Human Granulocytic Ehrlichiosis in New York

Wallace, Barbara J.; Brady, G S; Ackman, David M.; Wong, Susan J.; Jacquette, Germaine; Lloyd, Elizabeth E.; Birkhead, Guthrie S.

doi:10.1001/archinte.158.7.769

Cited by 45 publications

(44 citation statements)

References 22 publications

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“…None of the patients in our study demonstrated signs of chronic disease, which is consistent with previous findings from the United States (1,6,23). Whether ehrlichiae persisted in our patients beyond the acute stage is unknown.…”

Section: Discussionsupporting

confidence: 91%

Clinical and Serological Follow-Up of Patients with Human Granulocytic Ehrlichiosis in Slovenia

Lotrič‐Furlan¹,

Avšič–Županc

Petrovec

et al. 2001

Clin Diagn Lab Immunol

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An evaluation of the clinical outcome and the duration of the antibody response of patients with human granulocytic ehrlichiosis (HGE) was undertaken in Slovenia. Adult patients with a febrile illness occurring within 6 weeks of a tick bite were classified as having probable or confirmed HGE based on the outcome of serological or PCR testing. Thirty patients (median age, 44 years) were enrolled, and clinical evaluations and serum collection were undertaken at initial presentation and at 14 days, 6 to 8 weeks, and 3 to 4, 6, 12, 18, and 24 months. An indirect immunofluorescence assay (IFA) was performed, and reciprocal titers of >128 were interpreted as positive. Patients presented a median of 4 days after the onset of fever and were febrile for a median of 7.5 days; four (13.3%) received doxycycline. Seroconversion was observed in 3 of 30 (10.0%) patients, and 25 (83.3%) showed >4-fold change in antibody titer. PCR results were positive in 2 of 3 (66.7%) seronegative patients but in none of 27 seropositive patients at the first presentation. IFA antibody titers of >128 were found in 14 of 29 (48.3%), 17 of 30 (56.7%), 13 of 30 (43.4%), and 12 of 30 (40.0%) patients 6, 12, 18, and 24 months after presentation, respectively. Patients reporting additional tick bites during the study had significantly higher antibody titers at most time points during follow-up. No long-term clinical consequences were found during follow-up.Human granulocytic ehrlichiosis (HGE) is an emerging tickborne disease described for the first time in 1994 in the United States (4). The first European case of acute HGE was uncovered in Slovenia in 1996 and reported in 1997 (20). Through September 2000, nine patients with acute HGE confirmed by positive PCR results and/or at least fourfold change in antibody titers contracted their illness in Central Europe, in Slovenia (15,16,24; S. Lotric-Furlan, M. Petrovec, T. AvsicZupanc, T. Lejko-Zupanc, and F. Strle, Abstr. II Croatian Congr. Infect. Dis. Int. Participation, abstr. 71, p. 30, 2000).The epidemiology and ecology of HGE have not been completely elucidated. The etiological agent of HGE is closely related to the veterinary pathogen Ehrlichia phagocytophila, which has been a recognized cause of disease among ruminants in Europe for decades (25). In Europe, E. phagocytophila is transmitted by Ixodes ricinus ticks (21).The clinical presentation of HGE is generally nonspecific and usually consists of fever, headache, malaise, myalgias, and/or arthralgias. A history of tick bite or tick exposure, while suggestive, is not diagnostic. Similarly, clinical laboratory findings of leukopenia, thrombocytopenia, and elevated liver enzymes are typical but relatively nonspecific, making the diagnosis problematic.Infection with E. phagocytophila in the acute stage has been confirmed by identification of morulae in granulocytes, positive PCR results using whole blood as a substrate, and/or isolation of E. phagocytophila from the blood. Serological tests, particularly indirect immunofluorescence assay (IFA), ar...

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Section: Discussionsupporting

confidence: 91%

Clinical and Serological Follow-Up of Patients with Human Granulocytic Ehrlichiosis in Slovenia

Lotrič‐Furlan¹,

Avšič–Županc

Petrovec

et al. 2001

Clin Diagn Lab Immunol

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“…uman granulocytic anaplasmosis (HGA) and Lyme disease typically occur in the same geographic areas since both are acquired by the bite of infected Ixodes ticks (1)(2)(3)(4)(5). The etiologic agents, however, are quite different.…”

mentioning

confidence: 99%

“…Erythema migrans usually can be diagnosed clinically without the need for laboratory confirmation (1). In contrast, HGA is not known to be associated with a distinctive clinical feature, and therefore, laboratory testing is required to establish the diagnosis (2)(3)(4)(5).…”

