomma americanum tick (lone star tick) 1,2.

E. Incubation Period: Symptoms usually occur within 1-2 weeks after a tick bite1,2.

F. Period of Communicability: Ehrlichiosis is not directly transmitted person-to-person1,2. There is a possibility of transmission of Ehrlichia through blood transfusion or organ transplantation1,2.

G. Treatment: Doxycycline is the first line treatment for adults and children1,2. This should be prescribed immediately whenever ehrlichiosis is suspected. The recommended dosage is 100 mg every 12 hours for adults and 2.2 mg/kg body weight given twice a day for children under 45 kg (100 lbs) 1,2. Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement. Standard duration of treatment is 7–14 days1,2. Some patients may continue to experience headache, weakness and malaise for weeks after adequate treatment1,2.

Ehrlichiosis Protocol Last Revised: 3/25/2020 Ehrlichiosis Disease Management

H. Clinical Case Definition3: A tick-borne illness characterized by acute onset of fever and one or more of the following signs or symptoms: headache, myalgia, malaise, anemia, leukopenia, thrombocytopenia, or elevated liver enzymes. Nausea, vomiting, or rash may be present in some cases1,2,3. The following categories of confirmed or probable ehrlichiosis should be reported: • Human ehrlichiosis caused by E. chaffeensis (formerly Human Monocytic Ehrlichiosis/HME) • Human ehrlichiosis caused by E. ewingii (formerly unspecified or other agent) • Human ehrlichiosis—undetermined. Cases in this category can only be reported as probable because the cases are only weakly supported by ambiguous laboratory test results.

NOTE: The clinical signs of disease from infection with anaplasmosis are similar to ehrlichiosis, and the range distributions overlap, so testing for one or more species may be indicated. Serologic cross-reactions may occur among tests for these agents.

I. Laboratory Criteria for Diagnosis3: Confirmatory Testing (E. chaffeensis infection (formerly HME)) • Serological evidence of a four-fold change in immunoglobulin G (IgG)-specific antibody titer to E. chaffeensis 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 E. chaffeensis DNA in a clinical specimen via PCR assay, OR • Demonstration of ehrlichial antigen in a biopsy or autopsy sample by IHC, OR • Isolation of E. chaffeensis from a clinical specimen in cell culture. Supportive Testing • Serological evidence of elevated IgG or IgM antibody reactive with E. chaffeensis antigen by IFA, ELISA, dot-ELISA, or assays in other acceptable formats, OR • Identification of morulae in the cytoplasm of monocytes or macrophages by microscopic examination. Confirmatory Testing (E. ewingii infection) • Detection of E. ewingii DNA in a clinical specimen via PCR assay. E. ewingii has never been cultured; therefore, antigens are not available and this infection can only be diagnosed by molecular detection methods.

Case Classification3 Confirmed A clinically compatible case that meets the criteria for clinical evidence criteria and for confirmatory laboratory testing. Probable A clinically compatible case that meets clinical evidence criteria and has supportive laboratory results. For ehrlichiosis, an undetermined case can only be classified as probable. An undetermined case has compatible clinical criteria with lab evidence to support Ehrlichia spp infection, but not with sufficient clarity to definitively place it in one of the categories described. This may include identification of morulae in white cells by microscopic examination in the absence of other supportive lab results.

Ehrlichiosis Protocol Last Revised: 3/25/2020 Suspect A case with lab evidence of past or present infection but no clinical information available (e.g., a lab report). NOTE: 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 using PCR, IHC, and isolation via cell culture may be needed for further clarification. Cases involving persons infected with more than a single agent, while possible, are extremely rare and every effort should be made to resolve cases that appear as such by other explanations.

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

J. Laboratory Testing1,2,3: • During the early phase of illness, whole blood can be tested using PCR. Antibodies may be undetectable in the first 7–10 days of illness in about 85% of patients. Negative PCR results, however, do not rule out illness. • A blood smear is also helpful and may reveal “morulae” (microcolonies of ehrlichiae) in the cytoplasm of white blood cells in about 20% of patients. E. chaffeensis commonly infect monocytes and E. ewingii commonly infect granulocytes. • The gold standard for serologic testing for ehrlichiosis diagnosis is IFA on paired sera to look for a four-fold rise in antibody titer. An acute titer should be taken upon illness onset and a convalescent titer should be taken 2–4 weeks later.

