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Ehrlichia Species • the E Ehrlichia Species • The E. muris-like or EML agent was first described in Wis- consin and Minnesota during 2009; represents the third Disease Agent: Ehrlichia sp. described to cause disease in humans in the United States. • Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia muris-like (EML) Common Human Exposure Route: Disease Agent Characteristics: • Bite of infected tick • Obligate intracellular Gram-negative bacterium of mono- Likelihood of Secondary Transmission: cytes (E. chaffeensis) and granulocytes (E. ewingii) • Order: Rickettsiales; Family: Anaplasmataceae • None documented • Size: 0.5-0.8 μm x 1.2-3 μm • Nucleic acid: Rickettsial genomes are among the smallest of At-Risk Populations: bacteria. Ehrlichia are approximately 1200-1600 kb. • Individuals at enhanced risk for exposure to infected ticks • Physicochemical properties: The rickettsiae are susceptible through outdoor activity, including those involved in hiking, to 1% sodium hypochlorite, 70% ethanol, glutaraldehyde, gardening, clearing brush, etc. formaldehyde, and quaternary ammonium disinfectants. • The frequency of reported cases is higher among males and Sensitive to moist heat (121°C) for at least 15 minutes and anyone 50 years of age. dry heat (160-170°C) for at least 1 hour > • A compromised immune system due to cancer treatments, Disease Name: advanced HIV infection, prior organ transplants, or immune suppression may increase the risk of severe outcome. • Human ehrlichiosis, human monocytic ehrlichiosis (HME) Priority Level: Vector and Reservoir Involved: • Scientific/Epidemiologic evidence regarding blood safety: • Lone star tick, Amblyomma americanum, distributed Low throughout southeastern and south central US; transmits • Public perception and/or regulatory concern regarding both E. chaffeensis and E. ewingii. Dermacentor variabilis blood safety: Very low (American dog tick) and Rhipicephalus sanguineus (brown • Public concern regarding disease agent: Very low/low in dog tick) have been identified as secondary vectors of E. focal/endemic areas chaffeensis and/or E. ewingii. • Cases in the western US suggest additional tick vectors that Background: are thought to be D. variabilis and Ixodes pacificus. • Human ehrlichiosis is an emerging tick-borne zoonosis • Tick vector for EML found in Wisconsin and Minnesota has with exposure occurring in rural and suburban tick habi- not been identified, but may be I. scapularis. tats during recreational and peridomestic activities. First • White-tailed deer are thought to be the primary reservoir for became a reportable disease (i.e., HME) in 1999. Infections E. chaffeensis. E. ewingii has been demonstrated to infect caused by E. ewingii became a separate reportable disease white-tailed deer, but the current status of deer as a reservoir in 2008. host has not been established. • Documented HME has been reported from 47 states, • Dogs are the definitive host for E. ewingii. especially in the south central and southeast US. This corresponds to the distribution of the major vector tick, Blood Phase: Amblyomma americanum, and the white-tailed deer • Although data are scant, the recently reported transfusion (Odocoileus virginianus) that serves as the reservoir host. transmission of E. ewingii demonstrates asymptomatic bac- • Concern over potential transfusion transmission first arose teremia for this species. in 1997 during an outbreak of febrile disease at Fort Chaffee, • Experimental infection in dogs suggests that the agent may where a large blood drive was conducted just after military circulate in blood for over 3 weeks. donors had extensive exposure to infected ticks. No transfu- • Asymptomatic human infection is suspected. An Ehrlichia sion transmission was documented in the subsequent species related to E. canis was isolated from the blood of investigations. an asymptomatic persistently infected patient in South • E. ewingii was first documented as a cause of human disease America. in 1999. Relatively few cases reported, but agent likely widely distributed throughout the central and southeastern US. In Survival/Persistence in Blood Products: some cases, infections with E. ewingii may be misdiagnosed and attributed to infection with E. chaffeensis. This species • E. chaffeensis remains viable when infected monocytes are also reported in a single transfusion transmission. inoculated into RBCs stored at 4-6°C for at least 11 days, with July 2013: update to TRANSFUSION 2009;49(Suppl):175-77S 1 supernatant organisms found, suggesting the potential for Primary Disease Symptoms: transfusion transmission. • Fever with headache, myalgia, and malaise • E. ewingii transmitted by platelets at day 5 of storage. • Gastrointestinal, respiratory, or central nervous system Transmission by Blood