Interference Between the Agents of Lyme Disease and Human Granulocytic Ehrlichiosis in a Natural Reservoir Host

ABSTRACT We describe a patient with human granulocytic ehrlichiosis (HGE), a diagnosis confirmed by PCR and immunoblot analysis. Unexpectedly, immunoglobulin G (IgG) directed towards an 80-kDa ehrlichial antigen (without detectable IgM) was present in the patient’s serum in the first week of illness. Lyme disease immunoblots were reactive for IgG (but not IgM), a result indicative of prior exposure to the Lyme disease spirochete. Amino-terminal sequencing revealed that the 80-kDa ehrlichial antigen was an HSP-70 homolog similar to Borrelia burgdorferi HSP-70. We conclude that antibodies against B. burgdorferi HSP-70 may cross-react with the ehrlichial heat shock protein and that this possibility must be considered when serologic test results for HGE and Lyme disease are interpreted.

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Geographic Risk for Lyme Disease and Human Granulocytic Ehrlichiosis in Southern New York State

Applied and Environmental Microbiology ◽

10.1128/aem.64.12.4663-4669.1998 ◽

1998 ◽

Vol 64 (12) ◽

pp. 4663-4669 ◽

Cited By ~ 67

Author(s):

Thomas J. Daniels ◽

Theresa M. Boccia ◽

Shobha Varde ◽

Jonathan Marcus ◽

Jianhua Le ◽

...

Keyword(s):

New York ◽

Lyme Disease ◽

Case Reports ◽

Risk Index ◽

New York State ◽

Fold Increase ◽

York State ◽

Granulocytic Ehrlichiosis ◽

Human Granulocytic Ehrlichiosis ◽

Pathogen Surveillance

ABSTRACT Ixodes scapularis, the tick vector of Lyme disease and human granulocytic ehrlichiosis (HGE), is prevalent in much of southern New York state. The distribution of this species has increased, as have reported cases of both Lyme disease and HGE. The unreliability of case reports, however, demonstrates the need for tick and pathogen surveillance in order to accurately define areas of high risk. In this study, a total of 89,550 m2 at 34 study sites was drag sampled in 1995 and a total of 51,540 m2 at 40 sites was sampled in 1996 to determine tick and pathogen distribution in southern New York state. I. scapularis was collected from 90% of the sites sampled, and regionally, a 2.5-fold increase in nymphal abundance occurred from 1995 to 1996. I. scapularisindividuals from all sites were infected with Borrelia burgdorferi in 1995, while an examination of ticks for bothB. burgdorferi and the agent of HGE in 1996 confirmed that these organisms were present in all counties; the average coinfection rate was 1.9%. No correlation was found between estimated risk and reported cases of Lyme disease. The geographic disparity of risk observed among sites in this study underscores the need for vector and pathogen surveillance on a regional level. An entomologic risk index can help identify sites for targeted tick control efforts.

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Immunodiagnosis of Human Granulocytic Ehrlichiosis by Using Culture-Derived Human Isolates †

Journal of Clinical Microbiology ◽

10.1128/jcm.36.6.1480-1488.1998 ◽

1998 ◽

Vol 36 (6) ◽

pp. 1480-1488 ◽

Cited By ~ 18

Author(s):

M. Dana Ravyn ◽

Jesse L. Goodman ◽

Carrie B. Kodner ◽

Deborah K. Westad ◽

Lisa A. Coleman ◽

...

Keyword(s):

Lyme Disease ◽

Immunoblot Analysis ◽

Cross Reactivity ◽

Immunofluorescence Assay ◽

Etiologic Agent ◽

Immunoglobulin M ◽

Test Method ◽

Serum Samples ◽

Granulocytic Ehrlichiosis ◽

Human Granulocytic Ehrlichiosis

Human granulocytic ehrlichiosis (HGE) is an emerging infection caused by an Ehrlichia species closely related toEhrlichia equi and Ehrlichia phagocytophila. Recent advances in the isolation and cultivation of this organism have allowed us to develop an immunofluorescence assay (IFA), enzyme immunoassay (EIA), and Western immunoblotting (WB) using HL-60 cell culture-derived human isolates. Antibody was detected in sera from culture-confirmed HGE patients by IFA and EIA, and these samples were reactive when analyzed by immunoblot analysis. HGE patient sera had high antibody titers and did not react with uninfected HL-60 cells. When IFA, EIA, and WB were used to analyze sera from healthy donors or those with a range of other disorders, including infections caused byEhrlichia chaffeensis, Rickettsia rickettsii, and Coxiella burnetti, no significant cross-reactivity could be detected by EIA or immunoblot analysis with the exception of two of four serum samples from R. rickettsii-infected patients that were reactive by IFA only. Sera from HGE patients did not significantly cross-react in serologic tests for Borrelia burgdorferi. Using sera from patients previously enrolled in two clinical trials of treatment for early Lyme disease, we evaluated a two-step approach for estimation of the seroprevalence of antibodies reactive with the etiologic agent of HGE. On the basis of the immunoblot assay results for sera from culture-confirmed HGE patients, WB was used to confirm the specificity of the antibody detected by EIA and IFA. EIA was found to be superior to IFA in the ability to detect WB-confirmed antibodies to the HGE agent. When EIA and WB were used, 56 (19.9%) patients with early Lyme disease (n = 281) had either specific immunoglobulin M (IgM) or IgG antibodies; 38 patients (13.5%) had IgM only, 6 (2.1%) had IgG only, and 12 (4.3%) had both IgM and IgG. Therefore, Lyme disease patients are at high potential risk for exposure to Ehrlichia. Analysis by immunoblotting of serial samples from persons with culture-confirmed HGE or patients with Lyme disease and antibodies to the agent of HGE revealed a reproducible pattern of the immune response to specific antigens. These samples confirmed the importance of the 42- to 45-kDa antigens as early, persistent, and specific markers of HGE infection. Other significant immunogenic proteins appear at 20, 21, 28, 30, and 60 kDa. Use of the two-test method of screening by EIA and confirming the specificity by WB appears to offer a sound approach to the clinical immunodiagnosis of HGE.

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