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confidence: 99%

Differences and Similarities between Culture-Confirmed Human Granulocytic Anaplasmosis and Early Lyme Disease

et al. 2013

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Lyme disease is transmitted by the bite of certain Ixodes ticks, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Although culture can be used to identify patients infected with A. phagocytophilum and is the microbiologic gold standard, few studies have evaluated culture-confirmed patients with HGA. We conducted a prospective study in which blood culture was used to detect HGA infection in patients with a compatible clinical illness. Early Lyme disease was defined by the presence of erythema migrans. The epidemiologic, clinical, and laboratory features of 44 patients with culture-confirmed HGA were compared with those of a convenience sample of 62 patients with early Lyme disease. Coinfected patients were excluded. Patients with HGA had more symptoms (P ‫؍‬ 0.003) and had a higher body temperature on presentation (P < 0.001) than patients with early Lyme disease. HGA patients were also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes. A direct correlation between the number of symptoms and the duration of illness at time of presentation (rho ‫؍‬ 0.389, P ‫؍‬ 0.009) was observed for HGA patients but not for patients with Lyme disease. In conclusion, although there are overlapping features, culture-confirmed HGA is a more severe illness than early Lyme disease. Human granulocytic anaplasmosis (HGA) and Lyme disease typically occur in the same geographic areas since both are acquired by the bite of infected Ixodes ticks (1-5). The etiologic agents, however, are quite different. HGA is caused by Anaplasma phagocytophilum, an obligate intracellular bacterium, whereas Lyme disease is caused by an extracellular spirochetal bacterium, Borrelia burgdorferi (1, 2).The hallmark of early Lyme disease is a distinctive annular erythematous skin lesion, called erythema migrans, that occurs at the site of tick inoculation of B. burgdorferi. Erythema migrans usually can be diagnosed clinically without the need for laboratory confirmation (1). In contrast, HGA is not known to be associated with a distinctive clinical feature, and therefore, laboratory testing is required to establish the diagnosis (2-5).Although A. phagocytophilum can be cultured in vitro, few laboratories offer such testing. Consequently, most of the reported cases have been diagnosed serologically or through PCR detection of A. phagocytophilum DNA. These laboratory methods, while generally reliable, are not necessarily equivalent to the diagnostic gold standard in microbiology of a positive culture. No systematic comparison of culture-confirmed HGA with Lyme disease has been reported. In this study, we compare the epidemiologic, clinical, and laboratory features of culture-confirmed HGA with those of early Lyme disease. MATERIALS AND METHODSStudy design. This was a prospective, observational study that recorded the baseline epidemiologic, clinical, and laboratory features of patients with culture-confirmed HGA ...

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“…HGE has recently been described in the United States and Europe and is found in areas where Borrelia burgdorferi and Babesia microti, pathogens transmitted by Ixodes scapularis or Ixodes ricinus ticks, are prevalent (3,8,9,15,16,30,31,33,34,43). Fever, malaise, headache, myalgia, and leukopenia are common during infection.…”

mentioning

confidence: 99%

Gamma Interferon Dominates the Murine Cytokine Response to the Agent of Human Granulocytic Ehrlichiosis and Helps To Control the Degree of Early Rickettsemia

Akkoyunlu

Fikrig

2000

Infect Immun

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The cytokine response to the agent of human granulocytic ehrlichiosis (HGE) was assessed in a murine infection model and the role of gamma interferon (IFN-␥), a cytokine that is crucial for host defenses against intracellular pathogens, was investigated by using IFN-␥-deficient mice. The agent of HGE (aoHGE) is an obligate intracellular bacterium that survives within neutrophils: morulae (vacuoles containing HGE organisms) are evident in polymorphonuclear leukocytes of experimentally infected immunocompetent mice for 1 to 2 weeks. We now show that IFN-␥ levels increase during early infection of C3H/HeN or C57BL/6 mice with HGE bacteria. Moreover, in response to aoHGE extracts or concanavalin A, splenocytes from ehrlichia-infected mice produced more IFN-␥ and less interleukin-4 than controls, suggesting that aoHGE partially skewed the immune response towards a Th1 phenotype. Absolute concentration of morulae containing neutrophils in blood was 122 ؎ 22 cells/l on day 8. The bacterial DNA burden was also highest on day 8 and then declined after IFN-␥ levels peaked. In contrast, IFN-␥-deficient mice had a markedly elevated HGE bacteria burden with morulae concentration of 282 ؎ 48 cells/l on day 5 (P ‫؍‬ 0.004) and 242 ؎ 63 cells/l on day 8 (P ‫؍‬ 0.005). Rickettsemia resolved in immunocompetent and IFN-␥ deficient mice after 2 weeks, while both the immunocompetent and the IFN-␥-deficient mice had increased serum antibodies against aoHGE antigens at this time point. These data demonstrate that the HGE agent elicits a prominent IFN-␥ response in mice and that IFN-␥ is important in controlling the degree of rickettsemia during the early phase of infection, while IFN-␥ independent mechanisms play a role at later time points.

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Human Granulocytic Ehrlichiosis in New York

Cited by 45 publications

References 22 publications

Clinical and Serological Follow-Up of Patients with Human Granulocytic Ehrlichiosis in Slovenia

Clinical and Serological Follow-Up of Patients with Human Granulocytic Ehrlichiosis in Slovenia

Differences and Similarities between Culture-Confirmed Human Granulocytic Anaplasmosis and Early Lyme Disease

Gamma Interferon Dominates the Murine Cytokine Response to the Agent of Human Granulocytic Ehrlichiosis and Helps To Control the Degree of Early Rickettsemia

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