K. Outbreak Definition: There are no formal outbreak definitions.

Ehrlichiosis Protocol Last Revised: 3/25/2020

Ehrlichiosis Investigation Guidelines

L. Time Frame: Ehrlichiosis is a nationally notifiable condition and should be reported within 5 working days. Local county public health is responsible for conducting an investigation on any reported cases.

M. Forms: - CDC Tick-borne Disease Investigation Form: http://www.cdc.gov/ticks/forms/2010_tbrd_crf.pdf

N. Investigation Steps: § Confirm Diagnosis i. Contact medical provider who reported or ordered the testing of the case and determine if the needed epidemiologic data can be found in the clinical record alone. ii. Collect case demographic data and contact information: • Birth date, county, sex, race/ethnicity, address, and phone number(s). iii. Collect additional information including: • Symptom onset, hospitalizations, laboratory test results, and outcome status (survived or date of death). • If pregnant: obtain the due date.

§ Conduct Case Investigation i. If data found in patient charts does not provide information on risk factors, interview the case to determine source, risk factors, and transmission settings. ii. Focus case investigation within the incubation period of the specific infectious agent, and consider recent travel to endemic areas, history of tick attachment, or possible tick exposure. iii. If there was no travel to an endemic area AND the confirmed case definition is met, list geographic location(s) and date(s) of: • Recent travel to endemic areas or history of possible exposure to ticks • Exposure to animals or pets with ticks. • Outdoor activities. • Occupational risks (e.g., forestry worker, landscape worker, etc. • Any travel 30 days prior to onset that was outside the county

§ Environmental Measures Community-based integrated tick management strategies may reduce the incidence of tick-borne infections, but limiting exposure to ticks is the most effective method of prevention.

§ Education and Prevention Messages for ehrlichiosis prevention are similar to all tick-borne diseases. Educate on endemic areas for ehrlichiosis and proper prevention when outdoors, including wearing long clothing and insect repellant with DEET.

Ehrlichiosis Protocol Last Revised: 3/25/2020

Resources

1. Ehrlichiosis (Internet). Centers for Disease Control and Prevention. Retrieved April 2017 from: http://www.cdc.gov/ehrlichiosis

2. Diagnosis and Management of Tick-borne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States: A Practical Guide for Health Care and Public Health Professionals. MMWR Recommendations and Reports May 13, 2016 / 65(2); 1-44: https://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htm?s_cid=rr6502a1_w

3. ADHS Case Definitions for Reportable Communicable Morbidities, 2017: http://www.azdhs.gov/documents/preparedness/epidemiology-disease control/disease- investigation-resources/case-definitions.pdf

4. Harris, R., Couturier, B., Sample, S., Coulter, K., Casey, K., & Schlaberg, R. (2016, May). Expanded Geographic Distribution and Clinical Characteristics of Ehrlichia ewingii Infections, United States Emerging Infectious Diseases. 22(5): 862-865.

5. Dumler JS, Madigan JE, Pusterla N, Bakken JS. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2007;45(Suppl 1):S45–51. http://dx.doi.org/10.1086/518146

6. Dahlgren FS, Mandel EJ, Krebs JW, Massung RF, McQuiston JH. Increasing incidence of Ehrlichia chaffeensis and Anaplasma phagocytophilum in the United States, 2000–2007. Am J Trop Med Hyg. 2011;85:124–31. http://dx.doi.org/10.4269/ajtmh.2011.10-0613.

Ehrlichiosis Protocol Last Revised: 3/25/2020 Ehrlichiosis Protocol

Date Revised by Epi Manager Signature 12/29/2014 Hayley Yaglom 11/16/2015 Laura Adams Laura Adams 4/26/2017 Hayley Yaglom Heather Venkat

Ehrlichiosis Protocol Last Revised: 3/25/2020