Transfusion: involvement also may occur. • Rash appears in up to 60% of children and less than 30% of • One case involving E. ewingii occurred in 2011. Recipient adults with HME. Not common in patients infected with was a 9-year old boy with a history of acute lymphoblastic E. ewingii or EML. leukemia and anemia secondary to chemotherapy. Morulae • Leukopenia, thrombocytopenia and elevated transaminases (microcolonies of Ehrlichia) were identified in granulocytes, are common laboratory signs. infection was confirmed by PCR, patient was treated with doxycycline and recovered within 48 hours. Patient denied Severity of Clinical Disease: any risk factors for exposure other than transfusion. Impli- • Currently most infections are not diagnosed, but HME can cated donor (IgG titer 1:512) reported frequent tick attach- be a life-threatening disease, with hospitalization in 41-63% ment at home in Florida and wooded property in South of recognized cases. Carolina in the month prior to donation. Transfused product • Severely affected patients can develop acute respiratory was a day 5 leukoreduced and irradiated apheresis platelet failure, renal failure, meningoencephalitis, coagulopathy, unit. and GI bleeding. • In 1997, following deployment to Fort Chaffee, AR, a number • Untreated disease may progress to death as early as the of National Guard personnel developed febrile illnesses. second week of illness. Investigation of both symptomatic and asymptomatic indi- viduals demonstrated serological evidence for infection with Mortality: both Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, and E. chaffeensis. Blood drives had been con- • 1-2% ducted during the deployment. Evaluation of 10 recipients • Since HME became a reportable disease in 1999, the annual of components from 377 personnel with confirmed or prob- case fatality rate has declined. able infections did not demonstrate transmission of either Chronic Carriage: organism. • Not documented Cases/Frequency in Population: Treatment Available/Efficacious: • 3.6% seroprevalence for HME has been documented in selected areas. • Tetracyclines (e.g., doxycycline) are effective. • Among 413 patients from Missouri with possible ehrlichio- • Rifampin may be an alternative when tetracyclines cannot sis, 60 (15%) tested positive by PCR from EDTA whole blood be used (pregnancy and tetracycline allergy), but data are for Ehrlichia spp: 56 (14%) for E. chaffeensis and 4 (1%) for limited. E. ewingii. • The number of ehrlichiosis cases due to E. chaffeensis has Agent-Specific Screening Question(s): increased steadily, from 200 cases in 2000 ( < 1 case/million • No specific question is in use. population), to 961 cases in 2008 (3.4/million). A decrease • Not indicated because to date transfusion transmission has in the number of E. chaffeensis cases was noted in 2010 been rare. (2.5/million). • No sensitive or specific question is likely to be feasible. In • 28 cases of E. ewingii infection reported to the CDC from endemic areas, a question on exposure to tick bites has been 2008-2010. shown to be ineffective in distinguishing Babesia-infected • Majority of cases have an illness onset during the summer from Babesia-uninfected donors, and probably also lacks months, peaking in June/July. sensitivity and specificity for Ehrlichia spp. Incubation Period: Laboratory Test(s) Available: • 1-2 weeks (median: 9 days) • No FDA-licensed blood donor screening test exists. • Available diagnostic tests include IFA (some cross reactivity Likelihood of Clinical Disease: with other Ehrlichia species) and western blot, PCR, visual- • Low/Moderate, based on serosurveys ization of morulae in blood smear, immunohistochemical • Symptoms are often subclinical or are usually mild and staining, and culture isolation. flu-like. s During the first week of infection, examination of • Immunocompromised individuals who are infected may peripheral blood smears may reveal morulae in the develop more severe manifestations of disease. cytoplasm of white blood cells (2-38% for HME). 2 s Specialized cell culture techniques can be used to Other Prevention Measures: amplify the infection and observe infected cells (highly • Tick avoidance measures (e.g., long pants, long sleeves, variable sensitivity and may be delayed for weeks for insect/tick repellant) HME). • Riboflavin/Light has been effective in inactivating Orientia s IFA is considered the gold standard serologic test. A tsutsugamushi, a related organism. four-fold rise in IgG antibody level is considered diag- nostic for a recent infection (for HME sensitivity ranges Other Comments: from 22-55% in the first week after onset, to > 90% after • Dogs may serve as regional or local sentinels of potential risk 3 weeks). for human infection with ehrlichial agents. s PCR detection primarily
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