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      Severe Ehrlichia chaffeensis Infection in a Lung Transplant Recipient: A Review of Ehrlichiosis in the Immunocompromised Patient

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          Abstract

          We describe a case of human ehrlichiosis in a lung transplant recipient and review published reports on ehrlichiosis in immunocompromised patients. Despite early therapy with doxycycline, our patient had unusually severe illness with features of thrombotic thrombocytopenic purpura. Of 23 reported cases of ehrlichiosis in immunocompromised patients, organ failure occurred in all patients and 6 (25%) died.

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          Most cited references31

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          Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis.

          Human ehrlichiosis is a recently recognized tick-borne infection. Four species infect humans: Ehrlichia chaffeensis, E. sennetsu, E. canis, and the agent of human granulocytic ehrlichiosis. We tested peripheral-blood leukocytes from 413 patients with possible ehrlichiosis by broad-range and species-specific polymerase-chain-reaction (PCR) assays for ehrlichia. The species present were identified by species-specific PCR assays and nucleotide sequencing of the gene encoding ehrlichia 16S ribosomal RNA. Western blot analysis was used to study serologic responses. In four patients, ehrlichia DNA was detected in leukocytes by a broad-range PCR assay, but not by assays specific for E. chaffeensis or the agent of human granulocytic ehrlichiosis. The nucleotide sequences of these PCR products matched that of E. ewingii, an agent previously reported as a cause of granulocytic ehrlichiosis in dogs. These four patients, all from Missouri, presented between May and August 1996, 1997, or 1998 with fever, headache, and thrombocytopenia, with or without leukopenia. All had been exposed to ticks, and three were receiving immunosuppressive therapy. Serum samples obtained from three of these patients during convalescence contained antibodies that reacted with E. chaffeensis and E. canis antigens in a pattern different from that of humans with E. chaffeensis infection but similar to that of a dog experimentally infected with E. ewingii. Morulae were identified in neutrophils from two patients. All four patients were successfully treated with doxycycline. These findings provide evidence of E. ewingii infection in humans. The associated disease may be clinically indistinguishable from infection caused by E. chaffeensis or the agent of human granulocytic ehrlichiosis.
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            The tribe Ehrlichieae and ehrlichial diseases.

            Y Rikihisa (1991)
            The tribe Ehrlichieae consists of gram-negative minute cocci that are obligate intracellular parasites classified in the family Rickettsiaceae. Although ehrlichial organisms have been observed in leukocytes for many years, only a few species have been cultured in quantities sufficient for biochemical and molecular analyses. Recents studies on 16S-rRNA sequence analysis and energy metabolism showed that the genus Ehrlichia is closely related to the genus Rickettsia. There is, however, no antigenic cross-reactivity between these genera. Ehrlichial organisms cause a disease called "ehrlichiosis," a noncontagious infectious disease known to be transmitted by a tick in several cases and by a fluke in one case. Ehrlichia spp. infect dogs, ruminants, horses, and humans. Recently, two new ehrlichial diseases, Potomac horse fever and human ehrlichiosis, were discovered in the United States. The etiologic agent of Potomac horse fever, Ehrlichia risticii, is closely related to the known human pathogen Ehrlichia sennetsu. The etiologic agent of human ehrlichiosis is related to Ehrlichia canis, a canine pathogen. In contrast to the genus Rickettsia, members of the tribe Ehrlichieae reside primarily in the cytoplasmic vacuoles of monocytes or granulocytes and cause hematologic abnormalities, lymphadenopathy, and other pathologic changes in the host. However, the actual mechanisms whereby Ehrlichia spp. infect leukocytes, multiply in them, and produce various forms of systemic disease have not been defined. Depending on the ehrlichial species involved, serologic or direct microscopic observation of stained blood smears is currently used to diagnose ehrlichial disease.
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              Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging?

              To characterize the clinical presentation and course, laboratory findings, and treatment outcome of 12 patients with human granulocytic ehrlichiosis. The 12 patients were male, ranged in age from 29 to 91 years, and contracted their illness in Wisconsin or Minnesota. Cases were recognized by the presence of intracytoplasmic inclusions (morulae) in peripheral neutrophils of patients presenting with temperature of 38.5 degrees C or higher, chills, severe headache, and myalgias. All patients had a complete blood cell count and blood chemistry profile. Blood smears were examined by light microscopy. All available paired serum samples were analyzed for presence of indirect fluorescent antibodies against Ehrlichia chaffeensis, Ehrlichia phagocytophila, and Ehrlichia equi. Blood samples from 12 patients were subjected to polymerase chain reaction analysis using primers specific for the E phagocytophila/E equi group, primers that include the agent identified in our patients, as well as E chaffeensis. Varying combinations of leukopenia, anemia, and thrombocytopenia were found in all but one patient. All 12 patients demonstrated morulae in the cytoplasm of neutrophils, but not in mononuclear white blood cells. Serum assays failed to detect antibodies against E chaffeensis, but eight of 10 patients and seven of 10 patients tested had antibody titers of 1:80 or more for E phagocytophila and E equi, respectively. Polymerase chain reaction products obtained with primers for E phagocytophila, E equi, and the granulocytotropic Ehrlichia revealed that seven patients were infected with the same agent. The results of serological assays or polymerase chain reaction strongly suggest that all 12 patients were infected by E phagocytophila, E equi, or a closely related Ehrlichia species. Two of the 12 patients died. The other 10 patients improved rapidly with oral doxycycline treatment. We believe that all 12 patients have been infected with a granulocytic Ehrlichia species, reflecting a recently described new disease entity. The infective organism appears to be closely related to E phagocytophila and E equi. The geographic domain of human granulocytic ehrlichiosis is currently unknown. This novel granulocytic Ehrlichia species is capable of causing fatal infections in humans. Early detection and treatment with tetracycline drugs appear to offer the best chance for complete recovery.
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                Author and article information

                Journal
                Emerg Infect Dis
                Emerging Infect. Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                March 2002
                : 8
                : 3
                : 320-323
                Affiliations
                [1]University of Wisconsin Medical School, Madison, Wisconsin, USA
                Author notes
                Address for correspondence: Nasia Safdar, Section of Infectious Diseases, University of Wisconsin, Madison, H4/574 CSC, 600 Highland Avenue, Madison, WI 53792, USA; fax: 608-263-4464; e-mail: n.safdar@ 123456hosp.wisc.edu
                Article
                01-0249
                10.3201/eid0803.010249
                2732464
                11927032
                2e2ee0fb-135d-40c1-91ed-7d7536877222
                History
                Categories
                Dispatch

                Infectious disease & Microbiology
                thrombotic thrombocytopenia purpura,ehrlichiosis,immunocompromised host

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